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Sample records for cancer invasion partly

  1. Management of invasive bladder cancer

    International Nuclear Information System (INIS)

    Muscle invasive disease accounts for a quarter of all cases of bladder cancer. A bewildering variety of treatment options are available for patients with this disease, with combinations of surgery and/or radiotherapy, with or without chemotherapy. This review discusses these treatment options and their relative merits for patients with muscle invasive bladder cancer. 22 refs., 3 figs., 7 tabs

  2. 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

  3. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    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.

  4. EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer

    Science.gov (United States)

    Han, Ting; Jiao, Feng; Hu, Hai; Yuan, Cuncun; Wang, Lei; Jin, Zi-Liang; Song, Wei-feng; Wang, Li-Wei

    2016-01-01

    Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E-cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer. PMID:26848980

  5. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available Minimally Invasive Treatment for Lung Cancer June 15, 2009 Welcome to this “OR-Live” webcast presentation, premiering from Beth Israel Medical Center in New York City. During ...

  6. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available Minimally Invasive Treatment for Lung Cancer June 15, 2009 Welcome to this “OR-Live” webcast presentation, premiering from Beth Israel Medical Center in New ... can have. My role is to deliver radiation therapy in these lung cancer patients. And what radiation therapy is is the ...

  7. [Minimally Invasive Open Surgery for Lung Cancer].

    Science.gov (United States)

    Nakagawa, Kazuo; Watanabe, Shunichi

    2016-07-01

    Significant efforts have been made to reduce the invasiveness of surgical procedures by surgeons for a long time. Surgeons always keep it in mind that the basic principle performing less invasive surgical procedures for malignant tumors is to decrease the invasiveness for patients without compromising oncological curability and surgical safety. Video-assisted thoracic surgery (VATS) has been used increasingly as a minimally invasive approach to lung cancer surgery. Whereas, whether VATS lobectomy is a less invasive procedure and has equivalent or better clinical effect compared with open lobectomy for patients with lung cancer remains controversial because of the absence of randomized prospective studies. The degree of difficulty for anatomical lung resection depends on the degree of the fissure development, mobility of hilar lymph nodes, and the degree of pleural adhesions. During pulmonary surgery, thoracic surgeons always have to deal with not only these difficulties but other unexpected events such as intraoperative bleeding. Recently, we perform pulmonary resection for lung cancer with minimally invasive open surgery (MIOS) approach. In this article, we introduce the surgical procedure of MIOS and demonstrate short-term results. Off course, the efficacy of MIOS needs to be further evaluated with long-term results. PMID:27440030

  8. Aquatic invasive species: Lessons from cancer research

    Science.gov (United States)

    Sepulveda, Adam; Ray, Andrew; Al-Chokhachy, Robert K.; Muhlfeld, Clint C.; Gresswell, Robert E.; Gross, Jackson A.; Kershner, Jeffrey L.

    2014-01-01

    Aquatic invasive species are disrupting ecosystems with increasing frequency. Successful control of these invasions has been rare: Biologists and managers have few tools for fighting aquatic invaders. In contrast, the medical community has long worked to develop tools for preventing and fighting cancer. Its successes are marked by a coordinated research approach with multiple steps: prevention, early detection, diagnosis, treatment options and rehabilitation. The authors discuss how these steps can be applied to aquatic invasive species, such as the American bullfrog (Lithobates catesbeianus), in the Northern Rocky Mountain region of the United States, to expedite tool development and implementation along with achievement of biodiversity conservation goals.

  9. 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....

  10. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available Minimally Invasive Treatment for Lung Cancer June 15, 2009 Welcome to this “OR-Live” webcast presentation, premiering from Beth Israel Medical ... when detected, you know, and when patients get treatment. Okay. So it’s very important, you know, to ...

  11. Nucleostemin expression in invasive breast cancer

    International Nuclear Information System (INIS)

    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

  12. Minimally Invasive Colorectal Cancer Surgery in Europe

    OpenAIRE

    Babaei, Masoud; Balavarca, Yesilda; Jansen, Lina; Gondos, Adam; Lemmens, Valery; Sjövall, Annika; B⊘rge Johannesen, Tom; Moreau, Michel; Gabriel, Liberale; Gonçalves, Ana Filipa; Bento, Maria José; van de Velde, Tony; Kempfer, Lana Raffaela; Becker, Nikolaus; Ulrich, Alexis

    2016-01-01

    Abstract Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse. In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared ...

  13. Minimal Invasive Surgery for Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    A.H.Hoelscher; Ch.Gutschow

    2004-01-01

    Thoracoscopic esophagectomy is only established in some centers and affords a cervical anastomosis because intrathoracic anastomosis as a routine is technically too difficult. Laparoscopic mobilisation of the stomach (gastrolysis) is an important contribution for minimal invasive surgery of esophageal cancer.This procedure reduces the stress of the two cavity operation for the patient and allows the construction of a comparable gastric conduit like by open surgery. The technique of laparoscopic gastrolysis as preparation for transthoracic en bloc esophagectomy is described in detail and preliminary results are briefly mentioned.

  14. Minimally invasive local therapies for liver cancer.

    Science.gov (United States)

    Li, David; Kang, Josephine; Golas, Benjamin J; Yeung, Vincent W; Madoff, David C

    2014-12-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed. PMID:25610708

  15. Minimally invasive local therapies for liver cancer

    Institute of Scientific and Technical Information of China (English)

    David Li; Josephine Kang; Benjamin J Golas; Vincent W Yeung; David C Madoff

    2014-01-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have iflled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.

  16. Minimally invasive local therapies for liver cancer

    International Nuclear Information System (INIS)

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed

  17. Clinicopathological features of early gastric cancer with duodenal invasion

    Institute of Scientific and Technical Information of China (English)

    Tsutomu Namikawa; Kazuhiro Hanazaki

    2009-01-01

    The incidence of early gastric cancer (EGC) with duodenal invasion is ext remely low, al though advanced gastric cancer that arises in the antrum occasionally invades the duodenum. We investigated the clinicopathological features of EGC with duodenal invasion and provided strategies for clinical management. A Medline search was performed using the keyword "early gastric cancer" and "duodenal invasion". Additional articles were obtained from references within the papers identified by the Medline search. We revealed that EGC with duodenal invasion was of the superficial spreading type of tumor. Tumors > 60 mm in size invaded the duodenum more extensively, and the distance of duodenal invasion from the pyloric ring was further in the elevated type than in the depressed type of tumor. There was no significant difference between the length of duodenal invasion and the histological type of the tumor. Gastric cancer located adjacent to the pyloric ring, even if cancer invasion was confined to the mucosa or submucosa, was more likely to invade the duodenum. The present study reveals that the elevated type of EGC is associated with more extensive duodenal invasion when the tumor size is > 60 mm, thus highlighting the importance of identification of duodenal invasion in these cases. We also reveal that sufficient duodenal resection with a cancer-free distal surgical margin should be performed in cases of duodenal invasion.

  18. TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases

    Directory of Open Access Journals (Sweden)

    Chih-Hung Hsu

    2012-09-01

    Full Text Available Tumor suppressor gene silencing through cytosine methylation contributes to cancer formation. Whether DNA demethylation enzymes counteract this oncogenic effect is unknown. Here, we show that TET1, a dioxygenase involved in cytosine demethylation, is downregulated in prostate and breast cancer tissues. TET1 depletion facilitates cell invasion, tumor growth, and cancer metastasis in prostate xenograft models and correlates with poor survival rates in breast cancer patients. Consistently, enforced expression of TET1 reduces cell invasion and breast xenograft tumor formation. Mechanistically, TET1 suppresses cell invasion through its dioxygenase and DNA binding activities. Furthermore, TET1 maintains the expression of tissue inhibitors of metalloproteinase (TIMP family proteins 2 and 3 by inhibiting their DNA methylation. Concurrent low expression of TET1 and TIMP2 or TIMP3 correlates with advanced node status in clinical samples. Together, these results illustrate a mechanism by which TET1 suppresses tumor development and invasion partly through downregulation of critical gene methylation.

  19. Association of diabetes and perineural invasion in pancreatic cancer

    OpenAIRE

    Sahin, Ibrahim Halil; Shama, Mohamed A; Tanaka, Motofumi; James L. Abbruzzese; Curley, Steven A; Hassan, Manal; Li, Donghui

    2012-01-01

    Diabetes and perineural invasion are frequently observed in pancreatic cancer. In this study, we tested possible relations between diabetes and perineural invasion in patients with resected pancreatic cancer. We conducted a retrospective study in 544 cases of resected pancreatic adenocarcinoma seen at the University of Texas MD Anderson Cancer Center during 1996–2011. Information on tumor characteristics, diabetes history, and survival time was collected by personal interview and medical reco...

  20. 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.

  1. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... of cancer-related deaths in this country. It far exceeds breast cancer, colon cancer, and prostate cancer, ... enough information to give patients good advice as far as what sort of treatments they need for ...

  2. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... for Lung Cancer June 15, 2009 Welcome to this “OR-Live” webcast presentation, premiering from Beth Israel ... number one cause of cancer-related deaths in this country. It far exceeds breast cancer, colon cancer, ...

  3. A microscopic landscape of the invasive breast cancer genome

    OpenAIRE

    Zheng Ping; Yuchao Xia; Tiansheng Shen; Vishwas Parekh; Siegal, Gene P; Isam-Eldin Eltoum; Jianbo He; Dongquan Chen; Minghua Deng; Ruibin Xi; Dejun Shen

    2016-01-01

    Histologic grade is one of the most important microscopic features used to predict the prognosis of invasive breast cancer and may serve as a marker for studying cancer driving genomic abnormalities in vivo. We analyzed whole genome sequencing data from 680 cases of TCGA invasive ductal carcinomas of the breast and correlated them to corresponding pathology information. Ten genetic abnormalities were found to be statistically associated with histologic grade, including three most prevalent ca...

  4. High-risk nonmuscle invasive bladder cancer: Definition and epidemiology

    OpenAIRE

    Porten, SP; Cooperberg, MR

    2012-01-01

    PURPOSE OF REVIEW: Nonmuscle invasive bladder cancer represents a large majority of patients diagnosed with this disease. Precise definition and risk stratification are paramount in this group as high-risk patients have higher rates of progression and mortality and may benefit from early identification and aggressive treatment. RECENT FINDINGS: The mainstay definitions of high-risk nonmuscle invasive bladder cancer are based on grade and stage. Recently, efforts have been made to incorporate ...

  5. Nonmuscle invasive bladder cancer: a primer on immunotherapy

    Science.gov (United States)

    Maruf, Mahir; Brancato, Sam J.; Agarwal, Piyush K.

    2016-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer.

  6. Invasive thymoma associated with lung cancer: report of a case.

    Science.gov (United States)

    Shimada, T; Terashima, H; Shimizu, T; Hirayama, K

    2001-01-01

    We report herein a case of invasive thymoma simultaneously associated with lung cancer. A 64-year-old man presented with a cough and anterior chest pain, and preoperative examinations revealed an anterior mediastinal tumor as well as lung cancer. The patient underwent a total thymectomy, partial resection of the right lung, left lower lobectomy, and mediastinal lymph node dissection, followed by radiotherapy. Although it is well known that thymomas may be accompanied by nonthymic cancers, invasive thymomas occurring coincidentally with lung cancer are rarely reported in Japan. This case is very interesting in its relation to the oncogenesis of thymomas. PMID:11428602

  7. Obesity is associated with increased risk of invasive penile cancer

    OpenAIRE

    Barnes, Kerri T.; McDowell, Bradley D.; Button, Anna; Smith, Brian J.; Lynch, Charles F.; Gupta, Amit

    2016-01-01

    Background To validate the association between obesity and penile cancer at a population level, we conducted a matched case–control study linking the Iowa Department of Motor Vehicles Drivers’ License Database (DLD) with cancer surveillance data collected by the State Health Registry of Iowa (SHRI). Methods All men diagnosed with invasive penile squamous cell carcinoma from 1985 to 2010 were identified by SHRI. Two hundred sixty-six cancer cases and 816 cancer-free male controls, selected fro...

  8. Neoplastic extracellular matrix environment promotes cancer invasion in vitro.

    Science.gov (United States)

    Sundquist, Elias; Renko, Outi; Salo, Sirpa; Magga, Johanna; Cervigne, Nilva K; Nyberg, Pia; Risteli, Juha; Sormunen, Raija; Vuolteenaho, Olli; Zandonadi, Flávia; Paes Leme, Adriana F; Coletta, Ricardo D; Ruskoaho, Heikki; Salo, Tuula

    2016-06-10

    The invasion of carcinoma cells is a crucial feature in carcinogenesis. The penetration efficiency not only depends on the cancer cells, but also on the composition of the tumor microenvironment. Our group has developed a 3D invasion assay based on human uterine leiomyoma tissue. Here we tested whether human, porcine, mouse or rat hearts as well as porcine tongue tissues could be similarly used to study carcinoma cell invasion in vitro. Three invasive human oral tongue squamous cell carcinoma (HSC-3, SCC-25 and SCC-15), melanoma (G-361) and ductal breast adenocarcinoma (MDA-MB-231) cell lines, and co-cultures of HSC-3 and carcinoma-associated or normal oral fibroblasts were assayed. Myoma tissue, both native and lyophilized, promoted invasion and growth of the cancer cells. However, the healthy heart or tongue matrices were unable to induce the invasion of any type of cancer cells tested. Moreover, when studied in more detail, small molecular weight fragments derived from heart tissue rinsing media inhibited HSC-3 horizontal migration. Proteome analysis of myoma rinsing media, on the other hand, revealed migration enhancing factors. These results highlight the important role of matrix composition for cancer invasion studies in vitro and further demonstrate the unique properties of human myoma organotypic model. PMID:27090016

  9. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... 2009, lung cancer is really the number one cause of cancer-related deaths in this country. It ... that, you know, lung cancer is the leading cause of mortality. And unfortunately, it’s normally detected in ...

  10. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... related deaths in this country. It far exceeds breast cancer, colon cancer, and prostate cancer, and, in fact, ... and try and get a biopsy of the lesion. There are other ways to approach the lesion, ...

  11. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... related deaths in this country. It far exceeds breast cancer, colon cancer, and prostate cancer, and, in fact, ... when detected, you know, and when patients get treatment. Okay. So it’s very important, you know, to ...

  12. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... really the number one cause of cancer-related deaths in this country. It far exceeds breast cancer, ... is still less than the total number of deaths from lung cancer in general. I hope that ...

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

    Science.gov (United States)

    Bhatia, Maneet; McGrath, Kelly L; Di Trapani, Giovanna; Charoentong, Pornpimol; Shah, Fenil; King, Mallory M; Clarke, Frank M; Tonissen, Kathryn F

    2016-08-01

    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. PMID:26760912

  14. 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.

  15. h-prune affects anaplastic thyroid cancer invasion and metastasis.

    Science.gov (United States)

    Nambu, Junko; Kobayashi, Tsuyoshi; Hashimoto, Masakazu; Tashiro, Hirotaka; Sugino, Keizo; Shimamoto, Fumio; Kikuchi, Akira; Ohdan, Hideki

    2016-06-01

    Anaplastic thyroid cancer is one of the most aggressive human malignancies and is resistant to multimodal treatments. The expression of h-prune, the human homologue of Drosophila prune, has been reported to be correlated with progression and aggressiveness in various cancers including breast, colorectal and pancreatic cancers. We examined the role of h-prune in anaplastic thyroid cancer cell migration, invasion and metastasis. Immunohistochemical analysis of h-prune was performed with 15 surgically resected specimens of anaplastic thyroid cancers. To investigate cell motility, Boyden chamber, wound healing and matrigel invasion assays were performed using cells from anaplastic thyroid cancer cell lines. A murine orthotopic thyroid cancer model was used to investigate metastatic ability. In the immunohistochemical analysis, only weak focal or no staining of h-prune was observed in non-tumor tissue. In contrast, diffuse staining of h-prune was observed in anaplastic thyroid cancer and lymph node metastasis samples. Both inhibition of h-prune phosphodiesterase activity with dipyridamole and small interfering RNA for h-prune suppressed 8505C and KTC-3 cell motility. In addition, treatment with dipyridamole and decreased expression of h-prune suppressed tumor invasion and pulmonary metastasis in a NOD/Shi-scid, IL-2Rγnull (NOG) mouse orthotopic thyroid cancer model. In conclusion, h-prune is frequently expressed in anaplastic thyroid cancer cells and lymph nodes metastasis, and promotes migration and invasion of anaplastic thyroid cancer cells and metastasis in an anaplastic thyroid cancer model. Thus, h-prune shows promise as a targeting candidate against anaplastic thyroid cancer. PMID:27109060

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

    OpenAIRE

    Maneet Bhatia; Kelly L. McGrath; Giovanna Di Trapani; Pornpimol Charoentong; Fenil Shah; Mallory M. King; Clarke, Frank M.; Tonissen, Kathryn F

    2016-01-01

    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 ...

  17. 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.

  18. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... the effects of years and years of tobacco exposure and maybe a lifetime of living in the ... and minimally-invasive surgery to have the best exposure that you can. What we like about our ...

  19. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... kinds of impossible crevices, and it’s really a big advantage to have these flexible instruments versus some ... cannot tolerate, you know, large incisions, you know, big lobes being removed. And using the minimally invasive ...

  20. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... is still less than the total number of deaths from lung cancer in general. I hope that our discussion today will be informative to you and help us to help you understand lung cancer as it ...

  1. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... to try and determine if the cancer has spread beyond the primary lesion itself, you know. And ... Okay. And with most cancers, you know, they spread first by going through what we call the “ ...

  2. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... an oropharyngeal cancer, the cancer of the upper airway here in the throat. And during the workup ... room and performed a thoracoscopic lobectomy because we wanted to minimize the effects of surgery, major lung ...

  3. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... and prostate cancer, and, in fact, if you add up the mortalities from those three cancers alone, ... for this patient or in other cases a combined approach of radiation, with or without chemotherapy, in ...

  4. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... Center in New York City. During the program, it’s easy for you to make referrals, make appointments ... to try to tackle the lung cancer as it stands in 2009. In 2009, lung cancer is ...

  5. THE PROBLEM OF INVASIVE MYCOSES IN RHEUMATOLOGY(Part I

    Directory of Open Access Journals (Sweden)

    Boris Sergeyevich Belov

    2009-12-01

    Full Text Available The problem of invasive mycoses is becoming ever more urgent in modern rheumatology. The fact that physicians are unalert to mycoses in patients with systemic rheumatic diseases and that there are difficulties in their lifetime diagnosis and treatment is noteworthy. The significance of this problem substantially increases with the active clinical introduction of biologicals, primarily tumor necrosis factor а inhibitors (infliximab, adalimumab, etanercept, which goes on concurrently with the increasing risk for opportunistic infections. Part I presents information on different aspects of systemic aspergillosis, including the tactics of its diagnosis and rational therapy

  6. Perineural Invasion in Pancreatic Cancer: Advanced Research in the Neuro-cancer Interactions

    Directory of Open Access Journals (Sweden)

    Xiao-hong SHEN

    2010-12-01

    Full Text Available Pancreatic Cancer (PCa is characterized by prominently local nerve alterations and perineural invasion (PNI, which frequently affects the extrapancreatic nerve plexus, causing severe pain and retropancreatic tumor extension. It precludes curative resection, promotes local recurrence, and at the last negatively influences the prognosis of patients. Recent research on PNI in PCa has revealed the critical involvement of numerous nerve- or cancer cell-derived molecules in vitro and in vivo. However, the mechanisms contributing to alteration and invasion of intrapancreatic nerves and the spread of cancer cells along extrapancreatic nerves in pancreatic cancer patients are still poorly understood. This review focuses on perineural invasion in pancreatic cancer and provides an outline of the characteristics and molecular mechanisms of perineural invasion in pancreatic cancer.

  7. Minimally Invasive Esophagectomy for Cancer -Short Up-to-Date

    Directory of Open Access Journals (Sweden)

    Radu Mircea Neagoe

    2014-07-01

    Full Text Available Surgery remains the main treatment for localized resectable esophageal cancer. Open esophagectomy is still the standard surgical approach for esophageal cancer but it has a lower patient satisfaction when compared with other treatment options. In the era of “key-hole” surgeries, minimally invasive esophagectomy (MIE stands as a solution to improve the results after standard open esophagectomies. The aim of the present paper is to provide a short update regarding the minimally invasive esophagectomy, with special emphasis on its indications, results and current controversies.

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

    International Nuclear Information System (INIS)

    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.

  9. A microscopic landscape of the invasive breast cancer genome

    Science.gov (United States)

    Ping, Zheng; Xia, Yuchao; Shen, Tiansheng; Parekh, Vishwas; Siegal, Gene P.; Eltoum, Isam-Eldin; He, Jianbo; Chen, Dongquan; Deng, Minghua; Xi, Ruibin; Shen, Dejun

    2016-01-01

    Histologic grade is one of the most important microscopic features used to predict the prognosis of invasive breast cancer and may serve as a marker for studying cancer driving genomic abnormalities in vivo. We analyzed whole genome sequencing data from 680 cases of TCGA invasive ductal carcinomas of the breast and correlated them to corresponding pathology information. Ten genetic abnormalities were found to be statistically associated with histologic grade, including three most prevalent cancer driver events, TP53 and PIK3CA mutations and MYC amplification. A distinct genetic interaction among these genomic abnormalities was revealed as measured by the histologic grading score. While TP53 mutation and MYC amplification were synergistic in promoting tumor progression, PIK3CA mutation was found to have alleviated the oncogenic effect of either the TP53 mutation or MYC amplification, and was associated with a significant reduction in mitotic activity in TP53 mutated and/or MYC amplified breast cancer. Furthermore, we discovered that different types of genetic abnormalities (mutation versus amplification) within the same cancer driver gene (PIK3CA or GATA3) were associated with opposite histologic changes in invasive breast cancer. In conclusion, our study suggests that histologic grade may serve as a biomarker to define cancer driving genetic events in vivo. PMID:27283966

  10. A microscopic landscape of the invasive breast cancer genome.

    Science.gov (United States)

    Ping, Zheng; Xia, Yuchao; Shen, Tiansheng; Parekh, Vishwas; Siegal, Gene P; Eltoum, Isam-Eldin; He, Jianbo; Chen, Dongquan; Deng, Minghua; Xi, Ruibin; Shen, Dejun

    2016-01-01

    Histologic grade is one of the most important microscopic features used to predict the prognosis of invasive breast cancer and may serve as a marker for studying cancer driving genomic abnormalities in vivo. We analyzed whole genome sequencing data from 680 cases of TCGA invasive ductal carcinomas of the breast and correlated them to corresponding pathology information. Ten genetic abnormalities were found to be statistically associated with histologic grade, including three most prevalent cancer driver events, TP53 and PIK3CA mutations and MYC amplification. A distinct genetic interaction among these genomic abnormalities was revealed as measured by the histologic grading score. While TP53 mutation and MYC amplification were synergistic in promoting tumor progression, PIK3CA mutation was found to have alleviated the oncogenic effect of either the TP53 mutation or MYC amplification, and was associated with a significant reduction in mitotic activity in TP53 mutated and/or MYC amplified breast cancer. Furthermore, we discovered that different types of genetic abnormalities (mutation versus amplification) within the same cancer driver gene (PIK3CA or GATA3) were associated with opposite histologic changes in invasive breast cancer. In conclusion, our study suggests that histologic grade may serve as a biomarker to define cancer driving genetic events in vivo. PMID:27283966

  11. Cancer-Associated Adipocytes Exhibit an ActivatedPhenotype and Contribute to Breast Cancer Invasion

    OpenAIRE

    2011-01-01

    Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and matureadipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and humantumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, usingan original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit analtered phenotype in terms of delipidation and decreased ...

  12. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... be very, very effective, and most of the data, you know, show that it’s a 90 percent, ... the chest cavity, and it’s important in both open and minimally-invasive surgery to have the best ...

  13. Receptor-interacting protein-1 promotes the growth and invasion in gastric cancer.

    Science.gov (United States)

    Zhu, Guangwei; Ye, Jianxin; Huang, Yongjian; Zheng, Wei; Hua, Jin; Yang, Shugang; Zhuang, Jinfu; Wang, Jinzhou

    2016-06-01

    The receptor-interacting protein-1 (RIP-1) is an important molecular in inflammation signaling pathways, but the role of RIP-1 in gastric cancer is largely unknown. In this study, we tested the expression of RIP-1 in gastric cancer samples and analyzed the effects of expression of RIP-1 on the prognosis in gastric cancer patients. We analyzed the role of the RIP-1 in gastric cancer cells and addressed the functional role of RIP-1 using a xenograft mouse model. A lentivirus-based effective RIP-1 siRNA vector was infected into HGC and AGS cells. The effect of RIP-1 siRNA on HGC and AGS cells were investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of RIP-1-siRNA on HGC cells in the mice with subcutaneous xenograft tumor, and preliminarily analyzed the underlying mechanisms. The results indicated that the expression of RIP-1 in the gastric cancer tissues was significantly higher than the expression in the normal gastric tissues. Additionally, RIP-1 immunoreactivity was positive at the site of invasion, but little or no immunoreactivity was detected at the gastric cancer parts of interstitial substance. Gastric cancer patients with high expression of RIP-1 had a poor survival rate. RIP-1 expression in the gastric cancer cell lines were general. HGC-R-1-RNAi-LV inhibited HGC and AGS cell proliferation and invasion ability in vitro. RIP-NF-κB/AP-1-VEGF-C signaling pathways have a crucial role in the regulate the biological functions of HGC cells. HGC-R-1-RNAi-LV suppressed tumor growth in the HGC cell subcutaneous xenograft model. In conclusion, our data indicate that RIP-1 promote the growth and invasion of gastric cancer in vitro and in vivo, additionally providing evidence that targeting RIP-1 may be useful in the treatment of gastric cancer. PMID:27035122

  14. Minimally Invasive Treatment for Lung Cancer

    Science.gov (United States)

    ... me reiterate what Sam was saying about the importance of a multidisciplinary team when managing such a complicated disease as lung cancer, and we really do have a great team here to do that because we work so closely together so often. My role, after Sam assists in diagnosing cancers, is to ...

  15. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... me reiterate what Sam was saying about the importance of a multidisciplinary team when managing such a complicated disease as lung cancer, and we really do have a great team here to do that because we work so closely together so often. My role, after Sam assists in diagnosing cancers, is to ...

  16. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... glucose into the patient’s body and the cancer cells, you know, take up glucose more than the regular cells in the body, and it will give us ... high-energy X-rays that preferentially kill cancer cells with minimal damage overall to the normal surrounding ...

  17. Numerical simulation of a contractivity based multiscale cancer invasion model

    OpenAIRE

    Kolbe, Niklas; Lukacova-Medvidova, Maria; Sfakianakis, Nikolaos; Wiebe, Bettina

    2016-01-01

    We present a problem-suited numerical method for a particularly challenging cancer invasion model. This model is a multiscale haptotaxis advection-reaction-diffusion system that describes the macroscopic dynamics of two types of cancer cells coupled with microscopic dynamics of the cells adhesion on the extracellular matrix. The difficulties to overcome arises from the non-constant advection and diffusion coefficients, a time delay term, as well as stiff reaction terms. Our numerical method i...

  18. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    OpenAIRE

    K. M. Figurin

    2014-01-01

    The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  19. INTRAVESICAL BCG THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    K. M. Figurin

    2014-07-01

    Full Text Available The paper considers the state-of-the-art of BCG vaccine treatment for non-muscle invasive bladder cancer. It gives data on the meta-analyses of foreign studies of the efficiency of BCG therapy in this pathology.

  20. CT of invasive pulmonary aspergillosis in children with cancer

    International Nuclear Information System (INIS)

    In treating cases of malignancy, the use of chemotherapy carries a high risk of lower respiratory tract infections, especially fungal pneumonopathy. This complication is a major cause of mortality and is often difficult to diagnose because of non-specific clinical or radiological changes, but the early recognition of invasive fungal disease is imperative. CT is an important non-invasive method for the detection and evaluation of opportunistic fungal infections. In these patients am improved survival rate can be achieved when early detection by CT leads to the prompt institution of high-dose antifungal therapy. We illustrate the spectrum of CT findings of invasive pulmonary aspergillosis encountered in children with cancer. These patients had previously been treated with high-dose chemotherapy with or without bone marrow rescue, and underwent radiological examinations because of clinical evidence of pneumonopathy. Representative cases demonstrate the clinical applications of CT in the evaluation and management of invasive fungal disease. (orig.)

  1. CT of invasive pulmonary aspergillosis in children with cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taccone, A. (Dept. of Radiology, Gaslini Children' s Hospital, Genoa (Italy)); Occhi, M. (Dept. of Radiology, Gaslini Children' s Hospital, Genoa (Italy)); Garaventa, A. (Div. of Hematology and Oncology, Gaslini Children' s Hospital, Genoa (Italy)); Manfredini, L. (Div. of Hematology and Oncology, Gaslini Children' s Hospital, Genoa (Italy)); Viscoli, C. (Dept. of Infectious Diseases, Gaslini Children' s Hospital, Genoa (Italy))

    1993-06-01

    In treating cases of malignancy, the use of chemotherapy carries a high risk of lower respiratory tract infections, especially fungal pneumonopathy. This complication is a major cause of mortality and is often difficult to diagnose because of non-specific clinical or radiological changes, but the early recognition of invasive fungal disease is imperative. CT is an important non-invasive method for the detection and evaluation of opportunistic fungal infections. In these patients am improved survival rate can be achieved when early detection by CT leads to the prompt institution of high-dose antifungal therapy. We illustrate the spectrum of CT findings of invasive pulmonary aspergillosis encountered in children with cancer. These patients had previously been treated with high-dose chemotherapy with or without bone marrow rescue, and underwent radiological examinations because of clinical evidence of pneumonopathy. Representative cases demonstrate the clinical applications of CT in the evaluation and management of invasive fungal disease. (orig.)

  2. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... she actually could have gone home on the second day after surgery, but we were a little ... ve got to fight it. This was my second bout with cancer, so I’ve had experience ...

  3. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... fact that, you know, lung cancer is the leading cause of mortality. And unfortunately, it’s normally detected ... CAT scan with you, Angelo. And the main question we have at that point is whether or ...

  4. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... chief of thoracic surgery in their Brooklyn division. We would like to talk to you today about out multidisciplinary approach to lung cancer, how we help to support the patients, how we help ...

  5. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... lung cancer, how we help to support the patients, how we help to treat them both before, ... and how they apply their expertise to our patients. Sam, why don’t you start. Thanks, Dr. ...

  6. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... was saying about the importance of a multidisciplinary team when managing such a complicated disease as lung cancer, and we really do have a great team here to do that because we work so ...

  7. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... any further adieu, I’d like to maybe introduce you to Sister Sullivan, and let’s listen to some of her words. Larynx cancer. PET scan and CAT was ordered. And from that PET ...

  8. CHEMOTHERAPY FOR MUSCLE INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Rusakov

    2014-08-01

    Full Text Available The paper considers treatment regimens for metastatic bladder cancer (MBC and gives the data of trials of the efficiency of using different chemotherapy schemes and regimens in patients with MBC.

  9. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... need to try and determine if the cancer has spread beyond the primary lesion itself, you know. ... As Dr. Reyes mentioned, you know, traditionally staging has been done by surgical mean, which means doing ...

  10. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... the physicians, the nurse practitioners and the nursing staff, but we’re also very rigorous in maintaining ... both cancers, my case was taken before the staff board and I was discussed at the staff ...

  11. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... abnormality is due to cancer or do to something else. Okay. Once we’ve done that, you ... half centimeters in greatest diameter, and that’s about something about like this, maybe the size of a ...

  12. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... unit and the director of the endobronchial ultrasound service on the pulmonary division of Beth Israel. Our ... the lung cancer division of the radiation oncology service. Good morning, Walter? Good morning. How are you? ...

  13. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... medical conditions and are also relatively advanced in age. Here you can see me just trying to ... function tests and preoperative evaluation and her young age that we would address the lung cancer -- the ...

  14. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... sedition and sleeping. We’ll go through your mouth and go through your main windpipe and go ... Sullivan, and let’s listen to some of her words. Larynx cancer. PET scan and CAT was ordered. ...

  15. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... like each of them to tell you some words about what they do and how they apply ... Sullivan, and let’s listen to some of her words. Larynx cancer. PET scan and CAT was ordered. ...

  16. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... she turned out to be a very happy person. Now she had two cancers, which makes her ... recommend Dr. Reyes, and I would tell the person, make an appointment as soon as possible, get ...

  17. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... in between the ribs. We divide just the soft tissue of the thorax, the chest wall. And, ... therapy is is the use of high-energy X-rays that preferentially kill cancer cells with minimal damage ...

  18. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... presented in a multidisciplinary fashion to our tumor board, and we discussed her case, as we do ... cancers, my case was taken before the staff board and I was discussed at the staff meeting. ...

  19. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... history, as well as her very, very excellent pulmonary function tests and preoperative evaluation and her young age that we would address the lung cancer -- the lung mass first, and that’s essentially all ...

  20. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... a multidisciplinary team when managing such a complicated disease as lung cancer, and we really do have ... a preoperative evaluation of the extent of the disease that you’re dealing with, especially when you ...

  1. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... need for their cancer. I’d like to stress to everyone that what we do here at ... is really on target. You know it’s pretty anxiety provoking for a patient to be sitting in ...

  2. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... rigid instruments that are applicable in an earlier generation of thoracic and thoracoscopic devices and definitely better ... therapy is is the use of high-energy X-rays that preferentially kill cancer cells with minimal ...

  3. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... cancer surgery was done. It’s really an elaborate video game, and I would like to show you ... a whole lobe, you know, by doing the video-assisted thorascopic surgery alone? Absolutely. And you know ...

  4. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... is really the number one cause of cancer-related deaths in this country. It far exceeds breast ... we approach everything really with thoracoscopic surgery in mind because it’s a way to minimize postoperative pain, ...

  5. Biological markers of invasive breast cancer.

    Science.gov (United States)

    Matsumoto, Akiko; Jinno, Hiromitsu; Ando, Tomofumi; Fujii, Taku; Nakamura, Tetsuya; Saito, Junichi; Takahashi, Maiko; Hayashida, Tetsu; Kitagawa, Yuko

    2016-02-01

    Biological markers for breast cancer are biomolecules that result from cancer-related processes and are associated with particular clinical outcomes; they thus help predict responses to therapy. In recent years, gene expression profiling has made the molecular classification of breast cancer possible. Classification of breast cancer by immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67 is standard practice for clinical decision-making. Assessments of hormone receptor expression and human epidermal growth factor receptor 2 overexpression help estimate benefits from targeted therapies and have greatly improved prognoses for women with these breast cancer types. Although Ki-67 positivity is associated with an adverse outcome, its clear identification is an aid to optimal disease management. Standardization of testing methodology to minimize inter-laboratory measurement variations is a remaining issue. Multi-gene assays provide prognostic information and identify those most likely to benefit from systemic chemotherapy. Incorporating molecular profiles with conventional pathological classification would be more precise, and could enhance the clinical development of personalized therapy in breast cancer. PMID:26486826

  6. Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells.

    Science.gov (United States)

    Suzuki, Katsuo; Takahashi, Kazuhide

    2008-04-01

    Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1-CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1-CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1. PMID:18237546

  7. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    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.

  8. Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available Dysregulation of Ras and Rho family small GTPases drives the invasion and metastasis of multiple cancers. For their biological functions, these GTPases require proper subcellular localization to cellular membranes, which is regulated by a series of post-translational modifications that result in either farnesylation or geranylgeranylation of the C-terminal CAAX motif. This concept provided the rationale for targeting farnesyltransferase (FTase and geranylgeranyltransferases (GGTase for cancer treatment. However, the resulting prenyl transferase inhibitors have not performed well in the clinic due to issues with alternative prenylation and toxicity. As an alternative, we have developed a unique class of potential anti-cancer therapeutics called Prenyl Function Inhibitors (PFIs, which are farnesol or geranyl-geraniol analogs that act as alternate substrates for FTase or GGTase. Here, we test the ability of our lead PFIs, anilinogeraniol (AGOH and anilinofarnesol (AFOH, to block the invasion of breast cancer cells. We found that AGOH treatment effectively decreased invasion of MDA-MB-231 cells in a two-dimensional (2D invasion assay at 100 µM while it blocked invasive growth in three-dimensional (3D culture model at as little as 20 µM. Notably, the effect of AGOH on 3D invasive growth was phenocopied by electroporation of cells with C3 exotransferase. To determine if RhoA and RhoC were direct targets of AGOH, we performed Rho activity assays in MDA-MB-231 and MDA-MB-468 cells and found that AGOH blocked RhoA and RhoC activation in response to LPA and EGF stimulation. Notably, the geranylgeraniol analog AFOH was more potent than AGOH in inhibiting RhoA and RhoC activation and invasive growth. Interestingly, neither AGOH nor AFOH impacted 3D growth of MCF10A cells. Collectively, this study demonstrates that AGOH and AFOH dramatically inhibit breast cancer invasion, at least in part by blocking Rho function, thus, suggesting that targeting

  9. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... blade come across there. See how nice and clean the staple line is? Yeah. There’s just a ... radiation therapy is is the use of high-energy X-rays that preferentially kill cancer cells with ...

  10. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... cancer surgery was done. It’s really an elaborate video game, and I would like to show you some of the images from some of our operations. Right here you’re looking at ... thorascopic surgery alone? Absolutely. And you know ...

  11. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... today is Dr. Walter Choi who is the director of the lung cancer division of the radiation oncology service. Good morning, Walter? Good morning. How are you? Morning Sam, thank you for coming. I really appreciate that you took time out of your day to come. As an ...

  12. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... medical doctor, you know, with an abnormal chest X-ray. As you know, the suspicion of lung cancer, ... to reach a diagnosis. Once you have abnormal X-ray, I think the next thing to do would ...

  13. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... out multidisciplinary approach to lung cancer, how we help to support the patients, how we help to treat them both before, during, and after ... you to some members of our team and help you understand some of the things that we ...

  14. Exploring molecular links between lymph node invasion and cancer prognosis in human breast cancer

    OpenAIRE

    Kim, Sangwoo; Nam, Hojung; Lee, Doheon

    2011-01-01

    Abstract Background Lymph node invasion is one of the most powerful clinical factors in cancer prognosis. However, molecular level signatures of their correlation are remaining poorly understood. Here, we propose a new approach, monotonically expressed gene analysis (MEGA), to correlate transcriptional patterns of lymph node invasion related genes with clinical outcome of breast cancer patients. Results Using MEGA, we scored all genes with their transcriptional patterns ov...

  15. Exploring molecular links between lymph node invasion and cancer prognosis in human breast cancer

    OpenAIRE

    Kim Sangwoo; Nam Hojung; Lee Doheon

    2011-01-01

    Abstract Background Lymph node invasion is one of the most powerful clinical factors in cancer prognosis. However, molecular level signatures of their correlation are remaining poorly understood. Here, we propose a new approach, monotonically expressed gene analysis (MEGA), to correlate transcriptional patterns of lymph node invasion related genes with clinical outcome of breast cancer patients. Results Using MEGA, we scored all genes with their transcriptional patterns over progression level...

  16. Enhanced invasion of metastatic cancer cells via extracellular matrix interface.

    Directory of Open Access Journals (Sweden)

    Jiangrui Zhu

    Full Text Available Cancer cell invasion is a major component of metastasis and is responsible for extensive cell diffusion into and major destruction of tissues. Cells exhibit complex invasion modes, including a variety of collective behaviors. This phenomenon results in the structural heterogeneity of the extracellular matrix (ECM in tissues. Here, we systematically investigated the environmental heterogeneity facilitating tumor cell invasion via a combination of in vitro cell migration experiments and computer simulations. Specifically, we constructed an ECM microenvironment in a microfabricated biochip and successfully created a three-dimensional (3D funnel-like matrigel interface inside. Scanning electron microscopy demonstrated that the interface was at the interior defects of the nano-scale molecular anisotropic orientation and the localized structural density variations in the matrigel. Our results, particularly the correlation of the collective migration pattern with the geometric features of the funnel-like interface, indicate that this heterogeneous in vitro ECM structure strongly guides and promotes aggressive cell invasion in the rigid matrigel space. A cellular automaton model was proposed based on our experimental observations, and the associated quantitative analysis indicated that cell invasion was initiated and controlled by several mechanisms, including microenvironment heterogeneity, long-range cell-cell homotype and gradient-driven directional cellular migration. Our work shows the feasibility of constructing a complex and heterogeneous in vitro 3D ECM microenvironment that mimics the in vivo environment. Moreover, our results indicate that ECM heterogeneity is essential in controlling collective cell invasive behaviors and therefore determining metastasis efficiency.

  17. Predictors of Outcome of Non–Muscle-Invasive and Muscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Ramy F. Youssef

    2011-01-01

    Full Text Available Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non–muscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10–30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non–muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinoma in situ are the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies.

  18. FGFR1 amplification and the progression of non-invasive to invasive breast cancer

    OpenAIRE

    Gru, Alejandro A.; Allred, D. Craig

    2012-01-01

    The incidence of invasive breast cancer (IBC) can be dramatically reduced by improving our abilities to detect and treat ductal carcinoma in situ (DCIS). Progress will be based on a detailed understanding of molecular mechanisms responsible for tumor progression. An interesting study by Jang and colleagues evaluated and compared the frequency of amplification of four oncogenes (HER2, c-MYC, CCND1 and FGFR1) in large cohorts of pure DCIS, in the DCIS component of IBC, and in corresponding IBC....

  19. Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles

    OpenAIRE

    Chen Kun-Wan; Pienta Kenneth J

    2011-01-01

    Abstract Background The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species) before proliferating (invasive spread). Proliferation in the new site has...

  20. The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy

    OpenAIRE

    Liu, Ying; Cao, Wei; Zhang, Bo; Liu, Yong-Qiang; Wang, Zhong-yuan; Wu, Yan-ping; Yu, Xian-jun; Zhang, Xu-Dong; Ming, Ping-hong; Zhou, Guang-Biao; Huang, Laiqiang

    2013-01-01

    Invasion and metastasis are the main causes of treatment failure and death in breast cancer. Thus, novel invasion-based therapies such as those involving natural agents are urgently required. In this study, we examined the effects of magnolol (Mag), a compound extracted from medicinal herbs, on breast cancer cells in vitro and in vivo. Highly invasive cancer cells were found to be highly sensitive to treatment. Mag markedly inhibited the activity of highly invasive MDA-MB-231 cells. Furthermo...

