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Sample records for cancer trends progress

  1. Skin Cancer Trends

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Skin Cancer Note: Javascript is disabled or is not supported ... Cervical Colorectal (Colon) Lung Ovarian Prostate Cancer Home Skin Cancer Trends Language: English Español (Spanish) Recommend on Facebook ...

  2. Progress against Prostate Cancer

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  3. Cancer Stem Cells Accountability in Progression of Head and Neck Squamous Cell Carcinoma: The Most Recent Trends!

    Directory of Open Access Journals (Sweden)

    Samapika Routray

    2014-01-01

    Full Text Available Cancer stem cells (CSCs play a major role in local recurrence and metastatic spread in head and neck squamous cell carcinomas (HNSCC. Evidence suggests that cancer stem cells are resistant to conventional therapy. So the emerging concepts of the role of cancer stem cells in the pathobiology of HNSCC should be understood carefully to be able to create new paradigms in treatment plans.

  4. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... inhibitor, can do an even better job of preventing breast cancer than the SERMs. Aromatase inhibitors stop an enzyme ...

  5. Declining death rates reflect progress against cancer.

    Directory of Open Access Journals (Sweden)

    Ahmedin Jemal

    Full Text Available BACKGROUND: The success of the "war on cancer" initiated in 1971 continues to be debated, with trends in cancer mortality variably presented as evidence of progress or failure. We examined temporal trends in death rates from all-cancer and the 19 most common cancers in the United States from 1970-2006. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed trends in age-standardized death rates (per 100,000 for all cancers combined, the four most common cancers, and 15 other sites from 1970-2006 in the United States using joinpoint regression model. The age-standardized death rate for all-cancers combined in men increased from 249.3 in 1970 to 279.8 in 1990, and then decreased to 221.1 in 2006, yielding a net decline of 21% and 11% from the 1990 and 1970 rates, respectively. Similarly, the all-cancer death rate in women increased from 163.0 in 1970 to 175.3 in 1991 and then decreased to 153.7 in 2006, a net decline of 12% and 6% from the 1991 and 1970 rates, respectively. These decreases since 1990/91 translate to preventing of 561,400 cancer deaths in men and 205,700 deaths in women. The decrease in death rates from all-cancers involved all ages and racial/ethnic groups. Death rates decreased for 15 of the 19 cancer sites, including the four major cancers, with lung, colorectum and prostate cancers in men and breast and colorectum cancers in women. CONCLUSIONS/SIGNIFICANCE: Progress in reducing cancer death rates is evident whether measured against baseline rates in 1970 or in 1990. The downturn in cancer death rates since 1990 result mostly from reductions in tobacco use, increased screening allowing early detection of several cancers, and modest to large improvements in treatment for specific cancers. Continued and increased investment in cancer prevention and control, access to high quality health care, and research could accelerate this progress.

  6. Targeting ECM Disrupts Cancer Progression

    DEFF Research Database (Denmark)

    Venning, Freja A; Wullkopf, Lena; Erler, Janine T

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the ex...... is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.......Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings......, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread...

  7. Trends and progress in system identification

    CERN Document Server

    Eykhoff, Pieter

    1981-01-01

    Trends and Progress in System Identification is a three-part book that focuses on model considerations, identification methods, and experimental conditions involved in system identification. Organized into 10 chapters, this book begins with a discussion of model method in system identification, citing four examples differing on the nature of the models involved, the nature of the fields, and their goals. Subsequent chapters describe the most important aspects of model theory; the """"classical"""" methods and time series estimation; application of least squares and related techniques for the e

  8. [Landscape classification: research progress and development trend].

    Science.gov (United States)

    Liang, Fa-Chao; Liu, Li-Ming

    2011-06-01

    Landscape classification is the basis of the researches on landscape structure, process, and function, and also, the prerequisite for landscape evaluation, planning, protection, and management, directly affecting the precision and practicability of landscape research. This paper reviewed the research progress on the landscape classification system, theory, and methodology, and summarized the key problems and deficiencies of current researches. Some major landscape classification systems, e. g. , LANMAP and MUFIC, were introduced and discussed. It was suggested that a qualitative and quantitative comprehensive classification based on the ideology of functional structure shape and on the integral consideration of landscape classification utility, landscape function, landscape structure, physiogeographical factors, and human disturbance intensity should be the major research directions in the future. The integration of mapping, 3S technology, quantitative mathematics modeling, computer artificial intelligence, and professional knowledge to enhance the precision of landscape classification would be the key issues and the development trend in the researches of landscape classification.

  9. Trends of cervical cancer in Greenland

    DEFF Research Database (Denmark)

    Sander, Bente B; Rebolj, Matejka; Lynge, Elsebeth

    2014-01-01

    supplemented this with data for 1980-2009 obtained from the Chief Medical Officer of Greenland. RESULTS: Incidence of cervical cancer was around 10 per 100 000 women (age-standardised, world population, ASW) in the 1950s, 30 per 100 000 in the 1960s, and in the 1980s around 60 per 100 000. From 1985 onwards......BACKGROUND: Due to its extraordinarily fast economic and social transition, virtually closed borders before 1940 and, moreover, that 85% of the population has the distinctive genetics of the Inuit, Greenland is a very interesting country to study cervical cancer from a historical perspective....... Nevertheless, little has been reported about long-term cancer trends in Greenland. Our aim was to describe and interpret the incidence of cervical cancer from 1950 to 2009. MATERIAL AND METHODS: We systematically searched PubMed for articles reporting the incidence of cervical cancer in Greenland. We...

  10. Cancer progression modeling using static sample data.

    Science.gov (United States)

    Sun, Yijun; Yao, Jin; Nowak, Norma J; Goodison, Steve

    2014-01-01

    As molecular profiling data continues to accumulate, the design of integrative computational analyses that can provide insights into the dynamic aspects of cancer progression becomes feasible. Here, we present a novel computational method for the construction of cancer progression models based on the analysis of static tumor samples. We demonstrate the reliability of the method with simulated data, and describe the application to breast cancer data. Our findings support a linear, branching model for breast cancer progression. An interactive model facilitates the identification of key molecular events in the advance of disease to malignancy.

  11. Zinc finger proteins in cancer progression

    OpenAIRE

    Jen, Jayu; Wang, Yi-Ching

    2016-01-01

    Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer...

  12. A novel web informatics approach for automated surveillance of cancer mortality trends.

    Science.gov (United States)

    Tourassi, Georgia; Yoon, Hong-Jun; Xu, Songhua

    2016-06-01

    Cancer surveillance data are collected every year in the United States via the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI). General trends are closely monitored to measure the nation's progress against cancer. The objective of this study was to apply a novel web informatics approach for enabling fully automated monitoring of cancer mortality trends. The approach involves automated collection and text mining of online obituaries to derive the age distribution, geospatial, and temporal trends of cancer deaths in the US. Using breast and lung cancer as examples, we mined 23,850 cancer-related and 413,024 general online obituaries spanning the timeframe 2008-2012. There was high correlation between the web-derived mortality trends and the official surveillance statistics reported by NCI with respect to the age distribution (ρ=0.981 for breast; ρ=0.994 for lung), the geospatial distribution (ρ=0.939 for breast; ρ=0.881 for lung), and the annual rates of cancer deaths (ρ=0.661 for breast; ρ=0.839 for lung). Additional experiments investigated the effect of sample size on the consistency of the web-based findings. Overall, our study findings support web informatics as a promising, cost-effective way to dynamically monitor spatiotemporal cancer mortality trends. PMID:27044930

  13. Trends of lung cancer mortality in Mexico.

    Science.gov (United States)

    Lazcano Ponce, E C; Tovar Guzman, V; Meneses Gonzalez, F; Rascon Pacheco, R A; Hernandez Avila, M

    1997-01-01

    Lung cancer (LC) is one of the most important public health problems in the world; 1,035,000 annual deaths are estimated each year and more than 80% of these are attributed to tobacco. The trend of lung cancer mortality in Mexico City from 1979 - 1993 was determined, as was the rate ratio of lung cancer mortality in 31 states in Mexico, taking Mexico City as a reference by means of a Poisson model. A strong linear regression model was used to evaluate the rate, where the dependent variable was LC mortality rate and the independent variable the year observed. In 15 years, 73,807 deaths from LC were reported, with an increase in mortality from 5.01 - 7.25 per 100,000 inhabitants. Mortality increases significantly after 60 years of age (B not equal to 0), ptax on cigarettes should be increased, smoking restricted in squares and public spaces, and the risks should be announced on cigarette packages, among other measures. With respect to other emergent risk factors, the sources of industrial pollution and toxic emissions should be regulated.

  14. Psychological aspect of cancer: From stressor to cancer progression

    OpenAIRE

    Yuan, Aihua; Wang, Shukui; Li, Zongfang; Huang, Chen

    2010-01-01

    Substantial evidence indicates that psychological stress can influence the incidence and progression of cancers, and adequate psychotherapies are beneficial to cancer patients. Recently, the mechanisms responsible for the effects of psychological stress on cancer cells have been extensively investigated at the systemic, biochemical and molecular levels. Accumulating data indicate that the effects of psychological stress on cancer cells are mainly mediated by key stress-related mediators and t...

  15. Dysadherin: a new player in cancer progression.

    OpenAIRE

    Nam, Jeong-Seok; Hirohashi, Setsuo; Wakefield, Lalage M.

    2007-01-01

    Dysadherin is a cancer-associated cell membrane glycoprotein that promotes experimental cancer metastasis. Here we review recent work that has provided insights into possible mechanisms of action of this newly recognized player in the cancer progression process. Dysadherin modulates cell phenotype in a number of ways, including down-regulation of E-cadherin-mediated cell adhesion, and up-regulation of chemokine production. In this way, expression of dysadherin in a tumor can influence both th...

  16. Muscarinic receptor signaling and colon cancer progression

    Institute of Scientific and Technical Information of China (English)

    Guofeng Xie; Jean-Pierre Raufman

    2016-01-01

    Due to the lack of effective treatments, advanced colorectal cancer (CRC) remains a leading cause of cancer death in the United States. Emerging evidence supports the observation that muscarinic receptor (MR) signaling plays a critical role in growth and progression of CRC. MR activation by acetylcholine and bile acids results in transactivation of epidermal growth factor receptors (EGFR) and post-EGFR signal transduction that enhances cell proliferation, migration, and invasion. Here, the authors review recent progress in understanding the molecular mechanisms underlying MR-mediated CRC progression and its therapeutic implications.

  17. Progress and controversies in developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Speiser Daniel E

    2005-04-01

    Full Text Available Abstract Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2 and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

  18. Membrane potential and cancer progression

    Directory of Open Access Journals (Sweden)

    Ming eYang

    2013-07-01

    Full Text Available Membrane potential (Vm, the voltage across the plasma membrane, arises because of the presence of different ion channels/transporters with specific ion selectivity and permeability. Vm is a key biophysical signal in non-excitable cells, modulating important cellular activities, such as proliferation and differentiation. Therefore, the multiplicities of various ion channels/transporters expressed on different cells are finely tuned in order to regulate the Vm. It is well established that cancer cells possess distinct bioelectrical properties. Notably, electrophysiological analyses in many cancer cell types have revealed a depolarized Vm that favors cell proliferation. Ion channels/transporters control cell volume and migration, and emerging data also suggest that the level of Vm has functional roles in cancer cell migration. In addition, hyperpolarization is necessary for stem cell differentiation. For example, both osteogenesis and adipogenesis are hindered in human mesenchymal stem cells under depolarizing conditions. Therefore, in the context of cancer, membrane depolarization might be important for the emergence and maintenance of cancer stem cells, giving rise to sustained tumor growth. This review aims to provide a broad understanding of the Vm as a bioelectrical signal in cancer cells by examining several key types of ion channels that contribute to its regulation. The mechanisms by which Vm regulates cancer cell proliferation, migration and differentiation will be discussed. In the long term, Vm might be a valuable clinical marker for tumor detection with prognostic value, and could even be artificially modified in order to inhibit tumor growth and metastasis.

  19. Temporal trend of mortality from major cancers in Xuanwei, China.

    Science.gov (United States)

    Lin, Hualiang; Ning, Bofu; Li, Jihua; Zhao, Guangqiang; Huang, Yunchao; Tian, Linwei

    2015-12-01

    Although a number of studies have examined the etiology of lung cancer in Xuanwei County, China, other types of cancer in this county have not been reported systematically. This study aimed to investigate the temporal trend of eight major cancers in Xuanwei County using data from three mortality surveys (1973-1975, 1990-1992, and 2004-2005). The Chinese population in 1990 was used as a standard population to calculate agestandardized mortality rates. Cancers of lung, liver, breast, brain, esophagus, leukemia, rectum, and stomach were identified as the leading cancers in this county in terms of mortality rate. During the three time periods, lung cancer remained as the most common type of cancer. The mortality rates for all other types of cancer were lower than those of the national average, but an increasing trend was observed for all the cancers, particularly from 1990-1992 to 2004-2005. The temporal trend could be partly explained by changes in risk factors, but it also may be due to the improvement in cancer diagnosis and screening. Further epidemiological studies are warranted to systematically examine the underlying reasons for the temporal trend of the major cancers in Xuanwei County.

  20. Progress against cancer in the Netherlands since the late 1980s: an epidemiological evaluation.

    NARCIS (Netherlands)

    Karim-Kos, H.E.; Kiemeney, L.A.L.M.; Louwman, M.W.; Coebergh, J.W.W.; Vries, E. de

    2012-01-01

    Progress against cancer through prevention and treatment is often measured by survival statistics only instead of analyzing trends in incidence, survival and mortality simultaneously because of interactive influences. This study combines these parameters of major cancers to provide an overview of th

  1. Interleukin-8 in breast cancer progression.

    Science.gov (United States)

    Todorović-Raković, Nataša; Milovanović, Jelena

    2013-10-01

    Interleukin-8 (IL-8) is a chemokine that has an autocrine and/or paracrine tumor-promoting role and significant potential as a prognostic and/or predictive cancer biomarker. In breast cancer, which is mostly determined by expression of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), IL-8 could play a specific role. IL-8 is highly expressed in ER- breast cancers, but it increases invasiveness and metastatic potential of both ER- and ER+ breast cancer cells. It is also highly expressed in HER2+ breast cancers. Because of the complex crosstalk between these receptors and IL-8, its role is mainly determined by delicate balance in their signaling pathways. Therefore, the main point of this review was to analyze the possible influence of IL-8 in breast cancer progression related to its interaction with ER and HER2 and the consequent therapeutic implications of these relations.

  2. Current progress in immunotherapy for pancreatic cancer.

    Science.gov (United States)

    Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth; Zheng, Lei

    2016-10-10

    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.

  3. Study Progress and Trends of Strategic Environmental Assessment in China

    Institute of Scientific and Technical Information of China (English)

    Cai Chunmiao; Shang Jincheng

    2009-01-01

    Strategic environmental assessment (SEA) in China has developed rapidly since it was introduced into China in the 1990s.Chinese government promulgated the Environmental Impact As-sessment Law of China (hereinafter referred to as the EIA Law) in 2002.In this law, it is stipulated clearly that regional and sector plans should be assessed.Through investigating materials and ana-lyzing literatures, this article analyses the practical and academic study achievements of SEA in China that have been achieved since the EIA Law was implemented, probes into the current situation of the main level of SEA in China--plan EIA, then summarizes the development characteristics, and eventually, puts forward the development trends of SEA in China.The research conclusions can offer the foundations for comprehending systematically the progress of SEA in China.

  4. Trends of Thyroid Cancer in Israel: 1980–2012

    Directory of Open Access Journals (Sweden)

    Lital Keinan-Boker

    2016-01-01

    Full Text Available Objectives: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980–2012, in light of the global trends. Methods: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. Results: In 1980–2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC range of 3.98–6.93, driven almost entirely by papillary carcinoma (APCs 5.75–8.86, while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980–2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC −1.07 with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders. Conclusions: The Israeli secular trends of thyroid cancer incidence (increasing, mortality (mostly stable, and survival (modestly increasing closely follow reported global trends.

  5. Trends of Thyroid Cancer in Israel: 1980–2012

    Science.gov (United States)

    Keinan-Boker, Lital; Silverman, Barbara G.

    2016-01-01

    Objectives: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980–2012, in light of the global trends. Methods: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. Results: In 1980–2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98–6.93, driven almost entirely by papillary carcinoma (APCs 5.75–8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980–2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC −1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders. Conclusions: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends. PMID:26886958

  6. Cost trend analysis of initial cancer treatment in Taiwan.

    Directory of Open Access Journals (Sweden)

    Tsai-Yun Li

    Full Text Available BACKGROUND: Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment. METHODOLOGY/PRINCIPAL FINDINGS: The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05. Hospitalization costs comprised the largest portion of payments for all cancers. During 1996-2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05. In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share. CONCLUSIONS/SIGNIFICANCE: In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit

  7. Cancer initiation and progression: an unsimplifiable complexity

    Directory of Open Access Journals (Sweden)

    Frezza Eldo E

    2006-10-01

    Full Text Available Abstract Background Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated. Conclusion There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours.

  8. Trends in lung cancer incidence rates, Oklahoma 2005-2010.

    Directory of Open Access Journals (Sweden)

    Dana S Mowls

    Full Text Available Lung cancer is the second most frequently diagnosed cancer among men and women in the United States. With cigarette smoking causing the majority of cases, patterns in lung cancer are often monitored to understand the impact of anti-tobacco efforts. The purpose of this research was to investigate trends in lung cancer incidence rates for the period 2005-2010 in Oklahoma.Data on Oklahoma's incident cases of lung cancer (2005-2010 were obtained from the Centers for Disease Control and Prevention WONDER system. Annual percent change (APC was calculated by linear regression to characterize trends in lung cancer incidence rates over time for the overall population, by gender, by age group, and by age group within gender. Rates were considered to increase or decrease if the p-value for trend was <0.05.From 2005 through 2010, lung cancer incidence rates declined from 81.96 to 68.19 per 100,000 population, with an APC of -3.58% (p-value: 0.0220. When subgroups were examined, declines were observed among all males (APC: -4.25%; p-value: 0.0270, males <65 years (APC: -5.32%; p-value: 0.0008, females <65 years (APC: -4.85%; p-value: 0.0044, and persons aged 55-64 years (APC: -6.38%; p-value: 0.0017.Declines in lung cancer incidence rates occurred during 2005-2010 among the overall population and within select demographic groups in Oklahoma. Although trends were stable for several demographic groups, rates of lung cancer incidence were lower in 2010 compared to 2005. Continued evidence-based tobacco control efforts are needed to ensure further reductions in lung cancer incidence rates in the state of Oklahoma.

  9. Motesanib diphosphate in progressive differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Sherman, Steven I; Wirth, Lori J; Droz, Jean-Pierre;

    2008-01-01

    point was an objective response as assessed by an independent radiographic review. Additional end points included the duration of the response, progression-free survival, safety, and changes in serum thyroglobulin concentration. RESULTS: Of the 93 patients, 57 (61%) had papillary thyroid carcinoma......BACKGROUND: The expression of vascular endothelial growth factor (VEGF) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome. Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet......-derived growth-factor receptor, and KIT. METHODS: In an open-label, single-group, phase 2 study, we treated 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer with 125 mg of motesanib diphosphate, administered orally once daily. The primary end...

  10. Relating Single Cell Heterogeneity To Genotype During Cancer Progression

    Science.gov (United States)

    Rajaram, Satwik

    2013-03-01

    Progression of normal cells towards cancer is driven by a series of genetic changes. Traditional population-averaged measurements have found that cell signalling activities are increasingly altered during this progression. Despite the fact that cancer cells are known to be highly heterogeneous, the response of individual pathways to specific genetic changes remains poorly characterized at a single cell level. Do signalling alterations in a pathway reflect a shift of the whole population, or changes to specific subpopulations? Are alterations to pathways independent, or are cells with alterations in one pathway more likely to be abnormal in another due to crosstalk? We are building a computational framework that analyzes immunofluorescence microscopy images of cells to identify alterations in individual pathways at a single-cell level. A primary novelty of our approach is a ``change of basis'' that allows us to understand signalling in cancer cells in terms of the much better understood patterns of signalling in normal cells. This allows us to model heterogeneous populations of cancer cells as a mixture of distinct subpopulations, each with a specific combination of signalling pathways altered beyond the normal baseline. We used this framework to analyze human bronchial epithelial cell lines containing a series of genetic modifications commonly seen in lung cancer. We confirmed expected trends (such as a population-wide epithelial mesenchymal transition following the last of our series of modifications) and are presently studying the relation between the mutational profiles of cancer cells and pathway crosstalk. Our framework will help establish a more natural basis for future investigations into the phenotype-genotype relationship in heterogeneous populations.

  11. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities.

    Science.gov (United States)

    DeSantis, Carol E; Siegel, Rebecca L; Sauer, Ann Goding; Miller, Kimberly D; Fedewa, Stacey A; Alcaraz, Kassandra I; Jemal, Ahmedin

    2016-07-01

    In this article, the American Cancer Society provides the estimated number of new cancer cases and deaths for blacks in the United States and the most recent data on cancer incidence, mortality, survival, screening, and risk factors for cancer. Incidence data are from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, and mortality data are from the National Center for Health Statistics. Approximately 189,910 new cases of cancer and 69,410 cancer deaths will occur among blacks in 2016. Although blacks continue to have higher cancer death rates than whites, the disparity has narrowed for all cancers combined in men and women and for lung and prostate cancers in men. In contrast, the racial gap in death rates has widened for breast cancer in women and remained level for colorectal cancer in men. The reduction in overall cancer death rates since the early 1990s translates to the avoidance of more than 300,000 deaths among blacks. In men, incidence rates from 2003 to 2012 decreased for all cancers combined (by 2.0% per year) as well as for the top 3 cancer sites (prostate, lung, and colorectal). In women, overall rates during the corresponding time period remained unchanged, reflecting increasing trends in breast cancer combined with decreasing trends in lung and colorectal cancer rates. Five-year relative survival is lower for blacks than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Progress in reducing cancer death rates could be accelerated by ensuring equitable access to prevention, early detection, and high-quality treatment. CA Cancer J Clin 2016;66:290-308. © 2016 American Cancer Society. PMID:26910411

  12. Current trends in staging rectal cancer

    Institute of Scientific and Technical Information of China (English)

    Abdus Samee; Chelliah Ramachandran Selvasekar

    2011-01-01

    Management of rectal cancer has evolved over the years.In this condition preoperative investigations assist in deciding the optimal treatment.The relation of the tumor edge to the circumferential margin (CRM) is an important factor in deciding the need for neoadjuvant treatment and determines the prognosis.Those with threatened or involved margins are offered long course chemoradiation to enable R0 surgical resection.Endoanal ultrasound (EUS) is useful for tumor (T) staging;hence EUS is a useful imaging modality for early rectal cancer.Magnetic resonance imaging (MRI) is useful for assessing the mesorectum and the mesorectal fascia which has useful prognostic significance and for early identification of local recurrence.Computerized tomography (CT) of the chest,abdomen and pelvis is used to rule out distant metastasis.Identification of the malignant nodes using EUS,CT and MRI is based on the size,morphology and internal characteristics but has drawbacks.Most of the common imaging techniques are suboptimal for imaging following chemoradiation as they struggle to differentiate fibrotic changes and tumor.In this situation,EUS and MRI may provide complementary information to decide further treatment.Functional imaging using positron emission tomography (PET) is useful,particularly PET/CT fusion scans to identify areas of the functionally hot spots.In the current state,imaging has enabled the multidisciplinary team of surgeons,oncologists,radiologists and pathologists to decide on the patient centered management of rectal cancer.In future,functional imaging may play an active role in identifying patients with lymph node metastasis and those with residual and recurrent disease following neoadjuvant chemoradiotherapy.

  13. Cancer stem cells: progress and challenges in lung cancer.

    Science.gov (United States)

    Templeton, Amanda K; Miyamoto, Shinya; Babu, Anish; Munshi, Anupama; Ramesh, Rajagopal

    2014-01-01

    The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called "cancer stem cells" (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs. PMID:27358855

  14. Bedtime misalignment and progression of breast cancer

    Science.gov (United States)

    Hahm, Bong-Jin; Jo, Booil; Dhabhar, Firdaus S.; Palesh, Oxana; Aldridge-Gerry, Arianna; Bajestan, Sepideh N.; Neri, Eric; Nouriani, Bita; Spiegel, David; Zeitzer, Jamie M.

    2016-01-01

    Disruption of circadian rhythms, which frequently occurs during night shift work, may be associated with cancer progression. The effect of chronotype (preference for behaviors such as sleep, work, or exercise to occur at particular times of day, with an associated difference in circadian physiology) and alignment of bedtime (preferred vs. habitual), however, have not yet been studied in the context of cancer progression in women with breast cancer. Chronotype and alignment of actual bedtime with preferred chronotype were examined using the Morningness–Eveningness Scale (MEQ) and sleep-wake log among 85 women with metastatic breast cancer. Their association with disease-free interval (DFI) was retrospectively examined using the Cox proportional hazards model. Median DFI was 81.9 months for women with aligned bedtimes (“going to bed at preferred bedtime”) (n=72), and 46.9 months for women with misaligned bedtimes (“going to bed later or earlier than the preferred bedtime”) (n=13) (log rank p=0.001). In a multivariate Cox proportional hazard model, after controlling for other significant predictors of DFI, including chronotype (morning type/longer DFI; HR=0.539, 95% CI=0.320–0.906, p=0.021), estrogen receptor (ER) status at initial diagnosis (negative/shorter DFI; HR=2.169, 95% CI=1.124–4.187, p=0.028) and level of natural-killer cell count (lower levels/shorter DFI; HR=1.641, 95% CI=1.000–2.695, p=0.050), misaligned bedtimes was associated with shorter DFI, compared to aligned bedtimes (HR=3.180, 95% CI=1.327–7.616, p=0.018). Our data indicate that a misalignment of bedtime on a daily basis, an indication of circadian disruption, is associated with more rapid breast cancer progression as measured by DFI. Considering the limitations of small sample size and study design, a prospective study with a larger sample is necessary to explore their causal relationship and underlying mechanisms. PMID:24156520

  15. Trends in incidence of gallbladder cancer – Indian scenario

    Directory of Open Access Journals (Sweden)

    Nandagudi Srinivasa Murthy

    2011-01-01

    Full Text Available Nandagudi Srinivasa Murthy1, Dinesh Rajaram1, MS Gautham1, NS Shivraj1, Sreekantaiah Pruthvish1, Preethi Sara George2, Aleyamma Mathew21MS Ramaiah Medical College, Bangalore, Karnataka, India; 2Regional Cancer Centre, Thiruvananthapuram, Kerala, IndiaBackground: Reports of increasing incidence rates of gallbladder cancer in several areas in India prompted the analysis of time trends. The present communication reports its geographic and gender distribution and trends in occurrence of this disease over time.Materials and methods: The data published in Cancer Incidence in Five Continents for various Indian registries for different periods and/or publication by the individual registries served as the source material. Mean annual percentage change (MAPC in incidence rates was computed using relative difference between two time periods (earliest and latest, and estimation of annual percent change (EAPC was computed by log-linear regression model.Results: In 1998–2006, incidence rates of gallbladder cancer (age-standardized rate, ASR were high in Delhi and Kamrup ((3.6 and 7.4 and (5.3 and 14.3 per 105 person years in males and females, respectively and lowest in Aurangabad, 0.0 in both genders. The incidence rate revealed an increase in all registries. MAPC in ASR ranged from 1.0% to 8.10%. EAPC for Mumbai, Chennai, and Bangalore for the period 1983–2002 revealed statistically significant increase in crude, age-standardized, and truncated rate (TR (35–64 years incidence rates. The largest EAPC in ASR was in Chennai (almost 6.0% in both genders and smallest in Mumbai (3.5% and 2.1% in males and females, respectively.Conclusions: Statistically significant increase in gallbladder cancer incidence rates has been reported for Mumbai, Chennai, and Bangalore. Further studies are required in identifying factors that may be operative in etiology of cancer of gallbladder.Keywords: gallbladder cancer, trend, Indian scenario, calendar year

  16. Antioxidants accelerate lung cancer progression in mice.

    Science.gov (United States)

    Sayin, Volkan I; Ibrahim, Mohamed X; Larsson, Erik; Nilsson, Jonas A; Lindahl, Per; Bergo, Martin O

    2014-01-29

    Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.

  17. Antioxidants accelerate lung cancer progression in mice.

    Science.gov (United States)

    Sayin, Volkan I; Ibrahim, Mohamed X; Larsson, Erik; Nilsson, Jonas A; Lindahl, Per; Bergo, Martin O

    2014-01-29

    Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production. PMID:24477002

  18. Nuclear morphometry, nucleomics and prostate cancer progression

    Institute of Scientific and Technical Information of China (English)

    Robert W Veltri; Christhunesa S Christudass; Sumit Isharwal

    2012-01-01

    Prostate cancer (PCa) results from a multistep process.This process includes initiation,which occurs through various aging events and multiple insults (such as chronic infection,inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks),followed by a multistep process of progression.These steps include several genetic and epigenetic alterations,as well as alterations to the chmmatin structure,which occur in response to the carcinogenic stress-related events that sustain proliferative signaling.Events such as evading growth suppressors,resisting cell death,enabling replicative immortality,inducing angiogenesis,and activating invasion and metastasis are readily observed.In addition,in conjunction with these critical drivers of caminogenesis,other factors related to the etiopathogenesis of PCa,involving energy metabolism and evasion of the immune surveillance system,appear to be involved.In addition,when cancer spread and metastasis occur,the 'tumor microenvironment' in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a 'seed and soil' site where PCa proliferation and growth may occur over time.When PCa is initiated and progression ensues,significant alterations in nuclear size,shape and hetemchmmatin (DNA transcription) organization are found,and key nuclear transcriptional and structural proteins,as well as multiple nuclear bodies can lead to precancerous and malignant changes.These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management.

  19. Global progress against cancer-challenges and oppor tunities

    Institute of Scientific and Technical Information of China (English)

    Frédéric Biemar; Margaret Foti

    2013-01-01

    The last ten years have seen remarkable progress in cancer research. However, despite significant breakthroughs in the understanding, prevention, and treatment of cancer, the disease continues to affect millions of people worldwide. Cancer’s complexity compounded with ifnancial, policy and regulatory roadblocks has slowed the rate of progress being made against cancer. In this paper, we review a few of the most recent breakthroughs that are fueling medical advances and bringing new hope for patients affected by this devastating disease. We also address the challenges facing us and the opportunities to accelerate future progress against cancer. The efforts of the American Association for Cancer Research (AACR) to address the cancer burden already extend beyond the borders of the United States of America. hTe AACR is committed to increasing its efforts to stem the tide of cancer worldwide by promoting innovative programs, strategies, and initiatives for cancer researchers and all those engaged in cancer-related biomedical sciences around the world.

  20. Cancer burden trends in Umbria region using a joinpoint regression

    Directory of Open Access Journals (Sweden)

    Giuseppe Michele Masanotti

    2015-09-01

    Full Text Available INTRODUCTION. The analysis of the epidemiological data on cancer is an important tool to control and evaluate the outcomes of primary and secondary prevention, the effectiveness of health care and, in general, all cancer control activities. MATERIALS AND METHODS. The aim of the this paper is to analyze the cancer mortality in the Umbria region from 1978 to 2009 and incidence from 1994-2008. Sex and site-specific trends for standardized rates were analyzed by "joinpoint regression", using the surveillance epidemiology and end results (SEER software. RESULTS. Applying the jointpoint analyses by sex and cancer site, to incidence spanning from 1994 to 2008 and mortality from 1978 to 2009 for all sites, both in males and females, a significant joinpoint for mortality was found; moreover the trend shape was similar and the joinpoint years were very close. In males standardized rate significantly increased up to 1989 by 1.23% per year and significantly decreased thereafter by -1.31%; among females the mortality rate increased in average of 0.78% (not significant per year till 1988 and afterward significantly decreased by -0.92% per year. Incidence rate showed different trends among sexes. In males was practically constant over the period studied (not significant increase 0.14% per year, in females significantly increased by 1.49% per year up to 2001 and afterward slowly decreased (-0.71% n.s. estimated annual percent change − EAPC. CONCLUSIONS. For all sites combined trends for mortality decreased since late '80s, both in males and females; such behaviour is in line with national and European Union data. This work shows that, even compared to health systems that invest more resources, the Umbria public health system achieved good health outcomes.

  1. Global trends of lung cancer mortality and smoking prevalence.

    Science.gov (United States)

    Islami, Farhad; Torre, Lindsey A; Jemal, Ahmedin

    2015-08-01

    Lung cancer killed approximately 1,590,000 persons in 2012 and currently is the leading cause of cancer death worldwide. There is large variation in mortality rates across the world in both males and females. This variation follows trend of smoking, as tobacco smoking is responsible for the majority of lung cancer cases. In this article, we present estimated worldwide lung cancer mortality rates in 2012 using the World Health Organization (WHO) GLOBOCAN 2012 and changes in the rates during recent decades in select countries using WHO Mortality Database. We also show smoking prevalence and trends globally and at the regional level. By region, the highest lung cancer mortality rates (per 100,000) in 2012 were in Central and Eastern Europe (47.6) and Eastern Asia (44.8) among males and in Northern America (23.5) and Northern Europe (19.1) among females; the lowest rates were in sub-Saharan Africa in both males (4.4) and females (2.2). The highest smoking prevalence among males is generally in Eastern and South-Eastern Asia and Eastern Europe, and among females is in European countries, followed by Oceania and Northern and Southern America. Many countries, notably high-income countries, have seen a considerable decrease in smoking prevalence in both males and females, but in many other countries there has been little decrease or even an increase in smoking prevalence. Consequently, depending on whether or when smoking prevalence has started to decline, the lung cancer mortality trend is a mixture of decreasing, stable, or increasing. Despite major achievements in tobacco control, with current smoking patterns lung cancer will remain a major cause of death worldwide for several decades. The main priority to reduce the burden of lung cancer is to implement or enforce effective tobacco control policies in order to reduce smoking prevalence in all countries and prevent an increase in smoking in sub-Saharan Africa and women in low- and middle-income countries (LMICs).

  2. Progression of Recent Warming Trends Across the Continents and Oceans

    Science.gov (United States)

    Abram, N.

    2014-12-01

    As part of the PAGES (Past Global Changes) Ocean2k project1-2 we examine the features of recent sea surface temperature trends in ocean regions where palaeoclimate data allow for moderate to high-resolution reconstructions that extend back over several centuries. Centennial-scale resolution marine observations independently suggest that the global ocean cooling trend observed from 0-1800 CE was reversed in the last two centuries. Building on the results of earlier continental-scale temperature reconstructions from the PAGES 2k community3, we compare the initiation point for recent significant warming between various land and ocean regions. Preliminary results suggest recent significant warming in the tropical oceans was near synchronous with warming of the Northern Hemisphere land masses, in contrast with a potential poleward lag in warming of the Southern Hemisphere land masses. Multi-model climate simulations are used to assess where there is high fidelity between recent warming trends determined by palaeoclimate observations and simulations, and to examine regions of data-model divergence. References: 1. Tierney, J.E., Abram, N.J., Anchukaitis, K.J., Evans, M.N., Giry, C., Kilbourne, K.H., Saenger, C.P., Wu, H.C., Zinke, J. (in prep). Tropical sea-surface temperatures for the past 400 years reconstructed from coral archives. 2. PAGES Ocean2k LR Group (in prep.) Robust global ocean cooling trend for the pre-industrial Common Era. 3. PAGES 2k Consortium (2013). Continental-scale temperature variability during the last two millennia. doi: 10.1038/NGEO1797 Website: http://www.pages-igbp.org/workinggroups/ocean2k

  3. On the rising trends of incidence and prognosis for breast cancer patients diagnosed 1975-2004: a long-term population-based study in southeastern Netherlands.

    NARCIS (Netherlands)

    Louwman, W.J.; Voogd, A.C.; Dijck, J.A.A.M. van; Nieuwenhuijzen, G.A.P; Ribot, J.; Pruijt, J.F.M.; Coebergh, J.W.W.

    2008-01-01

    BACKGROUND: Much progress has been made in the early diagnosis and treatment of breast cancer. We have assessed the changing burden of this disease, by means of a comprehensive description of trends in incidence, survival, and mortality. METHODS: Data on breast cancer patients diagnosed between 1975

  4. Expression of OATP family members in hormone-related cancers: potential markers of progression.

    Directory of Open Access Journals (Sweden)

    Heather Pressler

    Full Text Available The organic anion transporting polypeptide (OATP family of transporters has been implicated in prostate cancer disease progression probably by transporting hormones or drugs. In this study, we aimed to elucidate the expression, frequency, and relevance of OATPs as a biomarker in hormone-dependent cancers. We completed a study examining SLCO1B3, SLCO1B1 and SLCO2B1 mRNA expression in 381 primary, independent patient samples representing 21 cancers and normal tissues. From a separate cohort, protein expression of OATP1B3 was examined in prostate, colon, and bladder tissue. Based on expression frequency, SLCO2B1 was lower in liver cancer (P = 0.04 which also trended lower with decreasing differentiation (P = 0.004 and lower magnitude in pancreatic cancer (P = 0.05. SLCO2B1 also had a higher frequency in thyroid cancer (67% than normal (0% and expression increased with stage (P = 0.04. SLCO1B3 was expressed in 52% of cancerous prostate samples and increased SLCO1B3 expression trended with higher Gleason score (P = 0.03. SLCO1B3 expression was also higher in testicular cancer (P = 0.02. SLCO1B1 expression was lower in liver cancer (P = 0.04 which trended lower with liver cancer grade (P = 0.0004 and higher with colon cancer grade (P = 0.05. Protein expression of OATP1B3 was examined in normal and cancerous prostate, colon, and bladder tissue samples from an independent cohort. The results were similar to the transcription data, but showed distinct localization. OATPs correlate to differentiation in certain hormone-dependent cancers, thus may be useful as biomarkers for assessing clinical treatment and stage of disease.

  5. Dietary energy balance modulates ovarian cancer progression and metastasis

    OpenAIRE

    Al-Wahab, Zaid; Tebbe, Calvin; Chhina, Jasdeep; Dar, Sajad A.; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2014-01-01

    A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian ...

  6. Is human cytomegalovirus associated with breast cancer progression?

    OpenAIRE

    Utrera-Barillas, Dolores; Valdez-Salazar, Hilda-Alicia; Gómez-Rangel, David; Alvarado-Cabrero, Isabel; Aguilera, Penélope; Gómez-Delgado, Alejandro; Ruiz-Tachiquin, Martha-Eugenia

    2013-01-01

    Background It has been hypothesized that human cytomegalovirus (HCMV) may be associated with breast cancer progression. However, the role of HCMV infection in breast cancer remains controversial. We aimed to assess whether HCMV genes (UL122 and UL83) could be detected in breast carcinomas and reinvestigated their possible association with breast cancer progression. DNA from paraffin-embedded tissues was analyzed by real-time PCR. We investigated 20 fibroadenomas and 27 primary breast carcinom...

  7. Targeting clotting proteins in cancer therapy - progress and challenges.

    Science.gov (United States)

    Ruf, Wolfram; Rothmeier, Andrea S; Graf, Claudine

    2016-04-01

    Cancer-associated thrombosis remains a significant complication in the clinical management of cancer and interactions of the hemostatic system with cancer biology continue to be elucidated. Here, we review recent progress in our understanding of tissue factor (TF) regulation and procoagulant activation, TF signaling in cancer and immune cells, and the expanding roles of the coagulation system in stem cell niches and the tumor microenvironment. The extravascular functions of coagulant and anti-coagulant pathways have significant implications not only for tumor progression, but also for the selection of appropriate target specific anticoagulants in the therapy of cancer patients. PMID:27067961

  8. Survival trends in gastric cancer patients of Northeast China

    Institute of Scientific and Technical Information of China (English)

    HaoZhang; Ling—LingSun; Yan—LiMeng; Guang-YuSong; ]ing-.1ingHu; PingLu; BinJl

    2011-01-01

    AIM: To describe survival trends in patients in Northeast China diagnosed as gastric cancer. METHODS: A review of all inpatient and outpatient records of gastric cancer patients was conducted in the First Affiliated Hospital of China Medical University. All the gastric cancer patients who satisfied the inclusion criteria from January 1, 1980 through December 31, 2003 were included in the study. The main outcomes were based on median survival and 3-year and 5-year survival rates, by decade of diagnosis. RESULTS: From 1980 through 2003, the median survival for patients with gastric cancer (n = 1604) increased from 33 mo to 49 mo. The decade of diagnosis was not significantly associated with patient survival for gastric cancer (P = 0.084 for overall survival, and P = 0.150 for 5-year survival); however, the survival rate of the 2000s was remarkably higher than that of the 1980s (P = 0.019 for overall survival, and P = 0.027 for 5-year survival).CONCLUSION: There was no significant difference of survival among each period; however, the survival rate of the 2000s was remarkably higher than that of the 1980s.

  9. Better environmental decision making - recent progress and future trends.

    Science.gov (United States)

    Pollard, S J T; Davies, G J; Coley, F; Lemon, M

    2008-08-01

    Recent trends in risk-based decision making are reviewed in relation to novel developments in comparative risk analysis, strategic risk analysis, weight of evidence frameworks, and participative decision making. Delivery of these innovations must take account of organisational capabilities in risk management and the institutional culture that implements decision on risk. We stress the importance of managing risk knowledge within organisations, and emphasise the use of core criteria for effective risk-based decisions by reference to decision process, implementation and the security of strategic added value. PMID:18774589

  10. Current cancer incidence and trends in Yaounde, Cameroon

    Directory of Open Access Journals (Sweden)

    Enow Orock GE

    2014-05-01

    Full Text Available Background: Except for some information on relative frequencies of different cancers in selected areas, the epidemiology of cancer in Cameroon is relatively unknown. Though there is no reliable data on its incidence and pattern, with an estimated 15,000 new cases diagnosed annually and a prevalence of about 25.000 cases throughout the country, cancer is being increasingly recognized as a public health problem in Cameroon. The Yaounde Cancer Registry is a population registry physically located at the General Hospital Yaounde that has been operating since 2004. It collects data from about 20 sources that cover the entire population of Yaounde estimated in 2010 at about 1,299,369. Objectives: The objective of this study was to find out the incidence and trends of cancer in the Yaounde population in the period 2004 – 2006/2010 – 2011. It is hoped that this will enable policy makers, health providers and other stake holders plan appropriate health management policy in this population. Materials and Methods: This report presents the cancer incidence for 5 years, 2004 – 2006/2010 – 2011 in the Yaounde population estimated at 1,299,369. Data of the Yaounde Cancer Registry was reviewed for the period under study using Canreg5 software. Only malignant cases registered during the period under study were used in the analysis while benign and other uncertain tumours were excluded. The 2010 census estimates by the National Institute of Statistics was employed to calculate the incidence, age-standardized and crude rates. Other software like excel, epi info were also used for analysis. Survival studies were not carried out in this study. Results: A total of 4,689 new malignant cases were reported, of which 2,901 (68% were females and 1,788 (32% were males. The incidence showed an average of 358 for men and 580 for women. The average age of cancer patients in Yaounde is 44.8 years. Morphologically confirmed cases accounted for 89% .The annual number of

  11. Progress and trend of narrow-linewidth lasers

    Institute of Scientific and Technical Information of China (English)

    CHEN; HaiQin; JIANG; YanYi; BI; ZhiYi; MA; LongSheng

    2013-01-01

    High frequency stability, narrow-linewidth lasers have been long dreamed of since the invention of the laser. They have recently developed dramatically due to the advent of optical clocks. State-of-the-art narrow-linewidth lasers have been constructed by using the Pound-Drever-Hall (PDH) technique to lock the laser frequencies to the resonance of ultra-stable external optical cavities with high finesse. This paper introduces the developments of narrow-linewidth lasers, with a focus on the improvements of length stability of optical reference cavities, including optical cavity designs of vibration insensitivity and low thermal noise. Future trends and alternative methods for narrow-linewidth lasers are also discussed.

  12. Research Progress and Development Trend of Mycelial Pellets

    Directory of Open Access Journals (Sweden)

    Lixin Li

    2015-06-01

    Full Text Available Mycelial pellets are generated by the fermentation of microorganisms as a particle, it has good biological activity, rapid subsidence performance and simple solid-liquid separation technology, so that it can better be used in fermentation production, wastewater treatment and as biological carrier. The researches of using mycelial pellets to ferment production, treat some kinds of wastewater as biological adsorbent and enhance efficiency of treatment wastewater as bio-carrier, were discussed in detail. Development trend of mycelial pellets was presented at end of the article. It was also pointed out that the mycelial pellets as bio-carrier or biological adsorbent will be considered as a wide range of application prospects in wastewater treatment.

  13. Research progress and development trends of highway tunnels in China

    Institute of Scientific and Technical Information of China (English)

    Chuan He; Bo Wang

    2013-01-01

    The highway tunnel system in China has in recent years surpassed Europe, the United States, and other developed countries in terms of mileage, scale, complexity, and technical achievement. Much scientific research has been conducted, and the results have greatly facilitated the rapid development of China’s highway tunnel building capacity. This article presents the historical development of highway tunneling in China, according to specific charac-teristics based on construction and operation. It provides a systematic analysis of the major achievements and chal-lenges with respect to construction techniques, operation, monitoring, repair, and maintenance. Together with future trends of highway tunneling in China, suggestions have been made for further research, and development prospects have been identified with the aim of laying the foundation for a Chinese-style highway tunnel construction method and technical architecture.

  14. Esophageal Cancer in Canada: Trends according to Morphology and Anatomical Location

    Directory of Open Access Journals (Sweden)

    Michael C Otterstatter

    2012-01-01

    Full Text Available BACKGROUND: Esophageal adenocarcinoma has one of the fastest rising incidence rates and one of the lowest survival rates of any cancer type in the Western world. However, in many countries, trends in esophageal cancer differ according to tumour morphology and anatomical location. In Canada, incidence and survival trends for esophageal cancer subtypes are poorly known.

  15. CXCL5 Promotes Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Lesa A Begley

    2008-03-01

    Full Text Available CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. Unlike many other chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and macrophage and nonimmune (epithelial, endothelial, and fibroblastic cell types. The current study was intended to determine which of these cell types express CXCL5 in normal and malignant human prostatic tissues, whether expression levels correlated with malignancy and whether CXCL5 stimulated biologic effects consistent with a benign or malignant prostate epithelial phenotype. The results of these studies show that CXCL5 protein expression levels are concordant with prostate tumor progression, are highly associated with inflammatory infiltrate, and are frequently detected in the lumens of both benign and malignant prostate glands. Exogenous administration of CXCL5 stimulates cellular proliferation and gene transcription in both nontransformed and transformed prostate epithelial cells and induces highly aggressive prostate cancer cells to invade through synthetic basement membrane in vitro. These findings suggest that the inflammatory mediator, CXCL5, may play multiple roles in the etiology of both benign and malignant proliferative diseases in the prostate.

  16. Progress in Gene Therapy for Prostate Cancer

    OpenAIRE

    KamranAliAhmed; BrianJamesDavis; TorrenceMWilson; GregoryAWiseman; MarkJFederspiel; JohnCMorris

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our...

  17. Epidemiologic contributions to recent cancer trends among HIV-infected people in the United States

    Science.gov (United States)

    Robbins, Hilary A.; Shiels, Meredith S.; Pfeiffer, Ruth M.; Engels, Eric A.

    2016-01-01

    Objective HIV-infected people have elevated risk for some cancers. Changing incidence of these cancers over time may reflect changes in three factors: HIV population demographic structure (e.g. age distribution), general population (background) cancer rates, and HIV-associated relative risks. We assessed the contributions of these factors to time trends for 10 cancers during 1996–2010. Design Population-based registry linkage study. Methods We applied Poisson models to data from the U.S. HIV/AIDS Cancer Match Study to estimate annual percent changes (APCs) in incidence rates of AIDS-defining cancers (ADCs: Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), and cervical cancer) and 7 non-AIDS-defining cancers (NADCs). We evaluated HIV-infected cancer trends with and without adjustment for demographics, trends in background rates, and trends in standardized incidence ratios (SIRs, to capture relative risk). Results Cancer rates among HIV-infected people rose over time for anal (APC 3.8%), liver (8.5%), and prostate (9.8%) cancers, but declined for KS (1996–2000: −29.3%; 2000–2010: −7.8%), NHL (1996–2003: −15.7%; 2003–2010: −5.5%), cervical cancer (−11.1%), Hodgkin lymphoma (HL, −4.0%), and lung cancer (−2.8%). Breast and colorectal cancer incidence did not change over time. Based on comparison to adjusted models, changing demographics contributed to trends for KS and breast, colorectal, liver, lung, and prostate cancers (all p<0.01). Trends in background rates were notable for liver (APC 5.6%) and lung (−3.2%) cancers. SIRs declined for ADCs, HL (APC −3.2%), and lung cancer (−4.4%). Conclusions Demographic shifts influenced several cancer trends among HIV-infected individuals. Falling relative risks largely explained ADC declines, while background incidence contributed to some NADC trends. PMID:24300545

  18. Targeting the extracellular matrix to disrupt cancer progression

    Directory of Open Access Journals (Sweden)

    Freja Albjerg Venning

    2015-10-01

    Full Text Available Metastatic complications are responsible for more than 90% of cancer related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multi-step process, with each step involving intricate cross-talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM. Many ECM proteins are significantly de-regulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.

  19. Active debris removal: Recent progress and current trends

    Science.gov (United States)

    Bonnal, Christophe; Ruault, Jean-Marc; Desjean, Marie-Christine

    2013-04-01

    According to all available findings at international level, the Kessler syndrome, increase of the number of space debris in Low Earth Orbits due to mutual collisions, appears now to be a fact, triggered mainly by several major break-ups in orbit which occurred since 2007. The time may have come to study how to clean this fundamentally useful orbital region in an active way. CNES has studied potential solutions for more than 12 years! The paper aims at reviewing the current status of these activities. The high level requirements are fundamental, and have to be properly justified. The working basis, as confirmed through IADC studies consists in the removal of 5-10 integer objects from the overcrowded orbits, spent upper stages or old satellites, as identified by NASA. The logic of CNES activities consider a stepped approach aiming at progressively gaining the required Technological Readiness Level on the features required for Active Debris Removal which have not yet been demonstrated in orbit. The rendezvous with a non-cooperative, un-prepared, tumbling debris is essential. Following maturation gained with Research and Technology programs, a set of small orbital demonstrators could enable a confidence high enough to perform a full end to end demonstration performing the de-orbiting of a large debris and paving the way for the development of a first generation operational de-orbiter. The internal CNES studies, led together by the Toulouse Space Centre and the Paris Launcher Directorate, have started in 2008 and led to a detailed System Requirements Document used for the Industrial studies. Three industrial teams did work under CNES contract during 2011, led by Thales Alenia Space, Bertin Technologies and Astrium Space Transportation, with numerous sub-contractors. Their approaches were very rich, complementary, and innovative. The second phase of studies began mid-2012. Some key questions nevertheless have to be resolved, and correspond generally to current IADC

  20. FGF Signaling in Prostate Cancer Progression

    Institute of Scientific and Technical Information of China (English)

    Nora M. NAVONE

    2009-01-01

    @@ Objective: prostate cancer is the second leading cause of cancer death in men in the United States. Localized prostate cancer can be cured by andro-gen ablation, but when the disease escapes the confines of the gland, the prospects for cure decrease drastically and the disease becomes "castrate resistant.

  1. International trends in technological progress: stylized facts from patent citations, 1980-2011

    OpenAIRE

    Kwon, Soonwoo; Lee, Jihong; Lee, Sokbae

    2014-01-01

    We analyze cross-country trends in technological progress over the period of 1980-2011 by examining citations data from almost 4 million utility patents granted by the US Patent and Trademark Office (USPTO). Our estimation results on patent quality and distance to the knowledge frontier reveal the following stylized facts. The emerging Asian economies of Korea, Taiwan and China have indeed achieved substantial catch-up towards the technology frontier. In the case of Korea and Taiwan, progress...

  2. Recent Trends in Prostate Cancer Incidence by Age, Cancer Stage, and Grade, the United States, 2001–2007

    Directory of Open Access Journals (Sweden)

    Jun Li

    2012-01-01

    Full Text Available Objective. To examine prostate cancer trends by demographic and tumor characteristics because a comprehensive examination of recent prostate cancer incidence rates is lacking. Patients and Methods. We described prostate cancer incidence rates and trends using the 2001–2007 National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program data (representing over 93% of US population. Because of coding changes in cancer grade, we restricted analysis to 2004–2007. We conducted descriptive and trend analyses using SEER*Stat. Results. The overall prostate cancer incidence rate was stable from 2001 to 2007; however, rates significantly increased among men aged 40–49 years (APC = 3.0 and decreased among men aged 70–79 years (APC = 2.3, and 80 years or older (APC = −4.4. About 42% of localized prostate cancers diagnosed from 2004 to 2007 were poorly differentiated. The incidence of poorly differentiated cancer significantly increased among localized (APC = 8.0 and regional stage (APC = 6.1 prostate cancers during 2004–2007. Conclusions. The recent trend in prostate cancer incidence was stable but varied dramatically by age. Given the large proportion of poorly differentiated disease among localized prostate cancers and its increasing trend in more recent years, continued monitoring of prostate cancer incidence and trends by demographic and tumor characteristics is warranted.

  3. Cancer-Related Information Seeking Among Cancer Survivors: Trends Over a Decade (2003-2013).

    Science.gov (United States)

    Finney Rutten, Lila J; Agunwamba, Amenah A; Wilson, Patrick; Chawla, Neetu; Vieux, Sana; Blanch-Hartigan, Danielle; Arora, Neeraj K; Blake, Kelly; Hesse, Bradford W

    2016-06-01

    The demonstrated benefits of information seeking for cancer patients, coupled with increases in information availability, underscore the importance of monitoring patient information seeking experiences over time. We compared information seeking among cancer survivors to those with a family history of cancer and those with no history of cancer. We identified characteristics associated with greater information seeking among cancer survivors, key sources of cancer-related information, and changes in information source use over time. Data from five iterations of the Health Information National Trends Survey (HINTS) spanning 2003 to 2013 were merged and analyzed. Frequencies, cross-tabulations, multivariate logistic regression, and multinomial regression analyses were conducted. All data were weighted to provide representative estimates of the adult US population. Cancer information seeking was reported most frequently by cancer survivors (69.8 %). The percentage of cancer survivors who reported information seeking increased from 66.8 % in 2003 to 80.8 % in 2013. Cancer information seeking was independently associated with age, education, and income; seeking was less likely among older adults, those with less education, and those with lower incomes. Compared to respondents in 2003, those in 2005 (odds ratio (OR) = 0.40, 95 % confidence interval (CI) = 0.24-0.65) and 2008 (OR = .43, 95 % CI = 0.26-0.70) were about half as likely to use the Internet as the first source of cancer information compared to a healthcare provider. Despite overall increases in cancer information seeking and access to health information from a variety of sources, healthcare providers remain a key source of health information for cancer survivors. PMID:25712202

  4. Liver cancer stem cell markers: Progression and therapeutic implications

    Science.gov (United States)

    Sun, Jing-Hui; Luo, Qing; Liu, Ling-Ling; Song, Guan-Bin

    2016-01-01

    Cancer stem cells (CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets. PMID:27053846

  5. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Directory of Open Access Journals (Sweden)

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  6. Role of glutathione in cancer progression and chemoresistance.

    Science.gov (United States)

    Traverso, Nicola; Ricciarelli, Roberta; Nitti, Mariapaola; Marengo, Barbara; Furfaro, Anna Lisa; Pronzato, Maria Adelaide; Marinari, Umberto Maria; Domenicotti, Cinzia

    2013-01-01

    Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH homeostasis are involved in the etiology and progression of many human diseases including cancer. While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells. The present review highlights the role of GSH and related cytoprotective effects in the susceptibility to carcinogenesis and in the sensitivity of tumors to the cytotoxic effects of anticancer agents.

