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Sample records for invasive cancer overview

  1. Bladder cancer: overview and disease management. Part 1: non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Anderson, Beverley

    2018-05-10

    Part 1 of this two-part article provides an overview of bladder cancer and discusses its management. Since publication of a previous article entitled 'Understanding the role of smoking in the aetiology of bladder cancer' ( Anderson, 2009 ), the author has received many requests for an update. This article provides an overview of bladder cancer and its current management practices, underlining the continued role of smoking as the predominant risk factor in the disease's development. The management of bladder cancer is governed by specific guidelines. Management of non-muscle-invasive cancers, including surgical intervention with transurethral resection, and intravesical therapy using chemotherapy and immunotherapy agents, is discussed. Cystectomy (removal of the bladder), is sometimes necessary. Treatments are effective in reducing tumour recurrence, but the effects of the risks and side-effects on the individual's quality of life can be significant. The prevalence of bladder cancer, and the nature of its management make this cancer one of the most expensive for the NHS to treat. The effectiveness of health promotional strategies in increasing peoples' awareness of their risk of developing the disease, and in enabling them to change long-term health behaviours is discussed. The role of the multidisciplinary team is explored, along with that of the uro-oncology cancer nurse specialist. Part 2 will consider the management of muscle-invasive and metastatic bladder cancer.

  2. Overview and Prevention of Cervical Cancer | Ogu | Nigerian Health ...

    African Journals Online (AJOL)

    Background: Cervical cancer though a preventable disease, still has an estimated mortality of 80% from invasive cervical cancer in developing countries. The aim of this paper is to present an overview of cervical cancer and the various modalities available for screening and prevention of cervical cancer. Methodology: ...

  3. Protocols for Migration and Invasion Studies in Prostate Cancer.

    Science.gov (United States)

    van de Merbel, Arjanneke F; van der Horst, Geertje; Buijs, Jeroen T; van der Pluijm, Gabri

    2018-01-01

    Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype. This way prostate cancer cells often lose polarity and epithelial characteristics (e.g., expression of E-cadherin homotypic adhesion receptor), and acquire mesenchymal phenotype (for example, cytoskeletal rearrangements, enhanced expression of proteolytic enzymes and other repertory of integrins). This process is referred to as epithelial-to-mesenchymal transition (EMT). Cellular invasion, one of the hallmarks of cancer, is characterized by the movement of cells through a three-dimensional matrix, resulting in remodeling of the cellular environment. Cellular invasion requires adhesion, proteolysis of the extracellular matrix, and migration of cells. Studying the migratory and invasive ability of cells in vitro represents a useful tool to assess the aggressiveness of solid cancers, including those of the prostate.This chapter provides a comprehensive description of the Transwell migration assay, a commonly used technique to investigate the migratory behavior of prostate cancer cells in vitro. Furthermore, we will provide an overview of the adaptations to the Transwell migration protocol to study the invasive capacity of prostate cancer cells, i.e., the Transwell invasion assay. Finally, we will present a detailed description of the procedures required to stain the Transwell filter inserts and quantify the migration and/or invasion.

  4. Breast Cancer Overview

    Science.gov (United States)

    ... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

  5. Epigenetic suppression of neprilysin regulates breast cancer invasion.

    Science.gov (United States)

    Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

    2016-03-07

    In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

  6. Transcriptomic and genomic features of invasive lobular breast cancer.

    Science.gov (United States)

    Desmedt, Christine; Zoppoli, Gabriele; Sotiriou, Christos; Salgado, Roberto

    2017-06-01

    Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

    Science.gov (United States)

    Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

    2016-07-01

    Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. ©2016 American

  8. CT evaluation of gastric cancer. Depth of tumor invasion and pancreas invasion

    International Nuclear Information System (INIS)

    Banba, Yoshihisa; Kanazawa, Tadayoshi; Seto, Hikaru

    1998-01-01

    To compare the internal structure of tumor and the contiguous organ configuration on computed tomography (CT) with the depth of tumor invasion on the pathological specimen. Sixty-four gastric cancers depicted on incremental dynamic CT were classified according to the internal structure of the tumor, and correlated with the depth of tumor invasion. In addition, the cancers were classified according to the contiguous pancreatic configuration, and correlated with the degree of pancreatic invasion. Eleven tumors with thickened gastric wall consisting of both a thick inner layer of high attenuation and a thin outer layer of low attenuation (two-layered tumor with a thin outer layer) did not invade the serosa: mucosa (n=5) and submucosa (n=6). Of 59 gastric cancers with a regular margin to the contiguous pancreas, pancreatic invasion was absent in 58 and present in one. Pancreatic invasion was present in all of five gastric cancers with an irregular margin. Our results indicate that two-layered gastric tumors with a thin outer layer never invade the serosa. Furthermore, pancreatic invasion is predicted only when the margin of the contiguous pancreas is irregular. (author)

  9. Extracellular Molecules Involved in Cancer Cell Invasion

    International Nuclear Information System (INIS)

    Stivarou, Theodora; Patsavoudi, Evangelia

    2015-01-01

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion

  10. HPV genotypes in invasive cervical cancer in Danish women

    DEFF Research Database (Denmark)

    Kirschner, Benny; Junge, Jette; Holl, Katsiaryna

    2013-01-01

    Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer.......Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer....

  11. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  12. Pepducin Based Intervention of Breast Cancer Invasion

    Science.gov (United States)

    2006-08-01

    Metalloprotease-1 Receptor that Promotes Invasion and Tumorigenesis of Breast Cancer Cells. Cell 120, 303-313. (6) Arribas , J. (2005) Matrix Metalloproteases...promotes invasion and tumorigenesis of breast cancer cells. Cell 2005;120:303–13. 6. Arribas J. Matrix metalloproteases and tumor inva- sion. N Engl J Med...to ala - provide a model for more aggressive, tamoxifen-insen- nine. The F43A PAR1 mutant does not transduce a sig- sitive, breast cancers. MDA-MB-231

  13. Cancer invasion and the microenvironment: plasticity and reciprocity.

    NARCIS (Netherlands)

    Friedl, P.H.A.; Alexander, S.

    2011-01-01

    Cancer invasion is a cell- and tissue-driven process for which the physical, cellular, and molecular determinants adapt and react throughout the progression of the disease. Cancer invasion is initiated and maintained by signaling pathways that control cytoskeletal dynamics in tumor cells and the

  14. MicroRNA-96 Promotes Tumor Invasion in Colorectal Cancer via RECK.

    Science.gov (United States)

    Iseki, Yasuhito; Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Hirakawa, Kosei; Ohira, Masaichi

    2018-04-01

    miR-96 is reported to inhibit reversion cysteine-rich Kazal motif (RECK), which is associated with tumor invasion, in solid cancer types (e.g. breast cancer, non-small cell lung cancer, esophageal cancer). The purpose of this study is to clarify whether miR-96 is similarly associated with tumor invasion in colorectal cancer. We performed western blotting to investigate the expression of RECK when miR-96 mimics or inhibitors were transferred into HCT-116 colorectal cancer cells. The RECK mRNA level was assessed by a reverse transcription polymerase chain reaction. An invasion assay was used to evaluate tumor invasion. The expression of RECK was inhibited by the transfection of miR-96 mimics. RECK mRNA level was reduced by miR-96 mimics and increased by miR-96 inhibitor. In the invasion assay, miR-96 mimics were shown to promote tumor invasion. miR-96 may be associated with tumor invasion through inhibition of RECK expression in colorectal cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Radiolabeled antibodies in cancer. Oncology Overview

    International Nuclear Information System (INIS)

    1984-11-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories through the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiolabeled antibodies--labeling and imaging techniques; Radiolabeled antibodies--carcinoembryonic antigen; Radiolabeled antibodies--alpha-fetoprotein; Radiolabeled antibodies--human chorionic gonadotropin; Radiolabeled antibodies--ferritin; Radiolabeled antibodies--imaging of colorectal tumors; Radiolabeled antibodies--imaging of malignant melanoma; Radiolabeled antibodies--imaging of urogenital tumors; Radiolabeled antibodies--imaging of thyroid tumors; Radiolabeled antibodies--other clinical studies; Radiolabeled antibodies--selected preclinical studies; Radiolabeled antibodies--reviews

  16. Five-Year Risk of Interval-Invasive Second Breast Cancer

    Science.gov (United States)

    Buist, Diana S. M.; Houssami, Nehmat; Dowling, Emily C.; Halpern, Elkan F.; Gazelle, G. Scott; Lehman, Constance D.; Henderson, Louise M.; Hubbard, Rebecca A.

    2015-01-01

    Background: Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. Methods: We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. Results: The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. Conclusions: PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans. PMID:25904721

  17. Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

    2012-01-01

    The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

  18. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-14-1-0080 TITLE: Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer . PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer . 5a. CONTRACT NUMBER 5b. GRANT NUMBER GRANT11489...institutional, NIH-funded study of genetic and epigenetic alterations of pre-invasive DCIS that did or did not progress to invasive breast cancer , with an

  19. Diagnosis and treatment of pancreatic cancer. Oncology overview

    International Nuclear Information System (INIS)

    1982-09-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiological diagnosis of pancreatic cancer; Biopsy and cytology in the diagnosis of pancreatic cancer; Pathology and morphology of pancreatic cancer; Staging and prognosis of pancreatic cancer; Biological and immunological markers in the diagnosis of pancreatic cancer; Surgical treatment of pancreatic cancer; Drug therapy of pancreatic cancer; Radiation therapy of pancreatic cancer; Selected studies on the epidemiology of pancreatic cancer; Clinical correlates and syndromes associated with pancreatic neoplasia

  20. [Lobular neoplasms and invasive lobular breast cancer].

    Science.gov (United States)

    Sinn, H-P; Helmchen, B; Heil, J; Aulmann, S

    2014-02-01

    The term lobular neoplasia (LN) comprises both atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) and thus a spectrum of morphologically heterogeneous but clinically and biologically related lesions. LN is regarded as a nonobligatory precursor lesion of invasive breast cancer and at the same time as an indicator lesion for ipsilateral and contralateral breast cancer risk of the patient. Rare pleomorphic or florid variants of LCIS must be differentiated from classical LCIS. The classical type of invasive lobular carcinoma (ILC) can be distinguished from the non-special type of invasive breast cancer (NST) by E-cadherin inactivation, loss of E-cadherin related cell adhesion and the subsequent discohesive growth pattern. Variant forms of ILC may show different molecular features, and solid and pleomorphic differentiation patterns in cases of high grade variants. Important parameters for the prognostic assessment of ILC are tumor grading and the recognition of morphological variants.

  1. Skin invasion and prognosis in node negative breast cancer: a retrospective study

    Directory of Open Access Journals (Sweden)

    Horii Rie

    2008-01-01

    Full Text Available Abstract Background The impact of skin invasion in node negative breast cancer is uncertain. Methods We determined the prognosis in 97 node negative breast cancer patients (case group who had tumors with skin invasion. Then we compared these patients with 4500 node negative invasive breast cancer patients treated surgically in the same period. Results Patients with skin invasion tended to be older, had more invasive lobular carcinoma and larger tumor size, and were less likely to have breast conserving surgery than those in the control group. The 5-year disease-free survival rate in the case group was 94.0%. There was no significant difference in the 10-year disease-specific overall survival rates in terms of skin invasion in node negative patients (90.7% in the case group, 92.9% in the control group; p = 0.2032. Conclusion Results suggest that skin invasion has no impact on survival in node negative invasive breast cancer patients. The adjuvant regimens which the individual institute applies for node negative breast cancer should be used regardless of skin invasion.

  2. Five-year risk of interval-invasive second breast cancer.

    Science.gov (United States)

    Lee, Janie M; Buist, Diana S M; Houssami, Nehmat; Dowling, Emily C; Halpern, Elkan F; Gazelle, G Scott; Lehman, Constance D; Henderson, Louise M; Hubbard, Rebecca A

    2015-07-01

    Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans. © The Author 2015. Published by Oxford University Press. All rights reserved

  3. Accuracy and consequences of same-day, invasive lung cancer workup

    DEFF Research Database (Denmark)

    Madsen, Kirsten Riis; Høegholm, Asbjørn; Bodtger, Uffe

    2016-01-01

    BACKGROUND: Though widely used, little is known about accuracy and efficacy of same-day, invasive workup of suspected lung cancer. OBJECTIVE: To evaluate the accuracy and efficacy of same-day, invasive lung cancer workup (diagnosis and mediastinal staging), and to identify differences between...... patients without (Group A) or with (Group B) need for resampling. METHODS: A retrospective study was performed on all consecutive patients referred for surgical treatment for localised lung cancer after invasive diagnostic and staging workup at our unit. Data were extracted from electronic medical files...... pulmonary disease. Tumour located in right upper lobe was associated with need for resampling. DISCUSSION: Our retrospective study suggests that same-day, invasive workup for lung cancer is safe, accurate, and efficacious in reducing time to therapy, even in patients with small lesions and low tumour burden....

  4. Postoperative adjuvant therapy of breast cancer. Oncology Overview

    International Nuclear Information System (INIS)

    1984-12-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Postoperative chemotherapy; Postoperative radiotherapy; Postoperative hormone therapy; Postoperative immunotherapy and chemoimmunotherapy; Postoperative multimodal therapy; Prognostic factors in postoperative adjuvant therapy

  5. Perspectives of Nanotechnology in Minimally Invasive Therapy of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yamin Yang

    2013-01-01

    Full Text Available Breast cancer, the most common type of cancer among women in the western world, affects approximately one out of every eight women over their lifetime. In recognition of the high invasiveness of surgical excision and severe side effects of chemical and radiation therapies, increasing efforts are made to seek minimally invasive modalities with fewer side effects. Nanoparticles (<100 nm in size have shown promising capabilities for delivering targeted therapeutic drugs to cancer cells and confining the treatment mainly within tumors. Additionally, some nanoparticles exhibit distinct properties, such as conversion of photonic energy into heat, and these properties enable eradication of cancer cells. In this review, current utilization of nanostructures for cancer therapy, especially in minimally invasive therapy, is summarized with a particular interest in breast cancer.

  6. The thioredoxin system in breast cancer cell invasion and migration

    Directory of Open Access Journals (Sweden)

    Maneet Bhatia

    2016-08-01

    Full Text Available Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1 in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1 expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

  7. Cancer Genetics Overview (PDQ®)—Health Professional Version

    Science.gov (United States)

    Cancer Genetics Overview discusses hereditary cancers and the role of genetic variants (mutations). Get information about genetic counseling, familial cancer syndromes, genomic sequencing, germline and somatic testing, ethical and legal issues and more in this summary for clinicians.

  8. miR-146a Suppresses Invasion of Pancreatic Cancer Cells

    Science.gov (United States)

    Li, Yiwei; VandenBoom, Timothy G.; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan; Philip, Philip A.; Sarkar, Fazlul H.

    2010-01-01

    The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-κB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-κB regulatory kinase interleukin 1 receptor–associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IκBα, NF-κB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3′-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-κB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents. PMID:20124483

  9. Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

    Science.gov (United States)

    Lim, Won-Chul; Kim, Hyunhee; Kim, Young-Joo; Park, Seung-Ho; Song, Ji-Hye; Lee, Ki Heon; Lee, In Ho; Lee, Yoo-Kyung; So, Kyeong A; Choi, Kyung-Chul; Ko, Hyeonseok

    2017-12-01

    Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Results of radiotherapy on ureteric obstruction in muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Honnens De Lichtenberg, Mette; Miskowiak, J; Rolff, H

    1995-01-01

    To evaluate the effect of radiotherapy on ureteric obstruction due to muscle-invasive bladder cancer.......To evaluate the effect of radiotherapy on ureteric obstruction due to muscle-invasive bladder cancer....

  11. Non-muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Malmström, Per-Uno; Agrawal, Sachin; Bläckberg, Mats

    2017-01-01

    The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden...

  12. Invasive cancer incidence - Puerto Rico, 2007-2011.

    Science.gov (United States)

    O'Neil, Mary Elizabeth; Henley, S Jane; Singh, Simple D; Wilson, Reda J; Ortiz-Ortiz, Karen J; Ríos, Naydi Pérez; Torres Cintrón, Carlos R; Luna, Guillermo Tortolero; Zavala Zegarra, Diego E; Ryerson, A Blythe

    2015-04-17

    Cancer is a leading cause of morbidity and death in Puerto Rico. To set a baseline for identifying new trends and patterns of cancer incidence, Puerto Rico Central Cancer Registry staff and CDC analyzed data from Puerto Rico included in U.S. Cancer Statistics (USCS) for 2007-2011, the most recent data available. This is the first report of invasive cancer incidence rates for 2007-2011 among Puerto Rican residents by sex, age, cancer site, and municipality. Cancer incidence rates in Puerto Rico were compared with those in the U.S. population for 2011. A total of 68,312 invasive cancers were diagnosed and reported in Puerto Rico during 2007-2011. The average annual incidence rate was 330 cases per 100,000 persons. The cancer sites with the highest cancer incidence rates included prostate (152), female breast (84), and colon and rectum (43). Cancer incidence rates varied by municipality, particularly for prostate, lung and bronchus, and colon and rectum cancers. In 2011, cancer incidence rates in Puerto Rico were lower for all cancer sites and lung and bronchus, but higher for prostate and thyroid cancers, compared with rates within the U.S. Identifying these variations can aid evaluation of factors associated with high incidence, such as cancer screening practices, and development of targeted cancer prevention and control efforts. Public health professionals can monitor cancer incidence trends and use these findings to evaluate the impact of prevention efforts, such as legislation prohibiting tobacco use in the workplace and public places and the Puerto Rico Cessation Quitline in decreasing lung and other tobacco-related cancers.

  13. Orbital invasion routes of non-melanoma skin cancers and survival outcomes.

    Science.gov (United States)

    Dundar, Yusuf; Cannon, Richard; Wiggins, Richard; Monroe, Marcus M; Buchmann, Luke O; Hunt, Jason P

    2018-02-21

    Overall non-melanoma head and neck skin cancer has a good prognosis; however, rarely patients have an aggressive variant which results in orbital invasion via perineural spread or direct extension. Despite these consequences, there are limited published studies defining this clinical entity. The main objectives of the current study are to describe orbital invasion patterns of non-melanoma head and neck skin cancers and their impact on survival. Retrospective case series from a tertiary-care, academic institution performed between 2004 and 2014. Demographic and tumour characteristics are reported as well as patterns of orbital invasion, types of treatments received, and survival outcomes. There were 17 consecutive patients with non-melanoma skin cancer and orbital invasion who met inclusion criteria. Average age at orbital invasion diagnosis was 70.8 years old. 76% were male. Mean follow-up time was 28.5 months. Of these patients, 71% had squamous cell carcinoma and 29% had basal cell carcinoma. Brow (41%) was the most common primary sub-site followed by cheek (23%) and temple (12%). 76% of patients had a history of prior treatment. The lateral orbital wall (41%) was the most common site of invasion, followed by the medial orbital wall (29%) and antero-superior invasion (23%). Age, histology, and location of orbital invasion were associated with disease-specific and overall survival. Orbital invasion for non-melanoma head and neck skin cancers creates a treatment dilemma and the patterns of invasion are described. In addition, the location of orbital invasion is associated with survival outcomes.

  14. Perioperative management of nonmuscle-invasive bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    PURPOSE OF REVIEW: The management of nonmuscle-invasive bladder cancer is a challenge. Despite current guidelines, the treatment is suboptimal as illustrated by the high risk of recurrence and progression. Transurethral resection plays a pivotal role in the management of bladder cancer, but the

  15. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Ji, S.Q.; Cao, J.; Zhang, Q.Y.; Li, Y.Y.; Yan, Y.Q.; Yu, F.X.

    2013-01-01

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis

  16. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  17. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    International Nuclear Information System (INIS)

    Rosenkrantz, Andrew B.; Mussi, Thais C.; Melamed, Jonathan; Taneja, Samir S.; Huang, William C.

    2012-01-01

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

  18. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    Energy Technology Data Exchange (ETDEWEB)

    Rosenkrantz, Andrew B. [Dept. of Radiology, NYU Langone Medical Center, New York (United States)], E-mail: Andrew.rosenkrantz@nyumc.org; Mussi, Thais C. [Dept. of Radiology, NYU Langone Medical Center, New York (United States); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Melamed, Jonathan [Dept. of Pathology, NYU Langone Medical Center, New York (United States); Taneja, Samir S.; Huang, William C. [Dept. of Urology, Div. of Urologic Oncology, NYU Langone Medical Center, New York (United States)

    2012-07-15

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

  19. PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.

    Directory of Open Access Journals (Sweden)

    Hiroaki Ono

    Full Text Available Protein Tyrosine Kinase 6 (PTK6 is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each. In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05. Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.

  20. Our approach for breast cancer screening using both mammography and echography, with special reference to detection of nonpalpable minute invasive cancer

    International Nuclear Information System (INIS)

    Takebe, Koji; Izumori, Ayumi; Yasumo, Naomi

    2007-01-01

    We present the results of our approach for breast cancer screening using both mammography and echography. A total of 4,632 participants underwent screening with our own combined method using mammography and echography at our clinic during a two-year period in 2005 and 2006. Recall studies were carried out in 364 women (recall rate, 79%), and breast cancer was detected in 36 women (cancer detection rate, 0.78%). When the detected cancers were classified histopathologically, 22 were invasive ductal cancers and the remaining 14 were non-invasive cancers. Of the 22 women who proved to have invasive cancers, 14 had been unaware of their tumors, which were non-palpable. If an invasive cancer is overlooked, the consequences may be more serious than if a non-invasive cancer is missed, because the former is can be potentially fatal. In order to decrease breast cancer mortality, invasive cancers must be detected when they are small. Since we were able to detect many small and non-palpable breast cancers that had not been noticed by the participants, our current breast cancer screening system appears to be more efficient for life-saving than other systems. (author)

  1. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer

    NARCIS (Netherlands)

    Witjes, J.A.; Lebret, T.; Comperat, E.M.; Cowan, N.C.; Santis, M. de; Bruins, H.M.; Hernandez, V.; Espinos, E.L.; Dunn, J.; Rouanne, M.; Neuzillet, Y.; Veskimae, E.; Heijden, A.G. van der; Gakis, G.; Ribal, M.J.

    2017-01-01

    CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis,

  2. BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG

    NARCIS (Netherlands)

    Kamat, A.M.; Colombel, M.; Sundi, D.; Lamm, D.; Boehle, A.; Brausi, M.; Buckley, R.; Persad, R.; Palou, J.; Soloway, M.; Witjes, J.A.

    2017-01-01

    Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established

  3. Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    De Oliveira Tiago

    2012-04-01

    Full Text Available Abstract Background We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC cells. Methods Syndecan-2 (SDC-2 expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling. Results SDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and - further downstream - phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered. Conclusion SDC-2 is a novel (perineural invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

  4. Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls

    OpenAIRE

    Varga, Z; Mallon, E

    2009-01-01

    Invasive lobular carcinomas (ILC) represent the most common subtype of invasive breast cancer and account for about 5-15% of all breast cancer cases. Invasive lobular carcinoma is often accompanied by in situ lesions, by lobular neoplasia (LN). Invasive lobular carcinomas display diverse histologic patterns varying from classical through solid to pleomorphic subtypes. When analyzing histological subtypes, the classical variant is reported to have a more favorable outcome. The majority of inva...

  5. Non-invasive spectroscopic techniques in the diagnosis of non-melanoma skin cancer

    Science.gov (United States)

    Drakaki, E.; Sianoudis, IA; Zois, EN; Makropoulou, M.; Serafetinides, AA; Dessinioti, C.; Stefanaki, E.; Stratigos, AJ; Antoniou, C.; Katsambas, A.; Christofidou, E.

    2017-11-01

    The number of non-melanoma skin cancers is increasing worldwide and has become an important health and economic issue. Early detection and treatment of skin cancer can significantly improve patient outcome. Therefore there is an increase in the demand for proper management and effective non-invasive diagnostic modalities in order to avoid relapses or unnecessary treatments. Although the gold standard of diagnosis for non-melanoma skin cancers is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of non-melanoma skin cancers include high-definition optical coherence tomography, fluorescence spectroscopy, oblique incidence diffuse reflectance spectrometry among others spectroscopic techniques. Our findings establish how those spectrometric techniques can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic.

  6. CT Accuracy of Extrinsic Tongue Muscle Invasion in Oral Cavity Cancer.

    Science.gov (United States)

    Junn, J C; Baugnon, K L; Lacayo, E A; Hudgins, P A; Patel, M R; Magliocca, K R; Corey, A S; El-Deiry, M; Wadsworth, J T; Beitler, J J; Saba, N F; Liu, Y; Aiken, A H

    2017-02-01

    Extrinsic tongue muscle invasion in oral cavity cancer upstages the primary tumor to a T4a. Despite this American Joint Committee on Cancer staging criterion, no studies have investigated the accuracy or prognostic importance of radiologic extrinsic tongue muscle invasion, the feasibility of standardizing extrinsic tongue muscle invasion reporting, or the degree of agreement across different disciplines: radiology, surgery, and pathology. The purpose of this study was to assess the agreement among radiology, surgery, and pathology for extrinsic tongue muscle invasion and to determine the imaging features most predictive of extrinsic tongue muscle invasion with surgical/pathologic confirmation. Thirty-three patients with untreated primary oral cavity cancer were included. Two head and neck radiologists, 3 otolaryngologists, and 1 pathologist prospectively evaluated extrinsic tongue muscle invasion. Fourteen of 33 patients had radiologic extrinsic tongue muscle invasion; however, only 8 extrinsic tongue muscle invasions were confirmed intraoperatively. Pathologists were unable to determine extrinsic tongue muscle invasion in post-formalin-fixed samples. Radiologic extrinsic tongue muscle invasion had 100% sensitivity, 76% specificity, 57% positive predictive value, and 100% negative predictive value with concurrent surgical-pathologic evaluation of extrinsic tongue muscle invasion as the criterion standard. On further evaluation, the imaging characteristic most consistent with surgical-pathologic evaluation positive for extrinsic tongue muscle invasion was masslike enhancement. Evaluation of extrinsic tongue muscle invasion is a subjective finding for all 3 disciplines. For radiology, masslike enhancement of extrinsic tongue muscle invasion most consistently corresponded to concurrent surgery/pathology evaluation positive for extrinsic tongue muscle invasion. Intraoperative surgical and pathologic evaluation should be encouraged to verify radiologic extrinsic tongue

  7. Is axillary sonographic staging less accurate in invasive lobular breast cancer than in ductal breast cancer?

    Science.gov (United States)

    Sankaye, Prashant; Chhatani, Sharmila; Porter, Gareth; Steel, Jim; Doyle, Sarah

    2014-10-01

    The purpose of this study was to determine whether axillary sonography is less accurate in invasive lobular breast cancer than in ductal breast cancer. Patients with invasive breast cancer were retrospectively identified from histologic records from 2010 to 2012. Staging axillary sonograms from 96 patients with primary breast cancer in each of 2 subgroups, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), were reviewed. Preoperative sonographically guided 14-gauge core biopsy was performed on morphologically abnormal lymph nodes. Thirty-one of 96 patients (32%) in each subgroup were node positive on final postoperative histopathologic analysis. Axillary staging sensitivity was 17 of 31 patients (54%) in the IDC subgroup and 15 of 31(48%) in the ILC subgroup. Further analysis of the data showed no statistically significant differences between these subgroups. We found that there was no statistically significant difference in the accuracy of axillary sonographic staging between ILC and IDC. © 2014 by the American Institute of Ultrasound in Medicine.

  8. Nucleostemin expression in invasive breast cancer

    International Nuclear Information System (INIS)

    Kobayashi, Takayuki; Masutomi, Kenkichi; Tamura, Kenji; Moriya, Tomoyuki; Yamasaki, Tamio; Fujiwara, Yasuhiro; Takahashi, Shunji; Yamamoto, Junji; Tsuda, Hitoshi

    2014-01-01

    Recently, the cancer stem cell hypothesis has become widely accepted. Cancer stem cells are thought to possess the ability to undergo self-renewal and differentiation, similar to normal stem cells. Nucleostemin (NS), initially cloned from rat neural stem cells, binds to various proteins, including p53, in the nucleus and is thought to be a key molecule for stemness. NS is expressed in various types of cancers; therefore, its role in cancer pathogenesis is thought to be important. This study was conducted to clarify the clinicopathological and prognostic impact of NS in invasive breast cancers. The correlation between NS immunoreactivity and clinicopathological parameters was examined in 220 consecutive surgically resected invasive breast cancer tissue samples by using tissue microarrays. The presence of nuclear NS and p53 immunoreactivity in 10% or more of cancer cells was considered as a positive result. Among the 220 patients, 154 were hormone-receptor (HR)-positive, 22 HER2-positive/HR-negative, and 44 HR-negative/HER2-negative. One hundred and forty-two tumors (64.5%) showed NS positivity, and this positivity was significantly correlated with estrogen receptor (ER) (P = 0.050), human epidermal growth factor receptor 2 (HER2) (P = 0.021), and p53 (P = 0.031) positivity. The patients with NS-positive tumors showed significantly shorter disease-free survival than those with NS-negative tumors. Furthermore, the patient group with NS- and p53-positive tumors showed significantly poorer prognosis than other patient groups. Multivariate analysis showed that NS status was an independent prognostic indicator. NS may play a significant role in the determination of breast cancer progression in association with p53 alterations. The NS status of patients with luminal and HER2 type breast cancers may be a useful prognostic marker

  9. URG11 Regulates Prostate Cancer Cell Proliferation, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    Bin Pan

    2018-01-01

    Full Text Available Upregulated gene 11 (URG11, a new gene upregulated by hepatitis B virus X protein, is involved in the development and progression of several tumors, including liver, stomach, lung, and colon cancers. However, the role of URG11 in prostate cancer remains yet to be elucidated. By determined expression in human prostate cancer tissues, URG11 was found significantly upregulated and positively correlated with the severity of prostate cancer, compared with that in benign prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were significantly upregulated in human prostate cancer cell lines (DU145, PC3, and LNCaP, compared with human prostate epithelial cell line (RWPE-1. Moreover, by the application of siRNA against URG11, the proliferation, migration, and invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and decreased the expression level of β-catenin in prostate cancer cells. Overexpression of URG11 promoted the expression of β-catenin, the growth, the migration, and invasion ability of prostate cancer cells. Taken together, this study reveals that URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells, providing the evidence of URG11 to be a novel potential therapeutic target of prostate cancer.

  10. TRPM7 is required for ovarian cancer cell growth, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Liao, Qian-jin [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Yi [Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410078 (China); Zhou, Hui; Luo, Chen-hui; Tang, Jie; Wang, Ying; Tang, Yan; Zhao, Min; Zhao, Xue-heng [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Qiong-yu [Department of Basic Medical Science, Yongzhou Vocational Technical College, Yong Zhou 425100 (China); Xiao, Ling, E-mail: lingxiaocsu@126.com [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013 (China); Institute of Clinical Pharmacology, Central South University, Changsha 410018 (China)

    2014-11-28

    Highlights: • Silence of TRPM7 in ovarian cancer cells inhibits cell proliferation, migration and invasion. • Silence of TRPM7 decreases phosphorylation levels of Akt, Src and p38 in ovarian cancer cells. • Silence of TRPM7 increases expression of filamentous actin and number of focal adhesions in ovarian cancer cells. - Abstract: Our previous study demonstrated that the melastatin-related transient receptor potential channel 7 (TRPM7) was highly expressed in ovarian carcinomas and its overexpression was significantly associated with poor prognosis in ovarian cancer patients. However, the function of TRPM7 in ovarian cancer is mostly unknown. In this study, we examined the roles of TRPM7 in ovarian cancer cell proliferation, migration and invasion. We found that short hairpin RNA interference-mediated silence of TRPM7 significantly inhibited cell proliferation, colony formation, migration and invasion in multiple ovarian cancer cell lines. Mechanistic investigation revealed that silence of TRPM7 decreased phosphorylation levels of Akt, Src and p38 and increased filamentous actin and focal adhesion number in ovarian cancer cells. Thus, our results suggest that TRPM7 is required for proliferation, migration and invasion of ovarian cancer cells through regulating multiple signaling transduction pathways and the formation of focal adhesions.

  11. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    International Nuclear Information System (INIS)

    Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

    2011-01-01

    Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

  12. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

  13. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  14. Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition.

    Science.gov (United States)

    Lamm, Donald; Persad, Raj; Brausi, Maurizio; Buckley, Roger; Witjes, J Alfred; Palou, Joan; Böhle, Andreas; Kamat, Ashish M; Colombel, Marc; Soloway, Mark

    2014-01-01

    Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. SLUG promotes prostate cancer cell migration and invasion via CXCR4/CXCL12 axis.

    Science.gov (United States)

    Uygur, Berna; Wu, Wen-Shu

    2011-11-10

    SLUG is a zinc-finger transcription factor of the Snail/Slug zinc-finger family that plays a role in migration and invasion of tumor cells. Mechanisms by which SLUG promotes migration and invasion in prostate cancers remain elusive. Expression level of CXCR4 and CXCL12 was examined by Western blot, RT-PCR, and qPCR analyses. Forced expression of SLUG was mediated by retroviruses, and SLUG and CXCL12 was downregulated by shRNAs-expressing lentiviruses. Migration and invasion of prostate cancer were measured by scratch-wound assay and invasion assay, respectively. We demonstrated that forced expression of SLUG elevated CXCR4 and CXCL12 expression in human prostate cancer cell lines PC3, DU145, 22RV1, and LNCaP; conversely, reduced expression of SLUG by shRNA downregulated CXCR4 and CXCL12 expression at RNA and protein levels in prostate cancer cells. Furthermore, ectopic expression of SLUG increased MMP9 expression and activity in PC3, 22RV1, and DU-145 cells, and SLUG knockdown by shRNA downregulated MMP9 expression. We showed that CXCL12 is required for SLUG-mediated MMP9 expression in prostate cancer cells. Moreover, we found that migration and invasion of prostate cancer cells was increased by ectopic expression of SLUG and decreased by SLUG knockdown. Notably, knockdown of CXCL12 by shRNA impaired SLUG-mediated migration and invasion in prostate cancer cells. Lastly, our data suggest that CXCL12 and SLUG regulate migration and invasion of prostate cancer cells independent of cell growth. We provide the first compelling evidence that upregulation of autocrine CXCL12 is a major mechanism underlying SLUG-mediated migration and invasion of prostate cancer cells. Our findings suggest that CXCL12 is a therapeutic target for prostate cancer metastasis.

  16. The role of pre-invasive disease in overdiagnosis: A microsimulation study comparing mass screening for breast cancer and cervical cancer.

    Science.gov (United States)

    van Luijt, Paula A; Rozemeijer, Kirsten; Naber, Steffie K; Heijnsdijk, Eveline Am; van Rosmalen, Joost; van Ballegooijen, Marjolein; de Koning, Harry J

    2016-12-01

    Although early detection of cancer through screening can prevent cancer deaths, a drawback of screening is overdiagnosis. Overdiagnosis has been much debated in breast cancer screening, but less so in cervical cancer screening. We examined the impact of overdiagnosis by comparing two screening programmes in the Netherlands. We estimated overdiagnosis rates by microsimulation for breast cancer screening and cervical cancer screening, using a cohort of women born in 1982 with lifelong follow-up. Overdiagnosis estimates were made analogous to two definitions formed by the UK 2012 breast screening review. Pre-invasive disease was included in both definitions. Screening prevented 921 cervical cancers (-55%) and 378 cervical cancer deaths (-59%), and 169 (-1.3%) breast cancer cases and 970 breast cancer deaths (-21%). The cervical cancer overdiagnosis rate was 74.8% (including pre-invasive disease). Breast cancer overdiagnosis was estimated at 2.5% (including pre-invasive disease). For women of all ages in breast cancer screening, an excess of 207 diagnoses/100,000 women was found, compared with an excess of 3999 diagnoses/100,000 women in cervical cancer screening. For breast cancer, the frequency of overdiagnosis in screening is relatively low, but consequences are evident. For cervical cancer, the frequency of overdiagnosis in screening is high, because of detection of pre-invasive disease, but the consequences per case are relatively small due to less invasive treatment. This illustrates that it is necessary to present overdiagnosis in relation to disease stage and consequences. © The Author(s) 2016.

  17. Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells

    Science.gov (United States)

    Okumura, Takashi; Ohuchida, Kenoki; Sada, Masafumi; Abe, Toshiya; Endo, Sho; Koikawa, Kazuhiro; Iwamoto, Chika; Miura, Daisuke; Mizuuchi, Yusuke; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Manabe, Tatsuya; Ohtsuka, Takao; Nagai, Eishi; Mizumoto, Kazuhiro; Oda, Yoshinao; Hashizume, Makoto; Nakamura, Masafumi

    2017-01-01

    Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion. Mice fed a high fat diet had significantly larger primary pancreatic tumors and a significantly higher rate of distant organ metastasis than mice fed a standard diet. In the organotypic fat invasion model, pancreatic cancer cell clusters were smaller and more elongated in shape and showed increased fibrosis. Adipose tissue-derived conditioned medium enhanced pancreatic cancer cell invasiveness and gemcitabine resistance, as well as inducing morphologic changes in cancer cells and increasing the numbers of lipid droplets in their cytoplasm. The concentrations of oleic, palmitoleic, and linoleic acids were higher in adipose tissue-derived conditioned medium than in normal medium, with these fatty acids significantly enhancing the migration of cancer cells. Mature adipocytes were smaller and the concentration of fatty acids in the medium higher when these cells were co-cultured with cancer cells. These findings indicate that lipolytic and fibrotic changes in peripancreatic adipose tissue enhance local invasiveness and metastasis via adipocyte-released fatty acids. Inhibition of fatty acid uptake by cancer cells may be a novel therapy targeting interactions between cancer and stromal cells. PMID:28407685

  18. MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer

    International Nuclear Information System (INIS)

    Jian, Pan; Yanfang, Tao; Zhuan, Zhou; Jian, Wang; Xueming, Zhu; Jian, Ni

    2011-01-01

    The purpose of this study was to investigate invasion and metastasis related genes in gastric cancer. The transwell migration assay was used to select a highly invasive sub-line from minimally invasive parent gastric cancer cells, and gene expression was compared using a microarray. MMP28 upregulation was confirmed using qRT-PCR. MMP28 immunohistochemistry was performed in normal and gastric cancer specimens. Invasiveness and tumor formation of stable cells overexpressing MMP28 were tested in vitro and in vivo. MMP28 was overexpressed in the highly invasive sub-cell line. Immunohistochemistry revealed MMP28 expression was markedly increased in gastric carcinoma relative to normal epithelia, and was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Ectopic expression of MMP28 indicated MMP28 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo. This study indicates MMP28 is frequently overexpressed during progression of gastric carcinoma, and contributes to tumor cell invasion and metastasis. MMP28 may be a novel therapeutic target for prevention and treatment of metastases in gastric cancer

  19. Invasive bladder cancer treated by radical external radiotherapy

    International Nuclear Information System (INIS)

    Corcoran, M.O.; Thomas, D.M.; Lim, A.; Berry, R.J.; Milroy, E.J.G.

    1985-01-01

    Fifty-three consecutive unselected patients with invasive bladder cancer, Stage T2 to T3, treated by radical radiotherapy have been reviewed. Cystectomy was reserved for patients with significant worsening of disease during treatment, histologically confirmed persistent or recurrent invasive tumour after treatment, or patients with intolerable symptoms due to radiation cystitis. In 64% of our patients a favourable tumour response to radiotherapy was seen, while a further 31% showed disease progression either during or on completion of radiotherapy. Cystectomy was performed on 22% of patients, mainly for radiation cystitis, and was not associated with a significant operative mortality rate. The crude 5-year survival rate was 42%. We conclude that radical radiotherapy is as effective as other forms of treatment for invasive bladder cancer, but that there remains a need to identify those bladder tumours destined to respond poorly to radiotherapy at an earlier stage. (author)

  20. A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

    Science.gov (United States)

    2017-06-28

    TYPE 08/ 03/20 17 Publ ication/Journal 4. TITLE AND SUBTITLE A unique case of muscle-invasive metastatic breast cancer mimicking myositis 6...Rev. 8/98) Prescnbed by ANSI Std Z39. 18 Adobe Profes11on11 7.0 Title: A Unique Case of M uscle-Invasive Metastatic Breast Cancer M imicking...an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid

  1. Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

    Abe, Toyofumi; Yoshioka, Toshiaki; Sato, Mototaka; Mori, Naoki; Sekii, Ken-Ichiro; Itatani, Hiroaki

    2011-01-01

    We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

  2. Imaging Prostate Cancer Invasion with Multi-Nuclear Magnetic Resonance Methods: The Metabolic Boyden Chamber

    Directory of Open Access Journals (Sweden)

    Ulrich Pilatus

    2000-05-01

    Full Text Available The physiological milieu within solid tumors can influence invasion and metastasis. To determine the impact of the physiological environment and cellular metabolism on cancer cell invasion, it is necessary to measure invasion during well-controlled modulation of the physiological environment. Recently, we demonstrated that magnetic resonance imaging can be used to monitor cancer cell invasion into a Matrigel layer [Artemov D, Pilatus U, Chou S, Mori N, Nelson JB, and Bhujwalla ZM. (1999. Dynamics of prostate cancer cell invasion studied in vitro by NMR microscopy. Mag Res Med 42, 277–282.]. Here we have developed an invasion assay (“Metabolic Boyden Chamber” that combines this capability with the properties of our isolated cell perfusion system. Long-term experiments can be performed to determine invasion as well as cellular metabolism under controlled environmental conditions. To characterize the assay, we performed experiments with prostate cancer cell lines preselected for different invasive characteristics. The results showed invasion into, and degradation of the Matrigel layer, by the highly invasive/metastatic line (MatLyLu, whereas no significant changes were observed for the less invasive/metastatic cell line (DU-145. With this assay, invasion and metabolism was measured dynamically, together with oxygen tensions within the cellular environment and within the Matrigel layer. Such a system can be used to identify physiological and metabolic characteristics that promote invasion, and evaluate therapeutic interventions to inhibit invasion.

  3. Intra-arterial chemotherapy combined with irradiation for invasive bladder cancer

    International Nuclear Information System (INIS)

    Fujimoto, Naohiro; Sato, Hideki; Harada, Shuji; Matsumoto, Tetsuro; Ikuyama, Toshihiro

    2004-01-01

    Total cystectomy and urinary diversion are the standard treatments for invasive bladder cancer. However, total cystectomy is not possible in some patients due to advanced age, a poor general condition, or refusal to undergo cystectomy. In such cases, intra-arterial chemotherapy (IAC) and/or radiotherapy are the alternative treatments. We performed IAC with cisplatin and adriamycin in 9 patients with invasive bladder cancer and obtained complete response (CR) in 5 out of the 9 patients (55.6%). However, 3 of these 5 CR patients developed local recurrence within 1 year. In an effort to improve the efficacy, we performed combination therapy comprising IAC plus radiotherapy in 12 patients with invasive bladder cancer. CR was obtained in 58.3% and the bladder was preserved in 91.7% with this combination therapy. However, distant metastases developed in 33.3% after the combined treatment of IAC plus radiation therapy. These findings suggest that the combination of radiotherapy and IAC is useful for local control of invasive bladder cancer. Data from more cases and results from a longer follow-up are needed to fully confirm the efficacy of this type of treatment. In addition, therapeutic modalities to prevent distant metastasis need to be considered. (author)

  4. Src-homology 2 domain-containing tyrosine phosphatase 2 promotes oral cancer invasion and metastasis

    Science.gov (United States)

    2014-01-01

    Background Tumor invasion and metastasis represent a major unsolved problem in cancer pathogenesis. Recent studies have indicated the involvement of Src-homology 2 domain-containing tyrosine phosphatase 2 (SHP2) in multiple malignancies; however, the role of SHP2 in oral cancer progression has yet to be elucidated. We propose that SHP2 is involved in the progression of oral cancer toward metastasis. Methods SHP2 expression was evaluated in paired oral cancer tissues by using immunohistochemical staining and real-time reverse transcription polymerase chain reaction. Isogenic highly invasive oral cancer cell lines from their respective low invasive parental lines were established using a Boyden chamber assay, and changes in the hallmarks of the epithelial-mesenchymal transition (EMT) were assessed to evaluate SHP2 function. SHP2 activity in oral cancer cells was reduced using si-RNA knockdown or enforced expression of a catalytically deficient mutant to analyze migratory and invasive ability in vitro and metastasis toward the lung in mice in vivo. Results We observed the significant upregulation of SHP2 in oral cancer tissues and cell lines. Following SHP2 knockdown, the oral cancer cells markedly attenuated migratory and invasion ability. We observed similar results in phosphatase-dead SHP2 C459S mutant expressing cells. Enhanced invasiveness was associated with significant upregulation of E-cadherin, vimentin, Snail/Twist1, and matrix metalloproteinase-2 in the highly invasive clones. In addition, we determined that SHP2 activity is required for the downregulation of phosphorylated ERK1/2, which modulates the downstream effectors, Snail and Twist1 at a transcript level. In lung tissue sections of mice, we observed that HSC3 tumors with SHP2 deletion exhibited significantly reduced metastatic capacity, compared with tumors administered control si-RNA. Conclusions Our data suggest that SHP2 promotes the invasion and metastasis of oral cancer cells. These results

  5. [An analysis of 68 invasive lobular breast cancer cases in clinicopathological characteristics and the prognostic determinants].

    Science.gov (United States)

    Liu, Q; Xiang, H Y; Ye, J M; Xu, L; Zhang, H; Zhang, S; Duan, X N; Liu, Y H

    2018-02-01

    Objective: To study the clinicopathological characteristics and the prognostic determinants of the invasive lobular carcinoma breast cancer. Methods: This was a retrospective single-center study of invasive lobular breast cancer cases diagnosed from January 2008 to December 2014 at Peking University First Hospital Breast Disease Center. The study enrolled 68 invasive lobular breast cancer patients, which represented 3.64% (68/1 870) of total invasive breast cancer. The median age of all selected patients was 46 years ranging from 36 to 83 years. All patients were restaged based on the 8(th) edition of AJCC cancer staging system and follow-up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore the prognostic determinants. The 5-year OS and DFS were calculated using Kaplan-Meier method; the significance of correlations between clinicopathological features and prognostic factors was estimated using log-rank test. Results: There were significant differences in OS between patients with different anatomic stage, prognostic stage, lymph node metastasis, progesterone receptor (PR) expression, lymphvascular invasion and perineural invasion (χ(2:) 4.318 to 32.394, all P invasion (χ(2:) 4.347 to 27.369, all P invasion are the prognostic factors of invasive lobular breast cancer. Regard to invasive lobular breast cancer patients, clinicians should pay close attention to the differences between prognostic stage and anatomic stage.

  6. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  7. Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

    Science.gov (United States)

    Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

  8. Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy.

    NARCIS (Netherlands)

    Schrier, B.P.; Hollander, M.P.; Rhijn, B.W. van; Kiemeney, L.A.L.M.; Witjes, J.A.

    2004-01-01

    OBJECTIVE: To evaluate the difference in prognosis between progressive and primary muscle-invasive bladder cancer. MATERIALS AND METHODS: From 1986 to 2000, 74 patients with progressive muscle-invasive bladder cancer were identified. Eighty-nine patients with primary muscle-invasive bladder cancer

  9. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  10. The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

    Directory of Open Access Journals (Sweden)

    Brábek Jan

    2010-09-01

    Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

  11. p63 expression defines a lethal subset of muscle-invasive bladder cancers.

    Directory of Open Access Journals (Sweden)

    Woonyoung Choi

    Full Text Available p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear.We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT in human bladder cancer cell lines (n = 15 and primary tumors (n = 101. We correlated tumor marker expression with stage, disease-specific (DSS, and overall survival (OS. Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1 bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2-T4 tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p<0.0001. However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007.Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the "epithelial" marker p63 in muscle-invasive tumors is associated with a worse outcome.

  12. Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound

    Directory of Open Access Journals (Sweden)

    Andrew C. Weitz

    2017-08-01

    Full Text Available Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145 and bladder (T24/83 cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84. In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making.

  13. Multidetector CT of Locally Invasive Advanced Gastric Cancer: Value of Oblique Coronal Reconstructed Images for the Assessment of Local Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jin Hee; Kim, Ah Yong; Kim, Hye Jin; Yook, Jeong Hwan; Yu, Eun Sil; Jang, Yoon Jin; Park, Seong Ho; Shin, Yong Moon; Ha, Hyun Kwon [Asan Medical Center, Seoul (Korea, Republic of)

    2010-01-15

    To evaluate the diagnostic value of oblique coronal reconstructed CT images to determine the local invasion of advanced gastric cancer (AGC). Thirty-four consecutive patients, who were suspected to have locally invasive advanced gastric cancer (more than T3 stage) on a preoperative MDCT scan and underwent a diagnostic or curative laparotomy, were enrolled in this study. Two reviewers performed an independent blind review of three series of MDCT images in random order; axial (AXI), conventional coronal (CCI), and oblique coronal (OCI) (parallel to long axis of gastric body and pancreas) images. In assessing the local invasion, the reader's confidence for the local invasion of AGC was graded using a five point scale (1 = definitely negative, 5 = definitely positive: T4). With surgical findings and histopathological proofs as reference standards, the diagnostic performance of the three different plans of CT images was employed for the verification of local invasion of AGC on a preoperative CT scan using the receiver operating characteristic (ROC) method. Agreements between the two reviewers were analyzed using weighted kappa statistics. Results: In 19 out of 34 patients, local invasion was confirmed surgically or histopathologically (13 pancreas invasion, 6 liver invasion, 4 major vascular invasion, 3 colon and mesocolon invasion, and 2 spleen invasion). The diagnostic performance of OCI was superior to AXI or CCI in the local invasion of AGC. The differences in the area under the curve of AXI (0.770 {+-} 0.087, 0.700 {+-} 0.094), CCI (0.884 {+-} 0.058, 0.958 {+-} 0.038), and OCI (0.954 {+-} 0.050, 0.956 {+-} 0.049), were statistically significant for both reviewers. Inter-observer agreement was excellent for OCI ({kappa}= .973), which was greater than CCI (({kappa}= .839), and AXI (({kappa}= .763). On a CT scan, OCI might be a useful imaging technique in evaluating locally invasive advanced gastric cancer.

  14. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

    International Nuclear Information System (INIS)

    Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong; Kim, Donghern; Wang, Lei; Poyil, Pratheeshkumar; Luo, Jia; Zhang, Zhuo

    2016-01-01

    Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

  15. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong; Kim, Donghern [Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 (United States); Wang, Lei; Poyil, Pratheeshkumar [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Luo, Jia [Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo, E-mail: Zhuo.Zhang@uky.edu [Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 (United States)

    2016-11-15

    Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

  16. High resolution MR imaging of bladder cancer: new criteria for determining depth of wall invasion

    International Nuclear Information System (INIS)

    Suh, Chang Hae; Kressel, Herbert Y

    1993-01-01

    To establish new criteria to determine the depth of bladder cancer as well as to obtain the findings of each stage of bladder cancer we reviewed high resolution MR images of 18 bladder cancer patients including seven cases (26%) with superficial bladder wall invasion. All MR scans were done before biopsy or surgery. Multiple layers of the bladder wall (inner black, middle white, outer black) were demonstrated in 11 cases out of a total 18 cases. Thickening of the middle layer caused by tumor infiltration or edema of lamina propria was seen in 8 of 12 patients with stage T2 or greater, and was suggestive of superficial muscle invasion when multiple layers were demonstrated. Disruption of outer layer (as well as inner layer) and external protrusion of tumor itself were indicative of perivesical invasion. When multiple layers were not demonstrated, the depth of tumor invasion could not be judged. High resolution MR imaging can depict submucosal invasion, muscle invasion, and perivesical invasion secondary to bladder cancer

  17. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

    Directory of Open Access Journals (Sweden)

    Yan-fei Liu

    Full Text Available Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2, which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.

  18. Chemokine CXCL16 Expression Suppresses Migration and Invasiveness and Induces Apoptosis in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yeying Fang

    2014-01-01

    Full Text Available Background. Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cells in vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells. Methods. Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels. In vitro and in vivo studies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells. Results. We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with the in vitro data, CXCL16 overexpression inhibited tumorigenesis in vivo. Conclusions. Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.

  19. Effects of omega-3 fatty acids on progestin stimulation of invasive properties in breast cancer.

    Science.gov (United States)

    Moore, Michael R; King, Rebecca A

    2012-12-01

    Clinical studies have shown that progestins increase breast cancer risk in hormone replacement therapy, while we and others have previously reported that progestins stimulate invasive properties in progesterone receptor (PR)-rich human breast cancer cell lines. Based on others' reports that omega-3 fatty acids inhibit metastatic properties of breast cancer, we have reviewed the literature for possible connections between omega-3 fatty-acid-driven pathways and progestin-stimulated pathways in an attempt to suggest theoretical mechanisms for possible omega-3 fatty acid inhibition of progestin stimulation of breast cancer invasion. We also present some data suggesting that fatty acids regulate progestin stimulation of invasive properties in PR-rich T47D human breast cancer cells, and that an appropriate concentration of the omega-3 fatty acid eicosapentaenoic acid inhibits progestin stimulation of invasive properties. It is hoped that focus on the inter-relationship between pathways by which omega-3 fatty acids inhibit and progestins stimulate breast cancer invasive properties will lead to further in vitro, in vivo, and clinical studies testing the hypothesis that omega-3 fatty acids can inhibit progestin stimulation of invasive properties in breast cancer, and ameliorate harmful effects of progestins which occur in combined progestin-estrogen hormone replacement therapy.

  20. Prostate Cancer Susceptibility Polymorphism rs2660753 Is Not Associated with Invasive Ovarian Cancer

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang

    2011-01-01

    BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1...

  1. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Science.gov (United States)

    Kagawa, Yoshinori; Matsumoto, Shinji; Kamioka, Yuji; Mimori, Koshi; Naito, Yoko; Ishii, Taeko; Okuzaki, Daisuke; Nishida, Naohiro; Maeda, Sakae; Naito, Atsushi; Kikuta, Junichi; Nishikawa, Keizo; Nishimura, Junichi; Haraguchi, Naotsugu; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Ishii, Hideshi; Doki, Yuichiro; Matsuda, Michiyuki; Kikuchi, Akira; Mori, Masaki; Ishii, Masaru

    2013-01-01

    The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  2. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Directory of Open Access Journals (Sweden)

    Yoshinori Kagawa

    Full Text Available The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP, was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  3. [Clinical guidelines for diagnosis, treatment and monitoring of patients with non-invasive breast cancer].

    Science.gov (United States)

    Brnijć, Zoran; Brkljacić, Boris; Drinković, Ivan; Jakić-Razumović, Jasminka; Kardum-Skelin, Ika; Krajina, Zdenko; Margaritoni, Marko; Strnad, Marija; Sarcević, Bozena; Tomić, Snjezana; Zic, Rado

    2012-01-01

    Breast cancer is the most common malignancy in women. Early diagnosis and more effective treatment of invasive breast cancer resulted in significant mortality reduction, improvement of survival and the quality of life of the patients. The management od non-invasive breast cancer, on the contrary, is still controversial and the problem of overdiagnosis and overtreatment of patients come to evidence. In the following text a multidisciplinary team of experts brings the first consensus guidelines aimed to standardize and optimize the criteria and management in diagnosis, treatment and monitoring of non-invasive breast cancer patients in the Republic of Croatia.

  4. Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer.

    Science.gov (United States)

    Vlug, Eva J; van de Ven, Robert A H; Vermeulen, Jeroen F; Bult, Peter; van Diest, Paul J; Derksen, Patrick W B

    2013-10-01

    Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p cancers and conditional mouse models of human lobular breast cancer. Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.

  5. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

    Scarpato, Kristen R; Tyson, Mark D; Clark, Peter E

    2016-01-01

    PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has...... in low-risk patients. SUMMARY: NMIBC represents a variety of disease states and continues to pose management challenges. As our understanding of tumor biology improves and technology advances, achieving better outcomes through individualized care may be possible.......PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has...... helped triage patients but improved tools, including biomarkers, are still needed. Enhanced endoscopy with photodynamic imaging, narrow band imaging, optical coherence tomography and confocal laser endomicroscopy show promise for diagnosis, risk stratification and disease monitoring. Attempts at better...

