WorldWideScience

Sample records for invasive cancer overview

  1. Breast Cancer Overview

    Science.gov (United States)

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

  2. Perioperative chemotherapy in muscle-invasive bladder cancer: overview and the unmet clinical need for alternative adjuvant therapy as studied in the MAGNOLIA trial

    NARCIS (Netherlands)

    Colombel, M.; Heidenreich, A.; Martinez-Pineiro, L.; Babjuk, M.; Korneyev, I.; Surcel, C.; Yakovlev, P.; Colombo, R.; Radziszewski, P.; Witjes, F.; Schipper, R.; Mulders, P.F.; Witjes, W.P.J.

    2014-01-01

    The European Association of Urology Research Foundation has proposed that alternatives to perioperative chemotherapy should be evaluated. The MAGNOLIA study represents a unique opportunity to investigate the concept of immunotherapy in muscle-invasive bladder cancer.

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

    African Journals Online (AJOL)

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

  4. Gallbladder Cancer Overview

    Science.gov (United States)

    ... Content Español ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  5. Vulvar Cancer Overview

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  6. Vaginal Cancer Overview

    Science.gov (United States)

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  7. Interstitial guidance of cancer invasion.

    NARCIS (Netherlands)

    Gritsenko, P.G.; Ilina, O.; Friedl, P.H.

    2012-01-01

    Cancer cell invasion into healthy tissues develops preferentially along pre-existing tracks of least resistance, followed by secondary tissue remodelling and destruction. The tissue scaffolds supporting or preventing guidance of invasion vary in structure and molecular composition between organs. In

  8. Cancer Prevention Overview (PDQ)

    Science.gov (United States)

    ... have been shown to reduce the risk of breast cancer in women at high risk. SERMS may cause side effects , such as hot flashes , so they are not often used for prevention of cancer. See the PDQ summary on Breast Cancer Prevention for more information. Finasteride has been ...

  9. Overview of oropharyngeal cancer

    Directory of Open Access Journals (Sweden)

    Gustavo Nader Marta

    2013-09-01

    Head and neck cancer designates a variety of neoplasms that are originated in the head and neck region, which involves the oropharinx, nasal cavity, oral cavity, pharynx, among other organs and tissues. The worldwide incidence of head and neck cancer exceeds half a million cases per year, being it ranked as the fifth most common tumor worldwide. This article's purpose is to describe the main concepts of anatomy, pathology, risk factors, clinical features and diagnosis of oropharyngeal cancer.

  10. Interstitial guidance of cancer invasion.

    Science.gov (United States)

    Gritsenko, Pavlo G; Ilina, Olga; Friedl, Peter

    2012-01-01

    Cancer cell invasion into healthy tissues develops preferentially along pre-existing tracks of least resistance, followed by secondary tissue remodelling and destruction. The tissue scaffolds supporting or preventing guidance of invasion vary in structure and molecular composition between organs. In the brain, the guidance is provided by myelinated axons, astrocyte processes, and blood vessels which are used as invasion routes by glioma cells. In the human breast, containing interstitial collagen-rich connective tissue, disseminating breast cancer cells preferentially invade along bundled collagen fibrils and the surface of adipocytes. In both invasion types, physical guidance prompted by interfaces and space is complemented by molecular guidance. Generic mechanisms shared by most, if not all, tissues include (i) guidance by integrins towards fibrillar interstitial collagen and/or laminins and type IV collagen in basement membranes decorating vessels and adipocytes, and, likely, CD44 engaging with hyaluronan; (ii) haptotactic guidance by chemokines and growth factors; and likely (iii) physical pushing mechanisms. Tissue-specific, resticted guidance cues include ECM proteins with restricted expression (tenascins, lecticans), cell-cell interfaces, and newly secreted matrix molecules decorating ECM fibres (laminin-332, thrombospondin-1, osteopontin, periostin). We here review physical and molecular guidance mechanisms in interstitial tissue and brain parenchyma and explore shared principles and organ-specific differences, and their implications for experimental model design and therapeutic targeting of tumour cell invasion. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. 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

  12. Treatment Option Overview (Rectal Cancer)

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Rectal Cancer Treatment (PDQ®)–Patient Version General Information About Rectal Cancer Go to Health Professional Version Key Points Rectal ...

  13. Treatment Option Overview (Breast Cancer)

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  14. Treatment Option Overview (Esophageal Cancer)

    Science.gov (United States)

    ... the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds , ... stage of the cancer being treated. External and internal radiation therapy are used to treat esophageal cancer. A plastic ...

  15. Treatment Option Overview (Anal Cancer)

    Science.gov (United States)

    ... the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds , ... stage of the cancer being treated. External and internal radiation therapy are used to treat anal cancer. Chemotherapy Chemotherapy ...

  16. Treatment Option Overview (Penile Cancer)

    Science.gov (United States)

    ... the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds , ... stage of the cancer being treated. External and internal radiation therapy are used to treat penile cancer. Chemotherapy Chemotherapy ...

  17. Dynamics of cancerous tissue correlates with invasiveness

    Science.gov (United States)

    West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

    2017-03-01

    Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

  18. Treatment Option Overview (Thyroid Cancer)

    Science.gov (United States)

    ... of cancer. Tracheostomy : Surgery to create an opening ( stoma ) into the windpipe to help you breathe. The ... information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come ...

  19. Treatment Option Overview (Endometrial Cancer)

    Science.gov (United States)

    ... uterus. See the PDQ summary on Uterine Sarcoma Treatment for more information about uterine sarcoma . Obesity and having metabolic syndrome may increase the risk of endometrial cancer. Anything ...

  20. Treatment Option Overview (Colon Cancer)

    Science.gov (United States)

    ... types of surgery : Local excision or simple polypectomy . Resection and anastomosis . This is done when the tumor is too ... stage I colon cancer usually includes the following: Resection and anastomosis . Use our clinical trial search to find NCI- ...

  1. Treatment Option Overview (Parathyroid Cancer)

    Science.gov (United States)

    ... sign of disease. Sestamibi scan : A type of radionuclide scan used to find an overactive parathyroid gland. ... speech problems caused by this nerve damage. Radiation therapy Radiation therapy is a cancer treatment that uses ...

  2. Treatment Option Overview (Gastric Cancer)

    Science.gov (United States)

    ... may be at risk. Risk factors for gastric cancer include the following: Having any of the following medical conditions : Helicobacter pylori (H. pylori) infection of the stomach. Chronic gastritis ( inflammation of the stomach). Pernicious anemia . Intestinal metaplasia ( ...

  3. Treatment Option Overview (Vaginal Cancer)

    Science.gov (United States)

    ... Nearby lymph nodes are also removed. Artificial openings ( stoma ) are made for urine and stool to flow ... information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come ...

  4. Treatment Option Overview (Vulvar Cancer)

    Science.gov (United States)

    ... nearby lymph nodes are also removed. Artificial openings ( stoma ) are made for urine and stool to flow ... information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come ...

  5. Treatment Option Overview (Urethral Cancer)

    Science.gov (United States)

    ... nodes by the time it is diagnosed . A history of bladder cancer can affect the risk of ... can be described as distal or proximal . Enlarge Anatomy of the distal and proximal urethra. Urine flows ...

  6. Treatment Option Overview (Bladder Cancer)

    Science.gov (United States)

    ... cyclophosphamide or ifosfamide . Taking Aristolochia fangchi , a Chinese herb . Drinking water from a well that has high ... patients may be given chemotherapy after surgery to kill any cancer cells that are left. Treatment given ...

  7. Treatment Option Overview (Prostate Cancer)

    Science.gov (United States)

    ... of bisphosphonate drugs to prevent or slow the growth of bone metastases is being studied in clinical trials. There are treatments for bone pain caused by bone metastases or hormone therapy. Prostate cancer that has spread to the ...

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

    Science.gov (United States)

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

    2014-02-01

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

  9. 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.

  10. Reprogramming cancer cells: overview & current progress.

    Science.gov (United States)

    Lim, Kian Lam; Teoh, Hoon Koon; Choong, Pei Feng; Teh, Hui Xin; Cheong, Soon Keng; Kamarul, Tunku

    2016-07-01

    Cancer is a disease with genetic and epigenetic origins, and the possible effects of reprogramming cancer cells using the defined sets of transcription factors remain largely uninvestigated. In the handful of publications available so far, findings have shown that reprogramming cancer cells changed the characteristics of the cells to differ from the parental cancer cells. These findings indicated the possibility of utilizing reprogramming technology to create a disease model in the laboratory to be used in studying the molecular pathogenesis or for drug screening of a particular cancer model. Despite numerous methods employed in generating induced pluripotent stem cells (iPSCs) from cancer cells only a few studies have successfully reprogrammed malignant human cells. In this review we will provide an overview on i) methods to reprogram cancer cells, ii) characterization of the reprogrammed cancer cells, and iii) the differential effects of reprogramming on malignancy, epigenetics and response of the cancer cells to chemotherapeutic agents. Continued technical progress in cancer cell reprogramming technology will be instrumental for more refined in vitro disease models and ultimately for the development of directed and personalized therapy for cancer patients in the future.

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

    Science.gov (United States)

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

    2012-06-01

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

  12. Treatment Option Overview (Cervical Cancer)

    Science.gov (United States)

    ... removed. These procedures are done using a low transverse incision or a vertical incision. Radical hysterectomy : Surgery ... tubes. Pelvic exenteration : Surgery to remove the lower colon , ... Radiation therapy is a cancer treatment that uses high-energy x-rays or ...

  13. 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....

  14. Non-muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  15. Cancer stem cell contribution to glioblastoma invasiveness.

    Science.gov (United States)

    Ortensi, Barbara; Setti, Matteo; Osti, Daniela; Pelicci, Giuliana

    2013-02-28

    Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. Its invasive nature currently represents the most challenging hurdle to surgical resection. The mechanism adopted by GBM cells to carry out their invasive strategy is an intricate program that recalls what takes place in embryonic cells during development and in carcinoma cells during metastasis formation, the so-called epithelial-to-mesenchymal transition. GBM cells undergo a series of molecular and conformational changes shifting the tumor toward mesenchymal traits, including extracellular matrix remodeling, cytoskeletal re-patterning, and stem-like trait acquisition. A deeper understanding of the mechanisms driving the whole infiltrative process represents the first step toward successful treatment of this pathology. Here, we review recent findings demonstrating the invasive nature of GBM cancer stem cells, together with novel candidate molecules associated with both cancer stem cell biology and GBM invasion, like doublecortin and microRNAs. These findings may affect the design of effective therapies currently not considered for GBM invasive progression.

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

    Science.gov (United States)

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

    2017-06-01

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

  17. Apoptosis and Tumor Invasion in Breast Cancer

    Science.gov (United States)

    2000-08-01

    while down- regulating the synthesis of at least one inhibitor S~ < of the matrix metalloproteases (TIMP-1) and f / / ,,"* , cystatin C . We are...UNCLASSIFIED AD Award Number: DAMD17-97-1-7268 TITLE: Apoptosis and Tumor Invasion in Breast Cancer PRINCIPAL INVESTIGATOR: Martin Tenniswood, Ph.D...preparing the same or similar computer software, or ( c ) used by a party other than the Government, except that the Government may release or disclose

  18. Minimally invasive surgery for stomach cancer.

    Science.gov (United States)

    Nunobe, Souya; Kumagai, Koshi; Ida, Satoshi; Ohashi, Manabu; Hiki, Naoki

    2016-05-01

    Laparoscopic surgery for gastric cancer has become extremely widespread in recent years especially in Asian countries due to its low invasiveness. As to evidence of indication for laparoscopic surgery for gastric cancer, laparoscopic surgery for gastric cancer often appears to be indicated for early gastric cancer at many institutions, while evidence was considered to be insufficient to recommend laparoscopic surgery for gastric cancer at Stage II and above. There are also problems with indications for cases other than tumour factors. No meta-analyses and prospective studies have been reported, but outcomes of laparoscopic surgery for gastric cancer in gastric cancer patients with co-morbid and/or existing diseases have been reported in retrospective studies. Indications in the elderly appear to be favourable in terms of post-operative ambulation considering factors such as the degree of dissection in accordance with the status of the patient. Meta-analyses, randomized controlled trials and several retrospective studies have compared the short-term usefulness of laparoscopic surgery for gastric cancer with that of conventional gastrectomy. The superiority of laparoscopic surgery for gastric cancer has been reported in terms of the reduced amount of bleeding, a reduction in the administration frequency and period of analgesic doses, a reduction in the duration of fever, early recovery of intestinal movement and early return to oral intake. A small-scale randomized controlled trial and several retrospective studies have demonstrated no significant differences in survival rate, recurrence rate and type of recurrence between laparoscopic surgery for gastric cancer and conventional gastrectomy. The results of the aforementioned trials in early gastric cancer in Japan and Korea for which enrolment is complete remain to be published. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Primary cilia are lost in preinvasive and invasive prostate cancer.

    Directory of Open Access Journals (Sweden)

    Nadia B Hassounah

    Full Text Available Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Little is known about the role of primary cilia in preinvasive and invasive prostate cancer. However, reduced cilia expression has been observed in human cancers including pancreatic cancer, renal cell carcinoma, breast cancer, cholangiocarcinoma, and melanoma. The aim of this study was to characterize primary cilia expression in preinvasive and invasive human prostate cancer, and to investigate the correlation between primary cilia and the Wnt signaling pathway. Human prostate tissues representative of stages of prostate cancer formation (normal prostate, prostatic intraepithelial neoplasia (PIN, and invasive prostate cancer (including perineural invasion were stained for ciliary proteins. The frequency of primary cilia was determined. A decrease in the percentage of ciliated cells in PIN, invasive cancer and perineural invasion lesions was observed when compared to normal. Cilia lengths were also measured to indirectly test functionality. Cilia were shorter in PIN, cancer, and perineural invasion lesions, suggesting dysfunction. Primary cilia have been shown to suppress the Wnt pathway. Increased Wnt signaling has been implicated in prostate cancer. Therefore, we investigated a correlation between loss of primary cilia and increased Wnt signaling in normal prostate and in preinvasive and invasive prostate cancer. To investigate Wnt signaling in our cohort, serial tissue sections were stained for β-catenin as a measure of Wnt signaling. Nuclear β-catenin was analyzed and Wnt signaling was found to be higher in un-ciliated cells in the normal prostate, PIN, a subset of invasive cancers, and perineural invasion. Our results suggest that cilia normally function to suppress the Wnt signaling pathway in epithelial cells and that cilia loss may play a role in increased Wnt signaling in some prostate cancers. These results suggest that cilia are dysfunctional in human

  20. Immune Infiltration in Invasive Lobular Breast Cancer.

    Science.gov (United States)

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

    2018-02-20

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

  1. Minimally invasive approaches for diagnosis and treatment of early-stage breast cancer.

    Science.gov (United States)

    Vlastos, Georges; Verkooijen, Helena M

    2007-01-01

    Breast cancer management has been evolving toward minimally invasive approaches. Image-guided percutaneous biopsy techniques provide accurate histologic diagnosis without the need for surgical biopsy. Breast conservation therapy has become the treatment standard for early-stage breast cancer. Sentinel lymph node biopsy is a new procedure that can predict axillary lymph node status without the need of axillary lymph node dissection. The next challenge is to treat primary tumors without surgery. For this purpose, several new minimally invasive procedures, including radiofrequency ablation, interstitial laser ablation, focused ultrasound ablation, and cryotherapy, are currently under development and may offer effective tumor management and provide treatment options that are psychologically and cosmetically more acceptable to the patients than are traditional surgical therapies. In this review, we give an overview of minimally invasive approaches for the diagnostic and therapeutic management of early-stage breast cancer.

  2. Pancreatic cancer: overview of descriptive epidemiology.

    Science.gov (United States)

    Bosetti, Cristina; Bertuccio, Paola; Negri, Eva; La Vecchia, Carlo; Zeegers, Maurice P; Boffetta, Paolo

    2012-01-01

    Pancreatic cancer mortality rates have been increasing in high-income countries between the 1950s and the 1980s, and have leveled off or declined thereafter, particularly in men. To provide a global overview of recent pancreatic cancer mortality, we analyzed official death of the world certification data derived from the World Health Organization for 35 European countries and 19 other countries over the period 1980-2007. In 2007, the highest mortality rates from pancreatic cancer were in the Baltic countries, and some central/eastern and northern European countries (over 9.5/100 000 men and 6/100 000 women), whereas the lowest ones were in Latin America and Hong Kong (below 5/100 000 men and 3/100 000 women). Japan, the USA, Russia and the European Union (EU), as well as the largest countries in the EU, had rates around 7-9/100 000 men and 5-6/100 000 women. In the early 2000s, rates have been approximately stable in many European countries, as in the USA, Japan, and Australia. In Nordic countries and the UK, where declines in rates have been observed between the 1980s and the 1990s, mortality from pancreatic cancer has tended to rise over most recent calendar years. Some persisting rises were still found in men from a few countries of southern and central/eastern Europe (with low rates in the past), as well as in the EU overall, and in women from European and Asian countries. Recent trends were generally more favorable in young adults (30-49 yr), suggesting that overall trends are likely to improve in the near future. Copyright © 2011 Wiley Periodicals, Inc.

  3. Red swamp crayfish: biology, ecology and invasion - an overview

    Directory of Open Access Journals (Sweden)

    Tainã Gonçalves Loureiro

    Full Text Available ABSTRACTAlien species have been transported and traded by humans for many centuries. However, with the era of globalization, biological invasions have reached notable magnitudes. Currently, introduction of alien species is one of the major threats to biodiversity and ecosystem functioning. The North American crayfish Procambarus clarkii is one of the most widely introduced freshwater species in the world, especially due to its high economic importance. It is responsible for great modifications in invaded environments causing irreparable ecological and economic damages. Its impressive ability to successfully colonize a wide range of environments is a consequence of its behavioural and biological characteristics that can adapt to features of the invaded location, conferring to this species a notable ecological plasticity. This review summarizes the available information regarding P. clarkii's biology and invasive dynamics around the world in order to contribute to the understanding of the threats posed by its establishment, as well as to support management and impact mitigation efforts.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  5. Clinicopathological features of stomach cancer with invasive micropapillary component.

    Science.gov (United States)

    Fujita, Takeo; Gotohda, Naoto; Kato, Yuichiro; Kinoshita, Takahiro; Takahashi, Shinichiro; Konishi, Masaru; Daiko, Hiroyuki; Nishimura, Mitsuyo; Kuwata, Takeshi; Ochiai, Atsushi; Kinoshita, Taira

    2012-04-01

    Invasive micropapillary carcinoma has been recognized as a rare disease entity with aggressive tumor behavior. However, few reports have described invasive micropapillary carcinoma in the gastrointestinal tract, particularly its involvement in gastric cancer. We retrospectively analyzed 930 patients diagnosed with gastric cancer who underwent gastrectomy, and we then histopathologically evaluated the existence of a regional invasive micropapillary component. Clinicopathological features were investigated in patients with an invasive micropapillary component and compared with such features in 100 patients with gastric adenocarcinoma, selected as stage-matched controls, who underwent gastrectomy during the same period. Of the 930 patients, 14 were histopathologically diagnosed with gastric cancer with a regional invasive micropapillary component. There were no significant differences in age, gender, tumor location, macroscopic type, or type of surgery between patients with an invasive micropapillary component and the pT-matched controls. Histopathologically, significant differences were observed in lymphatic infiltration, venous invasion, the percentage of cases with lymph node metastasis, and the median number of metastatic lymph nodes. The three-year disease-free and overall survival rates of patients with an invasive micropapillary component were 40.5 and 59.3%, respectively, compared with those for the stage-matched controls, which were 72.6 and 80.6%, respectively (p = 0.02 and 0.07). Patients with gastric cancer with a regional invasive micropapillary component showed marked cancer infiltration in the lymphatic pathway and poor prognosis after gastrectomy.

  6. Hypofractionated radiotherapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Scholten, Astrid N.; Leer, Jan-Willem H.; Collins, C. David; Wondergem, Jan; Hermans, Jo; Timothy, Adrian

    1997-01-01

    Background and purpose: The policy of the Radiotherapy Department of St. Thomas' Hospital in London for patients with invasive bladder cancer, used to be treatment with hypofractionated radiotherapy. The advantages of this fractionation scheme included reduction of the number of treatment sessions and better use of limited resources. Our results after hypofractionation were compared to series with more conventional radiotherapy. Material and methods: Between 1975 and 1985, 123 patients with a T2-T3 transitional cell carcinoma of the bladder were treated by a radical course of hypofractionated radiotherapy. Local control, survival and morbidity rates were analysed retrospectively. Results: The actuarial local control rates at 5 and 10 years were 31 and 29%, respectively. The actuarial cancer-specific 5- and 10-year survival rates were 48 and 39%, respectively. Acute side effects were observed in 87% of patients. The actuarial overall and severe late complication rates at 5 years were 33 and 9%, respectively. The local control, survival and early side effect rates we found, were in the same range as those reported in literature. Late radiation side effects however, were more common after hypofractionated radiotherapy compared to conventional radiotherapy schedules. Conclusions: We conclude that the potential advantage of a reduced number of treatment sessions may be lost in the long term, because of the higher incidence of late morbidity after hypofractionated radiotherapy. Hypofractionation however, remains a valuable technique for palliation and deserves further investigation for radical treatment where access to equipment is difficult or resources are limited

  7. 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.

  8. 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.

  9. Treatment Option Overview (Small Intestine Cancer)

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  10. Elevated incidence of fractures in women with invasive breast cancer.

    Science.gov (United States)

    Edwards, B J; Gradishar, W J; Smith, M E; Pacheco, J A; Holbrook, J; McKoy, J M; Nardone, B; Tica, S; Godinez-Puig, V; Rademaker, A W; Helenowski, I B; Bunta, A D; Stern, P H; Rosen, S T; West, D P; Guise, T A

    2016-02-01

    This study evaluates the incidence of bone fractures in women with BC.We found that women with invasive breast cancer are at an increased risk for bone fractures, with fractures most commonly occurring at lower extremity and vertebral sites. The risk is further increased in women undergoing cancer therapy. Bone loss and fractures in breast cancer have generally been attributed to aromatase inhibitor use. This study assessed the incidence of fractures after invasive breast cancer diagnosis and evaluated bone density and FRAX risk calculation at time of fracture occurrence. Retrospective cohort study of women with invasive breast cancer [June 2003-December 2011] who participated in an academic hospital based genetic biobank. Demographic and clinical characteristics were abstracted from the electronic medical record (EMR). A total of 422 women with invasive breast cancer were assessed; 79 (28 %) sustained fractures during the observation period; fractures occurred at multiple skeletal sites in 27 cases (116 fractures). The incidence of fractures was 40 per 1000 person-years. Women who sustained fractures were mostly white and had a family history of osteoporosis (36.9 %, p = 0.03) or history of a prior fracture (6/79, p = 0.004). Fractures occurred 4.0 years (range 0-12 years) after cancer diagnosis. Fracture cases had femoral neck bone mineral density (BMD) of 0.72 + 0.12 g/cm(2), T-score of -1.2, that is, within the low bone mass range. Fractures most commonly occurred in lower extremities, vertebral, and wrist sites. Hip fractures accounted for 11 % of fractures, occurring at a median age of 61 years. Fractures occur shortly after commencing cancer therapy. Rapid bone loss associated with cancer therapy may precipitate fractures. Fractures occur at relatively higher BMD in BC. Occurrence of fractures in invasive breast cancer raises the possibility of cancer-induced impairment in bone quality.

  11. Perioperative management of nonmuscle-invasive bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

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

  12. 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.

  13. Drug Resistance in Cancer: An Overview

    Science.gov (United States)

    Housman, Genevieve; Byler, Shannon; Heerboth, Sarah; Lapinska, Karolina; Longacre, Mckenna; Snyder, Nicole; Sarkar, Sibaji

    2014-01-01

    Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance. It also describes the epigenetic modifications that can induce drug resistance and considers how such epigenetic factors may contribute to the development of cancer progenitor cells, which are not killed by conventional cancer therapies. Lastly, this review concludes with a discussion on the best treatment options for existing drug resistant cancers, ways to prevent the formation of drug resistant cancers and cancer progenitor cells, and future directions of study. PMID:25198391

  14. IKKε coordinates invasion and metastasis of ovarian cancer

    Science.gov (United States)

    Hsu, Sarah; Kim, Marianne; Hernandez, Lidia; Grajales, Valentina; Noonan, Anne; Anver, Miriam; Davidson, Ben; Annunziata, Christina M.

    2012-01-01

    I-κB kinases (IKKs) are key regulators of NF-κB signaling. Three IKK isoforms – α, β and ε – have been linked to oncogenesis, yet the precise components of NF-κB signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKKε expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (p=0.03). Therefore, we hypothesized that IKKε drives ovarian cancer metastasis. IKKε was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. We now define an ovarian cancer-specific IKKε-regulated gene expression signature using stably expressed shRNA targeting IKKε. Pathway analysis of the signature indicated that IKKε regulates expression of genes involved in cell motility and inflammation. We further showed that IKKε depletion in metastatic ovarian cancer cell lines decreased growth, adhesion, and invasion. Consistently, human xenografts depleted of IKKε in mice demonstrated decreased aggressiveness, while overexpression of IKKε in a less invasive ovarian cancer cell line increased metastasis in vivo. Taken together, these data provide evidence that IKKε is a key coordinator of invasion and metastasis programs in ovarian cancer. Inhibition of IKKε signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer demonstrates aberrant activation of this pathway. PMID:22942254

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

    Science.gov (United States)

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

    2015-04-17

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

  16. 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.

  17. Association of diabetes and perineural invasion in pancreatic cancer.

    Science.gov (United States)

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

    2012-12-01

    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 record review. Patients with diabetes before or at the time of the pancreatic cancer diagnosis were considered diabetes only. Pearson χ(2) test was used to compare categorical variables in diabetic and nondiabetic groups. Kaplan-Meier plot, log-rank test, and Cox proportional regression models were applied in survival analysis. The prevalence of diabetes and perineural invasion was 26.5% and 86.9%, respectively, in this study population. Patients with diabetes had a significantly higher prevalence of perineural invasion (92.4%) than those without diabetes (85%) (P = 0.025, χ(2) test). Diabetes was not associated with other pathological characteristics of the tumor, such as tumor size, lymphovascular invasion, tumor grade, lymph node metastasis, and resection margin status. Diabetic patients had a significantly lower frequency of abdominal pain (P = 0.01), but a slightly higher frequency of weight loss (P = 0.078) as early symptoms of their cancer. Both diabetes and perineural invasion were related to worse survival and increased risk of death after adjusting for tumor grade and margin and node status (P = 0.036 and 0.019, respectively). The observed associations of diabetes and perineural invasion as well as reduced frequency of pain as early symptom of pancreatic cancer support the hypothesis that diabetes may contribute to pancreatic progression via the mechanism of nerve damage.

  18. Treatment Option Overview (Male Breast Cancer)

    Science.gov (United States)

    ... and improve quality of life . Strontium-89 (a radionuclide ) to relieve pain from cancer that has spread to bones throughout the body. Other treatment options Other treatment options for metastatic breast cancer include: Drug therapy with bisphosphonates or denosumab to reduce bone disease ...

  19. Non Melanoma Skin Cancer Pathogenesis Overview.

    Science.gov (United States)

    Didona, Dario; Paolino, Giovanni; Bottoni, Ugo; Cantisani, Carmen

    2018-01-02

    (1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

  20. Micrornas in prostate cancer: an overview

    Science.gov (United States)

    Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

    2017-01-01

    Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis. PMID:28445135

  1. Nutrition and prostate cancer: an overview.

    Science.gov (United States)

    Patel, Venita H

    2014-11-01

    There is increasing evidence for a link between nutrition, lifestyle and prostate cancer development. There is also growing interest from patients, with significant numbers of men using complementary and alternative medicines, such as vitamins and types of diet. Obesity and metabolic syndrome are important risk factors for prostate cancer and their management is key. The amount and type of fats consumed are also clearly related to prostate cancer risk. Saturated fats and trans fats are identified as having a negative impact. Nutraceuticals and supplements, particularly antioxidants, polyphenols and soy have evidence for benefit for prevention of prostate cancer and progression of the disease. A selection of nutrients is highlighted in this article. Nutritional therapists advise patients on how to incorporate these beneficial nutrients into their diet and guide them on supplement use. Further research is required to elucidate the connection between diet, nutrients and prostate cancer, including the field of nutrigenetics.

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

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

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

  3. Treatment Option Overview (Adult Primary Liver Cancer)

    Science.gov (United States)

    ... transplant Ablation therapy Embolization therapy Targeted therapy Radiation therapy New types of treatment are being tested in clinical trials. ... needles and tumor which kills cancer cells . Microwave therapy : A type of treatment in which the tumor is exposed ...

  4. Cancer-related fatigue treatment: An overview

    Directory of Open Access Journals (Sweden)

    Hemanth Mohandas

    2017-01-01

    Full Text Available Cancer-related fatigue is a symptom of cancer where most patients or the general practitioners tend to misinterpret due to the insufficient understanding or knowledge of cancer-related fatigue (CRF. This paper will provide a better perspective for the patients and the health professionals on how to manage and handle CRF for both mild and severe fatigue patients. Articles were selected from the searches of PubMed database that had the terms “randomized controlled trials,” “cancer,” “fatigue,” “pharmacologic treatment,” and “nonpharmacologic treatment” using both Mesh terms and keywords. The authors have reviewed the current hypothesis and evidence of the detailed etiology of the CRF present in the literature for healthier management, directives, and strategies to improve the treatment of cancer-related fatigue. An algorithm has been blueprinted on screening, and management, of the CRF, and various kinds of effective treatments and assessment tools have been briefly studied and explained. Although many strategies seemed promising, the quality of randomized controlled trials is generally quite low in studies, making it difficult to draw conclusions about the effectiveness of each self-care strategies. Therefore, future studies require better design and reporting of methodological issues to ensure evidence-based self-care recommendations for people receiving cancer treatment.

  5. Childhood Cancer Survivor Study: An Overview

    Science.gov (United States)

    ... Study (Jul. 2014, Lancet Oncology; see the journal article ) Aging and risk of severe, disabling, life-threatening, and ... 2013, Journal of Clinical Oncology; see the journal article ) Radiation-related risk of basal cell carcinoma : A Report from the Childhood Cancer Survivor ...

  6. Psychosomatic Aspects of Cancer: An Overview.

    Science.gov (United States)

    Murray, John B.

    1980-01-01

    It is suggested in this literature review on the psychosomatic aspects of cancer that psychoanalytic interpretations which focused on intrapsychic elements have given way to considerations of rehabilitation and assistance with the complex emotional reactions of patients and their families to terminal illness and death. (Author/DB)

  7. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... being treated. See Drugs Approved for Kidney (Renal Cell) Cancer for more information. Biologic therapy Biologic therapy is a treatment that uses ... called biotherapy or immunotherapy. The following types of biologic therapy are being used or ... Nivolumab : Nivolumab is a monoclonal antibody that boosts ...

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  9. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has...... helped triage patients but improved tools, including biomarkers, are still needed. Enhanced endoscopy with photodynamic imaging, narrow band imaging, optical coherence tomography and confocal laser endomicroscopy show promise for diagnosis, risk stratification and disease monitoring. Attempts at better...

  10. Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion.