  7. New trends in molecular and cellular biomarker discovery for colorectal cancer.

    Science.gov (United States)

    Aghagolzadeh, Parisa; Radpour, Ramin

    2016-07-01

    Colorectal cancer (CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches, selection of appropriate therapeutic strategies and efficient follow-up programs are essential to reduce CRC mortalities. Biomarker discovery for CRC based on the personalized genotype and clinical information could facilitate the classification of patients with certain types and stages of cancer to tailor preventive and therapeutic approaches. These cancer-related biomarkers should be highly sensitive and specific in a wide range of specimen(s) (including tumor tissues, patients' fluids or stool). Reliable biomarkers which enable the early detection of CRC, can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Advances in our understanding of the natural history of CRC have led to the development of different CRC associated molecular and cellular biomarkers. This review highlights the new trends and approaches in CRC biomarker discovery, which could be potentially used for early diagnosis, development of new therapeutic approaches and follow-up of patients. PMID:27433083

  8. New trends in molecular and cellular biomarker discovery for colorectal cancer

    Science.gov (United States)

    Aghagolzadeh, Parisa; Radpour, Ramin

    2016-01-01

    Colorectal cancer (CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches, selection of appropriate therapeutic strategies and efficient follow-up programs are essential to reduce CRC mortalities. Biomarker discovery for CRC based on the personalized genotype and clinical information could facilitate the classification of patients with certain types and stages of cancer to tailor preventive and therapeutic approaches. These cancer-related biomarkers should be highly sensitive and specific in a wide range of specimen(s) (including tumor tissues, patients’ fluids or stool). Reliable biomarkers which enable the early detection of CRC, can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Advances in our understanding of the natural history of CRC have led to the development of different CRC associated molecular and cellular biomarkers. This review highlights the new trends and approaches in CRC biomarker discovery, which could be potentially used for early diagnosis, development of new therapeutic approaches and follow-up of patients. PMID:27433083

  9. Trends in cancer incidence in female breast, cervix uteri, corpus uteri, and ovary in India.

    Science.gov (United States)

    Yeole, Balkrishna B

    2008-01-01

    Trends in breast, cervix uteri, corpus uteri and ovarian cancers in six population based cancer registries (Mumbai, Bangalore, Chennai, Delhi, Bhopal, and Barshi) were evaluated over a period of the last two decades. For studying trends we used a model that fits this data is the logarithm of Y=ABx which represents a Linear Regression model. This approach showed a decreasing trend for cancer of the cervix and increasing trends for cancers of breast, ovary and corpus uteri throughout the entire period of observation in most of the registries. The four cancers, breast, cervix, corpus uteri and ovary, constitute more than 50% of total cancers in women. As all these cancers are increasing, to understand their etiology in depth, analytic epidemiology studies should be planned in a near future on a priority basis.

  10. Burden of cancer in Malawi; common types, incidence and trends: National population-based cancer registry

    Directory of Open Access Journals (Sweden)

    Msyamboza Kelias

    2012-03-01

    data on common types and trends of cancer that could be used to focus prevention, treatment and control interventions in the context of limited resources. The problem of under-reporting and misdiagnosis of cancer cases has been highlighted.

  11. Recent Progress in Cancer-Related Lymphedema Treatment and Prevention

    OpenAIRE

    Shaitelman, Simona F; Cromwell, Kate D.; Rasmussen, John C.; Stout, Nicole L; Armer, Jane M.; Lasinski, Bonnie B.; Cormier, Janice N

    2014-01-01

    This article provides an overview of the recent developments in the diagnosis, treatment, and prevention of cancer-related lymphedema. Lymphedema incidence by tumor site is evaluated. Measurement techniques and trends in patient education and treatment are also summarized to include current trends in therapeutic and surgical treatment options as well as longer-term management. Finally, an overview of the policies related to insurance coverage and reimbursement will give the clinician an overv...

  12. Diverging trends in colorectal cancer morbidity and mortality. Earlier diagnosis comes at a price

    NARCIS (Netherlands)

    L.G.A. Bonneux (Luc); J.J.M. Barendregt (Jan); C.W.N. Looman (Caspar); P.J. van der Maas (Paul)

    1995-01-01

    textabstractIn developed countries, time trends in the incidence of colorectal cancer differ markedly from trends in mortality. This study sought to explain simultaneously changes in both colorectal cancer incidence and mortality. Data on first admissions, interventions and outcome from the national

  13. Divergent estrogen receptor-positive and -negative breast cancer trends and etiologic heterogeneity in Denmark

    DEFF Research Database (Denmark)

    Anderson, William F; Rosenberg, Philip S; Petito, Lucia;

    2013-01-01

    Long-term breast cancer trends in incidence in the United States (US) show rising estrogen receptor (ER)-positive rates and falling ER-negative rates. We hypothesized that these divergent trends reflect etiologic heterogeneity and that comparable trends should be observed in other countries with...

  14. Molecular genetics of breast cancer progression

    OpenAIRE

    Sigurður Ingvarsson 1956

    1999-01-01

    Somatic changes in the genome of breast cancer cells include amplifications, deletions and gene mutations. Several chromosome regions harboring known oncogenes are found amplified in breast tumors. Despite the high number of chromosome regions deleted in breast tumors the functional relationship to known genes at these locations and cancer growth is mainly undiscovered. Mutations in two tumor suppressor genes (TSG) have been described in a subset of breast carcinomas. These TSG are the TP53, ...

  15. Heparin as an inhibitor of cancer progression

    OpenAIRE

    Borsig, L

    2010-01-01

    Heparin is frequently used for treatment of cancer-associated thromboembolism. Accumulating clinical evidence indicates that cancer patients treated with unfractionated and low-molecular weight heparin survives longer that patients treated by other anticoagulants, especially patients in the early stage of a disease. Experimental analysis from a number of animal models constantly provides evidence about the ability of heparin to attenuate metastasis. The non-anticoagulant activity of heparin o...

  16. Clinical trends and outcomes of male breast cancer: Experience of a tertiary oncology centre in India

    Directory of Open Access Journals (Sweden)

    Anindya Mukherjee

    2014-08-01

    Full Text Available Purpose: Because of its rarity in any oncology centre, the clinical trends of male breast cancer specific to its geographical distribution have remained relatively unexplored. This study was done to analyze the clinico-pathological data, treatment given and survival patterns of male breast cancer patients visiting our tertiary medical centre and compare our results with available literature. Methods: All male breast cancer patients registered at our clinic from 2003 to 2009 were included. Frequency distribution analysis of the demographic and clinico-pathological data and treatment variables was done. Treatment outcome was examined from Kaplan-Meir survival estimates. Results: Thirty-three male breast cancer patients were encountered. The median age of presentation was sixty years. Mostly (87.9% they presented with lump in breast or axilla and were clinically staged to be ‘3’ (57.6%.Obesity and alcohol were the commonest risk factors identified. Modified radical mastectomy was the commonest (69.6% definitive therapy rendered with (only for clinically staged 3 patients or without neo-adjuvant chemotherapy. Infiltrating ductal carcinoma was identified in most cases. Twenty-two patients received adjuvant chemotherapy and twenty-four received adjuvant radiotherapy. Eighteen (54.5% patients were hormone-receptor positive and received tamoxifen. The median Overall survival (OS and Progression-free survival (PFS came out to be 14.3 months (standard error, SE of 1.185; 95% confidence interval, CI 12-16.6 and 15.7 (SE 5.35, 95% CI 5.2-26.19 months respectively.Conclusion: Male breast cancers usually carry a poor prognosis due to presentation at later stages. Most of our results correlate with previous literature. Multi-centric prospective studies are required to validate the etiological factors and prognostic determinants of survival.-----------------------------Cite this article as: Mukherjee A, Saha A, Chattopadhyay S, Sur P. Clinical trends and

  17. Regulation of prostate cancer progression by the tumor microenvironment.

    Science.gov (United States)

    Shiao, Stephen L; Chu, Gina Chia-Yi; Chung, Leland W K

    2016-09-28

    Prostate cancer remains the most frequently diagnosed cancer in men in North America, and despite recent advances in treatment patients with metastatic disease continue to have poor five-year survival rates. Recent studies in prostate cancer have revealed the critical role of the tumor microenvironment in the initiation and progression to advanced disease. Experimental data have uncovered a reciprocal relationship between the cells in the microenvironment and malignant tumor cells in which early changes in normal tissue microenvironment can promote tumorigenesis and in turn tumor cells can promote further pro-tumor changes in the microenvironment. In the tumor microenvironment, the presence of persistent immune infiltrates contributes to the recruitment and reprogramming of other non-immune stromal cells including cancer-associated fibroblasts and a unique recently identified population of metastasis-initiating cells (MICs). These MICs, which can also be found as part of the circulating tumor cell (CTC) population in PC patients, promote cancer cell transformation, enhance metastatic potential and confer therapeutic resistance. MICs act can on other cells within the tumor microenvironment in part by secreting exosomes that reprogram adjacent stromal cells to create a more favorable tumor microenvironment to support continued cancer growth and progression. We review here the current data on the intricate relationship between inflammation, reactive stroma, tumor cells and disease progression in prostate cancer. PMID:26828013

  18. Metabolic, autophagic, and mitophagic activities in cancer initiation and progression.

    Science.gov (United States)

    Hjelmeland, Anita; Zhang, Jianhua

    2016-04-01

    Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species-induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. PMID:27372165

  19. Secular trend analysis oflung cancer incidence inSihui city, China between1987 and 2011

    Institute of Scientific and Technical Information of China (English)

    JinLinDu; MingHuangHong; QiHongHuang; ZhengErLiao; SuMeiCao; XiaoLin; LiFangZhang; YanHuaLi; ShangHangXie; MengJieYang; JieGuo; ErHongLin; QingLiu

    2015-01-01

    Background:With industrial and economic development in recent decades in South China, cancer incidence may have changed due to the changing lifestyle and environment. However, the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear. The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends. Methods:Joinpoint regression analysis and the age–period–cohort (APC) model were used to analyze the lung can‑cer incidence trends in Sihui, Guangdong province, China between 1987 and 2011, and explore the possible causes of these trends. Results:A total of 2,397 lung cancer patients were involved in this study. A 3‑fold increase in the incidence of lung cancer in both sexes was observed over the 25‑year period. Joinpoint regression analysis showed that while the inci‑dence continued to increase steadily in females during the entire period, a sharp acceleration was observed in males starting in 2005. The full APC model was selected to describe age, period, and birth cohort effects on lung cancer inci‑dence trends in Sihui. The age cohorts in both sexes showed a continuously signiifcant increase in the relative risk (RR) of lung cancer, with a peak in the eldest age group (80–84years). The RR of lung cancer showed a lfuctuating curve in both sexes. The birth cohorts identiifed an increased trend in both males and females; however, males had a plateau in the youngest cohorts who were born during 1955–1969. Conclusions:Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts. Social aging, smoking, and environmental changes may play important roles in such trends.

  20. Transcriptional network of androgen receptor in prostate cancer progression.

    Science.gov (United States)

    Takayama, Ken-ichi; Inoue, Satoshi

    2013-08-01

    The androgen receptor belongs to the nuclear receptor superfamily and functions as a ligand-dependent transcription factor. It binds to the androgen responsive element and recruits coregulatory factors to modulate gene transcription. In addition, the androgen receptor interacts with other transcription factors, such as forkhead box A1, and other oncogenic signaling pathway molecules that bind deoxyribonucleic acid and regulate transcription. Androgen receptor signaling plays an important role in the development of prostate cancer. Prostate cancer cells proliferate in an androgen-dependent manner, and androgen receptor blockade is effective in prostate cancer therapy. However, patients often progress to castration-resistant prostate cancer with elevated androgen receptor expression and hypersensitivity to androgen. Recently, comprehensive analysis tools, such as complementary DNA microarray, chromatin immunoprecipitation-on-chip and chromatin immunoprecipitation-sequence, have described the androgen-mediated diverse transcriptional program and gene networks in prostate cancer. Furthermore, functional and clinical studies have shown that some of the androgen receptor-regulated genes could be prognostic markers and potential therapeutic targets for the treatment of prostate cancer, particularly castration-resistant prostate cancer. Thus, identifying androgen receptor downstream signaling events and investigating the regulation of androgen receptor activity is critical for understanding the mechanism of carcinogenesis and progression to castration-resistant prostate cancer.

  1. Relaxin/RXFP1 Signaling in Prostate Cancer Progression

    OpenAIRE

    Feng, Shu; Agoulnik, Irina U; Li, Zhen; Han, Hee Dong; Lopez-Berestein, Gabriel; Sood, Anil; Ittmann, Michael M.; Agoulnik, Alexander I.

    2009-01-01

    We have shown that relaxin peptide expression was significantly elevated in recurrent human prostate cancer. Stimulation with relaxin increased migration, invasiveness, proliferation, and adhesion of LNCaP and PC3 cells in vitro. Opposite effects on cellular phenotype were observed after suppression of endogenous relaxin/RXFP1 expression or signaling. We showed an accelerated progression of prostate cancer in TRAMP males with transgenic relaxin overexpression and a longer survival of TRAMP, R...

  2. Research progress and developing trends on microorganisms of Xinjiang specific environments

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Microorganisms and its metabolic types are diverse in Xinjiang because of those extreme/special environments of drought, high or low temperature, saline and alkaline, oligotrophy. This article reviewed the research progress and achievements of various microbial resources (bacteria, fungi and actinomycete) in the special environments from the point of its ecology, development and application. Meanwhile, the development trend, protection and sustainable utilization of the microorganism resources were discussed.

  3. The physics of cancer: The role of epigenetics and chromosome conformation in cancer progression

    Science.gov (United States)

    Naimark, Oleg B.; Nikitiuk, Aleksandr S.; Baudement, Marie-Odile; Forné, Thierry; Lesne, Annick

    2016-08-01

    Cancer progression is generally described in terms of accumulated genetic alterations and ensuing changes in cell properties. However, intermediary modifications are involved in the establishment of cancer cell phenotypes, at different levels of nuclear organization: DNA damages and their structural consequences, epigenetic modifications and their impact on chromatin architecture, changes in chromosome 3D organization. We review some of these alterations with a focus on their physical aspects. The challenge is to understand the multiscale interplay between generic physical mechanisms and specific biological factors in cancer cells. We argue that such an interdisciplinary perspective offers a novel viewpoint on cancer progression, early diagnosis and possibly therapeutic targets.

  4. Embryonic morphogen nodal promotes breast cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Daniela F Quail

    Full Text Available Breast cancers expressing human embryonic stem cell (hESC-associated genes are more likely to progress than well-differentiated cancers and are thus associated with poor patient prognosis. Elevated proliferation and evasion of growth control are similarly associated with disease progression, and are classical hallmarks of cancer. In the current study we demonstrate that the hESC-associated factor Nodal promotes breast cancer growth. Specifically, we show that Nodal is elevated in aggressive MDA-MB-231, MDA-MB-468 and Hs578t human breast cancer cell lines, compared to poorly aggressive MCF-7 and T47D breast cancer cell lines. Nodal knockdown in aggressive breast cancer cells via shRNA reduces tumour incidence and significantly blunts tumour growth at primary sites. In vitro, using Trypan Blue exclusion assays, Western blot analysis of phosphorylated histone H3 and cleaved caspase-9, and real time RT-PCR analysis of BAX and BCL2 gene expression, we demonstrate that Nodal promotes expansion of breast cancer cells, likely via a combinatorial mechanism involving increased proliferation and decreased apopotosis. In an experimental model of metastasis using beta-glucuronidase (GUSB-deficient NOD/SCID/mucopolysaccharidosis type VII (MPSVII mice, we show that although Nodal is not required for the formation of small (<100 cells micrometastases at secondary sites, it supports an elevated proliferation:apoptosis ratio (Ki67:TUNEL in micrometastatic lesions. Indeed, at longer time points (8 weeks, we determined that Nodal is necessary for the subsequent development of macrometastatic lesions. Our findings demonstrate that Nodal supports tumour growth at primary and secondary sites by increasing the ratio of proliferation:apoptosis in breast cancer cells. As Nodal expression is relatively limited to embryonic systems and cancer, this study establishes Nodal as a potential tumour-specific target for the treatment of breast cancer.

  5. Lineage factors and differentiation states in lung cancer progression.

    Science.gov (United States)

    Cheung, W K C; Nguyen, D X

    2015-11-19

    Lung cancer encompasses a heterogeneous group of malignancies. Here we discuss how the remarkable diversity of major lung cancer subtypes is manifested in their transforming cell of origin, oncogenic dependencies, phenotypic plasticity, metastatic competence and response to therapy. More specifically, we review the increasing evidence that links this biological heterogeneity to the deregulation of cell lineage-specific pathways and the transcription factors that ultimately control them. As determinants of pulmonary epithelial differentiation, these poorly characterized transcriptional networks may underlie the etiology and biological progression of distinct lung cancers, while providing insight into innovative therapeutic strategies. PMID:25823023

  6. Genome evolution during progression to breast cancer

    KAUST Repository

    Newburger, D. E.

    2013-04-08

    Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.

  7. Time trends of incidence of digestive system cancers in changle of China during :1988-2002

    Institute of Scientific and Technical Information of China (English)

    Jun Tian; Jian-Shun Chen

    2006-01-01

    AIM: To analyze the incidence of digestive system cancer in Changle of China over a 15-year period.METHODS: The datasets were presented as timeseries of China-standardized annual incidence during 1988-2002. Linear regression model was used to analyze the incidence of stomach, liver, esophagus and colorectal cancers.RESULTS: Linear regression models for the time-series of stomach and esophagus cancer incidences for both men and women were statistically significant (P<0.05);Regression models for liver cancer and for colorectal cancer were statistically significant for men (P<0.05).CONCLUSION: The incidence rates of stomach and esophagus cancers for both men and women had down tendencies. For men, liver cancer had a down trend of the incidence and colorectal cancer had an upward trend of the incidence rate.

  8. Epithelial-mesenchymal transition in breast cancer progression and metastasis

    Institute of Scientific and Technical Information of China (English)

    Yifan Wang; Binhua P. Zhou

    2011-01-01

    Breast cancer is the most common cancer in women,and approximately 90% of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells.Epithelial-mesenchymal transition (EMT) is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development.Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis.Several transcription factors and signals are involved in these events.In this review,we summarize recent advances in breast cancer researches that have provided new insights in the molecular mechanisms underlying EMT regulation during breast cancer progression and metastasis.We especially focus on the molecular pathways that control EMT.

  9. The Cancer Stem Cell Concept in Progression of Head and Neck Cancer

    OpenAIRE

    Zhuo Chen

    2009-01-01

    Human head and neck cancer (HNC) is a highly heterogeneous disease. Understanding the biology of HNC progression is necessary for the development of novel approaches to its prevention, early detection, and treatment. A current evolutional progression model has limitations in explaining the heterogeneity observed in a single tumor nest. Accumulating evidence supports the existence of cancer stem cells (CSCs) as small subpopulations in solid tumors, including HNC. These CSCs can be selected by ...

  10. Analysis of oral cancer epidemiology in the US reveals state-specific trends: implications for oral cancer prevention

    OpenAIRE

    Ditmyer Marcia; O'Malley Susan; Kingsley Karl; Chino Michelle

    2008-01-01

    Abstract Background Downward trends have been observed in oral cancer incidence and mortality in the US over the past 30 years; however, these declines are not uniform within this population. Several studies have now demonstrated an increase in the incidence and mortality from oral cancers among certain demographic groups, which may have resulted from increased risks or risk behaviors. This study examines the underlying data that comprise these trends, to identify specific populations that ma...

  11. Epidemiological trends of hormone-related cancers in Slovenia.

    Science.gov (United States)

    Zadnik, Vesna; Krajc, Mateja

    2016-06-01

    The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association. PMID:27331295

  12. Epigenetic reduction of DNA repair in progression togastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Deficiencies in DNA repair due to inherited germ-linemutations in DNA repair genes cause increased risk ofgastrointestinal (GI) cancer. In sporadic GI cancers,mutations in DNA repair genes are relatively rare.However, epigenetic alterations that reduce expressionof DNA repair genes are frequent in sporadic GI cancers.These epigenetic reductions are also found in fielddefects that give rise to cancers. Reduced DNA repairlikely allows excessive DNA damages to accumulatein somatic cells. Then either inaccurate translesionsynthesis past the un-repaired DNA damages or errorproneDNA repair can cause mutations. ErroneousDNA repair can also cause epigenetic alterations (i.e. ,epimutations, transmitted through multiple replicationcycles). Some of these mutations and epimutations maycause progression to cancer. Thus, deficient or absentDNA repair is likely an important underlying cause ofcancer. Whole genome sequencing of GI cancers showthat between thousands to hundreds of thousands ofmutations occur in these cancers. Epimutations thatreduce DNA repair gene expression and occur early inprogression to GI cancers are a likely source of this highgenomic instability. Cancer cells deficient in DNA repairare more vulnerable than normal cells to inactivation byDNA damaging agents. Thus, some of the most clinicallyeffective chemotherapeutic agents in cancer treatmentare DNA damaging agents, and their effectivenessoften depends on deficient DNA repair in cancer cells.Recently, at least 18 DNA repair proteins, each activein one of six DNA repair pathways, were found to besubject to epigenetic reduction of expression in GIcancers. Different DNA repair pathways repair differenttypes of DNA damage. Evaluation of which DNA repairpathway(s) are deficient in particular types of GI cancerand/or particular patients may prove useful in guidingchoice of therapeutic agents in cancer therapy.

  13. Global Major Progress and Trends in the Implementation of Agenda 21

    Institute of Scientific and Technical Information of China (English)

    Guo Risheng

    2012-01-01

    This paper summarizes, from a global perspective, the major progress in the implementation of the Agenda 21 since the UN Conference on Environment and Development. The results show that global economy has achieved a substantial growth, and positive progress has been made in poverty eradication, urban- ization, and conservation and intensive use of natural resources. However, relevant international conventions and commitments have not yet been completely fulfilled. The paper further analyzes the current major challenges and future trends of global sustainable development. It is argued that there are three major challenges: 1) fatal global environmental issues posing an increasing threat to human survival; 2) more and more severe global competition for developing spaces; and 3) issues highlighting global people's live- lihood. There are four trends of global sustainable development: 1) sustainable development will further turn from concept into global action; 2) green will be the main trend of global develop- ment; 3) emerging developing countries will become the main driving force of global sustainable development; and 4) interna- tional relations in the field of sustainable development will turn to competitive co-operation.

  14. Cancer care. Cancer plan--progress report: must try even harder.

    Science.gov (United States)

    Coombes, Rebecca

    2004-11-25

    Despite progress in some areas, major obstacle achieving a uniformly good service for cancer patients remain. PCTs' lack of expertise is holding back progress ending delays in diagnosis and treatment. SHAs need to be clearer with PCTs about the importance of meeting national targets. PMID:15597927

  15. An updated report on the trends in cancer incidence and mortality in Japan, 1958-2013.

    Science.gov (United States)

    Katanoda, Kota; Hori, Megumi; Matsuda, Tomohiro; Shibata, Akiko; Nishino, Yoshikazu; Hattori, Masakazu; Soda, Midori; Ioka, Akiko; Sobue, Tomotaka; Nishimoto, Hiroshi

    2015-04-01

    The analysis of cancer trends in Japan requires periodic updating. Herein, we present a comprehensive report on the trends in cancer incidence and mortality in Japan using recent population-based data. National cancer mortality data between 1958 and 2013 were obtained from published vital statistics. Cancer incidence data between 1985 and 2010 were obtained from high-quality population-based cancer registries of three prefectures (Yamagata, Fukui and Nagasaki). Joinpoint regression analysis was performed to examine the trends in age-standardized rates of cancer incidence and mortality. All-cancer mortality decreased from the mid-1990s, with an annual percent change of -1.3% (95% confidence interval [CI]: -1.4, -1.3). During the most recent 10 years, over 60% of the decrease in cancer mortality was accounted for by a decrease in stomach and liver cancers (63% for males and 66% for females). The long-term increase in female breast cancer mortality, beginning in the 1960s, plateaued in 2008. All-cancer incidence continuously increased, with annual percent changes of 0.6% (95% CI: 0.5, 0.8) between 1985 and 2005, and 1.8% (95% CI: 0.6, 2.9) between 2005 and 2010. During the most recent 10 years, almost half of the increase in cancer incidence was accounted for by an increase in prostate cancer (60%) in males and breast cancer (46%) in females. The cancer registry quality indices also began to increase from ∼2005. Decreases in stomach and liver cancers observed for incidence and mortality reflect the reduced attribution of infection-related factors (i.e. Helicobacter pylori and hepatitis virus). However, it should be noted that cervical cancer incidence and mortality rates began to increase from ∼1990.

  16. Progression and metastasis of lung cancer.

    Science.gov (United States)

    Popper, Helmut H

    2016-03-01

    Metastasis in lung cancer is a multifaceted process. In this review, we will dissect the process in several isolated steps such as angiogenesis, hypoxia, circulation, and establishment of a metastatic focus. In reality, several of these processes overlap and occur even simultaneously, but such a presentation would be unreadable. Metastasis requires cell migration toward higher oxygen tension, which is based on changing the structure of the cell (epithelial-mesenchymal transition), orientation within the stroma and stroma interaction, and communication with the immune system to avoid attack. Once in the blood stream, cells have to survive trapping by the coagulation system, to survive shear stress in small blood vessels, and to find the right location for extravasation. Once outside in the metastatic locus, tumor cells have to learn the communication with the "foreign" stroma cells to establish vascular supply and again express molecules, which induce immune tolerance.

  17. Progress in Immunotherapy for Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan XU

    2014-01-01

    Full Text Available In recent years, the five-year survival rate of patients with advanced stage non-small cell lung cancer (NSCLC remains low despite recent advances in surgery, irradiation, chemotherapy, and targeted therapy. Immunotherapy which utilizes the immune system to control and eradicate cancer is a viable treatment approach for malignancy. Immunotherapy in patients with lung cancer has made breakthrough progress recently. Novel immunotherapeutic agents, such as antigen-specific tumour vaccines, checkpoint inhibitors, etc, have all been evaluated in lung cancer, and some have shown prolonged survival time in phase II trials and III trails. The immune-related response criteria for the evaluation of antitumor responses with immunotherapeutic agents have been made. Now, immunotherapy will likely be a fundamentally new concept for the treatment of NSCLC.

  18. Dual role of GRK5 in cancer development and progression.

    Science.gov (United States)

    Gambardella, J; Franco, A; Giudice, C Del; Fiordelisi, A; Cipolletta, E; Ciccarelli, M; Trimarco, B; Iaccarino, G; Sorriento, D

    2016-05-01

    GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Several reports underline the involvement of GRK5 in the regulation of tumor growth even if they appear controversial. Indeed, depending on its subcellular localization and on the type of cancer, GRK5 is able to both inhibit cancer progression, through the desensitization of GPCR and non GPCR-receptors (TSH, PGE2R, PDGFR), and induce tumor growth, acting on non-receptor substrates (p53, AUKA and NPM1). All these findings suggest that targeting GRK5 could be an useful anti-cancer strategy, for specific tumor types. In this review, we will discuss the different effects of this kinase in the induction and progression of tumorigenesis, the molecular mechanisms by which GRK5 exerts its effects, and the potential therapeutic strategies to modulate them.

  19. Inferring tree causal models of cancer progression with probability raising.

    Directory of Open Access Journals (Sweden)

    Loes Olde Loohuis

    Full Text Available Existing techniques to reconstruct tree models of progression for accumulative processes, such as cancer, seek to estimate causation by combining correlation and a frequentist notion of temporal priority. In this paper, we define a novel theoretical framework called CAPRESE (CAncer PRogression Extraction with Single Edges to reconstruct such models based on the notion of probabilistic causation defined by Suppes. We consider a general reconstruction setting complicated by the presence of noise in the data due to biological variation, as well as experimental or measurement errors. To improve tolerance to noise we define and use a shrinkage-like estimator. We prove the correctness of our algorithm by showing asymptotic convergence to the correct tree under mild constraints on the level of noise. Moreover, on synthetic data, we show that our approach outperforms the state-of-the-art, that it is efficient even with a relatively small number of samples and that its performance quickly converges to its asymptote as the number of samples increases. For real cancer datasets obtained with different technologies, we highlight biologically significant differences in the progressions inferred with respect to other competing techniques and we also show how to validate conjectured biological relations with progression models.

  20. Trend Analysis of Cancer Mortality in the Jinchang Cohort, China, 2001-2010

    Institute of Scientific and Technical Information of China (English)

    QU Hong Mei; REN Xiao Wei; SHANG Hui; BAI Ya Na; CHENG Ning; DAI Min; ZHENG Tong Zhang; WANG Dennis; LI Hai Yan; HU Xiao Bin; LI Juan Sheng

    2015-01-01

    Objective To describe the baseline data of cancers in the Jinchang Cohort, this paper examined trends in cancer mortality among adults investigated in Jinchang, Gansu province from 2001 to 2010. Methods Mortality data were collected from company departments through administrative documents, death certificates, etc. Trend analyses of cancer mortality were performed on the basis of 925 cancer deaths between 2001 and 2010. Results The crude mortality rate of cancer continuously increased from 161.86 per 100,000 in 2001 to 315.32 per 100,000 in 2010, with an average increase of 7.69%per year in the Jinchang Cohort (16.41%in females compared to 6.04% in males), but the age-standardized mortality rate increased only in females. Thirteen leading cancers accounted for 92.10%of all cancer deaths. The five leading causes of cancer mortality in males were lung, gastric, liver, esophageal, and colorectal cancer, whereas those in females were lung, liver, gastric, breast, and esophageal cancer. Conclusion The overall cancer mortality rate increased from 2001 to 2010 in the Jinchang Cohort, with greater rate of increase in females than in males. Lung, breast, and gastric cancer, in that order, were the leading causes of increased cancer mortality in females.

  1. The Cancer Genome Anatomy Project: EST Sequencing and the Genetics of Cancer Progression

    Directory of Open Access Journals (Sweden)

    David B. Krizman

    1999-06-01

    Full Text Available As the process of tumor progression proceeds from the normal cellular state to a preneoplastic condition and finally to the fully invasive form, the molecular characteristics of the cell change as well. These characteristics can be considered a molecular fingerprint of the cell at each stage of progression and, analogous to fingerprinting a criminal, can be used as markers of the progression process. Based on this premise, the Cancer Genome Anatomy Project was initiated with the broad goal of determining the comprehensive molecular characterization of normal, premalignant, and malignant tumor cells, thus making a reality the identification of all major cellular mechanisms leading to tumor initiation and progression ([Strausberg, R.L., Dahl, C.A., and Klausner, R.D. (1997. “New opportunities for uncovering the molecular basis of cancer.” Nat. Genet., 16: 415-516.], www.ncbi.nlm.nih.gov/ncicgap/. The expectation of determining the genetic fingerprints of cancer progression will allow for 1 correlation of disease progression with therapeutic outcome; 2 improved evaluation of disease treatment; 3 stimulation of novel approaches to prevention, detection, and therapy; and 4 enhanced diagnostic tools for clinical applications. Whereas acquiring the comprehensive molecular analysis of cancer progression may take years, results from initial, short-term goals are currently being realized and are proving very fruitful.

  2. Daxx regulates mitotic progression and prostate cancer predisposition.

    Science.gov (United States)

    Kwan, Pak Shing; Lau, Chi Chiu; Chiu, Yung Tuen; Man, Cornelia; Liu, Ji; Tang, Kai Dun; Wong, Yong Chuan; Ling, Ming-Tat

    2013-04-01

    Mitotic progression of mammalian cells is tightly regulated by the E3 ubiquitin ligase anaphase promoting complex (APC)/C. Deregulation of APC/C is frequently observed in cancer cells and is suggested to contribute to chromosome instability and cancer predisposition. In this study, we identified Daxx as a novel APC/C inhibitor frequently overexpressed in prostate cancer. Daxx interacts with the APC/C coactivators Cdc20 and Cdh1 in vivo, with the binding of Cdc20 dependent on the consensus destruction boxes near the N-terminal of the Daxx protein. Ectopic expression of Daxx, but not the D-box deleted mutant (DaxxΔD-box), inhibited the degradation of APC/Cdc20 and APC/Cdh1 substrates, leading to a transient delay in mitotic progression. Daxx is frequently upregulated in prostate cancer tissues; the expression level positively correlated with the Gleason score and disease metastasis (P = 0.027 and 0.032, respectively). Furthermore, ectopic expression of Daxx in a non-malignant prostate epithelial cell line induced polyploidy under mitotic stress. Our data suggest that Daxx may function as a novel APC/C inhibitor, which promotes chromosome instability during prostate cancer development.

  3. Supramolecular nanofibrils inhibit cancer progression in vitro and in vivo

    Science.gov (United States)

    Kuang, Yi; Du, Xuewen; Zhou, Jie; Xu, Bing

    2014-01-01

    The recent discovery of the inverse comorbidity between cancer and Alzheimer’s disease implies that one may use amyloids to inhibit tumors. During the conversion of a dipeptide segment (Phe-Phe) in β-amyloid into a supramolecular hydrogelator, we obtained a small molecule (1) that can self-assembly into nanofibrils via multiple intermolecular hydrogen bonding and aromatic-aromatic interactions. Interestingly, while the monomers of 1 are innocuous, the nanofibrils formed by 1 can selectively inhibit the growth of glioblastoma cells over neuronal cells. To further assess the potential of this small molecular nanofibrils as anti-cancer agent, we exam the biological activity of the nanofibrils and demonstrate that the nanofibrils of 1 efficiently inhibit the progression of cancer cells (e.g., HeLa cells) both in cell assays and on xenograft mice model. This work suggests that nanofibrils derived from core motif of amyloid are effective agents for inhibiting cancer progression. Thus, this work contributes to a new approach that uses supramolecular nanofibrils as de novo molecular amyloids for inhibiting the growth of cancer cells. PMID:24574174

  4. Analysis of oral cancer epidemiology in the US reveals state-specific trends: implications for oral cancer prevention

    Directory of Open Access Journals (Sweden)

    Ditmyer Marcia

    2008-03-01

    Full Text Available Abstract Background Downward trends have been observed in oral cancer incidence and mortality in the US over the past 30 years; however, these declines are not uniform within this population. Several studies have now demonstrated an increase in the incidence and mortality from oral cancers among certain demographic groups, which may have resulted from increased risks or risk behaviors. This study examines the underlying data that comprise these trends, to identify specific populations that may be at greater risk for morbidity and mortality from oral cancers. Methods Oral cancer incidence and mortality data analyzed for this study were generated using the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER program. Results While oral cancer incidence and mortality rates have been declining over the past thirty years, these declines have reversed in the past five years among some demographic groups, including black females and white males. Sorting of these data by state revealed that eight states exhibited increasing rates of oral cancer deaths, Nevada, North Carolina, Iowa, Ohio, Maine, Idaho, North Dakota, and Wyoming, in stark contrast to the national downward trend. Furthermore, a detailed analysis of data from these states revealed increasing rates of oral cancer among older white males, also contrary to the overall trends observed at the national level. Conclusion These results signify that, despite the declining long-term trends in oral cancer incidence and mortality nationally, localized geographic areas exist where the incidence and mortality from oral cancers have been increasing. These areas represent sites where public health education and prevention efforts may be focused to target these specific populations in an effort to improve health outcomes and reduce disparities within these populations.

  5. Trends in cancer incidence in Maputo, Mozambique, 1991-2008.

    Directory of Open Access Journals (Sweden)

    Cesaltina Lorenzoni

    Full Text Available Very limited information is available regarding the incidence of cancer in sub-Saharan Africa. We analyzed changes in cancer patterns from 1991 to 2008 in Maputo (Mozambique.We calculated the rates of incidence of different cancer sites by sex in the 5-year age-group of the population of Maputo city as well as age-standardized rates (ASRs and average annual percentage changes (AAPC.Over the 18-year study period a total of 12,674 cases of cancer (56.9% females were registered with an overall increase in the risk of cancer in both sexes. In males, the most common cancers were those of the prostate, Kaposi sarcoma (KS and the liver. Prostate cancer showed the most dramatic increase over the whole study period (AAPC +11.3%; 95% CI: 9.7-13.0, with an ASR of 61.7 per 105 in 2003-2008. In females, the most frequent cancers were of the uterine cervix, the breast and KS, with the former increasing along the whole study period (AAPC + 4.7%; 95% CI: 3.4-6 with an ASR of 62.0 per 105 in 2003-2008 as well as breast cancer (AAPC +6.5%; 95%CI: 4.3-8.7.Overall, the risk of cancer rose in both sexes during the study period, particularly among cancers associated with westernization of lifestyles (prostate, breast, combined with increasingly rising incidences or limited changes in cancers associated with infection and poverty (uterine cervix, liver. Moreover, the burden of AIDS-associated cancers has shown a marked increase.

  6. Time-space trends in cancer incidence in The Netherlands in 1989–2003

    NARCIS (Netherlands)

    Siesling, Sabine; Aa, van der Maaike A.; Coebergh, Jan W.W.; Pukkala, Eero

    2008-01-01

    Incidence of cancer may vary within a country and over time because of previous differences in exposure to risk factors or interventions for early detection (screening). This study describes time-space trends of incidence of common cancer sites across the Netherlands during the period 1989–2003 and

  7. Predicted trends in long-term breast cancer survival in England and Wales

    OpenAIRE

    Woods, L. M.; Rachet, B; Cooper, N.; Coleman, M P

    2007-01-01

    Trends in long-term relative survival from breast cancer are examined for women diagnosed in England and Wales up to 2001, using both period and hybrid approaches. Large improvements in long-term survival are predicted. Women with breast cancer still experience persistent excess mortality up to at least 20 years after diagnosis.

  8. Trends in inequalities in premature cancer mortality by educational level in Colombia, 1998-2007

    NARCIS (Netherlands)

    E. de Vries (Esther); I. Arroyave (Ivan); C. Pardo (Constanza); C. Wiesner (Carolina); R. Murillo (Raul); D. Forman (David); A. Burdorf (Alex); M. Avendano (Mauricio)

    2014-01-01

    textabstractBackground There is a paucity of studies on socioeconomic inequalities in cancer mortality in developing countries. We examined trends in inequalities in cancer mortality by educational attainment in Colombia during a period of epidemiological transition and rapid expansion of health ins

  9. Trends in inequalities in premature cancer mortality by educational level in Colombia, 1998-2007

    NARCIS (Netherlands)

    E. de Vries (Esther); I. Arroyave (Ivan); C. Pardo (Constanza); C. Wiesner (Carolina); R. Murillo (Raul); D. Forman (David); A. Burdorf (Alex); M. Avendano (Mauricio)

    2015-01-01

    textabstractBackground: There is a paucity of studies on socioeconomic inequalities in cancer mortality in developing countries. We examined trends in inequalities in cancer mortality by educational attainment in Colombia during a period of epidemiological transition and rapid expansion of health in

  10. SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis.

    Science.gov (United States)

    Tseng, Ruo-Chia; Lee, Shih-Hua; Hsu, Han-Shui; Chen, Ben-Han; Tsai, Wan-Ching; Tzao, Ching; Wang, Yi-Ching

    2010-01-15

    Chromosome 4p15.3 is frequently deleted in late-stage lung cancer. We investigated the significance of the SLIT2 gene located in this region to lung cancer progression. SLIT2 encodes an extracellular glycoprotein that can suppress breast cancer by regulating beta-catenin. In this study, we examined alterations in the structure or expression of SLIT2, its receptor ROBO1, and beta-catenin, along with the AKT/glycogen synthase kinase 3beta (GSK3beta)/beta-transducin repeat-containing protein (betaTrCP) pathway in lung cancer cell lines and patients. Low SLIT2 expression correlated with an upward trend of pathological stage and poorer survival in lung cancer patients. Importantly, SLIT2, betaTrCP, and beta-catenin expression levels predicted postoperative recurrence of lung cancer in patients. Stimulating SLIT2 expression by various methods increased the level of E-cadherin caused by attenuation of its transcriptional repressor SNAI1. Conversely, knocking down SLIT2 expression increased cell migration and reduced cell adhesion through coordinated deregulation of beta-catenin and E-cadherin/SNAI1 in the AKT/GSK3beta/betaTrCP pathway. Our findings indicate that SLIT2 suppresses lung cancer progression, defining it as a novel "theranostic" factor with potential as a therapeutic target and prognostic predictor in lung cancer. Cancer Res; 70(2); 543-51.

  11. Dietary energy balance modulates ovarian cancer progression and metastasis.

    Science.gov (United States)

    Al-Wahab, Zaid; Tebbe, Calvin; Chhina, Jasdeep; Dar, Sajad A; Morris, Robert T; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2014-08-15

    A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian surface epithelial ID8 cancer cells. Tumor evaluation revealed that mice group on HED displayed the most extensive tumor formation with the highest tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of insulin, leptin, insulin growth factor-1 (IGF-1), monocyte chemoattractant protein-1 (MCP-1), VEGF and interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least tumor burden associated with a significant reduction in levels of insulin, IGF-1, leptin, MCP-1, VEGF and IL-6. Immunohistochemistry analysis of tumors from HED mice showed higher activation of Akt and mTOR with decreased adenosine monophosphate activated kinase (AMPK) and SIRT1 activation, while tumors from the CRD group exhibited the reverse profile. In conclusion, ovarian cancer growth and metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of growth factors, cytokines and altered regulation of AMPK and SIRT1 that converges on mTOR inhibition. While the role of a high energy state in ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer therapies and as possible individualized treatment strategy of epithelial ovarian cancer.

  12. Changing Trends of Breast Cancer Survival in Sultanate of Oman

    OpenAIRE

    Shiyam Kumar; Burney, Ikram A; Adel Al-Ajmi; Al-Moundhri, Mansour S

    2011-01-01

    Breast cancer is the leading cause of cancer-associated mortality in women, with elevated incidence in developing countries. This retrospective study included all 122 patients diagnosed with breast cancer from January 2003 to December 2008 in the Sultanate of Oman. Age at presentation was 47.41 years (SD ± 12.88), with one-third of patients younger than 40 years. The majority of patients presented with stage III (41.2%) and IV (18.2%) breast cancer. T size ( = . 0 2 3 ), skin involvement ( ...

  13. Cancer Information Seeking and Cancer-Related Health Outcomes: A Scoping Review of the Health Information National Trends Survey Literature.

    Science.gov (United States)

    Wigfall, Lisa T; Friedman, Daniela B

    2016-09-01

    Cancer is a leading cause of death among adults in the United States. Only 54% of U.S. adults reported seeking cancer information in 2014. Cancer information seeking has been positively associated with cancer-related health outcomes such as screening adherence. We conducted a scoping review of studies that used data from the Health Information National Trends Survey (HINTS) in order to examine cancer information seeking in depth and the relationship between cancer information seeking and cancer-related health outcomes. We searched five databases and the HINTS website. The search yielded a total of 274 article titles. After review of 114 de-duplicated titles, 66 abstracts, and 50 articles, 22 studies met inclusion criteria. Cancer information seeking was the outcome in only four studies. The other 18 studies focused on a cancer-related health outcome. Cancer beliefs, health knowledge, and information seeking experience were positive predictors of cancer information seeking. Cancer-related awareness, knowledge, beliefs, preventive behaviors, and screening adherence were higher among cancer information seekers. Results from this review can inform other research study designs and primary data collection focused on specific cancer sites or aimed at populations not represented or underrepresented in the HINTS data (e.g., minority populations, those with lower socioeconomic status). PMID:27466828

  14. Tristetraprolin inhibits gastric cancer progression through suppression of IL-33

    OpenAIRE

    Kaiyuan Deng; Hao Wang; Ting Shan; Yigang Chen; Hong Zhou; Qin Zhao; Jiazeng Xia

    2016-01-01

    Tristetraprolin (TTP) is an adenine/uridine (AU)-rich element (ARE)-binding protein that can induce degradation of mRNAs. In this study, we report that TTP suppresses the expression of interleukin-33 (IL-33), a tumor-promoting inflammatory cytokine, and thereby inhibits the progression of gastric cancer (GC). Overexpression of TTP decreased the level of IL-33, whereas knockdown of TTP increased IL-33 levels. We also discovered that TTP inhibited the proliferation, migration, and invasion of G...

  15. Glaucoma Progression Detection by Retinal Nerve Fiber Layer Measurement Using Scanning Laser Polarimetry: Event and Trend Analysis

    OpenAIRE

    Moon, Byung Gil; Sung, Kyung Rim; Cho, Jung Woo; Kang, Sung Yong; Yun, Sung-Cheol; Na, Jung Hwa; Lee, Youngrok; Kook, Michael S.

    2012-01-01

    Purpose To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma. Methods Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA,...

  16. Oct-4 is associated with gastric cancer progression and prognosis

    Directory of Open Access Journals (Sweden)

    Jiang WL

    2016-01-01

    Full Text Available Wen-Li Jiang,1 Peng-Fei Zhang,2 Guo-Feng Li,1 Jian-Hua Dong,1 Xue-Song Wang,1 Yuan-Yu Wang3 1Department of Surgery, Juxian People’s Hospital, 2Department of Surgery, Rizhao People’s Hospital of Traditional Chinese Medicine, Rizhao, 3Department of Gastrointestinal Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China Aim: To investigate the clinical significance of Oct-4 in the development and progression of gastric cancer.Methods: Immunohistochemistry was used to analyze Oct-4 expression in 412 gastric cancer cases. Oct-4 protein levels were upregulated in gastric cancer tissues compared with adjacent noncancerous tissues.Results: Positive expression of Oct-4 correlated with age, depth of invasion, Lauren classification, lymph node metastasis, distant metastasis, and TNM stage. In stages I, II, and III, the 5-year survival rate of patients with high expression of Oct-4 was significantly lower than that in patients with low expression of Oct-4. In stage IV, Oct-4 expression did not correlate with the 5-year survival rate. Furthermore, multivariate analysis suggested that the depth of invasion, lymph node metastasis, distant metastasis, TNM stage, and upregulation of Oct-4 were independent prognostic factors of gastric cancer.Conclusion: Oct-4 protein is a useful marker in predicting tumor progression and prognosis. Keywords: gastric carcinoma, invasion, metastasis, survival rate

  17. Tpl2 induces castration resistant prostate cancer progression and metastasis.

    Science.gov (United States)

    Lee, Hye Won; Cho, Hyun Jung; Lee, Se Jeong; Song, Hye Jin; Cho, Hee Jin; Park, Min Chul; Seol, Ho Jun; Lee, Jung-Il; Kim, Sunghoon; Lee, Hyun Moo; Choi, Han Yong; Nam, Do-Hyun; Joo, Kyeung Min

    2015-05-01

    Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC. PMID:25274482

  18. An assessment of recent Iranian fertility trends using parity progression ratios

    Directory of Open Access Journals (Sweden)

    Peter McDonald

    2015-06-01

    Full Text Available Background: In 2013 a draft population bill was introduced in the Iranian Parliament. Based on the presumption that fertility in Iran had fallen to a very low level, the bill proposed a wide range of pronatalist policies with the aim of increasing fertility to 2.5 births per woman. The draft law called for restrictions on the employment of women and young single people and inducements for women to marry in their late teens. New estimates of fertility, such as those provided in this paper, cast doubt upon the view that fertility had fallen to a very low level. In May 2014 a statement issued by the Supreme Leader provided guidelines for a more moderate approach to sustaining fertility at around the replacement level. Objective: To measure the trend in fertility in Iran, especially from 2000 onwards. Methods: Using the 2010 IDHS, the synthetic cohort parity progression ratio method is used to measure the fertility trend in Iran. Synthetic parity progressions are compared with real cohort parity progressions to examine the presence of tempo effects. Comparison is made with age-based measures from surveys, censuses, and the birth registration system. Results: This paper demonstrates that fertility in Iran was constant for the decade 2000-2009, at a level of around 1.8-2.0 births per woman. Conclusions: Our findings provide evidence supporting a more moderate approach to sustaining fertility in Iran at around the replacement level. Comments: The paper demonstrates the advantages of parity-based measurement over age-based measurement when tempo effects may be involved.

  19. Life time risk for development of ten major cancers in India and its trends over the years 1982 to 2000

    Directory of Open Access Journals (Sweden)

    Satyanarayana L

    2008-02-01

    Full Text Available Background : Understanding cancer magnitude, risk and trends will be of help in cancer control programs. Aim : To study trends in cumulative risk up to 64 years of age as lifetime risk of developing major cancers in India during the years 1982 to 2000. Design : Retrospective. Setting : Secondary sources of cancer-registration data. Materials and Methods : Data on age-specific cancer-incidence rates were collected for patients 0-64 years of age of either sex for 10 major cancer sites from the National Cancer Registry Program (NCRP reports of India from Mumbai, Chennai, Bangalore, Bhopal and Delhi; and Barshi registries for the years 1982 or 1988 to 2000. Statistical Analysis : Cumulative risks computed for lifetime development of cancer. Linear trends were studied using simple linear regressions. Results : The lifetime risk among females for the10 cancer sites ranged from 0.02 to 3.3% and from 0.04 to 2.4% for the years 1982 and 2000 respectively; whereas among males, it ranged from 0.04 to 0.89% and from 0.05 to 0.95% respectively. Significant (P < 0.05 increasing trends were observed for breast, non-Hodgkin′s lymphoma (NHL, gallbladder, thyroid and ovary cancers among females; while declining trends were observed for cervix, mouth, stomach, esophagus and tongue cancers. Among males, significant (P < 0.05 increasing trends were observed for NHL and prostate cancer; whereas declining trends were observed for stomach, liver, hypopharynx and tongue cancers. Cancers of mouth and esophagus showed increasing trends (P < 0.05 in some regions and declining trends (P < 0.05 in some other. Conclusion : Significant and higher rates of positive trends in lifetime cancer risks for breast cancer among females and for NHL among both sexes were observed.

  20. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu

    2015-01-01

    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  1. Progress in adjuvant chemotherapy for breast cancer: an overview.

    Science.gov (United States)

    Anampa, Jesus; Makower, Della; Sparano, Joseph A

    2015-01-01

    Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.

  2. Tumor-Derived Exosomes and Their Role in Cancer Progression.

    Science.gov (United States)

    Whiteside, Theresa L

    2016-01-01

    Tumor cells actively produce, release, and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis, and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as noninvasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation.

  3. Trends in lung cancer in elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Schytte, Tine; Holmskov, Karin;

    2016-01-01

    of lung cancer is closely linked to the pattern of tobacco smoking with the differences between gender and age groups reflecting smoking behavior in birth cohorts. Elderly patients with lung cancer are a heterogeneous group in whom treatment should be offered according to comorbidity and a geriatric......Background Lung cancer is an increasing problem in the older patient population due to the improvement in life expectation of the Western population. In this study we examine trends in lung cancer incidence and mortality in Denmark from 1980 to 2012 with special focus on the elderly. Material...... and methods Lung cancer was defined as ICD-10 codes C33-34. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence, and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death...

  4. Validating the use of Medicare Australia billing data to examine trends in skin cancer

    OpenAIRE

    Eshini Perera; Neiraja Gnaneswaran; Marlon Perera; Rodney Sinclair

    2015-01-01

    Background:  Epidemiological data surrounding non-melanomatous skin cancer (NMSC) is highly variable, in part due to the lack of government cancer registries. Several studies employ the use of Medical Australia (MA) rebate data in assessing such trends, the validity of which has not been studied in the past. Conversely, melanoma skin cancer is a notifiable disease, and thus, MA and cancer registry data is readily available. The aim of the current study is to assess the use of MA for epidemiol...

  5. The role of S100 genes in breast cancer progression.

    LENUS (Irish Health Repository)

    McKiernan, Eadaoin

    2011-06-01

    The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman\\'s correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

  6. The role of S100 genes in breast cancer progression.

    LENUS (Irish Health Repository)

    McKiernan, Eadaoin

    2012-02-01

    The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman\\'s correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

  7. Cyr61 promotes breast tumorigenesis and cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Miaw-Sheue; Bogart, Daphne F.; Castaneda, Jessica M.; Li, Patricia; Lupu, Ruth

    2002-01-16

    Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the ''normal'' estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that under E2-depleted condition, Cyr61 is sufficient to induce MCF-7 cells grow in the absence of E2. MCF-7 cells transfected with Cyr61 (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7/vector cells remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorage-independent and capable of forming Matrigel outgrowth patterns in the absence of E2. ERa expression in MCF-7/Cyr61 cells is decreased although still functional. Additionally, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and anti-E2 resistance, and to promote invasiveness in vitro, and to induce tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.

  8. The influence of death-certificate errors on cancer mortality trends

    International Nuclear Information System (INIS)

    Over the past few years, several reports have suggested a recent increase in cancer mortality based on death-certificate diagnoses. To explore the effect of death-certificate errors on temporal trends in cancer mortality rates, we analyzed the data from the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation's autopsy program in Hiroshima and Nagasaki. This series includes 5886 autopsies conducted between 1961 and 1987. Our analyses were focused on lymphoma, cancer of the breast, neoplasms of the brain, multiple myeloma, and melanoma (172 cases, total) because of concern over reports of their increased mortality. These 172 autopsy cases were referred to as Cancers of Interest. A significant increase in detection rates was observed for these Cancers of Interest primarily due to a large rise in mortality between 1976 and 1987. For the remaining cancers excluding stomach and lung (defined as Other), the pattern was similar to that seen for Cancers of Interest, but the fluctuation over time was not statistically significant. Confirmation rates generally increased with time except for Cancers of Interest. As a measure of bias in mortality rates due to death-certification errors and as a method to quantify under- or overestimation of death-certificate-based mortality rates,an adjustment factor (confirmation rate divided by detection rate) was calculated. The higher the adjustment factor, the greater the need to compensate for underreporting. For Cancers of Interest the adjustment factor decreased dramatically over time, but it did not change significantly for Other cancers. When the adjustment factors for Cancers of Interest and Other were compared, a statistically significant difference was found. For Cancers of Interest, a significant interaction between type of cancer and period was seen. Our findings indicate that considerable care must be shown when interpreting temporal trends in cancer vital statistics. (author)

  9. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    International Nuclear Information System (INIS)

    Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min). These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients

  10. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    Directory of Open Access Journals (Sweden)

    Mazen A. Juratli

    2014-01-01

    Full Text Available Circulating tumor cells (CTCs are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min. These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.

  11. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    Energy Technology Data Exchange (ETDEWEB)

    Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Melerzanov, Alexander V. [Moscow Institute of Physics and Technology (MIPT), Moscow Region, 141700 (Russian Federation); Zharov, Vladimir P. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Moscow Institute of Physics and Technology (MIPT), Moscow Region, 141700 (Russian Federation); Galanzha, Ekaterina I., E-mail: egalanzha@uams.edu [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2014-01-15

    Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min). These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.

  12. Hypothermia activates adipose tissue to promote malignant lung cancer progression.

    Directory of Open Access Journals (Sweden)

    Gangjun Du

    Full Text Available Microenvironment has been increasingly recognized as a critical regulator of cancer progression. In this study, we identified early changes in the microenvironment that contribute to malignant progression. Exposure of human bronchial epithelial cells (BEAS-2B to methylnitrosourea (MNU caused a reduction in cell toxicity and an increase in clonogenic capacity when the temperature was lowered from 37°C to 28°C. Hypothermia-incubated adipocyte media promoted proliferation in A549 cells. Although a hypothermic environment could increase urethane-induced tumor counts and Lewis lung cancer (LLC metastasis in lungs of three breeds of mice, an increase in tumor size could be discerned only in obese mice housed in hypothermia. Similarly, coinjections using differentiated adipocytes and A549 cells promoted tumor development in athymic nude mice when adipocytes were cultured at 28°C. Conversely, fat removal suppressed tumor growth in obese C57BL/6 mice inoculated with LLC cells. Further studies show hypothermia promotes a MNU-induced epithelial-mesenchymal transition (EMT and protects the tumor cell against immune control by TGF-β1 upregulation. We also found that activated adipocytes trigger tumor cell proliferation by increasing either TNF-α or VEGF levels. These results suggest that hypothermia activates adipocytes to stimulate tumor boost and play critical determinant roles in malignant progression.

  13. Role of ADAMs in cancer formation and progression.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    The ADAMs (a disintegrin and metalloproteinase) comprise a family of multidomain transmembrane and secreted proteins. One of their best-established roles is the release of biologically important ligands, such as tumor necrosis factor-alpha, epidermal growth factor, transforming growth factor-alpha, and amphiregulin. Because these ligands have been implicated in the formation and progression of tumors, it might be expected that the specific ADAMs involved in their release would also be involved in malignancy. Consistent with this hypothesis, emerging data from model systems suggest that ADAMs, such as ADAM-9, ADAM-12, ADAM-15, and ADAM-17, are causally involved in tumor formation\\/progression. In human cancer, specific ADAMs are up-regulated, with levels generally correlating with parameters of tumor progression and poor outcome. In preclinical models, selective ADAM inhibitors against ADAM-10 and ADAM-17 have been shown to synergize with existing therapies in decreasing tumor growth. The ADAMs are thus a new family of potential targets for the treatment of cancer, especially malignancies that are dependent on human epidermal growth factor receptor ligands or tumor necrosis factor-alpha.