  6. Molecular Landscape of Non-Muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Meeks, Joshua J; Lerner, Seth P

    2017-11-13

    In this issue of Cancer Cell, Hurst et al. report an integrated analysis of non-invasive (stage Ta) bladder cancer. Two genomic subtypes are distinguished by chromosome 9q loss, resulting in increased AKT/PI3K/mTOR signaling. Tumors from female patients have a higher frequency of KDM6A mutations. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Minimally invasive radical pancreatectomy for left-sided pancreatic cancer: Current status and future perspectives

    Science.gov (United States)

    Kang, Chang Moo; Lee, Sung Hwan; Lee, Woo Jung

    2014-01-01

    Minimally invasive distal pancreatectomy with splenectomy has been regarded as a safe and effective treatment for benign and borderline malignant pancreatic lesions. However, its application for left-sided pancreatic cancer is still being debated. The clinical evidence for radical antegrade modular pancreatosplenectomy (RAMPS)-based minimally invasive approaches for left-sided pancreatic cancer was reviewed. Potential indications and surgical concepts for minimally invasive RAMPS were suggested. Despite the limited clinical evidence for minimally invasive distal pancreatectomy in left-sided pancreatic cancer, the currently available clinical evidence supports the use of laparoscopic distal pancreatectomy under oncologic principles in well-selected left sided pancreatic cancers. A pancreas-confined tumor with an intact fascia layer between the pancreas and left adrenal gland/kidney positioned more than 1 or 2 cm away from the celiac axis is thought to constitute a good condition for the use of margin-negative minimally invasive RAMPS. The use of minimally invasive (laparoscopic or robotic) anterior RAMPS is feasible and safe for margin-negative resection in well-selected left-sided pancreatic cancer. The oncologic feasibility of the procedure remains to be determined; however, the currently available interim results indicate that even oncologic outcomes will not be inferior to those of open radical distal pancreatosplenectomy. PMID:24605031

  8. Effects of Src on Proliferation and Invasion of Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Rui ZHENG

    2011-04-01

    Full Text Available Background and objective It has been proven that Src played pivotal roles in carcinogenesis, cancer progression and metastasis. The aim of this study is to explore the roles of Src phosphorylation on lung cancer cells. Methods Western blot and immunoprecipitation was used to detect the expression and phosphorylation of Src in lung cancer cells. MTT and Boyden chamber assay was used to examine the effects of inhibition of Src phosphorylation on proliferation and invasion of lung cancer cells in vitro, respectively. Results pp60src was expressed in all lung cancer cell lines in this study. All 5 non-small cell lung cancer (NSCLC cell lines had increased autophosphorylated tyrosine-418, while nearly no phosphorylated Src in small cell lung cancer SBC5 cell line was detected. The effect of inhibition of Src tyrosine kinase on cell proliferation varied among the lung cancer cell lines. Submicromolar Src tyrosine kinase inhibitor (≤1 μM remarkably suppressed the proliferation of PC-9 and A549 cells in a dose dependent manner (P < 0.05, while the same concentration of Src tyrosine kinase inhibitor had no significant effect on proliferation of H226, PC14PE6 and RERFLCOK cells. Invasiveness of lung cancer cells was significantly suppressed by Src tyrosine kinase in a dose-dependent manner (P < 0.05. Conclusion Phosphorylation of Src, but not over-expression, plays a pivotal role in proliferation and invasion of NSCLC cell lines in vitro.

  9. Results of radiotherapy for ureteric obstruction in muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Holm, M.; Miskowiak, J.; Rolff, H.

    1996-01-01

    Retrospective evaluation of the records of 574 patients with muscle-invasive bladder cancer revealed 90 patients (16%) with ureteric obstruction; the obstruction was bilateral in 24%. The effect of radiotherapy was assessed in 55 patients with 68 obstructed kidneys. Six patients with eight obstructed kidneys required percutaneous nephrostomy or ureteric catheters in addition to radiotherapy. Drainage improved in only 20% of kidneys and the diverting catheter could be withdrawn permanently in only one (17%) of the diverted patients. The median survival was 11 months. Irradiation was followed by significant complications in 37 patients (67%). This raises doubts about the assumed beneficial effect of irradiation on ureteric obstruction due to muscle invasive bladder cancer. The short median survival of 11 months confirms that ureteric obstruction is a poor prognostic factor in muscle invasive bladder cancer. (au) 10 refs

  10. Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion

    KAUST Repository

    Tochhawng, Lalchhandami

    2016-07-07

    The actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells. Herein, we show that increased gelsolin enhances the invasive capacity of colon cancer cells, and this is mediated via gelsolin\\'s effects in elevating intracellular superoxide (O2 .-) levels. We also provide evidence for a novel physical interaction between gelsolin and Cu/ZnSOD, that inhibits the enzymatic activity of Cu/ZnSOD, thereby resulting in a sustained elevation of intracellular O2 .-. Using microarray data of human colorectal cancer tissues from Gene Omnibus, we found that gelsolin gene expression positively correlates with urokinase plasminogen activator (uPA), an important matrix-degrading protease invovled in cancer invasion. Consistent with the in vivo evidence, we show that increased levels of O2 .- induced by gelsolin overexpression triggers the secretion of uPA. We further observed reduction in invasion and intracellular O2 .- levels in colon cancer cells, as a consequence of gelsolin knockdown using two different siRNAs. In these cells, concurrent repression of Cu/ ZnSOD restored intracellular O2 .- levels and rescued invasive capacity. Our study therefore identified gelsolin as a novel regulator of intracellular O2 .- in cancer cells via interacting with Cu/ZnSOD and inhibiting its enzymatic activity. Taken together, these findings provide insight into a novel function of gelsolin in promoting tumor invasion by directly impacting the cellular redox milieu.

  11. Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis

    Science.gov (United States)

    2011-01-01

    affect breast cancer metastasis with a subcutaneous mouse tumor implantation model of breast cancer metastasis. HMLE -Twist1 cells expressing shRNAs...13 4 Introduction Distant metastases are responsible for the vast majority of breast cancer deaths. This process...to migrate and invade is therefore essential to the metastatic process. The initial steps of breast cancer metastasis, local invasion and

  12. Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

    International Nuclear Information System (INIS)

    Oliveira, Cristina Mendes de; Fregnani, José Humberto Tavares Guerreiro; Carvalho, Jesus Paula; Longatto-Filho, Adhemar; Levi, José Eduardo

    2013-01-01

    Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted

  13. Tetraspanin 1 promotes invasiveness of cervical cancer cells.

    Science.gov (United States)

    Hölters, Sebastian; Anacker, Jelena; Jansen, Lars; Beer-Grondke, Katrin; Dürst, Matthias; Rubio, Ignacio

    2013-08-01

    Tetraspanins are a heterogeneous group of 4-transmembrane proteins that segregate into so-called tetraspanin-enriched microdomains (TEMs) along with other cell surface proteins such as integrins. TEMs of various types are reportedly involved in the regulation of cell growth, migration and invasion of several tumour cell types, both as suppressors or supporting structures. Tetraspanin 1 (Tspan1, NET-1), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, is overexpressed in high-grade cervical intraepithelial neoplasia (CIN) and terminal carcinomas but its precise function in the context of carcinoma of the cervix uteri is not known. Here, we present a comprehensive investigation of the role of tetraspanin 1 in the cervical cancer cell lines SiHa and HeLa. We document that tetraspanin 1 increases the invasive potential of cervical cancer cells, whereas proliferation, growth in soft agar and adhesion are largely unaffected. In line with the latter findings, our data exclude the participation of testraspanin in integrin-mediated activation of focal adhesion kinase (FAK), paxillin and phosphoinositide-3-kinase (PI3K) and in EGFR-dependent signalling to the Ras/Erk pathway. In conclusion, our data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion.

  14. Invasive Candidiasis: An Overview from Taiwan

    Directory of Open Access Journals (Sweden)

    Sheng-Yuan Ruan

    2009-06-01

    Full Text Available Invasive candidiasis has emerged as an important nosocomial infection, especially in critically ill patients. We review the epidemiology of invasive candidiasis with an emphasis on data from Taiwan. An increasing incidence of candidemia became apparent from 1980 to the end of the 1990s, followed by relative stability. Crude mortality rates of patients with candidemia were in the range of 35% to 60%. Candida albicans remains the predominant cause of invasive candidiasis in Taiwan and accounts for more than 50% of all cases. Candida tropicalis, Candida glabrata and Candida parapsilosis are the three most common nonalbicansCandida species that cause invasive candidiasis. The above four Candida species account for more than 90% of invasive candidiasis in Taiwan. Overall, invasive Candida isolates have remained highly susceptible to fluconazole (> 90% susceptibility over the past two decades. However, periodic surveillance is needed to monitor antifungal resistance because reduced fluconazole susceptibility in non-albicans Candida is not an uncommon trend. Voriconazole and echinocandins continue to exhibit excellent in vitro activity against invasive Candida isolates.

  15. Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.

    Science.gov (United States)

    Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K; Schouten, Philip C; Rueda, Oscar M; Bosma, Astrid J; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J C; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O'Hurley, Gillian; Lehn, Sophie; Muris, Jettie J F; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A; Barbet, Aurélie S; Bard, Floriane; Lecerf, Caroline; O'Connor, Darran P; Vis, Daniël J; Benes, Cyril H; McDermott, Ultan; Garnett, Mathew J; Simon, Iris M; Jirström, Karin; Dubois, Thierry; Linn, Sabine C; Gallagher, William M; Wessels, Lodewyk F A; Caldas, Carlos; Bernards, Rene

    2016-01-05

    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.

  16. Epidemiology of testicular cancer: an overview.

    Science.gov (United States)

    Garner, Michael J; Turner, Michelle C; Ghadirian, Parviz; Krewski, Daniel

    2005-09-01

    Testicular cancer is a rare disease, accounting for 1.1% of all malignant neoplasms in Canadian males. Despite the low overall incidence of testicular cancer, it is the most common malignancy among young men. The incidence rate of testicular cancer has been increasing since the middle of the 20th century in many western countries. However, the etiology of testicular cancer is not well understood. A search of the peer-reviewed literature was conducted to identify important articles for review and inclusion in this overview of the epidemiology of testicular cancer. Most of the established risk factors are related to early life events, including cryptorchidism, carcinoma in situ and in utero exposure to estrogens. Occupational, lifestyle, socioeconomic and other risk factors have demonstrated mixed associations with testicular cancer. Although there are few established risk factors for testicular cancer, some appear to be related to hormonal balance at various life stages. Lifestyle and occupational exposures occurring later in life may play a role in promoting the disease, although they are not likely involved in cancer initiation. In addition to summarizing the current epidemiologic evidence on risk factors for testicular cancer, we suggest future research directions that may elucidate the etiology of testicular cancer.

  17. Role of ErbB receptors in cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Aline eAppert-Collin

    2015-11-01

    Full Text Available Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival by binding to and activating cell-surface receptors with intrinsic protein kinase activity named Receptor Tyrosine Kinases (RTKs. About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1, ErbB2 (neu, HER2, ErbB3 (HER3 and ErbB4 (HER4. ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix components. Recent findings indicate that extracellular matrix components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.

  18. Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ.

    Science.gov (United States)

    Maxwell, Anthony J; Clements, Karen; Hilton, Bridget; Dodwell, David J; Evans, Andrew; Kearins, Olive; Pinder, Sarah E; Thomas, Jeremy; Wallis, Matthew G; Thompson, Alastair M

    2018-04-01

    The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. Eighty-nine women with DCIS diagnosed 1998-2010 were identified. The median age at diagnosis was 75 (range 44-94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12-180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12-144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  19. Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion

    International Nuclear Information System (INIS)

    Braig, Simone; Stoiber, Katharina; Zahler, Stefan; Vollmar, Angelika M

    2015-01-01

    The invasive potential of cancer cells strongly depends on cellular stiffness, a physical quantity that is not only regulated by the mechanical impact of the cytoskeleton but also influenced by the membrane rigidity. To analyze the specific role of membrane rigidity in cancer progression, we treated cancer cells with the Acetyl-CoA carboxylase inhibitor Soraphen A and revealed an alteration of the phospholipidome via mass spectrometry. Migration, invasion, and cell death assays were employed to relate this alteration to functional consequences, and a decrease of migration and invasion without significant impact on cell death has been recorded. Fourier fluctuation analysis of giant plasma membrane vesicles showed that Soraphen A increases membrane rigidity of carcinoma cell membranes. Mechanical measurements of the creep deformation response of whole intact cells were performed using the optical stretcher. The increase in membrane rigidity was observed in one cell line without changing the creep deformation response indicating no restructuring of the cytoskeleton. These data indicate that the increase of membrane rigidity alone is sufficient to inhibit invasiveness of cancer cells, thus disclosing the eminent role of membrane rigidity in migratory processes. (paper)

  20. miR-613 inhibits proliferation and invasion of breast cancer cell via VEGFA

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Junzhao; Yuan, Peng; Mao, Qixin [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Henan (China); Xie, Tian; Yang, Hanzhao [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Wang, Chengzheng, E-mail: wangchengzheng@126.com [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China)

    2016-09-09

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in breast cancer, has remained elusive. Here, we identified that miR-613 inhibits breast cancer cell proliferation by negatively regulates its target gene VEGFA. In breast cancer cell lines, CCK-8 proliferation assay indicated that the cell proliferation was inhibited by miR-613, while miR-613 inhibitor significantly promoted the cell proliferation. Transwell assay showed that miR-613 mimics significantly inhibited the migration and invasion of breast cancer cells, whereas miR-613 inhibitors significantly increased cell migration and invasion. Luciferase assays confirmed that miR-613 directly bound to the 3′ untranslated region of VEGFA, and western blotting showed that miR-613 suppressed the expression of VEGFA at the protein levels. This study indicated that miR-613 negatively regulates VEGFA and inhibits proliferation and invasion of breast cancer cell lines. Thus, miR-613 may represent a potential therapeutic molecule for breast cancer intervention.

  1. An mDia2/ROCK signaling axis regulates invasive egress from epithelial ovarian cancer spheroids.

    Science.gov (United States)

    Pettee, Krista M; Dvorak, Kaitlyn M; Nestor-Kalinoski, Andrea L; Eisenmann, Kathryn M

    2014-01-01

    Multi-cellular spheroids are enriched in ascites of epithelial ovarian cancer (OvCa) patients. They represent an invasive and chemoresistant cellular population fundamental to metastatic dissemination. The molecular mechanisms triggering single cell invasive egress from spheroids remain enigmatic. mDia formins are Rho GTPase effectors that are key regulators of F-actin cytoskeletal dynamics. We hypothesized that mDia2-driven F-actin dynamics promote single cell invasive transitions in clinically relevant three-dimensional (3D) OvCa spheroids. The current study is a dissection of the contribution of the F-actin assembly factor mDia2 formin in invasive transitions and using a clinically relevant ovarian cancer spheroid model. We show that RhoA-directed mDia2 activity is required for tight spheroid organization, and enrichment of mDia2 in the invasive cellular protrusions of collagen-embedded OVCA429 spheroids. Depleting mDia2 in ES-2 spheroids enhanced invasive dissemination of single amoeboid-shaped cells. This contrasts with spheroids treated with control siRNA, where a mesenchymal invasion program predominated. Inhibition of another RhoA effector, ROCK, had no impact on ES-2 spheroid formation but dramatically inhibited spheroid invasion through induction of a highly elongated morphology. Concurrent inhibition of ROCK and mDia2 blocked single cell invasion from ES-2 spheroids more effectively than inhibition of either protein alone, indicating that invasive egress of amoeboid cells from mDia2-depleted spheroids is ROCK-dependent. Our findings indicate that multiple GTPase effectors must be suppressed in order to fully block invasive egress from ovarian cancer spheroids. Furthermore, tightly regulated interplay between ROCK and mDia2 signaling pathways dictates the invasive capacities and the type of invasion program utilized by motile spheroid-derived ovarian cancer cells. As loss of the gene encoding mDia2, DRF3, has been linked to cancer progression and

  2. An mDia2/ROCK signaling axis regulates invasive egress from epithelial ovarian cancer spheroids.

    Directory of Open Access Journals (Sweden)

    Krista M Pettee

    Full Text Available Multi-cellular spheroids are enriched in ascites of epithelial ovarian cancer (OvCa patients. They represent an invasive and chemoresistant cellular population fundamental to metastatic dissemination. The molecular mechanisms triggering single cell invasive egress from spheroids remain enigmatic. mDia formins are Rho GTPase effectors that are key regulators of F-actin cytoskeletal dynamics. We hypothesized that mDia2-driven F-actin dynamics promote single cell invasive transitions in clinically relevant three-dimensional (3D OvCa spheroids. The current study is a dissection of the contribution of the F-actin assembly factor mDia2 formin in invasive transitions and using a clinically relevant ovarian cancer spheroid model. We show that RhoA-directed mDia2 activity is required for tight spheroid organization, and enrichment of mDia2 in the invasive cellular protrusions of collagen-embedded OVCA429 spheroids. Depleting mDia2 in ES-2 spheroids enhanced invasive dissemination of single amoeboid-shaped cells. This contrasts with spheroids treated with control siRNA, where a mesenchymal invasion program predominated. Inhibition of another RhoA effector, ROCK, had no impact on ES-2 spheroid formation but dramatically inhibited spheroid invasion through induction of a highly elongated morphology. Concurrent inhibition of ROCK and mDia2 blocked single cell invasion from ES-2 spheroids more effectively than inhibition of either protein alone, indicating that invasive egress of amoeboid cells from mDia2-depleted spheroids is ROCK-dependent. Our findings indicate that multiple GTPase effectors must be suppressed in order to fully block invasive egress from ovarian cancer spheroids. Furthermore, tightly regulated interplay between ROCK and mDia2 signaling pathways dictates the invasive capacities and the type of invasion program utilized by motile spheroid-derived ovarian cancer cells. As loss of the gene encoding mDia2, DRF3, has been linked to cancer

  3. Thermal dosimetry for bladder hyperthermia treatment. An overview.

    Science.gov (United States)

    Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

    2016-06-01

    The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

  4. Moscatilin Inhibits Lung Cancer Cell Motility and Invasion via Suppression of Endogenous Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Akkarawut Kowitdamrong

    2013-01-01

    Full Text Available Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS, in which hydroxyl radical (OH∙ was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397 and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473, whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy.

  5. Tensile Forces Originating from Cancer Spheroids Facilitate Tumor Invasion.

    Directory of Open Access Journals (Sweden)

    Katarzyna S Kopanska

    Full Text Available The mechanical properties of tumors and the tumor environment provide important information for the progression and characterization of cancer. Tumors are surrounded by an extracellular matrix (ECM dominated by collagen I. The geometrical and mechanical properties of the ECM play an important role for the initial step in the formation of metastasis, presented by the migration of malignant cells towards new settlements as well as the vascular and lymphatic system. The extent of this cell invasion into the ECM is a key medical marker for cancer prognosis. In vivo studies reveal an increased stiffness and different architecture of tumor tissue when compared to its healthy counterparts. The observed parallel collagen organization on the tumor border and radial arrangement at the invasion zone has raised the question about the mechanisms organizing these structures. Here we study the effect of contractile forces originated from model tumor spheroids embedded in a biomimetic collagen I matrix. We show that contractile forces act immediately after seeding and deform the ECM, thus leading to tensile radial forces within the matrix. Relaxation of this tension via cutting the collagen does reduce invasion, showing a mechanical relation between the tensile state of the ECM and invasion. In turn, these results suggest that tensile forces in the ECM facilitate invasion. Furthermore, simultaneous contraction of the ECM and tumor growth leads to the condensation and reorientation of the collagen at the spheroid's surface. We propose a tension-based model to explain the collagen organization and the onset of invasion by forces originating from the tumor.

  6. The value of CT in the detection of mural invasion in colon cancer

    International Nuclear Information System (INIS)

    Katayama, Hiroshi; Totani, Kimiaki; Fujikawa, Koichi; Kagemoto, Masayuki; Itoh, Sachiko.

    1984-01-01

    Thirty five patients with rectal and rectosigmoid cancer were evaluated by computed tomography using olive oil enema method. All of them underwent surgical operation and were grouped into 4 groups (PM, A 1 .S 1 , A 2 .S 2 , Ai.Si,) according to the degree of macroscopic mural invasion classified by Japan Colon Cancer Society. The results of CT exam and macroscopic mural invading findings were compared in all of 4 groups. The overall accuracy rate CT exam was 86.1% for the estimation of mural and extramural invasion. In each group classified by the degree of mural invasion, the accuracy rate of CT was 71.4% in PM + A 1 .S 1 , 86.4% in A 2 .S 2 , and 100% in Ai.Si. In conclusion, CT using olive oil enema method in useful for the estimation of extramural invasion of rectal and rectosigmoid cancer. (author)

  7. TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion.

    Directory of Open Access Journals (Sweden)

    Agathe Oulidi

    Full Text Available Adrenomedullin (AM is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level.

  8. A combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Okuno, Yumiko; Zaitsu, Masayoshi; Mikami, Koji; Takeuchi, Takumi; Matsuda, Izuru; Arahira, Satoko

    2017-01-01

    The gold standard for the treatment of muscle-invasive bladder cancer Without metastasis is radical cystectomy. However, there increase patients very elderly and with serious complications. They are not good candidates for invasive surgical operation. Intraarterial infusion of 70 mg/m"2 of cisplatin and 30 mg/m"2 of pirarubicin into bilateral bladder arteries was conducted for 5 patients diagnosed with muscle invasive bladder cancers without distant metastasis. Right and left distribution of anti-cancer drugs was determined based on the location of bladder tumor(s). External beam radiation therapy was commenced immediately following intraarterial infusion. The patients were followed up with clinical and radiographic investigations and bladderbiopsy was performed as needed. Patients were all males who are smoking or with smoking history ranging from 73 to 85 years of age (median 82). The duration between transurethral resection of bladder tumors (TUR-Bt) and intraarterial infusion of anti-cancer drugs was 47.4 days (range 26-68), the median follow-up period after intraarterial infusion was 21.5 months (range 87-547) without death. Total radiation dose was 59.2 ±3.0 Gy. Complete remission was accomplished in all cases. One patient showed intravesical recurrence of non muscle-invasive tumors 45.8 months following intraarterial infusion and underwent TUR-Bt. Two cases underwent bladder biopsies showing no tumors. All patients but one case with bladder recurrence were free of tumor recurrence with radiographic investigation. For adverse events, acute renal failure was in one case and leukocytopenia was in all 5 cases, Grade 2 for one and Grade 3 for 4 cases. Follow-up periods are not long enough, but early results of a combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer were good. (author)

  9. Inhibition of Zoledronic Acid on Cell Proliferation and Invasion of Lung Cancer Cell Line 95D

    Directory of Open Access Journals (Sweden)

    Mingming LI

    2009-03-01

    Full Text Available Background and objective Abnormal proliferation and metastasis is the basic characteristic of malignant tumors. The aim of this work is to explore the effects of zoledronic acid on cell proliferation and invasion in lung cancer cell line 95D. Methods The effect of zoledrnic acid (ZOL on proliferation of lung cancer cell line 95D was detected by MTT. The expression of proliferation and invasion-relation genes and proteins were detected by Western blot, RT-PCR and immunofluorescence. Changes of invasion of lung cancer cell numbers were measured by polycarbonates coated with Matrigel. Results ZOL could inhibit the proliferation of lung cancer cell line 95D in vitro in a time-dependant and a dose-dependant manner. With time extending after ZOL treated, the mRNA expresion of VEGF, MMP9, MMP2 and protein expression of VEGF, MMP9, ERK1/ ERK2 were decreased. The results of Tanswell invasion showed the numbers of invasive cells were significantly reduced in 95D cells treated with ZOL 4 d and 6 d later. Conclusion ZOL could inhibit cell proliferation and invasion of lung cancer cell line 95D.

  10. Overview of bladder heating technology: matching capabilities with clinical requirements

    Science.gov (United States)

    Stauffer, Paul R.; van Rhoon, Gerard C.

    2016-01-01

    Moderate temperature hyperthermia (40–450°C for one hour) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for heating bladder cancer. Systems are described for thermal conduction heating of bladder wall via circulation of hot fluid, intravesical microwave antenna heating, capacitively coupled RF current heating, and radiofrequency phased array deep regional heating of the pelvis. Relative heating characteristics of the available technologies are compared based on published feasibility studies, and the systems correlated with clinical requirements for effective treatment of MIBC and NMIBC. PMID:26939993

  11. GSE1 negative regulation by miR-489-5p promotes breast cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Chai, Peng; Tian, Jingzhong; Zhao, Deyin; Zhang, Hongyan; Cui, Jian; Ding, Keshuo; Liu, Bin

    2016-01-01

    Gse1 coiled-coil protein (GSE1), also known as KIAA0182, is a proline rich protein. However, the function of GSE1 is largely unknown. In this study, we reported that GSE1 is overexpression in breast cancer and silencing of GSE1 significantly suppressed breast cancer cells proliferation, migration and invasion. Furthermore, GSE1 was identified as a direct target of miR-489-5p, which is significantly reduced in breast cancer tissues. In addition, forced expression of miR-489-5p suppressed breast cancer cells proliferation, migration and invasion. Moreover, depletion of GSE1 by siRNAs significantly abrogated the enhanced proliferation, migration and invasion of breast cancer cells consequent to miR-489-5p depletion. Taken together, these findings suggest that GSE1 may function as a novel oncogene in breast cancer and it can be regulated by miR-489-5p. - Highlights: • GSE1 is overexpressed in breast cancer and increased GSE1 expression predicts poor prognosis in breast cancer patients. • Knockdown of GSE1 inhibits breast cancer cell proliferation, migration and invasion. • GSE1 is a direct target of miR-489-5p. • Forced expression of miR-489-5p inhibits breast cancer cell proliferation, migration and invasion.

  12. Technetium-99m sestamibi: an indicator of breast cancer invasiveness

    Energy Technology Data Exchange (ETDEWEB)

    Scopinaro, F. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Schillaci, O. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Scarpini, M. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Mingazzini, P.L. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Di Macio, L. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Banci, M. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Danieli, R. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy)); Zerilli, M. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Limiti, M.R. (1st Inst. of Surgery, Univ. ' La Sapienza' , Rome (Italy)); Centi Colella, A. (Section of Nuclear Medicine, Dept. of Experimental Medicine, Univ. ' La Sapienza' , Rome (Italy))

    1994-09-01

    As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with [sup 99m]Tc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revesion showed a positive [sup 99m]Tc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm[sup 2] and one showed 99 microvessels/mm[sup 2]; by contrast there were 71.6[+-]12.1 microvessels/mm[sup 2] in the nine N- and sestamibi-negative tumours. Our study suggests that [sup 99m]Tc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour. (orig.)

  13. New method for evaluation of perigastric invasion of gastric cancer by right lateral position CT

    International Nuclear Information System (INIS)

    Shirakawa, T.; Fukuda, K.; Tada, S.

    1996-01-01

    The purpose of this study was to evaluate usefulness of right lateral position CT in determining invasion of gastric cancer into adjacent organs. We assessed whether position shift, a change in the relative location of a gastric tumor and adjacent organs between the supine position and right lateral position CT, was a useful sign for absence of invasion into perigastric organs. In 37 patients with advanced gastric cancer with doubtful invasion into adjacent organs by conventional CT after 500 ml water oral intake, additive right lateral CT was performed. Of 24 cases of lesions in the gastric body, 16 had a position shift and no invasion into adjacent organs at surgery (T3), and 8 had no position shift and invasion (T4). The accuracy was 100%. Six gastric cardial and 7 pyloric tumors showed no position shift, and 3 cardial and 2 pyloric tumors were proved to be nonivasive (T3). The accuracy of cardial and pyloric tumor was 50 and 71%. We concluded that position shift may be useful in the diagnosis of invasion of adjacent organs by gastric cancer, limited to in cases with gastric body cancer. (orig.)

  14. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    Science.gov (United States)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  15. Human bone marrow mesenchymal stem cells induce collagen production and tongue cancer invasion.

    Directory of Open Access Journals (Sweden)

    Sirpa Salo

    Full Text Available Tumor microenvironment (TME is an active player in carcinogenesis and changes in its composition modify cancer growth. Carcinoma-associated fibroblasts, bone marrow-derived multipotent mesenchymal stem cells (BMMSCs, and inflammatory cells can all affect the composition of TME leading to changes in proliferation, invasion and metastasis formation of carcinoma cells. In this study, we confirmed an interaction between BMMSCs and oral tongue squamous cell carcinoma (OTSCC cells by analyzing the invasion progression and gene expression pattern. In a 3-dimensional myoma organotypic invasion model the presence of BMMSCs inhibited the proliferation but increased the invasion of OTSCC cells. Furthermore, the signals originating from OTSCC cells up-regulated the expression of inflammatory chemokines by BMMSCs, whereas BMMSC products induced the expression of known invasion linked molecules by carcinoma cells. Particularly, after the cell-cell interactions, the chemokine CCL5 was abundantly secreted from BMMSCs and a function blocking antibody against CCL5 inhibited BMMSC enhanced cancer invasion area. However, CCL5 blocking antibody did not inhibit the depth of invasion. Additionally, after exposure to BMMSCs, the expression of type I collagen mRNA in OTSCC cells was markedly up-regulated. Interestingly, also high expression of type I collagen N-terminal propeptide (PINP in vivo correlated with the cancer-specific mortality of OTSCC patients, whereas there was no association between cancer tissue CCL5 levels and the clinical parameters. In conclusion, our results suggest that the interaction between BMMSC and carcinoma cells induce cytokine and matrix molecule expression, of which high level of type I collagen production correlates with the prognosis of OTSCC patients.

  16. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  17. Minimally invasive approaches for gastric cancer-Korean experience.

    Science.gov (United States)

    Yang, Han-Kwang; Suh, Yun-Suhk; Lee, Hyuk-Joon

    2013-03-01

    Laparoscopic surgery in Korea increased rapidly because of the early detection of gastric cancer by the development of diagnostic tools and nationwide screening. The Korean Laparoscopic Gastrointestinal Surgery Study Group (KLASS group) played a leading role in various projects related with minimally invasive surgery. The justification of minimally invasive procedures including robotic surgery, sentinel-node biopsy, or single-port surgery/Natural Orifice Transluminal Endoscopic Surgery (NOTES) must be predetermined by the clinical trial before a wide application, and the medical industry as well as surgeons should have great responsibility. Copyright © 2012 Wiley Periodicals, Inc.

  18. Radical perineal prostatectomy: cost efficient, outcome effective, minimally invasive prostate cancer management.

    Science.gov (United States)

    Harris, Michael J

    2003-09-01

    Localized prostate cancer is a common disease for which minimally invasive treatment methods are being explored. Perineal prostatectomy, as a historical open procedure, is modified to incorporate contemporary surgical ideas. There is relatively little in the literature regarding modern adaptations of perineal prostatectomy. This method of anatomic radical perineal prostatectomy has been developed to accomplish a minimally invasive method of achieving goals of disease control and preservation of genito-urinary functions. Prospective outcome data is accumulated on 508 consecutive radical perineal prostatectomies by a single surgeon. Pathologic stage and PSA detectability are measures of cancer control. Pad use and ability to complete intercourse measure urinary and sexual function. General complications and other outcome measures are evaluated. Freedom from PSA detectability by pathologic stage is 96.3%, 79.4%, and 69.4% for organ confined, specimen confined and margin positive in the absence of seminal vesical invasion with an average 4 years follow up (3-114 months). Margins are positive in 18% of cases. The average cancer size is 9.4g and 36% of cases have extracapsular invasion. By the first, third, sixth months and one year, 38%, 65%, 88% and 96% are free of pad use and report being dry. While over 80% of nerve-spared patients enjoy the return of spontaneous erectile function, the men with bilateral nerve preservation note earlier and more complete return of function. There are no cardiopulmonary complications or deaths. Transfusions occurred in 1%, none in the past 400 cases. Average total hospital charges are USD$4889.00 in 1999 and 2000. Anterior urethral strictures, anastomotic strictures and fecal urgency/stress flatus occur 2%, 2% and 2-4%, respectively. This method of prostatectomy is able to achieve complete cancer resection while preserving urinary and sexual function as well as laparoscopic or retropubic prostatectomy. The simplicity and minimally

  19. microRNA-495 promotes bladder cancer cell growth and invasion by targeting phosphatase and tensin homolog

    International Nuclear Information System (INIS)

    Tan, Mingyue; Mu, Xingyu; Liu, Zhihong; Tao, Le; Wang, Jun; Ge, Jifu; Qiu, Jianxin

    2017-01-01

    Accumulating evidence has linked deregulation of microRNA-495 (miR-495) to tumorigenesis; however, its function in tumor progression is controversial. This work was undertaken to explore the expression and biological roles of miR-495 in bladder cancer. The expression of miR-495 was examined in 67 pairs of bladder cancer and adjacent normal bladder tissues. The roles of miR-495 in bladder cancer cell proliferation and invasion in vitro and tumorigenesis in vivo were determined. Direct target gene(s) mediating the activity of miR-495 in bladder cancer cells was identified. It was found that miR-495 was expressed at greater levels in bladder tissues and cell lines. High expression of miR-495 was significantly associated with larger tumor size, advanced TNM stage, and lymph node metastasis. Overexpression of miR-495 significantly promoted bladder cancer cell proliferation and invasion, whereas inhibition of miR-495 suppressed cell proliferation and invasion. PTEN, a well-defined tumor suppressor was identified to be a target gene of miR-495. A significant inverse correlation between miR-495 and PTEN expression was noted in bladder cancer tissues (r = −0.3094, P = 0.0125). Overexpression of miR-495 led to reduction of PTEN expression in bladder cancer cells. Rescue experiments showed that enforced expression of PTEN impaired miR-495-mediated bladder cancer proliferation and invasion. In vivo mouse studies demonstrated that overexpression of miR-495 accelerated the growth of subcutaneous bladder cancer xenografts, which was associated with downregulation of PTEN. Overall, these findings indicate that miR-495 upregulation contributes to bladder cancer cell growth, invasion, and tumorigenesis by targeting PTEN and offer a potential therapeutic target for bladder cancer. - Highlights: • miR-495 upregulation induces aggressive phenotype in bladder cancer. • miR-495 is inversely correlated with PTEN in bladder cancer. • miR-495 promotes bladder cancer cell

  20. Identifying cost-effective treatment with raloxifene in postmenopausal women using risk algorithms for fractures and invasive breast cancer.

    Science.gov (United States)

    Ivergård, M; Ström, O; Borgström, F; Burge, R T; Tosteson, A N A; Kanis, J

    2010-11-01

    The National Osteoporosis Foundation (NOF) recommends considering treatment in women with a 20% or higher 10-year probability of a major fracture. However, raloxifene reduces both the risk of vertebral fractures and invasive breast cancer so that raloxifene treatment may be clinically appropriate and cost-effective in women who do not meet a 20% threshold risk. The aim of this study was to identify cost-effective scenarios of raloxifene treatment compared to no treatment in younger postmenopausal women at increased risk of invasive breast cancer and fracture risks below 20%. A micro-simulation model populated with data specific to American Caucasian women was used to quantify the costs and benefits of 5-year raloxifene treatment. The population evaluated was selected based on 10-year major fracture probability as estimated with FRAX® being below 20% and 5-year invasive breast cancer risk as estimated with the Gail risk model ranging from 1% to 5%. The cost per QALY gained ranged from US $22,000 in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture probability, to $110,000 in women age 55 with 1% invasive breast cancer risk and 5-9.9% fracture probability. Raloxifene was progressively cost-effective with increasing fracture risk and invasive breast cancer risk for a given age cohort. At lower fracture risk in combination with lower invasive breast cancer risk or when no preventive raloxifene effect on invasive breast cancer was assumed, the cost-effectiveness of raloxifene worsened markedly and was not cost-effective given a willingness-to-pay of US $50,000. At fracture risk of 15-19.9% raloxifene was cost-effective also in women at lower invasive breast cancer risk. Raloxifene is potentially cost-effective in cohorts of young postmenopausal women, who do not meet the suggested NOF 10-year fracture risk threshold. The cost-effectiveness is contingent on their 5-year invasive breast cancer risk. The result highlights the importance of considering

  1. Risk communication and decision-making in the prevention of invasive breast cancer.

    Science.gov (United States)

    Partridge, Ann H

    2017-08-01

    Risk communication surrounding the prevention of invasive breast cancer entails not only understanding of the disease, risks and opportunities for intervention. But it also requires understanding and implementation of optimal strategies for communication with patients who are making these decisions. In this article, available evidence for the issues surrounding risk communication and decision making in the prevention of invasive breast cancer are reviewed and strategies for improvement are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10

    International Nuclear Information System (INIS)

    Chen, Yating; Zhang, Hongwei; Ma, Duan; Zhang, Jin; Wang, Huijun; Zhao, Jiayi; Xu, Cheng; Du, Yingying; Luo, Xin; Zheng, Fengyun; Liu, Rui

    2012-01-01

    miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. HOXA10 however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because HOXA10 is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type. Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including HOXA10. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student's t-test. Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. HOXA10, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of HOXA10 both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of HOXA10. In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. HOXA10 is a target gene for mi

  3. MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Korvala, Johanna, E-mail: johanna.korvala@oulu.fi [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Jee, Kowan [Department of Pathology, University of Turku, Turku University Hospital, Turku (Finland); Department of Pathology, Haartman Institute, University of Helsinki, Helsinki (Finland); Porkola, Emmi [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Almangush, Alhadi [Department of Pathology, Haartman Institute, University of Helsinki, Helsinki (Finland); Mosakhani, Neda [Department of Pathology, HUSLAB, Helsinki (Finland); Bitu, Carolina [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Cervigne, Nilva K. [Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Av. Limeira, 901 – Bairro Areião, CEP: 13414-903 Piracicaba, São Paulo (Brazil); Department of Clinical and Pathology, Faculty of Medicine of Jundiai - FMJ, Jundiai, SP (Brazil); Zandonadi, Flávia S.; Meirelles, Gabriela V.; Leme, Adriana Franco Paes [Laboratório Nacional de Biociências, LNBio, CNPEM, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas/SP, P.O.Box 6192, CEP 13083-970 Campinas, São Paulo (Brazil); Coletta, Ricardo D. [Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Av. Limeira, 901 – Bairro Areião, CEP: 13414-903 Piracicaba, São Paulo (Brazil); and others

    2017-01-01

    Complex molecular pathways regulate cancer invasion. This study overviewed proteins and microRNAs (miRNAs) involved in oral tongue squamous cell carcinoma (OTSCC) invasion. The human highly aggressive OTSCC cell line HSC-3 was examined in a 3D organotypic human leiomyoma model. Non-invasive and invasive cells were laser-captured and protein expression was analyzed using mass spectrometry-based proteomics and miRNA expression by microarray. In functional studies the 3D invasion assay was replicated after silencing candidate miRNAs, miR-498 and miR-940, in invasive OTSCC cell lines (HSC-3 and SCC-15). Cell migration, proliferation and viability were also studied in the silenced cells. In HSC-3 cells, 67 proteins and 53 miRNAs showed significant fold-changes between non-invasive vs. invasive cells. Pathway enrichment analyses allocated “Focal adhesion” and “ECM-receptor interaction” as most important for invasion. Significantly, in HSC-3 cells, miR-498 silencing decreased the invasion area and miR-940 silencing reduced invasion area and depth. Viability, proliferation and migration weren’t significantly affected. In SCC-15 cells, down-regulation of miR-498 significantly reduced invasion and migration. This study shows HSC-3 specific miRNA and protein expression in invasion, and suggests that miR-498 and miR-940 affect invasion in vitro, the process being more influenced by mir-940 silencing in aggressive HSC-3 cells than in the less invasive SCC-15.

  4. Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    David G. Menter

    2012-01-01

    Full Text Available Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2 and microsomal prostaglandin E2 synthase-1 (mPGES-1 are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2, which binds to and activates G-protein-coupled prostaglandin E1-4 receptors (EP1-4. Selectively targeting the COX-2/mPGES-1/PGE2/EP1-4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM. Interactions with the ECM are mediated by cell surface integrins by “outside-in signaling” through Src and focal adhesion kinase (FAK and/or “inside-out signaling” through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/EP1-4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy.

  5. Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

    International Nuclear Information System (INIS)

    Guo, Hongsheng; Wu, Fenping; Wang, Yan; Yan, Chong; Su, Wenmei

    2014-01-01

    Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found that Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management

  6. Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hongsheng [Department of Histology and Embryology, Guangdong Medical College, Dongguan 523808, Guangdong (China); Wu, Fenping [The 7th People’s Hospital of Chengdu, Chengdu 610041, Sichuan (China); Wang, Yan [The Second School of Clinical Medicine, Guangdong Medical College, Dongguan 523808, Guangdong (China); Yan, Chong [School of Pharmacy, Guangdong Medical College, Dongguan 523808, Guangdong (China); Su, Wenmei, E-mail: wenmeisutg@126.com [Oncology of Affiliated Hospital Guangdong Medical College, Zhanjiang 524000, Guangdong (China)

    2014-08-08

    Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found that Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.

  7. Functional characterization of E- and P-cadherin in invasive breast cancer cells

    International Nuclear Information System (INIS)

    Sarrió, David; Palacios, José; Hergueta-Redondo, Marta; Gómez-López, Gonzalo; Cano, Amparo; Moreno-Bueno, Gema

    2009-01-01

    Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer

  8. Functional characterization of E- and P-cadherin in invasive breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cano Amparo

    2009-03-01

    Full Text Available Abstract Background Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. Methods To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Results Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. Conclusion E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer.

  9. MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells

    International Nuclear Information System (INIS)

    Li, Tao; Li, Dong; Sha, Jianjun; Sun, Peng; Huang, Yiran

    2009-01-01

    Prostate cancer is one of the most common malignant cancers in men. Recent studies have shown that microRNA-21 (miR-21) is overexpressed in various types of cancers including prostate cancer. Studies on glioma, colon cancer cells, hepatocellular cancer cells and breast cancer cells have indicated that miR-21 is involved in tumor growth, invasion and metastasis. However, the roles of miR-21 in prostate cancer are poorly understood. In this study, the effects of miR-21 on prostate cancer cell proliferation, apoptosis, and invasion were examined. In addition, the targets of miR-21 were identified by a reported RISC-coimmunoprecipitation-based biochemical method. Inactivation of miR-21 by antisense oligonucleotides in androgen-independent prostate cancer cell lines DU145 and PC-3 resulted in sensitivity to apoptosis and inhibition of cell motility and invasion, whereas cell proliferation were not affected. We identified myristoylated alanine-rich protein kinase c substrate (MARCKS), which plays key roles in cell motility, as a new target in prostate cancer cells. Our data suggested that miR-21 could promote apoptosis resistance, motility, and invasion in prostate cancer cells and these effects of miR-21 may be partly due to its regulation of PDCD4, TPM1, and MARCKS. Gene therapy using miR-21 inhibition strategy may therefore be useful as a prostate cancer therapy.

  10. Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric cancer: A case report.

    Science.gov (United States)

    Kim, Dae Hoon; Son, Seung-Myoung; Choi, Young Jin

    2018-03-01

    Gastric metastasis from invasive lobular breast cancer is relatively rare, commonly presented among multiple metastases, several years after primary diagnosis of breast cancer. Importantly, gastric cancer that is synchronously presented with lobular breast cancer can be misdiagnosed as primary gastric cancer; therefore, accurate differential diagnosis is required. A 39-year-old woman was visited to our hospital because of right breast mass and progressive dyspepsia. Invasive lobular carcinoma of breast was diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on biopsy. Synchronous double primary breast and gastric cancers were considered. Detailed pathological analysis focused on immunohistochemical studies of selected antibodies, including those of estrogen receptors, gross cystic disease fluid protein-15, and caudal-type homeobox transcription factor 2, were studied. As a result, gastric lesion was diagnosed as metastatic gastric cancer originating from breast. Right breast conserving surgery was performed, and duodenal stent was inserted under endoscopic guidance to relieve the patient's symptoms. Systemic chemotherapy with combined administration of paclitaxel and trastuzumab was initiated. Forty-one months after the diagnosis, the patient is still undergoing the same therapy. No recurrent lesion has been identified in the breast and evidence of a partial remission of gastric wall thickening has been observed on follow-up studies without new metastatic lesions. Clinical suspicion, repeat endoscopic biopsy, and detailed histological analysis, including immunohistochemistry, are necessary for diagnosis of metastatic gastric cancer from the breast.

  11. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion.

    Science.gov (United States)

    Shimura, Takaya; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2012-05-30

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation

  12. Immune Infiltration in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Desmedt, Christine; Salgado, Roberto; Fornili, Marco; Pruneri, Giancarlo; Van den Eynden, Gert; Zoppoli, Gabriele; Rothé, Françoise; Buisseret, Laurence; Garaud, Soizic; Willard-Gallo, Karen; Brown, David; Bareche, Yacine; Rouas, Ghizlane; Galant, Christine; Bertucci, François; Loi, Sherene; Viale, Giuseppe; Di Leo, Angelo; Green, Andrew R; Ellis, Ian O; Rakha, Emad A; Larsimont, Denis; Biganzoli, Elia; Sotiriou, Christos

    2018-02-20

    Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC. We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided. TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition. This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.

  13. Tyk2 expression and its signaling enhances the invasiveness of prostate cancer cells

    International Nuclear Information System (INIS)

    Ide, Hisamitsu; Nakagawa, Takashi; Terado, Yuichi; Kamiyama, Yutaka; Muto, Satoru; Horie, Shigeo

    2008-01-01

    Protein tyrosine kinase plays a central role in the proliferation and differentiation of various types of cells. One of these protein kinases, Tyk2, a member of the Jak family kinases, is known to play important roles in receptor signal transduction by interferons, interleukins, growth factors, and other hormones. In the present study, we investigated Tyk2 expression and its role in the growth and invasiveness of human prostate cancer cells. We used a small interfering RNA targeting Tyk2 and an inhibitor of Tyk2, tyrphostin A1, to suppress the expression and signaling of Tyk2 in prostate cancer cells. We detected mRNAs for Jak family kinases in prostate cancer cell lines by RT-PCR and Tyk2 protein in human prostate cancer specimens by immunohistochemistry. Inhibition of Tyk2 signaling resulted in attenuation of the urokinase-type plasminogen activator-enhanced invasiveness of prostate cancer cells in vitro without affecting the cellular growth rate. These results suggest that Tyk2 signaling in prostate cancer cells facilitate invasion of these cells, and interference with this signaling may be a potential therapeutic pathway

  14. HIF1 Contributes to Hypoxia-Induced Pancreatic Cancer Cells Invasion via Promoting QSOX1 Expression

    Directory of Open Access Journals (Sweden)

    Chen-Ye Shi

    2013-08-01

    Full Text Available Background: Quiescin sulfhydryl oxidase 1 (QSOX1, which oxidizes sulfhydryl groups to form disulfide bonds in proteins, is found to be over-expressed in various pancreatic cancer cell lines and patients. QSOX1 promotes invasion of pancreatic cancer cells by activating MMP-2 and MMP-9. However, its regulatory mechanism remains largely undefined. Methods: Real-time PCR and Western blot were employed to detect the expression of QSOX1 in human pancreatic cancer cell lines under hypoxic condition. Luciferase reporter and ChIP assays were used to assess the regulation of QSOX1 by hypoxia-inducible factor 1 (HIF-1. Small interfering RNA (siRNA was applied to knock down endogenous expression of QSOX1. Matrigel-coated invasion chamber essays were conducted to detect the invasion capacity of QSOX1-depleted cells. Results: Both hypoxia and hypoxia mimicking reagent up-regulated the expression of QSOX1 in human pancreatic cancer cell lines. Knockdown of HIF-1α eliminated hypoxia induced QSOX1 expression. HIF-1α was found directly bound to two hypoxia-response elements (HRE of QSOX1 gene, both of which were required for HIF-1 induced QSOX1 expression. Moreover, QSOX1 silencing blocked hypoxia-induced pancreatic cancer cells invasion. Conclusion: QSOX1 is a direct target of HIF-1 and may contribute to hypoxia-induced pancreatic cancer cells invasion.

  15. Quality of life in patients with muscle invasive and non-muscle invasive bladder cancer.

    Science.gov (United States)

    Singer, S; Ziegler, C; Schwalenberg, T; Hinz, A; Götze, H; Schulte, T

    2013-05-01

    Compared to the literature on other malignancies, data on quality of life (QoL) in bladder cancer are sparse. This study sought answers to the following questions: In what QoL domains do patients with bladder cancer differ from the general population? Do patients with radical cystectomy differ in QoL compared to those who received conservative treatment? Do patients with neobladder generally have better QoL compared to patients with other diversion methods? At the beginning of inpatient rehabilitation, N = 823 patients with bladder cancer were assessed. Data of a representative community sample (N = 2037) were used for comparison. The questionnaire EORTC QLQ-C30 was used to measure QoL. Multivariate linear regression models were computed to investigate differences between groups. Patients with both non-muscle invasive and muscle invasive bladder cancer reported significantly more problems and worse functioning than the general population. Radiotherapy is associated with clinically relevant more pain, dyspnoea, constipation, appetite loss and decreased social functioning while chemotherapy is associated more with dyspnoea. Cystectomy patients reported more fatigue, appetite loss and decreased role functioning. Male patients ≥70 years with conduit experienced more sleep and emotional problems. These effects of urinary diversion were not observed in women and younger patients. Patients with bladder cancer experience various QoL concerns at the beginning of inpatient rehabilitation. These problems can partly be explained by the type of treatment the patients receive. Type of urinary diversion is relevant for QoL in subgroups of patients.

  16. Parietal pleural invasion/adhesion of subpleural lung cancer: Quantitative 4-dimensional CT analysis using dynamic-ventilatory scanning

    Energy Technology Data Exchange (ETDEWEB)

    Sakuma, Kotaro, E-mail: ksakuma@ohara-hp.or.jp [Department of Radiology, Ohara General Hospital, 6-11 Omachi, Fukushima City, Fukushima 960-8611 (Japan); Department of Radiology and Nuclear Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima City, Fukushima 960-1295 (Japan); Yamashiro, Tsuneo, E-mail: clatsune@yahoo.co.jp [Department of Radiology, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan); Moriya, Hiroshi, E-mail: hrshmoriya@gmail.com [Department of Radiology, Ohara General Hospital, 6-11 Omachi, Fukushima City, Fukushima 960-8611 (Japan); Murayama, Sadayuki, E-mail: sadayuki@med.u-ryukyu.ac.jp [Department of Radiology, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan); Ito, Hiroshi, E-mail: h-ito@fmu.ac.jp [Department of Radiology and Nuclear Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima City, Fukushima 960-1295 (Japan)

    2017-02-15

    Highlights: • 4DCT can be used for assessment of pleural invasion/adhesion by lung cancer. • Quantitative 4DCT indices of lung cancer and adjacent structures are described. • An automatic analysis of pleural invasion/adhesion would be developed in the future. - Abstract: Purpose: Using 4-dimensional dynamic-ventilatory scanning by a 320-row computed tomography (CT) scanner, we performed a quantitative assessment of parietal pleural invasion and adhesion by peripheral (subpleural) lung cancers. Methods: Sixteen patients with subpleural lung cancer underwent dynamic-ventilation CT during free breathing. Neither parietal pleural invasion nor adhesion was subsequently confirmed by surgery in 10 patients, whereas the other 6 patients were judged to have parietal pleural invasion or adhesion. Using research software, we tracked the movements of the cancer and of an adjacent structure such as the rib or aorta, and converted the data to 3-dimensional loci. The following quantitative indices were compared by the Mann-Whitney test: cross-correlation coefficient between time curves for the distances moved from the inspiratory frame by the cancer and the adjacent structure, the ratio of the total movement distances (cancer/adjacent structure), and the cosine similarities between the inspiratory and expiratory vectors (from the cancer to the adjacent structure) and between vectors of the cancer and of the adjacent structure (from inspiratory to expiratory frames). Results: Generally, the movements of the loci of the lung cancer and the adjacent structure were similar in patients with parietal pleural invasion/adhesion, while they were independent in patients without. There were significant differences in all the parameters between the two patient groups (cross-correlation coefficient and the movement distance ratio, P < 0.01; cosine similarities, P < 0.05). Conclusion: These observations suggest that quantitative indices by dynamic-ventilation CT can be utilized as a

  17. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    International Nuclear Information System (INIS)

    Choi, Yoon Pyo; Kim, Baek Gil; Gao, Ming-Qing; Kang, Suki; Cho, Nam Hoon

    2012-01-01

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  18. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  19. Selective bladder preservation with curative intent for muscle-invasive bladder cancer. A contemporary review

    International Nuclear Information System (INIS)

    Koga, Fumitaka; Kihara, Kazunori

    2012-01-01

    Radical cystectomy plus urinary diversion, the reference standard treatment for muscle-invasive bladder cancer, associates with high complication rates and compromises quality of life as a result of long-term effects on urinary, gastrointestinal and sexual function, and changes in body image. As a society ages, the number of elderly patients unfit for radical cystectomy as a result of comorbidity will increase, and thus the demand for bladder-sparing approaches for muscle-invasive bladder cancer will also inevitably increase. Trimodality bladder-sparing approaches consisting of transurethral resection, chemotherapy and radiotherapy (Σ55-65 Gy) yield overall survival rates comparable with those of radical cystectomy series (50-70% at 5 years), while preserving the native bladder in 40-60% of muscle-invasive bladder cancer patients, contributing to an improvement in quality of life for such patients. Limitations of the trimodality therapy include muscle-invasive bladder cancer recurrence in the preserved bladder, which most often arises in the original muscle-invasive bladder cancer site; potential lack of curative intervention for regional lymph nodes; and increased morbidity in the event of salvage radical cystectomy for remaining or recurrent disease as a result of high-dose pelvic irradiation. Consolidative partial cystectomy with pelvic lymph node dissection followed by induction chemoradiotherapy at lower dose (exempli gratia (e.g.) 40 Gy) is a rational strategy for overcoming such limitations by strengthening locoregional control and reducing radiation dosage. Molecular profiling of the tumor and functional imaging might play important roles in optimal patient selection for bladder preservation. Refinement of radiation techniques, intensified concurrent or adjuvant chemotherapy, and novel sensitizers, including molecular targeting agent, are also expected to improve outcomes and consequently provide more muscle-invasive bladder cancer patients with favorable

  20. KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Keisuke Taniuchi

    2014-12-01

    Full Text Available Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.

  1. Cancer/testis Antigen-Plac1 Promotes Invasion and Metastasis of Breast Cancer through Furin/NICD/PTEN Signaling Pathway.

    Science.gov (United States)

    Li, Yongfei; Chu, Jiahui; Li, Jun; Feng, Wanting; Yang, Fan; Wang, Yifan; Zhang, Yanhong; Sun, Chunxiao; Yang, Mengzhu; Vasilatos, Shauna N; Huang, Yi; Fu, Ziyi; Yin, Yongmei

    2018-04-28

    Plac1 is a cancer-testis antigen that plays a critical role in promoting cancer initiation and progression. However, the clinical significance and mechanism of Plac1 in cancer progression remains elusive. Here we report that Plac1 is an important oncogenic and prognostic factor which physically interacts with Furin to drive breast cancer invasion and metastasis. We have shown that Plac1 expression positively correlates with clinical stage, lymph node metastasis, HR status and overall patient survival. Overexpression of Plac1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo. Co-immunoprecipitation and immunofluorescence cell staining assays revealed that interaction of Plac1 and Furin degraded Notch1 and generated Notch1 intracellular domain (NICD) that could inhibit PTEN activity. These findings are consistent with the results of microarray study in MDA-MB-231 cells overexpressing Plac1. A rescue study showed that inhibition of Furin and overexpression of PTEN in Plac1 overexpression cells blocked Plac1-induced tumor cell progression. Taken together, our findings suggest that functional interaction between Plac1 and Furin enhances breast cancer invasion and metastasis and the Furin/NICD/PTEN axis may act as an important therapeutic target for breast cancer treatment. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  2. Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer

    International Nuclear Information System (INIS)

    Banyard, Jacqueline; Chung, Ivy; Migliozzi, Matthew; Phan, Derek T; Wilson, Arianne M; Zetter, Bruce R; Bielenberg, Diane R

    2014-01-01

    Understanding the complex, multistep process of metastasis remains a major challenge in cancer research. Metastasis models can reveal insights in tumor development and progression and provide tools to test new intervention strategies. To develop a new cancer metastasis model, we used DU145 human prostate cancer cells and performed repeated rounds of orthotopic prostate injection and selection of subsequent lymph node metastases. Tumor growth, metastasis, cell migration and invasion were analyzed. Microarray analysis was used to identify cell migration- and cancer-related genes correlating with metastasis. Selected genes were silenced using siRNA, and their roles in cell migration and invasion were determined in transwell migration and Matrigel invasion assays. Our in vivo cycling strategy created cell lines with dramatically increased tumorigenesis and increased ability to colonize lymph nodes (DU145LN1-LN4). Prostate tumor xenografts displayed increased vascularization, enlarged podoplanin-positive lymphatic vessels and invasive margins. Microarray analysis revealed gene expression profiles that correlated with metastatic potential. Using gene network analysis we selected 3 significantly upregulated cell movement and cancer related genes for further analysis: EPCAM (epithelial cell adhesion molecule), ITGB4 (integrin β4) and PLAU (urokinase-type plasminogen activator (uPA)). These genes all showed increased protein expression in the more metastatic DU145-LN4 cells compared to the parental DU145. SiRNA knockdown of EpCAM, integrin-β4 or uPA all significantly reduced cell migration in DU145-LN4 cells. In contrast, only uPA siRNA inhibited cell invasion into Matrigel. This role of uPA in cell invasion was confirmed using the uPA inhibitors, amiloride and UK122. Our approach has identified genes required for the migration and invasion of metastatic tumor cells, and we propose that our new in vivo model system will be a powerful tool to interrogate the metastatic

  3. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

    2014-05-09

    Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.