    Science.gov (United States)

    Tamura, Masato; Matsui, Hirofumi; Tomita, Tsutomu; Sadakata, Hisato; Indo, Hiroko P; Majima, Hideyuki J; Kaneko, Tsuyoshi; Hyodo, Ichinosuke

    2014-01-01

    Tumor invasion is the most important factor to decide patient's prognosis. The relation between reactive oxygen species and tumor invasion is mainly reported that nicotinamide adenine dinucleotide phosphate oxidase in the cell membrane is a reactive oxygen species producer for formulating an invadopodia. On the other hand, mitochondrion was known as one of the most important reactive oxygen species-producer in the cell via an energy transfer system. However, the relation between mitochondrial reactive oxygen species and the tumor invasion was not well clarified. In this study, we evaluated the relation between mitochondrial reactive oxygen species and tumor invasion using a normal gastric mucosal cell-line (RGM-1) and a cancerous mutant RGM-1 cell-line (RGK-1). Manganese superoxide dismutase-expressing RGK-1 cell-lines were used for a scavenging mitochondrial reactive oxygen species. The cells have been evaluated their movement ability as follows; cellular ruffling frequencies, wound healing assay to evaluate horizontal cellular migration, and invasion assay using matrigel to analyze vertical cellular migration. All cellular movement abilities were inhibited by scavenging mitochondrial reactive oxygen species with manganese superoxide dismutase. Therefore mitochondrial reactive oxygen species was one of factors enhancing the tumor invasion in gastric cancer.

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

    Science.gov (United States)

    Gordon, Randy

    2013-08-01

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

  12. Hypoxia stimulates invasion and migration of human cervical cancer ...

    Indian Academy of Sciences (India)

    Hao Xu

    2017-07-25

    Jul 25, 2017 ... cervical cancer cell lines invasion and migration are not yet clearly understood. Furthermore, and perhaps more importantly, tumour cells must survive in environmental conditions not present in normal tissue (Brown 1999). One of the most formidable barriers to their survival is hypoxia (Yoon et al. 2005).

  13. The major thoracic vascular invasion of lung cancer

    Directory of Open Access Journals (Sweden)

    Soichi Oka

    2017-08-01

    Conclusion: The positive predictive value of the preoperative CT findings for tumor invasion of the thoracic vessels was low. Therefore, surgical opportunities that offer the chance of a cure shouldn't be missed in advanced lung cancer patients because the tumor is located near the major thoracic vessels on preoperative CT.

  14. Cervical intra-epithelial neoplasia and invasive cervical cancer in ...

    African Journals Online (AJOL)

    The relative incidences of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer were studied in black and white patients at the academic hospitals of the University of the Orange Free State. A statistically highly significant difference was found between black and white patients, with a higher incidence of ...

  15. Overview of genes, diet and cancer

    OpenAIRE

    Mathers, J. C.

    2007-01-01

    Quantitative epidemiological analysis suggests that about one third of the variation in cancer risk can be attributed to variation in dietary exposure but it has proved difficult, using conventional epidemiological approaches, to identify which dietary components, in what amounts and over what time-scales are protective or potentially hazardous. Work in this area has been hampered by the lack of robust surrogate endpoints. However, the rapidly accumulating knowledge of the biological basis of...

  16. ATMPs for Cancer Immunotherapy: A Regulatory Overview.

    Science.gov (United States)

    Galli, Maria Cristina

    2016-01-01

    This chapter discusses European regulatory requirements for development of advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches, describing the framework for clinical trials and for marketing authorization.Regulatory critical issues and challenges for developing ATMP are also discussed, with focus on potency determination, long-term follow-up, comparability, and insertional mutagenesis issues. Some of the most critical features of GMP application to ATMP are also described.

  17. Overview of mechanisms of cancer chemopreventive agents

    International Nuclear Information System (INIS)

    De Flora, Silvio; Ferguson, Lynnette R.

    2005-01-01

    Epidemiological data provide evidence that it is possible to prevent cancer and other chronic diseases, some of which share common pathogenetic mechanisms, such as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is avoidance of exposure to recognized risk factors. As complementary strategies, it is possible to render the organism more resistant to mutagens/carcinogens and/or to inhibit progression of the disease by administering chemopreventive agents. In a primary prevention setting, addressed to apparently healthy individuals, it is possible to inhibit mutation and cancer initiation by triggering protective mechanisms either in the extracellular environment or inside cells, e.g., by modifying transmembrane transport, modulating metabolism, blocking reactive species, inhibiting cell replication, maintaining DNA structure, modulating DNA metabolism and repair, and controlling gene expression. Tumor promotion can be counteracted by inhibiting genotoxic effects, favoring antioxidant and anti-inflammatory activity, inhibiting proteases and cell proliferation, inducing cell differentiation, modulating apoptosis and signal transduction pathways, and protecting intercellular communications. In a secondary prevention setting, when a premalignant lesion has been detected, it is possible to inhibit tumor progression via the same mechanisms, and in addition by affecting the hormonal status and the immune system in various ways, and by inhibiting tumor angiogenesis. Although tertiary prevention, addressed to cancer patients after therapy, is outside the classical definition of chemoprevention, it exploits similar mechanisms. It is also possible to affect cell-adhesion molecules, to activate antimetastasis genes, and to inhibit proteases involved in basement membrane degradation

  18. 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.

  19. Overview of Photogrammetric Measurement Techniques in Minimally Invasive Surgery Using Endoscopes

    Science.gov (United States)

    Conen, N.; Luhmann, T.

    2017-05-01

    This contribution provides an overview of various photogrammetric measurement techniques in minimally invasive surgery and presents a self-developed prototypical trinocular endoscope for reliable surface measurements. Most of the presented techniques focus on applications regarding laparoscopy, which mean endoscopic operations in the abdominal or pelvic cavities. Since endoscopic operations are very demanding to the surgeon, various assistant systems have been developed. Imaging systems may use photogrammetric techniques in order to perform 3D measurements during operation. The intra-operatively acquired 3D data may be used for analysis, model registration, guidance or documentation. Passive and active techniques have been miniaturised, integrated into endoscopes and investigated by several research groups. The main advantages and disadvantages of several active and passive techniques adapted to laparoscopy are described in this contribution. Additionally, a self-developed trinocular endoscope is described and evaluated.

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

    Science.gov (United States)

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

    2014-10-01

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

  1. Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.

    Science.gov (United States)

    Hallou, Adrien; Jennings, Joel; Kabla, Alexandre J

    2017-08-01

    Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo , such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  3. Globular adiponectin enhances invasion in human breast cancer cells

    Science.gov (United States)

    FALK LIBBY, EMILY; LIU, JIANZHONG; LI, YI; LEWIS, MONICA J.; DEMARK-WAHNEFRIED, WENDY; HURST, DOUGLAS R.

    2016-01-01

    Every year, a large number of women succumb to metastatic breast cancer due to a lack of curative approaches for this disease. Adiponectin (AdipoQ) is the most abundant of the adipocyte-secreted adipokines. In recent years, there has been an interest in the use of AdipoQ and AdipoQ receptor agonists as therapeutic agents for the treatment of breast cancer. However, while multiple epidemiological studies have previously indicated that low levels of circulating plasma AdipoQ portend poor prognosis in patients with breast cancer, recent studies have reported that elevated expression levels of AdipoQ in breast tissue are correlated with advanced stages of the disease. Thus, the aim of the present study was to clarify the mechanism by which AdipoQ in breast tissue acts directly on tumor cells to regulate the early steps of breast cancer metastasis. In the present study, the effects of different AdipoQ isoforms on the metastatic potential of human breast cancer cells were investigated. The results revealed that globular adiponectin (gAd) promoted invasive cell morphology and significantly increased the migration and invasion abilities of breast cancer cells, whereas full-length adiponectin (fAd) had no effect on these cells. Additionally, gAd, but not fAd, increased the expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B)-II and intracellular LC3B puncta, which are indicators of autophagosome formation, thus suggesting autophagic induction by gAd. Furthermore, the inhibition of autophagic function by autophagy-related protein 7 knockdown attenuated the gAd-induced increase in invasiveness in breast cancer cells. Therefore, the results of the present study suggested that a specific AdipoQ isoform may enhance breast cancer invasion, possibly via autophagic induction. Understanding the roles of the different AdipoQ isoforms as microenvironmental regulatory molecules may aid the development of effective AdipoQ-based treatments for breast cancer

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

    Science.gov (United States)

    Porten, Sima P; Cooperberg, Matthew R

    2012-09-01

    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. The mainstay definitions of high-risk nonmuscle invasive bladder cancer are based on grade and stage. Recently, efforts have been made to incorporate other clinical variables into multivariate risk assessment tools and nomograms to predict disease behavior and guide management. Variant histology and molecular biomarkers are being explored as tools to refine risk stratification; however, results are still preliminary and need validation. Future research should concentrate on ways to better risk-stratify patients and identify early those that are most likely to recur and progress quickly. Topics of focus should be on better multivariate risk assessment tools and nomograms providing continuous scales and incorporating molecular markers with validation in large multi-institutional cohorts.

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

    Directory of Open Access Journals (Sweden)

    Li Li

    2013-07-01

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

  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...

  7. 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.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-15

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

  10. Prescription of Chinese herbal products is associated with a decreased risk of invasive breast cancer

    Science.gov (United States)

    Tsai, Yueh-Ting; Lai, Jung-Nien; Lo, Pei-Chia; Chen, Chin-Nu; Lin, Jaung-Geng

    2017-01-01

    Abstract The finding of a decrease in endometrial cancer incidence among breast cancer survivors following the use of Chinese herbal products (CHPs) has led to speculation that CHPs might play a role in breast cancer prevention. This study provides an overview of breast cancer incidence, comparing CHP users with those who do not use traditional Chinese medicine (TCM), referred to as non-TCM users. The results can provide information to clinicians for counseling women about the preventive use of TCM. A total of 184,386 women (20–79 years of age) were recruited from a nationwide 1-million-person representative sample of those covered by National Health Insurance in Taiwan and were followed from 1999 to 2012. A total of 1853 incidents of invasive breast cancer were diagnosed. The person-year approach with the Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios of breast cancer in relation to either CHP or siwutang (SWT) use were calculated with multivariate Cox proportional hazard regression. More than 78% of patients had used a CHP at some point previously. The overall incidence density rate of breast cancer for non-TCM users was estimated at 1.73 per 10,000 patient-years. The corresponding values for CHP and SWT users were lower than those of the non-TCM group (CHP group = 0.85; SWT group = 0.63 per 10,000 patient-years). The covariate adjusted HRs for breast cancer were 0.57 (95% confidence interval [CI] 0.50–0.65) and 0.36 (95% CI 0.28–0.46) in women using CHPs and SWT, respectively. The findings were confirmed using propensity score matching. Consumption of CHPs reduces the incidence of invasive breast cancer. Although the mechanism of action of these products is unclear, their use as a preventive agent for breast cancer is appropriate for many women at an increased risk of breast cancer. PMID:28858112

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

    Marenčák, J; Ondrušová, M; Ondruš, D

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

  13. Small invasive colon cancer with systemic metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Sakamoto Taku

    2011-05-01

    Full Text Available ABSTRACT Background Recently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size. Case Presentation A 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy. Conclusions In this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

  14. Overview of CDK9 as a target in cancer research.

    Science.gov (United States)

    Morales, Fatima; Giordano, Antonio

    2016-01-01

    CDK9 is a protein in constant development in cancer therapy. Herein we present an overview of the enzyme as a target for cancer therapy. We provide data on its characteristics and mechanism of action. In recent years, CDK9 inhibitors that have been designed with molecular modeling have demonstrated good antitumoral activity in vitro. Clinical studies of the drugs flavopiridol, dinaciclib, seliciclib, SNS-032 and RGB-286638 used as CDK9 inhibitors are also reviewed, with their additional targets and their relative IC50 values. Unfortunately, treatment with these drugs remains unsuccessful and involves many adverse effects. We could conclude that there are many small molecules that bind to CDK9, but their lack of selectivity against other CDKs do not allow them to get to the clinical use. However, drug designers currently have the tools needed to improve the selectivity of CDK9 inhibitors and to make successful treatment available to patients.

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

    OpenAIRE

    Varga, Z; Mallon, E

    2009-01-01

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

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

    International Nuclear Information System (INIS)

    Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

    2012-01-01

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

  17. 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.

  18. Invasive Haemophilus influenzae Infection in Patients With Cancer.

    Science.gov (United States)

    Singh, Vivek; Nanjappa, Sowmya; Pabbathi, Smitha; Greene, John N

    2017-01-01

    A major cause of morbidity and mortality in patients with cancer is infection. Since the introduction of the Haemophilus influenzae type b (Hib) vaccine in the United States in the 1990s, invasive H influenzae infection has become less common. We report on 5 patients with cancer and invasive H influenzae infection. A literature review was also performed of the dominant Haemophilus subtype and the clinical features associated with the infection and concomitant cancer. Of the 17 cases found in the literature, had hematological malignancies and 1 case each had thymoma, schwannoma, teratoma, and pancreatic, Merkel cell, pharyngeal, laryngeal, and rectal carcinomas. Two cases occurred with AIDS and Kaposi sarcoma. Pneumonia with bacteremia was seen in 8 cases, whereas pleuritis, neck cellulitis, septic arthritis, meningitis, and mediastinitis were diagnosed in the others. No focus of infection was identified in 2 cases. Nontypable H influenzae (NTHi) occurred in 4 cases, and Hib was isolated in 2 cases; serotyping was not reported in the others. Leukocytosis occurred in 7 cases and lymphopenia in 3; no cases presented with neutropenia. Four isolates were positive for beta-lactamase. Susceptibility data were unavailable in 5 case patients. Among serotyped cases, 67% were of the NTHi strain - a finding consistent with the change in the epidemiology of H influenzae since the introduction of the Hib vaccine.

  19. Proanthocyanidin in red rice inhibits MDA-MB-231 breast cancer cell invasion via the expression control of invasive proteins.

    Science.gov (United States)

    Pintha, Komsak; Yodkeeree, Supachai; Limtrakul, Pornngarm

    2015-01-01

    Proanthocyanidin is one of the main active compounds found in red jasmine rice. We previously reported that red rice extract could reduce cancer cell invasion. However, the direct effect of proanthocyanidin from red rice on the invasion of cancer cells and the exact molecular mechanism remained unclear. Here, we report for the first time that proanthocyanidin-rich fraction from red rice (PRFR) reduced the migration and invasion of MDA-MB-231 human breast cancer cells. The types of proanthocyanidin in PRFR were identified as procyanidins and prodelphinidins by acid hydrolysis. For cancer cell invasion, degradation of the extracellular matrix (ECM) is required. Treatment of the cells with PRFR reduced the expression of ECM degradation-associated proteins, including matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase, urokinase plasminogen activator, urokinase plasminogen activator receptor and plasminogen activator-1. Moreover, PRFR also reduced the activity of collagenase and MMP-9. Furthermore, PRFR significantly suppressed the expression of intercellular adhesion molecule-1 and interleukin-6. We also found that PRFR reduced the DNA-binding activity of nuclear factor kappa B (NF-κB), which is the expressed mediator of ECM degradation-associated proteins. These results suggest that proanthocyanidin from red rice mediates MDA-MB-231 breast cancer cell invasion by altering the expression of the invasion-associated proteins, possibly by targeting NF-κB activity.

  20. Usefulness of three dimensional MRI for invasive breast cancer

    International Nuclear Information System (INIS)

    Nakada, Yutaka; Kakizaki, Dai; Kurata, Chishio; Akata, Soichi; Tokuuye, Koichi; Araki, Youchi; Katsuyama, Katsuhiro; Sasaki, Kazuhiro

    2011-01-01

    The first step in the therapeutic plan for breast cancer is to determine the presence and location of the lesion. In a significant number of cases, however, the lesion is difficult to detect, even using various diagnostic imaging modalities. MRI is therefore highly anticipated as a modality for breast cancer detection. In this study we evaluated the diagnostic efficacy of dynamic imaging and 3D imaging with high-resolution MRI in 236 cases of papillo-tubular carcinoma, solid-tubular carcinoma and scirrhous carcinoma: the 3 most common histological types of invasive ductal cancer. The cases were examined by fat-saturated T1/T2-weighted and dynamic MRI imaging, and 3D images were generated for comparison. Breast cancer lesions were detected in 100% of the 3D images obtained by dynamic imaging using contrast media and equilibrium phase, versus 12.2% and 31.4% of the T1- and T2-weighted images, respectively. These results show that 3D imaging is highly useful for detecting the presence of breast cancer. Similar methods are expected to be applied for stereoscopic imaging of tumors and lymph nodes, as well as for surgical simulation. (author)

  1. MCP-1 is overexpressed in triple-negative breast cancers and drives cancer invasiveness and metastasis.

    Science.gov (United States)

    Dutta, Pranabananda; Sarkissyan, Marianna; Paico, Kimberly; Wu, Yanyuan; Vadgama, Jaydutt V

    2018-03-28

    Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks ER/PR and HER2 receptors. Hence, there is urgency in developing new or novel therapeutic strategies for treatment of TNBC. Our study shows that the Monocyte Chemoattractant Protein-1 (MCP-1) is a marker associated with TNBC and may play a key role in TNBC disease progression. ELISA method was used to measure secreted MCP-1, and mRNA levels were determined by Real-time PCR in numerous cancer cell lines, representing various breast cancer subtypes. Cellular invasiveness was determined by Boyden chamber assay. Our data show that MCP-1 is upregulated in TNBC cell lines both transcriptionally as well as in secreted protein levels compared to ER-positive luminal cell line, MCF-7. Breast cancer patients, with Basal or Claudin-low subtypes, also showed high expression of MCP-1. MCP-1 treatment induced cell invasion in various breast cancer cell types, without affecting cell proliferation. Small molecule antagonists against Chemokine Receptor 2 (CCR2), cognate receptor for MCP-1 as well as the MAP kinase pathway inhibitor U0126 negatively affected MCP-1 induced MCF-7 cell invasion. This suggests that MCP-1-CCR2 axis may regulate invasiveness via the MAP Kinase pathway. Knocking down MCP-1 decreased cell invasion in TNBC cell line BT-549, along with downregulation of key epithelial to mesenchymal transition markers, N-cadherin and Vimentin. Our study suggests that MCP-1 mediated pathways could be potential therapeutic targets for the treatment of TNBC, and could reduce cancer health disparities.

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

  4. Update on the management of invasive bladder cancer 2012

    Directory of Open Access Journals (Sweden)

    Goethuys H

    2012-07-01

    Full Text Available Hans Goethuys,1 Hein Van Poppel1,21Department of Urology, Ziekenhuis Oost-Limburg, Genk, Belgium; 2Department of Urology, University Hospital Leuven, Leuven, BelgiumAbstract: Muscle-invasive bladder cancer is a deadly disease for which a number of new approaches have become available to improve prognosis. A recent review emphasized the importance of timely indication of surgery and highlighted current views regarding the adequate extent of the surgery and the importance of lymph node dissection. Furthermore, treatment using neoadjuvant and adjuvant systemic chemotherapy has become more prominent, while cystectomy and diversion should be conducted only in experienced centers. Optimal methods of urinary diversion and the use of robot-assisted laparoscopic cystectomy require further study.Keywords: bladder cancer, surgery, chemotherapy, urinary diversion

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

    Science.gov (United States)

    De Oliveira, Tiago; Abiatari, Ivane; Raulefs, Susanne; Sauliunaite, Danguole; Erkan, Mert; Kong, Bo; Friess, Helmut; Michalski, Christoph W; Kleeff, Jörg

    2012-04-03

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

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

    Directory of Open Access Journals (Sweden)

    De Oliveira Tiago

    2012-04-01

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

  7. Preoperative breast MRI in patients with invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Schelfout, K.; Colpaert, C.; Van Goethem, M.; Verslegers, I.; Biltjes, I.; De Schepper, A.; Kersschot, E.; Leyman, P.; Thienpont, L.; Van den Haute, J.; Gillardin, J.P.; Tjalma, W.; Buytaert, Ph.

    2004-01-01

    To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC. (orig.)

  8. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Science.gov (United States)

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

    2015-10-08

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

  9. Preoperative breast MRI in patients with invasive lobular breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schelfout, K.; Colpaert, C. [Department of Pathology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Van Goethem, M.; Verslegers, I.; Biltjes, I.; De Schepper, A. [Department of Radiology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Kersschot, E.; Leyman, P. [Department of Radiology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Thienpont, L. [Department of Pathology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Van den Haute, J. [Department of Gynecology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Gillardin, J.P. [Department of Surgery, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Tjalma, W.; Buytaert, Ph. [Department of Gynecology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

    2004-07-01

    To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC. (orig.)

  10. 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)

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

    Science.gov (United States)

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

    2015-09-01

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

  12. 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.

  13. Cellular immunotherapy of cancer: an overview and future directions.

    Science.gov (United States)

    Tao, Ziqi; Li, Shuang; Ichim, Thomas E; Yang, Junbao; Riordan, Neil; Yenugonda, Venkata; Babic, Ivan; Kesari, Santosh

    2017-06-01

    The clinical success of checkpoint inhibitors has led to a renaissance of interest in cancer immunotherapies. In particular, the possibility of ex vivo expanding autologous lymphocytes that specifically recognize tumor cells has attracted much research and clinical trial interest. In this review, we discuss the historical background of tumor immunotherapy using cell-based approaches, and provide some rationale for overcoming current barriers to success of autologous immunotherapy. An overview of adoptive transfer of lymphocytes, tumor infiltrating lymphocytes and dendritic cell therapies is provided. We conclude with discussing the possibility of gene-manipulating immune cells in order to augment therapeutic activity, including silencing of the immune-suppressive zinc finger orphan nuclear receptor, NR2F6, as an attractive means of overcoming tumor-associated immune suppression.

  14. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yun, Chae-Ok [Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of); Han, Deok-Jong [Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Young, E-mail: choieun@ulsan.ac.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-12-04

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  15. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

    2015-01-01

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

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

    Science.gov (United States)

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

    2018-03-01

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

  17. Genomic Characterization of Primary Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Desmedt, Christine; Zoppoli, Gabriele; Gundem, Gunes; Pruneri, Giancarlo; Larsimont, Denis; Fornili, Marco; Fumagalli, Debora; Brown, David; Rothé, Françoise; Vincent, Delphine; Kheddoumi, Naima; Rouas, Ghizlane; Majjaj, Samira; Brohée, Sylvain; Van Loo, Peter; Maisonneuve, Patrick; Salgado, Roberto; Van Brussel, Thomas; Lambrechts, Diether; Bose, Ron; Metzger, Otto; Galant, Christine; Bertucci, François; Piccart-Gebhart, Martine; Viale, Giuseppe; Biganzoli, Elia; Campbell, Peter J; Sotiriou, Christos

    2016-06-01

    Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal breast cancer (IDBC). Despite clinical and pathologic differences, ILBC is still treated as IDBC. We aimed to identify genomic alterations in ILBC with potential clinical implications. From an initial 630 ILBC primary tumors, we interrogated oncogenic substitutions and insertions and deletions of 360 cancer genes and genome-wide copy number aberrations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinicopathologic and outcome features. Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than in IDBC. The histologic diversity of ILBC was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype. Survival analyses revealed that chromosome 1q and 11p gains showed independent prognostic value in ILBC and that HER2 and AKT1 mutations were associated with increased risk of early relapse. This study demonstrates that we can now begin to individualize the treatment of ILBC, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets and FOXA1 mutations and ESR1 gains deserving urgent dedicated clinical investigation, especially in the context of endocrine treatment. © 2016 by American Society of Clinical Oncology.

  18. Results of chemoradiotherapyfor muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Yu. V. Gumenetskaya

    2013-01-01

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

  19. Probing cooperative force generation in collective cancer invasion

    Science.gov (United States)

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

    2017-08-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  3. 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.

  4. 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

  5. [Epithelial cadherins and associated molecules in invasive lobular breast cancer].

    Science.gov (United States)

    Brilliant, Yu M; Brilliant, A A; Sazonov, S V

    to estimate the expression of cell adhesion molecules E- and P-cadherin, as well as that of cadherin-catenin complexes in invasive lobular breast cancer (BC) cells. 250 cases of postoperative material from patients diagnosed with invasive lobular BC were studied. The expressions of cell adhesion molecules E-cadherin, P-cadherin, β-catenin, p120 catenin, and vimentin were determined by immunohistochemical assay in all cases. The examined cases were divided into molecular biological subtypes, based on the evaluation of estrogen receptors (ER), progesterone receptors (PR), HER-2/neu, and Ki-67 proliferative index. The membrane expression of E-cadherin on the tumor cells was found to be preserved in 93%; the cytoplasmic expression of β-catenin and p120-catenin appeared in 60 and 72% of cases, respectively. The expression of P-cadherin was detected in 82% of cases. The coexpression of E- and P-cadherin was noted in 90% of all the examined cases. There was a correlation between the expression of E- and P-cadherins (V=0.34; pcancer and its metastasis.

  6. Intravesical chemotherapy in non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Sima P Porten

    2015-01-01

    Full Text Available Non-muscle-invasive bladder cancer (NMIBC is characterized by a tendency for recurrence and capacity for progression. Intravesical instillation therapy has been employed in various clinical settings, which are summarized within this review. Several chemotherapeutic agents have shown clinical efficacy in reducing recurrence rates in the post-transurethral resection of bladder tumor (TURBT setting, including mitomycin C (MMC, doxorubicin, and epirubicin. Mounting evidence also supports the use of intravesical MMC following nephroureterectomy to reduce later urothelial bladder recurrence. In the adjuvant setting, bacillus Calmette-Guérin (BCG immunotherapy is an established first-line agent in the management of carcinoma in situ (CIS and high-grade non muscle invasive urothelial carcinoma (UC. Among high and intermediate-risk patients (based on tumor grade, size, and focality improvements in disease-free intervals have been seen with adjunctive administration of MMC prior to scheduled BCG dosing. Following failure of first-line intravesical therapy, gemcitabine and valrubicin have demonstrated modest activity, though valrubicin remains the only agent currently Food and Drug Administration (FDA-approved for the treatment of BCG-refractory CIS. Techniques to optimize intravesical chemotherapy delivery have also been explored including pharmacokinetic methods such as urinary alkalization and voluntary dehydration. Chemohyperthermia and electromotive instillation have been associated with improved freedom from recurrence intervals but may be associated with increased urinary toxicity. Improvements in therapeutic selection may be heralded by novel opportunities for genomic profiling and refinements in clinical risk stratification.

  7. 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

  8. Overview of non-invasive factors (low level laser and low intensity pulsed ultrasound) accelerating tooth movement during orthodontic treatment.

    Science.gov (United States)

    Jawad, Mohammed Mahmood; Husein, Adam; Alam, Mohammad Khursheed; Hassan, Rozita; Shaari, Rumaizi

    2014-01-01

    The need for orthodontic treatment is increasing all the time. As the treatment is time consuming ranging from a year to several years, any method of reducing the period of treatment and increasing the quality of the tissue will be beneficial to patients. The use of non-invasive techniques such as low level laser therapy and low intensity pulsed ultasound in accelerating orthodontic tooth movement are promising. Thus, this overview study will help to generate more understanding about the background information and the possible applications of them in daily orthodontics, depending on previous literature searching for reviews and original research articles.

  9. Invasive bladder cancer: Our experience with bladder sparing approach

    International Nuclear Information System (INIS)

    Cervek, Jozica; Cufer, Tanja; Zakotnik, Branko; Kragelj, Borut; Borstnar, Simona; Matos, Tadeja; Zumer-Pregelj, Mirjana

    1998-01-01

    Purpose: Muscle-invasive bladder cancer (MIBC) is a disease associated with several unresolved therapeutic questions. Radical cystectomy still represents the most frequent treatment approach. The aim of our study was to evaluate the effect and feasibility of bladder-sparing treatment by transurethral resection (TUR) and sequential chemoradiotherapy in patients with biopsy-proven invasive bladder cancer. Methods and Materials: After maximal TUR, 105 patients were treated with two to four cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders, the treatment was continued by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas in nonresponders, cystectomy was performed when feasible. Results: Complete response after TUR and chemotherapy was achieved in 52% of patients. After a median follow-up of 42 months, 52 of 75 patients (69%) selected for bladder preservation were without evidence of disease in the bladder. Freedom from local failure in complete responders to chemotherapy was 80% [95% confidence interval (CI), 69-91%) at 4 years. The actuarial survival of the entire group was 58% (95% CI, 47-69%), whereas the survival rate with the bladder intact was 45% (95% CI, 34-56%) at 4 years. Survival was significantly better in patients who responded to chemotherapy (79%) than in nonresponders (35%, p < 0.0001). There was no significant difference in survival between nonresponders who underwent cystectomy and nonresponders who completed treatment with radiotherapy (approximately 30% at 3 years). Conclusion: The present study confirms that MIBC is a heterogeneous disease, and that in more than half of patients who are affected, a bladder-sparing approach is safe. Our study has also demonstrated that in nonresponders, radical cystectomy as the treatment of choice is questionable

  10. Minimally invasive surgery in the treatment of esophageal cancer

    International Nuclear Information System (INIS)

    Janik, M.; Lucenic, M.; Juhos, P.; Harustiak, S.

    2016-01-01

    Esophageal cancer represents the sixth most common cause of the death caused by malignant diseases. The incidence is 11.5/100 000 in men population and 4.7/100 000 in women. It is the eighth most common malignancy. The incidence grows up, it doubled in Slovakia in last period and 5-year survival is only 18 %. Esophagectomy is a huge burden for organism. Mortality varies from 8.1 % to 23 % in low-volume departments in comparison with high-volume centres, where it is lower then 5 %. Complications range after operations is 30 – 80 %. Minimally invasive approach leads to the reduction of mortality and morbidity according to lot of studies. We performed 121 esophagectomies in cancer in period 2010 – 2015 and in 2015 it was 32 operations. We performed 29 totally minimally invasive esophagectomies, 16 hybrid MIE and 66 open esophagectomies. The chylothorax occurs twice, we managed it by surgery. The anastomotic dehiscence represents 9.09 %. Cardiovascular system complications occur in 43 %, need for vasopressors caused by hypotensia was in 44 %. It concluded from that we started with restrictive management of patients during the operation and need for vasopressors last only for two days after the operation and did not cause renal failure or any other complications.30 days mortality was related to MODS evolved by sepsis caused by pneumonia, most common in cirrhotic patients in very poor condition. Tracheoneoesophageal fistula occur in three patients, they all underwent operation, one of them died because of severe pneumonia. We recorded grow number of patient in our institution, which is probably related to better cooperation with gastroenterologists all over Slovakia. (author)

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

    Science.gov (United States)

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

    2014-01-01

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

  12. 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.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  15. c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.

    Science.gov (United States)

    Wang, Liyang; Hou, Yixuan; Sun, Yan; Zhao, Liuyang; Tang, Xi; Hu, Ping; Yang, Jiajia; Zeng, Zongyue; Yang, Guanglun; Cui, Xiaojiang; Liu, Manran

    2013-12-01

    Aberrant expression of c-Ski oncoprotein in some tumor cells has been shown to be associated with cancer development. However, the role of c-Ski in cancer-associated fibroblasts (CAFs) of tumor microenvironment has not been characterized. In the current study, we found that c-Ski is highly expressed in CAFs derived from breast carcinoma microenvironment and this CAF-associated c-Ski expression is associated with invasion and metastasis of human breast tumors. We showed that c-Ski overexpression in immortalized breast normal fibroblasts (NFs) induces conversion to breast CAFs by repressing p53 and thereby upregulating SDF-1 in NFs. SDF-1 treatment or p53 knockdown in NFs had similar effects on the activation of NFs as c-Ski overexpression. The c-Ski-activated CAFs show increased proliferation, migration, invasion and contraction compared with NFs. Furthermore, c-Ski-activated CAFs facilitated the migration and invasion of MDA-MB-231 breast cancer cells. Our data suggest that c-Ski is an important regulator in the activation of CAFs and may serve as a potential therapeutic target to block breast cancer progression. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. 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.