  1. Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

    Science.gov (United States)

    Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki

    2014-03-01

    We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed. PMID:21140247

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

    International Nuclear Information System (INIS)

    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

  3. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... the outset, we would not be able to offer the appropriate treatment for that patient. So without ... discuss it also a team, you know, and offer the patient different treatment options. Part of the ...

  4. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... the patient different treatment options. Part of the assessment of whether they can be surgical candidates, you ... pulmonary function test, you know, to get an assessment of their lung function, and then make a ...

  5. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... 2009 is very sophisticated. We have very advanced computer modeling, and we work very closely with our ... Sam both pointed out, we tried to be part of that support staff as well and to ...

  6. 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.......0-1.2, P(trend) = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. CONCLUSIONS: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study.......1-1.5, P(trend) = 0.003). METHODS: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. RESULTS: No evidence for an association with all cancers or serous cancers was observed in a...

  7. 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

  8. Human papillomavirus genotype prevalence in invasive penile cancers from a registry-based United States population

    Directory of Open Access Journals (Sweden)

    BrendaYHernandez

    2014-02-01

    Full Text Available Background. Human papillomavirus (HPV is estimated to play an etiologic role in 40%-50% of penile cancers worldwide. Estimates of HPV prevalence in U.S. penile cancer cases are limited. Methods. HPV DNA was evaluated in tumor tissue from 79 invasive penile cancer patients diagnosed in 1998-2005 within the catchment areas of 7 U.S. cancer registries. HPV was genotyped using PCR-based Linear Array and INNO-LiPA assays and compared by demographic, clinical, and pathologic characteristics and survival. Histological classification was also obtained by independent pathology review. Results. HPV DNA was present in 50 of 79 (63% of invasive penile cancer cases. Sixteen viral genotypes were detected. HPV 16, found in 46% (36/79 of all cases (72% of HPV-positive cases was the most prevalent genotype followed equally by HPV 18, 33, and 45, which each comprised 5% of all cases. Multiple genotypes were detected in 18% of viral positive cases. HPV prevalence did not significantly vary by age, race/ethnicity, population size of geographic region, cancer stage, histology, grade, penile subsite, or prior cancer history. Penile cases diagnosed in more recent years were more likely to be HPV positive. Overall survival did not significantly vary by HPV status. Conclusions. The relatively high prevalence of HPV in our study population provides limited evidence of a more prominent and, possibly, increasing role of infection in penile carcinogenesis in the U.S. compared to other parts of the world.

  9. Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis.

    Science.gov (United States)

    Foda, H D.; Zucker, S

    2001-05-01

    Matrix metalloproteinases (MMPs) are a family of proteinases that play an important role in cancer as well as in numerous other diseases. In this article, we summarize the current views on the role of MMPs in cancer with respect to invasion, metastasis and angiogenesis. A positive correlation between tumor progression and the expression of multiple MMP family members in tumor tissues has been demonstrated in numerous human and animal studies. It has been assumed that cancer cells are responsible for producing the MMPs in human tumors. However, recent evidence suggests that tumor cells have docking sites that bind stromal-cell-secreted MMPs. Furthermore, the role of MMPs produced by endothelial cells, especially MMP-2 and MT1-MMP, appear to be crucial for tumor angiogenesis, which is a requirement for cancer growth and dissemination. PMID:11344033

  10. Contemporary management of muscle-invasive bladder cancer

    OpenAIRE

    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 p...

  11. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... And unfortunately, it’s normally detected in a late stage, you know, and even when detected early, you ... the bronchoscopy, the next important part is to stage. And that’s very critical in determining the outcome ...

  12. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... as I’m sure that you feel as well. It’s really a pleasure when the outcome turns out to be positive for the patients, and I think everybody ... and Sam both pointed out, we tried to be part of that support staff as well and to offer her the most efficient way ...

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

    International Nuclear Information System (INIS)

    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 99mTc-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 99mTc-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/mm2 and one showed 99 microvessels/mm2; by contrast there were 71.6±12.1 microvessels/mm2 in the nine N- and sestamibi-negative tumours. Our study suggests that 99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour. (orig.)

  14. 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.)

  15. Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells.

    Science.gov (United States)

    Jiang, Jiahua; Sliva, Daniel

    2010-12-01

    Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases. Currently mushrooms or their extracts are used globally in the form of dietary supplements. In the present study we have evaluated the anticancer effects of the dietary supplement, MycoPhyto® Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and β-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae. Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231. DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion. The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells. In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer. PMID:21042722

  16. A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness

    Science.gov (United States)

    Yi, Cao; Li, Chen Chen; Yu, Patricia; Arakelian, Ani; Tanvir, Imrana; Khan, Haseeb Ahmed; Rabbani, Shafaat

    2015-01-01

    Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from non-invasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes in cellular invasiveness from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness. SUMMARY Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins that could serve as drug targets. PMID:26427334

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

    International Nuclear Information System (INIS)

    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. 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.

  19. Neoadjuvant or adjuvant chemotherapy: what is the best treatment of muscle invasive bladder cancer?

    Directory of Open Access Journals (Sweden)

    Nabil Ismaili

    2011-09-01

    Full Text Available Bladder cancer is the fourth most common cancer for men and the eighth most common cancer for women. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting the treatment is based on cisplatin chemotherapy regimens type MVAC, MVAC-HD or gemcitabine plus cisplatin. The standard treatment of muscle invasive operable bladder cancer (T2–T4 used widely was radical cystectomy with pelvic lymph nodes dissection; the anatomical extent of pelvic lymphadenectomy has not accurately been defined so far. However, in the last decade, the treatment of tumors was improved by the introduction of chemotherapy as part of the management of the disease. Neoadjuvant chemotherapy should be considered at first, as standard treatment of choice, before local treatment for patients with good performance status (0–1 and good renal function–glomerular filtration rate (GFR >60 mL/min. For patients treated with primary surgery, adjuvant chemotherapy is a valuable option in the case of lymph nodes involvement. This brief review would provide the evidence of the role of neoadjuvant chemotherapy in the management of operable muscle invasive (T2–T4 bladder cancer.

  20. Non-invasive Optical Molecular Imaging for Cancer Detection

    Science.gov (United States)

    Luo, Zhen

    Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide

  1. Reviewing and reconsidering invasion assays in head and neck cancer.

    Science.gov (United States)

    Inglehart, Ronald C; Scanlon, Christina S; D'Silva, Nisha J

    2014-12-01

    Head and neck squamous cell carcinomas (HNSCC) are malignant tumors that arise from the surface epithelium of the oral cavity, oropharynx and larynx, primarily due to exposure to chemical carcinogens or the human papilloma virus. Due to their location, dental practitioners are well-positioned to detect the lesions. Deadlier than lymphoma or melanoma, HNSCC is incompletely understood. For these reasons, dental practitioners and researchers are focused on understanding HNSCC and the processes driving it. One of these critical processes is invasion, the degradation of the basement membrane by HNSCC cells with subsequent movement into the underlying connective tissue, blood vessels or nerves. Cancer cells metastasize to distant sites via the blood vessels, lymphatics and nerves. Metastasis is associated with poor survival. Since invasion is essential for development and metastasis of HNSCC, it is essential to understand the mechanism(s) driving this process. Elucidation of the mechanisms involved will facilitate the development of targeted treatment, thereby accelerating development of precision/personalized medicine to treat HNSCC. Robust in vitro and in vivo assays are required to investigate the mechanistic basis of invasion. This review will focus on in vitro and in vivo assays used to study invasion in HNSCC, with special emphasis on some of the latest assays to study HNSCC. PMID:25448226

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

    International Nuclear Information System (INIS)

    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)

  3. Role of ATF5 in the invasive potential of diverse human cancer cell lines.

    Science.gov (United States)

    Nukuda, Akihiro; Endoh, Hiroki; Yasuda, Motoaki; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

    2016-06-01

    Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding protein family. Our research group recently revealed that ATF5 expression increases the invasiveness of human lung carcinoma cells. However, the effects of ATF5 on the invasive potential of other cancer cells lines remain unclear. Therefore, in this study, we investigated the role of ATF5 in the invasive activity of diverse human cancer cell lines. Invasiveness was assessed using Matrigel invasion assays. ATF5 knockdown resulted in decreased invasiveness in seven of eight cancer cell lines tested. These results suggest that ATF5 promotes invasiveness in several cancer cell lines. Furthermore, the roles of ATF5 in the invasiveness were evaluated in three-dimensional (3D) culture conditions. In 3D collagen gel, HT-1080 and MDA-MB-231 cells exhibited high invasiveness, with spindle morphology and high invasion speed. In both cell lines, knockdown of ATF5 resulted in rounded morphology and decreased invasion speed. Next, we showed that ATF5 induced integrin-α2 and integrin-β1 expression and that the depletion of integrin-α2 or integrin-β1 resulted in round morphology and decreased invasion speed. Our results suggest that ATF5 promotes invasion by inducing the expression of integrin-α2 and integrin-β1 in several human cancer cell lines. PMID:27125458

  4. 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.

  5. 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.

  6. Mitochondrial targeted catalase suppresses invasive breast cancer in mice

    International Nuclear Information System (INIS)

    Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential. Transgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined. PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm2/cm2 of lung tissue compared with 1.3 mm2/cm2 of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for

  7. Mitochondrial targeted catalase suppresses invasive breast cancer in mice

    Directory of Open Access Journals (Sweden)

    Morton John

    2011-05-01

    Full Text Available Abstract Background Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential. Methods Transgenic mice expressing a human catalase gene (mCAT were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined. Results PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05. PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm2/cm2 of lung tissue compared with 1.3 mm2/cm2 of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01, indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK

  8. Can high frequency ultrasound predict metastatic lymph nodes in patients with invasive breast cancer?

    International Nuclear Information System (INIS)

    Purpose: Use high frequency ultrasound to predict the presence of metastatic axillary lymph nodes, with a high specificity and positive predictive value, in patients with invasive breast cancer. The clinical aim is to improve the surgical management and possible survival rate of groups of patients who would not normally have conventional axillary dissections. Materials and methods: The ipsilateral and contralateral axillas of 42 consecutive patients with invasive breast cancer were scanned prior to treatment using a B-mode frequency of 13 MHz and a Doppler frequency of 7 MHz. The presence or absence of an echogenic centre for each lymph node detected was recorded, measurements were also taken to determine the L/S (long axis/short axis) ratio of the node and the widest and narrowest part of the cortex. Power Doppler was also used to determine vascularity. The contralateral axilla was used as a control for each patient. Results: In this study of patients with invasive breast cancer, where ipsilateral lymph nodes had a cortical bulge of ≥3 mm and/or at least two lymph nodes had absent echogenic centres, all had disease spread to the axillary lymph nodes (10 patients). Sensitivity and specificity were 52.6% and 100%, respectively, positive and negative predictive values were 100% and 71.9%, respectively, the P-value was 0.001 and the Kappa score was 0.55. Conclusion: This would indicate that high frequency ultrasound could be used to accurately predict metastatic lymph nodes in a proportion of patients with invasive breast cancer, which may alter patient management

  9. DNA From Dead Cancer Cells Induces TLR9-Mediated Invasion and Inflammation In Living Cancer Cells

    Science.gov (United States)

    Tuomela, Johanna; Sandholm, Jouko; Kaakinen, Mika; Patel, Ankita; Kauppila, Joonas H.; Ilvesaro, Joanna; Chen, Dongquan; Harris, Kevin W.; Graves, David; Selander, Katri S.

    2014-01-01

    TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple negative, human MDA-MB-231 breast cancer cells stably expressing control or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. PMID:24212717

  10. Malignant cancer and invasive placentation: A case for positive pleiotropy between endometrial and malignancy phenotypes.

    Science.gov (United States)

    D'Souza, Alaric W; Wagner, Günter P

    2014-01-01

    Cancer metastasis is an invasive process that involves the transplantation of cells into new environments. Since human placentation is also invasive, hypotheses about a relationship between invasive placentation in eutherian mammals and metastasis have been proposed. The relationship between metastatic cancer and invasive placentation is usually presented in terms of antagonistic pleiotropy. According to this hypothesis, evolution of invasive placentation also established the mechanisms for cancer metastasis. Here, in contrast, we argue that the secondary evolution of less invasive placentation in some mammalian lineages may have resulted in positive pleiotropic effects on cancer survival by lowering malignancy rates. These positive pleiotropic effects would manifest themselves as resistance to cancer cell invasion. To provide a preliminary test of this proposal, we re-analyze data from Priester and Mantel (Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 1971; 47: :1333-44) about malignancy rates in cows, horses, cats and dogs. From our analysis we found that equines and bovines, animals with less invasive placentation, have lower rates of metastatic cancer than felines and canines in skin and glandular epithelial cancers as well as connective tissue sarcomas. We conclude that a link between type of placentation and species-specific malignancy rates is more likely related to derived mechanisms that suppress invasion rather than different degrees of fetal placental aggressiveness. PMID:25324490

  11. 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.

  12. Intra-arterial chemotherapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ozono, Seiichiro; Kim, Sung-Chul; Takashima, Kenji [Nara Medical Univ., Kashihara (Japan)] [and others

    1999-02-01

    The present investigation was conducted to examine the effects of intra-arterial chemotherapy (IAC) for patients with invasive bladder cancer. A total of 37 patients were treated with IAC at Nara Medical University and its affiliated hospitals between January, 1993 and August, 1997. There were 27 patients in the poor risk group. The remaining 10 patients underwent anti-tumor IAC. Thirty of the 37 patients received chemotherapeutic agents via a reservoir, and the remaining 7 patients received a one-shot injection of agents followed by transcatheter arterial embolization (TAE). In the reservoir group, there were 18 patients who received IAC in combination with radiation therapy. As a result, reduction of tumor size was noted in 53%, and the 3-year cause-specific survival rate was 54% in all cases. There was a significant difference in the 3-year survival rate between the radiation-treated group and the group without radiation. The adverse events included anemia, leukopenia, thrombocytopenia and gastrointestinal symptoms, but none of them were severe. The results of the present study indicate that IAC is useful in the treatment of invasive bladder cancer for poor risk patients. (author)

  13. Concomitant boost radiotherapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    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. Intra-arterial chemotherapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    The present investigation was conducted to examine the effects of intra-arterial chemotherapy (IAC) for patients with invasive bladder cancer. A total of 37 patients were treated with IAC at Nara Medical University and its affiliated hospitals between January, 1993 and August, 1997. There were 27 patients in the poor risk group. The remaining 10 patients underwent anti-tumor IAC. Thirty of the 37 patients received chemotherapeutic agents via a reservoir, and the remaining 7 patients received a one-shot injection of agents followed by transcatheter arterial embolization (TAE). In the reservoir group, there were 18 patients who received IAC in combination with radiation therapy. As a result, reduction of tumor size was noted in 53%, and the 3-year cause-specific survival rate was 54% in all cases. There was a significant difference in the 3-year survival rate between the radiation-treated group and the group without radiation. The adverse events included anemia, leukopenia, thrombocytopenia and gastrointestinal symptoms, but none of them were severe. The results of the present study indicate that IAC is useful in the treatment of invasive bladder cancer for poor risk patients. (author)

  15. Loss of GATA3 in bladder cancer promotes cell migration and invasion

    OpenAIRE

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Kashiwagi, Eiji; Izumi, Koji; Miyamoto, Hiroshi

    2014-01-01

    The transcription factor GATA3 is known as a breast tumor suppressor as well as a urothelial marker, and its loss is often seen in high-grade invasive bladder cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of bladder cancer. GATA3 expression was downregulated in all four bladder cancer lines examined, compared with a non-neoplastic...

  16. THE PROBLEM OF INVASIVE MYCOSES IN RHEUMATOLOGY(Part I)

    OpenAIRE

    Boris Sergeyevich Belov; O N Egorova; G. M. Tarasova; M V Polyanskaya; R M Balabanova

    2009-01-01

    The problem of invasive mycoses is becoming ever more urgent in modern rheumatology. The fact that physicians are unalert to mycoses in patients with systemic rheumatic diseases and that there are difficulties in their lifetime diagnosis and treatment is noteworthy. The significance of this problem substantially increases with the active clinical introduction of biologicals, primarily tumor necrosis factor а inhibitors (infliximab, adalimumab, etanercept), which goes on concurrently with the ...

  17. Study on Invasion of Artesunate on Inhibiting Human Colon Cancer Cell SW620

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2013-09-01

    Full Text Available Objective: To observe the invasive effect of Chinese extraction artesunate on human colon cancer cell SW620 and explore its possible mechanisms. Methods: Colon cancer cell SW620 was managed by different concentrations of artesunate, and soft agar colony-cultivating trial was applied to detect anchorage independent proliferation of cancer cells, Boyden chamber model method to detect the invasive capability of cancer cells and Western blot method to detect the change of intercellular adhesion molecule-1 (ICAM-1 proteins. Results: Artesunate can effectively inhibit malignant proliferation and invasive capability of colon cancer cell SW620, and was dose-dependent (P < 0.01. Artesunate can effectively inhibit the expression of cancer cell ICAM-1 gene proteins, and was time- and concentration-dependant (P <0.01. Conclusion: Artesunate can significantly inhibit the invasion of colon cancer cell SW620, which can be related to down-regulation of ICAM-1 protein level.

  18. Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

    OpenAIRE

    Rajamahanty, Srinivas; Louie, Brandon; O’Neill, Cormac; Choudhury, Muhammad; Konno, Sensuke

    2009-01-01

    Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, invasive disease. We here report an 87-year-old white male patient with invasive bladder cancer who received...

  19. Molecular subtyping of DCIS: heterogeneity of breast cancer reflected in pre-invasive disease

    OpenAIRE

    Clark, S. E.; Warwick, J.; Carpenter, R.; Bowen, R L; Duffy, S W; Jones, J L

    2010-01-01

    Background: Molecular profiling has identified at least four subtypes of invasive breast carcinoma, which exhibit distinct clinical behaviour. There is good evidence now that DCIS represents the non-obligate precursor to invasive breast cancer and therefore it should be possible to identify similar molecular subtypes at this stage. In addition to a limited five-marker system to identify molecular subtypes in invasive breast cancer, it is evident that other biological molecules may identify di...

  20. Suppression of TPA-induced cancer cell invasion by Peucedanum japonicum Thunb. extract through the inhibition of PKCα/NF-κB-dependent MMP-9 expression in MCF-7 cells

    OpenAIRE

    Kim, Jeong-Mi; NOH, EUN-MI; KIM, HA-RIM; KIM, MI-SEONG; SONG, HYUN-KYUNG; LEE, MINOK; Yang, Sei-Hoon; Lee, Guem-San; Moon, Hyoung-Chul; Kwon, Kang-Beom; Lee, Young-Rae

    2015-01-01

    Metastatic cancers spread from their site of origin (the primary site) to other parts of the body. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is important in metastatic cancers as it plays a major role in cancer cell invasion. The present study examined the inhibitory effect of an ethanol extract of Peucedanum japonicum Thunb. (PJT) on MMP-9 expression and the invasion of MCF-7 breast cancer cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Western...

  1. 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

  2. Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Jeffrey J Tomaszewski

    2010-05-01

    Full Text Available Jeffrey J Tomaszewski, Marc C SmaldoneDepartment of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Transitional cell carcinoma (TCC is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC. Intravesical bacillus Calmette-Guerin (BCG is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel, and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.Keywords: transitional cell carcinoma, nonmuscle, invasive, intravesical therapy, BCG

  3. GENETIC RISK MARKERS FOR SUPERFICIAL AND INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2011-01-01

    Full Text Available To reveal possible associations of the polymorphic variants of the cytochrome P450 and enzymes glutathione-S-transferase genes with the risk for bladder cancer (BC, the authors analyzed the frequency of genotypes and alleles at the polymorphic loci of the CYP1A1 (A2454G, GSTM1 (del, and GSTP1 (A313G genes in 208 patients diagnosed as having BC (104 patients with invasive BC and 104 with superficial BC and in 367 patients without identified oncopathology. The *1A*2C (OR = 3.42 and *2C*2С (OR = 6.98 genotypes, *2C (OR = 3.73 allele of the CYP1A1 gene and the GG (OR = 2.53 genotype of the GSTP1 gene were ascertained to be genetic markers for a risk for BC. The presence of the *2C (OR = 1.69 allele of the CYP1A1 gene, the G (OR = 2.40 allele and the AG genotype (OR = 2.40 of the GSTP1 gene was associated with the invasive forms of BC. There were no substantial differences in the distribution of the frequency of genotypes of the GSTM1 gene between the samples of patients and healthy individuals.

  4. 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.

  5. Effects of osthole on migration and invasion in breast cancer cells.

    Science.gov (United States)

    Yang, Dapeng; Gu, Tianwei; Wang, Ting; Tang, Qingjiu; Ma, Changyan

    2010-01-01

    Osthole, a natural coumarin derivative, is extracted from the fruit of Cnidium monnieri Cusson. Breast cancer is one of the most commonly diagnosed cancers and the leading cause of death in women. Recent studies have shown that Osthole has anti-tumor activity. However, the effects of Osthole on the migration and invasion of cancer cells have not yet been reported. Here, we found that Osthole is effective in inhibiting the migration and invasion of breast cancer cells by wound healing and transwell assays. Luciferase and zymography assays revealed that Osthole effectively inhibits matrix metalloproteinase-2 promoter and enzyme activity, which might be one of the causes that lead to the inhibition of migration and invasion by Osthole. This is the first report on the inhibitory function of Osthole in migration and invasion in breast cancer cells. Our findings indicate a need for further evaluation of Osthole in breast cancer chemotherapy and chemoprevention. PMID:20622464

  6. Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2014-12-30

    In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGFβ superfamily ligands, TGFβ, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGFβs and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFβ and highlights how its dysregulation contributes to cancer progression and cell invasion.

  7. Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion

    International Nuclear Information System (INIS)

    In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGFβ superfamily ligands, TGFβ, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGFβs and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFβ and highlights how its dysregulation contributes to cancer progression and cell invasion

  8. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan.

    Science.gov (United States)

    Loya, Asif; Serrano, Beatriz; Rasheed, Farah; Tous, Sara; Hassan, Mariam; Clavero, Omar; Raza, Muhammad; De Sanjosé, Silvia; Bosch, F Xavier; Alemany, Laia

    2016-01-01

    Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases. PMID:27483322

  9. 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

  10. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger;

    2009-01-01

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive.......01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast...... ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially...

  11. S100P interacts with integrin α7 and increases cancer cell migration and invasion in lung cancer.

    Science.gov (United States)

    Hsu, Ya-Ling; Hung, Jen-Yu; Liang, Yung-Yu; Lin, Yi-Shiuan; Tsai, Ming-Ju; Chou, Shah-Hwa; Lu, Chi-Yu; Kuo, Po-Lin

    2015-10-01

    S100P, a Ca2+ binding protein, has been shown to be overexpressed in various cancers. However, its functional character in lung cancer remains largely unknown. In this study, we show that S100P increases cancer migration, invasion and metastasis in lung cancer cells. Ectopic expression of S100P increases migration, invasion and EMT in less invasive CL1-0 lung cancer cells. Conversely, knockdown of S100P suppressed migration and invasion, and caused a reversion of EMT in highly invasive lung cancer cells. These effects were transduced by increasing the interaction of S100P with integrin α7, which activated focal adhesion kinase (FAK) and AKT. Blocking FAK significantly decreased S100P-induced migration by decreasing Src and AKT activation, whereas inhibiting AKT reduced S100P upregulation on ZEB1 expression. Further study has indicated that S100P knockdown prevents the spread of highly metastatic human lung cancer in animal models. This study therefore suggests that S100P represents a critical activator of lung cancer metastasis. Detection and targeted treatment of S100P-expressing cancer is an attractive therapeutic strategy in treating lung cancer. PMID:26320193

  12. Changes in autofluorescence based organoid model of muscle invasive urinary bladder cancer.

    Science.gov (United States)

    Palmer, Scott; Litvinova, Karina; Dunaev, Andrey; Fleming, Stewart; McGloin, David; Nabi, Ghulam

    2016-04-01

    Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. PMID:27446646

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

    Directory of Open Access Journals (Sweden)

    Uygur Berna

    2011-11-01

    Full Text Available Abstract Background 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. Methods 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. Research 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. Conclusion 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.

  14. Dual-function CXCR4 Antagonist Polyplexes to Deliver Gene Therapy and Inhibit Cancer Cell Invasion**

    OpenAIRE

    Li, Jing; Zhu, Yu; Hazeldine, Stuart T.; Li, Chunying; Oupický, David

    2012-01-01

    A bicyclam-based biodegradable polycation with CXCR4 antagonistic activity was developed with potential for combined drug/gene cancer therapies. The dual-function polycation prevents cancer cell invasion by inhibiting CXCL12 stimulated CXCR4 activation, while at the same time efficiently and safely delivers plasmid DNA into cancer cells.

  15. Clinical pitfalls in diagnosis of nonmuscle-invasive bladder cancer.

    Science.gov (United States)

    Serretta, Vincenzo; Scalici Gesolfo, Cristina

    2015-10-01

    Current global economic crisis imposes healthcare system to reduce unnecessary investigations and increase early detection of tumors, to decrease the costs of an advanced disease. Several diagnostic pitfalls may occur dealing with bladder cancer (BC), particularly in nonmuscle-invasive (NMIBC) one. Hematuria, the commonest sign in NMIBC, is often underestimated. Urinary cytology is highly specific for high-grade tumors, but has a low sensitivity for low-grade BC, is operator dependent, and not always obtainable in clinical practice. Numerous urinary tests are available to ameliorate the accuracy of cytology, but none of them is routinly used in urological practice. Ultrasound could hardly detect a small bladder tumor, especially if located in the bladder neck or in the anterior wall. Computed tomography (CT) is widely adopted as an alternative to conventional urography, but its usefulness in patients with hematuria is still debated. MRI has a higher accuracy than CT for staging BC and evaluate the bladder-wall invasion. A negative cystoscopy cannot exclude Tis and should be accompanied by urinary cytology in patients with suspected Tis or high-risk NMIBC; however, new techniques such as narrow band imaging (NBI) and photodynamic (PDD) increase the detection rate of BC and flat lesions. Nearly half of all diagnostic resections present omission of muscle in the specimen or its mention in the pathology report, which is associated with an increased mortality. An adequate muscle sampling during endoscopic resection is mandatory, particularly in patients with high-grade disease. Recognition of pitfalls in diagnosis and management of BC represents the first step for a correct approach. PMID:26481718

  16. 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

  17. Enhanced proliferation, invasion, and epithelial-mesenchymal transition of nicotine-promoted gastric cancer by periostin

    Institute of Scientific and Technical Information of China (English)

    Yu Liu; Bao-An Liu

    2011-01-01

    AIM: To investigate the contribution of periostin in nicotine-promoted gastric cancer cell proliferation, survival, invasion, drug resistance, and epithelial-mesenchymal transition (EMT). METHODS: Gastric cancer cells were treated with nicotine and periostin protein expression was determined by immunoblotting. Periostin mRNA in gastric cancer cells was silenced using small interfering RNA (siRNA) techniques and periostin gene expression was evaluated by quantitative reverse transcription-polymerase chain reaction. Gastric cancer cells transfected with control or periostin siRNA plasmid were compared in terms of cell proliferation using the methylthiazolyldiphenyl-tetrazolium bromide assay. Cell apoptosis was compared using annexin V-fluoresceine isothiocyanate and propidium iodine double staining. Tumor invasion was determined using the Boyden chamber invasion assay, and the EMT marker Snail expression was evaluated by immunoblotting. RESULTS: Nicotine upregulated periostin in gastric cancer cells through a COX-2 dependent pathway, which was blocked by the COX-2-specific inhibitor NS398. Periostin mRNA expression was decreased by ~87.2% by siRNA in gastric cancer cells, and stable periostinsilenced cells were obtained by G418 screening. Periostin- silenced gastric cancer cells exhibited reduced cell proliferation, elevated sensitivity to chemotherapy with 5-fluorouracil, and decreased cell invasion and Snail expression (P < 0.05). CONCLUSION: Periostin is a nicotine target gene in gastric cancer and plays a role in gastric cancer cell growth, invasion, drug resistance, and EMT facilitated by nicotine.

  18. 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.

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

    International Nuclear Information System (INIS)

    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

  20. 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

  1. Identification of pancreatic cancer invasion-related proteins by proteomic analysis

    Directory of Open Access Journals (Sweden)

    Clynes Martin

    2009-02-01

    Full Text Available Abstract Background Markers of pancreatic cancer invasion were investigated in two clonal populations of the cell line, MiaPaCa-2, Clone #3 (high invasion and Clone #8 (low invasion using proteomic profiling of an in vitro model of pancreatic cancer. Materials and methods Using 2D-DIGE followed by MALDI-TOF MS, two clonal sub-populations of the pancreatic cancer cell line, MiaPaCa-2 with high and low invasive capacities were incubated on matrigel 24 hours prior to analysis to stimulate cell-ECM contact and mimic in vivo interaction with the basement membrane. Results Sixty proteins were identified as being differentially expressed (> 1.2 fold change and p ≤ 0.05 between Clone #3 and Clone #8. Proteins found to have higher abundance levels in the highly invasive Clone #3 compared to the low invasive Clone #8 include members of the chaperone activity proteins and cytoskeleton constituents whereas metabolism-associated and catalytic proteins had lower abundance levels. Differential protein expression levels of ALDH1A1, VIM, STIP1 and KRT18 and GAPDH were confirmed by immunoblot. Using RNAi technology, STIP1 knockdown significantly reduced invasion and proliferation of the highly invasive Clone #3. Knockdown of another target, VIM by siRNA in Clone #3 cells also resulted in decreased invasion abilities of Clone #3. Elevated expression of STIP1 was observed in pancreatic tumour tissue compared to normal pancreas, whereas ALDH1A1 stained at lower levels in pancreatic tumours, as detected by immunohistochemistry. Conclusion Identification of targets which play a role in the highly invasive phenotype of pancreatic cancer may help to understand the biological behaviour, the rapid progression of this cancer and may be of importance in the development of new therapeutic strategies for pancreatic cancer.

  2. Loss of P53 facilitates invasion and metastasis of prostate cancer cells.

    Science.gov (United States)

    Wang, Yi; Zhang, Y X; Kong, C Z; Zhang, Z; Zhu, Y Y

    2013-12-01

    Prostate cancer is a lethal cancer for the invasion and metastasis in its earlier period. P53 is a tumor suppressor gene which plays a critical role on safeguarding the integrity of genome. However, loss of P53 facilitates or inhibits the invasion and metastasis of tumor is still suspended. In this study, we are going to explain whether loss of P53 affect the invasion and metastasis of prostate cancer cells. To explore whether loss of P53 influences the invasion and metastasis ability of prostate cancer cells, we first compared the invasion ability of si-P53 treated cells and control cells by wound healing, transwell assay, and adhesion assay. We next tested the activity of MMP-2, MMP-9, and MMP-14 by western blot and gelatin zymography. Moreover, we employed WB and IF to identify the EMT containing E-cad, N-cad, vimentin, etc. We also examined the expression of cortactin, cytoskeleton, and paxillin by immunofluorescence, and tested the expression of ERK and JNK by WB. Finally, we applied WB to detect the expression of FAK, Src, and the phosphorylation of them to elucidate the mechanism of si-P53 influencing invasion and metastasis. According to the inhibition rate of si-P53, we choose the optimized volume of si-P53. With the volume, we compare the invasion and metastasis ability of Du145 and si-P53 treated cells. We find si-P53 promotes the invasion and metastasis in prostate cancer cells, increases the expression and activity of MMP-2/9 and MMP-14. Also, si-P53 promotes EMT and cytoskeleton rearrangement. Further analyses explain that this effect is associated with FAK-Src signaling pathway. Loss of P53 promotes the invasion and metastasis ability of prostate cancer cells and the mechanism is correlated with FAK-Src signaling pathway. P53 is involved in the context of invasion and metastasis. PMID:23982184

  3. Rectal cancer staging: Multidetector-row computed tomography diagnostic accuracy in assessment of mesorectal fascia invasion

    OpenAIRE

    Ippolito, Davide; Drago, Silvia Girolama; Franzesi, Cammillo Talei; Fior, Davide; Sironi, Sandro

    2016-01-01

    AIM: To assess the diagnostic accuracy of multidetector-row computed tomography (MDCT) as compared with conventional magnetic resonance imaging (MRI), in identifying mesorectal fascia (MRF) invasion in rectal cancer patients.

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

    International Nuclear Information System (INIS)

    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

  5. 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...

  6. 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.

  7. Inhibition of nuclear factor-kappa B differentially affects thyroid cancer cell growth, apoptosis, and invasion

    OpenAIRE

    Schweppe Rebecca E; Bauerle Kevin T; Haugen Bryan R

    2010-01-01

    Abstract Background Nuclear factor-κB (NF-κB) is constitutively activated in many cancers and plays a key role in promoting cell proliferation, survival, and invasion. Our understanding of NF-κB signaling in thyroid cancer, however, is limited. In this study, we have investigated the role of NF-κB signaling in thyroid cancer cell proliferation, invasion, and apoptosis using selective genetic inhibition of NF-κB in advanced thyroid cancer cell lines. Results Three pharmacologic inhibitors of N...

  8. 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.; Ramus, S.J.; Kjaer, S.K.; DiCioccio, R.A.; Wozniak, E.; Whittemore, A.S.; McGuire, V.; Ponder, B.A.; Turnbull, C.; Hines, S.; Rahman, N.; Eeles, R.A.; Easton, D.F.; Gayther, S.A.; Dunning, A.M.; Pharoah, P.D.; Høgdall, Estrid Vilma Solyom

    2008-01-01

    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...... cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor...

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

    OpenAIRE

    ZHENG, Rui; Qin, Xiaosong; Li, Wenjie; Kang, Jian

    2011-01-01

    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 i...

  10. Ionizing Radiation Promotes the Migratory and Invasive Potential of Lung Cancer Cells by Different Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Jin Nyoung; Kang, Ga Young; Um, Hong Duck [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-05-15

    Although radiation therapy is a major therapeutic modality for cancer treatment, previous reports have suggested that ionizing radiation (IR) can promote the invasive and metastatic potential of cancer cells. It was consistently reported that IR can induce certain types of matrix metalloproteinases, which are critical to the degradation of extracellular matrix. Given that the motility of cancer cells is an additional requirement for their metastasis, this study investigated whether IR can also influence the migratory potential of cancer cells.

  11. A Combination of Targeted Sunitinib Liposomes and Targeted Vinorelbine Liposomes for Treating Invasive Breast Cancer.

    Science.gov (United States)

    Shi, Ji-Feng; Sun, Meng-Ge; Li, Xiu-Ying; Zhao, Yao; Ju, Rui-Jun; Mu, Li-Min; Yan, Yan; Li, Xue-Tao; Zeng, Fan; Lu, Wan-Liang

    2015-09-01

    Regular chemotherapy cannot eradicate invasive breast cancer cells and the residual cancer cells will form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for cancer masses prior to angiogenesis. This phenomenon is a major reason for the recurrence of invasive breast cancer after treatment. In this study, a novel type of targeted liposomes was developed by modifying a mitochondria-tropic material, D-a-tocopheryl polyethylene glycol 1000 succinate- triphenylphosphine conjugate (TPGS1000-TPP), to encapsulate sunitinib and vinorelbine separately and a combination of the two targeted drug liposomes was used to treat invasive breast cancer as well as VM channels. Evaluations were performed in breast cancer MCF-7 cells and highly invasive breast cancer MDA-MB-435S cells in vitro and in mice. The results determined that the functional material (TPGS1000-TPP) and suitable size of the liposomes (90-100 nm) resulted in prolonged blood circulation, an enhanced permeability retention (EPR) effect in cancer tissue, and a mitochondrial targeting effect. Targeted drug liposomes were internalized via cellular uptake and accumulated in the mitochondria of invasive breast cancer cells or VM channel-forming cancer cells to induce acute cytotoxic injury and apoptosis. Activated apoptotic enzymes caspase 9 and caspase 3 as well as down-regulated VM channel-forming indicators (MMP-9, EphA2, VE-Cadherin, FAK and HIF-1α) contributed to significantly enhanced efficacy. Therefore, a combination of targeted sunitinib liposomes and targeted vinorelbine liposomes may provide an effective strategy for treating invasive breast cancer and prevent relapse arising from VM channels. PMID:26485927

  12. Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles

    Directory of Open Access Journals (Sweden)

    Chen Kun-Wan

    2011-10-01

    Full Text Available Abstract Background The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport. Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species before proliferating (invasive spread. Proliferation in the new site has an impact on the target organ microenvironment (ecological impact and eventually the human host (biosphere impact. Results Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells. Conclusions The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models.

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

    International Nuclear Information System (INIS)

    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.)

  14. Cancer-associated fibroblasts promote non-small cell lung cancer cell invasion by upregulation of glucose-regulated protein 78 (GRP78) expression in an integrated bionic microfluidic device.

    Science.gov (United States)

    Yu, Ting; Guo, Zhe; Fan, Hui; Song, Jing; Liu, Yuanbin; Gao, Zhancheng; Wang, Qi

    2016-05-01

    The tumor microenvironment is comprised of cancer cells and various stromal cells and their respective cellular components. Cancer-associated fibroblasts (CAFs), a major part of the stromal cells, are a key determinant in tumor progression, while glucose-regulated protein (GRP)78 is overexpressed in many human cancers and is involved in tumor invasion and metastasis. This study developed a microfluidic-based three dimension (3D) co-culture device to mimic an in vitro tumor microenvironment in order to investigate tumor cell invasion in real-time. This bionic chip provided significant information regarding the role of GRP78, which may be stimulated by CAFs, to promote non-small cell lung cancer cell invasion in vitro. The data showed that CAF induced migration of NSCLC A549 and SPCA-1 cells in this three-dimensional invasion microdevice, which is confirmed by using the traditional Transwell system. Furthermore, CAF induced GRP78 expression in A549 and SPCA-1 cells to facilitate NSCLC cell migration and invasion, whereas knockdown of GRP78 expression blocked A549 and SPCA-1 cell migration and invasion capacity. In conclusion, these data indicated that CAFs might promote NSCLC cell invasion by up-regulation of GRP78 expression and this bionic chip microdevice is a robust platform to assess the interaction of cancer and stromal cells in tumor environment study. PMID:27016417

  15. [Radical trachelectomy -- surgery for preserving woman's fertility in patients with invasive cervical cancer].

    Science.gov (United States)

    Kostov, I; Vasilev, N; Nacheva, A; Lazarov, I

    2013-01-01

    For the past 15 years gynecological oncologists have been seeking ways to preserve woman's fertility when treating invasive cervical cancer. Many cases of cervical cancer are diagnosed in young woman who wish to preserve their fertility. As more women are delaying childbearing, fertility preservation has become an important consideration. The standard surgical treatment for stage IA2-IB1 cervical cancer is a radical hysterectomy and bilateral pelvic lymphadenectomy. This surgery includes removal of the uterus and cervix, radical resection of the parametrial tissue and upper vagina, and complete pelvic lymphadenectomy. Obviously, the standard treatment does not allow future childbearing. For some women with small localized invasive cervical cancers, there is hope for pregnancy after treatment. Radical trachelectomy is a fertility-sparing surgical approach developed in France in 1994 by Dr. Daniel Dargent for the treatment of early invasive cervical cancer. The radical trachelectomy operation has been described and performed abdominally, assisted vaginally by laparoscopy and robotically. PMID:24505637

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

    International Nuclear Information System (INIS)

    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

  17. 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.

  18. Invasive Cervical Cancer and Antidepressants: A Nationwide Population-Based Study.

    Science.gov (United States)

    Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Liang, Hsin-Yi; Huang, Kuo-You; Chiu, Wei-Che; Lee, Yena; McIntyre, Roger S; Chen, Vincent Chin-Hung

    2015-10-01

    To our knowledge, no prior population-based study has been published wherein the primary aim was to evaluate whether an association between psychotropic drug prescription and cervical cancer exists. Herein we have conducted the first study that primarily aimed to determine the association between antidepressants use and risk of invasive cervical cancer in the general population.This is a population-based study utilizing Taiwan's National Health Insurance Research Database. We identified 26,262 cases with invasive cervical cancer and 129,490 controls. We adopted the conditional logistic regression model as the statistical method and adjusted for potential confounding factors.The prescription of selective serotonin reuptake inhibitors (SSRIs) (adjusted OR = 0.93, 95% CI = 0.84-1.04), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine and bupropion, adjusting for cumulative dose, was not associated with an increased, or decreased, risk for invasive cervical cancer. An association between trazodone prescription and invasive cervical cancer was observed (adjusted OR = 1.22, 95% CI = 1.03-1.43).An association between the major classes of antidepressants and invasive cervical cancer was not observed herein. Our preliminary finding regarding a possible association between trazodone and cervical cancer requires replication. PMID:26496343

  19. An Analytical Approach Differentiates Between Individual and Collective Cancer Invasion

    OpenAIRE

    Katz, Elad; Verleyen, Wim; Blackmore, Colin G.; Edward, Michael; Smith, V. Anne; David J. Harrison

    2011-01-01

    Tumour cells employ a variety of mechanisms to invade their environment and to form metastases. An important property is the ability of tumour cells to transition between individual cell invasive mode and collective mode. The switch from collective to individual cell invasion in the breast was shown recently to determine site of subsequent metastasis. Previous studies have suggested a range of invasion modes from single cells to large clusters. Here, we use a novel image analysis method to qu...