  4. Minimally invasive diagnostics and immunotherapy of lung cancer

    NARCIS (Netherlands)

    Talebian-Yazdi, M.

    2017-01-01

    This thesis deals with aspects of diagnostics and immunotherapy of lung cancer. The first aim of this thesis is to investigate how the implementation of minimally invasive endoscopic ultrasound techniques (EUS and EBUS) in the staging algorithm of NSCLC can be optimized. The second aim of this

  5. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

    Science.gov (United States)

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

  6. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M

    2015-10-08

    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.

    Science.gov (United States)

    Nakamura, Koji; Sawada, Kenjiro; Kinose, Yasuto; Yoshimura, Akihiko; Toda, Aska; Nakatsuka, Erika; Hashimoto, Kae; Mabuchi, Seiji; Morishige, Ken-Ichirou; Kurachi, Hirohisa; Lengyel, Ernst; Kimura, Tadashi

    2017-01-01

    Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMC) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications is exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and cocultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, whereas CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion. Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR. ©2016 American

  8. Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Mizoguchi, Hiroaki; Nomura, Yoshio; Terada, Katsuhiko; Nakagawa, Masayuki; Ogata, Jiro

    1995-01-01

    Twenty-three patients with invasive bladder cancer (T2 in 17, T3 in 6) were treated initially with combined intraarterial cisplatin infusion and radiation therapy. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was given. In 23 patients, 6 received additional cisplatin infusion and the other 17 had transurethral resection of bladder tumor (TURBT). Two of the patients undergoing total cystectomy exhibited a complete response (CR). Thus overall response rate was 87% (CR in 13 and partial response in 7). CR was achieved in 53% for T2 patients and 67% for T3 patients. CR was slightly higher in patients with non-papillary cancer than those with papillary one. Toxic reaction included a decrease in bladder capacity in 2 patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. The other toxicities, including nausea, vomiting, neurotoxicity and myelosuppression, were tolerable. All except for one are alive. Seven patients had a local recurrence of bladder cancer. One patient developed invasive bladder cancer reaching the prostatic urethra. One other patient had recurrence at the same site as the previous tumor. Five others had superficial bladder cancer and were managed by TURBT. Bladder function was preserved in 65% at a mean follow-up of 29 months. In conclusion, the combined intraarterial cisplatin infusion and radiation therapy is useful for the initial treatment of invasive bladder cancer. (N.K.)

  9. Skin cancer: an overview of epidemiology and risk factors.

    Science.gov (United States)

    Gordon, Randy

    2013-08-01

    To provide a general overview of malignant melanoma and non-melanoma skin cancer, with an emphasis on epidemiology, clinical presentation, and the multiple and varied risk factors associated with skin cancer. Peer-reviewed journal articles, government health reports, book chapters, and Web-based resources. Skin cancer is the most common carcinoma, affecting millions worldwide. Incidence is increasing yearly, making it a pre-eminent public health threat. Myriad factors increase the risk of skin cancer and may serve as important prognostic indicators for the disease. To provide nurses with a clearer understanding of the causative mechanisms of skin cancer and an improved awareness of the risk factors associated with the disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-01-01

    The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3high or αvβ3low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3high cells showed a threefold increased cell invasion compared to αvβ3low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3high cells but not in αvβ3low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3high cells, whereas the invasiveness of β3 specific knock

  11. The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

    International Nuclear Information System (INIS)

    Mierke, Claudia Tanja

    2013-01-01

    The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3 high or αvβ3 low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3 high cells showed a threefold increased cell invasion compared to αvβ3 low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3 high cells but not in αvβ3 low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3 low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3 high cells, whereas the invasiveness of β3 specific knock

  12. IL1β-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

    International Nuclear Information System (INIS)

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-01-01

    COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1β in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts with or without stimulation of IL-1β, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1β. Further analysis indicated that the major COX-2 product, prostaglandin E 2 , directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1β. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1β in the fibroblasts.

  13. ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α.

    Science.gov (United States)

    Lee, Joon Ho; Hur, Wonhee; Hong, Sung Woo; Kim, Jung-Hee; Kim, Sung Min; Lee, Eun Byul; Yoon, Seung Kew

    2017-02-01

    Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the third most common cause of cancer-related mortality. HCC develops via a multistep process associated with genetic aberrations that facilitate HCC invasion and migration and promote metastasis. A growing body of evidence indicates that cancer stem cells (CSCs) are responsible for tumorigenesis, cancer cell invasion and metastasis. Despite the extremely small proportion of cancer cells represented by this subpopulation of HCC cells, CSCs play a key role in cancer metastasis and poor prognosis. ELK3 (Net/SAP-2/Erp) is a transcription factor that is activated by the Ras/extracellular signal-regulated kinase (ERK) signaling pathway. It plays several important roles in various physiological processes, including cell migration, invasion, wound healing, angiogenesis and tumorigenesis. In the present study, we investigated the role of ELK3 in cancer cell invasion and metastasis in CD133+/CD44+ liver cancer stem cells (LCSCs). We isolated LCSCs expressing CD133 and CD44 from Huh7 HCC cells and evaluated their metastatic potential using invasion and migration assays. We found that CD133+/CD44+ cells had increased metastatic potential compared with non-CD133+/CD44+ cells. We also demonstrated that ELK3 expression was upregulated in CD133+/CD44+ cells and that this aberration enhanced cell migration and invasion. In addition, we identified the molecular mechanism by which ELK3 promotes cancer cell migration and invasion. We found that silencing of ELK3 expression in CD133+/CD44+ LCSCs attenuated their metastatic potential by modulating the expression of heat shock-induced factor-1α (HIF-1α). Collectively, the results of the present study demonstrated that ELK3 overexpression promoted metastasis in CD133+/CD44+ cells by regulating HIF-1α expression and that silencing of ELK3 expression attenuated the metastatic potential of CD133+/CD44+ LCSCs. In conclusion, modulation of ELK3 expression may

  14. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  15. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    International Nuclear Information System (INIS)

    Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

    2009-01-01

    The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BK Ca ) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BK Ca channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BK Ca channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BK Ca channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BK Ca channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BK Ca channel expression in breast cancer metastatic to brain and the mechanism of its

  16. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. | Office of Cancer Genomics

    Science.gov (United States)

    We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival.

  17. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Cekanova, Maria, E-mail: mcekanov@utk.edu [Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Fernando, Romaine I. [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Siriwardhana, Nalin [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Sukhthankar, Mugdha [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Parra, Columba de la [Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR (United States); Woraratphoka, Jirayus [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Malone, Christine [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Ström, Anders [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Baek, Seung J. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Wade, Paul A. [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Saxton, Arnold M. [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Donnell, Robert M. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Pestell, Richard G. [Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); and others

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.

  18. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    International Nuclear Information System (INIS)

    Cekanova, Maria; Fernando, Romaine I.; Siriwardhana, Nalin; Sukhthankar, Mugdha; Parra, Columba de la; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J.; Wade, Paul A.; Saxton, Arnold M.; Donnell, Robert M.; Pestell, Richard G.

    2015-01-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis

  19. Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Schildkraut, Joellen M; Goode, Ellen L; Clyde, Merlise A

    2009-01-01

    The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2,829...

  20. Spiral (Helical) computed tomographic imaging for the diagnosis of bile duct cancer. Vascular and pancreatic invasions

    International Nuclear Information System (INIS)

    Kon, Masanori

    1997-01-01

    The development of several imaging techniques for diagnosing bile duct cancer have improved, however, its diagnosis at the early stage is still difficult. We discuss the significance of the spiral (helical) computed tomography (SCT) imaging for the diagnosis of bile duct cancer at an early stage. We performed, as a preoperative examination, SCT under intravenous angiography (IV-SCT) for all cases, which included 233 cases of benign bile duct diseases, 42 cases of gallbladder cancer and 22 cases of bile duct cancer. The accuracy rate of diagnosis ability of 42 cases of gallbladder cancer by IV-SCT was 91%, and that of portal vein invasion was 91%. In the cases of bile duct cancer, IV-SCT showed destructive images of the bile duct wall and the tumor images invaded into the pancreatic parenchyma, in the cases of invasion at the splenic vein and confluence site of the portal vein, IV-SCT gave clearer 3D images than conventional angiography. The accuracy rate of diagnosing pancreatic invasion in bile duct cancer by IV-SCT was 80%. However, it is still difficult to determine completely the layer structures of the bile duct and the invasion into the walls along the long axis. As the future development of SCT for the diagnosis of bile duct cancer, we expect further progression of diagnosis ability of bile duct cancer and the invasion level by the applying high resolution thin-section CT images or endoscopical images of the luminal organs in examining the bile duct. (K.H.)

  1. Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion.

    Science.gov (United States)

    Rodriguez, M; Siwko, S; Liu, M

    2016-01-01

    Prostate cancer is highly prevalent among men in developed countries, but a significant proportion of detected cancers remain indolent, never progressing into aggressive carcinomas. This highlights the need to develop refined biomarkers that can distinguish between indolent and potentially dangerous cases. The prostate-specific G-protein coupled receptor (PSGR, or OR51E2) is an olfactory receptor family member with highly specific expression in human prostate epithelium that is highly overexpressed in PIN and prostate cancer. PSGR has been functionally implicated in prostate cancer cell invasiveness, suggesting a potential role in the transition to metastatic PCa. Recently, transgenic mice overexpressing PSGR in the prostate were reported to develop an acute inflammatory response followed by emergence of low grade PIN, whereas mice with compound PSGR overexpression and loss of PTEN exhibited accelerated formation of invasive prostate adenocarcinoma. This article will review recent PSGR findings with a focus on its role as a potential prostate cancer biomarker and regulator of prostate cancer invasion and inflammation.

  2. Expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer.

    Science.gov (United States)

    Mikami, Koji; Hirano, Yukiko; Futami, Kitaro; Maekawa, Takafumi

    2017-07-18

    Mixed-type early gastric cancer (differentiated and undifferentiated components) incurs a higher risk of lymph node metastasis than pure-type early gastric cancer (only differentiated or only undifferentiated components). Therefore, we investigated the expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer in order to establish the most appropriate treatment for mixed-type cancer. We retrospectively analyzed 279 consecutive patients with submucosal invasive gastric cancer who underwent curative gastrectomy for gastric cancer between 1996 and 2015. We classified the patients into the mixed-type and pure-type groups according to histologic examination and evaluated the expansion of lymph node metastasis. The rate of lymph node metastasis was 23.7% (66/279) in the total patients, 36.4% (36/99) in the mixed-type group, and 16.6% (30/180) in the pure-type group. The significant independent risk factors for lymph node metastasis were tumor size ≥2.0 cm (P = 0.014), mixed-type gastric cancer (P mixed-type group. The rates of no. 7 lymph node metastasis in the total patients and mixed-type group were 2.9% (8/279) and 5.1% (5/99), respectively; the rates of no. 8a lymph node metastasis were 1.4% (4/279) and 4.0% (4/99), respectively. Mixed histological type is an independent risk factor for lymph node metastasis. Lymph node metastasis in mixed-type gastric cancer involves expansion to the no. 7 and no. 8a lymph nodes. Therefore, lymphadenectomy for mixed-type submucosal invasive gastric cancer requires D1+ or D2 dissection. Copyright © 2017. Published by Elsevier Taiwan.

  3. MicroRNA-410 suppresses migration and invasion by targeting MDM2 in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jianjun Shen

    Full Text Available Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs play important roles in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In this study, we found that the levels of miR-410 in gastric cancer and cell lines were much lower than that in the normal control, respectively, and the lower level of miR-410 was significantly associated with lymph-node metastasis. Transfection of miR-410 mimics could significantly inhibit the cell proliferation, migration and invasion in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had the opposite effect on the cell proliferation, migration and invasion. Moreover, we also found that MDM2 was negatively regulated by miR-410 at the post-transcriptional level, via a specific target site with the 3'UTR by luciferase reporter assay. The expression of MDM2 was inversely correlated with miR-410 expression in gastric cancer tissues, and overexpression of MDM2 in miR-410-transfected gastric cancer cells effectively rescued the inhibition of cell proliferation and invasion caused by miR-410. Thus, our findings suggested that miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion. The findings of this study contributed to the current understanding of these functions of miR-410 in gastric cancer.

  4. Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis

    International Nuclear Information System (INIS)

    Yuan, Bo; Cui, Jinquan; Wang, Wuliang; Deng, Kehong

    2016-01-01

    Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation. -- Highlights: •Gα12/Gα13 is upregulated in cervical cancer cell lines. •Gα12/Gα13 is not involved in cervical cancer cell proliferation. •Gα12/Gα13 promotes cervical cancer cell invasion. •The role of Rho G proteins in G12-promoted cervical cancer cell invasion. •G12 promotes cell invasion through activation of the ROCK-JNK signaling axis.

  5. Transcription factor HBP1 is a direct anti-cancer target of transcription factor FOXO1 in invasive oral cancer.

    Science.gov (United States)

    Chan, Chien-Yi; Huang, Shih-Yi; Sheu, Jim Jinn-Chyuan; Roth, Mendel M; Chou, I-Tai; Lien, Chia-Hsien; Lee, Ming-Fen; Huang, Chun-Yin

    2017-02-28

    Either FOXO1 or HBP1 transcription factor is a downstream effector of the PI3K/Akt pathway and associated with tumorigenesis. However, the relationship between FOXO1 and HBP1 in oral cancer remains unclear. Analysis of 30 oral tumor specimens revealed that mean mRNA levels of both FOXO1 and HBP1 in non-invasive and invasive oral tumors were found to be significantly lower than that of the control tissues, and the status of low FOXO1 and HBP1 (oral tumors. To investigate if HBP1 is a direct transcription target of FOXO1, we searched potential FOXO1 binding sites in the HBP1 promoter using the MAPPER Search Engine, and two putative FOXO1 binding sites located in the HBP1 promoter -132 to -125 bp and -343 to -336 bp were predicted. These binding sites were then confirmed by both reporter gene assays and the in cellulo ChIP assay. In addition, Akt activity manipulated by PI3K inhibitor LY294002 or Akt mutants was shown to negatively affect FOXO1-mediated HBP1 promoter activation and gene expression. Last, the biological significance of the FOXO1-HBP1 axis in oral cancer malignancy was evaluated in cell growth, colony formation, and invasiveness. The results indicated that HBP1 knockdown potently promoted malignant phenotypes of oral cancer and the suppressive effect of FOXO1 on cell growth, colony formation, and invasion was alleviated upon HBP1 knockdown in invasive oral cancer cells. Taken together, our data provide evidence for HBP1 as a direct downstream target of FOXO1 in oral cancer malignancy.

  6. ERβ inhibits proliferation and invasion of breast cancer cells

    Science.gov (United States)

    Lazennec, Gwendal; Bresson, Damien; Lucas, Annick; Chauveau, Corine; Vignon, Françoise

    2001-01-01

    Recent studies indicate that the expression of ERβ in breast cancer is lower than in normal breast, suggesting that ERβ could play an important role in carcinogenesis. To investigate this hypothesis, we engineered estrogen-receptor negative MDA-MB-231 breast cancer cells to reintroduce either ERα or ERβ protein with an adenoviral vector. In these cells, ERβ (as ERα) expression was monitored using RT-PCR and Western blot. ERβ protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of estradiol. ERβ and ERα induced the expression of several endogenous genes such as pS2, TGFα or the cyclin kinase inhibitor p21, but in contrast to ERα, ERβ was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ERα and ERβ estrogen-induced activities. ERβ inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ERα inhibition of proliferation is hormone-dependent. Moreover, ERβ and ERα, decreased cell motility and invasion. Our data bring the first evidence that ERβ is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ERβ expression could be one of the events leading to the development of breast cancer. PMID:11517191

  7. Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Dehu Chen

    2017-06-01

    Full Text Available Background/Aims: Gastric cancer (GC is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5 has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

  8. Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Wu Qian

    2012-01-01

    Full Text Available Abstract Background Carcinoma cells must circumvent the normally suppressive signals to disseminate. While often considered 'stop' signals for adherent cells, CXCR3-binding chemokines have recently been correlated positively with cancer progression though the molecular basis remains unclear. Results Here, we examined the expression and function of two CXCR3 variants in human prostate cancer biopsies and cell lines. Globally, both CXCR3 mRNA and protein were elevated in localized and metastatic human cancer biopsies compared to normal. Additionally, CXCR3A mRNA level was upregulated while CXCR3B mRNA was downregulated in these prostate cancer specimens. In contrast to normal prostate epithelial cells (RWPE-1, CXCR3A was up to half the receptor in the invasive and metastatic DU-145 and PC-3 prostate cancer cells, but not in the localized LNCaP cells. Instead of inhibiting cell migration as in RWPE-1 cells, the CXCR3 ligands CXCL4/PF4 and CXCL10/IP10 promoted cell motility and invasiveness in both DU-145 and PC-3 cells via PLCβ3 and μ-calpain activation. CXCR3-mediated diminution of cell motility in RWPE-1 cells is likely a result of cAMP upregulation and m-calpain inhibition via CXCR3B signal transduction. Interestingly, overexpression of CXCR3B in DU-145 cells decreased cell movement and invasion. Conclusion These data suggest that the aberrant expression of CXCR3A and down-regulation of CXCR3B may switch a progression "stop" to a "go" signal to promote prostate tumor metastasis via stimulating cell migration and invasion.

  9. Managing the risk of invasive breast cancer in women at risk for breast cancer and osteoporosis: the role of raloxifene

    Directory of Open Access Journals (Sweden)

    Victor G Vogel

    2008-12-01

    Full Text Available Victor G VogelThe University of Pittsburgh Cancer Institute, Magee-Womens Hospital, Pittsburgh, PA, USAAbstract: Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but it has no significant effect on the risk of primary coronary events. A meta-analysis of randomized, double-blind, placebo-controlled trials of raloxifene for osteoporosis showed the odds of fracture risk were 0.60 (95% confidence interval [CI] = 0.49–0.74 for raloxifene 60 mg/day compared with placebo. During 8 years of follow-up in an osteoporosis trial, the raloxifene group had a 76% reduction in the incidence of invasive ER-positive breast cancer compared with the placebo group. In the STAR trial, the incidence of invasive breast cancer was 4.30 per 1000 women-years with raloxifene and 4.41 per 1000 with tamoxifen; RR = 1.02; 95% CI, 0.82–1.28. The effect of raloxifene on invasive breast cancer was, therefore, equivalent to that of tamoxifen with more favorable rates of adverse effects including uterine malignancy and clotting events. Millions of postmenopausal women could derive net benefit from raloxifene through reduced rates of fracture and invasive breast cancer.Keywords: raloxifene, osteoporosis, breast cancer risk reduction

  10. The prognosis significance and application value of peritoneal elastic lamina invasion in colon cancer.

    Science.gov (United States)

    Lu, Jun; Hu, Xiumei; Meng, Yutong; Zhao, Hongying; Cao, Qing; Jin, Mulan

    2018-01-01

    The aims of this study were to evaluate the associations between peritoneal elastic lamina invasion (ELI) and the clinicopathological prognostic factors of colon cancer, to evaluate the feasibility of ELI with use of an elastic stain to help diagnose serosal invasion of colon cancer in routine practice, so as to help us to provide a more accurate estimate for prognosis and stage of patients and a marker for postoperative treatment. 254 cases with colon cancer were included in the study. According to the presence of elastic lamina (EL) and elastic lamina invasion (ELI), all cases were divided into four groups: pT3 EL negative (pT3 EL (-)), pT3 ELI positive (pT3 ELI (+)), pT3 ELI negative (pT3 ELI (-)) and pT4a. Statistical analysis was used to analyze the relationship between elastic lamina invasion and other established adverse histologic features. The EL and ELI positive rates were 81.5% and 42.1% respectively. There were significant differences in mph node metastasis, venous invasion and tumor buds between pT3 ELI (-) and pT3 ELI (+), pT3 ELI (-) and pT4a. There was no significant difference in same factors between pT3 ELI (+) and pT4a. In pT3 stage, there were significant differences in lymph node metastasis, perineural invasion and tumor buds between EL (-) and ELI (+). There were no significant differences in same factors between EL (-) and ELI (-). EL was detected less frequently in right-sided tumors compared with left-sided tumors. ELI might be the prognostic factors of colon cancer with II stage and might be the marker of postoperative adjuvant chemotherapy. Patients with pT3 ELI (+) might have similar prognosis to patients with pT4a. For patients with pT3 colon cancer, EL(-) might have similar prognosis as ELI (-) and might take the same therapy. In addition, the right half colon EL positive rate was lower than the left colon. Elastic staining might be a useful tool to help determine the invasive depth and stage of colon cancer.

  11. MINIMALLY INVASIVE OPEN THYROIDECTOMY IN THYROID CANCER WITH COEXISTENT HASHIMOTO THYROIDITIS

    Directory of Open Access Journals (Sweden)

    Rumen Nenkov

    2013-06-01

    Full Text Available One of the minimally invasive thyroidectomy challenges is the application of this technique in the surgical treatment of thyroid cancer. The use of minimally invasive open approach in co-existence of thyroid cancer with Hashimoto thyroiditis is well known provocation to the skills of the surgeon working in the field of thyroid surgery.Aim: To report our results and to present the possibilities of minimally invasive open approach in the surgical treatment of thyroid carcinoma and coexistent Hashimoto thyroiditis. Patients and methods: For the period from 2008 to 2011, 641 patients were operated on in our clinic using minimally invasive open approach. In 32 of these patients presence of Hashimoto thyroiditis was found in combination with thyroid cancer. All patients were females, 26 to 46 years age. Patients were selected according to designed and accepted for our institution criteria. The procedures were performed using ultrasound (harmonic shears (Harmonic Focus® and Harmonic Ace®, Ethicon Endo-Surgery. The operative time, incidence, type and severity of complications, length of hospital stay, safety and reliability of the surgical procedure were analyzed. Results: The operative incision length in all cases was between 2.0-2.5 cm. In 27 patients papillary thyroid carcinoma and in 5 patients – follicular variant of the neoplasm were found. The tumor size ranged between 0.5 and 1.5 cm. In all patients total thyroidectomy using harmonic scalpel was performed. Lymph node metastases in the central neck compartment were not found in any of the cases. The rate, type and severity of complications did not exceed those for patients who underwent conventional thyroidectomy. All patients leaved the hospital in the first 24 postoperative hours. The follow-up did not reveal remnant thyroid tissue in thyroid gland bed or recurrence of the disease.Conclusions: Our results demonstrate the feasibility and reliability of minimally invasive open approach with

  12. miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα.

    Science.gov (United States)

    Tribollet, Violaine; Barenton, Bruno; Kroiss, Auriane; Vincent, Séverine; Zhang, Ling; Forcet, Christelle; Cerutti, Catherine; Périan, Séverine; Allioli, Nathalie; Samarut, Jacques; Vanacker, Jean-Marc

    2016-01-01

    MicroRNA-135a (miR-135a) down-modulates parameters of cancer progression and its expression is decreased in metastatic breast cancers (as compared to non-metastatic tumors) as well as in prostate tumors relative to normal tissue. These expression and activity patterns are opposite to those of the Estrogen-Related Receptor α (ERRα), an orphan member of the nuclear receptor family. Indeed high expression of ERRα correlates with poor prognosis in breast and prostate cancers, and the receptor promotes various traits of cancer aggressiveness including cell invasion. Here we show that miR-135a down-regulates the expression of ERRα through specific sequences of its 3'UTR. As a consequence miR-135a also reduces the expression of downstream targets of ERRα. miR-135a also decreases cell invasive potential in an ERRα-dependent manner. Our results suggest that the decreased expression of miR-135a in metastatic tumors leads to elevated ERRα expression, resulting in increased cell invasion capacities.

  13. [Recent Overview of Kidney Cancer Diagnostics and Treatment].

    Science.gov (United States)

    Marenčák, J; Ondrušová, M; Ondruš, D

    The incidence of kidney cancer has increased in the majority of countries worldwide, and this disease has relatively high lethality. For many years, the Slovak Republic has been among the countries with the highest kidney cancer incidence, in particular in 2012 (according to global estimated values) in both genders, although mainly in females. In the last few years, the Czech Republic has had the highest incidence of kidney cancer worldwide. The use of imaging techniques such as ultrasound and computerized tomography has increased the detection of asymptomatic renal cell cancer. Etiological factors include lifestyle factors such as smoking, obesity, and hypertension. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged by pharmacotherapy with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain or osseal metastases that are painful or increase the risk of fracture. Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress.Key words: kidney cancer - epidemiology - risk factors - pathology - diagnosis - therapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 2. 12. 2016Accepted: 3. 1. 2017.

  14. Aberrant glycogen synthase kinase 3β is involved in pancreatic cancer cell invasion and resistance to therapy.

    Directory of Open Access Journals (Sweden)

    Ayako Kitano

    Full Text Available BACKGROUND AND PURPOSE: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. METHODS: Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined. RESULTS: Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2 and decreased phosphorylation of focal adhesion kinase (FAK. The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. CONCLUSION: The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.

  15. Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers.

    Science.gov (United States)

    Terracciano, Daniela; Ferro, Matteo; Terreri, Sara; Lucarelli, Giuseppe; D'Elia, Carolina; Musi, Gennaro; de Cobelli, Ottavio; Mirone, Vincenzo; Cimmino, Amelia

    2017-06-01

    Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer. Although lncRNAs have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless, a growing body of evidence suggests that several lncRNAs expression profiles in bladder malignancies are associated with poor prognosis, and they can be detected in biological fluids, such as urines. Here, we review current progress in the biology and the implication of lncRNAs associated with bladder cancer, and we discuss their potential use as diagnosis and prognosis biomarkers in bladder malignancies with a focus on their role in high-risk nonmuscle-invasive tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. MicroRNA-218 inhibits cell invasion and migration of pancreatic cancer via regulating ROBO1.

    Science.gov (United States)

    He, Hang; Hao, Si-Jie; Yao, Lie; Yang, Feng; Di, Yang; Li, Ji; Jiang, Yong-Jian; Jin, Chen; Fu, De-Liang

    2014-10-01

    miRNA-218 is a highlighted tumor suppressor and its underlying role in tumor progression is still unknown. Here, we restored the expression of miRNA-218 in pancreatic cancer to clarify the function and potent downstream pathway of miRNA-218. The expressions of both miRNA-218 and its potent target gene ROBO1 were revealed by RT-PCR and western blotting analysis. Transfection of miRNA-218 precursor mimics and luciferase assay were performed to elucidate the regulation mechanism between miRNA-218 and ROBO1. Cells, stably expressing miRNA-218 followed by forced expression of mutant ROBO1, were established through co-transfections of both lentivirus vector and plasmid vector. The cell migration and invasion abilities were evaluated by migration assay and invasion assay respectively. An increased expression of ROBO1 was revealed in cell BxPC-3-LN compared with cell BxPC-3. Elevated expression of miRNA-218 would suppress the expression of ROBO1 via complementary binding to a specific region within 3'UTR of ROBO1 mRNA (sites 971-978) in pancreatic cancer cells. Stably restoring the expression of miRNA-218 in pancreatic cancer significantly downregulated the expression of ROBO1 and effectively inhibited cell migration and invasion. Forced expression of mutant ROBO1 could reverse the repression effects of miRNA-218 on cell migration and invasion. Consequently, miRNA-218 acted as a tumor suppressor in pancreatic cancer by inhibiting cell invasion and migration. ROBO1 was a functional target of miRNA-218's downstream pathway involving in cell invasion and migration of pancreatic cancer.

  17. Histone methylation-mediated silencing of miR-139 enhances invasion of non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Watanabe, Kousuke; Amano, Yosuke; Ishikawa, Rie; Sunohara, Mitsuhiro; Kage, Hidenori; Ichinose, Junji; Sano, Atsushi; Nakajima, Jun; Fukayama, Masashi; Yatomi, Yutaka; Nagase, Takahide; Ohishi, Nobuya; Takai, Daiya

    2015-01-01

    MicroRNA expression is frequently altered in human cancers, and some microRNAs act as oncogenes or tumor suppressors. MiR-139-5p (denoted thereafter as miR-139) has recently been reported to function as a tumor suppressor in several types of human cancer (hepatocellular carcinoma, colorectal cancer, breast cancer, and gastric cancer), but its function in non-small-cell lung cancer (NSCLC) and the mechanism of its suppression have not been studied in detail. MiR-139 was suppressed frequently in primary NSCLCs. MiR-139 is located within the intron of PDE2A and its expression was significantly correlated with the expression of PDE2A. A chromatin immunoprecipitation assay revealed that miR-139 was epigenetically silenced by histone H3 lysine 27 trimethylation (H3K27me3) of its host gene PDE2A and this process was independent of promoter DNA methylation. Pharmacological inhibition of both histone methylation and deacetylation-induced miR-139 with its host gene PDE2A. Ectopic expression of miR-139 in lung cancer cell lines did not affect the proliferation nor the migration but significantly suppressed the invasion through the extracellular matrix. In primary NSCLCs, decreased expression of miR-139 was significantly associated with distant lymph node metastasis and histological invasiveness (lymphatic invasion and vascular invasion) on both univariate and multivariate analyses. Collectively, these results suggest that H3K27me3-mediated silencing of miR-139 enhances an invasive and metastatic phenotype of NSCLC

  18. BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion

    Directory of Open Access Journals (Sweden)

    Michalski Christoph W

    2007-12-01

    Full Text Available Abstract Background Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP, and pancreatic ductal adenocarcinoma (PDAC using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules. Results Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells. Conclusion BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.

  19. Locally advanced colon cancer with cutaneous invasion: case report.

    Science.gov (United States)

    Tenreiro, Nádia; Ferreira, Cátia; Silva, Silvia; Marques, Rita; Ribeiro, Artur; Sousa, Paulo Jorge; Luís, Fernando Próspero

    2017-03-01

    Locally advanced colon cancer with direct abdominal wall and skin invasion is an extremely rare finding with most data being derived from case reports, historical autopsy-based or single-center retrospective studies. We present a unique case of a colon cancer with direct cutaneous invasion and colocutaneous fistulization. Eighty-six year old Caucasian female with multiple comorbidities, referred to Surgical Consultation due to ulcerated skin lesion in the abdomen. She had a long-standing large umbilical hernia but with no previous episodes of incarceration or occlusive symptoms. She denied any digestive or constitutional symptoms. Physical examination showed a large non-reducible umbilical hernia, with an associated painless firm mass within the hernia sac and cutaneous ulcerated growth. Colonoscopy revealed transverse colon cancer (endoscopic biopsy of the tumor and skin punch biopsy confirmed adenocarcinoma of the colon). Computed tomography showed a tumoral mass within the umbilical hernia, with cutaneous infiltration and enlarged regional lymph nodes. Rapid local progression led to colocutaneous fistula with total fecal diversion. We performed an extended right hemicolectomy with en bloc excision of the hernia sac and infiltrating cutaneous mass. In the current era of widespread use of screening colonoscopies, initial diagnosis of locally advanced colon cancer is decreasing. However, this unique case presented an opportunity to recall the advantages of multivisceral resections.

  20. Protein kinase Cδ signaling downstream of the EGF receptor mediates migration and invasiveness of prostate cancer cells

    International Nuclear Information System (INIS)

    Kharait, Sourabh; Dhir, Rajiv; Lauffenburger, Douglas; Wells, Alan

    2006-01-01

    Tumor progression to the invasive phenotype occurs secondary to upregulated signaling from growth factor receptors that drive key cellular responses like proliferation, migration, and invasion. We hypothesized that Protein kinase Cδ (PKCδ)-mediated transcellular contractility is required for migration and invasion of prostate tumor cells. Two invasive human prostate cancer cell lines, DU145 cells overexpressing wildtype human EGFR (DU145WT) and PC3 cells, were studied. PKCδ is overexpressed in these cells relative to normal prostate epithelial cells, and is activated downstream of EGFR leading to cell motility via modulation of myosin light chain activity. Abrogation of PKCδ using Rottlerin and specific siRNA significantly decreased migration and invasion of both cell lines in vitro. Both PKCδ and phosphorylated PKCδ protein levels were higher in human prostate cancer tissue relative to normal donor prostate as assessed by Western blotting and immunohistochemistry. Thus, we conclude that PKCδ inhibition can limit migration and invasion of prostate cancer cells

  1. Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma.

    Science.gov (United States)

    Park, Cheol Keun; Jung, Woo Hee; Koo, Ja Seung

    2016-08-01

    Cancer-associated fibroblasts (CAFs) are classified into various functional subtypes such as fibroblast activation protein-α (FAP-α), fibroblast specific protein-1 (FSP-1), platelet-derived growth factor receptor-α (PDGFR-α), and PDGFR-β. In this study, we compared the expression of CAF-related proteins in invasive lobular carcinoma (ILC) with those in invasive carcinoma of no special type (NST) and assessed the implications of the differences observed. Using tissue microarrays of 104 ILC and 524 invasive carcinoma (NST) cases, immunohistochemistry for CAF-related proteins [podoplanin, prolyl 4-hydroxylase, FAP-α, FSP-1/S100A4, PDGFR-α, PDGFR-β, and chondroitin sulfate proteoglycan (NG2)] was conducted. In invasive carcinoma (NST), tumor cells expressed a high level of PDGFR-α, whereas ILC tumor cells expressed high levels of podoplanin, prolyl 4-hydroxylase, FAP-α, and FSP-1/S100A4. In stromal cells of invasive carcinoma (NST), high expression levels of prolyl 4-hydroxylase, PDGFR-α, and NG2 were observed, whereas ILC stromal cells expressed high levels of FAP-α, FSP-1/S100A4, and PDGFR-β. In ILC, tumoral FSP-1/S100A4 positivity was associated with higher Ki-67 labeling index (p = 0.010) and non-luminal A type cancer (p = 0.014). Stromal PDGFR-α positivity was associated with lymph node metastasis (p = 0.011). On survival analysis of entire cases, tumoral FSP-1/S100A4 positivity (p = 0.002), stromal podoplanin positivity (p = 0.041), and stromal FSP-1/S100A4 negativity (p = 0.041) were associated with shorter disease-free survival; only tumoral FSP-1/S100A4 positivity (p = 0.044) was associated with shorter overall survival. In ILC, the expression of FAP-α and FSP-1/S100A4 was higher in both tumor and stromal cells than that observed in invasive carcinoma (NST). These results indicate that CAFs are a potential target in ILC treatment.

  2. Methyl jasmonate abolishes the migration, invasion and angiogenesis of gastric cancer cells through down-regulation of matrix metalloproteinase 14

    International Nuclear Information System (INIS)

    Zheng, Liduan; Li, Dan; Xiang, Xuan; Tong, Ling; Qi, Meng; Pu, Jiarui; Huang, Kai; Tong, Qiangsong

    2013-01-01

    Recent evidence indicates that methyl jasmonate (MJ), a plant stress hormone, exhibits anti-cancer activity on human cancer cells. The aim of this study is to determine whether sub-cytotoxic MJ can abolish the migration, invasion and angiogenesis gastric cancer cells. Human gastric cancer cell lines SGC-7901 and MKN-45 were treated with diverse concentrations of MJ. Cell viability, proliferation, migration, invasion and angiogenesis capabilities of cancer cells were measured by MTT colorimetry, EdU incorporation, scratch assay, matrigel invasion assay, and tube formation assay. Gene expression was detected by western blot and real-time quantitative RT-PCR. Binding of transcription factor on gene promoter was detected by chromatin immunoprecipitation. Sub-cytotoxic (0.05 to 0.2 mM) MJ attenuated the migration, invasion and angiogenesis, but not the cell viability or proliferation, of gastric cancer cells in a time- and dose-dependent manner, with down-regulation of matrix metalloproteinase 14 (MMP-14) and its downstream gene vascular endothelial growth factor. Restoration of MMP-14 expression rescued the SGC-7901 and MKN-45 cells from sub-cytotoxic MJ-inhibited migration, invasion and angiogenesis. In addition, sub-cytotoxic MJ decreased the specificity protein 1 (Sp1) expression and binding on MMP-14 promoter, while restoration of Sp1 expression rescued the cancer cells from sub-cytotoxic MJ-mediated defects in MMP-14 expression, migration, invasion and angiogenesis. Sub-cytotoxic MJ attenuates the MMP-14 expression via decreasing the Sp1 expression and binding on MMP-14 promoter, thus inhibiting the migration, invasion and angiogenesis of gastric cancer cells

  3. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    International Nuclear Information System (INIS)

    Shimura, Takaya; Higashiyama, Shigeki; Joh, Takashi; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi

    2012-01-01

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P < 0.01). The growth of wt-HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for

  4. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Science.gov (United States)

    2012-01-01

    Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Conclusions Both the function of HB-EGF as an EGFR ligand

  5. miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells

    International Nuclear Information System (INIS)

    Peng, Ruiqing; Men, Jianlong; Ma, Rui; Wang, Qian; Wang, Yang; Sun, Ying; Ren, Jing

    2017-01-01

    Increasing evidence has shown that miRNAs are implicated in carcinogenesis and can function as oncogenes or tumor suppressor genes in human cancers. In this study, we confirmed that miR-214 is frequently down-regulated in cervical cancer compared with normal cervical tissues. Ectopic expression of miR-214 suppressed proliferation, migration and invasion of HeLa and C33A cervical cancer cells. Bioinformatics analysis revealed that ADP ribosylation factor like 2 (ARL2) was a potential target of miR-214 and was remarkably up-regulated in cervical cancer. Knockdown of ARL2 markedly inhibited cervical cancer cell proliferation, migration and invasion, similarly to over-expression of miR-214, indicating that ARL2 may function as an oncogene in cervical cancer. In conclusion, our study revealed that miR-214 acts as a tumor suppressor via inhibiting proliferation, migration and invasion of cervical cancer cells through targeting ARL2, and that both miR-214 and ARL2 may serve as prognostic or therapeutic targets for cervical cancer. - Highlights: • miR-214 targets ARL2. • ARL2 maybe an oncogene in cervical cancer. • ARL2 rescues miR-214.

  6. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells

    International Nuclear Information System (INIS)

    Sun, Qing; Liang, Ying; Zhang, Tianli; Wang, Kun; Yang, Xingsheng

    2017-01-01

    Objective: Estrogen receptor alpha 36 (ER-α36), a truncated variant of ER-α, is different from other nuclear receptors of the ER-α family. Previous findings indicate that ER-α36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-α36 and cervical cancer are rare. This study aimed to detect the expression of ER-α36 in cervical cancer; the role of ER-α36 in 17-β-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-α36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-α36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. Results: ER-α36 expression was detected in both cervical cell lines and cervical cancer tissues. Downregulation of ER-α36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-α36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation. Conclusion: ER-α36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells. - Highlights: • ER-α36 is expressed on both cervical cell lines and cervical cancer tissues. • ER-α36 mediates estrogen

  7. YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion.

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    Said Rahim

    2011-04-01

    Full Text Available Genomic rearrangements involving the ETS family of transcription factors occur in 40-70% of prostate cancer cases. ERG and ETV1 are the most common ETS members observed in these genetic alterations. The high prevalence of these rearrangements and their biological significance represents a novel therapeutic target for the treatment of prostate cancer.We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing's Sarcoma. Since ERG and ETV1 belong to the same class of ETS factors as FLI1, we tested the ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279.These data demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostate cancer cells leading to decreased motility and invasion. Therefore, YK-4-279 may have an impact on metastasis in prostate cancer and it may be further evaluated for its clinical applications in prostate cancer in addition to Ewing's sarcoma.

  8. Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis.

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    Hiromitsu Ito

    Full Text Available Patients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs, but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs. In the present study, we found that CSCs were highly metastatic and dominantly localized at the invading tumor margins in a liver metastasis model. Microarray and siRNA screening assays showed that doublecortin-like kinase 1 (DCLK1 was predominantly expressed with histone modification in pancreatic CSCs with invasive and metastatic potential. Overexpression of DCLK1 led to amoeboid morphology, which promotes the migration of pancreatic cancer cells. Knockdown of DCLK1 profoundly suppressed in vivo liver metastasis of pancreatic CSCs. Clinically, DCLK1 was overexpressed in the metastatic tumors in patients with pancreatic cancer. Our studies revealed that DCLK1 is essential for the invasive and metastatic properties of CSCs and may be a promising epigenetic and therapeutic target in human pancreatic cancer.

  9. Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change.

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    Shiaw-Wei Tyan

    Full Text Available Microenvironment plays an important role in cancer development. We have reported that the cancer-associated stromal cells exhibit phenotypic and functional changes compared to stromal cells neighboring to normal tissues. However, the molecular mechanisms as well as the maintenance of these changes remain elusive. Here we showed that through co-culture with breast cancer cells for at least three to four passages, breast normal tissue-associated fibroblasts (NAFs gained persistent activity for promoting cancer cell invasion, partly via up-regulating ADAM metallopeptidase with thrombospondin type 1 motif, 1 (ADAMTS1. Furthermore, we demonstrated that the DNA methylation pattern in the ADAMTS1 promoter has no alteration. Instead, the loss of EZH2 binding to the ADAMTS1 promoter and the resulting decrease of promoter-associated histone H3K27 methylation may account for the up-regulation of ADAMTS1. Importantly, the lack of EZH2 binding and the H3K27 methylation on the ADAMTS1 promoter were sustained in cancer cell-precocultured NAFs after removal of cancer cells. These results suggest that cancer cells are capable of inducing stromal fibroblasts to secrete ADAMTS1 persistently for their invasion and the effect is epigenetically inheritable.

  10. Invasive ductal breast cancer metastatic to the sigmoid colon

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    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  11. CENPI is overexpressed in colorectal cancer and regulates cell migration and invasion.

    Science.gov (United States)

    Ding, Na; Li, Rongxin; Shi, Wenhao; He, Cui

    2018-06-21

    Centromere protein I (CENPI),an important member of centromere protein family, has been suggest to serve as a oncogene in breast cancer, but the clinical significance and biological function of CENPI in colorectal cancer (CRC) is still unclear. In our results, we found CENPI was overexpressed in CRC tissues and cells, and associated with clinical stage, tumor depth, lymph node metastasis, distant metastasis and differentiation in CRC patients. However, there was no significant association between CENPI protein expression and overall survival time in colon cancer patients and rectal cancer patients through analyzing TCGA survival data. Moreover, CENPI mRNA and protein were increased in metastatic lymph nodes compared with primary CRC tissues. Down-regulation of CENPI expression suppresses CRC cell migration, invasion and epithelial mesenchymal transition process. In conclusion, CENPI is overexpressed in CRC and functions as oncogene in modulating CRC cell migration, invasion and EMT process. Copyright © 2018. Published by Elsevier B.V.

  12. Quantitative assessment of invasive mena isoforms (Menacalc) as an independent prognostic marker in breast cancer.

    Science.gov (United States)

    Agarwal, Seema; Gertler, Frank B; Balsamo, Michele; Condeelis, John S; Camp, Robert L; Xue, Xiaonan; Lin, Juan; Rohan, Thomas E; Rimm, David L

    2012-09-12

    Mena, an Ena/VASP protein family member, is a key actin regulatory protein. Mena is up-regulated in breast cancers and promotes invasion and motility of tumor cells. Mena has multiple splice variants, including Mena invasive (MenaINV) and Mena11a, which are expressed in invasive or non-invasive tumor cells, respectively. We developed a multiplex quantitative immunofluorescence (MQIF) approach to assess the fraction of Mena lacking 11a sequence as a method to infer the presence of invasive tumor cells represented as total Mena minus Mena11a (called Menacalc) and determined its association with metastasis in breast cancer. The MQIF method was applied to two independent primary breast cancer cohorts (Cohort 1 with 501 and Cohort 2 with 296 patients) using antibodies against Mena and its isoform, Mena11a. Menacalc was determined for each patient and assessed for association with risk of disease-specific death. Total Mena or Mena11a isoform expression failed to show any statistically significant association with outcome in either cohort. However, assessment of Menacalc showed that relatively high levels of this biomarker is associated with poor outcome in two independent breast cancer cohorts (log rank P = 0.0004 for Cohort 1 and 0.0321 for Cohort 2). Multivariate analysis on combined cohorts revealed that high Menacalc is associated with poor outcome, independent of age, node status, receptor status and tumor size. High Menacalc levels identify a subgroup of breast cancer patients with poor disease-specific survival, suggesting that Menacalc may serve as a biomarker for metastasis.

  13. miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα.

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    Violaine Tribollet

    Full Text Available MicroRNA-135a (miR-135a down-modulates parameters of cancer progression and its expression is decreased in metastatic breast cancers (as compared to non-metastatic tumors as well as in prostate tumors relative to normal tissue. These expression and activity patterns are opposite to those of the Estrogen-Related Receptor α (ERRα, an orphan member of the nuclear receptor family. Indeed high expression of ERRα correlates with poor prognosis in breast and prostate cancers, and the receptor promotes various traits of cancer aggressiveness including cell invasion. Here we show that miR-135a down-regulates the expression of ERRα through specific sequences of its 3'UTR. As a consequence miR-135a also reduces the expression of downstream targets of ERRα. miR-135a also decreases cell invasive potential in an ERRα-dependent manner. Our results suggest that the decreased expression of miR-135a in metastatic tumors leads to elevated ERRα expression, resulting in increased cell invasion capacities.

  14. Curative effect analysis of invasive bladder cancer by joint surgical operation with interventional therapy

    International Nuclear Information System (INIS)

    Xu Biao; Wen Bin; Liu Tisheng; Wei Liqian

    2007-01-01

    Objective: To explore the effective therapy for invasive bladder cancer. Methods: Forty patients with invasive bladder cancer were divided into group A and group B. Intra-internal lilac-arterial chemotherapy and infusion pump chemotherapy combined with surgical operation were performed in group A and only surgical operation for group B. The differences of recurrence rates and survival rates between the two groups together with the effectiveness of intra-arterial chemotherapy combined surgical operation were evaluated at the same time. Results: Reduction in volumes of cancer and hematuria were obvious and nearly disappeared in group A patients with pathomorphological features demonstrating large pachyareas of necrosis together with degeneration and inflammatory changes of carcinoma tissue; outcoming with five recurrent cases (20%) and 2 deaths (10%). In group B, 9 cases relapsed(45%) and 4 eases died(20%). Conclusion: The combination of intra-internal lilac-arterial chemoembolization with infusion pump chemotherapy together with surgical operation is safe, effective for invasive bladder cancer, resulting in high raise of survival and life quality. (authors)

  15. Correlation of MRI apparent diffusion coefficient of invasive breast cancer with tumor tissue growth and angiogenesis

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    Ze-Hong Fu

    2017-08-01

    Full Text Available Objective: To study the correlation of MRI apparent diffusion coefficient (ADC value of invasive breast cancer with tumor tissue growth and angiogenesis. Methods: Patients with breast mass who were treated in Wuhan No. 6 Hospital between March 2014 and May 2017 were selected as the research subjects and divided into group A with invasive ductal carcinoma, group B with intraductal carcinoma and group C with benign lesion according to the biopsy results, magnetic resonance diffusion-weighted imaging was conducted to determine ADC values, and biopsy tissue was taken to determine the expression of proliferation genes and angiogenesis genes. Results: USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A and group B were significantly higher than those of group C while ADC value as well as ALEX1 and Bax protein expression levels were significantly lower than those of group C; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A were significantly higher than those of group B while ADC value as well as ALEX1 and Bax protein expression levels was significantly lower than those of group B; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in invasive breast cancer tissue with high ADC value were significantly lower than those in invasive breast cancer tissue with low ADC value while ALEX1 and Bax protein expression levels were significantly higher than those in invasive breast cancer tissue with low ADC value. Conclusion: The decrease of ADC value of invasive breast cancer is closely related to cancer cell proliferation and angiogenesis.

  16. Collective cell migration: Implications for wound healing and cancer invasion

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    Li Li

    2013-07-01

    Full Text Available During embryonic morphogenesis, wound repair and cancer invasion, cells often migrate collectively via tight cell-cell junctions, a process named collective migration. During such migration, cells move as coherent groups, large cell sheets, strands or tubes rather than individually. One unexpected finding regarding collective cell migration is that being a "multicellular structure" enables cells to better respond to chemical and physical cues, when compared with isolated cells. This is important because epithelial cells heal wounds via the migration of large sheets of cells with tight intercellular connections. Recent studies have gained some mechanistic insights that will benefit the clinical understanding of wound healing in general. In this review, we will briefly introduce the role of collective cell migration in wound healing, regeneration and cancer invasion and discuss its underlying mechanisms as well as implications for wound healing.

  17. Potential of non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy

    Science.gov (United States)

    Huang, Shaohua; Wang, Lan; Chen, Weisheng; Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Li, Buhong; Chen, Rong

    2014-11-01

    Non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy (SERS) analysis was presented. Urine SERS spectra were measured on esophagus cancer patients (n = 56) and healthy volunteers (n = 36) for control analysis. Tentative assignments of the urine SERS spectra indicated some interesting esophagus cancer-specific biomolecular changes, including a decrease in the relative content of urea and an increase in the percentage of uric acid in the urine of esophagus cancer patients compared to that of healthy subjects. Principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to analyze and differentiate the SERS spectra between normal and esophagus cancer urine. The diagnostic algorithms utilizing a multivariate analysis method achieved a diagnostic sensitivity of 89.3% and specificity of 83.3% for separating esophagus cancer samples from normal urine samples. These results from the explorative work suggested that silver nano particle-based urine SERS analysis coupled with PCA-LDA multivariate analysis has potential for non-invasive detection of esophagus cancer.

  18. Potential of non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy

    International Nuclear Information System (INIS)

    Huang, Shaohua; Wang, Lan; Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Li, Buhong; Chen, Rong; Chen, Weisheng

    2014-01-01

    Non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy (SERS) analysis was presented. Urine SERS spectra were measured on esophagus cancer patients (n = 56) and healthy volunteers (n = 36) for control analysis. Tentative assignments of the urine SERS spectra indicated some interesting esophagus cancer-specific biomolecular changes, including a decrease in the relative content of urea and an increase in the percentage of uric acid in the urine of esophagus cancer patients compared to that of healthy subjects. Principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to analyze and differentiate the SERS spectra between normal and esophagus cancer urine. The diagnostic algorithms utilizing a multivariate analysis method achieved a diagnostic sensitivity of 89.3% and specificity of 83.3% for separating esophagus cancer samples from normal urine samples. These results from the explorative work suggested that silver nano particle-based urine SERS analysis coupled with PCA–LDA multivariate analysis has potential for non-invasive detection of esophagus cancer. (letter)

  19. Superimposed dual-isotope SPECT using 99mTc-hydroxymethylene diphosphonate and 201Tl-chloride to assess cartilage invasion in laryngohypopharyngeal cancer

    International Nuclear Information System (INIS)

    Nishiyama, Yoshihiro; Yamamoto, Yuka; Yokoe, Koiku; Miyabe, Kazunori; Iwasaki, Takanobu; Toyama, Yoshihiro; Satoh, Katashi; Ohkawa, Motoomi

    2004-01-01

    Cartilage invasion in laryngohypopharyngeal cancer has a significant impact on the choice of treatment modality and outcome of the disease. We examined invasion of cartilage in laryngohypopharyngeal cancer by simultaneous bone and tumor dual-isotope SPECT using 99m Tc-hydroxymethylene diphosphonate and 201 Tl-chloride. Early and delayed simultaneous bone and tumor dual-isotope SPECT were performed on 19 patients with laryngohypopharyngeal cancer. Dual-isotope SPECT images were superimposed to project tumor location from tumor SPECT onto the osseous structures shown by bone SPECT. The presence or absence of cartilage invasion was evaluated histopathologically or by radiological studies such as CT and/or MRI. Histopathological or radiological examination of the cartilage revealed invasion in 5 patients and no invasion in 14 patients. The results of both early and delayed dual-isotope SPECT were exactly the same. Using dual-isotope SPECT, the sensitivity, specificity, and accuracy in detecting cartilage invasion by laryngohypopharyngeal cancer were: 80% (4/5), 92.9% (13/14), and 89.5% (17/19), respectively. Results of the present study suggest that superimposed early bone and tumor dual-isotope SPECT images may be sufficient for the diagnostic evaluation of cartilage invasion by laryngohypopharyngeal cancer. Superimposed dual-isotope SPECT imaging is a useful technique in the evaluation of cartilage invasion in laryngohypopharyngeal cancer. (author)

  20. Differential nuclear shape dynamics of invasive andnon-invasive breast cancer cells are associated with actin cytoskeleton organization and stability.

    Science.gov (United States)

    Chiotaki, Rena; Polioudaki, Hara; Theodoropoulos, Panayiotis A

    2014-08-01

    Cancer cells often exhibit characteristic aberrations in their nuclear architecture, which are indicative of their malignant potential. In this study, we have examined the nuclear and cytoskeletal composition, attachment configuration dynamics, and osmotic or drug treatment response of invasive (Hs578T and MDA-MB-231) and non-invasive (MCF-10A and MCF-7) breast cancer cell lines. Unlike MCF-10A and MCF-7, Hs578T and MDA-MB-231 cells showed extensive nuclear elasticity and deformability and displayed distinct kinetic profiles during substrate attachment. The nuclear shape of MCF-10A and MCF-7 cells remained almost unaffected upon detachment, hyperosmotic shock, or cytoskeleton depolymerization, while Hs578T and MDA-MB-231 revealed dramatic nuclear contour malformations following actin reorganization.

  1. A new generation of optical diagnostics for bladder cancer: technology, diagnostic accuracy, and future applications

    NARCIS (Netherlands)

    Cauberg, Evelyne C. C.; de Bruin, Daniël M.; Faber, Dirk J.; van Leeuwen, Ton G.; de La Rosette, Jean J. M. C. H.; de Reijke, Theo M.

    2009-01-01

    CONTEXT: New developments in optical diagnostics have a potential for less invasive and improved detection of bladder cancer. OBJECTIVE: To provide an overview of the technology and diagnostic yield of recently developed optical diagnostics for bladder cancer and to outline their potential future

  2. Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy

    Science.gov (United States)

    Li, Lu; Douville, Christopher; Wang, Yuxuan; Cohen, Joshua David; Taheri, Diana; Silliman, Natalie; Schaefer, Joy; Ptak, Janine; Dobbyn, Lisa; Papoli, Maria; Kinde, Isaac; Afsari, Bahman; Tregnago, Aline C; Bezerra, Stephania M; VandenBussche, Christopher; Fujita, Kazutoshi; Ertoy, Dilek; Cunha, Isabela W; Yu, Lijia; Bivalacqua, Trinity J; Grollman, Arthur P; Diaz, Luis A; Karchin, Rachel; Danilova, Ludmila; Huang, Chao-Yuan; Shun, Chia-Tung; Turesky, Robert J; Yun, Byeong Hwa; Rosenquist, Thomas A; Pu, Yeong-Shiau; Hruban, Ralph H; Tomasetti, Cristian; Papadopoulos, Nickolas; Kinzler, Ken W

    2018-01-01

    Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer. PMID:29557778

  3. MicroRNA-613 represses prostate cancer cell proliferation and invasion through targeting Frizzled7

    International Nuclear Information System (INIS)

    Ren, Wei; Li, Chan; Duan, Wanli; Du, Shuangkuan; Yang, Fan; Zhou, Jiancheng; Xing, Junping

    2016-01-01

    A growing number of studies have indicated that microRNAs (miRNAs) are critical regulators of carcinogenesis and cancer progression and may serve as potential therapeutic tools for cancer therapy. Frizzled7 (Fzd7), the most important receptor of the Wnt signaling pathway, is extensively involved in cancer development and progression. However, the role of Fzd7 in prostate cancer remains unclear. In this study, we aimed to explore the expression of Fzd7 in prostate cancer and test whether modulating Fzd7 expression by miR-613 would have an impact on prostate cancer cell proliferation and invasion. We found that Fzd7 was highly expressed in prostate cancer cell lines. Through bioinformatics analysis, Fzd7 was predicted as a target gene of miR-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and Western blot analysis. By gain of function experiments, we showed that overexpression of miR-613 significantly suppressed prostate cancer cell proliferation and invasion. Furthermore, miR-613 overexpression markedly downregulated the Wnt signaling pathway. Through a rescue experiment, we showed that overexpression of Fzd7 could abrogate the inhibitory effect of miR-613 on cell proliferation and invasion as well as Wnt signaling. Additionally, these results were further strengthened by data showing that miR-613 was significantly downregulated in prostate cancer tissues, exhibiting an inverse correlation with Fzd7 expression. In conclusion, our study suggests that miR-613 functions as a tumor suppressor, partially through targeting Fzd7, and is a potential therapeutic target for prostate cancer. - Highlights: • Fzd7 was highly expressed in prostate cancer. • Fzd7 was predicted as a target gene of miR-613. • MiR-613 negatively regulated prostate cancer by Fzd7. • MiR-613 inversely correlated with Fzd7 in prostate cancer.