  17. Colorectal cancer desmoplastic reaction up-regulates collagen synthesis and restricts cancer cell invasion.

    Science.gov (United States)

    Coulson-Thomas, Vivien J; Coulson-Thomas, Yvette M; Gesteira, Tarsis F; de Paula, Cláudia A A; Mader, Ana M; Waisberg, Jaques; Pinhal, Maria A; Friedl, Andreas; Toma, Leny; Nader, Helena B

    2011-11-01

    During cancer cell growth many tumors exhibit various grades of desmoplasia, unorganized production of fibrous or connective tissue, composed mainly of collagen fibers and myofibroblasts. The accumulation of an extracellular matrix (ECM) surrounding tumors directly affects cancer cell proliferation, migration and spread; therefore the study of desmoplasia is of vital importance. Stromal fibroblasts surrounding tumors are activated to myofibroblasts and become the primary producers of ECM during desmoplasia. The composition, density and organization of this ECM accumulation play a major role on the influence desmoplasia has upon tumor cells. In this study, we analyzed desmoplasia in vivo in human colorectal carcinoma tissue, detecting an up-regulation of collagen I, collagen IV and collagen V in human colorectal cancer desmoplastic reaction. These components were then analyzed in vitro co-cultivating colorectal cancer cells (Caco-2 and HCT116) and fibroblasts utilizing various co-culture techniques. Our findings demonstrate that direct cell-cell contact between fibroblasts and colorectal cancer cells evokes an increase in ECM density, composed of unorganized collagens (I, III, IV and V) and proteoglycans (biglycan, fibromodulin, perlecan and versican). The desmoplastic collagen fibers were thick, with an altered orientation, as well as deposited as bundles. This increased ECM density inhibited the migration and invasion of the colorectal tumor cells in both 2D and 3D co-culture systems. Therefore this study sheds light on a possible restricting role desmoplasia could play in colorectal cancer invasion.

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

    Directory of Open Access Journals (Sweden)

    Horii Rie

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  20. 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

  1. 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.

  2. Mitosis Detection for Invasive Breast Cancer Grading in Histopathological Images.

    Science.gov (United States)

    Paul, Angshuman; Mukherjee, Dipti Prasad

    2015-11-01

    Histopathological grading of cancer not only offers an insight to the patients' prognosis but also helps in making individual treatment plans. Mitosis counts in histopathological slides play a crucial role for invasive breast cancer grading using the Nottingham grading system. Pathologists perform this grading by manual examinations of a few thousand images for each patient. Hence, finding the mitotic figures from these images is a tedious job and also prone to observer variability due to variations in the appearances of the mitotic cells. We propose a fast and accurate approach for automatic mitosis detection from histopathological images. We employ area morphological scale space for cell segmentation. The scale space is constructed in a novel manner by restricting the scales with the maximization of relative-entropy between the cells and the background. This results in precise cell segmentation. The segmented cells are classified in mitotic and non-mitotic category using the random forest classifier. Experiments show at least 12% improvement in F1 score on more than 450 histopathological images at 40× magnification.

  3. Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway

    Directory of Open Access Journals (Sweden)

    Poh Karen

    2011-08-01

    Full Text Available Abstract Background Alcohol consumption is an established risk factor for breast cancer metastasis. Yet, the mechanism by which alcohol promotes breast cancer metastases is unknown. The ability of cancer cells to invade through tissue barriers (such as basement membrane and interstitial stroma is an essential step towards establishing cancer metastasis. In the present study, we identify and examine the roles of two genes, Nm23 and ITGA5, in alcohol-induced breast cancer cell invasion. Methods Human breast cancer T47D cells were treated with ethanol at various concentrations. Boyden chamber invasion assays were used to measure cellular invasive ability. The mRNA expression level of metastasis suppressor genes including Nm23 was determined by qRT-PCR. ITGA5 was identified using a qRT-PCR array of 84 genes important for cell-cell and cell-extracellular matrix interactions. Nm23 overexpression in addition to Nm23- and ITGA5 knock-down were used to determine the role of the Nm23-ITGA5 pathway on cellular invasive ability of T47D cells. Protein expression levels were verified by Western blot. Results Alcohol increased the invasive ability of human breast cancer T47D cells in a dose-dependent manner through the suppression of the Nm23 metastatic suppressor gene. In turn, Nm23 down-regulation increased expression of fibronectin receptor subunit ITGA5, which subsequently led to increased cellular invasion. Moreover, Nm23 overexpression was effective in suppressing the effects of alcohol on cell invasion. In addition, we show that the effects of alcohol on invasion were also inhibited by knock-down of ITGA5. Conclusions Our results suggest that the Nm23-ITGA5 pathway plays a critical role in alcohol-induced breast cancer cell invasion. Thus, regulation of this pathway may potentially be used to prevent the establishment of alcohol-promoted metastases in human breast cancers.

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

    Directory of Open Access Journals (Sweden)

    Agathe Oulidi

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

  5. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian......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...

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

    Science.gov (United States)

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

    2017-11-01

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

  7. 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.

  8. 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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  10. 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.

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

    Science.gov (United States)

    Ballard, Ashley James

    2015-12-01

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

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

    Science.gov (United States)

    Moore, Michael R; King, Rebecca A

    2012-12-01

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

  13. Uniportal VATS: A Sublimation of Micro-invasive Lung Cancer Resection

    Directory of Open Access Journals (Sweden)

    Chengwu LIU

    2014-07-01

    Full Text Available Micro-invasive thoracic surgery, especially represented by video-assisted thoracic surgery (VATS, has become the mainstream of lung cancer resection. Traditional multi-portal VATS techniques, including four-port, three-port, and two-port VATS, have been widely used to perform nearly all kinds of lung cancer resections. However, how to make lung cancer resection less invasive is always the subject that all thoracic surgeons never stop pursuing. Compared with multi-portal VATS, uniportal VATS causes less postoperative pain and paresthesia because only one small incision is made and one intercoastal space is involved. In recent years, good clinical results have been obtained from uniportal VATS in lung cancer resections. In this paper, we’d like to present a brief summary about the progresses made in the application of uniportal VATS in lung cancer resection. Uniportal VATS is a sublimation of micro-invasive lung cancer resection.

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

    Science.gov (United States)

    Mierke, Claudia T.

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

  15. A Systematic Overview of Radiation Therapy Effects in Rectal Cancer

    International Nuclear Information System (INIS)

    Glimelius, Bengt; Groenberg, Henrik; Jaerhult, Johannes; Wallgren, Arne; Cavallin-Staahl, Eva

    2003-01-01

    A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for rectal cancer is based on data from 42 randomized trials and 3 meta-analyses. Moreover, data from 36 prospective studies, 7 retrospective studies and 17 other articles were used. A total of 131 scientific articles are included, involving 25,351 patients. The results were compared with those of a similar overview from 1996 including 15,042 patients. The conclusions reached can be summarized thus: The results after rectal cancer surgery have improved during the past decade. It is likely that local failure rates after 5 years of follow-up at hospitals adopting the TME-concept (TME=total mesorectal excision) have decreased from about 28% to 10-15%. Preoperative radiotherapy at biological effective doses above 30 Gy decreases the relative risk of a local failure by more than half (50-70%). Postoperative radiotherapy decreases the risk by 30-40% at doses that generally are higher than those used preoperatively. There is strong evidence that preoperative radiotherapy is more effective than postoperative. There is moderate evidence that preoperative radiotherapy significantly decreases the local failure rate (from 8% to 2% after 2 years) also with TME. There is strong evidence that preoperative radiotherapy improves survival (by about 10%). There is no evidence that postoperative radiotherapy improves survival. There is some indication that survival is prolonged when postoperative radiotherapy is combined with concomitant chemotherapy. Preoperative radiotherapy at adequate doses can be given with low acute toxicity. Higher, and unacceptable acute toxicity has been seen in some preoperative radiotherapy trials using suboptimal techniques. Postoperative radiotherapy can also be

  16. Ginkgolic acid inhibits the invasiveness of colon cancer cells through AMPK activation.

    Science.gov (United States)

    Qiao, Lina; Zheng, Jianbao; Jin, Xianzhen; Wei, Guangbing; Wang, Guanghui; Sun, Xuejun; Li, Xuqi

    2017-11-01

    Tumor cell invasion and metastasis are important processes in colorectal cancer that exert negative effects on patient outcomes; consequently, a prominent topic in the field of colorectal cancer study is the identification of safe and affordable anticancer drugs against cell invasion and metastasis, with limited side effects. Ginkgolic acid is a phenolic acid extracted from ginkgo fruit, ginkgo exotesta and ginkgo leaves. Previous studies have indicated that ginkgolic acid inhibits tumor growth and invasion in a number of types of cancer; however, limited studies have considered the effects of ginkgolic acid on colon cancer. In the present study, SW480 colon cancer cells were treated with a range of concentrations of ginkgolic acid; tetrazolium dye-based MTT, wound-scratch and transwell migration assays were performed to investigate the effects on the proliferation, migration and invasion of colon cancer cells, and potential mechanisms for the effects were explored. The results indicated that ginkgolic acid reduced the proliferation and significantly inhibited the migration and invasion of SW480 cells in a concentration-dependent manner. Additional experiments indicated that ginkgolic acid significantly decreased the expression of invasion-associated proteins, including matrix metalloproteinase (MMP)-2, MMP-9, urinary-type plasminogen activator and C-X-C chemokine receptor type 4, and activated adenosine monophosphate activated protein kinase (AMPK) in SW480 cells. Small interfering RNA silencing of AMPK expression reversed the effect of ginkgolic acid on the expression of invasion-associated proteins. This result suggested that ginkgolic acid inhibited the proliferation, migration and invasion of SW480 colon cancer cells by inducing AMPK activation and inhibiting the expression of invasion-associated proteins.

  17. 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.

  18. GPU-based RFA simulation for minimally invasive cancer treatment of liver tumours

    NARCIS (Netherlands)

    Mariappan, P.; Weir, P.; Flanagan, R.; Voglreiter, P.; Alhonnoro, T.; Pollari, M.; Moche, M.; Busse, H.; Futterer, J.J.; Portugaller, H.R.; Sequeiros, R.B.; Kolesnik, M.

    2017-01-01

    PURPOSE: Radiofrequency ablation (RFA) is one of the most popular and well-standardized minimally invasive cancer treatments (MICT) for liver tumours, employed where surgical resection has been contraindicated. Less-experienced interventional radiologists (IRs) require an appropriate planning tool

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  20. The situation of radiotherapy in the treatment of lymph node invasion of gynecological cancers

    International Nuclear Information System (INIS)

    Dubois, J.B.; Gerbaulet, A.

    1993-01-01

    In this article, the authors explain the role and possibilities of radiotherapy in the treatment of lymph node invasion in gynecological cancers as uterine cervix carcinoma, uterus carcinoma, ovary carcinoma and vulva carcinoma

  1. Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer.

    NARCIS (Netherlands)

    Hendricksen, K.; Witjes, J.A.

    2007-01-01

    PURPOSE OF REVIEW: Nonmuscle invasive bladder cancer is a common malignancy, usually treated by transurethral resection and adjuvant intravesical instillations of chemotherapy or immunotherapy. Appropriate adjuvant treatment can be selected based on several prognostic factors that determine risk for

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  4. Global solution for a chemotactic haptotactic model of cancer invasion

    Science.gov (United States)

    Tao, Youshan; Wang, Mingjun

    2008-10-01

    This paper deals with a mathematical model of cancer invasion of tissue recently proposed by Chaplain and Lolas. The model consists of a reaction-diffusion-taxis partial differential equation (PDE) describing the evolution of tumour cell density, a reaction-diffusion PDE governing the evolution of the proteolytic enzyme concentration and an ordinary differential equation modelling the proteolysis of the extracellular matrix (ECM). In addition to random motion, the tumour cells are directed not only by haptotaxis (cellular locomotion directed in response to a concentration gradient of adhesive molecules along the ECM) but also by chemotaxis (cellular locomotion directed in response to a concentration gradient of the diffusible proteolytic enzyme). In one space dimension, the global existence and uniqueness of a classical solution to this combined chemotactic-haptotactic model is proved for any chemotactic coefficient χ > 0. In two and three space dimensions, the global existence is proved for small χ/μ (where μ is the logistic growth rate of the tumour cells). The fundamental point of proof is to raise the regularity of a solution from L1 to Lp (p > 1). Furthermore, the existence of blow-up solutions to a sub-model in two space dimensions for large χ shows, to some extent, that the condition that χ/μ is small is necessary for the global existence of a solution to the full model.

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

    Directory of Open Access Journals (Sweden)

    Andrew C. Weitz

    2017-08-01

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

  6. Cardiovascular Toxicity of Common Chemotherapy Drugs Used to Treat Breast Cancer: An Overview

    Directory of Open Access Journals (Sweden)

    Charles A. Bomzer

    2014-08-01

    Full Text Available Treatment of breast cancer often exposes patients to many different drugs. Some of these drugs have toxic effects involving the cardiovascular system. This review provides an overview of the drugs most commonly used to treat breast cancer and their potential adverse impact on the cardiovascular system.

  7. Cardiovascular Toxicity of Common Chemotherapy Drugs Used to Treat Breast Cancer: An Overview

    OpenAIRE

    Charles A. Bomzer

    2014-01-01

    Treatment of breast cancer often exposes patients to many different drugs. Some of these drugs have toxic effects involving the cardiovascular system. This review provides an overview of the drugs most commonly used to treat breast cancer and their potential adverse impact on the cardiovascular system.

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

    Science.gov (United States)

    2015-09-01

    Assay Kits respectively on the Qubit 2.0 Fluorometer (Life Technologies). The BioRad Experion Automated Electrophoresis System RNA kit was used to...AWARD NUMBER: W81XWH-14-1-0080 TITLE: Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. PRINCIPAL INVESTIGATOR...Aug 2015 4. TITLE AND SUBTITLE Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. 5a. CONTRACT NUMBER 5b. GRANT

  9. 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...

  10. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Directory of Open Access Journals (Sweden)

    Alicja M Kmiecik

    Full Text Available It has been recently found that metallothionein-3 (MT3 enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001. Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC, nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  11. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Science.gov (United States)

    Kmiecik, Alicja M; Pula, Bartosz; Suchanski, Jaroslaw; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Owczarek, Tomasz; Kruczak, Anna; Ambicka, Aleksandra; Rys, Janusz; Ugorski, Maciej; Podhorska-Okolow, Marzena; Dziegiel, Piotr

    2015-01-01

    It has been recently found that metallothionein-3 (MT3) enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001). Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC), nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  12. 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.

  13. Minimally Invasive Surgery for Early-Stage Lung Cancer: From Innovation to Standard of Care.

    Science.gov (United States)

    White, Abby; Swanson, Scott J

    2016-11-15

    The era of minimally invasive surgery for lung cancer follows decades of research; the collection and interpretation of countless qualitative and quantitative data points; and tireless efforts by a few pioneering thoracic surgeons who believed they could deliver a safe and oncologically sound operation with less tissue trauma, an improved physiologic profile, and fewer complications than traditional open surgery. This review highlights those efforts and the role of minimally invasive surgery for early-stage lung cancer in light of evolving technology, the emerging understanding of the biology of early-stage lung cancer, and lung cancer screening.

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

    Science.gov (United States)

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

    2013-10-01

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

  15. Identification of EDIL3 on extracellular vesicles involved in breast cancer cell invasion.

    Science.gov (United States)

    Lee, Jeong-Eun; Moon, Pyong-Gon; Cho, Young-Eun; Kim, Young-Bum; Kim, In-San; Park, Hoyong; Baek, Moon-Chang

    2016-01-10

    Cancer cell-derived extracellular vesicles have been linked to the pathogenesis of various cancers; however, the role of extracellular vesicles in tumorigenesis remains unclear. To identify extracellular vesicle proteins involved in cancer metastasis, quantitative proteomic analyses were performed on extracellular vesicles derived from two representative breast cancer cell lines: the less invasive MCF-7 and the invasive MDA-MB-231. Proteomic analysis allowed for the identification of 270 proteins in the extracellular vesicles. Here we report a new function of EDIL3 on extracellular vesicles, which are sufficient for enhancement of cell invasion and for acceleration of lung metastasis in vivo. This invasion is most likely mediated via the integrin-FAK signaling cascade in breast cancer cells. However, these effects are suppressed when EDIL3 is inactivated, providing evidence for a critical role of EDIL3 in development of cancer. Consistently, in human patients with metastatic breast cancer, the levels of EDIL3 on circulating extracellular vesicles are significantly elevated. This information is a remarkable breakthrough in understanding of the molecular mechanism underlying metastasis of breast cancer as well as in the research for cancer biomarkers using circulating extracellular vesicles. Furthermore, targeting EDIL3 on extracellular vesicles may lead to a new therapeutic option for treatment of breast cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or precursor for invasive lobular carcinoma.

    Science.gov (United States)

    Wallace, A S; Xiang, D; Hockman, L; Arya, M; Jeffress, J; Wang, Z; Dale, P S

    2014-10-01

    Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC). Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lin Ling

    2011-09-01

    Full Text Available Abstract Background Tumor-associated macrophages (TAMs are alternatively activated cells induced by interleukin-4 (IL-4-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells. Results We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway. Conclusions We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.

  18. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

    Science.gov (United States)

    2011-01-01

    Background Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells. Results We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway. Conclusions We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells. PMID:21939504

  19. Biologic markers in axillary node-negative breast cancer: differential expression in invasive ductal carcinoma versus invasive lobular carcinoma.

    Science.gov (United States)

    Gonzalez-Angulo, Ana Maria; Sahin, Aysegul; Krishnamurthy, Savitry; Yang, Ying; Kau, Shu-Wan; Hortobagyi, Gabriel N; Cristofanilli, Massimo

    2006-12-01

    The objective of this study was to compare the differential expression of established histopathologic and biologic markers of proliferation, apoptosis, and angiogenesis in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in a group of axillary node-negative breast cancers. Two hundred twenty patients with axillary node-negative ILC and IDC who underwent surgery at the University of Texas M. D. Anderson Cancer Center between 1978 and 1995 had tissue available for analysis. Of these, 206 (94%) had IDC and 14 (6%) had ILC. Estrogen receptors, progesterone receptors, tumor and stromal expression of vascular endothelial growth factor receptor 2, CD44, laminin-5, E-cadherin, and topoisomerase-2 were evaluated by immunohistochemical analysis. HER2/neu and alpha6beta4 integrin were evaluated by in situ hybridization. The Fisher exact test was used to calculate significant differences between ILC and IDC. Median age was 59 years. Invasive lobular carcinoma was more likely to occur in patients aged > 50 years. Invasive lobular carcinoma tended to be > 2 cm (50% vs. 39%), have a nuclear grade of 1/2 (100% vs. 72%), be estrogen receptor positive (93% vs. 70%), HER2/neu negative (92% vs. 68%), have high CD44 expression (31% vs. 16%), low stromal vascular endothelial growth factor receptor 2 expression (36% vs. 47%), no E-cadherin expression (0 vs. 90%), and low laminin-5 expression (15% vs. 25%), compared with IDC. Invasive lobular carcinoma and IDC might be distinct histologic types of breast cancer with different expression of biologic markers. These differences, not all being statistically significant in this small study, might generate hypotheses to develop tailored options for future systemic therapy.

  20. Slug contributes to cadherin switch and malignant progression in muscle-invasive bladder cancer development.

    Science.gov (United States)

    Wu, Kaijie; Zeng, Jin; Zhou, Jiancheng; Fan, Jinhai; Chen, Yule; Wang, Zhiqiang; Zhang, TingTing; Wang, Xinyang; He, Dalin

    2013-11-01

    The Snail family of zinc finger transcription factors (i.e., Snail and Slug) predicts the tumor recurrence in superficial bladder cancers, while their roles in the development of muscle-invasion, metastasis, and chemoresistance in muscle-invasive bladder cancers with poor prognosis have not been investigated. This study evaluates the clinical significance of Slug in aggressive bladder cancer. A pair of sublines (i.e., T24-P and T24-L) from a unique orthotropic metastatic model of bladder cancer was firstly utilized to identify the potential precursors contributing to those aggressive phenotypes. The coexpression of Slug, E-cadherin, and N-cadherin in bladder cancer cell lines (i.e., 5637, RT4, 253 J, J82, and T24) and tissues was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry staining analysis. The function of Slug expression on E- to N-cadherin switch, cell invasion, and chemoresistance to proapoptotic treatment was validated by gain-in-function and knockdown strategy in vitro. Slug was identified as one of the novel targets contributed to the aggressive phenotypes of T24-L cells, which showed enhanced cell invasive, metastatic, and chemoresistant potentials in vitro and in vivo as previously described. Up-regulation of Slug was significantly correlated with a higher tumor stage and the E- to N-cadherin switch in bladder cancer cells and tissues, whereas ectopic expression of Slug in bladder cancer 5637 and RT-4 cell lines promoted epithelial-to-mesenchymal transition (EMT), increased cell invasiveness and chemoresistance. By contrast, knocking down Slug using siRNA in T24-L cell lines reversed these changes. Slug elevates in invasive or metastatic bladder cancer and plays a critical role in EMT via control of cadherin switch. Slug may be a potential marker or target for improving the diagnosis and treatment of muscle-invasive bladder cancers. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Chen, Kun-Wan; Pienta, Kenneth J

    2011-10-03

    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). 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. 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.

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

    International Nuclear Information System (INIS)

    Wenz, Frederik; Sperk, Elena; Budach, Wilfried; Dunst, Juergen; Feyer, Petra; Fietkau, Rainer; Sauer, Rolf; Haase, Wulf; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Fussl, Christoph; Souchon, Rainer

    2014-01-01

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

  4. Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview

    International Nuclear Information System (INIS)

    Guermazi, Ali; Gluckman, Eliane; Tabti, Bachir; Miaux, Yves

    2003-01-01

    Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered. (orig.)

  5. Evaluation of myometrial invasion in patients with endometrial cancer by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yusuke; Kashimura, Masamichi; Shinohara, Michioki; Sakamoto, Chikara (University of Occupational and Environmental Health, Kitakyushu (Japan))

    1992-07-01

    Magnetic Resonance Imaging (MRI) has been widely used for the diagnosis of gynecologic disease. We studied the clinical usefulness of MRI in 34 patients with endometrial cancer from July 1988 to August 1991. Pre-operative pelvic MRI was carried out to evaluate the myometrial invasion in these patients. MRI was accurate in predicting the presence or absence of myometrial invasion in 23 of 34 cases (68%), while echo or CT (computed tomography) was accurate in 26% and 8%. In conclusion, MRI is considered to be the most useful examination for the evaluation of myometrial invasion in endometrial cancer. (author).

  6. Treatment of intervertebral disc degenerative disease using percutaneous nucleotomy–an overview of less invasive procedures

    Directory of Open Access Journals (Sweden)

    Miran Jeromel

    2014-04-01

    Full Text Available Background: Less invasive treatment methods for intervertebral disc disease and decompression of neural structures as a consequence of contained disc herniation represent an alternative to surgical procedure. Percutaneus nucleotomy uses a percutaneous approach to the intervertebral disc. The article presents the evolution of numerous procedureds in clinical practice.Methods: Percutaneous nucleoplasty is a fluoroscopy-guided procedure which enables controlled and safe entrance into the intervertebral disc. The procedure is performed under strict aseptic conditions, using a local anaesthesia with the patient under analgosedation. Based on the principle of therapeutic intradiscal action, the procedures can be divided into three groups: chemical (chemonucleolysis with chimopapain, alcohol, ozone, mechanical (automated percutaneous lumbar discectomy – APLD, arthroscopic discectomy and thermical methods (laser, radiofrequency ablation, intradiscal electrothermal annuloplasty – IDET, Coblation®.Results: Percutaneous nucleotomy by the majority of the mentioned procedures results in a therapeutic effect (reduction of pain and decompression of neural structures. Fast recovery represents a major advantage of less invasive treatment.Conclusions: Less invasive method (nucleotomy using different procedures represents a successful alternative approach to surgical discectomy. Proper patient selection and safe technique are mandatory in order to achieve a good clinical outcome.

  7. microRNA-664 enhances proliferation, migration and invasion of lung cancer cells.

    Science.gov (United States)

    Zhu, Xinhai; Ju, Sheng; Yuan, Feng; Chen, Guoping; Shu, Yue; Li, Chuanchuan; Xu, Yanhui; Luo, Jing; Xia, Lilong

    2017-06-01

    Altered microRNA (miR) expression serves an important role in the development and progression of lung cancer. In the present study, the effect of miR-664 on proliferation, migration and invasion of lung cancer cells was assessed. The proliferation of lung cancer cells with an overexpression of miR-664 was examined via MTT assay. The Caspase-Glo3/7 assay was used to examine the effect of miR-664 on cisplatin-induced apoptosis in lung cancer cells. The migration and invasion of lung cancer cells were assessed by Transwell migration and matrigel invasion assays. Western blot analysis was used to examine the protein expression levels. miR-664 improved the proliferation of lung cancer cells and inhibited cisplatin-induced apoptosis of A549 and A427 cells. Furthermore, altered expression of miR-664 affected migration and invasion of lung cancer cells. In addition, a miR-664 mimic decreased E-cadherin expression and increased vementin and Snail expression in lung cancer cells. Notably, the expression level of protein kinase B in A549 cells was changed following altered expression of miR-664. The results of the present study suggest that miR-664 serves an essential role in tumor development and progression in lung cancer.

  8. 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.

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

    International Nuclear Information System (INIS)

    Suh, Chang Hae; Kressel, Herbert Y

    1993-01-01

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

  10. Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Rank, Fritz

    2009-01-01

    report forms, central review, and querying, were specified in advance. Kaplan-Meier analyses were used to estimate disease-free intervals and overall survival rates among patients with and without lymphovascular invasion, and multivariable analysis was used to adjust for differences in baseline...... alive. These differences persisted in a multivariable analysis, and for overall survival, a statistically significant interaction (P = .03) was observed between lymphovascular invasion and risk group. CONCLUSIONS: In this prospective population-based study, lymphovascular invasion was not an independent......BACKGROUND: Lymphovascular invasion has been associated with poor prognosis in women with breast cancer, but it is unclear whether the presence of lymphovascular invasion should be considered sufficient to reclassify breast cancer patients who are at a low risk of recurrence into a high...

  11. [Lobular invasive breast cancer prognostic factors: About 940 patients].

    Science.gov (United States)

    Jauffret, C; Houvenaeghel, G; Classe, J-M; Garbay, J-R; Giard, S; Charitansky, H; Cohen, M; Bélichard, C; Faure, C; Darai, É; Hudry, D; Azuar, P; Villet, R; Gimbergues, P; Tunon de Lara, C; Martino, M; Coutant, C; Dravet, F; Chauvet, M-P; Chéreau Ewald, E; Penault-Llorca, F; Goncalves, A; Lambaudie, É

    2015-11-01

    To assess the prognostic factors of T1 and T2 infiltrating lobular breast cancers, and to investigate predictive factors of axillary lymph node involvement. This is a retrospective multicentric study, conducted from 1999 to 2008, among 13 french centers. All data concerning patients with breast cancer who underwent a primary surgical treatment including a sentinel lymph node procedure have been collected (tumors was stage T1 or T2). Patients underwent partial or radical mastectomy. Axillary lymph node dissection was done systematically (at the time of sentinel procedure evaluation), or in case of sentinel lymph node involvement. Among all the 8100 patients, 940 cases of lobular infiltrating tumors were extracted. Univariate analysis was done to identify significant prognosis factors, and then a Cox regression was applied. Analysis interested factors that improved disease free survival, overall survival and factors that influenced the chemotherapy indication. Different factors that may be related with lymph node involvement have been tested with univariate than multivariate analysis, to highlight predictive factors of axillary involvement. Median age was 60 years (27-89). Most of patients had tumours with a size superior to 10mm (n=676, 72%), with a minority of high SBR grade (n=38, 4%), and a majority of positive hormonal status (n = 880, 93, 6%). The median duration of follow-up was 59 months (1-131). Factors significantly associated with decreased disease free survival was histological grade 3 (hazard ratio [HR]: 3,85, IC 1,21-12,21), tumour size superior to 2cm (HR: 2,85, IC: 1,43-5,68) and macrometastatic lymph node status (HR: 3,11, IC: 1,47-6,58). Concerning overall survival, multivariate analysis demonstrated a significant impact of age less than 50 years (HR: 5,2, IC: 1,39-19,49), histological grade 3 (HR: 5,03, IC: 1,19-21,25), tumour size superior to 2cm (HR: 2,53, IC: 1,13-5,69). Analysis concerning macrometastatic lymph node status nearly reached

  12. 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.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Hypoxia stimulates invasion and migration of human cervical cancer ...

    Indian Academy of Sciences (India)

    Here we show that hypoxiaincreases tumour cell invasion and migration by the modulation of Rab11, an important molecule for vesicular trafficking.In our study, we found that Rab11, together with the activation of Rac1, could stimulate invasion and migration of cervicalcancer cell lines HeLa/SiHa in hypoxia. Activation of ...

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  17. 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

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

    Science.gov (United States)

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

    2018-04-01

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

  19. Recruitment & Regulation of N-Wasp by F-Bar Family Member CIP4 in Invasive Breast Cancer Cells

    Science.gov (United States)

    2009-07-01

    The focus of this project is the contribution of the Cdc42-interacting protein CIP4 to the invasive phenotype of MDA-MB-231 cancer cells . CIP4 is a...breast cancer cell lines. My research investigates the role of CIP4 in promoting invasion and invadopodia in breast cancer cells in vitro through its

  20. 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

  1. cd4 t-lymphocyte subsets in women with invasive cervical cancer

    African Journals Online (AJOL)

    2013-10-01

    Oct 1, 2013 ... Invasive cervical cancer (ICC) is common in populations with high HIV prevalence in sub-Sahara. Africa (1,2). Depressed systemic as well as local immune responses have been observed in patients with advanced cervical cancer (3,4). Patients with iatrogenic CD4 cell depression following organ.

  2. Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters

    NARCIS (Netherlands)

    H. Verloop (Herman); F.E. van Leeuwen (F.); T.J.M. Helmerhorst (Theo); I.M.C.M. de Kok (Inge); van Erp, E.J.M.; H.H. van Boven (Hester); M.A. Rookus (Matti)

    2017-01-01

    textabstractObjective: Women exposed to diethylstilbestrol in utero (DES) have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix, while their risk of non-CCA invasive cervical cancer is still unclear. Methods: We studied the risk of pre-cancerous (CIN) lesions and non-CCA

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

    Science.gov (United States)

    Expert-reviewed information summary in which the features of hereditary cancer and the structure and content of other PDQ cancer genetics summaries are described. The summary also contains an extensive list of genetics resources available online.

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

    Directory of Open Access Journals (Sweden)

    Chen-Ye Shi

    2013-08-01

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

  5. p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug.

    Science.gov (United States)

    Wang, Shu-Ping; Wang, Wen-Lung; Chang, Yih-Leong; Wu, Chen-Tu; Chao, Yu-Chih; Kao, Shih-Han; Yuan, Ang; Lin, Chung-Wu; Yang, Shuenn-Chen; Chan, Wing-Kai; Li, Ker-Chau; Hong, Tse-Ming; Yang, Pan-Chyr

    2009-06-01

    The tumour suppressor p53 is known to prevent cancer progression by inhibiting proliferation and inducing apoptosis of tumour cells. Slug, an invasion promoter, exerts its effects by repressing E-cadherin transcription. Here we show that wild-type p53 (wtp53) suppresses cancer invasion by inducing Slug degradation, whereas mutant p53 may stabilize Slug protein. In non-small-cell lung cancer (NSCLC), mutation of p53 correlates with low MDM2, high Slug and low E-cadherin expression. This expression profile is associated with poor overall survival and short metastasis-free survival in patients with NSCLC. wtp53 upregulates MDM2 and forms a wtp53-MDM2-Slug complex that facilitates MDM2-mediated Slug degradation. Downregulation of Slug by wtp53 or MDM2 enhances E-cadherin expression and represses cancer cell invasiveness. In contrast, mutant p53 inactivates Slug degradation and leads to Slug accumulation and increased cancer cell invasiveness. Our findings indicate that wtp53 and p53 mutants may differentially control cancer invasion and metastasis through the p53-MDM2-Slug pathway.

  6. An overview of cancer research in South African academic and ...

    African Journals Online (AJOL)

    [1] Based on the most recent. South African National Cancer Registry data, 1 in 9 women and .... Research activity in the five most commonly diagnosed male and female cancers in SA was assessed. .... that there were no costing or costeffectiveness cancer research projects. However, it is possible that deskbased economic ...