  14. Current trends in the chemotherapy of colorectal cancer.

    Science.gov (United States)

    Berciano-Guerrero, M A; Villa-Guzmán, J C; Acosta-Guerrero, R; Castañeda-Peñalvo, G; Rodríguez-Flores, J

    2012-01-01

    The increase in the therapeutic arsenal in the last 20 years, has given rise to changes in treating colorectal cancer (CRC) with only pyrimidines to combine several cytotoxic drugs. However, the present question is to determine the optimal sequence of this combination. This review presents an update of data on chemical and clinical features of chemotherapy used for colorectal cancer and the mechanisms of cellular resistance and potential predictive and prognostic biomarkers, which may contribute to a better selection of a therapeutic strategy. PMID:22830343

  15. Trends in socioeconomic inequalities in cancer mortality in Barcelona: 1992–2003

    Directory of Open Access Journals (Sweden)

    Pasarín M Isabel

    2009-01-01

    Full Text Available Abstract Background The objective of this study was to assess trends in cancer mortality by educational level in Barcelona from 1992 to 2003. Methods The study population comprised Barcelona inhabitants aged 20 years or older. Data on cancer deaths were supplied by the system of information on mortality. Educational level was obtained from the municipal census. Age-standardized rates by educational level were calculated. We also fitted Poisson regression models to estimate the relative index of inequality (RII and the Slope Index of Inequalities (SII. All were calculated for each sex and period (1992–1994, 1995–1997, 1998–2000, and 2001–2003. Results Cancer mortality was higher in men and women with lower educational level throughout the study period. Less-schooled men had higher mortality by stomach, mouth and pharynx, oesophagus, larynx and lung cancer. In women, there were educational inequalities for cervix uteri, liver and colon cancer. Inequalities of overall and specific types of cancer mortality remained stable in Barcelona; although a slight reduction was observed for some cancers. Conclusion This study has identified those cancer types presenting the greatest inequalities between men and women in recent years and shown that in Barcelona there is a stable trend in inequalities in the burden of cancer.

  16. Gastric cancer mortality trends in Spain, 1976-2005, differences by autonomous region and sex

    Directory of Open Access Journals (Sweden)

    Fernández-Navarro Pablo

    2009-09-01

    Full Text Available Abstract Background Gastric cancer is the second leading cause of oncologic death worldwide. One of the most noteworthy characteristics of this tumor's epidemiology is the marked decline reported in its incidence and mortality in almost every part of the globe in recent decades. This study sought to describe gastric cancer mortality time trends in Spain's regions for both sexes. Methods Mortality data for the period 1976 through 2005 were obtained from the Spanish National Statistics Institute. Cases were identified using the International Classification of Diseases 9th and 10th revision (codes 151 and C16, respectively. Crude and standardized mortality rates were calculated by geographic area, sex, and five-year period. Joinpoint regression analyses were performed to ascertain whether changes in gastric cancer mortality trends had occurred, and to estimate the annual percent change by sex and geographic area. Results Gastric cancer mortality decreased across the study period, with the downward trend being most pronounced in women and in certain regions situated in the interior and north of mainland Spain. Across the study period, there was an overall decrease of 2.90% per annum among men and 3.65% per annum among women. Generally, regions in which the rate of decline was sharpest were those that had initially registered the highest rates. However, the rate of decline was not constant throughout the study period: joinpoint analysis detected a shift in trend for both sexes in the early 1980s. Conclusion Gastric cancer mortality displayed in both sexes a downward trend during the study period, both nationally and regionally. The different trend in rates in the respective geographic areas translated as greater regional homogeneity in gastric cancer mortality by the end of the study period. In contrast, rates in women fell more than did those in men. The increasing differences between the sexes could indicate that some risk factors may be modifying

  17. Gastric cancer mortality trends in Spain, 1976-2005, differences by autonomous region and sex

    International Nuclear Information System (INIS)

    Gastric cancer is the second leading cause of oncologic death worldwide. One of the most noteworthy characteristics of this tumor's epidemiology is the marked decline reported in its incidence and mortality in almost every part of the globe in recent decades. This study sought to describe gastric cancer mortality time trends in Spain's regions for both sexes. Mortality data for the period 1976 through 2005 were obtained from the Spanish National Statistics Institute. Cases were identified using the International Classification of Diseases 9th and 10th revision (codes 151 and C16, respectively). Crude and standardized mortality rates were calculated by geographic area, sex, and five-year period. Joinpoint regression analyses were performed to ascertain whether changes in gastric cancer mortality trends had occurred, and to estimate the annual percent change by sex and geographic area. Gastric cancer mortality decreased across the study period, with the downward trend being most pronounced in women and in certain regions situated in the interior and north of mainland Spain. Across the study period, there was an overall decrease of 2.90% per annum among men and 3.65% per annum among women. Generally, regions in which the rate of decline was sharpest were those that had initially registered the highest rates. However, the rate of decline was not constant throughout the study period: joinpoint analysis detected a shift in trend for both sexes in the early 1980s. Gastric cancer mortality displayed in both sexes a downward trend during the study period, both nationally and regionally. The different trend in rates in the respective geographic areas translated as greater regional homogeneity in gastric cancer mortality by the end of the study period. In contrast, rates in women fell more than did those in men. The increasing differences between the sexes could indicate that some risk factors may be modifying the sex-specific pattern of this tumor

  18. Immunological network signatures of cancer progression and survival

    Directory of Open Access Journals (Sweden)

    Lavelle Timothy J

    2011-03-01

    Full Text Available Abstract Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding

  19. Towards Laser Driven Hadron Cancer Radiotherapy: A Review of Progress

    CERN Document Server

    Ledingham, K W D; Shikazono, N; Ma, C-M

    2014-01-01

    It has been known for about sixty years that proton and heavy ion therapy is a very powerful radiation procedure for treating tumours. It has an innate ability to irradiate tumours with greater doses and spatial selectivity compared with electron and photon therapy and hence is a tissue sparing procedure. For more than twenty years powerful lasers have generated high energy beams of protons and heavy ions and hence it has been frequently speculated that lasers could be used as an alternative to RF accelerators to produce the particle beams necessary for cancer therapy. The present paper reviews the progress made towards laser driven hadron cancer therapy and what has still to be accomplished to realise its inherent enormous potential.

  20. Trends in corrected lung cancer mortality rates in Brazil and regions

    Science.gov (United States)

    Malta, Deborah Carvalho; de Abreu, Daisy Maria Xavier; de Moura, Lenildo; Lana, Gustavo C; Azevedo, Gulnar; França, Elisabeth

    2016-01-01

    ABSTRACT OBJECTIVE To describe the trend in cancer mortality rates in Brazil and regions before and after correction for underreporting of deaths and redistribution of ill-defined and nonspecific causes. METHODS The study used data of deaths from lung cancer among the population aged from 30 to 69 years, notified to the Mortality Information System between 1996 and 2011, corrected for underreporting of deaths, non-registered sex and age , and causes with ill-defined or garbage codes according to sex, age, and region. Standardized rates were calculated by age for raw and corrected data. An analysis of time trend in lung cancer mortality was carried out using the regression model with autoregressive errors. RESULTS Lung cancer in Brazil presented higher rates among men compared to women, and the South region showed the highest death risk in 1996 and 2011. Mortality showed a trend of reduction for males and increase for women. CONCLUSIONS Lung cancer in Brazil presented different distribution patterns according to sex, with higher rates among men and a reduction in the mortality trend for men and increase for women. PMID:27355467

  1. Recent adverse trends in semen quality and testis cancer incidence among Finnish men

    DEFF Research Database (Denmark)

    Jørgensen, N; Vierula, M; Jacobsen, R;

    2011-01-01

    -2008 were included in the registry study, which confirmed the increasing incidence of testicular cancer in recent cohorts. These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and, as such, preventable. Our findings necessitate not only further......Impaired semen quality and testicular cancer may be linked through a testicular dysgenesis syndrome of foetal origin. The incidence of testis cancer has been shown to increase among Finnish men, whereas there is no recent publication describing temporal trends in semen quality. Therefore, we......-60) for birth cohorts 1979-81, 1982-83 and 1987; total sperm counts 227 (189-272) million, 202 (170-240) and 165 (132-207); total number of morphologically normal spermatozoa 18 (14-23) million, 15 (12-19) and 11 (8-15). Men aged 10-59 years at the time of diagnosis with testicular cancer during 1954...

  2. Trends in breast cancer in the elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Jensen, Jeanette D; Cold, Søren; Holck Nielsen, Mette;

    2016-01-01

    Background Breast cancer is the most frequent malignancy among women worldwide and the second most common cause of cancer-related death in developed countries. The aim of the present analysis is to describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980...... in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. Results The proportion of patients diagnosed with breast cancer over the age of 70 years increased with time to 29...... to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years. Material and methods Cancer of the breast was defined as ICD-10 code C50. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival...

  3. The Cancer Stem Cell Concept in Progression of Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Zhuo (Georgia Chen

    2009-01-01

    Full Text Available Human head and neck cancer (HNC is a highly heterogeneous disease. Understanding the biology of HNC progression is necessary for the development of novel approaches to its prevention, early detection, and treatment. A current evolutional progression model has limitations in explaining the heterogeneity observed in a single tumor nest. Accumulating evidence supports the existence of cancer stem cells (CSCs as small subpopulations in solid tumors, including HNC. These CSCs can be selected by appropriate cell surface markers, which are cancer type specific and have been confirmed by unique in vitro and in vivo assays. Selected CSC populations maintain a self-renewal capability and show aggressive behaviors, such as chemoresistance and metastasis. In addition to introducing the CSC concept in solid tumors, this short review summarizes current publications in HNC CSC and the prospective development and application of the CSC concept to HNC in the clinic.

  4. Current trends in cancer vaccines--a bioinformatics perspective.

    Science.gov (United States)

    Sankar, Shanju; Nayanar, Sangeetha K; Balasubramanian, Satheesan

    2013-01-01

    Cancer vaccine development is in the process of becoming reality in future, due to successful phase II/III clinical trials. However, there are still problems due to the specificity of tumor antigens and weakness of tumor associated antigens in eliciting an effective immune response. Computational models to assess the vaccine efficacy have helped to improve and understand what is necessary for personalized treatment. Further research is needed to elucidate the mechanisms of activation of antigen specific cytotoxic T lymphocytes, decreased TREG number functionality and antigen cascade, so that overall improvement in vaccine efficacy and disease free survival can be attained. T cell epitomic based in sillico approaches might be very effective for the design and development of novel cancer vaccines.

  5. Chemokines in Cancer Development and Progression and Their Potential as Targeting Molecules for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Naofumi Mukaida

    2014-01-01

    Full Text Available Chemokines were initially identified as bioactive substances, which control the trafficking of inflammatory cells including granulocytes and monocytes/macrophages. Moreover, chemokines have profound impacts on other types of cells associated with inflammatory responses, such as endothelial cells and fibroblasts. These observations would implicate chemokines as master regulators in various inflammatory responses. Subsequent studies have further revealed that chemokines can regulate the movement of a wide variety of immune cells including lymphocytes, natural killer cells, and dendritic cells in both physiological and pathological conditions. These features endow chemokines with crucial roles in immune responses. Furthermore, increasing evidence points to the vital effects of several chemokines on the proliferative and invasive properties of cancer cells. It is widely acknowledged that cancer develops and progresses to invade and metastasize in continuous interaction with noncancerous cells present in cancer tissues, such as macrophages, lymphocytes, fibroblasts, and endothelial cells. The capacity of chemokines to regulate both cancerous and noncancerous cells highlights their crucial roles in cancer development and progression. Here, we will discuss the roles of chemokines in carcinogenesis and the possibility of chemokine targeting therapy for the treatment of cancer.

  6. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    International Nuclear Information System (INIS)

    It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does

  7. Trends in gastric cancer mortality and in the prevalence of Helicobacter pylori infection in Portugal.

    Science.gov (United States)

    Morais, Samantha; Ferro, Ana; Bastos, Ana; Castro, Clara; Lunet, Nuno; Peleteiro, Bárbara

    2016-07-01

    Portugal has the highest gastric cancer mortality rates in Western Europe, along with high prevalences of Helicobacter pylori infection. Monitoring their trends is essential to predict the burden of this cancer. We aimed to quantify time trends in gastric cancer mortality in Portugal and in each administrative region, and to compute short-term predictions, as well as to describe the prevalence of H. pylori infection, through a systematic review. Joinpoint analyses were used to identify significant changes in sex-specific trends in gastric cancer age-standardized mortality rates (ASMR) and to estimate annual percent changes (APC). The most recent trends were considered to compute estimates up to 2020 by adjusting Poisson regression models. We searched PubMed and IndexRMP to identify studies carried out in Portugal reporting the prevalence of H. pylori. Gastric cancer mortality has been decreasing in Portugal since 1971 in men (from ASMR=55.3/100 000; APC=-2.4, 95% confidence interval: -2.5 to -2.3) and since 1970 in women (from ASMR=28.0/100 000; APC=-2.8, 95% confidence interval: -2.9 to -2.7), although large regional differences were observed. Predicted ASMR for 2015 and 2020 were 18.8/100 000 and 16.7/100 000 for men and 8.5/100 000 and 7.4/100 000 for women, respectively. The prevalence of H. pylori varied from almost 5% at 0.5-2 years to just over 90% at 70 years or more. No consistent variation was observed since the 1990s. The downward trends in mortality rates are expected to remain in the next decades. The high prevalence of H. pylori infection across age groups and studies from different periods shows a large potential for decrease in the burden of gastric cancer in Portugal.

  8. STAT3 activation in monocytes accelerates liver cancer progression

    Directory of Open Access Journals (Sweden)

    Wu Wen-Yong

    2011-12-01

    Full Text Available Abstract Background Signal transducer and activator of transcription 3 (STAT3 is an important transcription factor ubiquitously expressed in different cell types. STAT3 plays an essential role in cell survival, proliferation, and differentiation. Aberrantly hyper-activated STAT3 signaling in cancer cells and in the tumor microenvironment has been detected in a wide variety of human cancers and is considered an important factor for cancer initiation, development, and progression. However, the role of STAT3 activation in monocytes in the development of HCC has not been well understood. Methods Immunohistochemical analysis of phosphorylated STAT3 was performed on tissue microarray from HCC patients. Using a co-culture system in vivo, HCC cell growth was determined by the MTT assay. In vivo experiments were conducted with mice given diethylinitrosamine (DEN, which induces HCC was used to investigate the role of STAT3 expression in monocytes on tumor growth. Real-time PCR was used to determine the expression of cell proliferation and cell arrest associated genes in the tumor and nontumor tissue from liver. Results Phosphorylated STAT3 was found in human hepatocellular carcinoma tissue samples and was expressed in tumor cells and also in monocytes. Phosphorylated STAT3 expression in monocyte was significantly correlated to advanced clinical stage of HCC and a poor prognosis. Using a co-culture system in vivo, monocytes promoted HCC cell growth via the IL-6/STAT3 signaling pathway. The STAT3 inhibitor, NSC 74859, significantly suppressed tumor growth in vivo in mice with diethylinitrosamine (DEN-induced HCC. In this animal model, blockade of STAT3 with NSC 74859 induced tumor cell apoptosis, while inhibiting both tumor cells and monocytes proliferation. Furthermore, NSC 74859 treatment suppressed cancer associated inflammation in DEN-induce HCC. Conclusion Our data suggest constitutively activated STAT3 monocytes promote liver tumorigenesis in clinical

  9. STAT3 activation in monocytes accelerates liver cancer progression

    International Nuclear Information System (INIS)

    Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor ubiquitously expressed in different cell types. STAT3 plays an essential role in cell survival, proliferation, and differentiation. Aberrantly hyper-activated STAT3 signaling in cancer cells and in the tumor microenvironment has been detected in a wide variety of human cancers and is considered an important factor for cancer initiation, development, and progression. However, the role of STAT3 activation in monocytes in the development of HCC has not been well understood. Immunohistochemical analysis of phosphorylated STAT3 was performed on tissue microarray from HCC patients. Using a co-culture system in vivo, HCC cell growth was determined by the MTT assay. In vivo experiments were conducted with mice given diethylinitrosamine (DEN), which induces HCC was used to investigate the role of STAT3 expression in monocytes on tumor growth. Real-time PCR was used to determine the expression of cell proliferation and cell arrest associated genes in the tumor and nontumor tissue from liver. Phosphorylated STAT3 was found in human hepatocellular carcinoma tissue samples and was expressed in tumor cells and also in monocytes. Phosphorylated STAT3 expression in monocyte was significantly correlated to advanced clinical stage of HCC and a poor prognosis. Using a co-culture system in vivo, monocytes promoted HCC cell growth via the IL-6/STAT3 signaling pathway. The STAT3 inhibitor, NSC 74859, significantly suppressed tumor growth in vivo in mice with diethylinitrosamine (DEN)-induced HCC. In this animal model, blockade of STAT3 with NSC 74859 induced tumor cell apoptosis, while inhibiting both tumor cells and monocytes proliferation. Furthermore, NSC 74859 treatment suppressed cancer associated inflammation in DEN-induce HCC. Our data suggest constitutively activated STAT3 monocytes promote liver tumorigenesis in clinical patients and animal experiments. Thus, STAT3 in tumor

  10. Prostate cancer: trends in incidence, survival and mortality in the Netherlands, 1989-2006.

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Karim-Kos, H.E.; Houterman, S.; Verhoeven, R.H.; Schroder, F.H.; Kwast, T.H. van der; Kil, P.J.M.; Coebergh, J.W.W.; Kiemeney, L.A.L.M.

    2010-01-01

    BACKGROUND: Prostate cancer occurrence and stage distribution changed dramatically during the end of the 20th century. This study aimed to quantify and explain trends in incidence, stage distribution, survival and mortality in the Netherlands between 1989 and 2006. METHODS: Population-based data fro

  11. Time trends in educational inequalities in cancer mortality in Colombia, 1998-2012

    NARCIS (Netherlands)

    E. de Vries (Esther); I. Arroyave (Ivan); C. Pardo (Constanza)

    2016-01-01

    textabstractObjectives: To evaluate trends in premature cancer mortality in Colombia by educational level in three periods: 1998-2002 with low healthcare insurance coverage, 2003-2007 with rapidly increasing coverage and finally 2008-2012 with almost universal coverage (2008-2012). Setting: Colombia

  12. Lung cancer mortality trends in Chile and six-year projections using Bayesian dynamic linear models.

    Science.gov (United States)

    Torres-Avilés, Francisco; Moraga, Tomás; Núñez, Loreto; Icaza, Gloria

    2015-09-01

    The objectives were to analyze lung cancer mortality trends in Chile from 1990 to 2009, and to project the rates six years forward. Lung cancer mortality data were obtained from the Chilean Ministry of Health. To obtain mortality rates, population projections were used, based on the 2002 National Census. Rates were adjusted using the world standard population as reference. Bayesian dynamic linear models were fitted to estimate trends from 1990 to 2009 and to obtain projections for 2010-2015. During the period under study, there was a 19.9% reduction in the lung cancer mortality rate in men. In women, there was increase of 28.4%. The second-order model showed a better fit for men, and the first-order model a better fit for women. Between 2010 and 2015 the downward trend continued in men, while a trend to stabilization was projected for lung cancer mortality in women in Chile. This analytical approach could be useful implement surveillance systems for chronic non-communicable disease and to evaluate preventive strategies. PMID:26578021

  13. Prostate cancer in East Asia:evolving trend over the last decade

    Institute of Scientific and Technical Information of China (English)

    Yao Zhu; HongKai Wang; YuanYuan Qu; DingWei Ye

    2015-01-01

    Prostate cancer is now becoming an emerging health priority in East Asia. Most of our current knowledge on Prostate cancer has been generated from studies conducted in Western population; however, there is considerable heterogeneity of Prostate cancer between East and West. In this article, we reviewed epidemiologic trends, risk factors, disease characteristics and management of Prostate cancer in East Asian population over the last decade. Growing evidence from East Asia suggests an important role of genetic and environmental risk factors interactions in the carcinogenesis of Prostate cancer. Exposure to westernized diet and life style and improvement in health care in combination contribute substantially to the increasing epidemic in this region. Diagnostic and treatment guidelines in East Asia are largely based on Western knowledge. Although there is a remarkable improvement in the outcome over the last decade, ample evidence suggests an inneglectable difference in diagnostic accuracy, treatment efficacy and adverse events between different populations. The knowledge from western countries should be calibrated in the Asian setting to provide a better race‑based treatment approach. In this review, we intend to reveal the evolving trend of Prostate cancer in the last decade, in order to gain evidence to improve Prostate cancer prevention and control in East Asia.

  14. Tumor-derived exosomes in cancer progression and treatment failure.

    Science.gov (United States)

    Yu, Shaorong; Cao, Haixia; Shen, Bo; Feng, Jifeng

    2015-11-10

    Exosomes have diameter within the range of 30-100 nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy. PMID:26452221

  15. Tumor-derived exosomes in cancer progression and treatment failure.

    Science.gov (United States)

    Yu, Shaorong; Cao, Haixia; Shen, Bo; Feng, Jifeng

    2015-11-10

    Exosomes have diameter within the range of 30-100 nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy.

  16. Imaging in Colorectal Cancer: Progress and Challenges for the Clinicians

    Science.gov (United States)

    Van Cutsem, Eric; Verheul, Henk M. W.; Flamen, Patrik; Rougier, Philippe; Beets-Tan, Regina; Glynne-Jones, Rob; Seufferlein, Thomas

    2016-01-01

    The use of imaging in colorectal cancer (CRC) has significantly evolved over the last twenty years, establishing important roles in surveillance, diagnosis, staging, treatment selection and follow up. The range of modalities has broadened with the development of novel tracer and contrast agents, and the fusion of technologies such as positron emission tomography (PET) and computed tomography (CT). Traditionally, the most widely used modality for assessing treatment response in metastasised colon and rectal tumours is CT, combined with use of the RECIST guidelines. However, a growing body of evidence suggests that tumour size does not always adequately correlate with clinical outcomes. Magnetic resonance imaging (MRI) is a more versatile technique and dynamic contrast-enhanced (DCE)-MRI and diffusion-weighted (DW)-MRI may be used to evaluate biological and functional effects of treatment. Integrated fluorodeoxyglucose (FDG)-PET/CT combines metabolic and anatomical imaging to improve sensitivity and specificity of tumour detection, and a number of studies have demonstrated improved diagnostic accuracy of this modality in a variety of tumour types, including CRC. These developments have enabled the progression of treatment strategies in rectal cancer and improved the detection of hepatic metastatic disease, yet are not without their limitations. These include technical, economical and logistical challenges, along with a lack of robust evidence for standardisation and formal guidance. In order to successfully apply these novel imaging techniques and utilise their benefit to provide truly personalised cancer care, advances need to be clinically realised in a routine and robust manner. PMID:27589804

  17. Desmoglein 3: A Help or a Hindrance in Cancer Progression?

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Louise [Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Center for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Blizard Building, London E1 2AT (United Kingdom); Department of Cellular and Molecular Physiology, University of Liverpool, Institute of Translational Medicine, Liverpool L69 3BX (United Kingdom); Wan, Hong, E-mail: h.wan@qmul.ac.uk [Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Center for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Blizard Building, London E1 2AT (United Kingdom)

    2015-01-26

    Desmoglein 3 is one of seven desmosomal cadherins that mediate cell-cell adhesion in desmosomes. Desmosomes are the intercellular junctional complexes that anchor the intermediate filaments of adjacent cells and confer strong cell adhesion thus are essential in the maintenance of tissue architecture and structural integrity. Like adherens junctions, desmosomes function as tumour suppressors and are down regulated in the process of epithelial-mesenchymal transition and in tumour cell invasion and metastasis. However, recently several studies have shown that various desmosomal components, including desmoglein 3, are up-regulated in cancer with increased levels of expression correlating with the clinical stage of malignancy, implicating their potentiality to serve as a diagnostic and prognostic marker. Furthermore, in vitro studies have demonstrated that overexpression of desmoglein 3 in cancer cell lines activates several signal pathways that have an impact on cell morphology, adhesion and locomotion. These additional signalling roles of desmoglein 3 may not be associated to its adhesive function in desmosomes but rather function outside of the junctions, acting as a key regulator in the control of actin based cellular processes. This review will discuss recent advances which support the role of desmoglein 3 in cancer progression.

  18. Desmoglein 3: A Help or a Hindrance in Cancer Progression?

    International Nuclear Information System (INIS)

    Desmoglein 3 is one of seven desmosomal cadherins that mediate cell-cell adhesion in desmosomes. Desmosomes are the intercellular junctional complexes that anchor the intermediate filaments of adjacent cells and confer strong cell adhesion thus are essential in the maintenance of tissue architecture and structural integrity. Like adherens junctions, desmosomes function as tumour suppressors and are down regulated in the process of epithelial-mesenchymal transition and in tumour cell invasion and metastasis. However, recently several studies have shown that various desmosomal components, including desmoglein 3, are up-regulated in cancer with increased levels of expression correlating with the clinical stage of malignancy, implicating their potentiality to serve as a diagnostic and prognostic marker. Furthermore, in vitro studies have demonstrated that overexpression of desmoglein 3 in cancer cell lines activates several signal pathways that have an impact on cell morphology, adhesion and locomotion. These additional signalling roles of desmoglein 3 may not be associated to its adhesive function in desmosomes but rather function outside of the junctions, acting as a key regulator in the control of actin based cellular processes. This review will discuss recent advances which support the role of desmoglein 3 in cancer progression

  19. Trends in cancer in the elderly population in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Ewertz, Marianne; Christensen, Kaare; Engholm, Gerda;

    2016-01-01

    Background Age is the strongest risk factor for developing cancer. The aim of the present analysis is to give an overview of the trends in cancer incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those...... aged less than 70 years. Material and methods Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries. The Danish data originate from the Danish Cancer Registry and the Danish Cause of Death Registry...... with follow-up for death or emigration until the end of 2013. Results Incidence and mortality rates of all sites, but non-melanoma skin cancer, were higher and relative survival was lower among persons aged 70 years or more than those aged less than 70 years. The age distribution (age group...

  20. Trends in kidney cancer among the elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Azawi, Nessn H; Joergensen, Simon Moeller; Jensen, Niels Viggo;

    2016-01-01

    Background The purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark. Material and methods Cancer of the kidney was defined as ICD-10 code DC 64. Data derived from the NORDCAN database...... with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. Results The proportion...... of patients diagnosed with kidney cancer over the age of 70 years has decreased from 43% in 1980 to 32% in 2012 in men and remained almost constant in women, around 50%. Incidence rates were at least five times higher in men aged 70 years more but there was no particular trend with time. In men aged less than...

  1. Measuring trends in performance across time: providing information to cancer patients.

    Science.gov (United States)

    Fitch, Margaret I; McAndrew, Alison; Harth, Tamara

    2013-01-01

    Providing relevant, up-to-date information is identified as a quality standard of cancer care. Cancer programs need to be able to evaluate whether they are meeting the standard and to monitor their performance on an ongoing basis. Routine collection of clearly defined data, using reliable and valid measures, provides cancer program leaders with dependable information upon which to make decisions and monitor trends in performance over time. This article describes one cancer centre's experience in using standardized data collection regarding provision of patient information. The Cancer Patient Information Importance-Satisfaction Scale has been administered routinely in an outpatient setting over eight years. The profile we create from the data assists us in making informed decisions about patient education initiatives.

  2. Gender and racial inequalities in trends of oral cancer mortality in Sao Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Jose Leopoldo Ferreira Antunes

    2013-06-01

    Full Text Available OBJECTIVE: To analyse recent trends in oral cancer mortality, focusing specifically on differences concerning gender and race. METHODS: Official information on deaths and population in the city of Sao Paulo, 2003 to 2009, were used to estimate mortality rates from oral cancer (C00 to C10, International Classification of Diseases, 10th Revision, adjusted for age and stratified by gender (females and males and race (blacks and whites. The Prais-Winsten auto-regression procedure was used to analyse the time series. RESULTS: During the study period, 8,505 individuals living in the city of Sao Paulo died of oral cancer. Rates increased for females (rate of yearly increase = 4.4%, 95%CI 1.4;7.5, and levelled off for men, which represents an inversion of previous trends among genders in the city. Increases were identified for blacks, with a high rate of yearly increase of 9.1% (95%CI 5.5;12.9, and levelled off for whites. Oral cancer mortality in blacks almost doubled during the study period, and surpassed mortality in whites for almost all categories. CONCLUSIONS: Mortality presented a higher increase among women than in men, and it doubled among backs. The surveillance of trends of oral cancer mortality across gender and racial groups may contribute to implementing socially appropriate health policies, which concurrently reduce the burden of disease and the attenuation of unfair, avoidable and unnecessary inequalities in health.

  3. Trends in Research on Energy Balance Supported by the National Cancer Institute

    OpenAIRE

    Ballard-Barbash, Rachel; Siddiqi, Sameer M.; Berrigan, David A.; Ross, Sharon A.; Nebeling, Linda C.; Dowling, Emily C.

    2013-01-01

    Over the past decade, the body of research linking energy balance to the incidence, development, progression and treatment of cancer has grown substantially. No prior NIH portfolio analyses have focused on energy balance within one institute. This portfolio analysis describes the growth of National Cancer Institute (NCI) grant research on energy balance–related conditions and behaviors from 2004 to 2010 following the release of an NCI research priority statement in 2003 on energy balance and ...

  4. Cancer incidence and mortality trends in Australian adolescents and young adults, 1982–2007

    Directory of Open Access Journals (Sweden)

    Haggar Fatima A

    2012-04-01

    Full Text Available Abstract Background Increasing incidence and lack of survival improvement in adolescents and young adults (AYAs with cancer have led to increased awareness of the cancer burden in this population. The objective of this study was to describe overall and type-specific cancer incidence and mortality trends among AYAs in Western Australia from 1982–2007. Methods Age–adjusted incidence and mortality rates were calculated for all malignancies combined and for each of the most common diagnostic groups, using five-year age–specific rates. Joinpoint regression analysis was used to derive annual percentage changes (APC for incidence and mortality rates. Results The annual incidence rate for all cancers combined increased in males from 1982 until 2000 (APC = 1.5%, 95%CI: 0.9%; 2.1% and then plateaued, whilst rates for females remained stable across the study period (APC = −0.1%; 95%CI: −0.2%; 0.4% across the study period. For males, significant incidence rate increases were observed for germ cell tumors, lymphoblastic leukemia and thyroid cancer. In females, the incidence of Hodgkin’s lymphoma, colorectal and breast cancers increased. Significant incidence rate reductions were noted for cervical, central nervous system and lung cancers. Mortality rates for all cancers combined decreased from 1982 to 2005 for both males (APC = −2.6%, 95%CI:−3.3%;−2.0% and females (APC = −4.6%, 95%CI:−5.1%;−4.1%. With the exception of bone sarcoma and lung cancer in females, mortality rates for specific cancer types decreased significantly for both sexes during the study period. Conclusions Incidence of certain AYA cancers increased, whilst it decreased for others. Mortality rates decreased for most cancers, with the largest improvement observed for breast carcinomas. Further research is needed to identify the reasons for the increasing incidence of certain cancers.

  5. Trend and forecasting rate of cancer deaths at a public university hospital using univariate modeling

    Science.gov (United States)

    Ismail, A.; Hassan, Noor I.

    2013-09-01

    Cancer is one of the principal causes of death in Malaysia. This study was performed to determine the pattern of rate of cancer deaths at a public hospital in Malaysia over an 11 year period from year 2001 to 2011, to determine the best fitted model of forecasting the rate of cancer deaths using Univariate Modeling and to forecast the rates for the next two years (2012 to 2013). The medical records of the death of patients with cancer admitted at this Hospital over 11 year's period were reviewed, with a total of 663 cases. The cancers were classified according to 10th Revision International Classification of Diseases (ICD-10). Data collected include socio-demographic background of patients such as registration number, age, gender, ethnicity, ward and diagnosis. Data entry and analysis was accomplished using SPSS 19.0 and Minitab 16.0. The five Univariate Models used were Naïve with Trend Model, Average Percent Change Model (ACPM), Single Exponential Smoothing, Double Exponential Smoothing and Holt's Method. The overall 11 years rate of cancer deaths showed that at this hospital, Malay patients have the highest percentage (88.10%) compared to other ethnic groups with males (51.30%) higher than females. Lung and breast cancer have the most number of cancer deaths among gender. About 29.60% of the patients who died due to cancer were aged 61 years old and above. The best Univariate Model used for forecasting the rate of cancer deaths is Single Exponential Smoothing Technique with alpha of 0.10. The forecast for the rate of cancer deaths shows a horizontally or flat value. The forecasted mortality trend remains at 6.84% from January 2012 to December 2013. All the government and private sectors and non-governmental organizations need to highlight issues on cancer especially lung and breast cancers to the public through campaigns using mass media, media electronics, posters and pamphlets in the attempt to decrease the rate of cancer deaths in Malaysia.

  6. In situ quantification of genomic instability in breast cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz de Solorzano, Carlos; Chin, Koei; Gray, Joe W.; Lockett, Stephen J.

    2003-05-15

    Genomic instability is a hallmark of breast and other solid cancers. Presumably caused by critical telomere reduction, GI is responsible for providing the genetic diversity required in the multi-step progression of the disease. We have used multicolor fluorescence in situ hybridization and 3D image analysis to quantify genomic instability cell-by-cell in thick, intact tissue sections of normal breast epithelium, preneoplastic lesions (usual ductal hyperplasia), ductal carcinona is situ or invasive carcinoma of the breast. Our in situ-cell by cell-analysis of genomic instability shows an important increase of genomic instability in the transition from hyperplasia to in situ carcinoma, followed by a reduction of instability in invasive carcinoma. This pattern suggests that the transition from hyperplasia to in situ carcinoma corresponds to telomere crisis and invasive carcinoma is a consequence of telomerase reactivation afertelomere crisis.

  7. Paracrine effects of stem cells in wound healing and cancer progression

    OpenAIRE

    DITTMER, JÜRGEN; Leyh, Benjamin

    2014-01-01

    Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific stem cells to rebuild damaged tissue and cancer stem cells to initiate and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer, facilitate wound healing and support cancer progression primarily by secreting bioactive factors. There is now growing evidence that, like mesenchymal stem cells, also tissue-specific...

  8. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  9. Tobacco and lung cancer: risks, trends, and outcomes in patients with cancer.

    Science.gov (United States)

    Warren, Graham W; Cummings, K Michael

    2013-01-01

    Tobacco use, primarily associated with cigarette smoking, is the largest preventable cause of cancer mortality, responsible for approximately one-third of all cancer deaths. Approximately 85% of lung cancers result from smoking, with an additional fraction caused by secondhand smoke exposure in nonsmokers. The risk of lung cancer is dose dependent, but can be dramatically reduced with tobacco cessation, especially if the person discontinues smoking early in life. The increase in lung cancer incidence in different countries around in the world parallels changes in cigarette consumption. Lung cancer risks are not reduced by switching to filters or low-tar/low-nicotine cigarettes. In patients with cancer, continued tobacco use after diagnosis is associated with poor therapeutic outcomes including increased treatment-related toxicity, increased risk of second primary cancer, decreased quality of life, and decreased survival. Tobacco cessation in patients with cancer may improve cancer treatment outcomes, but cessation support is often not provided by oncologists. Reducing the health related effects of tobacco requires coordinated efforts to reduce exposure to tobacco, accurately assess tobacco use in clinical settings, and increase access to tobacco cessation support. Lung cancer screening and coordinated international tobacco control efforts offer the promise to dramatically reduce lung cancer mortality in the coming decades.

  10. Trends in colorectal cancer survival in northern Denmark: 1985-2004

    DEFF Research Database (Denmark)

    Iversen, Lene Hjerrild; Nørgaard, Mette; Jepsen, Peter;

    2007-01-01

    in four Danish counties. METHOD: We used hospital discharge registry data for the period January 1985-March 2004 in the counties of north Jutland, Ringkjøbing, Viborg and Aarhus. We computed crude survival and used Cox proportional hazards regression analysis to compare mortality over time, adjusted......OBJECTIVE: The prognosis for colorectal cancer (CRC) is less favourable in Denmark than in neighbouring countries. To improve cancer treatment in Denmark, a National Cancer Plan was proposed in 2000. We conducted this population-based study to monitor recent trends in CRC survival and mortality...... for age and gender. A total of 19,515 CRC patients were identified and linked with the Central Office of Civil Registration to ascertain survival through January 2005. Results: From 1985 to 2004, 1-year and 5-year survival improved both for patients with colon and rectal cancer. From 1995-1999 to 2000...

  11. Correlation of DNA Ploidy with Progression of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    M. Singh

    2008-01-01

    Full Text Available The majority of squamous cell carcinomas of cervix are preceded by visible changes in the cervix, most often detected by cervical smear. As cervical cancer is preceded by long precancerous stages, identification of the high-risk population through detection of DNA ploidy may be of importance in effective management of this disease. Here we attempted to correlate aneuploid DNA patterns and their influence on biological behavior of flow-cytometry analysis of DNA ploidy which was carried out in cytologically diagnosed cases of mild (79, moderate (36, and severe (12 dysplasia, as well as “atypical squamous cells of unknown significance (ASCUS” (57 along with controls (69, in order to understand its importance in malignant progression of disease. Cytologically diagnosed dysplasias, which were employed for DNA ploidy studies, 39 mild, 28 moderate, and 11 severe dysplasia cases were found to be aneuploid. Out of the 69 control subjects, 6 cases showed aneuploidy pattern and the rest 63 subjects were diploid. An aneuploidy pattern was observed in 8 out of 57 cases of cytologically evaluated ASCUS. The results of the followup studies showed that aberrant DNA content reliably predicts the occurrence of squamous cell carcinoma in cervical smear. Flow cytometric analysis of DNA ploidy may provide a strategic diagnostic tool for early detection of carcinoma cervix. Therefore, it is a concept of an HPV screening with reflex cytology in combination with DNA flow cytometry to detect progressive lesions with the greatest possible sensitivity and specificity.

  12. Time trends of cancer mortality among elderly in Italy, 1970–2008: an observational study

    Directory of Open Access Journals (Sweden)

    Bidoli Ettore

    2012-10-01

    Full Text Available Abstract Background The aging of the Italian population will unavoidably lead to a growing number of persons diagnosed and living with cancer. A comprehensive description of the burden of cancer mortality among Italian elderly (65-84 years of age in the last four decades has not been carried out yet. Cancer mortality rates were used to describe time trends between 1970-2008. Methods Mortality counts, provided by the Italian National Institute of Statistics, were grouped according to data availability: in quinquennia from 1970-74 through 1995-99, and in 2000-03 and 2006-08 groups. Age-standardized rates (world population were computed by calendar periods while annual percent changes (APCs were computed for elderly and middle aged (35-64 years people for the period 1995-2008. Results The number of cancer deaths in elderly nearly doubled between 1970-74 (31,400 deaths/year in men, and 24,000 in women and 2006-08 (63,000 deaths/year in men, and 42,000 in women. Overall cancer mortality rates peaked during the quinquennia 1985-89 and 1990-94 (about 1,500/100,000 in men and 680 in women and declined thereafter. Throughout 1995-2008 cancer mortality rates decreased by -1.6%/year in men and -0.9%/year in women. These decreases were mainly driven by cancers of the stomach, bladder, prostate, and lung (APC = -3.3%, -2.7%, -2.5%, -2.2%, respectively in men, and by cancers of the stomach, bladder, and breast (APC = -3.5%, -1.9%, -1.1%, respectively in women. Conversely, increases in mortality rates between 1995 and 2008 were recorded for lung cancer (APC = +0.6% in women, cutaneous melanoma (APC = +1.7% in men, and pancreatic cancer (APC = +0.6% in men and +0.9% in women. Conclusions Overall favorable trends in cancer mortality were observed among Italian elderly between 1995 and 2008. Early diagnosis, improved efficacy of anti-cancer treatments and management of comorbidities are the most likely explanations of these positive

  13. Effect of Proton Beam on Cancer Progressive and Metastatic Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Y. H.; Nam, K. S.; Oh, Y. H.; Kim, M. K.; Kim, M. Y.; Jang, J. S. [Dongguk University, Seoul (Korea, Republic of)

    2008-04-15

    The purpose of this study was to investigate the effect of proton beam on enzymes for promotion/progression of carcinogenesis and metastasis of malignant tumor cells to clarify proton beam-specific biological effects. The changes of cancer chemopreventive enzymes in human colorectal adenocarcinoma HT-29 cells irradiated with proton beams were tested by measuring the activities of quinine reductase (QR), glutathione S-transferase (GST), and ornithine decarboxylase (ODC), glutathione (GSH) levels, and expression of cyclooxygenase-2 (COX-2). We also examined the effect of proton beam on the ODC activity and expression of COX-2 in human breast cancer cell. We then assessed the metastatic capabilities of HT-29 and MDA-MB-231 cells irradiated with proton beam by measuring the invasiveness of cells through Matrigel-coated membrane and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP activity in MDA-MB-231 and HT-29 cells. QR activity of irradiated HT-29 cells was slightly increased. Proton irradiation at dose of 32 Gy in HT-29 cells increased GST activity by 1.23-fold. In addition GSH levels in HT-29 cells was significantly increased 1.23- (p<0.05), 1.32- (p<0.01) and 1.34-fold (p<0.01) with the proton irradiation at doses of 8, 16 and 32 Gy, respectively. These results suggest that colon cancer chemopreventive activity was increased with the proton irradiation by increasing QR and GST activities and GSH levels and inhibiting ODC activity. Proton ion irradiation decreased the invasiveness of TPA-treated HT-29 cells and MDA-MB-231 cells through Matrigel-coated membrane. Proton ion irradiation pretreatment decreased TPA-induced MMP activity in MDA-MB-231 and HT-29 cells. Further studies are necessary to investigate if these findings could be translated to in vivo situations

  14. Role of Proprotein Convertases in Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Frédéric Couture

    2012-11-01

    Full Text Available Better understanding of the distinct and redundant functions of the proprotein convertase (PC enzyme family within pathophysiological states has a great importance for potential therapeutic strategies. In this study, we investigated the functional redundancy of PCs in prostate cancer in the commonly used androgen-sensitive LNCaP and the androgen-independent DU145 human cell lines. Using a lentiviral-based shRNA delivery system, we examined in vitro and in vivo cell proliferation characteristics of knockdown cell lines for the endogenous PCs furin, PACE4, and PC7 in both cell lines. Of the three PCs, only PACE4 was essential to maintain a high-proliferative status, as determined in vitro using XTT proliferation assays and in vivo using tumor xenografts in nude mice. Furin knockdowns in both cell lines had no effects on cell proliferation or tumor xenograft growth. Paradoxically, PC7 knockdowns reduced in vitro cellular proliferation but had no effect in vivo. Because PCs act within secretion pathways, we showed that conditioned media derived from PACE4 knockdown cells had very poor cell growth-stimulating effects in vitro. Immunohistochemistry of PACE4 knockdown tumors revealed reduced Ki67 and higher p27KIP levels (proliferation and cell cycle arrest markers, respectively. Interestingly, we determined that the epidermal growth factor receptor signaling pathway was activated in PC7 knockdown tumors only, providing some explanations of the paradoxical effects of PC7 silencing in prostate cancer cell lines. We conclude that PACE4 has a distinct role in maintaining proliferation and tumor progression in prostate cancer and this positions PACE4 as a relevant therapeutic target for this disease.

  15. Current Trends in Numerical Simulation for Parallel Engineering Environments New Directions and Work-in-Progress

    International Nuclear Information System (INIS)

    In today's world, the use of parallel programming and architectures is essential for simulating practical problems in engineering and related disciplines. Remarkable progress in CPU architecture, system scalability, and interconnect technology continues to provide new opportunities, as well as new challenges for both system architects and software developers. These trends are paralleled by progress in parallel algorithms, simulation techniques, and software integration from multiple disciplines. ParSim brings together researchers from both application disciplines and computer science and aims at fostering closer cooperation between these fields. Since its successful introduction in 2002, ParSim has established itself as an integral part of the EuroPVM/MPI conference series. In contrast to traditional conferences, emphasis is put on the presentation of up-to-date results with a short turn-around time. This offers a unique opportunity to present new aspects in this dynamic field and discuss them with a wide, interdisciplinary audience. The EuroPVM/MPI conference series, as one of the prime events in parallel computation, serves as an ideal surrounding for ParSim. This combination enables the participants to present and discuss their work within the scope of both the session and the host conference. This year, eleven papers from authors in nine countries were submitted to ParSim, and we selected five of them. They cover a wide range of different application fields including gas flow simulations, thermo-mechanical processes in nuclear waste storage, and cosmological simulations. At the same time, the selected contributions also address the computer science side of their codes and discuss different parallelization strategies, programming models and languages, as well as the use nonblocking collective operations in MPI. We are confident that this provides an attractive program and that ParSim will be an informal setting for lively discussions and for fostering new

  16. Historical Trends in the Use of Radiation Therapy for Pediatric Cancers: 1973-2008

    Energy Technology Data Exchange (ETDEWEB)

    Jairam, Vikram [Yale School of Medicine, Department of Therapeutic Radiology, New Haven, Connecticut (United States); Roberts, Kenneth B. [Yale School of Medicine, Department of Therapeutic Radiology, New Haven, Connecticut (United States); Yale Cancer Center, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center at Yale, New Haven, Connecticut (United States); Yu, James B., E-mail: james.b.yu@yale.edu [Yale School of Medicine, Department of Therapeutic Radiology, New Haven, Connecticut (United States); Yale Cancer Center, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center at Yale, New Haven, Connecticut (United States)

    2013-03-01

    Purpose: This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database of the 9 original tumor registries (SEER-9) was queried to identify patients aged 0 to 19 years with acute lymphoblastic leukemia, acute myeloid leukemia, bone and joint cancer, cancer of the brain and nervous system, Hodgkin lymphoma, neuroblastoma, non-Hodgkin lymphoma, soft tissue cancer, Wilms tumor, or retinoblastoma from 1973 to 2008. Patients were grouped into 4-year time epochs. The number and percentage of patients who received RT as part of their initial treatment were calculated per epoch by each diagnosis group from 1973 to 2008. Results: RT use for acute lymphoblastic leukemia, non-Hodgkin lymphoma, and retinoblastoma declined sharply from 57%, 57%, and 30% in 1973 to 1976 to 11%, 15%, and 2%, respectively, in 2005 to 2008. Similarly, smaller declines in RT use were also seen in brain cancer (70%-39%), bone cancer (41%-21%), Wilms tumor (75%-53%), and neuroblastoma (60%-25%). RT use curves for Wilms tumor and neuroblastoma were nonlinear with nadirs in 1993 to 1996 at 39% and 19%, respectively. There were minimal changes in RT use for Hodgkin lymphoma, soft tissue cancer, or acute myeloid leukemia, roughly stable at 72%, 40%, and 11%, respectively. Almost all patients treated with RT were given external beam RT exclusively. However, from 1985 to 2008, treatments involving brachytherapy, radioisotopes, or combination therapy increased in frequency, comprising 1.8%, 4.6%, and 11.9% of RT treatments in brain cancer, soft tissue cancer, and retinoblastoma, respectively. Conclusions: The use of RT is declining over time in 7 of 10 pediatric cancer categories. A limitation of this study is a potential under-ascertainment of RT use in the SEER-9 database including the delayed use of RT.

  17. Greenhouse gas emission trends and projections in Europe 2011. Tracking progress towards Kyoto and 2020 targets

    Energy Technology Data Exchange (ETDEWEB)

    Busche, J.; Scheffler, M.; Graichen, V. (Umweltbundesamt, Vienna (Austria)) (and others)

    2011-10-15

    At the end of 2010, the EU-15 was on track to achieve its Kyoto target but three EU-15 Member States (Austria, Italy and Luxembourg) were not on track to meet their burden-sharing targets. These countries must therefore seriously consider further action to ensure compliance, in particular revising their plans on using flexible mechanisms. Among the EEA member countries outside the EU, Liechtenstein and Switzerland were not on track to achieve their Kyoto target at the end of 2009. All other European countries are on track to meet their targets, either based on domestic emissions only or with the assistance of Kyoto mechanisms. The economic recession had a significant impact on the EU's total greenhouse gas (GHG) emission trends but a more limited effect on progress towards Kyoto targets. This is because emissions in the sectors covered by the EU Emissions Trading Scheme (ETS), which were most affected by the crisis, do not affect Kyoto compliance once ETS caps have been set. With existing national measures, Member States do not project enough emission reductions for the EU to meet its unilateral 20 % reduction commitment in 2020. Additional measures currently planned by Member States will help further reduce emissions but will be insufficient to achieve the important emission cuts needed in the longer term. By 2020 Member States must enhance their efforts to reduce emissions in non-EU ETS sectors, such as the residential, transport or agriculture sectors, where legally binding national targets have been set under the EU's 2009 climate and energy package. (Author)

  18. High prevalence and upward trend of pulmonary tuberculosis in leukemia, lymphoma and lung cancer patients

    International Nuclear Information System (INIS)

    Objective: To document the prevalence and any increasing or decreasing trend of tuberculosis in cancer patients. Design: An analysis and comparison of patients suffering from cancers along with tuberculosis for years 1976, 1987 and 1999. Place and Duration of study: The record of all these patients was collected from different hospitals of Lahore, specially Mayo Hospital, Services Hospital and patients managed privately by the authors of this study. Subjects and Methods: In the years 1976, 1987 and 1999, total cancer patients were 1100, 1481 and 1628 respectively. Patients were diagnosed on the basis of history, physical examination, sputum for AFB, culture for AFB tuberculin skin test and x ray chest. In few difficult cases, Mycodot blood test was also performed. Results: in patients with head and neck cancers, 3.6 %, 3.9% and 4.4% had tuberculosis in the years 1976, 1987 and 1999 respectively. In lung cancer patient the prevalen of tuberculosis was 6.5%, 4.9% and 6.9% for each respective year. In case of leukemia and lymphoma, the prevalence of tuberculosis was 9.8%, 11.25% and 11.21% for the years 1976, 1987 and 1999 respectively. Conclusion: A statistically significant difference was seen in leukemia, lymphoma and lung cancer cases for prevalence of pulmonary tuberculosis as compared to all other cancers combined over respective years. (author)

  19. Cancer trends in Kashmir; common types, site incidence and demographic profiles: National Cancer Registry 2000-2012

    Directory of Open Access Journals (Sweden)

    M A Wani

    2014-01-01

    Full Text Available Background: An assessment of cancer incidence in population is required for prevention, early diagnosis, treatment and resource allocation. This will also guide in the formation of facilities for diagnosis, treatment, rehabilitation and follow-up for these patients. The demographic trend of cancer will help to identify common types and etiological factors. Efforts at clinical, research and administrative levels are needed to overcome this problem. Settings and Design: Present retro prospective study was conducted in regional cancer center of a tertiary care hospital. Materials and Methods: After permission from ethics committee, a retro prospective study of 1 year duration was undertaken to study the profile of cancer patients and to compare it with other cancer registries in India. Statistical Analysis: Pearson′s Chi-square test and simple linear regression were used. Statistical Package for the Social Sciences version-16 (University of Bristol information services (www.bristol.ac.uk/is/learning/resources was used. RESULTS: The overall incidence of cancer in Kashmir is on the increase and common sites of cancer are esophagus and gastroesophageal (GE junction, lung, stomach, colorectal, lymphomas, skin, laryngopharynx, acute leukemias, prostate and brain in males.In females common sites are breast, esophagus and GE junction, ovary, colorectal, stomach, lung, gallbladder, lymphomas, acute leukemias and brain. Conclusion: Cancers of esophagus, stomach and lungs have a high incidence both in men and women in Kashmir. Future studies on sources and types of environmental pollution and exposures in relation to these cancers may improve our understanding of risk factors held responsible for causation of these malignancies in this region. This will help in the allocation of available resources for prevention and treatment strategies.

  20. Trends in oral cavity cancer incidence, mortality, survival and treatment in the Netherlands.

    Science.gov (United States)

    van Dijk, Boukje A C; Brands, Marieke T; Geurts, Sandra M E; Merkx, Matthias A W; Roodenburg, Jan L N

    2016-08-01

    Information on epidemiology is essential to evaluate care for the growing group of oral cancer patients. We investigated trends in incidence, mortality and relative survival rates for oral cavity cancer (OCC) and its subsites in the Netherlands from 1991 to 2010, and relate these to changes in stage and treatment. Patient (age, sex), tumour (subsite, stage) and treatment characteristics of patients diagnosed with OCC (ICD-O-3: C02-C06) in 1991-2010 were extracted from the Netherlands Cancer Registry. Incidence, mortality and 5-year relative survival rates over time are presented, as well as trends in type of treatment. The incidence of OCC increased with +1.2% (95%CI: +0.9%;+1.6%) per year: more strongly in women, stage I and IV disease, and in cancers of the tongue and gum. The mortality rate slightly rose (+0.8%, 95%CI: +0.3%;+1.3% per year), but differed by subsite. The 5-year relative survival improved from 57% in 1991-1995 to 62% in 2006-2010. The 5-year relative survival was better for women compared with men (64% and 55%, respectively), decreased with increasing stage, was the best for tongue cancer (63%) and the worst for cancer of the gum (56%) and floor of mouth cancer (55%). The relative excess risk of dying was higher for non-surgery-based treatments. Surgery was the main treatment option and the proportion of "surgery only" rose in stage I and III disease. The incidence and, to a lesser extent, mortality of OCC are increasing and therefore, even with slightly improving survival rates, OCC is an increasingly important health problem. PMID:27038013

  1. International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007.

    Science.gov (United States)

    Petrick, Jessica L; Braunlin, Megan; Laversanne, Mathieu; Valery, Patricia C; Bray, Freddie; McGlynn, Katherine A

    2016-10-01

    Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence.

  2. Trends of cancer incidence and mortality in Cali, Colombia. 50 years experience

    Directory of Open Access Journals (Sweden)

    Luis Eduardo Bravo

    2012-12-01

    Full Text Available Objetive: The Population-based Cancer Registry of Cali aims to report all new cases in permanent residents within the limits of the city of Cali. Time trends of cancer incidence and mortality are described. The registry has been in continuous operation for 50 years. Methods: Cancer cases reports are obtained actively by visiting all sources of information: hospitals, pathology departments, hematology laboratories, radiotherapy centers, government offices where death certificates are processed and physician’s offices. It is estimated that the reporting is at least 95% complete. Results: Drastic decreases are documented in rates for tumors causally related to infectious agents, especially cancers of the uterine cervix and the stomach. Gradual increases are documented in rates of tumors linked to affluence and the metabolic syndrome, especially cancers of the colon and the female breast. An unexpected increase in the incidence of papillary carcinoma of the thyroid gland in women is reported. Tobacco-related cancers, especially cancer of the lung, showed marked increase in incidence rates around 1970, apparently the beginning of an epidemic similar to the one reported in Western societies. But the increase in incidence stopped around 1980, resulting from a strong anti-smoking campaign launched in Colombia in the 1970s. Conclusions: The findings have influenced prevention strategies implemented by public health authorities, specially the establishment of a city-wide program to prevent cervix cancer via widespread use of vaginal cytology and anti-smoking campaigns. Also, new population-based cancer registries have been established in other Colombian cities as well as in Ecuador.

  3. Trends of cancer incidence and mortality in Cali, Colombia. 50 years experience

    Directory of Open Access Journals (Sweden)

    Bravo, Luis Eduardo

    2012-12-01

    Full Text Available Purpose :The Population-based Cancer Registry of Cali aims to report all new cases in permanent residents within the limits of the city of Cali. Time trends of cancer incidence and mortality are described. The registry has been in continuous operation for 50 years. Methods: Cancer cases reports are obtained actively by visiting all sources of information: hospitals, pathology departments, hematology laboratories, radiotherapy centers, government offices where death certificates are processed and physician’s offices. It is estimated that the reporting is at least 95% complete. Results: Drastic decreases are documented in rates for tumors causally related to infectious agents, especially cancers of the uterine cervix and the stomach. Gradual increases are documented in rates of tumors linked to affluence and the metabolic syndrome, especially cancers of the colon and the female breast. An unexpected increase in the incidence of papillary carcinoma of the thyroid gland in women is reported. Tobacco-related cancers, especially cancer of the lung, showed marked increase in incidence rates around 1970, apparently the beginning of an epidemic similar to the one reported in Western societies. But the increase in incidence stopped around 1980, resulting from a strong anti-smoking campaign launched in Colombia in the 1970s. Conclusions: The findings have influenced prevention strategies implemented by public health authorities, specially the establishment of a city-wide program to prevent cervix cancer via widespread use of vaginal cytology and anti-smoking campaigns. Also, new population-based cancer registries have been established in other Colombian cities as well as in Ecuador.

  4. 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.