  4. MicroRNA-613 represses prostate cancer cell proliferation and invasion through targeting Frizzled7

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Wei [Medical College of Xi' an Jiao Tong University, Xi' an 710061 (China); Department of Urology, Shaanxi Provincial People' s Hospital, The Third Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710068 (China); Li, Chan [Department of Ophthalmology, Shaanxi Provincial People' s Hospital, The Third Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710068 (China); Duan, Wanli; Du, Shuangkuan; Yang, Fan; Zhou, Jiancheng [Department of Urology, Shaanxi Provincial People' s Hospital, The Third Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710068 (China); Xing, Junping, E-mail: junpingxing@163.com [Department of Urology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710061 (China)

    2016-01-15

    A growing number of studies have indicated that microRNAs (miRNAs) are critical regulators of carcinogenesis and cancer progression and may serve as potential therapeutic tools for cancer therapy. Frizzled7 (Fzd7), the most important receptor of the Wnt signaling pathway, is extensively involved in cancer development and progression. However, the role of Fzd7 in prostate cancer remains unclear. In this study, we aimed to explore the expression of Fzd7 in prostate cancer and test whether modulating Fzd7 expression by miR-613 would have an impact on prostate cancer cell proliferation and invasion. We found that Fzd7 was highly expressed in prostate cancer cell lines. Through bioinformatics analysis, Fzd7 was predicted as a target gene of miR-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and Western blot analysis. By gain of function experiments, we showed that overexpression of miR-613 significantly suppressed prostate cancer cell proliferation and invasion. Furthermore, miR-613 overexpression markedly downregulated the Wnt signaling pathway. Through a rescue experiment, we showed that overexpression of Fzd7 could abrogate the inhibitory effect of miR-613 on cell proliferation and invasion as well as Wnt signaling. Additionally, these results were further strengthened by data showing that miR-613 was significantly downregulated in prostate cancer tissues, exhibiting an inverse correlation with Fzd7 expression. In conclusion, our study suggests that miR-613 functions as a tumor suppressor, partially through targeting Fzd7, and is a potential therapeutic target for prostate cancer. - Highlights: • Fzd7 was highly expressed in prostate cancer. • Fzd7 was predicted as a target gene of miR-613. • MiR-613 negatively regulated prostate cancer by Fzd7. • MiR-613 inversely correlated with Fzd7 in prostate cancer.

  5. Minimally invasive esophagectomy for cancer: Single center experience after 44 consecutive cases

    Directory of Open Access Journals (Sweden)

    Bjelović Miloš

    2015-01-01

    Full Text Available Introduction. At the Department of Minimally Invasive Upper Digestive Surgery of the Hospital for Digestive Surgery in Belgrade, hybrid minimally invasive esophagectomy (hMIE has been a standard of care for patients with resectable esophageal cancer since 2009. As a next and final step in the change management, from January 2015 we utilized total minimally invasive esophagectomy (tMIE as a standard of care. Objective. The aim of the study was to report initial experiences in hMIE (laparoscopic approach for cancer and analyze surgical technique, major morbidity and 30-day mortality. Methods. A retrospective cohort study included 44 patients who underwent elective hMIE for esophageal cancer at the Department for Minimally Invasive Upper Digestive Surgery, Hospital for Digestive Surgery, Clinical Center of Serbia in Belgrade from April 2009 to December 2014. Results. There were 16 (36% middle thoracic esophagus tumors and 28 (64% tumors of distal thoracic esophagus. Mean duration of the operation was 319 minutes (approximately five hours and 20 minutes. The average blood loss was 173.6 ml. A total of 12 (27% of patients had postoperative complications and mean intensive care unit stay was 2.8 days. Mean hospital stay after surgery was 16 days. The average number of harvested lymph nodes during surgery was 31.9. The overall 30-day mortality rate within 30 days after surgery was 2%. Conclusion. As long as MIE is an oncological equivalent to open esophagectomy (OE, better relation between cost savings and potentially increased effectiveness will make MIE the preferred approach in high-volume esophageal centers that are experienced in minimally invasive procedures.

  6. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

  7. Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia

    DEFF Research Database (Denmark)

    Nygard, Mari; Hansen, Bo Terning; Dillner, Joakim

    2014-01-01

    BACKGROUND: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination...... with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order...... to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. METHODS: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias...

  8. ETV4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion

    International Nuclear Information System (INIS)

    Moss, Alan C.; Lawlor, Garrett; Murray, David; Tighe, Donal; Madden, Stephen F.; Mulligan, Anne-Marie; Keane, Conor O.; Brady, Hugh R.; Doran, Peter P.; MacMathuna, Padraic

    2006-01-01

    We have identified novel colorectal cancer-associated genes using NCBI's UNIGENE cDNA libraries. Colon cancer libraries were examined using Digital Differential Display and disease-associated genes were selected. Among these were ETV4 and MYEOV, novel colorectal cancer-associated genes. Samples of matched normal and neoplastic colon were obtained from human subjects and gene expression was quantified using real-time PCR. ETV4 gene expression was significantly increased in colonic neoplasia in comparison to matched normal colonic tissue (p < 0.05). Myeov expression was also increased in colon neoplasia in comparison to matched normal tissue. The effect of siRNA-mediated knockdown of ETV4 and Myeov on cell proliferation and invasion was assessed. ETV4 knockdown resulted in a 90% decrease in cell proliferation (p < 0.05) and a 67% decrease in cell invasion. Myeov knockdown resulted in a 48% decrease in cell proliferation (p < 0.05) and a 36% decrease in cell invasion. These data suggest that ETV4 and Myeov may provide novel targets for therapeutic intervention

  9. DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis.

    Science.gov (United States)

    Tan, Cong; Qiao, Fan; Wei, Ping; Chi, Yayun; Wang, Weige; Ni, Shujuan; Wang, Qifeng; Chen, Tongzhen; Sheng, Weiqi; Du, Xiang; Wang, Lei

    2016-04-01

    DIXDC1 (Dishevelled-Axin domain containing 1) is a DIX (Dishevelled-Axin) domain-possessing protein that promotes colon cancer cell proliferation and increases the invasion and migration ability of non-small-cell lung cancer via the PI3K pathway. As a positive regulator of the Wnt/β-catenin pathway, the biological role of DIXDC1 in human gastric cancer and the relationship between DIXDC1 and the Wnt pathway are unclear. In the current study, the upregulation of DIXDC1 was detected in gastric cancer and was associated with advanced TNM stage cancer, lymph node metastasis, and poor prognosis. We also found that the overexpression of DIXDC1 could promote the invasion and migration of gastric cancer cells. The upregulation of MMPs and the downregulation of E-cadherin were found to be involved in the process. DIXDC1 enhanced β-catenin nuclear accumulation, which activated the Wnt pathway. Additionally, the inhibition of β-catenin in DIXDC1-overexpressing cells reversed the metastasis promotion effects of DIXDC1. These results demonstrate that the expression of DIXDC1 is associated with poor prognosis of gastric cancer patients and that DIXDC1 promotes gastric cancer invasion and metastasis through the activation of the Wnt pathway; E-cadherin and MMPs are also involved in this process. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  10. BART Inhibits Pancreatic Cancer Cell Invasion by Rac1 Inactivation through Direct Binding to Active Rac1

    Directory of Open Access Journals (Sweden)

    Keisuke Taniuchi

    2012-05-01

    Full Text Available We report that Binder of Arl Two (BART plays a role in inhibiting cell invasion by regulating the activity of the Rho small guanosine triphosphatase protein Rac1 in pancreatic cancer cells. BART was originally identified as a binding partner of ADP-ribosylation factor-like 2, a small G protein implicated as a regulator of microtubule dynamics and folding. BART interacts with active forms of Rac1, and the BART-Rac1 complex localizes at the leading edges of migrating cancer cells. Suppression of BART increases active Rac1, thereby increasing cell invasion. Treatment of pancreatic cancer cells in which BART is stably knocked down with a Rac1 inhibitor decreases invasiveness. Thus, BART-dependent inhibition of cell invasion is likely associated with decreased active Rac1. Suppression of BART induces membrane ruffling and lamellipodial protrusion and increases peripheral actin structures in membrane ruffles at the edges of lamellipodia. The Rac1 inhibitor inhibits the lamellipodia formation that is stimulated by suppression of BART. Our results imply that BART regulates actin-cytoskeleton rearrangements at membrane ruffles through modulation of the activity of Rac1, which, in turn, inhibits pancreatic cancer cell invasion.

  11. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

    Science.gov (United States)

    Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna; Seyfried, Thomas N

    2010-07-23

    GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  12. Calorie Restriction as an Anti-Invasive Therapy for Malignant Brain Cancer in the VM Mouse

    Directory of Open Access Journals (Sweden)

    Laura M Shelton

    2010-07-01

    Full Text Available GBM (glioblastoma multiforme is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  13. Radiotherapy of invasive breast cancer: French national guidelines

    International Nuclear Information System (INIS)

    Besnard, S.; Mazeau-Woynar, V.; Verdoni, L.; Cutuli, B.; Fourquet, A.; Giard, S.; Hennequin, C.; Leblanc-Onfroy, M.

    2012-01-01

    The French National Cancer Institute (INCa) and Societe francaise de senologie et pathologie mammaire (SFSPM), in collaboration with a multidisciplinary experts group, have published the French national clinical practice guidelines on a selection of 11 currently debated questions regarding the management of invasive breast cancer. Those guidelines are based on a comprehensive analysis of the current published evidence dealing with those issues, secondly reviewed by 100 reviewers. Radiotherapy was concerned by five of the 11 questions: indications for the boost after whole gland irradiation; hypo-fractionated radiotherapy; partial breast irradiation; indications for mammary internal nodes irradiation, and indications of radiotherapy after neo-adjuvant chemotherapy. (authors)

  14. Radiation induces invasiveness of pancreatic cancer via up-regulation of heparanase

    International Nuclear Information System (INIS)

    Lerner, I.; Bensoussan, E.; Meirovitz, A.; Elkin, M.; Vlodavsky, I.

    2013-01-01

    The full text of the publication follows. Pancreatic cancer is one of the most aggressive neoplasms with an extremely low survival rate. Because most pancreatic carcinoma patients miss the opportunity for complete surgical resection at the time of diagnosis, radiotherapy remains a major component of treatment modalities. However, pancreatic cancer often shows resistance to radiation therapy. Ionizing radiation (IR)-induced aggressiveness is emerging as one of the important mechanisms responsible for the limited benefit of radiation therapy in pancreatic cancer, but the identity of downstream effectors responsible for this effect remains poorly investigated. Here we report that IR promotes pancreatic cancer aggressiveness through up-regulation of the heparanase. Heparanase is a predominant mammalian enzyme capable of degrading heparan sulfate (HS), the main polysaccharide component of the basement membrane and other types of extracellular matrix (ECM). Cleavage of HS by heparanase leads to disassembly of ECM, enables cell invasion, releases HS-bound angiogenic and growth factors from the ECM depots, and generates bioactive HS fragments. We found that clinically relevant doses of IR augment invasive ability of pancreatic cells in vitro and in vivo via induction of heparanase. Our results indicate that the effect of IR on heparanase expression is mediated by Egr1 transcription factor. Moreover, specific inhibitor of heparanase enzymatic activity abolished IR-induced invasiveness of pancreatic carcinoma cells in vitro, while combined treatment with IR and the heparanase inhibitor, but not IR alone, attenuated ortho-topic pancreatic tumor progression in vivo. The proposed up-regulation of heparanase by IR represents a new molecular pathway through which IR may promote pancreatic tumor aggressiveness, providing explanation for the limited benefit from radiation therapy in pancreatic cancer. Our research is expected to offer a new approach to improve the efficacy of

  15. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer

    NARCIS (Netherlands)

    Truin, W.; Voogd, A.C.; Vreugdenhil, G.; van der Heiden-van der Loo, M.; Siesling, Sabine; Roumen, R.M.

    2012-01-01

    Background On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Patients and methods Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast

  16. Thermo-chemotherapy Induced miR-218 upregulation inhibits the invasion of gastric cancer via targeting Gli2 and E-cadherin.

    Science.gov (United States)

    Ruan, Qiang; Fang, Zhi-Yuan; Cui, Shu-Zhong; Zhang, Xiang-Liang; Wu, Yin-Bing; Tang, Hong-Sheng; Tu, Yi-Nuo; Ding, Yan

    2015-08-01

    Thermo-chemotherapy has been proven to reduce the invasion capability of cancer cells. However, the molecular mechanism underlying this anti-invasion effect is still unclear. In this study, the role of thermo-chemotherapy in the inhibition of tumor invasion was studied. The results demonstrated that expression of miR-218 was downregulated in gastric cancer tissues, which had a positive correlation with tumor invasion and metastasis. In vitro thermo-chemotherapy increased miR-218 expression in SGC7901 cells and inhibited both proliferation and invasion of cancer cells. Gli2 was identified as a downstream target of miR-218, and its expression was negatively regulated by miR-218. The thermo-chemotherapy induced miR-218 upregulation was also accompanied by increasing of E-cadherin expression. In conclusion, the present study indicates that thermo-chemotherapy can effectively decrease the invasion capability of cancer cells and increase cell-cell adhesion. miR-218 and its downstream target Gli2, as well as E-cadherin, participate in the anti-invasion process.

  17. Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells

    International Nuclear Information System (INIS)

    Zhao, Gang; Chen, Jiawei; Deng, Yanqiu; Gao, Feng; Zhu, Jiwei; Feng, Zhenzhong; Lv, Xiuhong; Zhao, Zheng

    2011-01-01

    Highlights: → NDRG1 was knockdown in cervical and ovarian cancer cell lines by shRNA technology. → NDRG1 knockdown resulted in increased cell invasion activities. → Ninety-six common deregulated genes in both cell lines were identified by cDNA microarray. → Eleven common NDRG1-regulated genes might enhance cell invasive activity. → Regulation of invasion by NDRG1 is an indirect and complicated process. -- Abstract: N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, migration and invasion activities without affecting cell proliferation. cDNA microarray analysis revealed 96 deregulated genes with more than 2-fold changes in both cell lines after NDRG1 knockdown. Ten common upregulated genes (LPXN, DDR2, COL6A1, IL6, IL8, FYN, PTP4A3, PAPPA, ETV5 and CYGB) and one common downregulated gene (CLCA2) were considered to enhance tumor cell invasive activity. BisoGenet network analysis indicated that NDRG1 regulated these invasion effector genes/proteins in an indirect manner. Moreover, NDRG1 knockdown also reduced pro-invasion genes expression such as MMP7, TMPRSS4 and CTSK. These results suggest that regulation of invasion and metastasis by NDRG1 is a highly complicated process.

  18. Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion.

    Science.gov (United States)

    Gupta, Sounak; Hau, Andrew M; Al-Ahmadie, Hikmat A; Harwalkar, Jyoti; Shoskes, Aaron C; Elson, Paul; Beach, Jordan R; Hussey, George S; Schiemann, William P; Egelhoff, Thomas T; Howe, Philip H; Hansel, Donna E

    2016-05-01

    Our prior work identified the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migration and invasion, although upstream growth factor mediators of this pathway in bladder cancer have not been well delineated. We tested whether transforming growth factor (TGF)-β, which can function as a promotility factor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasion. In human bladder cancers, the highest levels of phosphorylated SMAD2, a TGF-β signaling intermediate, were present in high-grade invasive bladder cancers and associated with more frequent recurrence and decreased disease-specific survival. Increased expression of TGF-β isoforms, receptors, and signaling components was detected in invasive high-grade bladder cancer cells that expressed Vimentin and lacked E-cadherin. Application of TGF-β induced phosphorylation of the Ser473 residue of AKT, a selective target of mTORC2, in a SMAD2- and SMAD4-independent manner and increased bladder cancer cell migration in a modified scratch wound assay and invasion through Matrigel. Inhibition of TGF-β receptor I using SB431542 ablated TGF-β-induced migration and invasion. A similar effect was seen when Rictor, a key mTORC2 component, was selectively silenced. Our results suggest that TGF-β can induce bladder cancer cell invasion via mTORC2 signaling, which may be applicable in most bladder cancers. Copyright © 2016. Published by Elsevier Inc.

  19. Resveratrol Regulates Colorectal Cancer Cell Invasion by Modulation of Focal Adhesion Molecules.

    Science.gov (United States)

    Buhrmann, Constanze; Shayan, Parviz; Goel, Ajay; Shakibaei, Mehdi

    2017-09-27

    Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response of two human colorectal cancer (CRC) cells (HCT116 and SW480) to resveratrol and studied the effect of specific pharmacological inhibitors, cytochalasin D (CytD) and focal adhesion kinase-inhibitor (FAK-I) on FAK, cell viability and migration in CRC. We found that resveratrol altered cell phenotype of both CRC cells, reduced cell viability and the results were comparable to FAK-I and CytD. These effects of resveratrol were associated with marked Sirt1 up-regulation, FAK down-regulation, inhibition of focal adhesion and potentiation of effects by combinatorial treatment of resveratrol and inhibitors. Interestingly, inhibition of FAK with FAK-I or treatment with CytD suppressed resveratrol-induced Sirt1 up-regulation and markedly down-regulated FAK expression. Resveratrol or combination treatment with inhibitors significantly activated caspase-3 and potentiated apoptosis. Moreover, resveratrol suppressed invasion and colony forming capacity, cell proliferation, β1-Integrin expression and activation of FAK of cells in alginate tumor microenvironment, similar to FAK-I or CytD. Finally, we demonstrated that resveratrol, FAK-I or CytD inhibited activation of NF-κB, suppressed NF-κB-dependent gene end-products involved in invasion, metastasis, and apoptosis; and these effects of resveratrol were potentiated by combination treatment with FAK-I or CytD. Our data illustrated that the anti-invasion effect of resveratrol by inhibition of FAK activity has a potential beneficial role in disease prevention and therapeutic management of CRC.

  20. Urokinase plasminogen activator receptor on invasive cancer cells: A prognostic factor in distal gastric adenocarcinoma

    DEFF Research Database (Denmark)

    Alpizar, Warner Enrique Alpizar; Christensen, Ib Jarle; Santoni-Rugiu, Eric

    2012-01-01

    Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation...... by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. u...... association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

  1. Anti-Inflammatory Agent Indomethacin Reduces Invasion and Alters Metabolism in a Human Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-03-01

    Full Text Available Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the antiinflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME-based or Roswell Park Memorial Institute (RPMI-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenaseindependent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.

  2. Two-photon laser-generated microtracks in 3D collagen lattices: principles of MMP-dependent and -independent collective cancer cell invasion

    Science.gov (United States)

    Ilina, Olga; Bakker, Gert-Jan; Vasaturo, Angela; Hoffman, Robert M.; Friedl, Peter

    2011-02-01

    Cancer invasion into an extracellular matrix (ECM) results from a biophysical reciprocal interplay between the expanding cancer lesion and tissue barriers imposed by the adjacent microenvironment. In vivo, connective tissue provides both densely packed ECM barriers adjacent to channel/track-like spaces and loosely organized zones, both of which may impact cancer invasion mode and efficiency; however little is known about how three-dimensional (3D) spaces and aligned tracks present in interstitial tissue guide cell invasion. We here describe a two-photon laser ablation procedure to generate 3D microtracks in dense 3D collagen matrices that support and guide collective cancer cell invasion. Whereas collective invasion of mammary tumor (MMT) breast cancer cells into randomly organized collagen networks required matrix metalloproteinase (MMP) activity for cell-derived collagen breakdown, re-alignment and track generation, preformed tracks supported MMP-independent collective invasion down to a track caliber of 3 µm. Besides contact guidance along the track of least resistance and initial cell deformation (squeezing), MMP-independent collective cell strands led to secondary track expansion by a pushing mechanism. Thus, two-photon laser ablation is useful to generate barrier-free microtracks in a 3D ECM which guide collective invasion independently of pericellular proteolysis.

  3. Two-photon laser-generated microtracks in 3D collagen lattices: principles of MMP-dependent and -independent collective cancer cell invasion

    International Nuclear Information System (INIS)

    Ilina, Olga; Bakker, Gert-Jan; Hoffman, Robert M; Friedl, Peter; Vasaturo, Angela

    2011-01-01

    Cancer invasion into an extracellular matrix (ECM) results from a biophysical reciprocal interplay between the expanding cancer lesion and tissue barriers imposed by the adjacent microenvironment. In vivo, connective tissue provides both densely packed ECM barriers adjacent to channel/track-like spaces and loosely organized zones, both of which may impact cancer invasion mode and efficiency; however little is known about how three-dimensional (3D) spaces and aligned tracks present in interstitial tissue guide cell invasion. We here describe a two-photon laser ablation procedure to generate 3D microtracks in dense 3D collagen matrices that support and guide collective cancer cell invasion. Whereas collective invasion of mammary tumor (MMT) breast cancer cells into randomly organized collagen networks required matrix metalloproteinase (MMP) activity for cell-derived collagen breakdown, re-alignment and track generation, preformed tracks supported MMP-independent collective invasion down to a track caliber of 3 µm. Besides contact guidance along the track of least resistance and initial cell deformation (squeezing), MMP-independent collective cell strands led to secondary track expansion by a pushing mechanism. Thus, two-photon laser ablation is useful to generate barrier-free microtracks in a 3D ECM which guide collective invasion independently of pericellular proteolysis

  4. Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2015-10-01

    Full Text Available The goal of this article is to provide a critical review of the transient receptor potential melastatin-subfamily member 8 (TRPM8 in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca²⁺ homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating evidence has demonstrated that TRPM8 is aberrantly expressed in a variety of malignant solid tumors. Clinicopathological analysis has shown that over-expression of TRPM8 correlates with tumor progression. Experimental data have revealed important roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which appear to be dependent on the cancer type. Recent reports have begun to reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the impact of thermal and chemical stimuli on the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will help exploit these ion channels as molecular biomarkers and therapeutic targets for developing precision cancer medicine.

  5. Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.

    Science.gov (United States)

    Ballard, Ashley James

    2015-12-01

    The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

    International Nuclear Information System (INIS)

    Voss, Marise R Heerma van; Groep, Petra van der; Bart, Jos; Wall, Elsken van der; Diest, Paul J van

    2010-01-01

    Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like) type that is known to have a low rate of lympho-vascular invasion (LVI), we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78). LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation

  7. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

    Directory of Open Access Journals (Sweden)

    van der Wall Elsken

    2010-04-01

    Full Text Available Abstract Background Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like type that is known to have a low rate of lympho-vascular invasion (LVI, we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. Methods A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. Results LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78. Conclusion LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.

  8. The evaluation of slow injection dynamic CT scan for the vascular invasion of cancer of biliary system and pancreas

    International Nuclear Information System (INIS)

    Kikuchi, Toshiyuki

    1985-01-01

    Dynamic CT body scans were performed under an injection rate of 3 ml/sec with a total amount of 100 ml angiografin by rapid table shift, upon 64 cancer patients, 21 patients with cancer of the bile duct, 21 with pancreatic cancer, 14 with cancer of the gallbladder and 8 with cancer of ampulla of papilla vater. In this study, the detectability of these cancers and the accuracy of their vascular invasion were compared between the above mentioned CT scan (slow injection D. CT) and angiography by our criteria. The detectability of the main tumors was 33.3 % by plain CT but 85.7 % by slow injection D. CT. The criteria of the vascular invasion by slow injection D. CT were classified to four types; separated type, contact type, contact invasive type and involved type. By this criteria, the diagnostic overall accuracy of the arterial invasion was 96.8 % in SMA, 98.4 % in celiac axis, 92.1 % in CH and 46.1 % in proper and bilateral hepatic arteries. The larger the arterial caliber was, the higher the diagnostic accuracy was in slow injection D. CT. On the other hand, the angiographic diagnostic accuracy of the arterial invasion was 79 % in SMA, 88.7 % in celiac axis, 90.3 % in CH and 98.4 % in proper and bilateral hepatic arteries. So, the smaller the arterial caliber was, the higher the diagnostic accuracy was in angiography. The overall accuracy of the portal venous invasion was 90.6 % by means of slow injection D. CT and 88.7 % by means of angiography. 33 of 64 cases were with portal venous invasion, and 15 of 33 cases were resectable by reconstraction of the portal vein. 4 of 15 were contact type, 10 of 15 were contact invasive type, 1 of 15 was involved type. 10 of 11 contact invasive type were resectable, and only 1 of 18 involved type was resectable, so it was safe to say the case of contact invasive type was resectable, and the case of involved type was unresectable. (author)

  9. Gemifloxacin, a Fluoroquinolone Antimicrobial Drug, Inhibits Migration and Invasion of Human Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jung-Yu Kan

    2013-01-01

    Full Text Available Gemifloxacin (GMF is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT. In addition, GMF suppresses the activation of NF-κB and cell migration and invasion induced by TNF-α and inhibits the TAK1/TAB2 interaction, resulting in decreased IκB phosphorylation and NF-κB nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

  10. Epigenetic regulation of CpG promoter methylation in invasive prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Farrar William L

    2010-10-01

    Full Text Available Abstract Background Recently, much attention has been focused on gaining a better understanding of the different populations of cells within a tumor and their contribution to cancer progression. One of the most commonly used methods to isolate a more aggressive sub-population of cells utilizes cell sorting based on expression of certain cell adhesion molecules. A recently established method we developed is to isolate these more aggressive cells based on their properties of increased invasive ability. These more invasive cells have been previously characterized as tumor initiating cells (TICs that have a stem-like genomic signature and express a number of stem cell genes including Oct3/4 and Nanog and are more tumorigenic compared to their 'non-invasive' counterpart. They also have a profile reminiscent of cells undergoing a classic pattern of epithelial to mesenchymal transition or EMT. Using this model of invasion, we sought to investigate which genes are under epigenetic control in this rare population of cells. Epigenetic modifications, specifically DNA methylation, are key events regulating the process of normal human development. To determine the specific methylation pattern in these invasive prostate cells, and if any developmental genes were being differentially regulated, we analyzed differences in global CpG promoter methylation. Results Differentially methylated genes were determined and select genes were chosen for additional analyses. The non-receptor tyrosine kinase BMX and transcription factor SOX1 were found to play a significant role in invasion. Ingenuity pathway analysis revealed the methylated gene list frequently displayed genes from the IL-6/STAT3 pathway. Cells which have decreased levels of the targets BMX and SOX1 also display loss of STAT3 activity. Finally, using Oncomine, it was determined that more aggressive metastatic prostate cancers in humans also have higher levels of both Stat3 and Sox1. Conclusions Using this

  11. High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin.

    Science.gov (United States)

    Wang, Zhi-Na; Liu, Dan; Yin, Bin; Ju, Wen-Yi; Qiu, Hui-Zhong; Xiao, Yi; Chen, Yuan-Jia; Peng, Xiao-Zhong; Lu, Chong-Mei

    2017-05-30

    Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro. Denovirus shRNA knockdown of PTBP1 inhibited colorectal cancer growth in vivo. Furthermore, PTBP1 regulates alternative splicing of many target genes involving in tumorgenesis in colon cancer cells. We confirmed that the splicing of cortactin exon 11 which was only contained in cortactin isoform-a, as a PTBP1 target. Knockdown of PTBP1 decreased the expression of cortactin isoform-a by exclusion of exon 11. Also the mRNA levels of PTBP1 and cortactin isoform-a were cooperatively expressed in colorectal cancer tissues. Knocking down cortactin isoform-a significantly decreased cell migration and invasion in colorectal cancer cells. Overexpression of cortactin isoform-a could rescue PTBP1-knockdown effect of cell motility. In summary the study revealed that PTBP1 facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11.

  12. The mammographic correlations of a new immunohistochemical classification of invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taneja, S. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom)], E-mail: sheeba_taneja@yahoo.co.uk; Evans, A.J. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom); Rakha, E.A.; Green, A.R. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom); Ball, G. [Nottingham Trent University, School of Biomedical and Natural Sciences, Nottingham (United Kingdom); Ellis, I.O. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom)

    2008-11-15

    Aim: Recent protein expression profiling of breast cancer has identified specific subtypes with clinical, biological, and therapeutic implications. The aim of this study was to identify the mammographic correlates of these novel molecular classes of invasive breast cancer. Materials and methods: The mammographic findings of 415 patients with operable breast cancer were correlated with the previously described protein expression classes identified by our group using immunohistochemical (IHC) assessment of a large series of breast cancer cases prepared as tissue microarrays (TMAs). Twenty-five proteins of known relevance in breast cancer were assessed, including hormone receptors, HER-2 status, basal and luminal markers, p53 expression, and E-cadherin. Results: The mammographic background pattern and proportion of lesions that were mammographically occult were similar in all groups. Groups characterized by luminal and hormone receptor positivity had significantly more spiculate lesions at mammography. Groups characterized by HER-2 overexpression, basal characteristics, and E-cadherin positivity had a significantly higher proportion of ill-defined masses. These findings were independent of histological grade. Conclusion: The mammographic features of breast cancer show significant correlation with molecular classes of invasive breast cancer identified by protein expression IHC analysis. The biological reasons for the findings and implications of these regarding imaging protocols require further study and may provide mechanisms for improvement of detection of these lesions.

  13. Prospective Clinical Trial of 18F-Fluciclovine PET/CT for Determining the Response to Neoadjuvant Therapy in Invasive Ductal and Invasive Lobular Breast Cancers.

    Science.gov (United States)

    Ulaner, Gary A; Goldman, Debra A; Corben, Adriana; Lyashchenko, Serge K; Gönen, Mithat; Lewis, Jason S; Dickler, Maura

    2017-07-01

    18 F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ( 18 F-fluciclovine) is a leucine analog radiotracer that depicts amino acid transport into cells. 18 F-fluciclovine PET/CT visualizes malignancy, including prostate cancer, invasive ductal breast cancer, and invasive lobular breast cancer. Whether changes in 18 F-fluciclovine avidity reflect changes in tumor burden resulting from treatment has not been shown. In this prospective clinical trial (clinical trials.gov: NCT01864083), changes in 18 F-fluciclovine avidity after neoadjuvant therapy were compared to breast cancer therapy response, as determined by residual tumor burden on pathology, were evaluated. Methods: Twenty-four women with a new diagnosis of locally advanced invasive ductal breast cancer ( n = 18) or invasive lobular breast cancer ( n = 6) underwent 18 F-fluciclovine PET/CT before and after the completion of neoadjuvant systemic therapy. SUV max , SUV mean , metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes on each examination and corrected for background 18 F-fluciclovine avidity. The relationship between changes in 18 F-fluciclovine avidity and the percentage of reduction of tumor on pathology was assessed with the Spearman rank correlation. Results: The median decrease in the corrected SUV max of the primary breast lesions was 99% (range, 33%-100%). The median reduction of tumor on pathology was 92% (range, 10%-100%). Changes in 18 F-fluciclovine avidity were strongly correlated with the percentage of reduction of tumor on pathology (Spearman ρ, 0.79; 95% CI, 0.56-0.90; P < 0.001). Conclusion: Changes in 18 F-fluciclovine avidity strongly correlated with the tumor response on pathology in this pilot study. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  14. MicroRNA-1297 inhibits prostate cancer cell proliferation and invasion by targeting the AEG-1/Wnt signaling pathway

    International Nuclear Information System (INIS)

    Liang, Xuan; Li, Hecheng; Fu, Delai; Chong, Tie; Wang, Ziming; Li, Zhaolun

    2016-01-01

    MicroRNAs (miRNAs) have been known to be implicated in tumorigenic programs. miR-1297 has been reported to be dysregulated and involved in cancer progression in many types of human cancers. However, the expression level and the role of miR-1297 in prostate cancer remain unclear. Herein, we aimed to investigate the potential role and molecular mechanism of miR-1297 in prostate cancer progression. We found that miR-1297 was significantly downregulated in human prostate cancer specimens as well as in several prostate cancer cell lines. In addition, functional experiments demonstrated that overexpression of miR-1297 remarkably inhibited prostate cancer cell proliferation and invasion whereas miR-1297 suppression significantly promoted prostate cancer cell proliferation and invasion. Bioinformatics analysis showed that the Astrocyte elevated gene-1 (AEG-1), a well-known oncogene, is a predicted target of miR-1297. Dual-luciferase reporter assay showed that miR-1297 was able to directly target the 3’-untranslated region of AEG-1. In addition, RT-qPCR and Western blot analysis showed that miR-1297 regulated the mRNA and protein expression levels of AEG-1. We also showed that miR-1297 was able to regulate the Wnt signaling pathway. Moreover, rescue assays indicated that AEG-1 contributed to miR-1297-endowed effects on cell proliferation and invasion as well as Wnt signaling pathway. Taken together, these findings suggest that miR-1297 inhibits prostate cancer proliferation and invasion by targeting AEG-1, thereby providing novel insight into understanding the pathogenesis of prostate cancer. Thus, miR-1297 may be a novel potential therapeutic candidate to treat prostate cancer. - Highlights: • miR-1297 is decreased in prostate cancer. • miR-1297 inhibits prostate cancer cell proliferation and invasion. • miR-1297 targets and inhibits AEG-1. • miR-1297 regulates AEG-1/Wnt signaling pathway.

  15. Invasive lobular breast cancer and its variants: how special are they for systemic therapy decisions?

    Science.gov (United States)

    Guiu, Séverine; Wolfer, Anita; Jacot, William; Fumoleau, Pierre; Romieu, Gilles; Bonnetain, Franck; Fiche, Maryse

    2014-12-01

    The WHO classification of breast tumors distinguishes, besides invasive breast cancer 'of no special type' (former invasive ductal carcinoma, representing 60-70% of all breast cancers), 30 special types, of which invasive lobular carcinoma (ILC) is the most common (5-15%). We review the literature on (i) the specificity and heterogeneity of ILC biology as documented by various analytical techniques, including the results of molecular testing for risk of recurrence; (ii) the impact of lobular histology on prediction of prognosis and effect of systemic therapies in patients. Though it is generally admitted that ILC has a better prognosis than IDC, is endocrine responsive, and responds poorly to chemotherapy, currently available data do not unanimously support these assumptions. This review demonstrates some lack of specific data and a need for improving clinical research design to allow oncologists to make informed systemic therapy decisions in patients with ILC. Importantly, future studies should compare various endpoints in ILC breast cancer patients among the group of hormonosensitive breast cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

    2018-04-01

    We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

  17. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    International Nuclear Information System (INIS)

    Vermeulen, Jeroen F; Brussel, Aram SA van; Groep, Petra van der; Morsink, Folkert HM; Bult, Peter; Wall, Elsken van der; Diest, Paul J van

    2012-01-01

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate

  18. Urinary high molecular weight matrix metalloproteinases as non-invasive biomarker for detection of bladder cancer

    OpenAIRE

    Mohammed, Mohammed A; Seleim, Manar F; Abdalla, Mohga S; Sharada, Hayat M; Abdel Wahab, Abdel Hady A

    2013-01-01

    Background Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Over-expression of different MMPs in tumor tissues can disturb the homeostasis and increase the level of various body fluids. Many MMPs including high molecular weights (HMWs) were detected in the urine of prostate and bladder cancer patients. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients. Methods The activ...

  19. Results of chemoradiotherapyfor muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Yu. V. Gumenetskaya

    2013-01-01

    Full Text Available This study presents the results of chemoradiotherapy (CRT in 108 patients with muscle-invasive bladder cancer in whom surgery was contraindicated. The efficacies and toxicities of three variants of CRT were evaluated. Group 1 (neoadjuvant chemotherapy: 2–3 cycles of cisplatin-containing combination chemotherapy followed by a continuous course of external beam radiation therapy (EBRT. Group 2: concurrent CRT – cisplatin i.v., 70–100 mg/m 2 during the first and last weeks of continuous-course EBRT. Group 3: sequential neoadjuvant chemotherapy, 2–3 cycles and concurrent CRT. The comparative analysis of long-term outcomes following CRT indicated an improvement in survival rates in group 3 in which the 5-and 10-year cancer-specific survival rates were 42,3 ± 8,8 % and 31,3 ± 9,4 %, respectively, compared with 28,6 ± 9,7 % and 28,6 ± 9,7 % in group 1, and 29,5 ± 8,5 % and 14,8 ± 7,4 % in group 2, respectively (р=0,093. Acute toxicity (GU Grade 1 or 2 arose more often from concurrent radiation and chemotherapy: in 40,0 % and 40,5 % of cases in groups 2 and 3, respectively, whereas in group 1 it occurred in 25,9 % of cases (р<0,2. Late radiation toxicity (GU Grade 2 occurred more often in the concurrent CRT groups: 11,4 % and 11,9 % versus 3,2 % in the neoadjuvant chemotherapy group; Grade 3 was noted in 5,7 % and 2,4 % of patients in groups 2 and 3, respectively. The results indicated that chemoradiotherapy including neoadjuvant and concomitant chemotherapy improved the outcomes in patients with muscle-invasive bladder cancer in whom surgery was contraindicated. There was an acceptable rate of clinically significant complications.

  20. Inhibitory effect of blue light emitting diode on migration and invasion of cancer cells.

    Science.gov (United States)

    Oh, Phil-Sun; Kim, Hyun-Soo; Kim, Eun-Mi; Hwang, Hyosook; Ryu, Hyang Hwa; Lim, SeokTae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2017-12-01

    The aim of this study was to determine the effects and molecular mechanism of blue light emitting diode (LED) in tumor cells. A migration and invasion assay for the metastatic behavior of mouse colon cancer CT-26 and human fibrosarcoma HT-1080 cells was performed. Cancer cell migration-related proteins were identified by obtaining a 2-dimensional gel electrophoresis (2-DE) in total cellular protein profile of blue LED-irradiated cancer cells, followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of proteins. Protein levels were examined by immunoblotting. Irradiation with blue LED inhibited CT-26 and HT-1080 cell migration and invasion. The anti-metastatic effects of blue LED irradiation were associated with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression. P38 MAPK phosphorylation was increased in blue LED-irradiated CT-26 and HT-1080 cells, but was inhibited after pretreatment with SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK phosphorylation by SB203580 treatment increased number of migratory cancer cells in CT-26 and HT-1080 cells, indicating that blue LED irradiation inhibited cancer cell migration via phosphorylation of p38 MAPK. Additionally blue LED irradiation of mice injected with CT-26 cells expressing luciferase decreased early stage lung metastasis compared to untreated control mice. These results indicate that blue LED irradiation inhibits cancer cell migration and invasion in vitro and in vivo. © 2017 Wiley Periodicals, Inc.

  1. [Knock-down of ZEB1 inhibits the proliferation, invasion and migration of gastric cancer cells].

    Science.gov (United States)

    Chen, Dengyu; Chu, Yifan; Zheng, Qingwei; Xu, Zhiben; Zhou, Ping; Li, Sheng

    2017-08-01

    Objective To down-regulate the expression of zinc-finger E-box binding homeobox 1 (ZEB1) gene by shRNA, and investigate its effect on invasion, migration and proliferation, as well as the related gene expressions of lncRNA HOTAIR and E-cadherin in human gastric cancer BGC823 cells. Methods RNA interfering (RNAi) was used to knock down ZEB1 in gastric cancer BGC823 cells. The recombinant plasmid shZEB1 was constructed and transfected into the gastric cancer BGC823 cells by Lipofectamine TM 2000, and the stably transfected cells were isolated by G418 selection and limited dilution. The expression of ZEB1 mRNA and protein was detected by real-time quantitative PCR and Western blot analysis. Cell proliferation was determined by MTT assay, and the invasion and migration abilities of BGC823 cells were monitored by Transwell TM invasion assay and wound healing assay, respectively. The expressions of lncRNA HOTAIR and E-cadherin mRNA were detected by real-time quantitative PCR. Results After ZEB1 expression was successfully down-regulated in BGC823 cells by siRNA, the proliferation, invasion and migration rates in shZEB1 transfection group were significantly lower than those in control group; meanwhile, the expression of lncRNA HOTAIR was reduced and E-cadherin expression was enhanced. Conclusion Knock-down of ZEB1 expression by RNA interference can decease lncRNA HOTAIR expression and restrain cell proliferation, invasion and migration in gastric cancer BGC823 cells.

  2. 1,25D3 differentially suppresses bladder cancer cell migration and invasion through the induction of miR-101-3p.

    Science.gov (United States)

    Ma, Yingyu; Luo, Wei; Bunch, Brittany L; Pratt, Rachel N; Trump, Donald L; Johnson, Candace S

    2017-09-01

    Metastasis is the major cause of bladder cancer death. 1,25D 3 , the active metabolite of vitamin D, has shown anti-metastasis activity in several cancer model systems. However, the role of 1,25D 3 in migration and invasion in bladder cancer is unknown. To investigate whether 1,25D 3 affects migration and invasion, four human bladder cell lines with different reported invasiveness were selected: low-invasive T24 and 253J cells and highly invasive 253J-BV and TCCSUP cells. All of the four bladder cancer cells express endogenous and inducible vitamin D receptor (VDR) as examined by immunoblot analysis. 1,25D 3 had no effect on the proliferation of bladder cancer cells as assessed by MTT assay. In contrast, 1,25D 3 suppressed migration and invasion in the more invasive 253J-BV and TCCSUP cells, but not in the low-invasive 253J and T24 cells using "wound" healing, chemotactic migration and Matrigel-based invasion assays. 1,25D 3 promoted the expression of miR-101-3p and miR-126-3p in 253J-BV cells as examined by qRT-PCR. miR-101-3p inhibitor partially abrogated and pre-miR-101-3p further suppressed the inhibition of 1,25D 3 on migration and invasion in 253J-BV cells. Further, 1,25D 3 enhanced VDR recruitment to the promoter region of miR-101-3p using ChIP-qPCR assay. 1,25D 3 enhanced the promoter activity of miR-101-3p as evaluated by luciferase reporter assay. Taken together, 1,25D 3 suppresses bladder cancer cell migration and invasion in two invasive/migration competent lines but not in two less invasive/motile lines, which is partially through the induction of miR-101-3p expression at the transcriptional level.

  3. Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

    Science.gov (United States)

    Evans, Andrew; Rauchhaus, Petra; Whelehan, Patsy; Thomson, Kim; Purdie, Colin A; Jordan, Lee B; Michie, Caroline O; Thompson, Alastair; Vinnicombe, Sarah

    2014-01-01

    Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer® ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness 150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging.

  4. Probing cooperative force generation in collective cancer invasion

    Science.gov (United States)

    Alobaidi, Amani A.; Xu, Yaopengxiao; Chen, Shaohua; Jiao, Yang; Sun, Bo

    2017-08-01

    Collective cellular dynamics in the three-dimensional extracellular matrix (ECM) plays a crucial role in many physiological processes such as cancer invasion. Both chemical and mechanical signaling support cell-cell communications on a variety of length scales, leading to collective migratory behaviors. Here we conduct experiments using 3D in vitro tumor models and develop a phenomenological model in order to probe the cooperativity of force generation in the collective invasion of breast cancer cells. In our model, cell-cell communication is characterized by a single parameter that quantifies the correlation length of cellular migration cycles. We devise a stochastic reconstruction method to generate realizations of cell colonies with specific contraction phase correlation functions and correlation length a. We find that as a increases, the characteristic size of regions containing cells with similar contraction phases grows. For small a values, the large fluctuations in individual cell contraction phases smooth out the temporal fluctuations in the time-dependent deformation field in the ECM. For large a values, the periodicity of an individual cell contraction cycle is clearly manifested in the temporal variation of the overall deformation field in the ECM. Through quantitative comparisons of the simulated and experimentally measured deformation fields, we find that the correlation length for collective force generation in the breast cancer diskoid in geometrically micropatterned ECM (DIGME) system is a≈ 25~μ \\text{m} , which is roughly twice the linear size of a single cell. One possible mechanism for this intermediate cell correlation length is the fiber-mediated stress propagation in the 3D ECM network in the DIGME system.

  5. MiR-132 prohibits proliferation, invasion, migration, and metastasis in breast cancer by targeting HN1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhan-Guo, E-mail: zhang_zhanguo@hotmail.com; Chen, Wei-Xun, E-mail: chenweixunclark@163.com; Wu, Yan-Hui, E-mail: wuyanhui84@126.com; Liang, Hui-Fang, E-mail: lianghuifang1997@126.com; Zhang, Bi-Xiang, E-mail: bixiangzhang@163.com

    2014-11-07

    Highlights: • MiR-132 is down-regulated in breast cancer tissues and cell lines. • MiR-132 directly regulates HN1 by binding its 3′ UTR. • MiR-132 shows regulatory role in proliferation, invasion, migration and metastasis. • HN1 is involved in miR-132-mediated cell behavior. • Aberrant HN1 is associated with worse overall survival of breast cancer patients. - Abstract: Accumulating evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. This study aims to investigate the role and the underlying mechanism of miR-132 in breast cancer. Here, we report that miR-132 is significantly down-regulated in breast cancer tissues and cancer cell lines. Additional study identifies HN1 as a novel direct target of miR-132. MiR-132 down-regulates HN1 expression by binding to the 3′ UTR of HN1 transcript, thereby, suppressing multiple oncogenic traits such as cancer cell proliferation, invasion, migration and metastasis in vivo and in vitro. Overexpression of HN1 restores miR-132-suppressed malignancy. Importantly, higher HN1 expression is significantly associated with worse overall survival of breast cancer patients. Taken together, our data demonstrate a critical role of miR-132 in prohibiting cell proliferation, invasion, migration and metastasis in breast cancer through direct suppression of HN1, supporting the potential utility of miR-132 as a novel therapeutic strategy against breast cancer.

  6. Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group

    NARCIS (Netherlands)

    Kamat, A.M.; Sylvester, R.J.; Bohle, A.; Palou, J.; Lamm, D.L.; Brausi, M.; Soloway, M.; Persad, R.; Buckley, R.; Colombel, M.; Witjes, J.A.

    2016-01-01

    PURPOSE: To provide recommendations on appropriate clinical trial designs in non-muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses, and reviews and

  7. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessita......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each...

  8. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer.

    Science.gov (United States)

    Truin, W; Voogd, A C; Vreugdenhil, G; van der Heiden-van der Loo, M; Siesling, S; Roumen, R M

    2012-11-01

    On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50-70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy. In total, 19,609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 [95% confidence interval (CI) 0.64-0.76; P lobular cancer was 1.00 (95% CI 0.82-1.21; P = 0.97). Adjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.

  9. Factors influencing treatment results of definitive radiotherapy following transurethral surgery for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Abe, Tatsuyuki; Kanehira Chihiro

    1999-01-01

    To determine the prognostic factors influencing the outcome of bladder cancer patients treated with definitive radiotherapy following transurethral tumor resection (TURBT). From March 1977 through August 1991, 83 patients with muscle-invasive bladder cancer were treated with TURBT (as thoroughly as possible) and definitive radiotherapy (median total dose: 64 Gy, median fractional dose: 2 Gy). Cystectomy was performed when possible for the residual or recurrent invasive cancer following radiotherapy. The median follow-up period was 76 months. The overall survival (OS) and bladder-preserving survival (BPS) rates at 5 years were 38% and 28%, respectively. Univariate analysis indicated that depth of invasion (T2 vs T3), tumor diameter (<3 cm vs. ≥3 cm), and visible (R1) or not visible (R0) residual tumor after TURBT influenced both OS and BPS. In multivariate analysis, absence of visible residual tumor after TURBT was the only significant prognostic factor related to OS (p<0.001) and BPS (p=0.002). Five-year OS and BPS were 54% and 43% in T2-3R0 and 14% and 7% in T2-3R1, respectively. Absence of visible residual tumor after TURBT was significantly associated with better overall survival and bladder-preserving survival for muscle-invasive bladder cancer patients treated with definitive radiotherapy following TURBT. (author)

  10. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

    Science.gov (United States)

    Bharti, Rashmi; Dey, Goutam; Das, Anjan Kumar; Mandal, Mahitosh

    2018-04-26

    Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis. We employed various in-vitro and in-vivo techniques and clinical samples. We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen. Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

  11. Expression of Caspase-1 in breast cancer tissues and its effects on cell proliferation, apoptosis and invasion.

    Science.gov (United States)

    Sun, Yanxia; Guo, Yingzhen

    2018-05-01

    The present study aimed to detect the expression of Caspase-1 in the tumor tissues and tumor-adjacent tissues of patients with breast cancer, and to investigate the effects of Caspase-1 on the proliferation, apoptosis and invasion of breast cancer cells. Reverse transcription-quantitative polymerase chain reaction was used to detect Caspase-1 mRNA expression in breast cancer tissues and tumor-adjacent tissues from patients. Additionally, the human breast cancer MDA-MB-231 cell line was treated with the Caspase-1 small molecule inhibitor Ac-YVAD-CMK, following which the changes to Caspase-1 protein expression were detected via western blotting. The MTT method detected the changes to cell proliferation, flow cytometry detected the rate of apoptosis, and a Transwell assay was employed to assess invasion. Caspase-1 mRNA expression was significantly decreased in the breast cancer tissues of patients, compared with in the tumor-adjacent tissues, a difference that was statistically significant (P<0.05). Treatment with the Ac-YVAD-CMK markedly decreased the protein expression of Caspase-1 in MDA-MB-231 cells, and the difference was statistically significant (P<0.05). Following this treatment of Ac-YVAD-CMK cells, the proliferation and invasion abilities markedly increased, while the apoptotic levels significantly decreased (P<0.05). In conclusion, the expression of Caspase-1 is low in breast cancer tissues, which may promote the proliferation and invasion of breast cancer cells and could be closely associated with the occurrence and development of breast cancer.

  12. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Directory of Open Access Journals (Sweden)

    Shimura Takaya

    2012-05-01

    Full Text Available Abstract Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C, translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF and mutated HB-EGF (HB-EGF-mC, which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 % and in the cytoplasm only in 25 cases (26.0 %. The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P  Conclusions Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  13. Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN.

    Science.gov (United States)

    Menck, Kerstin; Scharf, Christian; Bleckmann, Annalen; Dyck, Lydia; Rost, Ulrike; Wenzel, Dirk; Dhople, Vishnu M; Siam, Laila; Pukrop, Tobias; Binder, Claudia; Klemm, Florian

    2015-04-01

    Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologous and heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  14. Expression profiling of migrated and invaded breast cancer cells predicts early metastatic relapse and reveals Krüppel-like factor 9 as a potential suppressor of invasive growth in breast cancer

    Science.gov (United States)

    Limame, Ridha; de Beeck, Ken Op; Van Laere, Steven; Croes, Lieselot; De Wilde, Annemieke; Dirix, Luc; Van Camp, Guy; Peeters, Marc; De Wever, Olivier; Lardon, Filip; Pauwels, Patrick

    2014-01-01

    Cell motility and invasion initiate metastasis. However, only a subpopulation of cancer cells within a tumor will ultimately become invasive. Due to this stochastic and transient nature, in an experimental setting, migrating and invading cells need to be isolated from the general population in order to study the gene expression profiles linked to these processes. This report describes microarray analysis on RNA derived from migrated or invaded subpopulations of triple negative breast cancer cells in a Transwell set-up, at two different time points during motility and invasion, pre-determined as “early” and “late” in real-time kinetic assessments. Invasion- and migration-related gene expression signatures were generated through comparison with non-invasive cells, remaining at the upper side of the Transwell membranes. Late-phase signatures of both invasion and migration indicated poor prognosis in a series of breast cancer data sets. Furthermore, evaluation of the genes constituting the prognostic invasion-related gene signature revealed Krüppel-like factor 9 (KLF9) as a putative suppressor of invasive growth in breast cancer. Next to loss in invasive vs non-invasive cell lines, KLF9 also showed significantly lower expression levels in the “early” invasive cell population, in several public expression data sets and in clinical breast cancer samples when compared to normal tissue. Overexpression of EGFP-KLF9 fusion protein significantly altered morphology and blocked invasion and growth of MDA-MB-231 cells in vitro. In addition, KLF9 expression correlated inversely with mitotic activity in clinical samples, indicating anti-proliferative effects. PMID:25593984

  15. Patient Preferences for Minimally Invasive and Open Locoregional Treatment for Early-Stage Breast Cancer

    NARCIS (Netherlands)

    Knuttel, Floor; van den Bosch, Maurice A A J; Young-Afat, Danny A.; Emaus, Marleen J.; van den Bongard, Desirée H J G; Witkamp, Arjen J.; Verkooijen, Helena M.

    Background: Noninvasive or minimally invasive treatments are being developed as alternatives to surgery for patients with early-stage breast cancer. Patients' preferences with regard to these new treatments have not been investigated. Objectives: To assess preferences of patients with breast cancer

  16. TGFβ1 induces apoptosis in invasive prostate cancer and bladder cancer cells via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases

    International Nuclear Information System (INIS)

    Al-Azayzih, Ahmad; Gao, Fei; Goc, Anna; Somanath, Payaningal R.

    2012-01-01

    Highlights: ► TGFβ induced apoptosis in invasive prostate cancer and bladder cancer cells. ► TGFβ inhibited prostate/bladder cancer cell proliferation and colony/foci formation. ► TGFβ induced prostate/bladder cancer cell apoptosis independent of Akt inhibition. ► TGFβ inhibited ERK1/2 phosphorylation in prostate/bladder cancer cells. ► TGFβ induced p38 MAPK and JNK-mediated activation of caspases-9, -8 and -3. -- Abstract: Recent findings indicate that advanced stage cancers shun the tumor suppressive actions of TGFβ and inexplicably utilize the cytokine as a tumor promoter. We investigated the effect of TGFβ1 on the survival and proliferation of invasive prostate (PC3) and bladder (T24) cancer cells. Our study indicated that TGFβ1 decreased cell viability and induced apoptosis in invasive human PC3 and T24 cells via activation of p38 MAPK-JNK-Caspase9/8/3 pathway. Surprisingly, no change in the phosphorylation of pro-survival Akt kinase was observed. We postulate that TGFβ1 pathway may be utilized for specifically targeting urological cancers without inflicting side effects on normal tissues.

  17. Invasive Breast Cancer Incidence in 2,305,427 Screened Asymptomatic Women: Estimated Long Term Outcomes during Menopause Using a Systematic Review.

    Directory of Open Access Journals (Sweden)

    Winnifred Cutler

    Full Text Available Earlier studies of breast cancer, screening mammography, and mortality reduction may have inflated lifetime and long-term risk estimates for invasive breast cancer due to limitations in their data collection methods and interpretation.To estimate the percentage of asymptomatic peri/postmenopausal women who will be diagnosed with a first invasive breast cancer over their next 25 years of life.A systematic review identified peer-reviewed published studies that: 1 enrolled no study participants with a history of invasive breast cancer; 2 specified the number of women enrolled; 3 reported the number of women diagnosed with a first invasive breast cancer; 4 did not overcount [count a woman multiple times]; and, 5 defined the length of follow-up. Data sources included PubMed, Cochrane Library, and an annotated library of 4,409 full-text menopause-related papers collected and reviewed by the first author from 1974 through 2008. Linear regression predicted incidence of first invasive breast cancer, based on follow-up duration in all studies that met the our inclusion criteria, and in a subset of these studies that included only women who were 1 at least 50 years old and 2 either at least 50 or less than 50 but surgically menopausal at enrollment.Nineteen studies met the inclusion criteria. They included a total of 2,305,427 peri/postmenopasual women. The mean cumulative incidence rate of first invasive breast cancer increased by 0.20% for each year of age (95% CI: 0.17, 0.23; p < 0.01; R2 = 0.90. Over 25 years of follow-up, an estimated 94.55% of women will remain breast cancer-free (95% CI: 93.97, 95.13. In the 12 studies (n = 1,711,178 that enrolled only postmenopausal women, an estimated 0.23% of women will be diagnosed with a first invasive breast cancer each year (95% CI: 0.18, 0.28; p < 0.01, R2 = 0.88.The vast majority (99.75% of screened asymptomatic peri/postmenopasual women will not be diagnosed with invasive breast cancer each year

  18. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    International Nuclear Information System (INIS)

    Martowicz, Agnieszka; Spizzo, Gilbert; Gastl, Guenther; Untergasser, Gerold

    2012-01-01

    The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAM high breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAM low breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAM high cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAM low cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

  19. Enantioselective Effects of o,p'-DDT on Cell Invasion and Adhesion of Breast Cancer Cells: Chirality in Cancer Development.