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

    Science.gov (United States)

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

    2016-01-05

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

  8. Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, Ali [Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, Suite 150, San Francisco, CA 94117 (United States); Department of Radiology, Saint-Louis Hospital, AP-HP, Paris (France); Gluckman, Eliane [Department of Bone Marrow Transplantation, Saint-Louis Hospital, AP-HP, Paris (France); Tabti, Bachir [Department of Radiology, Saint-Louis Hospital, AP-HP, Paris (France); Miaux, Yves [Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, Suite 150, San Francisco, CA 94117 (United States)

    2003-02-01

    Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered. (orig.)

  9. Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview

    Directory of Open Access Journals (Sweden)

    Jorge Pereira

    2015-01-01

    Full Text Available Currently, a small number of diseases, particularly cardiovascular (CVDs, oncologic (ODs, neurodegenerative (NDDs, chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc. allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases.

  10. [History and development trend of minimally invasive techniques for gastric cancer in China].

    Science.gov (United States)

    Yu, Peiwu; Hao, Yingxue

    2016-08-25

    Laparoscopic gastrectomy is one of the main directions of minimally invasive surgery for gastric cancer. Since 1999, the first laparoscopic gastrectomy was reported, minimally invasive laparoscopic surgery for gastric cancer in China has undergone three stages: initial exploration period, rapid development period and gradual maturation period. The hospitals which performed laparoscopic gastrectomy and the reported cases have been increasing, at the same time the clinical efficacy is satisfied. However, there is still lack of standard and insufficient evidence in the treatment of gastric cancer by laparoscopic gastrectomy. The 3D laparoscopic and robotic gastrectomies still can not be performed in the most hospitals in China. So we should strengthen the standardization training of laparoscopic gastrectomy, develop the evidence-based medical research, promote the 3D laparoscopic and robotic gastrectomies to enhance the level of minimally invasive surgery for gastric cancer.

  11. Mixed Lineage Kinase3 as a Novel Target for Invasive Breast Cancer

    Science.gov (United States)

    2013-04-01

    myeloid M1 cell line. J Cell Biochem 86: 1–11. Hanahan D, Weinberg RA. (2000). The hallmarks of cancer. Cell 100: 57–70. Jacinto A, Woolner S, Martin P...papillomavirus E7 repression in cervical carcinoma cells initiates a transcriptional cascade driven by the retinoblastoma family, resulting in...axis induces expression of several breast cancer invasion genes (16). The mechanics of cancer cell migration involve cytoskeletal remodeling and focal

  12. Use of Exogenous Progestins and Risk or In Situ and Invasive Breast Cancer

    Science.gov (United States)

    2011-10-01

    IRREGULAR OR HEAVY BLEEDING ........................................... [3] CANCER (OVARY, ENDOMETRIUM/UTERUS, CERVIX ) ........... [4] ENDOMETRIOSIS...maximum height is reached as a risk factor for breast cancer among young U.S. women. Epidemiology 1997;8:559-565. 3. van Oers HJJ, de Kloet ER, Li C...05-1-0482 TITLE: Use of Exogenous Progestins and Risk or In Situ and Invasive Breast Cancer PRINCIPAL INVESTIGATOR: Dr

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  14. Effect of laminin 332 on motility and invasion in bladder cancer

    Directory of Open Access Journals (Sweden)

    Sung-Gu Kang

    2013-08-01

    Full Text Available We examined the correlation between laminin 332 and malignancy in bladder cancer patients, and, using a strain of invasive bladder cancer cells, determined whether laminin 332 causes bladder cancer motility and invasion. To investigate the correlation between laminin 332 g2 distribution and patient outcome, we performed a semiquantitative immunohistochemical analysis of 35 paraffin-embedded samples using the antibody D4B5, which is specific for the laminin 5 γ2 chain. To evaluate the role of laminin 332 in NBT-II cell motility and invasion, we used a scratch assay and the Boyden chamber chemoinvasion system. Tumor stage and grade were significantly correlated with a loss of laminin 332 γ2 chain from the basement membrane (p = 0.001 and its retention in the cytoplasm (p = 0.001 (Kruskal–Wallis test. Kaplan–Meier survival curves revealed an association between the risk of progression and cytoplasmic retention of the laminin 332 γ2 chain. In addition, an in vitro scratch assay showed an increase in the migration of cells treated with laminin 332 from their cluster. The Boyden chamber assay showed that laminin 332 potentiated NBT-II cell invasion. Immunohistochemistry results showed that bladder cancer patients with a higher malignancy expressed more laminin 332. The in vitro scratch and invasion assay showed that laminin 332 stimulated the motility and invasion of bladder cancer cells. The invasion assay explains the correlation between laminin 332 expression and bladder cancer malignancy.

  15. 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.

  16. Epithelial-mesenchymal transition in prostate cancer: an overview

    Science.gov (United States)

    Montanari, Micaela; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Malzone, Maria Gabriella; Vanacore, Daniela; Franco, Rossella Di; Mantia, Elvira La; Iovane, Gelsomina; Piscitelli, Raffaele; Muscariello, Raffaele; Berretta, Massimiliano; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Bianchi, Attilio Antonio Montano; Veneziani, Bianca Maria; Facchini, Gaetano

    2017-01-01

    Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer. Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance. In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance. PMID:28430640

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Kon, Masanori

    1997-01-01

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

  19. Resveratrol as MDR reversion molecule in breast cancer: An overview.

    Science.gov (United States)

    Alamolhodaei, Nafiseh Sadat; Tsatsakis, Aristidis M; Ramezani, Mohammad; Hayes, A Wallace; Karimi, Gholamreza

    2017-05-01

    Breast cancer is the most common cause of cancer mortality among women worldwide; therefore, a strategy to defeat breast cancer is an extremely important medical issue. One of the major challenges in this regard is multidrug resistance (MDR). Resveratrol, a well-known phytoestrogen, may be helpful as part of an overall strategy to defeat breast cancer. The mixed agonist and antagonist role of resveratrol for the estrogen receptor makes it a controversial but interesting molecule in cancer therapy, especially in hormone dependent cancers. Several in vitro investigations have suggested that resveratrol can reverse multidrug resistance. However, poor bioavailability of resveratrol is a potential limitation for resveratrol treatment and cancer outcome in vivo. Fortunately, combination therapy with other selected compounds improves resveratrol's bioavailability and/or a delay in its metabolism. This review summaries the available published literature dealing with the effects of resveratrol on multidrug resistance in cancer and more specifically, breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. MINIMALLY-INVASIVE SURGERY FOR COLLORECTAL CANCER IN ELDERLY PATIENTS

    OpenAIRE

    I. L. Chernikovskiy; V. M. Gelfond; A. S. Zagryadskikh; S. A. Savchuk

    2016-01-01

    Introduction. The patient’s age is one of the major risk factors of death from colorectal cancer. The role of laparo- scopic radical surgeries in the treatment of colorectal cancer in elderly patients is being studied. The purpose of the study was to evaluate the experience of surgical treatment for elderly patients with colorectal cancer. material and methods. The treatment outcomes of 106 colorectal cancer patients aged 75 years or over, who underwent surgery between 2013 and 2015 were pres...

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

    Directory of Open Access Journals (Sweden)

    Victor G Vogel

    2008-12-01

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

  2. Complication of radiotherapy in the management of invasive cancer ...

    African Journals Online (AJOL)

    Background: Cancer of the cervix is not only the second most common cancer affecting women worldwide but is also the most common gynecological cancer in Kenya. An estimated 500,000 cases occur every year of which 80% are from the developing countries. Presentation is usually during late stages requiring ...

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

    Science.gov (United States)

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

    2016-08-01

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

  4. An overview of innovative techniques to improve cervical cancer screening

    NARCIS (Netherlands)

    Nijhuis, Esther R.; Reesink-Peters, Nathalie; Wisman, G. Bea A.; Nijman, Hans W.; van Zanden, Jelmer; Volders, Haukeline; Hollema, Harry; Suurmeijer, Albert J. H.; Schuuring, Ed; van der Zee, Ate G. J.

    2006-01-01

    Although current cytomorphology-based cervical cancer screening has reduced the incidence of cervical cancer, Pap-smears are associated with high false positive and false negative rates. This has spurred the search for new technologies to improve current screening. New methodologies are automation

  5. An overview of risk factors for recurrent breast cancer | Mannell ...

    African Journals Online (AJOL)

    Summary: The multidisciplinary management of Breast Cancer (BC) has evolved over the past 50 years: the patient is offered a choice of surgical procedures with or without radiation therapy, cytotoxics and treatments targeting the nuclei of the cancer cells. This has resulted in a reduction of disease recurrence and a ...

  6. Nest expansion assay: a cancer systems biology approach to in vitro invasion measurements

    Directory of Open Access Journals (Sweden)

    Estrada Lourdes

    2009-07-01

    Full Text Available Abstract Background Traditional in vitro cell invasion assays focus on measuring one cell parameter at a time and are often less than ideal in terms of reproducibility and quantification. Further, many techniques are not suitable for quantifying the advancing margin of collectively migrating cells, arguably the most important area of activity during tumor invasion. We have developed and applied a highly quantitative, standardized, reproducible Nest Expansion Assay (NEA to measure cancer cell invasion in vitro, which builds upon established wound-healing techniques. This assay involves creating uniform circular "nests" of cells within a monolayer of cells using a stabilized, silicone-tipped drill press, and quantifying the margin expansion into an overlaid extracellular matrix (ECM-like component using computer-assisted applications. Findings The NEA was applied to two human-derived breast cell lines, MCF10A and MCF10A-CA1d, which exhibit opposite degrees of tumorigenicity and invasion in vivo. Assays were performed to incorporate various microenvironmental conditions, in order to test their influence on cell behavior and measures. Two types of computer-driven image analysis were performed using Java's freely available ImageJ software and its FracLac plugin to capture nest expansion and fractal dimension, respectively – which are both taken as indicators of invasiveness. Both analyses confirmed that the NEA is highly reproducible, and that the ECM component is key in defining invasive cell behavior. Interestingly, both analyses also detected significant differences between non-invasive and invasive cell lines, across various microenvironments, and over time. Conclusion The spatial nature of the NEA makes its outcome susceptible to the global influence of many cellular parameters at once (e.g., motility, protease secretion, cell-cell adhesion. We propose the NEA as a mid-throughput technique for screening and simultaneous examination of factors

  7. 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.

  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. 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.......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...

  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...... cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.......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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-15

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

  12. MRI evaluation of invasion to the costal pleura by lung cancer

    International Nuclear Information System (INIS)

    Kusumoto, Masahiko; Nakamura, Toru; Endo, Masahiro

    1994-01-01

    To evaluate the costo-pleural invasion of lung cancer adjacent to the chest wall, MR images of 16 lung cancer patients were studied. No tumor invasion to the pleura were seen pathologically, when the zone observed between the tumor and the chest wall showed low signal intensity on both the T1- and T2-weighted images or the low signal intensity on the T1-weighted images and the high signal intensity in the T2-weighted images. In the other six cases the zone showed the high signal intensity on both T1- and T2-weighted images, the extrapleural fat was indented by the tumor together with the pleurae pathologically in five of these 6 cases. MR imaging can allow detection of costo-pleural invasion by lung cancer. (author)

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  14. 3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

    Science.gov (United States)

    2017-12-29

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

  15. Post-Traumatic Growth and Resilience in Adolescent and Young Adult Cancer Patients: An Overview

    NARCIS (Netherlands)

    Greup, Suzanne R.; Kaal, Suzanne E. J.; Jansen, Rosemarie; Manten-Horst, Eveliene; Thong, Melissa S. Y.; van der Graaf, Winette T. A.; Prins, Judith B.; Husson, Olga

    2018-01-01

    The aim of this study was to provide an overview of the literature on post-traumatic growth (PTG) and resilience among adolescent and young adult (AYA) cancer patients. A literature search in Embase, PsychInfo, PubMed, Web of Science, Cochrane Library, and Cinahl was carried out. Thirteen articles

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

    Directory of Open Access Journals (Sweden)

    Ze-Hong Fu

    2017-08-01

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

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

    International Nuclear Information System (INIS)

    Koga, Fumitaka; Kihara, Kazunori

    2012-01-01

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

  18. BRCA1/2 associated cancer susceptibility: a clinical overview

    Directory of Open Access Journals (Sweden)

    Lypas Georgios

    2016-06-01

    Full Text Available The most frequently identified genetic cause of breast cancer is the germline mutation of BRCA1 and 2 genes. The carriers of these mutations are at high risk for breast and ovarian cancers and increased risk for pancreatic and prostate cancers. Personal and family history are routinely used to identify individuals at risk for carrying such mutations. Genetic counselling is required to guide them through genetic testing and risk management. Positive testing corresponds to a deleterious mutation, whereas negative testing is considered as uninformative; variants of unknown clinical significance are also classified as uninformative.

  19. Treatment Option Overview (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Atomic bomb radiation. Living where there is air pollution. Having a family history of lung cancer. Being ... the endoscope is used to bounce high-energy sound waves ( ultrasound ) off internal tissues or organs and ...

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

    Science.gov (United States)

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

    2012-11-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  4. 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.

  5. 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.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-26

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

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

    Directory of Open Access Journals (Sweden)

    Jianjun Shen

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

  9. Cell polarity signaling in the plasticity of cancer cell invasiveness

    Czech Academy of Sciences Publication Activity Database

    Gandalovičová, A.; Vomastek, Tomáš; Rosel, D.; Brábek, J.

    2016-01-01

    Roč. 7, č. 18 (2016), s. 25022-25049 ISSN 1949-2553 R&D Projects: GA ČR GA13-06405S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : polarity * invasion * plasticity Subject RIV: EE - Microbiology, Virology Impact factor: 5.168, year: 2016

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-09

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

  11. Impact of a prior diagnosis of DCIS on survival from invasive breast cancer.

    Science.gov (United States)

    Sopik, Victoria; Iqbal, Javaid; Sun, Ping; Narod, Steven A

    2016-07-01

    A diagnosis of invasive breast cancer after DCIS can be described as a new primary cancer or as a local invasive recurrence. It is of interest to determine if, among women with early-stage breast cancer, a past history of DCIS influences survival. We retrieved the records of 306,249 women diagnosed with stage I or stage II breast cancer between 2004 and 2012, in the surveillance, epidemiology, and end results registries database, of whom 5395 had a previous diagnosis of DCIS. For each patient, we extracted information on the year of diagnosis, age at diagnosis, tumor size, nodal status, grade, estrogen receptor status, type of surgery (lumpectomy/mastectomy), use of radiotherapy (no/yes), prior DCIS (no/yes), cause of death, and follow-up time. For each case with prior DCIS, we recorded information on the year of diagnosis of DCIS, laterality of DCIS, and treatments received for DCIS. We matched 3979 patients with a prior DCIS to 3979 patients without a prior DCIS, according to the various prognostic features of the invasive cancer. We estimated the risk of death from breast cancer for patients with invasive ductal carcinoma, with and without a prior diagnosis of DCIS. We identified 306,249 women with stage I/II breast cancer, of whom 2335 had a prior ipsilateral DCIS and 3060 had a prior contralateral DCIS. Breast cancer-specific survival at 9 years was 94.6 % for patients with a prior DCIS (ipsilateral or contralateral) and was 95.2 % for patients with no prior DCIS (p = 0.32). In a matched analysis (3979 matched pairs), the hazard ratio for death from breast cancer for patients with a prior ipsilateral DCIS, compared to patients with no prior DCIS, was 0.91 (95 % CI = 0.49-1.68; p = 0.75). A prior diagnosis of ipsilateral DCIS does not impact upon the prognosis of women with early-stage invasive breast cancer. This suggests that primary breast cancers and local invasive recurrences following DCIS are similar conditions and should be treated in the same

  12. Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Douglas G Ward

    Full Text Available Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA.DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+ and 91 bladder cancer patients post-TURBT (89 cancer-free.Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage, FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity.This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.

  13. Diagnosis of chest wall invasion by lung cancer. Useful criteria for exclusion of the possibility of chest wall invasion with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shiotani, Seiji [Tsukuba Medical Center, Ibaraki (Japan); Sugimura, Kazuro; Sugihara, Masaki (and others)

    2000-10-01

    To compare the accuracy of thin-section CT, conventional static MR imaging (conventional MRI), and breathing dynamic echo planar magnetic resonance imaging (BDEPI) in evaluating lung cancer invasion to the chest wall. Thin-section CT, conventional MRI, and BDEPI were performed preoperatively in 20 patients suspected of having primary lung cancers adjacent to the chest wall on conventional CT. The results of imaging findings were compared with those of surgical and histopathological findings. All patients were confirmed to have no chest wall invasion after surgery. By thin-section CT, 10 of 20 patients were correctly diagnosed as having no chest wall invasion (50% specificity). Two of the 20 patients were incorrectly diagnosed as having chest wall invasion by conventional MRI and BDEPI (90% specificity). When chest wall invasion is suspected on CT scans, static and breathing dynamic MRI are recommended to avoid false positive interpretations. (author)

  14. Prolactin signaling stimulates invasion via Na+/H+ exchanger NHE1 in T47D human breast cancer cells

    DEFF Research Database (Denmark)

    Pedraz Cuesta, Elena; Fredsted, Jacob; Jensen, Helene H.

    2016-01-01

    Prolactin (PRL) and its receptor the PRLR are implicated in breast cancer invasiveness, although their exact roles remain controversial. The Na(+)/H(+) exchanger NHE1 plays essential roles in cancer cell motility and invasiveness, but the PRLR and NHE1 have not previously been linked. Here, we show...

  15. 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...

  16. Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression

    International Nuclear Information System (INIS)

    Lee, Young-Rae; Noh, Eun-Mi; Oh, Hyun Ju; Hur, Hyun; Kim, Jeong-Mi; Han, Ji-Hey; Hwang, Jin-Ki; Park, Byung-Hyun; Park, Jin-Woo; Youn, Hyun Jo; Jung, Sung Hoo; Kim, Byeong-Soo; Jung, Ji-Youn; Lee, Sung-Ho; Park, Chang-Sik; Kim, Jong-Suk

    2011-01-01

    Research highlights: → MMP-9 plays a pivotal role in the invasion of MCF-7 breast cancer cells. → TPA stimulates MMP-9 expression through activation of MAPK/NF-κB and MAPK/AP-1 pathways. → Dihydroavenanthramide D suppresses MMP-9 expression via inhibition of TPA-induced MAPK/NF-κB and MAPK/AP-1 activations. → Dihydroavenanthramide D blocks cell invasion of MCF-7 breast cancer cells. -- Abstract: Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.

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

    International Nuclear Information System (INIS)

    Takebe, Koji; Izumori, Ayumi; Yasumo, Naomi

    2007-01-01

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

  18. An Overview of Immune Checkpoint Inhibitors in Gynecologic Cancers.

    Science.gov (United States)

    Castellano, Tara; Moore, Kathleen N; Holman, Laura L

    2018-03-01

    The goal of this study was to compile a review of topics pertinent to the use of immune checkpoint inhibitors in gynecologic malignancies, including foundation for use, current agents available and trials in gynecologic cancers, special populations of interest, identification and management of toxicities, and considerations in predictive biomarkers and response assessment. A literature review of selected topics in reference to immune checkpoint inhibitors and gynecologic cancers was conducted on PubMed and the US Food and Drug Administration drug search application. A review of current and ongoing clinical trials was performed in clinicaltrials.gov, and selected preliminary results reported in PubMed abstracts and through the American Society of Clinical Oncologists were compiled. Although immunotherapy in gynecologic malignancy is relatively new, 7 agents are currently approved for use in other oncologic indications, and a multitude of trials in gynecologic cancer are ongoing. Immunotherapy has a specific set of drug toxicities that manifest and are managed unlike traditional cytotoxic therapies. Application of the knowledge of immune checkpoint inhibitor use in gynecologic cancers will improve care for women with cancers of the female reproductive tract. As more complex and newer immunotherapies evolve, it will be vital to accurately characterize each specific drug class and management thereof. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  19. Magnetic resonance imaging of invasive breast cancer | Corr | SA ...

    African Journals Online (AJOL)

    Breast MR is a sensitive but nonspecific imaging investigation to detect breast cancer. MR imaging strengths lie in the accurate staging of the primary tumour, detecting recurrent cancer following lumpectomy and radiation therapy, problem solving in cases where there are equivocal mammographic findings, and screening ...

  20. Cervical intra-epithelial neoplasia and invasive cervical cancer in ...

    African Journals Online (AJOL)

    cancer in black and white patients. J. T. NEL, L. DE LANGE, P. J. MEIRING ... cervical cancer. This serious yet preventable disease is still very prevalent in South Africa, especially among black women. S AIr Med J 1994; 84: 18-19. Aanalysis of rime trends in .... therapy in users of oral contraceptives. Am J Clill Nucr 1982; 35:.

  1. Fertility preservation in female cancer patients: An overview

    Science.gov (United States)

    Mahajan, Nalini

    2015-01-01

    Fertility preservation is becoming increasingly important to improve the quality of life in cancer survivors. Despite guidelines suggesting that discussion of fertility preservation should be done prior to starting cancer therapies, there is a lack of implementation in this area. A number of techniques are available for fertility preservation, and they can be used individually or together in the same patient to maximize efficiency. Oocyte and embryo cryopreservation are now established techniques but have their limitations. Ovarian tissue cryopreservation though considered experimental at present, has a wider clinical application and the advantage of keeping the fertility window open for a longer time. Both chemotherapy and radiotherapy have a major impact on reproductive potential and fertility preservation procedures should be carried out prior to these treatments. The need for fertility preservation has to be weighed against morbidity and mortality associated with cancer. There is thus a need for a multidisciplinary collaboration between oncologists and reproductive specialists to improve awareness and availability. PMID:25838742

  2. Intracervical US with a high-frequency miniature probe: a method for diagnosing early invasive cervical cancer.

    Science.gov (United States)

    Kikuchi, A; Okai, T; Kobayashi, K; Yoshikawa, H; Shiromizu, K; Matsuzawa, M; Taketani, Y

    1996-02-01

    To determine whether intracervical ultrasound (US) with a high-frequency miniature probe can depict cervical neoplasms, especially in early invasive stages. Forty-eight women with cervical cancer underwent preoperative transvaginal and intracervical US. US scans were compared with findings from histologic examination or surgery. Intracervical US was completed in 45 of the 48 patients. Both intracervical and transvaginal US were unable to depict preinvasive cancer. Intracervical US depicted the lesion in eight of 16 patients (50%) in whom the depth of cancer invasion was less than or equal to 5 mm, whereas transvaginal US failed to depict the lesion in all 16 patients. Intracervical US depicted the lesions in all 19 patients in whom the depth of cancer invasion was more than 5 mm, whereas transvaginal US was successful only in 14 (74%). Intracervical US is useful for evaluating invasive cervical cancer and is especially suitable for detecting early invasion in the endocervix.

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  4. Should patients with muscle-invasive bladder cancer undergo more-extensive pelvic lymph node dissection?

    DEFF Research Database (Denmark)

    Steven, Kenneth Eric

    2008-01-01

    This Practice Point commentary discusses the paper by Dhar and colleagues, which compared outcomes between two cohorts of patients with muscle-invasive bladder cancer who received either 'limited' pelvic lymph node dissection (LND) or 'extended' pelvic LND at clinics in the US or Switzerland...... as an essential component of radical cystectomy and applied to all patients undergoing radical surgery for bladder cancer Udgivelsesdato: 2008/10...

  5. Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells.

    Science.gov (United States)

    Díaz-Valdivia, Natalia I; Calderón, Claudia C; Díaz, Jorge E; Lobos-González, Lorena; Sepulveda, Hugo; Ortíz, Rina J; Martinez, Samuel; Silva, Veronica; Maldonado, Horacio J; Silva, Patricio; Wehinger, Sergio; Burzio, Verónica A; Torres, Vicente A; Montecino, Martín; Leyton, Lisette; Quest, Andrew F G

    2017-12-19

    Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits. Here, we used in vitro [2D, invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question. Colon and breast cancer cells were identified where CAV1 levels were low due to epigenetic suppression and could be reverted by treatment with the methyltransferase inhibitor 5'-azacytidine. Exposure of these cells to anti-neoplastic drugs for short periods of time (24-48 h) increased CAV1 expression through ROS production and MEK/ERK activation. In colon cancer cells, increased CAV1 expression enhanced migration and invasion in vitro via pathways requiring Src-family kinases, as well as Rac-1 activity. Finally, elevated CAV1 expression in colon cancer cells following exposure in vitro to sub-cytotoxic drug concentrations increased their metastatic potential in vivo . Therefore exposure of cancer cells to anti-neoplastic drugs at non-lethal drug concentrations induces signaling events and changes in transcription that favor CAV1-dependent migration, invasion and metastasis. Importantly, this may occur in the absence of selection for drug-resistance.

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

    Science.gov (United States)

    2016-09-01

    for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT: This project is designed to complement a multi-institutional, NIH...the minority of cases of preinvasive breast cancer (DCIS), that do in fact progress to invasive disease (IBC), and complements our multi-institutional...Pathology & Laboratory Medicine Lineberger Comprehensive Cancer Center 125 Mason Farm Road The University of North Carolina at Chapel Hill Chapel

  7. A cell-based, high content screening assay reveals activators and inhibitors of cancer cell invasion

    Science.gov (United States)

    Quintavalle, Manuela; Elia, Leonardo; Price, Jeffrey H.; Heynen-Genel, Susanne; Courtneidge, Sara A.

    2012-01-01

    Acquisition of invasive cell behavior underlies tumor progression and metastasis. To define in more molecular detail the mechanisms underlying invasive behavior, we developed a high throughput screening strategy to quantitate invadopodia; actin-rich membrane protrusions of cancer cells which contribute to tissue invasion and matrix remodeling. We developed a high content, imaged-based assay, and tested the LOPAC 1280 collection of pharmacologically active agents. We found compounds that potently inhibited invadopodia formation without overt toxicity, as well as compounds that increased invadopodia number. One of the two compounds that increased both invadopodia number and invasive behavior was the chemotherapeutic agent paclitaxel, which has potential clinical implications for its use in the neoadjuvant and resistance settings. Several of the invasion inhibitors were annotated as cyclin-dependent kinase (cdk) inhibitors. Loss-of-function experiments determined that Cdk5 was the relevant target. We further determined that the mechanism by which Cdk5 promotes both invadopodia formation and cancer invasion is by phosphorylation and down regulation of the actin regulatory protein caldesmon. PMID:21791703

  8. Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44.

    Science.gov (United States)

    Dohadwala, M; Luo, J; Zhu, L; Lin, Y; Dougherty, G J; Sharma, S; Huang, M; Pold, M; Batra, R K; Dubinett, S M

    2001-06-15

    Elevated tumor cyclooxygenase (COX-2) expression is associated with increased angiogenesis, tumor invasion, and suppression of host immunity. We have previously shown that genetic inhibition of tumor COX-2 expression reverses the immunosuppression induced by non-small cell lung cancer (NSCLC). To assess the impact of COX-2 expression in lung cancer invasiveness, NSCLC cell lines were transduced with a retroviral vector expressing the human COX-2 cDNA in the sense (COX-2-S) and antisense (COX-2-AS) orientations. COX-2-S clones expressed significantly more COX-2 protein, produced 10-fold more prostaglandin E(2), and demonstrated an enhanced invasive capacity compared with control vector-transduced or parental cells. CD44, the cell surface receptor for hyaluronate, was overexpressed in COX-2-S cells, and specific blockade of CD44 significantly decreased tumor cell invasion. In contrast, COX-2-AS clones had a very limited capacity for invasion and showed diminished expression of CD44. These findings suggest that a COX-2-mediated, CD44-dependent pathway is operative in NSCLC invasion. Because tumor COX-2 expression appears to have a multifaceted role in conferring the malignant phenotype, COX-2 may be an important target for gene or pharmacologic therapy in NSCLC.

  9. Anti-invasive activity against cancer cells of phytochemicals in red jasmine rice (Oryza sativa L.).

    Science.gov (United States)

    Pintha, Komsak; Yodkeeree, Supachai; Pitchakarn, Pornsirit; Limtrakul, Pornngarm

    2014-01-01

    Red rice contains pharmacological substances including phenolics, oryzanol, tocotrienol and tocopherol. Recently, red rice extract has been employed as a source of antioxidants for inhibition of tumor growth. This study was carried out to evaluate the anti-invasion effects of red rice extract fractions on cancer cells. It was found that at 100 μg/ml of crude ethanolic extract (CEE), hexane fraction (Hex) and dichloromethane fraction (DCM) could reduce HT1080 and MDA-MB-231 cancer cell invasion. Hex and DCM revealed higher potency levels than CEE, whereas an ethyl acetate fraction (EtOAc) had no effect. Gelatin zymography revealed that Hex decreased the secretion and activity of matrix metalloproteinase-2 and -9 (MMP-2 and-9). In contrast, the DCM fraction exhibited slightly effect on MMPs secretion and had no effect on MMPs activity. Collagenase activity was significantly inhibited by the Hex and DCM fractions. High amounts of γ-oryzanol and γ-tocotrienol were found in the Hex and DCM fractions and demonstrated an anti-invasion property. On the other hand, proanthocyanidin was detected only in the CEE fraction and reduced MDA-MB-231 cells invasion property. These observations suggest that proanthocyanidin, γ-oryzanol and γ-tocotrienol in the red rice fractions might be responsible for the anti invasion activity. The red rice extract may have a potential to serve as a food-derived chemotherapeutic agent for cancer patients.

  10. 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.

  11. Overview of Microarray Analysis of Gene Expression and its Applications to Cervical Cancer Investigation

    Directory of Open Access Journals (Sweden)

    Angel Chao

    2007-12-01

    Full Text Available Cervical cancer is one of the leading female cancers in Taiwan and ranks as the fifth cause of cancer death in the female population. Human papillomavirus has been established as the causative agent for cervical neoplasia and cervical cancer. However, the tumor biology involved in the prognoses of different cell types in early cancers and tumor responses to radiation in advanced cancers remain largely unknown. The introduction of microarray technologies in the 1990s has provided genome-wide strategies for searching tens of thousands of genes simultaneously. In this review, we first summarize the two types of microarrays: oligonucleotides microarray and cDNA microarray. Then, we review the studies of functional genomics in cervical cancer. Gene expression studies that involved cervical cancer cell lines, cervical cells of cancer versus normal ectocervix, cancer tissues of different histology, radioresistant versus radiosensitive patients, and the combinatorial gene expression associated with chromosomal amplifications are discussed. In particular, CEACAM5, TACSTD1, S100P, and MSLN have shown to be upregulated in adenocarcinoma, and increased expression levels of CEACAM5 and TACSTD1 were significantly correlated with poorer patient outcomes. On the other hand, 35 genes, including apoptotic genes (e.g. BIK, TEGT, SSI-3, hypoxia-inducible genes (e.g. HIF1A, CA12, and tumor cell invasion and metastasis genes (e.g. CTSL, CTSB, PLAU, CD44, have been noted to echo the hypothesis that increased tumor hypoxia leads to radiation resistance in cervical cancer during radiation.

  12. Non-muscle invasive bladder cancer risk stratification

    Directory of Open Access Journals (Sweden)

    Sumit Isharwal

    2015-01-01

    Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

  13. 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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  15. An overview about mitochondrial DNA mutations in ovarian cancer ...

    African Journals Online (AJOL)

    Background: Ovarian tumour is the second most common form of cancer affecting female reproductive system and the most lethal of the gynaecological malignancies. Since past decades, tremendous efforts have been made to illuminate the molecular basis for initiation and progression of ovarian carcinoma. A low quantity ...

  16. Viruses cancer - an overview | Buhari | African Journal of Clinical ...

    African Journals Online (AJOL)

    ... by the immune system. The mechanism o f transformation o f a normal cell into a neoplastic cell can either be direct or indirect. Better understanding o f the role o f viruses in human cancer will have therapeutic implication as control can be instituted. African Journal of Clinical and Experimental Microbiology Vol. 7(2) 2006: ...