  20. Hypoxia and the Presence of Human Vascular Endothelial Cells Affect Prostate Cancer Cell Invasion and Metabolism

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-12-01

    Full Text Available Tumor progression and metastasis are influenced by hypoxia, as well as by interactions between cancer cells and components of the stroma, such as endothelial cells. Here, we have used a magnetic resonance (MRcompatible invasion assay to further understand the effects of hypoxia on human prostate cancer cell invasion and metabolism in the presence and absence of human umbilical vein endothelial cells (HUVECs. Additionally, we compared endogenous activities of selected proteases related to invasion in PC-3 cells and HUVECs, profiled gene expression of PC-3 cells by microarray, evaluated cell proliferation of PC-3 cells and HUVECs by flow cytometry, under hypoxic and oxygenated conditions. The invasion of less-invasive DU-145 cells was not affected by either hypoxia or the presence of HUVECs. However, hypoxia significantly decreased the invasion of PC-3 cells. This hypoxia-induced decrease was attenuated by the presence of HUVECs, whereas under oxygenated conditions, HUVECs did not alter the invasion of PC-3 cells. Cell metabolism changed distinctly with hypoxia and invasion. The endogenous activity of selected extracellular proteases, although altered by hypoxia, did not fully explain the hypoxia-induced changes in invasion. Gene expression profiling indicated that hypoxia affects multiple cellular functions and pathways.

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

    International Nuclear Information System (INIS)

    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

  2. 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

  3. Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

    Institute of Scientific and Technical Information of China (English)

    Lukui Yang; Long Li; Xiangyu Cui; Dalei Yang

    2015-01-01

    Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor (VEGF) and CD105-microvessel density (MVD) in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods Immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expres-sion. Positively stained microvessels were counted in dense vascular foci under 400× magnification. MVD in the peripheral area adjacent to the lesion and in the central area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue (22.0%, P 0.05). MVD of the peripheral area adja-cent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benign breast disease groups (P 50 years) or the two tumor diameter groups (≤2 cm vs.>2 cm), P > 0.05. Conclusion Overexpression of VEGF and MVD may be important biological markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor mark-ers could provide better prognostic monitoring for disease recurrence and metastasis, as wel as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as wel as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better fol ow-up regimens and appro-priate treatment strategies for breast cancer patients.

  4. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Lamm, D.; Brausi, M.; O'Donnell, M.A.; Witjes, J.A.

    2014-01-01

    OBJECTIVES: In this article, we review the various options for and the potential role of interferon alfa (IFN-alpha) in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: PubMed was searched for journal articles on IFN-alpha use in treating bladder cancer. The references listed in

  5. Single Nucleotide Polymorphisms in the TP53 Region and Susceptibility to Invasive Epithelial Ovarian Cancer

    OpenAIRE

    Schildkraut, J M; Goode, E.L.; Clyde, M. A.; Iversen, E. S.; Moorman, P. G.; Berchuck, A.; Marks, J R; Lissowska, J; Brinton, L.; Peplonska, B.; Cunningham, J. M.; Vierkant, R A; Rider, D. N.; Chenevix-Trench, G; Webb, P M

    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 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independ...

  6. Novel Suppressive Effects of Ketotifen on Migration and Invasion of MDA-MB-231 and HT-1080 Cancer Cells

    OpenAIRE

    Kim, Hyun Ji; Park, Mi Kyung; Kim, Soo Youl; Lee, Chang Hoon

    2014-01-01

    The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additi...

  7. IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines

    OpenAIRE

    ZHU, XINGWU; Mulcahy, Lori A; Mohammed, Rabab AA; Lee, Andrew HS; Franks, Hester A; Kilpatrick, Laura; Yilmazer, Acelya; Paish, E. Claire; Ellis, Ian O; Patel, Poulam M; Jackson, Andrew M

    2008-01-01

    Introduction IL-17 plays an important role in autoimmunity, promoting autoimmunity, inflammation and invasion in multiple sclerosis, rheumatoid arthritis and type I diabetes. The role of IL-17 in cancer is unclear, however, as there are few studies examining IL-17 protein expression in cancer. We therefore examined IL-17 protein expression in human breast cancer and modelled its potential biological significance in vitro. Methods Immunohistochemistry was used to determine IL-17 expression in ...

  8. Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration, Invasion, and In Vivo Invasive Growth Through Targeting C-Met.

    Science.gov (United States)

    Ebrahim, Hassan Y; Elsayed, Heba E; Mohyeldin, Mohamed M; Akl, Mohamed R; Bhattacharjee, Joydeep; Egbert, Susan; El Sayed, Khalid A

    2016-04-01

    Breast cancer is a major health problem affecting the female population worldwide. The triple-negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto-oncogenic receptor tyrosine kinase c-Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c-Met is proposed as a promising candidate target for the control of TNBCs. Lichens-derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen-derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer-guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone-derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA-MB-231 cell proliferation, migration, and invasion, with minimal toxicity to non-tumorigenic MCF-10A mammary epithelial cells. Molecular modeling, Z'-LYTE biochemical kinase assay and Western blot analysis identified c-Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA-MB-231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen-derived natural products are promising resources to discover novel c-Met inhibitors useful to control TNBCs. PMID:26744260

  9. CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway.

    Science.gov (United States)

    Lin, Fu; Chengyao, Xie; Qingchang, Li; Qianze, Dong; Enhua, Wang; Yan, Wang

    2015-06-01

    CRKL is recently defined as a new oncogene, which plays a role in the lung cancer progression. However, the potential mechanism of CRKL in human non-small cell lung cancer cell invasion is obscure. We investigated the potential mechanism of CRKL in lung cancer cell invasion using immunohistochemistry, plasmid transfection, Western blotting, real-time PCR, matrigel invasion assay, chromatin immunoprecipitation assay, and luciferase reporter assay. CRKL expression is higher in lymph node metastatic tumor compared with primary tumor. CRKL overexpression enhanced cell invasion and MMP9 expression in both HBE and H1299 cell lines. There was a significant correlation between CRKL overexpression and high MMP9 expression in primary tumors. MMP-9 antibody treatment significantly blocked cell invasion. CRKL overexpression also activated AP-1 luciferase reporter activity, ERK phosphorylation and association of c-fos to MMP9 promoter. Treatment with ERK inhibitor PD98059 in cells with CRKL transfection inhibited ERK activity, cell invasion, and MMP9 expression. These results suggested that overexpression of CRKL promoted cell invasion through upregulation of MMP9 expression and activation of ERK pathway. PMID:24664993

  10. Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells

    International Nuclear Information System (INIS)

    Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells. Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA. We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment. We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade

  11. Detection and minimally invasive treatment of early squamous lung cancer

    OpenAIRE

    DANIELS, JOHANNES M.A.; Sutedja, Thomas G.

    2013-01-01

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer deaths worldwide. The majority of patents presenting with NSCLC have advanced disease, which precludes curative treatment. Early detection and treatment might result in the identification of more patients with early central lung cancer and improve survival. In addition, the study of early lung cancer improves understanding of lung carcinogenesis and might also reveal new treatment targets for advanced lung cancer. Bronchosc...

  12. Differentiating pre- and minimally invasive from invasive adenocarcinoma using CT-features in persistent pulmonary part-solid nodules in Caucasian patients

    International Nuclear Information System (INIS)

    Highlights: •We analyzed CT-features of part-solid ground glass nodules in Caucasians. •These CT-features were compared to pathology on full resection specimen. •Several CT-features can help differentiating invasive adenocarcinoma. •A solid component larger than 5 mm had 100% sensitivity for invasive adenocarcinoma. -- Abstract: Objective: To retrospectively investigate the diagnostic value of pre-operative CT-features between pre/minimally invasive and invasive lesions in part-solid persistent pulmonary ground glass nodules in a Caucasian population. Materials and methods: Retrospective review of two pre-operative CTs for 31 nodules in 30 patients. There were 10 adenocarcinomas in situ, 1 minimally invasive adenocarcinoma, 20 invasive adenocarcinomas. We analyzed the correlation between histopathology and the following CT-features: maximal axial diameter, maximal orthogonal axial diameter, height, density, size of solid component, air bronchogram, pleural retraction, nodule mass, disappearance rate and their evolution during follow-up. Results: In univariate analysis, invasive adenocarcinomas had a higher maximal height, density, solid component size, mass, a lower disappearance rate and presented more often with pleural retraction (p < 0.05). After logistic regression performed with the uncorrelated parameters using a method of selection of variables, only the size of solid component remained significant, with 100% sensitivity for invasive adenocarcinoma when larger than 5 mm. Conclusion: Preoperative CT-features can help differentiating in situ and minimally invasive adenocarcinomas from invasive adenocarcinomas in Caucasian patients. A solid component larger than 5 mm in diameter had 100% sensitivity for the diagnosis of invasive adenocarcinoma

  13. Differentiating pre- and minimally invasive from invasive adenocarcinoma using CT-features in persistent pulmonary part-solid nodules in Caucasian patients

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Julien G., E-mail: JCohen@chu-grenoble.fr [Clinique Universitaire de Radiologie et Imagerie Médicale (CURIM), Université Joseph Fourier, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043 Grenoble Cedex 9 (France); Reymond, Emilie [Clinique Universitaire de Radiologie et Imagerie Médicale (CURIM), Université Joseph Fourier, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043 Grenoble Cedex 9 (France); Lederlin, Mathieu [Service de Radiologie, Université Segalen Bordeaux, Centre Hospitalier Universitaire de Bordeaux, 12 rue Dubernat, 33404 Bordeaux Cedex (France); Medici, Maud [Centre d’Investigation Clinique – Innovation Technologique (CIC-IT), Pavillon Taillefer, 38706 La Tronche Cedex (France); Lantuejoul, Sylvie [Departement d’Anatomie et Cytologie Pathologique (DACP), Université Joseph Fourier, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043 Grenoble Cedex 9 (France); Laurent, François [Service de Radiologie, Université Segalen Bordeaux, Centre Hospitalier Universitaire de Bordeaux, 12 rue Dubernat, 33404 Bordeaux Cedex (France); Arbib, François [Departement de Pneumologie, Université Joseph Fourier, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043 Grenoble Cedex 9 (France); Jankowski, Adrien [Clinique Universitaire de Radiologie et Imagerie Médicale (CURIM), Université Joseph Fourier, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043 Grenoble Cedex 9 (France); and others

    2015-04-15

    Highlights: •We analyzed CT-features of part-solid ground glass nodules in Caucasians. •These CT-features were compared to pathology on full resection specimen. •Several CT-features can help differentiating invasive adenocarcinoma. •A solid component larger than 5 mm had 100% sensitivity for invasive adenocarcinoma. -- Abstract: Objective: To retrospectively investigate the diagnostic value of pre-operative CT-features between pre/minimally invasive and invasive lesions in part-solid persistent pulmonary ground glass nodules in a Caucasian population. Materials and methods: Retrospective review of two pre-operative CTs for 31 nodules in 30 patients. There were 10 adenocarcinomas in situ, 1 minimally invasive adenocarcinoma, 20 invasive adenocarcinomas. We analyzed the correlation between histopathology and the following CT-features: maximal axial diameter, maximal orthogonal axial diameter, height, density, size of solid component, air bronchogram, pleural retraction, nodule mass, disappearance rate and their evolution during follow-up. Results: In univariate analysis, invasive adenocarcinomas had a higher maximal height, density, solid component size, mass, a lower disappearance rate and presented more often with pleural retraction (p < 0.05). After logistic regression performed with the uncorrelated parameters using a method of selection of variables, only the size of solid component remained significant, with 100% sensitivity for invasive adenocarcinoma when larger than 5 mm. Conclusion: Preoperative CT-features can help differentiating in situ and minimally invasive adenocarcinomas from invasive adenocarcinomas in Caucasian patients. A solid component larger than 5 mm in diameter had 100% sensitivity for the diagnosis of invasive adenocarcinoma.

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

    International Nuclear Information System (INIS)

    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

  15. 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.

  16. CO-029 is overexpressed in gastric cancer and mediates the effects of EGF on gastric cancer cell proliferation and invasion.

    Science.gov (United States)

    Zhu, Hongyu; Wu, Yulian; Zheng, Wen; Lu, Shiliu

    2015-03-01

    Tetraspanins are cell-surface glycoproteins and have received attention recently as both suppressors and promoters of metastasis. CO-029 is a member of the tetraspanin family and is implicated to be a metastasis-promoting tetraspanin in some cancers. However, the role of CO-029 in gastric cancer remains unexplored. The present study aimed to investigate the expression of CO-029 in gastric cancer tissues and to determine whether CO-029 is involved in the effects of epidermal growth factor (EGF) on gastric cancer cell proliferation and invasion. We collected clinical samples and found that the expression of CO-029 was increased both at the mRNA level and protein level in gastric cancer tissues in comparison to normal and tumor-adjacent tissues, as demonstrated by RT-qPCR and western blot analysis, respectively. Furthermore, we performed an in vitro experiment using AGS cells and observed that EGF promoted AGS cell proliferation and enhanced the invasion ability of the AGS cells, as shown by MTT assay and cell invasion assay, respectively. To the best of our knowledge, our results reveal for the first time, that CO-029 expression was affected by EGF in a concentration- time-dependent manner. The knockdown of CO-029 attenuated the effects of EGF on gastric cancer cell proliferation and invasion. These findings suggest that CO-029 is an oncogene in human gastric cancer and that CO-029 at least partially mediates the effects of EGF on gastric cancer cell proliferation and invasion. Our data may provide a novel target for therapeutic intervention in human gastric cancer. PMID:25592989

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

    International Nuclear Information System (INIS)

    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

  18. 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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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. The Features of Naturalization of Invasive Fraction of Flora in the Voronezh Region and in Some Regions of the European Part of Russia

    OpenAIRE

    Vladimirov D.R.; Grigoryevskaya A.Ya.

    2015-01-01

    The article is about naturalization features of invasive fraction of flora in Voronezh and some other regions of the European part of Russia. The summary table represents all invasive and potentially invasive plants of the European part of Russia with their level of naturalization (or invasive status). Invasive fraction of flora in the Voronezh region numbers 120 plants. All of them are on different stages of naturalization process in an anthropogenic areal. Invasive plants represent by agrio...

  2. MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition

    OpenAIRE

    Roy, Lopamudra Das; Sahraei, Mahnaz; Subramani, Durai B.; Besmer, Dahlia; Nath, Sritama; Tinder, Teresa L; Bajaj, Ekta; Shanmugam, Kandavel; Lee, Yong Yook; Hwang, Sun IL; Gendler, Sandra J.; Mukherjee, Pinku

    2010-01-01

    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 adenocarcinomas (P...

  3. 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.

  4. Does preoperative radiation for thoracic esophageal cancer promote intramural lymphatic invasion ?

    International Nuclear Information System (INIS)

    Between 1976 and 1983, 43 patients with carcinoma of the thoracic esophagus underwent esophagectomy in the Department of Surgery, Tottori University. Of these 43, 22 received a total dose of 30 to 40 Gy of Co60 (2 Gy/day) preoperatively: 21 were not given preoperative irradiation treatments. The spread of intramural lymphatic cancer invasion into the esophageal wall was compared in these two groups. The preoperatively irradiated patients manifested a significantly lower rate of lymphatic cancer invasion and the depth of invasion tended to be less than in the non-irradiated patients. However, in preoperatively irradiated subjects, the horizontal cancer spread into the extra-radiation field anal to the cancer site was greater than in the other group. In addition, a significantly higher intra-abdominal lymph node metastasis rate was found in the irradiated group than in the non-irradiated group. Our findings suggest that patients with thoracic esophageal cancer who are treated with preoperative radiotherapy must be carefully monitored for the occurrence of intramural lymphatic cancer invasion and distant lymph node metastasis. (author)

  5. 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.

  6. 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 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 single nucleotide polymorphisms (SNP) in.......07-1.57) and rs12951053 (median per allele OR, 1.19; 95% PI, 1.01-1.38). Analyses of other histologic subtypes suggested similar associations with endometrioid but not with mucinous or clear cell cancers. This large study provides statistical evidence for a small increase in risk of ovarian cancer associated...

  7. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    Science.gov (United States)

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  8. Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Nisa, Lluís, E-mail: lluis.nisa@dkf.unibe.ch [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, MEM-E807, Murtenstrasse 35, Bern 3010 (Switzerland); Department of Otorhinolaryngology-Head and Neck Surgery, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Aebersold, Daniel Matthias [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, MEM-E807, Murtenstrasse 35, Bern 3010 (Switzerland); Giger, Roland; Caversaccio, Marco Domenico; Borner, Urs [Department of Otorhinolaryngology-Head and Neck Surgery, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Medová, Michaela; Zimmer, Yitzhak, E-mail: lluis.nisa@dkf.unibe.ch [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, MEM-E807, Murtenstrasse 35, Bern 3010 (Switzerland)

    2015-03-31

    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.

  9. Why Do Parents Prefer to Know the Fetal Sex as Part of Invasive Prenatal Testing?

    OpenAIRE

    Kooper, Angelique J.A.; Pieters, Jacqueline J. P. M.; Eggink, Alex J.; Ton B. Feuth; Ilse Feenstra; Wijnberger, Lia D. E.; Rijnders, Robbert J. P.; Quartero, Rik W. P.; Boekkooi, Peter F.; van Vugt, John M. G.; Smits, Arie P.T.

    2012-01-01

    Objectives. The aim of this study was to determine whether prospective parents, primarily referred for prenatal diagnosis to exclude Down syndrome, prefer to know the fetal sex as part of invasive testing. Methods. In this prospective study 400 pregnant women undergoing amniocentesis were invited to answer a questionnaire, including information about demographic factors, current pregnancy, and previous children. In two open-ended questions they were asked why they wanted to know the fetal sex...

  10. Upregulation of HYAL1 expression in breast cancer promoted tumor cell proliferation, migration, invasion and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Jin-Xiang Tan

    Full Text Available Hyaluronic acid (HA is a component of the Extra-cellular matrix (ECM, it is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronidase (HAase is a HA-degrading endoglycosidase, levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1 is the major tumor-derived HAase. We previously demonstrated that HYAL1 were overexpression in human breast cancer. Breast cancer cells with higher HAase expression, exhibited significantly higher invasion ability through matrigel than those cells with lower HAase expression, and knockdown of HYAL1 expression in breast cancer cells resulted in decreased cell growth, adhesion, invasion and angiogenesis. Here, to further elucidate the function of HYAL1 in breast cancer, we investigated the consequences of forcing HYAL1 expression in breast cancer cells by transfection of expression plasmid. Compared with control, HYAL1 up-regulated cells showed increased the HAase activity, and reduced the expression of HA in vitro. Meantime, upregulation of HYAL1 promoted the cell growth, migration, invasion and angiogenesis in vitro. Moreover, in nude mice model, forcing HYAL1 expression induced breast cancer cell xenograft tumor growth and angiogenesis. Interestingly, the HA expression was upregulated by forcing HYAL1 expression in vivo. These findings suggested that HYAL1-HA system is correlated with the malignant behavior of breast cancer.

  11. CXCL12/CXCR4 axis induces proliferation and invasion in human endometrial cancer

    Science.gov (United States)

    Liu, Pingping; Long, Ping; Huang, Yu; Sun, Fengyi; Wang, Zhenyan

    2016-01-01

    Objective: Since that we have previously found CXCL12/CXCR4, an important biological axis is highly transcribed in several cancer cells. We aim to investigate whether CXCL12/CXCR4 axis regulates critical processes in neoplastic transformation that affects endometrial cancer cell biology. Methods: The expression levels of CXCR4 were analyzed in human normal endometrial tissue, simple hyperplasia, atypical hyperplasia and endometrial cancer cells by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Serum CXCL12 was measured by Enzyme-Linked Immunosorbent Assay (ELISA) in Ishikawa endometrial cancer cell line. To study the biological function of CXCL12/CXCR4 in endometrial cancer, short interfering RNA silencing of CXCR4 was established to analyze the roles of CXCL12/CXCR4 in proliferation, migration, invasion and apoptosis of Ishikawa cells in vitro. Results: The expression level of CXCR4 in endometrial cancer tissue was higher as compared to atypical hyperplasia, simple hyperplasia and normal cycling endometrium cells. Ishikawa cells secreted CXCL12 spontaneously and continuously for 96 hrs in culture. The proliferation, migration and invasion of Ishikawa cells was significantly induced, and the apoptosis was significantly reduced by CXCL12 in combination with CXCR4. Moreover, CXCR4 silencing could significantly antagonize all these functions. Conclusions: CXCL12/CXCR4 axis plays an important role in the proliferation, invasion and metastasis of endometrial cancer, indicating that CXCR4 could be the target for the treatment of endometrial cancer. PMID:27186295

  12. Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate cancer cells.

    Science.gov (United States)

    Chen, Zhi-Yuan; Chen, Hui; Qiu, Tao; Weng, Xiao-Dong; Guo, Jia; Wang, Lei; Liu, Xiu-Heng

    2016-09-01

    Prostate cancer poses a major public health problem in men. Metastatic prostate cancer is incurable, and ultimately threatens the life of patients. Lysine‑specific demethylase 1 (LSD1) is an androgen receptor‑interacting protein that exerts a key role in regulating gene expression and is involved in numerous biological processes associated with prostate cancer. Cisplatin, also known as cis‑diamminedichloroplatinum or DDP, is a standard chemotherapeutic agent used to treat prostate cancer; however, it has the disadvantage of various serious side effects. The present study aimed to investigate the effects of LSD1 knockdown, and the interplay between LSD1 and DDP, on prostate cancer cell proliferation, apoptosis and invasion, and, therefore, the potential of LSD1 as a target for prostate cancer therapy. Flow cytometric analysis, Cell Counting kit 8 assay, Transwell assay and western blotting results revealed that LSD1 knockdown, in combination with DDP treatment, exerted antiproliferative, proapoptotic and anti‑invasive effects on PC3 prostate cancer cells. In addition, knockdown of LSD1 acted synergistically with DDP, thereby enhancing the induction of apoptosis, and the inhibition of proliferation and invasion in prostate cancer cells. These results indicated that LSD1 may serve as a potential therapeutic target, and may enhance the sensitivity of PC3 cells to DDP. PMID:27484796

  13. In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model.

    Science.gov (United States)

    Na'ara, Shorook; Gil, Ziv; Amit, Moran

    2016-01-01

    One way that solid tumors disseminate is through neural invasion. This route is well-known in cancers of the head and neck, prostate, and pancreas. These neurotropic cancer cells have a unique ability to migrate unidirectionally along nerves towards the central nervous system (CNS). The dorsal root ganglia (DRG)/cancer cell model is a three dimensional (3D) in vitro model frequently used for studying the interaction between neural stroma and cancer cells. In this model, mouse or human cancer cell lines are grown in ECM adjacent to preparations of freshly dissociated cultured DRG. In this article, the DRG isolation protocol from mice, and implantation in petri dishes for co-culturing with pancreatic cancer cells are demonstrated. Five days after implantation, the cancer cells made contact with the DRG neurites. Later, these cells formed bridgeheads to facilitate more extensive polarized, neurotropic migration of cancer cells. PMID:27167037

  14. Assessment of vascular invasion in pancreatic head cancer with multislice spiral CT: value of multiplanar reconstructions

    Energy Technology Data Exchange (ETDEWEB)

    Bruegel, Melanie; Link, Thomas M.; Rummeny, Ernst J.; Lange, Peter; Dobritz, Martin [Department of Radiology, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675, Munich (Germany); Theisen, Joerg [Department of Surgery, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675, Munich (Germany)

    2004-07-01

    The use of multiplanar reconstructions (MPRs) generated from multislice spiral CT (MSCT) data sets in the preoperative assessment of vascular invasion in pancreatic cancer was evaluated. Forty patients underwent biphasic high-resolution MSCT prior to surgery for pancreatic head cancer. Image reconstruction included thin-slice axial, sagittal and coronal MPRs as well as an MPR perpendicular to the course of a major peripancreatic vessel in proximity to the tumor. CT criteria for vascular invasion were: (1) circumferential involvement >180 and (2) vessel narrowing. Imaging findings of 52 vessels were correlated with surgical and histopathological reports. Regarding the CT criterion circumferential involvement, vascular invasion was demonstrated on axial MPRs with a sensitivity and specificity of 58 and 97%. For the assessment with coronal and sagittal MPRs sensitivity was only 47%. Vascular invasion was recognized best on perpendicular MPRs with a sensitivity, specificity and accuracy of 74, 97 and 88%, respectively. Vessel narrowing was a less reliable CT criterion for vascular invasion, mainly due to the lower specificity of 91% obtained with each available MPR. Thin-slice MPRs oriented perpendicularly to a possibly invaded vessel exactly depict the grade of circumferential involvement and thus have the capability to improve the assessment of vascular invasion in pancreatic cancer. (orig.)

  15. Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling.

    Science.gov (United States)

    Bao, Cheng; Kim, Min Chae; Chen, Jing; Song, Jieun; Ko, Hyuk Wan; Lee, Hong Jin

    2016-07-13

    Although inhibition of mammary tumorigenesis by isothiocyanates has been widely studied, little is known about the effects of sulforaphene on invasiveness of breast cancer. Here, sulforaphene significantly inhibited the migration and invasion of triple-negative SUM159 human breast cancer cells and suppressed the expression and activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). The Hedgehog (Hh) pathway, as an upstream signaling modulator, was significantly suppressed by sulforaphene. In particular, ciliary localization of Gli1 and its nuclear translocation were blocked by sulforaphene in a time-dependent manner. Consistently, downregulation of Hh signaling by vismodegib and Gli1 knockdown reduced the cellular migration and invasion as well as the expression of MMP-2 and MMP-9. These results indicate that the suppression of Hh/Gli1 signaling by sulforaphene may reduce the MMP-2 and MMP-9 activities and cellular invasiveness of human breast cancer cells, suggesting the potential efficacy of sulforaphene against breast cancer invasion and metastasis. PMID:27327035

  16. CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion.

    Science.gov (United States)

    Sasaki, Yasushi; Koyama, Ryota; Maruyama, Reo; Hirano, Takehiro; Tamura, Miyuki; Sugisaka, Jun; Suzuki, Hiromu; Idogawa, Masashi; Shinomura, Yasuhisa; Tokino, Takashi

    2012-12-01

    The tumor suppressor p53 transcriptionally regulates a number of genes that are involved in cell-cycle inhibition, apoptosis and the maintenance of genetic stability. Recent studies suggest that p53 also contributes to the regulation of cell migration and invasion. Here, we show that human chloride channel accessory-2 (CLCA2) is a target gene of the p53 family (p53, p73 and p63). CLCA2 is induced by DNA damage in a p53-dependent manner. The p53 family proteins activate the CLCA2 promoter by binding directly to the conserved consensus p53-binding site present in the CLCA2 promoter. In terms of function, ectopic expression of CLCA2 inhibited cancer cell migration. In contrast, silencing CLCA2 with siRNA stimulated cancer cell migration and invasion. We also found that inactivation of CLCA2 enhanced the expression of focal adhesion kinase (FAK), as well as its promoter activation. A small-molecule FAK inhibitor reduced the effect of CLCA2 siRNA on cell migration and invasion, suggesting that CLCA2 inhibits cancer cell migration and invasion through suppression of the FAK signaling pathway. Furthermore, there was an inverse correlation between CLCA2 and FAK expression in 251 human breast cancer tissues. These results strongly suggest that CLCA2 is involved in the p53 tumor suppressor network and has a significant effect on cell migration and invasion. PMID:22990203

  17. LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth and invasion

    OpenAIRE

    Li, Yirong; Wang, Longgui; Zhang, Miao; Melamed, Jonathan; Liu, Xiaomei; Reiter, Robert; Wei, Jianjun; Peng, Yi; Zou, Xuanyi; Pellicer, Angel; Garabedian, Michael J.; Ferrari, Anna; Lee, Peng

    2009-01-01

    A major obstacle in treating prostate cancer is the development of androgen-independent disease. In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate cancer growth and invasion in androgen-independent prostate cancer cells. Affymetrix microarray analysis of LNCaP and LNCaP-AI (androgen-independent variant LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells. We showed that LE...

  18. The impact of postmastectomy radiotherapy on local control in patients with invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Purpose: The aim of this population-based study was to examine the impact of postmastectomy radiotherapy on the risk of local recurrence in patients with invasive lobular breast cancer (ILC). Methods: The population-based Eindhoven Cancer Registry was used to select all patients with ILC, who underwent mastectomy in five general hospitals in the southern part of Netherlands between 1995 and 2002. Of the 499 patients 383 patients fulfilled the eligibility criteria. Of these patients, 170 (44.4%) had received postmastectomy radiotherapy. The median follow-up was 7.2 years. Fourteen patients (3.7%) were lost to follow-up. Results: During follow-up 22 patients developed a local recurrence, of whom 4 had received postmastectomy radiotherapy. The 5-year actuarial risk of local recurrence was 2.1% for the patients with and 8.7% for the patients without postmastectomy radiotherapy. After adjustment for age at diagnosis, tumour stage and adjuvant systemic treatment, the patients who underwent postmastectomy radiotherapy were found to have a more than 3 times lower risk of local recurrence compared to the patients without (Hazard Ratio 0.30; 95% Confidence Interval: 0.10-0.89). Conclusion: Local control is excellent for patients with ILC who undergo postmastectomy radiotherapy and significantly better than for patients not receiving radiotherapy.

  19. Buried penis: An unrecognized risk factor in the development of invasive penile cancer

    OpenAIRE

    Abdulla, Alym; Daya, Dean; Pinthus, Jehonathan; Davies, Timothy

    2012-01-01

    One of the documented benefits of neonatal circumcision is protection against invasive penile cancer. To date there have been a handful of published cases of invasive penile cancer in men circumcised as neonates. We report a case of a 73-year-old man, with a history of neonatal circumcision with no evidence of previous human papillomavirus exposure, who developed a buried penis secondary to obesity. He was diagnosed with Grade 2, pT3N0 squamous cell carcinoma of the penis. This report suggest...

  20. Incidence of invasive cancers following carcinoma in situ of the cervix.

    OpenAIRE

    Levi, F; Randimbison, L.; La Vecchia, C; Franceschi, S.

    1996-01-01

    Women with carcinoma in situ (CIS) of the cervix uteri, notified to the population-based Cancer Registry of the Swiss Canton of Vaud between 1974 and 1993, were actively followed up to 31 December 1993 for the occurrence of subsequent invasive neoplasms. Among 2190 incident cases of CIS, followed for a total of 22,225 person-years, 95 metachronous cancers were observed vs 77.9 expected, corresponding to a significant standardised incidence ratio (SIR) of 1.2. Ten cases of invasive cervical ca...

  1. PEG10 promotes human breast cancer cell proliferation, migration and invasion.

    Science.gov (United States)

    Li, Xinran; Xiao, Ruijing; Tembo, Kingsley; Hao, Ling; Xiong, Meng; Pan, Shan; Yang, Xiangyong; Yuan, Wen; Xiong, Jie; Zhang, Qiuping

    2016-05-01

    Paternally expressed imprinted gene 10 (PEG10), derived from the Ty3/Gypsy family of retrotransposons, has been implicated as a genetic imprinted gene. Accumulating evidence suggests that PEG10 plays an important role in tumor growth in various cancers, including hepatocellular carcinoma, lung cancer and prostate cancer. However, the correlation between PEG10 and breast cancer remains unclear. In the present study, we evaluated and characterized the role of PEG10 in human breast cancer proliferation, cell cycle, clone formation, migration and invasion. The expression level of PEG10 was significantly elevated in breast cancer tissues and associated with distant metastasis and poor clinical outcome. Gene set enrichment analysis indicated that high expression of PEG10 could enrich cell cycle-related processes in breast cancer tissues. Ectopic overexpression of PEG10 in breast cancer cells enhanced cell proliferation, cell cycle, clone formation along with migration and invasion. Cell-to-cell junction molecule E-cadherin was downregulated and matrix degradation proteases MMP-1, MMP-2, MMP-9 were up-regulated after PEG10 overexpression. Our results demonstrated that PEG10 is a crucial oncogene and has prognostic value for breast cancer, which could be applied in breast cancer diagnosis and targeting therapy in future. PMID:26934961

  2. Esophagectomy - minimally invasive

    Science.gov (United States)

    Minimally invasive esophagectomy; Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the ...

  3. Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

    Science.gov (United States)

    2016-02-09

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  4. Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Feng, Jianguo; Zhang, Shirong; Wu, Kan; Wang, Bing; Wong, Jeffrey Y C; Jiang, Hong; Xu, Rujun; Ying, Lisha; Huang, Haixiu; Zheng, Xiaoliang; Chen, Xufeng; Ma, Shenglin

    2016-05-01

    Lung cancer is a leading cause of cancer-related mortality worldwide, and concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of the chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs, and determined the combination effects of SAHA and cisplatin on human non-small cell lung cancer (NSCLC) cells in response to treatment of ionizing radiation (IR), and on tumor growth of lung cancer H460 xenografts receiving radiotherapy. We also investigated the potential differentiation effect of SAHA and its consequences on cancer cell invasion. Our results showed that SAHA and cisplatin compromise distinct DNA damage repair pathways, and treatment with SAHA enhanced synergistic radiosensitization effects of cisplatin in established NSCLC cell lines in a p53-independent manner, and decreased the DNA damage repair capability in cisplatin-treated primary NSCLC tumor tissues in response to IR. SAHA combined with cisplatin also significantly increased inhibitory effect of radiotherapy on tumor growth in the mouse xenograft model. In addition, SAHA can induce differentiation in stem cell-like cancer cell population, reduce tumorigenicity, and decrease invasiveness of human lung cancer cells. In conclusion, our data suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of a chemoradiotherapy regimen for NSCLC. Mol Cancer Ther; 15(5); 842-53. ©2016 AACR. PMID:26839308

  5. DDRs: receptors that mediate adhesion, migration and invasion in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Emmanuel Reyes-Uribe

    2015-08-01

    Full Text Available Discoidin domain receptors (DDRs are receptor tyrosine kinases that are activated by native collagens and have an important role during cell adhesion, development, differentiation, proliferation, and migration. DDR deregulation is associated with progression of several different cancers. However, there is limited information about the role of DDRs in the progression of breast cancer. In this review we attempt to collect the most relevant information about DDR signaling and their role in various cancer-related processes such as adhesion, epithelial to mesenchymal transition, migration, invasion, and survival, with a focus on breast cancer.

  6. Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells.

    Science.gov (United States)

    Rivera, Io-Guané; Ordoñez, Marta; Presa, Natalia; Gangoiti, Patricia; Gomez-Larrauri, Ana; Trueba, Miguel; Fox, Todd; Kester, Mark; Gomez-Muñoz, Antonio

    2016-02-15

    Pancreatic cancer is an aggressive and devastating disease characterized by invasiveness, rapid progression and profound resistance to treatment. Despite years of intense investigation, the prognosis of this type of cancer is poor and there is no efficacious treatment to overcome the disease. Using human PANC-1 and MIA PaCa-2 cells, we demonstrate that the bioactive sphingolipid ceramide 1-phosphate (C1P) increases pancreatic cancer cell migration and invasion. Treatment of these cells with selective inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt1, or mammalian target of rapamycin 1 (mTOR1), or with specific siRNAs to silence the genes encoding these kinases, resulted in potent inhibition of C1P-induced cell migration and invasion. Likewise, the extracellularly regulated kinases 1 and 2 (ERK1-2), and the small GTPase RhoA, which regulates cytoskeleton reorganization, were also found to be implicated in C1P-stimulated ROCK1-dependent cancer cell migration and invasion. In addition, pre-treatment of the cancer cells with pertussis toxin abrogated C1P-induced cell migration, suggesting the intervention of a Gi protein-coupled receptor in this process. Pancreatic cancer cells engineered to overexpress ceramide kinase (CerK), the enzyme responsible for C1P biosynthesis in mammalian cells, showed enhanced spontaneous cell migration that was potently blocked by treatment with the selective CerK inhibitor NVP-231, or by treatment with specific CerK siRNA. Moreover, overexpression of CerK with concomitant elevations in C1P enhanced migration of pancreatic cancer cells. Collectively, these data demonstrate that C1P is a key regulator of pancreatic cancer cell motility, and suggest that targeting CerK expression/activity and C1P may be relevant factors for controlling pancreatic cancer cell dissemination. PMID:26707801

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

    International Nuclear Information System (INIS)

    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.

  8. Tetrandrine suppresses proliferation, induces apoptosis, and inhibits migration and invasion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Wei Liu

    2015-01-01

    Full Text Available Tetrandrine (TET, a traditional Chinese medicine, exerts remarkable anticancer activity on various cancer cells. However, little is known about the effect of TET on human prostate cancer cells, and the mechanism of function of TET on prostate cancer has not yet been elucidated. To investigate the effects of TET on the suppression of proliferation, induction of apoptosis, and inhibition of migration and invasion in human prostate cancer cell lines, DU145 and PC-3. Inhibition of growth was determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and clone formation assay, and flow cytometry analysis was performed to detect the induction of apoptosis. Activation of poly (ADP-ribose polymerase, caspase-3, Akt, phospho-Akt, Bcl-2, and Bax was analyzed by Western blotting. Wound healing assay and transwell migration assay were used to evaluate the effect of TET on migration and invasion of cancer cells. TET inhibited the growth of DU145 and PC-3 cells in a dose- and time-dependent manner. Cell cloning was inhibited in the presence of TET in DU145 and PC-3 cells. TET suppressed the migration of DU145 and PC-3 cells. Transwell invasion assay showed that TET significantly weakened invasion capacity of DU145 and PC-3 cells. TET exhibited strong inhibitory effect on proliferation, migration, and invasion of prostate cancer cells. In addition, TET induced apoptosis in a dose-dependent manner by activating the caspase cascade and inhibiting phosphoinositide 3-kinase-Akt signal pathway. The accumulating evidence suggests that TET could be a potential therapeutic candidate against prostate cancer in a clinical setting.

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

    International Nuclear Information System (INIS)

    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

  10. 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.

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

    International Nuclear Information System (INIS)

    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

  12. PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation, Migration and Invasion.

    Directory of Open Access Journals (Sweden)

    Lei Yang

    Full Text Available PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer.

  13. miR-708/LSD1 axis regulates the proliferation and invasion of breast cancer cells.

    Science.gov (United States)

    Ma, Lin; Ma, Shan; Zhao, Guimei; Yang, Longqiu; Zhang, Peng; Yi, Qingting; Cheng, Shuguang

    2016-04-01

    Breast cancer is one of the most common malignant tumors in women worldwide. The microRNAs (miRNAs) are small, noncoding RNAs that regulate various biological processes, including breast cancer. miR-708 played an important role in a variety of cancers. However, its involvement in breast cancer remains largely unclear. In this study, we found that forced the expression of miR-708 in breast cancer cell lines decreased cell proliferation and invasion, whereas inhibition of miR-708 increased cell growth and invasion. miR-708 could directly target the LSD1 3'UTR to downregulate the expression. Further studies suggested that inhibition of LSD1 could phenocopied function of the miR-708 overexpression in MDA-MB-231 cells .Overexpression of LSD1 could counteract the effects of miR-708 on the proliferation and invasion. Taken together, the results indicate that miR-708 may function as a tumor suppressor gene in breast cancer development, and miR-708/LSD1 axis may be a therapeutic intervention in breast cancer in the future. PMID:26833707

  14. PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation, Migration and Invasion.

    Science.gov (United States)

    Yang, Lei; Zhu, Jia; Huang, Hua; Yang, Qichang; Cai, Jing; Wang, Qiuhong; Zhu, Junya; Shao, Mengting; Xiao, Jinzhang; Cao, Jie; Gu, Xiaodan; Zhang, Shusen; Wang, Yingying

    2015-01-01

    PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer. PMID:26488471

  15. Multifocal invasive ductal breast cancer with osteoclast-like giant cells: a case report

    Directory of Open Access Journals (Sweden)

    Uleer Christoph

    2011-02-01

    Full Text Available Abstract Introduction To the best of our knowledge, this is the first case report of a multifocal (trifocal invasive carcinoma of the breast containing osteoclast-like giant cells. Case presentation A 64-year-old Caucasian woman presented for routine mammography screening with three radiodense lesions in the lower inner quadrant of the right breast, a primary breast cancer. Microscopic examination showed three foci of invasive ductal carcinoma with multinucleated osteoclast-like giant cells. Osteoclast-like giant cells in breast cancer are a rare phenomenon. They are described in less than two percent of all breast cancers and occur in association with invasive ductal cancer and invasive lobular cancer. In addition, osteoclast-like giant cells have been described in several sarcomas and metaplastic carcinomas of the breast. Conclusion To the best of our knowledge, this is the first report of a multifocal infiltrating ductal carcinoma of the breast containing osteoclast-like giant cells. This could be an indication for a possible early event in carcinogenesis associated with a biological event or secretion that indicates the differentiation and/or migration of stromal cells or macrophages.

  16. Amygdalin Influences Bladder Cancer Cell Adhesion and Invasion In Vitro

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Igor Tsaur; Karen Nelson; Jesco Pfitzenmaier; Axel Haferkamp; Blaheta, Roman A.

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as...

  17. Socioeconomic disparities in the decline in invasive breast cancer incidence

    OpenAIRE

    Sprague, Brian L.; Trentham-Dietz, Amy; Burnside, Elizabeth S.

    2010-01-01

    Breast cancer incidence in the United States has declined dramatically since the year 2002. To improve our understanding of the underlying factors driving breast cancer trends, we explored potential socioeconomic disparities in the recent decline in incidence. We examined the decline in breast cancer incidence according to county-level socioeconomic indicators using data from the Surveillance, Epidemiology and End Results (SEER) program. Since socioeconomic status is associated with mammograp...

  18. 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)

    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)

  19. Detectability and clinicohistological characteristics of small (≤1 cm) invasive breast cancer

    International Nuclear Information System (INIS)

    Purpose: To investigate the detectability and imaging characteristics of primary tumors according to imaging modalities and to identify clinical features and histological prognostic factors for axillary metastases in patients with small (≤1 cm, T1a and T1b) invasive breast cancer. Materials and methods: A total of 221 patients with histologically confirmed small invasive cancers were included for the statistical analysis. At mammography, ultrasonography and MRI, the detectability, and imaging characteristics of primary tumors were compared in patients with or without axillary metastases. Clinical features and histological prognostic factors for axillary metastases were investigated. Results: Of 221 patients examined, axillary metastasis was found in 42 (19%) at the time of surgery. There was no significant difference in detectability of small tumors using ultrasonography and MRI between patients with and without axillary metastasis. However, mammography had a higher positive rate of primary tumors in patients with axillary metastasis than without metastasis (92.9% vs. 77.1%, p = 0.023). Patients with axillary metastasis in small cancers showed more common architectural distortion than negative (p = 0.0147) or mass (p = 0.0356) on mammography. Clinical features were not different in the two groups. Only lymphovascular invasion was independently associated with axillary metastasis (p = 0.0051, 95% CI, 1.527–11.597). Conclusion: The detectability of small invasive breast cancers among patients with and without axillary metastasis is different with mammography, but not with US and MRI. Lymphovascular invasion is only a predictor for axillary metastasis in small invasive cancers

  20. Choropleth Map Design for Cancer Incidence, Part 2

    Directory of Open Access Journals (Sweden)

    Thomas B. Richards, MD

    2010-01-01

    Full Text Available Choropleth maps are commonly used in cancer reports and community discussions about cancer rates. Cancer registries increasingly use geographic information system techniques. The Centers for Disease Control and Prevention’s Division of Cancer Prevention and Control convened a Map Work Group to help guide application of geographic information system mapping techniques and to promote choropleth mapping of data from central cancer registries supported by the National Program of Cancer Registries, especially for comprehensive cancer control planning and evaluation purposes. In this 2-part series, we answer frequently asked questions about choropleth map design to display cancer incidence data. We recommend that future initiatives consider more advanced mapping, spatial analysis, and spatial statistics techniques and include usability testing with representatives of state and local programs and other cancer prevention partners.