    Science.gov (United States)

    He, Xiangming; Dong, Xiaowu; Zou, Dehong; Yu, Yang; Fang, Qunying; Zhang, Quan; Zhao, Meirong

    2015-08-18

    The o,p'-dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(-)-o,p'-DDT exerts a more potent estrogenic effect than S-(+)-o,p'-DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p'-DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p'-DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(-)-o,p'-DDT promoted more cancer cell invasion mediated by the human estrogen receptor (ER) by inducing invasion-promoted genes (matrix metalloproteinase-2 and -9 and human telomerase reverse transcriptase) and inhibiting invasion-inhibited genes (tissue inhibitor of metalloproteinase-1 and -4). Molecular docking verified that the binding affinity between R-(-)-o,p'-DDT and human ER was stronger than that of S-(+)-o,p'-DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and β-catenin). For the first time, these results reveal that estrogenic-like chiral compounds are of significant concern in the progression of human cancers and that human health risk assessment of chiral chemicals should consider enantioselectivity.

  20. Effect of helicobacter pylori L-form infection on proliferation, apoptosis and invasion molecule expression in gastric cancer tissue

    Directory of Open Access Journals (Sweden)

    Hua Xin

    2017-05-01

    Full Text Available Objective: To study the effect of Helicobacter pylori L-form infection on proliferation, apoptosis and invasion molecule expression in gastric cancer tissue. Methods: The gastric cancer tissues surgically removed in our hospital between May 2013 and October 2016 were collected and divided into Hp negative, Hp-L negative and Hp-L positive according to the condition of helicobacter pylori infection. The proliferation, apoptosis and invasion gene expression were detected. Results: LOXL2, PCNA, CyclinD1, Rab1A, Bcl-2, Snail, N-cadherin, UHRF1 and AnnexinII mRNA expression in Hp-L-positive gastric cancer tissues were significantly higher than those in Hp-L-negative and Hp-negative gastric cancer tissues while ING5, PTPN13, Beclin1 and Mst1 mRNA expression were significantly lower than those in Hp-L-negative and Hp-negative gastric cancer tissues; LOXL2, PCNA, CyclinD1, Rab1A, Bcl-2, ING5, PTPN13, Beclin1, Mst1, Snail, N-cadherin, UHRF1 and AnnexinII mRNA expression in Hp-L-negative gastric cancer tissues were not different from those in Hpnegative gastric cancer tissues. Conclusion: Helicobacter pylori L-form infection can influence the proliferation, apoptosis and invasion gene expression to promote cell proliferation and invasion, and inhibit cell apoptosis.

  1. Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

    Science.gov (United States)

    Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

    2018-01-01

    Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

  2. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    Rose, Peter; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

    2005-01-01

    A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables

  3. Fentanyl inhibits proliferation and invasion of colorectal cancer via β-catenin

    Science.gov (United States)

    Zhang, Xiu-Lai; Chen, Min-Li; Zhou, Sheng-Li

    2015-01-01

    Background and aim: Fentanyl is widely used for relieving pain and narcotizing in cancer patients. However, there are few published reports regarding the effects of fentanyl on tumor control and treatment. Here we investigated the effects of fentanyl on tumor growth and cell invasion in the human colorectal carcinoma (HCT116) cells. Methods: Nude mice xenografts of HCT116 cells were established to assess the inhibition effect on tumor growth by fentanyl. MTT and Transwell were employed to determine the cell survival rate and cell invasion, respectively. MicroRNAs and mRNAs expression were quantified by real-time PCR. β-catenin and matrix metalloproteinases (MMP-2 and MMP-9) expression were assayed by western blotting. β-Catenin-specific small interfering RNA (Si-β-catenin) and miR-182 mimics were transfected in cells to investigate the mechanism underlying the effects of fentanyl on the colorectal tumor and HCT116 cells. Results: Treatment with fentanyl inhibited the tumor growth and HCT116 cells invasion. Fentanyl also downregulated the expression of β-catenin and miR-182 in both xenograft tumors and HCT116 cells, and decreased the protein level of MMP-9 in HCT116 cells. Downregulation of β-Catenin resulted in the decrease of miR-182 expression in colorectal cells. In addition, the overexpression of miR-182 reversed the effect of fentanyl on MMP-9 expression and cell invasion of HCT116 cells. Conclusions: The current study demonstrated that the inhibition of tumor growth and cell invasion in colorectal cancer by fentanyl is probably due to downregulation of miR-182 and MMP-9 expression by β-catenin. PMID:25755709

  4. Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines.

    Science.gov (United States)

    Emadi Baygi, Modjtaba; Soheili, Zahra-Soheila; Essmann, Frank; Deezagi, Abdolkhaleg; Engers, Rainer; Goering, Wolfgang; Schulz, Wolfgang A

    2010-08-01

    Many metastatic cancers recapitulate the epithelial-to-mesenchymal transition (EMT) resulting in enhanced cell motility and invasiveness. The EMT is regulated by several transcription factors, including the zinc finger protein SNAI2, also named Slug, which appears to exert additional functions during development and cancer progression. We have studied the function of SNAI2 in prostate cancer cells. Quantitative RT-PCR analysis showed strong SNAI2 expression particularly in the PC-3 and PC3-16 prostate carcinoma cell lines. Knockdown of SNAI2 by specific siRNA induced changes in EMT markers and inhibited invasion of both cell lines into a matrigel matrix. SNAI2 siRNA-treated cells did not tolerate detachment from the culture plates, likely at least in part due to downregulation of integrin alpha6beta4. SNAI2 knockdown disturbed the microtubular and actin cytoskeletons, especially severely in PC-3 cells, resulting in grossly enlarged, flattened, and sometimes multinuclear cells. Knockdown also decreased cell proliferation, with a prominent G0/G1 arrest in PC3-16. Together, our data imply that SNAI2 exerts strong effects on the cytoskeleton and adhesion of those prostate cancer cells that express it and is necessary for their proliferation and invasiveness.

  5. MicroRNA-215 suppresses cell proliferation, migration and invasion of colon cancer by repressing Yin-Yang 1

    International Nuclear Information System (INIS)

    Chen, Zehong; Han, Siqi; Huang, Wensheng; Wu, Jialin; Liu, Yuyi; Cai, Shirong; He, Yulong; Wu, Suijing; Song, Wu

    2016-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide with rising incidence. MicroRNAs are small non-coding RNAs that implicate in multiple physiological or pathological processes. The aberrant expression of miRNA-215 (miR-215) has been illustrated in various types of cancers. However, the expression of miR-215 in human colon cancer and the biological roles of it remain largely unknown. We conducted this study to explore the expression and the function of miR-215 in human colon cancer. The results showed that miR-215 was remarkably downregulated in colon cancer tissues and cell lines. Overexpression of miR-215 by miR-215 mimic significantly inhibited colon cancer cell proliferation, migration and invasion while knockdown of miR-215 by miR-215 inhibitor exerted reverse effects. Furthermore, we newly identified Yin-Yang 1(YY1) as a direct target of miR-215 which could rescue the effects of miR-215 on colon cancer cells. In summary, our investigation revealed that miR-215 was downregulated in colon cancer and it suppressed colon cancer cell proliferation, migration and invasion by directly targeting YY1. - Highlights: • MiR-215 expression was decreased in colon cancer tissues and cell lines. • Mir-215 inhibited colon cancer cell proliferation, migration and invasion. • MiR-215 targeted YY1 directly. • The effects of miR-215 on colon cancer cells were mediated by YY1.

  6. Effect of Twist, Snail and YB-1 gene expression in cervical cancer tissue on cell invasion and epithelial-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Xin-Qin Kang1

    2017-05-01

    Full Text Available Objective: To study the effect of Twist, Snail and YB-1 gene expression in cervical cancer tissue on cell invasion and epithelial-mesenchymal transition. Methods: Cervical cancer tissue samples and tissue samples adjacent to carcinoma were collected from 138 patients with radical operation for cervical cancer, fluorescence quantitative PCR method was used to detect the mRNA expression of Twist, Snail and YB-1 genes, cell invasion-related genes and epithelial-mesenchymal transition marker genes, the Pearson test was used to analyze the correlation of Twist, Snail and YB-1 gene mRNA expression in cervical cancer tissue with cell invasion and epithelial-mesenchymal transition. Results: Twist, Snail and YB-1 gene mRNA expression in cervical cancer tissue were higher than those in tissue adjacent to carcinoma, the invasion genes STAT3, YAP1, TUG1, FoxM1 and Rab11 mRNA expression were higher than those in tissue adjacent to carcinoma, and the epithelial-mesenchymal transition markers E-cadherin and β-catenin gene mRNA expression were lower than those in tissue adjacent to carcinoma while vimentin gene mRNA expression was higher than that in tissue adjacent to carcinoma. Pearson test showed that Twist, Snail and YB-1 gene mRNA expression in cervical cancer tissue were directly correlated with cell invasion and epithelial-mesenchymal transition. Conclusion: Twist, Snail and YB-1 genes are highly expressed in cervical cancer tissue, and their abnormal expression directly leads to the increased tumor cell invasion activity and the aggravated epithelial-mesenchymal transition.

  7. Prognostic Value of MammaPrint® in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Beumer, Inès J; Persoon, Marion; Witteveen, Anke; Dreezen, Christa; Chin, Suet-Feung; Sammut, Stephen-John; Snel, Mireille; Caldas, Carlos; Linn, Sabine; van 't Veer, Laura J; Bernards, Rene; Glas, Annuska M

    2016-01-01

    MammaPrint® is a microarray-based gene expression test cleared by the US Food and Drug Administration to assess recurrence risk in early-stage breast cancer, aimed to guide physicians in making neoadjuvant and adjuvant treatment decisions. The increase in the incidence of invasive lobular carcinomas (ILCs) over the past decades and the modest representation of ILC in the MammaPrint development data set calls for a stratified survival analysis dedicated to this specific subgroup. The current study aimed to validate the prognostic value of the MammaPrint test for breast cancer patients with early-stage ILCs. Univariate and multivariate survival associations for overall survival (OS), distant metastasis-free interval (DMFI), and distant metastasis-free survival (DMFS) were studied in a study population of 217 early-stage ILC breast cancer patients from five different clinical studies. A significant association between MammaPrint High Risk and poor clinical outcome was shown for OS, DMFI, and DMFS. A subanalysis was performed on the lymph node-negative study population. In the lymph node-negative study population, we report an up to 11 times higher change in the diagnosis of an event in the MammaPrint High Risk group. For DMFI, the reported hazard ratio is 11.1 (95% confidence interval = 2.3-53.0). Study results validate MammaPrint as an independent factor for breast cancer patients with early-stage invasive lobular breast cancer. Hazard ratios up to 11 in multivariate analyses emphasize the independent value of MammaPrint, specifically in lymph node-negative ILC breast cancers.

  8. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    International Nuclear Information System (INIS)

    Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

    2014-01-01

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

  9. Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data.

    Science.gov (United States)

    Hirth, Jacqueline M; Hatch, Sandra S; Lin, Yu-Li; Giordano, Sharon H; Silva, H Colleen; Kuo, Yong-Fang

    2018-04-18

    Overtreatment is a common concern for patients with ductal carcinoma in situ (DCIS), but this entity is difficult to distinguish from invasive breast cancers in administrative claims data sets because DCIS often is coded as invasive breast cancer. Therefore, the authors developed and validated algorithms to select DCIS cases from administrative claims data to enable outcomes research in this type of data. This retrospective cohort using invasive breast cancer and DCIS cases included women aged 66 to 70 years in the 2004 through 2011 Texas Cancer Registry (TCR) data linked to Medicare administrative claims data. TCR records were used as "gold" standards to evaluate the sensitivity, specificity, and positive predictive value (PPV) of 2 algorithms. Women with a biopsy enrolled in Medicare parts A and B at 12 months before and 6 months after their first biopsy without a second incident diagnosis of DCIS or invasive breast cancer within 12 months in the TCR were included. Women in 2010 Medicare data were selected to test the algorithms in a general sample. In the TCR data set, a total of 6907 cases met inclusion criteria, with 1244 DCIS cases. The first algorithm had a sensitivity of 79%, a specificity of 89%, and a PPV of 62%. The second algorithm had a sensitivity of 50%, a specificity of 97%. and a PPV of 77%. Among women in the general sample, the specificity was high and the sensitivity was similar for both algorithms. However, the PPV was approximately 6% to 7% lower. DCIS frequently is miscoded as invasive breast cancer, and thus the proposed algorithms are useful to examine DCIS outcomes using data sets not linked to cancer registries. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  10. DEGRO practical guidelines for radiotherapy of breast cancer IV. Radiotherapy following mastectomy for invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wenz, Frederik; Sperk, Elena [Universitaetsmedizin Mannheim, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany); Budach, Wilfried [Heinrich-Heine-University, Duesseldorf (Germany); Dunst, Juergen [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, Petra [Vivantes Hospital Neukoelln, Berlin (Germany); Fietkau, Rainer; Sauer, Rolf [University Hospital Erlangen, Erlangen (Germany); Haase, Wulf [Formerly St.-Vincentius-Hospital, Karlsruhe (Germany); Harms, Wolfgang [St. Clara Hospital, Basel (Switzerland); Piroth, Marc D. [Helios Hospital, Wuppertal (Germany); Sautter-Bihl, Marie-Luise [Municipal Hospital, Karlsruhe (Germany); Sedlmayer, Felix; Fussl, Christoph [Paracelsus Medical University Hospital, Salzburg (Germany); Souchon, Rainer; Collaboration: Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

    2014-08-15

    Since the last recommendations from the Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008, evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown. This growth is based on updates of the national S3 and international guidelines, as well as on new data and meta-analyses. New aspects were considered when updating the DEGRO recommendations. The authors performed a comprehensive survey of the literature. Data from recently published (meta-)analyses, randomized clinical trials and international cancer societies' guidelines yielding new aspects compared to 2008 were reviewed and discussed. New aspects were included in the current guidelines. Specific issues relating to particular PMRT constellations, such as the presence of risk factors (lymphovascular invasion, blood vessel invasion, positive lymph node ratio > 20 %, resection margins < 3 mm, G3 grading, young age/premenopausal status, extracapsular invasion, negative hormone receptor status, invasive lobular cancer, size > 2 cm or a combination of ≥ 2 risk factors) and 1-3 positive lymph nodes are emphasized. The evidence for improved overall survival and local control following PMRT for T4 tumors, positive resection margins, > 3 positive lymph nodes and in T3 N0 patients with risk factors such as lymphovascular invasion, G3 grading, close margins, and young age has increased. Recently identified risk factors such as invasive lobular subtype and negative hormone receptor status were included. For patients with 1-3 positive lymph nodes, the recommendation for PMRT has reached the 1a level of evidence. PMRT is mandatory in patients with T4 tumors and/or positive lymph nodes and/or positive resection margins. PMRT should be strongly considered in patients with T3 N0 tumors and risk factors, particularly when two or more risk factors are present. (orig.) [German] Seit der letzten Aktualisierung der 2008 publizierten Leitlinie der &apos

  11. Association between cervical screening and prevention of invasive cervical cancer in Ontario: a population-based case-control study.

    Science.gov (United States)

    Vicus, Danielle; Sutradhar, Rinku; Lu, Yan; Kupets, Rachel; Paszat, Lawrence

    2015-01-01

    The aim of this study was to estimate the effect of cervical screening in the prevention of invasive cervical cancer among age groups, using a population-based case-control study in the province of Ontario, Canada. Exposure was defined as cervical cytology history greater than 3 months before the diagnosis date of cervical cancer (index date). Cases were women who were diagnosed with cervical cancer between January 1, 1998, and December 31, 2008. Controls were women without a diagnosis of cervical cancer on, or before, December 31, 2008. Two controls were matched to each case on year of birth and income quintile, as of the index date. Conditional logistic regression was used to estimate the odds ratio for having been screened among those with cervical cancer. Cervical cancer screening performed between 3 and 36 months before the index date was protective against invasive cervical cancer in women aged 40 through 69 years. In women younger than 40 years, cervical cancer screening performed 3 to 36 months before the index date was not protective. Cervical screening is associated with a reduced risk for invasive cervical cancer among women older than 40 years. Cervical cancer resources should be focused on maximizing the risk reduction.

  12. Effects of CD44 and E-cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells.

    Science.gov (United States)

    Mao, Meiya; Zheng, Xiaojiao; Jin, Bohong; Zhang, Fubin; Zhu, Linyan; Cui, Lining

    2017-12-01

    CD44 is a prognostic indicator of shorter survival time in ovarian cancer. E-cadherin fragmentation promotes the progression of ovarian cancer. However, the effects of CD44 and E-cadherin overexpression on ovarian cancer cells have remained elusive. The present study aimed to investigate the effects of overexpression of CD44 and E-cadherin on cell proliferation, adhesion and invasion of SKOV-3 and OVCAR-3 ovarian cancer cells. Overexpression of CD44 and E-cadherin was achieved by transfecting SKOV-3 and OVCAR-3 cells with viruses carrying the CD44 or E-cadherin gene, respectively. Expression of CD44 and E-cadherin was detected by western blot analysis. The proliferation of SKOV-3 and OVCAR-3 cells was measured by a Cell Counting Kit-8 at 0, 24 and 48 h after viral transfection. The adhesion ability of SKOV-3 and OVCAR-3 cells to the endothelial layer was detected. A Transwell invasion assay was utilized to assess the invasion ability of the cells. Overexpression of CD44 and E-cadherin in SKOV-3 and OVCAR-3 cells was confirmed by western blot. Compared with the blank or negative control groups, the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells exhibited an increased cell proliferation rate at 24 and 48 h, whereas overexpression of E-cadherin did not alter the proliferation of these cells. Furthermore, compared with the blank and negative control groups, the cell adhesion and invasion ability in the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells was markedly higher. There were no significant differences in adhesion ability between the E-cadherin overexpression group and the blank/negative control group. Of note, overexpression of E-cadherin decreased the invasive ability of SKOV-3 and OVCAR-3 cells. In conclusion, Overexpression of CD44 increased the proliferation, adhesion and invasion of ovarian cancer cells, while overexpression of E-cadherin decreased the invasion of ovarian cancer cells.

  13. Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms

    DEFF Research Database (Denmark)

    Law, M E; Corsino, P E; Jahn, S C

    2013-01-01

    Aggressive cancers often express E-cadherin in cytoplasmic vesicles rather than on the plasma membrane and this may contribute to the invasive phenotype of these tumors. Therapeutic strategies are not currently available that restore the anti-invasive function of E-cadherin in cancers. MDA-MB-231...

  14. Hybrid minimally invasive esophagectomy for cancer: impact on postoperative inflammatory and nutritional status.

    Science.gov (United States)

    Scarpa, M; Cavallin, F; Saadeh, L M; Pinto, E; Alfieri, R; Cagol, M; Da Roit, A; Pizzolato, E; Noaro, G; Pozza, G; Castoro, C

    2016-11-01

    The purpose of this case-control study was to evaluate the impact of hybrid minimally invasive esophagectomy for cancer on surgical stress response and nutritional status. All 34 consecutive patients undergoing hybrid minimally invasive esophagectomy for cancer at our surgical unit between 2008 and 2013 were retrospectively compared with 34 patients undergoing esophagectomy with open gastric tubulization (open), matched for neoadjuvant therapy, pathological stage, gender and age. Demographic data, tumor features and postoperative course (including quality of life and systemic inflammatory and nutritional status) were compared. Postoperative course was similar in terms of complication rate. Length of stay in intensive care unit was shorter in patients undergoing hybrid minimally invasive esophagectomy (P = 0.002). In the first postoperative day, patients undergoing hybrid minimally invasive esophagectomy had lower C-reactive protein levels (P = 0.001) and white cell blood count (P = 0.05), and higher albumin serum level (P = 0.001). In this group, albumin remained higher also at third (P = 0.06) and seventh (P = 0.008) postoperative day, and C-reactive protein resulted lower at third post day (P = 0.04). Hybrid minimally invasive esophagectomy significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter length of stay in intensive care unit. © 2015 International Society for Diseases of the Esophagus.

  15. Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor

    International Nuclear Information System (INIS)

    Chen, Zhi-ao; Bao, Mei-yan; Xu, Yong-fen; Zha, Ruo-peng; Shi, Hai-bing; Chen, Tao-yang; He, Xiang-huo

    2012-01-01

    To investigate the roles of the γ-aminobutyric acid (GABA) in the metastasis of hepatocellular carcinoma (HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC. The expression levels of GABA receptor subunit genes in various HCC cell lines and patients‘ tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABA A receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system

  16. Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients.

    Science.gov (United States)

    Wang, Tingting; Abou-Ouf, Hatem; Hegazy, Samar A; Alshalalfa, Mohammed; Stoletov, Konstantin; Lewis, John; Donnelly, Bryan; Bismar, Tarek A

    2016-12-01

    Ankyrin G (ANK3) is a member of the Ankyrin family, which functions to provide cellular stability by anchoring the cytoskeleton to the plasma membrane. Deregulation of ANK3 expression has been observed in multiple human cancers but its mechanism remains unknown. ANK3 expression in relation to disease progression and patients' outcome was investigated in two cohorts of prostate cancer (PCA). Mechanistic studies were carried out in vitro and in vivo using several PCA cell lines and the avian embryo model. Silencing ANK3 resulted in significant reduction of cell proliferation through an AR-independent mechanism. Decreased ANK3 expression delayed S phase to G2/M cell cycle transition and reduced the expression of cyclins A and B. However, cells with knocked-down ANK3 exhibited significant increase in cell invasion through an AR-dependent mechanism. Furthermore, we found that ANK3 is a regulator of AR protein stability. ANK3 knockdown also promoted cancer cell invasion and extravasations in vivo using the avian embryo model (p cancer tissues was correlated with better cancer-specific survival of PCA patients (p = 0.012). Silencing ANK3 results in significant reduction of cell proliferation through an AR-independent mechanism. ANK3 knockdown results in significant increase in cell invasion through an AR-dependent mechanism. ANK3 is a regulator of AR protein stability. ANK3 knockdown also promotes cancer cell invasion and extravasation in vivo using the avian embryo model.

  17. Effect of cell-phone radiofrequency on angiogenesis and cell invasion in human head and neck cancer cells.

    Science.gov (United States)

    Alahmad, Yaman M; Aljaber, Mohammed; Saleh, Alaaeldin I; Yalcin, Huseyin C; Aboulkassim, Tahar; Yasmeen, Amber; Batist, Gerald; Moustafa, Ala-Eddin Al

    2018-05-13

    Today, the cell phone is the most widespread technology globally. However, the outcome of cell-phone radiofrequency on head and neck cancer progression has not yet been explored. The chorioallantoic membrane (CAM) and human head and neck cancer cell lines, FaDu and SCC25, were used to explore the outcome of cell-phone radiofrequency on angiogenesis, cell invasion, and colony formation of head and neck cancer cells, respectively. Western blot analysis was used to investigate the impact of the cell phone on the regulation of E-cadherin and Erk1/Erk2 genes. Our data revealed that cell-phone radiofrequency promotes angiogenesis of the CAM. In addition, the cell phone enhances cell invasion and colony formation of human head and neck cancer cells; this is accompanied by a downregulation of E-cadherin expression. More significantly, we found that the cell phone can activate Erk1/Erk2 in our experimental models. Our investigation reveals that cell-phone radiofrequency could enhance head and neck cancer by stimulating angiogenesis and cell invasion via Erk1/Erk2 activation. © 2018 Wiley Periodicals, Inc.

  18. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  19. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

    Science.gov (United States)

    Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

    2017-01-01

    Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  20. ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study

    DEFF Research Database (Denmark)

    Doherty, Jennifer A; Rossing, Mary Anne; Cushing-Haugen, Kara L

    2010-01-01

    , respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat...... through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95......% CI, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190...

  1. Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4 activated Wnt pathway.

    Science.gov (United States)

    Lin, Xiao-Lin; Xu, Qi; Tang, Lei; Sun, Li; Han, Ting; Wang, Li-Wei; Xiao, Xiu-Ying

    2017-01-01

    Regorafenib is an oral small-molecule multi kinase inhibitor. Recently, several clinical trials have revealed that regorafenib has an anti-tumor activity in gastric cancer. However, only part of patients benefit from regorafenib, and the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In this study, we would assess the potential anti-tumor effects and the underlying mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers for patients selecting of regorafenib. The anti-tumor effects of regorafenib on gastric cancer cells were analyzed via cell proliferation and invasion. The underlying mechanisms were demonstrated using molecular biology techniques. We found that regorafenib inhibited cell proliferation and invasion at the concentration of 20μmol/L and in a dose dependent manner. The anti-tumor effects of regorafenib related to the decreased expression of CXCR4, and elevated expression and activation of CXCR4 could reverse the inhibition effect of regorafenib on gastric cancer cells. Further studies revealed that regorafenib reduced the transcriptional activity of Wnt/β-Catenin pathway and led to decreased expression of Wnt pathway target genes, while overexpression and activation of CXCR4 could attenuate the inhibition effect of regorafenib on Wnt/β-Catenin pathway. Our findings demonstrated that regorafenib effectively inhibited cell proliferation and invasion of gastric cancer cells via decreasing the expression of CXCR4 and further reducing the transcriptional activity of Wnt/β-Catenin pathway.

  2. Cell-ECM Interactions During Cancer Invasion

    Science.gov (United States)

    Jiang, Yi

    The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

  3. Prognostic factors in invasive bladder cancer

    International Nuclear Information System (INIS)

    Maulard-Durdux, C.; Housset, M.

    1998-01-01

    In France, invasive bladder cancer is the more frequent urologic malignancy after prostate carcinoma. Treatment of bladder cancer is radical cystectomy. New therapeutic approaches such as chemo-radiation combination for a conservative procedure, neo-adjuvant or adjuvant chemotherapy are still developing. In this way, a rigorous selection of patients is needed. This selection is based on prognostic criteria that could be divided into four groups: the volume of the tumor including the tumor infiltration depth, the nodal status, the presence or not of hydronephrosis and the residual tumor mass after trans-urethral resection; the histologic aspects of the tumor including histologic grading, the presence or not of an epidermoid metaplasia, of in situ carcinoma or of thrombi; the expression of tumor markers tissue polypeptide antigen, bladder tumor antigen; the biologic aspects of the tumor as ploidy, cytogenetic abnormalities, expression of Ki67, expression of oncogenes or tumor suppressor genes, expression of tumor antigens or growth factor receptors. This paper reviews the prognostic value of the various parameters. (authors)

  4. Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

    International Nuclear Information System (INIS)

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-01-01

    Highlights: ► Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE 2 . ► The fibroblasts interact with human colonic epithelial cancer cells. ► Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. ► Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

  5. PAX2 is activated by estradiol in breast cancer cells of the luminal subgroup selectively, to confer a low invasive phenotype

    Science.gov (United States)

    2011-01-01

    Background Metastasis is the leading cause of death among breast cancer patients. Identifying key cellular factors controlling invasion and metastasis of breast cancer cells should pave the way to new therapeutic strategies efficiently interfering with the metastatic process. PAX2 (paired box 2) transcription factor is expressed by breast cancer cells in vivo and recently, it was shown to negatively regulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented pro-invasive and pro-metastastic gene, in luminal/ERalpha-positive (ERα+) breast cancer cells. The objective of the present study was to investigate a putative role for PAX2 in the control of luminal breast cancer cells invasion, and to begin to characterize its regulation. Results PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype, and activation of PAX2 by estradiol was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by ICI 182780 and could be antagonized by IGF-1. Knockdown of PAX2 in luminal MCF-7 cells completely abrogated estradiol-induced downregulation of ERBB2 and decrease of cell invasion, whereas overexpression of PAX2 in these cells enhanced estradiol effects on ERBB2 levels and cell invasion. Conclusions The study demonstrates that PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα, and identifies IGF-1 as a negative regulator of PAX2 activity in these cells. Further, it reveals a new role for PAX2 in the maintenance of a low invasive behavior in luminal breast cancer cells upon exposure to estradiol, and shows that overexpression and activation of PAX2 in these cells is sufficient to reduce their invasive ability. PMID:22168360

  6. Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion

    Science.gov (United States)

    House, Carrie D.; Vaske, Charles J.; Schwartz, Arnold M.; Obias, Vincent; Frank, Bryan; Luu, Truong; Sarvazyan, Narine; Irby, Rosalyn; Strausberg, Robert L.; Hales, Tim G.; Stuart, Joshua M.; Lee, Norman H.

    2010-01-01

    Voltage-gated Na+ channels (VGSCs) have been implicated in the metastatic potential of human breast, prostate and lung cancer cells. Specifically, the SCN5A gene encoding the VGSC isotype Nav1.5 has been defined as a key driver of human cancer cell invasion. In this study, we examined the expression and function of VGSCs in a panel of colon cancer cell lines by electrophysiological recordings. Na+ channel activity and invasive potential were inhibited pharmacologically by tetrodotoxin or genetically by siRNAs specifically targeting SCN5A. Clinical relevance was established by immunohistochemistry of patient biopsies, where there was strong Nav1.5 protein staining in colon cancer specimens but little to no staining in matched-paired normal colon tissues. We explored the mechanism of VGSC-mediated invasive potential on the basis of reported links between VGSC activity and gene expression in excitable cells. Probabilistic modeling of loss-of-function screens and microarray data established an unequivocal role of VGSC SCN5A as a high level regulator of a colon cancer invasion network, involving genes that encompass Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process and cell cycle control. siRNA-mediated knockdown of predicted downstream network components caused a loss of invasive behavior, demonstrating network connectivity and its function in driving colon cancer invasion. PMID:20651255

  7. FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition.

    Science.gov (United States)

    Ogunbolude, Yetunde; Dai, Chenlu; Bagu, Edward T; Goel, Raghuveera Kumar; Miah, Sayem; MacAusland-Berg, Joshua; Ng, Chi Ying; Chibbar, Rajni; Napper, Scott; Raptis, Leda; Vizeacoumar, Frederick; Vizeacoumar, Franco; Bonham, Keith; Lukong, Kiven Erique

    2017-12-22

    The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells. Finally, we interrogated the TCGA and GENT gene expression databases to determine the correlation between the expression of FRK and epithelial/mesenchymal markers. We observed that FRK overexpression suppressed cell proliferation, migration, and invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and suppressed the expression of some STAT3 target genes. Also, FRK overexpression increased the expression of epithelial markers including E-cadherin mRNA and down-regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we observed an inverse correlation between FRK expression and mesenchymal markers in a large cohort of breast cancer cells. Our data, therefore, suggests that FRK represses cell proliferation, migration and invasiveness by suppressing epithelial to mesenchymal transition.

  8. Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer : An international validation in primary tumours

    NARCIS (Netherlands)

    M.M. Vedder (Moniek); M. Márquez (Mirari); E.W. de Bekker-Grob (Esther); M.L. Calle (Malu); L. Dyrskjot (Lars); M. Kogevinas (Manolis); U. Segersten (Ulrika); P.-U. Malmström (Per-Uno); F. Algaba (Ferran); W. Beukers (Willemien); T.F. Orntoft (Torben); E.C. Zwarthoff (Ellen); F.X. Real (Francisco); N. Malats (Núria); E.W. Steyerberg (Ewout)

    2014-01-01

    textabstractObjective: We aimed to determine the validity of two risk scores for patients with non-muscle invasive bladder cancer in different European settings, in patients with primary tumours. Methods: We included 1,892 patients with primary stage Ta or T1 non-muscle invasive bladder cancer who

  9. Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells.

    Science.gov (United States)

    Sigstedt, Sophia C; Hooten, Carla J; Callewaert, Manika C; Jenkins, Aaron R; Romero, Anntherese E; Pullin, Michael J; Kornienko, Alexander; Lowrey, Timothy K; Slambrouck, Severine Van; Steelant, Wim F A

    2008-05-01

    Ethnotraditional use of plant-derived natural products plays a significant role in the discovery and development of potential medicinal agents. Plants of the genus Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat a variety of diseases including cancer. To date, however, very few studies have been reported on the anti-carcinogenic activity of Taraxacum officinale (TO). In the present study, three aqueous extracts were prepared from the mature leaves, flowers and roots, and investigated on tumor progression related processes such as proliferation and invasion. Our results show that the crude extract of dandelion leaf (DLE) decreased the growth of MCF-7/AZ breast cancer cells in an ERK-dependent manner, whereas the aqueous extracts of dandelion flower (DFE) and root (DRE) had no effect on the growth of either cell line. Furthermore, DRE was found to block invasion of MCF-7/AZ breast cancer cells while DLE blocked the invasion of LNCaP prostate cancer cells, into collagen type I. Inhibition of invasion was further evidenced by decreased phosphorylation levels of FAK and src as well as reduced activities of matrix metalloproteinases, MMP-2 and MMP-9. This study provides new scientific data on TO and suggests that TO extracts or individual components present in the extracts may be of value as novel anti-cancer agents.

  10. In vitro characterization of cancer cell morphology, chemokinesis, and matrix invasion using a novel microfabricated system

    Science.gov (United States)

    Blaha, Laura

    A diagnosis of metastatic cancer reduces a patient's 5-year survival rate by nearly 80% compared to a primary tumor diagnosed at an early stage. While gene expression arrays have revealed unique gene signatures for metastatic cancer cells, we are lacking an understanding of the tangible physical changes that distinguish metastatic tumor cells from each other and from their related primary tumors. At the fundamental level, this translates into first characterizing the phenotype of metastatic cancer cells in vitro both in 2D - looking at morphology and migration - and in 3D - focusing on matrix invasion. While 2D in vitro studies have provided insight into the effects of specific environmental conditions on specific cancer cell lines, the unique details included in each experimental design make it challenging to compare cell phenotype across different in vitro platforms as well as between laboratories and disciplines that share the goal of understanding cancer. While 3D phenotype studies have employed more standardized and ubiquitous assays, most available tools lack the imaging capability and geometry to effectively characterize all factors driving 3D matrix invasion. In this work, we present protocols and platforms aimed at addressing the problems identified in the tools currently available for studying metastatic cancer in vitro. First, we present a 2D study of morphology and migration using widely accepted protocols. The study is applied to characterizing phenotypes of three breast cancer cell lines with different metastatic organ tropisms. The results show that general populations of cells from each of the 3 lines are unique in shape and motility despite being derived from the same tumor line and that the observed phenotype differences may be related to differences in focal adhesion assembly. More broadly, these studies suggest that standardizing phenotype studies using commonly available techniques may provide a platform by which to compare phenotypic studies

  11. Histological outcomes in conventional cervical cytology for invasive carcinoma: not always cancer.

    Science.gov (United States)

    Peixoto Pereira, Flávia Regina; Soares, Leila Cristina; de Oliveira, Marco Aurélio Pinho

    2017-11-01

    The value of cytology for the detection of invasive cancer remains unknown. We performed a retrospective cohort study with 884 patients diagnosed of premalignant lesions and invasive carcinoma in cytology. 382 (43.2%) of them had cytological results of high-grade squamous intraepithelial lesions (HSIL), 244 (27.6%) showed low-grade squamous intraepithelial lesions (LSIL), 120 (13.6%) patients had atypical squamous cells of undetermined significance (ASC-US), 67 (7.6%) patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 38 (4.3%) had invasive carcinoma and 33 (3.7%) patients presented with atypical glandular cells (ACG). From 38 patients with cytological results of invasive carcinoma, 24 had confirmatory histological results (63.2%). The other 14 had 4 benign lesions and 10 HSIL. The predictive positive value (PPV) was 63.2%. Cytology results of carcinoma do not confer a definitive diagnosis of invasive lesion, but it is strongly an indication of, at least, a precancerous lesion.

  12. Concomitant boost radiotherapy for muscle invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pos, Floris J; Tienhoven, Geertjan van; Hulshof, Maarten C.C.M.; Koedooder, Kees; Gonzalez Gonzalez, Dionisio

    2003-07-01

    Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity {>=}G3 was observed in seven patients (14%). Severe late toxicity {>=}G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity.

  13. Concomitant boost radiotherapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Pos, Floris J.; Tienhoven, Geertjan van; Hulshof, Maarten C.C.M.; Koedooder, Kees; Gonzalez Gonzalez, Dionisio

    2003-01-01

    Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity ≥G3 was observed in seven patients (14%). Severe late toxicity ≥G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity

  14. Vascular endothelial growth factor C promotes cervical cancer cell invasiveness via regulation of microRNA-326/cortactin expression.

    Science.gov (United States)

    Cheng, Yang; Jiang, Shuyi; Yuan, Jin; Liu, Junxiu; Simoncini, Tommaso

    2018-04-16

    Vascular endothelial growth factor C (VEGF-C) accelerates cervical cancer metastasis, while the detailed mechanism remains largely unknown. Recent evidence indicates that microRNA play a crucial role in controlling cancer cell invasiveness. In the present study, we investigated the role of miR-326 in VEGF-C-induced cervical cancer cell invasion. VEGF-C expression was higher and miR-326 was much lower in primary cervical cancer specimens than that in non-cancerous specimens, and a negative correlation between VEGF-C and miR-326 was found. On cervical carcinoma cell line SiHa cells, treatment with VEGF-C downregulated miR-326 level and increased cortactin protein expression. Transfection with miR-326 mimic reversed cortactin expression induced by VEGF-C, suggesting that VEGF-C increased cortactin via downregulation of miR-326. VEGF-C activated c-Src and c-Src inhibitor PP2 abolished VEGF-C effect on miR-326 and cortactin expression, implying that VEGF-C regulated miR-326/cortactin via c-Src signaling. VEGF-C promoted SiHa cell invasion index, which was largely inhibited by transfection with miR-326 antagonist or by siRNA against cortactin. In conclusion, our findings implied that VEGF-C reduced miR-326 expression and increased cortactin expression through c-Src signaling, leading to enhanced cervical cancer invasiveness. This may shed light on potential therapeutic strategies for cervical cancer therapy.

  15. Skin cancer of the head and neck with incidental microscopic perineural invasion

    International Nuclear Information System (INIS)

    McCord, Mark W.; Mendenhall, William M.; Parsons, James T.; Flowers, Franklin P.

    1999-01-01

    Purpose: To address outcomes in clinically asymptomatic patients in whom the unexpected finding of microscopic perineural invasion is noted at the time of surgery. Methods and Materials: The 35 patients included in this study had skin cancers of the head and neck treated with curative intent between January 1965 and April 1995 at the University of Florida. All patients were without clinical or radiographic evidence of perineural invasion but, at the time of biopsy or surgical excision, had the incidental finding of microscopic perineural invasion. Definitive therapy consisted of radiotherapy alone after lesion biopsy (3 patients) or surgical excision preceded (2 patients) or followed (30 patients) by radiotherapy. All patients had follow-up for at least 1 year, 13 patients (37%) had follow-up for at least 5 years. Results: The 5-year local control rate was 78%. The 5-year local control rate for the few patients treated with radiotherapy alone was statistically similar to that for patients treated with surgery and radiotherapy (100% vs. 77%, p = 0.4). Multivariate analysis for factors affecting local control included sex, histology, age, treatment group, clinical T stage, initial histologic differentiation, and previously untreated vs. recurrent tumors, none of which was found to be significant. Conclusions: Both surgery plus radiotherapy and radiotherapy alone provide a relatively high rate of local control for patients with incidentally discovered perineural invasion secondary to skin cancer

  16. Kinematic design considerations for minimally invasive surgical robots: an overview.

    Science.gov (United States)

    Kuo, Chin-Hsing; Dai, Jian S; Dasgupta, Prokar

    2012-06-01

    Kinematic design is a predominant phase in the design of robotic manipulators for minimally invasive surgery (MIS). However, an extensive overview of the kinematic design issues for MIS robots is not yet available to both mechanisms and robotics communities. Hundreds of archival reports and articles on robotic systems for MIS are reviewed and studied. In particular, the kinematic design considerations and mechanism development described in the literature for existing robots are focused on. The general kinematic design goals, design requirements, and design preferences for MIS robots are defined. An MIS-specialized mechanism, namely the remote center-of-motion (RCM) mechanism, is revisited and studied. Accordingly, based on the RCM mechanism types, a classification for MIS robots is provided. A comparison between eight different RCM types is given. Finally, several open challenges for the kinematic design of MIS robotic manipulators are discussed. This work provides a detailed survey of the kinematic design of MIS robots, addresses the research opportunity in MIS robots for kinematicians, and clarifies the kinematic point of view to MIS robots as a reference for the medical community. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  18. MINIMALLY INVASIVE SURGERY FOR GASTRIC CANCER: TIME TO CHANGE THE PARADIGM.

    Science.gov (United States)

    Barchi, Leandro Cardoso; Jacob, Carlos Eduardos; Bresciani, Cláudio José Caldas; Yagi, Osmar Kenji; Mucerino, Donato Roberto; Lopasso, Fábio Pinatel; Mester, Marcelo; Ribeiro-Júnior, Ulysses; Dias, André Roncon; Ramos, Marcus Fernando Kodama Pertille; Cecconello, Ivan; Zilberstein, Bruno

    2016-01-01

    Minimally invasive surgery widely used to treat benign disorders of the digestive system, has become the focus of intense study in recent years in the field of surgical oncology. Since then, the experience with this kind of approach has grown, aiming to provide the same oncological outcomes and survival to conventional surgery. Regarding gastric cancer, surgery is still considered the only curative treatment, considering the extent of resection and lymphadenectomy performed. Conventional surgery remains the main modality performed worldwide. Notwithstanding, the role of the minimally invasive access is yet to be clarified. To evaluate and summarize the current status of minimally invasive resection of gastric cancer. A literature review was performed using Medline/PubMed, Cochrane Library and SciELO with the following headings: gastric cancer, minimally invasive surgery, robotic gastrectomy, laparoscopic gastrectomy, stomach cancer. The language used for the research was English. 28 articles were considered, including randomized controlled trials, meta-analyzes, prospective and retrospective cohort studies. Minimally invasive gastrectomy may be considered as a technical option in the treatment of early gastric cancer. As for advanced cancer, recent studies have demonstrated the safety and feasibility of the laparoscopic approach. Robotic gastrectomy will probably improve outcomes obtained with laparoscopy. However, high cost is still a barrier to its use on a large scale. A cirurgia minimamente invasiva amplamente usada para tratar doenças benignas do aparelho digestivo, tornou-se o foco de intenso estudo nos últimos anos no campo da oncologia cirúrgica. Desde então, a experiência com este tipo de abordagem tem crescido, com o objetivo de fornecer os mesmos resultados oncológicos e sobrevivência à cirurgia convencional. Em relação ao câncer gástrico, o tratamento cirúrgico ainda é considerado o único tratamento curativo, considerando a extensão da

  19. Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy

    International Nuclear Information System (INIS)

    Wallin, Asa R.; Svanvik, Joar; Adell, Gunnar; Sun Xiaofeng

    2006-01-01

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients. Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT. Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes' stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01). Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT

  20. Summary and Recommendations from the National Cancer Institute's Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

    NARCIS (Netherlands)

    Lerner, S.P.; Bajorin, D.F.; Dinney, C.P.; Efstathiou, J.A.; Groshen, S.; Hahn, N.M.; Hansel, D.; Kwiatkowski, D.; O'Donnell, M.; Rosenberg, J.; Svatek, R.; Abrams, J.S.; Al-Ahmadie, H.; Apolo, A.B.; Bellmunt, J.; Callahan, M.; Cha, E.K.; Drake, C.; Jarow, J.; Kamat, A.; Kim, W.; Knowles, M.; Mann, B.; Marchionni, L.; McConkey, D.; McShane, L.; Ramirez, N.; Sharabi, A.; Sharpe, A.H.; Solit, D.; Tangen, C.M.; Amiri, A.T.; Allen, E. Van; West, P.J.; Witjes, J.A.; Quale, D.Z.

    2016-01-01

    The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from

  1. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gaoyang; Liu, Boning [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Meng, Zhaowei [Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052 (China); Liu, Yunde [School of Laboratory Medicine, Tianjin Medical University, Tianjin 300052 (China); Li, Xuebing [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Wu, Xiang [Core Facility Center, Tianjin Medical University General Hospital, Tianjin 300052 (China); Zhou, Qinghua [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Xu, Ke, E-mail: ke_xu@hotmail.com [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China)

    2017-03-15

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. - Highlights: • miR-26a enhances migration and invasion of lung cancer cells. • GSK3β is identified as a direct target of miR-26a. • miR-26a activates β-catenin pathway by targeting GSK3β. • miR-26a promotes lung cancer cell growth in vivo.

  2. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells

    International Nuclear Information System (INIS)

    Lin, Gaoyang; Liu, Boning; Meng, Zhaowei; Liu, Yunde; Li, Xuebing; Wu, Xiang; Zhou, Qinghua; Xu, Ke

    2017-01-01

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. - Highlights: • miR-26a enhances migration and invasion of lung cancer cells. • GSK3β is identified as a direct target of miR-26a. • miR-26a activates β-catenin pathway by targeting GSK3β. • miR-26a promotes lung cancer cell growth in vivo.

  3. Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer.

    Science.gov (United States)

    Jencks, David S; Adam, Jason D; Borum, Marie L; Koh, Joyce M; Stephen, Sindu; Doman, David B

    2018-02-01

    Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation.

  4. A core invasiveness gene signature reflects epithelial-to-mesenchymal transition but not metastatic potential in breast cancer cell lines and tissue samples.

    Directory of Open Access Journals (Sweden)

    Melike Marsan

    Full Text Available INTRODUCTION: Metastases remain the primary cause of cancer-related death. The acquisition of invasive tumour cell behaviour is thought to be a cornerstone of the metastatic cascade. Therefore, gene signatures related to invasiveness could aid in stratifying patients according to their prognostic profile. In the present study we aimed at identifying an invasiveness gene signature and investigated its biological relevance in breast cancer. METHODS & RESULTS: We collected a set of published gene signatures related to cell motility and invasion. Using this collection, we identified 16 genes that were represented at a higher frequency than observed by coincidence, hereafter named the core invasiveness gene signature. Principal component analysis showed that these overrepresented genes were able to segregate invasive and non-invasive breast cancer cell lines, outperforming sets of 16 randomly selected genes (all P<0.001. When applied onto additional data sets, the expression of the core invasiveness gene signature was significantly elevated in cell lines forced to undergo epithelial-mesenchymal transition. The link between core invasiveness gene expression and epithelial-mesenchymal transition was also confirmed in a dataset consisting of 2420 human breast cancer samples. Univariate and multivariate Cox regression analysis demonstrated that CIG expression is not associated with a shorter distant metastasis free survival interval (HR = 0.956, 95%C.I. = 0.896-1.019, P = 0.186. DISCUSSION: These data demonstrate that we have identified a set of core invasiveness genes, the expression of which is associated with epithelial-mesenchymal transition in breast cancer cell lines and in human tissue samples. Despite the connection between epithelial-mesenchymal transition and invasive tumour cell behaviour, we were unable to demonstrate a link between the core invasiveness gene signature and enhanced metastatic potential.

  5. Knockdown of ZFR suppresses cell proliferation and invasion of human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Xiaolan Zhao

    Full Text Available BACKGROUND: Zinc finger RNA binding protein (ZFR is involved in the regulation of growth and cancer development. However, little is known about ZFR function in pancreatic cancer. METHODS: Herein, to investigate whether ZFR is involved in tumor growth, Oncomine microarray data was firstly used to evaluate ZFR gene expression in human pancreatic tumors. Then short hairpin RNA (shRNA targeting ZFR was designed and delivered into PANC-1 pancreatic cancer cells to knock down ZFR expression. Cell viability, cell proliferation and cell cycle analysis after ZFR knockdown were determined by MTT, colony forming and FACS, respectively. In addition, cell migration and invasion were assessed using the Transwell system. RESULTS: The expression of ZFR was significantly higher in pancreatic tumors than normal pancreas tissues by Oncomine database analysis. Knockdown of ZFR by shRNA-expressing lentivirus significantly decreased the viability and invasion ability of pancreatic cancer cells. Moreover, FACS analysis showed that knockdown of ZFR in PANC-1 cells caused a significant cell cycle arrest at G0/G1 phase. Furthermore, knockdown of ZFR decreased the levels of CDK2, CDK4, CyclinA and CyclinD1 and enhanced the expression of p27, which has evidenced by qRT-PCR and Western blot analysis. CONCLUSIONS: Knockdown of ZFR might provide a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.

  6. Introducing a prognostic score for pretherapeutic assessment of seminal vesicle invasion in patients with clinically localized prostate cancer

    International Nuclear Information System (INIS)

    Salomon, Laurent; Porcher, Raphaeel; Anastasiadis, Aristotelis G.; Levrel, Olivier; Saint, Fabian; Taille, Alexandre de la; Vordos, Dimitrios; Cicco, Antony; Hoznek, Andras; Chopin, Dominique; Abbou, Clement-Claude; Lagrange, Jean-Leon

    2003-01-01

    Purpose: To identify prostate cancer patients who will have the most likely benefit from sparing the seminal vesicles during 3D conformal radiation therapy. Methods and materials: From 1988 to 2001, 532 patients underwent radical prostatectomy for clinically localized prostate cancer. Primary endpoint was the pathological evidence of seminal vesicle invasion. Variables for univariate and multivariate analyses were age, prostate weight, clinical stage, PSA level, Gleason score, number and site of positive prostate sextant biopsies. Multivariate logistic regression with backward stepwise variable selection was used to identify a set of independent predictors of seminal vesicle invasion, and the variable selection procedure was validated by non-parametric bootstrap. Results: Seminal vesicle invasion was reported in 14% of the cases. In univariate analysis, all variables except age and prostate weight were predictors of seminal vesicle invasion. In multivariate analysis, only the number of positive biopsies (P<0.0001), Gleason score (P<0.007) and PSA (P<0.0001) were predictors for seminal vesicles invasion. Based on the multivariate model, we were able to develop a prognostic score for seminal vesicle invasion, which allowed us to discriminate two patient groups: A group with low risk of seminal vesicles invasion (5.7%), and the second with a higher risk of seminal vesicles invasion (32.7%). Conclusions: Using the number of positive biopsies, Gleason score and PSA, it is possible to identify patients with low risk of seminal vesicles invasion. In this population, seminal vesicles might be excluded as a target volume in radiation therapy of prostate cancer

  7. Silencing of the integrin-linked kinase gene suppresses the proliferation, migration and invasion of pancreatic cancer cells (Panc-1).

    Science.gov (United States)

    Zhu, Xiang-Yu; Liu, Ning; Liu, Wei; Song, Shao-Wei; Guo, Ke-Jian

    2012-04-01

    Integrin-linked kinase (ILK) is an ankyrin repeat-containing serine-threonine protein kinase that is involved in the regulation of integrin-mediated processes such as cancer cell proliferation, migration and invasion. In this study, we examined the effect of a lentivirus-mediated knockdown of ILK on the proliferation, migration and invasion of pancreatic cancer (Panc-1) cells. Immunohistochemical staining showed that ILK expression was enhanced in pancreatic cancer tissue. The silencing of ILK in human Panc-1 cells led to cell cycle arrest in the G0/G1 phase and delayed cell proliferation, in addition to down-regulating cell migration and invasion. The latter effects were mediated by up-regulating the expression of E-cadherin, a key protein in cell adhesion. These findings indicate that ILK may be a new diagnostic marker for pancreatic cancer and that silencing ILK could be a potentially useful therapeutic approach for treating pancreatic cancer.

  8. Myometrial invasion in endometrial cancer: diagnostic performance of diffusion-weighted MR imaging at 1.5-T

    International Nuclear Information System (INIS)

    Rechichi, Gilda; Sironi, Sandro; Galimberti, Stefania; Valsecchi, Maria Grazia; Signorelli, Mauro; Perego, Patrizia

    2010-01-01

    To determine the diagnostic accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging in the preoperative assessment of myometrial invasion by endometrial cancer. In this prospective study, 47 patients with histologically confirmed endometrial cancer underwent preoperative MR imaging and total hysterectomy. The MR protocol included spin-echo multishot T2-weighted, dynamic T1-weighted and DW images acquired with b-values of 0 and 500 s/mm 2 . Myometrial tumour spread was classified as superficial (<50%) or deep (≥50% myometrial thickness). Postoperative histopathological findings served as a reference standard. Indices of diagnostic performance were assessed for each sequence. At histopathological examination, superficial myometrial invasion was found in 34 patients and deep myometrial invasion in 13. In the assessment of tumour invasion, sensitivity, specificity, positive and negative predictive values of T2-weighted images were 92.3%, 76.5%, 60.0% and 96.3%, respectively. The corresponding values for dynamic images were 69.2%, 61.8%, 40.9% and 84.0%, and for DW images 84.6%, 70.6%, 52.4% and 92.3%. T2-weighted and DW imaging proved to be the most accurate techniques for tumour spread determination. DW imaging proved to be accurate in assessing myometrial invasion, and it could replace dynamic imaging as an adjunct to routine T2-weighted imaging for preoperative evaluation of endometrial cancer. (orig.)

  9. Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Yijing; Tang, Huijuan; Guo, Yan; Guo, Jing; Huang, Bangxing; Fang, Fang; Cai, Jing, E-mail: caijingmmm@hotmail.com; Wang, Zehua, E-mail: zehuawang@163.net

    2015-09-10

    Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs.

  10. Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Chu, Yijing; Tang, Huijuan; Guo, Yan; Guo, Jing; Huang, Bangxing; Fang, Fang; Cai, Jing; Wang, Zehua

    2015-01-01

    Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs

  11. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    Science.gov (United States)

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

  12. RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13.

    Directory of Open Access Journals (Sweden)

    Ila Datar

    Full Text Available Raf Kinase Inhibitory Protein or RKIP was initially identified as a Raf-1 binding protein using the yeast 2-hybrid screen. RKIP inhibits the activation phosphorylation of MEK by Raf-1 by competitively inhibiting the binding of MEK to Raf-1 and thus exerting an inhibitory effect on the Raf-MEK-Erk pathway. RKIP has been identified as a metastasis suppressor gene. Expression of RKIP is low in cancer metastases. Although primary tumor growth remains unaffected, re- expression of RKIP inhibits cancer metastasis. Mechanistically, RKIP constrains metastasis by inhibiting angiogenesis, local invasion, intravasation, and colonization. The molecular mechanism of how RKIP inhibits these individual steps remains undefined. In our present study, using an unbiased PCR based screening and by analyzing DNA microarray expression datasets we observe that the expression of multiple metalloproteases (MMPs including MMP1, MMP3, MMP10 and MMP13 are negatively correlated with RKIP expression in breast cancer cell lines and clinical samples. Since expression of MMPs by cancer cells is important for cancer metastasis, we hypothesize that RKIP may mediate suppression of breast cancer metastasis by inhibiting multiple MMPs. We show that the expression signature of RKIP and MMPs is better at predicting high metastatic risk than the individual gene. Using a combination of loss- and gain-of-function approaches, we find that MMP13 is the cause of RKIP-mediated inhibition of local cancer invasion. Interestingly expression of MMP13 alone is not sufficient to reverse the inhibition of breast cancer cell metastasis to the lung due to the expression of RKIP. We find that RKIP negatively regulates MMP13 through the Erk2 signaling pathway and the repression of MMP13 by RKIP is transcription factor AP-1 independent. Together, our findings indicate that RKIP inhibits cancer cell invasion, in part, via MMP13 inhibition. These data also implicate RKIP in the regulation of MMP

  13. P2Y2 Receptor and EGFR Cooperate to Promote Prostate Cancer Cell Invasion via ERK1/2 Pathway.

    Science.gov (United States)

    Li, Wei-Hua; Qiu, Ying; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

    2015-01-01

    As one member of G protein-coupled P2Y receptors, P2Y2 receptor can be equally activated by extracellular ATP and UTP. Our previous studies have proved that activation of P2Y2 receptor by extracellular ATP could promote prostate cancer cell invasion and metastasis in vitro and in vivo via regulating the expressions of some epithelial-mesenchymal transition/invasion-related genes (including IL-8, E-cadherin, Snail and Claudin-1), and the most significant change in expression of IL-8 was observed after P2Y2 receptor activation. However, the signaling pathway downstream of P2Y2 receptor and the role of IL-8 in P2Y2-mediated prostate cancer cell invasion remain unclear. Here, we found that extracellular ATP/UTP induced activation of EGFR and ERK1/2. After knockdown of P2Y2 receptor, the ATP -stimulated phosphorylation of EGFR and ERK1/2 was significantly suppressed. Further experiments showed that inactivation of EGFR and ERK1/2 attenuated ATP-induced invasion and migration, and suppressed ATP-mediated IL-8 production. In addition, knockdown of IL-8 inhibited ATP-mediated invasion and migration of prostate cancer cells. These findings suggest that P2Y2 receptor and EGFR cooperate to upregulate IL-8 production via ERK1/2 pathway, thereby promoting prostate cancer cell invasion and migration. Thus blocking of the P2Y2-EGFR-ERK1/2 pathway may provide effective therapeutic interventions for prostate cancer.