  17. Childhood cancer: Overview of incidence trends and environmental carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Zahm, S.H.; Devesa, S.S. [National Cancer Inst., Rockville, MD (United States)

    1995-09-01

    An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively. From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia, gliomas, and, to a much lesser extent, Wilms` tumor. There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol. Many other agents such as electromagnetic fields, pesticides, and some parental occupational exposures are suspected of playing roles, but the evidence is not conclusive at this time. Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood. For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults. 143 refs., 1 fig., 3 tabs.

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

    Science.gov (United States)

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

    2017-12-01

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

  19. Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers

    Directory of Open Access Journals (Sweden)

    Yoshida Sayaka

    2004-04-01

    Full Text Available Abstract Background We have previously described an alternative invasion-independent pathway of cancer metastasis in a murine mammary tumor model. This pathway is initiated by intravasation of tumor nests enveloped by endothelial cells of sinusoidal vasculature within the tumor. In this study, we examined whether evidence for the invasion-independent pathway of metastasis is present in human cancers. Methods Archival specimens of 10 common types of human cancers were examined for the presence of sinusoidal vasculature enveloping tumor nests and subsequently generated endothelial-covered tumor emboli in efferent veins. Results A percentage of tumor emboli in all cancers was found to be enveloped by endothelial cells, but these structures were particularly prevalent in renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. A common feature of the vasculature in these tumors was the presence of dilated sinusoid-like structures surrounding tumor nests. A high mean vascular area within tumors, an indication of sinusoidal vascular development, was significantly related to the presence of endothelial-covered tumor emboli. Conclusions These results suggest that an invasion-independent metastatic pathway is possible in a wide variety of human cancers. Further investigation of this phenomenon may present new therapeutic strategies for the amelioration of cancer metastasis.

  20. The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer.

    Science.gov (United States)

    Nishikawa, Hiroshi; Ozaki, Yasuhiko; Nakanishi, Tamao; Blomgren, Klas; Tada, Toyohiro; Arakawa, Atsushi; Suzumori, Kaoru

    2004-03-01

    The aim of this study was to investigate the contribution of cathepsin B and cystatin C to the mechanisms of invasion by ovarian cancer. Using surgical materials from patients with ovarian cancer, immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis were performed using antibodies against cathepsin B or cystatin C. Serum levels of cathepsin B and cystatin C in patients with benign and malignant ovarian lesions were determined by enzyme-linked immunosorbent assay (ELISA). An invasion assay using an ovarian cancer cell line was performed by addition of cystatin C or specific inhibitors of cathepsin B. While immunohistochemical staining of cathepsin B and cystatin C was evident in cancer cells and associated stromal tissue, this was not the case in benign tumors. The malignancies were also found to be positive for cathepsin B and cystatin C by SDS-PAGE and Western blotting analysis. No significant difference in serum cathepsin B levels was observed between patients with benign and malignant disease. However, the concentration of cystatin C in cases with ovarian cancer was significantly higher in benign cases (Pcancer cells was dose-dependently suppressed by cystatin C and cathepsin B inhibitors. The results provided convincing evidence that cathepsin B and cystatin C may contribute to the mechanisms of invasion of ovarian cancer.

  1. 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.

  2. Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in Human Colorectal Cancer.

    Science.gov (United States)

    He, Guoyang; Zou, Liyuan; Zhou, Lin; Gao, Peiqiong; Qian, Xinlai; Cui, Jing

    2017-01-01

    Cysteine-rich intestinal protein 1 (CRIP1), a member of the LIM/double zinc finger protein family, is abnormally expressed in several tumour types. However, few data are available on the role of CRIP1 in cancer. In the present study, we aimed to investigate the expression profile and functions of CRIP1 in colorectal cancer. To examine the protein expression level of CRIP1, immunohistochemistry (IHC) was performed on 56 pairs of colon cancer tissue samples. Western blotting was performed to investigate CRIP1 protein expression in four colon cancer cell lines. The endogenous expression of CRIP1 was suppressed using short interfering RNAs (siRNAs). Cell proliferation assays were used to determine whether CRIP1 silencing affected cell proliferation. Flow cytometry analysis was used to detect cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion was detected using the transwell and wound-healing assays. IHC analysis showed that protein level of CRIP1 was significantly higher in tumour tissue samples than in paired non-tumour tissue samples and that the CRIP1 level was higher in metastatic tissue samples than in non-metastatic tissue samples. In addition, protein levels of CRIP1 were higher in highly metastatic colon cancer cell lines than in colon cancer cell lines with low metastasis. Further, CRIP1 silencing had no effect on cell proliferation or apoptosis in SW620 and HT29 cells. CRIP1 silencing suppressed cell migration and invasion obviously in SW620 and HT29 cells. The present study provides new evidence that abnormal expression of CRIP1 might be related to the degree of metastasis in colorectal cancer and that CRIP1 silencing could effectively inhibit migration and invasion during colorectal cancer development. These findings might aid the development of a biomarker for colon cancer prognosis and metastasis, and thus help to treat this common type of cancer. © 2017 The Author(s). Published by S. Karger AG, Basel.

  3. 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

    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...

  4. Intracellular Hyper-Acidification Potentiated by Hydrogen Sulfide Mediates Invasive and Therapy Resistant Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Zheng-Wei Lee

    2017-10-01

    Full Text Available Slow and continuous release of H2S by GYY4137 has previously been demonstrated to kill cancer cells by increasing glycolysis and impairing anion exchanger and sodium/proton exchanger activity. This action is specific for cancer cells. The resulting lactate overproduction and defective pH homeostasis bring about intracellular acidification-induced cancer cell death. The present study investigated the potency of H2S released by GYY4137 against invasive and radio- as well as chemo-resistant cancers, known to be glycolytically active. We characterized and utilized cancer cell line pairs of various organ origins, based on their aggressive behaviors, and assessed their response to GYY4137. We compared glycolytic activity, via lactate production, and intracellular pH of each cancer cell line pair after exposure to H2S. Invasive and therapy resistant cancers, collectively termed aggressive cancers, are receptive to H2S-mediated cytotoxicity, albeit at a higher concentration of GYY4137 donor. While lactate production was enhanced, intracellular pH of aggressive cancers was only modestly decreased. Inherently, the magnitude of intracellular pH decrease is a key determinant for cancer cell sensitivity to H2S. We demonstrated the utility of coupling GYY4137 with either simvastatin, known to inhibit monocarboxylate transporter 4 (MCT4, or metformin, to further boost glycolysis, in bringing about cell death for aggressive cancers. Simvastatin inhibiting lactate extrusion thence contained excess lactate induced by GYY4137 within intracellular compartment. In contrast, the combined exposure to both GYY4137 and metformin overwhelms cancer cells with lactate over-production exceeding its expulsion rate. Together, GYY4137 and simvastatin or metformin synergize to induce intracellular hyper-acidification-mediated cancer cell death.

  5. Ezrin mediates c-Myc actions in prostate cancer cell invasion

    DEFF Research Database (Denmark)

    Chuan, Yin Choy; Iglesias Gato, Diego; Fernandez-Perez, L

    2010-01-01

    The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens...... in the regulation of prostate cancer cell invasion. We found that c-Myc induces cell invasion and anchorage-independent growth by regulating ezrin protein expression in the presence of androgens. The activity of the ezrin promoter is controlled by androgens through c-Myc, which binds to a phylogenetically conserved...... E-Box located in the proximal promoter region. Besides, we also show that ezrin is an important regulator of c-Myc protein levels. These effects are achieved through androgen-induced changes in ezrin phosphorylation, which results in the regulation of downstream signals. These downstream signals...

  6. [Reflection on the Biological Significance of Minimally Invasive Surgery for Lung Cancer].

    Science.gov (United States)

    Luo, Qingquan; Huang, Jia

    2018-03-20

    Minimal invasive surgery with short operation time and enhanced recovery after surgery can truly achieve biological minimal invasiveness. The minimal invasive lung cancer surgery includes several kinds, such as uni-portal video-assisted thoracoscopic surgery (VATS) and multi-portal VATS. Robotic-assisted thoracic surgery (RATS) can be categorized into multi-portal VATS. As a frontier technology of minimal invasive surgical technique, surgical robotic system has been broadly applied in many areas. The average RATS operation time is (91.51±30.80) min among our team, which is much shorter than reported uni-portal VATS operation time. For now, RATS has some drawbacks and is lacking of national practice guidelines, which, we believe, will be solved by technology development and large-scale randomized controlled trials. 
.

  7. Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer

    NARCIS (Netherlands)

    Truin, Wilfred; Roumen, Rudi M.; Siesling, Sabine; van der Heiden-van der Loo, Margriet; Lobbezoo, Dorien J.; Tjan-Heijnen, Vivianne C.G.; Voogd, Adri C.

    2016-01-01

    Background Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification

  8. 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

  9. Treatment Options Available for Bacillus Calmette-Guerin Failure in Non-muscle-invasive Bladder Cancer

    NARCIS (Netherlands)

    Yates, D.R.; Brausi, M.A.; Catto, J.W.; Dalbagni, G.; Roupret, M.; Shariat, S.F.; Sylvester, R.J.; Witjes, J.A.; Zlotta, A.R.; Palou-Redorta, J.

    2012-01-01

    CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Many patients will experience recurrence or progression following BCG and are termed BCG failures. OBJECTIVE: To summarise the current

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  11. Invasive adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp and synchronous transverse colon cancer.

    Science.gov (United States)

    Chen, Chuang-Wei; Hsiao, Koung-Hong; Yue, Chung-Tai; Wang, Chia-Chi

    2013-08-28

    An admixture of hyperplastic and adenomatous components within the same polyp is unusual. Adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp (MHAP) occurs even more rarely. We report the first case of a 59-year-old male who presented with invasive adenocarcinoma originating from a MHAP at a sigmoid colon and synchronous transverse colon cancer.

  12. Invasive adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp and synchronous transverse colon cancer

    OpenAIRE

    Chen, Chuang-Wei; Hsiao, Koung-Hong; Yue, Chung-Tai; Wang, Chia-Chi

    2013-01-01

    An admixture of hyperplastic and adenomatous components within the same polyp is unusual. Adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp (MHAP) occurs even more rarely. We report the first case of a 59-year-old male who presented with invasive adenocarcinoma originating from a MHAP at a sigmoid colon and synchronous transverse colon cancer.

  13. Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1

    Directory of Open Access Journals (Sweden)

    Hirotada Tajiri

    2017-05-01

    Full Text Available Oncogenic Ras plays a key role in cancer initiation but also contributes to malignant phenotypes by stimulating nutrient uptake and promoting invasive migration. Because these latter cellular responses require Rac-mediated remodeling of the actin cytoskeleton, we hypothesized that molecules involved in Rac activation may be valuable targets for cancer therapy. We report that genetic inactivation of the Rac-specific guanine nucleotide exchange factor DOCK1 ablates both macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells. By screening chemical libraries, we have identified 1-(2-(3′-(trifluoromethyl-[1,1′-biphenyl]-4-yl-2-oxoethyl-5-pyrrolidinylsulfonyl-2(1H-pyridone (TBOPP as a selective inhibitor of DOCK1. TBOPP dampened DOCK1-mediated invasion, macropinocytosis, and survival under the condition of glutamine deprivation without impairing the biological functions of the closely related DOCK2 and DOCK5 proteins. Furthermore, TBOPP treatment suppressed cancer metastasis and growth in vivo in mice. Our results demonstrate that selective pharmacological inhibition of DOCK1 could be a therapeutic approach to target cancer cell survival and invasion.

  14. Andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity.

    Science.gov (United States)

    Chao, Hsueh-Ping; Kuo, Cheng-Deng; Chiu, Jen-Hwey; Fu, Shu-Ling

    2010-11-01

    Andrographolide, a major constituent of Andrographis paniculata, was previously shown to exhibit anti-inflammatory, antiviral, and anticancer activities. The anticancer activity of andrographolide includes growth suppression, apoptosis promotion, antiangiogenesis, and antitransformation. However, the effect of andrographolide on cancer metastasis, the most malignant feature of cancer, has not been elucidated extensively. In the present study, we demonstrated that andrographolide at nontoxic to subtoxic concentrations (0.3-3 µM) suppressed the invasion ability of CT26 cells in Matrigel-based invasion assays. In addition, the expression of cell adhesion regulators (β-catenin and ILK) was not altered by andrographolide treatment. However, andrographolide indeed inhibited matrix metalloproteinase 2 (MMP2) activity without affecting its expression. Furthermore, the activation of ERK, but not Akt, was attenuated by andrographolide treatment. Notably, a similar inhibitory effect of andrographolide on the invasion and MMP2 activity of the human colon cancer cell line HT29 was also observed. In summary, our results indicate that andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Can we improve transurethral resection of the bladder tumour for nonmuscle invasive bladder cancer?

    NARCIS (Netherlands)

    Liem, Esmee Iml; de Reijke, Theo M.

    2017-01-01

    Purpose of review The recurrence rate in patients with nonmuscle invasive bladder cancer is high, and the quality of transurethral resection of the bladder (TURB) tumour influences recurrence risk. We review new methods that aim to improve the effectiveness of TURB, and highlight studies of the past

  16. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer

    NARCIS (Netherlands)

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

    2014-01-01

    PURPOSE: Low, intermediate and high risk categories have been defined to help guide the treatment of patients with nonmuscle invasive bladder cancer (Ta, T1, CIS). However, while low and high risk disease has been well classified, the intermediate risk category has traditionally comprised a

  17. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, J. F.; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P

    PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  18. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, Jeroen F.; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B; van Diest, Paul J.; van Bergen En Henegouwen, Paul M P

    Purpose: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. Procedures: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  19. 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.

  20. An overview of pregnancy and fertility issues in breast cancer patients.

    Science.gov (United States)

    Dabrosin, Charlotta

    2015-01-01

    Breast cancer is one of the most common malignancies of women in the reproductive years. In the Western world there is a trend towards delaying pregnancy to later in life, and in combination with an increased incidence of breast cancer an increased number of women are diagnosed with breast cancer before they have completed their reproductive plans. In addition, breast cancer during pregnancy may affect an increased number of women as the childbearing years are delayed. The survival rate after breast cancer has improved during the last decades, and many young breast cancer survivors will consider a pregnancy subsequent to the completion of adjuvant breast cancer therapy. Traditionally, many women are advised against a pregnancy due to a fear of increased risk of recurrence, especially women with estrogen receptor-positive breast cancer. Due to feasibility issues, evidence from large prospective randomized trials is missing regarding the safety of pregnancy after breast cancer. Today guidelines are based on cohort studies and population-based registry evidence with its limitations. Overall, data suggest that pregnancy after breast cancer therapy is safe, and the current evidence is summarized in this overview.

  1. Fatty acid amide hydrolase inhibitors confer anti-invasive and antimetastatic effects on lung cancer cells

    Science.gov (United States)

    Winkler, Katrin; Ramer, Robert; Dithmer, Sophie; Ivanov, Igor; Merkord, Jutta; Hinz, Burkhard

    2016-01-01

    Inhibition of endocannabinoid degradation has been suggested as tool for activation of endogenous tumor defense. One of these strategies lies in blockade of fatty acid amide hydrolase (FAAH) which catalyzes the degradation of endocannabinoids (anandamide [AEA], 2-arachidonoylglycerol [2-AG]) and endocannabinoid-like substances (N-oleoylethanolamine [OEA], N-palmitoylethanolamine [PEA]). This study addressed the impact of two FAAH inhibitors (arachidonoyl serotonin [AA-5HT], URB597) on A549 lung cancer cell metastasis and invasion. LC-MS analyses revealed increased levels of FAAH substrates (AEA, 2-AG, OEA, PEA) in cells incubated with either FAAH inhibitor. In athymic nude mice FAAH inhibitors were shown to elicit a dose-dependent antimetastatic action yielding a 67% and 62% inhibition of metastatic lung nodules following repeated administration of 15 mg/kg AA-5HT and 5 mg/kg URB597, respectively. In vitro, a concentration-dependent anti-invasive action of either FAAH inhibitor was demonstrated, accompanied with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Using siRNA approaches, a causal link between the TIMP-1-upregulating and anti-invasive action of FAAH inhibitors was confirmed. Moreover, knockdown of FAAH by siRNA was shown to confer decreased cancer cell invasiveness and increased TIMP-1 expression. Inhibitor experiments point toward a role of CB2 and transient receptor potential vanilloid 1 in conferring anti-invasive effects of FAAH inhibitors and FAAH siRNA. Finally, antimetastatic and anti-invasive effects were confirmed for all FAAH substrates with AEA and OEA causing a TIMP-1-dependent anti-invasive action. Collectively, the present study provides first-time proof for an antimetastatic action of FAAH inhibitors. As mechanism of its anti-invasive properties an upregulation of TIMP-1 was identified. PMID:26930716

  2. Clinical significance of CD151 overexpression in subtypes of invasive breast cancer.

    Science.gov (United States)

    Kwon, M J; Park, S; Choi, J Y; Oh, E; Kim, Y J; Park, Y-H; Cho, E Y; Kwon, M J; Nam, S J; Im, Y-H; Shin, Y K; Choi, Y-L

    2012-02-28

    CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated. The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (Pbreast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer. CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.

  3. The roles of ARHGAP10 in the proliferation, migration and invasion of lung cancer cells.

    Science.gov (United States)

    Teng, Ji-Ping; Yang, Zhi-Ying; Zhu, Yu-Ming; Ni, Da; Zhu, Zhi-Jun; Li, Xiao-Qiang

    2017-10-01

    Lung cancer is a leading cause of cancer-related mortalities worldwide. In the present study, a comparison of To determine the roles of ARHGAP10 in the proliferation, migration and invasion of lung cancer cells expression levels between normal lung tissues and lung cancer tissues were compared using immunoblotting, and CCK-8 and Transwell assays. Lung cancer tissues had a decreased ARHGAP10 mRNA expression level compared to the adjacent normal tissues. The ectopic expression of ARHGAP10 significantly suppressed the migration, invasion and proliferation of lung cancer cells. Gene set enrichment analysis revealed that metastasis and Wnt signaling pathways were negatively correlated with ARHGAP10 expression. Immunoblotting analysis revealed that ARHGAP10 overexpression inhibited metastasis [matrix metalloproteinase (MMP)-2, MMP-9 and VEGF] and the expression of Wnt pathway-related proteins (β-catenin and c-Myc). Moreover, the stimulation effects of lithium chloride, a GSK3β inhibitor, on the accumulation of β-catenin were notably suppressed by ARHGAP10 overexpression. Collectively, ARHGAP10 acts to suppress tumor within lung cancer by affecting metastasis and Wnt signaling pathways. The results therefore suggest that ARHGAP10 is a potentially attractive target for the treatment of lung cancer.

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

    Science.gov (United States)

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

    2017-02-28

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

  5. Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance

    Directory of Open Access Journals (Sweden)

    Li Yan

    2010-10-01

    Full Text Available Abstract Background Cancer invasion results from constant interactions between cancer cells and their microenvironment. Major components of the cancer microenvironment are stromal cells, infiltrating inflammatory cells, collagens, matrix metalloproteinases (MMP and newly formed blood vessels. This study was to determine the roles of MMP-9, MMP-2, type IV collagen, infiltrating macrophages and tumor microvessels in gastric cancer (GC invasion and their clinico-pathological significance. Methods Paraffin-embedded tissue sections from 37 GC patients were studied by Streptavidin-Peroxidase (SP immunohistochemical technique to determine the levels of MMP-2, MMP-9, type IV collagen, macrophages infiltration and microvessel density (MVD. Different invasion patterns were delineated and their correlation with major clinico-pathological information was explored. Results MMP2 expression was higher in malignant gland compared to normal gland, especially nearby the basement membrane (BM. High densities of macrophages at the interface of cancer nests and stroma were found where BM integrity was destroyed. MMP2 expression was significantly increased in cases with recurrence and distant metastasis (P = 0.047 and 0.048, respectively. Infiltrating macrophages were correlated with serosa invasion (P = 0.011 and TNM stage (P = 0.001. MVD was higher in type IV collagen negative group compared to type IV collagen positive group (P = 0.026. MVD was related to infiltrating macrophages density (P = 0.040. Patients with negative MMP9 expression had better overall survival (OS compared to those with positive MMP9 expression (Median OS 44.0 vs 13.5 mo, P = 0.036. Median OS was significantly longer in type IV collagen positive group than negative group (Median OS 25.5 vs 10.0 mo, P = 0.044. The cumulative OS rate was higher in low macrophages density group than in high macrophages density group (median OS 40.5 vs 13.0 mo, P = 0.056. Median OS was significantly longer in low

  6. 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

  7. SHP2 overexpression enhances the invasion and metastasis of ovarian cancer in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Hu ZQ

    2017-08-01

    Full Text Available ZhongQian Hu,1,* Jia Li,2,* Qi Gao,2,* Shuping Wei,1 Bin Yang1 1Department of Ultrasound, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China; 2Department of Ultrasound, Zhongda Hospital, Southeast University, Nanjing, China *These authors contributed equally to this work Purpose: SHP2 has roles in a variety of signal transduction pathways and in many important cellular processes, including proliferation, differentiation, movement regulation, and apoptosis. In addition, SHP2 expression is closely associated with multiple types of malignancies. In this study, we examined the role of SHP2 in epithelial ovarian cancer.Patients and methods: SHP2 expression in cancer and normal ovarian tissue specimens was evaluated by immunohistochemical staining and Western blot analyses. The correlation between the SHP2 expression level and clinicopathological features was analyzed. The role of SHP2 in epithelial ovarian cancer was evaluated by assessing SHP2 expression patterns in vitro and in vivo, and activation of the PI3K/AKT pathway was examined.Results: SHP2 is expressed at higher levels in ovarian cancer tissues than in normal ovarian tissues and in an ovarian cancer cell line than in a normal ovarian cell line. On the basis of these findings, SHP2 is overexpressed in ovarian cancer both in vitro and in vivo. In addition, SHP2 overexpression is associated with tumor stage and differentiation, enhanced cell proliferation and invasion, and tumorigenesis and metastasis.Conclusion: SHP2 overexpression enhances ovarian tumor proliferation and invasion by activating the PI3K-AKT axis, indicating that SHP2 potentially plays a direct role in the pathogenesis of ovarian epithelial cell cancer. These novel findings provide key insights that are applicable to basic cancer research and to the prevention and treatment of cancer. Keywords: ovarian tumor, SHP2, overexpression, proliferation, invasion, metastasis

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  9. DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.

    Science.gov (United States)

    Toiyama, Yuji; Inoue, Yasuhiro; Yasuda, Hiromi; Saigusa, Susumu; Yokoe, Takeshi; Okugawa, Yoshinaga; Tanaka, Koji; Miki, Chikao; Kusunoki, Masato

    2011-02-01

    We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease. The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer. DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients. DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

  10. HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity.

    Science.gov (United States)

    Zhang, Chen; Xu, Bingfei; Lu, Shi; Zhao, Ying; Liu, Pian

    2017-05-11

    Hematological and neurological expressed 1 (HN1) is upregulated in many tumors, but the role of HN1 in breast cancer progression and its regulatory mechanism have not been well understood. To study the role of HN1 in the initiation and progression of breast cancer, we examined HN1 levels in breast cancer cells and tissues and analyzed the relationship between HN1 levels and patient survival. We used mammosphere formation assay, side population analysis, wound healing assay, transwell assay, soft agar formation assay, and xenografted tumor model to determine the effect of HN1 on the expansion of breast cancer stem cells, and the migration, invasion and tumorigenesis of breast cancer. To determine whether HN1 regulates MYC, we used quantitative real-time PCR and Western blot analysis to assess the expression of MYC and their targeted genes to determine the phenotype caused by knockdown of MYC in breast cancer cell with HN1 overexpression. In this study, we found that HN1 was upregulated in breast cancer tissues. Patients with high levels of HN1 expression had significantly shorter survival than those with low HN1 expression. In breast cancer cell line, ectopic overexpression of HN1 not only promoted the expansion of breast cancer stem cells, but also promoted cell migration, invasion, and tumorigenesis, while knockdown of HN1 reduced these effects. Furthermore, there was a positive correlation between MYC (also known as c-MYC) level and HN1 level, mechanism analysis suggested HN1 promoted the expression of MYC and its targeted genes like CDK4, CCND1, p21, CAV1, and SFRP1. Downregulation of MYC abrogated the effect of HN1 overexpression in breast cancer cell lines. Taken together, these data reveal that HN1 promotes the progression of breast cancer by upregulating MYC expression, and might be a therapeutic target for breast cancer.

  11. Minimum (minimal) invasive techniques in early colorectal cancer treatment

    International Nuclear Information System (INIS)

    Slezak, V.

    2007-01-01

    Minimally invasive non-operating techniques for treatment of early tumors of colon present a convenient approach for the patient. At most times they can be performed on outpatient basis or with minimal hospital stay. They are non-demanding procedures for the patient and can be used even in patients with high surgical risk. These techniques include classical polypectomy and endoscopic mucosal resection. Other methods used include argon plasma coagulation and laser therapy, if available. These techniques are indicated in findings limited to muscularis mucosa. Risk of complication during and after procedure is low. Endoscopic ultrasound is recommended prior procedure in large size or high-risk polyps. (author)

  12. The Runx transcriptional co-activator, CBFβ, is essential for invasion of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lopez-Camacho Cesar

    2010-06-01

    Full Text Available Abstract Background The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFβ is a transcriptional co-activator that is recruited to promoters by Runx transcription factors and there is considerable evidence that CBFβ is essential for the function of Runx factors. However, overexpression of Runx1 can partially rescue the lethal phenotype in CBFβ-deficient mice, indicating that increased levels of Runx factors can, in some situations, overcome the requirement for CBFβ. Since Runx2 is overexpressed in metastatic breast cancer cells, and there are no reports of CBFβ expression in breast cells, we sought to determine whether Runx2 function in these cells was dependent on CBFβ. Such an interaction might represent a viable target for therapeutic intervention to inhibit bone metastasis. Results We show that CBFβ is expressed in the metastatic breast cancer cells, MDA-MB-231, and that it associates with Runx2. Matrigel invasion assays and RNA interference were used to demonstrate that CBFβ contributes to the invasive capacity of these cells. Subsequent analysis of Runx2 target genes in MDA-MB-231 cells revealed that CBFβ is essential for the expression of Osteopontin, Matrixmetalloproteinase-13, Matrixmetalloproteinase-9, and Osteocalcin but not for Galectin-3. Chromatin immunoprecipitation analysis showed that CBFβ is recruited to both the Osteopontin and the Galectin-3 promoters. Conclusions CBFβ is expressed in metastatic breast cancer cells and is essential for cell invasion. CBFβ is required for expression of several Runx2-target genes known to be involved in cell invasion. However, whilst CBFβ is essential for invasion, not all Runx2-target genes require CBFβ. We conclude that CBFβ is required for a subset of Runx2-target genes

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

    Science.gov (United States)

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

    2017-01-01

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

  14. TNF-α promotes colon cancer cell migration and invasion by upregulating TROP-2.

    Science.gov (United States)

    Zhao, Peng; Zhang, Zhongtao

    2018-03-01

    High levels of tumor-associated calcium signal transduction protein (TROP)-2 have been demonstrated to be strongly associated with tumor necrosis factor (TNF)-α levels in colon cancer. In the present study, the effect of TNF-α on the regulation of TROP-2 expression and its effect in colon cancer cell migration and invasion were investigated in vitro . TROP-2 protein levels were evaluated in HCT-116 human colon cancer cells cultured with various concentrations of TNF-α using western blot analysis. Changes in the migratory and invasive potential of the cells were evaluated using a wound healing and transwell assay, respectively. Then, TROP-2 expression was downregulated in cells by use of siRNA, and TROP-2 knockdown was confirmed at the mRNA and protein level by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The migration and invasion potential of cells transfected with TROP-2 siRNA was also evaluated. Levels of several mitogen-activated protein kinase proteins, namely p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), were detected in cells treated with TNF-α using western blot analysis. The results demonstrated that TROP-2 protein levels increased in cells treated with lower concentrations of TNF-α, but decreased in cells treated with higher concentrations of TNF-α, compared with untreated control. Maximum TROP-2 levels were observed in cells treated with 20 µg/l TNF-α. Migration and invasion were enhanced in cells treated with 20 µg/l TNF-α. When TROP-2 was silenced in colon cancer cells by siRNA, migration and invasion were significantly decreased compared with control cells. TNF-α stimulation activated the ERK1/2 pathway, but did not significantly affect p38 and JNK phosphorylation levels. Treatment with a specific ERK1/2 inhibitor suppressed the TNF-α-induced upregulation of TROP-2 and the TNF-α-induced colon cancer cell migration and invasion. In conclusion, the

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

    Directory of Open Access Journals (Sweden)

    Shiaw-Wei Tyan

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

  16. Studies on MRI diagnostic accuracy of invasion to body muscular layer and cervix of endometrial cancer

    International Nuclear Information System (INIS)

    Takemoto, Yumi; Fujiyoshi, Keizou; Takemoto, Shuji; Kawano, Kouichirou; Ohta, Shunichirou; Murakami, Fumihiro; Komai, Kan; Ushijima, Kimio; Kamura, Toshiharu

    2008-01-01

    This study was conducted to know usefulness of preoperative MRI to detect invasions of endometrial cancer to uterine body muscular layer and cervix. Subjects were 132 patients (median age of 57 y, pre- and post-menopause, 11.2 and 78.8%, respectively) with the cancer at stage I (66 cases) and >II in authors' facility, who had undergone the preoperative MRI with 1.5T Siemens machine by imaging with T1 and T2 weighted, Gd-enhanced T1 weighted, dynamic study and STIR. Imaging findings were compared with histopathological ones to assess the accuracy of imaging diagnosis. Positive predictive accuracy for muscular invasion was found to be as high as 95.5% and negative one, as low as 29.5%: especially, in pre-menopause group, tendency of underestimation for the invasion was thought notable. In contrast, negative accuracy was found low for cervical invasion and positive one, high: overestimation was possibly occurring. Thus, MRI diagnosis of those invasions should be seriously judged with careful consideration of menopause state. (R.T.)

  17. Ki-67 marker useful for classification of malignant invasive ductal breast cancer

    Directory of Open Access Journals (Sweden)

    Irmawati Hassan

    2013-12-01

    Full Text Available BACKGROUND Breast cancer is an important health problem in the world. Uncontrolled cell proliferation represents a malignant characteristic of neoplasia such as breast cancer, and can be examined immunohistochemically by measuring the Ki-67 proliferative marker. The objective of this study was to determine the role of Ki-67 for classification of the degree of malignancy in women with invasive ductal breast cancer. METHODS A cross-sectional study was conducted on 20 women with invasive ductal breast cancer. The samples were immuno-histochemically tested for Ki-67 using anti-Ki-67 primary antibody. The Ki-67 proliferative index was determined by enumerating the proportion of Ki-67 positive nuclei among the total number of cells in ten areas observed at 400x magnification, using a 20% cut-off value to distinguish between low and high proliferative indices. Statistical analysis was by means of the chi-square test. RESULTS Seventy five persent of the high grade malignancies had a high Ki-67 proliferative index (>20%, while only 12.5% of the low grade malignancies had a high Ki-67 index (>20%. The difference in grade malignancy was statistically significant (p=0.022, whereas tumor size was not associated with a statistically significant difference in Ki-67 index (p=0.648. CONCLUSION The study showed that invasive ductal breast cancer with high Ki-67 index was significantly associated with high grade of malignacy. The high Ki-67 marker index can be used for classification of the grade of malignancy of invasive ductal breast cancer.

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

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

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

  19. Curcumin inhibition of integrin (alpha6beta4)-dependent breast cancer cell motility and invasion.

    Science.gov (United States)

    Kim, Hong Im; Huang, Huang; Cheepala, Satish; Huang, Shile; Chung, Jun

    2008-10-01

    Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. However, the mechanism by which curcumin inhibits cancer cell functions such as cell growth, survival, and cell motility is largely unknown. We explored whether curcumin affects the function of integrin alpha(6)beta(4), a laminin adhesion receptor with an established role in invasion and migration of cancer cells. Here we show that curcumin significantly reduced alpha(6)beta(4)-dependent breast cancer cell motility and invasion in a concentration-dependent manner without affecting apoptosis in MDA-MB-435/beta4 (beta(4)-integrin transfectants) and MDA-MB-231 breast cancer cell lines. Further, curcumin selectively reduced the basal phosphorylation of beta(4) integrin (Y1494), which has been reported to be essential in mediating alpha(6)beta(4)-dependent phosphatidylinositol 3-kinase activation and cell motility. Consistent with this finding, curcumin also blocked alpha(6)beta(4)-dependent Akt activation and expression of the cell motility-promoting factor ENPP2 in MDA-MB-435/beta4 cell line. A multimodality approach using curcumin in combination with other pharmacologic inhibitors of alpha(6)beta(4) signaling pathways showed an additive effect to block breast cancer cell motility and invasion. Taken together, these findings show that curcumin inhibits breast cancer cell motility and invasion by directly inhibiting the function of alpha(6)beta(4) integrin, and suggest that curcumin can serve as an effective therapeutic agent in tumors that overexpress alpha(6)beta(4).

  20. Stromal proteome expression profile and muscle-invasive bladder cancer research

    Directory of Open Access Journals (Sweden)

    Niu Haitao

    2012-08-01

    Full Text Available Abstract Background To globally characterize the cancer stroma expression profile of muscle-invasive transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stroma. Laser capture micro dissection was used to harvest purified muscle-invasive bladder cancer stromal cells and normal urothelial stromal cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature. Results We identified 868/872 commonly expressed proteins and 978 differential proteins from 4 paired cancer and normal stromal samples using laser capture micro dissection coupled with two-dimensional liquid chromatography tandem mass spectrometry. 487/491 proteins uniquely expressed in cancer/normal stroma. Differential proteins were compared with the entire list of the international protein index (IPI, and there were 42/42 gene ontology (GO terms exhibited as enriched and 8/5 exhibited as depleted in cellular Component, respectively. Significantly altered pathways between cancer/normal stroma mainly include metabolic pathways, ribosome, focal adhesion, etc. Finally, descriptive statistics show that the stromal proteins with extremes of PI and MW have the same probability to be a biomarker. Conclusions Based on our results, stromal cells are essential component of the cancer, biomarker discovery and network based multi target therapy should consider neoplastic cells itself and corresponding stroma as whole one.

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

    Directory of Open Access Journals (Sweden)

    Brenda Y Hernandez

    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.

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

    Science.gov (United States)

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

    2014-11-01

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

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

    International Nuclear Information System (INIS)

    Cho, Nancy L.; Lin, Chi-Iou; Du, Jinyan; Whang, Edward E.; Ito, Hiromichi; Moore, Francis D.; Ruan, Daniel T.

    2012-01-01

    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

  4. Cancer chemoresistance; biochemical and molecular aspects: a brief overview.

    Science.gov (United States)

    Kachalaki, Saeed; Ebrahimi, Mina; Mohamed Khosroshahi, Leila; Mohammadinejad, Sina; Baradaran, Behzad

    2016-06-30

    The effectiveness of chemotherapy is one of the main challenges in cancer treatment and resistance to classic drugs and traditional treatment processes is an obstacle to this goal. Drug resistance that may be inherent or adventitious can cause poor treatment outcome and tumor relapse. In most cases, resistance to a drug can lead to resistance to many other drugs structure and function of which is not necessarily similar to the first drug. This phenomenon is the main mechanism behind failure of many of metastatic cancers. There are various molecular mechanisms involved in multidrug resistance, including change in the activity of membrane transporters (such as ABC transporters), increase of drug metabolism, change of the target enzyme (such as mutations that change thymidylate synthase and topoisomerases), promotion of DNA damage repair, and escape from drug induced apoptosis. Clinical and laboratory investigations on biomarkers involved in the response to chemotherapy have characterized the key factors behind the failure of treatments. Knowing the molecular factors involved in drug resistance may help us to develop new strategies for more promising chemotherapy and reduce the rate of relapse. In this brief review, molecular mechanisms and tumor microenvironment leading to decreased drug sensitivity, and strategies of reversing drug resistance are described. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Management of lung cancer brain metastasis: An overview

    Directory of Open Access Journals (Sweden)

    Himanshu Srivastava

    2017-01-01

    Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

  6. Dietary Cadmium and Risk of Invasive Postmenopausal Breast Cancer in the VITAL Cohort

    Science.gov (United States)

    Adams, Scott V.; Newcomb, Polly A.; White, Emily

    2012-01-01

    Purpose Estimate the association between dietary intake of cadmium, a carcinogenic heavy metal, and risk of invasive breast cancer. Methods Study subjects were 30,543 postmenopausal women in the VITamins And Lifestyle (VITAL) cohort who completed a food frequency questionnaire (FFQ) at baseline (2000–2002). Dietary cadmium consumption was estimated by combining FFQ responses with US Food and Drug Administration data on food cadmium content. Incidence of invasive breast cancer was ascertained through linkage of the cohort to the western Washington Surveillance, Epidemiology, and End Results cancer registry through December 31, 2009. Cox regression was applied to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for breast cancer with increasing dietary cadmium intake, adjusted for total energy intake, smoking history, consumption of vegetables, potatoes, and whole grains, multivitamin use, education, race, body mass index, physical activity, age at first birth, postmenopausal hormone use, and mammography. Results Vegetables and grains together contributed an average of 66% of estimated dietary cadmium. During a mean of 7.5 years of follow-up, 1,026 invasive postmenopausal breast cancers were identified. Among 899 cases with complete covariate information, no evidence of an association between dietary cadmium intake and breast cancer risk was observed (aHR (95% CI), highest to lowest quartile cadmium: 1.00 (0.72–1.41), Ptrend=0.95). No evidence was found for interactions between dietary cadmium and breast cancer risk factors, smoking habits, or total intake of calcium, iron, or zinc from diet, supplements, and multivitamins. Conclusions This study does not support the hypothesis that dietary cadmium intake is a risk factor for breast cancer. However, non-differential measurement error in the estimate of cadmium intake is likely the most important factor that could have obscured an association. PMID:22527162

  7. A Systematic Overview of Radiation Therapy Effects in Prostate Cancer

    International Nuclear Information System (INIS)

    Nilsson, Sten; Norlen, Bo Johan; Widmark, Anders

    2004-01-01

    A systematic review of radiation therapy trials in prostate cancer has been performed according to principles adopted by the Swedish Council of Technology Assessment in Health Care (SBU). This synthesis of the literature is based on data from one meta-analysis, 30 randomized trials, many dealing with hormonal therapy, 55 prospective trials, and 210 retrospective studies. Totally the studies included 152,614 patients. There is a lack of properly controlled clinical trials in most important aspects of radiation therapy in prostate cancer. The conclusions reached can be summarized as follows: There are no randomized studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer. However, with the advent of widely accepted prognostic markers for prostate cancer (pre-treatment PSA, Gleason score, and T-stage), such comparisons have been made possible. There is substantial documentation from large single-institutional and multi-institutional series on patients with this disease category (PSA T2) disease, i.e. patients normally not suited for surgery, benefit from higher than conventional total dose. No overall survival benefit has yet been shown. Dose escalation to patients with intermediate-risk or high-risk disease can be performed with 3D conformal radiotherapy (photon or proton) boost, with Ir-192 high dose rate brachytherapy boost, or brachytherapy boost with permanent seed implantation. Despite an increased risk of urinary tract and/or rectal side effects, dose-escalated therapy can generally be safely delivered with all three techniques. There is some evidence that 3D conformal radiotherapy results in reduced late rectal toxicity and acute anal toxicity compared with radiotherapy administered with non-conformal treatment volumes. There is some evidence that postoperative external beam radiotherapy after radical prostatectomy in patients with

  8. Low doses ionizing radiation enhances the invasiveness of breast cancer cells by inducing epithelial-mesenchymal transition

    International Nuclear Information System (INIS)

    Zhang, Xin; Li, Xiaoyan; Zhang, Ning; Yang, Qifeng; Moran, Meena S.

    2011-01-01

    Highlights: → Low doses ionizing irradiation would enhance the invasiveness of breast cancer cells by inducing EMT. → Low doses ionizing radiation induced morphologic changes in breast cancer cells. → Low doses ionizing radiation led to upregulation of mesenchymal markers and down-regulation of epithelial markers. → Low doses ionizing radiation increased migration and invasion of breast cancer cells. -- Abstract: Epithelial-mesenchymal transition (EMT) is a process cellular morphologic and molecular alterations facilitate cell invasion. We hypothesized that low dose ionizing irradiation (LDIR) enhances the invasiveness of breast cancer cells by inducing EMT. The effects of LDIR on cellular morphology and the EMT markers of MCF-7 breast cancer cells were analyzed by western blot/RT-PCR and migration/invasion was examined using the transwell assay. We found that LDIR led to the phenotypic changes of EMT in MCF-7 cells and down-regulation of epithelial differentiation markers and transcriptional induction of mesenchymal markers. Furthermore, the radiated cells demonstrated enhanced migration/invasion MCF-7 cells compared with non-radiated cells. In summary, LDIR promotes the invasiveness of breast cancer cells through epithelial to mesenchymal transition. These findings may ultimately provide a new targeted approach for improving the therapeutic effectiveness of radiation in breast cancer.

  9. Toll Like Receptor-9 Mediated Invasion in Breast Cancer

    Science.gov (United States)

    2012-07-01

    Ilvesaro D. Chen C. Pressey K. W. Harris K. S. Selander (&) Department of Medicine, Division of Hematology -Oncology, University of Alabama at...Oncology, Cancer Center of Eastern Finland, Kuopio University Hospital, Kuopio, Finland Y. Soini Department of Pathology and Forensic Medicine

  10. A preclinical mouse model of invasive lobular breast cancer metastasis

    NARCIS (Netherlands)

    Doornebal, Chris W.; Klarenbeek, Sjoerd; Braumuller, Tanya M.; Klijn, Christiaan N.; Ciampricotti, Metamia; Hau, Cheei-Sing; Hollmann, Markus W.; Jonkers, Jos; de Visser, Karin E.

    2013-01-01

    Metastatic disease accounts for more than 90% of cancer-related deaths, but the development of effective antimetastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here, we report the development of a mouse model of spontaneous

  11. Multivitamin supplement use and risk of invasive breast cancer

    NARCIS (Netherlands)

    Meulepas, J.M.; Newcomb, P.A.; Burnett-Hartman, A.N.; Hampton, J.M.; Trentham-Dietz, A.

    2010-01-01

    Objective: Multivitamin supplements are used by nearly half of middle-aged women in the USA. Despite this high prevalence of multivitamin use, little is known about the effects of multivitamins on health outcomes, including cancer risk. Our main objective was to determine the association between

  12. Adaptive radiotherapy for invasive bladder cancer: a feasibility study

    NARCIS (Netherlands)

    Pos, Floris J.; Hulshof, Maarten; Lebesque, Joos; Lotz, Heidi; van Tienhoven, Geertjan; Moonen, Luc; Remeijer, Peter

    2006-01-01

    To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation. Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV(CONV)). During the first treatment week, five daily

  13. Lactoferrin- Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple Negative Breast Cancer Phenotypes

    Science.gov (United States)

    Ha, Ngoc-Han; Nair, Vasudha; Reddy, Divijendra Natha Sirigiri; Mudvari, Prakriti; Ohshiro, Kazufumi; Ghanta, Krishna Sumanth; Pakala, Suresh B.; Li, Da-Qiang; Costa, Luis; Lipton, Allan; Badwe, Rajendra A.; Fuqua, Suzanne; Wallon, Margaretha; Prendergast, George C.; Kumar, Rakesh

    2013-01-01

    Triple-negative breast cancer (TNBC) is characterized by the lack of expression of ERα, PR and HER-2 receptors and the pathway(s) responsible for this downregulation and thus aggressiveness, remains unknown. Here we discovered that lactoferrin (Lf) efficiently downregulates the levels of ERα, PR and HER-2 receptors in a proteasome-dependent manner in breast cancer cells, and accounts for the loss of responsiveness to ER- or HER-2- targeted therapies. Further we found that Lf increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that Lf directly stimulates the transcription of endothelin-1 (ET-1), a secreted pro-invasive polypeptide that acts through a specific receptor ET(A)R, leading to secretion of bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor antagonist drug completely blocked Lf-dependent motility and invasiveness of breast cancer cells. Physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue Lf and ET-1 levels in TNBC patients as compared to those in ER+ cases. These findings describe the first physiologically relevant polypeptide as a functional determinant of downregulating all three therapeutic receptors in breast cancer which utilizes another secreted ET-1 system to confer invasiveness. Results presented here provide proof-of-principle evidence in support of therapeutic effectiveness of ET-1 receptor antagonist to completely block the Lf-induced motility and invasiveness of the TNBC as well as non-TBNC cells, and thus, opening a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug. PMID:22006997

  14. 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...... basement membrane. However, when injected into nude mice, both control and NCAM-expressing cell lines produced equally invasive tumors. Tumors generated from NCAM-transfected cells were heterogeneous, containing NCAM-positive as well as NCAM-negative areas, indicating the existence of host factors capable...

  15. Cancer prevention and detection centers: an overview and critique.

    Science.gov (United States)

    Humphrey, L J; Lester, P

    1989-01-01

    Cancer screening is ideally carried out in free standing centers that are located near shopping centers, are quite visible, and have a warm, friendly appearance. This chapter describes the basic elements of such a center, including the use of a mobile mammogram van based at the center. While the precise size, location, and design of a center will vary depending on the specific demographics of an area, these data should facilitate such planning. Programs that can be carried out in this center are described utilizing information from preceding chapters. This chapter enlarges upon their application and then outlines criteria and services. Furthermore, a large section on general or whole-body screening is included. As in other programs, those at risk and the benefits are discussed. While not a high volume, income producer, this program is a requisite component offering great service to the customer.

  16. The pattern of invasive lobular carcinoma in the patients diagnosed with breast cancer from Balochistan.

    Science.gov (United States)

    Baloch, A H; Khosa, A N; Bangulzai, N; Sadia, H; Ahmed, M; Khan, F; Jan, M; Tareen, M; Kakar, M H; Shuja, J; Naseeb, H K; Ahmad, J

    2016-01-01

    Invasive lobular carcinoma (ILC) is the second most common type of breast cancer accounting for 5%-15% of all the breast cancer cases. The present study was performed on 171 breast cancer patients from Balochistan registered in CENAR (Center for Nuclear Medicine and Radiotherapy), Quetta. Written consent was obtained from the patients. The history of the disease was taken from the patients, and the patients' enrollment files were retrieved. Of the 171 patients, 5 (2.96%) were diagnosed with ILC with tumor Grade II, and stage of the cancer reported was Grade III in all the 5 patients affected with ILC. ILC is the second most common type of breast cancer diagnosed with comparatively lower grade but almost reported infiltrating.

  17. MINIMALLY-INVASIVE SURGERY FOR COLLORECTAL CANCER IN ELDERLY PATIENTS

    Directory of Open Access Journals (Sweden)

    I. L. Chernikovskiy

    2016-01-01

    Full Text Available Introduction. The patient’s age is one of the major risk factors of death from colorectal cancer. The role of laparo- scopic radical surgeries in the treatment of colorectal cancer in elderly patients is being studied. The purpose of the study was to evaluate the experience of surgical treatment for elderly patients with colorectal cancer. material and methods. The treatment outcomes of 106 colorectal cancer patients aged 75 years or over, who underwent surgery between 2013 and 2015 were presented. Out of them, 66 patients underwent laparatomy and 40 patients underwent laparoscopy. Patients were matched for ASA and CR-PОSSUM scales, age-and body mass index, dis- ease stage and type of surgery. Results. The mean duration of surgery was significantly less for laparoscopy than for laparotomy (127 min versus 146 min. Intraoperative blood loss was higher in patients treated by laparotomy than by laparoscopy (167 ml versus 109 ml, but the differences were insignificant (р=0.36. No differences in lymphodissection quality and adequate resection volume between the groups were found. The average hospital stay was not significantly shorter in the laparoscopic group (р=0.43. Complications occurred with equal frequency in both groups (13.6 % compared to 15.0 %. The median follow-up time was 16 months (range, 6-30 months. The number of patients died during a long-term follow-up was 2 times higher after laparotomic surgery than after laparoscopic surgery, however, the difference was not statistically significant. Conclusion. Postoperative compli- cations in elderly patients with colorectal cancer did not exceed the average rates and did not depend on the age. Both groups were matched for the intraoperative bleeding volume and quality of lymphodenectomy. Significantly shorter duration of laparoscopic surgery was explained by the faster surgical access however, it showed no benefit in reducing the average length of hospital stay and decreasing the number of

  18. 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

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

    Science.gov (United States)

    Zhang, Lian; Kim, Sungkyoung; Ding, Wenping; Tong, Yingying; Zhang, Xiuli; Pan, Minggui; Chen, Siyu

    2015-01-01

    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. 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. 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 invasion in the xenograft tumor model. We found that As4S4 upregulated the expression of E-cadherin and downregulated the expression of β-catenin, Sp1, VEGF, and CD34 in mouse tumor tissues, consistent with the results in vitro. As4S4 inhibited the migration and invasion of gastric cancer cells by blocking tumor cell adhesion, decreasing the ability of tumor cells to destroy the basement

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Peng, E-mail: chaiyisheng0508@sina.com [Department of General Surgery, The People' s Hospital of Bozhou, Bozhou 236800 (China); Tian, Jingzhong [Department of General Surgery, The People' s Hospital of Bozhou, Bozhou 236800 (China); Zhao, Deyin [Dept of General Surgery, The Hospital of Suzhou, Suzhou 234000 (China); Zhang, Hongyan; Cui, Jian [Department of General Surgery, The People' s Hospital of Bozhou, Bozhou 236800 (China); Ding, Keshuo [Department of Pathology, Anhui Medical University, Hefei 230022 (China); Liu, Bin, E-mail: 13399519008@163.com [Dept of Vascular Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China)

    2016-02-26

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

    Blaha, Laura

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

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2014-12-01

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

  7. 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.

  8. Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Sim, Y.T.; Vinnicombe, S.; Whelehan, P.; Thomson, K.; Evans, A.

    2015-01-01

    Aim: To investigate the contribution of shear-wave elastography (SWE) in diagnosing invasive lobular breast cancer (ILC) in symptomatic patients. Materials and methods: A retrospective case-controlled study of 52 patients with ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour size, was performed. Breast density and mammographic and greyscale ultrasound features were graded using Breast Imaging-Reporting and Data System (BI-RADS) classification by two radiologists, blinded to SWE and pathology findings. Forty-four benign lesions were also included. The sensitivity of SWE was assessed, using a cut-off value of 50 kPa for mean elasticity. Statistical significance was evaluated using Chi-square and Chi-square for trend tests. Results: Mean age for both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37 mm. The sensitivity for detection of ILC and IDC for mammography, greyscale ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%, respectively. SWE had significantly higher sensitivities than mammography for the detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was not significantly more sensitive than greyscale ultrasound for the detection of either tumour type. Four (8%) lobular cancers were benign/normal at both mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain in sensitivity by using SWE in ILC was statistically significant compared to IDC (p = 0.01). Conclusion: SWE can diagnose lobular cancers that have benign/normal findings on conventional imaging as suspicious. - Highlights: • Sensitivity of shear-wave elastography (SWE) for detecting lobular cancers is 94%. • Sensitivity of SWE for detecting invasive ductal cancers is 100%. • SWE is more sensitive than mammography for detecting ductal and lobular cancers. • SWE can diagnose ILC as suspicious, which are benign/normal on conventional imaging

  9. 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.

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

    International Nuclear Information System (INIS)

    Zhan, Yu; Abi Saab, Widian F.; Modi, Nidhi; Stewart, Amanda M.; Liu, Jinsong; Chadee, Deborah N.

    2012-01-01

    Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates MAPK signaling pathways and regulates cellular responses such as proliferation, migration and apoptosis. Here we report high levels of total and phospho-MLK3 in ovarian cancer cell lines in comparison to immortalized nontumorigenic ovarian epithelial cell lines. Using small interfering RNA (siRNA)-mediated gene silencing, we determined that MLK3 is required for the invasion of SKOV3 and HEY1B ovarian cancer cells. Furthermore, mlk3 silencing substantially reduced matrix metalloproteinase (MMP)-1, -2, -9 and -12 gene expression and MMP-2 and -9 activities in SKOV3 and HEY1B ovarian cancer cells. MMP-1, -2, -9 and-12 expression, and MLK3-induced activation of MMP-2 and MMP-9 requires both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activities. In addition, inhibition of activator protein-1 (AP-1) reduced MMP-1, MMP-9 and MMP-12 gene expression. Collectively, these findings establish MLK3 as an important regulator of MMP expression and invasion in ovarian cancer cells. -- Highlights: ► Ovarian cancer cell lines have high levels of total and phosphorylated MLK3. ► MLK3 is required for MMP expression and activity in ovarian cancer cells. ► MLK3 is required for invasion of SKOV3 and HEY1B ovarian cancer cells. ► MLK3-dependent regulation of MMP-2 and MMP-9 activities requires ERK and JNK.

  11. Spinal Anesthesia is Associated with Lower Recurrence Rates after Resection of Nonmuscle Invasive Bladder Cancer.

    Science.gov (United States)

    Koumpan, Yuri; Jaeger, Melanie; Mizubuti, Glenio Bitencourt; Tanzola, Rob; Jain, Kunal; Hosier, Gregory; Hopman, Wilma; Siemens, D Robert

    2017-11-14

    We sought to determine whether anesthetic type (general vs spinal) would influence cancer recurrence following transurethral resection of bladder tumors. With institutional ethics board approval we examined the electronic medical records of all patients who underwent transurethral bladder tumor resection for nonmuscle invasive urothelial bladder cancer between 2011 and 2013 at a single tertiary care center. Followup information was gathered on all patients in December 2016. The time to first cancer recurrence and the incidence of cancer recurrence were the main outcome measures. A total of 231 patients underwent 1 or more transurethral bladder tumor resections between 2011 and 2013. Of the 231 patients 135 received spinal anesthesia and 96 received general anesthesia. On univariable analysis the 135 patients who received spinal anesthesia had a longer median time to recurrence than the 96 who received general anesthesia (42.1 vs 17.2 months, p = 0.014). As anticipated, adjuvant therapies and risk category were associated with recurrence rates (p = 0.003 and 0.042, respectively). On multivariable analyses incorporating a priori variables of nonmuscle invasive bladder cancer risk stratification and postoperative therapies the patients who received general anesthesia had a higher incidence of recurrence (OR 2.06, 95% CI 1.14-3.74, p = 0.017) and an earlier time to recurrence (HR 1.57, 95% CI 1.13-2.19, p = 0.008) than those who received spinal anesthesia. Anesthetic type was not associated with cancer progression or overall mortality. Patients who received spinal anesthesia had a lower incidence of recurrence and a delayed time to recurrence following transurethral bladder tumor resection for nonmuscle invasive bladder cancer. These findings should prompt large-scale prospective studies to confirm this association. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  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.

    2016-01-01

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

    KAUST Repository

    Tochhawng, Lalchhandami

    2016-07-07

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

  15. In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

    DEFF Research Database (Denmark)

    Damstrup, L; Rude Voldborg, B; Spang-Thomsen, M

    1998-01-01

    receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot...... analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16......-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition...

  16. A novel minimally invasive dual-modality fiber optic probe for prostate cancer detection

    Science.gov (United States)

    Sharma, Vikrant

    Prostate cancer is the most common form of cancer in males, and is the second leading cause of cancer related deaths in United States. In prostate cancer diagnostics and therapy, there is a critical need for a minimally invasive tool for in vivo evaluation of prostate tissue. Such a tool finds its niche in improving TRUS (trans-rectal ultrasound) guided biopsy procedure, surgical margin assessment during radical prostatectomy, and active surveillance of patients with a certain risk levels. This work is focused on development of a fiber-based dual-modality optical device (dMOD), to differentiate prostate cancer from benign tissue, in vivo. dMOD utilizes two independent optical techniques, LRS (light reflectance spectroscopy) and AFLS (auto-fluorescence lifetime spectroscopy). LRS quantifies scattering coefficient of the tissue, as well as concentrations of major tissue chromophores like hemoglobin derivatives, β-carotene and melanin. AFLS was designed to target lifetime signatures of multiple endogenous fluorophores like flavins, porphyrins and lipo-pigments. Each of these methods was independently developed, and the two modalities were integrated using a thin (1-mm outer diameter) fiber-optic probe. Resulting dMOD probe was implemented and evaluated on animal models of prostate cancer, as well as on human prostate tissue. Application of dMOD to human breast cancer (invasive ductal carcinoma) identification was also evaluated. The results obtained reveal that both LRS and AFLS are excellent techniques to discriminate prostate cancer tissue from surrounding benign tissue in animal models. Each technique independently is capable of providing near absolute (100%) accuracy for cancer detection, indicating that either of them could be used independently without the need of implementing them together. Also, in case of human breast cancer, LRS and AFLS provided comparable accuracies to dMOD, LRS accuracy (96%) being the highest for the studied population. However, the

  17. 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

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

    Science.gov (United States)

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

    2018-04-01

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

  19. Occult invasive cervical cancer after simple hysterectomy: a multi-center retrospective study of 89 cases

    International Nuclear Information System (INIS)

    Bai, Huimin; Cao, Dongyan; Yuan, Fang; Wang, Huilan; Chen, Jie; Wang, Yue; Shen, Keng; Zhang, Zhenyu

    2016-01-01

    Occult invasive cervical cancer (OICC) is sometimes incidentally found in surgical specimens after a simple hysterectomy (SH). This study was aimed at identifying a subset of patients with OICC who have a favorable prognosis. This patient group may not require adjuvant radiotherapy and other procedures. The medical records of women in whom OICC was detected after an inadvertent SH were retrospectively reviewed. The relevant data, including clinicopathological characteristics, treatment and clinical outcome were evaluated. The primary and secondary endpoints were overall survival (OS) and relapse-free survival (RFS), respectively. Eighty-nine patients who met the inclusion criteria were included for analysis, and the risk of OICC was found to be 1.9 %. Finding an invasive cancer in a hysterectomy specimen after a conization procedure that shows positive margins was the most common reason (41.6 %) for the performance of inadvertent SH. In the univariate analysis, a tumor width > 20 mm, deep stromal invasion, and lymph node metastasis (LNM) were adversely associated with relapse (P < 0.001, < 0.001, and = 0.001, respectively) and survival (P = 0.003, 0.004, and 0.027, respectively), although these parameters were not independently associated with patient prognoses in the multivariate analysis. In patients with a tumor width ≤ 20 mm and superficial stromal invasion in the observation subgroup, the 5-year RFS and 5-year OS were both 100 %, whereas they were 57.1 % and 66.7 %, respectively, in patients with a tumor size > 20 mm and deep stromal invasion in the radiotherapy or chemotherapy subgroup (P < 0.001, and = 0.008, respectively). Simple observation after a lymphadenectomy procedure may be feasible in OICC patients with a tumor width ≤ 20 mm, superficial stromal invasion, a negative section margin in hysterectomy specimens, and no LNM

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

    Directory of Open Access Journals (Sweden)

    Bjelović Miloš

    2015-01-01

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

  1. Complementary and Alternative Medicine for Cancer Pain: An Overview of Systematic Reviews

    Directory of Open Access Journals (Sweden)

    Yanju Bao

    2014-01-01

    Full Text Available Background and Objective. Now with more and more published systematic reviews of Complementary and Alternative Medicine (CAM on adult cancer pain, it is necessary to use the methods of overview of systematic review to summarize available evidence, appraise the evidence level, and give suggestions to future research and practice. Methods. A comprehensive search (the Cochrane Library, PubMed, Embase, and ISI Web of Knowledge was conducted to identify all systematic reviews or meta-analyses of CAM on adult cancer pain. And the evidence levels were evaluated using GRADE approach. Results. 27 systematic reviews were included. Based on available evidence, we could find that psychoeducational interventions, music interventions, acupuncture plus drug therapy, Chinese herbal medicine plus cancer therapy, compound kushen injection, reflexology, lycopene, TENS, qigong, cupping, cannabis, Reiki, homeopathy (Traumeel, and creative arts therapies might have beneficial effects on adult cancer pain. No benefits were found for acupuncture (versus drug therapy or shame acupuncture, and the results were inconsistent for massage therapy, transcutaneous electric nerve stimulation (TENS, and Viscum album L plus cancer treatment. However, the evidence levels for these interventions were low or moderate due to high risk of bias and/or small sample size of primary studies. Conclusion. CAM may be beneficial for alleviating cancer pain, but the evidence levels were found to be low or moderate. Future large and rigor randomized controlled studies are needed to confirm the benefits of CAM on adult cancer pain.

  2. Adaptive radiotherapy for invasive bladder cancer: A feasibility study

    International Nuclear Information System (INIS)

    Pos, Floris J.; Hulshof, Maarten; Lebesque, Joos; Lotz, Heidi; Tienhoven, Geertjan van; Moonen, Luc; Remeijer, Peter

    2006-01-01

    Purpose: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation. Methods and Materials: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV CONV ). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV ART ). The GTV ART was expanded with a 1 cm margin for the construction of a PTV ART . Starting in the third week, patients were treated to PTV ART . Repeat CT scans were used to evaluate treatment accuracy. Results: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV ART . On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV ART with PTV CONV (p < 0.0001). Conclusion: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes

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

    Science.gov (United States)

    Harris, Michael J

    2003-09-01

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

  4. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines

    DEFF Research Database (Denmark)

    Viticchiè, Giuditta; Lena, Anna Maria; Latina, Alessia

    2011-01-01

    transition and invasion of healthy tissues (usually bones). MicroRNA-203 (miR-203) is a tumor suppressor microRNA often silenced in different malignancies. Here, we show that miR-203 is downregulated in clinical primary prostatic tumors compared to normal prostate tissue, and in metastatic prostate cancer...... cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2......, LASP1, BIRC5, WASF1, ASAP1 and RUNX2 as new miR-203 direct target mRNAs involved in these events. Therefore, miR-203 could be a potentially new prognostic marker and therapeutic target in metastatic prostate cancer....

  5. Low Expression of miR-491 Promotes Esophageal Cancer Cell Invasion by Targeting TPX2

    Directory of Open Access Journals (Sweden)

    Hongyan Niu

    2015-07-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs have a key role in carcinogenesis and cancer development, but the role of miRNAs in the progression of esophageal cancer (EC remains unclear. Methods: The TE-1 and Eca-109 EC cell lines were used. The expression of miR-491 and candidate gene TPX2 in EC samples (n=99 were detected by RT-PCR. The cells invasive ability was determined by transwell assay. The luciferase reporter assay was used to confirm the regulation mechanism. Results: A decreased expression of miR-491 was detected in the EC clinical samples compared with the corresponding adjacent tumor tissues. Aberrant expression of miR-491 regulated cells invasion and EMT markers. Furthermore, we verified that TPX2 was a target gene of miR-491. Conclusions: miR-491 may play a critical role in EC.

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

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  7. 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.

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

    Science.gov (United States)

    Härmä, Ville; Haavikko, Raisa; 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-10

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

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  11. 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.)

  12. Novel multisensor probe for monitoring bladder temperature during locoregional chemohyperthermia for nonmuscle-invasive bladder cancer: technical feasibility study

    NARCIS (Netherlands)

    Cordeiro, Ernesto R.; Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

    2013-01-01

    The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional

  13. 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.

  14. An improved in vitro model to characterize invasive growing cancer cells simultaneously by function and genetic aberrations.

    Science.gov (United States)

    Jung, V; Wullich, B; Kamradt, J; Stöckle, M; Unteregger, G

    2007-03-01

    Invasion into the surrounding tissue and bone metastasis is a common feature of advanced prostate cancer. Chromosomal and other genetic or epigenetic abnormalities were aligned to this behaviour mostly by using permanent cell lines, paraffin embedded tissue or primary tumour samples. Both attempts fail to reflect either the original situation or functional information in the patient's tissue. Thus, we developed an improved in vitro assay to follow invasion of prostate cancer cells derived from fresh samples of radical prostatectomy specimens. Fresh tumour samples were applied onto Matrigeltrade mark-coated invasion chambers using a cocultivation model. Invasive growing cells were harvested from the bottom of the membrane or from the underlying gel and further characterized using comparative genomic hybridization. Prostate cancer cells have the capability to invasively grow through the barrier of a Matrigeltrade mark and could easily be sampled in a pad of Matrigeltrade mark. Comparative genomic hybridization revealed characteristic chromosomal aberrations of the invasive growing cells. Noteworthy is their ability to spheroid formation, which allows for further cell propagation by standard cell culture methods. Thus, our improved invasion model is a tool for the sampling of invasive growing cancer cells from fresh human tumour material allowing for functional as well as genetic studies.

  15. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-02-15

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

  17. Role of SDF-1 and CXCR4 in the proliferation, migration and invasion of cervical cancer.

    Science.gov (United States)

    Wang, Chen; Cheng, Hailing; Li, Yanyun

    2016-11-01

    This study was to investigate the role of stromal cell-derived factor 1 (SDF-1) and its corresponding receptor CXCR4 in the proliferation, migration and invasion of cervical cancer HeLa cells. CXCR4 expression in HeLa cells was measured by flow cytometry and Western Blot. Role of SDF-1 and CXCR4 in the HeLa cells proliferation was measured by MTT. Role of SDF-1 and CXCR4 in the migration and invasion of HeLa cell was measured by Boyden chamber. High expression of CXCR4 was observed on the surface of HeLa cells. Proliferation ability of HeLa cells was significantly increased after SDF-1 stimulation, which showed dose-dependent manner. After knock-down of CXCR4 expression by RNAi, SDF-1-stimulated HeLa cells proliferation was significantly blocked (PSDF-1 can induce migration and invasion of Hela cells, SDF-1-stimulated HeLa cells migration and invasion was significantly blocked (P<0.05) after knock-down of CXCR4 expression by RNAi. High expression of surface CXCR4 plays an important role in the proliferation, migration and invasion of HeLa cells.

  18. 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.

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

    Science.gov (United States)

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

    2018-01-01

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

  20. L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling

    Science.gov (United States)

    Jacquemet, Guillaume; Baghirov, Habib; Georgiadou, Maria; Sihto, Harri; Peuhu, Emilia; Cettour-Janet, Pierre; He, Tao; Perälä, Merja; Kronqvist, Pauliina; Joensuu, Heikki; Ivaska, Johanna

    2016-01-01

    Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src. Moreover, L-type calcium channels promote filopodia stability and maturation into talin-rich adhesions through the spatially restricted regulation of calcium entry and subsequent activation of the protease calpain-1. Altogether we uncover a novel and clinically relevant signalling pathway that regulates filopodia formation in cancer cells and propose that cycles of filopodia stabilization, followed by maturation into focal adhesions, directs cancer cell migration and invasion. PMID:27910855

  1. Survival of endometrial cancer patients with lymphatic invasion and deficient mismatch repair expression.

    Science.gov (United States)

    Terada, Keith Y; Black, Michael; Terada, Laura H; Davis, James; Shimizu, David M

    2013-04-01

    This study examines patients under the age of 70 with endometrial cancer and lymphatic invasion or lymph node metastases. Survival of patients with loss of tumor mismatch repair expression is compared to survival of patients with normal mismatch repair expression. This is a retrospective review of patients treated from 1998-2009 for carcinoma of the endometrium. All patients with lymphatic invasion, including lymph node metastases, had immunohistochemical staining of the primary tumor for loss of expression of the mismatch repair genes MLH1, PMS2, MSH6, and MSH2. Overall survival and disease specific survival were compared using Kaplan-Meier plots. Sixty-six patients were identified for inclusion; 26 demonstrated loss of mismatch repair expression and 40 demonstrated normal mismatch repair expression. Overall survival and disease specific survival were significantly better in the group with defective mismatch repair expression. Subgroup analysis of FIGO stage 3C patients also showed significantly better survival in patients with deficient mismatch repair expression. For patients with endometrial cancer and lymphatic invasion, patients demonstrating loss of mismatch repair expression in the primary tumor appear to have a significantly better survival than patients with normal mismatch repair expression. Further investigation appears warranted to examine a possible role of mismatch repair expression as a prognostic marker for high risk patients with endometrial cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2017-12-22

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

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

    Directory of Open Access Journals (Sweden)

    Farrar William L

    2010-10-01

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

  5. Identification of extracapsular invasion of the metastatic lymph nodes as a useful prognostic sign in patients with resectable colorectal cancer.

    Science.gov (United States)

    Komuta, K; Okudaira, S; Haraguchi, M; Furui, J; Kanematsu, T

    2001-12-01

    The present study was undertaken to evaluate whether the microscopic patterns of distribution and extracapsular invasion of cancer cells in the regional lymph nodes were linked to the survival rates for patients with advanced colorectal cancer who undergo a curative surgical resection. Two hundred ninety-six surgically resected metastatic lymph nodes from 84 patients with node-positive colorectal cancer were microscopically examined. The distribution of cancer cells in the lymph nodes were grouped into two types: type A (> or =50 percent cancer) and type B (cancer). The extracapsular invasion of cancer cells in the nodes were divided into three subgroups: pattern X (no evidence of cancer cell invasion into the adjacent tissue); pattern Y (less than five cancer cells were seen in the adjacent tissue); and pattern Z (more than five cancer cells invaded the adjacent tissue). The patients, based on these microscopic manifestations of metastatic patterns in the nodes, were divided into three groups: Group 1, patients with pattern X nodal metastases only; Group 2, patients with pattern Y and pattern (X + Y) nodal metastases; and Group 3, patients with pattern Z, pattern (X + Z), pattern (Y + Z), and pattern (X + Y + Z) nodal metastases. The survival rates and disease-free survival rates for patients with metastatic lymph nodes showing an extracapsular invasion pattern (Groups 2 and 3) were significantly worse than those for patients with metastatic nodes showing no extracapsular invasion pattern only (Group 1; P thesis of this article that the identification of extracapsular invasion of the metastatic lymph nodes can be taken as a useful prognostic sign in patients with resectable colorectal cancer.

  6. Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer.

    Science.gov (United States)

    Yang, Fei; Gao, Jun-Yi; Chen, Hua; Du, Zhen-Hua; Zhang, Xue-Qun; Gao, Wei

    2017-01-01

    Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim) were also detected. We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 μM) and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

    Directory of Open Access Journals (Sweden)

    Claudia Ceci

    2016-11-01

    Full Text Available Ellagic acid (EA is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A, an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376 by in vitro proliferation tests (measuring metabolic and foci forming activity, invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1, an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer.

  9. Utilization of neoadjuvant chemotherapy varies in the treatment of women with invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Adedayo A Onitilo

    Full Text Available BACKGROUND: Treatment with neoadjuvant chemotherapy (NAC has made it possible for some women to be successfully treated with breast conservation therapy (BCT who were initially considered ineligible. Factors related to current practice patterns of NAC use are important to understand particularly as the surgical treatment of invasive breast cancer has changed. The goal of this study was to determine variations in neoadjuvant chemotherapy use in a large multi-center national database of patients with breast cancer. METHODS: We evaluated NAC use in patients with initially operable invasive breast cancer and potential impact on breast conservation rates. Records of 2871 women ages 18-years and older diagnosed with 2907 invasive breast cancers from January 2003 to December 2008 at four institutions across the United States were examined using the Breast Cancer Surgical Outcomes (BRCASO database. Main outcome measures included NAC use and association with pre-operatively identified clinical factors, surgical approach (partial mastectomy [PM] or total mastectomy [TM], and BCT failure (initial PM followed by subsequent TM. RESULTS: Overall, NAC utilization was 3.8%l. Factors associated with NAC use included younger age, pre-operatively known positive nodal status, and increasing clinical tumor size. NAC use and BCT failure rates increased with clinical tumor size, and there was significant variation in NAC use across institutions. Initial TM frequency approached initial PM frequency for tumors >30-40 mm; BCT failure rate was 22.7% for tumors >40 mm. Only 2.7% of patients undergoing initial PM and 7.2% undergoing initial TM received NAC. CONCLUSIONS: NAC use in this study was infrequent and varied among institutions. Infrequent NAC use in patients suggests that NAC may be underutilized in eligible patients desiring breast conservation.

  10. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer Screening Overview Screening ... Statistics Cancer Disparities Causes & Prevention Risk ... Overview Screening Cancer Screening Overview Screening Tests Diagnosis & ...

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

    Directory of Open Access Journals (Sweden)

    Shimura Takaya

    2012-05-01

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

  12. New Roles of Osteocytes in Proliferation, Migration and Invasion of Breast and Prostate Cancer Cells.

    Science.gov (United States)

    Cui, Yu-Xin; Evans, Bronwen A J; Jiang, Wen G

    2016-03-01

    Most cases of prostate and breast cancer metastasis occur to the bone, and are responsible for the majority of cancer-related deaths. Osteocytes constitute over 90% of adult bone cells. They orchestrate bone remodelling through determining osteoclast activity and affecting osteoblasts. The osteocyte lacuno-canalicular network is also intimately associated with the blood vessel network in the bone matrix. However, the roles of osteocytes in cancer cell invasion and metastasis remain unknown. In this study, we investigated the effects of early osteocytes on the behaviour of breast and prostate cancer cells. The proliferation of cultured cells was assessed using the AlamarBlue assay. The electric cell-substrate impedance sensing (ECIS) system was used to measure spreading, attachment and migratory behaviour of cancer cells in response to conditioned medium (CM) from mouse osteocytes. Other cell assays, including in vitro wound healing and transwell migration/invasion assays, were also applied to evaluate the effect of osteocytes on cancer cells. We found that CM from osteocytes from both monolayer and three-dimensional (3D) cultures, stimulated proliferation of DU145 and PC3 prostate cancer cells but not LNCaP cells compared to control medium. Osteocyte CM also stimulated proliferation of MDA-MB-231 and MCF-7 breast cancer cells. However, osteocyte CM promoted the migration and adhesion of PC3 and DU145 in prostate cancer cells but had the reverse effect on PZHPV7, a normal prostate epithelial cell line. In the breast cancer cells studied, osteocyte CM inhibited post-wound migration of MCF-7 and ZR-75.1 cells but not MDA-MB-231 cells. Moreover, osteocyte CM stimulated transwell chemotactic migration of MDA-MB-231 cells but not of MCF-7 and ZR-75.1 cells. Osteocytes play diverse roles in the proliferative and migratory potential of breast and prostate cancer cells that may be associated with cancer-specific bone metastasis and requires further investigation. Copyright

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Jing Wan

    2017-04-01

    Full Text Available Objective: To study the correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion. Methods: A total of 128 patients with thyroid papillary carcinoma who received surgical treatment in the hospital between May 2013 and May 2016 were collected, CEUS was used to make clear the peak intensity (PI and area under the curve (AUC of tumor tissue and surrounding normal tissue, and the median of PI and AUC was referred to further divide the patients into high PI group and low PI group as well as high AUC group and low AUC group, 64 cases in each group. Fluorescent quantitative PCR was used to determine proliferation and invasion gene mRNA expression in tumor tissues. Results: PI and AUC levels in tumor tissue were lower than those in surrounding normal tissue; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low PI group were higher than those of high PI group, and invasion gene Ki-67 mRNA expression was higher than that of high PI group while P53 and MRP-1 mRNA expression were lower than those of high PI group; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low AUC group were higher than those of high AUC group, and invasion gene Ki-67 mRNA expression was higher than that of high AUC group while P53 and MRP-1 mRNA expression were lower than those of high AUC group. Conclusion: Thyroid papillary carcinoma CEUS parameters PI and AUC levels can quantifiably reflect the cancer cell proliferation and invasion activity.

  15. Design and pharmacophore modeling of biaryl methyl eugenol analogs as breast cancer invasion inhibitors.

    Science.gov (United States)

    Abdel Bar, Fatma M; Khanfar, Mohammad A; Elnagar, Ahmed Y; Badria, Farid A; Zaghloul, Ahmed M; Ahmad, Kadria F; Sylvester, Paul W; El Sayed, Khalid A

    2010-01-15

    Cell invasion and migration are required for the parent solid tumor cells to metastasize to distant organs. Microtubules form a polarized network, enabling organelle and protein movement throughout the cell. Cytoskeletal elements coordinately regulate cell's motility, adhesion, migration, exocytosis, endocytosis, and division. Thus, microtubule disruption can be a useful target to control cancer cell invasion and metastasis. The phenolic ether methyl eugenol (1), the major component of the essential oil of the leaves of Melaleuca ericifolia Sm. (Myrtaceae), was used as a starting scaffold to design eleven new and three known anti-tubulin agents 2-15 using carbon-carbon coupling reactions. A computer-assisted approach was used to design these new biaryl derivatives using colchicine-binding site of tubulin as the molecular target and colchicine as an active ligand. Several derivatives showed potent inhibitory activity against MDA-MB-231 cell migration at the 1-4microM dose range. The Z isomers, 4 and 15 were more active as invasion inhibitors compared to their structurally related E isomers, 2 and 14. The cytotoxic activities of compounds 2-15 against two breast cancer cell lines MDA-MB-231 and MCF-7 were evaluated. Anti-invasive activity of the semisynthetic derivatives is not due to a direct cytotoxic effect on MDA-MB-231. Analogs 2-15 may promote their anti-invasive activity through the induction of changes in cell morphology. A pharmacophore model was generated involving seven essential features for activity, which was consistent with a previously generated colchicine site inhibitors model. Copyright 2009 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Mierke, Claudia Tanja

    2013-01-01

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

  18. Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia.

    Science.gov (United States)

    Asyikeen, Wan Adnan Wan Nor; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Zin, Anani Aila Mat; Othman, Nor Hayati

    2016-11-01

    Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.

  19. 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.

  20. Estrogen Receptor α Is Crucial in Zearalenone-Induced Invasion and Migration of Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Karolina Kowalska

    2018-02-01

    Full Text Available Zearalenone (ZEA, a mycotoxin produced in the genus Fusarium, binds to estrogen receptors (ER and is therefore regarded as an endocrine disruptor. ZEA has also been found to modulate the proliferation and apoptosis of prostate cancer cells in a dose-dependent manner. This study evaluates whether the effect of a low dose of ZEA (0.1 and 0.001 nM on the invasion and migration of prostate cancer cell line PC3 is associated with ERs expression. The invasion and migration was evaluated by modified Boyden chamber assay, scratch assay, gelatin zymography, Real Time qPCR (RTqPCR and Western blot. The involvement of ERs was evaluated with the selective ER antagonists: estrogen receptor α (ERα antagonist 1,3-bis (4-hydroxyphenyl-4-methyl-5-[4-(2-piperidinylethoxy phenol]-1H-pyrazole dihydrochloride (MPP and estrogen receptor β (ERβ antagonist 4-[2–phenyl-5,7–bis (trifluoromethyl pyrazolo [1,5-a]-pyrimidin-3-yl] phenol (PHTPP. ZEA was found to modulate cell motility dependent on estrogen receptors, particularly ERα. Increased cell migration and invasion were associated with increased MMP-2 and MMP-9 activity as well as the up-regulation of the EMT-associated genes vimentin (VIM, zinc finger E-box-binding homeobox 1/2 (ZEB1/2 and transforming growth factor β 1 (TGFβ1. In conclusion, ZEA might modulate the invasiveness of prostate cancer cells dependently on ERα expression.

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

    International Nuclear Information System (INIS)

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-01-01

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug

  2. Radiation-induced relief of pain in an animal model with bone invasion from cancer

    International Nuclear Information System (INIS)

    Seong, J.; Kim, J.; Kim, K.H.; Kim, U.J.; Lee, B.W.

    2003-01-01

    In clinic, local radiation is effective for relief of pain from cancer invasion into the bones. This effect is usually observed before the regression of tumor occurs, which implies radiation-induced pain relief by mechanisms other than tumor irradication. In this study, possible mechanisms were explored in animal model system. To establish an animal model, syngeneic hepatocarcinoma, HCa-I was transplanted on femoral periosteum of C3H/HeJ male mice and bone-invasive tumor growth was identified through the histological analysis. Development of tumor-induced pain was assessed by von Frey filament test, acetone test, and radiant heat test. Animals were also irradiated for their tumors. Any change in pain was analyzed by above tests for the quantitative change and by immunohistochemical stain for the expression of molecules such as c-fos, substance P, and calcitonin gene-related peptide (CGRP) in lumbar spinal cord. Cancer invasion into the bone was started from 7th day after transplantation and became evident at day 14. Objective increase of pain in the ipsilateral thigh was observed at day 14 on von Frey filament test and acetone test, while there was no remarkable regression of the tumors. In this model system, local radiation of tumor resulted in decrease in objective pain on von Frey filament test and acetone test. In the immunohistochemical stain for lumbar spinal cord, the expression of substance P and CGRP but not c-fos increased in tumor-bearing animal compared to the control. The expression of these molecules decreased in animals given local radiation. In summary, an animal model system was established for objective pain from cancer invasion into the bones. Local radiation of tumor induced objective pain relief and this effect seems to be mediated not by tumor regression but through altered production of pain-related molecules

  3. Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1β dependent upregulation of MYO3A gene in breast cancer cells

    Science.gov (United States)

    Baghel, Khemraj Singh; Tewari, Brij Nath; Shrivastava, Richa; Malik, Showkat Ahmad; Lone, Mehraj U-Din; Jain, Nem Kumar; Tripathi, Chakrapani; Kanchan, Ranjana Kumari; Dixit, Sameer; Singh, Kavita; Mitra, Kalyan; Negi, Mahendra Pal Singh; Srivastava, Mukesh; Misra, Sanjeev; Bhatt, Madan Lal Brahma; Bhadauria, Smrati

    2016-01-01

    ABSTRACT The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or “niche” interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cells with neighboring TAMs actively drive cancer progression and metastatic transformation through intercellular signaling networks that need better elucidation. Thus, current study was planned for discerning paracrine communication networks operational between TAMs, and breast cancer cells with special reference to cancer cell invasion and dissemination to distant sites. Here, we report role of MIP-1β in enhancing invasive potential of metastatic breast cancer MDA-MB-231 and MDA-MB-468 cells. In addition, the poorly metastatic MCF-7 cells were also rendered invasive by MIP-1β. The MIP-1β-driven cancer cell invasion was dependent on upregulated expression levels of MYO3A gene, which encodes an unconventional myosin super-family protein harboring a kinase domain. Ex ovo study employing Chick-embryo-model and in vivo Syngenic 4T1/BALB/c mice-model further corroborated aforementioned in vitro findings, thereby substantiating their physiological relevance. Concordantly, human breast cancer specimen exhibited significant association between mRNA expression levels of MIP-1β and MYO3A. Both, MIP-1β and MYO3A exhibited positive correlation with MMP9, an established molecular determinant of cancer cell invasion. Higher expression of these genes correlated with poor survival of breast cancer patients. Collectively, these results point toward so far undisclosed MIP-1β/MYO3A axis being operational during metastasis, wherein macrophage-derived MIP-1β potentiated cancer cell invasion and metastasis via up regulation of MYO3A gene within cancer cells. Our study exposes opportunities for devising potential anti-metastatic strategies for efficient

  4. An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Felts, Jesse L; Zhu, Junjia; Han, Bing; Smith, Stanley J; Truica, Cristina I

    2017-11-01

    The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone-positive, Her-2-negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow-up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost-effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated. © 2017 Wiley Periodicals, Inc.

  5. Increased beta1 integrin is associated with decreased survival in invasive breast cancer.

    Science.gov (United States)

    Yao, Evelyn S; Zhang, Hui; Chen, Yunn-Yi; Lee, Brian; Chew, Karen; Moore, Dan; Park, Catherine

    2007-01-15

    Aberrant microenvironments and loss of balance in cell-extracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased beta1 integrin signaling is involved in malignant progression and that inhibitory antibody to beta1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of beta1 integrin and extracellular beta1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest beta1 integrin intensity score (3+ versus 0-2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (Pintegrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b=0.19; P=0.03). In a multivariate Cox proportional hazards model, beta1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19-2.38; Pintegrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy.

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

    Science.gov (United States)

    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 non-synonymous 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 through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02–1.17, p=0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n=3,545; OR=1.09, 95% CI, 1.01–1.18, p=0.025), and our findings were strongest for the mucinous subtype (n=447; OR=1.32, 95% CI, 1.11–1.58, p=0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer. PMID:20056644

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

    International Nuclear Information System (INIS)

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-01-01

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

  8. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer Screening ... Cancer Statistics Cancer Disparities Causes & Prevention Risk Factors Genetics Cancer Prevention Overview Screening Cancer Screening Overview Screening ...

  9. Overview of childhood cancers at a regional cancer centre in North-East India.

    Science.gov (United States)

    Hazarika, Munlima; Krishnatreya, Manigreeva; Bhuyan, Cidananda; Saikia, Bhargab Jyoti; Kataki, Amal Chandra; Nandy, Pintu; Hazarika, Monalisha; Roy, Partha Sarathi

    2014-01-01

    Childhood cancers are relatively uncommon in comparison to adult cancers. There is no literature available to shed light on clinic-pathological types and patterns of care for childhood cancers in our population in North-East India. In this analysis we therefore tried to determine the common childhood cancers diagnosed in our institute, clinical profile of the patients, types of treatment and compliance, and median survival estimates. Leukemia was most common, followed by retinoblastoma, central nervous system tumours and lymphomas. Ascertaining the clinic-pathological profile of childhood cancers in our population is essential for allocation and management of resources for this small but important group of patients.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

    2012-01-01

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

  12. IGF-1 regulates Cyr61 induced breast cancer cell proliferation and invasion.

    Directory of Open Access Journals (Sweden)

    Suren Sarkissyan

    Full Text Available Studies from our laboratory and others have shown that cysteine-rich 61 (Cyr61 may be involved in tumor proliferation and invasion. In earlier studies, we demonstrated increased insulin-like growth factor-I (IGF-1 is associated with breast tumor formation and poor clinical outcomes. In our current study we have investigated IGF-1 regulation of Cyr61 and whether targeting IGF-1 could inhibit Cyr61 induced tumor growth and proliferation.Several ATCC derived normal and breast cancer cell lines were used in this study: MDA-MB231, BT474, MCF-7, and SKBR3. We also tested cells stably transfected in our laboratory with active Akt1 (pAkt; SKBR3/AA and MCF-7/AA and dominant negative Akt1 (SKBR3/DN and MCF-7/DN. In addition, we used MCF-7 cells transfected with full length Cyr61 (CYA. Monolayer cultures treated with IGF-1 were analyzed for Cyr61 expression by RT-PCR and immunohistochemical staining. Migration assays and MTT based proliferation assays were used to determine invasive characteristics in response to IGF-1/Cyr61 activation.Cells with activated Akt have increased levels of Cyr61. Conversely, cells with inactive Akt have decreased levels of Cyr61. IGF-1 treatment increased Cyr61 expression significantly and cells with high level of Cyr61 demonstrate increased invasiveness and proliferation. Cyr61 overexpression and activation led to decrease in E-cadherin and decrease in FOXO1. Inhibition of the PI3K and MAPK pathways resulted in significant decrease in invasiveness and proliferation, most notably in the PI3K pathway inhibited cells.The findings of this study show that IGF-1 upregulates Cyr61 primarily through activation of the Akt-PI3K pathway. IGF-1 induced MAPK plays a partial role. Increase in Cyr61 leads to increase in breast cancer cell growth and invasion. Hence, targeting Cyr61 and associated pathways may offer an opportunity to inhibit IGF-1 mediated Cyr61 induced breast cancer growth and invasion.

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

    Science.gov (United States)

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

    2017-07-01

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

  14. Late adverse effects of radiation therapy for rectal cancer - a systematic overview

    International Nuclear Information System (INIS)

    Birgisson, Helgi; Paahlman, Lars; Gunnarsson, Ulf; Glimelius, Bengt

    2007-01-01

    Purpose. The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. Methods. Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5x5 Gy radiation therapy with surgery alone. Results. The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. Conclusions. These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued

  15. Late adverse effects of radiation therapy for rectal cancer - a systematic overview

    Energy Technology Data Exchange (ETDEWEB)

    Birgisson, Helgi; Paahlman, Lars; Gunnarsson, Ulf [Dept. of Surgery, Univ. Hospital, Univ. of Uppsala, Uppsala (Sweden); Glimelius, Bengt [Dept. of Oncology, Radiology and Clinical Immunology, Univ. Hospital, Univ. of Uppsala, Uppsala (Sweden); Dept. of Oncology and Pathology, Karolinska Inst., Stockholm (Sweden)

    2007-05-15

    Purpose. The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. Methods. Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5x5 Gy radiation therapy with surgery alone. Results. The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. Conclusions. These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued.

  16. Lactobacillus rhamnosus GG: An Overview to Explore the Rationale of Its Use in Cancer

    Directory of Open Access Journals (Sweden)

    Giuseppe L. Banna

    2017-09-01

    Full Text Available Cancer is the second leading cause of death in the western world. In the era of precision medicine, a significant number of cancer patients can be cured with several anti-cancer therapeutic regimens. However, therapy failure may be caused by treatment side effects, such as diarrhea, especially occurring in patients with gastrointestinal or pelvic malignancies. In particular, diarrhea is one of the most frequent gastrointestinal toxicity during cancer treatment and it can result from nearly bot chemo- and radio-therapeutic strategies currently used. Diarrhea has a serious impact on patients’ quality of life and treatment dosing and schedule modification due to its severity can negatively influence treatment outcomes. In this context, probiotics may play an interesting role in several human diseases with an inflammatory bowel involvement and, among these, Lactobacillus rhamnosus GG (LGG is one of the most characterized and utilized. In particular, LGG is able to reverse intestinal dysbiosis and moderate diarrhea. Moreover, preclinical studies have documented its effects in reducing chronic inflammation associated with cancer development. This review summarizes the preclinical results of LGG on cancer cells proliferation and tumor invasion as well as the potential role of LGG use in cancer patients for the prevention and management of diarrhea associated with cancer treatment. Overall, these encouraging data support further investigation on the use of LGG in stratified patients undergoing specific therapeutic protocols, including chemotherapy and pelvic radiotherapy, in order to reduce the development of severe diarrhea and thus improve the adherence to the therapy and patients’ quality of life.

  17. 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.

  18. Inhibitory effect of maple syrup on the cell growth and invasion of human colorectal cancer cells.

    Science.gov (United States)

    Yamamoto, Tetsushi; Uemura, Kentaro; Moriyama, Kaho; Mitamura, Kuniko; Taga, Atsushi

    2015-04-01

    Maple syrup is a natural sweetener consumed by individuals of all ages throughout the world. Maple syrup contains not only carbohydrates such as sucrose but also various components such as organic acids, amino acids, vitamins and phenolic compounds. Recent studies have shown that these phenolic compounds in maple syrup may possess various activities such as decreasing the blood glucose level and an anticancer effect. In this study, we examined the effect of three types of maple syrup, classified by color, on the cell proliferation, migration and invasion of colorectal cancer (CRC) cells in order to investigate whether the maple syrup is suitable as a phytomedicine for cancer treatment. CRC cells that were administered maple syrup showed significantly lower growth rates than cells that were administered sucrose. In addition, administration of maple syrup to CRC cells caused inhibition of cell invasion, while there was no effect on cell migration. Administration of maple syrup clearly inhibited AKT phosphorylation, while there was no effect on ERK phosphorylation. These data suggest that maple syrup might inhibit cell proliferation and invasion through suppression of AKT activation and be suitable as a phytomedicine for CRC treatment, with fewer adverse effects than traditional chemotherapy.

  19. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. The Role of MicroRNAs in Breast Cancer Migration, Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Joy Tang

    2012-10-01

    Full Text Available MicroRNAs (miRNAs are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. Many miRNAs have been implicated in several human cancers, including breast cancer. miRNAs are known to regulate cell cycle and development, and thus may serve as useful targets for exploration in anticancer therapeutics. The link between altered miRNA signatures and breast cancer development and metastasis can be observed either through the loss of tumor suppressor miRNAs, such as let-7s, miR-30a/31/34a/125s/200s/203/205/206/342 or the overexpression of oncogenic miRNAs, such as miR-10b/21/135a/155/221/222/224/373/520c in breast cancer cells. Some of these miRNAs have also been validated in tumor specimens of breast cancer patients, underscoring their potential roles in diagnostics, as well as targets for novel therapeutics for breast cancer. In this review article, we will provide an overview and update of our current understanding of the mode of action of several of these well characterized miRNAs in breast cancer models. Therefore, better understanding of the gene networks orchestrated by these miRNAs may help exploit the full potential of miRNAs in regards to cancer diagnosis, treatment, and therapeutics.

  2. Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer.

    Science.gov (United States)

    Rummel, Seth K; Lovejoy, Leann; Shriver, Craig D; Ellsworth, Rachel E

    2017-08-01

    Although breast cancer in young women accounts for cancer predisposition genes is needed to improve the understanding of breast cancer etiology in young women. All female patients enrolled in the Clinical Breast Cancer Project between 2001 and 2015 and diagnosed with invasive breast cancer before age 40 were included in this study. Family history was classified using the NCCN Familial Risk Assessment guidelines. Targeted sequencing of 94 cancer predisposition genes was performed using peripheral blood DNA. Variants were detected using VariantStudio and classified using ClinVar. Seven percent (141/1980) of patients were young women and 44 had a significant family history. Sequencing was completed for 118 women with genomic DNA. Pathogenic mutations were present in 27 patients: BRCA1 (n = 10), BRCA2 (n = 12), TP53 (n = 1), and CHEK2 (n = 4). Mutations classified as pathogenic were also detected in APC (n = 1) and MUTYH (n = 2). Variants of uncertain significance (VUS) were detected in an additional 17 patients in ten genes. Pathogenic mutations in high- and moderate-risk breast cancer genes were detected in 23% of young women with an additional 3% having pathogenic mutations in colon cancer predisposition genes. VUS were observed in 14% of women in genes such as ATM, BRCA2, CDH1, CHEK2, and PALB2. Identification of those non-genetic factors is critical to reduce the burden of breast cancer in this population.

  3. Long Noncoding RNA ROR Regulates Proliferation, Invasion, and Stemness of Gastric Cancer Stem Cell.

    Science.gov (United States)

    Wang, Shuai; Liu, Feng; Deng, Junji; Cai, Xinsheng; Han, Junqing; Liu, Qi

    2016-10-01

    Gastric cancer remains an incurable malignance and the second leading cause of cancer death globally. Recent progress in gastric cancer research has demonstrated the crucial roles of cancer stem cells (CSCs) in the development, metastasis, and drug resistance of this disease. Various studies have highlighted the role of long noncoding RNAs (lncRNAs) in the pathogenesis of gastric cancer. In this study, through fluorescence-activated cell sorting, we isolated gastric CSCs (GCSCs) from MKN-45 cells and demonstrated for the first time that lncRNA ROR was highly expressed in CD133 + GCSCs. Overexpression of lncRNA ROR significantly increased, but knockdown of lncRNA ROR inhibited the proliferation and invasion of GCSCs. Most importantly, lncRNA ROR led to upregulation of several key stemness transcriptional factors, such as OCT4, SOX2, and NANOG, as well as CD133 GCSC. Our data demonstrated that lncRNA ROR was associated with core stemness transcriptional factors and the pluripotent state of GCSCs. These results further improved our understanding of the functional cross talking network during development of GCSCs and may provide novel target for the diagnostics and therapeutics of gastric cancer.