  5. Exosomes from the tumor microenvironment as reciprocal regulators that enhance prostate cancer progression.

    Science.gov (United States)

    Liu, Che-Ming; Hsieh, Chia-Ling; Shen, Chia-Ning; Lin, Cheng-Chieh; Shigemura, Katsumi; Sung, Shian-Ying

    2016-09-01

    Distant organ metastasis of prostate cancer is a puzzle, and various theories have successively arisen to explain the mechanism of lethal cancer progression. While perhaps agreeable to many cancer biologists, the very statement of "seed and soil" proposed by Stephan Paget in 1881 is arguably still the major statement for organ-specific cancer metastasis. Since recent studies showed important correlations of regulation of cancer cells and the microenvironment, exosomes from cancer and stromal cells seem to create another important niche for metastasis. Stromal cells pretreated with exosomes from metastatic cancer cells increase the potential of change stromal cells. The poorly metastatic cancer cells could also enhance malignancy through transfer of proteins, microribonucleic acid and messenger ribonucleic acid to recipient cancer cells. Herein, we reviewed extracellular exosomes as a factor involved in cross-talk between stromal and prostate cancer epithelial cells. PMID:27397852

  6. The fundamental role of mechanical properties in the progression of cancer disease and inflammation

    Science.gov (United States)

    Mierke, Claudia Tanja

    2014-07-01

    The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in

  7. Increasing Trend in Colorectal Cancer Incidence in the Southeast of Iran 2003-2013: A Population Based Cancer Registry Study.

    Science.gov (United States)

    Baniasadi, Nadieh; Moghtader, Elahe; Khajehkazemi, Razieh; Mohebbi, Elham

    2015-01-01

    Rates based on age-adjusted incidence of colorectal cancers over a 10-year period in Kerman, the biggest province of Iran, were estimated from 2003 to 2013. Data were obtained from the population-based cancer registry unit of Kerman University of Medical Sciences (CR-KMU). Information included age, sex, city, ICD-O and year of registry. Our trend analyses cover 3.91% of the Iranian population. The data set comprised cases diagnosed from 2003 to 2013.The population of over 20 years was interpolated using 2003 and 2010 censuses. Then, truncated age-adjusted incidence rates were calculated. Increase was noted from 2003-2009 to 2010-2013 for 731 cancer cases considered in the analysis. The increases was most prominent in 2009. Totally, the frequency of the cancer was greater in males. Moreover, calculating truncated age-adjusted incidence rate indicated that the most prevalent age of colorectal incidence was in the 50-59 year age group except in 2007-2008 and 2012- 2013, when greatest incidences occurred in people aged 60-69 years. Our data revealed that the incidence rates of colorectal cancer have increased over the past decade in our region of Iran.

  8. Age-specific cancer survival in Estonia: recent trends and data quality

    Directory of Open Access Journals (Sweden)

    Innos K

    2015-07-01

    Full Text Available Kaire Innos,1 Katrin Lang,2 Kersti Pärna,2 Tiiu Aareleid11Department of Epidemiology and Biostatistics, National Institute for Health Development, Tallinn, Estonia; 2Department of Public Health, University of Tartu, Tartu, EstoniaBackground: A number of population-based studies have demonstrated lower cancer survival in elderly patients than among middle-aged or younger patients. Also, data quality in cancer registries has been shown to be associated with age. The objective of this study was to examine the recent age-specific cancer survival trends and age-specific quality of cancer data in Estonia.Methods: Using Estonian Cancer Registry data, we calculated relative survival ratios (RSRs for eight common cancers in Estonia in 1995–1999 (cohort method and 2005–2009 (period method for four major age groups (15–54, 55–64, 65–74, and 75–84 years at diagnosis. The main data quality indicators were calculated, and the age-specific effect of missing death certificate initiated (DCI cases on survival was estimated comparing 5-year RSRs computed from the complete data set with those from data set without DCI cases.Results: We observed overall rise in 5-year RSR for all eight cancers over the study period, with a considerable variation by age, with the lowest survival among the oldest patients. The widest age gradient in 5-year RSR was seen for bladder cancer (20% units in 2005–2009, followed by cancers of lung (16% units, kidney (15% units, breast and prostate (13% units, stomach and rectum (11% units, and colon (5% units. All data quality indicators, including proportion of cases with unknown stage showed a similar age-related pattern with the lowest quality in the oldest age group. The effect of missing DCI cases on survival estimates increased by age and was around 3% units for prostate and kidney cancers among the oldest patients.Conclusion: Young or middle-aged patients in Estonia experienced larger survival gain since the late 1990s

  9. Nano-mechanical Phenotype as a Promising Biomarker to Evaluate Cancer Development, Progression, and Anti-cancer Drug Efficacy.

    Science.gov (United States)

    Park, Soyeun

    2016-06-01

    Since various bio-mechanical assays have been introduced for studying mechanical properties of biological samples, much progress has been made in cancer biology. It has been noted that enhanced mechanical deformability can be used as a marker for cancer diagnosis. The relation between mechanical compliances and the metastatic potential of cancer cells has been suggested to be a promising prognostic marker. Although it is yet to be conclusive about its clinical application due to the complexity in the tissue integrity, the nano-mechanical compliance of human cell samples has been evaluated by several groups as a promising marker in diagnosing cancer development and anticipating its progression. In this review, we address the mechanical properties of diverse cancer cells obtained by atomic force microscopy-based indentation experiments and reiterate prognostic relations between the nano-mechanical compliance and cancer progression. We also review the nano-mechanical responses of cancer cells to the anti-cancer drug treatment in order to interrogate a possible use of nano-mechanical compliance as a means to evaluate the effectiveness of anti-cancer drugs.

  10. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective.

    Science.gov (United States)

    Betof, Allison S; Dewhirst, Mark W; Jones, Lee W

    2013-03-01

    Over the past decade there has been increasing research and clinical interest in the role of exercise therapy/rehabilitation as an adjunct therapy to improve symptom control and management following a cancer diagnosis. More recently, the field of 'exercise - oncology' has broadened in scope to investigate whether the benefits extend beyond symptom control to modulate cancer-specific outcomes (i.e., cancer progression and metastasis). Here we review the extant epidemiological evidence examining the association between exercise behavior, functional capacity/exercise capacity, and cancer-specific recurrence and mortality as well as all-cause mortality individuals following a cancer diagnosis. We also evaluate evidence from clinical studies investigating the effects of structured exercise on blood-based biomarkers associated with cancer progression/metastasis as well findings from preclinical investigations examining the effects and molecular mechanisms of exercise in mouse models of cancer. Current gaps in knowledge are also discussed. PMID:22610066

  11. Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nagla Abdel Karim

    2015-01-01

    Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

  12. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance.

    Science.gov (United States)

    Moreel, Xavier; Allaire, Janie; Léger, Caroline; Caron, André; Labonté, Marie-Ève; Lamarche, Benoît; Julien, Pierre; Desmeules, Patrice; Têtu, Bernard; Fradet, Vincent

    2014-07-01

    The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer.

  13. Ethnic differences in the time trend of female breast cancer incidence: Singapore, 1968 – 2002

    Directory of Open Access Journals (Sweden)

    Tan Chuen-Seng

    2006-11-01

    Full Text Available Abstract Background From 1968 to 2002, Singapore experienced an almost three-fold increase in breast cancer incidence. This increase appeared to be different across the three main ethnic groups: Chinese, Malays and Indians. This paper used age-period-cohort (APC modelling, to determine the effects of age at diagnosis, calendar period, and birth cohort on breast cancer incidence for each ethnic group. Methods This study included all breast cancer cases (n = 15,269 in the three ethnic groups, reported to the Singapore Cancer Registry from 1968 to 2002 between the ages 25 to 79. Age-specific fertility rates from the Department of Statistics were used to explore the role of fertility. Results In the 1970s, Indian women had the highest age-standardized breast cancer but by the mid-1980s the highest rates were seen among the Chinese. Remarkable differences were seen in the age-specific incidence rates by ethnic groups. After age 49, the incidence rates for the Chinese and Malays leveled off whereas it continued to rise in the Indians. While our analyses provided some evidence that an age-drift model described the trend seen in the Indians, age-period-cohort model and age-cohort model had the best fit for the Chinese and Malays aged 25 to 79 respectively. Overall, Chinese and Malay women born in later cohorts were at increased risk of developing breast cancer relative to their counterparts in the earlier cohorts. The three ethnic groups experienced similar changes in their fertility in the 1970s, which likely explained much of the increase in their breast cancer incidence but not the ethnic differences. There was a stronger inverse association between total fertility rate and pre-menopausal breast cancer incidence in the Chinese and Malays than the Indians. Conclusion The observed dissimilarity among ethnic groups suggests ethnic differences in exposure or response to certain risk factors. It is likely that longer and subtler differences in

  14. Clonal selection for transcriptionally active viral oncogenes during progression to cancer.

    NARCIS (Netherlands)

    Tine, BA Van; Kappes, JC; Banerjee, NS; Knops, J; Lai, L; Steenbergen, R.D.M.; Meijer, C.J.L.M.; Snijders, P.J.F.; Chatis, P; Broker, TR; Moen, PTJr; Chow, L.T.

    2004-01-01

    Primary keratinocytes immortalized by human papillomaviruses (HPVs), along with HPV-induced cervical carcinoma cell lines, are excellent models for investigating neoplastic progression to cancer. By simultaneously visualizing viral DNA and nascent viral transcripts in interphase nuclei, we demonstra

  15. Progress through Collaboration - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI), through the Office of Cancer Clinical Proteomics Research (OCCPR), has signed two Memorandums of Understanding (MOUs) in the areas of sharing proteomics reagents and protocols and also in regulatory science.

  16. Kidney cancer progression linked to shifts in tumor metabolism

    Science.gov (United States)

    Investigators in The Cancer Genome Atlas Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma.

  17. A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Mao Yu

    2009-07-01

    Full Text Available Abstract Background The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. Results In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method. This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS and Progression Score (PS in progression analysis, True Positive Rate (TPR in gene pair analysis, and Pathway Enrichment Score (PES in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From

  18. Molecular markers′ progress of breast cancer treatment efficacy

    OpenAIRE

    Dan Wang; Jingwei Xu; Guang Shi; Guanghao Yin

    2015-01-01

    Breast cancer is a famous malignant tumor which is caused by varieties of mutation in multiple genes. In order to detect breast cancer in an earlier time and take appropriate treatment which includes  predicting treatment efficacy, we need a more accurate method of discovering the occurrence of breast cancer. With the development of molecular biology and biological detection technologies continue to emerge, molecular markers of breast cancer have gaining more and more widespread attention, an...

  19. Depth-resolved nanoscale nuclear architecture mapping for early prediction of cancer progression

    Science.gov (United States)

    Uttam, Shikhar; Pham, Hoa V.; LaFace, Justin; Hartman, Douglas J.; Liu, Yang

    2016-03-01

    Effective management of patients who are at risk of developing invasive cancer is a primary challenge in early cancer detection. Techniques that can help establish clear-cut protocols for successful triaging of at-risk patients have the potential of providing critical help in improving patient care while simultaneously reducing patient cost. We have developed such a technique for early prediction of cancer progression that uses unstained tissue sections to provide depth-resolved nanoscale nuclear architecture mapping (nanoNAM) of heterogeneity in optical density alterations manifested in precancerous lesions during cancer progression. We present nanoNAM and its application to predicting cancer progression in a well-established mouse model of spontaneous carcinogenesis: ApcMin/+ mice.

  20. The microenvironment in breast cancer progression: biology and implications for treatment

    OpenAIRE

    Place, Andrew Elliott; Polyak, Kornelia; Huh, Sung Jin

    2011-01-01

    Breast cancer comprises a heterogeneous group of malignancies derived from the ductal epithelium. The microenvironment of these cancers is now recognized as a critical participant in tumor progression and therapeutic responses. Recent data demonstrate significant gene expression and epigenetic alterations in cells composing the microenvironment during disease progression, which can be explored as biomarkers and targets for therapy. Indeed, gene expression signatures derived from tumor stroma ...

  1. Mathematical modeling of prostate cancer progression in response to androgen ablation therapy

    OpenAIRE

    Jain, Harsh Vardhan; Clinton, Steven K.; Bhinder, Arvinder; Friedman, Avner

    2011-01-01

    Prostate cancer progression depends in part on the complex interactions between testosterone, its active metabolite DHT, and androgen receptors. In a metastatic setting, the first line of treatment is the elimination of testosterone. However, such interventions are not curative because cancer cells evolve via multiple mechanisms to a castrate-resistant state, allowing progression to a lethal outcome. It is hypothesized that administration of antiandrogen therapy in an intermittent, as opposed...

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

    OpenAIRE

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

    2013-01-01

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

  3. Trends in mouth cancer incidence in Mumbai, India (1995–2009): An age-period-cohort analysis

    OpenAIRE

    Shridhar, Krithiga; Rajaraman, Preetha; Koyande, Shravani; Parikh, Purvish M; Chaturvedi, Pankaj; Dhillon, Preet K; Dikshit, Rajesh P.

    2016-01-01

    Introduction Despite tobacco control and health promotion efforts, the incidence rates of mouth cancer are increasing across most regions in India. Analysing the influence of age, time period and birth cohort on these secular trends can point towards underlying factors and help identify high-risk populations for improved cancer control programmes. Methods We evaluated secular changes in mouth cancer incidence among men and women aged 25–74 years in Mumbai between 1995 and 2009 by calculating ...

  4. Progress in diagnosis of breast cancer: Advances in radiology technology

    Directory of Open Access Journals (Sweden)

    J Mari Beth Linder

    2015-01-01

    Full Text Available Breast cancer is the leading cause of cancer in females between the ages of 15 and 54, and the second leading cause of cancer death in women in the United States. Diagnosis begins with detection by breast examination (clinical breast exam or breast self-exam or by radiologic studies, like mammography. Many advances in the diagnosis of breast cancer have taken place in recent years. This article will review the history of radiologic advances in the diagnosis of breast cancer. Use of technological advancements in digital breast tomosynthesis, magnetic resonance imaging, and ultrasound in breast cancer diagnosis will be presented. Advantages and disadvantages of these diagnostic interventions when compared to older, traditional X-ray films will be discussed. It is important for all nurses, including radiology and oncology nurses, to be well informed about these varied diagnostic modalities, and appreciate the fact that advances in radiologic imaging technologies can yield improved outcomes for breast cancer patients.

  5. Trends in Breast Cancer Incidence Rates by Age and Stage at Diagnosis in Gharbiah, Egypt, over 10 Years (1999–2008)

    OpenAIRE

    Hirko, Kelly A; Soliman, Amr S.; Ahmed Hablas; Seifeldin, Ibrahim A.; Mohamed Ramadan; Mousumi Banerjee; Harford, Joe B.; Chamberlain, Robert M; Sofia D. Merajver

    2013-01-01

    Background. This study was undertaken to evaluate trends in breast cancer incidence in Egypt from 1999 to 2008 and to make projections for breast cancer occurrence for the years 2009–2015. Patients and Methods. We utilized joinpoint regression and average annual percent change (AAPC) measures with 95% confidence intervals (CI) to describe the trends in breast cancer incidence rates from the Gharbiah Cancer Registry by age and stage at diagnosis and to estimate expected breast cancer caseloads...

  6. Modern trends in radioimmunotherapy of cancer. Pre targeting strategies for the treatment of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mcquarrie, S.A.; Xiao, Z.; Mercer, J. R.; Suresh, M. R. [Edmonton Univ. of Alberta, Edmonton, AL (Canada). Faculty of Pharmacy and Pharmaceutical Sciences; Miller, G. G. [University of Alberta, Noujaim Institute for Pharmaceutical Oncology Research, Edmonton, AL (Canada)

    2001-06-01

    A review of published data on some of the problems associated in treating cancer using radioimmunotherapy is presented. Potential improvements for this type of therapy using pretargeting strategies are discussed and preliminary results on a novel multistep regimen to treat human ovarian cancer are presented. A pretargeting strategy using ovarian cancer are presented. A pretargeting strategy using a biotinylated, anti-CA 125 monoclonal antibody (MAb) to attract biotinylated long-circulating liposomes to the surface of CA 125-expressing ovarian cancer cells, was employed. Confocal laser scanning microscopy and fluorescent labels were used to establish the biodistribution patterns in NIH:OVCAR-3 (CA-125 positive) and SK-OV-3 (CA-125 negative) human ovarian cancer cells. Shedding kinetics of the pretargeted stage were measured using {sup 125}I labeled MAbs. No significant internalization of the MAb used in the pretargeting step was observed by 4 hrs. The antibody was gradually internalized starting at 6 hrs, and most of the labelled MAb was detected in cytoplasm by 24 hrs. Shedding and exocytosis of the antigen-MAb complex was not significant for up to 6-hours following administration of the iodinated MAb. Biotinylated liposomes were shown to specifically target the biotinylated MAb/streptavidin complex on the cell surface. It has been demonstrated that by a three-step pretargeting approach, biotinylated liposomes can be specifically delivered to cells pretargeted with biotinylated MAb/SAv complex. The slow internalization and shedding properties of the two MAbs are ideal for multistep pretargeting methods. A successful multistep linkage was established with the biotinylated MAb B27.1, streptavidin and biotinylated liposomes to OVCAR-3 cells, but not to SK-OV-3 cells.

  7. Incidence and Trend of Childhood and Adolescent Cancers in Yazd, Iran

    Science.gov (United States)

    Binesh, F; Hashemi, A; VakilI, M; Shakeri, MM; Masoumi Dehshiri, R

    2016-01-01

    Background Data on childhood and adolescent malignant tumors incidence are skimp in developing countries. In this study, we analyzed the incidence and trend of childhood and adolescent cancers in Yazd city, center of Iran between Jan 2004 and Dec 2013. Material and Methods The various types of malignant tumors were grouped pursuant to the International Classification for Cancer in Children. To analyze the data, descriptive and illative statistical methods were used. Results Two hundred twenty-two patients with a malignancy aged less than 18 years were studied with a male to female ratio of 1.36.The mean age of patients was 9.88 (±5.7) years. Leukemia with the frequency of 84 (37.8%) and after that lymphoid malignancies with the frequency of 49 (22.1%) were the most common cancers. There was a low range of oscillation in the incidence rate of malignancies during this period of time (P value= 0.081). Malignancies were mostly in males (P value=0.057) but the whole process of malignancy incidence had gone toward the higher rate of incidence in females. Incidence rate of cancers types was steady. Malignancy incidence was 3-7 cases in hundred of thousands except a year of which this incidence rate was estimated 13.4. Conclusion Leukemias and lymphomas were the main cancers in the center of Iran. Childhood and adolescent malignancies may be considerably under-recorded in our province .A childhood and adolescent cancer registry is necessary for exact analysis of these types of malignancies. PMID:27222698

  8. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation

    OpenAIRE

    Mahajan, Nupam P.; Liu, Yuanbo; Majumder, Samarpan; Warren, Maria R.; Parker, Carol E.; Mohler, James L.; Earp, H. Shelton; Whang, Young E.

    2007-01-01

    Activation of the androgen receptor (AR) may play a role in androgen-independent progression of prostate cancer. Multiple mechanisms of AR activation, including stimulation by tyrosine kinases, have been postulated. We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in advanced human prostate cancer. Here we provide the molecular basis for interplay between Ack1 and AR in prostate cancer cells. Activated Ack1 promoted androgen-independent growth o...

  9. Diagnosis of lung cancer in a patient with pneumoconiosis and progressive massive fibrosis using MRI

    International Nuclear Information System (INIS)

    We report the MRI features and correlative pathologic findings of a lung cancer in a patient with progressive massive fibrosis (PMF). In this case, MRI was able to distinguish the lung cancer as a high signal intensity area, and the fibrotic mass as a low signal intensity area, on both T1-weighted and T2-weighted images when compared with muscle. MRI is potentially useful in distinguishing cancer tissue from PMF in patients with pneumoconiosis. (orig.)

  10. Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression

    OpenAIRE

    Zu, Xuyu; Ma, Jun; Liu, Hongxia; Liu, Feng; Tan, Chunyan; Yu, Lingling; Wang, Jue; Xie, Zhenhua; Cao, Deliang; Jiang, Yuyang

    2011-01-01

    Introduction Pokemon is an oncogenic transcription factor involved in cell growth, differentiation and oncogenesis, but little is known about its role in human breast cancer. In this study, we aimed to reveal the role of Pokemon in breast cancer progression and patient survival and to understand its underlying mechanisms. Methods Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years of follow-up were used to evaluate Po...

  11. Effects and potential mechanisms of exercise training on cancer progression: A translational perspective

    OpenAIRE

    Betof, Allison S.; Dewhirst, Mark W.; Jones, Lee W.

    2012-01-01

    Over the past decade there has been increasing research and clinical interest in the role of exercise therapy/rehabilitation as an adjunct therapy to improve symptom control and management following a cancer diagnosis. More recently, the field of ‘exercise – oncology’ has broadened in scope to investigate whether the benefits extend beyond symptom control to modulate cancer-specific outcomes (i.e., cancer progression and metastasis). Here we review the extant epidemiological evidence examinin...

  12. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO

    Science.gov (United States)

    Ramadani, Naser; Dedushi, Kreshnike; Muçaj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-01-01

    The aim: The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. Materials and methodology: This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, 2011-2015 at the University Clinical Center of Kosovo in Pristina. The main important factors included in this study are: age, sex and risk factors that altogether have considerable influence in incidence of pancreatic cancer. The imaging diagnostics are performed with the use of 2D ECHO Phillips, MSCT Sensation 64 and 6 and 1.5T MRI Symphony Siemens that are situated in the Radiologic Clinic of UCCK. The statistic data were obtained from NIPH of Kosovo and Agency of Statistics of Kosovo. Results: Out of the total number of the 362 patients diagnosed with pancreatic cancer, the mortality in all age groups was higher at male patients–61.6 % of cases (n=223) with the highest number found at 51–60 years age group. The 38.4 % (n= 139) were female patients with the highest incidence frequency at F 61–70 years age group. The F/M ratio is 1:1.6. The “plane” nicotine users were found at 34 % (n=123) while the joined, nicotine/alcohol addiction was detected at 26 % (n= 94). The 18.5% (n=67) have had established diagnose of the diabetes mellitus tip II and 9.6 % (n=35) have undergone the medical treatment of the gastroduodenal peptic ulcerations. The total number of deaths is 310 (85.6%) and there are only 52 patients (14.4%) still alive. The mortality rate of the pancreatic cancer in Kosovo was 17.2 in 100.000 residents while the morbidity rate was 2.8 in 100.000 residents. Discussion and conclusion: This

  13. [Research progression of translational medicine in gastric cancer].

    Science.gov (United States)

    Li, Maoran; Zhao, Gang; Zhu, Chunchao

    2014-02-01

    Gastric cancer is one of the most common malignant tumors which is a great threat to human health. In recent years, the reform of surgical mordalities and the optimization of radiation and chemotherapy is still far from reducing morbidity and mortality of gastric cancer. As a new research pattern, translational medicine has emerged in various clinical subjects, which leads to remarkable effects. In this paper, the definition and development of translational medicine, molecular markers and drug treatment of gastric cancer will be discussed and the feasibility of translational medicine in the treatment of gastric cancer will be explained. In our opinion, the intervention of translational medicine could change the current situation that scientific researches is severely disconnected with clinical practice and increase the detection rate of gastric cancer and the effective rate of adjuvant therapy after surgery to improve the prognosis of patients with gastric cancer.

  14. Neural Cell Adhesion Protein CNTN1 Promotes the Metastatic Progression of Prostate Cancer.

    Science.gov (United States)

    Yan, Judy; Ojo, Diane; Kapoor, Anil; Lin, Xiaozeng; Pinthus, Jehonathan H; Aziz, Tariq; Bismar, Tarek A; Wei, Fengxiang; Wong, Nicholas; De Melo, Jason; Cutz, Jean-Claude; Major, Pierre; Wood, Geoffrey; Peng, Hao; Tang, Damu

    2016-03-15

    Prostate cancer metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention. In this study, we performed gene-expression profiling of prostate cancer stem-like cells (PCSC) derived from DU145 human prostate cancer cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a prostate cancer-promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. In addition, CNTN1 overexpression in DU145 cells and corresponding xenograft tumors resulted in elevated AKT activation and reduced E-cadherin (CDH1) expression. CNTN1 expression was not readily detected in normal prostate glands, but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with prostate cancer progression and worse biochemical recurrence-free survival following radical prostatectomy (P prostate cancer progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies.

  15. The multifaceted mechanism of Leptin signaling within tumor microenvironment in driving breast cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Sebastiano eAndò

    2014-11-01

    Full Text Available Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied in both metabolism in general and in cancer due to the fact that leptin levels increase in proportion of fat mass. Leptin is primarily synthesized from adipocytes, but it is also produced by other cells including fibroblasts. In this latter case, it has been well demonstrated how cancer-associated fibroblasts express leptin receptor and secrete leptin which sustains a short autocrine loop and is able to target tumor epithelial cells enhancing breast cancer cell motility and invasiveness. In addition, it has been reported that leptin may induce breast cancer to undergo a transition from epithelial to spindle-like mesenchymal morphology, activating the signaling pathways devoted to the EMT. Thus, it emerges how leptin may play a crucial role in mediating malignant cell and tumor microenvironment interactions. Here, we present an overview of the role of leptin in breast cancer, covering the following topics: 1 leptin as an amplifier of estrogen signaling in tumor epithelial cells contributing to the promotion of carcinogenesis; 2 leptin as a crucial player in mediating tumor-stroma interaction and influencing EMT-linked mechanisms, that may sustain breast cancer growth and progression; 3 leptin and leptin receptor targeting as novel therapeutic strategies for breast cancer treatment.

  16. CD4+ lymphocytes modulate prostate cancer progression in mice

    OpenAIRE

    Poutahidis, Theofilos; Rao, Varada P.; Olipitz, Werner; Taylor, Christie L.; Jackson, Erin A.; Levkovich, Tatiana; Lee, Chung Wei; Fox, James G.; Ge, Zhongming; Erdman, Susan E

    2009-01-01

    Chronic inflammation contributes to the development of prostate cancer in humans. Here, we show that male ApcMin/+ mice also develop prostate carcinoma with increasing age, mimicking that seen in humans in their 5th or 6th decade of life. Proinflammatory cytokines were significantly linked with cancer and increasing age in our mouse model; however, prostate and bowel tissues lacked evidence of inflammatory cell infiltrates other than mast cells. Lymphocytes protected against cancer, and prote...

  17. 肺癌遗传易感性研究进展%Research progress on genetic susceptibility to lung cancer

    Institute of Scientific and Technical Information of China (English)

    陆丽杰

    2016-01-01

    Lung cancer is currently one of the most common malignant tumors in the world, with an increasing trend of morbidity and mortality.The major causes of lung cancer are inhaled carcinogens, such as tobacco and environmental pollution, but a growing number of researches suggest that the incidence of lung cancer is closely related to genetic factors.In the past few years, great progress has been made in research on single nucleotide polymorphism of susceptibility gene in lung cancer, and the most studies that have aimed to ultimately provide scientific basis for preventing and controlling the lung cancer have focused on screening of lung cancer etiology and developing gene therapy.In this review, the new findings of genetic susceptibility in lung cancer have been summarized.%肺癌是目前全球范围内最常见的恶性肿瘤之一,发病率和病死率均呈上升趋势.烟草、环境污染物质等吸入性致癌物是引发肺癌的主要因素,但越来越多的研究表明肺癌发病与遗传因素关系密切.近年来,对肺癌易感基因单核苷酸多态性的研究取得了较大进展,全球学者致力于筛选肺癌病因、寻找基因治疗方法,最终为预防和控制肺癌提供科学依据.文章针对目前肺癌遗传易感性研究进展作一综述.

  18. Surfactant Protein A Suppresses Lung Cancer Progression by Regulating the Polarization of Tumor-Associated Macrophages

    OpenAIRE

    Mitsuhashi, Atsushi; Goto, Hisatsugu; Kuramoto, Takuya; Tabata, Sho; Yukishige, Sawaka; Abe, Shinji; Hanibuchi, Masaki; Kakiuchi, Soji; Saijo, Atsuro; Aono, Yoshinori; Uehara, Hisanori; Yano, Seiji; Ledford, Julie G.; Sone, Saburo; Nishioka, Yasuhiko

    2013-01-01

    Surfactant protein A (SP-A) is a large multimeric protein found in the lungs. In addition to its immunoregulatory function in infectious respiratory diseases, SP-A is also used as a marker of lung adenocarcinoma. Despite the finding that SP-A expression levels in cancer cells has a relationship with patient prognosis, the function of SP-A in lung cancer progression is unknown. We investigated the role of SP-A in lung cancer progression by introducing the SP-A gene into human lung adenocarcino...

  19. Time trends in educational inequalities in cancer mortality in Colombia, 1998–2012

    Science.gov (United States)

    Arroyave, Ivan; Pardo, Constanza

    2016-01-01

    Objectives To evaluate trends in premature cancer mortality in Colombia by educational level in three periods: 1998–2002 with low healthcare insurance coverage, 2003–2007 with rapidly increasing coverage and finally 2008–2012 with almost universal coverage (2008–2012). Setting Colombian population-based, national secondary mortality data. Participants We included all (n=188 091) cancer deaths occurring in the age group 20–64 years between 1998 and 2012, excluding only cases with low levels of quality of registration (n=2902, 1.5%). Primary and secondary outcome measures In this descriptive study, we linked mortality data of ages 20–64 years to census data to obtain age-standardised cancer mortality rates by educational level. Using Poisson regression, we modelled premature mortality by educational level estimating rate ratios (RR), relative index of inequality (RII) and the Slope Index of Inequality (SII). Results Relative measures showed increased risks of dying among the lower educated compared to the highest educated; this tendency was stronger in women (RRprimary 1.49; RRsecondary 1.22, both p<0.0001) than in men (RRprimary 1.35; RRsecondary 1.11, both p<0.0001). In absolute terms (SII), cancer caused a difference per 100 000 deaths between the highest and lowest educated of 20.5 in males and 28.5 in females. RII was significantly higher among women and the younger age categories. RII decreased between the first and second periods; afterwards (2008–2012), it increased significantly back to their previous levels. Among women, no significant increases or declines in cancer mortality over time were observed in recent periods in the lowest educated group, whereas strong recent declines were observed in those with secondary education or higher. Conclusions Educational inequalities in cancer mortality in Colombia are increasing in absolute and relative terms, and are concentrated in young age categories. This trend was not curbed by increases in

  20. The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, Jennifer L.; Thaper, Daksh; Zoubeidi, Amina, E-mail: azoubeidi@prostatecentre.com [The Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver British Columbia, V6H 3Z6 (Canada)

    2014-04-09

    The signal transducer and activator of transcription (STAT)3 governs essential functions of epithelial and hematopoietic cells that are often dysregulated in cancer. While the role for STAT3 in promoting the progression of many solid and hematopoietic malignancies is well established, this review will focus on the importance of STAT3 in prostate cancer progression to the incurable metastatic castration-resistant prostate cancer (mCRPC). Indeed, STAT3 integrates different signaling pathways involved in the reactivation of androgen receptor pathway, stem like cells and the epithelial to mesenchymal transition that drive progression to mCRPC. As equally important, STAT3 regulates interactions between tumor cells and the microenvironment as well as immune cell activation. This makes it a major factor in facilitating prostate cancer escape from detection of the immune response, promoting an immunosuppressive environment that allows growth and metastasis. Based on the multifaceted nature of STAT3 signaling in the progression to mCRPC, the promise of STAT3 as a therapeutic target to prevent prostate cancer progression and the variety of STAT3 inhibitors used in cancer therapies is discussed.

  1. Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis

    Directory of Open Access Journals (Sweden)

    Jian Cao

    2014-03-01

    Full Text Available Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis.

  2. Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

    Science.gov (United States)

    Suzuki, H.; Mizuguchi, R.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

    2015-03-01

    Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, plung cancer.

  3. Tight junctions: a barrier to the initiation and progression of breast cancer?

    LENUS (Irish Health Repository)

    Brennan, Kieran

    2010-01-01

    Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression.

  4. Expression of the Y-Encoded TSPY is Associated with Progression of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2010-09-01

    Full Text Available TSPY is a Y-encoded gene that is expressed in normal testicular germ cells and various cancer types including germ cell tumor, melanoma, hepatocellular carcinoma, and prostate cancer. Currently, the correlation between TSPY expression and oncogenic development has not been established, particularly in somatic cancers. To establish such correlation, we analyzed the expression of TSPY, in reference to its interactive oncoprotein, EEF1A, tumor biomarker, AMACR, and normal basal cell biomarker, p63, in 41 cases of clinical prostate cancers (CPCa, 17 cases of latent prostate cancers (LPCa, and 19 cases of non-cancerous prostate (control by immunohistochemistry. Our results show that TSPY was detected more frequently (78% in the clinical prostate cancer specimens than those of latent prostate cancer (47% and control (50%. In the latent cancer group, the levels of TSPY expression could be correlated with increasing Gleason grades. TSPY expression was detected in seven out of nine high-grade latent cancer samples (Gleason 7 and more. The expression of the TSPY binding partner EEF1A was detectable in all prostate specimens, but the levels were higher in cancer cells in clinical and latent prostate cancer specimens than normal prostatic cells. These observations suggest that expressions of TSPY and its binding partner EEF1A are associated with the development and progression of prostate cancer.

  5. Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure.

    Science.gov (United States)

    Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Ito, Masahiro; Tokuoka, Shoji; Sugiyama, Hiromi; Soda, Midori; Ozasa, Kotaro; Mabuchi, Kiyohiko

    2013-03-01

    Thyroid cancer risk following exposure to ionizing radiation in childhood and adolescence is a topic of public concern. To characterize the long-term temporal trend and age-at-exposure variation in the radiation-induced risk of thyroid cancer, we analyzed thyroid cancer incidence data for the period from 1958 through 2005 among 105,401 members of the Life Span Study cohort of Japanese atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases (excluding those with microcarcinoma with a diameter 50 years after exposure. PMID:22847218

  6. Strategies and resources for coping with fear of disease progression in women with reproductive system cancer

    Directory of Open Access Journals (Sweden)

    Moskovchenko, Denis V.

    2016-06-01

    Full Text Available Fear of disease progression is one of the most common sources of psychological distress in patients suffering from chronic diseases. Fear of disease progression is a situationspecific and fully discernible (reportable emotion based on personal experience of a life-threatening disease. This article presents the results of a study of cancer patients’ coping behavior according to the levels of fear of disease progression experienced. The presence of pronounced fear of disease progression reflects a negative cognitive-affective response to one’s expectations for one’s own future; this response is related to a decrease in adaptive capacity. To determine the particular characteristics of coping strategies and coping resources in women with reproductive-system cancers according to the level of fear of disease progression. A total of 177 women with reproductive-system cancers were examined, among them 59 with breast cancer and 118 with gynecological cancers. Women with reproductive-system cancers have varying sets of coping strategies and coping resources according to their level of fear of disease progression. For each of the differentiated groups, specific characteristics of the strategies of coping with difficult life situations are described, along with cognitive self-regulation strategies specific to the illness and to coping resources. The women exhibiting moderate fear of disease progression significantly more often adhered to problem-oriented strategies of coping with difficult life situations and illness and had an internal locus of control regarding treatment. Patients with a low level of fear of disease progression tended to use strategies of positive reinterpretation of difficult life situations and illness; an external locus of control regarding treatment prevailed in this group. Patients found to have a dysfunctional level of fear of disease progression displayed significantly higher rates of using cognitive-regulation strategies

  7. Trends in Clinically Significant Pain Prevalence Among Hospitalized Cancer Patients at an Academic Hospital in Taiwan

    Science.gov (United States)

    Wang, Wei-Yun; Ho, Shung-Tai; Wu, Shang-Liang; Chu, Chi-Ming; Sung, Chun-Sung; Wang, Kwua-Yun; Liang, Chun-Yu

    2016-01-01

    Abstract Clinically significant pain (CSP) is one of the most common complaints among cancer patients during repeated hospitalizations, and the prevalence ranges from 24% to 86%. This study aimed to characterize the trends in CSP among cancer patients and examine the differences in the prevalence of CSP across repeated hospitalizations. A hospital-based, retrospective cohort study was conducted at an academic hospital. Patient-reported pain intensity was assessed and recorded in a nursing information system. We examined the differences in the prevalence of worst pain intensity (WPI) and last evaluated pain intensity (LPI) of ≥4 or ≥7 points among cancer inpatients from the 1st to the 18th hospitalization. Linear mixed models were used to determine the significant difference in the WPI and LPI (≥4 or ≥7 points) at each hospitalization. We examined 88,133 pain scores from the 1st to the 18th hospitalization among cancer patients. The prevalence of the 4 CSP types showed a trend toward a reduction from the 1st to the 18th hospitalization. There was a robust reduction in the CSP prevalence from the 1st to the 5th hospitalization, except in the case of LPI ≥ 7 points. The prevalence of a WPI ≥ 4 points was significantly higher (0.240-fold increase) during the 1st hospitalization than during the 5th hospitalization. For the 2nd, 3rd, and 4th hospitalizations, there was a significantly higher prevalence of a WPI ≥ 4 points compared with the 5th hospitalization. We also observed significant reductions in the prevalence of a WPI ≥ 7 points during the 1st to the 4th hospitalizations, an LPI ≥ 4 points during the 1st to the 3rd hospitalizations, and an LPI ≥ 7 points during the 1st to the 2nd hospitalization. Although the prevalence of the 4 CSP types decreased gradually, it is impossible to state the causative factors on the basis of this observational and descriptive study. The next step will examine the factors that determine the CSP prevalence among

  8. The Trend of Age-Group Effect on Prognosis in Differentiated Thyroid Cancer

    Science.gov (United States)

    Shi, Rong-liang; Qu, Ning; Liao, Tian; Wei, Wen-jun; Wang, Yu-Long; Ji, Qing-hai

    2016-01-01

    Age has been included in various prognostic scoring systems for differentiated thyroid cancer (DTC). The aim of this study is to re-examine the relationship between age and prognosis by using Surveillance, Epidemiology, and End Results (SEER) population-based database. We identified 51,061 DTC patients between 2004 and 2012. Patients were separated into 10-year age groups. Cancer cause-specific survival (CSS) and overall survival (OS) data were obtained. Kaplan-Meier and multivariable Cox models were built to analyze the outcomes and risk factors. Increasing age gradient with a 10-year interval was associated with the trend of higher proportions for male gender, grade III/IV and summary stage of distant metastases. Both CSS and OS continued to worsen with increasing age, being poorest in in the oldest age group (≥71); multivariate analysis confirmed that CSS continued to fall with each age decade, significantly starting at 60 years (HR = 7.5, 95% 1.0–54.1, p = 0.047) compared to the young group (≤20). Similarly, multivariate analysis suggested that OS continued worsening with increasing age, but starting at 40 years (HR = 3.7, 95% 1.4–10.1, p = 0.009) compared to the young group. The current study suggests that an age exceeding 60 years itself represents an unfavorable prognostic factor and high risk for cancer-specific death in DTC. PMID:27272218

  9. Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

    Science.gov (United States)

    Willis, Rudolph E.

    2016-01-01

    It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

  10. Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages.

    Science.gov (United States)

    Tsuboki, Junko; Fujiwara, Yukio; Horlad, Hasita; Shiraishi, Daisuke; Nohara, Toshihiro; Tayama, Shingo; Motohara, Takeshi; Saito, Yoichi; Ikeda, Tsuyoshi; Takaishi, Kiyomi; Tashiro, Hironori; Yonemoto, Yukihiro; Katabuchi, Hidetaka; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    It is well known that tumour-associated macrophages (TAMs) play an important role in tumour development by modulating the tumour microenvironment, and targeting of protumour activation or the M2 polarization of TAMs is expected to be an effective therapy for cancer patients. We previously demonstrated that onionin A (ONA), a natural low molecular weight compound isolated from onions, has an inhibitory effect on M2 macrophage polarization. In the present study, we investigated whether ONA had a therapeutic anti-ovarian cancer effect using in vitro and in vivo studies. We found that ONA reduced the extent of ovarian cancer cell proliferation induced by co-culture with human macrophages. In addition, we also found that ONA directly suppressed cancer cell proliferation. A combinatorial effect with ONA and anti-cancer drugs was also observed. The activation of signal transducer and activator of transcription 3 (STAT3), which is involved in cell proliferation and chemo-resistance, was significantly abrogated by ONA in ovarian cancer cells. Furthermore, the administration of ONA suppressed cancer progression and prolonged the survival time in a murine ovarian cancer model under single and combined treatment conditions. Thus, ONA is considered useful for the additional treatment of patients with ovarian cancer owing to its suppression of the protumour activation of TAMs and direct cytotoxicity against cancer cells. PMID:27404320

  11. The role of mitochondria in the development and progression of lung cancer

    Directory of Open Access Journals (Sweden)

    Emily R Roberts

    2013-03-01

    Full Text Available The influence of mitochondria in human health and disease is a rapidly expanding topic in the scientific literature due to their integral roles in cellular death and survival. Mitochondrial biology and alterations in function were first linked to cancer in the 1920s with the discovery of the Warburg effect. The utilization of aerobic glycolysis in ATP synthesis was the first of many observations of metabolic reprogramming in cancer. Mitochondrial dysfunction in cancer has expanded to include defects in mitochondrial genomics and biogenesis, apoptotic signaling and mitochondrial dynamics. This review will focus on the role of mitochondria and their influence on cancer initiation, progression and treatment in the lung.

  12. Lung Cancer Mortality Trends in China from 1988 to 2013: New Challenges and Opportunities for the Government

    Directory of Open Access Journals (Sweden)

    Lijun Wang

    2016-10-01

    Full Text Available Background: As lung cancer has shown a continuously increasing trend in many countries, it is essential to stay abreast of lung cancer mortality information and take informed actions with a theoretical basis derived from appropriate and practical statistical methods. Methods: Age-specific rates were collected by gender and region (urban/rural and analysed with descriptive methods and age-period-cohort models to estimate the trends in lung cancer mortality in China from 1988 to 2013. Results: Descriptive analysis revealed that the age-specific mortality rates of lung cancer in rural residents increased markedly over the last three decades, and there was no obvious increase in urban residents. APC analysis showed that the lung cancer mortality rates significantly increased with age (20–84, rose slightly with the time period, and decreased with the cohort, except for the rural cohorts born during the early years (1909–1928. The trends in the patterns of the period and cohort effects showed marked disparities between the urban and rural residents. Conclusions: Lung cancer mortality remains serious and is likely to continue to rise in China. Some known measures are suggested to be decisive factors in mitigating lung cancer, such as environmental conservation, medical security, and tobacco control, which should be implemented more vigorously over the long term in China, especially in rural areas.

  13. Genomic and genetic alterations influence the progression of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Stefania Nobili; Lorenzo Bruno; Ida Landini; Cristina Napoli; Paolo Bechi; Francesco Tonelli; Carlos A Rubio; Enrico Mini; Gabriella Nesi

    2011-01-01

    Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Twomain gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.

  14. An investigation of the apparent breast cancer epidemic in France: screening and incidence trends in birth cohorts

    Directory of Open Access Journals (Sweden)

    Olsen Jørn

    2011-09-01

    Full Text Available Abstract Background Official descriptive data from France showed a strong increase in breast-cancer incidence between 1980 to 2005 without a corresponding change in breast-cancer mortality. This study quantifies the part of incidence increase due to secular changes in risk factor exposure and in overdiagnosis due to organised or opportunistic screening. Overdiagnosis was defined as non progressive tumours diagnosed as cancer at histology or progressive cancer that would remain asymptomatic until time of death for another cause. Methods Comparison between age-matched cohorts from 1980 to 2005. All women residing in France and born 1911-1915, 1926-1930 and 1941-1945 are included. Sources are official data sets and published French reports on screening by mammography, age and time specific breast-cancer incidence and mortality, hormone replacement therapy, alcohol and obesity. Outcome measures include breast-cancer incidence differences adjusted for changes in risk factor distributions between pairs of age-matched cohorts who had experienced different levels of screening intensity. Results There was an 8-fold increase in the number of mammography machines operating in France between 1980 and 2000. Opportunistic and organised screening increased over time. In comparison to age-matched cohorts born 15 years earlier, recent cohorts had adjusted incidence proportion over 11 years that were 76% higher [95% confidence limits (CL 67%, 85%] for women aged 50 to 64 years and 23% higher [95% CL 15%, 31%] for women aged 65 to 79 years. Given that mortality did not change correspondingly, this increase in adjusted 11 year incidence proportion was considered as an estimate of overdiagnosis. Conclusions Breast cancer may be overdiagnosed because screening increases diagnosis of slowly progressing non-life threatening cancer and increases misdiagnosis among women without progressive cancer. We suggest that these effects could largely explain the reported

  15. [Biology of cancer cell-stroma interaction in carcinogenesis and cancer progression].

    Science.gov (United States)

    Fujita, S; Sugihara, H; Ito, R; Tsuchihashi, Y

    1984-03-01

    Cancer cells are dependent on physical and chemical supports of stroma no less than non-cancerous cells and tissues are. The role of stroma should, therefore, be important in genesis and progression of cancers growing in vivo. But this aspect underlying carcinogenesis and manifestation of human cancers has long been neglected or attracted less attention in the investigations of oncology. Focusing particular attention on parenchyma-stromal interaction in gastrointestinal mucosa, the authors have found that, quite unexpectedly, in normal gastric as well as intestinal mucosa of all the animal species so for studied, vascularity is always poorly developed in the generative cell zones. Cross-sectional area of vascular bed is markedly reduced in this zone. Application of Hagen-Poiseulle law revealed that the reduced total cross-sectional area, resulting in a rapid drop in hydrostatic pressure, creates here a situation particularly favorable for proliferating cell population. Since the transport of water soluble material together with tissue fluid through the capillary wall is driven by the hydrostatic pressure, the generative cell zones are found to be present at the site where the turnover of the material is the most active. Before the zone of the rapid pressure drop, there appears zone of relatively high intravascular hydrostatic pressure, where secretory function seems to be facilitated. This zone, as is well known, corresponds to glandular portion of the mucosa. After the zone of the rapid pressure drop (in surface of the mucosa), zone of a low intravascular hydrostatic pressure appears, where absorptive function is to be facilitated. Within such zones, in gastric mucosa surface epithelium and in intestinal mucosa absorptive villi cells are located. It is likely that architecture of gastrointestinal epithelium and vascular pattern in the stroma is closely correlated and that the former is determined, at least partly, by the latter. When human gastric mucosa shows

  16. Cancer Stem Cells – Basics, Progress and Future Potential

    OpenAIRE

    Bapat S.A

    2010-01-01

    The primary characteristics of adult stem cells are maintaining prolonged quiescence, ability to self-renew and plasticity to differentiate into multiple cell types. These properties are evolutionarily conserved from fruit fly to humans. Similar to normal tissue repair in organs, the stem cell concept is inherently impregnated in the etiology of cancer. Tumors contain a minor population of tumor-initiating cells, called "cancer stem cells" that maintain some similarities in self-renewal and d...

  17. Steps in Prostate Cancer Progression that lead to Bone Metastasis

    OpenAIRE

    Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

    2011-01-01

    Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current...

  18. Algorithmic methods to infer the evolutionary trajectories in cancer progression

    OpenAIRE

    Caravagna, Giulio; Graudenzi, Alex; Ramazzotti, Daniele; Sanz-Pamplona, Rebeca; De Sano, Luca; Mauri, Giancarlo; Moreno, Victor; Antoniotti, Marco; Mishra, Bud

    2016-01-01

    The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next generation sequencing (NGS) data, and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the di...

  19. Exosomes in Tumor Microenvironment Influence Cancer Progression and Metastasis

    OpenAIRE

    Kahlert, Christoph; Kalluri, Raghu

    2013-01-01

    Exosomes are small membrane vesicles of endocytic origin with a size of 50 – 100 nm. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donar cell to recipient cells. Many different cell types including immune cells, mesenchymal cells and cancer cells release exosomes. There is emerging evidence that cancer-derived exosomes contribute to the recruitment and reprogramming of constituents associated with tumor environment. Here, we discuss different mechani...

  20. DKC1 overexpression associated with prostate cancer progression

    OpenAIRE

    Sieron, P; Hader, C; Hatina, J; Engers, R; Wlazlinski, A; Müller, M.; Schulz, W A

    2009-01-01

    Background: Dyskerin encoded by the DKC1 gene is a predominantly nucleolar protein essential for the formation of pseudouridine in RNA and the telomerase RNA subunit hTR. Inherited mutations inactivating dyskerin cause dyskeratosis congenita, a syndrome with progeroid features characterised by skin defects and haematopoiesis failure, as well as cancer susceptibility. In this study, we report DKC1 overexpression in prostate cancers. Methods: Expression of DKC1 was measured by quantitative RT–P...

  1. Biomarkers to Distinguish Aggressive Cancers from Non-aggressive or Non-progressing Cancer — EDRN Public Portal

    Science.gov (United States)

    Distinguishing aggressive cancers from non-aggressive or non-progressing cancers is an issue of both clinical and public health importance particularly for those cancers with an available screening test. With respect to breast cancer, mammographic screening has been shown in randomized trials to reduce breast cancer mortality, but given the limitations of its sensitivity and specificity some breast cancers are missed by screening. These so called interval detected breast cancers diagnosed between regular screenings are known to have a more aggressive clinical profile. In addition, of those cancers detected by mammography some are indolent while others are more likely to recur despite treatment. The pilot study proposed herein is highly responsive to the EDRN supplement titled “Biomarkers to Distinguish Aggressive Cancers from Nonaggressive or Non-progressing Cancers” in that it addresses both of the research objectives related to these issues outlined in the notice for this supplement: Aim 1: To identify biomarkers in tumor tissue related to risk of interval detected vs. mammography screen detected breast cancer focusing on early stage invasive disease. We will compare gene expression profiles using the whole genome-cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay of 50 screen detected cancers to those of 50 interval detected cancers. Through this approach we will advance our understanding of the molecular characteristics of interval vs. screen detected breast cancers and discover novel biomarkers that distinguish between them. Aim 2: To identify biomarkers in tumor tissue related to risk of cancer recurrence among patients with screen detected early stage invasive breast cancer. Using the DASL assay we will compare gene expression profiles from screen detected early stage breast cancer that either recurred within five years or never recurred within five years. These two groups of patients will be matched on multiple factors including

  2. The progress of study on pathogenesis in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; LI Hai-jiao; YU Lei; LIU Guang-da; PANG Lin-lin; YANG Hai-fan

    2008-01-01

    Ovarian cancer is one of the three malignant tumors in female reproductive system, the death rate locates in the first place of gynecological cancer. Most patients are already at the advanced stage when examine their bodies, five-year survival rate are only about 20 % to 30 %. So gynecological cancer has bedome one of tumor which the most waiting to be considered. It happens refer to the incidence of chromosomal abnormalities, cancer gene change. The inactivation of tumor suppressor gene, inhibitor of apoptosis and other genetic changes, the imbalance in the regulatory network due to the interaction of multiple genes and their product. Chromosomal abnormalities play an important role in the development of ovarian cancer, the chromosomes of common characteristic and non-random changes are 1,3, 5, 6, 7, 8, 11, 12, 15, 17, 18, 20, 22 etc. Cancer gene including K-ras, c-erb-B2/HER-2, D1 (CyclinD1), AIB1 etc. K-ras coded protein p21 is activated through point mutation, cause the enzyme activity deprivation of GMP, slowed down the speed of GTP degrdn into GMP, activate target molecule persistently, make cells proliferate persistently, then leading to cancer. HER-2 gene amplification result in the over expression of HER-2 protein, made cells over proliferate,Protein over expression convey the strong signal of proliferation, over activate the early transcription factor and certain gene in the nuclear, then promote the occurrence of cancer. Cyclin D1 promote cells enter from S to Gl phase, thus contribute to the proliferation of cell division, then canceration. AIB1 gene over express, will cause tumor cells immortalized. Tumor suppressor gene, such as BRCA1, p53, p73, p16 etc. The expression depl of BRCA1 protein in ovarian Cystadenocarcinoma prompt that the reduction of BRCA1 protein synthesis, resulting in apoptosis decreased, the cell proliferation disinhibit, then disorder and proliferate, thus leading to cancer, p53 mutation happened in about 30 percents to 80 percents

  3. Trends of surgical treatment of hilar bile duct cancer: clinical andexperimental perspectives

    Institute of Scientific and Technical Information of China (English)

    Zhi Qiang Huang; Ning Xin Zhou; Da Dong Wang; Jian Guo Lu; Ming Yi Chen

    2000-01-01

    AIM To summarize the experience of surgical treatment of hilar cholangiocarcinoma and the results of aseries of experiments.METHODS AND RESULTS Personal perspectives of surgical treatment of hilar cholangiocarcinoma werebased on the experience of a series of patients with hilar bile duct cancer treated in the General Hospital ofPLA, Beijing from 1986 to 1999. A total of 157 cases were treated surgically, with 106 (67.5%) resections ofthe tumor , 37.6% of the resections was proved to be radical. The 1-, 2-, 3-, and 5-year survival rate of theradical resection group was 96.7%, 40.0%, 23.3% and 13.3%, respectively. No patient of the palliativeresection group lived beyond 3 years postoperatively. The recent trends of surgical management of hilar bileduct cancer were discussed. Experiments were carried out for cooperative clinicopathological study toevaluate the perineural space involvement, the neural cell adhesion molecule expression, p16 geneexpression, and the 3-dimensional reconstruction of the bile duct cancer specimens. The pathogeneticrelationship of HBV and HCV with extrahepatic cholangiocarcinoma was evaluated by histochemical and IS-PCR methods. And an inquiry into the possibility of gene therapy was made.CONCLUSION Hilar bile duct cancer rarely runs a “benign” course. It is a regional disease rather than alocal affection and may be related to HBV and HCV infection in China. It possesses the metastasing abilityalong the perineural space by a “jumping” fashion, therefore, in most cases, conventional surgical excision isbound to be unradical in the region of the porta hepatis for anatomical reasons.

  4. Role of Procalcitonin and Interleukin-6 in Predicting Cancer, and Its Progression Independent of Infection.

    Directory of Open Access Journals (Sweden)

    Anne-Marie Chaftari

    Full Text Available Procalcitonin (PCT and Interleukin-6 (IL-6 have emerged as biomarkers for different inflammatory conditions. The purpose of the study was to evaluate the role of PCT and IL-6 as biomarkers of cancer and its progression in a large cohort of patients. This cross-sectional study included residual plasma samples collected from cancer patients, and control subjects without cancer. Levels of PCT and IL-6 were determined by Kryptor compact bioanalyzer. We identified 575 febrile cancer patients, 410 non-febrile cancer patients, and 79 non-cancer individuals. The median PCT level was lower in control subjects (0.029 ng/ml compared to cancer patients with stage I-III disease (0.127 ng/ml (p<0.0001 and stage IV disease (0.190 ng/ml (p<0.0001. It was also higher in febrile cancer patients (0.310 ng/ml compared to non-febrile cancer patients (0.1 ng/ml (p<0.0001. Median IL-6 level was significantly lower in the control group (0 pg/ml than in non-febrile cancer patients with stages I-III (7.376 pg/ml or stage IV (9.635 pg/ml (p<0.0001. Our results suggest a potential role for PCT and IL-6 in predicting cancer in non-febrile patients. In addition, PCT is useful in detecting progression of cancer and predicting bacteremia or sepsis in febrile cancer patients.

  5. A comprehensive review on host genetic susceptibility to human papillomavirus infection and progression to cervical cancer

    Directory of Open Access Journals (Sweden)

    Koushik Chattopadhyay

    2011-01-01

    Full Text Available Cervical cancer is the second most common cancer in women worldwide. This is caused by oncogenic types of human papillomavirus (HPV infection. Although large numbers of young sexually active women get HPV-infected, only a small fraction develop cervical cancer. This points to different co-factors for regression of HPV infection or progression to cervical cancer. Host genetic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review is to compile the advances in the field of host genetics of cervical cancer. MEDLINE database was searched using the terms, ′HPV′, ′cervical′, ′CIN′, ′polymorphism(s′, ′cervical′ + FNx01the name of the geneFNx01 and ′HPV′ + FNx01the name of the geneFNx01. This review focuses on the major host genes reported to affect the progression to cervical cancer in HPV infected individuals.

  6. A tissue biomarker panel predicting systemic progression after PSA recurrence post-definitive prostate cancer therapy.