  14. Activation of the PI3K/Akt pathway mediates bone morphogenetic protein 2-induced invasion of pancreatic cancer cells Panc-1.

    Science.gov (United States)

    Chen, Xiong; Liao, Jie; Lu, YeBin; Duan, XiaoHui; Sun, WeiJia

    2011-06-01

    Bone morphogenetic proteins (BMPs) signaling has an emerging role in pancreatic cancer. However, because of the multiple effects of different BMPs, no final conclusions have been made as to the role of BMPs in pancreatic cancer. In our studies, we have focused on bone morphogenetic protein 2(BMP-2) because it induces an epithelial to mesenchymal transition (EMT) and accelerates invasion in the human pancreatic cancer cell line Panc-1. It has been reported that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediates invasion of gastric and colon cancer cells, which is unrevealed in pancreatic cancer cells. The objective of our study was to investigate whether BMP-2 mediated invasion might pass through the PI3K/Akt pathway. Our results show that expression of phosphorylation of Akt was increased by treatment with BMP-2, but not Noggin, a BMP-2 antagonist. Then pretreatment of Panc-1 cells with LY294002, an inhibitor of the PI3K/AKT pathway, significantly inhibited BMP-2-induced EMT and invasiveness. The data suggest that BMP-2 accelerates invasion of panc-1 cells via the PI3K/AKT pathway in panc-1 cells, which gives clues to searching new therapy targets in advanced pancreatic cancer.

  15. Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Faber, Mette T; Jensen, Allan

    2013-01-01

    PURPOSE: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

  16. GPU-based RFA simulation for minimally invasive cancer treatment of liver tumours

    NARCIS (Netherlands)

    Mariappan, P.; Weir, P.; Flanagan, R.; Voglreiter, P.; Alhonnoro, T.; Pollari, M.; Moche, M.; Busse, H.; Futterer, J.J.; Portugaller, H.R.; Sequeiros, R.B.; Kolesnik, M.

    2017-01-01

    PURPOSE: Radiofrequency ablation (RFA) is one of the most popular and well-standardized minimally invasive cancer treatments (MICT) for liver tumours, employed where surgical resection has been contraindicated. Less-experienced interventional radiologists (IRs) require an appropriate planning tool

  17. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    allele OR, 0.95; 95% CI, 0.91-0.99; P(trend) = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

  18. Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Yingting, E-mail: yitizhu@yahoo.com [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States); Tissue Tech Inc., Miami, FL 33173 (United States); Zhu, Min; Lance, Peter [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE{sub 2}. Black-Right-Pointing-Pointer The fibroblasts interact with human colonic epithelial cancer cells. Black-Right-Pointing-Pointer Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. Black-Right-Pointing-Pointer Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

  19. Lentivirus mediated RNA interference of EMMPRIN (CD147) gene inhibits the proliferation, matrigel invasion and tumor formation of breast cancer cells.

    Science.gov (United States)

    Yang, Jing; Wang, Rong; Li, Hongjiang; Lv, Qing; Meng, Wentong; Yang, Xiaoqin

    2016-07-08

    Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), a glycoprotein enriched on the plasma membrane of tumor cells, promotes proliferation, invasion, metastasis, and survival of malignant tumor cells. In this study, we sought to examine the expression of EMMPRIN in breast tumors, and to identify the potential roles of EMMPRIN on breast cancer cells. EMMPRIN expression in breast cancer tissues was assessed by immunohistochemistry. We used a lentivirus vector-based RNA interference (RNAi) approach expressing short hairpin RNA (shRNA) to knockdown EMMPRIN gene in breast cancer cell lines MDA-MB-231 and MCF-7. In vitro, Cell proliferative, invasive potential were determined by Cell Counting Kit (CCK-8), cell cycle analysis and matrigel invasion assay, respectively. In vivo, tumorigenicity was monitored by inoculating tumor cells into breast fat pad of female nude mice. EMMPRIN was over-expressed in breast tumors and breast cancer cell lines. Down-regulation of EMMPRIN by lentivirus vector-based RNAi led to decreased cell proliferative, decreased matrigel invasion in vitro, and attenuated tumor formation in vivo. High expression of EMMPRIN plays a crucial role in breast cancer cell proliferation, matrigel invasion and tumor formation.

  20. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion.

    Science.gov (United States)

    Cekanova, Maria; Fernando, Romaine I; Siriwardhana, Nalin; Sukhthankar, Mugdha; De la Parra, Columba; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J; Wade, Paul A; Saxton, Arnold M; Donnell, Robert M; Pestell, Richard G; Dharmawardhane, Suranganie; Wimalasena, Jay

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Physical break-down of the classical view on cancer cell invasion and metastasis.

    Science.gov (United States)

    Mierke, Claudia T

    2013-03-01

    Eight classical hallmarks of cancer have been proposed and are well-defined by using biochemical or molecular genetic methods, but are not yet precisely defined by cellular biophysical processes. To define the malignant transformation of neoplasms and finally reveal the functional pathway, which enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific biomechanical properties of cancer cells and their microenvironment such as the extracellular matrix and embedded cells such as fibroblasts, macrophages or endothelial cells. Nonetheless a main novel ninth hallmark of cancer is still elusive in classical tumor biological reviews, which is the aspect of physics in cancer disease by the natural selection of an aggressive (highly invasive) subtype of cancer cells. The physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present current cancer research in a different light and will focus on novel physical methods to investigate the aggressiveness of cancer cells from a biophysicist's point of view. This may lead to novel insights into cancer disease and will overcome classical views on cancer. In addition, this review will discuss how physics of cancer can help to reveal whether cancer cells will invade connective tissue and metastasize. In particular, this review will point out how physics can improve, break-down or support classical approaches to examine tumor growth even across primary tumor boundaries, the invasion of single or collective cancer cells, transendothelial migration of cancer cells and metastasis in targeted organs. Finally, this review will show how physical measurements can be integrated into classical tumor biological analysis approaches. The insights into physical interactions between cancer cells, the primary tumor and the microenvironment may help to solve some "old" questions in cancer disease progression and may finally lead to novel

  2. Studies on MRI diagnostic accuracy of invasion to body muscular layer and cervix of endometrial cancer

    International Nuclear Information System (INIS)

    Takemoto, Yumi; Fujiyoshi, Keizou; Takemoto, Shuji; Kawano, Kouichirou; Ohta, Shunichirou; Murakami, Fumihiro; Komai, Kan; Ushijima, Kimio; Kamura, Toshiharu

    2008-01-01

    This study was conducted to know usefulness of preoperative MRI to detect invasions of endometrial cancer to uterine body muscular layer and cervix. Subjects were 132 patients (median age of 57 y, pre- and post-menopause, 11.2 and 78.8%, respectively) with the cancer at stage I (66 cases) and >II in authors' facility, who had undergone the preoperative MRI with 1.5T Siemens machine by imaging with T1 and T2 weighted, Gd-enhanced T1 weighted, dynamic study and STIR. Imaging findings were compared with histopathological ones to assess the accuracy of imaging diagnosis. Positive predictive accuracy for muscular invasion was found to be as high as 95.5% and negative one, as low as 29.5%: especially, in pre-menopause group, tendency of underestimation for the invasion was thought notable. In contrast, negative accuracy was found low for cervical invasion and positive one, high: overestimation was possibly occurring. Thus, MRI diagnosis of those invasions should be seriously judged with careful consideration of menopause state. (R.T.)

  3. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

    Science.gov (United States)

    Kalhori, Veronica; Törnquist, Kid

    2015-03-15

    The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Yu-Lin Zhao

    2017-07-01

    Full Text Available Objective: To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion. Methods: A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy. Results: Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, proproliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group; anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group; pro-invasion genes γ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group; anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group. Conclusions: Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

  5. In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

    DEFF Research Database (Denmark)

    Damstrup, L; Rude Voldborg, B; Spang-Thomsen, M

    1998-01-01

    receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot...... analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16......-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition...

  6. Genomic Characterization of Primary Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Desmedt, Christine; Zoppoli, Gabriele; Gundem, Gunes; Pruneri, Giancarlo; Larsimont, Denis; Fornili, Marco; Fumagalli, Debora; Brown, David; Rothé, Françoise; Vincent, Delphine; Kheddoumi, Naima; Rouas, Ghizlane; Majjaj, Samira; Brohée, Sylvain; Van Loo, Peter; Maisonneuve, Patrick; Salgado, Roberto; Van Brussel, Thomas; Lambrechts, Diether; Bose, Ron; Metzger, Otto; Galant, Christine; Bertucci, François; Piccart-Gebhart, Martine; Viale, Giuseppe; Biganzoli, Elia; Campbell, Peter J; Sotiriou, Christos

    2016-06-01

    Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal breast cancer (IDBC). Despite clinical and pathologic differences, ILBC is still treated as IDBC. We aimed to identify genomic alterations in ILBC with potential clinical implications. From an initial 630 ILBC primary tumors, we interrogated oncogenic substitutions and insertions and deletions of 360 cancer genes and genome-wide copy number aberrations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinicopathologic and outcome features. Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than in IDBC. The histologic diversity of ILBC was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype. Survival analyses revealed that chromosome 1q and 11p gains showed independent prognostic value in ILBC and that HER2 and AKT1 mutations were associated with increased risk of early relapse. This study demonstrates that we can now begin to individualize the treatment of ILBC, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets and FOXA1 mutations and ESR1 gains deserving urgent dedicated clinical investigation, especially in the context of endocrine treatment. © 2016 by American Society of Clinical Oncology.

  7. Lactoferrin- Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple Negative Breast Cancer Phenotypes

    Science.gov (United States)

    Ha, Ngoc-Han; Nair, Vasudha; Reddy, Divijendra Natha Sirigiri; Mudvari, Prakriti; Ohshiro, Kazufumi; Ghanta, Krishna Sumanth; Pakala, Suresh B.; Li, Da-Qiang; Costa, Luis; Lipton, Allan; Badwe, Rajendra A.; Fuqua, Suzanne; Wallon, Margaretha; Prendergast, George C.; Kumar, Rakesh

    2013-01-01

    Triple-negative breast cancer (TNBC) is characterized by the lack of expression of ERα, PR and HER-2 receptors and the pathway(s) responsible for this downregulation and thus aggressiveness, remains unknown. Here we discovered that lactoferrin (Lf) efficiently downregulates the levels of ERα, PR and HER-2 receptors in a proteasome-dependent manner in breast cancer cells, and accounts for the loss of responsiveness to ER- or HER-2- targeted therapies. Further we found that Lf increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that Lf directly stimulates the transcription of endothelin-1 (ET-1), a secreted pro-invasive polypeptide that acts through a specific receptor ET(A)R, leading to secretion of bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor antagonist drug completely blocked Lf-dependent motility and invasiveness of breast cancer cells. Physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue Lf and ET-1 levels in TNBC patients as compared to those in ER+ cases. These findings describe the first physiologically relevant polypeptide as a functional determinant of downregulating all three therapeutic receptors in breast cancer which utilizes another secreted ET-1 system to confer invasiveness. Results presented here provide proof-of-principle evidence in support of therapeutic effectiveness of ET-1 receptor antagonist to completely block the Lf-induced motility and invasiveness of the TNBC as well as non-TBNC cells, and thus, opening a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug. PMID:22006997

  8. DEGRO practical guidelines: radiotherapy of breast cancer II. Radiotherapy of non-invasive neoplasia of the breast

    International Nuclear Information System (INIS)

    Souchon, R.; Sautter-Bihl, M.L.; Sedlmayer, F.; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, R.; Sauer, R.; Harms, W.; Wenz, F.; Haase, W.

    2014-01-01

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly

  9. ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines.

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    Clément Chevalier

    Full Text Available The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.

  10. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    International Nuclear Information System (INIS)

    Zeng, Guo-fang; Cai, Shao-xi; Wu, Guang-Jer

    2011-01-01

    Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis

  11. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  12. Silencing of the integrin-linked kinase gene suppresses the proliferation, migration and invasion of pancreatic cancer cells (Panc-1

    Directory of Open Access Journals (Sweden)

    Xiang-Yu Zhu

    2012-01-01

    Full Text Available Integrin-linked kinase (ILK is an ankyrin repeat-containing serine-threonine protein kinase that is involved in the regulation of integrin-mediated processes such as cancer cell proliferation, migration and invasion. In this study, we examined the effect of a lentivirus-mediated knockdown of ILK on the proliferation, migration and invasion of pancreatic cancer (Panc-1 cells. Immunohistochemical staining showed that ILK expression was enhanced in pancreatic cancer tissue. The silencing of ILK in human Panc-1 cells led to cell cycle arrest in the G0/G1 phase and delayed cell proliferation, in addition to down-regulating cell migration and invasion. The latter effects were mediated by up-regulating the expression of E-cadherin, a key protein in cell adhesion. These findings indicate that ILK may be a new diagnostic marker for pancreatic cancer and that silencing ILK could be a potentially useful therapeutic approach for treating pancreatic cancer.

  13. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yun, Chae-Ok [Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of); Han, Deok-Jong [Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Young, E-mail: choieun@ulsan.ac.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-12-04

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  14. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

    2015-01-01

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  15. Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

    International Nuclear Information System (INIS)

    Ye, Shuangmei; Chen, Yin; You, Lanying; Zhang, Yiqun; Xu, Gang; Zhou, Jianfeng; Ma, Ding; Wang, Shixuan; Hao, Xing; Zhou, Ting; Wu, Mingfu; Wei, Juncheng; Wang, Yongjun; Zhou, Li; Jiang, Xuefeng; Ji, Li

    2010-01-01

    Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro. Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKT Ser473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining. Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not

  16. Evaluation of intratumoral HER-2 heterogeneity by fluorescence in situ hybridization in invasive breast cancer: a single institution study.

    Science.gov (United States)

    Lee, Sarah; Jung, Woohee; Hong, Soon-Won; Koo, Ja Seung

    2011-08-01

    This study aimed to determine the incidence and characteristics of HER-2 gene heterogeneity in invasive breast cancer in a single institution. Included were 971 cases of primary invasive breast cancer diagnosed between 2008 and 2010. Fluorescence in situ hybridization (FISH) image files were retrospectively reviewed and HER-2 gene heterogeneity was defined as more than 5% but less than 50% of analyzed invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2, according to the College of American Pathologists guidelines. HER-2 gene heterogeneity was identified in 24 (2.5%) cases. The mean proportion of invasive tumor cells with a HER-2/chromosome 17 ratio higher than 2.2 was 11.6% (range: 5%-25%). Of 24 cases, HER-2 gene status was not amplified in 8, showed borderline amplification in 2, and amplification in 14. All HER-2 amplification cases were low-grade. In conclusion, HER-2 gene heterogeneity of invasive breast cancer is identified in routine FISH examination. This may affect the results of HER-2 gene amplification status in FISH studies.

  17. FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells

    International Nuclear Information System (INIS)

    Lee, Hyung-Ok; Mullins, Stefanie R; Franco-Barraza, Janusz; Valianou, Matthildi; Cukierman, Edna; Cheng, Jonathan D

    2011-01-01

    Alterations towards a permissive stromal microenvironment provide important cues for tumor growth, invasion, and metastasis. In this study, Fibroblast activation protein (FAP), a serine protease selectively produced by tumor-associated fibroblasts in over 90% of epithelial tumors, was used as a platform for studying tumor-stromal interactions. We tested the hypothesis that FAP enzymatic activity locally modifies stromal ECM (extracellular matrix) components thus facilitating the formation of a permissive microenvironment promoting tumor invasion in human pancreatic cancer. We generated a tetracycline-inducible FAP overexpressing fibroblastic cell line to synthesize an in vivo-like 3-dimensional (3D) matrix system which was utilized as a stromal landscape for studying matrix-induced cancer cell behaviors. A FAP-dependent topographical and compositional alteration of the ECM was characterized by measuring the relative orientation angles of fibronectin fibers and by Western blot analyses. The role of FAP in the matrix-induced permissive tumor behavior was assessed in Panc-1 cells in assorted matrices by time-lapse acquisition assays. Also, FAP + matrix-induced regulatory molecules in cancer cells were determined by Western blot analyses. We observed that FAP remodels the ECM through modulating protein levels, as well as through increasing levels of fibronectin and collagen fiber organization. FAP-dependent architectural/compositional alterations of the ECM promote tumor invasion along characteristic parallel fiber orientations, as demonstrated by enhanced directionality and velocity of pancreatic cancer cells on FAP + matrices. This phenotype can be reversed by inhibition of FAP enzymatic activity during matrix production resulting in the disorganization of the ECM and impeded tumor invasion. We also report that the FAP + matrix-induced tumor invasion phenotype is β 1 -integrin/FAK mediated. Cancer cell invasiveness can be affected by alterations in the tumor

  18. CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Kenji Fujiwara

    Full Text Available CD166, also known as activated leukocyte cell adhesion molecule (ALCAM, is expressed by various cells in several tissues including cancer. However, the role of CD166 in malignant tumors is controversial, especially in pancreatic cancer. This study aimed to clarify the role and significance of CD166 expression in pancreatic cancer.We performed immunohistochemistry and flow cytometry to analyze the expression of CD166 in surgical pancreatic tissues and pancreatic cancer cell lines. The differences between isolated CD166+ and CD166- pancreatic cancer cells were analyzed by invasion and migration assays, and in mouse xenograft models. We also performed quantitative RT-PCR and microarray analyses to evaluate the expression levels of CD166 and related genes in cultured cells.Immunohistochemistry revealed high expression of CD166 in pancreatic cancer tissues (12.2%; 12/98 compared with that in normal pancreas controls (0%; 0/17 (p = 0.0435. Flow cytometry indicated that CD166 was expressed in 33.8-70.2% of cells in surgical pancreatic tissues and 0-99.5% of pancreatic cancer cell lines. Invasion and migration assays demonstrated that CD166- pancreatic cancer cells showed stronger invasive and migratory activities than those of CD166+ cancer cells (p<0.05. On the other hand, CD166+ Panc-1 cells showed a significantly stronger colony formation activity than that of CD166- Panc-1 cells (p<0.05. In vivo analysis revealed that CD166+ cells elicited significantly greater tumor growth than that of CD166- cells (p<0.05 in both subcutaneous and orthotopic mouse tumor models. mRNA expression of the epithelial-mesenchymal transition activator Zeb1 was over-expressed in CD166- cells (p<0.001. Microarray analysis showed that TSPAN8 and BST2 were over-expressed in CD166+ cells, while BMP7 and Col6A1 were over-expressed in CD166- cells.CD166+ pancreatic cancer cells are strongly tumorigenic, while CD166- pancreatic cancer cells exhibit comparatively stronger

  19. Skin cancer of the head and neck with clinical perineural invasion

    International Nuclear Information System (INIS)

    McCord, Mark W.; Mendenhall, William M.; Parsons, James T.; Amdur, Robert J.; Stringer, Scott P.; Cassisi, Nicholas J.; Million, Rodney R.

    2000-01-01

    Purpose: To review treatment and outcomes in 62 patients with clinical and/or gross evidence of perineural invasion from skin cancer of the head and neck. Methods and Materials: Sixty-two patients received radiotherapy at the University of Florida as part or all of their treatment between January 1965 and April 1995. All patients had clinical signs and symptoms of perineural involvement and/or documentation of tumor extending to grossly involve nerve(s). Twenty-one patients underwent therapy for previously untreated lesions, including 12 who received radiotherapy alone and nine who had surgery with postoperative radiotherapy. Forty-one patients underwent therapy for recurrent lesions, including 18 treated with radiotherapy alone and 23 who received preoperative or postoperative radiotherapy. Results: Factors on multivariate analysis that predicted local control included patient age, previously untreated vs. recurrent lesions, presence of clinical symptoms, and extent of radiotherapy fields. Recurrence patterns were predominantly local; 26 of 31 patients (84%) who developed local recurrence after treatment had recurrent cancer limited to the primary site. Conclusions: Many patients with skin cancer and symptomatic perineural invasion have disease that is incompletely resectable. Approximately half these patients will be cured with aggressive irradiation alone or combined with surgery. Age, prior treatment, and clinical symptoms influence the likelihood of cure

  20. Ionizing Radiation Promotes Migration and Invasion of Cancer Cells Through Transforming Growth Factor-Beta–Mediated Epithelial–Mesenchymal Transition

    International Nuclear Information System (INIS)

    Zhou Yongchun; Liu Junye; Li Jing; Zhang Jie; Xu Yuqiao; Zhang Huawei; Qiu Lianbo; Ding Guirong; Su Xiaoming; Mei Shi; Guo Guozhen

    2011-01-01

    Purpose: To examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-β)–mediated epithelial–mesenchymal transition (EMT). Methods and Materials: Six cancer cell lines originating from different human organs were irradiated by 60 Co γ-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-β in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-β signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. Results: After irradiation with γ-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-β were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-β signaling. Conclusions: These results suggest that EMT mediated by TGF-β plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.

  1. Ionizing Radiation Promotes Migration and Invasion of Cancer Cells Through Transforming Growth Factor-Beta-Mediated Epithelial-Mesenchymal Transition

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yongchun [Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi' an (China); Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China); Liu Junye; Li Jing; Zhang Jie [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China); Xu Yuqiao [Department of Pathology, Xijing Hospital Fourth Military Medical University, Xi' an (China); Zhang Huawei; Qiu Lianbo; Ding Guirong [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China); Su Xiaoming [Department of Radiation Oncology, 306th Hospital of PLA, Beijing (China); Mei Shi [Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi' an (China); Guo Guozhen, E-mail: guozhenguo@hotmail.com [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China)

    2011-12-01

    Purpose: To examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-{beta})-mediated epithelial-mesenchymal transition (EMT). Methods and Materials: Six cancer cell lines originating from different human organs were irradiated by {sup 60}Co {gamma}-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-{beta} in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-{beta} signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. Results: After irradiation with {gamma}-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-{beta} were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-{beta} signaling. Conclusions: These results suggest that EMT mediated by TGF-{beta} plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.

  2. Salvia miltiorrhiza extract inhibits TPA-induced MMP-9 expression and invasion through the MAPK/AP-1 signaling pathway in human breast cancer MCF-7 cells.

    Science.gov (United States)

    Kim, Jeong-Mi; Noh, Eun-Mi; Song, Hyun-Kyung; Lee, Minok; Lee, Soo Ho; Park, Sueng Hyuk; Ahn, Chan-Keun; Lee, Guem-San; Byun, Eui-Baek; Jang, Beom-Su; Kwon, Kang-Beom; Lee, Young-Rae

    2017-09-01

    Cancer cell invasion is crucial for metastasis. A major factor in the capacity of cancer cell invasion is the activation of matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix. Salvia miltiorrhiza has been used as a promotion for blood circulation to remove blood stasis. Numerous previous studies have demonstrated that S. miltiorrhiza extracts (SME) decrease lipid levels and inhibit inflammation. However, the mechanism behind the effect of SME on breast cancer invasion has not been identified. The inhibitory effects of SME on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression were assessed using western blotting, reverse transcription-quantitative polymerase chain reaction and zymography assays. MMP-9 upstream signal proteins, including mitogen-activated protein kinases and activator protein 1 (AP-1) were also investigated. Cell invasion was assessed using a matrigel invasion assay. The present study demonstrated the inhibitory effects of the SME ethanol solution on MMP-9 expression and cell invasion in TPA-treated MCF-7 breast cancer cells. SME suppressed TPA-induced MMP-9 expression and MCF-7 cell invasion by blocking the transcriptional activation of AP-1. SME may possess therapeutic potential for inhibiting breast cancer cell invasiveness.

  3. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    International Nuclear Information System (INIS)

    Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

    2007-01-01

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma

  4. Rab22a enhances CD147 recycling and is required for lung cancer cell migration and invasion.

    Science.gov (United States)

    Zhou, Yang; Wu, Bo; Li, Jiang-Hua; Nan, Gang; Jiang, Jian-Li; Chen, Zhi-Nan

    2017-08-01

    Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation. Taken together, our findings indicate that Rab22a enhances recycling of CD147, which is required for lung cancer cell migration and invasion,and targeting CD147 recycling may be a rational strategy for lung cancer therapy. Copyright © 2017. Published by Elsevier Inc.

  5. ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression

    DEFF Research Database (Denmark)

    Rafn, Bo; Nielsen, Christian Thomas Friberg; Andersen, Sofie Hagel

    2012-01-01

    Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function...... as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified...

  6. DEGRO practical guidelines for radiotherapy of breast cancer IV. Radiotherapy following mastectomy for invasive breast cancer

    International Nuclear Information System (INIS)

    Wenz, Frederik; Sperk, Elena; Budach, Wilfried; Dunst, Juergen; Feyer, Petra; Fietkau, Rainer; Sauer, Rolf; Haase, Wulf; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Fussl, Christoph; Souchon, Rainer

    2014-01-01

    Since the last recommendations from the Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008, evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown. This growth is based on updates of the national S3 and international guidelines, as well as on new data and meta-analyses. New aspects were considered when updating the DEGRO recommendations. The authors performed a comprehensive survey of the literature. Data from recently published (meta-)analyses, randomized clinical trials and international cancer societies' guidelines yielding new aspects compared to 2008 were reviewed and discussed. New aspects were included in the current guidelines. Specific issues relating to particular PMRT constellations, such as the presence of risk factors (lymphovascular invasion, blood vessel invasion, positive lymph node ratio > 20 %, resection margins 2 cm or a combination of ≥ 2 risk factors) and 1-3 positive lymph nodes are emphasized. The evidence for improved overall survival and local control following PMRT for T4 tumors, positive resection margins, > 3 positive lymph nodes and in T3 N0 patients with risk factors such as lymphovascular invasion, G3 grading, close margins, and young age has increased. Recently identified risk factors such as invasive lobular subtype and negative hormone receptor status were included. For patients with 1-3 positive lymph nodes, the recommendation for PMRT has reached the 1a level of evidence. PMRT is mandatory in patients with T4 tumors and/or positive lymph nodes and/or positive resection margins. PMRT should be strongly considered in patients with T3 N0 tumors and risk factors, particularly when two or more risk factors are present. (orig.) [de

  7. Transvaginal ultrasound assessment of myometrial and cervical stroma invasion in women with endometrial cancer -interobserver reproducibility among ultrasound experts and gynaecologists

    DEFF Research Database (Denmark)

    Eriksson, LS; Lindqvist, PG; Flöter Rådestad, A

    2014-01-01

    OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynaecologists in the prediction of deep myometrial- and cervical stroma invasion by transvaginal ultrasound in women with endometrial cancer. METHODS: Video-clips of the corpus- and cervix uteri of 53 women...... with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated in a digitalized survey. Nine ultrasound experts and 9 gynaecologists evaluated presence or absence of deep myometrial- and cervical stroma invasion. Histopathology from hysterectomy specimen was used as gold standard.......001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial- and cervical stroma invasion in endometrial cancer is best performed by ultrasound experts, as they show a higher degree of agreement to histopathology and higher interobserver reproducibility in the assessment of cervical stromal invasion....

  8. Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer

    Science.gov (United States)

    Adam, Jason D.; Borum, Marie L.; Koh, Joyce M.; Stephen, Sindu

    2018-01-01

    Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation. PMID:29606921

  9. Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells

    International Nuclear Information System (INIS)

    Zhan, Yu; Abi Saab, Widian F.; Modi, Nidhi; Stewart, Amanda M.; Liu, Jinsong; Chadee, Deborah N.

    2012-01-01

    Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates MAPK signaling pathways and regulates cellular responses such as proliferation, migration and apoptosis. Here we report high levels of total and phospho-MLK3 in ovarian cancer cell lines in comparison to immortalized nontumorigenic ovarian epithelial cell lines. Using small interfering RNA (siRNA)-mediated gene silencing, we determined that MLK3 is required for the invasion of SKOV3 and HEY1B ovarian cancer cells. Furthermore, mlk3 silencing substantially reduced matrix metalloproteinase (MMP)-1, -2, -9 and -12 gene expression and MMP-2 and -9 activities in SKOV3 and HEY1B ovarian cancer cells. MMP-1, -2, -9 and-12 expression, and MLK3-induced activation of MMP-2 and MMP-9 requires both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activities. In addition, inhibition of activator protein-1 (AP-1) reduced MMP-1, MMP-9 and MMP-12 gene expression. Collectively, these findings establish MLK3 as an important regulator of MMP expression and invasion in ovarian cancer cells. -- Highlights: ► Ovarian cancer cell lines have high levels of total and phosphorylated MLK3. ► MLK3 is required for MMP expression and activity in ovarian cancer cells. ► MLK3 is required for invasion of SKOV3 and HEY1B ovarian cancer cells. ► MLK3-dependent regulation of MMP-2 and MMP-9 activities requires ERK and JNK.

  10. Thymosin β4 induces invasion and migration of human colorectal cancer cells through the ILK/AKT/β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Piao, Zhengri [Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju (Korea, Republic of); Hong, Chang-Soo [Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Jung, Mi-Ran [Department of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Choi, Chan [Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Park, Young-Kyu, E-mail: parkyk@jnu.ac.kr [Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

    2014-09-26

    Highlights: • Tβ4 is overexpressed in human colorectal cancer cells. • The overexpression of Tβ4 is correlated with stage of colorectal cancer. • Tβ4 stimulates cell adhesion, invasion, migration and EMT. • Tβ4 activates the ILK/AKT/β-catenin signaling pathway. - Abstract: Thymosin β4 (Tβ4) is a 43-amino-acid peptide involved in many biological processes. However, the precise molecular signaling mechanism(s) of Tβ4 in cell invasion and migration remain unclear. In this study, we show that Tβ4 was significantly overexpressed in colorectal cancer tissues compared to adjacent normal tissues and high levels of Tβ4 were correlated with stage of colorectal cancer, and that Tβ4 expression was associated with morphogenesis and EMT. Tβ4-upregulated cancer cells showed increased adhesion, invasion and migration activity, whereas Tβ4-downregulated cells showed decreased activities. We also demonstrated that Tβ4 interacts with ILK, which promoted the phosphorylation and activation of AKT, the phosphorylation and inactivation of GSK3β, the expression and nuclear localization of β-catenin, and integrin receptor activation. These results suggest that Tβ4 is an important regulator of the ILK/AKT/β-catenin/Integrin signaling cascade to induce cell invasion and migration in colorectal cancer cells, and is a potential target for cancer treatment.

  11. miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7

    International Nuclear Information System (INIS)

    Zhou, Chuanyi; Shen, Liangfang; Mao, Lei; Wang, Bing; Li, Yang; Yu, Huizhi

    2015-01-01

    MicroRNAs (miRNAs) are involved in the cervical carcinogenesis and progression. In this study, we investigated the role of miR-92a in progression and invasion of cervical cancer. MiR-92a was significantly upregulated in cervical cancer tissues and cell lines. Overexpression of miR-92a led to remarkably enhanced proliferation by promoting cell cycle transition from G1 to S phase and significantly enhanced invasion of cervical cancer cells, while its knockdown significantly reversed these cellular events. Bioinformatics analysis suggested F-box and WD repeat domain-containing 7 (FBXW7) as a novel target of miR-92a, and miR-92a suppressed the expression level of FBXW7 mRNA by direct binding to its 3′-untranslated region (3′UTR). Expression of miR-92a was negatively correlated with FBXW7 in cervical cancer tissues. Furthermore, Silencing of FBXW7 counteracted the effects of miR-92a suppression, while its overexpression reversed oncogenic effects of miR-92a. Together, these findings indicate that miR-92a acts as an onco-miRNA and may contribute to the progression and invasion of cervical cancer, suggesting miR-92a as a potential novel diagnostic and therapeutic target of cervical cancer. - Highlights: • miR-92a is elevated in cervical cancer tissues and cell lines. • miR-92a promotes cervical cancer cell proliferation, cell cycle transition from G1 to S phase and invasion. • FBXW7 is a direct target of miR-92a. • FBXW7 counteracts the oncogenic effects of miR-92a on cervical cancer cells

  12. Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer.

    Science.gov (United States)

    Begnini, K R; Buss, J H; Collares, T; Seixas, F K

    2015-05-01

    In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer.

  13. Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database

    International Nuclear Information System (INIS)

    Huang, Baojun; Sun, Zhe; Wang, Zhenning; Lu, Chong; Xing, Chengzhong; Zhao, Bo; Xu, Huimian

    2013-01-01

    Peritoneal dissemination is the most common type of recurrence in advanced gastric cancer. The main mechanism is thought to be via the exfoliation of free cancer cells (FCCs) from tumor in the gastric serosa. The frequency of recurrence thus increases once the tumor cells penetrate the serosa. However, this type of recurrence also occurs in patients without serosal invasion, though the mechanisms responsible for have not been fully established. We therefore investigated the factors associated with peritoneal dissemination in patients with non-serosa-invasive gastric cancer. A total of 685 patients with non-serosa-invasive gastric cancer who underwent curative resection with retrieval of more than 15 nodes were selected. The associations between clinicopathological features and peritoneal dissemination were analyzed. Among them, the tumor infiltrating growth pattern (INF) were classified into α, β and γ according to the Japanese Classification of Gastric Carcinoma (JCGC). The overall incidence of peritoneal metastasis was 20% (137/685). Age, Borrmann type, differentiation, INF, nodal status and free cancer cells (FCCs) were correlated with peritoneal dissemination using univariate analysis. However, only INF, Borrmann type and TNM node stage were identified as independent correlated factors with peritoneal metastasis by multivariate analysis when FCCs were excluded, and these were also prognostic factors. Peritoneal dissemination was more common in patients with INFγ, Borrmann III/IV and N3 stage. Among patients without FCCs, nodal involvement or vessel invasion, only INF remained an independent associated factor according to multivariate analysis. Tumor infiltrating growth pattern (INF), together with Borrmann type and TNM node stage, are important factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer

  14. Defining Priorities to Improve Patient Experience in Non-Muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Garg, Tullika; Connors, Jill Nault; Ladd, Ilene G; Bogaczyk, Tyler L; Larson, Sharon L

    2018-01-20

    Although approximately 75% of bladder cancers are non-muscle invasive (NMIBC) at diagnosis, most research tends to focus on invasive disease (e.g., experiences related to radical cystectomy and urinary diversion). There is a lack of studies on quality of life, and especially qualitative research, in bladder cancer generally. As a result, relatively little is known about the experiences and needs of NMIBC patients. To understand patient experience, define care priorities, and identify targets for care improvement in NMIBC across the cancer continuum. Through focus groups, patients treated for NMIBC (stage influences on decision-making, and role of social support. Patients with NMIBC desired timely access to care and honest and caring provider communication. They described urinary function and emotional quality of life changes resulting from diagnosis and treatment. Avoiding cystectomy and being alive for family were the major decision influencers. In this qualitative study, we identified access to care, provider characteristics and communication, quality of life, values/influences on decision-making, and social support as priority areas to improve patient experience in NMIBC. Care redesign efforts should focus on improving access, enhancing provider communication, reducing side effects, and supporting caregiver roles.

  15. Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Z. N.; Sharma, V. P.; Beaty, B. T.; Roh-Johnson, M.; Peterson, E. A.; Van Rooijen, N.; Kenny, P. A.; Wiley, H. S.; Condeelis, J. S.; Segall, J. E.

    2014-10-13

    Increased expression of HBEGF in estrogen receptor-negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of colony-stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid in tumor cell invasion by secreting epidermal growth factor. To determine how the autocrine expression of epidermal growth factor receptor (EGFR) ligands by carcinoma cells would affect this paracrine loop mechanism, and in particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We found that autocrine HBEGF expression enhanced in vivo intravasation and metastasis and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of matrix metalloprotease 2 (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling.

  16. NON-INVASIVE RADIOFREQUENCY ABLATION OF CANCER TARGETED BY GOLD NANOPARTICLES

    Science.gov (United States)

    Cardinal, Jon; Klune, John Robert; Chory, Eamon; Jeyabalan, Geetha; Kanzius, John S.; Nalesnik, Michael; Geller, David A.

    2008-01-01

    Introduction Current radiofrequency ablation (RFA) techniques require invasive needle placement and are limited by accuracy of targeting. The purpose of this study was to test a novel non-invasive radiowave machine that uses RF energy to thermally destroy tissue. Gold nanoparticles were designed and produced to facilitate tissue heating by the radiowaves. Methods A solid state radiowave machine consisting of a power generator and transmitting/receiving couplers which transmit radiowaves at 13.56 MHz was used. Gold nanoparticles were produced by citrate reduction and exposed to the RF field either in solutions testing or after incubation with HepG2 cells. A rat hepatoma model using JM-1 cells and Fisher rats was employed using direct injection of nanoparticles into the tumor to focus the radiowaves for select heating. Temperatures were measured using a fiber-optic thermometer for real-time data. Results Solutions containing gold nanoparticles heated in a time- and power-dependent manner. HepG2 liver cancer cells cultured in the presence of gold nanoparticles achieved adequate heating to cause cell death upon exposure to the RF field with no cytotoxicity attributable to the gold nanoparticles themselves. In vivo rat exposures at 35W using gold nanoparticles for tissue injection resulted in significant temperature increases and thermal injury at subcutaneous injection sites as compared to vehicle (water) injected controls. Discussion These data show that non-invasive radiowave thermal ablation of cancer cells is feasible when facilitated by gold nanoparticles. Future studies will focus on tumor selective targeting of nanoparticles for in vivo tumor destruction. PMID:18656617

  17. DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.

    Science.gov (United States)

    Toiyama, Yuji; Inoue, Yasuhiro; Yasuda, Hiromi; Saigusa, Susumu; Yokoe, Takeshi; Okugawa, Yoshinaga; Tanaka, Koji; Miki, Chikao; Kusunoki, Masato

    2011-02-01

    We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease. The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer. DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients. DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

  18. LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Chakrabarti Ratna

    2011-01-01

    Full Text Available Abstract Background LIM kinase 1 (LIMK1 is an actin and microtubule cytoskeleton modulatory protein that is overexpressed in a number of cancerous tissues and cells and also promotes invasion and metastasis of prostate and breast cancer cells. Membrane type matrix metalloproteinase 1 (MT1-MMP is a critical modulator of extracellular matrix (ECM turnover through pericellular proteolysis and thus plays crucial roles in neoplastic cell invasion and metastasis. MT1-MMP and its substrates pro-MMP-2 and pro-MMP-9 are often overexpressed in a variety of cancers including prostate cancer and the expression levels correlate with the grade of malignancy in prostate cancer cells. The purpose of this study is to determine any functional relation between LIMK1 and MT1-MMP and its implication in cell invasion. Results Our results showed that treatment with the hydroxamate inhibitor of MT1-MMP, MMP-2 and MMP-9 ilomastat inhibited LIMK1-induced invasion of benign prostate epithelial cells. Over expression of LIMK1 resulted in increased collagenolytic activity of MMP-2, and secretion of pro-MMP2 and pro-MMP-9. Cells over expressing LIMK1 also exhibited increased expression of MT1-MMP, transcriptional activation and its localization to the plasma membrane. LIMK1 physically associates with MT1-MMP and is colocalized with it to the Golgi vesicles. We also noted increased expression of both MT1-MMP and LIMK1 in prostate tumor tissues. Conclusion Our results provide new information on regulation of MT1-MMP function by LIMK1 and showed for the first time, involvement of MMPs in LIMK1 induced cell invasion.

  19. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer

    NARCIS (Netherlands)

    Kamat, A.M.; Witjes, J.A.; Brausi, M.; Soloway, M.; Lamm, D.; Persad, R.; Buckley, R.; Bohle, A.; Colombel, M.; Palou, J.

    2014-01-01

    PURPOSE: Low, intermediate and high risk categories have been defined to help guide the treatment of patients with nonmuscle invasive bladder cancer (Ta, T1, CIS). However, while low and high risk disease has been well classified, the intermediate risk category has traditionally comprised a

  20. EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression.

    Science.gov (United States)

    Liu, Hongyan; Li, Zhenjie; Li, Liujuan; Peng, Haiying; Zhang, Zhijun

    2015-11-01

    Ebp1, a protein identified by its interactions with the ErbB3 receptor, has been characterized as a negative regulator of cancers. RAS GTPase-activating protein (RasGAP), RASAL1, was recently identified as a major tumor suppressor in thyroid cancer. In this study, we examined EBP1 expression in papillary and follicular thyroid cancer cells. We found that compared with normal thyroid cells, TPC1, WRO, and FTC133 thyroid tumor cells exhibited lower EBP1 expression at messenger RNA (mRNA) and protein levels. We then investigated the effects of forced EBP1 expression on growth, migration, and invasiveness of thyroid tumor cells. By using MTT and Boyden chamber assays, we showed that EBP1 overexpression dramatically reduced growth rate, migration, and invasiveness of K1 and FTC133 thyroid tumor cells. Furthermore, we explored the molecular mechanism underlying the effects of EBP1 on the cells by disclosing the correlation of EBP1 and RASAL1 expression. RASAL expression was elevated in thyroid tumor cells overexpressing EBP1. Knockdown RASAL by transduction of RASAL1 shRNA lentiviral particles markedly reduced RASAL levels with restoration of EBP1, and RASAL1 knockdown abrogated the effects of forced EBP1 expression on cell growth, migration, and invasiveness of thyroid tumor cells. These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression.

  1. Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters

    NARCIS (Netherlands)

    H. Verloop (Herman); F.E. van Leeuwen (F.); T.J.M. Helmerhorst (Theo); I.M.C.M. de Kok (Inge); van Erp, E.J.M.; H.H. van Boven (Hester); M.A. Rookus (Matti)

    2017-01-01

    textabstractObjective: Women exposed to diethylstilbestrol in utero (DES) have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix, while their risk of non-CCA invasive cervical cancer is still unclear. Methods: We studied the risk of pre-cancerous (CIN) lesions and non-CCA

  2. AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

    DEFF Research Database (Denmark)

    Rodriguez-Teja, Mercedes; Gronau, Julian H; Breit, Claudia

    2015-01-01

    Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways...... in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major......(Δ) (Ex2-6/) (Δ) (Ex2-6) mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour...

  3. Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Sim, Y.T.; Vinnicombe, S.; Whelehan, P.; Thomson, K.; Evans, A.

    2015-01-01

    Aim: To investigate the contribution of shear-wave elastography (SWE) in diagnosing invasive lobular breast cancer (ILC) in symptomatic patients. Materials and methods: A retrospective case-controlled study of 52 patients with ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour size, was performed. Breast density and mammographic and greyscale ultrasound features were graded using Breast Imaging-Reporting and Data System (BI-RADS) classification by two radiologists, blinded to SWE and pathology findings. Forty-four benign lesions were also included. The sensitivity of SWE was assessed, using a cut-off value of 50 kPa for mean elasticity. Statistical significance was evaluated using Chi-square and Chi-square for trend tests. Results: Mean age for both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37 mm. The sensitivity for detection of ILC and IDC for mammography, greyscale ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%, respectively. SWE had significantly higher sensitivities than mammography for the detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was not significantly more sensitive than greyscale ultrasound for the detection of either tumour type. Four (8%) lobular cancers were benign/normal at both mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain in sensitivity by using SWE in ILC was statistically significant compared to IDC (p = 0.01). Conclusion: SWE can diagnose lobular cancers that have benign/normal findings on conventional imaging as suspicious. - Highlights: • Sensitivity of shear-wave elastography (SWE) for detecting lobular cancers is 94%. • Sensitivity of SWE for detecting invasive ductal cancers is 100%. • SWE is more sensitive than mammography for detecting ductal and lobular cancers. • SWE can diagnose ILC as suspicious, which are benign/normal on conventional imaging

  4. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    OpenAIRE

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa...

  5. Role of IGF-1/IGF-1R in regulation of invasion in DU145 prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Setya Hemani

    2008-07-01

    Full Text Available Abstract Background Prostate cancer progression to androgen independence is the primary cause of mortality by this tumor type. The IGF-1/IGF-1R axis is well known to contribute to prostate cancer initiation, but its contribution to invasiveness and the downstream signalling mechanisms that are involved are unclear at present. Results We examined the invasive response of androgen independent DU145 prostate carcinoma cells to IGF-1 stimulation using Matrigel assays. We then examined the signaling mechanisms and protease activities that are associated with this response. IGF-1 significantly increased the invasive capacity of DU145 cells in vitro, and this increase was inhibited by blocking IGF-1R. We further demonstrated that specific inhibitors of the MAPK and PI3-K pathways decrease IGF-1-mediated invasion. To determine potential molecular mechanisms for this change in invasive capacity, we examined changes in expression and activity of matrix metalloproteinases. We observed that IGF-1 increases the enzymatic activity of MMP-2 and MMP-9 in DU145 cells. These changes in activity are due to differences in expression in the case of MMP-9 but not in the case of MMP-2. This observation is corroborated by the fact that correlated changes of expression in a regulator of MMP-2, TIMP-2, were also seen. Conclusion This work identifies a specific effect of IGF-1 on the invasive capacity of DU145 prostate cancer cells, and furthermore delineates mechanisms that contribute to this effect.

  6. Matrix-assisted laser desorption/ionization mass spectrometry imaging of cell cultures for the lipidomic analysis of potential lipid markers in human breast cancer invasion.

    Science.gov (United States)

    Wang, Shujuan; Chen, Xiaowu; Luan, Hemi; Gao, Dan; Lin, Shuhai; Cai, Zongwei; Liu, Jianjun; Liu, Hongxia; Jiang, Yuyang

    2016-02-28

    Breast cancer is the leading cause of cancer death among women worldwide. Identification of lipid targets that play a role in breast cancer invasion may advance our understanding of the rapid progression of cancer and may lead to the development of new biomarkers for the disease. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was applied for the lipidomic profiling of two poorly invasive and two highly invasive breast cancer cell lines to identify the differentially accumulated lipids related to the invasive phenotype. The four cell lines were individually grown on indium tin oxide (ITO)-coated glass slides, analyzed as cell cultures. The raster width and matrix for detection were optimized to improve detection sensitivity. Optimized MSI measurements were performed directly on the cell culture with 9-aminoacridine as matrix, resulting in 215 endogenous compounds detected in positive ion mode and 267 endogenous compounds in negative ion mode in all the four cell lines, representing the largest group of analytes that have been analyzed from cells by a single MSI study. In highly invasive cell lines, 31 lipids including phosphatidylglycerol (PG) and phosphatidic acids were found upregulated and eight lipids including sphingomyelin (SM) downregulated in negative ion mode. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, like oleic-acid-containing PG, may be involved in mitochondrial dysfunction and thus affect the invasion of breast cancer cells. The deficiency of SM may be related to the disruption of apoptosis in highly invasive cancer cells. This work uncovered more analytes in cells by MSI than previous reports, providing a better visualization and novel insights to advance our understanding of the relationship between rapid progression of breast cancer and lipid metabolism. The most altered lipids may aid the discovery of diagnostic markers and therapeutic targets of breast cancer. Copyright

  7. Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Karolina Kowalska

    2018-02-01

    Full Text Available Zearalenone (ZEA, a mycotoxin produced in the genus Fusarium, binds to estrogen receptors (ER and is therefore regarded as an endocrine disruptor. ZEA has also been found to modulate the proliferation and apoptosis of prostate cancer cells in a dose-dependent manner. This study evaluates whether the effect of a low dose of ZEA (0.1 and 0.001 nM on the invasion and migration of prostate cancer cell line PC3 is associated with ERs expression. The invasion and migration was evaluated by modified Boyden chamber assay, scratch assay, gelatin zymography, Real Time qPCR (RTqPCR and Western blot. The involvement of ERs was evaluated with the selective ER antagonists: estrogen receptor α (ERα antagonist 1,3-bis (4-hydroxyphenyl-4-methyl-5-[4-(2-piperidinylethoxy phenol]-1H-pyrazole dihydrochloride (MPP and estrogen receptor β (ERβ antagonist 4-[2–phenyl-5,7–bis (trifluoromethyl pyrazolo [1,5-a]-pyrimidin-3-yl] phenol (PHTPP. ZEA was found to modulate cell motility dependent on estrogen receptors, particularly ERα. Increased cell migration and invasion were associated with increased MMP-2 and MMP-9 activity as well as the up-regulation of the EMT-associated genes vimentin (VIM, zinc finger E-box-binding homeobox 1/2 (ZEB1/2 and transforming growth factor β 1 (TGFβ1. In conclusion, ZEA might modulate the invasiveness of prostate cancer cells dependently on ERα expression.

  8. Twist and YB-1 gene expression in cervical cancer and precancerous tissue and their correlation with cell invasion

    Directory of Open Access Journals (Sweden)

    Qin Tian

    2017-04-01

    Full Text Available Objective: To study the correlation of Twist and YB-1 gene expression in cervical cancer and precancerous tissue with cell invasion. Methods: Cervical cancer tissue, precancerous tissue and normal cervical tissue surgically removed in our hospital between May 2013 and April 2015 were collected; immunohistochemical staining kits were used to detect the positive protein expression rate of Twist and YB-1 gene; fluorescence quantitative PCR kits were used to detect Twist, YB-1 and invasion gene mRNA expression. Results: Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue were significantly higher than those in normal cervical tissue, Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue were significantly higher than those in precancerous tissue; USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue with positive Twist and YB-1 expression were significantly higher than those in cervical cancer tissue and precancerous tissue with negative Twist and YB-1 expression. Conclusion: Highly expressed Twist and YB-1 in cervical cancer and precancerous tissue can promote cell invasion.

  9. Knockdown of Uba2 inhibits colorectal cancer cell invasion and migration through downregulation of the Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Cheng, Hongjing; Sun, Xun; Li, Ji; He, Ping; Liu, Wanqi; Meng, Xiangwei

    2018-05-10

    Colorectal cancer is a serious threat to human health, and has a high mortality rate. There is currently no effective therapy for end-stage colorectal cancer. In recent years, molecular targeted therapy has received increasing attention for cancer treatment. In particular, the role of Uba2, a vital component of SUMO-activating enzyme, has been highlighted, which plays important roles in the progression of certain cancers; however, its role in colorectal cancer remains unclear. Accordingly, the aim of this study was to evaluate the relationship between Uba2 and colorectal cancer. Uba2 expression was knocked down in two colorectal cancer cell lines, and gene microarray analysis was conducted, followed by proliferation, migration, and invasion assays. Uba2 knockdown influenced the expression of several genes, and significantly inhibited the proliferation, migration, and invasion of cancer cells. To determine the underlying mechanism, the expression of related signaling pathways and molecules was evaluated in the knockdown cell lines. Overall, the results suggest that Uba2 participates in the progression, invasion, and metastasis of colorectal cancer, and the possible mechanism is via regulating the Wnt signaling pathway and enhancing epithelial-mesenchymal transition behaviors of colorectal cancer cells. Therefore, Uba2 is expected to be an important oncoprotein and potential therapeutic target in colorectal cancer. © 2018 Wiley Periodicals, Inc.

  10. 5'-Inositol phosphatase SHIP2 recruits Mena to stabilize invadopodia for cancer cell invasion.

    Science.gov (United States)

    Rajadurai, Charles V; Havrylov, Serhiy; Coelho, Paula P; Ratcliffe, Colin D H; Zaoui, Kossay; Huang, Bruce H; Monast, Anie; Chughtai, Naila; Sangwan, Veena; Gertler, Frank B; Siegel, Peter M; Park, Morag

    2016-09-12

    Invadopodia are specialized membrane protrusions that support degradation of extracellular matrix (ECM) by cancer cells, allowing invasion and metastatic spread. Although early stages of invadopodia assembly have been elucidated, little is known about maturation of invadopodia into structures competent for ECM proteolysis. The localized conversion of phosphatidylinositol(3,4,5)-triphosphate and accumulation of phosphatidylinositol(3,4)-bisphosphate at invadopodia is a key determinant for invadopodia maturation. Here we investigate the role of the 5'-inositol phosphatase, SHIP2, and reveal an unexpected scaffold function of SHIP2 as a prerequisite for invadopodia-mediated ECM degradation. Through biochemical and structure-function analyses, we identify specific interactions between SHIP2 and Mena, an Ena/VASP-family actin regulatory protein. We demonstrate that SHIP2 recruits Mena, but not VASP, to invadopodia and that disruption of SHIP2-Mena interaction in cancer cells leads to attenuated capacity for ECM degradation and invasion in vitro, as well as reduced metastasis in vivo. Together, these findings identify SHIP2 as a key modulator of carcinoma invasiveness and a target for metastatic disease. © 2016 Rajadurai et al.

  11. Carbon-ion radiation enhances migration ability and invasiveness of the pancreatic cancer cell, PANC-1, in vitro.

    Science.gov (United States)

    Fujita, Mayumi; Otsuka, Yoshimi; Imadome, Kaori; Endo, Satoshi; Yamada, Shigeru; Imai, Takashi

    2012-04-01

    Pancreatic cancer is an aggressive disease that responds poorly to conventional photon radiotherapy. Carbon-ion (C-ion) radiation has advantages compared with conventional radiotherapy, because it enables more accurate dose distribution and more efficient tumor cell killing. To elucidate the effects of local radiotherapy on the characteristics of metastatic tumors, it is necessary to understand the nature of motility in irradiated tumor cells; this will, in turn, facilitate the development of effective strategies to counter tumor cell motility, which can be used in combination with radiotherapy. The aim of the present study was to examine the invasiveness of pancreatic cancer cells exposed to C-ion irradiation. We found that C-ion irradiation suppressed the migration of MIAPaCa-2, BxPC-3 and AsPC-1; diminished the invasiveness of MIAPaCa-2; and tended to reduce the invasion of BxPC-3 and AsPC-1. However, C-ion irradiation increased the invasiveness of PANC-1 through the activation of plasmin and urokinase-type plasiminogen activator. Administration of serine protease inhibitor (SerPI) alone failed to reduce C-ion-induced PANC-1 invasiveness, whereas the combination of SerPI and Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor suppressed it. Furthermore, PANC-1 showed mesenchymal-amoeboid transition when we treated with SerPI alone. In conclusion, C-ion irradiation is effective in suppressing the invasive potential of several pancreatic tumor cell lines, but not PANC-1; this is the first study showing that C-ion irradiation induces the invasive potential of a tumor cell line. Further in vivo studies are required to examine the therapeutic effectiveness of radiotherapy combined with inhibitors of both mesenchymal and amoeboid modes of tumor cell motility. © 2011 Japanese Cancer Association.

  12. Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

    International Nuclear Information System (INIS)

    Nisa, Lluís; Aebersold, Daniel Matthias; Giger, Roland; Caversaccio, Marco Domenico; Borner, Urs; Medová, Michaela; Zimmer, Yitzhak

    2015-01-01

    High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC) have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches

  13. Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaojie [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Taizhou Polytechnic College, Taizhou (China); Zhang, Ling; Shao, Yueting; Liang, Zuowen; Shao, Chen; Wang, Bo; Guo, Baofeng; Li, Na; Zhao, Xuejian [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Li, Yang, E-mail: lyang@jlu.edu.cn [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Xu, Deqi [Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Neu3 is as one of the sialidases and regulates cell surface functions. Black-Right-Pointing-Pointer A Neu3-specific siRNA inhibited prostrate cancer cell invasion and migration. Black-Right-Pointing-Pointer The Neu3-specific siRNA inhibited prostate cancer metastasis in mice. Black-Right-Pointing-Pointer Targeting Neu3 may have utility for gene-based therapy of human cancer metastasis. -- Abstract: Human plasma membrane-associated sialidase (Neu3) is one of several sialidases that hydrolyze sialic acids in the terminal position of the carbohydrate groups of glycolipids and glycoproteins. Neu3 is mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. In this study, we investigated the effects and molecular mechanisms of Neu3 on cell invasion and migration in vivo and in vitro. Initially, we found that the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues based on RT-PCR and Western blotting analyses. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. Transwell invasion assays and wound assays showed significantly decreased invasion and migration potential in the Neu3 siRNA-transfected cells. RT-PCR and Western blotting analyses revealed that Neu3 knockdown decreased the expressions of the matrix metalloproteinases MMP-2 and MMP-9. In vivo, mice injected with PC-3M cell tumors were evaluated by SPECT/CT to determine the presence of bone metastases. Mice treated with attenuated Salmonella carrying the Neu3 siRNA developed fewer bone metastases than mice treated with attenuated Salmonella carrying a control Scramble siRNA, attenuated Salmonella alone or PBS. The results for bone metastasis detection by pathology were consistent with the data obtained by SPECT/CT. Tumor blocks were evaluated by histochemical, RT-PCR and Western blotting analyses. The results revealed

  14. A 3D Microfluidic Model to Recapitulate Cancer Cell Migration and Invasion

    Directory of Open Access Journals (Sweden)

    Yi-Chin Toh

    2018-04-01

    Full Text Available We have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a 3D microenvironment is engineered to culture metastatic breast cancer cells (MX1 in a 3D tumor model. A chemo-attractant was incorporated to stimulate motility across the membrane. We validated the usefulness of the chip by tracking the motilities of the cancer cells in the system, showing them to be migrating or invading (akin to metastasis. It is shown that our system can monitor cell migration in real time, as compare to Boyden chambers, for example. Thus, the chip will be of interest to the drug-screening community as it can potentially be used to monitor the behavior of cancer cell motility, and, therefore, metastasis, in the presence of anti-cancer drugs.