  1. Vascular invasion in pancreatic cancer:Imaging modalities,preoperative diagnosis and surgical management

    Institute of Scientific and Technical Information of China (English)

    Nicolas; C; Buchs; Michael; Chilcott; Pierre-Alexandre; Poletti; Leo; H; Buhler; Philippe; Morel

    2010-01-01

    Pancreatic cancer is associated with a poor prognosis,and surgical resection remains the only chance for curative therapy.In the absence of metastatic disease,which would preclude resection,assessment of vascular invasion is an important parameter for determining resectability of pancreatic cancer.A frequent error is to misdiagnose an involved major vessel.Obviously,surgical exploration with pathological examination remains the"gold standard"in terms of evaluation of resectability,especially from the point ...

  2. Effect of Inhibiting NGAL Gene Expression on A549 Lung Cancer Cell Migration and Invasion

    Directory of Open Access Journals (Sweden)

    Jian TANG

    2015-04-01

    Full Text Available Background and objective To detect the expression of neutrophil gelatinase-assoeiated lipocalin (NGAL in the different differentiations of lung cancer tissues and to study the mechanism of invasion of A549 cells affected by NGAL. Methods The expression of NGAL was detected by immunochemistry in lung cancer tissue and the tissue around edge of the cancer. The effect of NGAL expression on A549 cells was observed by using qRT-PCR and Western blot. The abilities of invasion and metastasis were evaluated by transwell invasion and migration assay, and cell scratch assay in vitro. The protein expression of E-cadherin, Vimentin was measured by immunofluoresence and Western blot. Results The positive expression rate of NGAL was 76.32% (58/76 in the lung cancer, 13.3% (4/30 in adjacent tissue by immunochemistry. NGAL expression levels in the lung cancer tissues were significantly higher than that in adjacent tissues. The rate of migration and invasion in NGAL-siRNA group was 60.4%±6.4% compared to 50.5%±4.4% in the control group, there was a significant difference (P<0.05. Vimentin was suppressed, and E-cadherin was upregulated when NGAL was inhibited. MMP-2 and MMP-9 decreased when NGAL was knocked down. Conclusion The expression level of NGAL is highly expressed in lung cancer. NGAL may be one of important indicators involved in lung cancer infiltrated and transferred. NGAL might be one of potential targets for lung cancer treatment.

  3. Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study

    OpenAIRE

    Taghipour, S.; Banjevic, D; Miller, A.B.; Montgomery, N; A K S Jardine; Harvey, B. J.

    2013-01-01

    Background: The aim of screening is to detect a cancer in the preclinical state. However, a false-positive or a false-negative test result is a real possibility. Methods: We describe invasive breast cancer progression in the Canadian National Breast Screening Study and construct progression models with and without covariates. The effect of risk factors on transition intensities and false-negative probability is investigated. We estimate the transition rates, the sojourn time and sensitivity o...

  4. Finasteride Inhibits Human Prostate Cancer Cell Invasion through MMP2 and MMP9 Downregulation

    OpenAIRE

    Moroz, Andrei; Delella, Flávia K; Almeida, Rodrigo; Lacorte, Lívia Maria; Fávaro, Wágner José; Deffune, Elenice; Felisbino, Sérgio L.

    2013-01-01

    Introduction The use of the 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in no...

  5. The candidate tumor suppressor gene ECRG4 inhibits cancer cells migration and invasion in esophageal carcinoma

    OpenAIRE

    Lu ShihHsin; Li Xiaoyan; Zhang Chunpeng; Li Linwei; Zhou Yun

    2010-01-01

    Abstract Background The esophageal cancer related gene 4 (ECRG4) was initially identified and cloned in our laboratory from human normal esophageal epithelium (GenBank accession no.AF325503). ECRG4 was a new tumor suppressor gene in esophageal squamous cell carcinoma (ESCC) associated with prognosis. In this study, we investigated the novel tumor-suppressing function of ECRG4 in cancer cell migration, invasion, adhesion and cell cycle regulation in ESCC. Methods Transwell and Boyden chamber e...

  6. Invasive Bladder Cancer after Cyclophosphamide Administration for Nephrotic Syndrome : A Case Report

    OpenAIRE

    Nakamoto, Takahisa; Kasaoka, Yoshinobu; Ikegami, Yoshihiko; Usui, Tsuguru

    2000-01-01

    We report a case of invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome, and briefly discuss the association of bladder cancer and cyclophosphamide.  A 6-year-old boy, who was diagnosed as having nephrotic syndrome, was treated with oral administration of prednisolone and cyclophosphamide for 4 years, receiving a total dose of 49.5 g cyclophosphamide. At age 27, a gross hematuria with bloody clots appeared and he presented with postrenal renal failure. He unde...

  7. Non-invasive biomarkers in pancreatic cancer diagnosis: what we need versus what we have

    OpenAIRE

    Herreros-Villanueva, Marta; Bujanda, Luis

    2016-01-01

    Pancreatic cancer (PC) is probably the most lethal tumor being forecast as the second most fatal cancer by 2020 in developed countries. Only the earliest forms of the disease are a curable disease but it has to be diagnosed before symptoms starts. Detection at curable phase demands screening intervention for early detection and differential diagnosis. Unfortunately, no successful strategy or image technique has been concluded as effective approach and currently non-invasive biomarkers are the...

  8. Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2

    Directory of Open Access Journals (Sweden)

    Zhang Lingmin

    2012-08-01

    Full Text Available Abstract Background Propofol is one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, but the effect of propofol on gallbladder cancer is not clear. NF-E2-related factor 2 (Nrf2 is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. The aims of the current study were to evaluate effects of propofol on the behavior of human GC cells and role of Nrf2 in these effects. Method The effects of propofol on cell proliferation, apoptosis, and invasion were detected by MTT assays, flow cytometry, and transwell assay. Also, activation of Nrf2 was determined by western blot, RT-PCR, and immunofluorescence assays. Nrf2 was knocked-down in GBC-SD cells by shRNA before evaluating the role of Nrf2 in the influence of propofol on biological behaviors. Results Propofol promoted the proliferation of GBC-SD cells in a dose- and time- dependent manner. After exposure to propofol for 48 h, GBC-SD cells showed decreased apoptosis and increased invasion. Also, propofol over-expressed Nrf2 at both the protein and mRNA levels and induced translocation of Nrf2 into the nucleus. Finally, loss of Nrf2 by shRNA reversed the effect of propofol on cell proliferation, apoptosis, and invasion. Conclusion Propofol induces proliferation and promotes invasion of GC cells through activation of Nrf2.

  9. 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...

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

    International Nuclear Information System (INIS)

    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. 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). 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. Determining the relative abundance of BKCa channel expression in breast cancer metastatic to brain and the mechanism of its action in

  11. 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

  12. Breast cancer and racial disparity between Caucasian and African American women, part 1 (BRCA-1).

    Science.gov (United States)

    Tariq, Khurram; Latif, Naeem; Zaiden, Robert; Jasani, Nick; Rana, Fauzia

    2013-08-01

    Breast cancer is a commonly diagnosed malignancy and the second leading cause of cancer-related death among American women today. Despite the lower incidence of breast cancer among African American women, they are more likely to die from the disease each year than their white counterparts. We present a retrospective cohort study of the tumor registry data from electronic medical records of patients diagnosed with breast cancer at the University of Florida Health, Jacksonville from 2000 to 2005. A total of 907 patients were diagnosed with breast cancer; 445 patients with invasive breast cancer had complete medical records and were selected for this review. Much like previously published research, we found that African American patients presented with a more advanced stage and aggressive subtype of breast cancer than white patients, and were less likely to have health insurance. However, we have yet to determine if universal health care insurance can lead to improved health care access, better breast cancer awareness, and an enhanced attitude toward breast cancer screenings. Such factors would ultimately lead to an earlier diagnosis and better outcomes in both African American and white patients. We plan to investigate this critical issue in a follow-up study (BRCA-2; Breast Cancer and Racial Disparity Between Caucasian and African American Women, Part 2), which will begin a few years after the complete implementation of the universal health care law enacted by President Obama in 2010. The higher frequency of aggressive tumor subtypes in African American women warrants more attention. We suggest further research to determine whether decreasing the initial age for screening or increasing the frequency of mammograms in African American women would improve breast cancer outcomes. This study underscores the importance of identifying and preventing obstacles in routine breast cancer screening, as well as increasing breast cancer awareness. PMID:24518421

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

    International Nuclear Information System (INIS)

    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. Microfabricated Tepui: probing into cancer invasion, metastasis and evolution in a 3D environment

    Science.gov (United States)

    Liu, Liyu

    2011-03-01

    Cancer metastasis and chemotherapeutic resistance are the major reasons why cancer remains recalcitrant to long-term therapy. We are interested to know: 1. How cancer cells invade tissues and metastasize in a 3D spatial environment? 2. How cancer cells evolve resistance to chemotherapeutic therapy? Answering these fundamental questions will require spatially propagating cancer cells in a 3D in vitro micro environment with dynamically controlled chemical stress. Here we attempt to realize this micro environment with a three-dimentional topology on a micro-chip which consist of isolated highlands (Tepui) and deep lower lands. Cancer cells are patterned in the lower lands and their spatial invasion to the mesas of Tepui is observed continuously with a microscope. Experiments have demonstrated that the cell invasion potential is time dependent, which is not only determined by cell motility, but also cell number and spatial stress. Quantitative analysis shows that the invasion rate fits logistic equation. Further more, we have also imbedded collagen based Extracellular Matrix (ECM) inside these structures and established a robust chemical gradient in a vertical space. With merit of real-time confocal imaging, cell propagation, metastasis and evolution in the 3D environment are studied with time as a model for cell behavior inside tissues. NCI grant: U54CA143803.

  15. Genetic diversity of HPV16 and HPV18 in Brazilian patients with invasive cervical cancer.

    Science.gov (United States)

    Vidal, Joao Paulo C B; Felix, Shayany Pinto; Chaves, Cláudia B P; Patury, Patrícia; Franco, Vanessa F; de Morais, Evaneide A; de Carvalho, Neile A; Carvalho, Aurenice C L; Almeida Neto, Olimpio F; Vieira, Lina Maria T M; Correa, Flavia Miranda; Martins, Luís Felipe Leite; Negrão, Antonio; de Almeida, Liz Maria; Moreira, Miguel Angelo Martins

    2016-07-01

    Cervical cancer is the fourth most common cancer among women, and ∼70-80% of these cancers are associated with two human papillomavirus types: HPV16 and HPV18. Several studies have reported that intra-type diversity is associated with the progression of infection to invasive cancer. Herein, we report the genetic diversity of HPV16 and HPV18 in a cohort of 594 Brazilian women with invasive cervical cancer and describe the prevalence of lineages and intra-type diversity prior to the implementation of the public immunization program in Brazil. HPV detection and genotyping were performed using PCR, PGMY/GP primers, and DNA extracted from fresh tumors. The HPV16 (378 women) and HPV18 (80 women) lineages were identified by PCR and sequencing of the LCR and E6 fragments, followed by SNV comparison and phylogenetic analysis. In our cohort, was found a higher frequency of the lineage A (in 217 women), followed by lineage D (in 97 women) and lineages B and C (in 10 women each) for HPV16; and a higher frequency of lineage A (in 56 women) followed by lineage B (in 15 women) in HPV18. The genetic diversity of HPV16 indicated a recent expansion of specific variants or a selective advantage that is associated with invasive cancer; this pattern was not observed for HPV18. J. Med. Virol. 88:1279-1287, 2016. © 2015 Wiley Periodicals, Inc. PMID:26694554

  16. Knockdown of RAGE inhibits growth and invasion of gastric cancer cells

    Directory of Open Access Journals (Sweden)

    X.C. Xu

    2013-11-01

    Full Text Available The receptor for advanced glycation endproducts (RAGE is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of RAGE in gastric cancer is still elusive. In this study, we investigated the expression and molecular mechanisms of RAGE in gastric cancer cells. Forty cases of gastric cancer and corresponding adjacent non-cancerous tissues (ANCT were collected, and the expression of RAGE was assessed using immunohistochemistry (IHC in biopsy samples. Furthermore, RAGE signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE used to transfect into human gastric cancer SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA and matrix metallopeptidase-2 (MMP-2 was detected by Real-time PCR and Western blot assays. Cell proliferative activities and invasive capability were respectively determined by MTT and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. As a consequence, RAGE was found highly expressed in cancer tissues compared with the ANCT (70.0% vs 45.0%, P=0.039, and correlated with lymph node metastases (P=0.026. Knockdown of RAGE reduced cell proliferation and invasion of gastric cancer with decreased expression of AKT, PCNA and MMP-2, and induced cell apoptosis and cycle arrest. Altogether, upregulation of RAGE expression is associated with lymph node metastases of gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of gastric cancer cells through AKT pathway, suggesting that RAGE may represent a potential therapeutic target for this aggressive malignancy.

  17. Breast conserving therapy for early stage invasive cancer and ductal carcinoma in-situ

    International Nuclear Information System (INIS)

    Purpose/Objective: To discuss a number of clinical, pathologic, and treatment related issues in the management of early stage invasive breast cancer and ductal carcinoma in situ. In the last 10 years, prospective randomized trials as well as retrospective series have established the role of conservative surgery and radiation in the treatment of early stage invasive breast cancer. This course will focus on some of the unresolved issues in breast conservation therapy including patient selection, the extent of surgery in the breast, and the importance of microscopic resection margins. The impact of adjuvant systemic therapy (chemotherapy or tamoxifen) on breast recurrence will be presented. Factors predicting for an increased risk of recurrence in the treated breast will be presented. Potential candidates for conservative surgery alone with minimally invasive breast cancer will be identified. The impact of improved local control on survival will be discussed. Treatment options for ductal carcinoma in situ (DCIS) including observation, radiation and mastectomy. Results from prospective randomized trials as well as retrospective series will be presented in an attempt to identify appropriate treatment strategies for the different clinical presentations and histologic subtypes of DCIS. As cost effective strategies are developed, the role of conservative surgery and radiation in minimally invasive breast cancer and DCIS must be defined

  18. 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......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

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

    NARCIS (Netherlands)

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

    2014-01-01

    PURPOSE: 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 stand

  20. How to improve the effectiveness of transurethral resection in nonmuscle invasive bladder cancer?

    NARCIS (Netherlands)

    E.C.C. Cauberg; J.J.M.C.H. de la Rosette; Th.M. de Reijke

    2009-01-01

    Purpose of review The high rate of early recurrences in nonmuscle invasive bladder cancer is considered to be strongly related to the effectiveness of transurethral resection (TUR). The aim of this article is to review methods, currently available or in development, that aim at improving TUR, with a

  1. Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs.

    Science.gov (United States)

    Ha, Na Hee; Park, Dae Gun; Woo, Bok Hee; Kim, Da Jeong; Choi, Jeom Il; Park, Bong Soo; Kim, Yong Deok; Lee, Ji Hye; Park, Hae Ryoun

    2016-10-01

    Recent studies indicate that chronic inflammation promotes the aggressiveness of cancers. However, the direct molecular mechanisms underlying a functional link between chronic periodontitis, the most common form of oral inflammatory diseases, and the malignancy of oral cancer remain unknown. To elucidate the role of chronic periodontitis in progression of oral cancer, we examined the effect of Porphyromonas gingivalis (P. gingivalis), a major pathogen that causes chronic periodontitis, on the invasiveness of oral squamous cell carcinoma (OSCC) cells, including SCC-25, OSC-20 and SAS cells. Exposures to P. gingivalis promoted the invasive ability of OSC-20 and SAS cells via the upregulation of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-2. However, P. gingivalis-infected SCC-25 cells did not exhibit changes in their invasive properties or the low expression levels of MMPs. In an effort to delineate the molecular players that control the invasiveness, we first assessed the level of interleukin-8 (IL-8), a well-known inflammatory cytokine, in P. gingivalis-infected OSCC cells. IL-8 secretion was substantially increased in the OSC-20 and SAS cells, but not in the SCC-25 cells, following P. gingivalis infection. When IL-8 was directly applied to SCC-25 cells, their invasive ability and MMP level were significantly increased. Furthermore, the downregulation of IL-8 in P. gingivalis-infected OSC-20 and SAS cells attenuated their invasive potentials and MMP levels. Taken together, our findings strongly suggest that P. gingivalis infection plays an important role in the promotion of the invasive potential of OSCC cells via the upregulation of IL-8 and MMPs. PMID:27468958

  2. Risk Factors for Invasive Epithelial Ovarian Cancer by Histologic Subtype

    Directory of Open Access Journals (Sweden)

    Quirk JT

    2004-10-01

    Full Text Available It is unclear whether the different histologic subtypes of epithelial ovarian carcinoma have different risk factors. We investigated the relationships between selected epidemiologic variables (i.e., parity, family history of ovarian cancer, oral contraceptive use, a history of tubal ligation and noncontraceptive estrogen use and the major histologic subtypes of epithelial ovarian cancer in a hospital-based case-control study of adult women at Roswell Park Cancer Institute in Buffalo, NY, USA. Multivariate unconditional logistic regression models were used for statistical analysis. We observed a pattern of increased risk associated with family history and a pattern of risk reduction associated with parity, noncontraceptive estrogen use and tubal ligation across all histologic subtype groups. However, we did not observe a consistent pattern of risk associated with oral contraceptive use. These results provide some additional support for the hypothesis that the effects of various ovarian cancer risk factors may differ according to the histologic subtype.

  3. Circulating microRNAs as minimally invasive biomarkers for cancer theragnosis and prognosis

    Directory of Open Access Journals (Sweden)

    William C. S. Cho

    2011-02-01

    Full Text Available Novel cancer biomarker discovery is urgently needed for cancer theragnosis and prognosis, and among the many possible types of samples, blood is regarded to be ideal for this discovery as it can be collected easily in a minimally invasive manner. Results of the last few years have ascertained the quantification of microRNA (miRNA as a promising approach for the detection and prognostication of cancer. Indeed, an increasing number of studies have shown that circulating cancer-associated miRNAs are readily measured in plasma or serum and they can robustly discriminate cancer patients from healthy controls, as well as distinguishing between good-prognosis and poor-prognosis patients. Furthermore, recent findings also suggest the potential of circulating miRNAs in the screening, monitoring, and treatment of cancer. This article summarizes the most significant and latest discoveries of original researches on circulating miRNAs involvement in cancer, focusing on the potential of circulating miRNAs as minimally invasive biomarkers for cancer theragnosis and prognosis.

  4. Recent advances in minimally invasive colorectal cancer surgery

    OpenAIRE

    Wichmann, Mathias W.; Meyer, G.; Angele, M. K.; Schildberg, Friedrich Wilhelm; Rau, H G

    2002-01-01

    Laparoscopy has improved surgical treatment of various diseases due to its limited surgical trauma and has developed as an interesting therapeutic alternative for the resection of colorectal cancer. Despite numerous clinical advantages (faster recovery, less pain, fewer wound and systemic complications, faster return to work) the laparoscopic approach to colorectal cancer therapy has also resulted in unusual complications, i.e. ureteral and bladder injury which are rarely observed with open l...

  5. Palliation of malignant rectal obstruction from invasive prostate cancer with multiple overlapping self-expanding metal stents.

    Science.gov (United States)

    Smith, Aja S; Cole, Matthew; Vega, Kenneth J; Munoz, Juan Carlos

    2009-12-01

    Self-expandable metal stents (SEMS) are used for colonic neoplastic and extracolonic metastatic obstruction relief. Limited data exists on their use for locally invasive prostate cancer. We describe a unique approach using overlapping SEMS to alleviate a rectosigmoid obstruction from locally invasive prostate cancer. A patient with locally advanced prostate cancer presented with obstipation and lymphedema. Placement of overlapping rectosigmoid SEMS was performed, relieving the visualized rectosigmoid obstruction. PMID:20016435

  6. Accessory Breast Cancer Occurring Concurrently with Bilateral Primary Invasive Breast Carcinomas: A Report of Two Cases and Literature Review

    OpenAIRE

    2012-01-01

    The development of accessory breast tissue, which is found anywhere along the milk line, is attributed to the failure of milk line remnants to regress during embryogenesis. Primary tumors may arise from any ectopic breast tissue. Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare. Two such cases were reported in this article. One was a 43-year-old Chinese female who exhibited bilateral breast cancer (invasive ductal carcinoma, not otherwise sp...

  7. Inhibition of nuclear factor-kappa B differentially affects thyroid cancer cell growth, apoptosis, and invasion

    Directory of Open Access Journals (Sweden)

    Schweppe Rebecca E

    2010-05-01

    Full Text Available Abstract Background Nuclear factor-κB (NF-κB is constitutively activated in many cancers and plays a key role in promoting cell proliferation, survival, and invasion. Our understanding of NF-κB signaling in thyroid cancer, however, is limited. In this study, we have investigated the role of NF-κB signaling in thyroid cancer cell proliferation, invasion, and apoptosis using selective genetic inhibition of NF-κB in advanced thyroid cancer cell lines. Results Three pharmacologic inhibitors of NF-κB differentially inhibited growth in a panel of advanced thyroid cancer cell lines, suggesting that these NF-κB inhibitors may have off-target effects. We therefore used a selective genetic approach to inhibit NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα. These studies revealed decreased cell growth in only one of five thyroid cancer cell lines (8505C, which occurred through a block in the S-G2/M transition. Resistance to TNFα-induced apoptosis was observed in all cell lines, likely through an NF-κB-dependent mechanism. Inhibition of NF-κB by mIκBα sensitized a subset of cell lines to TNFα-induced apoptosis. Sensitive cell lines displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK pathway, defining a potential mechanism of response. Finally, NF-κB inhibition by mIκBα expression differentially reduced thyroid cancer cell invasion in these thyroid cancer cell lines. Sensitive cell lines demonstrated approximately a two-fold decrease in invasion, which was associated with differential expression of MMP-13. MMP-9 was reduced by mIκBα expression in all cell lines tested. Conclusions These data indicate that selective inhibition of NF-κB represents an attractive therapeutic target for the treatment of advanced thyroid. However, it is apparent that global regulation of thyroid cancer cell growth and invasion is not achieved by NF-κB signaling alone. Instead, our

  8. Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis

    International Nuclear Information System (INIS)

    Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2. We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index. Grade 2 subgroup analysis showed that the PVI (p = 0.023) and the loss of membranous NHERF1 (p = 0.028) were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000). Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively). Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000), and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level. The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors

  9. Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis

    Directory of Open Access Journals (Sweden)

    Malfettone Andrea

    2012-03-01

    Full Text Available Abstract Background Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2. Methods We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index. Results Grade 2 subgroup analysis showed that the PVI (p = 0.023 and the loss of membranous NHERF1 (p = 0.028 were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000. Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively. Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000, and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level. Conclusions The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors.

  10. microRNA-21 Governs TORC1 Activation in Renal Cancer Cell Proliferation and Invasion

    OpenAIRE

    Dey, Nirmalya; Das, Falguni; Ghosh-Choudhury, Nandini; Mandal, Chandi Charan; Parekh, Dipen J.; Block, Karen; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

    2012-01-01

    Metastatic renal cancer manifests multiple signatures of gene expression. Deviation in expression of mature miRNAs has been linked to human cancers. Importance of miR-21 in renal cell carcinomas is proposed from profiling studies using tumor tissue samples. However, the role of miR-21 function in causing renal cancer cell proliferation and invasion has not yet been shown. Using cultured renal carcinoma cells, we demonstrate enhanced expression of mature miR-21 along with pre-and pri-miR-21 by...

  11. Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion-Preliminary Observations.

    Science.gov (United States)

    Sarosiek, Konrad; Gandhi, Ankit V; Saxena, Shivam; Kang, Christopher Y; Chipitsyna, Galina I; Yeo, Charles J; Arafat, Hwyda A

    2016-01-01

    According to the epidemiological studies, about 4.4% of American general elderly population has a pronounced hypothyroidism and relies on thyroid hormone supplements daily. The prevalence of hypothyroidism in our patients with pancreatic cancer was much higher, 14.1%. A retrospective analysis was performed on patients who underwent pancreaticoduodenectomy (Whipple procedure) or distal pancreatectomy and splenectomy (DPS) at Thomas Jefferson University Hospital, Philadelphia, from 2005 to 2012. The diagnosis of hypothyroidism was correlated with clinicopathologic parameters including tumor stage, grade, and survival. To further understand how thyroid hormone affects pancreatic cancer behavior, functional studies including wound-induced cell migration, proliferation, and invasion were performed on pancreatic cancer cell lines, MiaPaCa-2 and AsPC-1. We found that hypothyroid patients taking exogenous thyroid hormone were more than three times likely to have perineural invasion, and about twice as likely to have higher T stage, nodal spread, and overall poorer prognostic stage (P < 0.05). Pancreatic cancer cell line studies demonstrated that exogenous thyroid hormone treatment increased cell proliferation, migration, and invasion (P < 0.05). We conclude that exogenous thyroid hormone may contribute to the progression of pancreatic cancer. PMID:27123358

  12. Radical trachelectomy: a fertility-sparing option for early invasive cervical cancer.

    Science.gov (United States)

    Mejia-Gomez, Javier; Feigenberg, Tomer; Feigenber, Tomer; Arbel-Alon, Sagit; Kogan, Liron; Benshushan, Abraham

    2012-05-01

    For the past 15 years gynecological oncologists have been seeking ways to preserve woman's fertility when treating invasive cervical cancer. For some women with small localized invasive cervical cancers, there is now hope for pregnancy after treatment. Many cases of cervical cancer are diagnosed in young woman who wish to preserve their fertility. As more women are delaying childbearing, fertility preservation has become an important consideration. The standard surgical treatment for stage IA2-IB1 cervical cancer is a radical hysterectomy and bilateral pelvic lymphadenectomy. This surgery includes removal of the uterus and cervix, radical resection of the parametrial tissue and upper vagina, and complete pelvic lymphadenectomy. Obviously, the standard treatment does not allow future childbearing. Radical trachelectomy is a fertility-sparing surgical approach developed in France in 1994 by Dr. Daniel Dargent for the treatment of early invasive cervical cancer. Young women wishing to bear children in the future may be candidates for fertility-preservation options. The radical trachelectomy operation has been described and performed abdominally, assisted vaginally by laparoscopy and robotically. In this review we discuss the selection criteria for radical trachelectomy, the various possible techniques for the operation, the oncological and obstetric outcomes, and common complications. PMID:22799068

  13. Migration and invasion is inhibited by silencing ROR1 and ROR2 in chemoresistant ovarian cancer.

    Science.gov (United States)

    Henry, C E; Llamosas, E; Djordjevic, A; Hacker, N F; Ford, C E

    2016-01-01

    Ovarian cancer survival remains poor despite recent advances in our understanding of genetic profiles. Unfortunately, the majority of ovarian cancer patients have recurrent disease after chemotherapy and lack other treatment options. Wnt signalling has been extensively implicated in cancer progression and chemoresistance. Therefore, we investigated the previously described Wnt receptors ROR1 and ROR2 as regulators of epithelial-to-mesenchymal transition (EMT) in a clinically relevant cell line model. The parental A2780- and cisplatin-resistant A2780-cis cell lines were used as a model of ovarian cancer chemoresistance. Proliferation, adhesion, migration and invasion were measured after transient overexpression of ROR1 and ROR2 in the parental A2780 cell line, and silencing of ROR1 and ROR2 in the A2780-cis cell line. Here we show that ROR1 and ROR2 expression is increased in A2780-cis cells, alongside β-catenin-independent Wnt targets. Knockdown of ROR1 and ROR2 significantly inhibited cell migration and invasion and simultaneous knockdown of ROR1 and ROR2 significantly sensitised cells to cisplatin, whilereas ROR overexpression in the parental cell line increased cell invasion. Therefore, ROR1 and ROR2 have the potential as novel drug targets in metastatic and recurrent ovarian cancer patients. PMID:27239958

  14. Molecular changes in invasive front of oral cancer

    Directory of Open Access Journals (Sweden)

    Mohit Sharma

    2013-01-01

    Full Text Available Treatment planning for oral squamous cell carcinoma (OSCC is based on the clinical TNM (Tumor, Node and Metastasis classification. This system operates on the assumption that small tumours without clinical spread have a better prognosis than larger tumours with metastases. However, it is a well-known fact that some tumours with the same clinical staging show different growth patterns and clinical behaviour. This makes the prognosis for patients with OSCC difficult to predict on the basis of clinical staging alone. Although many histopathological characteristics of OSCC have been identified as prognostic factors, none is believed to be completely infallible. Therefore, a great need exists for more reliable prognostic markers, which will assist in treatment decisions. It is now well documented that several molecular events of significance for tumour spread, such as gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumour-host interface or invasive front, where the deepest and presumably most aggressive cells reside. This review describes the various molecular events and interactions, which take place in the invasive front of the OSCC, and elucidates their role as prognostic markers.

  15. Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers

    International Nuclear Information System (INIS)

    Highlights: ► Kinome profiling is a novel technique for identifying activated kinases in human cancers. ► Src activity is increased in invasive thyroid cancers. ► Inhibition of Src activity decreased proliferation and invasion in vitro. ► Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation. Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer

  16. Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nancy L., E-mail: nlcho@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Lin, Chi-Iou [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Du, Jinyan [Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02142 (United States); Whang, Edward E. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ito, Hiromichi [Department of Surgery, Michigan State University, Lansing, MI 48912 (United States); Moore, Francis D.; Ruan, Daniel T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Kinome profiling is a novel technique for identifying activated kinases in human cancers. Black-Right-Pointing-Pointer Src activity is increased in invasive thyroid cancers. Black-Right-Pointing-Pointer Inhibition of Src activity decreased proliferation and invasion in vitro. Black-Right-Pointing-Pointer Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation

  17. MiR-614 Inhibited Lung Cancer Cell Invasion and Proliferation via Targeting PSA

    Directory of Open Access Journals (Sweden)

    Fang LV

    2014-10-01

    Full Text Available Background and objective MicroRNAs (miRNAs is a group of non-coding small RNA molecules, which play important roles in the development of tumor. The mechanisms of various kinds of miRNAs in lung cancer still need to be further elucidated. This study investigated the function of miR-614 on lung cancer cell invasion and proliferation. Methods Real-time quantitative PCR was used to detect the expression of miR-614 in lung cancer cell PGCL3 and PGLH7. Transwell assay was used to test the role of miR-614 on regulating invasion and migration of cells. CCK8 assay and BrdU incorporation assay was used to assess the role of miR-614 on cell proliferation. Bioinformatics software predicted the potential target genes of miR-614 and dual luciferase reporter gene was used to analyze the binding between miR-614 and 3’UTR of puromycin-sensitive aminopeptidase (PSA. Western blot detected the PSA protein levels. Results The expression of miR-614 in PGCL3 cells with high metastasis potential was significantly lower than that in PGLH7 cells with low metastasis potential. Furthermore, altered expression of miR-614 by transfection of pre-miR-614 mimics and inhibitor significantly affected the ability of invasion and proliferation of lung cancer cells. Bioinformatics analysis predicted that PSA was one of the potential target genes of miR-614. Altered expression of miR-614 markedly down-regulated the PSA protein levels of lung cancer cells. In addition, dual luciferase reporter gene assay indicated that miR-614 regulated PSA expression by binding to the 3’UTR of PSA mRNA. Conclusion MiR-614 inhibited cell invasion and proliferationa targeting PSA in lung cancer cells, PGCL3.

  18. Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells

    Science.gov (United States)

    Kilgore, Joshua; Jackson, Amanda L; Clark, Leslie H; Guo, Hui; Zhang, Lu; Jones, Hannah M; Gilliam, Timothy P; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

    2016-01-01

    Objective: Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines. Methods: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting. Results: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines. Conclusion: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation. PMID:27398153

  19. Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion

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    Sitruk-Ware Regine

    2008-06-01

    Full Text Available Abstract Background Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted. Methods We investigated the effects of progesterone (P, medroxyprogesterone acetate (MPA, drospirenone (DRSP and nestorone (NES alone or with 17β-estradiol (E2 on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling. Results Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells. Conclusion These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.

  20. Silencing of HMGA2 promotes apoptosis and inhibits migration and invasion of prostate cancer cells

    Indian Academy of Sciences (India)

    Zhan Shi; Ding Wu; Run Tang; Xiang Li; Renfu Chen; Song Xue; Chengjing Zhang; Xiaoqing Sun

    2016-06-01

    The high mobility group protein A2 (HMGA2) has been demonstrated as an architectural transcription factor that is associated with pathogenesis of many malignant cancers, however, its role in prostate cancer cells remains largely unknown. To explore whether HMGA2 participates in the development and progression of prostate cancer, small interfering RNA (siRNA) targeted on human HMGA2 was transfected to suppress the HMGA2 expression in prostate cancer PC3 and DU145 cells, and then we examined the cellular biology changes after decreased the expression of HMGA2. Our results showed that knockdown of HMGA2 markedly inhibited cell proliferation, this reduced cell proliferation was due to the promotion of cell apoptosis as the Bcl-xl was decreased, whereas Bax was up-regulated. In addition, we found that HMGA2 knockdown resulted in reduction of cell migration and invasion, as well as repressed the expression of matrix metalloproteinases (MMPs) and affected the occurrence of epithelial-mesenchymal transition (EMT) in both cell types. We further found that decreased HMGA2 expression inhibited the transforming growth factor-β (TGF-β)/Smad signaling pathway in cancer cells. In conclusion, our data indicated that HMGA2 was associated with apoptosis, migration and invasion of prostate cancer, which might be a promising therapeutic target for prostate cancer.

  1. Daucus carota Pentane/Diethyl Ether Fraction Inhibits Motility and Reduces Invasion of Cancer Cells.

    Science.gov (United States)

    Zgheib, Perla; Daher, Costantine F; Mroueh, Mohamad; Nasrallah, Anita; Taleb, Robin I; El-Sibai, Mirvat

    2014-01-01

    Daucus carota (DC) is a herb used in folklore medicine in Lebanon to treat numerous diseases including cancer. Recent studies in our laboratory on DC oil and its fractions revealed potent anticancer activities in vitro and in vivo. The present study aims to investigate the effect of the most potent DC fraction, pentane/diethyl ether (50:50), on lung, skin, breast and glioblastoma cancer cell motility and invasion. Upon treatment, a pronounced decrease in cancer cell motility was observed in the 4 cell lines. The treatment also led to a decrease in cancer cell invasion and an increased cell adhesion. Additionally, the DC fraction caused a decrease in the activation of the ρ-GTPases Rac and CDC42, a finding that may partially explain the treatment-induced decrease in cell motility. The current study demonstrates a crucial effect of the DC pentane/diethyl ether fraction on cancer cell motility and metastasis, making it a potential candidate for cancer therapy specifically targeting cancer motility and metastasis. PMID:26088465

  2. Using of Telomerase Enzyme in Urine as a Non invasive Marker for Cancer Bladder Detection

    Directory of Open Access Journals (Sweden)

    Azza A Hassan*, Fawzia A . El- Sheshtawey** , Seliem A. Seliem

    2008-12-01

    Full Text Available Background: Urinary bladder cancer is one of the major health problem all over the world. Cystoscopy remains the gold standard for identifying bladder cancer but it is invasive and expensive, therefore, a simple, non invasive test for detecting bladder cancer would be helpful. Several biomarkers for bladder cancer have been used, but no single marker has been accurate and conclusive. Aim: The current study aimed to measure telomerase enzyme in urine as a useful non invasive marker for detection of bladder cancer. Methods : Forty eight patients ( 39 males and 9 females were included, They are complaining of urinary symptoms and undergo cystoscopy with biopsy of bladder lesions and histopathological examination. They were divided into groups: Group I: 16 patients ( 11 males and 5 females have benign urologic conditions. Group II: 32 patients (28 males and 4 females have proven bladder cancer patients underwent transurethral resection of bladder tumor or cystoscopy with biopsy of bladder lesions. Also, 15 apparently healthy volunteers with matched age and sex with patients were served as a control group. All subjects were submitted to laboratory estimation of the following in urine: urinary creatinine, urine cytology, telomerase enzyme in urine by telomerase PCR and complete urine examination. Results : The results of this study revealed that a highly significant increase in the frequency of cytolological positive cases for tumor cells in malignant group than each of benign group and healthy subjects, while no significant difference was detected between benign group and healthy subjects. The frequency of telomerase in urine was significantly higher in malignant group than each of benign group and healthy subjects, while no significant difference was detected between benign group and healthy subjects. The telomerase activity has sensitivity of 90.6% for diagnosis of cancer bladder with 93.7% for specificity and PPV was 96.6%, NPV was 83.3% and

  3. Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2.

    Directory of Open Access Journals (Sweden)

    Chen Wang

    Full Text Available A better understanding of the effects of human adipocytes on breast cancer cells may lead to the development of new treatment strategies. We explored the effects of adipocytes on the migration and invasion of breast cancer cells both in vitro and in vivo.To study the reciprocal effects of adipocytes and cancer cells, we co-cultured human mature adipocytes and breast cancer cells in a system devoid of heterogeneous cell-cell contact. To analyze the factors that were secreted from adipocytes and that affected the invasive abilities of breast cancer cells, we detected different cytokines in various co-culture media. To study the communication of mature adipocytes and breast cancer cells in vivo, we chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to do immunostaining.The co-culture media of human MCF-7 breast cancer cells and human mature adipocytes increased motility of MCF-7 cells. In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells. Based on our co-culture medium chip results, we chose four candidate cytokines and tested their influence on metastasis individually. We found that IGFBP-2 enhanced the invasion ability of MCF-7 cells in vitro more prominently than did the other factors. In vivo, metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue, whereas adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did adipocytes surrounding non-metastatic breast tumors.IGFBP-2 secreted by mature adipocytes plays a key role in promoting the metastatic ability of MCF-7 breast cancer cells.

  4. The candidate tumor suppressor gene ECRG4 inhibits cancer cells migration and invasion in esophageal carcinoma

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    Lu ShihHsin

    2010-10-01

    Full Text Available Abstract Background The esophageal cancer related gene 4 (ECRG4 was initially identified and cloned in our laboratory from human normal esophageal epithelium (GenBank accession no.AF325503. ECRG4 was a new tumor suppressor gene in esophageal squamous cell carcinoma (ESCC associated with prognosis. In this study, we investigated the novel tumor-suppressing function of ECRG4 in cancer cell migration, invasion, adhesion and cell cycle regulation in ESCC. Methods Transwell and Boyden chamber experiments were utilized to examined the effects of ECRG4 expression on ESCC cells migration, invasion and adhesion. And flow cytometric analysis was used to observe the impact of ECRG4 expression on cell cycle regulation. Finally, the expression levels of cell cycle regulating proteins p53 and p21 in human ESCC cells transfected with ECRG4 gene were evaluated by Western blotting. Results The restoration of ECRG4 expression in ESCC cells inhibited cancer cells migration and invasion (P P > 0.05. Furthermore, ECRG4 could cause cell cycle G1 phase arrest in ESCC (P Conclusion ECRG4 is a candidate tumor suppressor gene which suppressed tumor cells migration and invasion without affecting cell adhesion ability in ESCC. Furthermore, ECRG4 might cause cell cycle G1 phase block possibly through inducing the increased expression of p53 and p21 proteins in ESCC.

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

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    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 m

  6. Amygdalin influences bladder cancer cell adhesion and invasion in vitro.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK and total and activated focal adhesion kinase (FAK were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines may depend upon the cancer cell type.

  7. Music therapy as part of the alternative-complementary therapy in cancer patients in hospital

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    Efstratios Athanassakis

    2012-01-01

    Full Text Available Cancer is one of the modern health problems of people living in developed countries. Furthermore, therapeutic approaches to cancer patients is constantly updated with new data. Aim: The aim of the present study was to review the international literature referred to the application of music therapy in the treatment for pediatric and adult patients with cancer. Method and materials: The method of this study included bibliography research from both the review and the research literature on MEDLINE (2000-2010 database and using as key words music, music therapy, alternative-complementary therapy, cancer, children. Results: Music therapy, the last few years, seems to be one of the forms of alternative-complementary therapy for patients treated for cancer. Music therapy is applied as part of complementary therapy in pediatric and adult patients with cancer. Complementary-alternative methods are non-invasive, non-toxic, cheap, safe and can be easily used by the patients themselves. Primarily, the music therapy aimed to the reduction of the emotional trauma and the feeling of the pain during the process of the treatment (radiotherapy, chemotherapy, other painful procedures but also in the whole patients life. Conclusions: Scientific bibliographic databases research concerning the music therapy in patients with cancer seem encouraging, especially in children. Nevertheless, the further study of the role of the music during hospitalization in the outcome of the treatment is essential

  8. Low power ultrasound inhibits cell proliferation and invasion of human cancer cells in vitro

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    Etienne Mfoumou

    2012-01-01

    Full Text Available Background: Applications of ultrasound in medicine for therapeutic purposes have been accepted, and they have several beneficial uses for many years. However, the outcome of low power ultrasound waves on cell proliferation, especially cell cycle progression and invasion as well as their associated genes on human breast and cervical cancer cells has not been investigated yet. Therefore, we examined the effect of low power ultrasound on BT20, BT20-E6/E7 and HeLa cell lines. Materials and Methods: BT20, BT20-E6/E7 and HeLa cell lines were used in this study. On the other hand, cell proliferation, cell cycle, and invasion assays were applied to study the effect of low ultrasound irradiation on these cell lines. Meanwhile, western blot was performed to study the expression patterns of some selected genes associated with this effect. Results: We found that low power ultrasound inhibits cell proliferation and provokes G0-G1 cell cycle arrest and reduction of S as well as an increase in the G2-M phase of HeLa cells in comparison with the untreated cells. This is accompanied by a down-regulation of Cdk-6 (cyclin dependent kinase which is a major control switch for the cell cycle. Moreover, low power ultrasound inhibits cell invasion and consequently down-regulates the expression of Id-1, caveolin, and EGF-R which are widely considered as main regulators of cell invasion and metastasis of human cancer. Conclusion: These results suggest that application of low power ultrasound on human breast and cervical cancer could be an effective method to reduce cell proliferation and invasion of these cancers.