    Directory of Open Access Journals (Sweden)

    Tohru Nakagawa

    Full Text Available BACKGROUND: Many men develop a rising PSA after initial therapy for prostate cancer. While some of these men will develop a local or metastatic recurrence that warrants further therapy, others will have no evidence of disease progression. We hypothesized that an expression biomarker panel can predict which men with a rising PSA would benefit from further therapy. METHODOLOGY/PRINCIPAL FINDINGS: A case-control design was used to test the association of gene expression with outcome. Systemic (SYS progression cases were men post-prostatectomy who developed systemic progression within 5 years after PSA recurrence. PSA progression controls were matched men post-prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years. Using expression arrays optimized for paraffin-embedded tissue RNA, 1021 cancer-related genes were evaluated-including 570 genes implicated in prostate cancer progression. Genes from 8 previously reported marker panels were included. A systemic progression model containing 17 genes was developed. This model generated an AUC of 0.88 (95% CI: 0.84-0.92. Similar AUCs were generated using 3 previously reported panels. In secondary analyses, the model predicted the endpoints of prostate cancer death (in SYS cases and systemic progression beyond 5 years (in PSA controls with hazard ratios 2.5 and 4.7, respectively (log-rank p-values of 0.0007 and 0.0005. Genes mapped to 8q24 were significantly enriched in the model. CONCLUSIONS/SIGNIFICANCE: Specific gene expression patterns are significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence.

  7. The fundamental role of mechanical properties in the progression of cancer disease and inflammation

    International Nuclear Information System (INIS)

    The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in

  8. Cancer Development, Progression, and Therapy: An Epigenetic Overview

    Directory of Open Access Journals (Sweden)

    McKenna Longacre

    2013-10-01

    Full Text Available Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

  9. Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

    Directory of Open Access Journals (Sweden)

    Rajeswari Jinka

    2012-01-01

    Full Text Available Cancer progression is a multistep process during which normal cells exhibit molecular changes that culminate into the highly malignant and metastatic phenotype, observed in cancerous tissues. The initiation of cell transformation is generally associated with genetic alterations in normal cells that lead to the loss of intercellular- and/or extracellular-matrix- (ECM- mediated cell adhesion. Transformed cells undergo rapid multiplication and generate more modifications in adhesion and motility-related molecules which allow them to escape from the original site and acquire invasive characteristics. Integrins, which are multifunctional adhesion receptors, and are present, on normal as well as transformed cells, assist the cells undergoing tumor progression in creating the appropriate environment for their survival, growth, and invasion. In this paper, we have briefly discussed the role of ECM proteins and integrins during cancer progression and described some unique conditions where adhesion-related changes could induce genetic mutations in anchorage-independent tumor model systems.

  10. Esophageal cancer mortality trends in rural and urban China between 1987 and 2009.

    Science.gov (United States)

    Guo, Bill; Huang, Zheng-Liang

    2011-01-01

    Esophageal cancer is one of the most commonly diagnosed malignant tumors in China. This study aimed to examine the temporal trend of esophageal cancer mortality rates during the period 1987-2009 in both rural and urban settings and to detect the effects of year of death and year of birth on the trends using joinpoint regression analysis and an age-period-cohort model. Age-standardized mortality rates were calculated by the direct method using the world population of 1960, and joinpoint regression was performed to obtain the annual percentage change (APC) in mortality rate. Poisson regression models were fitted to evaluate the period and cohort effects after adjusting for age. During the period 1987-2009, age-standardized mortality rates showed an overall significant decrease for rural females (APC=-2.3, 95% confidence interval [CI]: -3.3%, -1.2%), urban males (APC=-1.8, 95% CI: -2.6%, -1.0%) and urban females (APC=-3.7, 95% CI: -4.9%, -2.4%), but the decrease was not statistically significant for rural males (APC=-0.9, 95% CI: -2.0%, 0.3%). After adjusting for age and with the birth cohort of 1900-1904 or period 1987-1991 as reference, the relative risk of successive cohorts decreased steadily and that of more recent periods kept relatively stable. The decreasing birth cohort effect in the recent generations could correspond to increased adoption of healthy dietary habits and life-styles in the population. PMID:22292660

  11. FYN promotes breast cancer progression through epithelial-mesenchymal transition.

    Science.gov (United States)

    Xie, Ye-Gong; Yu, Yue; Hou, Li-Kun; Wang, Xin; Zhang, Bin; Cao, Xu-Chen

    2016-08-01

    FYN, one of the members of the Src family of kinases (SFKs), has been reported to be overexpressed in various types of cancers and correlated with cell motility and proliferation. However, the mechanism is still unclear. In the present study, we found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. PMID:27349276

  12. Prolyl-4-hydroxylase α subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition

    International Nuclear Information System (INIS)

    Increased collagen deposition provides physical and biochemical signals to support tumor growth and invasion during breast cancer development. Therefore, inhibition of collagen synthesis and deposition has been considered a strategy to suppress breast cancer progression. Collagen prolyl-4-hydroxylase α subunit 2 (P4HA2), an enzyme hydroxylating proline residues in -X-Pro-Gly- sequences, is a potential therapeutic target for the disorders associated with increased collagen deposition. However, expression and function of P4HA2 in breast cancer progression are not well investigated. Gene co-expression analysis was performed in the published microarray datasets to identify potential regulators of collagen I, III, and IV in human breast cancer tissue. Expression of P4HA2 was silenced by shRNAs, and its activity was inhibited by 1, 4-DPCA, a prolyl-4-hydroxylase inhibitor. Three-dimensional culture assay was used to analyze roles of P4HA2 in regulating malignant phenotypes of breast cancer cells. Reduced deposition of collagen I and IV was detected by Western blotting and immunofluorescence. Control and P4HA2-silenced breast cancer cells were injected into fat pad and tail vein of SCID mice to examine effect of P4HA2 on tumor growth and lung metastasis. Using gene co-expression analysis, we showed that P4HA2 was associated with expression of Col1A1, Col3A1, and Col4A1 during breast cancer development and progression. P4HA2 mRNA levels were significantly upregulated in breast cancer compared to normal mammary tissue. Increased mRNA levels of P4HA2 correlated with poor clinical outcome in breast cancer patients, which is independent of estrogen receptor status. Silencing P4HA2 expression or treatment with the P4HA inhibitor significantly inhibited cell proliferation and suppressed aggressive phenotypes of breast cancer cells in 3D culture, accompanied by reduced deposition of collagen I and IV. We also found that knockdown of P4HA2 inhibited mammary tumor growth and

  13. [Research progress of relationship between exosomes and breast cancer].

    Science.gov (United States)

    Bi, Tao-Ling; Sun, Jin-Jian; Tian, Yu-Zi; Zhou, Ye-Fang

    2016-06-25

    Exosomes are nanosized small membrane microvesicles of endocytic origin secreted by most cell types. Exosomes, through its carrying protein or RNA from derived cells, affect gene regulation networks or epigenetic reorganization of receptor cell, and then modulate the physiological processes of cells. Studies have shown that external exosomes secreted by breast cancer cells or other cells play an important role in the development of tumor, including cell migration, cell differentiation and the immune response, etc. In this article, the latest studies were summarized to provide an overview of current understanding of exosomes in breast cancer. PMID:27350208

  14. Effects of Honey and Its Mechanisms of Action on the Development and Progression of Cancer

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa

    2014-02-01

    Full Text Available Honey is a natural product known for its varied biological or pharmacological activities—ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available evidence (some of which is very recent with regards to the antimetastatic, antiproliferative and anticancer effects of honey in various forms of cancer. These effects of honey have been thoroughly investigated in certain cancers such as breast, liver and colorectal cancer cell lines. In contrast, limited but promising data are available for other forms of cancers including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone cancer cells. The article also underscores the various possible mechanisms by which honey may inhibit growth and proliferation of tumors or cancers. These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic against tumor or cancer cells while it is non-cytotoxic to normal cells. The data indicate that honey can inhibit carcinogenesis by modulating the molecular processes of initiation, promotion, and progression stages. Thus, it may serve as a potential and promising anticancer agent which warrants further experimental and clinical studies.

  15. miR-340 and ZEB1 negative feedback loop regulates TGF-β- mediated breast cancer progression

    Science.gov (United States)

    Xie, Ye-Gong; Wang, Jie; Mao, Jie-Fei; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2016-01-01

    MicroRNAs act as key regulators in carcinogenesis and progression in various cancers. In present study, we explored the role of miR-340 in the breast cancer progression. Our results showed that overexpression of miR-340 inhibits breast cancer cell proliferation and invasion, whereas depletion of miR-340 promotes breast cancer progression. Molecularly, ZEB1 was identified as a target gene of miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the 3′-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340 expression. The negative feedback loop regulated TGF-β-mediated breast cancer progression. In conclusion, our data suggested that miR-340 acted as a tumor suppressor in breast cancer progression. PMID:27036021

  16. Progressive dry-core-wet-rim hydration trend in a nested-ring topology of protein binding interfaces

    Directory of Open Access Journals (Sweden)

    Li Zhenhua

    2012-03-01

    Full Text Available Abstract Background Water is an integral part of protein complexes. It shapes protein binding sites by filling cavities and it bridges local contacts by hydrogen bonds. However, water molecules are usually not included in protein interface models in the past, and few distribution profiles of water molecules in protein binding interfaces are known. Results In this work, we use a tripartite protein-water-protein interface model and a nested-ring atom re-organization method to detect hydration trends and patterns from an interface data set which involves immobilized interfacial water molecules. This data set consists of 206 obligate interfaces, 160 non-obligate interfaces, and 522 crystal packing contacts. The two types of biological interfaces are found to be drier than the crystal packing interfaces in our data, agreeable to a hydration pattern reported earlier although the previous definition of immobilized water is pure distance-based. The biological interfaces in our data set are also found to be subject to stronger water exclusion in their formation. To study the overall hydration trend in protein binding interfaces, atoms at the same burial level in each tripartite protein-water-protein interface are organized into a ring. The rings of an interface are then ordered with the core atoms placed at the middle of the structure to form a nested-ring topology. We find that water molecules on the rings of an interface are generally configured in a dry-core-wet-rim pattern with a progressive level-wise solvation towards to the rim of the interface. This solvation trend becomes even sharper when counterexamples are separated. Conclusions Immobilized water molecules are regularly organized in protein binding interfaces and they should be carefully considered in the studies of protein hydration mechanisms.

  17. Oncogenic Alternative Splicing Switches: Role in Cancer Progression and Prospects for Therapy

    OpenAIRE

    Serena Bonomi; Stefania Gallo; Morena Catillo; Daniela Pignataro; Giuseppe Biamonti; Claudia Ghigna

    2013-01-01

    Alterations in the abundance or activities of alternative splicing regulators generate alternatively spliced variants that contribute to multiple aspects of tumor establishment, progression and resistance to therapeutic treatments. Notably, many cancer-associated genes are regulated through alternative splicing suggesting a significant role of this post-transcriptional regulatory mechanism in the production of oncogenes and tumor suppressors. Thus, the study of alternative splicing in cancer ...

  18. Inducing pluripotency and immortality in prostate tumor cells : a stem cell model of cancer progression

    OpenAIRE

    Fiñones, Rita Roces

    2009-01-01

    The progression from local prostate tumor to lethal prostate cancer is not well understood. Although current treatments cure a majority of patients, a significant minority (̃12 %) of people are diagnosed with late-stage, hormone-independent disease. As yet, the origin of the hormone-independent prostate cancer cells is unknown. In the present study, the transition to the lethal form of this disease is hypothesized to occur when a genetically- compromised tumor cell undergoes (1) an immortaliz...

  19. MicroRNA-490 inhibits tumorigenesis and progression in breast cancer

    OpenAIRE

    Zhao L; Zheng XY

    2016-01-01

    Lin Zhao,1 Xin-Yu Zheng1,21Department of Breast Surgery, the First Hospital of China Medical University, 2The First Laboratory, Cancer Institute of China Medical University, Shenyang, People’s Republic of ChinaAbstract: MicroRNAs are consistently reported to regulate gene expression in all cancer cell types by modulating a wide range of biological processes, including cell proliferation, differentiation, and apoptosis, which are associated with tumor development and progression. Previou...

  20. A computational approach to resolve cell level contributions to early glandular epithelial cancer progression

    OpenAIRE

    Park Sunwoo; Mostov Keith; Debnath Jayanta; Kim Sean HJ; Hunt C Anthony

    2009-01-01

    Abstract Background Three-dimensional (3D) embedded cell cultures provide an appropriate physiological environment to reconstruct features of early glandular epithelial cancer. Although these are orders of magnitude simpler than tissues, they too are complex systems that have proven challenging to understand. We used agent-based, discrete event simulation modeling methods to build working hypotheses of mechanisms of epithelial 3D culture phenotype and early cancer progression. Starting with a...

  1. Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Kapil, E-mail: kmehta@mdanderson.org; Han, Amy [Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030 (United States)

    2011-02-25

    Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer.

  2. Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer

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

    OpenAIRE

    Gru, Alejandro A.; Allred, D. Craig

    2012-01-01

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

  4. Cancer and birth defects surveillance system for communities around the Savannah River Site. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Dunbar, J.B.

    1994-05-01

    The US DOE funded this grant to the Medical University of South Carolina for a cancer and birth defects registry for an initial three year period which was completed as of April 29, 1994. While this Technical Progress Report is prepared principally to document the activities of year 03, it also summarizes the accomplishments of the first two years in order to put into perspective the energy and progress of the program over the entire three year funding cycle.

  5. Cancer and birth defects surveillance system for communities around the Savannah River Site. Annual progress report

    International Nuclear Information System (INIS)

    The US DOE funded this grant to the Medical University of South Carolina for a cancer and birth defects registry for an initial three year period which was completed as of April 29, 1994. While this Technical Progress Report is prepared principally to document the activities of year 03, it also summarizes the accomplishments of the first two years in order to put into perspective the energy and progress of the program over the entire three year funding cycle

  6. The role of activated protein C in cancer progression

    NARCIS (Netherlands)

    G.L. van Sluis; H.R. Büller; C.A. Spek

    2010-01-01

    Activated protein C (APC) is best known as a natural anticoagulant that also has direct cell signaling properties which (among others) enhance vascular barrier function. We recently established the relevance of APC-induced barrier enhancement by showing that endogenous APC limits cancer cell extrava

  7. THE LATEST PROGRESS OF GASTRIC CANCER SURGERY IN JAPAN

    Institute of Scientific and Technical Information of China (English)

    Keiichi; Maruyama; Professor

    2007-01-01

    @@ Mortality rate of gastric cancer in Japan had been the highest in the world.Development of early detection and effective treatment was the most important social demand.For the early detection,Japan developed"double contrast X-ray","endoscopy and endoscopic biopsy", and"mass screening system".

  8. Research Progress of MicroRNA in Early Detection of Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    Ze-Hua Wang; Cong-Jian Xu

    2015-01-01

    Objective: This review aimed to update the progress ofmicroRNA (miRNA) in early detection of ovarian cancer.We discussed the current clinical diagnosis methods and biomarkers of ovarian cancer, especially the methods of miRNA in early detection of ovarian cancer.Data Sources: We collected all relevant studies about miRNA and ovarian cancer in PubMed and CNKI from 1995 to 2015.Study Selection: We included all relevant studies concerning miRNA in early detection of ovarian cancer, and excluded the duplicated articles.Results: miRNAs play a key role in various biological processes of ovarian cancer, such as development, proliferation, differentiation, apoptosis and metastasis, and these phenomena appear in the early-stage.Therefore, miRNA can be used as a new biomarker for early diagnosis of ovarian cancer, intervention on miRNA expression of known target genes, and potential target genes can achieve the effect of early prevention.With the development ofnanoscience and technology, analysis methods ofmiRNA are also quickly developed, which may provide better characterization of early detection of ovarian cancer.Conclusions: In the near future, miRNA therapy could be a powerful tool for ovarian cancer prevention and treatment, and combining with the new analysis technology and new nanomaterials, point-of-care tests for miRNA with high throughput, high sensitivity, and strong specificity are developed to achieve the application of diagnostic kits in screening of early ovarian cancer.

  9. Trends in incidence and prognosis of the histological subtypes of lung cancer in North America, Australia, New Zealand and Europe

    NARCIS (Netherlands)

    M.L.G. Janssen-Heijnen (Maryska); J.W.W. Coebergh (Jan Willem)

    2001-01-01

    textabstractBackground: Since the incidence of the histological subtypes of lung cancer in industrialised countries has changed dramatically over the last two decades, we reviewed trends in the incidence and prognosis in North America, Australia, New Zealand and Europe, according to period of diagno

  10. What Does the Public Know about Preventing Cancer? Results from the Health Information National Trends Survey (HINTS)

    Science.gov (United States)

    Hawkins, Nikki A.; Berkowitz, Zahava; Peipins, Lucy A.

    2010-01-01

    This study provides information about the public's familiarity with cancer prevention strategies and examines the association between this familiarity and actual prevention behavior. Data from interviews with 5,589 adults included in the 2003 Health Information National Trends Survey (HINTS) were analyzed. Most respondents were able to cite one or…

  11. Breast cancer incidence and mortality in the Nordic capitals, 1970-1998. Trends related to mammography screening programmes

    DEFF Research Database (Denmark)

    Törnberg, Sven; Kemetli, Levent; Lynge, Elsebeth;

    2006-01-01

    The aim of the present study was to relate the time trends in breast cancer incidence and mortality to the introduction of mammography screening in the Nordic capitals. Helsinki offered screening to women aged 50-59 starting in 1986. The other three capitals offered screening to women aged 50...

  12. Maspin expression and its clinicopathological significance in tumorigenesis and progression of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Meng-Chun Wang; Yan-Min Yang; Xiao-Han Li; Fang Dong; Yan Li

    2004-01-01

    AIM: To investigate maspin expression in tumorigenesis and progression of gastric cancer and to explore its relevant molecular mechanisms.METHODS: Formalin-fixed and paraffin-embedded tissues from normal mucosa (n=182), dysplasia (n=69), cancer (n=113) of the stomach were studied for maspin expression by immunohistochemistry. Microvessel density (MVD) in gastric cancer was labeled using anti-CD34 antibody. Maspin expression was compared with clinical parameters and MVD of tumors. Caspase-3 expression was also detected in gastric carcinoma by immunohistochemistry. The relationship between Caspase-3 and maspin expression was concerned as well.RESULTS: The positive rates of maspin expression were 79.8%(145/182), 75.4%(52/69) and 50.4%(57/113) in normal mucosa, dysplasia and cancer of the stomach,respectively. Cancer less frequently expressed maspin than normal mucosa and dysplasia (P<0.05). Maspin expression showed a significantly negative association with invasive depth, metastasis, Lauren's and Nakamura's classification (P<0.05), but not with tumor size, Borrmann's classification,growth pattern or TNM staging (P>0.05). The positive rate of Caspase-3 was significantly lower in gastric cancer than in normal gastric mucosa (P<0.05,32.7% vs 50.4%). It was noteworthy that maspin expression was negatively correlated with MVD, but positively correlated with expression of Caspase-3 in gastric cancer (P<0.05).CONCLUSION: Down-regulated maspin expression is a late molecular event in gastric carcinogenesis. Reduced expression of maspin contributes to progression of gastric cancer probably by inhibiting cell adhesion, enhancing cell mobility,decreasing cell apoptosis and facilitating angiogenesis.Additionally altered expression of maspin underlies the molecular mechanism of differentiation of gastric cancer and supports the different histogenetic pathways of intestinal and diffuse gastric cancers. Maspin expression can be considered as an effective and objective

  13. Multi-state relative survival modelling of colorectal cancer progression and mortality.

    Science.gov (United States)

    Gilard-Pioc, Séverine; Abrahamowicz, Michal; Mahboubi, Amel; Bouvier, Anne-Marie; Dejardin, Olivier; Huszti, Ella; Binquet, Christine; Quantin, Catherine

    2015-06-01

    Accurate identification of factors associated with progression of colorectal cancer remains a challenge. In particular, it is unclear which statistical methods are most suitable to separate the effects of putative prognostic factors on cancer progression vs cancer-specific and other cause mortality. To address these challenges, we analyzed 10 year follow-up data for patients who underwent curative surgery for colorectal cancer in 1985-2000. Separate analyses were performed in two French cancer registries. Results of three multivariable models were compared: Cox model with recurrence as a time-dependent variable, and two multi-state models, which separated prognostic factor effects on recurrence vs death, with or without recurrence. Conventional multi-state model analyzed all-cause mortality while new relative survival multi-state model focused on cancer-specific mortality. Among the 2517 and 2677 patients in the two registries, about 50% died without a recurrence, and 28% had a recurrence, of whom almost 90% died. In both multi-state models men had significantly increased risk of cancer recurrence in both registries (HR=0.79; 95% CI: 0.68-0.92 and HR=0.83; 95% CI: 0.71-0.96). However, the two multi-state models identified different prognostic factors for mortality without recurrence. In contrast to the conventional model, in the relative survival analyses gender had no independent association with cancer-specific mortality whereas patients diagnosed with stage III cancer had significantly higher risks in both registries (HR=1.67; 95% CI: 1.27-2.22 and HR=2.38; 95% CI: 1.29-3.27). In conclusion, relative survival multi-state model revealed that different factors may be associated with cancer recurrence vs cancer-specific mortality either after or without a recurrence.

  14. Saffron Aqueous Extract Inhibits the Chemically-induced Gastric Cancer Progression in the Wistar Albino Rat

    Directory of Open Access Journals (Sweden)

    S. Zahra Bathaie

    2013-01-01

    Full Text Available Objective(s: Gastric cancer is the first and second leading cause of cancer related death in Iranian men and women, respectively. Gastric cancer management is based on the surgery, radiotherapy and chemotherapy. In the present study, for the first time, the beneficial effect of saffron (Crocus sativus L. aqueous extract (SAE on the 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG-induced gastric cancer in rat was investigated. Materials and Methods: MNNG was used to induce gastric cancer and then, different concentrations of SAE were administered to rats. After sacrificing, the stomach tissue was investigated by both pathologist and flow cytometry, and several biochemical parameters was determined in the plasma (or serum and stomach of rats. Results: Pathologic data indicated the induction of cancer at different stages from hyperplasia to adenoma in rats; and the inhibition of cancer progression in the gastric tissue by SAE administration; so that, 20% of cancerous rats treated with higher doses of SAE was completely normal at the end of experiment and there was no rat with adenoma in the SAE treated groups. In addition, the results of the flow cytometry/ propidium iodide staining showed that the apoptosis/proliferation ratio was increased due to the SAE treatment of cancerous rats. Moreover, the significantly increased serum LDH and decreased plasma antioxidant activity due to cancer induction fell backwards after treatment of rats with SAE. But changes in the other parameters (Ca2+, tyrosine kinase activity and carcino-embryonic antigen were not significant. Conclusion: SAE inhibits the progression of gastric cancer in rats, in a dose dependent manner.

  15. 20 Years of Progress in Radiation Oncology: Prostate Cancer.

    Science.gov (United States)

    Lanciano; Thomas; Eifel

    1997-04-01

    Carcinoma of the cervix remains of special interest to the Patterns of Care Study (PCS) because of the prominent role that radiotherapy plays in the definitive management of all stages and extents of disease. Five PCS surveys have been conducted for squamous cell cancer of the uterine cervix beginning in 1973 and repeated thereafter at 5-year intervals. The records of over 2,700 women have been reviewed for these surveys. Changes in the pretreatment investigations of cervical cancer patients have occurred during these years, with an increase in the use of computed tomography (CT) and a decrease in the use of intravenous pyelography and cystoscopy. A marked increase in the use of linear accelerators has also occurred, with 98% of all facilities having a linear accelerator as the highest energy treatment machine in the 1988 survey. There has been a change in brachytherapy prescription over the time of the surveys, with most institutions reporting point dose calculations and dose distributions instead of milligram hours. Mean point A dose has increased to approximately 80cGy, reflecting the PCS recommendations of dose intensity to the paracentral point through use of brachytherapy. The outcome for stage I and II cervical cancer has remained stable over the time of the surveys, while the results have improved for stage III disease. This improvement in survival and local control for stage III cervical cancer is due in part to the PCS, which has developed standards of treatment with the goal of radiation dose intensity. A number of patient, tumor, and treatment factors significant in multivariate analysis have been described by the PCS with large cohorts of patients. The most important treatment factors associated with a decrease in pelvic failure and improved survival are the use of brachytherapy and higher paracentral dose. A significant dose response has been described for stage III cervical cancer and optimal pelvic control has been demonstrated with point A doses

  16. The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention

    Science.gov (United States)

    Vahora, Huzefa; Khan, Munawwar Ali; Alalami, Usama; Hussain, Arif

    2016-01-01

    Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment. PMID:27051643

  17. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    Directory of Open Access Journals (Sweden)

    Seher Balaban

    2015-01-01

    Full Text Available Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression.

  18. Metastatic colorectal cancer-past, progress and future

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The clinical management of metastatic (stage Ⅳ)colorectal cancer (CRC) is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage Ⅳ disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies,improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition.This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.

  19. Recent progress in 8igenomic research of liver cancer

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Along the course of occurrence and development of liver cancer,the corresponding somatic cells accumulate some important genetic variations.These variations may be divided into two categories.For the genetic changes closely related to etiology of liver cancer,the well-known cases include insertion and integration of the hepatitis B virus(HBV) DNA after infection,and mutations at site 249 of the tumor suppressor gene p53 induced by exposure to aflatoxin B1.The secondary genetic changes include amplification and deletion of certain chromosome regions,mutations in p53 at the sites other than 249,as well as the mutational activation of the Wnt/β-catenin signal pathway.The tumor cells with these genetic variations may gradually become the dominant clones under evolutionary selection.Besides,identification of genetic susceptible against risk of liver malignancy is also an important aspect of research in this field.

  20. Recent progress in 8igenomic research of liver cancer

    Institute of Scientific and Technical Information of China (English)

    HAN ZeGuang

    2009-01-01

    Along the course of occurrence and development of liver cancer, the corresponding somatic cells ac-cumulate some important genetic variations. These variations may be divided into two categories. For the genetic changes closely related to etiology of liver cancer, the well-known cases include insertion and integration of the hepatitis B virus (HBV) DNA after infection, and mutations at site 249 of the tumor suppressor gene p53 induced by exposure to aflatoxin B1. The secondary genetic changes include amplification and deletion of certain chromosome regions, mutations in p53 at the sites other than 249, as well as the mutational activation of the Wnt/β-catenin signal pathway. The tumor cells with these genetic variations may gradually become the dominant clones under evolutionary selection. Besides, identification of genetic susceptible against risk of liver malignancy is also an important aspect of re-search in this field.

  1. Supramolecular nanofibrils inhibit cancer progression in vitro and in vivo

    OpenAIRE

    Kuang, Yi; Du, Xuewen; Zhou, Jie; Xu, Bing

    2014-01-01

    The recent discovery of the inverse comorbidity between cancer and Alzheimer’s disease implies that one may use amyloids to inhibit tumors. During the conversion of a dipeptide segment (Phe-Phe) in β-amyloid into a supramolecular hydrogelator, we obtained a small molecule (1) that can self-assembly into nanofibrils via multiple intermolecular hydrogen bonding and aromatic-aromatic interactions. Interestingly, while the monomers of 1 are innocuous, the nanofibrils formed by 1 can selectively i...

  2. Trends in stomach cancer mortality in relation to living conditions in childhood : A study among cohorts born between 1860 and 1939 in seven European countries

    NARCIS (Netherlands)

    Amiri, M.; Kunst, A. E.; Janssen, F.; Mackenbach, J. P.

    2006-01-01

    Aim: To assess whether secular trends in stomach cancer mortality were correlated with trends in infant mortality rate (IMR) or gross domestic product (GDP). Methods: Data from seven European countries were analyzed. We used Poisson regression to describe mortality trends among birth cohorts of 1865

  3. Oncogenic Alternative Splicing Switches: Role in Cancer Progression and Prospects for Therapy

    Directory of Open Access Journals (Sweden)

    Serena Bonomi

    2013-01-01

    Full Text Available Alterations in the abundance or activities of alternative splicing regulators generate alternatively spliced variants that contribute to multiple aspects of tumor establishment, progression and resistance to therapeutic treatments. Notably, many cancer-associated genes are regulated through alternative splicing suggesting a significant role of this post-transcriptional regulatory mechanism in the production of oncogenes and tumor suppressors. Thus, the study of alternative splicing in cancer might provide a better understanding of the malignant transformation and identify novel pathways that are uniquely relevant to tumorigenesis. Understanding the molecular underpinnings of cancer-associated alternative splicing isoforms will not only help to explain many fundamental hallmarks of cancer, but will also offer unprecedented opportunities to improve the efficacy of anti-cancer treatments.

  4. Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting

    Science.gov (United States)

    Chaudhary, Belal; Elkord, Eyad

    2016-01-01

    Recent years have seen significant efforts in understanding and modulating the immune response in cancer. In this context, immunosuppressive cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), have come under intense investigation for their proposed roles in suppressing tumor-specific immune responses and establishing an immunosuppressive tumor microenvironment, thus enabling tumor immune evasion. Additionally, recent evidence indicates that Tregs comprise diverse and heterogeneous subsets; phenotypically and functionally distinct subsets of tumor-infiltrating Tregs could contribute differently to cancer prognosis and clinical outcomes. Understanding Treg biology in the setting of cancer, and specifically the tumor microenvironment, is important for designing effective cancer therapies. In this review, we critically examine the role of Tregs in the tumor microenvironment and in cancer progression focusing on human studies. We also discuss the impact of current therapeutic modalities on Treg biology and the therapeutic opportunities for targeting Tregs to enhance anti-tumor immune responses and clinical benefits. PMID:27509527

  5. Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer

    DEFF Research Database (Denmark)

    See, W; Iversen, P; Wirth, M;

    2003-01-01

    To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer.......To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer....

  6. Decreased levels of serum glutathione peroxidase 3 are associated with papillary serous ovarian cancer and disease progression

    Directory of Open Access Journals (Sweden)

    Agnani Deep

    2011-10-01

    Full Text Available Abstract Background Glutathione peroxidase 3 (GPX3 is a selenocysteine-containing antioxidant enzyme that reacts with hydrogen peroxide and soluble fatty acid hydroperoxides, thereby helping to maintain redox balance within cells. Serum levels of GPX3 have been found to be reduced in various cancers including prostrate, thyroid, colorectal, breast and gastric cancers. Intriguingly, GPX3 has been reported to be upregulated in clear cell ovarian cancer tissues and thus may have implications in chemotherapeutic resistance. Since clear cell and serous subtypes of ovarian cancer represent two distinct disease entities, the aim of this study was to determine GPX3 levels in serous ovarian cancer patients and establish its potential as a biomarker for detection and/or surveillance of papillary serous ovarian cancer, the most frequent form of ovarian tumors in women. Patients and Methods Serum was obtained from 66 patients (median age: 62 years, range: 22-89 prior to surgery and 65 controls with a comparable age-range (median age: 53 years, range: 25-83. ELISA was used to determine the levels of serum GPX3. The Mann Whitney U test was performed to determine statistical significance between the levels of serum GPX3 in patients and controls. Results Serum levels of GPX3 were found to be significantly lower in patients than controls (p = 1 × 10-2. Furthermore, this was found to be dependent on the stage of disease. While levels in early stage (I/II patients showed no significant difference when compared to controls, there was a significant reduction in late stage (III/IV, p = 9 × 10-4 and recurrent (p = 1 × 10-2 patients. There was a statistically significant reduction in levels of GPX3 between early and late stage (p = 5 × 10-4 as well as early and recurrent (p = 1 × 10-2 patients. Comparison of women and controls stratified to include only women at or above 50 years of age shows that the same trends were maintained and the differences became more

  7. The ghrelin axis--does it have an appetite for cancer progression?

    Science.gov (United States)

    Chopin, Lisa K; Seim, Inge; Walpole, Carina M; Herington, Adrian C

    2012-12-01

    Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHSR), is a peptide hormone with diverse physiological roles. Ghrelin regulates GH release, appetite and feeding, gut motility, and energy balance and also has roles in the cardiovascular, immune, and reproductive systems. Ghrelin and the GHSR are expressed in a wide range of normal and tumor tissues, and a fluorescein-labeled, truncated form of ghrelin is showing promise as a biomarker for prostate cancer. Plasma ghrelin levels are generally inversely related to body mass index and are unlikely to be useful as a biomarker for cancer, but may be useful as a marker for cancer cachexia. Some single nucleotide polymorphisms in the ghrelin and GHSR genes have shown associations with cancer risk; however, larger studies are required. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, inflammation, and angiogenesis; however, the role of ghrelin in cancer is currently unclear. Ghrelin has predominantly antiinflammatory effects and may play a role in protecting against cancer-related inflammation. Ghrelin and its analogs show promise as treatments for cancer-related cachexia. Further studies using in vivo models are required to determine whether ghrelin has a role in cancer progression.

  8. Global trends in breast cancer incidence and mortality Cáncer de mama en el mundo

    Directory of Open Access Journals (Sweden)

    Peggy L. Porter

    2009-01-01

    Full Text Available This review highlights the increasing incidence of breast cancer world-wide and the increasing burden of breast cancer deaths experienced by lower-income countries. The causes of increasing incidence have been attributed to changes in the prevalence of reproductive risk factors, lifestyle changes, and genetic and biological differences between ethnic and racial groups. All these factors may contribute, but data linking etiological factors to increased risk in developing countries is lacking. The challenge for lower-income countries is developing effective strategies to reverse the trend of increasing mortality. Down-staging of breast cancer by early detection is a promising long-term strategy for preventing disease-related deaths but it is difficult to make the economic investment required to carry out broad screening programs. Successful strategies for addressing the growing breast cancer burden will therefore take political will, reliable data, public and medical community awareness, and partnerships between community advocates, governments, non-governmental organizations and biotechnology.Se destaca el aumento en la incidencia de cáncer de mama (CaMa en el mundo y la creciente carga de muertes por la enfermedad en países en desarrollo. El aumento en la incidencia se atribuye a cambios en la prevalencia de factores de riesgo reproductivo, estilo de vida, y a diferencias biológicas entre grupos étnicos y raciales. Sin embargo, aún faltan datos que relacionen los factores etiológicos al incremento en el riesgo en países en desarrollo. El desafío es generar estrategias efectivas que reviertan la tendencia en la mortalidad. La detección en etapas más tempranas es una estrategia prometedora de largo plazo pero la inversión necesaria para los programas de tamizaje es muy alta. Las estrategias exitosas para hacer frente a la creciente carga de CaMa deben tener voluntad política, evidencia confiable, reconocimiento de la comunidad p

  9. Research Progress in the Use of Drugs for Breast Cancer Targeted Therapy

    Institute of Scientific and Technical Information of China (English)

    Shun'e Yang; Bing Zhao

    2008-01-01

    In recent years,many significant advances have been made on molecular target therapy to aim directly at epidermal growth factor receptors and vascular endothelial growth factor in breast cancers.Clinical studies of such agents as trastuzumab,lapatinib,erlotinib and bevacituzumab have been widely conducted.This paper will review the recent research progress related to targeted therapy.

  10. Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

    DEFF Research Database (Denmark)

    Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle;

    2010-01-01

    To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-a trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, ß-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer ...

  11. Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

    DEFF Research Database (Denmark)

    Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle;

    2010-01-01

    To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer ...

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

    NARCIS (Netherlands)

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

    2014-01-01

    PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A stand

  13. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske;

    2014-01-01

    BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the fina...

  14. Dual Roles of RNF2 in Melanoma Progression | Office of Cancer Genomics

    Science.gov (United States)

    Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic.

  15. High-throughput genomic technology in research and clinical management of breast cancer. Molecular signatures of progression from benign epithelium to metastatic breast cancer

    OpenAIRE

    Rennstam, Karin; Hedenfalk, Ingrid

    2006-01-01

    It is generally accepted that early detection of breast cancer has great impact on patient survival, emphasizing the importance of early diagnosis. In a widely recognized model of breast cancer development, tumor cells progress through chronological and well defined stages. However, the molecular basis of disease progression in breast cancer remains poorly understood. High-throughput molecular profiling techniques are excellent tools for the study of complex molecular alterations. By accurate...

  16. Nanochips of Tantalum Oxide Nanodots as artificial-microenvironments for monitoring Ovarian cancer progressiveness

    Science.gov (United States)

    Dhawan, Udesh; Wang, Ssu-Meng; Chu, Ying Hao; Huang, Guewha S.; Lin, Yan Ren; Hung, Yao Ching; Chen, Wen Liang

    2016-08-01

    Nanotopography modulates cell characteristics and cell behavior. Nanotopological cues can be exploited to investigate the in-vivo modulation of cell characteristics by the cellular microenvironment. However, the studies explaining the modulation of tumor cell characteristics and identifying the transition step in cancer progressiveness are scarce. Here, we engineered nanochips comprising of Tantalum oxide nanodot arrays of 10, 50, 100 and 200 nm as artificial microenvironments to study the modulation of cancer cell behavior. Clinical samples of different types of Ovarian cancer at different stages were obtained, primary cultures were established and then seeded on different nanochips. Immunofluorescence (IF) was performed to compare the morphologies and cell characteristics. Indices corresponding to cell characteristics were defined. A statistical comparison of the cell characteristics in response to the nanochips was performed. The cells displayed differential growth parameters. Morphology, Viability, focal adhesions, microfilament bundles and cell area were modulated by the nanochips which can be used as a measure to study the cancer progressiveness. The ease of fabrication of nanochips ensures mass-production. The ability of the nanochips to act as artificial microenvironments and modulate cell behavior may lead to further prospects in the markerless monitoring of the progressiveness and ultimately, improving the prognosis of Ovarian cancer.

  17. Copper and angiogenesis: unravelling a relationship key to cancer progression.

    Science.gov (United States)

    Finney, Lydia; Vogt, Stefan; Fukai, Tohru; Glesne, David

    2009-01-01

    1. Angiogenesis, the formation of new capillaries from existing vasculature, is a critical process in normal physiology as well as several physiopathologies. A desire to curb the supportive role angiogenesis plays in the development and metastasis of cancers has driven exploration into anti-angiogenic strategies as cancer therapeutics. Key to this, angiogenesis additionally displays an exquisite sensitivity to bioavailable copper. Depletion of copper has been shown to inhibit angiogenesis in a wide variety of cancer cell and xenograft systems. Several clinical trials using copper chelation as either an adjuvant or primary therapy have been conducted. Yet, the biological basis for the sensitivity of angiogenesis remains unclear. Numerous molecules important to angiogenesis regulation have been shown to be either directly or indirectly influenced by copper, yet a clear probative answer to the connection remains elusive. 2. Measurements of copper in biological systems have historically relied on techniques that, although demonstrably powerful, provide little or no information as to the spatial distribution of metals in a cellular context. Therefore, several new approaches have been developed to image copper in a biological context. One such approach relies on synchrotron-derived X-rays from third-generation synchrotrons and the technique of high resolution X-ray fluorescence microprobe (XFM) analysis. 3. Recent applications of XFM approaches to the role of copper in regulating angiogenesis have provided unique insight into the connection between copper and cellular behaviour. Using XFM, copper has been shown to be highly spatially regulated, as it is translocated from perinuclear areas of the cell towards the tips of extending filopodia and across the cell membrane into the extracellular space during angiogenic processes. Such findings may explain the heightened sensitivity of this cellular process to this transition metal and set a new paradigm for the kinds of

  18. Adjuvant Strategies for Resectable Pancreatic Cancer: Have We Made Progress?

    Directory of Open Access Journals (Sweden)

    Suzanne Russo

    2012-03-01

    Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.

  19. Potential Biomarker of L type Amino Acid Transporter 1 in Breast Cancer Progression

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Zhongxing; Cho, Heidi T.; Williams, Larry; Zhu, Aizhi; Liang, Ke; Huang, Ke; Wu, Hui; Jiang, Chunsu; Hong, Samuel; Crowe, Ronald; Goodman, Mark M.; Shim, Hyunsuk [Emory Univ. School of Medicine, Atlanta (United States)

    2011-06-15

    L type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with 1 amino 3 [{sup 18F}]fluorocyclo butane 1 carboxylic acid ([{sup 18F}]FACBC) PET was assessed for its diagnostic biomarker potential. Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced stage breast cancer. Furtermore, the blockade of LAT1 with its inhibitor, 2 amino bicyclo[2.2.1]heptane 2 carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, [{sup 18F}]FACBC, has been demonstrated to be an excellent PET tracer for the non invasive imaging og malignant breast cancer using an orthotopic animal model. The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. [{sup 18F}]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

  20. Recent trends in breast cancer incidence in US white women by county-level urban/rural and poverty status

    Directory of Open Access Journals (Sweden)

    Keegan Theresa HM

    2009-06-01

    Full Text Available Abstract Background Unprecedented declines in invasive breast cancer rates occurred in the United States between 2001 and 2004, particularly for estrogen receptor-positive tumors among non-Hispanic white women over 50 years. To understand the broader public health import of these reductions among previously unstudied populations, we utilized the largest available US cancer registry resource to describe age-adjusted invasive and in situ breast cancer incidence trends for non-Hispanic white women aged 50 to 74 years overall and by county-level rural/urban and poverty status. Methods We obtained invasive and in situ breast cancer incidence data for the years 1997 to 2004 from 29 population-based cancer registries participating in the North American Association of Central Cancer Registries resource. Annual age-adjusted rates were examined overall and by rural/urban and poverty of patients' counties of residence at diagnosis. Joinpoint regression was used to assess trends by annual quarter of diagnosis. Results Between 2001 and 2004, overall invasive breast cancer incidence fell 13.2%, with greater reductions among women living in urban (-13.8% versus rural (-7.5% and low- (-13.0% or middle- (-13.8% versus high- (-9.6% poverty counties. Most incidence rates peaked around 1999 then declined after second quarter 2002, although in rural counties, rates decreased monotonically after 1999. Similar but more attenuated patterns were seen for in situ cancers. Conclusion Breast cancer rates fell more substantially in urban and low-poverty, affluent counties than in rural or high-poverty counties. These patterns likely reflect a major influence of reductions in hormone therapy use after July 2002 but cannot exclude possible effects due to screening patterns, particularly among rural populations where hormone therapy use was probably less prevalent.

  1. New trends in guided nanotherapies for digestive cancers: A systematic review.

    Science.gov (United States)

    Fernandes, Elisabete; Ferreira, José Alexandre; Andreia, Peixoto; Luís, Lima; Barroso, Sérgio; Sarmento, Bruno; Santos, Lúcio Lara

    2015-07-10

    exploring glycans as homing molecules. Other ligands such as peptides/small proteins and antibodies/antibody fragments, with affinity to either tumor vasculature or tumor cells, have also been widely and successfully applied to guide nanodrugs to gastrointestinal carcinomas. Conversely, few solutions have been presented for pancreatic tumors. To this date only three nanocomplexes have progressed beyond pre-clinical stages: i) PK2, a galactosamine-functionalized polymeric-DOX formulation for hepatocarcinomas; ii) MCC-465, an anti-(myosin heavy chain a) immunoliposome for advanced stage metastatic solid tumors; and iii) MBP-426, a transferrin-liposome-oxaliplatin conjugate, also for advanced stage tumors. Still, none has been approved for clinical use. However, based on the high amount of pre-clinical studies showing enthusiastic results, the number of clinical trials is expected to increase in the near future. A more profound understanding about the molecular nature of chemoresistant clones and cancer stem cell biology will also contribute to boost the field of guided nanopharmacology towards more effective solutions. PMID:25957905

  2. Progress and remaining challenges for cancer control in Latin America and the Caribbean.

    Science.gov (United States)

    Strasser-Weippl, Kathrin; Chavarri-Guerra, Yanin; Villarreal-Garza, Cynthia; Bychkovsky, Brittany L; Debiasi, Marcio; Liedke, Pedro E R; Soto-Perez-de-Celis, Enrique; Dizon, Don; Cazap, Eduardo; de Lima Lopes, Gilberto; Touya, Diego; Nunes, Joāo Soares; St Louis, Jessica; Vail, Caroline; Bukowski, Alexandra; Ramos-Elias, Pier; Unger-Saldaña, Karla; Brandao, Denise Froes; Ferreyra, Mayra E; Luciani, Silvana; Nogueira-Rodrigues, Angelica; de Carvalho Calabrich, Aknar Freire; Del Carmen, Marcela G; Rauh-Hain, Jose Alejandro; Schmeler, Kathleen; Sala, Raúl; Goss, Paul E

    2015-10-01

    Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention. PMID:26522157

  3. MR Differentiation of Lung Cancer from Progressive Massive Fibrosis in Patients with Coal Worker's Pneumoconiosis

    International Nuclear Information System (INIS)

    To analyze the potential of MR to distinguish lung cancer from progressive massive fibrosis (PMF) in patients with coal worker's pneumoconiosis. The study consisted of 9 patients with pathologically proven lung cancer and 26 PMFs in 17 patients. All the patients had radiologic evidence of pneumoconiosis. T1-weighted FLASH images were obtained before and 0.5, 1, 2, 3, 4, 5, 7.5, 10, 12.5, and 15 minutes after injection of Gd-DTPA. T2-weighted fast spin-echo images were obtained. The imaging findings were evaluated for enhancement time curve, contrast uptake equivalent (CE), and enhancement factor (EF). On T1WI, there was no significant signal intensity difference between lung cancer and PMF. On T2WI, all lung cancer showed high signal intensity, as opposed to all PMFs which showed low signal intensity except for one PMF. Only one PMF showed high signal intensity on T2WI. For the dynamic contrast study, lung cancer showed faster and slightly stronger enhancement than PMFs. For a delayed image, most of the lung cancers (78%) showed washout, as opposed to a plateau in most of PMFs (73%) (p=0.0153). However, no difference was detected between the EFmax of lung cancer and PMFs (p=0.349). MR is potentially a useful tool in distinguishing lung cancer from PMFs in patients with coal worker's pneumoconiosis

  4. Prostate cancer in Denmark 1978-2009 - trends in incidence and mortality

    DEFF Research Database (Denmark)

    Outzen, Malene; Brasso, Klaus; Martinussen, Nick;

    2013-01-01

    calendar periods (1978-2007) and a two-year calendar period (2008-2009). Trends in incidence rates were estimated for specific age groups, birth cohorts, and clinical stage. Results. The age-standardised incidence rate of PC increased from 29.2 per 100 000 person-years in 1978-1982 to 76.2 per 100 000...... person-years in 2008-2009. The incidence increase began primarily in the mid-1990s. The corresponding mortality rates of PC remained largely unchanged during the entire study period; around 19 per 100 000 person-years. The incidence increase was most pronounced among men aged 60 + years. A clear pattern...... 15 years. Material and methods. From the nationwide Danish Cancer Registry and Register of Causes of Death, we obtained information on all cases of PC and all deaths in Denmark during 1978-2009. Age-standardised (World Standard Population) incidence and mortality rates were computed for five-year...

  5. Pneumonia after Major Cancer Surgery: Temporal Trends and Patterns of Care

    Directory of Open Access Journals (Sweden)

    Vincent Q. Trinh

    2016-01-01

    Full Text Available Rationale. Pneumonia is a leading cause of postoperative complication. Objective. To examine trends, factors, and mortality of postoperative pneumonia following major cancer surgery (MCS. Methods. From 1999 to 2009, patients undergoing major forms of MCS were identified using the Nationwide Inpatient Sample (NIS, a Healthcare Cost and Utilization Project (HCUP subset, resulting in weighted 2,508,916 patients. Measurements. Determinants were examined using logistic regression analysis adjusted for clustering using generalized estimating equations. Results. From 1999 to 2009, 87,867 patients experienced pneumonia following MCS and prevalence increased by 29.7%. The estimated annual percent change (EAPC of mortality after MCS was −2.4% (95% CI: −2.9 to −2.0, P<0.001; the EAPC of mortality associated with pneumonia after MCS was −2.2% (95% CI: −3.6 to 0.9, P=0.01. Characteristics associated with higher odds of pneumonia included older age, male, comorbidities, nonprivate insurance, lower income, hospital volume, urban, Northeast region, and nonteaching status. Pneumonia conferred a 6.3-fold higher odd of mortality. Conclusions. Increasing prevalence of pneumonia after MCS, associated with stable mortality rates, may result from either increased diagnosis or more stringent coding. We identified characteristics associated with pneumonia after MCS which could help identify at-risk patients in order to reduce pneumonia after MCS, as it greatly increases the odds of mortality.

  6. Specific changes in the expression of imprinted genes in prostate cancer-implications for cancer progression and epigenetic regulation

    Institute of Scientific and Technical Information of China (English)

    Teodora Ribarska; Klaus-Marius Bastian; Annemarie Koch; Wolfgang A Schulz

    2012-01-01

    Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation,enhancer of zeste homologue 2 (EZH2)overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer.DNA methylation,EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes.Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes,expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2).A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms.Instead,selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes,which might function in the prostate to limit cell growth induced viathe PI3K/Akt pathway,modulate androgen responses and regulate differentiation.Whereas dysregulation of IG F2 may constitute an early change in prostate carcinogenesis,inactivation of this imprinted gene network is rather associated with cancer progression.

  7. Research Progress of Nutrition Support for Patients with Lung Cancer 
During Chemotherapy

    Directory of Open Access Journals (Sweden)

    Yiqiao LUO

    2014-12-01

    Full Text Available Primary lung cancer is one of the most common malignancies. Nowadays, both its morbidity and mortality rank first, patients with lung cancer are often goes with some affiliating symptoms such as malnutrition and weight loss. The side effects of cytotoxicity during chemotherapy may lead to further deteriorate of the nutritional status and worsen the anti-tumor therapy’s efficacy and the patients’ quality of life. With the development of palliative treatment and the higher request of patients for quality of life, nutritional support will be an important adjunctive treatment to maintain a good nutritional status and enhance the patients’ immunity during chemotherapy. It will play an active role in improving tolerability of chemotherapy and prognosis for patients with lung cancer. Here is a review about research progress of nutrition support treatment during chemotherapy for the patients with lung cancer.

  8. Validating the use of Medicare Australia billing data to examine trends in skin cancer [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2015-11-01

    Full Text Available Background:  Epidemiological data surrounding non-melanomatous skin cancer (NMSC is highly variable, in part due to the lack of government cancer registries. Several studies employ the use of Medical Australia (MA rebate data in assessing such trends, the validity of which has not been studied in the past. Conversely, melanoma skin cancer is a notifiable disease, and thus, MA and cancer registry data is readily available. The aim of the current study is to assess the use of MA for epidemiological measures for skin cancers, by using melanoma as a disease sample.   Methods:  Following ethics approval, data from MA and Victorian Cancer Registry (VCR from 2004-2008 were extracted. Incidence of MA and VCR unique melanoma cases were compared and stratified by age and local government area (LGA. Regression and a paired-samples t-test were performed.   Results: During the study period; 15,150 and 13,886 unique melanoma patients were identified through VCR and MA data sources respectively. An outlier in the >80­ year age group was noted between MA and VCR data. When stratified by age, significant correlation between MA and VCR was observed for all patients (gradient 0.91, R²= 0.936 and following exclusion of >80 patients (gradient 0.96, R²= 0.995. When stratified by LGA, a high degree of observation was observed for all patients (gradient 0.94, R²= 0.977 and following exclusion of >80 patients (gradient 0.996, R²= 0.975.   Conclusion: Despite the inclusion of outlier data groups, acceptable correlation between MA and VCR melanoma data was observed, suggesting that MA may be suitable for assessing epidemiological trends. Such principals may be used to validate the use of MA data for similar calculations assessing NMSC trends.

  9. Breast cancer incidence and mortality in the Nordic capitals, 1970-1998. Trends related to mammography screening programmes

    Energy Technology Data Exchange (ETDEWEB)

    Toernberg, Sven; Kemetli, Levent [Karolinska Univ. Hospital, Stockholm (Sweden). Cancer Screening Unit, Oncologic Centre; Lynge, Elsebeth; Olsen, Anne Helene [Univ. of Copenhagen, (Denmark). Inst. of Public Health; Hofvind, Solveig; Wang, Hege [The Cancer Registry of Norway, Oslo (Norway); Anttila, Ahti [Finnish Cancer Registry, Helsinki (Finland); Hakama, Matti [Univ. of Tampere (Finland). School of Public Health; Nystroem, Lennarth [Umeaa Univ. (Sweden). Dept. of Public Health and Clinical Medicine

    2006-07-15

    The aim of the present study was to relate the time trends in breast cancer incidence and mortality to the introduction of mammography screening in the Nordic capitals. Helsinki offered screening to women aged 50-59 starting in 1986. The other three capitals offered screening to women aged 50-69 starting in 1989 in Stockholm, 1991 in Copenhagen, and 1996 in Oslo. Prevalence peaks in breast cancer incidence depended on the age groups covered by the screening, the length of the implementation of screening, and the extent of background opportunistic screening. No mortality reduction following the introduction of screening was visible after seven to 12 years of screening in any of the three capitals where significant effects of the screening on the breast cancer mortality had already been demonstrated by using other analytical methods for the evaluation. No visible effect on mortality reduction was expected in Oslo due to too short an observation period. The study showed that the population-based breast cancer mortality trend is too crude a measure to detect the effect of screening on breast cancer mortality during the first years after the start of a programme.

  10. Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

    International Nuclear Information System (INIS)

    Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms. First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues. Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion. Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer

  11. WNT5A modulates cell cycle progression and contributes to the chemoresistance in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Wei Wei; Hui-Hui Sun; Na Li; Hong-Yue Li; Xin Li; Qiang Li; Xiao-Hong Shen

    2014-01-01

    BACKGROUND: Although there are many studies on the mechanism of chemoresistance in cancers, studies on the relations between WNT5A and chemoresistance in pancreatic cancer are rare. The present study was to examine the role of WNT5A in the regulation of cell cycle progression and in chemoresistance in pancreatic cancer tissues and cell lines. METHODS: Fresh pancreatic cancer and paracarcinoma tissues were obtained from 32 patients. The expressions of WNT5A, AKT/p-AKT and Cyclin D1 were detected by immunohistochemistry, and the correlation between WNT5A expression and clinicopathological characteristics was analyzed. The relationship between WNT5A expression and gemcitabine resistance was studied in PANC-1 and MIAPaCa2 cell lines. The effect of WNT5A on the regulation of cell cycle and gemcitabine cytotoxicity were investigated. The associations among the expressions of p-AKT, Cyclin D1 and WNT5A were also analyzed in cell lines and the effect of WNT5A on restriction-point (R-point) progression was evaluated. RESULTS: WNT5A, p-AKT and Cyclin D1 were highly expressed in pancreatic cancer tissues, and the WNT5A expression was correlated with the TNM stages. In vitro, WNT5A expression was associated with gemcitabine chemoresistance. The percentage of cells was increased in G0/G1 phase and decreased in S phase after knockdown of WNT5A in PANC-1. WNT5A promoted Cyclin D1 expression through phosphorylation of AKT which consequently enhanced G1-S transition and gemcitabine resistance. Furthermore, WNT5A enhanced the cell cycle progression toward R-point through regulation of retinoblastoma protein (pRb) and pRb-E2F complex formation. CONCLUSIONS: WNT5A induced chemoresistance by regulation of G1-S transition in pancreatic cancer cells. WNT5A might serve as a predictor of gemcitabine response and as a potential target for tumor chemotherapy.

  12. The associations between the environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk and progression

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Polychlorinated biphenyls(PCBs) are chlorinated biphenyl compounds with wide applications in the industry.In spite of a ban on their production in the late 1970s,PCBs,as a group of POPs,are still persistent and widely spread in the environment,posing potential threats to human health.The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo,animal and epidemiologic studies.Initial investigations indicated higher levels of PCBs in mammary tissues or sera corresponded to the occurrence of breast cancer,but later studies showed no positive association between PCB exposure and breast cancer development.More recent data suggested that the CYP1A1 m2 polymorphisms might add increased risk to the etiology of breast cancer in women with environmental exposure to PCBs.PCBs are implicated in advancing breast cancer progression,and our unpublished data reveals that PCBs activate the ROCK signaling to enhance breast cancer metastasis.Therefore,the correlation between PCB exposure and breast cancer risk warrants further careful investigations.

  13. Overexpression of centromere protein H is significantly associated with breast cancer progression and overall patient survival

    Institute of Scientific and Technical Information of China (English)

    Wen-Ting Liao; Yan Feng; Men-Lin Li; Guang-Lin Liu; Man-Zhi Li; Mu-Sheng Zeng; Li-Bing Song

    2011-01-01

    Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H (CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Westem blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134 (43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage (P = 0.001),T classification (P = 0.032),N classification (P =0.018),and Ki-67 (P<0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.

  14. Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

    Science.gov (United States)

    Chaplain, Mark A. J.; Powathil, Gibin G.

    Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.

  15. FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy

  16. FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tian-Li [Department of General Surgery, The People’s Hospital of Wuqing, Tianjin (China); Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Yue [Department of Respiration, Affiliated Hospital of Medical College of Chinese People’s Armed Police Force, Tianjin (China); Chen, Ao-Xiang; Sun, Xuan [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie, E-mail: gejie198003@163.com [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2014-04-04

    Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.

  17. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.

    Science.gov (United States)

    Mura, M; Hopkins, T G; Michael, T; Abd-Latip, N; Weir, J; Aboagye, E; Mauri, F; Jameson, C; Sturge, J; Gabra, H; Bushell, M; Willis, A E; Curry, E; Blagden, S P

    2015-09-24

    RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression. PMID:25531318

  18. Progress of research in miR-218 and cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Kangkang Zeng; Wei Zhang; Xiaoxia Hu

    2013-01-01

    MicroRNAs (miRNAs) are smal endogenous non-coding RNAs which can specifical y silence gene expression, and thereby alter cel and organism phenotype. Deregulation of miRNA expression has been discovered in a variety of tumors and it is now clear that they contribute to cancer development and progression. Previous studies have indicated that miRNAs are involved in developmental timing, cel proliferation, apoptosis, morphogenesis [1], antiviral defense [2], and tumorigenesis [3]. In cancer pathways, altered expression of tumor suppressive or oncogenic miRNAs can disrupt regulatory mechanisms normal. Altered miRNAs expression patterns have been observed in a variety of diseased tissues. Cervical cancer is the most common malignant tumor in female reproductive tract. Recently more and more study showed a large number of miRNAs were down-regulated or up-regulated in cervical cancer. Recent data revealed that miRNA-218 (miR-218) played important roles in tumor initiation and development. This review focuses on analysis of miR-218 and wil provide some insight into the progress of cervical cancer.

  19. Breast cancer incidence and survival: registry-based studies of long-term trends and determinants

    NARCIS (Netherlands)

    M.W.J. Louwman (Marieke)

    2007-01-01

    markdownabstract__Abstract__ Breast cancer is the most frequent cancer among women in the Netherlands, and it is the most important cause of cancer death. Between age 35 and 55 about 20% of all deaths among women is due to breast cancer.1 The age-standardised incidence rate is among the highest in

  20. Bioluminescence imaging of estrogen receptor activity during breast cancer progression.

    Science.gov (United States)

    Vantaggiato, Cristina; Dell'Omo, Giulia; Ramachandran, Balaji; Manni, Isabella; Radaelli, Enrico; Scanziani, Eugenio; Piaggio, Giulia; Maggi, Adriana; Ciana, Paolo

    2016-01-01

    Estrogen receptors (ER) are known to play an important regulatory role in mammary gland development as well as in its neoplastic transformation. Although several studies highlighted the contribution of ER signaling in the breast transformation, little is known about the dynamics of ER state of activity during carcinogenesis due to the lack of appropriate models for measuring the extent of receptor signaling in time, in the same animal. To this aim, we have developed a reporter mouse model for the non-invasive in vivo imaging of ER activity: the ERE-Luc reporter mouse. ERE-Luc is a transgenic mouse generated with a firefly luciferase (Luc) reporter gene driven by a minimal promoter containing an estrogen responsive element (ERE). This model allows to measure receptor signaling in longitudinal studies by bioluminescence imaging (BLI). Here, we have induced sporadic mammary cancers by treating systemically ERE-Luc reporter mice with DMBA (9,10-dimethyl 1,2-benzanthracene) and measured receptor signaling by in vivo imaging in individual animals from early stage until a clinically palpable tumor appeared in the mouse breast. We showed that DMBA administration induces an increase of bioluminescence in the whole abdominal area 6 h after treatment, the signal rapidly disappears. Several weeks later, strong bioluminescence is observed in the area corresponding to the mammary glands. In vivo and ex vivo imaging analysis demonstrated that this bioluminescent signal is localized in the breast area undergoing neoplastic transformation. We conclude that this non-invasive assay is a novel relevant tool to identify the activation of the ER signaling prior the morphological detection of the neoplastic transformation.

  1. Influence of sex differences on the progression of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Uldall, Maria; Appel, Camilla;

    2013-01-01

    on the progression of cancer-induced bone pain. Materials and Methods: 4T1-luc2 mammary cancer cells were introduced into the femoral cavity of female and male BALB/cJ mice. Bioluminescence tumor signal, pain-related behavior and bone degradation were monitored for 14 days. Results: Female mice demonstrated...... a significantly greater bioluminescence signal on day 2 compared to male mice and, in addition, a significant earlier onset of pain-related behavior was observed in the females. No sex difference was observed for bone degradation. Finally, a strong correlation between pain-related behavior and bone degradation...

  2. Dynamics of cancer progression and suppression: A novel evolutionary game theory based approach.

    Science.gov (United States)

    Banerjee, Jeet; Ranjan, Tanvi; Layek, Ritwik Kumar

    2015-01-01

    In this paper, a novel mathematical approach is proposed for the dynamics of progression and suppression of cancer. We define mutant cell density, ρ(μ) (μ × ρ), as a primary factor in cancer dynamics, and use logistic growth model and replicator equation for defining the dynamics of total cell density (ρ) and mutant fraction (μ), respectively. Furthermore, in the proposed model, we introduce an analytical expression for a control parameter D (drug), to suppress the proliferation of mutants with extra fitness level σ. Lastly, we present a comparison of the proposed model with some existing models of tumour growth.

  3. A male patient with acromegaly and breast cancer: treating acromegaly to control tumor progression

    International Nuclear Information System (INIS)

    Acromegaly is a rare disease associated with an increased risk of developing cancer. We report the case of a 72-year-old man who was diagnosed with acromegaly (IGF-1 770 ng/ml) and breast cancer. Four years before he suffered from a colon-rectal cancer. Pituitary surgery and octreotide-LAR treatment failed to control acromegaly. Normalization of IGF-1 (97 ng/ml) was obtained with pegvisomant therapy. Four years after breast cancer surgery, 2 pulmonary metastases were detected at chest CT. The patient was started on anastrozole, but, contrary to medical advice, he stopped pegvisomant treatment (IGF-I 453 ng/ml). Four months later, chest CT revealed an increase in size of the metastatic lesion of the left lung. The patient was shifted from anastrozole to tamoxifen and was restarted on pegvisomant, with normalization of serum IGF-1 levels (90 ng/ml). Four months later, a reduction in size of the metastatic lesion of the left lung was detected by CT. Subsequent CT scans throughout a 24-month follow-up showed a further reduction in size and then a stabilization of the metastasis. This is the first report of a male patient with acromegaly and breast cancer. The clinical course of breast cancer was closely related to the metabolic control of acromegaly. The rapid progression of metastatic lesion was temporally related to stopping pegvisomant treatment and paralleled a rise in serum IGF-1 levels. Normalization of IGF-1 after re-starting pegvisomant impressively reduced the progression of metastatic breast lesions. Control of acromegaly is mandatory in acromegalic patients with cancer. The online version of this article (doi:10.1186/s12885-015-1400-0) contains supplementary material, which is available to authorized users

  4. Loss of p53 attenuates the contribution of IL-6 deletion on suppressed tumor progression and extended survival in Kras-driven murine lung cancer.

    Directory of Open Access Journals (Sweden)

    Xiaohong Tan

    Full Text Available Interleukin-6 (IL-6 is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6(-/- mice with Kras(G12D mutant mice, which develop lung tumors after activation of mutant Kras(G12D, to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. Kras(G12D; IL-6(-/- mice exhibited increased tumorigenesis, but slower tumor growth and longer survival, than Kras(G12D mice. Further, in order to investigate whether IL-6 deletion contributes to suppression of lung cancer metastasis, we generated Kras(G12D; p53(flox/flox; IL-6(-/- mice, which developed lung cancer with a trend for reduced metastases and longer survival than Kras(G12D; p53(flox/flox mice. Tumors from Kras(G12D; IL-6(-/- mice showed increased expression of TNFα and decreased expression of CCL-19, CCL-20 and phosphorylated STAT3(pSTAT3 than Kras(G12D mice; however, these changes were not present between tumors from Kras(G12D; p53(flox/flox; IL-6(-/- and Kras(G12D; p53(flox/flox mice. Upregulation of pSTAT3 and phosphorylated AKT(pAKT were observed in Kras(G12D tumors with p53 deletion. Taken together, these results indicate that IL-6 deletion accelerates tumorigenesis but delays tumor progression and prolongs survival time in a Kras-driven mouse model of lung cancer. However, these effects can be attenuated by p53 deletion.

  5. Plac8 Links Oncogenic Mutations to Regulation of Autophagy and Is Critical to Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Conan Kinsey

    2014-05-01

    Full Text Available Mutations in p53 and RAS potently cooperate in oncogenic transformation, and correspondingly, these genetic alterations frequently coexist in pancreatic ductal adenocarcinoma (PDA and other human cancers. Previously, we identified a set of genes synergistically activated by combined RAS and p53 mutations as frequent downstream mediators of tumorigenesis. Here, we show that the synergistically activated gene Plac8 is critical for pancreatic cancer growth. Silencing of Plac8 in cell lines suppresses tumor formation by blocking autophagy, a process essential for maintaining metabolic homeostasis in PDA, and genetic inactivation in an engineered mouse model inhibits PDA progression. We show that Plac8 is a critical regulator of the autophagic machinery, localizing to the lysosomal compartment and facilitating lysosome-autophagosome fusion. Plac8 thus provides a mechanistic link between primary oncogenic mutations and the induction of autophagy, a central mechanism of metabolic reprogramming, during PDA progression.

  6. 乳腺癌MRI检查的临床进展%THE CLINICAL PROGRESSION OF MRI OF BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    奥妮; 牛广明; 韩晓东

    2014-01-01

    乳腺癌为全世界女性最多发的恶性肿瘤之一,且有发病率、死亡率逐年上升和年轻化的趋势。然而乳腺癌早期症状及体征并不明显,较易被忽略。故其早期检出和诊断在提高病人生存率方面就显得尤为重要。近年来随着科学技术的进步,MRI技术也已经从单纯解剖学描述向分子生物学、病理生理学和功能性影像学的方向发展。本文将对MRI在乳腺癌诊断治疗方面的研究现状及临床价值加以综述。%Breast cancer is one of the world ' s most frequent female malignant tumors, and its morbidity and mortality has a tendency to rise year by year and the trend of getting younger. Because of a breast cancer early signs and symptoms are not obvious, so more easy to be ignored. So the early detection and diagnosis is particularly important in improving survival. With the progress of science and technology in recent years,MRI techniques have also been described from pure anatomy to molecular biology, pathology, physiology and the direction of functional imaging. This article of MRI in the diagnosis and treatment of breast cancer and clinical value of the current state of research on are re-viewed.

  7. Sympathetic Neurotransmitters and Tumor Angiogenesis—Link between Stress and Cancer Progression

    OpenAIRE

    Jason Tilan; Joanna Kitlinska

    2010-01-01

    Recent evidence supports a longstanding hypothesis that chronic stress can influence tumor growth and progression. It has been shown that sympathetic neurotransmitters, such as catecholamines and neuropeptides, can affect both cancer cell growth and tumor vascularization. Depending on neurotransmitter and type of tumor, these effects can be both stimulatory and inhibitory. Norepinephrine (NE) and epinephrine (E) are potent stimulators of vascularization, acting both by inducing the release of...

  8. Genomics and premalignant breast lesions: clues to the development and progression of lobular breast cancer

    OpenAIRE

    Mastracci, Teresa L; Boulos, Fouad I; Andrulis, Irene L.; Lam, Wan L.

    2007-01-01

    Advances in genomic technology have improved our understanding of the genetic events that parallel breast cancer development. Because almost all mammary carcinomas develop in the terminal duct lobular units of the breast, understanding the events involved in mammary gland development make it possible to recognize those events that, when altered, contribute to breast neoplasia. In this review we focus on lobular carcinomas, discussing the pathology, development, and progression of premalignant...

  9. The Significance of Histopathological Evaluation of Pancreatic Fibrosis to Estimate Pancreas Cancer Progression

    OpenAIRE

    Shinji Osada; Kaoru Tanaka; Satoshi Matsui; Yoshiyuki Sasaki; Hiroyuki Tomita; Yoshihiro Tanaka; Naoki Okumura; Nobuhisa Matsuhashi; Kazuhiro Yoshida

    2016-01-01

    Objective To estimate the importance of the role of pancreatic stellate cells in pancreas cancer progression, their properties were evaluated in relation to clinical details and patient prognosis. Patients and Methods Among patients who underwent surgical treatment from 2004 to 2013, the texture of the pancreatic specimens was evaluated by histopathological measurement length of fibrosis, fibrosis grade and the intensity of pancreatic stellate cell activity. Results 1. The histopathological m...

  10. Carbohydrate Antigen Sialyl Lewis a – Its Pathophysiological ignificance and Induction Mechanism in Cancer Progression

    OpenAIRE

    Reiji Kannagi

    2007-01-01

    Carbohydrate antigen sialyl Lewis a (CA19-9) is the mostfrequently applied serum tumor marker for diagnosis of cancersin the digestive organs. Recent progress disclosed thepresence of a normal counterpart of the determinant, namelydisialyl Lewis a, which is predominantly expressed in nonmalignantepithelial cells of the digestive organs, while sialylLewis a is preferentially expressed in cancers. The disialylLewis a determinant carries one extra sialic residue attachedthrough a 2 6 linkage to ...

  11. STAT5A/B Gene Locus Undergoes Amplification during Human Prostate Cancer Progression

    OpenAIRE

    Haddad, Bassem R.; Gu, Lei; Mirtti, Tuomas; Dagvadorj, Ayush; Vogiatzi, Paraskevi; Hoang, David T.; Bajaj, Renu; Leiby, Benjamin; Ellsworth, Elyse; Blackmon, Shauna; Ruiz, Christian; Curtis, Mark; Fortina, Paolo; Ertel, Adam; Liu, Chengbao

    2013-01-01

    The molecular mechanisms underlying progression of prostate cancer (PCa) to castrate-resistant (CR) and metastatic disease are poorly understood. Our previous mechanistic work shows that inhibition of transcription factor Stat5 by multiple alternative methods induces extensive rapid apoptotic death of Stat5-positive PCa cells in vitro and inhibits PCa xenograft tumor growth in nude mice. Furthermore, STAT5A/B induces invasive behavior of PCa cells in vitro and in vivo, suggesting involvement ...

  12. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan;

    2009-01-01

    ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

  13. The Micro environmental Effect in the Progression, Metastasis, and Dormancy of Breast Cancer: A Model System within Bone Marrow

    International Nuclear Information System (INIS)

    Despite diagnostic advances, breast cancer remains the most prevalent cancer among women in the United States. The armamentarium of treatment options for metastatic disease is limited and mostly ineffective with regards to eradicating cancer. However, there have been novel findings in the recent literature that substantiate the function of the microenvironment in breast cancer progression and the support of metastasis to tertiary sites such as bone marrow. The uncovered significance of the microenvironment in the pathophysiology of breast cancer metastasis has served to challenge previously widespread theories and introduce new perspectives for the future research to eradicate breast cancer. This paper delineates the current understanding of the molecular mechanisms involved in the interactions between breast cancer cells and the microenvironment in progression, metastasis, and dormancy. The information, in addition to other mechanisms described in bone marrow, is discussed in the paper

  14. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Cascio, Sandra, E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Fondazione Ri.Med, via Bandiera, Palermo 90133 (Italy); Finn, Olivera J., E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States)

    2015-02-10

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis.

  15. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

    International Nuclear Information System (INIS)

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis

  16. Mesenchymal Stem/Stromal Cells in Stromal Evolution and Cancer Progression

    Directory of Open Access Journals (Sweden)

    Francesca Cammarota

    2016-01-01

    Full Text Available The study of cancer biology has mainly focused on malignant epithelial cancer cells, although tumors also contain a stromal compartment, which is composed of stem cells, tumor-associated fibroblasts (TAFs, endothelial cells, immune cells, adipocytes, cytokines, and various types of macromolecules comprising the extracellular matrix (ECM. The tumor stroma develops gradually in response to the needs of epithelial cancer cells during malignant progression initiating from increased local vascular permeability and ending to remodeling of desmoplastic loosely vascularized stromal ECM. The constant bidirectional interaction of epithelial cancer cells with the surrounding microenvironment allows damaged stromal cell usage as a source of nutrients for cancer cells, maintains the stroma renewal thus resembling a wound that does not heal, and affects the characteristics of tumor mesenchymal stem/stromal cells (MSCs. Although MSCs have been shown to coordinate tumor cell growth, dormancy, migration, invasion, metastasis, and drug resistance, recently they have been successfully used in treatment of hematopoietic malignancies to enhance the effect of total body irradiation-hematopoietic stem cell transplantation therapy. Hence, targeting the stromal elements in combination with conventional chemotherapeutics and usage of MSCs to attenuate graft-versus-host disease may offer new strategies to overcome cancer treatment failure and relapse of the disease.

  17. Re-organisation of oesophago-gastric cancer care in England: progress and remaining challenges

    Directory of Open Access Journals (Sweden)

    Greenaway Kimberley

    2009-11-01

    Full Text Available Abstract Background Oesophago-gastric cancer services in England have been extensively reorganised since 2001 to deliver a centralised, specialist-led service. Our aim was to assess how well the National Health Service (NHS in England met organisational standards for oesophago-gastric cancer care. Methods Questionnaires that asked about the provision of staging investigations, curative and palliative treatments and key personnel were sent in September 2007 to the lead clinician for oesophago-gastric cancer at all 30 cancer networks and 156 NHS acute trusts in England. Results Responses were received from all networks and 81% of NHS trusts. All networks provided essential staging investigations and a range of endoscopic palliative therapies. Only 16 of the 30 cancer networks discussed all patients at the specialist multi-disciplinary team meeting and 11 networks had not fully centralised curative surgery. There was also variation between NHS trusts in the integration of the palliative care team, the availability of nurse specialists and the use of dieticians to provide nutritional support. Conclusion There has been considerable progress in reforming oesophago-gastric cancer services but the process of reorganisation is still incomplete and regional differences in service provision exist that may lead to variation in patient outcomes.

  18. The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular and Medical Genetics, University of North Texas Health Science Center, Institute for Cancer Research, and Focused on Resources for her Health Education and Research, Fort Worth, TX 76107 (United States)

    2014-04-10

    The protein kinase C (PKC) family proteins are important signal transducers and have long been the focus of cancer research. PKCε, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCε. While earlier research established the survival functions of PKCε, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCε has also been implicated in epithelial to mesenchymal transition (EMT), which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCε affects cell-extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCε signaling to cancer stem cell functioning. This review focuses on the role of PKCε in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCε as a target for cancer therapy.

  19. The fragile X protein binds mRNAs involved in cancer progression and modulates metastasis formation.

    Science.gov (United States)

    Lucá, Rossella; Averna, Michele; Zalfa, Francesca; Vecchi, Manuela; Bianchi, Fabrizio; La Fata, Giorgio; Del Nonno, Franca; Nardacci, Roberta; Bianchi, Marco; Nuciforo, Paolo; Munck, Sebastian; Parrella, Paola; Moura, Rute; Signori, Emanuela; Alston, Robert; Kuchnio, Anna; Farace, Maria Giulia; Fazio, Vito Michele; Piacentini, Mauro; De Strooper, Bart; Achsel, Tilmann; Neri, Giovanni; Neven, Patrick; Evans, D Gareth; Carmeliet, Peter; Mazzone, Massimiliano; Bagni, Claudia

    2013-10-01

    The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression. PMID:24092663

  20. The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

    International Nuclear Information System (INIS)

    The protein kinase C (PKC) family proteins are important signal transducers and have long been the focus of cancer research. PKCε, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCε. While earlier research established the survival functions of PKCε, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCε has also been implicated in epithelial to mesenchymal transition (EMT), which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCε affects cell-extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCε signaling to cancer stem cell functioning. This review focuses on the role of PKCε in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCε as a target for cancer therapy.

  1. Assessing the role of IL-35 in colorectal cancer progression and prognosis.

    Science.gov (United States)

    Zeng, Jin-Cheng; Zhang, Zhi; Li, Tian-Yu; Liang, Yan-Fang; Wang, Hong-Mei; Bao, Jing-Jing; Zhang, Jun-Ai; Wang, Wan-Dang; Xiang, Wen-Yu; Kong, Bin; Wang, Zhi-Yong; Wu, Bin-Hua; Chen, Xiao-Dong; He, Long; Zhang, Shu; Wang, Cong-Yi; Xu, Jun-Fa

    2013-01-01

    Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.

  2. HSET overexpression fuels tumor progression via centrosome clustering-independent mechanisms in breast cancer patients

    Science.gov (United States)

    Pannu, Vaishali; Rida, Padmashree C.G.; Ogden, Angela; Turaga, Ravi Chakra; Donthamsetty, Shashikiran; Bowen, Nathan J.; Rudd, Katie; Gupta, Meenakshi V.; Reid, Michelle D.; Cantuaria, Guilherme; Walczak, Claire E.; Aneja, Ritu

    2015-01-01

    Human breast tumors harbor supernumerary centrosomes in almost 80% of tumor cells. Although amplified centrosomes compromise cell viability via multipolar spindles resulting in death-inducing aneuploidy, cancer cells tend to cluster extra centrosomes during mitosis. As a result cancer cells display bipolar spindle phenotypes to maintain a tolerable level of aneuploidy, an edge to their survival. HSET/KifC1, a kinesin-like minus-end directed microtubule motor has recently found fame as a crucial centrosome clustering molecule. Here we show that HSET promotes tumor progression via mechanisms independent of centrosome clustering. We found that HSET is overexpressed in breast carcinomas wherein nuclear HSET accumulation correlated with histological grade and predicted poor progression-free and overall survival. In addition, deregulated HSET protein expression was associated with gene amplification and/or translocation. Our data provide compelling evidence that HSET overexpression is pro-proliferative, promotes clonogenic-survival and enhances cell-cycle kinetics through G2 and M-phases. Importantly, HSET co-immunoprecipitates with survivin, and its overexpression protects survivin from proteasome-mediated degradation, resulting in its increased steady-state levels. We provide the first evidence of centrosome clustering-independent activities of HSET that fuel tumor progression and firmly establish that HSET can serve both as a potential prognostic biomarker and as a valuable cancer-selective therapeutic target. PMID:25788277

  3. Humanized mouse model of ovarian cancer recapitulates patient solid tumor progression, ascites formation, and metastasis.

    Directory of Open Access Journals (Sweden)

    Richard B Bankert

    Full Text Available Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2Rγ(null (NSG mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma.

  4. Stimulatory versus suppressive effects of GM-CSF on tumor progression in multiple cancer types

    Science.gov (United States)

    Hong, In-Sun

    2016-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF, also called CSF-2) is best known for its critical role in immune modulation and hematopoiesis. A large body of experimental evidence indicates that GM-CSF, which is frequently upregulated in multiple types of human cancers, effectively marks cancer cells with a ‘danger flag' for the immune system. In this context, most studies have focused on its function as an immunomodulator, namely its ability to stimulate dendritic cell (DC) maturation and monocyte/macrophage activity. However, recent studies have suggested that GM-CSF also promotes immune-independent tumor progression by supporting tumor microenvironments and stimulating tumor growth and metastasis. Although some studies have suggested that GM-CSF has inhibitory effects on tumor growth and metastasis, an even greater number of studies show that GM-CSF exerts stimulatory effects on tumor progression. In this review, we summarize a number of findings to provide the currently available information regarding the anticancer immune response of GM-CSG. We then discuss the potential roles of GM-CSF in the progression of multiple types of cancer to provide insights into some of the complexities of its clinical applications. PMID:27364892

  5. Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis

    Institute of Scientific and Technical Information of China (English)

    Guocan Wang; Chia-Hsin Chan; Yuan Gao; Hui-Kuan Lin

    2012-01-01

    S-phase kinase-associated protein 2 (Skp2) belongs to the F-box protein family.It is a component of the SCF E3 ubiquitin ligase complex.Skp2 has been shown to regulate cellular proliferation by targeting several cell cycle-regulated proteins for ubiquitination and degradation,including cyclin-dependent kinase inhibitor p27.Skp2 has also been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers.This review discusses the recent discoveries on the novel roles of Skp2 in regulating cellular senescence,cancer progression,and metastasis,as well as the therapeutic potential of targeting Skp2 for human cancer treatment.

  6. Analysis of breast cancer progression using principal component analysis and clustering

    Indian Academy of Sciences (India)

    G Alexe; G S Dalgin; S Ganesan; C DeLisi; G Bhanot

    2007-08-01

    We develop a new technique to analyse microarray data which uses a combination of principal components analysis and consensus ensemble -clustering to find robust clusters and gene markers in the data. We apply our method to a public microarray breast cancer dataset which has expression levels of genes in normal samples as well as in three pathological stages of disease; namely, atypical ductal hyperplasia or ADH, ductal carcinoma in situ or DCIS and invasive ductal carcinoma or IDC. Our method averages over clustering techniques and data perturbation to find stable, robust clusters and gene markers. We identify the clusters and their pathways with distinct subtypes of breast cancer (Luminal, Basal and Her2+). We confirm that the cancer phenotype develops early (in early hyperplasia or ADH stage) and find from our analysis that each subtype progresses from ADH to DCIS to IDC along its own specific pathway, as if each was a distinct disease.

  7. Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis.

    Science.gov (United States)

    Konishi, Hiroaki; Fujiya, Mikihiro; Tanaka, Hiroki; Ueno, Nobuhiro; Moriichi, Kentaro; Sasajima, Junpei; Ikuta, Katsuya; Akutsu, Hiroaki; Tanabe, Hiroki; Kohgo, Yutaka

    2016-01-01

    Previous reports have suggested that some probiotics inhibit tumorigenesis and cancer progression. However, the molecules involved have not yet been identified. Here, we show that the culture supernatant of Lactobacillus casei ATCC334 has a strong tumour-suppressive effect on colon cancer cells. Using mass spectrometry, we identify ferrichrome as a tumour-suppressive molecule produced by L. casei ATCC334. The tumour-suppressive effect of ferrichrome is greater than that of cisplatin and 5-fluorouracil, and ferrichrome has less of an effect on non-cancerous intestinal cells than either of those agents. A transcriptome analysis reveals that ferrichrome treatment induces apoptosis, which is mediated by the activation of c-jun N-terminal kinase (JNK). Western blotting indicates that the induction of apoptosis by ferrichrome is reduced by the inhibition of the JNK signalling pathway. This we demonstrate that probiotic-derived ferrichrome exerts a tumour-suppressive effect via the JNK signalling pathway. PMID:27507542

  8. Another road leads to HIF-1 activation: implications for prostate cancer progression

    Institute of Scientific and Technical Information of China (English)

    Yao Dai1; Kyungmi Bae2; Dietmar W Siemann1

    2012-01-01

    Hypoxia has been identified as a common environmental stress factor associated with therapeutic resistance and metastasis in human cancers.A major player in regulating the response to hypoxia is the transcriptional factor hypoxia-inducible factor 1 alpha (HIF-1α).Although HIF-1α is well known to be stabilized under hypoxia,the regulatory mechanism of HIF-1α signaling in malignant cells is not fully understood.In a recent paper,Yuan et al.1 identified a novel pathway that acts as a ‘vicious cycle'to amplify HIF- 1 activation in prostate cancer cells,hence suggesting potential biomarkers that may predict progression and poor prognosis in human prostate cancer (Figure 1).

  9. Progress towards understanding heterotypic interactions in multi-culture models of breast cancer.

    Science.gov (United States)

    Regier, Mary C; Alarid, Elaine T; Beebe, David J

    2016-06-13

    Microenvironments in primary tumors and metastases include multiple cell types whose dynamic and reciprocal interactions are central to progression of the disease. However, the literature involving breast cancer studied in vitro is dominated by cancer cells in mono-culture or co-cultured with one other cell type. For in vitro studies of breast cancer the inclusion of multiple cell types has led to models that are more representative of in vivo behaviors and functions as compared to more traditional monoculture. Here, we review foundational co-culture techniques and their adaptation to multi-culture (including three or more cell types). Additionally, while macroscale methods involving conditioned media, direct contact, and indirect interactions have been informative, we examined many advances that have been made more recently using microscale systems with increased control over cellular and structural complexity. Throughout this discussion we consider the benefits and limitations of current multi-culture methods and the significant results they have produced.

  10. MLF1IP is correlated with progression and prognosis in luminal breast cancer.

    Science.gov (United States)

    Huang, Du-Ping; Luo, Rong-Cheng

    2016-09-01

    Myeloid leukemia factor 1-interacting protein (MLF1IP) has been found to be involved in the progression of several malignancies. The potential correlation between MLF1IP and clinical outcome in patients with luminal breast cancer, however, remains unknown. In the present study, we demonstrated that MLF1IP was significantly upregulated in luminal breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Upregulated expression of MLF1IP was correlated with more often lymph node metastasis and negative progesterone receptor expression in TCGA cohorts. Kaplan-Meier analysis indicated that patients with high MLF1IP expression had significantly lower overall survival. Moreover, multivariate analysis revealed that high MLF1IP expression was independent high risk factor as well as old age (>60) and distant metastasis. This study provides new insights and evidences that MLF1IP over-expression plays important roles in progression of luminal breast cancer. However, the precise cellular mechanisms for MLF1IP in luminal breast cancer need to be further explored. PMID:27378428

  11. Micronutrients attenuate progression of prostate cancer by elevating the endogenous inhibitor of angiogenesis, Platelet Factor-4

    Directory of Open Access Journals (Sweden)

    Fleshner Neil E

    2010-06-01

    Full Text Available Abstract Background Longstanding evidence implicates an inadequate diet as a key factor in the onset and progression of prostate cancer. The purpose herein was to discover, validate and characterize functional biomarkers of dietary supplementation capable of suppressing the course of prostate cancer in vivo. Methods The Lady transgenic mouse model that spontaneously develops prostate cancer received a diet supplemented with a micronutrient cocktail of vitamin E, selenium and lycopene ad libitum. A proteomic analysis was conducted to screen for serum biomarkers of this dietary supplementation. Candidate peptides were validated and identified by sequencing and analyzed for their presence within the prostates of all mice by immunohistochemistry. Results Dietary supplementation with the combined micronutrients significantly induced the expression of the megakaryocyte-specific inhibitor of angiogenesis, platelet factor-4 (P = 0.0025. This observation was made predominantly in mice lacking tumors and any manifestations associated with progressive disease beyond 37 weeks of life, at which time no survivors remained in the control group (P Conclusion We present unprecedented data whereby these combined micronutrients effectively promotes tumor dormancy in early prostate cancer, following initiation mutations that may drive the angiogenesis-dependent response of the tumor, by inducing platelet factor-4 expression and concentrating it at the tumor endothelium through enhanced platelet binding.

  12. Role of the tumor microenvironment in regulating apoptosis and cancer progression.

    Science.gov (United States)

    Yaacoub, Katherine; Pedeux, Remy; Tarte, Karin; Guillaudeux, Thierry

    2016-08-10

    Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient's treatment. Therefore, the ultimate knowledge of "tumor-microenvironment" interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented. PMID:27224890

  13. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  14. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    International Nuclear Information System (INIS)

    Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

  15. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bajenova, Olga, E-mail: o.bazhenova@spbu.ru [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Chaika, Nina [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Tolkunova, Elena; Davydov-Sinitsyn, Alexander [Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064 (Russian Federation); Gapon, Svetlana [Boston Children' s Hospital, Boston, MA 02115 (United States); Thomas, Peter [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); O’Brien, Stephen [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation)

    2014-06-10

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.

  16. A computational approach to resolve cell level contributions to early glandular epithelial cancer progression

    Directory of Open Access Journals (Sweden)

    Park Sunwoo

    2009-12-01

    Full Text Available Abstract Background Three-dimensional (3D embedded cell cultures provide an appropriate physiological environment to reconstruct features of early glandular epithelial cancer. Although these are orders of magnitude simpler than tissues, they too are complex systems that have proven challenging to understand. We used agent-based, discrete event simulation modeling methods to build working hypotheses of mechanisms of epithelial 3D culture phenotype and early cancer progression. Starting with an earlier software analogue, we validated an improved in silico epithelial analogue (ISEA for cardinal features of a normally developed MDCK cyst. A set of axiomatic operating principles defined simulated cell actions. We explored selective disruption of individual simulated cell actions. New framework features enabled recording detailed measures of ISEA cell activities and morphology. Results Enabled by a small set of cell operating principles, ISEA cells multiplied and self-organized into cyst-like structures that mimicked those of MDCK cells in a 3D embedded cell culture. Selective disruption of "anoikis" or directional cell division caused the ISEA to develop phenotypic features resembling those of in vitro tumor reconstruction models and cancerous tissues in vivo. Disrupting either process, or both, altered cell activity patterns that resulted in morphologically similar outcomes. Increased disruption led to a prolonged presence of intraluminal cells. Conclusions ISEA mechanisms, behaviors, and morphological properties may have biological counterparts. To the extent that in silico-to-in vitro mappings are valid, the results suggest plausible, additional mechanisms of in vitro cancer reconstruction or reversion, and raise potentially significant implications for early cancer diagnosis based on histology. Further ISEA development and use are expected to provide a viable platform to complement in vitro methods for unraveling the mechanistic basis of

  17. The decline in stomach cancer mortality: exploration of future trends in seven European countries

    NARCIS (Netherlands)

    M. Amiri (Masoud); F. Janssen (Fanny); A.E. Kunst (Anton)

    2010-01-01

    textabstractMortality from stomach cancer has fallen steadily during the past decades. The aim of this paper is to assess the implication of a possible continuation of the decline in stomach cancer mortality until the year 2030. Annual rates of decline in stomach cancer mortality from 1980 to 2005 w

  18. The decline in stomach cancer mortality: exploration of future trends in seven European countries

    NARCIS (Netherlands)

    M. Amiri; F. Janssen; A.E. Kunst

    2011-01-01

    Mortality from stomach cancer has fallen steadily during the past decades. The aim of this paper is to assess the implication of a possible continuation of the decline in stomach cancer mortality until the year 2030. Annual rates of decline in stomach cancer mortality from 1980 to 2005 were determin

  19. The decline in stomach cancer mortality : exploration of future trends in seven European countries

    NARCIS (Netherlands)

    Amiri, Masoud; Janssen, Fanny; Kunst, Anton E.

    2011-01-01

    Mortality from stomach cancer has fallen steadily during the past decades. The aim of this paper is to assess the implication of a possible continuation of the decline in stomach cancer mortality until the year 2030. Annual rates of decline in stomach cancer mortality from 1980 to 2005 were determin

  20. Breast cancer associated a2 isoform vacuolar ATPase immunomodulates neutrophils: potential role in tumor progression.

    Science.gov (United States)

    Ibrahim, Safaa A; Katara, Gajendra K; Kulshrestha, Arpita; Jaiswal, Mukesh K; Amin, Magdy A; Beaman, Kenneth D

    2015-10-20

    In invasive breast cancer, tumor associated neutrophils (TAN) represent a significant portion of the tumor mass and are associated with increased angiogenesis and metastasis. Identifying the regulatory factors that control TAN behavior will help in developing ideal immunotherapies. Vacuolar ATPases (V-ATPases), multi-subunit proton pumps, are highly expressed in metastatic breast cancer cells. A cleaved peptide from a2 isoform V-ATPase (a2NTD) has immunomodulatory role in tumor microenvironment. Here, we report for the first time the role of V-ATPase in neutrophils modulation. In invasive breast cancer cells, a2NTD was detected and a2V was highly expressed on the surface. Immunohistochemical analysis of invasive breast cancer tissues revealed that increased neutrophil recruitment and blood vessel density correlated with increased a2NTD levels. In order to determine the direct regulatory role of a2NTD on neutrophils, recombinant a2NTD was used for the treatment of neutrophils isolated from the peripheral blood of healthy volunteers. Neutrophils treated with a2NTD (a2Neuɸ) showed increased secretion of IL-1RA, IL-10, CCL-2 and IL-6 that are important mediators in cancer related inflammation. Moreover, a2Neuɸ exhibited an increased production of protumorigenic factors including IL-8, matrix metaloprotinase-9 and vascular endothelial growth factor. Further, functional characterization of a2Neuɸ revealed that a2Neuɸ derived products induce in vitro angiogenesis as well as increase the invasiveness of breast cancer cells. This study establishes the modulatory effect of breast cancer associated a2V on neutrophils, by the action of a2NTD, which has a positive impact on tumor progression, supporting that a2V can be a potential selective target for breast cancer therapy.

  1. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

    International Nuclear Information System (INIS)

    Highlights: ► A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. ► TAE226 suppressed proliferation and migration, with a modest effect on adhesion. ► Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. ► TAE226 treatment suppressed the progression of peritoneal dissemination. ► Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken together, a possible strategy for inhibiting peritoneal dissemination by targeting FAK with TAE226 appears to be applicable

  2. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Hui-fang [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Takaoka, Munenori [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Bao, Xiao-hong [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Wang, Zhi-gang [College of Life Science, Inner Mongolia University, The Key Laboratory of Mammal Reproductive Biology and Biotechnology, Ministry of Education, Hohhot 010021 (China); Tomono, Yasuko [Division of Molecular and Cell Biology, Shigei Medical Research Institute, 2117 Yamada, Okayama 700-0202 (Japan); Sakurama, Kazufumi; Ohara, Toshiaki [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Fukazawa, Takuya; Yamatsuji, Tomoki [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Fujiwara, Toshiyoshi [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Naomoto, Yoshio, E-mail: ynaomoto@med.kawasaki-m.ac.jp [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken

  3. Expression deregulation of mir31 and CXCL12 in two types of oral precancers and cancer: importance in progression of precancer and cancer

    Science.gov (United States)

    Chattopadhyay, Esita; Singh, Richa; Ray, Anindita; Roy, Roshni; de Sarkar, Navonil; Paul, Ranjan Rashmi; Pal, Mousumi; Aich, Ritesh; Roy, Bidyut

    2016-09-01

    Oral cancer generally progresses from precancerous lesions such as leukoplakia (LK), lichen planus (LP) and oral submucous fibrosis (OSMF). Since few of these precancers progress to cancers; it is worth to identify biological molecules that may play important roles in progression. Here, expression deregulation of 7 miRNAs (mir204, mir31, mir31*, mir133a, mir7, mir206 and mir1293) and their possible target genes in 23 cancers, 18 LK, 12 LP, 23 OSMF tissues compared to 20 healthy tissues was determined by qPCR method. Expression of mir7, mir31, mir31* and mir1293 was upregulated and that of mir133a, mir204 and mir206 was downregulated in cancer. Expression of most of these miRNAs was also upregulated in LK and LP tissues but not in OSMF. Expression deregulation of some of the target genes was also determined in cancer, LK and LP tissues. Significant upregulation of mir31 and downregulation of its target gene, CXCL12, in cancer, LK and LP tissues suggest their importance in progression of precancer to cancer. Expression upregulation of mir31 was also validated using GEO data sets. Although sample size is low, novelty of this work lies in studying expression deregulation of miRNAs and target genes in oral cancer and three types of precancerous lesions.

  4. Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse.

    Science.gov (United States)

    Sødring, Marianne; Gunnes, Gjermund; Paulsen, Jan Erik

    2016-04-15

    The C57BL/6J multiple intestinal neoplasia (Min/+) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/+ mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/+ mice ranging in age from 4 to 60 weeks. The A/J Min/+ mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/+ mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/+ mouse may be a relevant model for initiation, promotion and progression of colorectal cancer.

  5. Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Yixuan Gong

    2014-06-01

    Full Text Available Matrix metalloproteinases (MMPs, a group of zinc-dependent endopeptidases involved in the degradation of the extracellular matrix, play an important role in tissue remodeling associated with various physiological processes such as morphogenesis, angiogenesis, and tissue repair, as well as pathological processes including cirrhosis, arthritis and cancer. The MMPs are well established as mediators of tumor invasion and metastasis by breaking down connective tissue barriers. Although there has been a vast amount of literature on the role of MMPs in invasion, metastasis and angiogenesis of various cancers, the role of these endopeptidases in prostate cancer progression has not been systematically reviewed. This overview summarizes findings on the tissue and blood expression of MMPs, their function, regulation and prognostic implication in human prostate cancer, with a focus on MMP-2, -7, -9, MT1-MMP and tissue inhibitor of metalloproteinase 1 (TIMP-1. This review also summarizes the efficacy and failure of early-generation matrix metalloproteinase inhibitors (MMPIs in the treatment of metastatic prostate cancer and highlights the lessons and challenges for next generation MMPIs.

  6. The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

    Energy Technology Data Exchange (ETDEWEB)

    Schaal, Courtney [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States); Padmanabhan, Jaya [Department of Molecular Medicine and USF Health Byrd Alzheimer’s Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, FL 33612 (United States); Chellappan, Srikumar, E-mail: Srikumar.Chellappan@moffitt.org [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States)

    2015-07-31

    Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer.

  7. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy

    Directory of Open Access Journals (Sweden)

    Muz B

    2015-12-01

    Full Text Available Barbara Muz, Pilar de la Puente, Feda Azab, Abdel Kareem Azab Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine in St Louis, MO, USA Abstract: Hypoxia is a non-physiological level of oxygen tension, a phenomenon common in a majority of malignant tumors. Tumor-hypoxia leads to advanced but dysfunctional vascularization and acquisition of epithelial-to-mesenchymal transition phenotype resulting in cell mobility and metastasis. Hypoxia alters cancer cell metabolism and contributes to therapy resistance by inducing cell quiescence. Hypoxia stimulates a complex cell signaling network in cancer cells, including the HIF, PI3K, MAPK, and NFκB pathways, which interact with each other causing positive and negative feedback loops and enhancing or diminishing hypoxic effects. This review provides background knowledge on the role of tumor hypoxia and the role of the HIF cell signaling involved in tumor blood vessel formation, metastasis, and development of the resistance to therapy. Better understanding of the role of hypoxia in cancer progression will open new windows for the discovery of new therapeutics targeting hypoxic tumor cells and hypoxic microenvironment. Keywords: hypoxia, cancer, metastasis, angiogenesis, treatment resistance 

  8. Purine nucleoside analog--sulfinosine modulates diverse mechanisms of cancer progression in multi-drug resistant cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Mirjana Dačević

    progression qualify SF as multi-potent anti-cancer agent, which use must be considered, in particular for resistant malignancies.

  9. Highlights of recent developments and trends in cancer nanotechnology research--view from NCI Alliance for Nanotechnology in Cancer.

    Science.gov (United States)

    Hull, L C; Farrell, D; Grodzinski, P

    2014-01-01

    Although the incidence of cancer and cancer related deaths in the United States has decreased over the past two decades due to improvements in early detection and treatment, cancer still is responsible for a quarter of the deaths in this country. There is much room for improvement on the standard treatments currently available and the National Cancer Institute (NCI) has recognized the potential for nanotechnology and nanomaterials in this area. The NCI Alliance for Nanotechnology in Cancer was formed in 2004 to support multidisciplinary researchers in the application of nanotechnology to cancer diagnosis and treatment. The researchers in the Alliance have been productive in generating innovative solutions to some of the central issues of cancer treatment including how to detect tumors earlier, how to target cancer cells specifically, and how to improve the therapeutic index of existing chemotherapies and radiotherapy treatments. Highly creative ideas are being pursued where novelty in nanomaterial development enables new modalities of detection or therapy. This review highlights some of the innovative materials approaches being pursued by researchers funded by the NCI Alliance. Their discoveries to improve the functionality of nanoparticles for medical applications includes the generation of new platforms, improvements in the manufacturing of nanoparticles and determining the underlying reasons for the movement of nanoparticles in the blood.

  10. Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaolei Li

    2016-03-01

    Full Text Available (1 Background: Transient receptor potential vanilloid 3 (TRPV3 is a member of the TRP channels family of Ca2+-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC; (2 Methods: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca2+]i. Flow cytometry was used to analyze cell cycle; (3 Results: TRPV3 was overexpressed in 65 of 96 (67.7% human lung cancer cases and correlated with differentiation (p = 0.001 and TNM stage (p = 0.004. Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca2+]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4 Conclusions: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC.

  11. The Valuable Role of Measuring Serum Lipid Profile in Cancer Progression

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    Farahnaz Ghahremanfard

    2015-09-01

    Full Text Available Objective: Serum lipid levels are not only associated with etiology, but also with prognosis in cancer. To investigate this issue further, we aimed to evaluate the serum levels of lipids in association with the most important prognostic indicators in cancer patients at the start of chemotherapy. Methods: In a retrospective cross-sectional study, using existing medical records obtained from 2009–2014, the data of all incident cancer cases in Iranian patients referred to the Semnan oncology clinic for chemotherapy were analyzed. Data on demographics, cancer type, prognostic indicators (e.g. lymph node involvement, metastasis, and stage of disease, as well as the patient’s lipid profile were collected. We used multiple logistic regression models to show the relationship between prognosis indicators and lipid profile adjusting for age, gender, and type of cancer. Results: The data of 205 patients was gathered. We found a significant difference in the lipid profile between different types of cancers (breast, colon, gastric, and ovarian. With the exception of high-density lipoprotein levels in women, which were higher than in men, the means of other lipid profiles were similar between the genders. There was a significant association between higher levels of low-density lipoprotein (LDL >110mg/dL in the serum and metastasis (adjusted odds ratio=2.4, 95% CI 1.2–3.5. No significant association was reported between lipid profile and lymph nodes involvement and stage of the disease. Conclusion: Our study suggested a benefit of measuring serum levels of lipids for predicting cancer progression. Increased LDL levels can be considered a predictive factor for increasing the risk of metastasis.

  12. Foxp3 promoter polymorphism (rs3761548) in breast cancer progression: a study from India.

    Science.gov (United States)

    Jahan, Parveen; Ramachander, V R Vinish; Maruthi, G; Nalini, S; Latha, K Prasanna; Murthy, T S R

    2014-04-01

    Breast cancer is the most common female neoplasm that drives the transformation of normal mammary epithelial cells into highly malignant derivatives. Forkhead Box Protein3 (Foxp3), a tumor suppressor/immunomodulatory gene, which controls the function of Treg cells and oncogenes is down regulated in breast cancer. The main aim of the present study is to evaluate the potential influence of Foxp3-3279 C>A polymorphism (rs3761548) and -2383 C>T polymorphism (rs3761549) in 202 breast cancer patients and 130 normal healthy women of Indian origin. The genotypes were determined using ARMS-PCR for rs3761548 and PCR-RFLP method for rs3761549 using specific primers. The results revealed lack of association of these two polymorphisms with breast cancer susceptibility. However, with respect to AA genotype of rs3761548, we found highly significant association with the advanced stage (T3-4) of the tumor (OR = 3.90; 95% confidence interval (CI) = 1.56-9.70; p = 0.03). Stratified data also revealed an association of homozygous mutant genotype with advanced stage of tumor in premenopausal women (OR = 4.56; 95% CI = 1.07-19.38; p = 0.04) with disease duration of <6 months (OR =  .10; 95% CI = 1.80-20.50; p = 0.002) suggestive of modulating effect of rs3761548 in tumor progression. We conclude that Foxp3 rs37161548 has a potential to be a polymorphic marker for tumor progression in premenopausal breast cancer patients in Indian women. PMID:24338714

  13. Delineating an Epigenetic Continuum for Initiation, Transformation and Progression to Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kang Mei; Stephen, Josena K. [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, 1 Ford Place, 1D, Detroit, MI 48202 (United States); Raju, Usha [Department of Pathology, Henry Ford Hospital, Detroit, 1 Ford Place, 1D, Detroit, MI 48202 (United States); Worsham, Maria J., E-mail: mworsha1@hfhs.org [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, 1 Ford Place, 1D, Detroit, MI 48202 (United States)

    2011-03-29

    Aberrant methylation of promoter CpG islands is a hallmark of human cancers and is an early event in carcinogenesis. We examined whether promoter hypermethylation contributes to the pathogenesis of benign breast lesions along a progression continuum to invasive breast cancer. The exploratory study cohort comprised 17 breast cancer patients with multiple benign and/or in situ lesions concurrently present with invasive carcinoma within a tumor biopsy. DNA from tumor tissue, normal breast epithelium when present, benign lesions (fibroadenoma, hyperplasia, papilloma, sclerosing adenosis, apocrine metaplasia, atypical lobular hyperplasia or atypical ductal hyperplasia), and in situ lesions of lobular carcinoma and ductal carcinoma were interrogated for promoter methylation status in 22 tumor suppressor genes using the multiplex ligation-dependent probe amplification assay (MS-MLPA). Methylation specific PCR was performed to confirm hypermethylation detected by MS-MLPA. Promoter methylation was detected in 11/22 tumor suppressor genes in 16/17 cases. Hypermethylation of RASSF1 was most frequent, present in 14/17 cases, followed by APC in 12/17, and GSTP1 in 9/17 cases with establishment of an epigenetic monocloncal progression continuum to invasive breast cancer. Hypermethylated promoter regions in normal breast epithelium, benign, and premalignant lesions within the same tumor biopsy implicate RASSF1, APC, GSTP1, TIMP3, CDKN2B, CDKN2A, ESR1, CDH13, RARB, CASP8, and TP73 as early events. DNA hypermethylation underlies the pathogenesis of step-wise transformation along a monoclonal continuum from normal to preneoplasia to invasive breast cancer.

  14. Role of interleukin-8 in the progression of estrogen receptor-negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    YAO Chen; LIN Ying; YE Cai-sheng; BI Jiong; ZHU Yi-fan; WANG Shen-ming

    2007-01-01

    Background Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological mechanism is still unclear. ER negative breast cancer expresses high levels of interieukin-8 (IL-8). ER expression can downregulate IL-8 promotor activity. As a multifunctional cytokine, IL-8 has many important biological activities in tumor genesis and development. With the goal of investigating the role of IL-8 in ER-negative breast cancer progression, we applied RNA interference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell line MDA-MB-231.Methods Interfering pRNA-IL-8 and the control was transfected into ER(-) MDA-MB-231. The proliferation, cell apotosis,and invasive ability were recorded in transfected, untransfected and negative transfected cells. These cells were injected into nude mice to assess tumorigenicity, proliferation, metastasis and microvessel density (MVD).Results In vitro, decreased expression of IL-8 was associated with reduced cell invasion (P<0.001), but had no effect on cell proliferation (P>0.05). In vivo, neutrophils infiltration was significantly inhibited in pRNA-IL-8 transfected cells compared with untransfected and negatively transfected cells (P=0.001, P<0.001). Less metastasis was found in transfected cells compared with negatively transfected cells (0% vs 80%, P=0.048). Nevertheless, we observed less MVD in transfected cells compared with control in nude mice (P<0.001).Conclusions IL-8 inhibits ER-negative breast cancer cell growth and promotes its metastasis in vivo, which may be correlated with neutrophils infiltration induced by IL-8.

  15. Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model

    OpenAIRE

    Ru, Peng; Steele, Robert; Nerurkar, Pratibha V.; Phillips, Nancy; Ray, Ratna

    2011-01-01

    Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and...

  16. Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy

    OpenAIRE

    Sullivan, James P.; Minna, John D.; Shay, Jerry W.

    2010-01-01

    The discovery of rare tumor cells with stem cell features first in leukemia and later in solid tumors has emerged as an important area in cancer research. It has been determined that these stem-like tumor cells, termed cancer stem cells, are the primary cellular component within a tumor that drives disease progression and metastasis. In addition to their stem-like ability to self-renew and differentiate, cancer stem cells are also enriched in cells resistant to conventional radiation therapy ...

  17. DNA methylation changes in ovarian cancer are cumulative with disease progression and identify tumor stage

    Directory of Open Access Journals (Sweden)

    DeGeest Koen

    2008-09-01

    Full Text Available Abstract Background Hypermethylation of promoter CpG islands with associated loss of gene expression, and hypomethylation of CpG-rich repetitive elements that may destabilize the genome are common events in most, if not all, epithelial cancers. Methods The methylation of 6,502 CpG-rich sequences spanning the genome was analyzed in 137 ovarian samples (ten normal, 23 low malignant potential, 18 stage I, 16 stage II, 54 stage III, and 16 stage IV ranging from normal tissue through to stage IV cancer using a sequence-validated human CpG island microarray. The microarray contained 5' promoter-associated CpG islands as well as CpG-rich satellite and Alu repetitive elements. Results Results showed a progressive de-evolution of normal CpG methylation patterns with disease progression; 659 CpG islands showed significant loss or gain of methylation. Satellite and Alu sequences were primarily associated with loss of methylation, while promoter CpG islands composed the majority of sequences with gains in methylation. Since the majority of ovarian tumors are late stage when diagnosed, we tested whether DNA methylation profiles could differentiate between normal and low malignant potential (LMP compared to stage III ovarian samples. We developed a class predictor consisting of three CpG-rich sequences that was 100% sensitive and 89% specific when used to predict an independent set of normal and LMP samples versus stage III samples. Bisulfite sequencing confirmed the NKX-2-3 promoter CpG island was hypermethylated with disease progression. In addition, 5-aza-2'-deoxycytidine treatment of the ES2 and OVCAR ovarian cancer cell lines re-expressed NKX-2-3. Finally, we merged our CpG methylation results with previously published ovarian expression microarray data and identified correlated expression changes. Conclusion Our results show that changes in CpG methylation are cumulative with ovarian cancer progression in a sequence-type dependent manner, and that Cp

  18. Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges

    Institute of Scientific and Technical Information of China (English)

    Jia-Cheng Tang; Yi-Li Feng; Xiao Liang; Xiu-Jun Cai

    2016-01-01

    Objective: 5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice.This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system.Data Sources: All articles published in English from 1996 to date those assess the synergistic effect ofautophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed.The search terms were "autophagy" and "5-FU" and ("colorectal cancer" or"hepatocellular carcinoma" or"pancreatic adenocarcinoma" or"esophageal cancer" or"gallbladder carcinoma" or "gastric cancer").Study Selection: Critical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency ofautophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized.The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy;(2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers;and (3) immunogenic cell death for anticancer chemotherapy.Results: Most cell and animal experiments showed inhibition ofautophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death.Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce.The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials.Conclusion: Autophagy might be a therapeutic target that sensitizes the 5-FU treatment in gastrointestinal cancer.

  19. Aberrant nocturnal cortisol and disease progression in women with breast cancer.

    Science.gov (United States)

    Zeitzer, Jamie M; Nouriani, Bita; Rissling, Michelle B; Sledge, George W; Kaplan, Katherine A; Aasly, Linn; Palesh, Oxana; Jo, Booil; Neri, Eric; Dhabhar, Firdaus S; Spiegel, David

    2016-07-01

    While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p sleep disruption. A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer. PMID:27314577

  20. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

    Directory of Open Access Journals (Sweden)

    Howard Y Chang

    2004-02-01

    Full Text Available Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas.

  1. Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses.

    Science.gov (United States)

    Kim, S B; Bozeman, R G; Kaisani, A; Kim, W; Zhang, L; Richardson, J A; Wright, W E; Shay, J W

    2016-06-30

    Proton radiotherapy is becoming more common as protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared with conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole-body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIRs), which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence-associated gene (P19Arf), are markedly increased. Following these changes, loss of Casein kinase Iα and induction of chronic DNA damage and TP53 mutations are increased compared with X-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide (CDDO-EA), reduces proton irradiation-associated SIR and tumorigenesis. Thus exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA. PMID:26477319

  2. Role of deregulated microRNAs in breast cancer progression using FFPE tissue.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    Full Text Available MicroRNAs (miRNAs contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH, ductal carcinoma in situ (DCIS and invasive ductal carcinoma (IDC. To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.

  3. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  4. PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer

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    Jerfiz D. Constanzo

    2016-05-01

    Full Text Available The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation.

  5. Recent trends in surgical research of cancer treatment in the elderly, with a primary focus on lung cancer: Presentation at the 2015 annual meeting of SIOG.

    Science.gov (United States)

    Armstrong, Katherine W; Bravo-Iñiguez, Carlos E; Jacobson, Francine L; Jaklitsch, Michael T

    2016-09-01

    Surgical research concentrating on cancer in the elderly has changed from small single institution outcome studies of carefully selected patients to larger studies that test specific aspects of surgical selection, treatment, and outcome. The purpose of this paper is to review major new trends in surgical geriatric oncology research within the last decade. Reviewing PubMed listings of the last 10years reveals several identifiable areas of particular concentration. Although we use specific studies primarily from lung cancer treatment, the generalizations can be seen across the spectrum of geriatric cancers. These trends include screening for disease that can be successfully treated, integration of operative and non-operative therapies that are changing the indications for surgery, the use of prehabilitation to allow more borderline frail patients to be treated surgically, the use of rehabilitation to facilitate rapid and complete recovery, prevention and treatment of common morbidities, with a special recent focus on delirium and cognitive impairment. New areas of surgical research include research on team building in the OR and ICU. Recent surgical research is becoming quantitative and multi-institutionally based. Overall surgical mortality has dropped over the past 25years in both academic and community hospitals. Prevention of morbidity and loss of functional status is a major focus of research. Funding for new Quality Assurance Projects for elderly patients has been awarded to the American College of Surgeons, and should provide multi-institutional quality outcome data within 5years. PMID:27460994

  6. Trends in the Quality of Treatment for Patients With Intact Cervical Cancer in the United States, 1999 Through 2011

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Grace L. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Jiang, Jing [Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Giordano, Sharon H. [Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Meyer, Larissa A. [Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Gynecologic Oncology and Reproductive Medicine (LAM), The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eifel, Patricia J., E-mail: peifel@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: High-quality treatment for intact cervical cancer requires external radiation therapy, brachytherapy, and chemotherapy, carefully sequenced and completed without delays. We sought to determine how frequently current treatment meets quality benchmarks and whether new technologies have influenced patterns of care. Methods and Materials: By searching diagnosis and procedure claims in MarketScan, an employment-based health care claims database, we identified 1508 patients with nonmetastatic, intact cervical cancer treated from 1999 to 2011, who were <65 years of age and received >10 fractions of radiation. Treatments received were identified using procedure codes and compared with 3 quality benchmarks: receipt of brachytherapy, receipt of chemotherapy, and radiation treatment duration not exceeding 63 days. The Cochran-Armitage test was used to evaluate temporal trends. Results: Seventy-eight percent of patients (n=1182) received brachytherapy, with brachytherapy receipt stable over time (Cochran-Armitage P{sub trend}=.15). Among patients who received brachytherapy, 66% had high–dose rate and 34% had low–dose rate treatment, although use of high–dose rate brachytherapy steadily increased to 75% by 2011 (P{sub trend}<.001). Eighteen percent of patients (n=278) received intensity modulated radiation therapy (IMRT), and IMRT receipt increased to 37% by 2011 (P{sub trend}<.001). Only 2.5% of patients (n=38) received IMRT in the setting of brachytherapy omission. Overall, 79% of patients (n=1185) received chemotherapy, and chemotherapy receipt increased to 84% by 2011 (P{sub trend}<.001). Median radiation treatment duration was 56 days (interquartile range, 47-65 days); however, duration exceeded 63 days in 36% of patients (n=543). Although 98% of patients received at least 1 benchmark treatment, only 44% received treatment that met all 3 benchmarks. With more stringent indicators (brachytherapy, ≥4 chemotherapy cycles, and duration not exceeding 56

  7. Trends in prostate cancer in elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Poulsen, Mads Hvid; Dysager, Lars; Gerke, Oke;

    2016-01-01

    from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data are delivered from the Danish Cancer Registry and the Danish Cause of Death Registry. Results The average annual number of newly diagnosed...

  8. Expression of Eph receptor A10 is correlated with lymph node metastasis and stage progression in breast cancer patients

    International Nuclear Information System (INIS)

    Eph receptor A10 (EphA10) is a valuable breast cancer marker that is highly expressed in breast cancer tissues by comparison with normal breast tissues, as we previously reported. However, the role of EphA10 expression in breast cancer is not well understood. Here, we have analyzed the expression of EphA10 at the mRNA- and protein-level in clinical breast cancer tissues and then evaluated the relationship with clinicopathological parameters for each sample. EphA10 mRNA expression was quantified by real-time polymerase chain reaction using complimentary DNA (cDNA) samples derived from breast cancer patients. Lymph node (LN) metastasis and stage progression were significantly correlated with EphA10 expression at the mRNA level (P = 0.0091 and P = 0.034, respectively). Furthermore, immunohistochemistry (IHC) staining of breast cancer tissue microarrays (TMAs) revealed that EphA10 expression at the protein level was also associated with LN metastasis and stage progression (P = 0.016 and P = 0.011, respectively). These results indicate that EphA10 expression might play a role in tumor progression and metastasis. Our findings will help elucidate the role of EphA10 in clinical breast cancer progression

  9. Expression of Eph receptor A10 is correlated with lymph node metastasis and stage progression in breast cancer patients.

    Science.gov (United States)

    Nagano, Kazuya; Kanasaki, So-Ichiro; Yamashita, Takuya; Maeda, Yuka; Inoue, Masaki; Higashisaka, Kazuma; Yoshioka, Yasuo; Abe, Yasuhiro; Mukai, Yohei; Kamada, Haruhiko; Tsutsumi, Yasuo; Tsunoda, Shin-Ichi

    2013-12-01

    Eph receptor A10 (EphA10) is a valuable breast cancer marker that is highly expressed in breast cancer tissues by comparison with normal breast tissues, as we previously reported. However, the role of EphA10 expression in breast cancer is not well understood. Here, we have analyzed the expression of EphA10 at the mRNA- and protein-level in clinical breast cancer tissues and then evaluated the relationship with clinicopathological parameters for each sample. EphA10 mRNA expression was quantified by real-time polymerase chain reaction using complimentary DNA (cDNA) samples derived from breast cancer patients. Lymph node (LN) metastasis and stage progression were significantly correlated with EphA10 expression at the mRNA level (P = 0.0091 and P = 0.034, respectively). Furthermore, immunohistochemistry (IHC) staining of breast cancer tissue microarrays (TMAs) revealed that EphA10 expression at the protein level was also associated with LN metastasis and stage progression (P = 0.016 and P = 0.011, respectively). These results indicate that EphA10 expression might play a role in tumor progression and metastasis. Our findings will help elucidate the role of EphA10 in clinical breast cancer progression. PMID:24403271

  10. Twisted epithelial-to-mesenchymal transition promotes progression of surviving bladder cancer T24 cells with hTERT-dysfunction.

    Directory of Open Access Journals (Sweden)

    Yan Xue

    Full Text Available BACKGROUND: Human cancer cells maintain telomeres to protect cells from senescence through telomerase activity (TA or alternative lengthening of telomeres (ALT in different cell types. Moreover, cellular senescence can be bypassed by Epithelial-to-mesenchymal transition (EMT during cancer progression in diverse solid tumors. However, it has not been elucidated the characteristics of telomere maintenance and progression ability after long-term culture in bladder cancer T24 cells with hTERT dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: In this study, by using a dominant negative mutant human telomerase reverse transcriptase (hTERT vector to inhibit TA in bladder cancer T24 cells, we observed the appearance of long phenotype of telomere length and the ALT-associated PML body (APB complex after the 27(th passage, indicating the occurrence of ALT-like pathway in surviving T24/DN868A cells with telomerase inhibition. Meanwhile, telomerase inhibition resulted in significant EMT as shown by change in cellular morphology concomitant with variation of EMT markers. Consistently, the surviving T24/DN868A cells showed increased progression ability in vitro and in vivo. In addition, we found Twist was activated to mediate EMT in surviving T24/DN868A samples. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings indicate that bladder cancer T24 cells may undergo the telomerase-to-ALT-like conversion and promote cancer progression at advanced stages through promoting EMT, thus providing novel possible insight into the mechanism of resistance to telomerase inhibitors in cancer treatment.

  11. Radical External Beam Radiotherapy for Clinically Localized Prostate Cancer in Japan: Changing Trends in the Patterns of Care Process Survey

    International Nuclear Information System (INIS)

    Purpose: To delineate changing trends in radical external beam radiotherapy (EBRT) for prostate cancer in Japan. Methods and Materials: Data from 841 patients with clinically localized prostate cancer treated with EBRT in the Japanese Patterns of Care Study (PCS) from 1996 to 2005 were analyzed. Results: Significant increases in the proportions of patients with stage T1 to T2 disease and decrease in prostate-specific antigen values were observed. Also, there were significant increases in the percentages of patients treated with radiotherapy by their own choice. Median radiation doses were 65.0 Gy and 68.4 Gy from 1996 to 1998 and from 1999 to 2001, respectively, increasing to 70 Gy from 2003 to 2005. Moreover, conformal therapy was more frequently used from 2003 to 2005 (84.9%) than from 1996 to 1998 (49.1%) and from 1999 to 2001 (50.2%). On the other hand, the percentage of patients receiving hormone therapy from 2003 to 2005 (81.1%) was almost the same as that from 1996 to 1998 (86.3%) and from 1999 to 2001 (89.7%). Compared with the PCS in the United States, patient characteristics and patterns of treatments from 2003 to 2005 have become more similar to those in the United States than those from 1996 to 1998 and those from 1999 to 2001. Conclusions: This study indicates a trend toward increasing numbers of patients with early-stage disease and increasing proportions of patients treated with higher radiation doses with advanced equipment among Japanese prostate cancer patients treated with EBRT during 1996 to 2005 survey periods. Patterns of care for prostate cancer in Japan are becoming more similar to those in the United States.

  12. Ski regulates Hippo and TAZ signaling to suppress breast cancer progression.

    Science.gov (United States)

    Rashidian, Juliet; Le Scolan, Erwan; Ji, Xiaodan; Zhu, Qingwei; Mulvihill, Melinda M; Nomura, Daniel; Luo, Kunxin

    2015-02-10

    Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor-β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion. Hippo signaling activates the the Lats family of kinases, which phosphorylate TAZ and YAP, resulting in cytoplasmic retention and degradation and inhibition of their transcriptional activity. We showed that Ski interacted with multiple components of the Hippo pathway to facilitate activation of Lats2, resulting in increased phosphorylation and subsequent degradation of TAZ. Ski also promoted the degradation of a constitutively active TAZ mutant that is not phosphorylated by Lats, suggesting the existence of a Lats2-independent degradation pathway. Finally, we showed that Ski repressed the transcriptional activity of TAZ by binding to the TAZ partner TEAD and recruiting the transcriptional co-repressor NCoR1 to the TEAD-TAZ complex. Ski effectively reversed transformation and epithelial-to-mesenchyme transition in cultured breast cancer cells and metastasis in TAZ-expressing xenografted tumors. Thus, Ski inhibited the function of TAZ through multiple mechanisms in human cancer cells.

  13. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

    Science.gov (United States)

    Sciamanna, Ilaria; De Luca, Chiara; Spadafora, Corrado

    2016-02-01

    In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can “sequester” RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

  14. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

    Directory of Open Access Journals (Sweden)

    Ilaria eSciamanna

    2016-02-01

    Full Text Available In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1 retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT, which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can sequester RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

  15. Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Chatterjee Namita

    2010-03-01

    Full Text Available Abstract Background Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s of the secretory isoform in breast tumor progression and metastasis. Methods To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. Results In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. Conclusions These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells.

  16. Utility of SAM68 in the progression and prognosis for bladder cancer

    International Nuclear Information System (INIS)

    Muscle invasive bladder cancer (MIBC) is often lethal and non-MIBC (NMIBC) can recur and progress, yet prognostic markers are currently inadequate. SAM68, a member of RNA-binding proteins, has been reported to contribute to progression of other cancers. The aim of this study is to investigate the potential utility of SAM68 in the progression and prognosis of bladder cancer. Quantitative PCR and immunohistochemistry were utilized to examine the expression of SAM68 in ten pairs of MIBC and adjacent normal bladder urothelium, and eight pairs of MIBC and non-MIBC (NMIBC) tissues from the same patient. Moreover, SAM68 protein expression level and localization were examined by immunohistochemistry in 129 clinicopathologically characterized MIBC samples. Prognostic associations were determined by multivariable analysis incorporating standard prognostic factors. SAM68 expression was elevated in MIBC tissues compared with adjacent normal bladder urothelium, and was increased at both transcriptional and translational levels in MIBC tissues compared with NMIBC tissues of the same patient. For MIBC, high expression and nucleus-cytoplasm co-expression of SAM68 were associated with higher T-stage, higher N-stage and worse recurrence-free survival. Five-year recurrence-free survival was 80% and 52.9% for MIBC patients with low and high SAM68 expression, respectively (p = 0.001). SAM68 nucleus-cytoplasm co-expression associated with worse 5-year recurrence-free survival rate (49.2%) than SAM68 expression confined to the nucleus (82.5%) or cytoplasm (75.5%) alone. On multivariable analysis SAM68 expression level, SAM68 nucleus-cytoplasm co-expression, T-stage, and N-stage were all independent prognostic factors for recurrence-free survival of MIBC patients. SAM68 expression is increased in MIBC when compared to normal urothelium and NMIBC, and appears to be a potentially useful prognostic marker for MIBC

  17. Epigenetics of Estrogen Receptor Signaling: Role in Hormonal Cancer Progression and Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mann, Monica; Cortez, Valerie [Department of Cellular and Structural Biology, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229 (United States); Vadlamudi, Ratna K., E-mail: vadlamudi@uthscsa.edu [Department of Obstetrics and Gynecology, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229 (United States)

    2011-03-29

    Estrogen receptor (ERα) signaling plays a key role in hormonal cancer progression. ERα is a ligand-dependent transcription factor that modulates gene transcription via recruitment to the target gene chromatin. Emerging evidence suggests that ERα signaling has the potential to contribute to epigenetic changes. Estrogen stimulation is shown to induce several histone modifications at the ERα target gene promoters including acetylation, phosphorylation and methylation via dynamic interactions with histone modifying enzymes. Deregulation of enzymes involved in the ERα -mediated epigenetic pathway could play a vital role in ERα driven neoplastic processes. Unlike genetic alterations, epigenetic changes are reversible, and hence offer novel therapeutic opportunities to reverse ERα driven epigenetic changes. In this review, we summarize current knowledge on mechanisms by which ERα signaling potentiates epigenetic changes in cancer cells via histone modifications.

  18. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone.

    Science.gov (United States)

    Arrigoni, Chiara; Bersini, Simone; Gilardi, Mara; Moretti, Matteo

    2016-01-01

    Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps. PMID:27571063

  19. Recent progress in the identification of BRAF inhibitors as anti-cancer agents.

    Science.gov (United States)

    El-Nassan, Hala Bakr

    2014-01-24

    The "RAS/BRAF/MEK/ERK" pathway has been associated with human cancers due to the frequent oncogenic mutations identified in its members. In particular, BRAF is mutated at high frequency in many cancers especially melanoma. This mutation leads to activation of the MAPK signaling pathway, inducing uncontrolled cell proliferation, and facilitating malignant transformation. All these facts make BRAF an ideal target for antitumor therapeutic development. Many BRAF inhibitors have been discovered during the last decade and most of them exhibit potent antitumor activity especially on tumors that harbor BRAF(V600E) mutations. Some of these compounds have entered clinical trials and displayed encouraged results. The present review highlights the progress in identification and development of BRAF inhibitors especially during the last five years.

  20. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone

    Directory of Open Access Journals (Sweden)

    Chiara Arrigoni

    2016-08-01

    Full Text Available Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps.

  1. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone

    Science.gov (United States)

    Arrigoni, Chiara; Bersini, Simone; Gilardi, Mara; Moretti, Matteo

    2016-01-01

    Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps. PMID:27571063

  2. Epigenetics of Estrogen Receptor Signaling: Role in Hormonal Cancer Progression and Therapy

    International Nuclear Information System (INIS)

    Estrogen receptor (ERα) signaling plays a key role in hormonal cancer progression. ERα is a ligand-dependent transcription factor that modulates gene transcription via recruitment to the target gene chromatin. Emerging evidence suggests that ERα signaling has the potential to contribute to epigenetic changes. Estrogen stimulation is shown to induce several histone modifications at the ERα target gene promoters including acetylation, phosphorylation and methylation via dynamic interactions with histone modifying enzymes. Deregulation of enzymes involved in the ERα -mediated epigenetic pathway could play a vital role in ERα driven neoplastic processes. Unlike genetic alterations, epigenetic changes are reversible, and hence offer novel therapeutic opportunities to reverse ERα driven epigenetic changes. In this review, we summarize current knowledge on mechanisms by which ERα signaling potentiates epigenetic changes in cancer cells via histone modifications

  3. The role of miRNA regulation in cancer progression and drug resistance

    DEFF Research Database (Denmark)

    Joshi, Tejal

    RNAs in the context of cancer biology, drug resistance and disease progression. The first project described in Chapter 6 addresses the problem of tamoxifen resistance, an anti-estrogen drug that is generally highly effective in the treatment of ER-positive breast cancers. The underlying molecular mechanisms......This PhD thesis presents the work carried out at Center for Biological Sequence Analysis, Technical University of Denmark. The projects presented in this thesis are a purely bioinformatic in nature. Included in this thesis are the two projects that focus on the gene regulatory events mediated by mi...... for the acquired resistance to tamoxifen are not very well understood. Therefore, with the aid of miRNA and gene expression profiles for MCF7/S0.5 (tamoxifen sensitive) and three MCF7/S0.5 derived tamoxifen resistant cell lines, we obtained several miRNA-mediated regulatory events in the tamoxifen resistant cell...

  4. Fragment N2, a caspase-3-generated RasGAP fragment, inhibits breast cancer metastatic progression.

    Science.gov (United States)

    Barras, David; Lorusso, Girieca; Lhermitte, Benoît; Viertl, David; Rüegg, Curzio; Widmann, Christian

    2014-07-01

    The p120 RasGAP protein negatively regulates Ras via its GAP domain. RasGAP carries several other domains that modulate several signaling molecules such as Rho. RasGAP is also a caspase-3 substrate. One of the caspase-3-generated RasGAP fragments, corresponding to amino acids 158-455 and called fragment N2, was previously reported to specifically sensitize cancer cells to death induced by various anticancer agents. Here, we show that fragment N2 inhibits migration in vitro and that it impairs metastatic progression of breast cancer to the lung. Hence, stress-activated caspase-3 might contribute to the suppression of metastasis through the generation of fragment N2. These results indicate that the activity borne by fragment N2 has a potential therapeutic relevance to counteract the metastatic process.

  5. Recent progress in development of siRNA delivery vehicles for cancer therapy.

    Science.gov (United States)

    Kim, Hyun Jin; Kim, Ahram; Miyata, Kanjiro; Kataoka, Kazunori

    2016-09-01

    Recent progress in RNA biology has broadened the scope of therapeutic targets of RNA drugs for cancer therapy. However, RNA drugs, typically small interfering RNAs (siRNAs), are rapidly degraded by RNases and filtrated in the kidney, thereby requiring a delivery vehicle for efficient transport to the target cells. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic delivery of siRNA to solid tumors. This review describes the current status of clinical trials related to siRNA-based cancer therapy, as well as the remaining issues that need to be overcome to establish a successful therapy. It, then introduces various promising design strategies of delivery vehicles for stable and targeted siRNA delivery, including the prospects for future design.

  6. Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology-Genomic Integration Analysis.

    Directory of Open Access Journals (Sweden)

    Rachael Natrajan

    2016-02-01

    Full Text Available The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess the degree of microenvironmental heterogeneity in breast cancer and correlate this with genomic and clinical parameters.We developed a quantitative measure of microenvironmental heterogeneity along three spatial dimensions (3-D in solid tumors, termed the tumor ecosystem diversity index (EDI, using fully automated histology image analysis coupled with statistical measures commonly used in ecology. This measure was compared with disease-specific survival, key mutations, genome-wide copy number, and expression profiling data in a retrospective study of 510 breast cancer patients as a test set and 516 breast cancer patients as an independent validation set. In high-grade (grade 3 breast cancers, we uncovered a striking link between high microenvironmental heterogeneity measured by EDI and a poor prognosis that cannot be explained by tumor size, genomics, or any other data types. However, this association was not observed in low-grade (grade 1 and 2 breast cancers. The prognostic value of EDI was superior to known prognostic factors and was enhanced with the addition of TP53 mutation status (multivariate analysis test set, p = 9 × 10-4, hazard ratio = 1.47, 95% CI 1.17-1.84; validation set, p = 0.0011, hazard ratio = 1.78, 95% CI 1.26-2.52. Integration with genome-wide profiling data identified losses of specific genes on 4p14 and 5q13 that were enriched in grade 3 tumors with high microenvironmental diversity that also substratified patients into poor prognostic groups. Limitations of this study include the number of cell types included in the model, that EDI has prognostic value only in grade 3 tumors, and that our spatial heterogeneity measure was dependent on spatial scale and tumor size.To our knowledge, this is the first

  7. Social Networks and Physical Activity Behaviors Among Cancer Survivors: Data From the 2005 Health Information National Trends Survey

    Science.gov (United States)

    KIM, BANG HYUN; WALLINGTON, SHERRIE F.; MAKAMBI, KEPHER H.; ADAMS-CAMPBELL, LUCILE L.

    2015-01-01

    The study examined the relation between social networks and physical activity behaviors among cancer survivors. The authors examined 873 cancer survivors (596 women, 277 men) 50 years of age or older who participated in the 2005 Health Information National Trends Survey. Multivariate logistic regression analysis showed that survivors who talked about health with friends/family were more likely to pay attention to new physical activity recommendations (OR = 2.89, CI [1.01, 8.33]). Female survivors were more likely to pay attention to new physical activity recommendations (OR = 2.65, CI [1.55, 4.53]) and more likely to have seen, heard, or read physical activity/exercise and cancer information within the past 12 months (OR = 2.09, CI [1.13, 3.85]) compared with their male counterparts. For male survivors, those who were a member of at least one community organization were more likely to pay attention to new physical activity/exercise recommendations (OR = 5.31, CI [1.32, 21.22]) than the men who were not members. Overall, cancer survivors with a social network (i.e., talking to family/friends about health) were more likely to pay attention to new exercise recommendations compared with those who did not have a social network. Significant differences were also observed by gender with physical activity levels, knowledge, and attitudes. Social networking is an important component in cancer survivorship and further research is needed to encourage social networking strategies that might facilitate in increasing physical activity behaviors among cancer survivors. PMID:25978562

  8. Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Hisae Nakamura

    Full Text Available Genistein is an isoflavone found in soy, and its chemo-preventive and -therapeutic effects have been well established from in vitro studies. Recently, however, its therapeutic actions in vivo have been questioned due to contradictory reports from animal studies, which rely on rodent models or implantation of cell lines into animals. To clarify in vivo effects of genistein in advanced prostate cancer patients, we developed a patient-derived prostate cancer xenograft model, in which a clinical prostatectomy sample was grafted into immune deficient mice. Our results showed an increased lymph node (LN and secondary organ metastases in genistein-treated mice compared to untreated controls. Interestingly, invasive malignant cells aggregated to form islands/micrometastasis only in the secondary organs of the genistein-treated groups, not in the untreated control group. To understand the underlying mechanism for metastatic progression, we examined cell proliferation and apoptosis on paraffin-sections. Immunohistological data show that tumors of genistein-treated groups have more proliferating and fewer apoptotic cancer cells than those of the untreated group. Our immunoblotting data suggest that increased proliferation and metastasis are linked to enhanced activities of tyrosine kinases, EGFR and its downstream Src, in genistein-treated groups. Despite the chemopreventive effects proposed by earlier in vitro studies, the cancer promoting effect of genistein observed here suggests the need for careful selection of patients and safer planning of clinical trials.

  9. The importance of non-nuclear AR signaling in prostate cancer progression and therapeutic resistance.

    Science.gov (United States)

    Zarif, Jelani C; Miranti, Cindy K

    2016-05-01

    The androgen receptor (AR) remains the major oncogenic driver of prostate cancer, as evidenced by the efficacy of androgen deprivation therapy (ADT) in naïve patients, and the continued effectiveness of second generation ADTs in castration resistant disease. However, current ADTs are limited to interfering with AR ligand binding, either through suppression of androgen production or the use of competitive antagonists. Recent studies demonstrate 1) the expression of constitutively active AR splice variants that no longer depend on androgen, and 2) the ability of AR to signal in the cytoplasm independently of its transcriptional activity (non-genomic); thus highlighting the need to consider other ways to target AR. Herein, we review canonical AR signaling, but focus on AR non-genomic signaling, some of its downstream targets and how these effectors contribute to prostate cancer cell behavior. The goals of this review are to 1) re-highlight the continued importance of AR in prostate cancer as the primary driver, 2) discuss the limitations in continuing to use ligand binding as the sole targeting mechanism, 3) discuss the implications of AR non-genomic signaling in cancer progression and therapeutic resistance, and 4) address the need to consider non-genomic AR signaling mechanisms and pathways as a viable targeting strategy in combination with current therapies. PMID:26829214

  10. Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2013-01-01

    Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

  11. Research progress on chemopreventive effects of phytochemicals on colorectal cancer and their mechanisms

    Science.gov (United States)

    Yin, Teng-Fei; Wang, Min; Qing, Ying; Lin, Ying-Min; Wu, Dong

    2016-01-01

    Colorectal cancer (CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but also causes side effects. Many studies have shown that adequate intake of fruits and vegetables in the diet may have a protective effect on CRC occurrence, possibly due to the special biological protective effect of the phytochemicals in these foods. Numerous in vitro and in vivo studies have demonstrated that phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles by regulating specific signaling pathways and molecular markers to inhibit the occurrence and development of CRC. This review summarizes the progress on CRC prevention using the phytochemicals sulforaphane, curcumin and resveratrol, and elaborates on the specific underlying mechanisms. Thus, we believe that phytochemicals might provide a novel therapeutic approach for CRC prevention, but future clinical studies are needed to confirm the specific preventive effect of phytochemicals on cancer.

  12. SURGICAL TREATMENT OF PATIENTS WITH PROSTATE CANCER AT HIGH RISK OF PROGRESSION

    Directory of Open Access Journals (Sweden)

    K. M. Nyushko

    2014-07-01

    Full Text Available Prostate cancer (PC is one of the most burning problems of modern urologic oncology. Patients at its high risk are characterized by a more aggressive course of the disease and significantly lower tumor-specific and relapse-free survival rates. Hormone therapy and radiotherapy are one of the conventional treatments in patients with PC at high risk of progression. Nonetheless, more and more publications demonstrating the efficiency and safety of surgical therapy in this contingent of patients are recently appearing. This paper presents the results of surgical treat-ment in 499 patients with PC at high risk of progression, who have undergone radical prostatectomy with extended pelvic lymphadenectomy at the Department of Urologic Oncology, P.A. Herzen Moscow Oncology Research Institute. 

  13. Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.

    LENUS (Irish Health Repository)

    Quintyne, Keith Ian

    2011-09-01

    The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

  14. The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma.

    Science.gov (United States)

    Xiang, Yan; Yang, Ting; Pang, Bing-Yao; Zhu, Ying; Liu, Yong-Ning

    2016-01-01

    Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with "stem-like" characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a "global" marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies. PMID:27610139

  15. Real-time motion analysis reveals cell directionality as an indicator of breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Michael C Weiger

    Full Text Available Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize to distant sites. However, it remains unclear how migratory behaviors differ between tumor cells of different malignancy and whether these migratory behaviors can be utilized to assess the malignant potential of tumor cells. Here, we analyzed the migratory behaviors of cell lines representing different stages of breast cancer progression using conventional migration assays or time-lapse imaging and particle image velocimetry (PIV to capture migration dynamics. We find that the number of migrating cells in transwell assays, and the distance and speed of migration in unconstrained 2D assays, show no correlation with malignant potential. However, the directionality of cell motion during 2D migration nicely distinguishes benign and tumorigenic cell lines, with tumorigenic cell lines harboring less directed, more random motion. Furthermore, the migratory behaviors of epithelial sheets observed under basal conditions and in response to stimulation with epidermal growth factor (EGF or lysophosphatitic acid (LPA are distinct for each cell line with regard to cell speed, directionality, and spatiotemporal motion patterns. Surprisingly, treatment with LPA promotes a more cohesive, directional sheet movement in lung colony forming MCF10CA1a cells compared to basal conditions or EGF stimulation, implying that the LPA signaling pathway may alter the invasive potential of MCF10CA1a cells. Together, our findings identify cell directionality as a promising indicator for assessing the tumorigenic potential of breast cancer cell lines and show that LPA induces more cohesive motility in a subset of metastatic breast cancer cells.

  16. A role of autophagy in PTP4A3-driven cancer progression.

    Science.gov (United States)

    Huang, Yu-Han; Al-Aidaroos, Abdul Qader O; Yuen, Hiu-Fung; Zhang, Shu-Dong; Shen, Han-Ming; Rozycka, Ewelina; McCrudden, Cian M; Tergaonkar, Vinay; Gupta, Abhishek; Lin, You Bin; Thiery, Jean Paul; Murray, James T; Zeng, Qi

    2014-10-01

    Autophagy, a "self-eating" cellular process, has dual roles in promoting and suppressing tumor growth, depending on cellular context. PTP4A3/PRL-3, a plasma membrane and endosomal phosphatase, promotes multiple oncogenic processes including cell proliferation, invasion, and cancer metastasis. In this study, we demonstrate that PTP4A3 accumulates in autophagosomes upon inhibition of autophagic degradation. Expression of PTP4A3 enhances PIK3C3-BECN1-dependent autophagosome formation and accelerates LC3-I to LC3-II conversion in an ATG5-dependent manner. PTP4A3 overexpression also enhances the degradation of SQSTM1, a key autophagy substrate. These functions of PTP4A3 are dependent on its catalytic activity and prenylation-dependent membrane association. These results suggest that PTP4A3 functions to promote canonical autophagy flux. Unexpectedly, following autophagy activation, PTP4A3 serves as a novel autophagic substrate, thereby establishing a negative feedback-loop that may be required to fine-tune autophagy activity. Functionally, PTP4A3 utilizes the autophagy pathway to promote cell growth, concomitant with the activation of AKT. Clinically, from the largest ovarian cancer data set (GSE 9899, n = 285) available in GEO, high levels of expression of both PTP4A3 and autophagy genes significantly predict poor prognosis of ovarian cancer patients. These studies reveal a critical role of autophagy in PTP4A3-driven cancer progression, suggesting that autophagy could be a potential Achilles heel to block PTP4A3-mediated tumor progression in stratified patients with high expression of both PTP4A3 and autophagy genes.

  17. Micronutrients attenuate progression of prostate cancer by elevating the endogenous inhibitor of angiogenesis, Platelet Factor-4

    International Nuclear Information System (INIS)

    Longstanding evidence implicates an inadequate diet as a key factor in the onset and progression of prostate cancer. The purpose herein was to discover, validate and characterize functional biomarkers of dietary supplementation capable of suppressing the course of prostate cancer in vivo. The Lady transgenic mouse model that spontaneously develops prostate cancer received a diet supplemented with a micronutrient cocktail of vitamin E, selenium and lycopene ad libitum. A proteomic analysis was conducted to screen for serum biomarkers of this dietary supplementation. Candidate peptides were validated and identified by sequencing and analyzed for their presence within the prostates of all mice by immunohistochemistry. Dietary supplementation with the combined micronutrients significantly induced the expression of the megakaryocyte-specific inhibitor of angiogenesis, platelet factor-4 (P = 0.0025). This observation was made predominantly in mice lacking tumors and any manifestations associated with progressive disease beyond 37 weeks of life, at which time no survivors remained in the control group (P < 0.0001). While prostates of mice receiving standard chow were enlarged and burdened with poorly differentiated carcinoma, those of mice on the supplemented diet appeared normal. Immunohistochemical analysis revealed marked amplifications of both platelet binding and platelet factor-4 within the blood vessels of prostates from mice receiving micronutrients only. We present unprecedented data whereby these combined micronutrients effectively promotes tumor dormancy in early prostate cancer, following initiation mutations that may drive the angiogenesis-dependent response of the tumor, by inducing platelet factor-4 expression and concentrating it at the tumor endothelium through enhanced platelet binding

  18. Relevance of the neuropeptide Y system in the biology of cancer progression.

    Science.gov (United States)

    Ruscica, M; Dozio, E; Motta, M; Magni, P

    2007-01-01

    The peptides pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY) share a similar structure, known as PP-fold. Within this family of peptides, NPY, a highly conserved 36-aminoacid residue peptide, is involved in the regulation of a wide range of physiological functions, such as food intake and energy metabolism, as well as in the promotion of some remarkable aspects of tumor progression, including cell proliferation, matrix invasion, metastatization, and angiogenesis. NPY exerts its biological effects through five G-protein coupled receptors, named Y1-, Y2-, Y4-, Y5-, and y6-R, which appear associated with different aspects of oncogenesis. Y1-R seems involved in the modulation of cancer cell proliferation, whereas Y2-R activation appears to promote angiogenesis. The development of NPY receptor subtype selective analogs has helped to elucidate the physiological and pathophysiological role and localization of each receptor and may contribute to a better understanding of the receptor-ligand interaction. The NPY system appears to be variously associated with specific tumors, including neural crest-derived tumors, breast and prostate cancers. In addition to NPY, PYY is also able to affect cancer cell growth in a dose-dependent manner and through Y-Rs. In conclusion, peptides of the NPY family and the related receptors play an important role in the progression of different cancer types, with some molecular specificity according to each step of this process. On this basis, future studies may be directed to the implementation of novel diagnostic and therapeutic approaches targeting this system.

  19. HiJAK’d Signaling; the STAT3 Paradox in Senescence and Cancer Progression

    Energy Technology Data Exchange (ETDEWEB)

    Junk, Damian J.; Bryson, Benjamin L.; Jackson, Mark W., E-mail: mark.w.jackson@case.edu [Department of Pathology, Case Western Reserve University, Case Comprehensive Cancer Center, 2103 Cornell Road, WRB 3-134, Cleveland, OH 44106 (United States)

    2014-03-26

    Clinical and epidemiological data have associated chronic inflammation with cancer progression. Most tumors show evidence of infiltrating immune and inflammatory cells, and chronic inflammatory disorders are known to increase the overall risk of cancer development. While immune cells are often observed in early hyperplastic lesions in vivo, there remains debate over whether these immune cells and the cytokines they produce in the developing hyperplastic microenvironment act to inhibit or facilitate tumor development. The interleukin-6 (IL-6) family of cytokines, which includes IL-6 and oncostatin M (OSM), among others (LIF, CT-1, CNTF, and CLC), are secreted by immune cells, stromal cells, and epithelial cells, and regulate diverse biological processes. Each of the IL-6 family cytokines signals through a distinct receptor complex, yet each receptor complex uses a shared gp130 subunit, which is critical for signal transduction following cytokine binding. Activation of gp130 results in the activation of Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen-Activated Protein Kinase (MAPK) and Phosphatidylinositol 3-Kinase (PI3K) signaling cascades. Tumor suppressive signaling can often be observed in normal cells following prolonged STAT3 activation. However, there is mounting evidence that the IL-6 family cytokines can contribute to later stages of tumor progression in many ways. Here we will review how the microenvironmental IL-6 family cytokine OSM influences each stage of the transformation process. We discuss the intrinsic adaptations a developing cancer cell must make in order to tolerate and circumvent OSM-mediated growth suppression, as well as the OSM effectors that are hijacked during tumor expansion and metastasis. We propose that combining current therapies with new ones that suppress the signals generated from the tumor microenvironment will significantly impact an oncologist’s ability to treat cancer.

  20. Asian trends in primar y androgen depletion therapy on prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Hideyuki Akaza

    2013-01-01

    hTere are notable differences in the incidence and mortality rates for prostate cancer between Asia and Western countries. It is also recognized that there are differences in thinking with regard to treatment options. Recently it is also the case that opinions have been reported concerning the differences between Asian and Western patients with regard to their reaction to androgen depletion therapy (ADT). Given that ADT is a method of treatment that focuses on the elimination of testosterone, an inevitable symptom of its administration is testosterone losing syndrome. It is for this reason that in Western countries ADT has only been recommended in cases of advanced or metastatic cancer. On the other hand, in Asia, ADT is used in relatively many cases, including non-metastatic localized cancer and invasive localized cancer. To date, however, there has been little substantive discussion concerning this difference in utilization of ADT. ADT-related drugs for prostate cancer and the development of new drugs for castration resistant prostate cancer (CRPC) have been actively tested in recent years. It could be the case that analyzing the differences in concepts about ADT between Asia and the West could contribute to the effective use of ADT-related drugs and also help to build new treatment strategies for prostate cancer.

  1. Progress and trends in housing security research%住房保障研究进展与趋势

    Institute of Scientific and Technical Information of China (English)

    王湃; 凌雪冰; 郑崇明

    2015-01-01

    采用文献回顾法和归纳法综述了国内外有关住房保障的研究进展和趋势。从国内外相近研究比较、国内研究热点及存在问题、国内研究维度三个方面得出结论:国外学者侧重住房保障体系内部运行机制的应用研究;而基于我国住房保障建设尚处于不成熟阶段的现状,国内学者旨在探索完善住房保障制度体系,研究热点主要集中在理论研究、经验总结以及制度构想三个方面;国内研究普遍存在定量分析不足、研究维度单一等问题。研究提出,将我国住房保障制度中的两种基本形式——住房补贴和保障性住房政策同时纳入研究框架,构建多层次性与可选择性相匹配的住房保障制度,实现住房保障制度的可持续性与连续性,应成为下一步研究的重点。%This paper reviews the literature regarding progress and trends in housing security research. The study focuses on the following three aspects of this research: a comparison with international studies; the key elements and problems associated with domestic studies; and the scope of Chinese research. International scholars have focused on the application of the internal operation mechanisms of housing security systems. In contrast, Chinese scholars have focused on improving the poorly developed housing security systems in state-constructed housing. Domestic research has mainly focused on the theoretical aspects of this problem, from the standpoint of previous experience and construction systems. The lack of quantitative analysis and a single research objective are common problems in domestic research. This study suggests that the housing subsidy and social housing policies should be incorporated into the research framework at the same time if we are to develop multilevel and optional housing security systems, and that creating sustainable and resilient housing security systems should be the focus of future research.

  2. The Role of Adipose-Derived Stem Cells in Breast Cancer Progression and Metastasis

    Directory of Open Access Journals (Sweden)

    Riccardo Schweizer

    2015-01-01

    Full Text Available Conventional breast cancer extirpation involves resection of parts of or the whole gland, resulting in asymmetry and disfiguration. Given the unsatisfactory aesthetic outcomes, patients often desire postmastectomy reconstructive procedures. Autologous fat grafting has been proposed for reconstructive purposes for decades to restore form and anatomy after mastectomy. Fat has the inherent advantage of being autologous tissue and the most natural-appearing filler, but given its inconsistent engraftment and retention rates, it lacks reliability. Implementation of autologous fat grafts with cellular adjuncts, such as multipotent adipose-derived stem cells (ADSCs, has shown promising results. However, it is pertinent and critical to question whether these cells could promote any residual tumor cells to proliferate, differentiate, or metastasize or even induce de novo carcinogenesis. Thus far, preclinical and clinical study findings are discordant. A trend towards potential promotion of both breast cancer growth and invasion by ADSCs found in basic science studies was indeed not confirmed in clinical trials. Whether experimental findings eventually correlate with or will be predictive of clinical outcomes remains unclear. Herein, we aimed to concisely review current experimental findings on the interaction of mesenchymal stem cells and breast cancer, mainly focusing on ADSCs as a promising tool for regenerative medicine, and discuss the implications in clinical translation.

  3. 自噬与甲状腺癌的研究进展%Autophagy and its research progress in thyroid cancer

    Institute of Scientific and Technical Information of China (English)

    张思林; 罗庆; 余杰情

    2016-01-01

    To summarize the autophagy and its research progress in thyroid cancer.In combination with available literatures published in recent years involving the relationship between autophagy and thyroid cancer,the characteristics of autophagy,the role in thyroid cancer were reviewed.The changes of autophagy level will directly or indirectly participate in the pathogenesis and progression of thyroid cancer.Reagents regulating autophagy will have broad prospect of application in thyroid cancer therapy.The autophagy in the thyroid cancer is still poorly understood,and to clarify the molecular mechanism of autophagy and kill thyroid cancer cells by reasonable regulation of autophagy still needs more further studies.

  4. Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: the BEST study

    International Nuclear Information System (INIS)

    Cancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce. Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood. In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy. The BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed. The BEST study is the first randomized controlled trial comparing progressive

  5. Colon cancer trends in Norway and Denmark by socio-economic group

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Martinsen, Jan Ivar; Larsen, Inger Kristin;

    2015-01-01

    AIMS: Norway has experienced an unprecedented rapid and so far unexplained increase in colon cancer incidence. Norwegian rates passed Danish rates for men in 1985 and for women in 1990. This study aimed to unravel clues to the development in colon cancer incidence by investigating changes over time...... in incidence by socio-economic group. METHODS: Persons participating in the 1970 censuses in Norway and Denmark were aged 55-75 years in 1971-1980 (called pre-crossing period) and in 1991-2000 (called post-crossing period), respectively. Country, sex, age and socio-economic group-specific colon cancer...... incidence rates. Percent change in the average rate from the pre- to the post-crossing period. RESULTS: In the pre-crossing period, Norwegian male managers/administrators had the highest colon cancer incidence, but the largest increase in incidence from the pre-to the post-crossing period was seen...

  6. Opioid growth factor receptor (OGFR expression is downregulated with progression of triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Beth Worley

    2015-12-01

    Full Text Available Purpose: Triple negative breast cancer (TNBC is an aggressive form of breast cancer that accounts for approximately 15% of the newly diagnosed cancers worldwide, and disproportionately affects younger women and women of color. Although many forms of breast cancer are successfully treated, new therapies are needed for TNBC. A novel regulatory system, the opioid growth factor (OGF – opioid growth factor receptor (OGFr axis, plays a determining role in neoplasia. OGF is an endogenous peptide that binds specifically to OGFr to inhibit cell replication. As some human cancers grow, OGFr expression is diminished, thus limiting the therapeutic efficacy of OGF. The OGF-OGFr axis is present in human TNBC cell line MDA-MB-231 and OGF  inhibits cell replication in a dosage-related, receptor-mediated manner. Methods: The present study investigated whether OGFr protein expression in human breast cancer cell lines grown in vitro or transplanted into nude mice, changed with the stage of proliferation or size of tumor using western blotting, semi-quantitative immunohistochemistry, and DNA synthesis techniques. Results: Comparison of log and confluent TNBC cultures revealed that OGF expression was significantly decreased in confluent cultures relative to levels in log-phase cells. Western blot analyses confirmed that OGFr was reduced in confluent TNBC and MCF-7 breast cancer cells in comparison to corresponding log-phase cells. Moreover, BrdU labeling was reduced in confluent cells. Small (<500 mm3 and large (>1000 mm3 TNBC tumors grown in nude mice were processed for semiquantitative   measurement of OGF and OGFr. The expression of both peptide and receptor in large tumors was downregulated relative to small tumors. Conclusion: The reduced expression of the inhibitory peptide and receptor diminishes the efficacy of the OGF-OGFr axis as a biotherapy. These data suggest that the OGF-OGFr pathway is altered with cancer progression and one or more elements of

  7. The Trend of Age-Group Effect on Prognosis in Differentiated Thyroid Cancer

    OpenAIRE

    Rong-liang Shi; Ning Qu; Tian Liao; Wen-jun Wei; Yu-Long Wang; Qing-hai Ji

    2016-01-01

    Age has been included in various prognostic scoring systems for differentiated thyroid cancer (DTC). The aim of this study is to re-examine the relationship between age and prognosis by using Surveillance, Epidemiology, and End Results (SEER) population-based database. We identified 51,061 DTC patients between 2004 and 2012. Patients were separated into 10-year age groups. Cancer cause-specific survival (CSS) and overall survival (OS) data were obtained. Kaplan-Meier and multivariable Cox mod...

  8. Imaging and intervention in prostate cancer: Current perspectives and future trends

    OpenAIRE

    Sanjay Sharma

    2014-01-01

    Prostate cancer is the commonest malignancy in men that causes significant morbidity and mortality worldwide. Screening by digital rectal examination (DRE) and serum prostate-specific antigen (PSA) is used despite its limitations. Gray-scale transrectal ultrasound (TRUS), used to guide multiple random prostatic biopsies, misses up to 20% cancers and frequently underestimates the grade of malignancy. Increasing the number of biopsy cores marginally increases the yield. Evolving techniques of r...

  9. Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges

    OpenAIRE

    Jia-Cheng Tang; Yi-Li Feng; Xiao Liang; Xiu-Jun Cai

    2016-01-01

    Objective: 5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system. Data Sources: All articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-...

  10. Changing trends of breast cancer awareness in young females of north India: A pilot study from a rural cancer hospital

    Directory of Open Access Journals (Sweden)

    Vivek Tiwari

    2014-01-01

    Full Text Available Aim: To assess the spectrum of presentation of young (18-35 years females to a rural cancer hospital and to correlate it with the level of education. Materials and Methods: Ninety cases of the selected age group were prospectively studied for the manner of presentation and level of education. Results: Majority patients (57.77% presented with breast related symptoms. 81.1% of the patients were educated at least up to secondary school education. Conclusions: Owing to the improved education levels and awareness, the young rural females are more informed about breast related symptoms and are seeking proper care for the same. A robust rural cancer registry system may document this changing scenario that may well contrast with the traditional beliefs and learning of cancer epidemiology.

  11. Early decline in cancer antigen 125 as a surrogate for progression-free survival in recurrent ovarian cancer

    DEFF Research Database (Denmark)

    Lee, Chee K; Friedlander, Michael; Brown, Chris;

    2011-01-01

    [38.7%], P = .14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P = .007). These findings are opposite to what would be expected if these markers were good surrogates......We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority...... response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0...

  12. Modern Trends Of Computation, Simulation, and Communication, And Their Impacts On The Progress Of Scientific And Engineering Research, Development, And Education

    International Nuclear Information System (INIS)

    A short report on the modern trends of computation, simulation, and communication in the 1990s is presented, along with their impacts on the progress of scientific and engineering research, development, and education. A full description of this giant issue is certainly a mission impossiblefor the author. Nevertheless, it is the author's hope that it will at least give an overall view about what is going on in this very dynamic field in the advanced countries. After thinking globallythru reading this report, we should then decide on what and how to act locallyto respond to these global trends. The main source of information reported here were the computational science and engineering journals and books issued during the 1990s as listed in the references below

  13. Current trends in initial management of laryngeal cancer: the declining use of open surgery.

    Science.gov (United States)

    Silver, Carl E; Beitler, Jonathan J; Shaha, Ashok R; Rinaldo, Alessandra; Ferlito, Alfio

    2009-09-01

    The role of open surgery for management of laryngeal cancer has been greatly diminished during the past decade. The development of transoral endoscopic laser microsurgery (TLS), improvements in delivery of radiation therapy (RT) and the advent of multimodality protocols, particularly concomitant chemoradiotherapy (CCRT) have supplanted the previously standard techniques of open partial laryngectomy for early cancer and total laryngectomy followed by adjuvant RT for advanced cancer. A review of the recent literature revealed virtually no new reports of conventional conservation surgery as initial treatment for early stage glottic and supraglottic cancer. TLS and RT, with or without laser surgery or CCRT, have become the standard initial treatments for T1, T2 and selected T3 laryngeal cancer. Photodynamic therapy (PDT) may have an emerging role in the treatment of early laryngeal cancer. Anterior commissure involvement presents particular difficulties in application of TLS, although no definitive conclusions have been reached with regard to optimal treatment of these lesions. Results of TLS are equivalent to those obtained by conventional conservation surgery, with considerably less morbidity, less hospital time and better postoperative function. Oncologic results of TLS and RT are equivalent for glottic cancer, but with better voice results for RT in patients who require more extensive cordectomy. The preferred treatment for early supraglottic cancer, particularly for bulkier or T3 lesions is TLS, with or without postoperative RT. The Veterans Administration Study published in 1991 established the fact that the response to neoadjuvant CT predicts the response of a tumor to RT. Patients with advanced tumors that responded either partially or completely to CT were treated with RT, and total laryngectomy was reserved for non-responders. This resulted in the ability to preserve the larynx in a significant number of patients with locally advanced laryngeal cancer, while

  14. Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR-200b.

    Science.gov (United States)

    Zhang, Shaorong; Zhang, Guanli; Liu, Jingying

    2016-08-01

    Long noncoding RNA PVT1 has been reported to be dysregulated and play vital roles in a variety of cancers. However, the functions and molecular mechanisms of PVT1 in cervical cancer remain unclear. The objective of this study was to investigate the expression, clinical significance, biological roles, and underlying functional mechanisms of PVT1 in cervical cancer. Our results revealed that PVT1 is upregulated in cervical cancer tissues. Enhanced expression of PVT1 is associated with larger tumor size, advanced International Federation of Gynecology and Obstetrics stage, and poor prognosis of cervical cancer patients. Using gain-of-function and loss-of-function approaches, we demonstrated that overexpression of PVT1 promotes cervical cancer cells proliferation, cell cycle progression and migration, and depletion of PVT1 inhibits cervical cancer cell proliferation, cell cycle progression, and migration. Mechanistically, we verified that PVT1 binds to EZH2, recruits EZH2 to the miR-200b promoter, increases histone H3K27 trimethylation level on the miR-200b promoter, and inhibits miR-200b expression. Furthermore, the effects of PVT1 on cervical cell proliferation and migration depend upon silencing of miR-200b. Taken together, our findings confirmed that PVT1 functions as an oncogene in cervical cancer and indicated that PVT1 is not only an important prognostic marker, but also a potential therapy target for cervical cancer. PMID:27272214

  15. Retrotransposon-Encoded Reverse Transcriptase in the Genesis, Progression and Cellular Plasticity of Human Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sinibaldi-Vallebona, Paola; Matteucci, Claudia [Department of Experimental Medicine and Biochemical Sciences, University ‘Tor Vergata’, Rome (Italy); Spadafora, Corrado, E-mail: cspadaf@tin.it [Italian National Institute of Health (ISS), Rome (Italy)

    2011-03-07

    LINE-1 (Long Interspersed Nuclear Elements) and HERVs (Human Endogenous Retroviruses) are two families of autonomously replicating retrotransposons that together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly those encoding the reverse transcriptase (RT) enzyme, are generally expressed at low levels in differentiated cells, but their expression is upregulated in transformed cells and embryonic tissues. Here we discuss a recently discovered RT-dependent mechanism that operates in tumorigenesis and reversibly modulates phenotypic and functional variations associated with tumor progression. Downregulation of active LINE-1 elements drastically reduces the tumorigenic potential of cancer cells, paralleled by reduced proliferation and increased differentiation. Pharmacological RT inhibitors (e.g., nevirapine and efavirenz) exert similar effects on tumorigenic cell lines, both in culture and in animal models. The HERV-K family play a distinct complementary role in stress-dependent transition of melanoma cells from an adherent, non-aggressive, to a non-adherent, highly malignant, growth phenotype. In synthesis, the retrotransposon-encoded RT is increasingly emerging as a key regulator of tumor progression and a promising target in a novel anti-cancer therapy.

  16. The Role of Pulmonary Veins in Cancer Progression from a Computed Tomography Viewpoint

    Science.gov (United States)

    Chang, Hung; Liao, Tzu-Yao; Wen, Ming-Sheng; Yu, Chih-Teng

    2016-01-01

    Background. We studied the role of pulmonary veins in cancer progression using computed tomography (CT) scans. Methods. We obtained data from 260 patients with pulmonary vein obstruction syndrome (PVOS). We used CT scans to investigate pulmonary lesions in relation to pulmonary veins. We divided the lesions into central and peripheral lesions by their anatomical location: in the lung parenchymal tissue or pulmonary vein; in the superior or inferior pulmonary vein; and by unilateral or bilateral presence in the lungs. Results. Of the 260 PVOS patients, 226 (87%) had central lesions, 231 (89%) had peripheral lesions, and 190 (75%) had mixed central and peripheral lesions. Among the 226 central lesions, 93% had lesions within the superior pulmonary vein, either bilaterally or unilaterally. Among the 231 peripheral lesions, 65% involved bilateral lungs, 70% involved lesions within the inferior pulmonary veins, and 23% had obvious metastatic extensions into the left atrium. All patients exhibited nodules within their pulmonary veins. The predeath status included respiratory failure (40%) and loss of consciousness (60%). Conclusion. CT scans play an important role in following tumor progression within pulmonary veins. Besides respiratory distress, PVOS cancer cells entering centrally can result in cardiac and cerebral events and loss of consciousness or can metastasize peripherally from the pulmonary veins to the lungs.

  17. Network analysis of breast cancer progression and reversal using a tree-evolving network algorithm.

    Directory of Open Access Journals (Sweden)

    Ankur P Parikh

    2014-07-01

    Full Text Available The HMT3522 progression series of human breast cells have been used to discover how tissue architecture, microenvironment and signaling molecules affect breast cell growth and behaviors. However, much remains to be elucidated about malignant and phenotypic reversion behaviors of the HMT3522-T4-2 cells of this series. We employed a "pan-cell-state" strategy, and analyzed jointly microarray profiles obtained from different state-specific cell populations from this progression and reversion model of the breast cells using a tree-lineage multi-network inference algorithm, Treegl. We found that different breast cell states contain distinct gene networks. The network specific to non-malignant HMT3522-S1 cells is dominated by genes involved in normal processes, whereas the T4-2-specific network is enriched with cancer-related genes. The networks specific to various conditions of the reverted T4-2 cells are enriched with pathways suggestive of compensatory effects, consistent with clinical data showing patient resistance to anticancer drugs. We validated the findings using an external dataset, and showed that aberrant expression values of certain hubs in the identified networks are associated with poor clinical outcomes. Thus, analysis of various reversion conditions (including non-reverted of HMT3522 cells using Treegl can be a good model system to study drug effects on breast cancer.

  18. EFFECTS OF MUTATION AND EXPRESSION OF PTEN GENE mRNA ON TUMORIGENESIS AND PROGRESSION OF EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 郑华川; 杨雪飞; 孙丽梅; 辛彦

    2004-01-01

    Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary (n = 5), ovarian cyst (n =5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60), and ovarian cancer cell line (n= 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clinicopathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5 (7.1%) cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst (P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05). Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.

  19. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Beauchemin C

    2014-06-01

    Full Text Available Catherine Beauchemin,1 Dan Cooper,2 Marie-Ève Lapierre,1 Louise Yelle,3 Jean Lachaine11Université de Montréal, Faculté de pharmacie, Montreal, 2Institut national d'excellence en santé et en services sociaux (INESSS, 3Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, CanadaBackground: Progression-free survival (PFS and time to progression (TTP are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS remains a matter of uncertainty in metastatic breast cancer (mBC. This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach.Methods: We conducted a systematic literature review according to the PICO method: 'Population' consisted of women with mBC; 'Interventions' and 'Comparators' were standard treatments for mBC or best supportive care; 'Outcomes' of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP.Results: A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01. Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01. The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172 + 1.753 (95% CI 1.307–2.198 × ΔPFS (R2=0.86.Conclusion: Results of

  20. A quantitative assessment of changing trends in internet usage for cancer information.

    LENUS (Irish Health Repository)

    McHugh, Seamus M

    2012-02-01

    BACKGROUND: The internet is an important source of healthcare information. To date, assessment of its use as a source of oncologic information has been restricted to retrospective surveys. METHODS: The cancer-related searches of approximately 361,916,185 people in the United States and the United Kingdom were examined. Data were collected from two separate 100-day periods in 2008 and 2010. RESULTS: In 2008, there were 97,531 searches. The majority of searches related to basic cancer information (18,700, 19%), followed by treatment (8404, 9%) and diagnosis (6460, 7%). This compares with 179,025 searches in 2010 representing an increase of 183%. In 2008 breast cancer accounted for 21,102 (21%) individual searches, increasing to 85,825 searches in 2010. In 2010 a total of 0.2% (321) of searches focused on litigation, with those searching for breast cancer information most likely to research this topic (P=0.000). CONCLUSION: Use of the internet as a source of oncological information is increasing rapidly. These searches represent the most sensitive information relating to cancer, including prognosis and litigation. It is imperative now that efforts are made to ensure the reliability and comprehensiveness of this information.

  1. Trends in breast cancer mortality in Sweden before and after implementation of mammography screening.

    Directory of Open Access Journals (Sweden)

    Jari Haukka

    Full Text Available BACKGROUND: Incidence-based mortality modelling comparing the risk of breast cancer death in screened and unscreened women in nine Swedish counties has suggested a 39% risk reduction in women 40 to 69 years old after introduction of mammography screening in the 1980s and 1990s. OBJECTIVE: We evaluated changes in breast cancer mortality in the same nine Swedish counties using a model approach based on official Swedish breast cancer mortality statistics, robust to effects of over-diagnosis and treatment changes. Using mortality data from the NordCan database from 1974 until 2003, we estimated the change in breast cancer mortality before and after introduction of mammography screening in at least the 13 years that followed screening start. RESULTS: Breast mortality decreased by 16% (95% CI: 9 to 22% in women 40 to 69, and by 11% (95% CI: 2 to 20% in women 40 to 79 years of age. DISCUSSION: Without individual data it is impossible to completely separate the effects of improved treatment and health service organisation from that of screening, which would bias our results in favour of screening. There will also be some contamination of post-screening mortality from breast cancer diagnosed prior to screening, beyond our attempts to adjust for delayed benefit. This would bias against screening. However, our estimates from publicly available data suggest considerably lower benefits than estimates based on comparison of screened versus non-screened women.

  2. Trends in Clinically Significant Pain Prevalence Among Hospitalized Cancer Patients at an Academic Hospital in Taiwan: A Retrospective Cohort Study.

    Science.gov (United States)

    Wang, Wei-Yun; Ho, Shung-Tai; Wu, Shang-Liang; Chu, Chi-Ming; Sung, Chun-Sung; Wang, Kwua-Yun; Liang, Chun-Yu

    2016-01-01

    Clinically significant pain (CSP) is one of the most common complaints among cancer patients during repeated hospitalizations, and the prevalence ranges from 24% to 86%. This study aimed to characterize the trends in CSP among cancer patients and examine the differences in the prevalence of CSP across repeated hospitalizations. A hospital-based, retrospective cohort study was conducted at an academic hospital. Patient-reported pain intensity was assessed and recorded in a nursing information system. We examined the differences in the prevalence of worst pain intensity (WPI) and last evaluated pain intensity (LPI) of ≥ 4 or ≥ 7 points among cancer inpatients from the 1st to the 18th hospitalization. Linear mixed models were used to determine the significant difference in the WPI and LPI (≥ 4 or ≥ 7 points) at each hospitalization. We examined 88,133 pain scores from the 1st to the 18th hospitalization among cancer patients. The prevalence of the 4 CSP types showed a trend toward a reduction from the 1st to the 18th hospitalization. There was a robust reduction in the CSP prevalence from the 1st to the 5th hospitalization, except in the case of LPI ≥ 7 points. The prevalence of a WPI ≥ 4 points was significantly higher (0.240-fold increase) during the 1st hospitalization than during the 5th hospitalization. For the 2nd, 3rd, and 4th hospitalizations, there was a significantly higher prevalence of a WPI ≥ 4 points compared with the 5th hospitalization. We also observed significant reductions in the prevalence of a WPI ≥ 7 points during the 1st to the 4th hospitalizations, an LPI ≥ 4 points during the 1st to the 3rd hospitalizations, and an LPI ≥ 7 points during the 1st to the 2nd hospitalization. Although the prevalence of the 4 CSP types decreased gradually, it is impossible to state the causative factors on the basis of this observational and descriptive study. The next step will examine the factors that determine the CSP prevalence among cancer

  3. miRNA dynamics in tumor-infiltrating myeloid cells modulating tumor progression in pancreatic cancer.

    Science.gov (United States)

    Mühlberg, Leonie; Kühnemuth, Benjamin; Costello, Eithne; Shaw, Victoria; Sipos, Bence; Huber, Magdalena; Griesmann, Heidi; Krug, Sebastian; Schober, Marvin; Gress, Thomas M; Michl, Patrick

    2016-06-01

    Myeloid cells including tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) are known as important mediators of tumor progression in solid tumors such as pancreatic cancer. Infiltrating myeloid cells have been identified not only in invasive tumors, but also in early pre-invasive pancreatic intraepithelial precursor lesions (PanIN). The functional dynamics of myeloid cells during carcinogenesis is largely unknown. We aimed to systematically elucidate phenotypic and transcriptional changes in infiltrating myeloid cells during carcinogenesis and tumor progression in a genetic mouse model of pancreatic cancer. Using murine pancreatic myeloid cells isolated from the genetic mouse model at different time points during carcinogenesis, we examined both established markers of macrophage polarization using RT-PCR and FACS as well as transcriptional changes focusing on miRNA profiling. Myeloid cells isolated during carcinogenesis showed a simultaneous increase of established markers of M1 and M2 polarization during carcinogenesis, indicating that phenotypic changes of myeloid cells during carcinogenesis do not follow the established M1/M2 classification. MiRNA profiling revealed distinct regulations of several miRNAs already present in myeloid cells infiltrating pre-invasive PanIN lesions. Among them miRNA-21 was significantly increased in myeloid cells surrounding both PanIN lesions and invasive cancers. Functionally, miRNA-21-5p and -3p altered expression of the immune-modulating cytokines CXCL-10 and CCL-3 respectively. Our data indicate that miRNAs are dynamically regulated in infiltrating myeloid cells during carcinogenesis and mediate their functional phenotype by facilitating an immune-suppressive tumor-promoting micro-milieu. PMID:27471627

  4. Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression*

    Science.gov (United States)

    Mills, Lisa D.; Zhang, Lizhi; Marler, Ronald; Svingen, Phyllis; Fernandez-Barrena, Maite G.; Dave, Maneesh; Bamlet, William; McWilliams, Robert R.; Petersen, Gloria M.; Faubion, William; Fernandez-Zapico, Martin E.

    2014-01-01

    The role of GLI1 in pancreatic tumor initiation promoting the progression of preneoplastic lesions into tumors is well established. However, its function at later stages of pancreatic carcinogenesis remains poorly understood. To address this issue, we crossed the gli1 knock-out (GKO) animal with cre-dependent pancreatic activation of oncogenic kras concomitant with loss of the tumor suppressor tp53 (KPC). Interestingly, in this model, GLI1 played a tumor-protective function, where survival of GKO/KPC mice was reduced compared with KPC littermates. Both cohorts developed pancreatic cancer without significant histopathological differences in survival studies. However, analysis of mice using ultrasound-based imaging at earlier time points showed increased tumor burden in GKO/KPC mice. These animals have larger tumors, decreased body weight, increased lactate dehydrogenase production, and severe leukopenia. In vivo and in vitro expression studies identified FAS and FAS ligand (FASL) as potential mediators of this phenomenon. The FAS/FASL axis, an apoptotic inducer, plays a role in the progression of pancreatic cancer, where its expression is usually lost or significantly reduced in advanced stages of the disease. Chromatin immunoprecipitation and reporter assays identified FAS and FASL as direct targets of GLI1, whereas GKO/KPC mice showed lower levels of this ligand compared with KPC animals. Finally, decreased levels of apoptosis were detected in tumor tissue in the absence of GLI1 by TUNEL staining. Together, these findings define a novel pathway regulated by GLI1 controlling pancreatic tumor progression and provide a new theoretical framework to help with the design and analysis of trials targeting GLI1-related pathways. PMID:24737325

  5. Frederick W. Alt received the 2015 Szent-Györgi Prize forProgress inCancer Research

    Institute of Scientific and Technical Information of China (English)

    PeterScully; JieZhao; SujuanBa

    2016-01-01

    The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientiifc award established by the National Foundation for Cancer Research (NFCR)—a leading cancer research charitable organization in the United States that is committed to supporting scientiifc research and public education relating to the prevention, early diagnosis, better treatments, and ultimately, a cure for cancer. Each year, the Szent-Györgyi Prize honors an outstanding researcher, nominated by colleagues or peers, who has contributed outstanding, signiifcant research to the ifght against cancer, and whose accomplishments have helped improve treatment options for cancer patients. The Prize also promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. This report highlights the pio-neering work led by the 2015 Prize winner, Dr. Frederick Alt. Dr. Alt’s work in the area of cancer genetics over four decades has helped to shape the very roots of modern cancer research. His work continues to profoundly impact the approaches that doctors around the globe use to diagnose and treat cancer. In particular, his seminal discoveries of gene ampliifcation and his pioneering work on molecular mechanisms of DNA damage repair have helped to usher in the era of genetically targeted therapy and personalized medicine.

  6. James P. Allison received the 2014 Szent-Györgi Prize for Progress in Cancer Research

    Institute of Scientific and Technical Information of China (English)

    Jie Zhao,Peter Scully; Sujuan Ba

    2014-01-01

    The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientific award established by the National Foundation for Cancer Research (NFCR)-a leading cancer research charitable organization in the United States that is committed to supporting innovative cancer research on the global scale that aims to cure cancer. Each year, the Szent-Györgyi Prize honors an outstanding researcher whose original discoveries have expanded our understanding of cancer and resulted in notable advances in cancer prevention, diagnosis, or treatment. The prize also promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. This report highlights the history and mission of the Szent-Györgyi Prize, its role in promoting discovery-oriented cancer research, and the pioneering work led by the 2014 prize winner, Dr. James Alison. Dr. Alison’s work in the area of cancer immunotherapy led to the successful development of immune checkpoint therapy, and the first drug approved by the United States Food and Drug Administration for the treatment of metastatic melanoma.

  7. Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Qing; Yu, Tao; Ren, Yao-Yao; Gong, Ting; Zhong, Dian-Sheng, E-mail: zhongdsyx@126.com

    2014-11-07

    Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression.

  8. KAP1 promotes proliferation and metastatic progression of breast cancer cells.

    Science.gov (United States)

    Addison, Joseph B; Koontz, Colton; Fugett, James H; Creighton, Chad J; Chen, Dongquan; Farrugia, Mark K; Padon, Renata R; Voronkova, Maria A; McLaughlin, Sarah L; Livengood, Ryan H; Lin, Chen-Chung; Ruppert, J Michael; Pugacheva, Elena N; Ivanov, Alexey V

    2015-01-15

    KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers. KAP1 silencing in breast cancer cells reduced proliferation and inhibited the growth and metastasis of tumor xenografts. Conversely, KAP1 overexpression stimulated cell proliferation and tumor growth. In cells where KAP1 was silenced, we identified multiple downregulated genes linked to tumor progression and metastasis, including EREG/epiregulin, PTGS2/COX2, MMP1, MMP2, and CD44, along with downregulation of multiple KRAB-ZNF proteins. KAP1-dependent stabilization of KRAB-ZNF required direct interactions with KAP1. Together, our results show that KAP1-mediated stimulation of multiple KRAB-ZNF contributes to the growth and metastasis of breast cancer.

  9. Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

    International Nuclear Information System (INIS)

    Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression

  10. Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer.

    Science.gov (United States)

    Friedrich, Teresa; Söhn, Michaela; Gutting, Tobias; Janssen, Klaus-Peter; Behrens, Hans-Michael; Röcken, Christoph; Ebert, Matthias P A; Burgermeister, Elke

    2016-06-01

    Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive. PPARγ-agonist increased expression of endogenous DOK1 and interaction with PPARγ. Forward translation of this cell-based signaling model predicted compartmentalization of DOK1 in patients. In a large series of CRC patients, loss of DOK1 protein was associated with poor prognosis at early tumor stages (*p=0.001; n=1492). In tumors with cytoplasmic expression of DOK1, survival was improved, whereas nuclear localization of DOK1 correlated with poor outcome, indicating that compartmentalization of DOK1 is critical for CRC progression. Thus, DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARγ-agonist, may constitute a potential target for future cancer treatments. PMID:27428427

  11. Progress in gastric cancer surgery in Japan%日本胃癌外科治疗的进展

    Institute of Scientific and Technical Information of China (English)

    丸山圭一; 陈雨信

    2008-01-01

    The.progress in diagnosis and surgical treatment of gastric cancer contributes to the raised diagnosis rate and 5-year survival rate of gastric cancer patients in Japan. According to the clinical data of 273 142 Japanese gastric cancer patients from 1962 to 1991, the proportion of patients with stage I gastric cancer was increased from 22.5% to 58.1%, and the accumulative 5-year survival rate from 37.5% to 68.8%. The improvement of the accumulative 5-year survival rate was remarkable for patients with stage Ⅱ gastric cancer (from 47.7% to 70.3%) and stage Ⅲ gastric cancer (from 26.4% to 45.0%).

  12. HMGA1 induces intestinal polyposis in transgenic mice and drives tumor progression and stem cell properties in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Amy Belton

    Full Text Available BACKGROUND: Although metastatic colon cancer is a leading cause of cancer death worldwide, the molecular mechanisms that enable colon cancer cells to metastasize remain unclear. Emerging evidence suggests that metastatic cells develop by usurping transcriptional networks from embryonic stem (ES cells to facilitate an epithelial-mesenchymal transition (EMT, invasion, and metastatic progression. Previous studies identified HMGA1 as a key transcription factor enriched in ES cells, colon cancer, and other aggressive tumors, although its role in these settings is poorly understood. METHODS/PRINCIPAL FINDINGS: To determine how HMGA1 functions in metastatic colon cancer, we manipulated HMGA1 expression in transgenic mice and colon cancer cells. We discovered that HMGA1 drives proliferative changes, aberrant crypt formation, and intestinal polyposis in transgenic mice. In colon cancer cell lines from poorly differentiated, metastatic tumors, knock-down of HMGA1 blocks anchorage-independent cell growth, migration, invasion, xenograft tumorigenesis and three-dimensional colonosphere formation. Inhibiting HMGA1 expression blocks tumorigenesis at limiting dilutions, consistent with depletion of tumor-initiator cells in the knock-down cells. Knock-down of HMGA1 also inhibits metastatic progression to the liver in vivo. In metastatic colon cancer cells, HMGA1 induces expression of Twist1, a gene involved in embryogenesis, EMT, and tumor progression, while HMGA1 represses E-cadherin, a gene that is down-regulated during EMT and metastatic progression. In addition, HMGA1 is among the most enriched genes in colon cancer compared to normal mucosa. CONCLUSIONS: Our findings demonstrate for the first time that HMGA1 drives proliferative changes and polyp formation in the intestines of transgenic mice and induces metastatic progression and stem-like properties in colon cancer cells. These findings indicate that HMGA1 is a key regulator, both in metastatic

  13. The effect of progressive resistance training on lean body mass in post-treatment cancer patients - A systematic review

    DEFF Research Database (Denmark)

    Lønbro, Simon

    2014-01-01

    Loss of lean body mass is a common problem in many post-treatment cancer patients and may negatively affect physical capacity in terms of maximal muscle strength and functional performance. The purpose of this study was to systematically review the scientific evidence on the effect of progressive...... resistance training on lean body mass in post-treatment cancer patients. A comprehensive literature search was conducted and ultimately 12 studies were included. Methodological quality of the included studies was evaluated using the PEDro scale and the effect of progressive resistance training was reported...... on 12 heterogenic studies there is moderate evidence supporting a positive effect of progressive resistance training on lean body mass in post-treatment cancer patients....

  14. Lung cancer trends: smoking, obesity, and sex assessed in the Staten Island University’s lung cancer patients

    Directory of Open Access Journals (Sweden)

    Gupta S

    2014-07-01

    Full Text Available Shilpi Gupta,1 Samer Hassan,1 Vijaya R Bhatt,2 Houssein Abdul Sater,1 Asma Dilawari31Hematology-Oncology, Staten Island University Hospital, Staten Island, NY, USA; 2Hematology-Oncology, Nebraska Medical Ctr, Omaha, NE, USA; 3Hematology-Oncology, MedStar Georgetown University Hospital, Olney, Maryland, USAIntroduction: The incidence of lung cancer in the United States decreased by 1.8% from 1991 to 2005 while it increased by 0.5% in females. We assessed whether nonsmokers afflicted with lung cancer at Staten Island University Hospital are disproportionately female in comparison to national averages. We also evaluated different factors including race, histology, and body mass index (BMI in correlation with smoking history.Methods: A retrospective chart review was conducted from 2005 to 2011 on 857 patients. Patients were divided into two groups according to their smoking status: current or ever-smokers, and former or never-smokers. A chi-square test for categorical data and multivariate logistic regression analyses was used to study the relation between BMI and the other clinical and demographic data.Results: Forty-nine percent of patients were men and 51% were women with a mean age at diagnosis of 67.8 years. Current smokers were most common (50.2% followed by ever-smokers (18.2%, former smokers (15.8% and never-smokers (15.6%. Forty eight percent had stage IV lung cancer upon presentation. Never-smokers with lung cancer were 24 times more likely to be females. However, the proportion of female former smokers (31.6% was lower than the proportion of male former smokers (68.4% (P=0.001. There was no significant association between American Joint Committee on Cancer (AJCC stage, sex, race, and histological type in the two smoking groups. Current/ever-smokers tended to be younger at age of diagnosis (P=0.0003. BMI was lower in the current/ever-smokers (26.8 kg/m2 versus former/never-smokers (28.8 in males (P=0.0005. BMI was significantly higher in

  15. Proinflammatory Cytokines in Prostate Cancer Development and Progression Promoted by High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Hua Xu

    2015-01-01

    Full Text Available Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa development and progression promoted by high-fat diet (HFD. Methods. TRAMP (transgenic adenocarcinoma mouse prostate mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study. Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33% were from the normal diet group and 10 (27.78% from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P=0.032. Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P=0.045. Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice. Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.

  16. Imaging and intervention in prostate cancer: Current perspectives and future trends

    Directory of Open Access Journals (Sweden)

    Sanjay Sharma

    2014-01-01

    Full Text Available Prostate cancer is the commonest malignancy in men that causes significant morbidity and mortality worldwide. Screening by digital rectal examination (DRE and serum prostate-specific antigen (PSA is used despite its limitations. Gray-scale transrectal ultrasound (TRUS, used to guide multiple random prostatic biopsies, misses up to 20% cancers and frequently underestimates the grade of malignancy. Increasing the number of biopsy cores marginally increases the yield. Evolving techniques of real-time ultrasound elastography (RTE and contrast-enhanced ultrasound (CEUS are being investigated to better detect and improve the yield by allowing "targeted" biopsies. Last decade has witnessed rapid developments in magnetic resonance imaging (MRI for improved management of prostate cancer. In addition to the anatomical information, it is capable of providing functional information through diffusion-weighted imaging (DWI, magnetic resonance spectroscopy (MRS, and dynamic contrast-enhanced (DCE MRI. Multi-parametric MRI has the potential to exclude a significant cancer in majority of cases. Inclusion of MRI before prostatic biopsy can reduce the invasiveness of the procedure by limiting the number of cores needed to make a diagnosis and support watchful waiting in others. It is made possible by targeted biopsies as opposed to random. With the availability of minimally invasive therapeutic modalities like high-intensity focused ultrasound (HIFU and interstitial laser therapy, detecting early cancer is even more relevant today. [18F]--fluorodeoxyglucose positron emission tomography/computed tomography ( 18 FDG PET/CT has no role in the initial evaluation of prostate cancer. Choline PET has been recently found to be more useful. Fluoride-PET has a higher sensitivity and resolution than a conventional radionuclide bone scan in detecting skeletal metastases.

  17. MicroRNA-187-5p suppresses cancer cell progression in non-small cell lung cancer (NSCLC) through down-regulation of CYP1B1.

    Science.gov (United States)

    Mao, Ming; Wu, Zhouqing; Chen, Jiakuan

    2016-09-16

    Lung cancer remains a leading cause of cancer-associated mortality worldwide and non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related deaths. Identifying novel molecular biomarker that can inhibit the progression of lung cancer will facilitate the development of new treatment strategies. Herein, we demonstrated that miR-187-5p is a tumor-suppressor miRNA in NSCLC progression. We found that expression of miR-187-5p was decreased obviously in NSCLC tissues. Down-regulation of miR-187-5p was associated with TNM stage and postoperative survival. Overexpression of miR-187-5p inhibited the growth and metastasis of NSCLC cells. The CYP1B1 was a direct target of miR-187-5p and promoted the growth and metastasis of NSCLC cells. Further study showed that CYP1B1 could reverse the inhibitory effect of miR-187-5p on growth and metastasis of NSCLC cells. Taken together, our data highlight the pivotal role of miR-187-5p in the progression of NSCLC. Thus, miR-187-5p may be a potential prognostic marker and of treatment relevance for NSCLC progression intervention. PMID:27495872

  18. Trends in upper gastro-intestinal cancer among the elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Schønnemann, Katrine R; Mortensen, Michael B; Krogh, Merete;

    2016-01-01

    Background Upper gastro-intestinal cancer (UGIC) includes malignancies in esophagus, stomach and small intestine, and represents some of the most frequent malignancies worldwide. The aim of the present analysis was to describe incidence, mortality and survival in UGIC patients in Denmark from 1980...

  19. ORGAN-SPARING SURGERY FOR RECTAL CANCER: EVOLUTION, CURRENT TRENDS, AND PROSPECTS

    Directory of Open Access Journals (Sweden)

    R. I. Tamrazov

    2013-01-01

    Full Text Available The article describes the main stages of the development of sphincter-saving surgery for rectal cancer. An historical look at this issue from the standpoint of research of past years in our country and abroad, as well as analysis of current sphincter-preserving surgery and future directions in this area.

  20. Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations

    DEFF Research Database (Denmark)

    Skakkebaek, N E; Rajpert-De Meyts, Ewa; Jørgensen, N;

    2007-01-01

    in TGCC rates of a population may be 'whistle blowers' of other reproductive health problems. As cancer registries are often of excellent quality - in contrast to registries for congenital abnormalities - health authorities should consider an increase in TGCC as a warning that other reproductive health...

  1. Trends in Mortality from Ischemic Heart Disease, Stroke, and Stomach Cancer: from past to future

    NARCIS (Netherlands)

    M. Amiri (Masoud)

    2010-01-01

    textabstractThe common occurrence of chronic diseases – such as ischemic heart diseases (IHD, stroke, and stomach cancer in most populations and the attendant mortality, loss of independence, impaired quality of life, and social and economic costs are compelling reasons for public health concern. A

  2. An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jungsun Kim

    2013-06-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC lines were not of the expected cancer genotype, one PDAC line, 10–22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

  3. The global state of palliative care-progress and challenges in cancer care.

    Science.gov (United States)

    Reville, Barbara; Foxwell, Anessa M

    2014-07-01

    All persons have a right to palliative care during cancer treatment and at the end-of-life. The World Health Organization (WHO) defines palliative care as a medical specialty that addresses physical, psychological, social, legal, and spiritual domains of care by an interdisciplinary team of professional and lay health care providers. Widespread adoption of this universal definition will aid policy development and educational initiatives on a national level. The need for palliative care is expanding due to the aging of the world's population and the increase in the rate of cancer in both developed and developing countries. However, in one third of the world there is no access to palliative care for persons with serious or terminal illness. Palliative care improves symptoms, most frequently pain, and improves quality of life for patients and their families, especially in the terminal disease phase. Accessibility to palliative care services, adequately trained health care professionals, availability of essential medicines, and gaps in education vary greatly throughout the world. Pain management is an integral concept in the practice of palliative care; however, opioiphobia, insufficient supply of opioids, and regulatory restrictions contribute to undue suffering for millions. Ongoing advocacy efforts call for increased awareness, palliative care integration with cancer care, and public and professional education. Enacting necessary change will require the engagement of health ministries and the recognition of the unique needs and resources of each country. The aim of this review is to examine progress in palliative care development and explore some of the barriers influencing cancer care across the globe. PMID:25841689

  4. Net Platelet Angiogenic Activity (NPAA) Correlates with Progression and Prognosis of Non-Small Cell Lung Cancer

    OpenAIRE

    Lijuan Yao; Hang Dong; Yiqin Luo; Jianping Du; Wen Hu

    2014-01-01

    Circulating platelets are abundant sources of angiogensis molecules for the tumor vasculature affecting tumor growth and metastasis. The relationship between non-small cell lung cancer (NSCLC) and intra-platelet levels of VEGF, TSP-1 and net platelet angiogenic activity (NPAA) is unclear. The aim of this study was to better understand the role of these factors in the progression of NSCLC cancer and to assess its clinical significance. Platelet VEGF and TSP-1 and NPAA were measured preoperativ...

  5. Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression.

    Science.gov (United States)

    Li, Min; Zhang, Yuqing; Liu, Zijuan; Bharadwaj, Uddalak; Wang, Hao; Wang, Xinwen; Zhang, Sheng; Liuzzi, Juan P; Chang, Shou-Mei; Cousins, Robert J; Fisher, William E; Brunicardi, F Charles; Logsdon, Craig D; Chen, Changyi; Yao, Qizhi

    2007-11-20

    Zinc is an essential trace element and catalytic/structural component used by many metalloenzymes and transcription factors. Recent studies indicate a possible correlation of zinc levels with the cancer risk; however, the exact role of zinc and zinc transporters in cancer progression is unknown. We have observed that a zinc transporter, ZIP4 (SLC39A4), was substantially overexpressed in 16 of 17 (94%) clinical pancreatic adenocarcinoma specimens compared with the surrounding normal tissues, and ZIP4 mRNA expression was significantly higher in human pancreatic cancer cells than human pancreatic ductal epithelium (HPDE) cells. This indicates that aberrant ZIP4 up-regulation may contribute to the pancreatic cancer pathogenesis and progression. We studied the effects of ZIP4 overexpression in pancreatic cancer cell proliferation in vitro and pancreatic cancer progression in vivo. We found that forced expression of ZIP4 increased intracellular zinc levels, increased cell proliferation by 2-fold in vitro, and significantly increased tumor volume by 13-fold in the nude mice model with s.c. xenograft compared with the control cells. In the orthotopic nude mice model, overexpression of ZIP4 not only increased the primary tumor weight (7.2-fold), it also increased the peritoneal dissemination and ascites incidence. Moreover, increased cell proliferation and higher zinc content were also observed in the tumor tissues that overexpressed ZIP4. These data reveal an important outcome of aberrant ZIP4 expression in contributing to pancreatic cancer pathogenesis and progression. It may suggest a therapeutic strategy whereby ZIP4 is targeted to control pancreatic cancer growth. PMID:18003899

  6. Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression.

    Science.gov (United States)

    Li, Min; Zhang, Yuqing; Liu, Zijuan; Bharadwaj, Uddalak; Wang, Hao; Wang, Xinwen; Zhang, Sheng; Liuzzi, Juan P; Chang, Shou-Mei; Cousins, Robert J; Fisher, William E; Brunicardi, F Charles; Logsdon, Craig D; Chen, Changyi; Yao, Qizhi

    2007-11-20

    Zinc is an essential trace element and catalytic/structural component used by many metalloenzymes and transcription factors. Recent studies indicate a possible correlation of zinc levels with the cancer risk; however, the exact role of zinc and zinc transporters in cancer progression is unknown. We have observed that a zinc transporter, ZIP4 (SLC39A4), was substantially overexpressed in 16 of 17 (94%) clinical pancreatic adenocarcinoma specimens compared with the surrounding normal tissues, and ZIP4 mRNA expression was significantly higher in human pancreatic cancer cells than human pancreatic ductal epithelium (HPDE) cells. This indicates that aberrant ZIP4 up-regulation may contribute to the pancreatic cancer pathogenesis and progression. We studied the effects of ZIP4 overexpression in pancreatic cancer cell proliferation in vitro and pancreatic cancer progression in vivo. We found that forced expression of ZIP4 increased intracellular zinc levels, increased cell proliferation by 2-fold in vitro, and significantly increased tumor volume by 13-fold in the nude mice model with s.c. xenograft compared with the control cells. In the orthotopic nude mice model, overexpression of ZIP4 not only increased the primary tumor weight (7.2-fold), it also increased the peritoneal dissemination and ascites incidence. Moreover, increased cell proliferation and higher zinc content were also observed in the tumor tissues that overexpressed ZIP4. These data reveal an important outcome of aberrant ZIP4 expression in contributing to pancreatic cancer pathogenesis and progression. It may suggest a therapeutic strategy whereby ZIP4 is targeted to control pancreatic cancer growth.

  7. NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells.

    Science.gov (United States)

    Chang, Xiaojing; Xu, Xiaoyang; Ma, Jinguo; Xue, Xiaoying; Li, Zhenhua; Deng, Peng; Zhang, Shuanglong; Zhi, Yu; Chen, Jing; Dai, Dongqiu

    2014-09-01

    N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.

  8. Mast Cells in Adjacent Normal Colon Mucosa rather than Those in Invasive Margin are Related to Progression of Colon Cancer

    Institute of Scientific and Technical Information of China (English)

    Qing Xia; Xiao-shi Zhang; Ying-bo Chen; Ya Ding; Xiao-jun Wu; Rui-qing Peng; Qiang Zhou; Jing Zeng; Jing-hui Hou; Xing Zhang; Yi-xin Zeng

    2011-01-01

    Objective:Mast cells (MC) reside in the mucosa of the digestive tract as the first line against bacteria and toxins.Clinical evidence has implied that the infiltration of mast cells in colorectal cancers is related to malignant phenotypes and a poor prognosis.This study compared the role of mast cells in adjacent normal colon mucosa and in the invasive margin during the progression of colon cancer.Methods:Specimens were obtained from 39 patients with colon adenomas and 155 patients with colon cancers treated at the Sun Yat-sen University Cancer Center between January 1999 and July 2004.The density of mast cells was scored by an immunohistochemical assay.The pattern of mast cell distribution and its relationship with dinicopathologic parameters and 5-year survival were analyzed.Results:The majority of mast cells were located in the adjacent normal colon mucosa,followed by the invasive margin and least in the cancer stroma.Mast cell count in adjacent normal colon mucosa (MCCadjacent) was associated with pathologic classification,distant metastases and hepatic metastases,although it was not a prognostic factor.In contrast,mast cell count in the invasive margin (MCCinvasive) was associated with neither the clinicopathlogic parameters nor overall survival.Conclusion:Mast cells in the adjacent normal colon mucosa were related to the progression of colon cancer,suggesting that mast cells might modulate tumor progression via a long-distance mechanism.

  9. Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression

    International Nuclear Information System (INIS)

    Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution. In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed. We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01). A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions

  10. SOXs in human prostate cancer: implication as progression and prognosis factors

    International Nuclear Information System (INIS)

    SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. Our data offer the convince

  11. Regional trends in breast cancer incidence and mortality in Denmark prior to mammographic screening

    DEFF Research Database (Denmark)

    Andreasen, A H; Andersen, K W; Madsen, Mette;

    1994-01-01

    To provide a basis for the evaluation of mammographic screening programmes in Denmark, a study was undertaken of the regional differences in breast cancer incidence and mortality. All 16 regions were followed for the 20 year period, 1970-89, before the start of the first population...... among women below age 60. The mortality was more stable, changing only from 24 to 28 (per 100,000 standardised WSP), but a significant increase occurred in the late 1980s. The study showed regional differences in both incidence and mortality of breast cancer in Denmark. Both the incidence......-based mammographic screening programme in the Copenhagen municipality in 1991. Multiplicative Poisson models were used for the analysis. In general, the incidence increased during this period from 55 to 70 [per 100,000 standardised world standard population (WSP)], and the analysis shows this to be most pronounced...

  12. Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy.

    Science.gov (United States)

    Pfütze, Katrin; Benner, Axel; Hoffmeister, Michael; Jansen, Lina; Yang, Rongxi; Bläker, Hendrik; Herpel, Esther; Ulrich, Alexis; Ulrich, Cornelia M; Chang-Claude, Jenny; Brenner, Hermann; Burwinkel, Barbara

    2015-12-01

    DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. Here, we describe that DNA methylation levels at CpG loci of hyaluronoglucosaminidase 2 (HYLA2) could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival. PMID:26453961

  13. Smartphone apps as a source of cancer information: changing trends in health information-seeking behavior.

    Science.gov (United States)

    Pandey, Ambarish; Hasan, Sayeedul; Dubey, Divyanshu; Sarangi, Sasmit

    2013-03-01

    There is an increased interest in smartphone applications as a tool for delivery of health-care information. There have been no studies which evaluated the availability and content of cancer-related smartphone applications. This study aims to identify and analyze cancer-related applications available on the Apple iTunes platform. The Apple iTunes store was searched for cancer-related smartphone applications on July 29, 2011. The content of the applications was analyzed for cost, type of information, validity, and involvement of health-care agencies. A total of 77 relevant applications were identified. There were 24.6 % apps uploaded by health-care agencies, and 36 % of the apps were aimed at health-care workers. Among the apps, 55.8 % provided scientifically validated data. The difference in scientific validity between the apps aimed at general population versus health-care professionals was statistically significant (P smartphone applications and encourage participation by health-care agencies to ensure patient safety. PMID:23275239

  14. Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Yilong Zhang

    2015-03-01

    Full Text Available The hepatocyte growth factor (HGF: MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents—either as therapeutic proteins or small molecules that target the HGF/MET pathway—have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed.

  15. Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice.

    Science.gov (United States)

    Gu, Jian-Wei; Young, Emily; Patterson, Sharla G; Makey, Kristina L; Wells, Jeremy; Huang, Min; Tucker, Kevan B; Miele, Lucio

    2011-05-15

    Obese postmenopausal women have a 50% higher risk of breast cancer than non-obese women. There is not an animal model that mimics postmenopausal obesity related to breast cancer progression. Using age-relevant C57BL/6 mice, this study determined whether postmenopausal obesity increases VEGF expression, tumor angiogenesis, and breast tumor growth. Ovariectomy (OVX) was performed in 12 sixty week-old female mice, then followed by a low-fat (5%, LF, n=6) or a high-fat (60%, HF, n=6) diet for 12 weeks. In the eighth week of the dietary program, 10(6) E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland. Tumor size was monitored for 4 weeks. Body weights were monitored weekly. At the end of the experiment, blood samples, visceral fat and tumors were collected for measuring VEGF expression using ELISA and intratumoral microvessel density (IMD) using CD31 immunochemistry. Body weight was significantly increased in OVX/HF mice, compared to OVX/LF group (55.3±1.7 vs. 41.5±1.5 g; p < 0.01). There was a two-fold increase in the ratio of visceral fat/BW in OVX/HF mice, compared to those in OVX/LF group (0.062±0.005 vs. 0.032±0.003; p < 0.01). Postmenopausal obesity significantly increased breast tumor weight over the control (4.62±0.63 vs. 1.98±0.27 g; p < 0.01) and IMD (173±3.7 vs. 139±4.3 IM#/mm^2; p < 0.01). Tumor VEGF levels were higher in OVX/HF mice, compared to OVX/LF group (73.3±3.8 vs. 49.5±4.3 pg/mg protein; p < 0.01). Plasma VEGF levels (69±7.1 vs. 48±3.5 pg/ml) and visceral fat VEGF levels (424.4±39.5 vs. 208.5±22.4 pg/mg protein) were significantly increased in OVX/HF mice, compared to OVX/LF group, respectively (n=6; p < 0.01). Interestingly, adipose tissue primary culture showed that subcutaneous fat released more VEGF, compared to visceral fat (6.77±1.14 vs. 0.94±0.16 pg/mg tissue; n=6; p < 0.01). These findings support the hypothesis that postmenopausal obesity promotes tumor angiogenesis and breast cancer

  16. A novel long non-coding RNA FGF14-AS2 is correlated with progression and prognosis in breast cancer.

    Science.gov (United States)

    Yang, Fan; Liu, Ye-huan; Dong, Si-yang; Ma, Rui-ming; Bhandari, Adheesh; Zhang, Xiao-hua; Wang, Ou-chen

    2016-02-12

    Breast cancer is diverse in their natural history and in their responsiveness to treatments. It is urgent to generate candidate biomarkers for the stratification of patients and personalization of therapy to avoid overtreatment or inadequate treatment. Long noncoding RNAs (lncRNAs) have been found to be pervasively transcribed in the genome and played critical roles in cancer progression. A lot of lncRNAs have been reported as potential prognostic biomarkers and therapeutic targets in multiple cancers. In this study, we demonstrated that FGF14 antisense RNA 2 (FGF14-AS2), a novel long non-coding RNA, was significantly down-regulated in breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Reduced expression of FGF14-AS2 was correlated with larger tumor size, more lymph node metastasis and advanced clinical stage in both cohorts. Kaplan-Meier analysis indicated that patients with lower FGF14-AS2 expression had a worse overall survival. Moreover, multivariate analysis revealed that decreased expression of FGF14-AS2 was an independent predictor of overall survival. Together, these results suggested that FGF14-AS2 involved in the progress of breast cancer and might act as a tumor suppressor gene. To the best of our knowledge, it was firstly reported that FGF14-AS2 was involved in cancer. This study provided a potential new marker and a target for gene therapy in breast cancer treatment. PMID:26820525

  17. Rho GTPase RhoJ is Associated with Gastric Cancer Progression and Metastasis

    Science.gov (United States)

    Kim, Chan; Yang, Hannah; Park, Intae; Chon, Hong Jae; Kim, Joo Hoon; Kwon, Woo Sun; Lee, Won Suk; Kim, Tae Soo; Rha, Sun Young

    2016-01-01

    Rho GTPases play a pivotal role in tumor progression by regulating tumor cell migration and invasion. However, the role of Rho GTPases in gastric cancer (GC) remains unexplored. This study aimed to investigate the clinical implications of RhoJ, which is an uncharted member of Rho family. RhoJ expression in human GC cell lines and surgical specimens from GC patients were analyzed. Moreover, in vitro gain-of-function analysis was performed to evaluate the malignant phenotypes of RhoJ-overexpressing GC cells. The extent of RhoJ expression varied among GC cell lines and GC patients. YCC-9 cell line displayed the strongest expression, while YCC-10, -11, and -16 showed scant expressions. Of the 70 GC patients, 34 (48.6%) had RhoJ expression in their GC tissue, and patients with high RhoJ expression had more diffuse type GC (73.5% vs. 41.7%), were at more advanced stages (stage III, IV: 85.3% vs. 58.4%), and had more frequent metastasis (47.1% vs. 11.1%), denoting that RhoJ has a potential role in GC progression and metastasis. High RhoJ expression significantly correlated with poor overall survival and recurrence-free survival after surgical resection of gastric cancer. Finally, In vitro gain-of-function experiments showed 41.3% enhanced motility and 60.4% enhanced invasiveness in RhoJ-overexpressing GC cells compared to control, with negligible difference in cell proliferation. Collectively, high RhoJ expression is an independent negative prognostic factor for the survival outcome of GC and correlated with the increased cell motility and invasiveness. PMID:27471571

  18. Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression

    Directory of Open Access Journals (Sweden)

    Mansukhani Mahesh

    2006-05-01

    Full Text Available Abstract Background Cervical Cancer (CC exhibits highly complex genomic alterations. These include hemizygous deletions at 4p15.3, 10q24, 5q35, 3p12.3, and 11q24, the chromosomal sites of Slit-Robo pathway genes. However, no candidate tumor suppressor genes at these regions have been identified so far. Slit family of secreted proteins modulates chemokine-induced cell migration of distinct somatic cell types. Slit genes mediate their effect by binding to its receptor Roundabout (Robo. These genes have shown to be inactivated by promoter hypermethylation in a number of human cancers. Results To test whether Slit-Robo pathway genes are targets of inactivation at these sites of deletion, we examined promoter hypermethylation of SLIT1, SLIT2, SLIT3, ROBO1, and ROBO3 genes in invasive CC and its precursor lesions. We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs in CC cell lines failed to effectively reactivate the down-regulated expression. These results suggest a complex mechanism of inactivation in the Slit-Robo pathway in CC. By analysis of cervical precancerous lesions, we further show that promoter hypermethylation of Slit-Robo pathway occurs early in tumor progression. Conclusion Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i play a role in CC development, (ii further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii form epigenetic signatures to identify precancerous lesions at risk to progression.

  19. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG)

    DEFF Research Database (Denmark)

    Rustin, Gordon John Sampson; Vergote, Ignace; Eisenhauer, Elizabeth;

    2011-01-01

    The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using the se...

  20. Adipose-derived stems cells and their role in human cancer development, growth, progression, and metastasis: a systematic review.

    Science.gov (United States)

    Freese, Kyle E; Kokai, Lauren; Edwards, Robert P; Philips, Brian J; Sheikh, M Aamir; Kelley, Joseph; Comerci, John; Marra, Kacey G; Rubin, J Peter; Linkov, Faina

    2015-04-01

    Obesity is a well recognized risk factor for several types of cancers, many of which occur solely or disproportionately in women. Adipose tissue is a rich source of adipose-derived stem cells (ASC), which have received attention for their role in cancer behavior. The purpose of this systematic review is to present the existing literature on the role of ASCs in the growth, development, progression, and metastasis of cancer, with an emphasis on malignancies that primarily affect women. To accomplish this goal, the bibliographic database PubMed was systematically searched for articles published between 2001 and 2014 that address ASCs' relationship to human cancer. Thirty-seven articles on ASCs' role in human cancer were reviewed. Literature suggests that ASCs exhibit cancer-promoting properties, influence/are influenced by the tumor microenvironment, promote angiogenesis, and may be associated with pathogenic processes through a variety of mechanisms, such as playing a role in hypoxic tumor microenvironment. ASCs appear to be important contributors to tumor behavior, but research in areas specific to women's cancers, specifically endometrial cancer, is scarce. Also, because obesity continues to be a major health concern, it is important to continue research in this area to improve understanding of the impact adiposity has on cancer incidence.

  1. A Bayesian model for censored positive count data in evaluating breast cancer progression.

    Science.gov (United States)

    Yeh, Hung-Wen; Jiang, Yu; Garrard, Lili; Lei, Yang; Gajewski, Byron

    2013-01-01

    Basic science researchers transplant human cancer tissues from patients with ductal carcinoma in situ (DCIS) to animals and observe the progression of the disease. Successful transplants show invasion of human tissues across mammary ducts in animal fat pads and cause DCIS-like lesions in one or more ducts. In this work, we consider data from a recent publication of breast cancer research where positive counts of affected ducts may be subject to censoring. We fit the data with zero-truncated Poisson (ZTP) models with an informative prior of gamma. Due to the zero-truncation and right censoring, posterior distributions may not be conventional gamma and are estimated through Markov chain Monte Carlo and grid approximation. For each of the two cell lines, we fit a model with group-specific parameters for DCIS subtypes classified by the cell surface biomarkers, and another model with a homogeneous parameter across groups. Models are compared by the Deviance Information Criterion (DIC). For the chosen prior parameter values, Bayes estimates are comparative to the maximum likelihood estimates, and the DIC favors the simpler model in both cell lines. PMID:23997758

  2. Navigator-3, a modulator of cell migration, may act as a suppressor of breast cancer progression

    Science.gov (United States)

    Cohen-Dvashi, Hadas; Ben-Chetrit, Nir; Russell, Roslin; Carvalho, Silvia; Lauriola, Mattia; Nisani, Sophia; Mancini, Maicol; Nataraj, Nishanth; Kedmi, Merav; Roth, Lee; Köstler, Wolfgang; Zeisel, Amit; Yitzhaky, Assif; Zylberg, Jacques; Tarcic, Gabi; Eilam, Raya; Wigelman, Yoav; Will, Rainer; Lavi, Sara; Porat, Ziv; Wiemann, Stefan; Ricardo, Sara; Schmitt, Fernando; Caldas, Carlos; Yarden, Yosef

    2015-01-01

    Dissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify Navigator-3 (NAV3), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, NAV3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, NAV3 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that NAV3-depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing NAV3 increased metastasis, whereas ectopic expression of the wild-type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of > 2,500 breast and lung cancer patients associated low NAV3 with shorter survival. We propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells. PMID:25678558

  3. Recent progress in gene-directed enzyme prodrug therapy: an emerging cancer treatment.

    Science.gov (United States)

    Both, Gerald W

    2009-08-01

    The principle of gene-directed enzyme prodrug therapy (GDEPT) has existed for many years but, while simple in concept, the effective practical application of this therapy has proven to be challenging. Improvements in the efficacy of GDEPT have been achieved principally through the choice and development of more effective vectors, by optimizing and controlling gene expression and by increasing the activity of the delivered enzyme through mutation. While innovation continues in this field, the pioneering GDEPT systems designed to treat glioma and prostate cancer have completed or are now entering late-stage clinical trials, respectively. As the pace of innovation in GDEPT technology far exceeds its clinical application, these initial products are anticipated to be replaced by next-generation biologicals. This review highlights recent progress in the strategies and development of GDEPT and summarizes the status of current clinical trials. With the first GDEPT product for treatment of resected gliomas poised to gain marketing approval, a new era in cancer gene medicine is emerging. PMID:19649987

  4. Regulatory roles of LINE-1-encoded reverse transcriptase in cancer onset and progression.

    Science.gov (United States)

    Sciamanna, Ilaria; Gualtieri, Alberto; Piazza, Pier Francesco; Spadafora, Corrado

    2014-09-30

    LINE-1 retrotransposons encode the reverse transcriptase (RT) enzyme, required for their own mobility, the expression of which is inhibited in differentiated tissues while being active in tumors. Experimental evidence indicate that the inhibition of LINE-1-derived RT restores differentiation in cancer cells, inhibits tumor progression and yields globally reprogrammed transcription profiles. Newly emerging data suggest that LINE-1-encoded RT modulates the biogenesis of miRNAs, by governing the balance between the production of regulatory double-stranded RNAs and RNA:DNA hybrid molecules, with a direct impact on global gene expression. Abnormally high RT activity unbalances the transcriptome in cancer cells, while RT inhibition restores "normal" miRNA profiles and their regulatory networks. This RT-dependent mechanism can target the myriad of transcripts - both coding and non-coding, sense and antisense - in eukaryotic transcriptomes, with a profound impact on cell fates. LINE-1-encoded RT emerges therefore as a key regulator of a previously unrecognized mechanism in tumorigenesis.

  5. Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM).METHODS: IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6)colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16).RESULTS: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues.Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found.CONCLUSION: Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases.

  6. Trends of lip, oral cavity and oropharyngeal cancers in Australia 1982–2008: overall good news but with rising rates in the oropharynx

    International Nuclear Information System (INIS)

    Considerable global variation in the incidence of lip, of oral cavity and of pharyngeal cancers exists. Whilst this reflects regional or population differences in risk, interpretation is uncertain due to heterogeneity of definitions of sites and of sub-sites within this anatomically diverse region. For Australia, limited data on sub-sites have been published. This study examines age-standardised incidence trends and demography from 1982 to 2008, the latest data available. Numbers of cases within ICD10:C00-C14 were obtained from the Australian Institute of Health and Welfare, recorded by sex, age, and sub-site. Raw data were re-analysed to calculate crude, age-specific and age-standardised incidence using Segi’s world-standard population. Time-trends were analysed using Joinpoint regression. Lip, Oral Cavity and Pharyngeal (excluding nasopharynx) cancers, considered together, show a biphasic trend: in men rising 0.9% pa from 1982 to 1992, and declining 1.6% pa between 1992 and 2008. For females: rises of 2.0% pa 1982–1997; declines of 2.8% pa 1997–2008. Lip cancer is declining especially significantly. When the Oropharynx is considered separately, steadily increasing trends of 1.2% pa for men and 0.8% pa for women were observed from 1982 to 2008. Although overall rates of lip/oral/oropharyngeal cancer are declining in Australia, these are still high. This study revealed steady increases in cancers of the oropharynx, beginning in the late 1990s. Continued efforts to reduce the burden of these cancers are needed, focused on reduction of the traditional risk factors of alcohol and tobacco, and with special emphasis on the possible role of human papillomavirus and sexual hygiene for cancers of the oropharynx

  7. Subtype-specific micro-RNA expression signatures in breast cancer progression.

    Science.gov (United States)

    Haakensen, Vilde D; Nygaard, Vegard; Greger, Liliana; Aure, Miriam R; Fromm, Bastian; Bukholm, Ida R K; Lüders, Torben; Chin, Suet-Feung; Git, Anna; Caldas, Carlos; Kristensen, Vessela N; Brazma, Alvis; Børresen-Dale, Anne-Lise; Hovig, Eivind; Helland, Åslaug

    2016-09-01

    Robust markers of invasiveness may help reduce the overtreatment of in situ carcinomas. Breast cancer is a heterogeneous disease and biological mechanisms for carcinogenesis vary between subtypes. Stratification by subtype is therefore necessary to identify relevant and robust signatures of invasive disease. We have identified microRNA (miRNA) alterations during breast cancer progression in two separate datasets and used stratification and external validation to strengthen the findings. We analyzed two separate datasets (METABRIC and AHUS) consisting of a total of 186 normal breast tissue samples, 18 ductal carcinoma in situ (DCIS) and 1,338 invasive breast carcinomas. Validation in a separate dataset and stratification by molecular subtypes based on immunohistochemistry, PAM50 and integrated cluster classifications were performed. We propose subtype-specific miRNA signatures of invasive carcinoma and a validated signature of DCIS. miRNAs included in the invasive signatures include downregulation of miR-139-5p in aggressive subtypes and upregulation of miR-29c-5p expression in the luminal subtypes. No miRNAs were differentially expressed in the transition from DCIS to invasive carcinomas on the whole, indicating the need for subtype stratification. A total of 27 miRNAs were included in our proposed DCIS signature. Significant alterations of expression included upregulation of miR-21-5p and the miR-200 family and downregulation of let-7 family members in DCIS samples. The signatures proposed here can form the basis for studies exploring DCIS samples with increased invasive potential and serum biomarkers for in situ and invasive breast cancer. PMID:27082076

  8. Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression.

    Science.gov (United States)

    Heissig, Beate; Dhahri, Douaa; Eiamboonsert, Salita; Salama, Yousef; Shimazu, Hiroshi; Munakata, Shinya; Hattori, Koichi

    2015-12-01

    Tissue regeneration during wound healing or cancer growth and progression depends on the establishment of a cellular microenvironment. Mesenchymal stem cells (MSC) are part of this cellular microenvironment, where they functionally modulate cell homing, angiogenesis, and immune modulation. MSC recruitment involves detachment of these cells from their niche, and finally MSC migration into their preferred niches; the wounded area, the tumor bed, and the BM, just to name a few. During this recruitment phase, focal proteolysis disrupts the extracellular matrix (ECM) architecture, breaks cell-matrix interactions with receptors, and integrins, and causes the release of bioactive fragments from ECM molecules. MSC produce a broad array of proteases, promoting remodeling of the surrounding ECM through proteolytic mechanisms. The fibrinolytic system, with its main player plasmin, plays a crucial role in cell migration, growth factor bioavailability, and the regulation of other protease systems during inflammation, tissue regeneration, and cancer. Key components of the fibrinolytic cascade, including the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are expressed in MSC. This review will introduce general functional properties of the fibrinolytic system, which go beyond its known function of fibrin clot dissolution (fibrinolysis). We will focus on the role of the fibrinolytic system for MSC biology, summarizing our current understanding of the role of the fibrinolytic system for MSC recruitment and the functional consequences for tissue regeneration and cancer. Aspects of MSC origin, maintenance, and the mechanisms by which these cells contribute to altered protease activity in the microenvironment under normal and pathological conditions will also be discussed.

  9. Progress in Treatment of Cervical Cancer%宫颈癌的治疗进展

    Institute of Scientific and Technical Information of China (English)

    侯彩英; 宫荣杰; 姚元庆

    2011-01-01

    Cervical carcinoma is the second most common cancer in women and is the most prevalent female malignancy in Africa, Asia and South America. Its morbidity and mortality are only less than breast cancer. Radical surgery (hysterectomy plus pelvic lymph node dissection) and radiotherapy are the traditional treatment while chemotherapy is used for advanced stage and recurrent or metastatic patients. Following the development of science technical, it has progress in method of surgical and radiotherapy and chemotherapy. At the same time, some new therapies have adopted in clinics, including targeted therapy, gene therapy and vaccine prevention. The standard therapy for the locally advanced cervical cancer has been a combination of external pelvic radiation and brachytherapy.%宫颈癌是全世界妇女中第二常见的恶性肿瘤,在非洲、亚洲以及南美洲,是妇女最常见的恶性肿瘤.其发病率和死亡率仅次于乳腺癌.宫颈癌的传统治疗是根治性手术(包括广泛全子宫切除+盆腔淋巴结清扫术)和放疗,化疗主要用于晚期或复发转移的患者.近些年,随着科学技术的发展,其手术方式及放化疗方式都有了新的进展,同时,还出现了靶向治疗、基因治疗及疫苗预防等综合防治体系.

  10. Trends in the incidence of cervical cancer and severe precancerous lesions in Denmark, 1997-2012

    DEFF Research Database (Denmark)

    Baldur-Felskov, Birgitte; Munk, Christian; Nielsen, Thor Schütt Svane;

    2015-01-01

    papillomavirus (HPV) vaccination. METHODS: Using nationwide registries, we estimated age-specific and age-standardized incidence rates and estimated annual percentage change (EAPC). RESULTS: The incidence of SCC decreased significantly, especially in women aged ≥45 years [EAPC: -3.1 % (95 % CI -4.3 to -2...... or the incidence of adenocarcinoma, which is increasing. Decreases in the incidences of CIN3 and AIS in age groups with high HPV vaccine coverage may herald a future decrease in cervical cancer incidence in young Danish women....

  11. Incidence and Trends of Six Types of Cancer in Populations Environmentally Exposed to Obsolete Pesticides in the Colombian State of Cesar

    International Nuclear Information System (INIS)

    Objective: To determine incidence and trends related to the appearance of bladder, kidney, non melanoma skin (except head and neck),lung, liver and colon cancer in the State of Cesar and in the entirety of its municipalities from January 1, 1998-December 31, 2006. Methods: A descriptive, transverse epidemiologic study carried out in the municipalities of the State of Cesar where environmental exposure to obsolete or near obsolete pesticides had occurred. Census of secondary information sources was conducted at main geographical points where state residents sought medical care. Active data collection (at the source) was employed in accordance with Population Cancer Registry. Results: In the State of Cesar, between 1998-2006, average annual percentage and statistically significant changes occurred in the incidence of lung, colon, and rectal cancers for both sexes, and of non melanoma skin cancer for men. The municipalities of Agustin Codazzi and El Copey revealed age standard rates (ASR) above the state average for liver cancer in both sexes, and for bladder cancer in women. Gender related multiple ASR for the municipalities of Valledupar, Aguachica, Pailitas and La Paz stood out with respectively higher ASR than that for the entire State of Cesar. Conclusions: It is possible that there is a statistical and geospatial association between the incidence of the following cancers and the environmental exposure to PLADES: (a) bladder cancer in women, in Agustin Codazzi and El Copey; (b) bladder cancer in men, only in El Copey, and (c) non melanoma skin cancer in men, only in Agustin Codazzi.

  12. Circulating low IL-23: IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer.

    Science.gov (United States)

    Chen, Guanghui; Liang, Yanfang; Guan, Xin; Chen, Hui; Liu, Qiankun; Lin, Bihua; Chen, Can; Huang, Mingyuan; Chen, Jianan; Wu, Weiquan; Liang, Yi; Zhou, Keyuan; Zeng, Jincheng

    2016-01-01

    The interleukin (IL)-12 family, composed of heterodimeric cytokines including IL-12 (formed by IL-12p35 and IL-12p40 subunits), IL-23 (formed by IL-23p19 and IL-12p40 subunits), IL-27 (formed by IL-27p28 and EBI3 subunits) and IL-35 (formed by IL-12p35 and EBI3 subunits), establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines to tumors. However, the role of IL-12 family in breast cancer (BC) progression and prognosis remains unclear. In the present study, we demonstrated evidence indicating that EBI3, IL-12p35 and IL-12p40 but not IL-23p19 or IL-27p28 were highly expressed in BC tissues, suggested that tumor derived EBI3, IL-12p35 and IL-12p40 were associated with tumor progression. Circulating IL-12 and IL-23 low expressed, but IL-27 and IL-35 high expressed in BC patients, especially circulating IL-23 associated with IL-35 to mediate BC tumor resection. Ki-67, p53 and EGFR expression on BC tissues, as well as CA125, CA153 and CA199 levels on BC bloods increased when circulating IL-23: IL-35 ratio decreased. Together, for the first time, our data suggest that circulating IL-23: IL-35 ratio may be an important indicator association with BC progression and prognosis. However, further research should be carried out to assess the implications of circulating IL-23: IL-35 ratio in a larger sample size.

  13. Expression of XPG protein in the development, progression and prognosis of gastric cancer.

    Directory of Open Access Journals (Sweden)

    Na Deng

    Full Text Available BACKGROUND: Xeroderma pigmentosum group G (XPG plays a critical role in preventing cells from oxidative DNA damage. This study aimed to investigate XPG protein expression in different gastric tissues and in patients with diverse prognoses, thus providing insights into its role in the development, progression and prognosis of gastric cancer (GC. METHODS: A total of 176 GC, 131 adjacent non-tumour tissues, 53 atrophic gastritis (AG and 49 superficial gastritis (SG samples were included. Immunohistochemical staining was used to detect XPG protein expression. RESULTS: XPG expression was significantly higher in GC tissues compared with adjacent non-tumour tissues. In the progressive disease sequence SG→AG→GC, XPG expression was significantly higher in AG and GC compared with SG. Analysis of clinicopathological parameters and survival in GC patients demonstrated a significant association between XPG expression level and depth of tumour invasion, macroscopic type, Lauren's classification, smoking, Helicobacter pylori infection and family history. Cox multivariate survival analysis indicated that patients with positive XPG expression had significantly longer overall survival (P = 0.020, HR = 0.394, 95%CI 0.179-0.866, especially in aged younger than 60 years (P = 0.027, HR = 0.361, 95%CI 0.147-0.888 and male patients (P = 0.002, HR = 0.209, 95%CI 0.077-0.571. CONCLUSIONS: This study demonstrated that XPG protein expression was related to the development, progression and prognosis of GC, and might thus serve as a potential biomarker for its diagnosis and prognosis.