  15. Correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Jing Wan

    2017-04-01

    Full Text Available Objective: To study the correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion. Methods: A total of 128 patients with thyroid papillary carcinoma who received surgical treatment in the hospital between May 2013 and May 2016 were collected, CEUS was used to make clear the peak intensity (PI and area under the curve (AUC of tumor tissue and surrounding normal tissue, and the median of PI and AUC was referred to further divide the patients into high PI group and low PI group as well as high AUC group and low AUC group, 64 cases in each group. Fluorescent quantitative PCR was used to determine proliferation and invasion gene mRNA expression in tumor tissues. Results: PI and AUC levels in tumor tissue were lower than those in surrounding normal tissue; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low PI group were higher than those of high PI group, and invasion gene Ki-67 mRNA expression was higher than that of high PI group while P53 and MRP-1 mRNA expression were lower than those of high PI group; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low AUC group were higher than those of high AUC group, and invasion gene Ki-67 mRNA expression was higher than that of high AUC group while P53 and MRP-1 mRNA expression were lower than those of high AUC group. Conclusion: Thyroid papillary carcinoma CEUS parameters PI and AUC levels can quantifiably reflect the cancer cell proliferation and invasion activity.

  16. Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Ørntoft, Torben Falck

    2007-01-01

    individually contributed to the management of the disease. However, the development of high-throughput techniques for simultaneous assessment of a large number of markers has allowed classification of tumors into clinically relevant molecular subgroups beyond those possible by pathological classification. Here......Bladder cancer is the fifth most common neoplasm in industrialized countries. Due to frequent recurrences of the superficial form of this disease, bladder cancer ranks as one of the most common cancers. Despite the description of a large number of tumor markers for bladder cancers, none have......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

  17. The situation of radiotherapy in the treatment of lymph node invasion of gynecological cancers

    International Nuclear Information System (INIS)

    Dubois, J.B.; Gerbaulet, A.

    1993-01-01

    In this article, the authors explain the role and possibilities of radiotherapy in the treatment of lymph node invasion in gynecological cancers as uterine cervix carcinoma, uterus carcinoma, ovary carcinoma and vulva carcinoma

  18. Total glucosides of paeony inhibits lipopolysaccharide-induced proliferation, migration and invasion in androgen insensitive prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Zhang

    Full Text Available Previous studies demonstrated that inflammatory microenvironment promoted prostate cancer progression. This study investigated whether total glucosides of paeony (TGP, the active constituents extracted from the root of Paeonia Lactiflora Pall, suppressed lipopolysaccharide (LPS-stimulated proliferation, migration and invasion in androgen insensitive prostate cancer cells. PC-3 cells were incubated with LPS (2.0 μg/mL in the absence or presence of TGP (312.5 μg /mL. As expected, cells at S phase and nuclear CyclinD1, the markers of cell proliferation, were increased in LPS-stimulated PC-3 cells. Migration activity, as determined by wound-healing assay and transwell migration assay, and invasion activity, as determined by transwell invasion assay, were elevated in LPS-stimulated PC-3 cells. Interestingly, TGP suppressed LPS-stimulated PC-3 cells proliferation. Moreover, TGP inhibited LPS-stimulated migration and invasion of PC-3 cells. Additional experiment showed that TGP inhibited activation of nuclear factor kappa B (NF-κB and mitogen-activated protein kinase (MAPK/p38 in LPS-stimulated PC-3 cells. Correspondingly, TGP attenuated upregulation of interleukin (IL-6 and IL-8 in LPS-stimulated PC-3 cells. In addition, TGP inhibited nuclear translocation of signal transducer and activator of transcription 3 (STAT3 in LPS-stimulated PC-3 cells. These results suggest that TGP inhibits inflammation-associated STAT3 activation and proliferation, migration and invasion in androgen insensitive prostate cancer cells.

  19. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    International Nuclear Information System (INIS)

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel

    2011-01-01

    Highlights: ► Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. ► CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. ► GDNT inhibits expression of CDC20 in breast cancer cells. ► GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. ► GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes—ganoderic and lucidenic acids—the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  20. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  1. Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer

    Science.gov (United States)

    Yang, Li; Zha, Tian-Qi; He, Xiang; Chen, Liang; Zhu, Quan; Wu, Wei-Bing; Nie, Feng-Qi; Wang, Qian; Zang, Chong-Shuang; Zhang, Mei-Ling; He, Jing; Li, Wei; Jiang, Wen; Lu, Kai-Hua

    2018-01-01

    Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis. PMID:29138842

  2. The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

    International Nuclear Information System (INIS)

    Jolly, Shruti; Kestin, Larry L.; Goldstein, Neal S.; Vicini, Frank A.

    2006-01-01

    Purpose: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients. Methods and Materials: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years. Results: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p = 0.04). On multivariate analysis, positive margin (p < 0.01), positive/no reexcision (p = 0.04), and presence of LCIS (p = 0.02) remained independently associated with IBTR; positive margin (p < 0.01) and LCIS (p = 0.04) were also associated with TR/MM failure. When examining only cases with negative final margins, the presence of LCIS remained associated with higher IBTR and TR/MM rates (p < 0.01). Conclusion: The presence of LCIS was independently associated with higher rate of IBTR and TR/MM after BCT for invasive breast cancer. LCIS may have significant premalignant potential and progress to an invasive IBTR at the site of index lesion. The adequacy of excision of LCIS associated with invasive carcinoma should be considered in patients undergoing BCT

  3. Quality of Life and Breast Cancer: How Can Mind–Body Exercise Therapies Help? An Overview Study

    Directory of Open Access Journals (Sweden)

    Anne Marie Lunde Husebø

    2017-10-01

    Full Text Available Breast cancer survivors experience extensive treatments, threatening their quality of life. Complementary therapies used as a supplement to cancer treatment may control symptoms, enhance quality of life, and contribute to overall patient care. Mind–body exercise therapies might motivate cancer survivors to exercise, and assist them in regaining health. The purpose of this overview study is to study benefits from mind–body exercise of yoga, tai chi chuan and qigong upon quality of life in breast cancer populations. A systematic overview of reviews was applied. Literature search in five electronic databases and in reference lists was performed during April 2017. In addition, experts in the field were consulted. Of 38 identified titles, 11 review articles, including six meta-analyses were found eligible for review. Methodological quality was high for the majority of quality domains. Yoga, the most studied mind–body therapy, was found to benefit breast cancer patients’ psychological quality of life, while less support was established concerning physical quality of life elements. The evidence of improvements of quality of life from tai chi chuan and qigong remains unclear. Breast cancer survivors’ experiences of psychological and social well-being may be enhanced by practicing yoga.

  4. The diagnosis and management of pre-invasive breast disease: Promise of new technologies in understanding pre-invasive breast lesions

    International Nuclear Information System (INIS)

    Jeffrey, Stefanie S; Pollack, Jonathan R

    2003-01-01

    Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-invasive breast lesions is discussed, including methods that facilitate their implementation. Data indicate that atypical ductal hyperplasia and ductal carcinoma in situ are precursor lesions molecularly similar to adjacent invasive breast cancer. It is expected that molecular technologies will identify breast tissue at risk for the development of unfavorable subtypes of invasive breast cancer and reveal strategies for targeted chemoprevention or eradication

  5. [Advantages and disadvantages of minimally invasive surgery in colorectal cancer surgery].

    Science.gov (United States)

    Zheng, Minhua; Ma, Junjun

    2017-06-25

    Since the emergence of minimally invasive technology twenty years ago, as a surgical concept and surgical technique for colorectal cancer surgery, its obvious advantages have been recognized. Laparoscopic technology, as one of the most important technology platform, has got a lot of evidence-based support for the oncological safety and effectiveness in colorectal cancer surgery Laparoscopic technique has advantages in terms of identification of anatomic plane and autonomic nerve, protection of pelvic structure, and fine dissection of vessels. But because of the limitation of laparoscopic technology there are still some deficiencies and shortcomings, including lack of touch and lack of stereo vision problems, in addition to the low rectal cancer, especially male, obese, narrow pelvis, larger tumors, it is difficult to get better view and manipulating triangle in laparoscopy. However, the emergence of a series of new minimally invasive technology platform is to make up for the defects and deficiencies. The robotic surgical system possesses advantages, such as stereo vision, higher magnification, manipulator wrist with high freedom degree, filtering of tremor and higher stability, but still has disadvantages, such as lack of haptic feedback, longer operation time, high operation cost and expensive price. 3D system of laparoscopic surgery has similar visual experience and feelings as robotic surgery in the 3D view, the same operating skills as 2D laparoscopy and a short learning curve. The price of 3D laparoscopy is also moderate, which makes the 3D laparoscopy more popular in China. Transanal total mesorectal excision (taTME) by changing the traditional laparoscopic pelvic surgery approach, may have certain advantages for male cases with narrow pelvic and patients with large tumor, and it is in accordance with the technical concept of natural orifice, with less minimally invasive and better cosmetics, which can be regarded as a supplemental technique of the

  6. MetastamiRs: Non-Coding MicroRNAs Driving Cancer Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Sergio Rodriguez-Cuevas

    2012-01-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression.

  7. Propolin C Inhibited Migration and Invasion via Suppression of EGFR-Mediated Epithelial-to-Mesenchymal Transition in Human Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jih-Tung Pai

    2018-01-01

    Full Text Available Controlling lung cancer cell migration and invasion via epithelial-to-mesenchymal transition (EMT through the regulation of epidermal growth factor receptor (EGFR signaling pathway has been demonstrated. Searching biological active phytochemicals to repress EGFR-regulated EMT might prevent lung cancer progression. Propolis has been used as folk medicine in many countries and possesses anti-inflammatory, antioxidant, and anticancer activities. In this study, the antimigration and anti-invasion activities of propolin C, a c-prenylflavanone from Taiwanese propolis, were investigated on EGFR-regulated EMT signaling pathway. Cell migration and invasion activities were dose-dependently suppressed by noncytotoxic concentration of propolin C. Downregulations of vimentin and snail as well as upregulation of E-cadherin expressions were through the inhibition of EGFR-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt and extracellular signal-regulated kinase (ERK signaling pathway in propolin C-treated cells. In addition, EGF-induced migration and invasion were suppressed by propolin C-treated A549 lung cancer cells. No significant differences in E-cadherin expression were observed in EGF-stimulated cells. Interestingly, EGF-induced expressions of vimentin, snail, and slug were suppressed through the inhibition of PI3K/Akt and ERK signaling pathway in propolin C-treated cells. Inhibition of cell migration and invasion by propolin C was through the inhibition of EGF/EGFR-mediated signaling pathway, followed by EMT suppression in lung cancer.

  8. Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer.

    Science.gov (United States)

    Singh, Ramesh; Pochampally, Radhika; Watabe, Kounosuke; Lu, Zhaohui; Mo, Yin-Yuan

    2014-11-26

    Exosomes are 30-100 nm membrane vesicles of endocytic origin, mediating diverse biological functions including tumor cell invasion, cell-cell communication and antigen presentation through transfer of proteins, mRNAs and microRNAs. Recent evidence suggests that microRNAs can be released through ceramide-dependent secretory machinery regulated by neutral sphingomyelinase 2 (nSMase2) enzyme encoded by the smpd3 gene that triggers exosome secretion. However, whether exosome-mediated microRNA transfer plays any role in cell invasion remains poorly understood. Thus, the aim of this study was to identify the exosomal microRNAs involved in breast cancer invasion. The expression level of endogenous and exosomal miRNAs were examined by real time PCR and the expression level of target proteins were detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study its uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-10b was estimated by invasion assay. In this study, we demonstrate that microRNA carrying exosomes can be transferred among different cell lines through direct uptake. miR-10b is highly expressed in metastatic breast cancer MDA-MB-231 cells as compared to non-metastatic breast cancer cells or non-malignant breast cells; it is actively secreted into medium via exosomes. In particular, nSMase2 or ceramide promotes the exosome-mediated miR-10b secretion whereas ceramide inhibitor suppresses this secretion. Moreover, upon uptake, miR-10b can suppress the protein level of its target genes such as HOXD10 and KLF4, indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could induce the invasion ability of non-malignant HMLE cells. Together, our results suggest that a set of specific microRNAs may play an important role in modulating tumor microenvironment through

  9. Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development.

    Science.gov (United States)

    Knapp, Deborah W; Ramos-Vara, José A; Moore, George E; Dhawan, Deepika; Bonney, Patty L; Young, Kirsten E

    2014-01-01

    Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

    Science.gov (United States)

    Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

    2016-08-01

    Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

  11. Metastatic Invasive Lobular Breast Cancer Presenting Clinically with Esophageal Dysphagia

    OpenAIRE

    Lilit Karapetyan; Heather Laird-Fick; Reuben Cuison

    2017-01-01

    Background. Intra-abdominal metastases of invasive lobular breast cancer (ILBC) may be insidious. We report a case of metastatic ILBC that presented with dysphagia within weeks of a negative mammogram and before the development of intra-abdominal symptoms. Case. A 70-year-old female developed esophageal dysphagia. She underwent EGD which showed a short segment of stricture of the distal esophagus without significant mucosal changes. Biopsy was unremarkable and patient underwent lower esophage...

  12. MicroRNA-338 inhibits growth, invasion and metastasis of gastric cancer by targeting NRP1 expression.

    Directory of Open Access Journals (Sweden)

    Yang Peng

    Full Text Available NRP1 as multifunctional non-tyrosine-kinase receptors play critical roles in tumor progression. MicroRNAs (miRNAs are an important class of pervasive genes that are involved in a variety of biological functions, particularly cancer. It remains unclear whether miRNAs can regulate the expression of NRP1. The goal of this study was to identify miRNAs that could inhibit the growth, invasion and metastasis of gastric cancer by targeting NRP1 expression. We found that miR-338 expression was reduced in gastric cancer cell lines and in gastric cancer tissues. Moreover, we found that miR-338 inhibited gastric cancer cell migration, invasion, proliferation and promoted apoptosis by targeting NRP1 expression. As an upstream regulator of NRP1, miR-338 directly targets NRP1. The forced expression of miR-338 inhibited the phosphorylation of Erk1/2, P38 MAPK and Akt; however, the expression of phosphorylated Erk1/2, P38 MAPK and Akt was restored by the overexpression of NRP1. In AGS cells infected with miR-338 or transfected with SiNRP1, the protein levels of fibronectin, vimentin, N-cadherin and SNAIL were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-338-expressing cells was restored to normal levels by the restoration of NRP1 expression. In vivo, miR-338 also decreased tumor growth and suppressed D-MVA by targeting NRP1. Therefore, we conclude that miR-338 acts as a novel tumor suppressor gene in gastric cancer. miR-338 can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as gastric cancer EMT, by attenuating the expression of NRP1.

  13. Identification of a novel polyprenylated acylphloroglucinol-derived SIRT1 inhibitor with cancer-specific anti-proliferative and invasion-suppressing activities

    Science.gov (United States)

    ZHU, LIJIA; QI, JI; CHIAO, CHRISTINE YA-CHI; ZHANG, QIANG; PORCO, JOHN A.; FALLER, DOUGLAS V.; DAI, YAN

    2014-01-01

    SIRT1, a class III histone deacetylase, plays a critical role in regulating cancer cell growth, migration and invasion, which makes it a potential target for cancer therapeutics. In this study, we screened derivatives of several groups of natural products and identified a novel SIRT1 inhibitor JQ-101, a synthetic derivative of the polyprenylated acylphloroglucinol (PPAP) natural products, with an IC50 for SIRT1 of 30 μM in vitro, with 5-fold higher activity for SIRT1 vs. SIRT2. Exposure of tumor cells to JQ-101 significantly enhanced acetylation of p53 and histone H4K16 at known sites of SIRT1 deacetylation, validating SIRT1 as its cellular target. JQ-101 suppressed cancer cell growth and survival by targeting SIRT1, and also exhibited selective cytotoxicity towards a panel of human tumor cell lines, while producing no toxicity in two normal human cell types at comparable concentrations. JQ-101 induced both apoptosis and cell senescence, and suppressed cancer cell invasion in vitro. In summary, we have identified JQ-101 as a new SIRT1 inhibitor which may have potential application in cancer treatment through its ability to induce tumor cell apoptosis and senescence and suppress cancer cell invasion. PMID:25189993

  14. Increased cell motility and invasion upon knockdown of lipolysis stimulated lipoprotein receptor (LSR in SW780 bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Ørntoft Torben F

    2008-07-01

    Full Text Available Abstract Background Mechanisms underlying the malignant development in bladder cancer are still not well understood. Lipolysis stimulated lipoprotein receptor (LSR has previously been found to be upregulated by P53. Furthermore, we have previously found LSR to be differentially expressed in bladder cancer. Here we investigated the role of LSR in bladder cancer. Methods A time course siRNA knock down experiment was performed to investigate the functional role of LSR in SW780 bladder cancer cells. Since LSR was previously shown to be regulated by P53, siRNA against TP53 was included in the experimental setup. We used Affymetrix GeneChips for measuring gene expression changes and we used Ingenuity Pathway Analysis to investigate the relationship among differentially expressed genes upon siRNA knockdown. Results By Ingenuity Pathway analysis of the microarray data from the different timepoints we identified six gene networks containing genes mainly related to the functional categories "cancer", "cell death", and "cellular movement". We determined that genes annotated to the functional category "cellular movement" including "invasion" and "cell motility" were highly significantly overrepresented. A matrigel assay showed that 24 h after transfection the invasion capacity was significantly increased 3-fold (p Conclusion We conclude that LSR may impair bladder cancer cells from gaining invasive properties.

  15. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

    Science.gov (United States)

    2011-01-01

    Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi

  16. Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

    Directory of Open Access Journals (Sweden)

    Lluís Nisa

    2015-03-01

    Full Text Available High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches.

  17. Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

    Science.gov (United States)

    Geredeli, Caglayan; Dogru, Osman; Omeroglu, Ethem; Yilmaz, Farise; Cicekci, Faruk

    2015-05-05

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases.

  18. Vulvar Cancer Overview

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  19. Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP

    Directory of Open Access Journals (Sweden)

    Chanjuan Li

    2016-08-01

    Full Text Available Background/Aims: Forkhead Box Protein C2 (FOXC2 has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50 of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP and its parental cell line (SKOV3. Small hairpin RNA (shRNA was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM (PConclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

  20. Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

    Science.gov (United States)

    Ellingson, Marissa S; Hart, Steven N; Kalari, Krishna R; Suman, Vera; Schahl, Kimberly A; Dockter, Travis J; Felten, Sara J; Sinnwell, Jason P; Thompson, Kevin J; Tang, Xiaojia; Vedell, Peter T; Barman, Poulami; Sicotte, Hugues; Eckel-Passow, Jeanette E; Northfelt, Donald W; Gray, Richard J; McLaughlin, Sarah A; Moreno-Aspitia, Alvaro; Ingle, James N; Moyer, Ann M; Visscher, Daniel W; Jones, Katie; Conners, Amy; McDonough, Michelle; Wieben, Eric D; Wang, Liewei; Weinshilboum, Richard; Boughey, Judy C; Goetz, Matthew P

    2015-09-01

    When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled (median age 51) with the following subtypes: triple negative (n = 43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n = 13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%) patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2 (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n = 1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1). 121/124 (97.6%) patients consented to return of research results. Thirteen (10.5%) had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management.

  1. Pilot Study to Measure the Effects of NSAID Use on Angiogenesis and Apoptosis in Female Invasive Breast Cancer

    National Research Council Canada - National Science Library

    Richardson, John

    2003-01-01

    To examine the effects of NASIDs on invasive breast cancer we are performing a immunohistochemical analysis on 220 cases of breast cancer from Saskatchewan which has provided a complete drug history of each patient...

  2. Gallbladder Cancer Overview

    Science.gov (United States)

    ... Content Español ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  3. Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Joe Tien

    Full Text Available This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

  4. MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition.

    Science.gov (United States)

    Roy, L D; Sahraei, M; Subramani, D B; Besmer, D; Nath, S; Tinder, T L; Bajaj, E; Shanmugam, K; Lee, Y Y; Hwang, S I L; Gendler, S J; Mukherjee, P

    2011-03-24

    Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with β-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and β-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.

  5. Vaginal Cancer Overview

    Science.gov (United States)

    ... are here Home > Types of Cancer > Vaginal Cancer Vaginal Cancer This is Cancer.Net’s Guide to Vaginal Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Vaginal Cancer Introduction Statistics Medical Illustrations Risk Factors and ...

  6. miR-15a/miR-16 cluster inhibits invasion of prostate cancer cells by suppressing TGF-β signaling pathway.

    Science.gov (United States)

    Jin, Wei; Chen, Fangjie; Wang, Kefeng; Song, Yan; Fei, Xiang; Wu, Bin

    2018-05-23

    To determine whether and how miR15a/16 regulate TGF-β signaling pathways during the progression of prostate cancer. We used bioinformatics prediction, reporter gene assay, real-time PCR, Matrigel invasion assay and Western blot to dissect the molecular mechanism of how miR-15a/miR-16 may cause metastasis in prostate tumor. MiR-15a/16 targeted and inhibited the expression of endogenous Smad3 and ACVR2A proteins. The overexpression of miR15a/16 down-regulated p-smad3 expression, affected the expression of both MMP2 and E-cadherin, and down-regulated the expression of the EMT-mediated factors Snail and Twist in LNCaP prostate cancer cells. The overexpression of miR15a/16 decreased the invasion of LNCaP cells. MiR-15a/miR-16 cluster could reverse the invasion of activin A-mediated prostate cancer cells. After the inhibition of the activin/smad signaling pathway, the inhibitory effect of invasion in prostate cancer cells by miR-15a/miR-16 cluster disappeared. Our data indicated that miR15a/16 inhibited the components of TGF-β signaling pathways in LNCaP cell line, which might relate to the progression and metastasis of prostate cancer. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  7. Calycosin Inhibits the Migration and Invasion of Human Breast Cancer Cells by Down-Regulation of Foxp3 Expression

    Directory of Open Access Journals (Sweden)

    Shuangxi Li

    2017-12-01

    Full Text Available Background/Aims: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. Methods: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 μM of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3, vascular endothelial growth factor (VEGF and matrix metalloproteinase-9 (MMP-9 in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot. Results: Treatment with lower doses (6.25 or 12.5 μM promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells. Conclusion: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression.

  8. Mapping invasive weeds using airborne hyperspectral imagery

    Science.gov (United States)

    Invasive plant species present a serious problem to the natural environment and have adverse ecological and economic impacts on both terrestrial and aquatic ecosystems they invade. This article provides a brief overview on the use of remote sensing for mapping invasive plant species in both terrestr...

  9. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  10. Contemporary management of muscle-invasive bladder cancer

    Science.gov (United States)

    Dall’Era, Marc A; Cheng, Liang; Pan, Chong-Xian

    2012-01-01

    The current standard treatment for muscle-invasive nonmetastatic bladder cancer is neoadjuvant platinum-based chemotherapy followed by radical cystectomy. However, neoadjuvant chemotherapy is not widely accepted even with level 1 evidence. Adjuvant chemotherapy should be discussed if patients have not received neoadjuvant chemotherapy before surgery and have high-risk pathologic features. Although not considered standard of care, bladder-sparing therapy can be considered for highly selected patients and for those medically unfit for surgery. Even though there are no level 1 data, the treatment outcomes for highly select patients given bladder-sparing therapy appear promising, with many patients retaining a functional bladder. Personalized chemotherapy is currently being actively pursued to target the underlying molecular changes and tailor to individual needs. PMID:22845409

  11. Suppression of SOX18 by siRNA inhibits cell growth and invasion of breast cancer cells.

    Science.gov (United States)

    Zhang, Jianxiang; Ma, Yanmei; Wang, Shoujun; Chen, Fu; Gu, Yuanting

    2016-06-01

    Breast cancer is the most common malignancy in women around the world, and its incidence and mortality rates are still rising. An increasing number of studies have reported that SOX18 plays an important role in various cancers. However, the role of SOX18 in breast cancer remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of SOX18 in breast cancer. We found that the mRNA and protein expression levels of SOX18 were prevalently and significantly overexpressed in human breast cancer cell lines. Next, we performed loss-of-function experiments by transfection of two breast cancer cell lines, BT-474 and MCF-7, with SOX18 small interfering RNAs (siRNA). Results showed that SOX18 siRNA transfection significantly suppressed mRNA and protein expression of SOX18 in breast cancer cells. Furthermore, knockdown of SOX18 significantly inhibited cell proliferation and invasion, but promoted apoptosis in breast cancer cells. Importantly, several oncogenic proteins, including the Ras homolog gene family member A (RhoA), platelet-derived growth factor B (PDGFB), Insulin-like growth factor 1 receptor (IGF-1R), and matrix metalloproteinase-7 (MMP-7), were markedly decreased by SOX18 siRNA. Taken together, the results of our study suggest that knockdown of SOX18 inhibits breast cancer cell growth and invasion, possibly by downregulating downstream oncogenic proteins, providing novel insights into the development of breast cancer therapy through targeting of SOX18.

  12. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    International Nuclear Information System (INIS)

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-01-01

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug

  13. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Gang [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Zou, Xi [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Zhou, Jin-Yong [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Sun, Wei [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Wu, Jian [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Xu, Jia-Li [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Wang, Rui-Ping, E-mail: ruipingwang61@hotmail.com [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  14. Radiation-induced relief of pain in an animal model with bone invasion from cancer

    International Nuclear Information System (INIS)

    Seong, J.; Kim, J.; Kim, K.H.; Kim, U.J.; Lee, B.W.

    2003-01-01

    In clinic, local radiation is effective for relief of pain from cancer invasion into the bones. This effect is usually observed before the regression of tumor occurs, which implies radiation-induced pain relief by mechanisms other than tumor irradication. In this study, possible mechanisms were explored in animal model system. To establish an animal model, syngeneic hepatocarcinoma, HCa-I was transplanted on femoral periosteum of C3H/HeJ male mice and bone-invasive tumor growth was identified through the histological analysis. Development of tumor-induced pain was assessed by von Frey filament test, acetone test, and radiant heat test. Animals were also irradiated for their tumors. Any change in pain was analyzed by above tests for the quantitative change and by immunohistochemical stain for the expression of molecules such as c-fos, substance P, and calcitonin gene-related peptide (CGRP) in lumbar spinal cord. Cancer invasion into the bone was started from 7th day after transplantation and became evident at day 14. Objective increase of pain in the ipsilateral thigh was observed at day 14 on von Frey filament test and acetone test, while there was no remarkable regression of the tumors. In this model system, local radiation of tumor resulted in decrease in objective pain on von Frey filament test and acetone test. In the immunohistochemical stain for lumbar spinal cord, the expression of substance P and CGRP but not c-fos increased in tumor-bearing animal compared to the control. The expression of these molecules decreased in animals given local radiation. In summary, an animal model system was established for objective pain from cancer invasion into the bones. Local radiation of tumor induced objective pain relief and this effect seems to be mediated not by tumor regression but through altered production of pain-related molecules

  15. Radiation-induced relief of pain in an animal model with bone invasion from cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seong, J; Kim, J; Kim, K H; Kim, U J; Lee, B W [Yonsei University Medical College, (Korea, Republic of)

    2003-07-01

    In clinic, local radiation is effective for relief of pain from cancer invasion into the bones. This effect is usually observed before the regression of tumor occurs, which implies radiation-induced pain relief by mechanisms other than tumor irradication. In this study, possible mechanisms were explored in animal model system. To establish an animal model, syngeneic hepatocarcinoma, HCa-I was transplanted on femoral periosteum of C3H/HeJ male mice and bone-invasive tumor growth was identified through the histological analysis. Development of tumor-induced pain was assessed by von Frey filament test, acetone test, and radiant heat test. Animals were also irradiated for their tumors. Any change in pain was analyzed by above tests for the quantitative change and by immunohistochemical stain for the expression of molecules such as c-fos, substance P, and calcitonin gene-related peptide (CGRP) in lumbar spinal cord. Cancer invasion into the bone was started from 7th day after transplantation and became evident at day 14. Objective increase of pain in the ipsilateral thigh was observed at day 14 on von Frey filament test and acetone test, while there was no remarkable regression of the tumors. In this model system, local radiation of tumor resulted in decrease in objective pain on von Frey filament test and acetone test. In the immunohistochemical stain for lumbar spinal cord, the expression of substance P and CGRP but not c-fos increased in tumor-bearing animal compared to the control. The expression of these molecules decreased in animals given local radiation. In summary, an animal model system was established for objective pain from cancer invasion into the bones. Local radiation of tumor induced objective pain relief and this effect seems to be mediated not by tumor regression but through altered production of pain-related molecules.

  16. Update on raloxifene: role in reducing the risk of invasive breast cancer in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Vogel VG

    2011-10-01

    Full Text Available Victor G Vogel Cancer Institute, Geisinger Health System, Danville, PA, USA Abstract: Risk factors allow us to define women who are at increased lifetime risk for breast cancer, and the most important factor is age. Benign breast disease increases risk, and the most important histologies are atypical lobular or ductal hyperplasia and lobular carcinoma in situ. Family history of breast cancer among first-degree relatives (mother, sisters, daughters also increases risk. Quantitative measures of risk give accurate predictions of breast cancer incidence for groups of women but not for individual subjects. Multiple published, randomized controlled trials, which employed selective estrogen receptor (ER modulators (SERMs, have demonstrated consistent reductions of 35% or greater in the risk of ER-positive invasive and noninvasive breast cancer in postmenopausal women. Professional organizations in the US now recommend the use of SERMs to reduce the risk of breast cancer in high-risk, postmenopausal women. Raloxifene and tamoxifen reduce the risk of ER-positive invasive breast cancer with equal efficacy, but raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use. Keywords: selective estrogen receptor modulators (SERMs, raloxifene, risk reduction, chemoprevention

  17. The miR-599 promotes non-small cell lung cancer cell invasion via SATB2

    International Nuclear Information System (INIS)

    Tian, Wenjun; Wang, Guanghai; Liu, Yiqing; Huang, Zhenglan; Zhang, Caiqing; Ning, Kang; Yu, Cuixiang; Shen, Yajuan; Wang, Minghui; Li, Yuantang; Wang, Yong; Zhang, Bingchang; Zhao, Yaoran

    2017-01-01

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. Here, we identified that miR-599 is up-regulated in non-small cell lung cancer (NSCLC) patients. It promoted NSCLC cell proliferation by negatively regulating SATB2. In NSCLC cell lines, CCK-8 proliferation assay indicated that the cell proliferation is promoted by miR-599 mimics. Transwell assay showed that miR-599 mimics promoted the invasion and migration of NSCLC cells. Luciferase assays confirmed that miR-599 directly binds to the 3'untranslated region of SATB2, and western blotting showed that miR-599 suppresses the expression of SATB2 at the protein level. This study indicates that miR-599 promotes proliferation and invasion of NSCLC cell lines via SATB2. The miR-599 may represent a potential therapeutic target for NSCLC treatment. - Highlights: • miR-599 is up-regulated in NSCLC. • miR-599 promotes the proliferation and invasion of NSCLC cells. • miR-599 inhibitors inhibits the proliferation and invasion of NSCLC cells. • miR-599 targets 3′ UTR of SATB2 in NSCLC cells. • miR-599 inhibits SATB2 in NSCLC cells.

  18. Intracellular Hyper-Acidification Potentiated by Hydrogen Sulfide Mediates Invasive and Therapy Resistant Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Zheng-Wei Lee

    2017-10-01

    Full Text Available Slow and continuous release of H2S by GYY4137 has previously been demonstrated to kill cancer cells by increasing glycolysis and impairing anion exchanger and sodium/proton exchanger activity. This action is specific for cancer cells. The resulting lactate overproduction and defective pH homeostasis bring about intracellular acidification-induced cancer cell death. The present study investigated the potency of H2S released by GYY4137 against invasive and radio- as well as chemo-resistant cancers, known to be glycolytically active. We characterized and utilized cancer cell line pairs of various organ origins, based on their aggressive behaviors, and assessed their response to GYY4137. We compared glycolytic activity, via lactate production, and intracellular pH of each cancer cell line pair after exposure to H2S. Invasive and therapy resistant cancers, collectively termed aggressive cancers, are receptive to H2S-mediated cytotoxicity, albeit at a higher concentration of GYY4137 donor. While lactate production was enhanced, intracellular pH of aggressive cancers was only modestly decreased. Inherently, the magnitude of intracellular pH decrease is a key determinant for cancer cell sensitivity to H2S. We demonstrated the utility of coupling GYY4137 with either simvastatin, known to inhibit monocarboxylate transporter 4 (MCT4, or metformin, to further boost glycolysis, in bringing about cell death for aggressive cancers. Simvastatin inhibiting lactate extrusion thence contained excess lactate induced by GYY4137 within intracellular compartment. In contrast, the combined exposure to both GYY4137 and metformin overwhelms cancer cells with lactate over-production exceeding its expulsion rate. Together, GYY4137 and simvastatin or metformin synergize to induce intracellular hyper-acidification-mediated cancer cell death.

  19. Assessment of deep myometrial invasion of endometrial cancer on MRI: added value of second-opinion interpretations by radiologists subspecialized in gynaecologic oncology.

    Science.gov (United States)

    Woo, Sungmin; Kim, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup

    2017-05-01

    To investigate the added value of secondary reports issued by radiologists subspecializing in gynaecologic imaging for determining deep myometrial invasion of endometrial cancer on MRI. Initial (from referring institutions) and secondary (by subspecialized radiologists) interpretations of MRI of 55 patients with endometrial cancer were retrospectively reviewed. A radiologist blinded to clinicopathological information assessed both reports for the presence of deep myometrial invasion. Reference standard was based on hysterectomy specimens. Kappa coefficients (k) were used to measure their concordance. McNemar testing and receiver operating characteristic (ROC) analysis was used to compare sensitivities, specificities and areas under the curves (AUCs). Deep myometrial invasion was present in 25 (45.5 %) patients. Among 27.3 % (15/55; k = 0.458) patients with discrepant results, secondary interpretations were correct in 10 (66.7 %) cases. Sensitivity was higher in secondary than in initial reports (76.0 % vs. 48.0 %, p = 0.039) while no significant difference was seen in specificity (70.0 % vs. 76.7 %, p = 0.668). At ROC analysis, there was a tendency for higher AUCs in secondary reports (0.785 vs 0.669, p = 0.096). Secondary readings of MRI by subspecialized gynaecologic oncologic radiologists may provide incremental value in determining deep myometrial invasion of endometrial cancer. • Deep myometrial invasion is an important prognostic factor in endometrial cancer. • Assessment of deep myometrial invasion is often discrepant between initial and secondary reports. • Secondary reports showed higher sensitivity and accuracy. • Secondary review of MRI may provide incremental value in endometrial cancer patients.

  20. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Science.gov (United States)

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, J. F.; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P

    PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  2. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, Jeroen F.; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B; van Diest, Paul J.; van Bergen En Henegouwen, Paul M P

    Purpose: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. Procedures: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  3. Role of SMAD4 in the mechanism of valproic acid's inhibitory effect on prostate cancer cell invasiveness.

    Science.gov (United States)

    Jiang, Wei; Zheng, Yi; Huang, Zhongxian; Wang, Muwen; Zhang, Yinan; Wang, Zheng; Jin, Xunbo; Xia, Qinghua

    2014-05-01

    To investigate the influence of the histone deacetylase inhibitor valproic acid (VPA) on SMAD4 expression and invasive ability of prostate cancer cell lines. DU145 and PC3 cell lines were treated with 0, 2, and 5 mMol/l of VPA; invasion of DU145 and PC3 cells were then examined by transwell assay. Immunohistochemistry and Western blot were used to examine SMAD4 protein expression in DU145 and PC3 cells. Compared with controls, VPA significantly suppressed invasiveness in both PC3 and DU145 cells in a dose-dependent way (P AKT protein (which was regarded as an effective indicator here), and meanwhile, SMAD4 expression was down-regulated after VPA treatment in a dose-dependent manner in both DU145 (P SMAD4 enhancers could form a basis for a novel prostate cancer treatment.

  4. Treatment results of radiation therapy for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Langsenlehner, Tanja; Doeller, Carmen; Stranzl-Lawatsch, Heidi; Kapp, Karin S. [Univ. Clinic of Therapeutic Radiology and Oncology, Medical Univ. of Graz (Austria); Quehenberger, Franz [Inst. for Medical Informatics, Statistics and Documentation, Medical Univ. of Graz (Austria); Langsenlehner, Uwe [Internal Outpatient Dept., Steiermaerkische GKK, Graz (Austria); Pummer, Karl [Dept. of Urology, Medical Univ. of Graz (Austria)

    2010-04-15

    Purpose: To assess local control and survival rates in patients with muscle-invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. Patients and methods: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. Results: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. Conclusion: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy. (orig.)

  5. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

    Directory of Open Access Journals (Sweden)

    Hellevik Turid

    2012-04-01

    Full Text Available Abstract Background Cancer-Associated Fibroblasts (CAFs are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR, equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART for medically inoperable stage-I/II non-small-cell lung cancers. Methods CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs and their endogenous inhibitors (TIMPs were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining. Results Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed. Conclusions Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.

  6. Muscle invasive bladder cancer: examining survivor burden and unmet needs.

    Science.gov (United States)

    Mohamed, Nihal E; Chaoprang Herrera, Phapichaya; Hudson, Shawna; Revenson, Tracey A; Lee, Cheryl T; Quale, Diane Z; Zarcadoolas, Christina; Hall, Simon J; Diefenbach, Michael A

    2014-01-01

    Although improvements in perioperative care have decreased surgical morbidity after radical cystectomy for muscle invasive bladder cancer, treatment side effects still have a negative impact on patient quality of life. We examined unmet patient needs along the illness trajectory. A total of 30 patients (26.7% women) treated with cystectomy and urinary diversion for muscle invasive bladder cancer participated in the study. Patients were recruited from the Department of Urology at Mount Sinai and through advertisements on the Bladder Cancer Advocacy Network (BCAN) website between December 2011 and September 2012. Data were collected at individual interviews, which were audiotaped and transcribed. Transcribed data were quantitatively analyzed to explore key unmet needs. At diagnosis unmet informational needs were predominant, consisting of insufficient discussion of certain topics, including urinary diversion options and their side effects, self-care, the recovery process and medical insurance. Unmet psychological needs related to depression, and worries about changes in body image and sexual function were reported. Postoperative unmet needs revolved around medical needs (eg pain and bowel dysfunction) and instrumental needs (eg need of support for stomal appliances, catheters and incontinence). During survivorship (ie 6 to 72 months postoperatively) unmet needs centered around psychological support (ie depression, poor body image and sexual dysfunction) and instrumental support (eg difficulty adjusting to changes in daily living). Meeting patient needs is imperative to ensure adequate patient involvement in health care and enhance postoperative quality of life. An effective support provision plan should follow changes in patient needs. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. 5′-Inositol phosphatase SHIP2 recruits Mena to stabilize invadopodia for cancer cell invasion

    Science.gov (United States)

    Zaoui, Kossay; Huang, Bruce H.; Sangwan, Veena; Gertler, Frank B.

    2016-01-01

    Invadopodia are specialized membrane protrusions that support degradation of extracellular matrix (ECM) by cancer cells, allowing invasion and metastatic spread. Although early stages of invadopodia assembly have been elucidated, little is known about maturation of invadopodia into structures competent for ECM proteolysis. The localized conversion of phosphatidylinositol(3,4,5)-triphosphate and accumulation of phosphatidylinositol(3,4)-bisphosphate at invadopodia is a key determinant for invadopodia maturation. Here we investigate the role of the 5′-inositol phosphatase, SHIP2, and reveal an unexpected scaffold function of SHIP2 as a prerequisite for invadopodia-mediated ECM degradation. Through biochemical and structure-function analyses, we identify specific interactions between SHIP2 and Mena, an Ena/VASP-family actin regulatory protein. We demonstrate that SHIP2 recruits Mena, but not VASP, to invadopodia and that disruption of SHIP2–Mena interaction in cancer cells leads to attenuated capacity for ECM degradation and invasion in vitro, as well as reduced metastasis in vivo. Together, these findings identify SHIP2 as a key modulator of carcinoma invasiveness and a target for metastatic disease. PMID:27597754

  8. miR-206 inhibits cell proliferation, migration, and invasion by targeting BAG3 in human cervical cancer.

    Science.gov (United States)

    Wang, Yingying; Tian, Yongjie

    2018-01-02

    miR-206 and bcl2-associated athanogene 3 (BAG3) have been suggested as important regulators in various cancer types. However, the biological role of miR-206 and BAG3 in cervical cancer (CC) remains unclear. Here, we investigated the expressions and mechanisms of miR-206 and BAG3 in cervical cancer using in vitro and in vivo assays. In the present study, miR-206 expression was expressed at a lower level in CC tissues and cells than adjacent normal tissues and NEEC cells. By contrast, BAG3 mRNA and protein were expressed at higher levels in CC tissues and cells. Furthermore, miR-206 overexpression repressed cell proliferation, migration and invasion in vitro, and the 3'-untranslated region (3'-UTR) of BAG3 was a direct target of miR-206. miR-206 overexpression also inhibited EGFR, Bcl-2 and MMP2/9 protein expression, but promoted Bax protein expression. Besides, BAG3 over-expression partially abrogated miR-206-inhibited cell proliferation and invasion, while BAG3 silencing enhanced miR206-mediated inhibition. In vivo assay revealed that miR-206 repressed tumor growth in nude mice xenograft model. In conclusion, miR-206 inhibits cell proliferation, migration, and invasion by targeting BAG3 in human cervical cancer. Thus, miR-206-BAG3 can be used as a useful target for cervical cancer.

  9. CSF-1R as an inhibitor of apoptosis and promoter of proliferation, migration and invasion of canine mammary cancer cells

    Science.gov (United States)

    2013-01-01

    Background Tumor-associated macrophages (TAMs) have high impact on the cancer development because they can facilitate matrix invasion, angiogenesis, and tumor cell motility. It gives cancer cells the capacity to invade normal tissues and metastasize. The signaling of colony-stimulating factor-1 receptor (CSF-1R) which is an important regulator of proliferation and differentiation of monocytes and macrophages regulates most of the tissue macrophages. However, CSF-1R is expressed also in breast epithelial tissue during some physiological stages i.g.: pregnancy and lactation. Its expression has been also detected in various cancers. Our previous study has showed the expression of CSF-1R in all examined canine mammary tumors. Moreover, it strongly correlated with grade of malignancy and ability to metastasis. This study was therefore designed to characterize the role of CSF-1R in canine mammary cancer cells proliferation, apoptosis, migration, and invasion. As far as we know, the study presented hereby is a pioneering experiment in this field of veterinary medicine. Results We showed that csf-1r silencing significantly increased apoptosis (Annexin V test), decreased proliferation (measured as Ki67 expression) and decreased migration (“wound healing” assay) of canine mammary cancer cells. Treatment of these cells with CSF-1 caused opposite effect. Moreover, csf-1r knock-down changed growth characteristics of highly invasive cell lines on Matrigel matrix, and significantly decreased the ability of these cells to invade matrix. CSF-1 treatment increased invasion of cancer cells. Conclusion The evidence of the expression and functional role of the CSF-1R in canine mammary cancer cells indicate that CSF-1R targeting may be a good therapeutic approach. PMID:23561040

  10. Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Ping, Yu; Liu, Shasha [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); School of Life Sciences, Zhengzhou University, Zhengzhou 450000 (China); Shi, Xiaojuan; Li, Lifeng [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Wang, Liping [Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Huang, Lan [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Zhang, Bin [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Sun, Yan [Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (China); and others

    2015-08-01

    Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells. - Highlights: • Esophageal cancer sphere-forming cells possess cancer stem cell properties. • Sphere-forming cells enhance TGF-β1 pathway activity. • TGF-β 1 inhibitor suppresses the migration and invasion of sphere-forming cells.

  11. Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

    International Nuclear Information System (INIS)

    Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng; Ping, Yu; Liu, Shasha; Shi, Xiaojuan; Li, Lifeng; Wang, Liping; Huang, Lan; Zhang, Bin; Sun, Yan

    2015-01-01

    Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells. - Highlights: • Esophageal cancer sphere-forming cells possess cancer stem cell properties. • Sphere-forming cells enhance TGF-β1 pathway activity. • TGF-β 1 inhibitor suppresses the migration and invasion of sphere-forming cells

  12. Involvement of microRNAs-MMPs-E-cadherin in the migration and invasion of gastric cancer cells infected with Helicobacter pylori.

    Science.gov (United States)

    Yang, Yongmei; Li, Xiaohui; Du, Jie; Yin, Youcong; Li, Yuanjian

    2018-06-15

    It has been found that Helicobacter pylori (H. pylori)is not only the main cause of gastric cancer, but also closely related to its metastasis. E-cadherin cleavage induced by matrix metalloproteinases (MMPs) plays an important role in the tumor metastasis. In the present study, we investigated the role of microRNAs-MMPs-E-cadherin in migration and invasion of gastric cancer cells treated with H. pylori. The results showed that H. pylori induced migration and invasion of SGC-7901 cells with a down-regulation of E-cadherin expression, which were abolished by MMPs knock down, E-cadherin overexpression, mimics of miR128 and miR148a. MiR128/miR148a inhibitors restored MMP-3/MMP-7 expression, down-regulated E-cadherin level, and accelerated cellular migration and invasion. This study suggests that H. pylori induces migration and invasion of gastric cancer cells through reduction of E-cadherin function by activation of MMP-3, - 7. The present results also suggest that the activated MMPs/E-cadherin pathway is related with down-regulation of miR128/miR148a in the human gastric cancer cells infected with H. pylori. Copyright © 2018. Published by Elsevier Inc.

  13. Rocky Mountain Research Station invasive species visionary white paper

    Science.gov (United States)

    D. E. Pearson; M. Kim; J. Butler

    2011-01-01

    Invasive species represent one of the single greatest threats to natural ecosystems and the services they provide. Effectively addressing the invasive species problem requires management that is based on sound research. We provide an overview of recent and ongoing invasive species research conducted by Rocky Mountain Research Station scientists in the Intermountain...

  14. Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration.

    Science.gov (United States)

    Yang, Hui-ting; Chao, Pei-chun; Yin, Mei-chin

    2013-02-01

    The influence of riboflavin (vitamin B(2) ) upon growth, invasion, and migration in non-small cell lung cancer cell lines was evaluated. Riboflavin at 1, 10, 25, 50, 100, 200, or 400 μmol/L was added into A549, H3255, or Calu-6 cells. The effects of this compound upon level and/or expression of reactive oxygen species (ROS), inflammatory cytokines, intercellular adhesion molecule (ICAM)-1, fibronectin, matrix metalloproteinase (MMP)-9, MMP-2, focal adhesion kinase (FAK), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) were examined. Results showed that riboflavin at test doses did not affect the level of ROS and glutathione. Riboflavin at 200 and 400 μmol/L significantly enhanced cell growth in test lung cancer cell lines, and at 400 μmol/L significantly increased the release of interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. This agent at 200 and 400 μmol/L also upregulated protein production of ICAM-1, fibronectin, MMP-9, MMP-2, NF-κB p50, p-p38 MAPK, and FAK; and at 400 μmol/L enhanced invasion and migration in test cell lines. These findings suggested that riboflavin at high doses might promote lung cancer progression. © 2013 Institute of Food Technologists®

  15. [A Case of Performed Right Colectomy with Pancreato-Duodenectomy for Transverse Colon Cancer Invased to Duodenum].

    Science.gov (United States)

    Udo, Ryutaro; Enomoto, Masanobu; Tsurui, Kazushige; Kuboyama, Yuu; Kuwabara, Hiroshi; Shigoka, Masatoshi; Ishizaki, Tetsuo; Katsumata, Kenji; Obikane, Hiyo; Tsuchida, Akihiko

    2018-04-01

    There is a clear consensus regarding the combined resection of organs with cancer invasion, patients with colon cancer. However, there are very few reports to our knowledge regarding the use of pancreato-duodenectomy(PD)for colon cancer patients with cancer invasion in the duodenum. We here report a colon cancer patient in whom we performed PD and right hemicolectomy, who showed favorable results with no recurrence. The patient was a 69-year-old woman. Her chief complaint was hypogastric pain. Her previous doctor performed colonoscopy and a colonoscopic biopsy, and detected a type 2 lesion, throughout the entire circumference of the transverse colon near the liver, and she was diagnosed with adenocarcinoma. From further imaging analyses, she was diagnosed as having transverse colon cancer with invasion into the superior mesenteric vein(SMV), duodenum, and pancreatic head, and No. 223 lymph node metastasis. The patient's cancer was concluded to be unresectable, and she underwent chemotherapy, namely mFOLFOX6 with cetuxiumab(Cmab). One course of mFOLFOX with Cmab, the patient decided to consult our hospital for a second opinion. We concluded that her cancer was resectable, so we performed PD, right hemicolectomy, and resection and reconstruction of a part of the SMV. The operation time was 5 hours 17 minutes, and total blood loss was 190 mL. The histopathological diagnosis was tub2, T4b(duodenum and, tissue surrounding the SMV), int, INF b, ly1, v2, PN1b, EX(+)/ND(PN+, v+), PM0(25 cm), DM0(14.3 cm), N1(1/ 20), H0, P0, M0, pStage III a. She was discharged 15 days after surgery with no complications, and thereafter received ajduvant chemotherapy(capecitabine with oxaliplatin)as an outpatient. After 3 courses, capecitabine with oxaliplatin was changed to capecitabine because she developed a nervous system disorder, and she was further treated for approximately about 6 months. She is doing well at the time of writing, with no recurrences for 2 years. We suggest that PD

  16. Non-thermal atmospheric pressure plasma inhibits thyroid papillary cancer cell invasion via cytoskeletal modulation, altered MMP-2/-9/uPA activity.

    Directory of Open Access Journals (Sweden)

    Jae Won Chang

    Full Text Available Plasma, the fourth state of matter, is defined as a partially or completely ionized gas that includes a mixture of electrons and ions. Advances in plasma physics have made it possible to use non-thermal atmospheric pressure plasma (NTP in cancer research. However, previous studies have focused mainly on apoptotic cancer cell death mediated by NTP as a potential cancer therapy. In this study, we investigated the effect of NTP on invasion or metastasis, as well as the mechanism by which plasma induces anti-migration and anti-invasion properties in human thyroid papillary cancer cell lines (BHP10-3 and TPC1. Wound healing, pull-down, and Transwell assays demonstrated that NTP reduced cell migration and invasion. In addition, NTP induced morphological changes and cytoskeletal rearrangements, as detected by scanning electron microscopy and immunocytochemistry. We also examined matrix metalloproteinase (MMP-2/-9 and urokinase-type plasminogen activator (uPA activity using gelatin zymography, uPA assays and RT-PCR. FAK, Src, and paxillin expression was detected using Western blot analyses and immunocytochemistry. NTP decreased FAK, Src, and paxillin expression as well as MMP/uPA activity. In conclusion, NTP inhibited the invasion and metastasis of BHP10-3 and TPC1 cells by decreasing MMP-2/-9 and uPA activities and rearranging the cytoskeleton, which is regulated by the FAK/Src complex. These findings suggest novel actions for NTP and may aid in the development of new therapeutic strategies for locally invasive and metastatic cancers.

  17. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Contact Dictionary Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer ... Is Cancer Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening Overview ...

  18. RNA interference suppression of mucin 5AC (MUC5AC reduces the adhesive and invasive capacity of human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Yamada Nobuya

    2010-05-01

    Full Text Available Abstract Background MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC de novo expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells. Methods We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells in vitro and in vivo. We compared parental cells (SW1990 and BxPC3 with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3. Results MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP -3 and vascular endothelial growth factor (VEGF were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. In vivo, si-SW1990 did not establish subcutaneous tumor in nude mice. Conclusions Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.

  19. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination.

    Science.gov (United States)

    Jiang, Cheng-Gang; Lv, Ling; Liu, Fu-Rong; Wang, Zhen-Ning; Liu, Fu-Nan; Li, Yan-Shu; Wang, Chun-Yu; Zhang, Hong-Yan; Sun, Zhe; Xu, Hui-Mian

    2011-09-28

    Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P cancer cells and decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  20. Understanding Cancer Prognosis

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    Full Text Available ... Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer Screening ... Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening Overview Screening ...

  1. UWB based low-cost and non-invasive practical breast cancer early detection

    Science.gov (United States)

    Vijayasarveswari, V.; Khatun, S.; Fakir, M. M.; Jusoh, M.; Ali, S.

    2017-03-01

    Breast cancer is one of the main causes of women death worldwide. Breast tumor is an early stage of cancer that locates in cells of a human breast. As there is no remedy, early detection is crucial. Towards this, Ultra-Wideband (UWB) is a prominent candidate. It is a wireless communication technology which can achieve high bandwidth with low power utilization. UWB is suitable to be used for short range communication systems including breast cancer detection since it is secure, non-invasive and human health friendly. This paper presents the low-cost and non-invasive early breast cancer detection strategy using UWB sensor (or antenna). Emphasis is given here to detect breast tumor in 2D and 3D environments. The developed system consisted of hardware and software. Hardware included UWB transceiver and a pair of home-made directional sensor/antenna. The software included feed-forward back propagation Neural Network (NN) module to detect the tumor existence, size and location along with soft interface between software and hardware. Forward scattering technique was used by placing two sensors diagonally opposite sides of a breast phantom. UWB pulses were transmitted from one side of phantom and received from other side, controlled by the software interface in PC environment. Collected received signals were then fed into the NN module for training, testing and validation. The system exhibited detection efficiency on tumor existence, location (x, y, z), and size were approximately 100%, (78.17%, 70.66%, 92.46%), 85.86% respectively. The proposed UWB based early breast cancer detection system could be more practical with low-cost, user friendly and non-harmful features. This project may help users to monitor their breast health regularly at their home.

  2. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2016-02-01

    Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

  3. Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

    Science.gov (United States)

    Chikman, Bar; Davidson, Tima; Kais, Hasan; Jeroukhimov, Igor; Leshno, Ari; Sandbank, Judith; Halevy, Ariel; Lavy, Ron

    2016-01-01

    CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.

  4. Cancer risk diversity in non-western migrants to Europe: An overview of the literature.

    Science.gov (United States)

    Arnold, Melina; Razum, Oliver; Coebergh, Jan-Willem

    2010-09-01

    Cancer risk varies geographically and across ethnic groups that can be monitored in cancer control to respond to observed trends as well as ensure appropriate health care. The study of cancer risk in immigrant populations has great potential to contribute new insights into aetiology, diagnosis and treatment of cancer. Disparities in cancer risk patterns between immigrant and autochthonous populations have been reported many times, but up to now studies have been heterogeneous and may be discordant in their findings. The aim of this overview was to compile and compare studies on cancer occurrence in migrant populations from non-western countries residing in Western Europe in order to reflect current knowledge in this field and to appeal for further research and culturally sensitive prevention strategies. We included 37 studies published in the English language between 1990 and April 2010 focussing on cancer in adult migrants from non-western countries, living in the industrialised countries of the European Union. Migrants were defined based on their country of birth, ethnicity and name-based approaches. We conducted a between-country comparison of age-adjusted cancer incidence and mortality in immigrant populations with those in autochthonous populations. Across the board migrants from non-western countries showed a more favourable all-cancer morbidity and mortality compared with native populations of European host countries, but with considerable site-specific risk diversity: Migrants from non-western countries were more prone to cancers that are related to infections experienced in early life, such as liver, cervical and stomach cancer. In contrast, migrants of non-western origin were less likely to suffer from cancers related to a western lifestyle, e.g. colorectal, breast and prostate cancer. Confirming the great cancer risk diversity in non-western migrants in and between different European countries, this overview reaffirms the importance of exposures

  5. Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening

    DEFF Research Database (Denmark)

    Vitak, B; Olsen, K E; Månson, J C

    1999-01-01

    with invasive interval cancer detected from May 1978 to August 1995 (n = 544). The tumours were evaluated with regard to age, radiological category, interval between the latest screen and diagnosis and tumour characteristics at the time of diagnosis. We investigated possible relationships between the survival...... screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive......The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients...