  9. High Expression of the RECK Gene in Breast Cancer Cells is Related to Low Invasive Capacity

    Institute of Scientific and Technical Information of China (English)

    Tao Sun; Daqing Jiang; Jinming Li; Dongyun Han; Zhiguo Song

    2006-01-01

    OBJECTIVE To investigate the expression of the RECK gene in human breast (cancer) cell lines, and to determine the relationship between RECK gene expression and the invasive capacity of the breast cancer cell lines.METHODS The invasive capacity of breast (cancer) cell lines including HBL-100, MCF-7 and MDA-MB-435S were determined by the Transwell method. The protein expression levels of RECK, MMP-2 and MMP- 9 genes in these three cell lines were measured by immunocytochemical methods. The expressions of the RECK gene and protein level were measured by RT-PCR and Western blots in the cell lines respectively.RESULTS The order of the invasive capacity of the breast (cancer) cell lines was MDA-MB-435S, being the highest, and HBL-100, being the lowest. The invasive capacity difference between any two groups among the three groups was significant (P<0.01). The protein expression level of the RECK gene in the HBL-100 cell line was highest, and no expression was detected in MDA-MB-435S cells. Moreover, the expression of the RECK gene was negatively correlated with the expression of the MMP-2 and MMP-9 genes. The mRNA level of the RECK gene in HBL-100 cells was the highest, but no expression was found in the MDA-MB-435S cells (P<0.001).CONCLUSION There was a significant negative correlation between the expression level of the RECK gene and invasive capacity in vitro, and the RECK gene expression showed an inverse proportion to that of the MMP-2, MMP-9 genes.

  10. Ascertaining invasive breast cancer cases; the validity of administrative and self-reported data sources in Australia

    OpenAIRE

    Kemp, Anna; Preen, David B; Saunders, Christobel; Holman, C. D’Arcy J.; Bulsara, Max; Rogers, Kris; Roughead, Elizabeth E.

    2013-01-01

    Background Statutory State-based cancer registries are considered the ‘gold standard’ for researchers identifying cancer cases in Australia, but research using self-report or administrative health datasets (e.g. hospital records) may not have linkage to a Cancer Registry and need to identify cases. This study investigated the validity of administrative and self-reported data compared with records in a State-wide Cancer Registry in identifying invasive breast cancer cases. Methods Cases of inv...

  11. Pim-selective inhibitor DHPCC-9 reveals Pim kinases as potent stimulators of cancer cell migration and invasion

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    Prudhomme Michelle

    2010-10-01

    Full Text Available Abstract Background Pim family kinases are small constitutively active serine/threonine-specific kinases, elevated levels of which have been detected in human hematopoietic malignancies as well as in solid tumours. While we and others have previously shown that the oncogenic Pim kinases stimulate survival of hematopoietic cells, we now examined their putative role in regulating motility of adherent cancer cells. For this purpose, we inhibited Pim kinase activity using a small molecule compound, 1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde (DHPCC-9, which we had recently identified as a potent and selective inhibitor for all Pim family members. Results We now demonstrate that the Pim kinase inhibitor DHPCC-9 is very effective also in cell-based assays. DHPCC-9 impairs the anti-apoptotic effects of Pim-1 in cytokine-deprived myeloid cells and inhibits intracellular phosphorylation of Pim substrates such as Bad. Moreover, DHPCC-9 slows down migration and invasion of cancer cells derived from either prostate cancer or squamocellular carcinoma patients. Silencing of Pim expression reduces cell motility, while Pim overexpression enhances it, strongly suggesting that the observed effects of DHPCC-9 are dependent on Pim kinase activity. Interestingly, DHPCC-9 also abrogates NFATc-dependent migration of cancer cells, implying that NFATc factors mediate at least part of the pro-migratory effects of Pim kinases. Conclusions Altogether, our data indicate that DHPCC-9 is not only a powerful tool to investigate physiological effects of the oncogenic Pim family kinases, but also an attractive molecule for drug development to inhibit invasiveness of Pim-overexpressing cancer cells.

  12. The role of pneumothorax CT for the evaluation of aortic invasion by lung cancer

    International Nuclear Information System (INIS)

    To improve the accuracy of T3 diagnosis in lung cancer, Pneumothorax CT was carried out in four patients having diagnosis of plain CT and enhanced CT. Both plain and enhanced CT demonstrated obliteration of low density zone between tumor and the aorta in all cases. In three of four cases, Pneumothorax CT, however, demonstrated free air space where tumor was evaluated to be invaded. Remaining one presented the loss of such free air space even by Pneumothorax CT and was made the diagnosis of aortic invasion, which was confirmed by surgicopathological finding. Pneumothorax CT is useful for the diagnosis of ruling out tumor invasion to the aorta. (author)

  13. Diagnosis of gallbladder cancer by imaging techniques. Problems, limitations, and their explanations, especially with ss invasive cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Masao; Onoyama, Hirohiko; Sako, Tatsuo; Ajiki, Tetsuo; Ohara, Sigetsugu; Yamazaki, Iwao; Yamamoto, Masahiro; Saito, Yoichi (Kobe Univ. (Japan). School of Medicine)

    1994-11-01

    The preoperative diagnosis of less than ss depth gallbladder cancer is difficult. Its preoperative diagnosis rate was low (27.5%), and even lower with the presence of concomitant gallstone. In the latter case,the diagnosis rate was particularly low when the stones diameter was greater than 1 cm. Gallstones are frequently associated with macromorphologically invasive type of gallbladder cancer and this may be the reason for the lower diagnostic rate. We compared preoperative diagnosis rate of ultrasonography (US), computed tomography (CT) and drip infusion cholecystography (DIC) for each invasion depth. In US, the preoperative diagnosis rate for m depth invasion was 6/16 (37.5%), pm depth was 1/13 (7.7%), and ss depth was 14/41 (34.1%). In CT, its rate for m depth was 3/11 (27.3%), pm depth was 1/10 (10.0%), and ss depth was 11/37 (29.7%). In DIC, its rate for m depth was 3/11 (27.3%), pm depth was 1/10 (10.0%), and ss was depth 1/23 (4.3%). None of the currently used imaging techniques were very accurate in diagnosing gallbladder cancer. Thus, during preoperative work up, if one discovers a gallbladder full of stones, stones of greater than 1 cm in diameter, thickened gallbladder wall, or a non visualized gallbladder with DIC, gallbladder cancer must be highly suspected. (author).

  14. 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.

  15. Arsenic sulfide inhibits cell migration and invasion of gastric cancer in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Zhang L

    2015-10-01

    Full Text Available Lian Zhang,1 Sungkyoung Kim,1 Wenping Ding,1 Yingying Tong,1 Xiuli Zhang,1 Minggui Pan,2 Siyu Chen1 1Department of Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Oncology and Hematology, Kaiser Permanente Medical Center, Santa Clara, CA, USA Background: We previously showed that arsenic sulfide (As4S4 induced cell cycle arrest and apoptosis in several human solid tumor cell lines, including those of gastric cancer. In this study, we investigated the effect of As4S4 on the migration and invasion of gastric cancer cells both in vitro and in vivo.Methods: The human gastric cancer cell lines AGS and MGC803 were selected as in vitro models. Wound-healing migration assay and Transwell invasion assay were carried out to determine the effects of As4S4 on cell migration and invasion. The expressions of E-cadherin, β-catenin, Sp1, KLF4, and VEGF were measured by Western blotting analysis. The activities of matrix metalloproteinase (MMP-2 and MMP-9 in MGC803 cells were demonstrated by zymography assay. A mouse xenograft model was established by inoculation with MGC803 cells, then intraperitoneal injected with As4S4 for 3 weeks and monitored for body weight and tumor changes. Finally, the inhibition rate of tumor growth was calculated, and the expression of proteins and genes associated with tumor invasion and metastasis in tumor tissues were measured by immunohistochemistry, Western blotting, and real-time polymerase chain reaction assay.Results: As4S4 significantly inhibited the migration and invasion of gastric cancer cell lines. The expression of E-cadherin and KLF4 was upregulated, while the expressions of β-catenin, VEGF, and Sp1 were downregulated following treatment with As4S4. Moreover, the protease activities of MMP-2 and MMP-9 were suppressed by As4S4 in MGC803 cells. Meanwhile, As4S4 effectively suppressed the abilities of tumor growth and

  16. MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion

    Science.gov (United States)

    Vindigni, Carla; Pucci, Angela; Balsamo, Michele; Libro, Rosaliana; Senchenko, Vera; Dmitriev, Alexey; Jacchetti, Emanuela; Cecchini, Marco; Roviello, Franco; Lai, Michele; Broccoli, Vania; Andreazzoli, Massimiliano; Mazzanti, Chiara M.; Angeloni, Debora

    2016-01-01

    The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidation-reduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/undifferentiated, primary human epithelial cancers (gastric and renal). Immunohistochemistry showed MICAL2-positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was 'on' in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, and was turned 'off' upon homing at metastatic sites. In vitro, MICAL2 knock-down resulted in mesenchymal to epithelial transition, reduction of viability, and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. Altogether our data indicate that MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy. PMID:26689989

  17. α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression

    Directory of Open Access Journals (Sweden)

    Kun-Hung Shen

    2014-08-01

    Full Text Available α-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn., was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by α-solanine remains unclear. This study investigates the suppression mechanism of α-solanine on motility of the human prostate cancer cell PC-3. Results show that α-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of α-solanine, cell invasion is markedly suppressed by α-solanine. α-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial-mesenchymal transition (EMT. α-Solanine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2, MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN, but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK, and tissue inhibitor of metalloproteinase-1 (TIMP-1 and TIMP-2. Immunoblotting assays indicate α-solanine is effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K, Akt and ERK. Moreover, α-solanine downregulates oncogenic microRNA-21 (miR-21 and upregulates tumor suppressor miR-138 expression. Taken together, the results suggest that inhibition of PC-3 cell invasion by α-solanine may be, at least in part, through blocking EMT and MMPs expression. α-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates expression of miR-21 and miR-138. These findings suggest an attractive therapeutic potential of α-solanine for suppressing invasion of prostate cancer cell.

  18. 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...... cells are a frequently used model of invasive triple-negative breast cancer, and these cells express low levels of E-cadherin that is mislocalized to cytoplasmic vesicles. MDA-MB-231 cell lines stably expressing wild-type E-cadherin or E-cadherin fused to glutathione S-transferase or green fluorescent...

  19. THE USE OF ORGANOSPARING OPERATIONS IN COMBINED THERAPY FOR PATIENTS WITH INVASIVE SQUAMOUSE PENILE CANCER

    Directory of Open Access Journals (Sweden)

    E. A. Belova

    2014-08-01

    Full Text Available Background. Penis cancer is rare malignant tumor with morbidity 0,1−0,9 on 100 000 male in year. Most patients come to a doctor late, when performance of organosparing treatment is impossible. Organosparing operations associate with high frequency of development of local reccurence as compared with penectomy. Combined method is optimal treatment for patients with invasive penile cancer and provides good long-term results and preservation organ's function.Objectives. to increase of cure effectiveness by performance of organosparing operations into combined treatment.Subjects and methods. The investigation was included 72 patients with invasive squamouse penile cancer. Patients were divided into two groups subject to kind of treatment: I (42 — organosparing operations, II (30 — combined method. Surgical treatment was performing whole of 72 patients: 51 — resection, 12 — circumcision, 3 — local excision. Beam therapy was carrying out to 30 patients.Results. The frequency of relapse in I group was 52,4 %, in II — 13,2 % (p < 0,01. Duration of period without relapse was four times higher in group of combined method — 71,3 ± 13,4 monthes as compared with group of surgical treatment — 17 ± 5,7.Conclusion. The combined method of cure for patients with invasive squamous penile cancer provides good long-term results and preservation of organ's function.

  20. Ligand independent aryl hydrocarbon receptor inhibits lung cancer cell invasion by degradation of Smad4.

    Science.gov (United States)

    Lee, Chen-Chen; Yang, Wen-Hao; Li, Ching-Hao; Cheng, Yu-Wen; Tsai, Chi-Hao; Kang, Jaw-Jou

    2016-07-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Although AhR plays a crucial role in air toxicant-induced carcinogenesis, AhR expression was shown to negatively regulate tumorigenesis. Therefore, in the present study, we investigated the effect of AhR without ligand treatment on cancer invasion in lung cancer cell lines. Lung cancer cells expressing lower levels of AhR showed higher invasion ability (H1299 cells) compared with cells expressing higher levels of AhR (A549 cells). Overexpression of AhR in H1299 cells inhibited the invasion ability. We found that vimentin expression was inhibited in AhR-overexpressing H1299 cells. Additionally, the expression of EMT-related transcriptional factors Snail and ID-1 decreased. Interestingly, we found that Smad4 degradation was induced in AhR-overexpressing H1299 cells. Our data showed that AhR could interact with Jun-activation domain binding protein (Jab1) and Smad4, which may cause degradation of Smad4 by the proteasome. Our data suggest that AhR affects the transforming growth factor-β signaling pathway by inducing Smad4 degradation by the proteasome and suppressing tumor metastasis via epithelial to mesenchymal transition reduction in lung cancer cells. PMID:27060206

  1. THE USE OF ORGANOSPARING OPERATIONS IN COMBINED THERAPY FOR PATIENTS WITH INVASIVE SQUAMOUSE PENILE CANCER

    Directory of Open Access Journals (Sweden)

    E. A. Belova

    2012-01-01

    Full Text Available Background. Penis cancer is rare malignant tumor with morbidity 0,1−0,9 on 100 000 male in year. Most patients come to a doctor late, when performance of organosparing treatment is impossible. Organosparing operations associate with high frequency of development of local reccurence as compared with penectomy. Combined method is optimal treatment for patients with invasive penile cancer and provides good long-term results and preservation organ's function.Objectives. to increase of cure effectiveness by performance of organosparing operations into combined treatment.Subjects and methods. The investigation was included 72 patients with invasive squamouse penile cancer. Patients were divided into two groups subject to kind of treatment: I (42 — organosparing operations, II (30 — combined method. Surgical treatment was performing whole of 72 patients: 51 — resection, 12 — circumcision, 3 — local excision. Beam therapy was carrying out to 30 patients.Results. The frequency of relapse in I group was 52,4 %, in II — 13,2 % (p < 0,01. Duration of period without relapse was four times higher in group of combined method — 71,3 ± 13,4 monthes as compared with group of surgical treatment — 17 ± 5,7.Conclusion. The combined method of cure for patients with invasive squamous penile cancer provides good long-term results and preservation of organ's function.

  2. 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.

  3. 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. PMID:27227989

  4. STAT3: An Anti-Invasive Factor in Colorectal Cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Petrus Rudolf de [Department of Medicine, University of California, San Diego, 9500 Gilman Dr. MC 0663, La Jolla, CA 92093 (United States); Mo, Ji-Hun [Department of Otorhinolaryngology, Dankook University College of Medicine, 16-5 Anseo-dong, Cheonan, Chungcheongnam-do 330-715 (Korea, Republic of); Harris, Alexandra R.; Lee, Jongdae, E-mail: j142lee@ucsd.edu; Raz, Eyal [Department of Medicine, University of California, San Diego, 9500 Gilman Dr. MC 0663, La Jolla, CA 92093 (United States)

    2014-07-03

    Signal Transducer and Activator of Transcription 3 (STAT3) is activated in a majority of cancers, and promotes tumorigenesis and even metastasis through transcriptional activation of its target genes. Recently, we discovered that STAT3 suppresses epithelial-to-mesenchymal transition (EMT) and thus metastasis in a mouse model of colorectal cancer (CRC), while it did not affect the overall tumor burden. Furthermore, we found that STAT3 in intestinal epithelial cells (IEC) suppresses EMT by regulating stability of an EMT inducer, SNAI-1 (Snail-1). Here, STAT3 functions as an adaptor rather than a transcription factor in the post-translational modification of SNAI-1. In this review, we discuss the unexpected and contradictory role of STAT3 in metastasis of CRC and its clinical implications.

  5. VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells

    International Nuclear Information System (INIS)

    It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Western blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. Highlights: ► We report for the first time that VI-14 possesses anti-cancer properties. ► VI-14 weakens the adhesion, migration and invasion of human breast cancer cells. ► VI-14 decreases the activities and expressions of MMP-2/9. ► VI-14 suppresses the phosphorylation levels of the MAPK signaling pathway. ► VI-14 decreases the nuclear levels and the binding ability of NF-κB and AP-1.

  6. MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1.

    Science.gov (United States)

    Jiang, Qian; He, Miao; Ma, Meng-Tao; Wu, Hui-Zhe; Yu, Zhao-Jin; Guan, Shu; Jiang, Long-Yang; Wang, Yan; Zheng, Da-Di; Jin, Feng; Wei, Min-Jie

    2016-03-01

    Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis. PMID:26707142

  7. VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fanni; Li, Chenglin; Zhang, Haiwei; Lu, Zhijian [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Li, Zhiyu; You, Qidong [Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Lu, Na [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Guo, Qinglong, E-mail: anticancer_drug@yahoo.com.cn [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China)

    2012-06-01

    It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Western blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. Highlights: ► We report for the first time that VI-14 possesses anti-cancer properties. ► VI-14 weakens the adhesion, migration and invasion of human breast cancer cells. ► VI-14 decreases the activities and expressions of MMP-2/9. ► VI-14 suppresses the phosphorylation levels of the MAPK signaling pathway. ► VI-14 decreases the nuclear levels and the binding ability of NF-κB and AP-1.

  8. Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells

    International Nuclear Information System (INIS)

    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.

  9. MTA1 promotes proliferation and invasion in human gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Yao Y

    2015-07-01

    Full Text Available Yuan Yao,1 Shuting Feng,1 Mingming Xiao,2 Yan Li,1 Li Yang,1 Jiao Gong1 1Digestive System Department, 2Department of Pathology, The People’s Hospital of Liaoning Province, Shenyang, Liaoning, People’s Republic of China Abstract: Although metastasis-associated protein 1 (MTA1 has been widely li­nked to tumor metastasis, the relevant mechanisms remain to be elucidated, especially in gastric cancer. The aim of this study was to examine whether the MTA1 gene is associated with the process of proliferation and invasion by regulating several molecular targets in gastric cancer. MTA1 expression in 61 gastric cancer tissue and adjacent noncancerous tissues was analyzed by immunohistochemistry. The prognostic value of MTA1 for overall survival and disease-free survival was determined by Kaplan–Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. Furthermore, overexpression of MTA1 in SGC7901 and BGC823 cells promoted cell cycle progression, cell adhesion, and cell invasion. Our study found that MTA1 is overexpressed in gastric cancers, which contributes to malignant cell growth by facilitating cell cycle progression through upregulation of cyclin D1 and accelerates the migration and invasion of human gastric cancer cells by regulating expression of fibronectin and MMP2/MMP9. Taken together, MTA1 was involved in the pathogenesis of gastric cancer and might be a candidate therapeutic target in gastric cancer. Keywords: cell cycle, cell adhesion, migration

  10. Probing Three-dimensional Collective Cancer Invasion with DIGME

    OpenAIRE

    Alobaidi, Amani A.; Sun, Bo

    2016-01-01

    Multicellular migration and pattern formation play important roles in developmental biology, cancer metastasis and wound healing. To understand the collective cell dynamics in three dimensional extracellular matrix (ECM), we have developed a simple and mechanical-based strategy, Diskoid In Geometrically Micropatterned ECM (DIGME). DIGME allows easy engineering of the shape of 3-D tissue organoid, the mesoscale ECM heterogeneity, and the fiber alignment of collagen-based ECM all at the same ti...

  11. The Biological Effect of Hepsin on the Proliferation and Invasion of PC-3 Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Yong Xu; Zhiqiang Fan; Jantao Sun; Ranlu Liu; Weiming Zhao; Chunyu Wang; Ju Zhang

    2006-01-01

    OBJECTIVE Recent studies have shown that hepsin, a type of transmembrane serine protease, is highly upregulated in prostate cancer, but, little is known about its role in progression and invasion of this cancer. We constructed a hepsin-expressing plasmid and transfected it into PC-3 cells to investigate the effect of the hepsin gene on the biological behavior of the PC-3 cells.METHODS Plasmid pHepsin-IRES2 was transfected into prostate cancer PC-3 cells using Fugene6, and the cells with stable hepsin expression were screened and selected with Zeocin (600 mg/L). The hepsin mRNA level was measured by real-time PCR and the growth curve of the PC-3-transfected cells assessed using MTT and BrdU assays. A Boyden chamber was used to examine the difference in invasion and metastases between transfected and non-transfected cells.RESULTS The hepsin mRNA level in pHepsin-IRES2 transfected -PC-3 cells was significantly higher than that found in the control PC-3 cells. While the growth curve of the hepsin gene transfected PC-3 cells showed that there was no significant effect on proliferation, the invasive ability of the pHepsin-IRES2 transfected PC-3 cells, as compared with control cells, was significantly increased (P<0.05).CONCLUSION The results suggest that even though hepsin has no effect on the proliferation of prostate cancer PC-3 cells, it does promote cellular invasion and metastasis.Therefore hepsin may have a role in the development of prostate cancer.

  12. 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.

  13. Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health Initiative.

    Science.gov (United States)

    Adams, Scott V; Shafer, Martin M; Bonner, Matthew R; LaCroix, Andrea Z; Manson, JoAnn E; Meliker, Jaymie R; Neuhouser, Marian L; Newcomb, Polly A

    2016-05-01

    Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993-2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)(2)) less than 25. Results were consistent in both estrogen receptor-positive and estrogen receptor-negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer. PMID:27037269

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

    International Nuclear Information System (INIS)

    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

  15. Cell invasion through basement membrane

    OpenAIRE

    Morrissey, Meghan A; Hagedorn, Elliott J.; Sherwood, David R.

    2013-01-01

    Cell invasion through basement membrane is an essential part of normal development and physiology, and occurs during the pathological progression of human inflammatory diseases and cancer. F-actin-rich membrane protrusions, called invadopodia, have been hypothesized to be the “drill bits” of invasive cells, mediating invasion through the dense, highly cross-linked basement membrane matrix. Though studied in vitro for over 30 y, invadopodia function in vivo has remained elusive. We have recent...

  16. Effects of chitosan nanoparticle-mediated BRAF siRNA interference on invasion and metastasis of gastric cancer cells.

    Science.gov (United States)

    Huo, Jian

    2016-08-01

    To observe the changes in invasion capacity of gastric cancer BGC823 cells after being treated with chitosan-encapsulated BRAF siRNA nanoparticles, and to evaluate the effects of the nanoparticle-mediated BRAF siRNA interference on cell invasion and metastasis, BRAF siRNA was encapsulated with chitosan into nanoparticles sized 350 nm to treat gastric cancer cells. Silencing of BRAF was detected by Western blot and PCR, and cell invasion was observed by the Transwell assay. The nanoparticles significantly downregulated BRAF expression in BGC823 cells (P < 0.01) and inhibited their invasion (P < 0.001). Chitosan nanoparticle-mediated BRAF siRNA interference evidently reduced the invasion capacity of gastric cancers. PMID:25794798

  17. Development of a novel approach for breast cancer prediction and early detection using minimally invasive procedures and molecular analysis: how cytomorphology became a breast cancer risk predictor.

    Science.gov (United States)

    Masood, Shahla

    2015-01-01

    With enhanced public awareness, advances in breast imaging, and emphasis on early breast cancer detection and prevention, more women are seeking consultation to assess the status of their breast health. Risk assessment has become an integral part of established multi-disciplinary breast care, and breast cancer risk reduction interventions have received a great deal of attention. Similarly, interest in identification of high-risk individuals has increased significantly. Atypical proliferative changes in breast epithelial cells are ranked high among various known breast cancer risk factors and, in recent years, have been the subject of several investigations. Breast tissue and fluid in the ductal system provide a rich source of cells and biomarkers that have the potential to aid in the assessment of short-term risk of breast cancer development, and assess responses to interventional prevention efforts. There are three minimally invasive procedures currently being utilized to sample breast tissue in asymptomatic high-risk individuals. These procedures are: fine-needle aspiration biopsy, nipple aspiration fluid, and ductal lavage. In this review article, the merits and limitations of each procedure are presented, and the contribution of cytomorphology and molecular analysis in breast cancer prediction is highlighted. In addition, the role of Masood Cytology Index as a surrogate endpoint biomarker in chemopreventative trials is discussed. PMID:25556774

  18. 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

  19. IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation

    Directory of Open Access Journals (Sweden)

    Li Yijing

    2012-11-01

    Full Text Available Abstract Background IL-1β is a pleiotropic pro-inflammatory cytokine and its up-regulation is closely associated with various cancers including gastrointestinal tumors. However, it remains unclear how IL-1β may contribute to the initiation and development of these inflammation-associated cancers. Here we investigated the role of IL-1β in colon cancer stem cell (CSC development. Methods Using self-renewal assay, soft-agar assay, invasion assay, real-time PCR analysis, immunoblot assay and shRNA knockdown, we determined the effects of IL-1β on cancer stem cell development and epithelial-mesenchymal transition (EMT in human primary colon cancer cells and colon cancer cell line HCT-116. Results We found that IL-1β can increase sphere-forming capability of colon cancer cells in serum-free medium. IL-1β-induced spheres displayed an up-regulation of stemness factor genes (Bmi1 and Nestin and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activator Zeb1 was increased in IL-1β-induced spheres, indicating that there might be a close association between EMT and IL-1β-induced CSC self-renewal. Indeed, IL-1β treatment led to EMT of colon cancer cells with loss of E-cadherin, up-regulation of Zeb1, and gain of the mesenchymal phenotype. Furthermore, shRNA-mediated knockdown of Zeb1 in HCT-116 cells reversed IL-1β-induced EMT and stem cell formation. Conclusion Our findings indicate that IL-1β may promote colon tumor growth and invasion through activation of CSC self-renewal and EMT, and Zeb1 plays a critical role in these two processes. Thus, IL-1β and Zeb1 might be new therapeutic targets against colon cancer stem cells.

  20. The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. ► GPR30 mediates the proliferative effects induced by OHT. ► GPR30 mediates the invasive effects induced by OHT. ► GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17β-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

  1. The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxiaoping61@126.com [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); He, Yin-Yan [Department of Obstetrics and Gynecology, Shanghai First People' s Hospital, Shanghai Jiao Tong University, Shanghai (China)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

  2. Qigesan inhibits migration and invasion of esophageal cancer cells via inducing connexin expression and enhancing gap junction function.

    Science.gov (United States)

    Shi, Huijuan; Shi, Dongxuan; Wu, Yansong; Shen, Qiang; Li, Jing

    2016-09-28

    Qigesan (QGS), a well-known traditional Chinese medicinal formula, has long been used to treat patients with esophageal cancer. However, the anticancer mechanisms of action of QGS remain unknown. This study aims to determine whether QGS regulates gap junction (GJ) function and affects the invasiveness of esophageal cancer cells. Our results demonstrate that QGS markedly inhibits the migration and invasion of esophageal cancer cells in vitro. We further show that QGS enhances the function of GJ in esophageal cancer cells. We therefore hypothesized that enhanced connexin expression leads to enhanced GJ function and inhibition of metastasis. We found that QGS enhances expression of connexin 26 and connexin 43 in esophageal cancer cells. This study suggests that QGS increases GJ function via enhancing the expression of connexins, resulting in reduced esophageal cancer cell migration and invasion. PMID:27345741

  3. Mutant p53 proteins alter cancer cell secretome and tumour microenvironment: Involvement in cancer invasion and metastasis.

    Science.gov (United States)

    Cordani, Marco; Pacchiana, Raffaella; Butera, Giovanna; D'Orazi, Gabriella; Scarpa, Aldo; Donadelli, Massimo

    2016-07-01

    An ever-increasing number of studies highlight the role of mutant p53 proteins in the alteration of cancer cell secretome and in the modification of tumour microenvironment, sustaining an invasive phenotype of cancer cell. The knowledge of the molecular mechanisms underlying the interplay between mutant p53 proteins and the microenvironment is becoming fundamental for the identification of both efficient anticancer therapeutic strategies and novel serum biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells bearing mutant TP53 gene. In particular, we highlight data from available literature, suggesting that mutant p53 proteins are able to (i) alter the secretion of enzymes involved in the modulation of extracellular matrix components; (ii) alter the secretion of inflammatory cytokines; (iii) increase the extracellular acidification; and (iv) regulate the crosstalk between cancer and stromal cells. PMID:27045472

  4. 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.

  5. Endobronchial mucosa invasion predicts survival in patients with small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Pai-Chien Chou

    Full Text Available BACKGROUND: Current staging system for small cell lung cancer (SCLC categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion. METHODS: We studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated. RESULTS: 84% (364/432 of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30-3.10, age (HR, 1.04; 95% CI, 1.03-1.06, and extensive stage (HR, 1.39; 95% CI, 1.06-1.84 were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25-0.42 was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001. Among SCLC patients of either limited (median 180 vs. 460, p<0.0001 or extensive (median 125 vs. 207, p<0.0001 stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively. CONCLUSION: Endobronchial mucosal involvement is an independent prognostic factor for SCLC

  6. Exo70 Isoform Switching upon Epithelial-Mesenchymal Transition Mediates Cancer Cell Invasion

    Science.gov (United States)

    Lu, Hezhe; Liu, Jianglan; Liu, Shujing; Zeng, Jingwen; Ding, Deqiang; Carstens, Russ P.; Cong, Yusheng; Xu, Xiaowei; Guo, Wei

    2014-01-01

    Summary Epithelial-mesenchymal transition (EMT) is an important developmental process hijacked by cancer cells for their dissemination. Here we show that Exo70, a component of the exocyst complex, undergoes isoform switching mediated by ESRP1, a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial isoform of Exo70 affects the levels of key EMT transcriptional regulators such as Snail and ZEB2, and is sufficient to drive the transition to epithelial phenotypes. Differential Exo70 isoforms expression in human tumors correlates with cancer progression, and increased expression of the epithelial isoform of Exo70 inhibits tumor metastasis in mice. At the molecular level, the mesenchymal but not the epithelial isoform of Exo70 interacts with the Arp2/3 complex and stimulates actin polymerization for tumor invasion. Our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for EMT and tumor invasion. PMID:24331928

  7. 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.

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

    International Nuclear Information System (INIS)

    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

  9. Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development

    Science.gov (United States)

    Virtanen, Johannes; Ahonen, Ilmari; Schukov, Hannu-Pekka; Alakurtti, Sami; Purev, Enkhee; Rischer, Heiko; Yli-Kauhaluoma, Jari; Moreira, Vânia M.; Nees, Matthias; Oksman-Caldentey, Kirsi-Marja

    2015-01-01

    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. PMID:25965345

  10. 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

    2015-01-01

    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. PMID:25503107

  11. Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    SUN Bing-sheng; YOU Jian; LI Yue; ZHANG Zhen-fa; WANG Chang-li

    2013-01-01

    Background Osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of malignant tumor.However,the mechanism by which OPN mediates metastasis in non-small cell lung cancer (NSCLC) remains unknown.The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line.Methods Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic human NSCLC cell line (A549).The invasion,proliferation,and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo.The related mechanism was further investigated.Results Interestingly,OPN knockdown significantly suppressed the invasiveness of A549 cells,but had only a minor effect on the cellular migration and proliferation.Moreover,we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA),and led to an obviousinhibition of both in vitro invasion and in vivo lung metastasis of A549 cells (P <0.001).Conclusions Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion,independent of cellular migration and proliferation.OPN could be a new treatment target of NSCLC.

  12. 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.

  13. Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

    Science.gov (United States)

    Matsuda, Yoko; Naito, Zenya; Kawahara, Kiyoko; Nakazawa, Nando; Korc, Murray

    2011-01-01

    Nestin, is a class VI intermediate filament (IF) that is expressed in 30% of pancreatic ductal adenocarcinoma (PDAC) cases, and its expression in PDAC positively correlates with peripancreatic invasion. An expression vector carrying a short hairpin RNA (shRNA) targeting nestin was stably transfected into PANC-1 and PK-45H human pancreatic cancer cells, which express high nestin levels. Alterations in morphology and alignment of actin filaments and α-tubulin were examined by phase-contrast and immunocytochemistry. Effects on cell growth, migration in scratch and Boyden chamber assays, invasion, cell adhesion, and in vivo growth were determined. Differences in mRNA levels were examined by arrays. Nestin shRNA-transfected cells exhibited decreased nestin expression, a sheet-like appearance with tight cell-cell adhesion, increased expression of filamentous F-actin and E-cadherin, and attenuated migration and invasion, both of which were enhanced following nestin re-expression. Expression of α-tubulin, and in vitro cell growth and adhesion were not altered by nestin downregulation, whereas hepatic metastases were decreased. Thus, nestin plays important roles in pancreatic cancer cell migration, invasion and metastasis by selectively modulating the expression of actin and cell adhesion molecules, and may therefore be a novel therapeutic target in PDAC. PMID:21258211

  14. Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity

    Directory of Open Access Journals (Sweden)

    Giovanna Ferrari-Amorotti

    2014-12-01

    Full Text Available Most triple-negative breast cancers (TNBCs exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT, a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1; thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone.

  15. Rap2b promotes proliferation, migration, and invasion of lung cancer cells.

    Science.gov (United States)

    Peng, Yi-Gen; Zhang, Zheng-Qun; Chen, Yan-Bin; Huang, Jian-An

    2016-10-01

    Rap2b, a member of the guanosine triphosphate-binding proteins, is widely up-regulated in many types of tumors. However, the functional role of Rap2b in tumorigenesis of lung cancer remains to be fully elucidated. In this study, we investigated the effect of Rap2b on the lung cancer malignant phenotype, such as cell proliferation and metastasis. We found that Rap2b could promote the abilities of lung cancer cell wound healing, migration, and invasion via increasing matrix metalloproteinase-2 enzyme activity. Furthermore, Rap2b overexpression could increase the phosphorylation level of extracellular signal-regulated protein kinases 1/2. In conclusion, our results suggested that Rap2b may be a potential therapeutic target for lung cancer. PMID:26671640

  16. The Role of Chemokines in Promoting Colorectal Cancer Invasion/Metastasis

    Directory of Open Access Journals (Sweden)

    Yoshiro Itatani

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer-related death worldwide. Although most of the primary CRC can be removed by surgical resection, advanced tumors sometimes show recurrences in distant organs such as the liver, lung, lymph node, bone or peritoneum even after complete resection of the primary tumors. In these advanced and metastatic CRC, it is the tumor-stroma interaction in the tumor microenvironment that often promotes cancer invasion and/or metastasis through chemokine signaling. The tumor microenvironment contains numerous host cells that may suppress or promote cancer aggressiveness. Several types of host-derived myeloid cells reside in the tumor microenvironment, and the recruitment of them is under the control of chemokine signaling. In this review, we focus on the functions of chemokine signaling that may affect tumor immunity by recruiting several types of bone marrow-derived cells (BMDC to the tumor microenvironment of CRC.

  17. Lung cancer diagnosis and staging in the minimally invasive age with increasing demands for tissue analysis

    OpenAIRE

    Folch, Erik; Costa, Daniel B.; Wright, Jeffrey; VanderLaan, Paul A.

    2015-01-01

    The diagnosis and staging of patients with lung cancer in recent decades has increasingly relied on minimally invasive tissue sampling techniques, such as endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS) needle aspiration, transbronchial biopsy, and transthoracic image guided core needle biopsy. These modalities have been shown to have low complication rates, and provide adequate cellular material for pathologic diagnosis and necessary ancillary molecular testing. As an importan...

  18. Frondoside A Suppressive Effects on Lung Cancer Survival, Tumor Growth, Angiogenesis, Invasion, and Metastasis

    OpenAIRE

    Samir Attoub; Kholoud Arafat; An Gélaude; Mahmood Ahmed Al Sultan; Marc Bracke; Peter Collin; Takashi Takahashi; Thomas E Adrian; Olivier De Wever

    2013-01-01

    A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration...

  19. Oncologic Safety of Immediate Breast Reconstruction for Invasive Breast Cancer Patients: A Matched Case Control Study

    OpenAIRE

    Park, Shin-Hoo; Han, Wonshik; Yoo, Tae-Kyung; Lee, Han-Byoel; Jin, Ung Sik; Chang, Hak; Minn, Kyung Won; Noh, Dong-Young

    2016-01-01

    Purpose The purpose of this study was to compare locoregional recurrence-free survival (LRFS) and disease-free survival (DFS) between patients undergoing mastectomy and immediate breast reconstruction (IBR) and those undergoing mastectomy alone. Methods A retrospective review of patients who underwent mastectomy and immediate breast reconstruction for resectable invasive breast cancer between 2002 and 2010 at a single center was conducted. These cases were matched to patients who underwent ma...

  20. Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

    International Nuclear Information System (INIS)

    Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features. In 40 cases of invasive breast cancer, BNIP3 mRNA in situ hybridization was performed on frozen sections with a digoxigenin labeled anti-BNIP3 probe. Paraffin embedded sections of the same specimens were used to determine protein expression of BNIP3, Hypoxia Inducible Factor 1 alpha (HIF-1α) and its downstream targets Glucose Transporter 1 (Glut-1) and Carbonic Anhydrase (CAIX) by immunohistochemistry. BNIP3 mRNA was expressed in 16/40 (40%) of the cases and correlated with BNIP3 protein expression (p = 0.0218). Neither BNIP3 protein nor mRNA expression correlated with expression of HIF-1α expression or its downstream targets. Tumors which showed loss of expression of BNIP3 had significantly more often lymph node metastases (82% vs 39%, p = 0.010) and showed a higher mitotic activity index (p = 0.027). BNIP3 protein expression was often nuclear in normal breast, but cytoplasmic in tumor cells. BNIP3 expression is lost in a significant portion of invasive breast cancers, which is correlated with poor prognostic features such as positive lymph node status and high proliferation, but not with the hypoxic response

  1. 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.

  2. Effect of NCAM-transfection on growth and invasion of a human cancer cell line

    DEFF Research Database (Denmark)

    Edvardsen, K; Bock, E; Jirus, S;

    1997-01-01

    A cDNA encoding the human transmembrane 140 kDa isoform of the neural cell adhesion molecule (NCAM) was transfected into the highly invasive MDA-MB-231 human breast cancer cell line. Transfectants with a homogeneous expression of NCAM showed a restricted capacity for penetration of an artificial ...... of the NCAM-transfected cells. The fact that NCAM expression influences growth regulation attributes a pivotal role to this cell adhesion molecule during ontogenesis and tumor development....

  3. Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

    OpenAIRE

    Konno, Sensuke

    2009-01-01

    Srinivas Rajamahanty, Brandon Louie, Cormac O’Neill, Muhammad Choudhury, Sensuke KonnoDepartment of Urology, New York Medical College, Valhalla, New York, USAAbstract: Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim i...

  4. HPV type distribution in invasive cervical cancers in Italy: pooled analysis of three large studies

    OpenAIRE

    Giorgi Rossi Paolo; Sideri Mario; Carozzi Francesca; Vocaturo Amina; Buonaguro Franco; Tornesello Maria; Burroni Elena; Mariani Luciano; Boveri Sara; Zaffina Leandra; Chini Francesco

    2012-01-01

    Abstract Objective The aim of this study is to describe the prevalence of HPV types in invasive cervical cancers in Italy from 1996 to 2008. Methods A pooled analysis of the three largest case series typed to date was performed. HPV typing was performed on paraffin-embedded slices. Molecular analyses were performed in four laboratories. Multivariate analyses were performed to test the associations between calendar time, age, and geographical area and the proportion of types 16/18. Results Out...

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

    OpenAIRE

    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 det...

  6. The management of BCG failure in non-muscle-invasive bladder cancer: an update

    OpenAIRE

    Zlotta, Alexandre R.; Fleshner, Neil E.; Jewett, Michael A.

    2009-01-01

    Up to 40% of patients with non-muscle-invasive bladder cancer (NMIBC) will fail intravesical bacillus Calmette-Guérin (BCG) therapy. There is unfortunately no current gold standard for salvage intravesical therapy after appropriate BCG treatment. Indeed, outcomes are at best suboptimal. The vast majority of low-grade NMIBC are prone to recur but very rarely progress. Failure after intravesical BCG in these patients is usually superficial and low-grade. At the other end of the spectrum, failur...

  7. Hollow spheroids beyond the invasive margin indicate the malignant potential of colorectal cancer

    OpenAIRE

    Tamura, Koichi; Yokoyama, Shozo; Ieda, Junji; Takifuji, Katsunari; Hotta, Tsukasa; Matsuda, Kenji; Oku, Yoshimasa; Watanabe, Takashi; Nasu, Toru; Kiriyama, Shigehisa; YAMAMOTO, Naoyuki; "Nakamura, Yasushi"; Shively, John E.; Yamaue, Hiroki

    2011-01-01

    Objective Tumour budding formed by histologically undifferentiated cancer cells beyond the border of the tumour margin is associated with lymph node metastasis. However, hollow tumour nests, a possible histologically advanced phenotype of tumour budding, have not been discussed. We examined whether hollow spheroids exist beyond the border of the invasive margin and are associated with metastasis and prognosis. Moreover, we suggest that carcinoembryonic antigen-related cell adhesion molecule 1...

  8. Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

    OpenAIRE

    MATSUDA, YOKO; Naito, Zenya; KAWAHARA, KIYOKO; Nakazawa, Nando; Korc, Murray; Ishiwata, Toshiyuki

    2011-01-01

    Nestin, is a class VI intermediate filament (IF) that is expressed in 30% of pancreatic ductal adenocarcinoma (PDAC) cases, and its expression in PDAC positively correlates with peripancreatic invasion. An expression vector carrying a short hairpin RNA (shRNA) targeting nestin was stably transfected into PANC-1 and PK-45H human pancreatic cancer cells, which express high nestin levels. Alterations in morphology and alignment of actin filaments and α-tubulin were examined by phase-contrast and...

  9. Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

    Directory of Open Access Journals (Sweden)

    de Weger Roel A

    2009-06-01

    Full Text Available Abstract Background Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3 is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features. Methods In 40 cases of invasive breast cancer, BNIP3 mRNA in situ hybridization was performed on frozen sections with a digoxigenin labeled anti-BNIP3 probe. Paraffin embedded sections of the same specimens were used to determine protein expression of BNIP3, Hypoxia Inducible Factor 1 alpha (HIF-1α and its downstream targets Glucose Transporter 1 (Glut-1 and Carbonic Anhydrase (CAIX by immunohistochemistry. Results BNIP3 mRNA was expressed in 16/40 (40% of the cases and correlated with BNIP3 protein expression (p = 0.0218. Neither BNIP3 protein nor mRNA expression correlated with expression of HIF-1α expression or its downstream targets. Tumors which showed loss of expression of BNIP3 had significantly more often lymph node metastases (82% vs 39%, p = 0.010 and showed a higher mitotic activity index (p = 0.027. BNIP3 protein expression was often nuclear in normal breast, but cytoplasmic in tumor cells. Conclusion BNIP3 expression is lost in a significant portion of invasive breast cancers, which is correlated with poor prognostic features such as positive lymph node status and high proliferation, but not with the hypoxic response.

  10. Leptin promotes breast cancer cell migration and invasion via IL-18 expression and secretion.

    Science.gov (United States)

    Li, Kuangfa; Wei, Lan; Huang, Yunxiu; Wu, Yang; Su, Min; Pang, Xueli; Wang, Nian; Ji, Feihu; Zhong, Changli; Chen, Tingmei

    2016-06-01

    In recent years, crosstalk between tumor microenvironment and cancer cells have received increasing attention. Accumulating research data suggests that leptin, a key adipokine secreted from adipocytes, plays important roles in breast cancer development. In our study, the effects of leptin on polarization of tumor-associated macrophages (TAMs) and promotion of the invasiveness of tumor cells were investigated. THP1 cells were used to differentiate M2 polarization macrophages. After stimulated by leptin, we established a co-culture system of tumor cells and macrophages to evaluate the function of leptin-induced macrophages in the migration and invasion of breast cancer cells. The gene and protein expressions were analyzed and the underlying mechanisms were evaluated. Moreover, pathological human specimens, and xenografts in nude mice, were detected to strengthen the in vitro results. Leptin elevated the expression of an array of cytokines in TAMs, IL-18 was the most increased, with an activation of the NF-κB/NF-κB1 signalling pathway. Additionally, after treated with leptin, TAMs significantly promoted the migration and invasion of breast cancer cells. However, these effects of leptin were abolished by the co-incubation of Bay11‑7082, a pharmacological NF-κB inhibitor. Leptin also directly stimulated IL-18 expression in breast cancer cells, which, differently, was via the PI3K/AKT-ATF-2 signaling pathway. In vivo studies showed that malignant breast carcinoma exhibited strong higher expression of Leptin, IL-8, and TAMs markers. Xenograft tumor-bearing mouse models showed that leptin significantly increased tumor volume, enhanced lung metastases, and increased expression of IL-8 and TAM markers, which were abolished by depletion of macrophages by clophosome-clodronate liposomes (CCL). Leptin could induce IL-18 expression both in TAMs and breast cancer cells. Leptin-induced IL-18 expression was regulated via NF-κB/NF-κB1 signaling in TAMs, while via PI3K

  11. Autoimmunity against p53 predicts invasive cancer with poor survival in patients with an ovarian mass

    OpenAIRE

    Vogl, F D; M. Frey; Kreienberg, R; Runnebaum, I B

    2000-01-01

    Serum autoantibodies against the p53 protein (p53 AAb) were analysed with a newly developed enzyme-linked immunosorbent assay (ELISA) based on highly purified and renatured p53. In a hospital-based cohort study, preoperative sera from 113 patients with ovarian cancer, 15 patients with borderline tumours and 117 patients with benign tumours of the ovaries were studied. The prevalence of p53 AAb in patients with invasive cancer was 19% (21/113). No p53 AAb were found in patients with borderline...

  12. Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization

    OpenAIRE

    Driffort, Virginie; Gillet, Ludovic; Bon, Emeline; Marionneau-Lambot, Séverine; Oullier, Thibauld; Joulin, Virginie; Collin, Christine; Pagès, Jean-Christophe; Jourdan, Marie-Lise; Chevalier, Stéphan; Bougnoux, Philippe; Le Guennec, Jean-Yves; Besson, Pierre; Roger, Sébastien

    2014-01-01

    Background NaV1.5 voltage-gated sodium channels are abnormally expressed in breast tumours and their expression level is associated with metastatic occurrence and patients’ death. In breast cancer cells, NaV1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness. Findings In this study, we showed that the extinction of NaV1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodepressed mice (NMRI ...

  13. Investigational Study of Mesenchymal Stem Cells on Lung Cancer Cell Proliferation and Invasion

    Directory of Open Access Journals (Sweden)

    Mei LI

    2015-11-01

    Full Text Available Background and objective Mesenchymal stem cells (MSC are adult stem cells derived from mesoderm. Evidence has shown that MSC could migrate towards tumor tissue and differentiate into tumor associated fibroblast in tumor microenvironment, which influences tumor growth and metastasis. However, the reports of MSC in non-small cell lung cancer (NSCLC are few and controversial. The aim of this study is to explore the chemotaxis of MSC towards NSCLC and to test the effects of MSC on the proliferation and invasion ability of NSCLC. Methods Transwell assay was used to test MSC and NSCLC migration and invasion, and Thymidine incorporation assay was adopted to measure NSCLC cells proliferation. The expression of interleukin-6 (IL-6, insulinlike growth factor (IGF-1, vascular endothelial growth factor (VEGF and dickkopf-related protein 1 (DKK1 of MSCs were determined by real time PCR. A549 lung cancer xenograft animal tumor model was set up to evaluate the MSC effect in vivo. Results Lung cancer cells could attract MSC tropism. MSC conditioned medium favored lung cancer cell proliferation and lung cancer cells stimulated the expression of IL-6, IGF-1, VEGF and DKK1 on MSCs. In vivo animal study showed that the tumor with MSC injection grew much faster compared to control group. Conclusion MSCs could migrate towards NSCLC cells and favor tumor growth. In turn, NSCLC cells could stimulate the overexpression of cytokines on MSCs which are essential for the tumor growth.

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

    International Nuclear Information System (INIS)

    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 GABAA 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

  15. 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.

  16. LSD1-mediated epigenetic modification contributes to ovarian cancer cell migration and invasion.

    Science.gov (United States)

    Li, Yuanxia; Wan, Xiaolei; Wei, Ye; Liu, Xiuwen; Lai, Wensheng; Zhang, Liuping; Jin, Jie; Wu, Chaoyang; Shao, Qixiang; Shao, Genbao; Lin, Qiong

    2016-06-01

    Lysine-specific demethylase 1 (LSD1) has been implicated in the process of tumor progression at various steps, but its role in epithelial-messenchymal transition (EMT) and the migration of ovarian cancer cells remains obscure. In this study, we demonstrated the effect of LSD1 on ovarian cancer cell migration and the regulatory role of LSD1 in the expression of EMT markers. Inhibition of LSD1 expression impaired the migration and invasion of HO8910 ovarian cancer cells. In contrast, overexpression of LSD1 enhanced the cell migration and invasion of HO8910 cells. Mechanistic analyses showed that LSD1 promoted cell migration through induction of N-cadherin, vimentin, MMP-2 and inhibition of E-cadherin. Furthermore, LSD1 interacted with the promoter of E-cadherin and demethylated histone H3 lysine 4 (H3K4) at this region, downregulated E-cadherin expression, and consequently enhanced ovarian cancer cell migration. These data indicate that LSD1 acts as an epigenetic regulator of EMT and contributes to the metastasis of ovarian cancer. PMID:27109588

  17. Risk Factors of Submucosal or Lymphovascular Invasion in Early Gastric Cancer <2 cm.

    Science.gov (United States)

    Choi, Yu Yi; Kim, Su Jin; Choi, Cheol Woong; Kang, Dae Hwan; Kim, Hyung Wook; Park, Su Bum; Nam, Hyeong Seok

    2016-05-01

    Although prediction of submucosal (SM) or lymphovascular (LV) invasion is important before endoscopic resection of early gastric cancer (EGC), it can only be confirmed following endoscopic resection. After endoscopic resection, patients with SM or LV invasion may require additional surgery due to high risk of lymph node metastasis.We conducted a retrospective study to identify risk factors for SM or LV invasion before endoscopic submucosal dissection (ESD) of EGC. Between January 2009 and May 2014, we reviewed the data of patients with EGC who met the absolute indications for ESD before procedure: well and/or moderately differentiated adenocarcinomas, tumors ≤ 2 cm in length and absence of ulcer or ulcer-scar.During study period, a total of 308 lesions in 297 patients were included. SM or LV invasion was detected in 34 lesions (34/308, 11.0%). Multivariate analysis revealed that a moderately differentiated adenocarcinoma (odds ratio [OR] 4.157, P = 0.000) and location of the stomach (the upper and middle third; OR 3.100, P = 0.008) were significant risk factors for SM or LV invasion.Careful consideration of endoscopic treatment decision might be necessary for the patients with a moderately differentiated adenocarcinoma and EGC located on the upper and middle third of the stomach. PMID:27258528

  18. Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells

    OpenAIRE

    Shulan Zhang; Masao Iwamori; Changzhi Wang; Yifei Wang; Chuan Liu; Song Gao; Lili Gao; Bei Lin; Limei Yan

    2010-01-01

    Lewis (y) antigen is a difucosylated oligosaccharide present on the plasma membrane, and its overexpression is frequently found in human cancers and has been shown to be associated with poor prognosis. Our previous studies have shown that Lewis (y) antigen plays a positive role in the process of invasion and metastasis of ovarian cancer cells. However, the mechanisms by which Lewis (y) antigen enhances the invasion and tumor metastasis are still unknown. In this study, we established a stable...

  19. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling

    OpenAIRE

    Sliva, D; Jedinak, A; Kawasaki, J.; Harvey, K; Slivova, V

    2008-01-01

    The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer ce...

  20. LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells

    OpenAIRE

    Chakrabarti Ratna; Ottman Richard; Tapia Tenekua

    2011-01-01

    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-M...

  1. Breast conserving therapy for early state invasive cancer and ductal carcinoma in-situ

    International Nuclear Information System (INIS)

    Purpose/Objective: To discuss a number of clinical, pathologic, and treatment related issues in the management of early stage invasive breast cancer and ductal carcinoma in situ. In the last 10 years, prospective randomized trials as well as retrospective series have established the role of conservative surgery and radiation in the treatment of early stage invasive breast cancer. This course will focus on some of the unresolved issues in breast conservation therapy including patient selection, the extent of surgery in the breast, and the importance of microscopic resection margins. The impact of adjuvant systemic therapy (chemotherapy or tamoxifen) on breast recurrence and complications will be presented. The role of neoadjuvant chemotherapy will be reviewed. Factors predicting for an increased risk of recurrence in the treated breast will be presented. The diagnosis and treatment of a breast recurrence will be discussed. Treatment options for ductal carcinoma in situ (DCIS) including observation, radiation and mastectomy. Results from prospective randomized trials as well as retrospective series will be presented in an attempt to identify appropriate treatment strategies for the different clinical presentations and histologic subtypes of DCIS. As cost effective strategies are developed, the role of conservative surgery and radiation in minimally invasive breast cancer and DCIS must be defined

  2. Downregulation of microRNA-206 promotes invasion and angiogenesis of triple negative breast cancer.

    Science.gov (United States)

    Liang, Zhongxing; Bian, Xuehai; Shim, Hyunsuk

    2016-08-26

    Triple negative breast tumors don't respond to Tamoxifen and Herceptin, two of the most effective medications for treating breast cancer. Additionally, triple negative breast cancer (TNBC) intrinsically resists or will eventually acquire resistance to chemotherapy. The purpose of this study is to understand better the molecular basis of TNBC as well as develop new therapeutic strategies against it. Here, we analyzed miRNA-206 expression levels in breast cancer cell lines and tissues. In addition, we investigated whether miR-206 mimics inhibited TNBC tumor invasion and angiogenesis. The results showed that miR-206 was downregulated in TNBC compared to non-TNBC cell lines and tissues. Additionally, the decreased levels of miR-206 were inversely consistent with expression levels of VEGF. Furthermore, the forced expression of miR-206 in the mimic-transfected TNBC cells downregulated VEGF, MAPK3, and SOX9 expression levels. The miR-206 mimics inhibited TNBC breast cell invasion and angiogenesis. These findings demonstrate for the first time the involvement of miRNA-206 in TNBC invasion and angiogenesis and suggest that miR-206 may be an efficient agent for therapy of TNBC. PMID:27318091

  3. Predicting recurrence of non-muscle-invasive bladder cancer after transurethral resection

    Directory of Open Access Journals (Sweden)

    Haris Ðug

    2016-02-01

    Full Text Available Aim To determine clinical prognostic factors and their impact on the risk of recurrence of newly discovered non-muscle-invasive bladder cancer. Methods The study included 120 patients of both sexes aged 45-80 years with newly discovered non-muscle-invasive bladder cancer. All the patients were treated surgically by transurethral electro resection (TUER. The outcome of patients with and without recurrence was followed at intervals of three months after surgery, the total of two years. For monitoring the probability of early recurrence the criteria of the European Organization for Research and Treatment of Cancer (EORTC were used. Results The average age of the patients was 65.9 years, 79 (79.2% males and 21 (20.8% females. The total of 67 (55.8% patients had a recurrence during the period of monitoring. The average time to the first and fourth recurrence was 15.4 and 23.9 months, respectively. Numbers of tumors and a degree of invasion had a significant prognostic impact on the risk of recurrence. The EORTC score was a highly significant predictor of recurrence (OR=1.237; p<0.001. Conclusion Based on available clinical and pathological prognostic factors and by stratification of patients into three disease risk groups it is possible to predict the possibility of disease. Individual approach and recommendations for the treatment using EORTC risk tables should improve the quality of treatment.

  4. MR imaging of gastric cancer in vitro: accuracy of invasion depth diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Chiho; Naganawa, Shinji; Ishigaki, Takeo [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya (Japan); Kumada, Hisashi; Miura, Shunichi [Toyohashi Municipal Hospital, Toyohashi (Japan)

    2004-09-01

    The purpose of this study was to evaluate the accuracy of grading cancerous invasion of the gastric wall in vitro using magnetic resonance (MR) imaging. Twelve specimens of gastric carcinoma were examined at 1.5-T using a small, loop surface coil. They were imaged within 2 days of fixation in formalin. The field of view was 30 mm; the matrix size was 256 x 256, and the section thickness was 2 mm. T1-weighted, T2-weighted and short inversion time inversion recovery (STIR) images were obtained. Two radiologists evaluated the MR images independently, and in discrepant cases, consensus was obtained through discussion. Findings on MR images were compared with histopathologic findings. All T1-weighted, T2-weighted and STIR images depicted the normal gastric wall as consisting of six layers. STIR images depicted normal six layers most clearly. Histologically, the cancerous invasion was found to extend into the mucosa in 4 of the 12 specimens, the submucosa in 3, the muscularis propria in 2, the subserosa in 2 and the serosa in 1. The grading by MR imaging matched the histopathologic findings for all 12 tumors. The overall accuracy was 100%. Thus, MR imaging in vitro was sufficiently accurate for grading cancerous invasion of the gastric wall. (orig.)

  5. Utility of CT during arteriography in superselective transarterial chemoembolization for invasive bladder cancer

    International Nuclear Information System (INIS)

    The aims of this study were to assess the effectiveness of CT during arteriography (CTA) in superselective transarterial chemoembolization (TACE) for invasive bladder cancer, and to report preliminary results of superselective TACE. Angiography was performed in 20 patients with invasive bladder cancer, using a combined CT-Angiography system. Of the 20 tumors, 19 were T3, one was T2. The vesical arteries were selected using a 3F microcatheter, and perfusion was confirmed using CTA. TACE was performed after administrating 40 to 100 mg of cisplatin, with and without gelatin sponge particles. The effects of TACE were assessed by surgery or a combination of cystoscopy and CT in 15 cases. The vesical arteries were successfully selected in 18 of 20 patients. In 16 small tumors, the tumor stain was clearly depicted on CTA. In two large tumors, the vascular supply was identified as involving multiple arteries. One case showed complete remission, six showed partial remission, and eight showed no change. Complications included mild local pain around the perineum during TACE, and transient nausea in some patients. CTA may be useful in superselective TACE for invasive bladder cancer, and may contribute to effective treatment of bladder tumors. (author)

  6. Enhanced Expression of Keratinocyte Growth Factor and Its Receptor Correlates with Venous Invasion in Pancreatic Cancer

    Science.gov (United States)

    Cho, Kazumitsu; Ishiwata, Toshiyuki; Uchida, Eiji; Nakazawa, Nando; Korc, Murray; Naito, Zenya; Tajiri, Takashi

    2007-01-01

    Keratinocyte growth factor (KGF) and KGF receptor (KGFR) have been implicated in cancer growth as well as tissue development and repair. In this study, we examined whether KGF and KGFR have a role in human pancreatic ductal adenocarcinoma (PDAC). KGFR mRNA was expressed in eight pancreatic cancer cell lines, whereas the KGF mRNA was detected in seven of the cell lines and was absent in MIA PaCa-2 cells. KGFR and KGF immunoreactivity were localized in the cancer cells in 41.5 and 34.0% of patients, respectively. There was a significant correlation between KGFR or KGF immunoreactivity and venous invasion and a significant correlation between the presence of both markers and venous invasion, vascular endothelial growth factor (VEGF)-A expression, and poor prognosis. Exogenous KGF increased VEGF-A expression and release in MIA PaCa-2 cells, and PANC-1 cells stably transfected to overexpress KGF-exhibited increased VEGF-A expression. Moreover, short hairpin-KGFR transfection in MIA PaCa-2 cells reduced the stimulatory effect of exogenous KGF on VEGF-A expression. Short hairpin-KGF transfection in KLM-1 cells reduced VEGF-A expression in the cells. KGFR and KGF may act to promote venous invasion and tumor angiogenesis in PDAC, raising the possibility that they may serve as novel therapeutic targets in anti-angiogenic strategies in PDAC. PMID:17525264

  7. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    International Nuclear Information System (INIS)

    Highlights: ► This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. ► Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. ► TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. ► TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  8. Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Naoko; Mugikura, Shunji; Takasawa, Chiaki; Shimauchi, Akiko; Ota, Hideki; Takase, Kei; Takahashi, Shoki [Tohoku University Graduate School of Medicine, Department of Diagnostic Radiology, Sendai (Japan); Miyashita, Minoru; Ishida, Takanori [Tohoku University Graduate School of Medicine, Department of Surgical Oncology, Sendai (Japan); Kasajima, Atsuko [Tohoku University Graduate School of Medicine, Department of Pathology, Sendai (Japan); Kodama, Tetsuya [Tohoku University Graduate School of Medicine, Department of Biomedical Engineering, Sendai (Japan)

    2016-02-15

    To evaluate whether visual assessment of T2-weighted imaging (T2WI) or an apparent diffusion coefficient (ADC) could predict lymphovascular invasion (LVI) status in cases with clinically node-negative invasive breast cancer. One hundred and thirty-six patients with 136 lesions underwent MRI. Visual assessment of T2WI, tumour-ADC, peritumoral maximum-ADC and the peritumour-tumour ADC ratio (the ratio between them) were compared with LVI status of surgical specimens. No significant relationship was found between LVI and T2WI. Tumour-ADC was significantly lower in the LVI-positive (n = 77, 896 ± 148 x 10{sup -6} mm{sup 2}/s) than the LVI-negative group (n = 59, 1002 ± 163 x 10{sup -6} mm{sup 2}/s; p < 0.0001). Peritumoral maximum-ADC was significantly higher in the LVI-positive (1805 ± 355 x 10{sup -6} mm{sup 2}/s) than the LVI-negative group (1625 ± 346 x 10{sup -6} mm{sup 2}/s; p = 0.0003). Peritumour-tumour ADC ratio was significantly higher in the LVI-positive (2.05 ± 0.46) than the LVI-negative group (1.65 ± 0.40; p < 0.0001). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of the peritumour-tumour ADC ratio was the highest (0.81). The most effective threshold for the peritumour-tumour ADC ratio was 1.84, and the sensitivity, specificity, positive predictive value and negative predictive value were 77 % (59/77), 76 % (45/59), 81 % (59/73) and 71 % (45/63), respectively. We suggest that the peritumour-tumour ADC ratio can assist in predicting LVI status on preoperative imaging. (orig.)

  9. Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer

    International Nuclear Information System (INIS)

    To evaluate whether visual assessment of T2-weighted imaging (T2WI) or an apparent diffusion coefficient (ADC) could predict lymphovascular invasion (LVI) status in cases with clinically node-negative invasive breast cancer. One hundred and thirty-six patients with 136 lesions underwent MRI. Visual assessment of T2WI, tumour-ADC, peritumoral maximum-ADC and the peritumour-tumour ADC ratio (the ratio between them) were compared with LVI status of surgical specimens. No significant relationship was found between LVI and T2WI. Tumour-ADC was significantly lower in the LVI-positive (n = 77, 896 ± 148 x 10-6 mm2/s) than the LVI-negative group (n = 59, 1002 ± 163 x 10-6 mm2/s; p < 0.0001). Peritumoral maximum-ADC was significantly higher in the LVI-positive (1805 ± 355 x 10-6 mm2/s) than the LVI-negative group (1625 ± 346 x 10-6 mm2/s; p = 0.0003). Peritumour-tumour ADC ratio was significantly higher in the LVI-positive (2.05 ± 0.46) than the LVI-negative group (1.65 ± 0.40; p < 0.0001). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of the peritumour-tumour ADC ratio was the highest (0.81). The most effective threshold for the peritumour-tumour ADC ratio was 1.84, and the sensitivity, specificity, positive predictive value and negative predictive value were 77 % (59/77), 76 % (45/59), 81 % (59/73) and 71 % (45/63), respectively. We suggest that the peritumour-tumour ADC ratio can assist in predicting LVI status on preoperative imaging. (orig.)

  10. Expression of Rab25 correlates with the invasion and metastasis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Chuanwu Cao; Chenhui Lu; Jichong Xu; Jiaxing Zhang; Jun Zhang; Maoquan Li

    2013-01-01

    The objective of this study was to determine the expression of the important vesicle traffickingregulating factor Rab25 in human gastric cancer tissues,to analyze the correlation between Rab25 protein expression with gastric cancer occurrence and development,and to discuss the correlation of Rab25 protein expression with gastric cancer cell metastasis.The overall aim was to provide experimental evidence that can be used to design future biological treatments of human gastric cancer.Human gastric cancer tissue and the adjacent normal gastric tissue were surgically removed,and immunohistochemistry and Western blotting were used to detect Rab25 protein expression.The correlation between Rab25 protein expression with the development and pathological characteristics of gastric cancer was analyzed.Using RNAi,Rab25 expression was reduced in the gastric cancer cell line MGC80-3,and the changes in MGC80-3 cell invasiveness were then monitored.Immunohistochemistry showed that the Rab25 protein expression rates were 78.21% and 23.08% in gastric carcinoma and the adjacent normal gastric tissue,respectively.Immunohistochemistry and Western blot results showed that Rab25 protein expression in gastric cancer was significantly higher than in adjacent normal gastric tissues (P<0.01).Less differentiated gastric cancer cells had higher expression of Rab25 protein (P<0.01).Gastric carcinomas from patients with a late pathological stage (Ⅲ-Ⅳ) had significantly higher Rab25 protein expression than early stage (Ⅰ-Ⅱ) patients (P<0.01).Gastric carcinomas from patients with lymph node metastasis had significantly higher Rab25 protein expression than lymph node metastasis-free patients (P<0.01).Gastric carcinomas from patients with distant metastases had significantly higher Rab25 protein expression than the distant metastasis-negative patents (P<0.01).Rab25 protein expression in gastric cancer was not affected by the patients' sex,age,or tumor size (P>0.05).MGC80

  11. MUC4 potentiates invasion and metastasis of pancreatic cancer cells through stabilization of fibroblast growth factor receptor 1

    OpenAIRE

    Rachagani, Satyanarayana; Muzafar A Macha; Moorthy P Ponnusamy; Haridas, Dhanya; Kaur, Sukhwinder; Jain, Maneesh; Batra, Surinder K.

    2012-01-01

    MUC4 is a type-1 transmembrane mucin differentially expressed in multiple cancers and has previously been shown to potentiate progression and metastasis of pancreatic cancer. In this study, we investigated the molecular mechanisms associated with the MUC4-induced invasion and metastasis in pancreatic cancer. Stable silencing of MUC4 in multiple pancreatic cancer cells resulted in the downregulation of N-cadherin and its interacting partner fibroblast growth factor receptor 1 (FGFR1) through d...

  12. Interleukin-17-induced EMT promotes lung cancer cell migration and invasion via NF-κB/ZEB1 signal pathway

    OpenAIRE

    Gu, Kuo; Li, Ming-Ming; Shen, Jing; Liu, Fang; Cao, Jing-Yan; Jin, Shi; Yu, Yan

    2015-01-01

    Inflammatory cytokine interleukin-17 (IL-17) has been associated with the risk of progressive cancers including lung cancer. However, it remains unclear how IL-17 may contribute to the invasion and development of these inflammation-associated malignancies. Here we aimed to investigate the role of IL-17 in lung cancer cell development. Epithelial-mesenchymal transition (EMT) has been recently proposed as a developmental process which plays an important role in cancer progression and metastases...

  13. Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia.

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    Junhui Li

    Full Text Available BACKGROUND: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion. METHODOLOGY/PRINCIPAL FINDINGS: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5, Myelin P0 protein (MPP, NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2 were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively. The integrated optical density (IOD of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019, while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively. The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000. CONCLUSIONS/SIGNIFICANCE: Nerve damage and regeneration occur simultaneously in the tumor microenvironment of pancreatic cancer patients with hyperglycemia; the simultaneous occurrence may aggravate the process of perineural invasion. The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.

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

    International Nuclear Information System (INIS)

    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. LRP-1 promotes cancer cell invasion by supporting ERK and inhibiting JNK signaling pathways.

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    Benoit Langlois

    Full Text Available BACKGROUND: The low-density lipoprotein receptor-related protein-1 (LRP-1 is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated. The lack of mechanistic insights into the intracellular signaling networks downstream of LRP-1 has prevented the understanding of its contribution towards cancer. METHODOLOGY/PRINCIPAL FINDINGS: Through a short-hairpin RNA-mediated silencing approach, we identified LRP-1 as a main regulator of ERK and JNK signaling in a tumor cell context. Co-immunoprecipitation experiments revealed that LRP-1 constitutes an intracellular docking site for MAPK containing complexes. By using pharmacological agents, constitutively active and dominant-negative kinases, we demonstrated that LRP-1 maintains malignant cells in an adhesive state that is favorable for invasion by activating ERK and inhibiting JNK. We further demonstrated that the LRP-1-dependent regulation of MAPK signaling organizes the cytoskeletal architecture and mediates adhesive complex turnover in cancer cells. Moreover, we found that LRP-1 is tethered to the actin network and to focal adhesion sites and controls ERK and JNK targeting to talin-rich structures. CONCLUSIONS: We identified ERK and JNK as the main molecular relays by which LRP-1 regulates focal adhesion disassembly of malignant cells to support invasion.

  16. 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.

  17. URG11 promotes gastric cancer growth and invasion by activation of β-catenin signalling pathway

    Science.gov (United States)

    Du, Rui; Xia, Lin; Sun, Shiren; Lian, Zhaorui; Zou, Xue; Gao, Juan; Xie, Huahong; Fan, Rui; Song, Jiugang; Li, Xiaohua; Liu, Jie; Fan, Daiming

    2010-01-01

    Abstract Upregulated gene 11 (URG11), a new gene upregulated by Heptatitis B Virus X protein (HBx), was previously shown to activate β-catenin and promote hepatocellular growth and tumourigenesis. Although the oncogenic role of URG11 in the development of hepatocellular carcinoma has been well documented, its relevance to other human malignancies and the underlying molecular mechanisms remain largely unknown. Here we reported a novel function of URG11 to promote gastric cancer growth and metastasis. URG11 was found to be highly expressed in gastric cancer tissues compared with adjacent nontumourous ones by immunohistochemical staining and western blot. Knockdown of URG11 expression by small interfering RNA (siRNA) effectively attenuated the proliferation, anchorage-independent growth, invasiveness and metastatic potential of gastric cancer cells. URG11 inhibition led to decreased expression of β-catenin and its nuclear accumulation in gastric cancer cells and extensive costaining between URG11 and β-catenin was observed in gastric cancer tissues. Transient transfection assays with the β-catenin promoter showed that it was inhibited by URG11-specific small inhibitory RNA. Moreover, suppression of endogenous URG11 expression results in decreased activation of β-catenin/TCF and its downstream effector genes, cyclinD1 and membrane type 1 matrix metallopeptidase (MT1-MMP), which are known to be involved in cell proliferation and invasion, respectively. Taken together, our data suggest that URG11 contributes to gastric cancer growth and metastasis at least partially through activation of β-catenin signalling pathway. These findings also propose a promising target for gene therapy in gastric cancer. PMID:19413886

  18. Knockdown of Long Noncoding RNA GHET1 Inhibits Cell Proliferation and Invasion of Colorectal Cancer.

    Science.gov (United States)

    Zhou, Jianyu; Li, Xiaorong; Wu, Meirong; Lin, Changwei; Guo, Yihang; Tian, Buning

    2016-01-01

    Emerging evidence has identified the vital role of long noncoding RNAs (lncRNAs) in the development of colorectal cancer. In this study, we aimed to investigate the role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in colorectal cancer. We analyzed the expression of GHET1 in colorectal cancer (CRC) tissues by using ISH. We found that GHET1 expression was significantly increased in the CRC samples compared with adjacent tissues. Furthermore, the cancer tissues had higher GHET1 mRNA levels than their matched adjacent tissues. GHET1 expression was also significantly increased in the CRC cell lines compared with human normal colon epithelial cells. Downregulation of GHET1 mediated by shRNA suppressed the proliferation, cell cycle arrest, migration, and invasion of colorectal cancer cells in vitro. In addition, inhibition of GHET1 reversed the epithelial-mesenchymal transition in colorectal cancer cell lines. Taken together, our results suggest the potential use of GHET1 as a therapeutic target of colorectal cancer. PMID:27131316

  19. Nicotine Induced Lung Cancer Cells Epithelial-mesenchymal Transition 
and Promote Its Vitro Invasion Potential

    Directory of Open Access Journals (Sweden)

    Yanxu HOU

    2016-04-01

    Full Text Available Background and objective Our previous study found that nicotine could induce lung cancer cell epithelial-mesenchymal transition (EMT. The aim of this study is to explore the relationship between nicotine-induced EMT and lung cancer invasion and metastasis. Methods Real-time PCR and Western blot were used to detect the expression changes of EMT-related markers, E-cadherin and Vimentin, in A549 lung cancer cells treated with nicotine; The transposition of β-catenin protein expression was determined by immunofluorescence; Scratch test and Transwell invasion assay were used to detect the effects of nicotine on lung cancer cell migration and invasion. Results Nicotine can significantly down-regulate the expressional level of E-cadherin mRNA and protein of A549 cells in a manner of dose and time-dependent (P<0.01, P<0.01; Nicotine can significantly up-regulate the expressional level of Vimentin mRNA and protein of A549 cells in a manner of dose and time-dependent (P<0.01, P<0.01; Immunofluorescence results showed that β-catenin protein was significantly transfered to nucleus; Scratch test and Transwell assay showed that Nicotine could remarkably increase the migration and invasion potential of lung cancer cells (P<0.01, P<0.01. Conclusion Nicotine can induce cancer cells EMT, and promote the invasion and metastasis ability of lung cancer cells.

  20. Diffusion-Weighted Magnetic Resonance Imaging of Endometrial Cancer: Differentiation from Benign Endometrial Lesions and Preoperative Assessment of Myometrial Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, M.; Matsuzaki, K.; Nishitani, H. (Dept. of Radiology, Univ. of Tokushima, Tokushima (Japan))

    2009-10-15

    Background: Uterine endometrial cancer is the most common gynecologic malignancy, and benign endometrial hyperplasia or polyps should be differentiated from endometrial cancer. In evaluating endometrial cancer on magnetic resonance imaging (MRI), the assessment of the depth of myometrial invasion is important because it closely correlates with the patient's prognosis. Purpose: To verify the feasibility of diffusion-weighted magnetic resonance imaging (DWI) to distinguish benign and malignant endometrial lesions, and to evaluate myometrial invasion of endometrial cancer. Material and Methods: Sixty-seven endometrial lesions including 45 cancers and 22 benign lesions (hyperplasia and polyps) were evaluated by DWI with apparent diffusion coefficient (ADC) measurement. The staging accuracies of DWI and gadolinium-enhanced T1-weighted images in the assessment of myometrial invasion were evaluated in 33 patients with endometrial cancer. Results: The ADC values (x10-3 mm2/s) in cancer and benign lesions were 0.84+-0.19 and 1.58+-0.36, respectively (P<0.01). The staging accuracy (superficial or deep myometrial invasion) was 94% for DWI and 88% for gadolinium-enhanced T1-weighted images. Coexisting adenomyosis and infiltrative myometrial invasion caused staging errors on gadolinium-enhanced T1-weighted images, whereas DWI could demonstrate the tumor extent correctly. Conclusion: DWI provides helpful information in evaluating benign and malignant endometrial lesions.

  1. Diffusion-Weighted Magnetic Resonance Imaging of Endometrial Cancer: Differentiation from Benign Endometrial Lesions and Preoperative Assessment of Myometrial Invasion

    International Nuclear Information System (INIS)

    Background: Uterine endometrial cancer is the most common gynecologic malignancy, and benign endometrial hyperplasia or polyps should be differentiated from endometrial cancer. In evaluating endometrial cancer on magnetic resonance imaging (MRI), the assessment of the depth of myometrial invasion is important because it closely correlates with the patient's prognosis. Purpose: To verify the feasibility of diffusion-weighted magnetic resonance imaging (DWI) to distinguish benign and malignant endometrial lesions, and to evaluate myometrial invasion of endometrial cancer. Material and Methods: Sixty-seven endometrial lesions including 45 cancers and 22 benign lesions (hyperplasia and polyps) were evaluated by DWI with apparent diffusion coefficient (ADC) measurement. The staging accuracies of DWI and gadolinium-enhanced T1-weighted images in the assessment of myometrial invasion were evaluated in 33 patients with endometrial cancer. Results: The ADC values (x10-3 mm2/s) in cancer and benign lesions were 0.84±0.19 and 1.58±0.36, respectively (P<0.01). The staging accuracy (superficial or deep myometrial invasion) was 94% for DWI and 88% for gadolinium-enhanced T1-weighted images. Coexisting adenomyosis and infiltrative myometrial invasion caused staging errors on gadolinium-enhanced T1-weighted images, whereas DWI could demonstrate the tumor extent correctly. Conclusion: DWI provides helpful information in evaluating benign and malignant endometrial lesions

  2. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    International Nuclear Information System (INIS)

    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

  3. 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.

  4. Finasteride inhibits human prostate cancer cell invasion through MMP2 and MMP9 downregulation.

    Directory of Open Access Journals (Sweden)

    Andrei Moroz

    Full Text Available INTRODUCTION: The use of the 5-alpha reductase inhibitors (5-ARIs finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in normal human and tumoral prostatic cell lines. MATERIALS AND METHODS: RWPE-1, LNCaP, PC3 and DU145 cells were cultivated to 60% confluence and exposed for different periods to either 10 µM or 50 µM finasteride that was diluted in culture medium. The conditioned media were collected and concentrated, and MMP2 and MMP9 activities and TIMP-1 and TIMP-2 protein expression were determined. Cell viability, migration and invasion were analyzed, and the remaining cell extracts were submitted to androgen receptor (AR detection by western blotting techniques. Experiments were carried out in triplicate. RESULTS: Cell viability was not significantly affected by finasteride exposure. Finasteride significantly downregulated MMP2 and MMP9 activities in RWPE-1 and PC3 cells and MMP2 in DU145 cells. TIMP-2 expression in RWPE-1 cells was upregulated after exposure. The cell invasion of all four tested cell lines was inhibited by exposure to 50 µM of finasteride, and migration inhibition only occurred for RWPE-1 and LNCaP cells. AR was expressed by LNCaP, RWPE-1 and PC3 cells. CONCLUSIONS: Although the debate on the higher incidence of high-grade prostate cancer among 5-ARI-treated patients remains, our findings indicate that finasteride may attenuate tumor aggressiveness and invasion, which could vary depending on the androgen responsiveness of a patient's prostate cells.

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

    International Nuclear Information System (INIS)

    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 E2, 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.

  6. Hypoxia regulates Toll-like receptor-9 expression and invasive function in human brain cancer cells in vitro

    Science.gov (United States)

    SANDHOLM, JOUKO; TUOMELA, JOHANNA; KAUPPILA, JOONAS H.; HARRIS, KEVIN W.; GRAVES, DAVID; SELANDER, KATRI S.

    2014-01-01

    Toll-like receptor-9 (TLR9) is a cellular DNA sensor of the innate immune system. TLR9 is widely expressed in a number of tumors, including brain cancer; however, little is known regarding its regulation and involvement in cancer pathophysiology. The present study demonstrated that hypoxia upregulates and downregulates TLR9 expression in human brain cancer cells in vitro, in a cell-specific manner. In addition, hypoxia-induced TLR9 upregulation was associated with hypoxia-induced invasion; however, such invasion was not detected in cells where hypoxia had suppressed TLR9 expression. Furthermore, suppression of TLR9 expression through TLR9 siRNA resulted in an upregulation of matrix metalloproteinase (MMP)-2, -9 and -13 and tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) mRNA, and a decreased invasion of cells in normoxia, in a cell-specific manner. In cells where hypoxia induced TLR9 expression, TLR9 expression and invasion were reduced by TLR9 siRNA. The decreased invasion observed in hypoxia was associated with the decreased expression of the MMPs and a concomitant increase in TIMP-3 expression. In conclusion, hypoxia regulates the invasion of brain cancer cells in vitro in a TLR9-dependent manner, which is considered to be associated with a complex expression pattern of TLR9-regulated mediators and inhibitors of invasion. PMID:24959259

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

    International Nuclear Information System (INIS)

    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

  8. HIC1 attenuates invasion and metastasis by inhibiting the IL-6/STAT3 signalling pathway in human pancreatic cancer.

    Science.gov (United States)

    Hu, Bin; Zhang, Kundong; Li, Shaobo; Li, Hao; Yan, Zhaowen; Huang, Li; Wu, Jianghong; Han, Xiao; Jiang, Weiliang; Mulatibieke, Tunike; Zheng, Lin; Wan, Rong; Wang, Xingpeng; Hu, Guoyong

    2016-07-01

    Hypermethylated in cancer 1 (HIC1) is a tumour suppressor gene that is frequently deleted or epigenetically silenced in many human cancers. However, the molecular function of HIC1 in pancreatic cancer has not been fully elucidated, especially in cancer invasion and metastasis. We aimed to clarify the clinical relevance of HIC1 and human pancreatic cancer and the mechanism of its effect on invasion and metastasis .HIC1 was downregulated in pancreatic cancer patient cancer tissue and pancreatic cancer cell lines. A tissue microarray analysis demonstrated that negative HIC1 expression predicted advanced pathological stages and worse patient survival. In addition, HIC1 inhibited the invasion and metastasis of pancreatic cancer cells both in vitro and in vivo. Finally, HIC1 repressed the expression of STAT3 target genes, including c-Myc, VEGF, CyclinD1, MMP2 and MMP9, by binding and interacting with STAT3 to impede its DNA-binding ability but without affecting the protein levels of STAT3 and p-STAT3. Therefore, HIC1 appears to function as a STAT3 inhibitor and may be a promising target for cancer research and for the development of an optimal treatment approach for pancreatic cancer. PMID:27085461

  9. miR-136 suppresses tumor invasion and metastasis by targeting RASAL2 in triple-negative breast cancer

    Science.gov (United States)

    YAN, MEISI; LI, XIAOBO; TONG, DANDAN; HAN, CHANGSONG; ZHAO, RAN; HE, YAN; JIN, XIAOMING

    2016-01-01

    MicroRNAs play an important role in the regulation of cancer migration, invasion and metastasis. Patients with triple-negative breast cancer (TNBC) have a high incidence of early relapse and metastasis; however, the molecular basis for metastasis and recurrence in these individuals remains largely unknown. Herein, we demonstrate that miR-136 is an anti-invasive microRNA in TNBC and suppresses mesenchymal invasion and metastasis. Our results demonstrated that miR-136 was downregulated in TNBC and negative correlated with the WHO grades. However, RASAL2 was identified as a functional target of miR-136, and was overexpressed in TNBC and correlates with pathological grades. Moreover, overexpression of RASAL2 in a breast cancer cell line rescued miR-136-mediated cell migration and invasion. In conclusion, these results indicate that the miR-136/RASAL2/MET axis act as a suppressor of TNBC metastasis. PMID:27108696

  10. Knockdown of OLA1, a regulator of oxidative stress response, inhibits motility and invasion of breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Jia-wei ZHANG; Valentina RUBIO; Shu ZHENG; Zheng-zheng SHI

    2009-01-01

    To explore the role of a novel Obg-like ATPase 1 (OLA1) in cancer metastasis, small interference RNA (siRNA) was used to knockdown the protein, and the cells were subjected to in vitro cell migration and invasion assays. Knockdown of OLA1 significantly inhibited cell migration and invasion in breast cancer cell line MDA-MB-231. The knockdown caused no changes in cell growth but affected ROS production. In wound-healing assays, decreased ROS in OLA1-knockdown cells were in situ asso-ciated with the cells' decreased motile morphology. Further, treatment of N-acetylcysteine, a general ROS scavenger, blunted the motility and invasiveness of MDA-MB-231 cells, similar to the effect of OLA1-knockdown. These results suggest that knock-down of OLA1 inhibits breast cancer cell migration and invasion through a mechanism that involves the modulation of intracel-lular ROS levels.

  11. 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. PMID:21102519

  12. Minimally invasive esophagectomy for esophageal cancer in the People's Republic of China: an overview

    Directory of Open Access Journals (Sweden)

    Zhu C

    2013-03-01

    Full Text Available Chengchu Zhu,1 Ketao Jin2 1Department of Cardiothoracic Surgery, 2Department of Surgical Oncology, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang, People's Republic of China Abstract: Since its introduction in the People's Republic of China in 1992, minimally invasive esophagectomy (MIE has shown the classical advantages of minimally invasive surgery over its open counterpart. Like all pioneers of the technique, cardiothoracic surgeons in the People's Republic of China claim that MIE has a lower risk of pulmonary infection, faster recovery, a shorter hospital stay, and a more rapid return to daily activities than open esophagectomy, while offering the same functional and oncologic results. There has been burgeoning interest in MIE in the People's Republic of China since 1995. The last decade has witnessed nationwide growth in the application of MIE and yielded a significant amount of scientific data in support of its clinical merits and advantages. However, no prospective randomized controlled trials have actually investigated the benefits of MIE in the People's Republic of China. Here we review the current data and state of the art MIE treatment for esophageal cancer in the People's Republic of China. Keywords: esophagectomy, minimally invasive esophagectomy, esophageal cancer, review

  13. Myoferlin depletion in breast cancer cells promotes mesenchymal to epithelial shape change and stalls invasion.

    Directory of Open Access Journals (Sweden)

    Ruth Li

    Full Text Available Myoferlin (MYOF is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode protein that regulates spermatic membrane fusion, which underlies the amoeboid-like movements of its sperm. Studies in muscle and endothelial cells have reported on the role of myoferlin in membrane repair, endocytosis, myoblast fusion, and the proper expression of various plasma membrane receptors. In this study, using an in vitro human breast cancer cell model, we demonstrate that myoferlin is abundantly expressed in invasive breast tumor cells. Depletion of MYOF using lentiviral-driven shRNA expression revealed that MDA-MB-231 cells reverted to an epithelial morphology, suggesting at least some features of mesenchymal to epithelial transition (MET. These observations were confirmed by the down-regulation of some mesenchymal cell markers (e.g., fibronectin and vimentin and coordinate up-regulation of the E-cadherin epithelial marker. Cell invasion assays using Boyden chambers showed that loss of MYOF led to a significant diminution in invasion through Matrigel or type I collagen, while cell migration was unaffected. PCR array and screening of serum-free culture supernatants from shRNA(MYOF transduced MDA-MB-231 cells indicated a significant reduction in the steady-state levels of several matrix metalloproteinases. These data when considered in toto suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF.

  14. Advanced Glycation End-Products Enhance Lung Cancer Cell Invasion and Migration

    Science.gov (United States)

    Hsia, Te-Chun; Yin, Mei-Chin; Mong, Mei-Chin

    2016-01-01

    Effects of carboxymethyllysine (CML) and pentosidine, two advanced glycation end-products (AGEs), upon invasion and migration in A549 and Calu-6 cells, two non-small cell lung cancer (NSCLC) cell lines were examined. CML or pentosidine at 1, 2, 4, 8 or 16 μmol/L were added into cells. Proliferation, invasion and migration were measured. CML or pentosidine at 4–16 μmol/L promoted invasion and migration in both cell lines, and increased the production of reactive oxygen species, tumor necrosis factor-α, interleukin-6 and transforming growth factor-β1. CML or pentosidine at 2–16 μmol/L up-regulated the protein expression of AGE receptor, p47phox, intercellular adhesion molecule-1 and fibronectin in test NSCLC cells. Matrix metalloproteinase-2 protein expression in A549 and Calu-6 cells was increased by CML or pentosidine at 4–16 μmol/L. These two AGEs at 2–16 μmol/L enhanced nuclear factor κ-B (NF-κ B) p65 protein expression and p38 phosphorylation in A549 cells. However, CML or pentosidine at 4–16 μmol/L up-regulated NF-κB p65 and p-p38 protein expression in Calu-6 cells. These findings suggest that CML and pentosidine, by promoting the invasion, migration and production of associated factors, benefit NSCLC metastasis. PMID:27517907

  15. [Grape seed proanthocyanidins inhibits the invasion and migration of A549 lung cancer cells].

    Science.gov (United States)

    Zhou, Yehan; Ye, Xiufeng; Shi, Yao; Wang, Ke; Wan, Dan

    2016-02-01

    Objective To explore the effect of grape seed proanthocyanidins (GSPs) on the invasion and migration of A549 lung cancer cells and the underlying mechanism. Methods Trypan blue dye exclusion assay was used to determine the cytotoxic effect of varying doses of GSPs on the BEAS-2B normal human pulmonary epithelial cells. After treated with 0, 10, 20, 40, 80 μg/mL GSP, the proliferation of A549 cells was detected by MTT assay; the invasion and migration of A549 cells were determined by Transwell(TM) assay and scratch wound assay, respectively. The levels of epithelial growth factor receptor (EGFR), E-cadherin, N-cadherin in A549 cells treated with GSPs were detected by Western blotting. Results (0-40) μg/mL GSPs had no significant toxic effect on BEAS-2B cells, while 80 μg/mL GSPs had significant cytotoxicity to BEAS-2B cells. The proliferation of A549 cells was significantly inhibited within limited dosage in a dose-dependent manner, and the abilities of invasion and migration of A549 cells were also inhibited. Western blotting showed that the expression of EGFR and N-cadherin decreased, while E-cadherin increased after GSPs treatment. Conclusion GSPs could inhibit the abilities of proliferation, invasion and migration of A549 cells, which might be related to the dow-regulation of EGFR and N-cadherin and the up-regulation of E-cadherin. PMID:26927375

  16. Current status of surgical treatment of gastric cancer in the era of minimally invasive surgery in China: Opportunity and challenge.

    Science.gov (United States)

    Zhao, En-Hao; Ling, Tian-Long; Cao, Hui

    2016-04-01

    Gastric cancer is one of the most common cancers in China. In the past decade, with the developments in surgical instruments and technologies, minimally invasive surgery has rapidly become an accepted treatment for gastric cancer in China. Many Chinese surgeons and researchers have contributed to the rapid evolution of minimally invasive surgery for gastric cancer. Their efforts have transformed into unique laparoscopic technique, workshops, academic communications, education and international communications in China. Meanwhile, many retrospective comparative trials and randomized controlled trials have revealed the advantages in minimally invasive surgery for gastric cancer. However, multicenter randomized controlled trials are still needed to delineate significantly quantifiable differences between laparoscopic and open gastrectomy. With more and more experience has accumulated, laparoscopic gastrectomy has been performed on older and overweight patients. Moreover, advanced minimally invasive techniques, such as modified laparoscopic spleen-preserving splenic hilum lymphadenectomy, various laparoscopic gastric reconstruction methods and robotic gastrectomy have been developed. It seems that China owns the potential to keep up with her neighbor, Japan and Korea, to become one of leading countries utilizing minimally invasive surgery for gastric cancer. PMID:26889972

  17. Solitary pulmonary nodule and {sup 18}F-FDG PET/CT. Part 1: epidemiology, morphological evaluation and cancer probability

    Energy Technology Data Exchange (ETDEWEB)

    Mosmann, Marcos Pretto; Borba, Marcelle Alves; Macedo, Francisco Pires Negromonte; Liguori, Adriano de Araujo Lima; Villarim Neto, Arthur, E-mail: mosmann@gmail.com [Liga Norte Riograndense Contra o Cancer, Natal, RN (Brazil); Lima, Kenio Costa de [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Programa de Pos-Graduacao em Saude Coletiva

    2016-01-15

    Solitary pulmonary nodule corresponds to a common radiographic finding, which is frequently detected incidentally. The investigation of this entity remains complex, since characteristics of benign and malignant processes overlap in the differential diagnosis. Currently, many strategies are available to evaluate solitary pulmonary nodules with the main objective of characterizing benign lesions as best as possible, while avoiding to expose patients to the risks inherent to invasive methods, besides correctly detecting cases of lung cancer so as the potential curative treatment is not delayed. This first part of the study focuses on the epidemiology, the morphological evaluation and the methods to determine the likelihood of cancer in cases of indeterminate solitary pulmonary nodule. (author)

  18. Solitary pulmonary nodule and 18F-FDG PET/CT. Part 1: epidemiology, morphological evaluation and cancer probability

    International Nuclear Information System (INIS)

    Solitary pulmonary nodule corresponds to a common radiographic finding, which is frequently detected incidentally. The investigation of this entity remains complex, since characteristics of benign and malignant processes overlap in the differential diagnosis. Currently, many strategies are available to evaluate solitary pulmonary nodules with the main objective of characterizing benign lesions as best as possible, while avoiding to expose patients to the risks inherent to invasive methods, besides correctly detecting cases of lung cancer so as the potential curative treatment is not delayed. This first part of the study focuses on the epidemiology, the morphological evaluation and the methods to determine the likelihood of cancer in cases of indeterminate solitary pulmonary nodule. (author)

  19. 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; Chen, Chu; Van Den Berg, David J; Wu, Anna H; Pike, Malcolm C; Ness, Roberta B; Moysich, Kirsten; Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M; Chang-Claude, Jenny; Wang-Gohrke, Shan; Goodman, Marc T; Lurie, Galina; Thompson, Pamela J; Carney, Michael E; Hogdall, Estrid; Kjaer, Susanne Kruger; Hogdall, Claus; Goode, Ellen L; Cunningham, Julie M; Fridley, Brooke L; Vierkant, Robert A; Berchuck, Andrew; Moorman, Patricia G; Schildkraut, Joellen M; Palmieri, Rachel T; Cramer, Daniel W; Terry, Kathryn L; Yang, Hannah P; Garcia-Closas, Montserrat; Chanock, Stephen; Lissowska, Jolanta; Song, Honglin; Pharoah, Paul D P; Shah, Mitul; Perkins, Barbara; McGuire, Valerie; Whittemore, Alice S; Di Cioccio, Richard A; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Ziogas, Argyrios; Brewster, Wendy; Anton-Culver, Hoda; Pearce, Celeste Leigh

    2010-01-01

    We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls......, 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...... containing, nuclear envelope 1 (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies...

  20. Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion

    International Nuclear Information System (INIS)

    Highlights: ► Neu3 is as one of the sialidases and regulates cell surface functions. ► A Neu3-specific siRNA inhibited prostrate cancer cell invasion and migration. ► The Neu3-specific siRNA inhibited prostate cancer metastasis in mice. ► 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 decreased expressions of MMP-2 and MMP-9 at the mRNA and protein levels. Taken together, the present

  1. 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

  2. A novel circular invasion assay mimics in vivo invasive behavior of cancer cell lines and distinguishes single-cell motility in vitro

    International Nuclear Information System (INIS)

    Classical in vitro wound-healing assays and other techniques designed to study cell migration and invasion have been used for many years to elucidate the various mechanisms associated with metastasis. However, many of these methods are limited in their ability to achieve reproducible, quantitative results that translate well in vivo. Such techniques are also commonly unable to elucidate single-cell motility mechanisms, an important factor to be considered when studying dissemination. Therefore, we developed and applied a novel in vitro circular invasion assay (CIA) in order to bridge the translational gap between in vitro and in vivo findings, and to distinguish between different modes of invasion. Our method is a modified version of a standard circular wound-healing assay with an added matrix barrier component (Matrigel™), which better mimics those physiological conditions present in vivo. We examined 3 cancer cell lines (MCF-7, SCOV-3, and MDA-MB-231), each with a different established degree of aggressiveness, to test our assay's ability to detect diverse levels of invasiveness. Percent wound closure (or invasion) was measured using time-lapse microscopy and advanced image analysis techniques. We also applied the CIA technique to DLD-1 cells in the presence of lysophosphatidic acid (LPA), a bioactive lipid that was recently shown to stimulate cancer cell colony dispersal into single migratory cells, in order to validate our method's ability to detect collective and individual motility. CIA method was found to be highly reproducible, with negligible levels of variance measured. It successfully detected the anticipated low, moderate, and high levels of invasion that correspond to in vivo findings for cell lines tested. It also captured that DLD-1 cells exhibit individual migration upon LPA stimulation, and collective behavior in its absence. Given its ability to both determine pseudo-realistic invasive cell behavior in vitro and capture subtle

  3. Expression of glucosylceramide synthase in invasive ductal breast cancer may be correlated with high estrogen receptor status and low HER-2 status

    OpenAIRE

    Liu, Jiannan; Sun, Ping; Sun, Yuan; Liu, Aina; You, Dong; Jiang, Fenge; Sun, Yuping

    2014-01-01

    Abstract Background and objectives Breast cancer is one of the most common causes of cancer-related deaths in women worldwide. Studies on glucosylceramide synthase (GCS) activity suggest that this enzyme has a role in the development of multidrug resistance in many cancer cells. However, few studies have shown the expression of GCS in invasive ductal breast cancer and breast intraductal proliferative lesions. Methods In total, 196 samples from patients with invasive ductal breast cancer and 6...

  4. Time-to-administration in postoperative chemotherapy for colorectal cancer: does minimally-invasive surgery help?

    Science.gov (United States)

    Amore Bonapasta, Stefano; Checcacci, Paolo; Guerra, Francesco; Mirasolo, Vita M; Moraldi, Luca; Ferrara, Angelo; Annecchiarico, Mario; Coratti, Andrea

    2016-06-01

    The optimal delay in the start of chemotherapy following rectal cancer surgery has not yet been identified. However, postponed adjuvant therapy has been proven to be connected with a significant survival detriment. We aimed to investigate whether the time to initiation of adjuvant treatment can be influenced by the application of minimally invasive surgery rather than traditional open surgery. By comprehensively evaluating the available inherent literature, several factors appear to be associated with delayed postoperative chemotherapy. Some of them are strictly related to surgical short-term outcomes. Laparoscopy results in shortened length of hospital stay, reduced surgical morbidity and lower rate of wound infection compared to conventional surgery. Probably due to such advantages, the application of minimally-invasive surgery to treat rectal malignancies seems to impact favorably the possibility to start adjuvant chemotherapy within an adequate timeframe following surgical resection, with potential improvement in patient survival. PMID:26976732

  5. Effects of Curcumin on Invasion and Metastasis in the Human Cervical Cancer Cells Caski

    Institute of Scientific and Technical Information of China (English)

    Fang XU; Xiao-ling MU; Jing ZHAO

    2009-01-01

    Objective: To explore the effects of curcumin on invasion and metastasis in the human cervical cancer cells Caski.Methods: Caski cells were treated with 10, 25, 50μmol/L curcumin for 24, 48, 72 h. Proliferation of Caski cells was measured with MTT assay. When treated with 50μmol/L curcumin for 72 h, the expressions of MMP-2, MT1-MMP and NF-κB of cells were detected by Western-blot, and invasion and metastasis of Caski cells were evaluated with transwell chamber.Results: After being treated with 10μmol/L, 25μmol/L, 50μmol/L curcumin for 24, 48 and 72 h, the proliferation of Caski cells was inhibited in a dose-and time-dependent manner. The expression of MMP-2, MT1-MMP and NF-κB were decreased when being treated with 50μmol/L curcumin for 72 h. After treatment with 50μmol/L curcumin, in invasion assay, the number of cells in curcumin treated group to migrate to filter coated with Matrigel was reduced compared with control group(P<0.05). Meanwhile, in migration assay, the number of cells in curcumin treated group to migrate to filter was also decreased compared with control group (P<0.05).Conclusion: Curcumin could affect the invasion and metastasis of the human cervical cancer cells Caski. Inhibiting the expression of MMP-2, MT1-MMP and NF-κB was probably one of its molecular mechanisms.

  6. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Dharmawardhane Suranganie F

    2005-04-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. Results Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive properties to basal lamina, but SUM 149 showed a marked increase in adhesion to collagen I. In vitro haptotaxis assays demonstrate that SUM 149 was less invasive, while wound healing assays show a less in vitro migratory phenotype for SUM 149 cells relative to SUM 102 cells. We also demonstrate a role for Rho and E-cadherin in the unique invasive phenotype of IBC. Immunoblotting reveals higher E-cadherin and RhoA expression in the IBC cell line but similar RhoC expression. Rhodamine phalloidin staining demonstrates increased formation of actin stress fibers and larger focal adhesions in SUM 149 relative to the SUM 102 cell line. Conclusion The observed unique actin and cellular architecture as well as the invasive and adhesive responses to the extracellular matrix of SUM 149 IBC cells suggest that the preference of IBC cells for connective tissue, possibly a mediator important for the vasculogenic mimicry via tubulogenesis seen in IBC pathological specimens. Overexpression of E-cadherin and RhoA may contribute to passive dissemination of IBC by promoting cell-cell adhesion and actin cytoskeletal structures that maintain tissue integrity. Therefore, we believe that these findings indicate a passive metastatic mechanism by which IBC cells invade the circulatory system as tumor emboli rather than by active migratory mechanisms.

  7. Alternate estrogen receptors promote invasion of inflammatory breast cancer cells via non-genomic signaling.

    Directory of Open Access Journals (Sweden)

    Kazufumi Ohshiro

    Full Text Available Although Inflammatory Breast Cancer (IBC is a rare and an aggressive type of locally advanced breast cancer with a generally worst prognosis, little work has been done in identifying the status of non-genomic signaling in the invasiveness of IBC. The present study was performed to explore the status of non-genomic signaling as affected by various estrogenic and anti-estrogenic agents in IBC cell lines SUM149 and SUM190. We have identified the presence of estrogen receptor α (ERα variant, ERα36 in SUM149 and SUM190 cells. This variant as well as ERβ was present in a substantial concentration in IBC cells. The treatment with estradiol (E2, anti-estrogenic agents 4-hydroxytamoxifen and ICI 182780, ERβ specific ligand DPN and GPR30 agonist G1 led to a rapid activation of p-ERK1/2, suggesting the involvement of ERα36, ERβ and GPR30 in the non-genomic signaling pathway in these cells. We also found a substantial increase in the cell migration and invasiveness of SUM149 cells upon the treatment with these ligands. Both basal and ligand-induced migration and invasiveness of SUM149 cells were drastically reduced in the presence of MEK inhibitor U0126, implicating that the phosphorylation of ERK1/2 by MEK is involved in the observed motility and invasiveness of IBC cells. We also provide evidence for the upregulation of p-ERK1/2 through immunostaining in IBC patient samples. These findings suggest a role of non-genomic signaling through the activation of p-ERK1/2 in the hormonal dependence of IBC by a combination of estrogen receptors. These findings only explain the failure of traditional anti-estrogen therapies in ER-positive IBC which induces the non-genomic signaling, but also opens newer avenues for design of modified therapies targeting these estrogen receptors.

  8. Pepper seed extract suppresses invasion and migration of human breast cancer cells.

    Science.gov (United States)

    Kim, Hyeon-A; Kim, Min-Sook; Kim, Sang-Hyun; Kim, Yoo Kyeong

    2014-01-01

    This study was performed to determine the antimetastatic activities of chili pepper seed on human breast cancer cells. The water extract of chili pepper seeds was prepared and it contained a substantial amount of phenols (131.12 mg%) and no capsaicinoids. Pepper seed extract (PSE) suppressed the proliferation of MDA-MB-231 and MCF-7 cells at the concentration of 10, 25, and 50 μg/ml (MDA-MB-231: IC50 = 20.1 μg/ml, MCF-7: IC50 = 14.7 μg/ml). PSE increased the expression level of E-cadherin up to 1.2-fold of the control in MCF-7 cells. PSE also decreased the secretion of matrix metalloproteinase (MMP)-2 and MMP-9 in MDA-MB-231 and MCF-7 cells at the concentration of 25 and 50 μg/ml. PSE treatment significantly suppressed the invasion of MDA-MB-231 and MCF-7 cells in a dose-dependent manner. The motility of cancer cells was apparently retarded in the wound healing assay by the PSE treatment. Although our data collectively demonstrate that PSE inhibits invasion and migration of breast cancer cells, further study is needed to identify specific mechanisms and bioactive components contributing to antimetastatic effects of chili pepper seed. PMID:24341783

  9. 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.

  10. Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

    Institute of Scientific and Technical Information of China (English)

    Suvi Tuulia Avoranta; Eija Annika Korkeila; Kari Juhani Syrj(a)nen; Seppo Olavi Pyrh(o)nen; Jari Toivo Tapio Sundstr(o)m

    2012-01-01

    AIM:To investigate the prognostic value of CD44 variant 6 (CD44v6),a membranous adhesion molecule,in rectal cancer.METHODS:Altogether,210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT,n =90),long-course (chemo) RT (n =53) or surgery alone (n =71) were studied with immunohistochemistry for CD44v6.The extent and intensity of membranous and cytoplasmic CD44v6 staining,and the intratumoral membranous staining pattern,were analyzed.RESULTS:Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases.In 59% of the tumors with membranous CD44v6 expression,the staining pattern in the invasive front was determined as "front-positive" and in 41% as "front-negative".The latter pattern was associated with narrower circumferential margin (P =0.01),infiltrative growth pattern (P < 0.001),and shorter disease-free survival in univariate survival analysis (P =0.022) when compared to the "front-positive" tumors.CONCLUSION:The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.

  11. Pristimerin inhibits proliferation, migration and invasion, and induces apoptosis in HCT-116 colorectal cancer cells.

    Science.gov (United States)

    Yousef, Bashir A; Hassan, Hozeifa M; Guerram, Mounia; Hamdi, Aida M; Wang, Bin; Zhang, Lu-Yong; Jiang, Zhen-Zhou

    2016-04-01

    Colorectal cancer (CRC) is one of the world's most common cancers with a high mortality rate mainly due to metastasis. Our previous study showed that pristimerin had potent antitumor activities against human CRC cells. In the present study, we further evaluated pristimerin anti-tumor and anti-metastatic properties. MTT assay, Hoechst staining, Annexin V/PI double staining, reactive oxygen species (ROS) measurements were used to assess pristimerin cytotoxicity and apoptotic-inducing effects on HCT-116 cells. Wound healing assay and Transwell assay were used to estimate pristimerin anti-migration and anti-invasion activities on CRC cells. Meanwhile, HCT-116 xenograft model applied for investigating in vivo antitumor activities. Our results showed that pristimerin mediated in vitro HCT-116 cell death, through generation of intracellular ROS and apoptosis induction. Tumor volumes and weights measurements, pathological analysis and Tunnel assay proved that pristimerin inhibited in vivo HCT-116 xenografts growth. Pristimerin was also able to limit CRC invasion and metastasis. It caused downregulation of PI3K/AKT/mTOR pathway and its subsequent downstream p70S6K and E4-BP1 proteins. Collectively, pristimerin exerted both in vitro and in vivo cytotoxic and anti-metastatic effects on HCT-116 cells, suggesting that pristimerin has potential as a new anticancer drug for treatment of colon cancer. PMID:27044819

  12. Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells

    International Nuclear Information System (INIS)

    Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells. Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The in vitro invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells. Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the in vitro invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the in vitro angiogenesis of cancer cells in a dose-dependent manner. These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells in vitro, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer

  13. Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer

    Science.gov (United States)

    Sadeghi, Neda; Salazar, Guillermo; Shapiro, Edan; Ahn, Jennifer; Lipsky, Michael; Lin, James; Hruby, Greg W.; Badani, Ketan K.; Petrylak, Daniel P.; Benson, Mitchell C.; Donovan, Michael J.; Comper, Wayne D.; McKiernan, James M.

    2016-01-01

    Purpose The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. Experimental Design The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2. Results In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560–0.788), ERG (AUC 0.785 (CI:0.680–0.890), PCA3 (AUC 0.681 (CI:0.567–0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600–0.888), and TMPRSS2 (AUC 0.637 (CI:0.519–0.754). Conclusion This pilot study suggests that urinary EVs have the potential

  14. Inhibition of growth, migration and invasion of human bladder cancer cells by antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, and its molecular mechanisms.

    Science.gov (United States)

    Chiu, Kun-Yuan; Wu, Chun-Chi; Chia, Chi-Hao; Hsu, Shih-Lan; Tzeng, Yew-Min

    2016-04-10

    Bladder cancer is the ninth most common cancer around the world, and is a severe urological cancer irrespective of sex. Approximately 65% of the bladder cancers will recur following surgery; with more than 20% of those patients showing an advanced and metastatic stage, with reducing prognosis. Metastasis causes the most death of bladder cancer yet current therapeutic options remain limited. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, has been identified as a strong cytotoxic agent against lung and metastatic breast cancer cells; however, the effects and mechanisms of antrocin on cancer growth and metastasis remain largely unclear. This study showed that treatment with cytotoxic concentration of antrocin induced both intrinsic and extrinsic apoptotic pathways in human bladder cancer 5637 cells, evidenced by increase of Fas, DR5, Bax expression and caspase-3, -8 and -9 activation. Exposure to non-cytotoxic concentrations of antrocin significantly inhibited cell growth, migration, and invasion, which was associated with decreased phosphorylation of focal adhesion kinase (FAK) and paxillin. Antrocin also reduced subcellular distribution of FAK and paxillin at the focal adhesion contacts of the cell periphery site, and disrupted the formation of filopodia and lamellipodia. Moreover, antrocin increased epithelial-to-mesenchymal transition-related gene E-cadherin and decreased vimentin expression. Real-time PCR analysis showed that antrocin downregulated the expression of mRNA of several MMPs, including MMP-2. Moreover, the phosphorylation of ERK and c-Fos were also attenuated by antrocin. Data from chromatin immunoprecipitation assay demonstrated that antrocin decreased the DNA binding activity of c-Fos to the upstream/enhancer region of MMP-2 promoter, an action likely to result in the reducing MMP-2 expression. Overall, this is the first study which demonstrates that antrocin-inhibited migration and invasion of bladder cancer cells is partly

  15. Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

    OpenAIRE

    Lv, Tangfeng; Yuan, Dongmei; Xiaohui MIAO; Lv, Yanling; Zhan, Ping; Shen, Xiaokun; Song, Yong

    2012-01-01

    Background Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. Methods The protein levels of LSD1 in surgically resected samples from NSCL...

  16. Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence

    OpenAIRE

    Barnes, N.; Haywood, P.; Flint, P; Knox, W F; Bundred, N J

    2006-01-01

    In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking activated caspases. COX-2 expression limits the ubiquitination of survivin, protecting it from degradation. To determine if COX-2 expression in breast cancer showed an association with survivin expression, we assessed the levels of each protein in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC); relating expression p...

  17. The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyereen [Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul (Korea, Republic of); Ko, Jesang [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr [Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We evaluated the effect of ANXA1 on promoting migration and invasion in MDA-MB-231 cells. Black-Right-Pointing-Pointer ANXA1 siRNA inhibits invasion and migration. Black-Right-Pointing-Pointer ANXA1 regulates MMP-9 expression and activity. Black-Right-Pointing-Pointer ANX-1 siRNA inhibits the activation of NF-{kappa}B in MDA-MB-231 cells. -- Abstract: Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression and its biological effects on breast cancer development remain obscure. In the current study, we examined the potential role of annexin A1 (ANXA1) in regulating migration and invasion in breast cancer cell lines. Both ANXA1 mRNA and protein are expressed in the highly invasive, hormone-insensitive human breast cancer cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF-7 and T47D. Downregulation of ANXA1 expression with specific small interfering RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell migration and invasion. Ablation of ANXA1 expression decreases the expression of MMP-9 at both the mRNA and protein levels and also reduces the proteolytic activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing ANXA1 also decreases the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa-B (NF-{kappa}B) activity. Collectively, these results indicate that ANXA1 functions as a positive regulator of MMP-9 expression and invasion of breast cancer cells through specific activation of the NF-{kappa}B signaling pathway.

  18. G12 Signaling through c-Jun NH2-Terminal Kinase Promotes Breast Cancer Cell Invasion

    OpenAIRE

    Juhi Juneja; Ian Cushman; Casey, Patrick J.

    2011-01-01

    Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH(2)-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively-active Gα12 or activation of G12 signaling by thrombin leads to increased JNK and c-Jun phosphorylation. Pharmacologic inhibition of JNK or knockdown of JNK expression by siRNA significantly decreases G12-induced JN...

  19. 食管癌的微创术%Minimal Invasive Surgery for Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    A.H.H(o)lscher; Ch.Gutschow

    2004-01-01

    Thoracoscopic esophagectomy is only established in some centers and affords a cervical anastomosis because intrathoracic anastomosis as a routine is technically too difficult. Laparoscopic mobilisation of the stomach (gastrolysis) is an important contribution for minimal invasive surgery of esophageal cancer.This procedure reduces the stress of the two cavity operation for the patient and allows the construction of a comparable gastric conduit like by open surgery. The technique of laparoscopic gastrolysis as preparation for transthoracic en bloc esophagectomy is described in detail and preliminary results are briefly mentioned.

  20. Transurethral surgery in the treatment of invasive bladder cancer (T1 and T2)

    DEFF Research Database (Denmark)

    Wolf, H; Iversen, H G; Rosenkilde, P; Schrøder, T

    1987-01-01

    of them did not have local disease when treated. Twenty-five % of the total patient population did not within five years get a new tumour. They were cured by the first transurethral resection. 30% of the patients experienced new non-invasive tumour growth that could be managed by repeated resections...... patients at risk of getting a progressive bladder cancer disease. 5-year survival of these patients was about 50%. We conclude that transitional cell bladder tumours of category T1 and some of category T2 are well treated by transurethral resection....

  1. Inorganic sulfur reduces the motility and invasion of MDA-MB-231 human breast cancer cells

    OpenAIRE

    Kim, Jin Joo; Ha, Ae Wha; Kim, Hee Sun; Kim, Woo Kyoung

    2011-01-01

    This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 µmol/L within 48 h. Inorganic sulfur significantly d...

  2. Effect of salinomycin on metastasis and invasion of bladder cancer cell line T24

    Institute of Scientific and Technical Information of China (English)

    Hu; Qu; Bo; Ma; Hao-Feng; Yuan; Zhong-Yang; Wang; Sheng-Jie; Guo; Jing; Zhang

    2015-01-01

    Objective: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelialmesenchymal transition(EMT), and to provide experimental basis for the treatment of urological tumors. Methods: The bladder cancer cell line T24 was cultured in vitro. The rat bladder tumor model was established in vivo. The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of m RNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. Results: The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6(P<0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h(P<0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h(P<0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group(P<0.05). The serum m RNA level and E-cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group(P<0.05). Conclusions: Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated

  3. miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2

    OpenAIRE

    Yu, Li; Lu, Juan; Zhang, Bao; LIU, Xiong; Wang, Lu; Li, Si-Yang; Peng, Xiao-Hong; Xu, Xia; TIAN, WEN-DONG; Li, Xiang-ping

    2013-01-01

    Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic type of cancer that is widely prevalent in Southern China. Studies have shown that several microRNAs (miRNAs) are implicated in NPC metastasis. Our previous studies have demonstrated that miRNA miR-26a inhibits cell growth and tumorigenesis of NPC through the repression of enhancer of zeste homolog 2 (EZH2). However, the role of miR-26a in NPC metastasis remains unknown. In this study, we showed that ectopic expression of miR-...

  4. Molecular Markers as Prognostic Factors in DCIS and Small Invasive Breast Cancers

    OpenAIRE

    Sänger, N.; Engels, K; A. Graf; Ruckhäberle, E.; Effenberger, K. E.; Fehm, T.; Holtrich, U.; Becker, S.; Karn, T.

    2014-01-01

    Ductal carcinoma in situ (DCIS) accounts for up to half of screen-detected breast cancers and thus constitutes a major public health problem. Despite effective current treatment many patients with DCIS are either over- or undertreated because of the paucity of precise models to predict recurrence or progression. The combination of clinical and molecular factors as already applied for invasive disease may help to build such models also for DCIS. We compared 53 DCIS (36.6 %) and 92 (63.4 %) inv...

  5. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts.

    Science.gov (United States)

    Chowdhury, Ridwana; Webber, Jason P; Gurney, Mark; Mason, Malcolm D; Tabi, Zsuzsanna; Clayton, Aled

    2015-01-20

    Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood. We investigated the role of nano-metre sized vesicles (exosomes), secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM-MSC), and the subsequent functional consequences of such changes. Purified exosomes impaired classical adipogenic differentiation, skewing differentiation towards alpha-smooth muscle actin (αSMA) positive myofibroblastic cells. A single exosomes treatment generated myofibroblasts secreting high levels of VEGF-A, HGF and matrix regulating factors (MMP-1, -3 and -13). Differentiated MSC had pro-angiogenic functions and enhanced tumour proliferation and invasivity assessed in a 3D co-culture model. Differentiation was dependent on exosomal-TGFβ, but soluble TGFβ at matched dose could not generate the same phenotype. Exosomes present in the cancer cell secretome were the principal factors driving this phenotype. Prostate cancer exosomes dominantly dictate a programme of MSC differentiation generating myofibroblasts with functional properties consistent with disease promotion. PMID:25596732

  6. Minimally invasive surgery for upper gastrointestinal cancer: Our experience and review of the literature.

    Science.gov (United States)

    Suda, Koichi; Nakauchi, Masaya; Inaba, Kazuki; Ishida, Yoshinori; Uyama, Ichiro

    2016-05-21

    Minimally invasive surgery (MIS) for upper gastrointestinal (GI) cancer, characterized by minimal access, has been increasingly performed worldwide. It not only results in better cosmetic outcomes, but also reduces intraoperative blood loss and postoperative pain, leading to faster recovery; however, endoscopically enhanced anatomy and improved hemostasis via positive intracorporeal pressure generated by CO2 insufflation have not contributed to reduction in early postoperative complications or improvement in long-term outcomes. Since 1995, we have been actively using MIS for operable patients with resectable upper GI cancer and have developed stable and robust methodology in conducting totally laparoscopic gastrectomy for advanced gastric cancer and prone thoracoscopic esophagectomy for esophageal cancer using novel technology including da Vinci Surgical System (DVSS). We have recently demonstrated that use of DVSS might reduce postoperative local complications including pancreatic fistula after gastrectomy and recurrent laryngeal nerve palsy after esophagectomy. In this article, we present the current status and future perspectives on MIS for gastric and esophageal cancer based on our experience and a review of the literature. PMID:27217695

  7. Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Kinoshita, Takashi; Hanazawa, Toyoyuki; Nohata, Nijiro; Kikkawa, Naoko; Enokida, Hideki; Yoshino, Hirofumi; Yamasaki, Takeshi; Hidaka, Hideo; Nakagawa, Masayuki; Okamoto, Yoshitaka; Seki, Naohiko

    2012-11-01

    Recent our microRNA (miRNA) expression signature revealed that expression of microRNA-218 (miR-218) was reduced in cancer tissues, suggesting a candidate of tumor suppressor in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the functional significance of miR-218 and its mediated moleculer pathways in HNSCC. Restoration of miR-218 in cancer cells led to significant inhibition of cell migration and invasion activities in HNSCC cell lines (FaDu and SAS). Genome-wide gene expression analysis of miR-218 transfectants and in silico database analysis showed that focal adhesion pathway was a promising candidate of miR-218 target pathways. The laminins are an important and biologically active part of the basal lamina, the function of that are various such as influencing cell differentiation, migration and adhesion as well as proliferation and cell survival. Interestingly, all components of laminin-332 (LAMA3, LAMB3 and LAMC2) are listed on the candidate genes in focal adhesion pathway. Furthermore, we focused on LAMB3 which has a miR-218 target site and gene expression studies and luciferase reporter assays showed that LAMB3 was directly regulated by miR-218. Silencing study of LAMB3 demonstrated significant inhibition of cell migration and invasion. In clinical specimens with HNSCC, the expression levels of laminin-332 were significantly upregulated in cancer tissues compared to adjacent non-cancerous tissues. Our analysis data showed that tumor suppressive miR-218 contributes to cancer cell migration and invasion through regulating focal adhesion pathway, especially laminin-332. Tumor suppressive miRNA-mediated novel cancer pathways provide new insights into the potential mechanisms of HNSCC oncogenesis. PMID:23159910

  8. Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

    International Nuclear Information System (INIS)

    KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it

  9. EFEMP1 Suppresses Growth and Invasion of Lung Cancer Cells 
by Downregulating Matrix Metalloproteinase-7 Expression

    Directory of Open Access Journals (Sweden)

    Yuanyuan LANG

    2015-02-01

    Full Text Available Background and objective EFEMP1, a member of fibulin family proteins, is a very important extracellular matrix protein which is involved in cell metabolism and its role in tumor occurrence and progression is still poorly understood. The aim of this study is to investigate the functional effect and mechanism of EFEMP1 in lung cancer cell growth and invasion. Methods EFEMP1 expression in lung cancer cells was determined by Western blot. The promoter methylation status of EFEMP1 was detected by methylation-specific PCR (MSP. After transfection of control or EFEMP1 vector in lung cancer cells, the ability of colony formation and invasion was detected by colony formation experiment and matrigel invasion method. Western blot and real-time PCR were used to detect matrix metalloproteinase-7 (MMP-7 expression. Luciferase assay was used to detect expression of MMP-7 reporter construct transfected with or without EFEMP1 in lung cancer cells. Results Western blot result showed EFEMP1 expression was downregulated in lung cancer cells. The promoter region of EFEMP1 was methylated in A549 and H1299 and after treatment with 5-aza-2’-deoxycytidine, the EFEMP1 expression was upregulated. The growth and invasion of A549 and H1299 were all significantly suppressed by transfecting with EFEMP1 and the MMP-7 expression was dowanregulated by EFEMP1 as well. Expression activity of MMP-7 reporter construct was decreased by cotransfecting with EFEMP1. Conclusion Collectively, these results suggest that EFEMP1 functions as a suppressor of lung cancer growth and invasion. Epigenetic silencing of EFEMP1 promotes lung cancer invasion and metastasis by activating MMP-7 expression.

  10. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

  11. Radiologic localization of parathyroid adenomas in the previously operated patient; Part II: Invasive localization procedures

    International Nuclear Information System (INIS)

    The authors studied intraarterial digital subtraction angiography (DSA), conventional selective angiography (CA), parathyroid venous sampling (PVS), and intraoperative US as localization procedures in 53 patients with proved parathyroid adenomas and in whom parathyroid surgery had been unsuccessful. PVS had the highest overall sensitivity (80%), followed by intraoperative US (78%), CA (61%), and DSA (49%). Invasive procedures successfully localized adenomas in 41 of 43 patients (95%). False positive studies were uncommon. The optimum sequence of invasive procedures to localize parathyroid adenoma is determined by clinical factors. The authors recommend DSA first, followed by CA, PVS, and intraoperative US. All of the invasive localization procedures they studied are valuable

  12. Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

    International Nuclear Information System (INIS)

    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 AKTSer473 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 affected

  13. 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)

    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

  14. Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine

    OpenAIRE

    Makino, Tomoyuki; Kitagawa, Yasuhide; Namiki, Mikio

    2014-01-01

    Abstract Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of th...

  15. Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion

    OpenAIRE

    Adhikary, T; Brandt, D T; Kaddatz, K; Stockert, J; Naruhn, S; Meissner, W.; Finkernagel, F; Obert, J.; Lieber, S; Scharfe, M.; Jarek, M; Toth, P M; Scheer, F; Diederich, W E; Reinartz, S

    2012-01-01

    Besides its established functions in intermediary metabolism and developmental processes, the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has a less defined role in tumorigenesis. In the present study, we have identified a function for PPARβ/δ in cancer cell invasion. We show that two structurally divergent inhibitory ligands for PPARβ/δ, the inverse agonists ST247 and DG172, strongly inhibit the serum- and transforming growth factor β (TGFβ)-induced invasion of ...

  16. HER-2/neu Overexpression as a Predictor for the Transition from In situ to Invasive Breast Cancer

    OpenAIRE

    Roses, Robert E.; Paulson, E. Carter; Sharma, Anupama; Schueller, Jeanne E.; Nisenbaum, Harvey; Weinstein, Susan; Fox, Kevin R.; Zhang, Paul J.; Czerniecki, Brian J.

    2009-01-01

    The clinical implications of HER-2/neu (HER2) expression in ductal carcinoma in situ (DCIS) lesions have yet to be clearly elucidated; this despite the more frequent expression of HER2 in high-grade DCIS lesions compared with invasive cancers. We hypothesized that HER2 overexpression in DCIS is associated with more rapid progression to invasive disease. Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 was done on DCIS specimens. Univariate analysis and a mul...

  17. SRPX2 promotes cell migration and invasion via FAK dependent pathway in pancreatic cancer.

    Science.gov (United States)

    Gao, Zhenyuan; Zhang, Jingjing; Bi, Minghong; Han, Xiao; Han, Zhengquan; Wang, Hongya; Ou, Yimei

    2015-01-01

    Sushi repeat-containing protein, X-linked 2, abbreviated as SRPX2, is a candidate downstream target protein for E2A-HLF and involved in disorders of language cortex and cognition. Recent studies have demonstrated that elevated SRPX2 exhibits crucial roles in gastric cancer, however, underlying clinical significance and biological function of SRPX2 in pancreatic ductal adenocarcinoma (PDAC), remains unclear. Data from Oncomine database showed that higher SRPX2 expression is more commonly observed in PDAC compared with normal pancreatic duct, similar results were also found in 12 matched PDAC tissue samples, 7 PDAC cell lines and a tissue microarray containing 81 PDAC specimens as demonstrated by real-time quantitative PCR and immunohistochemistry, respectively. Besides, higher SRPX2 expression was closely correlated with advanced TNM stage. Silencing of endogenous SRPX2 expression reduced abilities of cell migration and invasion of PDAC cells. Further studies revealed that SRPX2 expression in PDAC tissues significantly correlated with the phosphorylation levels of FAK, indicating that FAK dependent pathway may be account for the effect of SRPX2 on cell migration and invasion in PDAC. Collectively, this study reveals that frequently elevated SRPX2 contributes to cell migration and invasion in PDAC and SRPX2-related pathways might be a potential therapeutic target for PDAC. PMID:26191169

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

    International Nuclear Information System (INIS)

    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

  19. Smad6 determines BMP-regulated invasive behaviour of breast cancer cells in a zebrafish xenograft model

    Science.gov (United States)

    de Boeck, Miriam; Cui, Chao; Mulder, Aat A; Jost, Carolina R; Ikeno, Souichi; ten Dijke, Peter

    2016-01-01

    The transforming growth factor-β (TGF-β) family is known to play critical roles in cancer progression. While the dual role of TGF-β is well described, the function of bone morphogenetic proteins (BMPs) is unclear. In this study, we established the involvement of Smad6, a BMP-specific inhibitory Smad, in breast cancer cell invasion. We show that stable overexpression of Smad6 in breast cancer MCF10A M2 cells inhibits BMP signalling, thereby mitigating BMP6-induced suppression of mesenchymal marker expression. Using a zebrafish xenograft model, we demonstrate that overexpression of Smad6 potentiates invasion of MCF10A M2 cells and enhances the aggressiveness of breast cancer MDA-MB-231 cells in vivo, whereas a reversed phenotype is observed after Smad6 knockdown. Interestingly, BMP6 pre-treatment of MDA-MB-231 cells induced cluster formation at the invasive site in the zebrafish. BMP6 also stimulated cluster formation of MDA-MB-231 cells co-cultured on Human Microvascular Endothelial Cells (HMEC)-1 in vitro. Electron microscopy illustrated an induction of cell-cell contact by BMP6. The clinical relevance of our findings is highlighted by a correlation of high Smad6 expression with poor distant metastasis free survival in ER-negative cancer patients. Collectively, our data strongly indicates the involvement of Smad6 and BMP signalling in breast cancer cell invasion in vivo. PMID:27113436

  20. Smad6 determines BMP-regulated invasive behaviour of breast cancer cells in a zebrafish xenograft model.

    Science.gov (United States)

    de Boeck, Miriam; Cui, Chao; Mulder, Aat A; Jost, Carolina R; Ikeno, Souichi; Ten Dijke, Peter

    2016-01-01

    The transforming growth factor-β (TGF-β) family is known to play critical roles in cancer progression. While the dual role of TGF-β is well described, the function of bone morphogenetic proteins (BMPs) is unclear. In this study, we established the involvement of Smad6, a BMP-specific inhibitory Smad, in breast cancer cell invasion. We show that stable overexpression of Smad6 in breast cancer MCF10A M2 cells inhibits BMP signalling, thereby mitigating BMP6-induced suppression of mesenchymal marker expression. Using a zebrafish xenograft model, we demonstrate that overexpression of Smad6 potentiates invasion of MCF10A M2 cells and enhances the aggressiveness of breast cancer MDA-MB-231 cells in vivo, whereas a reversed phenotype is observed after Smad6 knockdown. Interestingly, BMP6 pre-treatment of MDA-MB-231 cells induced cluster formation at the invasive site in the zebrafish. BMP6 also stimulated cluster formation of MDA-MB-231 cells co-cultured on Human Microvascular Endothelial Cells (HMEC)-1 in vitro. Electron microscopy illustrated an induction of cell-cell contact by BMP6. The clinical relevance of our findings is highlighted by a correlation of high Smad6 expression with poor distant metastasis free survival in ER-negative cancer patients. Collectively, our data strongly indicates the involvement of Smad6 and BMP signalling in breast cancer cell invasion in vivo. PMID:27113436

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

    International Nuclear Information System (INIS)

    Highlights: ► Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE2. ► 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.

  2. Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion

    Science.gov (United States)

    Henry, Claire; Llamosas, Estelle; Knipprath-Mészáros, Alexandra; Schoetzau, Andreas; Obermann, Ellen; Fuenfschilling, Maya; Caduff, Rosemarie; Fink, Daniel; Hacker, Neville; Ward, Robyn; Heinzelmann-Schwarz, Viola; Ford, Caroline

    2015-01-01

    AIM In recent years, the Wnt signalling pathway has been implicated in epithelial ovarian cancer and its members have potential as diagnostic, prognostic and therapeutic targets. Here we investigated the role of two Wnt receptor tyrosine kinases (RTKs), ROR1 and ROR2, and their putative ligand, Wnt5a, in ovarian cancer. METHODS Immunohistochemistry for ROR2 was performed in a large patient cohort, including benign controls, borderline tumours and epithelial ovarian cancer. In addition, siRNA was used to silence ROR1, ROR2 and Wnt5a individually, and together, in two ovarian cancer cell lines, and the effects on cell proliferation, adhesion, migration and invasion were measured. RESULTS ROR2 expression is significantly increased in ovarian cancer patients compared to patients with benign disease. In vitro assays showed that silencing either receptor inhibits ovarian cancer cell migration and invasion, and concurrently silencing both receptors has an even stronger inhibitory effect on proliferation, migration and invasion. CONCLUSIONS ROR2 expression is increased in epithelial ovarian cancer, and silencing ROR2 and its sister receptor ROR1 has a strong inhibitory effect on the ability of ovarian cancer cells to proliferate, migrate and invade through an extracellular matrix. PMID:26515598

  3. Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.

    Directory of Open Access Journals (Sweden)

    Makio Saeki

    Full Text Available Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

  4. A two-part measure of degree of invasion for cross-community comparisons

    Science.gov (United States)

    Guo, Q.; Symstad, A.

    2008-01-01

    Invasibility is a critical feature of ecological communities, especially for management decisions. To date, invasibility has been measured in numerous ways. Although most researchers have used the richness (or number) of exotic species as a direct or indirect measure of community invasibility, others have used alternative measures such as the survival, density, or biomass of either a single or all exotic species. These different measures, even when obtained from the same communities, have produced inconsistent results and have made comparisons among communities difficult. Here, we propose a measure of the degree of invasion (DI) of a community as a surrogate for community invasibility. The measure is expressed as 2 independent components: exotic proportion of total species richness and exotic proportion of total species abundance (biomass or cover). By including richness and abundance, the measure reflects that the factors that control invasibility affect both of these components. Expressing exotic richness and abundance relative to the richness and abundance of all species in a community makes comparisons across communities of different sizes and resource availability possible and illustrates the importance of dominance of exotic species relative to natives, which is a primary management concern associated with exotic species.

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

    International Nuclear Information System (INIS)

    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)

  7. Breast conserving therapy for early stage invasive cancer and ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Purpose/Objective: To discuss a number of clinical and treatment related issues in the management of early stage invasive breast cancer and ductal carcinoma in situ. Prospective randomized trials as well as retrospective series have established the role of conservative surgery and radiation as an alternative equal to mastectomy in the patient selection, the importance of microscopic margins of research, radiotherapy technique including the role of the boost and regional node irradiation and the integration of systemic therapy (tamoxifen or chemotherapy) with radiation. A subgroup of patients with minimally invasive breast cancer for whom radiation may be omitted after conservative surgery will be identified. Factors predicting for an increased risk of recurrence in the treated breast will be reviewed. The diagnosis and treatment of a breast recurrence will be presented as well as the impact of a local recurrence on distant metastases. Treatment options for ductal carcinoma in situ (DCIS) including observation, radiation and mastectomy will be reviewed. Results from prospective randomized trials as well as retrospective series will be presented in an attempt to identify appropriate treatment strategies for the different clinical presentations and histologic subtypes of DCIS

  8. Clinical results of a concomitant boost radiotherapy technique for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose: to update the results of external radiotherapy with a focal concomitant boost technique on local control and bladder function in patients with muscle-invasive bladder cancer. Patients and methods: the authors retrospectively evaluated 92 elderly or disabled patients with localized T2-4 N0-1 M0 transitional cell carcinoma of the bladder and a median age of 79 years, not suitable for radical surgery and treated between 1994 and 2005. Treatment consisted of a dose of 40 Gy/2 Gy to the small pelvis with a daily concomitant boost of 0.75 Gy to the tumor. Total dose was 55 Gy in 4 weeks. Results: complete remission rate after evaluation by means of cystoscopy at 3 months was 78%. 3-year local control rate amounted to 56%, and 3-year overall survival to 36%. The posttreatment bladder capacity was comparable with the pretreatment capacity and was ≥ 200 ml in 81% of the cases. Mean bladder capacity did not deteriorate at longer follow-up. Conclusion: the local control rate after external beam radiotherapy in elderly patients with a focal concomitant boost for localized muscle-invasive bladder cancer was 56% at 3 years. Functional bladder outcome was good. (orig.)

  9. Clinical results of a concomitant boost radiotherapy technique for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Piet, A.H.M.; Hulshof, M.C.C.M.; Pieters, B.R.; Koning, C.C.E. [Dept. of Radiation Oncology, Academic Medical Center, Univ. of Amsterdam (Netherlands); Pos, F.J. [Dept. of Radiation Oncology, The Netherlands Cancer Inst., Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Reijke, T.M. de [Dept. of Urology, Academic Medical Center, Univ. of Amsterdam (Netherlands)

    2008-06-15

    Purpose: to update the results of external radiotherapy with a focal concomitant boost technique on local control and bladder function in patients with muscle-invasive bladder cancer. Patients and methods: the authors retrospectively evaluated 92 elderly or disabled patients with localized T2-4 N0-1 M0 transitional cell carcinoma of the bladder and a median age of 79 years, not suitable for radical surgery and treated between 1994 and 2005. Treatment consisted of a dose of 40 Gy/2 Gy to the small pelvis with a daily concomitant boost of 0.75 Gy to the tumor. Total dose was 55 Gy in 4 weeks. Results: complete remission rate after evaluation by means of cystoscopy at 3 months was 78%. 3-year local control rate amounted to 56%, and 3-year overall survival to 36%. The posttreatment bladder capacity was comparable with the pretreatment capacity and was {>=} 200 ml in 81% of the cases. Mean bladder capacity did not deteriorate at longer follow-up. Conclusion: the local control rate after external beam radiotherapy in elderly patients with a focal concomitant boost for localized muscle-invasive bladder cancer was 56% at 3 years. Functional bladder outcome was good. (orig.)

  10. Core biopsy as a tool in planning the management of invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Garud Trivikram

    2005-01-01

    Full Text Available Abstract Background Core biopsy is a method of choice for the triple assessment of breast disease as it can reliably distinguish between benign and malignant tumours, between in-situ and invasive cancers and can be useful to assess oestrogen receptor status. This study was carried out to assess the reliability of core biopsy in predicting the grade and type of cancer accurately as obtaining this information can influence initial therapeutic decisions. Patients and methods A total of 105 patients who had invasive breast carcinoma diagnosed by core biopsy in year 2001 and who subsequently underwent surgical management were included. The core biopsy results were compared with final histology with the help of kappa statastics. Results A moderate level of agreement between the predicted grades and final grades was noted (kappa = 0.585. The agreement was good between predicted and final type of tumour (kappa = 0.639. Conclusions Core biopsy as a predictor of grade and type has limited use at present. We suggest that initial clinical decisions should not be based on the results of core biopsy.

  11. Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness

    International Nuclear Information System (INIS)

    Taxol is widely used in breast cancer chemotherapy. Its effects are primarily attributed to its anti-mitotic activity. Microtubule perturbators also exert antimetastatic activities which cannot be explained solely by the inhibition of proliferation. Voltage-dependent sodium channels (NaV) are abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468 cell line. Inhibiting NaV activity with tetrodotoxin is responsible for an approximately 0.4-fold reduction of MDA-MB-231 cell invasiveness. In this study, we focused on the effect of a single, 2-h application of 10 nM taxol on the two cell lines MDA-MB-231 and MDA-MB-468. At this concentration, taxol had no effect on proliferation after 7 days and on migration in any cell line. However it led to a 40% reduction of transwell invasion of MDA-MB-231 cells. There was no additive effect when taxol and tetrodotoxin were simultaneously applied. NaV activity, as assessed by patch-clamp, indicates that it was changed by taxol pre-treatment. We conclude that taxol can exert anti-tumoral activities, in cells expressing NaV, at low doses that have no effect on cell proliferation. This effect might be due to a modulation of signalling pathways involving sodium channels.

  12. Hypoxia/lncRNA-AK123072/EGFR pathway induced metastasis and invasion in gastric cancer

    Science.gov (United States)

    Yang, Zhen; Wang, Ruoming; Zhang, Tengteng; Dong, Xinhua

    2015-01-01

    Objective: To investigate the role of long noncoding RNAs (lncRNAs) in hypoxia-induced gastric cancer (GC) metastasis and invasion. Methods: We investigated the differentially expressed lncRNAs resulting from hypoxia-induced GC and normoxia conditions using microarrays and validated our results through real-time quantitative polymerase chain reaction. The role of the targeting lncRNA was further detected by in vivo and in vitro assays. Results: We found an lncRNA, AK123072, which was up-regulated by hypoxia. AK123072 was frequently up-regulated in GC samples and promoted GC migration and invasion in vivo and in vitro. Furthermore, AK123072 could mediate the metastasis of hypoxia-induced GC cells. Next, we identified EGFR, which was a metastasis-related gene regulated by AK123072. In addition, we found that the expression of EGFR was positively correlated with that of AK123072 in the clinical GC samples used in our study. Furthermore, we found that the EGFR gene CpG island methylation was significantly increased in GC cells depleted of AK123072. Intriguingly, EGFR expression was also increased by hypoxia, and EGFR up-regulation by AK123072 mediated hypoxia-induced GC cell metastasis. Conclusion: Our results identified hypoxia/lncRNA-AK123072/EGFR pathway in gastric cancer pathogenesis and this might help in the development of new therapeutics in clinics. PMID:26884908

  13. Non-invasive biomarkers in pancreatic cancer diagnosis: what we need versus what we have.

    Science.gov (United States)

    Herreros-Villanueva, Marta; Bujanda, Luis

    2016-04-01

    Pancreatic cancer (PC) is probably the most lethal tumor being forecast as the second most fatal cancer by 2020 in developed countries. Only the earliest forms of the disease are a curable disease but it has to be diagnosed before symptoms starts. Detection at curable phase demands screening intervention for early detection and differential diagnosis. Unfortunately, no successful strategy or image technique has been concluded as effective approach and currently non-invasive biomarkers are the hope. Multiple translational research studies have explored minimally or non-invasive biomarkers in biofluids-blood, urine, stool, saliva or pancreatic juice, but diagnostic performance has not been validated yet. Nowadays no biomarker, alone or in combination, has been superior to carbohydrate antigen 19-9 (CA19-9) in sensitivity and specificity. Although the number of novel biomarkers for early diagnosis of PC has been increasing during the last couple of years, no molecular signature is ready to be implemented in clinical routine. Under the uncertain future, miRNAs profiling and methylation status seem to be the most promising biomarkers. However, good results in larger validations are urgently needed before application. Industry efforts through biotech and pharmaceutical companies are urgently required to demonstrate accuracy and validate promising results from basic and translational results. PMID:27162784

  14. Epidermal growth factor mediates detachment from and invasion through collagen I and Matrigel in Capan-1 pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Kuver Rahul

    2005-03-01

    Full Text Available Abstract Background Pancreatic adenocarcinoma is a highly invasive neoplasm. Epidermal growth factor (EGF and its receptor are over expressed in pancreatic cancer, and expression correlates with invasion and metastasis. We hypothesized that EGF receptor and integrin signalling pathways interact in mediating cellular adhesion and invasion in pancreatic cancer, and that invasiveness correlates temporally with detachment from extracellular matrix. Methods We tested this hypothesis by investigating the role of EGF in mediating adhesion to and invasion through collagen I and Matrigel in the metastatic pancreatic adenocarcinoma cell line Capan-1. Adhesion and invasion were measured using in vitro assays of fluorescently-labeled cells. Adhesion and invasion assays were also performed in the primary pancreatic adenocarcinoma cell line MIA PaCa-2. Results EGF inhibited adhesion to collagen I and Matrigel in Capan-1 cells. The loss of adhesion was reversed by AG825, an inhibitor of erbB2 receptor signalling and by wortmannin, a PI3K inhibitor, but not by the protein synthesis inhibitor cycloheximide. EGF stimulated invasion through collagen I and Matrigel at concentrations and time courses similar to those mediating detachment from these extracellular matrix components. Adhesion to collagen I was different in MIA PaCa-2 cells, with no significant change elicited following EGF treatment, whereas treatment with the EGF family member heregulin-alpha elicited a marked increase in adhesion. Invasion through Matrigel in response to EGF, however, was similar to that observed in Capan-1 cells. Conclusion An inverse relationship exists between adhesion and invasion capabilities in Capan-1 cells but not in MIA PaCa-2 cells. EGF receptor signalling involving the erbB2 and PI3K pathways plays a role in mediating these events in Capan-1 cells.

  15. 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.)

  16. CT Lung Cancer Screening Program Development: Part 2.

    Science.gov (United States)

    Yates, Teri

    2015-01-01

    Radiology administrators must use innovative strategies around clinical collaboration and marketing to ensure that patients access the service in sufficient numbers. Radiology Associates of South Florida in collaboration with Baptist Health South Florida have developed a successful lung cancer screening program. The biggest factors in their success have been the affordability of their service and the quality of the program. Like mammography, lung cancer screening programs serve as an entry point to other services that generate revenue for the hospital. Patients may require further evaluation in the form of more imaging or surgical services for biopsy. Part 1 provided background and laid out fundamentals for starting a program. Part 2 focuses on building patient volume, marketing, and issues related to patient management after the screen is performed. PMID:26314180

  17. Retromolar trigone squamous cell cancers: A reappraisal of 16 section MDCT for assessing mandibular invasion

    International Nuclear Information System (INIS)

    Aim: To reinvestigate the accuracy of 16 section multidetector computed tomography (MDCT) in assessing mandibular invasion in retromolar trigone (RMT) squamous cell cancers (SCC). Materials and methods: A search for diagnosed cases of early RMT SCC that were both imaged and treated at Tata Memorial Centre, Mumbai, India, between 2007 and 2010, was undertaken and yielded 37 patients. The average tumour size was 2.6 cm. All patients had undergone segmental, marginal, or hemimandibulectomy within 2 weeks of imaging. Imaging records archived on the picture archiving and communication system (PACS) were analysed. Contrast-enhanced CT had been performed using a 16 section MDCT system using the puffed-cheek technique. Image acquisition was at 2.5 mm section thickness, but axial images and isotropic coronal and sagittal multiplanar reformations were generated ad hoc from 0.625 mm retro-reconstructed images. Optimal oblique reformations were generated at will by the radiologist to depict the RMT in its entirety. The soft-tissue algorithm and bone window or bone algorithm reformations and axial images were analysed on a volume viewer integrated within the PACS using triangulation. Two investigators independently studied the images and these were compared with the findings at histopathology. Results: The sensitivity, specificity, and accuracy of 16 section MDCT for mandibular cortical and marrow invasion was 94, 90, and 91.8% and 83, 92, and 89%, respectively. Use of ad hoc generated oblique reformation contributed to the enhanced sensitivity and specificity. The accuracy for inferior alveolar canal invasion was 100%. There was excellent agreement between the two observers. Conclusion: Sixteen-section MDCT used to its full potential has high accuracy for the detection of mandibular invasion in RMT SCC

  18. Melanoma differentiation-associated gene-7/interleukin 24 inhibits invasion and migration of human cervical cancer cells in vitro

    International Nuclear Information System (INIS)

    In this study, we used an adenoviral vector-melanaoma differentiation-associated gene-7 (A-mda7) to examine the effect of the ectopic production of MDA-7/IL-24 on cell migration and invasion by human cervical cancer cells. The study took place in the Department of Biochemistry and Molecular Biology, Chongqing, China, between April 2006 and November 2006. The change of metastasis of cervical cancer cells (Ca Ski) cells were detected by Cell Migration Assay and Cell Invasion Assay after treated with Ad-Ma7. The production of proteins associated with cell migration and invasion were detected by western blot. Cervical cancer cells treated in vitro with Ad-Ma7 migrated and invaded less than cells treated with phosphate buffered saline (PBS) or Ad-Luc (vector control). Melanoma differentiation-associated gene-7/IL-24 inhibited migration and invasion by down-regulating the production of matrix metalloproteinase-2 (MMP-2) and by up-regulating the production of p38 mitogen-activated protein kinase relative to PBS and Ad-Luc. These results show that MDA-7/IL-24 inhibits invasion and migration by cervical cancer cells by down-or up-regulating proteins associated with these processes, resulting in reduced metastasis. These, Ad-Mda7 should be considered a therapeutic agent that can inhibit primary tumor growth and prevent metastasis. (author)

  19. β-elemene decreases cell invasion by upregulating E-cadherin expression in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Zhang, Xian; Zhang, Yang; Li, Yinghua

    2013-08-01

    Inactivation of E-cadherin results in cell migration and invasion, hence leading to cancer aggressiveness and metastasis. Downregulation of E-cadherin is closely correlated with a poor prognosis in invasive breast cancer. Thus, re-introducing E-cadherin is a novel strategy for cancer therapy. The aim of the present study was to determine the effects of the traditional Chinese medicine, β-elemene (ELE), on E-cadherin expression, cell migration and invasion in the breast cancer cell line MCF-7. MCF-7 cells were treated with 50 and 100 µg/ml ELE. E-cadherin mRNA was analyzed by reverse transcription‑polymerase chain reaction. E-cadherin protein levels were determined by immunofluorescence and western blot assays. Cell motility was measured by a Transwell assay. ELE increased both the protein and mRNA levels of E-cadherin, accompanied by decreased cell migration and invasion. Further analysis demonstrated that ELE upregulated estrogen receptor‑α (ERα) and metastasis-associated protein 3 (MTA3), and decreased the nuclear transcription factor Snail. In conclusion, our results demonstrate that ELE decreases cell migration and invasion by upregulating E-cadherin expression via controlling the ERα/MTA3/Snail signaling pathway. PMID:23732279

  20. Lysine-specific demethylase-1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer.

    Science.gov (United States)

    Kosumi, Keisuke; Baba, Yoshifumi; Sakamoto, Akihisa; Ishimoto, Takatsugu; Harada, Kazuto; Nakamura, Kenichi; Kurashige, Junji; Hiyoshi, Yukiharu; Iwatsuki, Masaaki; Iwagami, Shiro; Sakamoto, Yasuo; Miyamoto, Yuji; Yoshida, Naoya; Oki, Eiji; Watanabe, Masayuki; Hino, Shinjiro; Nakao, Mitsuyoshi; Baba, Hideo

    2016-01-15

    Lysine-specific demethylase-1 (LSD1) removes the methyl groups from mono- and di-methylated lysine 4 of histone H3. Previous studies have linked LSD1 to malignancy in several human tumors, and LSD1 is considered to epigenetically regulate the energy metabolism genes in adipocytes and hepatocellular carcinoma. This study investigates the function of LSD1 in the invasive activity and the metabolism of esophageal cancer cells. We investigated whether LSD1 immunohistochemical expression levels are related to clinical and pathological features, including the maximum standard uptake value in fluorodeoxyglucose positron emission tomography assay. The influence of LSD1 on cell proliferation, invasion and glucose uptake was evaluated in vitro by using specific small interfering RNA for LSD1, and an LSD1 inhibitor. We also evaluated two major energy pathways (glycolytic pathway and mitochondrial respiration) by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) with an extracellular flux analyzer. High LSD1 immunohistochemical expression was significantly associated with high tumor stage, lymphovascular invasion, poor prognosis, and high maximum standard uptake value in esophageal cancer patients. In the in vitro analysis, LSD1 knockdown significantly suppressed the invasive activity and glucose uptake of cancerous cells, reduced their ECAR and increased their OCR and OCR/ECAR. LSD1 may contribute to malignant behavior by regulating the invasive activity and metabolism, activating the glycolytic pathway and inhibiting the mitochondrial respiration of esophageal cancer cells. The results support LSD1 as a potential therapeutic target. PMID:26240060

  1. Addressing future challenges for cancer services: part II.

    Science.gov (United States)

    Maher, Jane; Radford, Gina

    2016-02-01

    Jane Maher & Gina Radford speak to Gemma Westcott, Commissioning Editor Jane Maher has been Macmillan's Chief Medical Officer since 1999 and now shares the role as Joint Chief Medical Officer with general practitioner Rosie Loftus, reflecting the growing need for specialists and generalists to work more effectively together. She has been an National Health Service (NHS) improvement clinical leader for over 10 years and is a Consultant Clinical Oncologist at Mount Vernon Cancer Centre and Hillingdon Hospital where she has worked for more than 20 years, during which she helped develop nonsurgical oncology services in five district general hospitals. She is a senior Clinical Lecturer at University College London and Visiting Professor in Cancer and Supportive Care at the Centre for Complexity Management at the University of Hertfordshire. Jane chaired the Maher Committee for the Department of Health in 1995, led the UK National Audit of Late Effects Pelvic Radiotherapy for the Royal College of Radiologists (RCR) in 2000 and, most recently, chaired the National Cancer Survivorship Initiative Consequences of Treatment work stream. She co-founded one of the first Cancer Support and Information services in the UK, winning the Nye Bevan award in 1992 and there are now more than 60 units based on this model. She is a member of the Older People and Cancer Clinical Advisory Group. She has written more than 100 published articles and is a UK representative for cancer survivorship in Europe and advises on cancer survivorship programs in Denmark and Canada. Gina Radford is Deputy Chief Medical Officer for England, a post she took up in January 2015. Prior to that, she has held a number of roles in public health, at local and regional level. Most recently she was Centre Director for Anglia and Essex for Public Health England, and as a part of that role helped lead nationally on the public health response to Ebola. She was until very recently Chair of one of the NICE public health

  2. Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis

    Directory of Open Access Journals (Sweden)

    Lucio Dell’Atti

    2015-03-01

    Full Text Available Objectives: We retrospectively reviewed data of patients with incidental prostate cancer (PCa who underwent radical cystoprostatectomy (RCP for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Material and Methods: Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. Results: 11 out of 64 patients (17.2% who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3% were diagnosed as significant PCa, while 8 cases (72.7% were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79. During the follow-up, biochemical recurrence occurred in 1 patient (9%. Concernig the cancer specific survival there was no statistical significance (P = 0.326 between the clinically significant and clinical insignificant cancer group. Conclusions: In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

  3. Distribution analysis of the putative cancer marker S100A4 across invasive squamous cell carcinoma penile tissue

    Directory of Open Access Journals (Sweden)

    Brian Flatley

    2015-06-01

    Full Text Available MS-based proteomic methods were utilised for the first time in the discovery of novel penile cancer biomarkers. MALDI MS imaging was used to obtain the in situ biomolecular MS profile of squamous cell carcinoma of the penis which was then compared to benign epithelial MS profiles. Spectra from cancerous and benign tissue areas were examined to identify MS peaks that best distinguished normal epithelial cells from invasive squamous epithelial cells, providing crucial evidence to suggest S100A4 to be differentially expressed. Verification by immunohistochemistry resulted in positive staining for S100A4 in a sub-population of invasive but not benign epithelial cells.

  4. Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer

    OpenAIRE

    Hashimoto, I.; Kodama, J; Seki, N; Hongo, A; Yoshinouchi, M; Okuda, H.; Kudo, T.

    2001-01-01

    Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis, the process of new lymphatics formation. The present study investigated VEGF-C mRNA expression in invasive cervical cancer tissue. Additionally, the association of VEGF-C mRNA with clinicopathological features was examined. VEGF-C mRNA expression was assessed by reverse transcription-polymerase chain reaction using β-action as an internal control. 75 patients presenting with invasive cervical cancer were i...

  5. The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Okada Yuji

    2006-10-01

    Full Text Available Abstract Background The transmembrane protein c-kit is a receptor tyrosine kinase (KIT and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST, small-cell lung cancer and chronic myelogenous leukemia (CML. KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. Results RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2. 5 μM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 μM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. Conclusion Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were

  6. Esophagectomy - minimally invasive

    Science.gov (United States)

    ... Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the esophagus -esophagectomy - ...

  7. miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7

    International Nuclear Information System (INIS)

    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

  8. miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Chuanyi [Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008 (China); Shen, Liangfang, E-mail: lfshen2008@163.com [Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008 (China); Mao, Lei; Wang, Bing; Li, Yang; Yu, Huizhi [Department of Radiation Oncology, Yueyang Second People' s Hospital, Yueyang 414000 (China)

    2015-02-27

    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.

  9. Cyanidin-3-Glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2

    Directory of Open Access Journals (Sweden)

    Wang Shiow

    2010-10-01

    Full Text Available Abstract Background Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G, an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS. This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion. Results C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7ErbB2 in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130Cas, as well as interactions among these proteins. C3G abolished ethanol-mediated p130Cas/JNK interaction. Conclusions C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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 EpCAMhigh breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAMlow 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 EpCAMhigh 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. EpCAMlow 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

  12. Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

    Science.gov (United States)

    Gong, Zhihong; Aragaki, Aaron K; Chlebowski, Rowan T; Manson, JoAnn E; Rohan, Thomas E; Chen, Chu; Vitolins, Mara Z; Tinker, Lesley F; LeBlanc, Erin S; Kuller, Lewis H; Hou, Lifang; LaMonte, Michael J; Luo, Juhua; Wactawski-Wende, Jean

    2016-04-15

    Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p cancers (HR, 1.2-1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer. PMID:26616262

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

    International Nuclear Information System (INIS)

    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

  14. ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.

    Science.gov (United States)

    Das, Lopamudra; Kokate, Shrikant Babanrao; Rath, Suvasmita; Rout, Niranjan; Singh, Shivaram Prasad; Crowe, Sheila Eileen; Mukhopadhyay, Asish K; Bhattacharyya, Asima

    2016-06-01

    Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose. PMID:27048589

  15. 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.

  16. Small interfering RNA targeted to secretory clusterin blocks tumor growth, motility, and invasion in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhaohe Niu; Xinhui Li; Bin Hu; Rong Li; Ligang Wang; Lilin Wu; Xingang Wang

    2012-01-01

    Clusterin/apolipoprotein J (Clu) is a ubiquitously expressed secreted heterodimeric glycoprotein that is implicated in several physiological processes.It has been reported that the elevated level of secreted clusterin (sClu) protein is associated with poor survival in breast cancer patients and can induce metastasis in rodent models.In this study,we investigated the effects of sClu inhibition with small interfering RNAs (siRNAs) on cell motility,invasion,and growth in vitro and in vivo.MDA-MB-231 cells were transfected with pSuper-siRNA/sClu.Cell survival and proliferation were examined by 3-(4,5-dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and clonogenic survival assay.The results showed that sClu silencing significantly inhibited the proliferation of MDA-MB-231 cells.The invasion and migration ability were also dramatically decreased,which was detected by matrigel assays.TUNEL staining and caspase-3 activity assay demonstrated that sClu silencing also could increase the apoptosis rate of cells,resulting in the inhibition of cell growth.We also determined the effects of sClu silencing on tumor growth and metastatic progression in an orthotopic breast cancer model.The results showed that orthotopic primary tumors derived from MDA-MB-231/pSuper sClu siRNA cells grew significantly slower than tumors derived from parental MDA-MB-231 or MDA-MB-231/pSuper scramble siRNA cells,and metastasize less to the lungs.These data suggest that secretory clusterin plays a significant role in tumor growth and metastatic progression.Knocking-down sClu gene expression may provide a valuable method for breast cancer therapy.

  17. Addressing future challenges for cancer services: part I.

    Science.gov (United States)

    Maher, Jane; Radford, Gina

    2016-02-01

    Jane Maher & Gina Radford speak to Gemma Westcott, Commissioning Editor Jane Maher has been Macmillan's Chief Medical Officer since 1999 and now shares the role as Joint Chief Medical Officer with general practitioner Rosie Loftus, reflecting the growing need for specialists and generalists to work more effectively together. She has been a National Health Service (NHS) Improvement Clinical Leader for over 10 years and is a Consultant Clinical Oncologist at Mount Vernon Cancer Centre where she has worked for more than 20 years, during which she helped develop nonsurgical oncology services in five district general hospitals. Jane chaired the Maher Committee for the Department of Health in 1995, led the UK National Audit of Late Effects Pelvic Radiotherapy for the Royal College Of Radiologists (RCR) in 2000 and, most recently, chaired the 'National Cancer Survivorship Initiative, consequences of treatment work stream'. She co-founded one of the first Cancer Support and Information services in the UK, winning the Nye Bevan award in 1992 and there are now more than 60 units based on this model. She is a member of the Older People and Cancer Clinical Advisory Group. She has written more than 100 published articles and is a UK representative for cancer survivorship in Europe and advises on Cancer survivorship programs in Denmark and Canada. Gina Radford is Deputy Chief Medical Officer for England, a post she took up in January 2015. Prior to that, she has held a number of roles in public health, at local and regional level. Most recently she was as Centre Director for Anglia and Essex for Public Health England, and as part of that role helped lead nationally on the public health response to Ebola. She was until very recently Chair of one of the NICE public health advisory committees. She has previously worked on a number of national projects, including leading the Department of Health's response to the Shipman Enquiry, undertaking a review of specialist public health for

  18. miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells

    Science.gov (United States)

    Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; Zhang, Wen-Hua; Pan, Yong-Ying; Song, Xing-Rong

    2016-01-01

    Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3’UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5. PMID:27186275

  19. miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4.

    Science.gov (United States)

    Zhao, Lifen; Feng, Xiaobin; Song, Xiaobo; Zhou, Huimin; Zhao, Yongfu; Cheng, Lei; Jia, Li

    2016-08-01

    Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR‑493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR‑493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. PMID:27375041

  20. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    International Nuclear Information System (INIS)

    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

  1. Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells.

    Science.gov (United States)

    Sponziello, Marialuisa; Rosignolo, Francesca; Celano, Marilena; Maggisano, Valentina; Pecce, Valeria; De Rose, Roberta Francesca; Lombardo, Giovanni Enrico; Durante, Cosimo; Filetti, Sebastiano; Damante, Giuseppe; Russo, Diego; Bulotta, Stefania

    2016-08-15

    In this study we analyzed the expression levels of markers of epithelial-to-mesenchymal transition (EMT) in several papillary thyroid carcinomas (PTCs) and the relation with tumor genotypes and clinicopathological characteristics. The role of fibronectin-1 (FN1) was investigated by analyzing the effects of FN1 silencing in two human thyroid cancer cell lines. Most of EMT markers were significantly over-expressed in a group of 36 PTCs. In particular, FN1 mRNA levels were higher in tumor vs non-tumor tissue (117.3, p < 0.001) and also in aggressive and BRAF(V600E) samples. Similar results were observed (and confirmed at the protein level) when FN1 expression was analyzed in a validation group of 50 PTCs and six lymph node (LN) metastases. Silencing of FN1 in TPC-1 and BCPAP thyroid cancer cells significantly reduced proliferation, adhesion, migration, and invasion in both cell lines. Collectively, our data indicate that FN1 overexpression is an important determinant of thyroid cancer aggressiveness. PMID:27173027

  2. Antibodies against high-risk human papillomavirus proteins as markers for invasive cervical cancer.

    Science.gov (United States)

    Combes, Jean-Damien; Pawlita, Michael; Waterboer, Tim; Hammouda, Doudja; Rajkumar, Thangarajan; Vanhems, Philippe; Snijders, Peter; Herrero, Rolando; Franceschi, Silvia; Clifford, Gary

    2014-11-15

    Different human papillomavirus (HPV) genes are expressed during the various phases of the HPV life cycle and may elicit immune responses in the process towards malignancy. To evaluate their association with cervical cancer, antibodies against proteins from HPV16 (L1, E1, E2, E4, E6 and E7) and HPV18/31/33/35/45/52/58 (L1, E6 and E7) were measured in serum of 307 invasive cervical cancer cases and 327 controls from Algeria and India. Antibody response was evaluated using a glutathione S-transferase-based multiplex serology assay and HPV DNA detected from exfoliated cervical cells using a GP5+/6+-mediated PCR assay. Among HPV16 DNA-positive cases, seroprevalence of HPV16 antibodies ranged from 16% for HPV16 E1 to 50% for HPV16 E6 and all were significantly higher than controls. Seroprevalence of E6, E7 and L1 antibodies for HPV18 and for at least one of HPV31/33/35/45/52/58 were also higher in cases positive for DNA of the corresponding type (50% and 30% for E6 of HPV18 and HPV31/33/35/45/52/58 combined, respectively). E6 and E7 antibodies were rarely found in controls, but cross-reactivity was evident among cancer cases positive for DNA of closely phylogenetically-related HPV types. E6 or E7 antibodies against any of the eight HPV types were detected in 66.1% of all cervical cancer cases, as compared to 10.1% of controls. E6, and to a lesser extent E7, antibodies appear to be specific markers of HPV-related malignancy. However, even among cases positive for the same type of HPV DNA, approximately one-third of cervical cancer cases show no detectable immune response to either E6 or E7. PMID:24729277

  3. SNAIL transcription factor increases the motility and invasive capacity of prostate cancer cells.

    Science.gov (United States)

    Osorio, Luis A; Farfán, Nancy M; Castellón, Enrique A; Contreras, Héctor R

    2016-01-01

    The incidence and mortality rates of prostate cancer (PCa) are increasing, and PCa is almost the second‑leading cause of cancer‑associated mortality in men. During tumor progression, epithelial cells decrease the number of adhesion molecules, change their polarity and position, rearrange their cytoskeleton and increase their migratory and invasive capacities. These changes are known under the concept of epithelial‑mesenchymal transition (EMT). EMT is characterized by an upregulation of certain transcription factors, including SNAIL1, which represses genes that are characteristic of an epithelial phenotype, including E‑cadherin, and indirectly increase the expression levels of genes, which are associated with the mesenchymal phenotype. It has been suggested that the transcription factor, SNAIL1, decreases the proliferation and increases the migratory and invasive capacities of PCa cell lines. The present study was performed using LNCaP and PC3 cell lines, in which the expression levels of SNAIL1 were increased or silenced through the use of lentiviral vectors. The expression levels of EMT markers were quantified using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In addition, cell survival was analyzed using an MTS assay; cell proliferation was examined using an antibody targeting Ki‑67; migration on plates with 8 µm pores to allow the passage of cells; and invasiveness was analyzed using a membrane chamber covered in dried basement membrane matrix solution. The levels of apoptosis were determined using a Caspase 3/7 assay containing a substrate modified by caspases 3 and 7. The results demonstrated that the overexpression and silencing of SNAIL1 decreased cell proliferation and survival. However, the overexpression of SNAIL1 decreased apoptosis, compared with cells with the SNAIL1‑silenced cells, in which cell apoptosis increased. The migration and invasive capacities increased in the cells overexpressing

  4. EFEMP1 Suppresses Growth and Invasion of Lung Cancer Cells 
by Downregulating Matrix Metalloproteinase-7 Expression

    OpenAIRE

    Yuanyuan LANG; Meng, Jie; Song, Xiaomeng; Chen, Xiaojun

    2015-01-01

    Background and objective EFEMP1, a member of fibulin family proteins, is a very important extracellular matrix protein which is involved in cell metabolism and its role in tumor occurrence and progression is still poorly understood. The aim of this study is to investigate the functional effect and mechanism of EFEMP1 in lung cancer cell growth and invasion. Methods EFEMP1 expression in lung cancer cells was determined by Western blot. The promoter methylation status of EFEMP1 was detected by ...

  5. The new era of minimally invasive interventions for prostate cancer: robot-assisted laparoscopic radical prostatectomy and focal therapy

    OpenAIRE

    Schatloff O; Louis AS; Lindner U

    2011-01-01

    Oscar Schatloff1, Alyssa S Louis2, Uri Lindner21Global Robotics Institute, Florida Hospital Celebration Health, Celebration, FL, USA; 2Division of Urology, Department of Surgical Oncology, University Health Network, Toronto, ON, CanadaAbstract: Prostate cancer remains a common but highly treatable disease. Innovations in prostate cancer treatment have allowed a transition toward minimally invasive approaches in an attempt to avoid treatment-related morbidities. In the middle of the treatment ...

  6. Associations between antioxidant vitamins and the risk of invasive cervical cancer in Chinese women: A case-control study

    OpenAIRE

    Liyuan Guo; Hong Zhu; Chengjun Lin; Jianhua Che; Xiujuan Tian; Shiyu Han; Honghui Zhao; Yumei Zhu; Dongwei Mao

    2015-01-01

    Previous studies on the associations between dietary antioxidant vitamins and the risk of cervical cancer remain inconsistent, and little evidence is available for serum antioxidant vitamins, which provide more accurate measurements of these nutrients. We conducted a case-control study of 458 incident cases with invasive cervical cancer and 742 controls to assess the effects of diet or serum antioxidant vitamins. Higher serum antioxidant vitamins were associated with a lower risk of cervical ...

  7. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

    OpenAIRE

    Dharmawardhane Suranganie F; Wall Kristin M; Hoffmeyer Michaela R

    2005-01-01

    Abstract Background Inflammatory breast cancer (IBC) is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. Results Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive prop...

  8. Anal cytology in women with cervical intraepithelial or invasive cancer: interobserver agreement

    Directory of Open Access Journals (Sweden)

    Sandra A. Heráclio

    2015-10-01

    Full Text Available ABSTRACTIntroduction:Incidence rates of anal cancer have been rising worldwide in the last 20 years. Due to embryological, histological and immunohistochemical similarities between the anal canal and the cervix, routine screening with anal cytology for precursor lesions in high-risk groups has been adopted. Objective: To determine interobserver agreement for the diagnosis of anal neoplasia by anal cytology.Material and methods:A cross-sectional observational study was conducted in 324 women with cervical intraepithelial or invasive cancers, for screening of anal cancer, from December 2008 to June 2009. Three hundred twenty-four cytological samples were analyzed by three cytopathologists. Cytological evaluation was based on the revised Bethesda terminology; samples were also classified into negative and positive for atypical cells. We calculated the kappa statistic with 95% confidence interval (95% CI to assess agreement among the three cytopathologists.Results:Interobserver agreement in the five categories of the Bethesda terminology was moderate (kappa for multiple raters: 0.6. Agreement among cytopathologists 1, 2 and 3 with a consensus diagnosis was strong (kappa: 0.71, 0.85 and 0.82, respectively.Conclusion:Interobserver agreement in anal cytology was moderate to strong, indicating that cervical cytomorphological criteria are reproducible also in anal samples.