  4. Emerging minimally invasive procedures for focal treatment of organ-confined prostate cancer.

    Science.gov (United States)

    Habibian, David J; Katz, Aaron E

    2016-11-01

    Prostate cancer is the most common malignancy amongst American men. However, the majority of prostate cancer diagnoses are of low risk, organ-confined disease. Many men elect to undergo definitive treatment, but may benefit from focal therapy to maintain continence and potency. This review reports the mechanism of action and outcomes of emerging focal therapies for prostate cancer. We report the mechanism of action of focal cryotherapy, high intensity focused ultrasound, focal laser ablation, and irreversible electroporation. In addition, we reviewed the largest studies available reporting rates of urinary incontinence, erectile dysfunction, biochemical recurrence-free survival (ASTRO), and post-operative adverse events for each procedure. Each treatment modality stated has a unique mechanism in the ablation of cancerous cells. Genito-urinary symptoms following these studies report incontinence and erectile dysfunction rates ranging from 0-15% and 0-53%, respectively. Biochemical disease-free survival was reported using the ASTRO definition. Some treatment modalities lack the necessary follow-up to determine effectiveness in cancer control. No focal therapy studies reported serious adverse events. These minimally invasive procedures are feasible in a clinical setting and show promising functional and disease control results with short to medium-term follow-up. However, each treatment requires additional robust prospective studies as well as its own unique domain to determine biochemical recurrence free survival to properly determine their role in treatment of organ-confined prostate cancer.

  5. Onbaekwon Suppresses Colon Cancer Cell Invasion by Inhibiting Expression of the CXC Chemokine Receptor 4.

    Science.gov (United States)

    Kim, Buyun; Yoon, Jaewoo; Yoon, Seong Woo; Park, Byoungduck

    2017-06-01

    Cysteine X cysteine (CXC) chemokine receptor 4 (CXCR4) and C-X-C motif chemokine 12 (CXCL12) were originally identified as chemoattractants between immune cells and sites of inflammation. Since studies have validated an increased level of CXCL12 and its receptor in patients with colorectal cancers, CXCL12/CXCR4 axis has been considered as a valuable marker of cancer metastasis. Therefore, identification of CXCR4 inhibitors has great potential to abrogate tumor metastasis. Onbaekwon (OBW) is a complex herbal formula that is derived from the literature of traditional Korean medicine Dongeuibogam. In this study, we demonstrated that OBW suppressed CXCR4 expression in various cancer cell types in a concentration- and time-dependent manner. Both proteasomal and lysosomal inhibitors had no effect to prevent the OBW-induced suppression of CXCR4, suggesting that the inhibitory effect of OBW was not due to proteolytic degradation but occurred at the transcriptional level. Electrophoretic mobility shift assay further confirmed that OBW could block endogenous activation of nuclear factor kappa B, a key transcription factor that regulates the expression of CXCR4 in colon cancer cells. Consistent with the aforementioned molecular basis, OBW abolished cell invasion induced by CXCL12 in colon cancer cells. Together, our results suggest that OBW, as a novel inhibitor of CXCR4, could be a promising therapeutic agent contributing to cancer treatment.

  6. Effects of Benzoapyrene on migration and invasion of lung cancer cells functioning by TNF-α.

    Science.gov (United States)

    Zhao, Guangqiang; Zhou, Yongchun; Ye, Lianhua; Li, Guangjian; Chen, Xiaobo; Yang, Kaiyun; Huang, Qiubo; Zeng, Yujie; Chen, Ying; Huang, Yunchao

    2018-01-18

    In this study, we attempted to find out the underlying mechanism of Benzoapyrene and metastasis of lung cancer cells. We also did experiments to testify the connection between BaP and its potential target, TNF-α. Cell median lethal dose (IC 50 ) of both cells was measured by crystal violet method. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blot were employed to detect the expression of TNF-α. Wound healing assay and transwell assay were utilized to testify the impacts of BaP and TNF-α on the metastasis of lung cancer cells. Cell death rate was elevated with the increase of BaP concentration. BaP increased the number of metastatic cells of lung cancer. The expressions of TNF-α pathway-associated protein (TNF-α, NF-kB (P65), Caspase3 and Caspase8) were enhanced by overexpressed BaP. TNF-α shRNA suppressed the positive effects of BaP on migration and invasion of lung cancer cells. Our study validated the positive effects of BaP on the metastasis of lung cancer cells. We also revealed the instrumental role of TNF-α in helping the development of lung cancer cells induced by BaP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Surgical staging identified false HPV-negative cases in a large series of invasive cervical cancers.

    Science.gov (United States)

    Petry, Karl Ulrich; Liebrich, Clemens; Luyten, Alexander; Zander, Martina; Iftner, Thomas

    2017-12-01

    We examined a large series of biopsy-proven invasive cervical cancers with surgical staging and HPV re-testing to estimate the relevance of HPV-negative cervical cancers in a Caucasian population. We prospectively collected smears from 371 patients with a biopsy-proven diagnosis of cervical cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears and paraffin embedded tissue blocks underwent additional HPV genotyping. HC2 tests showed 31/371 cases (8.8%) had negative findings. Surgical staging showed that 21/31 HC2-negative cases (68%) were not cervical cancer. Overall, 340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2 positive (97.2%). Non-high-risk HPV subtypes were detected in five cases (one HPV-53, one HPV-70, and three HPV-73) and high-risk subtypes in four patients with HC2-negative cervical cancer (two HPV 16 and two HPV-18). The remaining case, a primary undifferentiated carcinoma of the uterine cervix, tested negative for HPV-DNA with all tests. The main explanation for HPV-negative cervical cancer was a false diagnosis, followed by cancers associated with non-HR-HPV types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare in Caucasian populations. Retrospective analyses without surgical staging may overestimate the proportion of HPV negative cervical cancers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. PTH-related protein enhances MCF-7 breast cancer cell adhesion, migration, and invasion via an intracrine pathway.

    Science.gov (United States)

    Shen, Xiaoli; Qian, Lihui; Falzon, Miriam

    2004-04-01

    Breast cancer is the most common carcinoma that metastasizes to the bone. Parathyroid hormone-related protein (PTHrP), a known stimulator of osteoclastic bone resorption, is a major mediator of the osteolytic process in breast cancer. PTHrP overexpression increases mitogenesis and decreases apoptosis in the human breast cancer cell line MCF-7. In this study, MCF-7 cells were used as a model system to study the effects of PTHrP on breast cancer cell adhesion, migration, and invasion. Clones of MCF-7 cells were established that overexpress wild-type PTHrP or PTHrP mutated in the nuclear localization sequence (NLS). Wild-type PTHrP-overexpressing cells showed significantly higher laminin adhesion and migration, and Matrigel invasion than empty vector-transfectants or cells overexpressing NLS-mutated PTHrP. Wild-type PTHrP also increased the cell surface expression of the pro-invasive integrins alpha6 and beta4; deletion of the NLS negated these effects. Exogenous PTHrP (1-34), (67-86), (107-139), and (140-173) had no effect on integrin expression, or on cell adhesion, migration, and invasion. These results indicate that PTHrP exerts its effects on cell adhesion, migration, invasion, and integrin expression via an intracrine pathway. PTHrP may play a role in breast cancer metastasis by upregulating proinvasive integrin expression, and controlling PTHrP production in breast cancer may provide therapeutic benefit.

  9. Trends in incidence and tumour grade in screen-detected ductal carcinoma in situ and invasive breast cancer.

    Science.gov (United States)

    Luiten, Jacky D; Voogd, Adri C; Luiten, Ernest J T; Duijm, Lucien E M

    2017-11-01

    In a biennial screening mammography programme, we analysed the trends in incidence of screen-detected DCIS and invasive breast cancers in the era of screen-film mammography (SFM) screening, the period of the transition to full-field digital mammography (FFDM) screening and the period of FFDM screening. We also investigated a possible association between the incidence and grading of screen-detected DCIS and invasive breast cancer. In the southern part of the Netherlands, FFDM screening gradually replaced SFM screening between May 2009 and April 2010. We included a consecutive series of 484, 422 screens obtained between July 2005 and July 2015 and divided these screens into three groups; SFM-only cohort, transition cohort and FFDM-only cohort. A total of 3059 referred women were diagnosed with DCIS (n = 623) or invasive breast cancer (n = 2436). The majority of DCIS were high-grade (48.2%), whereas the majority of the invasive breast cancers were low-grade (45.4%) or intermediate-grade (41.6%). The cancer detection rate (CDR) per 1000 screened women showed the same distribution by grade in both groups. The transition to FFDM was characterised by an increased overall detection rate of invasive cancers. Screening mammography detects mostly high-grade DCIS and low- or intermediate-grade invasive cancers. The grade distribution as well as the CDR in the years after the introduction of FFDM remained stable compared to the era of SFM screening. By diagnosing and treating high-grade DCIS, which otherwise may develop into high-grade invasive carcinoma, our findings provide new evidence for the beneficial value of screening mammography programmes.

  10. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  11. 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...... basement membrane. However, when injected into nude mice, both control and NCAM-expressing cell lines produced equally invasive tumors. Tumors generated from NCAM-transfected cells were heterogeneous, containing NCAM-positive as well as NCAM-negative areas, indicating the existence of host factors capable...... of modulating NCAM expression in vivo. In nude mice, NCAM-transfected cells developed tumors with longer latency periods and slower growth rates than tumors induced by NCAM-negative control cells, implying that NCAM may be involved not only in adhesive and motile behavior of tumor cells but also in their growth...

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

    Science.gov (United States)

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

    2015-01-01

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

  13. PHGDH is an independent prognosis marker and contributes cell proliferation, migration and invasion in human pancreatic cancer.

    Science.gov (United States)

    Song, Zhiwang; Feng, Chan; Lu, Yonglin; Lin, Yun; Dong, Chunyan

    2018-02-05

    To investigate the expression, clinical significance, biological function, and the potential mechanism of PHGDH in pancreatic cancer. The expression of PHGDH in human pancreatic cancer tissues and corresponding adjacent normal tissues were analyzed through immunohistochemistry staining. Simultaneously, the association between the PHGDH expression and the clinicopathological parameters and OS and DFS was evaluated. Human pancreatic cancer cell line BxPC-3 and SW1990 were selected to investigate the effect of PHGDH knockdown on cell proliferation, migration, and invasion. In addition, we performed western blot to assess the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9 protein. Our results suggested that the expression of PHGDH is increased in pancreatic cancer compared with adjacent normal tissues and the increased expression of PHGDH is associated with tumor size, lymph node metastasis, and TNM state of pancreatic cancer patients. Moreover, the expression of PHGDH is an independent prognostic indicator for pancreatic cancer patients. In addition, we found that knockdown of PHGDH in pancreatic cancer cells inhibits the cell proliferation, migration, and invasion abilities by down-regulating the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9. Our data indicated that the expression of PHGDH is increased in pancreatic cancer and is an independent molecular prognostic factor for pancreatic cancer patients. In addition, PHGDH controls cell proliferation, migration and invasion abilities. Therefore, PHGDH could serve as an important prognostic indicator and therapeutic target for pancreatic cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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......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...... 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...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  16. Estrogen switches pure mucinous breast cancer to invasive lobular carcinoma with mucinous features.

    Science.gov (United States)

    Jambal, Purevsuren; Badtke, Melanie M; Harrell, J Chuck; Borges, Virginia F; Post, Miriam D; Sollender, Grace E; Spillman, Monique A; Horwitz, Kathryn B; Jacobsen, Britta M

    2013-01-01

    Mucinous breast cancer (MBC) is mainly a disease of postmenopausal women. Pure MBC is rare and augurs a good prognosis. In contrast, MBC mixed with other histological subtypes of invasive disease loses the more favorable prognosis. Because of the relative rarity of pure MBC, little is known about its cell and tumor biology and relationship to invasive disease of other subtypes. We have now developed a human breast cancer cell line called BCK4, in which we can control the behavior of MBC. BCK4 cells were derived from a patient whose poorly differentiated primary tumor was treated with chemotherapy, radiation and tamoxifen. Malignant cells from a recurrent pleural effusion were xenografted in mammary glands of a nude mouse. Cells from the solid tumor xenograft were propagated in culture to generate the BCK4 cell line. Multiple marker and chromosome analyses demonstrate that BCK4 cells are human, near diploid and luminal, expressing functional estrogen, androgen, and progesterone receptors. When xenografted back into immunocompromised cycling mice, BCK4 cells grow into small pure MBC. However, if mice are supplemented with continuous estradiol, tumors switch to invasive lobular carcinoma (ILC) with mucinous features (mixed MBC), and growth is markedly accelerated. Tamoxifen prevents the expansion of this more invasive component. The unexpected ability of estrogens to convert pure MBC into mixed MBC with ILC may explain the rarity of the pure disease in premenopausal women. These studies show that MBC can be derived from lobular precursors and that BCK4 cells are new, unique models to study the phenotypic plasticity, hormonal regulation, optimal therapeutic interventions, and metastatic patterns of MBC.

  17. Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration.

    Science.gov (United States)

    Yang, Hui-ting; Chao, Pei-chun; Yin, Mei-chin

    2013-02-01

    The influence of riboflavin (vitamin B(2) ) upon growth, invasion, and migration in non-small cell lung cancer cell lines was evaluated. Riboflavin at 1, 10, 25, 50, 100, 200, or 400 μmol/L was added into A549, H3255, or Calu-6 cells. The effects of this compound upon level and/or expression of reactive oxygen species (ROS), inflammatory cytokines, intercellular adhesion molecule (ICAM)-1, fibronectin, matrix metalloproteinase (MMP)-9, MMP-2, focal adhesion kinase (FAK), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) were examined. Results showed that riboflavin at test doses did not affect the level of ROS and glutathione. Riboflavin at 200 and 400 μmol/L significantly enhanced cell growth in test lung cancer cell lines, and at 400 μmol/L significantly increased the release of interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. This agent at 200 and 400 μmol/L also upregulated protein production of ICAM-1, fibronectin, MMP-9, MMP-2, NF-κB p50, p-p38 MAPK, and FAK; and at 400 μmol/L enhanced invasion and migration in test cell lines. These findings suggested that riboflavin at high doses might promote lung cancer progression. © 2013 Institute of Food Technologists®

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    PURPOSE: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

  19. Defining Priorities to Improve Patient Experience in Non-Muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Garg, Tullika; Connors, Jill Nault; Ladd, Ilene G; Bogaczyk, Tyler L; Larson, Sharon L

    2018-01-20

    Although approximately 75% of bladder cancers are non-muscle invasive (NMIBC) at diagnosis, most research tends to focus on invasive disease (e.g., experiences related to radical cystectomy and urinary diversion). There is a lack of studies on quality of life, and especially qualitative research, in bladder cancer generally. As a result, relatively little is known about the experiences and needs of NMIBC patients. To understand patient experience, define care priorities, and identify targets for care improvement in NMIBC across the cancer continuum. Through focus groups, patients treated for NMIBC (stage influences on decision-making, and role of social support. Patients with NMIBC desired timely access to care and honest and caring provider communication. They described urinary function and emotional quality of life changes resulting from diagnosis and treatment. Avoiding cystectomy and being alive for family were the major decision influencers. In this qualitative study, we identified access to care, provider characteristics and communication, quality of life, values/influences on decision-making, and social support as priority areas to improve patient experience in NMIBC. Care redesign efforts should focus on improving access, enhancing provider communication, reducing side effects, and supporting caregiver roles.

  20. Urinary Cell-Free DNA Quantification as Non-Invasive Biomarker in Patients with Bladder Cancer.

    Science.gov (United States)

    Brisuda, Antonin; Pazourkova, Eva; Soukup, Viktor; Horinek, Ales; Hrbáček, Jan; Capoun, Otakar; Svobodova, Iveta; Pospisilova, Sarka; Korabecna, Marie; Mares, Jaroslav; Hanuš, Tomáš; Babjuk, Marek

    2016-01-01

    Concentration of urinary cell-free DNA (ucfDNA) belongs to potential bladder cancer markers, but the reported results are inconsistent due to the use of various non-standardised methodologies. The aim of the study was to standardise the methodology for ucfDNA quantification as a potential non-invasive tumour biomarker. In total, 66 patients and 34 controls were enrolled into the study. Volumes of each urine portion (V) were recorded and ucfDNA concentrations (c) were measured using real-time PCR. Total amounts (TA) of ucfDNA were calculated and compared between patients and controls. Diagnostic accuracy of the TA of ucfDNA was determined. The calculation of TA of ucfDNA in the second urine portion was the most appropriate approach to ucfDNA quantification, as there was logarithmic dependence between the volume and the concentration of a urine portion (p = 0.0001). Using this methodology, we were able to discriminate between bladder cancer patients and subjects without bladder tumours (p = 0.0002) with area under the ROC curve of 0.725. Positive and negative predictive value of the test was 90 and 45%, respectively. Quantification of ucf DNA according to our modified method could provide a potential non-invasive biomarker for diagnosis of patients with bladder cancer. © 2015 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2018-04-18

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

  2. The urokinase-system in tumor tissue stroma of the breast and breast cancer cell invasion.

    Science.gov (United States)

    Hildenbrand, Ralf; Schaaf, Antonela

    2009-01-01

    The urokinase-system has been implicated in tumor spread. The serine protease urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) are involved in the control of extracellular turnover, cell migration, invasion, cell signalling, proliferation, apoptosis and angiogenesis leading to a variety of different responses, under both physiological and pathological conditions. uPA and PAI-1 were the first novel tumor biological factors to be validated at the highest level of evidence regarding their clinical utility in breast cancer. However, it is unclear whether it is their (relative) levels in the tumor stroma or in the tumor cells themselves that is the most relevant to patients outcome. This is the first study in which tumor cells and stromal tissue of invasive breast carcinomas were separated by laser capture microdissection followed by ELISA-based determination of the uPA, uPAR and PAI-1 levels. In addition, we localized uPA, uPAR and PAI-1 distribution in invasive breast cancer (n=30) and in ductal carcinoma in situ (DCIS, n=30) by immunohistochemistry and in situ hybridization. We have demonstrated that no significant differences between uPA, uPAR and PAI-1 levels in tumor stroma only, tumor cells only and not separated breast cancer tissue exist (p>0.05). Our results suggest that similar expression levels of these factors in both compartments and in not separated breast cancer tissue may have the same impact on the clinical behavior of breast cancer. These results are an important issue for practical use of tissue sampling. For using uPA and PAI-1 levels as prognostic and predictive factors in breast cancer the quantity of tumor stroma in the tumor tissue specimen is not relevant for assessment patients outcome. Our results were confirmed by immunohistochemistry and in situ hybridization analysis showing that in nearly all cases of invasive carcinomas and DCIS fibroblasts as well as macrophages strongly express uPA, uPAR and PAI

  3. UWB based low-cost and non-invasive practical breast cancer early detection

    Science.gov (United States)

    Vijayasarveswari, V.; Khatun, S.; Fakir, M. M.; Jusoh, M.; Ali, S.

    2017-03-01

    Breast cancer is one of the main causes of women death worldwide. Breast tumor is an early stage of cancer that locates in cells of a human breast. As there is no remedy, early detection is crucial. Towards this, Ultra-Wideband (UWB) is a prominent candidate. It is a wireless communication technology which can achieve high bandwidth with low power utilization. UWB is suitable to be used for short range communication systems including breast cancer detection since it is secure, non-invasive and human health friendly. This paper presents the low-cost and non-invasive early breast cancer detection strategy using UWB sensor (or antenna). Emphasis is given here to detect breast tumor in 2D and 3D environments. The developed system consisted of hardware and software. Hardware included UWB transceiver and a pair of home-made directional sensor/antenna. The software included feed-forward back propagation Neural Network (NN) module to detect the tumor existence, size and location along with soft interface between software and hardware. Forward scattering technique was used by placing two sensors diagonally opposite sides of a breast phantom. UWB pulses were transmitted from one side of phantom and received from other side, controlled by the software interface in PC environment. Collected received signals were then fed into the NN module for training, testing and validation. The system exhibited detection efficiency on tumor existence, location (x, y, z), and size were approximately 100%, (78.17%, 70.66%, 92.46%), 85.86% respectively. The proposed UWB based early breast cancer detection system could be more practical with low-cost, user friendly and non-harmful features. This project may help users to monitor their breast health regularly at their home.

  4. [Breast cancer invasion: the key role of normal cells of host tissues].

    Science.gov (United States)

    Foidart, J M; Polette, M; Birembaut, P; Noel, A

    1994-03-01

    Tumor progression is influenced by extracellular matrices and by soluble factors or cytokines locally produced by host tissue cells (fibroblasts, immune cells ...). Such factors may also accumulate in close association with some extracellular matrix molecules in the tumor. They may also be unmasked during breaking down of extracellular matrices. The most insidious aspect of tumors is their propensity to locally invade normal tissues of the host and to form secondary foci in organs at distant sites from the primary tumor called metastases. During this process, invasive cells come into contact with host tissue cells such as fibroblasts, endothelial cells, macrophages, lymphocytes. These cells are not the passive witnesses of the metastatic cascade but actively participate to the malignant invasion. Through soluble messages (cytokines) and through insoluble molecules of the extracellular matrix, neoplastic and normal cells mutually modulate their activities. Cancer cells regulate the biosynthetic activities of fibroblasts and alter in this way the scaffold of the tumor. Reciprocally, host cells secrete extracellular matrix proteins and cytokines which influence the growth and activities of tumor cells. They also produce at the periphery of tumor cells proteolytic enzymes which promote host tissue destruction and cancerous cells migration. Among these enzymes, matrix metalloproteinases appear to play a key role during invasion and metastasis. Tumors represent thus a complex ecosystem. Tumor cells interact with several components of the extracellular matrix and with host cells (immune cells, fibroblasts, endothelial cells). Such multiple cell-cell and cell-matrix interactions condition angiogenesis, tumor growth, destruction of host tissues, local migration of cancer cells and their metastatic dissemination. It is probable that a precise knowledge of the genes which are selectively activated in tumors under the influence of the host cells or of the tumor cells will

  5. Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer

    Directory of Open Access Journals (Sweden)

    Yang F

    2017-09-01

    Full Text Available Fei Yang,1,* Jun-Yi Gao,2,* Hua Chen,1 Zhen-Hua Du,1 Xue-Qun Zhang,3 Wei Gao4 1Department of Pathology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 2Department of Clinical Medicine, Weifang Medical College, Weifang, 3Graduate School, Taishan Medical University, Xintai, 4Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. Methods: In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim were also detected. Results: We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 µM and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Conclusion: Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer. Keywords: human colon cancer, PI3K/Akt/mTOR pathway, BEZ235, PI3KCA knockdown

  6. Entirely Laparoscopic Gastrectomy and Colectomy for Remnant Gastric Cancer with Gastric Outlet Obstruction and Transverse Colon Invasion

    OpenAIRE

    Kim, Hyun Il; Kim, Min Gyu

    2015-01-01

    It is well known that gastrectomy with curative intent is the best way to improve outcomes of patients with remnant gastric cancer. Recently,several investigators reported their experiences with laparoscopic gastrectomy of remnant gastric cancer. We report the case of an 83-year-old female patient who was diagnosed with remnant gastric cancer with obstruction. She underwent an entirely laparoscopic distal gastrectomy with colectomy because of direct invasion of the transverse colon. The opera...

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

    Directory of Open Access Journals (Sweden)

    Hua Xin

    2017-05-01

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

  8. ADAMTS1-mediated targeting of TSP-1 by PPARδ suppresses migration and invasion of breast cancer cells.

    Science.gov (United States)

    Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Hwang, Jung Seok; Hur, Jinwoo; Paek, Kyung Shin; Lim, Dae-Seog; Han, Sung Gu; Lee, Chi-Ho; Seo, Han Geuk

    2017-11-07

    Migration and invasion of cancer cells into surrounding tissue is a key stage of cancer metastasis. Here, we show that peroxisome proliferator-activated receptor (PPAR) δ regulates migration and invasion of human breast cancer cells via thrombospondin-1 (TSP-1) and its degrading protease, a disintegrin and metalloprotease domains with thrombospondin motifs 1 (ADAMTS1). Activation of PPARδ by GW501516, a specific ligand for PPARδ, led to marked inhibition in the cell migration and TSP-1 expression of breast cancer. These effects were suppressed by small interfering RNA-mediated knock-down of ADAMTS1, indicating that ADAMTS1 is involved in PPARδ-mediated inhibition of migration and TSP-1 expression in breast cancer cells. In addition, ligand-activated PPARδ upregulated expression of ADAMTS1 at the transcriptional level via binding of PPARδ to a direct repeat-1 site within the ADAMTS1 gene promoter. Furthermore, ligand-activated PPARδ suppressed invasion of breast cancer cells in an ADAMTS1-dependent manner. Taken together, these results demonstrate that PPARδ suppresses migration and invasion of breast cancer cells by downregulating TSP-1 in a process mediated by upregulation of ADAMTS1.

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

    DEFF Research Database (Denmark)

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

    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...... 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....

  10. Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

    OpenAIRE

    Clifford, Gary M.; de Vuyst, Hugo; Tenet, Vanessa; Plummer, Martyn; Tully, Stephen; Franceschi, Silvia

    2016-01-01

    Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type. Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa. Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR). Results: HPV detection was similar in 770 HIV-positive (91.2%) and 384...

  11. [Ldr brachytherapy, a minimally invasive alternative in the treatment of organ-confined prostate cancer].

    Science.gov (United States)

    Siegsmund, M; Musial, A; Weiss, J; Alken, P

    2001-09-01

    LDR Brachytherapy, a Minimally Invasive Alternative in the Treatment of Organ-Confined Prostate Cancer In den letzten Jahren erlebte die Brachytherapie mit permanenten Implantaten beim organbegrenzten Prostatakarzinom besonders in den USA, wo im Jahre 1999 mehr als 40 000 Implantationen durchgeführt wurden, eine Renaissance. Mit einer gewissen Verzögerung nimmt die Popularität dieser Methode auch in Europa immer mehr zu. Dies, obwohl die Brachytherapie keine absolut neue Methode in der Behandlung des Prostatakarzinoms ist, sie hat im Gegenteil eine lange Tradition. Copyright 2001 S. Karger GmbH, Freiburg

  12. 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.

  13. The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion.

    Science.gov (United States)

    Puddefoot, J R; Udeozo, U K I; Barker, S; Vinson, G P

    2006-09-01

    As breast cancer remains the most common cause of cancer death in women, there is a continuing need not only to further characterise the processes of cancer progression, but also to improve accuracy of prognostic markers. Breast epithelial cells express components of the renin angiotensin system and studies suggest that these may be altered in disease progression. In addition, altered integrin expression correlates with lymph node metastasis. The aim of this study was to investigate the relationship between angiotensin II (AII) and integrins in breast tissue and, in particular, their role in breast cancer cell metastasis. Using in vitro assays, AII (10(-6) M)-treated MCF-7 and T47D breast cancer cells both show reduced adhesion to extracellular matrix proteins collagen-, fibronectin- and laminin-coated wells (Plaminin-coated membranes (Pintegrin alpha3 and beta1. Using specific inhibitors, this was shown to occur through protein kinase C signalling. These data suggest that AII reduces cell adhesion and invasion through the type 1 receptor and that this effect may be due to reduced expression of integrins, and in particular alpha3 and beta1.

  14. Imaging Features for the Prediction of Extensive Intraductal Components in Invasive Cancer in Addition to the Histopathologic Grades

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hye Yoen; Kim, Keum Won; Park, Yong Sung; Cho, Yong Jun; Hwang, Cheol Mog; Kim, Hyun Jin; Sul, Hae Jung; Yoon, Dae Sung [Konyang University, College of Medicine, Nonsan (Korea, Republic of); Kim, Gyu Soon [Eulji University, College of Medicine, Daejeon (Korea, Republic of)

    2009-12-15

    To evaluate the usefulness of US and mammography in detecting extensive intraductal component (EIC) in invasive cancer and correlating the results with the histopathologic grade. We retrospectively reviewed the mammographic and sonographic features of 125 invasive breast cancers, classified as 'invasive cancer with EIC' (n=57) and 'invasive cancer without EIC' (n=68). The mammographic features are classified as microcalcifications only, microcalcifications beyond the soft tissue density, soft tissue density without microcalcification, and sonographic features classified according to ten sonographic suspicious features for malignancy by Stavros. We calculated sensitivities, specificities, positive predictive value, negative predictive value, and accuracy to correlate them with histologic grade. Microcalcifications on mammography, calcification, duct extension, and a branching pattern on sonography were found to be statistically significant predictors of EIC. Also, a thick echogenic halo, angular margin, microlobuation, taller than wide feature on sonography, and soft tissue shadow without microcalcification on mammography showed a decreased risk of EIC. In addition, the presence of a branching pattern is an indicator of high histologic grade (p<0.05). Microcalcification on mammography, calcification, duct extension, and branching pattern on sonography are an indicator of the presence of EIC in invasive cancer. In addition, when a branching pattern is present, the tumor tends to have a high histologic grade.

  15. An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

    KAUST Repository

    Tirinato, Luca

    2017-08-13

    For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  17. 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.

  18. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

    Directory of Open Access Journals (Sweden)

    Nicolas D. Prionas, MD, PhD

    2015-01-01

    Full Text Available Dedicated breast computed tomography (bCT generates high-resolution, three-dimensional images of the pendent uncompressed breast. Intravenous iodinated contrast during bCT provides additional physiologic information. In this case, a 10.0-mm invasive ductal carcinoma was visualized using contrast-enhanced breast CT one year before mammographic detection. Mammography four months before bCT was negative. The bCT contrast enhancement pattern closely matched the dynamic contrast-enhanced MRI obtained after diagnosis. Lesion enhancement at contrast-enhanced breast CT matched previously published enhancement values of breast cancer. Contrast-enhanced dedicated bCT provided high-resolution tomographic images and physiologic contrast enhancement data that facilitated the detection of an early breast cancer.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Minimally invasive surgery for endometrial cancer: does operative start time impact surgical and oncologic outcomes?

    Science.gov (United States)

    Slaughter, Katrina N; Frumovitz, Michael; Schmeler, Kathleen M; Nick, Alpa M; Fleming, Nicole D; dos Reis, Ricardo; Munsell, Mark F; Westin, Shannon N; Soliman, Pamela T; Ramirez, Pedro T

    2014-08-01

    Recent literature in ovarian cancer suggests differences in surgical outcomes depending on operative start time. We sought to examine the effects of operative start time on surgical outcomes for patients undergoing minimally invasive surgery for endometrial cancer. A retrospective review was conducted of patients undergoing minimally invasive surgery for endometrial cancer at a single institution between 2000 and 2011. Surgical and oncologic outcomes were compared between patients with an operative start time before noon and those with a surgical start time after noon. A total of 380 patients were included in the study (245 with start times before noon and 135 with start times after noon). There was no difference in age (p=0.57), number of prior surgeries (p=0.28), medical comorbidities (p=0.19), or surgical complexity of the case (p=0.43). Patients with surgery starting before noon had lower median BMI than those beginning after noon, 31.2 vs. 35.3 respectively (p=0.01). No significant differences were observed for intraoperative complications (4.4% of patients after noon vs. 3.7% of patients before noon, p=0.79), estimated blood loss (median 100 cc vs. 100 cc, p=0.75), blood transfusion rates (7.4% vs. 8.2%, p=0.85), and conversion to laparotomy (12.6% vs. 7.4%, p=0.10). There was no difference in operative times between the two groups (198 min vs. 216.5 min, p=0.10). There was no association between operative start time and postoperative non-infectious complications (11.9% vs. 11.0%, p=0.87), or postoperative infections (17.8% vs. 12.3%, p=0.78). Length of hospital stay was longer for surgeries starting after noon (median 2 days vs. 1 day, p=0.005). No differences were observed in rates of cancer recurrence (12.6% vs. 8.8%, p=0.39), recurrence-free survival (p=0.97), or overall survival (p=0.94). Our results indicate equivalent surgical outcomes and no increased risk of postoperative complications regardless of operative start time in minimally invasive

  1. Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer

    Directory of Open Access Journals (Sweden)

    Wojciech Krajewski

    2014-03-01

    Full Text Available Bladder cancer (BCA is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines – IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

  2. 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 aberra