  6. Correlation between conductivity and prognostic factors in invasive breast cancer using magnetic resonance electric properties tomography (MREPT)

    International Nuclear Information System (INIS)

    Kim, Soo-Yeon; Kim, Min Jung; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Shin, Jaewook; Kim, Dong-Hyun

    2016-01-01

    To investigate the correlation between conductivity and prognostic factors of invasive breast cancer using magnetic resonance electric properties tomography (MREPT). This retrospective study was approved by the Institutional Review Board, and verbal informed consent was obtained prior to breast MRI. This study included 65 women with surgically confirmed invasive breast cancers measuring 1 cm or larger on T2-weighted fast spin echo (FSE). Phase-based MREPT and the coil combination technique were used to reconstruct conductivity. Simple and multiple linear regression analysis were used to find an independent factor associated with conductivity. In total tumours, tumours with HER-2 overexpression showed lower conductivity than those without, and HER-2 overexpression was independently associated with conductivity. In 37 tumours 2 cm or larger, tumours with high mitosis or PR positivity showed higher conductivity than those without, and high mitosis and PR positivity were independently associated with conductivity. In 28 tumours 1-2 cm in size, there were no differences in conductivity according to the prognostic factors. Conductivity values measured using MREPT are associated with the HER-2 overexpression status, and may provide information about mitosis and the PR status of invasive breast cancers 2 cm or larger. (orig.)

  7. Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Cho, O Yeon; Hwang, Hye Sook; Lee, Bok Soon; Oh, Young Taek; Kim, Chul Ho; Chun, Mi Son [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2015-12-15

    Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

  8. Expression of CD74 in bladder cancer and its suppression in association with cancer proliferation, invasion and angiogenesis in HT-1376 cells

    Science.gov (United States)

    Gai, Jun-Wei; Wahafu, Wasilijiang; Song, Liming; Ping, Hao; Wang, Mingshuai; Yang, Feiya; Niu, Yinong; Qing, Wei; Xing, Nianzeng

    2018-01-01

    The aim of the present study was to investigate the expression and potential roles of CD74 in human urothelial cell carcinoma of the bladder (UCB) in vitro and in vivo. CD74 and macrophage migration inhibitory factor (MIF) were located and assayed in normal and UCB samples and cell lines using immunostaining. CD74 was knocked down using CD74 shRNA lentiviral particles in HT-1376 cells. The proliferative, invasive potential and microvessel density (MVD) of knockdown-CD74 HT-1376 cells were analyzed in vitro or in vivo. The expression of CD74 in an additional high grade UCB J82 cell line was also verified in vivo. All experiments were repeated at least 3 times. The majority of muscle-invasive bladder cancer (MIBC) samples, and only one high grade UCB cell line, HT-1376, expressed CD74, compared with normal, non-muscle-invasive bladder cancer (NMIBC) samples and other cell lines. The levels of proliferation and invasion were decreased in the CD74 knockdown-HT-1376 cells, and western blotting assay indicated that the levels of proteins associated with proliferation, apoptosis and invasion in the cells were affected correspondingly by different treatments in vitro. The tumorigenesis and MVD assays indicated less proliferation and angiogenesis in the knockdown-HT-1376 cells compared with the scramble cells. Notably, J82 cells exhibiting no signal of CD74 in vitro presented the expression of CD74 in vivo. The present study revealed the potential roles of CD74 in the proliferation, invasion and angiogenesis of MIBC, and that it may serve as a potential therapeutic target for UCB, but additional studies are required.

  9. Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer.

    Science.gov (United States)

    Yang, Fei; Gao, Jun-Yi; Chen, Hua; Du, Zhen-Hua; Zhang, Xue-Qun; Gao, Wei

    2017-01-01

    Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim) were also detected. We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 μM) and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer.

  10. The effect of smoking and timing of smoking cessation on clinical outcome in non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Grotenhuis, A.J.; Ebben, C.W.; Aben, K.K.H.; Witjes, J.A.; Vrieling, A.; Vermeulen, H.H.; Kiemeney, B.

    2015-01-01

    OBJECTIVES: Cigarette smoking is the most important risk factor for urinary bladder cancer. The prognostic effect of cigarette smoking on disease recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC), however, is still unclear. We evaluated the effect of smoking

  11. Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development.

    Directory of Open Access Journals (Sweden)

    Ville Härmä

    Full Text Available The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D growth conditions using non-transformed prostate epithelial cells (EP156T, an androgen-sensitive prostate cancer cell line (LNCaP, and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.

  12. The value of ultrasound contrast for assessing cancer cell proliferation and invasion function as well as angiogenesis in lesions of in patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Qin Yang

    2017-06-01

    Full Text Available Objective: To study the value of ultrasound contrast for assessing cancer cell proliferation and invasion as well as angiogenesis in lesions of in patients with gastric cancer. Methods: A total of 39 patients with gastric cancer and 48 patients with gastric ulcer who were treated in our hospital between August 2012 and May 2016 were included in gastric cancer group and gastric ulcer group respectively, and 50 healthy subjects who accepted gastroscopy in our hospital during the same period were included in normal control group. The day after admission, color Doppler diasonograph was used to test the gastric ultrasound contrast parameters; fluorescence quantitative PCR method was used to detect the proliferation and invasion gene mRNA expression in stomach tissue; enzyme-linked immunosorbent assay (ELISA was used to detect the serum angiogenesis index levels. Results: Ultrasound contrast parameters ET and TTP levels of gastric cancer group and gastric ulcer group were significantly lower than those of normal control group, and ultrasound contrast parameters ET and TTP levels of gastric cancer group were significantly lower than those of gastric ulcer group; Stat3, Survivin, Bcl-2, 毬-catenin, eIF4E, CD44, UHRF1 and c-met mRNA expression in tissue as well as VEGF, EGFR, HIF-毩 and Ang-2 levels in serum of gastric cancer group were higher than those of gastric ulcer group and normal control group while E-cadherin mRNA expression in tissue was lower than those of gastric ulcer group and normal control group; Spearman correlation analysis showed that ultrasound contrast parameters ET and TTP levels were correlated with the cancer cell proliferation and invasion function as well as angiogenesis indexes in lesions. Conclusion: Ultrasound contrast parameters can accurately assess the malignant degree of gastric cancer, and is expected to become the reliable means for early diagnosis and treatment guidance of gastric cancer in the future.

  13. Elastic Laminal Invasion in Colon Cancer: Diagnostic Utility and Histological Features

    International Nuclear Information System (INIS)

    Kojima, Motohiro; Yokota, Mitsuru; Saito, Norio; Nomura, Shogo; Ochiai, Atsushi

    2012-01-01

    Primary tumors of the colorectal cancers are assessed pathologically based on the tumor spread into the bowel wall. The assessment of serosal involvement, which may be relevant to pT4, can be challenging for pathologists, making the consistency of diagnoses questionable. As solutions to this problem, the following two strategies could be adopted. One would be to use special staining or immunohistochemical staining techniques for diagnostic assistance. The other would be to construct recommendations for the assessment of tumor spreading and to obtain a world-wide consensus on the criteria used to assess tumor spreading. Using elastic staining, we previously reported that peritoneal elastic laminal invasion (ELI) could be objectively determined and would likely contribute to a simplified and more objective stratification of deep tumor invasion around the peritoneal surface. We also noted the importance of sampling, staining, and histo-anatomical knowledge in the application of elastic staining during routine pathological diagnosis. Here we review the history of primary tumor stratification leading to the present TNM classification and report on the current status of pathological assessments made at our hospital to summarize what has been established and what is further required for the pathological diagnosis of tumor spreading in patients with colorectal cancer.

  14. Understanding Cancer Prognosis

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    Full Text Available ... Overview Research Cancer Screening Cancer Screening Overview Screening Tests Research Diagnosis and Staging Symptoms Diagnosis Staging Prognosis ... Cancer Prevention Overview Screening Cancer Screening Overview Screening Tests Diagnosis & Staging Symptoms Diagnosis Staging Prognosis Treatment Types ...

  15. Mammographic features of screening detected pT1 (a–b) invasive breast cancer using BI-RADS lexicon

    Energy Technology Data Exchange (ETDEWEB)

    Bargalló, Xavier, E-mail: xbarga@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Santamaría, Gorane, E-mail: gsanta@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Velasco, Martín, E-mail: mvelasco@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Amo, Montse del, E-mail: mdelamo@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Arguis, Pedro, E-mail: parguis@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Burrel, Marta, E-mail: mburrel@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Capurro, Sebastian, E-mail: scapurro@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain)

    2012-10-15

    Aim: To describe mammographic features in screening detected invasive breast cancer less than or equal to 10 mm using Breast Imaging Reporting and Data System lexicon in full-field digital mammography. Patients and methods: A retrospective analysis of 123 pT1 (a–b) invasive breast cancers in women aged 50–69 years from our screening program. Radiologic patterns were: masses, calcifications, distortions, asymmetries and mixed. Masses: shape, margins and density, and calcifications: morphology, number of flecks and size of the cluster were taken into account, following Breast Imaging Reporting and Data System terminology. Results: We found 61 masses (49.6%), 8 masses with calcifications (6.5%), 30 groups of calcifications (24.4%), 19 architectural distortions (15.4%), 1 architectural distortion with calcifications (0.8%), 4 asymmetries (3.2%). Sixty out of 69 masses were irregular in shape, 6 lobular, 2 ovals and 1 round. Thirty-four showed ill-defined margins, 29 spiculated and 6 microlobulated. Most of them showed a density similar to surrounding fibroglandular tissue. Calcifications were pleomorphic or fine linear in 24 of 30 (80%). Most of cases showed more than 10 flecks and a size greater than 1 cm. Conclusion: The predominant radiologic finding is an irregular, isodense mass those margins tend to share different descriptors, being ill-defined margins the most constant finding. Calcifications representing invasive cancer are predominantly pleomorphic with more than 10 flecks per cm. Architectural distortion and invasive tubular carcinoma are more common than reported in general series.

  16. Mammographic features of screening detected pT1 (a–b) invasive breast cancer using BI-RADS lexicon

    International Nuclear Information System (INIS)

    Bargalló, Xavier; Santamaría, Gorane; Velasco, Martín; Amo, Montse del; Arguis, Pedro; Burrel, Marta; Capurro, Sebastian

    2012-01-01

    Aim: To describe mammographic features in screening detected invasive breast cancer less than or equal to 10 mm using Breast Imaging Reporting and Data System lexicon in full-field digital mammography. Patients and methods: A retrospective analysis of 123 pT1 (a–b) invasive breast cancers in women aged 50–69 years from our screening program. Radiologic patterns were: masses, calcifications, distortions, asymmetries and mixed. Masses: shape, margins and density, and calcifications: morphology, number of flecks and size of the cluster were taken into account, following Breast Imaging Reporting and Data System terminology. Results: We found 61 masses (49.6%), 8 masses with calcifications (6.5%), 30 groups of calcifications (24.4%), 19 architectural distortions (15.4%), 1 architectural distortion with calcifications (0.8%), 4 asymmetries (3.2%). Sixty out of 69 masses were irregular in shape, 6 lobular, 2 ovals and 1 round. Thirty-four showed ill-defined margins, 29 spiculated and 6 microlobulated. Most of them showed a density similar to surrounding fibroglandular tissue. Calcifications were pleomorphic or fine linear in 24 of 30 (80%). Most of cases showed more than 10 flecks and a size greater than 1 cm. Conclusion: The predominant radiologic finding is an irregular, isodense mass those margins tend to share different descriptors, being ill-defined margins the most constant finding. Calcifications representing invasive cancer are predominantly pleomorphic with more than 10 flecks per cm. Architectural distortion and invasive tubular carcinoma are more common than reported in general series

  17. Siegesbeckia orientalis Extract Inhibits TGFβ1-Induced Migration and Invasion of Endometrial Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chi-Chang Chang

    2016-08-01

    Full Text Available Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor β (TGFβ. The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFβ1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFβ1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors.

  18. Estrogen switches pure mucinous breast cancer to invasive lobular carcinoma with mucinous features.

    Science.gov (United States)

    Jambal, Purevsuren; Badtke, Melanie M; Harrell, J Chuck; Borges, Virginia F; Post, Miriam D; Sollender, Grace E; Spillman, Monique A; Horwitz, Kathryn B; Jacobsen, Britta M

    2013-01-01

    Mucinous breast cancer (MBC) is mainly a disease of postmenopausal women. Pure MBC is rare and augurs a good prognosis. In contrast, MBC mixed with other histological subtypes of invasive disease loses the more favorable prognosis. Because of the relative rarity of pure MBC, little is known about its cell and tumor biology and relationship to invasive disease of other subtypes. We have now developed a human breast cancer cell line called BCK4, in which we can control the behavior of MBC. BCK4 cells were derived from a patient whose poorly differentiated primary tumor was treated with chemotherapy, radiation and tamoxifen. Malignant cells from a recurrent pleural effusion were xenografted in mammary glands of a nude mouse. Cells from the solid tumor xenograft were propagated in culture to generate the BCK4 cell line. Multiple marker and chromosome analyses demonstrate that BCK4 cells are human, near diploid and luminal, expressing functional estrogen, androgen, and progesterone receptors. When xenografted back into immunocompromised cycling mice, BCK4 cells grow into small pure MBC. However, if mice are supplemented with continuous estradiol, tumors switch to invasive lobular carcinoma (ILC) with mucinous features (mixed MBC), and growth is markedly accelerated. Tamoxifen prevents the expansion of this more invasive component. The unexpected ability of estrogens to convert pure MBC into mixed MBC with ILC may explain the rarity of the pure disease in premenopausal women. These studies show that MBC can be derived from lobular precursors and that BCK4 cells are new, unique models to study the phenotypic plasticity, hormonal regulation, optimal therapeutic interventions, and metastatic patterns of MBC.

  19. Polycomb complex protein BMI-1 promotes invasion and metastasis of pancreatic cancer stem cells by activating PI3K/AKT signaling, an ex vivo, in vitro, and in vivo study

    Science.gov (United States)

    Wang, Min-Cong; Jiao, Min; Wu, Tao; Jing, Li; Cui, Jie; Guo, Hui; Tian, Tao; Ruan, Zhi-ping; Wei, Yong-Chang; Jiang, Li-Li; Sun, Hai-Feng; Huang, Lan-Xuan; Nan, Ke-Jun; Li, Chun-Li

    2016-01-01

    Cancer stem cell theory indicates cancer stem cells are the key to promote tumor invasion and metastasis. Studies showed that BMI-1 could promote self-renew, differentiation and tumor formation of CSCs and invasion/metastasis of human cancer. However, whether BMI-1 could regulate invasion and metastasis ability of CSCs is still unclear. In our study, we found that up-regulated expression of BMI-1 was associated with tumor invasion, metastasis and poor survival of pancreatic cancer patients. CD133+ cells were obtained by using magnetic cell sorting and identified of CSCs properties such as self-renew, multi-differentiation and tumor formation ability. Then, we found that BMI-1 expression was up-regulated in pancreatic cancer stem cells. Knockdown of BMI-1 expression attenuated invasion ability of pancreatic cancer stem cells in Transwell system and liver metastasis capacity in nude mice which were injected CSCs through the caudal vein. We are the first to reveal that BMI-1 could promote invasion and metastasis ability of pancreatic cancer stem cells. Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs. In summary, our findings indicate that BMI-1 could be used as the therapeutic target to inhibiting CSCs-mediated pancreatic cancer metastasis. PMID:26840020

  20. Preoperative Magnetic Resonance Volumetry in Predicting Myometrial Invasion, Lymphovascular Space Invasion, and Tumor Grade: Is It Valuable in International Federation of Gynecology and Obstetrics Stage I Endometrial Cancer?

    Science.gov (United States)

    Sahin, Hilal; Sarioglu, Fatma Ceren; Bagci, Mustafa; Karadeniz, Tugba; Uluer, Hatice; Sanci, Muzaffer

    2018-05-01

    The aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer. Preoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters. Receiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P volumetry, seems to predict deep MI independently in stage I endometrial cancer with insufficient sensitivity and specificity. Its value in clinical practice for

  1. Treatment of Muscle-Invasive and Metastatic Bladder Cancer: Update of the EAU Guidelines.

    NARCIS (Netherlands)

    Stenzl, A.; Cowan, N.C.; Santis, M. de; Kuczyk, M.A.; Merseburger, A.S.; Ribal, M.J.; Sherif, A.; Witjes, J.A.

    2012-01-01

    CONTEXT: New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC with a specific focus on treatment. EVIDENCE

  2. Should patients with muscle-invasive bladder cancer undergo more-extensive pelvic lymph node dissection?

    DEFF Research Database (Denmark)

    Steven, Kenneth Eric

    2008-01-01

    This Practice Point commentary discusses the paper by Dhar and colleagues, which compared outcomes between two cohorts of patients with muscle-invasive bladder cancer who received either 'limited' pelvic lymph node dissection (LND) or 'extended' pelvic LND at clinics in the US or Switzerland...

  3. The inhibition of migration and invasion of cancer cells by graphene via the impairment of mitochondrial respiration.

    Science.gov (United States)

    Zhou, Hejiang; Zhang, Bo; Zheng, Jiajia; Yu, Meifang; Zhou, Teng; Zhao, Kai; Jia, Yanxia; Gao, Xingfa; Chen, Chunying; Wei, Taotao

    2014-02-01

    Graphene and its derivatives have become important nanomaterials worldwide and have potential medical applications including in vivo diagnosis, drug delivery, and photothermal therapy of cancer. However, little is known about their effect on the metastasis of cancer cells, which is the cause of over 90% of patient deaths. In the present investigation, we provide direct evidence that low concentrations of pristine graphene and graphene oxide show no apparent influence on the viability of MDA-MB-231 human breast cancer cells, PC3 human prostate cancer cells, as well as B16F10 mouse melanoma cells. However, both pristine graphene and graphene oxide can effectively inhibit the migration and invasion of these cancer cells. Further studies indicate that exposure of cells to graphene led to the direct inhibition of the electron transfer chain complexes I, II, III and IV, most likely by disrupting electron transfer between iron-sulfur centers, which is due to its stronger ability to accept electrons compared to iron-sulfur clusters through theoretical calculations. The decreased electron transfer chain activity caused a reduction in the production of ATP and subsequent impairment of F-actin cytoskeleton assembly, which is crucial for the migration and invasion of metastatic cancer cells. The inhibition of cancer cell metastasis by graphene and graphene oxide might provide new insights into specific cancer treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Ubiquitin-specific peptidase 22 inhibits colon cancer cell invasion by suppressing the signal transducer and activator of transcription 3/matrix metalloproteinase 9 pathway.

    Science.gov (United States)

    Ao, Ning; Liu, Yanyan; Bian, Xiaocui; Feng, Hailiang; Liu, Yuqin

    2015-08-01

    Colon cancer is associated with increased cell migration and invasion. In the present study, the role of ubiquitin-specific peptidase 22 (USP22) in signal transducer and activator of transcription 3 (STAT3)-mediated colon cancer cell invasion was investigated. The messenger RNA levels of STAT3 target genes were measured by reverse transcription-quantitative polymerase chain reaction, following USP22 knockdown by RNA interference in SW480 colon cancer cells. The matrix metalloproteinase 9 (MMP9) proteolytic activity and invasion potential of SW480 cells were measured by zymography and Transwell assay, respectively, following combined USP22 and STAT3 short interfering (si)RNA treatment or STAT3 siRNA treatment alone. Similarly, a cell counting kit-8 assay was used to detect the proliferation potential of SW480 cells. The protein expression levels of USP22, STAT3 and MMP9 were detected by immunohistochemistry in colon cancer tissue microarrays (TMAs) and the correlation between USP22, STAT3 and MMP9 was analyzed. USP22/STAT3 co-depletion partly rescued the MMP9 proteolytic activity and invasion of SW480 cells, compared with that of STAT3 depletion alone. However, the proliferation of USP22/STAT3si-SW480 cells was decreased compared with that of STAT3si-SW480 cells. USP22 expression was positively correlated with STAT3 and MMP9 expression in colon cancer TMAs. In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3/MMP9 signaling pathway.

  5. Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2

    Directory of Open Access Journals (Sweden)

    Ning Song

    2016-01-01

    Full Text Available Background/Aims: The aggressive manner of ovarian cancer (OVC cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. Methods: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. Results: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF-overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. Conclusion: PLGF enhances OVC cell invasion through MAPK-p38-dependent activation of ZEB2.

  6. Preoperative prediction of lymph node metastasis and deep stromal invasion in women with invasive cervical cancer: prospective multicenter study using 2D and 3D ultrasound.

    Science.gov (United States)

    Pálsdóttir, K; Fischerova, D; Franchi, D; Testa, A; Di Legge, A; Epstein, E

    2015-04-01

    To determine how various objective two-dimensional (2D) and three-dimensional (3D) ultrasound parameters allow prediction of deep stromal tumor invasion and lymph node involvement, in comparison to subjective ultrasound assessment, in women scheduled for surgery for cervical cancer. This was a prospective multicenter trial including 104 women with cervical cancer at FIGO Stages IA2-IIB, verified histologically. Patients scheduled for surgery underwent a preoperative ultrasound examination. The value of various 2D (size, color score) and 3D (volume, vascular indices) ultrasound parameters was compared to that of subjective assessment in the prediction of deep stromal tumor invasion and lymph node involvement. Histology obtained from radical hysterectomy or trachelectomy and pelvic lymphadenectomy was considered as the gold standard for assessment. All women underwent pelvic lymphadenectomy, with 99 (95%) undergoing subsequent radical surgery; five underwent only pelvic lymphadenectomy because of the presence of a positive sentinel lymph node. Women with deep stromal invasion or lymph node involvement had significantly larger tumors (diameter and volume) but there was no correlation with vascular indices measured on 3D ultrasound. Subjective evaluation was superior (AUC, 0.93; sensitivity, 90.5%; specificity, 97.2%) in the prediction of deep stromal invasion when compared to any objective measurement technique, with maximal tumor diameter at 20.5-mm cut-off (AUC, 0.83; sensitivity, 90.5%; specificity, 61.1%) and 3D tumor volume at 9.1-mm(3) cut-off (AUC, 0.85; sensitivity, 79.4%; specificity, 83.3%) providing the best performance among the objective parameters. Both subjective assessment and objective measurements were poorly predictive of lymph node involvement. In women with cervical cancer, subjective ultrasound evaluation allowed better prediction of deep stromal invasion than did objective measurements; however, neither subjective evaluation nor objective

  7. Small invasive colon cancer with systemic metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Sakamoto Taku

    2011-05-01

    Full Text Available ABSTRACT Background Recently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size. Case Presentation A 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy. Conclusions In this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

  8. Upregulation of CD147 promotes cell invasion, epithelial-to-mesenchymal transition and activates MAPK/ERK signaling pathway in colorectal cancer.

    Science.gov (United States)

    Xu, Tao; Zhou, Mingliang; Peng, Lipan; Kong, Shuai; Miao, Ruizheng; Shi, Yulong; Sheng, Hongguang; Li, Leping

    2014-01-01

    Colorectal cancer (CRC) is one of the most common cancers in the world. CD147, a transmembrane protein, has been reported to be correlated with various cancers. In this study, we aimed to investigate the mechanism of CD147 in regulating drug resistance, cell invasion and epithelial-to-mesenchymal transition (EMT) in CRC cells. qRT-PCR and western blotting were used to evaluated the expression of CD147 in 40 CRC cases and 4 cell lines. Increased expression of CD147 at both mRNA and protein levels was found in CRC samples, and the level of CD147 was correlated with lymph node metastasis. CD147 overexpression increased the 5-Fluorouracil (5-FU) resistance, enhanced the invasion and EMT of CRC cells by regulating EMT markers and MMPs. Adverse results were obtained in CD147 knockdown CRC cell line. Further investigation revealed that CD147 activated MAPK/ERK pathway, ERK inhibitor U0126 suppressed the CD147-induced cell invasion, migration and MMP-2, MMP-9 expression. Taken together, our study indicates that CD147 promotes the 5-FU resistance, and MAPK/ERK signaling pathway is involved in CD147-promoted invasion and EMT of CRC cells.

  9. Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Juan; Xin, Beibei; Wang, Hui; He, Xiaodan [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China); Wei, Wei; Zhang, Ti [Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Tianjin 300060 (China); Shen, Xiaohong, E-mail: zebal2014@163.com [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China)

    2016-08-01

    Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. - Highlights: • Gastrin induces ABCG2 expression mediated by NF-κB activation. • Gastrin regulates NF-κB's function that binds to the ABCG2 promoter in BxPC-3 cells. • Gastrin promotes the SP proportion in BxPC-3 cells by modulating ABCG2 expression via activation of NF-κB molecule. • Gastrin induces an increase in migration and invasion potential in pancreatic cancer cell by regulating NF-κB/ABCG2 signaling.

  10. Effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice.

    Science.gov (United States)

    Song, Lin; Zhou, Xin; Jia, Hong-Jun; Du, Mei; Zhang, Jin-Ling; Li, Liang

    2016-08-01

    To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined. 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  11. A simultaneous minimally invasive approach to treat a patient with coronary artery disease and metastatic lung cancer.

    Science.gov (United States)

    Fu, Yuanhao; Zhang, Lufeng; Ji, Ling; Xu, Chenyang

    2016-01-01

    Concurrent lung cancer and coronary artery disease requiring treatment with percutaneous coronary intervention or coronary artery bypass grafting is not rare. An individualized perioperative anticoagulation regimen and minimal surgical trauma will benefit the patient's postoperative recovery. We successfully treated a 68-year-old female patient with a lesion in the left anterior descending artery and metastatic right lung carcinoma by simultaneous minimally invasive direct coronary artery bypass grafting via a small left thoracotomy and thoracoscopic wedge resection of the lung lesion. She recovered and was discharged on the eighth postoperative day. The patient showed no symptoms of myocardial ischemia postoperatively. Computed tomography scan did not indicate metastatic lesion of lung carcinoma at 1-year follow-up. In conclusion, minimally invasive direct coronary artery bypass grafting combined with thoracoscopic wedge resection is an effective minimally invasive treatment for concurrent lung cancer and coronary artery disease. This technique eliminates the risk of perioperative bleeding and provides satisfactory mid-term follow-up results.

  12. Protease-activated receptor 2 agonist increases cell proliferation and invasion of human pancreatic cancer cells

    Science.gov (United States)

    XIE, LIQUN; DUAN, ZEXING; LIU, CAIJU; ZHENG, YANMIN; ZHOU, JING

    2015-01-01

    The aim of this study was to determine the expression of protease-activated receptor 2 (PAR-2) in the human pancreatic cancer cell line SW1990, and to evaluate its effect on cell proliferation and invasion. The expression of PAR-2 protein and mRNA in SW1990 cells was determined by immunocytochemistry and reverse transcription polymerase chain reaction (PCR), respectively. MTT and cell invasion and migration assays, as well as semi-quantitative PCR and zymography analysis, were additionally performed. PAR-2 mRNA was significantly upregulated in the cells treated with trypsin or the PAR-2 activating peptide Ser-Leu-Ile-Gly-Lys-Val (SLIGKV) (P0.05). Trypsin and SLIGKV significantly promoted SW1990 cell proliferation in a dose- and time-dependent manner (P<0.05). Compared with the control group, trypsin and SLIGKV significantly increased the mRNA expression (P<0.01) and gelatinolytic activity (P<0.01) of matrix metalloproteinase (MMP)-2. In conclusion, PAR-2 is expressed in SW1990 cells. PAR-2 activation may promote the invasion and migration of human pancreatic cancer cells by increasing MMP-2 expression. PMID:25452809

  13. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Zhang Hong-Yan

    2011-09-01

    Full Text Available Abstract Background Connective tissue growth factor (CTGF has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P 1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  14. Treatment choices for patients with invasive lobular breast cancer: a doctor survey.

    Science.gov (United States)

    Jacobs, Carmel; Ibrahim, Mohamed F K; Clemons, Mark; Hutton, Brian; Simos, Demetrios; Caudrelier, Jean-Michel; Graham, Ian D; Smith, Stephanie; Addison, Christina; Arnaout, Angel

    2015-08-01

    Invasive lobular breast cancer (ILC) has distinct features that present challenges for management. We surveyed doctors regarding management approaches, opinions on quality of evidence supporting their practice, and future research needs. An online questionnaire was developed and circulated to breast cancer surgical, radiation and medical oncologists. The questionnaire was completed by 88/428 doctors (20.6%); 22/56 (39.3%) surgeons, 21/64 (32.8%) radiation oncologists and 45/308 (14.6%) medical oncologists. The majority (65%) of surgeons were comfortable treating ILC patients using the same surgical management as patients with invasive ductal cancers (IDC). Furthermore, 25% would perform a similar surgery but would obtain larger gross margins. There was equipoise for radiation oncologists regarding whether or not ILC was an independent risk factor for local-regional recurrence after either breast-conserving surgery or mastectomy. Of those radiation oncologists who believe ILC is an independent risk factor for recurrence after mastectomy, 44.4% would offer radiation in the absence of usual indications. Medical oncologists approached systemic therapy for ILC patients similarly to those with comparable IDCs. Areas identified as most controversial and requiring future research were preoperative magnetic resonance imaging, radiotherapy post-mastectomy and the responsiveness of ILC to adjuvant chemotherapy compared with endocrine therapy. There is a variation in doctors' beliefs, management and opinions regarding the quality of evidence for the management of ILC. Clinical trials specifically assessing the management of ILC are required to guide clinical practice. © 2015 John Wiley & Sons, Ltd.

  15. Can we improve transurethral resection of the bladder tumour for nonmuscle invasive bladder cancer?

    NARCIS (Netherlands)

    Liem, Esmee Iml; de Reijke, Theo M.

    2017-01-01

    Purpose of review The recurrence rate in patients with nonmuscle invasive bladder cancer is high, and the quality of transurethral resection of the bladder (TURB) tumour influences recurrence risk. We review new methods that aim to improve the effectiveness of TURB, and highlight studies of the past

  16. Preoperative breast MRI in patients with invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Schelfout, K.; Colpaert, C.; Van Goethem, M.; Verslegers, I.; Biltjes, I.; De Schepper, A.; Kersschot, E.; Leyman, P.; Thienpont, L.; Van den Haute, J.; Gillardin, J.P.; Tjalma, W.; Buytaert, Ph.

    2004-01-01

    To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC. (orig.)

  17. Preoperative breast MRI in patients with invasive lobular breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schelfout, K.; Colpaert, C. [Department of Pathology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Van Goethem, M.; Verslegers, I.; Biltjes, I.; De Schepper, A. [Department of Radiology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Kersschot, E.; Leyman, P. [Department of Radiology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Thienpont, L. [Department of Pathology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Van den Haute, J. [Department of Gynecology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Gillardin, J.P. [Department of Surgery, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Tjalma, W.; Buytaert, Ph. [Department of Gynecology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

    2004-07-01

    To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC. (orig.)

  18. Correlation between E-cadherin and p120 expression in invasive ductal breast cancer with a lobular component and MRI findings

    NARCIS (Netherlands)

    El Sharouni, Mary Ann; Postma, Emily L.; van Diest, Paul J.

    2017-01-01

    Invasive breast cancer comprises a spectrum of histological changes with purely lobular cancer on one side and purely ductal cancer on the other, with many mixed lesions in between. In a previous study, we showed that in patients with any percentage lobular component at core needle biopsy,

  19. Composite Biomarkers For Non-invasive Screening, Diagnosis And Prognosis Of Colorectal Cancer

    KAUST Repository

    Mansour, Hicham; Incitti, Roberto; Bajic, Vladimir B.

    2014-01-01

    The present invention concerns particular biomarkers for diagnosing and/or prognosticating colorectal cancer, in particular in a non-invasive manner. The methods and compositions concern analysis of methylation patterns of one or more genes from a set of 29 genes identified as described herein. In certain embodiments, the gene set includes at least P15.INK4b, SST, GAS7, CNRIP1, and PIK3CG.

  20. Composite Biomarkers For Non-invasive Screening, Diagnosis And Prognosis Of Colorectal Cancer

    KAUST Repository

    Mansour, Hicham

    2014-09-11

    The present invention concerns particular biomarkers for diagnosing and/or prognosticating colorectal cancer, in particular in a non-invasive manner. The methods and compositions concern analysis of methylation patterns of one or more genes from a set of 29 genes identified as described herein. In certain embodiments, the gene set includes at least P15.INK4b, SST, GAS7, CNRIP1, and PIK3CG.

  1. A novel minimally invasive dual-modality fiber optic probe for prostate cancer detection

    Science.gov (United States)

    Sharma, Vikrant

    Prostate cancer is the most common form of cancer in males, and is the second leading cause of cancer related deaths in United States. In prostate cancer diagnostics and therapy, there is a critical need for a minimally invasive tool for in vivo evaluation of prostate tissue. Such a tool finds its niche in improving TRUS (trans-rectal ultrasound) guided biopsy procedure, surgical margin assessment during radical prostatectomy, and active surveillance of patients with a certain risk levels. This work is focused on development of a fiber-based dual-modality optical device (dMOD), to differentiate prostate cancer from benign tissue, in vivo. dMOD utilizes two independent optical techniques, LRS (light reflectance spectroscopy) and AFLS (auto-fluorescence lifetime spectroscopy). LRS quantifies scattering coefficient of the tissue, as well as concentrations of major tissue chromophores like hemoglobin derivatives, β-carotene and melanin. AFLS was designed to target lifetime signatures of multiple endogenous fluorophores like flavins, porphyrins and lipo-pigments. Each of these methods was independently developed, and the two modalities were integrated using a thin (1-mm outer diameter) fiber-optic probe. Resulting dMOD probe was implemented and evaluated on animal models of prostate cancer, as well as on human prostate tissue. Application of dMOD to human breast cancer (invasive ductal carcinoma) identification was also evaluated. The results obtained reveal that both LRS and AFLS are excellent techniques to discriminate prostate cancer tissue from surrounding benign tissue in animal models. Each technique independently is capable of providing near absolute (100%) accuracy for cancer detection, indicating that either of them could be used independently without the need of implementing them together. Also, in case of human breast cancer, LRS and AFLS provided comparable accuracies to dMOD, LRS accuracy (96%) being the highest for the studied population. However, the

  2. Accuracy of preoperative urinary symptoms, urinalysis, computed tomography and cystoscopic findings for the diagnosis of urinary bladder invasion in patients with colorectal cancer.

    Science.gov (United States)

    Woranisarakul, Varat; Ramart, Patkawat; Phinthusophon, Kittipong; Chotikawanich, Ekkarin; Prapasrivorakul, Siriluck; Lohsiriwat, Varut

    2014-01-01

    To determine the accuracy of preoperative urinary symptoms, urinalysis, computed tomography (CT) and cystoscopic findings for the diagnosis of urinary bladder invasion in patients with colorectal cancer. Records of patients with colorectal cancer and a suspicion of bladder invasion, who underwent tumor resection with partial or total cystectomy between 2002 and 2013 at the Faculty of Medicine Siriraj Hospital, were reviewed. Correlations between preoperative urinary symptoms, urinalysis, cystoscopic finding, CT imaging and final pathological reports were analyzed. This study included 90 eligible cases (71% male). The most common site of primary colorectal cancer was the sigmoid colon (44%), followed by the rectum (33%). Final pathological reports showed definite bladder invasion in 53 cases (59%). Significant features for predicting definite tumor invasion were gross hematuria (OR 13.6, sensitivity 39%, specificity 73%), and visible tumor during cystoscopy (OR 5.33, sensitivity 50%, specificity 84%). Predictive signs in CT imaging were gross tumor invasion (OR 7.07, sensitivity 89%, specificity 46%), abnormal enhancing mass at bladder wall (OR 4.09, sensitivity 68%, specificity 66%), irregular bladder mucosa (OR 3.53, sensitivity 70%, specificity 60% ), and loss of perivesical fat plane (OR 3.17, sensitivity 81%, specificity 43%). However, urinary analysis and other urinary tract symptoms were poor predictors of bladder involvement. The present study demonstrated that the most relevant preoperative predictors of definite bladder invasion in patients with colorectal cancer are gross hematuria, a visible tumor during cystoscopy, and abnormal CT findings.

  3. Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Ose, Jennifer; Fortner, Renée T.; Rinaldi, Sabina; Schock, Helena; Overvad, Kim; Tjonneland, Anne; Hansen, Louise; Dossus, Laure; Fournier, Agnes; Baglietto, Laura; Romieu, Isabelle; Kuhn, Elisabetta; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Ramon Quiros, Jose; Obõn-Santacana, Mireia; Larrañaga, Nerea; Chirlaque, María Dolores; Sánchez, María José; Barricarte, Aurelio; Peeters, Petra H.; Bueno-De-Mesquita, H. B.; Onland-Moret, N. Charlotte; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Weiderpass, Elisabete; Gram, Inger T.; Lund, Eiliv; Kaw, Kay Tee; Travis, Ruth C.; Merritt, Melissa A.; Gunther, Marc J.; Riboli, Elio; Kaaks, Rudolf

    2015-01-01

    The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology,

  4. Post-Traumatic Growth and Resilience in Adolescent and Young Adult Cancer Patients: An Overview

    NARCIS (Netherlands)

    Greup, Suzanne R.; Kaal, Suzanne E. J.; Jansen, Rosemarie; Manten-Horst, Eveliene; Thong, Melissa S. Y.; van der Graaf, Winette T. A.; Prins, Judith B.; Husson, Olga

    2018-01-01

    The aim of this study was to provide an overview of the literature on post-traumatic growth (PTG) and resilience among adolescent and young adult (AYA) cancer patients. A literature search in Embase, PsychInfo, PubMed, Web of Science, Cochrane Library, and Cinahl was carried out. Thirteen articles

  5. Association of code status discussion with invasive procedures among advanced-stage cancer and noncancer patients

    Directory of Open Access Journals (Sweden)

    Sasaki A

    2017-07-01

    Full Text Available Akinori Sasaki,1 Eiji Hiraoka,1 Yosuke Homma,2 Osamu Takahashi,3 Yasuhiro Norisue,4 Koji Kawai,5 Shigeki Fujitani4 1Department of Internal Medicine, 2Department of Emergency Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu City, Chiba, 3Department of Internal Medicine, St. Luke’s International Hospital, Chuo-ku, Tokyo, 4Department of Critical Care Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu City, Chiba, 5Department of Gastroenterology, Ito Municipal Hospital, Ito City, Shizuoka, Japan Background: Code status discussion is associated with a decrease in invasive procedures among terminally ill cancer patients. We investigated the association between code status discussion on admission and incidence of invasive procedures, cardiopulmonary resuscitation (CPR, and opioid use among inpatients with advanced stages of cancer and noncancer diseases. Methods: We performed a retrospective cohort study in a single center, Ito Municipal Hospital, Japan. Participants were patients who were admitted to the Department of Internal Medicine between October 1, 2013 and August 30, 2015, with advanced-stage cancer and noncancer. We collected demographic data and inquired the presence or absence of code status discussion within 24 hours of admission and whether invasive procedures, including central venous catheter placement, intubation with mechanical ventilation, and CPR for cardiac arrest, and opioid treatment were performed. We investigated the factors associated with CPR events by using multivariate logistic regression analysis. Results: Among the total 232 patients, code status was discussed with 115 patients on admission, of which 114 (99.1% patients had do-not-resuscitate (DNR orders. The code status was not discussed with the remaining 117 patients on admission, of which 69 (59% patients had subsequent code status discussion with resultant DNR orders. Code status discussion on admission decreased the incidence of central venous

  6. miR-34a Inhibits Proliferation and Invasion of Bladder Cancer Cells by Targeting Orphan Nuclear Receptor HNF4G

    Directory of Open Access Journals (Sweden)

    Huaibin Sun

    2015-01-01

    Full Text Available miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3′-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells.

  7. Bone morphogenetic protein 4 is overexpressed in and promotes migration and invasion of drug-resistant cancer cells.

    Science.gov (United States)

    Zhou, Kairui; Shi, Xiaoli; Huo, Jinling; Liu, Weihua; Yang, Dongxiao; Yang, Tengjiao; Qin, Tiantian; Wang, Cong

    2017-08-01

    Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc). In these drug-resistant cell lines, we found the cell motility was enhanced and BMP4 was up-regulated relative to their respective parental cell lines. Consistent with in vitro assays, migration potential and BMP4 expression were increased in EC109/Taxol nude mice. Furthermore, to address whether BMP4 was required to enhance the metastatic in EC109/Taxol cells, the pharmacological inhibitor of BMP signaling dorsomorphin was used; meanwhile, we found that the migration and invasion abilities were inhibited. Moreover, the canonical Smad signaling pathway was investigated. Overall, our studies demonstrated that BMP4 participates in the regulation of invasion and migration by EC109/Taxol cells, and inhibition of BMP4 may be a novel strategy to interfere with metastasis in cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Entirely Laparoscopic Gastrectomy and Colectomy for Remnant Gastric Cancer with Gastric Outlet Obstruction and Transverse Colon Invasion

    OpenAIRE

    Kim, Hyun Il; Kim, Min Gyu

    2015-01-01

    It is well known that gastrectomy with curative intent is the best way to improve outcomes of patients with remnant gastric cancer. Recently,several investigators reported their experiences with laparoscopic gastrectomy of remnant gastric cancer. We report the case of an 83-year-old female patient who was diagnosed with remnant gastric cancer with obstruction. She underwent an entirely laparoscopic distal gastrectomy with colectomy because of direct invasion of the transverse colon. The opera...

  9. Minimally invasive surgery in the treatment of esophageal cancer

    International Nuclear Information System (INIS)

    Janik, M.; Lucenic, M.; Juhos, P.; Harustiak, S.

    2016-01-01

    Esophageal cancer represents the sixth most common cause of the death caused by malignant diseases. The incidence is 11.5/100 000 in men population and 4.7/100 000 in women. It is the eighth most common malignancy. The incidence grows up, it doubled in Slovakia in last period and 5-year survival is only 18 %. Esophagectomy is a huge burden for organism. Mortality varies from 8.1 % to 23 % in low-volume departments in comparison with high-volume centres, where it is lower then 5 %. Complications range after operations is 30 – 80 %. Minimally invasive approach leads to the reduction of mortality and morbidity according to lot of studies. We performed 121 esophagectomies in cancer in period 2010 – 2015 and in 2015 it was 32 operations. We performed 29 totally minimally invasive esophagectomies, 16 hybrid MIE and 66 open esophagectomies. The chylothorax occurs twice, we managed it by surgery. The anastomotic dehiscence represents 9.09 %. Cardiovascular system complications occur in 43 %, need for vasopressors caused by hypotensia was in 44 %. It concluded from that we started with restrictive management of patients during the operation and need for vasopressors last only for two days after the operation and did not cause renal failure or any other complications.30 days mortality was related to MODS evolved by sepsis caused by pneumonia, most common in cirrhotic patients in very poor condition. Tracheoneoesophageal fistula occur in three patients, they all underwent operation, one of them died because of severe pneumonia. We recorded grow number of patient in our institution, which is probably related to better cooperation with gastroenterologists all over Slovakia. (author)

  10. The pattern of invasive lobular carcinoma in the patients diagnosed with breast cancer from Balochistan.

    Science.gov (United States)

    Baloch, A H; Khosa, A N; Bangulzai, N; Sadia, H; Ahmed, M; Khan, F; Jan, M; Tareen, M; Kakar, M H; Shuja, J; Naseeb, H K; Ahmad, J

    2016-01-01

    Invasive lobular carcinoma (ILC) is the second most common type of breast cancer accounting for 5%-15% of all the breast cancer cases. The present study was performed on 171 breast cancer patients from Balochistan registered in CENAR (Center for Nuclear Medicine and Radiotherapy), Quetta. Written consent was obtained from the patients. The history of the disease was taken from the patients, and the patients' enrollment files were retrieved. Of the 171 patients, 5 (2.96%) were diagnosed with ILC with tumor Grade II, and stage of the cancer reported was Grade III in all the 5 patients affected with ILC. ILC is the second most common type of breast cancer diagnosed with comparatively lower grade but almost reported infiltrating.

  11. ICAM-3, radiation resistance gene, activates PI3K/Akt-CREB-MMPs pathway and promotes migration/invasion of the human non-small cell lung cancer cell NCI-H1299

    International Nuclear Information System (INIS)

    Park, Jong Kuk; Park, Seon Ho; Hong, Sung Hee; Um, Hong Duck; Yoo, Young Do

    2008-01-01

    Cancer cell is characterized by various distinctive functions difference from normal cell. The one of specific properties of cancer is invasion and metastasis. Invasion and metastasis is a multi-step process involving over-expression of proteolytic enzymes such as matrix metalloproteinases (MMPs) and critically dependent on the ability of cells to move away from the primary tumor to gain access to the vascular or lymphatic systems which disperses cells to distant sites, where they can grow in a permissive microenvironment at a secondary location. All of these processes are critically dependent upon the ability of cancer cells to breach the basement membrane and to migrate through neighboring tissues. Cancer cell invasion is an important, tightly regulated process that is related with development, immune response and wound healing. This invasive response is dependent on activation of signaling pathways that result in both short-term and long-term cellular responses. The gene expressions of the cancer cell invasion related-proteolytic enzymes are regulated at the transcriptional level (through AP-1 and NF-kB via mitogen activated protein kinases (MAPKs) and PI3K-Akt pathways) and post-transcriptional levels, and the protein level via their activators or inhibitors, and their cell surface localization. Therefore, the related proteins such as MMPs, MAPK, PI3K, Akt and their regulatory pathway have been considered as promising targets for anti-cancer drugs. In previous reports, Intercellular adherin molecule-3 (ICAM-3) showed increase of radio-resistance and proliferation. We have made ICAM-3 overexpressed cancer cells which shows elevated level of invasion compared with normal cancer cells and its invasion capacity was down regulated with treatment of specific inhibitor for PI3K. These results suggest that ICAM-3 related invasion is associated with PI3K signaling pathway

  12. Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer

    NARCIS (Netherlands)

    Truin, Wilfred; Roumen, Rudi M.; Siesling, Sabine; van der Heiden-van der Loo, Margriet; Lobbezoo, Dorien J.; Tjan-Heijnen, Vivianne C.G.; Voogd, Adri C.

    2016-01-01

    Background Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification

  13. [A patient treated with partial duodenectomy for invasive transverse colon cancer].

    Science.gov (United States)

    Notani, Hiroyuki; Kawamura, Toru; Sato, Taku; Hoshino, Akihiro; Sato, Yasushi; Nakajima, Akira

    2013-11-01

    The patient was an 83-year-old woman who visited our hospital with a chief complaint of weight loss. Duodenal invasion by transverse colon cancer was suspected on abdominal computed tomography( CT). An extramural tumor invading the second portion of the duodenum was noted on upper gastrointestinal endoscopy, and a circumferential type 2 lesion was observed in the transverse colon on lower intestinal endoscopy. The pathological diagnosis of both lesions was well-differentiated adenocarcinoma, and right hemicolectomy and partial duodenectomy were performed. The invaded duodenal region was located on the oral side of the papilla of Vater, and the resection involved approximately one-third of the circumference of the second portion of the duodenum and was approximately 5 cm in length. The jejunum was elevated using the Roux- en-Y method, and side-to-side duodenojejunostomy was performed for reconstruction. On histopathological examination, the lesion was diagnosed as SI, N0, Stage II. Tumor markers with elevated levels before surgery showed a rapid decrease to within normal ranges. No evidence of recurrence or metastasis has been observed for 3 years after surgery. Although pancreatoduodenectomy is the standard surgical procedure for duodenal tumorous lesions, this approach is very invasive for elderly patients. Partial duodenectomy may be a favorable treatment option for cancers invading other organs, as was the case for this patient.

  14. Establishment of human patient-derived endometrial cancer xenografts in NOD scid gamma mice for the study of invasion and metastasis.

    Directory of Open Access Journals (Sweden)

    Kenji Unno

    Full Text Available Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.Endometrial tumor tissue fragments (1.5 mm × 1.5 mm from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.

  15. ERK1/2 signalling pathway is involved in CD147-mediated gastric cancer cell line SGC7901 proliferation and invasion.

    Science.gov (United States)

    Chen, Liping; Pan, Yuqin; Gu, Ling; Nie, Zhenlin; He, Bangshun; Song, Guoqi; Li, Rui; Xu, Yeqiong; Gao, Tianyi; Wang, Shukui

    2013-08-01

    This study aimed to investigate the role of CD147 in the progression of gastric cancer and the signalling pathway involved in CD147-mediated gastric cancer cell line SGC7901 proliferation and invasion. Short hairpin RNA (shRNA) expression vectors targeting CD147 were constructed to silence CD147, and the expression of CD147 was monitored by quantitative realtime reverse transcriptase polymerase chain reaction and Western blot and further confirmed by immunohistochemistry in vivo. Cell proliferation was determined by Cell Counting Kit-8 assay, the activities of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by gelatin zymography, and the invasion of SGC7901 was determined by invasion assay. The phosphorylation and non-phosphorylation of the mitogen-activated protein kinases, extracellular signal-regulated kinase1/2 (ERK1/2), P38 and c-Jun NH2-terminal kinase were examined by Western blot. Additionally, the ERK1/2 inhibitor U0126 were used to confirm the signalling pathway involved in CD147-mediated SGC7901 progression. The BALB/c nude mice were used to study tumour progression in vivo. The results revealed that CD147 silencing inhibited the proliferation and invasion of SGC7901 cells, and down-regulated the activities of MMP-2 and MMP-9 and the phosphorylation of the ERK1/2 in SGC7901 cells. ERK1/2 inhibitor U0126 decreased the proliferation, and invasion of SGC7901 cells, and down-regulated the MMP-2 and MMP-9 activities. In a nude mouse model of subcutaneous xenografts, the tumour volume was significantly smaller in the SGC7901/shRNA group compared to the SGC7901 and SGC7901/snc-RNA group. Immunohistochemistry analysis showed that CD147 and p-ERK1/2 protein expressions were down-regulated in the SGC7901/shRNA2 group compared to the SGC7901 and SGC7901/snc-RNA group. These results suggest that ERK1/2 pathway involves in CD147-mediated gastric cancer growth and invasion. These findings further highlight the importance of CD147 in cancer progression

  16. A non-invasive modality: the US virtual touch tissue quantification (VTTQ) for evaluation of breast cancer.

    Science.gov (United States)

    Tamaki, Kentaro; Tamaki, Nobumitsu; Kamada, Yoshihiko; Uehara, Kano; Miyashita, Minoru; Ishida, Takanori; Sasano, Hironobu

    2013-09-01

    We evaluated the biologic features of breast tissues using a newly developed non-invasive diagnostic system, named virtual touch tissue quantification. A total of 180 patients including 115 invasive ductal carcinoma, 30 ductal carcinoma in situ, 4 mucinous carcinoma, 7 invasive lobular carcinoma, 8 fibroadenoma, 12 fibrocystic change and 4 intraductal papilloma were studied at Nahanishi Clinic, Okinawa. We first compared the results of virtual touch tissue quantification according to each histologic subtype and determined the optimal cutoff values for virtual touch tissue quantification to distinguish benign from malignant tissues, using the receiver operating characteristic method. In addition, we also examined the correlation between virtual touch tissue quantification velocities and Ki-67, estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 in cases of invasive ductal carcinoma using linear regression analyses and Student's t-test. Virtual touch tissue quantification velocities were statistically higher in malignant cases than in benign cases (P breast cancer pathology in a non-invasive fashion.

  17. Regulation of HGF and SDF-1 expression by oral fibroblasts--implications for invasion of oral cancer.

    Science.gov (United States)

    Daly, Aisling J; McIlreavey, Leanne; Irwin, Chris R

    2008-07-01

    Invasion and metastasis of oral squamous cell carcinoma (OSCC) is dependent on signals received from stromal fibroblasts present in the surrounding connective tissue. The aim of this study was to investigate the regulation of expression of two important signaling molecules--HGF and SDF-1--by both stromal fibroblasts and their 'activated' form, myofibroblasts, and to determine the role of these two factors in stimulating OSCC cell invasion in vitro. Fibroblasts and myofibroblasts produced similar levels of HGF and SDF-1. IL-1alpha and OSCC cell conditioned medium both stimulated HGF and SDF-1 expression, while TGF-beta(1) inhibited production of each factor. Myofibroblast-derived conditioned medium stimulated OSCC cell invasion through matrigel. Blocking antibodies to both HGF and SDF-1 reduced the level of invasion. In fibroblast-free organotypic raft cultures, addition of HGF and SDF-1 stimulated OSCC cell invasion into the underlying collagen gel, although the pattern of invasion differed from that induced by fibroblasts. Fibroblast-derived HGF and SDF-1 appear to play central roles in the reciprocal interactions between OSCC cells and underlying stromal fibroblasts leading to the local invasion of oral cancer.

  18. Quality-of-life survey for patients diagnosed with nonmuscle-invasive bladder cancer.

    Science.gov (United States)

    Abáigar-Pedraza, I; Megías-Garrigós, J; Sánchez-Payá, J

    2016-05-01

    To determine the reliability and validity of a quality-of-life survey for patients with nonmuscle-invasive bladder cancer. A total of 180 patients were included in the study. We developed a survey with 21 questions grouped into 5 areas. The patients filled in this survey and the Functional Assessment of Cancer Therapy - Bladder Cancer (FACT-BL) survey. To assess reliability, we calculated Cronbach's alpha coefficient and the kappa index. To determine criterion validity, we studied the association between the scores obtained from our survey and those from the FACT-BL survey using the Pearson correlation coefficient. To determine the construct validity (factorial and discriminatory), we performed a factor analysis, comparing it with Student's t-test for the scores obtained according to the tumour characteristics of reduced quality of life (e.g., malignancies located at the trigone of the bladder). Cronbach's alpha reliability coefficient was .83, and the kappa index varied between .7 and 1. For the association study between the new survey and the FACT-BL survey, we measured an r=.82 for the overall score and between r=.68 (disease) and r=.97 (sex life) in the various measures. In the factor analysis, we measured a Kaiser-Meyer-Olkin index of .77 and performed the Barlett test (P<.001). The comparison between the scores, in the presence or absence of certain tumour characteristics, has shown a reduced quality of life when those characteristics are present, which was statistically significant (P<.05) in the majority of cases. Our survey to measure the quality of life of patients with nonmuscle-invasive bladder cancer is reliable and valid. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Urinary Cell-Free DNA Quantification as Non-Invasive Biomarker in Patients with Bladder Cancer.

    Science.gov (United States)

    Brisuda, Antonin; Pazourkova, Eva; Soukup, Viktor; Horinek, Ales; Hrbáček, Jan; Capoun, Otakar; Svobodova, Iveta; Pospisilova, Sarka; Korabecna, Marie; Mares, Jaroslav; Hanuš, Tomáš; Babjuk, Marek

    2016-01-01

    Concentration of urinary cell-free DNA (ucfDNA) belongs to potential bladder cancer markers, but the reported results are inconsistent due to the use of various non-standardised methodologies. The aim of the study was to standardise the methodology for ucfDNA quantification as a potential non-invasive tumour biomarker. In total, 66 patients and 34 controls were enrolled into the study. Volumes of each urine portion (V) were recorded and ucfDNA concentrations (c) were measured using real-time PCR. Total amounts (TA) of ucfDNA were calculated and compared between patients and controls. Diagnostic accuracy of the TA of ucfDNA was determined. The calculation of TA of ucfDNA in the second urine portion was the most appropriate approach to ucfDNA quantification, as there was logarithmic dependence between the volume and the concentration of a urine portion (p = 0.0001). Using this methodology, we were able to discriminate between bladder cancer patients and subjects without bladder tumours (p = 0.0002) with area under the ROC curve of 0.725. Positive and negative predictive value of the test was 90 and 45%, respectively. Quantification of ucf DNA according to our modified method could provide a potential non-invasive biomarker for diagnosis of patients with bladder cancer. © 2015 S. Karger AG, Basel.

  20. Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer.

    Science.gov (United States)

    Zhao, Jing; Ye, Wei; Wu, Juan; Liu, Lijuan; Yang, Lina; Gao, Lu; Chen, Biliang; Zhang, Fanglin; Yang, Hong; Li, Yu

    2015-07-01

    CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells.