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Sample records for cancer increase study

  1. Study: California Ethnic Groups Seeing Increased Cancer Rates

    Science.gov (United States)

    Black Issues in Higher Education, 2005

    2005-01-01

    A statewide study on cancer and ethnicity hints that cancer rates among immigrant groups may be tied to their degree of assimilation into American culture. The study, released by the University of Southern California's Norris Comprehensive Cancer Center, marks the first statewide look at cancer rates among Vietnamese and South Asians and provides…

  2. Salivary total sialic acid levels increase in breast cancer patients: a preliminary study.

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    Oztürk, Leyla Koç; Emekli-Alturfan, Ebru; Kaşikci, Emel; Demir, Gokhan; Yarat, Aysen

    2011-09-01

    Breast cancer is the most common cancer in women living in the Western world, even though it occurs worldwide. Cancer and cancer therapy induce multiple oral complications including dental and periodontal disease. Saliva is a complex and dynamic biologic fluid, which reflects both oral and systemic changes. While saliva is easily accessible body fluid, there has been little effort to study its value in cancer diagnosis. Sialic acids (SA), the end moieties of the carbohydrate chains, are biologically important and essential for functions of glycoconjugates that are reported to be altered in both blood and saliva of various cancer patients. Increased sialylation has been shown to be a characteristic feature in cancer tissue and blood in breast cancer patients. However, there is no data about salivary SA in breast cancer. The aim of this study was to evaluate salivary total sialic acid (TSA) levels in breast cancer patients who were under chemotheraphy. The study included 15 breast cancer patients in different stages and 10 healthy individuals as age-matched controls. Unstimulated whole saliva was collected. Salivary total protein and SA levels were determined. Flow rate was calculated from salivary volume by the time of secretion. Salivary SA was significantly higher and total protein was lower in breast cancer patients compared to controls. It is concluded that sialylation may be increased in saliva of patients with breast cancer as the same way for cancer tissue and for blood . Increased salivary SA may therefore be useful as a non-invasive predictive marker for breast cancer patients and for the prevention and management of oral complications of cancer and cancer therapy to improve oral function and quality-of-life. The effects of different types of chemotherapies and different stages of the disease on salivary SA levels and salivary sialo-glycomic are worthy of being further investigated in breast cancer patients.

  3. Are cancer survivors at an increased risk for divorce? A Danish cohort study

    DEFF Research Database (Denmark)

    Carlsen, Kathrine; Dalton, Susanne Oksbjerg; Frederiksen, Kirsten;

    2007-01-01

    The purpose of this study was to determine the risk for divorce among cancer survivors. We conducted a nationwide, population-based study of 46,303 persons aged 30-60 years in whom selected cancers were diagnosed in 1981-2000 and 221,028 randomly sampled, cancer-free controls. Information...... for survivors of cervix cancer, who had an increased risk for divorce, we found that cancer survivors were not at greater risk for divorce than the general population (rate ratios (RR), 1.06; 95% confidence interval (CI), 1.0;1.1 and RR, 0.98; 95% CI, 0.9;1.0 for women and men, respectively). This finding shows...... that cancer survivors need not have unnecessary fears for their marriage....

  4. Increased risk of herpes zoster in children with cancer: A nationwide population-based cohort study.

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    Lin, Hsiao-Chuan; Chao, Yu-Hua; Wu, Kang-Hsi; Yen, Ting-Yu; Hsu, Yu-Lung; Hsieh, Tsung-Hsueh; Wei, Hsiu-Mei; Wu, Jhong-Lin; Muo, Chih-Hsin; Hwang, Kao-Pin; Peng, Ching-Tien; Lin, Cheng-Chieh; Li, Tsai-Chung

    2016-07-01

    Herpes zoster is rare in healthy children, but immunocompromised persons have an increased risk of herpes zoster and severe diseases. Considering the very limited information on herpes zoster in children with cancer, we performed a nationwide population-based cohort study to estimate the incidence of herpes zoster in children with cancer and to explore the association between the 2 diseases.Data were obtained from the National Health Research Institutes Database in Taiwan. A total of 4432 children with newly diagnosed cancer between 2000 and 2007 were identified as the cancer cohort, and 17,653 children without cancer frequency-matched by sex and age at entry were considered the noncancer cohort. The association between herpes zoster and childhood cancer was determined.Children with cancer had a higher risk of herpes zoster. The incidence rate of herpes zoster was higher in the cancer cohort than in the noncancer cohort (20.7 vs 2.4 per 10,000 person-years; IRR = 8.6; 95% CI = 4.8-15.6). The cumulative incidence was significantly higher in the cancer cohort (P herpes zoster. In addition to early antiviral treatment, vaccination with heat-treated zoster vaccine or adjuvanted subunit vaccine could be an appropriate policy to decrease the incidence in children with cancer.

  5. Increased Risk of Cancer in relation to Gout: A Review of Three Prospective Cohort Studies with 50,358 Subjects

    Science.gov (United States)

    Wang, Weijie; Xu, Donghua; Wang, Bin; Yan, Shushan; Wang, Xiaochen; Yin, Yin; Wang, Xuehao; Sun, Beicheng; Sun, Xiaoyang

    2015-01-01

    Gout is a common inflammatory disease characterized by acute arthritis and hyperuricemia. A number of epidemiological studies have suggested the critical role of gout in carcinogenesis. The aim of this study was to estimate the association between gout and cancer risk by meta-analysis of all relevant studies published to date. A comprehensive literature search in PubMed and Embase databases from their inception up to July 1, 2014, was performed to identify eligible studies. The strength for relationship between gout and the risk of different cancers was evaluated by calculating pooled relative risks (RRs) with 95% confidence intervals (95% CIs). All analyses were carried out by STATA 12.0 software. Gout patients were at an increased risk of cancer, particularly urological cancers, digestive system cancers, and lung cancer. No such significant association between gout and the risk of breast or brain cancers was observed. Sensitivity analysis did not materially alter the pooled results. Gout is a risk factor of cancer, particularly that of urological cancers, digestive system cancers, and lung cancer. The pooled data further support the hypothesis of a link between gout and carcinogenesis. PMID:26504360

  6. 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.

  7. Increased risk of cancer in patients with type 2 diabetes mellitus: A retrospective cohort study in China

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    Zhang Pian-Hong

    2012-07-01

    Full Text Available Abstract Background Previous studies indicated that type 2 diabetes mellitus (T2DM might be associated with the risk of cancer. The aim of this study was to investigate the association between T2DM and the risk of developing common cancers in a Chinese population. Methods A population-based retrospective cohort study was carried out in the Nan-Hu district of Jiaxing city, Zhejiang province, China. The incidence of cancer cases among type 2 diabetic patients were identified through record-linkage of the Diabetic Surveillance and Registry Database with the Cancer Database from January 2002 to June 2008. The standardized incidence ratio (SIR and 95% confidence interval (CI were estimated for the risk of cancer among the patients with type 2 diabetes. Results The overall incidence of cancer was 1083.6 per 105 subjects in male T2DM patients and 870.2 per 105 in females. Increased risk of developing cancer was found in both male and female T2DM patients with an SIR of 1.331 (95% CI = 1.143-1.518 and 1.737 (1.478-1.997, respectively. As for cancer subtypes, both male and female T2DM patients had a significantly increased risk of pancreatic cancer with the SIRs of 2.973 (1.73-4.21 and 2.687 (1.445-3.928, respectively. Elevated risk of liver and kidney cancers was only found in male T2DM patients with SIRs of 1.538 (1.005-2.072 and 4.091 (1.418-6.764, respectively. Increased risks of developing breast cancer [2.209 (1.487-2.93] and leukemia SIR: [4.167 (1.584- 6.749 ] were found in female patients. Conclusions These findings indicated that patients with T2DM have an increased risk of developing cancer. Additional cancer screening should be employed in the management of patients with T2DM.

  8. Recruitment to a physical activity intervention study in women at increased risk of breast cancer

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    Drinkard Bart

    2009-04-01

    Full Text Available Abstract Background Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging. Methods We conducted an analysis of recruitment techniques used for a prospective, randomized pilot study of physical activity in women at risk of breast cancer. We evaluated differences in proportion of eligible patients, enrolled patients, and successful patients identified by each individual recruitment method. The Fisher-Freeman-Halton test (an extension of Fisher's exact test from 2 × 2 tables to general row by column tables was used to compare the success of different recruitment strategies. Results We received 352 inquiries from women interested in participating, of whom 171 (54% were eligible. Ninety-nine women completed a baseline activity evaluation, and 58 (34% of eligible; 16% of total inquiries were randomized. Recruitment methods fell into three broad categories: media techniques, direct contact with potential participants, and contacts with health care providers. Recruitment strategies differed significantly in their ability to identify eligible women (p = 0.01, and women who subsequently enrolled in the study (p = 0.02. Conclusion Recruitment techniques had varying success. Our data illustrate the challenges in recruiting to behavior modification studies, and provide useful information for tailoring future recruitment efforts for lifestyle intervention trials. Trial Registration No(s CDR0000393790, NCI-04-C-0276, NCI-NAVY-B05-001

  9. Pioglitazone does not increase the risk of type II diabetes in patients with bladder cancer: A retrospective study.

    Science.gov (United States)

    Dong, Youhong; Wang, Anping

    2016-07-01

    The aim of the retrospective study was to analyze the effect of pioglitazone on the expression of tumor tissue inflammation factor interleukin (IL)-8, macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) of type II diabetes in bladder cancer patients. In addition, whether there was a correlation between pioglitazone and the occurrence of male bladder cancer was also investigated. In total, 42 male cases diagnosed with type II diabetes secondary to bladder cancer were selected. Forty male cases, with simplex type II diabetes but not with bladder cancer, served as the control. Tumor biopsy specimens were collected to detect the expression levels of IL-8, M-CSF and VEGF. The results showed that the expression of IL-8, M-CSF and VEGF of the simplex diabetes group was significantly lower than that of the secondary to tumor group (Ppioglitazone, duration of diabetes, average fasting blood sugar and glycated hemoglobin levels, was not statistically significant. Multivariable logistic regression analysis revealed that the expression levels of IL-8, M-CSF and VEGF were independent risk factors for the occurrence of bladder cancer (Ppioglitazone (P>0.05). In conclusion, oral pioglitazone may not increase the risk of type II diabetes patients with bladder cancer. However, the occurrence of bladder cancer be associated with the increasing expression levels of IL-8, M-CSF and VEGF.

  10. The GSTM1 null genotype increased risk of gastric cancer: a meta-analysis based on 46 studies.

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    Yi Zhao

    Full Text Available BACKGROUND: Glutathione S-transferases M1 (GSTM1 is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk. METHODS: This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren's classification, and other factors. Odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the association strength. RESULTS: A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, P(heterogeneity<0.001. Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, P(heterogeneity= 0.002, but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, P(heterogeneity=0.065, while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, P(heterogeneity=0.168. For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren's classification did not modify the association. CONCLUSIONS: In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.

  11. NIH-funded study shows increased prostate cancer risk from vitamin E supplements | Division of Cancer Prevention

    Science.gov (United States)

    Men who took 400 international units (I.U.) of vitamin E daily had more prostate cancers compared to men who took a placebo, according to an updated review of data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The findings showed that, per 1,000 men, there were 76 prostate cancers in men who took only vitamin E supplements, vs. |

  12. Study Finds Small Increase in Cancer Risk after Childhood CT Scans

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    A study published in the June 6, 2012, issue of The Lancet shows that radiation exposure from computed tomography (CT) scans in childhood results in very small but increased risks of leukemia and brain tumors in the first decade after exposure.

  13. Increase in mammography detected breast cancer over time at a community based regional cancer center: a longitudinal cohort study 1990–2005

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    Malmgren Judith A

    2008-05-01

    Full Text Available Abstract Background Coincident with the advent of mammography screening, breast carcinoma in situ has increased in the US population. Methods We conducted a prospective cohort study of all women presenting with primary breast cancer, aged 21–94, and biopsy confirmed Stage 0-IV from 1990–2005 identified and tracked by our registry. Clinical presentation characteristics including age, race, TNM stage, family and pregnancy history, histologic type and method of detection by patient (PtD, physician (PhysD or mammography (MgD were chart abstracted at time of diagnosis. Cases with unknown or other method of detection (n = 84, or unusual cell types (n = 26 were removed (n = 6074. Results From 1990 to 1998 the percentage of PtD and MgD cases was roughly equivalent. In 1999 the percentage of MgD cases increased to 56% and PtD dropped to 37%, a significant 20% differential, constant to 2005 (Pearson chi square = 120.99, p Conclusion In our cohort the relative proportion of mammography detected breast cancer increased over time with a higher increase among women age 50+ and an increase of breast carcinoma in situ exclusively among MgD cases. The increase among women currently targeted by mammography screening programs (age ≥ 50 combined with an increase of breast carcinoma in situ most often detected by mammography screening indicates a possible incidence shift to lower stage breast cancer as a result of mammographic detection.

  14. Increased risk of cancer among azoospermic men

    Science.gov (United States)

    Eisenberg, Michael L.; Betts, Paul; Herder, Danielle; Lamb, Dolores J.; Lipshultz, Larry I.

    2013-01-01

    Objective To determine if men with azoospermia are at an elevated risk of developing cancer in the years following an infertility evaluation. Design Cohort Study Setting United States andrology clinic Patients 2,238 men with complete records were evaluated for infertility at a single andrology clinic in Texas from 1989 to 2009. Interventions None Main Outcome Measures Cancer incidence was determined by linkage to the Texas Cancer Registry. Results In all, 451 men had azoospermia and 1,787 were not azoospermic with a mean age at infertility evaluation of 35.7 years. Compared to the general population, infertile men had a higher risk of cancer with 29 cases observed compared with 16.7 expected (SIR 1.7, 95% CI 1.2–2.5). When stratifying by azoospermia status, azoospermic men had an elevated risk of cancer (SIR 2.9, 95% CI 1.4–5.4). Infertile men without azoospermia had a trend towards a higher rate of cancer (SIR 1.4, 95% CI 0.9–2.2). The Cox regression model revealed that azoospermic men had 2.2-fold higher cancer risk compared to not azoospermic men (HR 2.2, 95% CI 1.0–4.8). Conclusions Men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common etiology between azoospermia and cancer development. Additional follow-up of azoospermic men after reproductive efforts end may be warranted. PMID:23790640

  15. How do women at increased, but unexplained, familial risk of breast cancer perceive and manage their risk? A qualitative interview study

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    Keogh Louise A

    2011-09-01

    Full Text Available Abstract Background The perception of breast cancer risk held by women who have not had breast cancer, and who are at increased, but unexplained, familial risk of breast cancer is poorly described. This study aims to describe risk perception and how it is related to screening behaviour for these women. Methods Participants were recruited from a population-based sample (the Australian Breast Cancer Family Study - ABCFS. The ABCFS includes women diagnosed with breast cancer and their relatives. For this study, women without breast cancer with at least one first- or second-degree relative diagnosed with breast cancer before age 50 were eligible unless a BRCA1 or BRCA2 mutation had been identified in their family. Data collection consisted of an audio recorded, semi-structured interview on the topic of breast cancer risk and screening decision-making. Data was analysed thematically. Results A total of 24 interviews were conducted, and saturation of the main themes was achieved. Women were classified into one of five groups: don't worry about cancer risk, but do screening; concerned about cancer risk, so do something; concerned about cancer risk, so why don't I do anything?; cancer inevitable; cancer unlikely. Conclusions The language and framework women use to describe their risk of breast cancer must be the starting point in attempts to enhance women's understanding of risk and their prevention behaviour.

  16. Breast cancer risk is not increased in individuals with TWIST1 mutation confirmed Saethre-Chotzen syndrome: an Australian multicenter study.

    Science.gov (United States)

    James, Paul A; Culling, Bronwyn; Mullan, Glenda; Jenkins, Mark; Elakis, George; Turner, Anne M; Mowat, David M; Wilson, Meredith; Anderson, Peter; Savarirayan, Ravi; Cliffe, Simon T; Caramins, Melody; Buckley, Michael F; Tucker, Kathy; Roscioli, Tony

    2009-07-01

    Saethre-Chotzen syndrome (SCS) is a rare autosomal dominant syndrome involving craniosynostosis, craniofacial abnormalities, and syndactyly. A recent Scandinavian study reported an increased risk of breast cancer in individuals with a clinical diagnosis of SCS. Because of the potential importance of this finding, we organized a multicenter study enrolling people with TWIST1 mutation confirmed SCS to determine if an increased risk of cancer is present. This study did not identify any cases of breast or ovarian cancer in a cohort of equivalent power to that reported previously. These results provide clinical reassurance that at present there is no evidence for breast cancer screening above standard practice for individuals with SCS.

  17. Diabetes Mellitus Increased Mortality Rates More in Gender-Specific than in Nongender-Specific Cancer Patients: A Retrospective Study of 149,491 Patients

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    Wen-Ko Chiou

    2012-01-01

    Full Text Available Aims. Hyperinsulinemia in overweight status, obesity, and type 2 diabetes mellitus (DM is often accompanied by cancer. Gender is important in cancer epidemiology, clinical presentation, and response to therapy in different histological types of malignancy. Insufficient information is available concerning gender differences in DM with organ-specific and nonorgan-specific cancers. This study aimed to analyze gender differences in hospitalized cancer patients with or without type 2 DM. Methods. We retrospectively reviewed ten years of patients hospitalized in one institution, enrolling 36,457 female and 50,004 male cancer patients of which 5,992 females and 8,345 males were diagnosed as type 2 DM. Results. Statistically significant increases in incidence of type 2 DM were found in patients of both genders with pancreatic, liver, and urinary tract cancer. Increased incidence of type 2 DM was found in lung and hematologic malignancies in females and prostate cancer in males. Increases in mortality rates of females with type 2 DM (2.98% were higher than those in males. DM increased mortality rates in gender-specific cancers from 1.91% (uterus, HR: 1.33 to 5.04% (ovary, HR: 1.49. Conclusion. Type 2 DM increased mortality of cancer patients of both genders, with higher increases in gender-specific than in nongender-specific cancers.

  18. Sun exposure may increase risk of prostate cancer in the high UV environment of New South Wales, Australia: a case-control study.

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    Nair-Shalliker, Visalini; Smith, David P; Egger, Sam; Hughes, Ann Maree; Kaldor, John M; Clements, Mark; Kricker, Anne; Armstrong, Bruce K

    2012-09-01

    Ultraviolet (UV) radiation in sunlight may influence risk of prostate cancer. In New South Wales (NSW), Australia, we examined the relationship between sun exposure at 30 and 50 years of age and risk of prostate cancer in a case-control study combining the NSW prostate cancer care and outcome study (cases) and the NSW non-Hodgkin's lymphoma study (controls). Prostate cancer risk increased with increasing estimated sun exposure (adjusted OR for highest vs. lowest quartiles of average weekly sun exposure in the warmer months 2.07 95% CI: 1.36-3.15) and this increase was most evident with weekend sun exposure (adjusted OR=5.55, 95% CI: 2.94-10.48). High sun sensitivity was also positively associated with risk for prostate cancer (adjusted OR=1.63, 95% CI: 1.09-2.44). The apparent effects of weekly sun exposure did not vary by disease aggressiveness. Our results suggest that increasing sun exposure in mid-adult years increases prostate cancer risk in a high ambient solar UV environment. Given that previous studies, conducted mainly in low solar UV environments, have generally found evidence of a negative association, our findings suggest there may be a U-shaped relationship between solar UV exposure and prostate cancer. Further studies are needed to test the hypothesis that high solar UV exposure is a risk factor for prostate cancer and to explore possible mechanisms for such an association.

  19. Does postmenopausal estrogen administration increase the risk of breast cancer? Contributions of animal, biochemical, and clinical investigative studies to a resolution of the controversy.

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    Zumoff, B

    1998-01-01

    Despite nearly six decades of epidemiological studies, meta-analyses, and reviews, there is still considerable controversy in the literature about the question, does postmenopausal estrogen administration increase the risk of breast cancer? In an effort to resolve the controversy, a number of animal, biochemical, and clinical investigative studies in this field have been reviewed. The following summary formulation is proposed: 1. Administration of estrogen is inherently capable of promoting the growth of breast cancer, and therefore of increasing the incidence of clinical breast cancer. 2. Human response to estrogen is like that of the low-cancer-incidence strains of mice studied by Lacassagne, in that large doses and prolonged administration are required to induce clinical breast cancer. 3. The blood levels of estradiol produced by the usual doses of postmenopausal estrogen are relatively low, equivalent to those of the follicular phase of the menstrual cycle. These levels may be near the threshold for producing breast-cancer-promoting effects; therefore, the tumor response will vary greatly in different populations, depending on genetic susceptibility factors: a. The prevalence of a family history of premenopausal breast cancer in a first-degree relative. b. The prevalence of abnormal BRCA1, BRCA2, and p53 genes. c. The prevalence of increased 16 alpha-hydroxylation of estradiol. d. The prevalence of smokers who are slow acetylators. 4. Consumption of alcohol (5 grams or more daily) along with the postmenopausal estrogen administration results in elevation of blood estradiol levels to values equivalent to those of the periovulatory peak of the menstrual cycle, which may be well above the threshold for producing breast-cancer-promoting effects in all women. The risk for cancer will therefore be uniformly increased in women who use alcohol and take estrogen. 5. Increased risk of breast cancer from postmenopausal estrogen administration can be eliminated by taking

  20. Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study

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    Darby Sarah

    2007-01-01

    Full Text Available Abstract Background Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right. Methods All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD or any cardiovascular disease (CVD. A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis. Results A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21–2.08; p = 0.001 and all CVD (hazard ratio 1.27; 95% confidence interval 1.07–1.51; p = 0.006. When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95–1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05–1.49; p = 0.014. Conclusion We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long

  1. Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage

    DEFF Research Database (Denmark)

    Hagmar, L; Brøgger, A; Hansteen, I L;

    1994-01-01

    Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target...... tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange.......0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk....

  2. Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: a Norwegian population-based cohort study

    Science.gov (United States)

    Ghaderi, S; Engeland, A; Moster, D; Ruud, E; Syse, A; Wesenberg, F; Bjørge, T

    2013-01-01

    Background: As the number of cancer survivors increases, their health and welfare have come into focus. Thus, long-term medical consequences of cancer at a young age (<25 years), obtained from social security benefit records, were studied. Methods: Standardised incidence ratios (SIRs) of long-term medical consequences for 5-year cancer survivors, born during 1965–1985, were explored by linking population-based registries in Norway. Results: Among the 5-year cancer survivors (4031 individuals), 29.7% received social security benefits. The survivors had an overall 4.4 times (95% confidence interval (95% CI): 4.1–4.6) higher risk of social security benefit uptake than the cancer-free population. Survivors of malignancies of bone and connective tissues (SIR: 10.8; 95% CI: 9.1–12.9), CNS tumours (SIR: 7.7; 95% CI: 6.9–8.6) and malignancies of the haematopoietic system (SIR: 6.1; 95% CI: 5.3–7.0) had the highest risks of social security benefits uptake. The most notified causes of social security benefit uptake were diseases of the nervous system, and injury and poisoning. Conclusion: The uptake of social security benefits among 5-year cancer survivors increased substantially and it may represent a solid outcome measure for the burden of the most severe late effects, especially in countries with comparable social welfare systems. PMID:23481179

  3. Breast cancer risk is not increased in individuals with TWIST1 mutation confirmed Saethre-Chotzen syndrome: an Australian multicenter study.

    NARCIS (Netherlands)

    James, P.A.; Culling, B.; Mullan, G.; Jenkins, M.; Elakis, G.; Turner, A.M.; Mowat, D.; Wilson, M.; Anderson, P.; Savarirayan, R.; Cliffe, S.T.; Caramins, M.; Buckley, M.F.; Tucker, K.; Roscioli, T.

    2009-01-01

    Saethre-Chotzen syndrome (SCS) is a rare autosomal dominant syndrome involving craniosynostosis, craniofacial abnormalities, and syndactyly. A recent Scandinavian study reported an increased risk of breast cancer in individuals with a clinical diagnosis of SCS. Because of the potential importance of

  4. Night-shift work increases morbidity of breast cancer and all-cause mortality: a meta-analysis of 16 prospective cohort studies.

    Science.gov (United States)

    Lin, Xiaoti; Chen, Weiyu; Wei, Fengqin; Ying, Mingang; Wei, Weidong; Xie, Xiaoming

    2015-11-01

    Night-shift work (NSW) has previously been related to incidents of breast cancer and all-cause mortality, but many published studies have reported inconclusive results. The aim of the present study was to quantify a potential dose-effect relationship between NSW and morbidity of breast cancer, and to evaluate the association between NSW and risk of all-cause mortality. The outcomes included NSW, morbidity of breast cancer, cardiovascular mortality, cancer-related mortality, and all-cause mortality. Sixteen investigations were included, involving 2,020,641 participants, 10,004 incident breast cancer cases, 7185 cancer-related deaths, 4820 cardiovascular end points, and 2480 all-cause mortalities. The summary risk ratio (RR) of incident breast cancer for an increase of NSW was 1.057 [95% confidence interval (CI) 1.014-1.102; test for heterogeneity p = 0.358, I(2) = 9.2%]. The combined RR (95% CI) of breast cancer risk for NSW vs daytime work was: 1.029 (0.969-1.093) in the 20-year exposure lengths. The overall RR was 1.089 (95% CI 1.016-1.166) in a fixed-effects model (test for heterogeneity p = 0.838, I(2) = 0%) comparing rotating NSW and day work. Night-shift work was associated with an increased risk of cardiovascular death (RR 1.027, 95% CI 1.001-1.053), and all-cause death 1.253 (95% CI 0.786-1.997). In summary, NSW increased the risk of breast cancer morbidity by: 1.9% for 5 years, 2.5% for 5-10 years, 7.4% for 10-20 years, and 8.8% for >20-years of NSW. Additionally, rotating NSW enhanced the morbidity of breast cancer by 8.9%. Moreover, NSW was associated with a 2.7% increase in cardiovascular death.

  5. Increased stomach cancer risk following radiotherapy for testicular cancer

    DEFF Research Database (Denmark)

    Hauptmann, M; Fossa, S D; Stovall, M

    2015-01-01

    BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated...... for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received...... radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend

  6. Thymoquinone Could Increase The Efficacy of Tamoxifen Induced Apoptosis in Human Breast Cancer Cells: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Sedigheh Ganji-Harsini

    2016-07-01

    Full Text Available Objective Thymoquinone (TQ, as the main component of Nigella Sativa plant, shows anticancer properties. This study was aimed to evaluate the combined effect of TQ and Tamoxifen (TAM on viability and apoptosis of human breast cancer cell lines. Materials and Methods In this experimental study, estrogen positive MCF-7 and estrogen negative MDA-MB-231 human breast cancer cell lines were induced by TAM (2 µM or different doses of TQ (50, 75, 100, 150 µM, individually or in combination. Cell viability and apoptosis were investigated by MTT assay and TdT-mediated deoxy-uracil nick end labeling (TUNEL assay; Acridine orange (AO/Ethidium bromide (EB staining respectively. Data were analyzed by one way ANOVA and P<0.05 was considered significant. Results In 24 hours treatment, TAM and all doses of TQ, solely or in combination, significantly reduced cell viability of both cell lines, except in MCF-7 cells treated with 50 µM TQ, and MDA-MB-231 cells treated with 50 or 75 µM TQ (P<0.01. After 48 hours treatment, cell viability of both cell lines was reduced in all treated groups (P<0.05. Remarkable apoptotic index was observed in combination treatment of MCF-7 or MDA-MB-231 cell lines with TAM and TQ (P<0.001. Conclusion The synergistic effect of TQ and TAM on human breast cancer cell lines showed cell viability reduction as well as apoptosis induction, independent to estrogen.

  7. Familial skin cancer syndromes: Increased melanoma risk.

    Science.gov (United States)

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.

  8. Spatial structure increases the waiting time for cancer

    DEFF Research Database (Denmark)

    Martens, Erik Andreas; Kostadinov, Rumen; Maley, Carlo C

    2011-01-01

    Cancer results from a sequence of genetic and epigenetic changes which lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells, and thus, to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has...... been experiencing increasing interest in recent years. Many efforts have been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured...... epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to asses two different paradigms of asexual evolution that have been suggested to delineate the process of cancer...

  9. Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

    Science.gov (United States)

    2005-07-01

    Madam , The project entitled INCREASING BREAST CANCER SURVEILLANCE AMONG AFRICAN AMERICAN BREAST CANCER SURVIVORS includes activities involving human...B b- d § fr. Thomisonwill Work e .y .With’Dra) Vdldf naTir, W and y Bo • rganif Janidorf on data a"_`l- ssi reatihfiutfor pres~entatidns and publi

  10. Increase of Prostate Cancer Incidence in Martinique

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    Dominique Belpomme

    2011-01-01

    Full Text Available Prostate cancer incidence is steadily increasing in many developed countries. Because insular populations present unique ethnic, geographical, and environmental characteristics, we analyzed the evolution of prostate cancer age-adjusted world standardized incidence rates in Martinique in comparison with that of metropolitan France. We also compared prostate cancer incidence rates, and lifestyle-related and socioeconomic markers such as life expectancy, dietary energy, and fat supply and consumption, with those in other Caribbean islands, France, UK, Sweden, and USA. The incidence rate of prostate cancer in Martinique is one of the highest reported worldwide; it is continuously growing since 1985 in an exponential mode, and despite a similar screening detection process and lifestyle-related behaviour, it is constantly at a higher level than in metropolitan France. However, Caribbean populations that are genetically close to that of Martinique have generally much lower incidence of prostate cancer. We found no correlation between prostate cancer incidence rates, life expectancy, and diet westernization. Since the Caribbean African descent-associated genetic susceptibility factor would have remained constant during the 1980–2005, we suggest that in Martinique some environmental change including the intensive use of carcinogenic organochlorine pesticides might have occurred as key determinant of the persisting highly growing incidence of prostate cancer.

  11. Increased risk for depression after breast cancer

    DEFF Research Database (Denmark)

    Suppli, Nis P; Johansen, Christoffer; Christensen, Jane

    2014-01-01

    PURPOSE: To investigate the risk for first depression, assessed as incident hospital contacts for depression and incident use of antidepressants, among women with breast cancer. PATIENTS AND METHODS: Danish national registries were used to identify 1,997,669 women with no diagnosis of cancer...... associated with use of antidepressants. CONCLUSION: Women with breast cancer are at long-term increased risk for first depression, including both severe episodes leading to hospital contact and use of antidepressants. Clinicians should be aware that the risk is highest in women with comorbid conditions, node...... or a major psychiatric disorder. This cohort was followed from 1998 to 2011 for a diagnosis of breast cancer and for the two outcomes, hospital contact for depression and redeemed prescriptions for antidepressants. Rate ratios for incident hospital contacts for depression and incident use of antidepressants...

  12. Increased metabolic activity detected by FLIM in human breast cancer cells with desmoplastic reaction: a pilot study

    Science.gov (United States)

    Natal, Rodrigo de Andrade; Pelegati, Vitor B.; Bondarik, Caroline; Mendonça, Guilherme R.; Derchain, Sophie F.; Lima, Carmen P.; Cesar, Carlos L.; Sarian, Luís. O.; Vassallo, José

    2015-07-01

    Introduction: In breast cancer (BC), desmoplastic reaction, assembled primarily by fibroblasts, is associated with unfavorable prognosis, but the reason of this fact remains still unclear. In this context, nonlinear optics microscopy, including Fluorescence Lifetime Imaging Microscopy (FLIM), has provided advancement in cellular metabolism research. In this paper, our purpose is to differentiate BC cells metabolism with or without contact to desmoplastic reaction. Formalin fixed, paraffin embedded samples were used at different points of hematoxylin stained sections. Methodology: Sections from 14 patients with invasive ductal breast carcinoma were analyzed with FLIM methodology to NAD(P)H and FAD fluorescence lifetime on a Confocal Upright LSM780 NLO device (Carl Zeiss AG, Germany). Quantification of the fluorescence lifetime and fluorescence intensity was evaluated by SPC Image software (Becker &Hickl) and ImageJ (NIH), respectively. Optical redox ratio was calculated by dividing the FAD fluorescence intensity by NAD(P)H fluorescence intensity. Data value for FLIM measurements and fluorescence intensities were calculated using Wilcoxon test; p< 0.05 was considered significant. Results: BC cells in contact with desmoplastic reaction presented a significantly lower NAD(P)H and FAD fluorescence lifetime. Furthermore, optical redox ratio was also lower in these tumor cells. Conclusion: Our results suggest that contact of BC cells with desmoplastic reaction increase their metabolic activity, which might explain the adverse prognosis of cases associated with higher peritumoral desmoplastic reaction.

  13. Terminate lung cancer (TLC) study-A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky.

    Science.gov (United States)

    Cardarelli, Roberto; Reese, David; Roper, Karen L; Cardarelli, Kathryn; Feltner, Frances J; Studts, Jamie L; Knight, Jennifer R; Armstrong, Debra; Weaver, Anthony; Shaffer, Dana

    2017-02-01

    For low dose CT lung cancer screening to be effective in curbing disease mortality, efforts are needed to overcome barriers to awareness and facilitate uptake of the current evidence-based screening guidelines. A sequential mixed-methods approach was employed to design a screening campaign utilizing messages developed from community focus groups, followed by implementation of the outreach campaign intervention in two high-risk Kentucky regions. This study reports on rates of awareness and screening in intervention regions, as compared to a control region.

  14. Increased risk of colon cancer after external radiation therapy for prostate cancer.

    Science.gov (United States)

    Rapiti, Elisabetta; Fioretta, Gerald; Verkooijen, Helena M; Zanetti, Roberto; Schmidlin, Franz; Shubert, Hyma; Merglen, Arnaud; Miralbell, Raymond; Bouchardy, Christine

    2008-09-01

    Radiotherapy can induce second cancers. Controversies still exist regarding the risk of second malignancies after irradiation for prostate cancer. We evaluated the risk of developing colon and rectum cancers after prostate cancer in irradiated and nonirradiated patients. Using data from the population-based Geneva cancer registry, we included in the study all men with prostate cancer diagnosed between 1980 and 1998 who survived at least 5 years after diagnosis. Of the 1,134 patients, 264 were treated with external radiotherapy. Patients were followed for occurrence of colorectal cancer up to 31 December, 2003. We calculated standardized incidence ratios (SIR) using incidence rates for the general population to obtain the expected cancer incidence. The cohort yielded to 3,798 person-years. At the end of follow-up 19 patients had developed a colorectal cancer. Among irradiated patients the SIR for colorectal cancer was 3.4 (95% confidence intervals [CI] 1.7-6.0). Compared to the general population, the risk was significantly higher for colon cancer (SIR = 4.0, 95% CI: 1.8-7.6), but not for rectal cancer (SIR = 2.0, 95% CI: 0.2-7.2). The risk of colon cancer was increased in the period of 5-9 years after diagnosis (SIR = 4.7, 95% CI: 2.0-9.2). The overall SIR of secondary cancer in patients treated with radiotherapy was 1.35 (p = 0.056). Nonirradiated patients did not have any increased risk of rectal or colon cancer. This study shows a significant increase of colon but not rectum cancer after radiotherapy for prostate cancer. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.

  15. Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case-control studies in Montreal.

    Science.gov (United States)

    Vallières, Eric; Pintos, Javier; Lavoué, Jérôme; Parent, Marie-Élise; Rachet, Bernard; Siemiatycki, Jack

    2012-08-01

    We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case-control studies were conducted in Montreal. Study I (1979-1986) included 857 cases and 1066 controls, and Study II (1996-2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist-hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9-1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8-1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7-4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3-3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes.

  16. Traditional Dietary Pattern Increases Risk of Prostate Cancer in Argentina: Results of a Multilevel Modeling and Bias Analysis from a Case-Control Study

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    Camila Niclis

    2015-01-01

    Full Text Available There is increasing evidence that dietary habits play a role in prostate cancer (PC occurrence. Argentinean cancer risk studies require additional attention because of the singular dietary pattern of this population. A case-control study (147 PC cases, 300 controls was conducted in Córdoba (Argentina throughout 2008–2013. A principal component factor analysis was performed to identify dietary patterns. A mixed logistic regression model was applied, taking into account family history of cancer. Possible bias was evaluated by probabilistic bias analysis. Four dietary patterns were identified: Traditional (fatty red meats, offal, processed meat, starchy vegetables, added sugars and sweets, candies, fats, and vegetable oils, Prudent (nonstarchy vegetables, whole grains, Carbohydrate (sodas/juices and bakery products, and Cheese (cheeses. High adherence to the Traditional (OR 2.82, 95%CI: 1.569–5.099 and Carbohydrate Patterns (OR 2.14, 95%CI: 1.470–3.128 showed a promoting effect for PC, whereas the Prudent and Cheese Patterns were independent factors. PC occurrence was also associated with family history of PC. Bias adjusted ORs indicate that the validity of the present study is acceptable. High adherence to characteristic Argentinean dietary patterns was associated with increased PC risk. Our results incorporate original contributions to knowledge about scenarios in South American dietary patterns and PC occurrence.

  17. Spatial structure increases the waiting time for cancer

    Science.gov (United States)

    Martens, Erik A.; Kostadinov, Rumen; Maley, Carlo C.; Hallatschek, Oskar

    2011-11-01

    Cancer results from a sequence of genetic and epigenetic changes that lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells and thus to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been attracting increasing interest in recent years. A great deal of effort has been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to assess two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones and decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale Lc. These characteristic features of clonal interference may help us to predict the onset of cancers with pronounced spatial structure and to interpret spatially sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progression of colon cancer and possibly other cancers where spatial structure matters.

  18. Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study

    DEFF Research Database (Denmark)

    Näslund-Koch, Charlotte; Nordestgaard, Børge G; Bojesen, Stig E

    2016-01-01

    and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were......% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1...

  19. CYP1A1 gene polymorphisms increase lung cancer risk in a high-incidence region of Spain: a case control study

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    San Jose Carmen

    2010-08-01

    Full Text Available Abstract Background A rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study. The present work was undertaken to ascertain the role of CYP1A1 gene polymorphisms and their interaction with tobacco smoking in the development of the disease in this location. Methods One-hundred-and-three cases of lung cancer and 265 controls participated in the study. The participants were screened for the presence of four CYP1A1 polymorphisms, namely MspI, Ile462Val, T3205C, and Thr461Asn. Lung cancer risk was estimated as odds ratios (OR and 95% confidence intervals (CI using unconditional logistic regression models adjusting for age, sex, and smoking. Results The distribution of the variant CYP1A1 alleles was different from that described for other Caucasian populations, with CYP1A1*2A showing an uncommonly high frequency (p CYP1A1*2B allele (carrying MspI and Ile462Val mutations was strongly associated with high lung cancer risk (OR = 4.59, CI:1.4-12.6, p p p = 0.04. Moreover, the Thr461Asn polymorphism was found to be associated with SCLC in a Caucasian population for the first time to our knowledge (OR = 8.33, CI: 1.3-15.2, p = 0.04. Conclusion The results suggest that CYP1A1 polymorphisms contribute to increase lung cancer susceptibility in an area with an uncommon high incidence rate.

  20. Does Hair Dye Use Increase the Risk of Breast Cancer? A Population-Based Case-Control Study of Finnish Women.

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    Sanna Heikkinen

    Full Text Available Role of hair dyes in the etiology of breast cancer has occasionally raised concern but previous research has concluded with mixed results. Remnants of prohibited aromatic amines have been found in many hair dye products, and elevated levels of DNA-adducts of these amines have been detected from breast epithelial cells of hair dye users. However, the IARC working group has concluded that there is inadequate evidence for carcinogenicity of personal hair dye use and limited evidence in experimental animals for carcinogenicity of hair colorants.We investigated whether the use of hair dyes is associated with breast cancer risk in women. The study design was a retrospective population-based case-control study in Finland, with a self-administered questionnaire from 6,567 breast cancer patients, aged 22-60 years and diagnosed in 2000-2007, and their 21,598 matched controls. We report odds ratios (OR with 95% confidence interval (95% CI from a conditional logistic regression model applied to the frequency matched sets of cases and controls. Bias-adjusted odds ratios from the sensitivity analysis are also presented.After adjusting for potential confounders, the odds of breast cancer increased by 23% (OR: 1.23, 95% CI: 1.11-1.36 among women who used hair dyes compared to those who did not. In women born before 1950 an increase of 28% was noted (OR: 1.28, 95% CI: 1.10-1.48. We also observed a significant trend between the OR and cumulative use of hair dyes (P: 0.005. Bias-adjusted odds ratios varied between 1.04 and 2.50.Our results suggest that use of hair dyes is associated with breast cancer incidence. The impact on public health may be substantial due to vast popularity of hair coloring in modern societies. It should be noted that regardless of all efforts, a possibility of bias cannot definitively be ruled out and use of a prospective design is warranted. Based on the present results, it may be concluded however that safety of hair dyes in relation to

  1. Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

    DEFF Research Database (Denmark)

    Leeming, Diana J; Byrjalsen, Inger; Qvist, Per

    2008-01-01

    BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover...... in breast and prostate cancer patients is associated with an increase in cartilage degradation and to test in vitro whether osteoclasts or cathepsin K alone generate CTXII from human bone. METHODS: The study included 132 breast and prostate cancer patient, where presence of bone metastases was graded...... according to the Soloway score. Total bone resorption (CTXItotal) and cartilage degradation (CTXII) were determined. RESULTS: Breast and prostate cancer patients with bone metastases revealed significant increased levels of CTXItotal at Soloway scores 1 and higher compared to patients without bone...

  2. Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression

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    Sabrina Bimonte

    2015-01-01

    Full Text Available Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Several in vitro and in vivo studies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performed in vitro studies on ER-negative human breast carcinoma cells, MDA.MB231 and in vivo studies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphine in vitro enhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells. In vivo studies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression.

  3. Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience

    Science.gov (United States)

    Cortesi, Laura; Turchetti, Daniela; Marchi, Isabella; Fracca, Antonella; Canossi, Barbara; Rachele, Battista; Silvia, Ruscelli; Rita, Pecchi Anna; Pietro, Torricelli; Massimo, Federico

    2006-01-01

    Background Breast cancer (BC) detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification. Methods We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44) were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC). The standardized incidence ratio (SIR) was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided. Results After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI) = 1.6 to 7.6; p < 0.001]. The incidence observed among BRCA carriers (SIR = 20.3; 95% CI = 3.1 to 83.9; P < 0.001), women at increased (SIR = 4.5; 95% CI = 1.5 to 8.3; P < 0.001) or intermediate risk (SIR = 7.0, 95% CI = 2.0 to 17.1; P = 0.0018) was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74). Conclusion The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in

  4. Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience

    Directory of Open Access Journals (Sweden)

    Cortesi Laura

    2006-08-01

    Full Text Available Abstract Background Breast cancer (BC detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification. Methods We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44 were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC. The standardized incidence ratio (SIR was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided. Results After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI = 1.6 to 7.6; p P P P = 0.0018 was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74. Conclusion The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in the slightly increased risk group. These results support the effectiveness of the proposed program to identify and monitor individuals at high risk, whereas prospective trials are needed for

  5. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Science.gov (United States)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  6. Idiopathic pulmonary fibrosis will increase the risk of lung cancer

    Institute of Scientific and Technical Information of China (English)

    Li Junyao; Yang Ming; Li Ping; Su Zhenzhong; Gao Peng; Zhang Jie

    2014-01-01

    Objective To review the studies investigating the increased risk of lung cancer in patients with idiopathic pulmonary fibrosis (IPF).Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1999 to 2013 and highly regarded older publications were also included.Study selection We identified,retrieved and reviewed the information on the frequency,risk factors,anatomical features,histological types,clinical manifestations,computed tomography findings and underlying mechanisms of lung cancer in IPF patients.Results The prevalence rates of lung cancer in patients with IPF (4.8% to 48%) are much higher than patients without IPF (2.0% to 6.4%).The risk factors for lung cancer in IPF include smoking,male gender,and age.Lung cancers often occur in the peripheral lung zones where fibrotic changes are predominant.Adenocarcinoma and squamous cell carcinoma are the most common types of lung cancer in patients with IPF.Radiologic features of these patients include peripherally located,ill-defined mass mimicking air-space disease.The underlying mechanisms of the development of lung cancer in patients with IPF have not been fully understood,but may include the inflammatory response,epithelial injury and/or abnormalities,aberrant fibroblast proliferation,epigenetic and genetic changes,reduced cell-to-cell communication,and activation of specific signaling pathways.Conclusions These findings suggest that IPF is associated with increased lung cancer risk.It is necessary to raise the awareness of lung cancer risk in IPF patients among physicians and patients.

  7. Increased Dietary Inflammatory Index (DII) Is Associated With Increased Risk of Prostate Cancer in Jamaican Men

    Science.gov (United States)

    Shivappa, Nitin; Jackson, Maria D.; Bennett, Franklyn; Hébert, James R.

    2015-01-01

    Purpose Prostate cancer is the most common non-skin malignancy; and it accounts for the most cancer deaths among Jamaican males. Diet has been implicated in the etiology of prostate cancer, including through its effects on inflammation. Method We examined the association between a newly developed dietary inflammatory index (DII) and prostate cancer in a case-control study of 40-80 year-old Jamaican males. A total of 229 incident cases and 250 controls attended the same urology out-patient clinics at 2 major hospitals and private practitioners in the Kingston, Jamaica Metropolitan area between March 2005 and July 2007. The DII was computed based on dietary intake assessed using a previously validated food frequency questionnaire (FFQ) that was expanded to assess diet and cancer in this Jamaican population. Multivariable logistic regression was used to estimate odds ratios, with DII as continuous and expressed as quartiles. Logistic regression analysis adjusted for age, total energy intake, education, body mass index (BMI), smoking status, physical activity and family history of prostate cancer. Results Men in the highest quartile of the DII were at higher risk of prostate cancer [odds ratio (OR) = 2.39; 95% confidence interval (CI) =1.14–5.04 (Ptrend = 0.08)] compared to men in the lowest DII quartile. Conclusion These data suggest a pro-inflammatory diet, as indicated by increasing DII score, may be a risk factor for prostate cancer in Jamaican men. PMID:26226289

  8. Increased entropy of signal transduction in the cancer metastasis phenotype

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    Teschendorff Andrew E

    2010-07-01

    Full Text Available Abstract Background The statistical study of biological networks has led to important novel biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Results Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis and provide examples of de-novo discoveries of gene modules with known roles in apoptosis, immune-mediated tumour suppression, cell-cycle and tumour invasion. Importantly, we also identify a novel gene module within the insulin growth factor signalling pathway, alteration of which may

  9. Is cancer mortality increasing in France?

    OpenAIRE

    Hill, C.; Jan, P; Doyon, F

    2001-01-01

    Long-term trends in cancer mortality are reported by site. Overall, cancer mortality has been decreasing in France since 1987 in the male population and since 1968 in the female population. Improvement in treatments and diagnosis should lead to persistently declining mortality rates, unless the tobacco epidemic reverses the trend in female mortality. © 2001 Cancer Research Campaign http://www.bjcancer.com

  10. Cervical cancer screening and adherence to follow-up among Hispanic women study protocol: a randomized controlled trial to increase the uptake of cervical cancer screening in Hispanic women

    Directory of Open Access Journals (Sweden)

    Duggan Catherine

    2012-05-01

    Full Text Available Abstract Background In the US, Hispanic women have a higher incidence of, and mortality from, cervical cancer than non-Hispanic white women. The reason for this disparity may be attributable to both low rates of screening and poor adherence to recommended diagnostic follow-up after an abnormal Pap test. The 'Cervical Cancer Screening and Adherence to Follow-up Among Hispanic Women' study is a collaboration between a research institution and community partners made up of members from community based organizations, the Yakima Valley Farm Workers Clinic and the Breast, Cervical, and Colon Health Program of the Yakima District . The study will assess the efficacy of two culturally-appropriate, tailored educational programs designed to increase cervical cancer screening among Hispanic women, based in the Yakima Valley, Washington, US. Methods/design A parallel randomized-controlled trial of 600 Hispanic women aged 21–64, who are non-compliant with Papanicolau (Pap test screening guidelines. Participants will be randomized using block randomization to (1 a control arm (usual care; (2 a low-intensity information program, consisting of a Spanish-language video that educates women on the importance of cervical cancer screening; or (3 a high-intensity program consisting of the video plus a ‘promotora’ or lay-community health educator-led, home based intervention to encourage cervical cancer screening. Participants who attend cervical cancer screening, and receive a diagnosis of an abnormal Pap test will be assigned to a patient navigator who will provide support and information to promote adherence to follow-up tests, and any necessary surgery or treatment. Primary endpoint: Participants will be tracked via medical record review at community-based clinics, to identify women who have had a Pap test within 7 months of baseline assessment. Medical record reviewers will be blinded to randomization arm. Secondary endpoint: An evaluation of the patient

  11. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals

    Directory of Open Access Journals (Sweden)

    Tsai Hsin-Ni

    2011-01-01

    Full Text Available Abstract Background Metformin protection against cancer risk in Orientals is uncertain. We examined the possible metformin effect on total, esophageal, gastric, colorectal (CRC, hepatocellular (HCC and pancreatic cancers in a Taiwanese cohort. Methods A representative sample of 800,000 was drawn from the Taiwanese National Health Insurance data of 2000. A cohort of 480,984 participants 20 years or older, diabetes-cancer-free on 1st January 2000 was formed and categorized as four groups by DM and metformin usage status. Eligible incident cancer events had to occur one year after the index date until the end of 2007. The Cox proportional-hazards model evaluated relative risk of cancer for treated DM patients with or without metformin. The covariates included age, gender, other oral anti-hyperglycemic medication, Charlson comorbidity index (CCI score and metformin exposure dosage and duration. Results With diabetes but no anti-hyperglycemic medication, cancer incidence density increased at least 2-fold for total, CRC and HCC. On metformin, total, CRC and HCC incidences decreased to near non-diabetic levels but to varying degrees depending on gender and cancer type (CRC in women, liver in men. Adjustment for other oral anti-hyperglycemic agents usage and CCI made the benefit of metformin more evident [hazard ratios (95% confidence intervals: total 0.12 (0.08-0.19, CRC 0.36 (0.13-0.98, liver 0.06 (0.02-0.16, pancreas 0.15 (0.03-0.79]. There was a significant gender interaction with metformin in CRC which favored women. Metformin dosage for a significant decrease in cancer incidence was ≤500 mg/day. Conclusions Metformin can reduce the incidences of several gastroenterological cancers in treated diabetes.

  12. Nutrition deficiency increases the risk of stomach cancer mortality

    Directory of Open Access Journals (Sweden)

    Da Li Qing

    2012-07-01

    Full Text Available Abstract Background The purpose of the study is to determine whether exposure to malnutrition during early life is associated with increased risk of stomach cancer in later life. Methods The design protocol included analyzing the trend of gastric cancer mortality and nutrition and evaluating the association between nutrient deficiency in early life and the risk of gastric cancer by hierarchical age–period–birth cohort (APC analysis using general log-linear Poisson models and to compare the difference between birth cohorts who were exposed to the 1959–1961 Chinese famine and those who were not exposed to the famine. Data on stomach cancer mortality from 1970 to 2009 and the dietary patterns from 1955 to 1985 which included the 1959–1961 Chinese famine period in the Zhaoyuan County population were obtained. The nutrition information was collected 15 years prior to the mortality data as based on the latest reference of disease incubation. Results APC analysis revealed that severe nutrition deficiency during early life may increase the risk of stomach cancer. Compared with the 1960–1964 birth cohort, the risk for stomach cancer in all birth cohorts from 1900 to 1959 significantly increased; compared with the 1970–1974 cohort, the risk for stomach cancer in the 1975–1979 cohort significantly increased, whereas the others had a steadily decreased risk; compared with 85–89 age group in the 2005–2009 death survey, the ORs decreased with younger age and reached significant levels for the 50–54 age group after adjusting the confounding factors. The 1930 to 1964 group (exposed to famine had a higher mortality rate than the 1965 to 1999 group (not exposed to famine. For males, the relative risk (RR was 2.39 and the 95% confidence interval (CI was 1.51 to 3.77. For females, RR was 1.64 and 95% CI was 1.02 to 2.62. Conclusion The results of the present study suggested that prolonged malnutrition during early life may increase the risk of

  13. Increasing Breast Cancer Surveillance Among African American Breast Cancer Survivors

    Science.gov (United States)

    2010-01-01

    Family history of breast cancer  specifically mother or sister diagnosed with breast cancer  Not the same as genetic risk for breast cancer...treatment. Table 5 presents sociodemographic variables for the first 20 SIS participants. The majority of participants were African American, unmarried

  14. Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.

    Science.gov (United States)

    Zick, Suzanna M; Turgeon, D Kim; Ren, Jianwei; Ruffin, Mack T; Wright, Benjamin D; Sen, Ananda; Djuric, Zora; Brenner, Dean E

    2015-09-01

    Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk.

  15. Determinants of increased primary health care use in cancer survivors.

    NARCIS (Netherlands)

    Heins, M.; Schellevis, F.; Rijken, M.; Hoek, L. van der; Korevaar, J.

    2012-01-01

    Purpose: The number of cancer survivors is increasing, and patients with cancer often experience long-lasting consequences of cancer and its treatment. Because of the variety of health problems and high prevalence of comorbidity, primary care physicians (PCPs) seem obvious candidates to take care of

  16. Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study

    DEFF Research Database (Denmark)

    Forner, Lone; Hansen, Ole Hyldegaard; von Brockdorff, Annet Schack

    2011-01-01

    Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO...

  17. Increased pancreatic cancer risk following radiotherapy for testicular cancer

    DEFF Research Database (Denmark)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S

    2016-01-01

    BACKGROUND: Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. METHODS: Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer...... patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). RESULTS: Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated...... with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. CONCLUSIONS: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small...

  18. Mortality salience increases defensive distancing from people with terminal cancer.

    Science.gov (United States)

    Smith, Lauren M; Kasser, Tim

    2014-01-01

    Based on principles of terror management theory, the authors hypothesized that participants would distance more from a target person with terminal cancer than from a target with arthritis, and that this effect would be stronger following mortality salience. In Study 1, adults rated how similar their personalities were to a target person; in Study 2, participants arranged two chairs in preparation for meeting the target person. Both studies found that distancing from the person with terminal cancer increased after participants wrote about their own death (vs. giving a speech). Thus, death anxiety may explain why people avoid close contact with terminally ill people; further analyses suggest that gender and self-esteem may also influence such distancing from the terminally ill.

  19. EPS8 inhibition increases cisplatin sensitivity in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Lidija K Gorsic

    Full Text Available Cisplatin, a commonly used chemotherapeutic, is associated with ototoxicity, renal toxicity and neurotoxicity, thus identifying means to increase the therapeutic index of cisplatin may allow for improved outcomes. A SNP (rs4343077 within EPS8, discovered through a genome wide association study of cisplatin-induced cytotoxicity and apoptosis in lymphoblastoid cell lines (LCLs, provided impetus to further study this gene. The purpose of this work was to evaluate the role of EPS8 in cellular susceptibility to cisplatin in cancerous and non-cancerous cells. We used EPS8 RNA interference to determine the effect of decreased EPS8 expression on LCL and A549 lung cancer cell sensitivity to cisplatin. EPS8 knockdown in LCLs resulted in a 7.9% increase in cisplatin-induced survival (P = 1.98 × 10(-7 and an 8.7% decrease in apoptosis (P = 0.004 compared to control. In contrast, reduced EPS8 expression in lung cancer cells resulted in a 20.6% decrease in cisplatin-induced survival (P = 5.08 × 10(-5. We then investigated an EPS8 inhibitor, mithramycin A, as a potential agent to increase the therapeutic index of cisplatin. Mithramycin A decreased EPS8 expression in LCLs resulting in decreased cellular sensitivity to cisplatin as evidenced by lower caspase 3/7 activation following cisplatin treatment (42.7% ± 6.8% relative to control P = 0.0002. In 5 non-small-cell lung carcinoma (NSCLC cell lines, mithramycin A also resulted in decreased EPS8 expression. Adding mithramycin to 4 NSCLC cell lines and a bladder cancer cell line, resulted in increased sensitivity to cisplatin that was significantly more pronounced in tumor cell lines than in LCL lines (p<0.0001. An EGFR mutant NSCLC cell line (H1975 showed no significant change in sensitivity to cisplatin with the addition of mithramycin treatment. Therefore, an inhibitor of EPS8, such as mithramycin A, could improve cisplatin treatment by increasing sensitivity of tumor relative to normal cells.

  20. Delayed diagnosis of coeliac disease increases cancer risk

    Directory of Open Access Journals (Sweden)

    Di Benedetto Rita

    2007-03-01

    Full Text Available Abstract Background The association between coeliac disease (CD and neoplasms has been long established, but few data are available about the risk factors. The aim of this paper is to estimate the risk of developing a neoplasm among non diagnosed coeliac patients and to evaluate if this risk correlates with the age of patients at diagnosis of coeliac disease. Methods The study population consists of patients (n = 1968 diagnosed with CD at 20 Italian gastroenterology referral Centers between 1st January 1982 and 31st March 2005. Results The SIR for all cancers resulted to be 1.3; 95% CI = 1.0–1.7 p Conclusion Coeliac patients have an increased risk of developing cancer in relation to the age of diagnosis of CD. This risk results higher for malignancies of the gastro-intestinal sites. An accurate screening for tumors should be performed in patients diagnosed with CD in adulthood and in advancing age.

  1. Increased risk of antidepressant use in childhood cancer survivors

    DEFF Research Database (Denmark)

    Lund, Lasse Wegener; Winther, J F; Cederkvist, L;

    2015-01-01

    AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage...... survivors were at increased risk of having antidepressants prescribed (HR, 1.4; 95% confidence interval (CI), 1.3-1.5). The excess absolute risk of antidepressant use was 2.5 per 1000 person-years (95% CI, 1.7-3.3), equivalent to an excess of 2.5 survivors for every 100 survivors followed for 10years....... Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk...

  2. What implementation interventions increase cancer screening rates? a systematic review

    Directory of Open Access Journals (Sweden)

    Lent Barbara

    2011-09-01

    Full Text Available Abstract Background Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. As part of a larger agenda to create an implementation guideline, we conducted a systematic review to evaluate interventions designed to increase the rate of breast, cervical, and colorectal cancer (CRC screening. The interventions considered were: client reminders, client incentives, mass media, small media, group education, one-on-one education, reduction in structural barriers, reduction in out-of-pocket costs, provider assessment and feedback interventions, and provider incentives. Our primary outcome, screening completion, was calculated as the overall median post-intervention absolute percentage point (PP change in completed screening tests. Methods Our first step was to conduct an iterative scoping review in the research area. This yielded three relevant high-quality systematic reviews. Serving as our evidentiary foundation, we conducted a formal update. Randomized controlled trials and cluster randomized controlled trials, published between 2004 and 2010, were searched in MEDLINE, EMBASE and PSYCHinfo. Results The update yielded 66 studies new eligible studies with 74 comparisons. The new studies ranged considerably in quality. Client reminders, small media, and provider audit and feedback appear to be effective interventions to increase the uptake of screening for three cancers. One-on-one education and reduction of structural barriers also appears effective, but their roles with CRC and cervical screening, respectively, are less established. More study is required to assess client incentives, mass media, group education, reduction of out-of-pocket costs, and provider incentive interventions. Conclusion The new evidence generally aligns with the evidence and conclusions from the original systematic

  3. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural...... history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe....

  4. Case Studies - Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2010-10-15

    Dr. Alan Waxman, a professor of obstetrics and gynecology at the University of New Mexico and chair of the American College of Obstetricians and Gynecologists (ACOG) committee for the underserved, talks about several case studies for cervical cancer screening and management.  Created: 10/15/2010 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  5. Thyroid cancer risk is not increased in diabetic patients.

    Directory of Open Access Journals (Sweden)

    Chin-Hsiao Tseng

    Full Text Available OBJECTIVE: This study evaluated thyroid cancer risk with regards to diabetes status and diabetes duration, and with the use of anti-diabetic drugs including sulfonylurea, metformin, insulin, acarbose, pioglitazone and rosiglitazone, by using a population-based reimbursement database in Taiwan. METHODS: A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. After excluding patients with type 1 diabetes, 999730 subjects (495673 men and 504057 women were recruited into the analyses. Logistic regression estimated the odds ratios (OR and their 95% confidence intervals (CI for independent variables including age, sex, diabetes status/duration, anti-diabetic drugs, other medications, comorbidities, living regions, occupation and examinations that might potentially lead to the diagnosis of thyroid cancer in various models. RESULTS: The diabetic patients had a significantly higher probability of receiving potential detection examinations (6.38% vs. 5.83%, P<0.0001. After multivariable-adjustment, the OR (95% CI for diabetes status was 0.816 (0.652-1.021; and for diabetes duration <1 year, 1-3 years, 3-5 years and ≥ 5 years vs. non-diabetes was 0.071 (0.010-0.507, 0.450 (0.250-0.813, 0.374 (0.203-0.689 and 1.159 (0.914-1.470, respectively. Among the anti-diabetic agents, only sulfonylurea was significantly associated with thyroid cancer, OR (95% CI: 1.882 (1.202-2.947. The OR (95% CI for insulin, metformin, acarbose, pioglitazone and rosiglitazone was 1.701 (0.860-3.364, 0.696 (0.419-1.155, 0.581 (0.202-1.674, 0.522 (0.069-3.926 and 0.669 (0.230-1.948, respectively. Furthermore, patients with benign thyroid disease or other cancer, living in Kao-Ping/Eastern regions, or receiving potential detection examinations might have a significantly higher risk; and male sex, hypertension, dyslipidemia, chronic obstructive pulmonary disease, vascular complications or use of statin, aspirin or non-steroidal anti

  6. Breast cancer patients with dense breasts do not have increased death risk

    Science.gov (United States)

    High mammographic breast density, which is a marker of increased risk of developing breast cancer, does not seem to increase the risk of death among breast cancer patients, according to a study led by Gretchen L. Gierach, Ph.D., NCI. Image shows physician

  7. Increased mean lung density: Another independent predictor of lung cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Sverzellati, Nicola, E-mail: nicola.sverzellati@unipr.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Randi, Giorgia, E-mail: giorgia.randi@marionegri.it [Department of Epidemiology, Mario Negri Institute, Via La Masa 19, 20156 Milan (Italy); Spagnolo, Paolo, E-mail: paolo.spagnolo@unimore.it [Respiratory Disease Unit, Center for Rare Lung Disease, Department of Oncology, Hematology and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo 71, 44124 Modena (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy); Silva, Mario, E-mail: mac.mario@hotmail.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Kuhnigk, Jan-Martin, E-mail: Jan-Martin.Kuhnigk@mevis.fraunhofer.de [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); La Vecchia, Carlo, E-mail: carlo.lavecchia@marionegri.it [Department of Occupational Health, University of Milan, Via Venezian 1, 20133 Milan (Italy); Zompatori, Maurizio, E-mail: maurizio.zompatori@unibo.it [Department of Radiology, Cardio-Thoracic Section, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna (Italy); Pastorino, Ugo, E-mail: ugo.pastorino@istitutotumori.mi.it [Department of Surgery, Section of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy)

    2013-08-15

    Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n = 119) and controls (n = 989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1 s (FEV{sub 1}) independently of MLD (OR 5.37, 95% CI: 2.63–10.97 for FEV{sub 1} < 60% vs. FEV{sub 1} ≥ 90%), and with increasing MLD independently of FEV{sub 1} (OR 3.00, 95% CI: 1.60–5.63 for MLD > −823 vs. MLD < −857 Hounsfield units). Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV{sub 1} was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.

  8. Epidemiological studies of cancer in aircrew.

    Science.gov (United States)

    Hammer, Gaël P; Blettner, Maria; Zeeb, Hajo

    2009-10-01

    Exposure to cosmic ionising radiation, in addition to other specific occupational risks, is of concern to aircrew members. Epidemiological studies provide an objective way to assess the health of this occupational group. We systematically reviewed the epidemiological literature on health of aircrew members since 1990, focusing on cancer as the endpoint of interest. Sixty-five relevant publications were identified and reviewed. Whereas overall cancer incidence and mortality was generally lower than in the comparison population, consistently elevated risks were reported for breast cancer incidence in female aircrew members and for melanoma in both male and female aircrew members. Brain cancer was increased in some studies among pilots. Occasionally trends of increasing cancer mortality or incidence with increasing estimated radiation dose were reported. Ionising radiation is considered to contribute little if at all to the elevated risks for cancers among aircrew, whereas excess ultraviolet radiation is a probable cause of the increased melanoma risk.

  9. Increased expression and aberrant localization of mucin 13 in metastatic colon cancer.

    Science.gov (United States)

    Gupta, Brij K; Maher, Diane M; Ebeling, Mara C; Sundram, Vasudha; Koch, Michael D; Lynch, Douglas W; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E; Jaggi, Meena; Chauhan, Subhash C

    2012-11-01

    MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer.

  10. Co-treatment of Salinomycin Sensitizes AZD5363-treated Cancer Cells Through Increased Apoptosis.

    Science.gov (United States)

    Choi, Ae-Ran; Jung, Myung-Ji; Kim, Ju-Hwa; Yoon, Sungpil

    2015-09-01

    AZD5363, an inhibitor of protein kinase B (AKT), is currently in clinical trials assessing the potential of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. The purpose of the present study was to identify conditions that increase the sensitivity of cancer cells to AZD5363. Microscopic examination revealed that treatment of cancer cells with a low concentration of salinomycin reduced cellular growth of AZD5363-treated breast cancer cells. Furthermore, fluorescence-activated cell sorting (FACS) analysis, Hoechst staining, and annexin V staining revealed that co-treatment with salinomycin sensitizes AZD5363-treated cancer cells via increased apoptosis with S-phase arrest. These results suggest that salinomycin can be applied to increase treatment efficacy for AZD5363-treated cancer cells. Our findings may contribute to improving the efficacy of the development of AZD5363-based sensitization therapies for patients with cancer.

  11. Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

    Science.gov (United States)

    Hung, Ming-Szu; Chen, I-Chuan; You, Liang; Jablons, David M; Li, Ya-Chin; Mao, Jian-Hua; Xu, Zhidong; Lung, Jr-Hau; Yang, Cheng-Ta; Liu, Shih-Tung

    2016-07-01

    Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung cancer cells. Moreover, increased expression of p21, transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) and TGF beta-induced (TGFBI) was observed in lung cancer cells after Cul4A knockdown, which may be partially related to increased chemosensitivity to gemcitabine. G0/G1 cell cycle arrest was also noted after Cul4A knockdown. Notably, decreased tumour growth and increased chemosensitivity to gemcitabine were also noted after Cul4A knockdown in lung cancer xenograft nude mice models. In summary, our study showed that targeting Cul4A with RNAi or other techniques may provide a possible insight to the development of lung cancer therapy in the future.

  12. Cancer knowledge increases after a brief intervention among Arab Americans in Michigan.

    Science.gov (United States)

    Dallo, Florence J; Zakar, Tabitha; Borrell, Luisa N; Fakhouri, Monty; Jamil, Hikmet

    2011-03-01

    The objective of this study was to examine which factors are associated with increased cancer knowledge among a sample of 866 Arab Americans 40 years of age or older. Individuals were invited to attend a cancer educational intervention and obtain a free cancer health screening. They were asked to complete a precancer and postcancer knowledge survey after the brief educational intervention. Using logistic regression, we found that the intervention increased cancer knowledge and the variables most associated with this improvement were having low education, being unemployed, having lived in the USA for 0-5 years, older age, not having insurance, and not exercising. Our study showed that these interventions may be more effective if tailored to the participant's educational, employment, duration in the US, and health behavior status. Future studies should examine whether cancer screening actually increases after an educational intervention.

  13. Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

    OpenAIRE

    Chang-Mo Oh; Sohee Park; Joo Young Lee; Young-Joo Won; Aesun Shin; Hyun-Joo Kong; Kui-Sun Choi; You Jin Lee; Ki-Wook Chung; Kyu-Won Jung

    2014-01-01

    Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by...

  14. Pregnancy-associated breast cancer and increased risk of pregnancy-associated recurrence: a case report

    Directory of Open Access Journals (Sweden)

    Schnabel Freya

    2012-06-01

    Full Text Available Abstract Introduction Pregnancy-associated breast cancer refers to breast cancer diagnosed during pregnancy, lactation, or within twelve months postpartum. Recent studies suggest that, when matched for age and stage, the prognosis of pregnancy-associated breast cancer is comparable to non-pregnancy-associated breast cancer. However, the risk for breast cancer recurrence associated with subsequent pregnancies in this population is not clear. Case presentation We describe the case of a Caucasian woman who was initially treated for pregnancy-associated breast cancer at age 23, three months after the birth of her third child. She underwent a total mastectomy with axillary node dissection, followed by chemotherapy and hormonal therapy. Ten years later, when the patient was 24 weeks pregnant with her fourth child, she presented with an ipsilateral chest wall recurrence of breast cancer. To the best of our knowledge, this represents the first reported case of a pregnancy-associated recurrence in a patient previously treated for pregnancy-associated breast cancer. Conclusion The case described here is the first report of a second occurrence of pregnancy-associated breast cancer. This case raises the possibility that pregnancy may represent a unique trigger for breast malignancy in a specific cohort of women. Although there is data showing no increase in the risk of recurrence for women who become pregnant after breast cancer treatment, pregnancy-associated breast cancer may be a distinct clinical category where subsequent pregnancies after treatment may confer an increased risk of recurrent disease.

  15. Glucose-deprivation increases thyroid cancer cells sensitivity to metformin.

    Science.gov (United States)

    Bikas, Athanasios; Jensen, Kirk; Patel, Aneeta; Costello, John; McDaniel, Dennis; Klubo-Gwiezdzinska, Joanna; Larin, Olexander; Hoperia, Victoria; Burman, Kenneth D; Boyle, Lisa; Wartofsky, Leonard; Vasko, Vasyl

    2015-12-01

    Metformin inhibits thyroid cancer cell growth. We sought to determine if variable glucose concentrations in medium alter the anti-cancer efficacy of metformin. Thyroid cancer cells (FTC133 and BCPAP) were cultured in high-glucose (20 mM) and low-glucose (5 mM) medium before treatment with metformin. Cell viability and apoptosis assays were performed. Expression of glycolytic genes was examined by real-time PCR, western blot, and immunostaining. Metformin inhibited cellular proliferation in high-glucose medium and induced cell death in low-glucose medium. In low-, but not in high-glucose medium, metformin induced endoplasmic reticulum stress, autophagy, and oncosis. At micromolar concentrations, metformin induced phosphorylation of AMP-activated protein kinase and blocked p-pS6 in low-glucose medium. Metformin increased the rate of glucose consumption from the medium and prompted medium acidification. Medium supplementation with glucose reversed metformin-inducible morphological changes. Treatment with an inhibitor of glycolysis (2-deoxy-d-glucose (2-DG)) increased thyroid cancer cell sensitivity to metformin. The combination of 2-DG with metformin led to cell death. Thyroid cancer cell lines were characterized by over-expression of glycolytic genes, and metformin decreased the protein level of pyruvate kinase muscle 2 (PKM2). PKM2 expression was detected in recurrent thyroid cancer tissue samples. In conclusion, we have demonstrated that the glucose concentration in the cellular milieu is a factor modulating metformin's anti-cancer activity. These data suggest that the combination of metformin with inhibitors of glycolysis could represent a new strategy for the treatment of thyroid cancer.

  16. Oesophageal cancer in The Netherlands : Increasing incidence and mortality but improving survival

    NARCIS (Netherlands)

    Crane, Lucia M. A.; Schaapveld, Michael; Visser, Otto; Louwmand, Marieke W. J.; Plukker, John T. M.; van Dam, Gooitzen M.

    2007-01-01

    Aim: Oesophageal cancer is highly lethal with a 5-year relative survival of 10-15%. An increasing incidence has been reported for several parts bf the Western world. We studied time trends in incidence, mortality and survival for oesophageal cancer in the Netherlands during 1989-2003. Methods: Data

  17. Increasing cancer detection yield of breast MRI using a new CAD scheme of mammograms

    Science.gov (United States)

    Tan, Maxine; Aghaei, Faranak; Hollingsworth, Alan B.; Stough, Rebecca G.; Liu, Hong; Zheng, Bin

    2016-03-01

    Although breast MRI is the most sensitive imaging modality to detect early breast cancer, its cancer detection yield in breast cancer screening is quite low (women) to date. The purpose of this preliminary study is to test the potential of developing and applying a new computer-aided detection (CAD) scheme of digital mammograms to identify women at high risk of harboring mammography-occult breast cancers, which can be detected by breast MRI. For this purpose, we retrospectively assembled a dataset involving 30 women who had both mammography and breast MRI screening examinations. All mammograms were interpreted as negative, while 5 cancers were detected using breast MRI. We developed a CAD scheme of mammograms, which include a new quantitative mammographic image feature analysis based risk model, to stratify women into two groups with high and low risk of harboring mammography-occult cancer. Among 30 women, 9 were classified into the high risk group by CAD scheme, which included all 5 women who had cancer detected by breast MRI. All 21 low risk women remained negative on the breast MRI examinations. The cancer detection yield of breast MRI applying to this dataset substantially increased from 16.7% (5/30) to 55.6% (5/9), while eliminating 84% (21/25) unnecessary breast MRI screenings. The study demonstrated the potential of applying a new CAD scheme to significantly increase cancer detection yield of breast MRI, while simultaneously reducing the number of negative MRIs in breast cancer screening.

  18. Increased prevalence of chronic lymphocytic thyroiditis in Korean patients with papillary thyroid cancer.

    Directory of Open Access Journals (Sweden)

    Chang-Mo Oh

    Full Text Available In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients.We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20-79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year.The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender.Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change.

  19. Increased consumption of fruit and vegetables and future cancer incidence in selected European countries.

    Science.gov (United States)

    Soerjomataram, Isabelle; Oomen, Dian; Lemmens, Valery; Oenema, Anke; Benetou, Vassiliki; Trichopoulou, Antonia; Coebergh, Jan Willem; Barendregt, Jan; de Vries, Esther

    2010-09-01

    Cancer is one of the major causes of death in western countries. Fruit and vegetable consumption may reduce the risk of cancers of the oropharynx, oesophagus, lung, stomach and colorectum. We investigated the potential effect of interventions aimed at increasing the intake of fruits and vegetables to the recommended level (500 g/d) on future cancer incidence in Europe. Data on cancer incidence and daily intake of fruit and vegetables were compiled for France, Germany, The Netherlands, Spain and Sweden. We also performed a meta-analysis of European observational studies to arrive at a quantitative estimate on the association between fruit and vegetable intake and cancer risk. Predictions on the future cancer incidence were modelled using PREVENT 3.01. Our study predicted 212,000 fruit- and vegetable-related cancer cases in these countries in 2050, out of which 398 (0.19%) might be prevented if the 500 g/d fruit and vegetable intake were achieved in the aforementioned countries. The largest absolute impact was observed for lung cancer with 257 (out of 136,517) preventable cases if the intervention was successfully implemented. Sweden would benefit the most from intervention to increase fruit and vegetable consumption with a 2% reduction in expected cases. Increasing fruit and vegetable consumption has a small impact on reducing the burden of cancer in Europe. Health impact assessment tools such as PREVENT can provide the basis for decision making in chronic disease prevention.

  20. Seroma indicates increased risk of lymphedema following breast cancer treatment

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jørgensen, Mads Gustaf; Haugaard, Karen

    2017-01-01

    Introduction Lymphedema is one of the most serious complications following breast cancer treatment. While many risk factors are well described the role of seroma formation has recently produced mixed results. Therefore, we aimed to evaluate if seroma is a risk factor for development of lymphedema...... in one of the largest retrospective cohort studies. Material and methods We included all patients with unilateral breast cancer treated in the period of 2008-2014. Data regarding treatment and breast cancer characteristics were retrieved from the national breast cancer registry. Data regarding lymphedema...... treatment and seroma aspirations were retrieved from local treatment codes. Results In total 1822 patients were included of which 291 developed lymphedema. Multivariate cox regression analysis showed that seroma was an independent risk factor (HR 1.92 CI 1.30-2.85, p= 0.001). Other independent risk factors...

  1. Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families.

    Science.gov (United States)

    Muranen, Taru A; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittomäki, Kristiina; Blomqvist, Carl; Easton, Douglas F; Nevanlinna, Heli

    2016-08-01

    The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on ~4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.

  2. Redes En Acción. Increasing Hispanic participation in cancer research, training, and awareness.

    Science.gov (United States)

    Ramirez, Amelie G; Talavera, Gregory A; Marti, Jose; Penedo, Frank J; Medrano, Martha A; Giachello, Aida L; Pérez-Stable, Eliseo J

    2006-10-15

    Hispanics are affected by many health care disparities. The National Cancer Institute (NCI), through its Special Populations Branch, is supporting networking and capacity-building activities designed to increase Hispanic participation and leadership in cancer research. Redes En Acción established a national network of cancer research centers, community-based organizations, and federal partners to facilitate opportunities for junior Hispanic scientists to participate in training and research projects on cancer control. Since 2000, Redes En Acción has established a network of more than 1800 Hispanic leaders involved in cancer research and education. The project has sustained 131 training positions and submitted 29 pilot projects to NCI for review, with 16 awards for a total of $800,000, plus an additional $8.8 million in competing grant funding based on pilot study results to date. Independent research has leveraged an additional $32 million in non-Redes funding, and together the national and regional network sites have participated in more than 1400 community and professional awareness events. In addition, the program conducted extensive national survey research that provided the basis for the Redes En Acción Latino Cancer Report, a national agenda on Hispanic cancer issues. Redes En Acción has increased participation in cancer control research, training, and awareness among Hispanic scientists and within Hispanic communities. Cancer 2006. (c) 2006 American Cancer Society.

  3. Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

    Directory of Open Access Journals (Sweden)

    Marija G Matic

    Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

  4. Public Awareness of Colorectal Cancer Screening: Knowledge, Attitudes, and Interventions for Increasing Screening Uptake

    Science.gov (United States)

    Gimeno Garcia, Antonio Z.; Hernandez Alvarez Buylla, Noemi; Nicolas-Perez, David; Quintero, Enrique

    2014-01-01

    Colorectal cancer ranks as one of the most incidental and death malignancies worldwide. Colorectal cancer screening has proven its benefit in terms of incidence and mortality reduction in randomized controlled trials. In fact, it has been recommended by medical organizations either in average-risk or family-risk populations. Success of a screening campaign highly depends on how compliant the target population is. Several factors influence colorectal cancer screening uptake including sociodemographics, provider and healthcare system factors, and psychosocial factors. Awareness of the target population of colorectal cancer and screening is crucial in order to increase screening participation rates. Knowledge about this disease and its prevention has been used across studies as a measurement of public awareness. Some studies found a positive relationship between knowledge about colorectal cancer, risk perception, and attitudes (perceived benefits and barriers against screening) and willingness to participate in a colorectal cancer screening campaign. The mentioned factors are modifiable and therefore susceptible of intervention. In fact, interventional studies focused on average-risk population have tried to increase colorectal cancer screening uptake by improving public knowledge and modifying attitudes. In the present paper, we reviewed the factors impacting adherence to colorectal cancer screening and interventions targeting participants for increasing screening uptake. PMID:24729896

  5. Estimation of cancer risks and benefits associated with a potential increased consumption of fruits and vegetables.

    Science.gov (United States)

    Reiss, Richard; Johnston, Jason; Tucker, Kevin; DeSesso, John M; Keen, Carl L

    2012-12-01

    The current paper provides an analysis of the potential number of cancer cases that might be prevented if half the U.S. population increased its fruit and vegetable consumption by one serving each per day. This number is contrasted with an upper-bound estimate of concomitant cancer cases that might be theoretically attributed to the intake of pesticide residues arising from the same additional fruit and vegetable consumption. The cancer prevention estimates were derived using a published meta-analysis of nutritional epidemiology studies. The cancer risks were estimated using U.S. Environmental Protection Agency (EPA) methods, cancer potency estimates from rodent bioassays, and pesticide residue sampling data from the U.S. Department of Agriculture (USDA). The resulting estimates are that approximately 20,000 cancer cases per year could be prevented by increasing fruit and vegetable consumption, while up to 10 cancer cases per year could be caused by the added pesticide consumption. These estimates have significant uncertainties (e.g., potential residual confounding in the fruit and vegetable epidemiologic studies and reliance on rodent bioassays for cancer risk). However, the overwhelming difference between benefit and risk estimates provides confidence that consumers should not be concerned about cancer risks from consuming conventionally-grown fruits and vegetables.

  6. Increasing intracellular bioavailable copper selectively targets prostate cancer cells.

    Science.gov (United States)

    Cater, Michael A; Pearson, Helen B; Wolyniec, Kamil; Klaver, Paul; Bilandzic, Maree; Paterson, Brett M; Bush, Ashley I; Humbert, Patrick O; La Fontaine, Sharon; Donnelly, Paul S; Haupt, Ygal

    2013-07-19

    The therapeutic efficacy of two bis(thiosemicarbazonato) copper complexes, glyoxalbis[N4-methylthiosemicarbazonato]Cu(II) [Cu(II)(gtsm)] and diacetylbis[N4-methylthiosemicarbazonato]Cu(II) [Cu(II)(atsm)], for the treatment of prostate cancer was assessed in cell culture and animal models. Distinctively, copper dissociates intracellularly from Cu(II)(gtsm) but is retained by Cu(II)(atsm). We further demonstrated that intracellular H2gtsm [reduced Cu(II)(gtsm)] continues to redistribute copper into a bioavailable (exchangeable) pool. Both Cu(II)(gtsm) and Cu(II)(atsm) selectively kill transformed (hyperplastic and carcinoma) prostate cell lines but, importantly, do not affect the viability of primary prostate epithelial cells. Increasing extracellular copper concentrations enhanced the therapeutic capacity of both Cu(II)(gtsm) and Cu(II)(atsm), and their ligands (H2gtsm and H2atsm) were toxic only toward cancerous prostate cells when combined with copper. Treatment of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model with Cu(II)(gtsm) (2.5 mg/kg) significantly reduced prostate cancer burden (∼70%) and severity (grade), while treatment with Cu(II)(atsm) (30 mg/kg) was ineffective at the given dose. However, Cu(II)(gtsm) caused mild kidney toxicity in the mice, associated primarily with interstitial nephritis and luminal distention. Mechanistically, we demonstrated that Cu(II)(gtsm) inhibits proteasomal chymotrypsin-like activity, a feature further established as being common to copper-ionophores that increase intracellular bioavailable copper. We have demonstrated that increasing intracellular bioavailable copper can selectively kill cancerous prostate cells in vitro and in vivo and have revealed the potential for bis(thiosemicarbazone) copper complexes to be developed as therapeutics for prostate cancer.

  7. Basic science and spine literature document bone morphogenetic protein increases cancer risk

    Directory of Open Access Journals (Sweden)

    Nancy E Epstein

    2014-01-01

    Full Text Available Background: Increasingly, clinical articles document that bone morphogenetic protein (BMP/INFUSE: Medtronic, Memphis, TN, USA and its derivatives utilized in spinal surgery increase the risk of developing cancer. However, there is also a large body of basic science articles that also document that various types of BMP and other members of the TGF-Beta (transforming growth factor beta family promote the growth of different types of cancers. Methods: This review looks at many clinical articles citing BMP/INFUSE′s role, largely "off-label", in contributing to complications encountered during spinal surgery. Next, however, specific attention is given to the clinical and basic science literature regarding how BMP and its derivatives (e.g. members of the TGF-beta family may also impact the development of breast and other cancers. Results: Utilizing BMP/INFUSE in spine surgery increased the risk of cancers/new malignancy as documented in several studies. For example, Carragee et al. found that for single-level instrumented posterolateral fusions (PLF using high-dose rhBMP-2 (239 patients vs. autograft (control group; n = 224, the risks of new cancers at 2 and 5 years postoperatively were increased. In laboratory studies, BMP′s along with other members of the TGF-Beta family also modulated/contributed to the proliferation/differentiation of breast cancer (e.g. bone formation/turnover, breast cancer-related solid tumors, and metastases, lung, adrenal, and colon cancer. Conclusions: BMP/INFUSE when utilized clinically in spinal fusion surgery appears to promote cancer at higher rates than observed in the overall population. Furthermore, BMP and TGF-beta are correlated with increased cancer growth both in the clinic and the laboratory.

  8. LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease.

    Science.gov (United States)

    Saunders-Pullman, Rachel; Barrett, Matthew J; Stanley, Kaili M; Luciano, Marta San; Shanker, Vicki; Severt, Lawrence; Hunt, Ann; Raymond, Deborah; Ozelius, Laurie J; Bressman, Susan B

    2010-11-15

    Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase. Small molecule kinase inhibitors have been developed for the treatment of certain cancers, and some antioncogenic agents such as sunitinib, may nonspecifically inhibit LRRK2. Few studies, however, have assessed cancer risk in LRRK2 mutation carriers. To explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients participating in genetic research. Charts were reviewed for 163 unrelated AJ PD patients, 31 of whom harbored the G2019S mutation. History of cancer was queried at baseline intake using a form reviewing medical conditions, and charts were reviewed for all follow-up visits. 9/31 LRRK2 G2019S mutation carriers had nonskin cancers, whereas 15/132 without mutations had nonskin cancers, representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3-6.6). Age at first nonskin cancer was younger in the LRRK2 carriers (56.0 years) than the noncarriers (62.0 years), but was not significant. 67% of the LRRK2 carriers had their cancer before the onset of PD, whereas only 40% of noncarriers developed their first nonskin cancer before onset of PD. While further evaluation is warranted, our findings indicate an increased risk of nonskin cancers in LRRK2 G2019S mutation carriers, which may be related to toxic gain of function of mutated LRRK2.

  9. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer...

  10. Increased risk of cancer mortality associated with cadmium exposures in older Americans with low zinc intake.

    Science.gov (United States)

    Lin, Yu-Sheng; Caffrey, James L; Lin, Jou-Wei; Bayliss, David; Faramawi, Mohammed F; Bateson, Thomas F; Sonawane, Babasaheb

    2013-01-01

    Cadmium (Cd) exposure has been associated with increased cancer risk, and zinc (Zn) appears to reduce that risk. However, little is known about the combined influence of Cd and Zn on cancer risk. The aim of this study was to examine relationships between Cd exposure, Zn intake, and cancer mortality risks. The analyses used 5204 subjects aged 50 yr or older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and the mortality follow-up through December 31, 2006. Cox proportional hazards models were used to test associations. In total, 569 cancer deaths were recorded during an average follow-up of 12.4 yr, including 155 from lung, 61 from prostate, and 26 from breast cancer. A positive association between Cd and cancer mortality risk was identified for both genders. Despite limited cause-specific deaths, the increased risk associated with Cd was significant for lung cancer in men. All-cause cancer mortality risk was significantly elevated among women with Zn intakes below the recommended dietary allowance (RDA) compared with women who met the RDA. The effect of low dietary Zn was not observed in men. Similar trends for prostate and breast cancer deaths were not significant. There was a significant inverse association between cancer deaths and the Zn-to-Cd ratio for both genders. Cd exposure is an important independent risk factor of cancer mortality in older Americans and the risk appears exaggerated in those with inadequate dietary Zn. Additional studies are required to elucidate the mechanism(s) by which Zn participates in the carcinogenic influence of Cd.

  11. Integrative exercise and lifestyle intervention increases leisure-time activity in breast cancer patients

    DEFF Research Database (Denmark)

    Casla, Soraya; Hojman, Pernille; Cubedo, Ricardo

    2014-01-01

    BACKGROUND: Physical activity has been demonstrated to increase survival in breast cancer patients, but few breast cancer patients meet the general recommendations for physical activity. The aim of this pilot study was to investigate if a supervised integrated counseling and group-based exercise...... program could increase leisure-time activity in women with breast cancer. METHODS: This pilot project, designed as a single-arm study with pre-post testing, consisted of 24 classes of combined aerobic and strength exercise training as well as classes on dietary and health behavior. A total of 48 women...... with breast cancer who were undergoing or had recently completed anticancer treatment completed the study. Leisure-time physical activity, grip strength, functional capacity, quality of life (QoL), and depression were assessed at baseline, after intervention, and at the 12-week follow-up after intervention...

  12. Increased frequency of single base substitutions in a population of transcripts expressed in cancer cells

    Directory of Open Access Journals (Sweden)

    Bianchetti Laurent

    2012-11-01

    Full Text Available Abstract Background Single Base Substitutions (SBS that alter transcripts expressed in cancer originate from somatic mutations. However, recent studies report SBS in transcripts that are not supported by the genomic DNA of tumor cells. Methods We used sequence based whole genome expression profiling, namely Long-SAGE (L-SAGE and Tag-seq (a combination of L-SAGE and deep sequencing, and computational methods to identify transcripts with greater SBS frequencies in cancer. Millions of tags produced by 40 healthy and 47 cancer L-SAGE experiments were compared to 1,959 Reference Tags (RT, i.e. tags matching the human genome exactly once. Similarly, tens of millions of tags produced by 7 healthy and 8 cancer Tag-seq experiments were compared to 8,572 RT. For each transcript, SBS frequencies in healthy and cancer cells were statistically tested for equality. Results In the L-SAGE and Tag-seq experiments, 372 and 4,289 transcripts respectively, showed greater SBS frequencies in cancer. Increased SBS frequencies could not be attributed to known Single Nucleotide Polymorphisms (SNP, catalogued somatic mutations or RNA-editing enzymes. Hypothesizing that Single Tags (ST, i.e. tags sequenced only once, were indicators of SBS, we observed that ST proportions were heterogeneously distributed across Embryonic Stem Cells (ESC, healthy differentiated and cancer cells. ESC had the lowest ST proportions, whereas cancer cells had the greatest. Finally, in a series of experiments carried out on a single patient at 1 healthy and 3 consecutive tumor stages, we could show that SBS frequencies increased during cancer progression. Conclusion If the mechanisms generating the base substitutions could be known, increased SBS frequency in transcripts would be a new useful biomarker of cancer. With the reduction of sequencing cost, sequence based whole genome expression profiling could be used to characterize increased SBS frequency in patient’s tumor and aid diagnostic.

  13. Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

    Energy Technology Data Exchange (ETDEWEB)

    Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Tabibzadeh, Siamak, E-mail: fbs@bioscience.org [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Dept of Oncologic Radiology, University of California, Irvine, CA (United States)

    2014-06-13

    Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.

  14. Intrathoracic anastomotic leakage after gastroesophageal cancer resection is associated with increased risk of recurrence

    DEFF Research Database (Denmark)

    Kofoed, Steen C; Calatayud, Dan; Jensen, Lone S

    2015-01-01

    OBJECTIVE: Intrathoracic anastomotic leakage after intended curative resection for cancer in the esophagus or gastroesophageal junction has a negative impact on long-term survival. The aim of this study was to investigate whether an anastomotic leakage was associated with an increased recurrence......]: 1.17-2.29, P = .004) and all-cause mortality (HR = 1.57; 95% CI: 1.23-2.05, P cancer resection....

  15. Increasing participation of cancer patients in randomised controlled trials: a systematic review

    Directory of Open Access Journals (Sweden)

    Stirk Lisa

    2006-05-01

    Full Text Available Abstract Background There are many barriers to patient participation in randomised controlled trials of cancer treatments. To increase participation in trials, strategies need to be identified to overcome these barriers. Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in randomised controlled trials (RCTs of cancer treatments. Methods A systematic review was conducted. Published and unpublished studies in any language were searched for in fifteen electronic databases, including MEDLINE, EMBASE, CINAHL and PsycINFO, from inception to the end of 2004. Studies of any interventions to improve cancer patient participation in RCTs, which reported the change in recruitment rates, were eligible for inclusion. RCTs and non-randomised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included. Data were extracted by one reviewer into structured summary tables and checked for accuracy by a second reviewer. Each included study was assessed against a checklist for methodological quality by one reviewer and checked by a second reviewer. A narrative synthesis was conducted. Results Eight studies were identified that met the inclusion criteria: three RCTs, two non-randomised controlled trials and three observational studies. Six of the studies had an intervention that had some relevance to the UK. There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs, though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer. Although there was no evidence of an effect in any of the studies, the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work. Conclusion There is not a strong evidence-base for interventions that

  16. Caspase 9 promoter polymorphisms confer increased susceptibility to breast cancer.

    Science.gov (United States)

    Theodoropoulos, George E; Michalopoulos, Nikolaos V; Pantou, Malena P; Kontogianni, Panagiota; Gazouli, Maria; Karantanos, Theodoros; Lymperi, Maria; Zografos, George C

    2012-10-01

    Caspases (CASPs), play a crucial role in the development and progression of cancer. We evaluated the association between two polymorphisms (rs4645978 and rs4645981) of the CASP9 gene and the risk of breast cancer (BC). Genotypes and allelic frequencies for the two polymorphisms were determined in 261 patients with breast cancer and 480 healthy controls. Polymerase chain reaction-restriction fragment length polymorphisms were used, and statistical significance was determined by the χ(2) test. Carriers of the rs4645978G allele (AG and GG genotypes) were at higher risk for BC than individuals with other genotypes (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.07-2.37, P = 0.022). The rs4645978GG genotype, in particular, was associated with the highest risk for BC development (OR 2.25, 95% CI 1.45-3.49, P = 0.0003). Similarly, individuals with at least one rs4645981T allele were at a significantly increased risk of developing BC compared with those harboring the CC genotype (OR 2.75, 95% CI 1.99-3.78, P < 0.0001), and the risk of BC increased with increasing numbers of rs4645981T alleles (OR 2.66, 95% CI 1.91-3.69, P < 0.0001 for the CT genotype; OR 3.95, 95% CI 1.58-9.88, P = 0.004 for the TT genotype). The CASP9 promoter polymorphisms rs4645978 and rs4645981 are associated with BC susceptibility and suggest that CASP9 transcriptional regulation is an important factor during BC development.

  17. NIH study shows increased risk for two types of myotonic muscular dystrophy

    Science.gov (United States)

    Adults with a form of muscular dystrophy called myotonic muscular dystrophy (MMD) may be at increased risk of developing cancer, according to a study by investigators at the National Cancer Institute (NCI), part of the National Institutes of Health.

  18. Increased risk of cancer in radon-exposed miners with elevated frequency of chromosomal aberrations.

    Science.gov (United States)

    Smerhovsky, Zdenek; Landa, Karel; Rössner, Pavel; Juzova, Dagmar; Brabec, Marek; Zudova, Zdena; Hola, Nora; Zarska, Hana; Nevsimalova, Emilie

    2002-02-15

    In spite of the extensive use of cytogenetic analysis of human peripheral blood lymphocytes in the biomonitoring of exposure to various mutagens and carcinogens, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 1323 cytogenetic assays and 225 subjects examined because of occupational exposures to radon (range of exposure from 1.7 to 662.3 working level month (WLM)). Seventy-five subjects were non-smokers. We found 36 cases of cancer in this cohort. Chromatid breaks were the most frequently observed type of aberrations (mean frequency 1.2 per 100 cells), which statistically significantly correlated with radon exposure (Spearman's correlation coefficient R=0.22, P<0.001). Also, the frequency of aberrant cells (median of 2.5%) correlated with radon exposure (Spearman's correlation coefficient R=0.16, P<0.02). Smoking and silicosis were not associated with results of cytogenetic analyses. The Cox regression models, which accounted for the age at time of first cytogenetic assay, radon exposure, and smoking showed strong and statistically significant associations between cancer incidence and frequency of chromatid breaks and frequency of aberrant cells, respectively. A 1% increase in the frequency of aberrant cells was paralleled by a 62% increase in risk of cancer (P<0.000). An increase in frequency of chromatid breaks by 1 per 100 cells was followed by a 99% increase in risk of cancer (P<0.000). We obtained similar results when we analyzed the incidence of lung cancer and the incidence other than lung cancer separately. Contrary to frequency of chromatid breaks and frequency of aberrant cells, the frequency of chromatid exchanges, and chromosome-type aberrations were not predictive of cancer.

  19. Does exposure to agricultural chemicals increase the risk of prostate cancer among farmers?

    Science.gov (United States)

    Parent, Marie-Elise; Désy, Marie; Siemiatycki, Jack

    2009-01-01

    Several studies suggest that farmers may be at increased risk of prostate cancer. The present analysis, based on a large population-based case-control study conducted among men in the Montreal area in the early 1980's, aim at identifying occupational chemicals which may be responsible for such increases. The original study enrolled 449 prostate cancer cases, nearly 4,000 patients with other cancers, as well as 533 population controls. Subjects were interviewed about their occupation histories, and a team of industrial hygienists assigned their past exposures using a checklist of some 300 chemicals. The present analysis was restricted to a study base of men who had worked as farmers earlier in their lives. There were a total of 49 men with prostate cancers, 127 with other cancers and 56 population controls. We created a pool of 183 controls combining the patients with cancers at sites other than the prostate and the population controls. We then estimated the odds ratio for prostate cancer associated with exposure to each of 10 agricultural chemicals, i.e., pesticides, arsenic compounds, acetic acid, gasoline engine emissions, diesel engine emissions, polycyclic aromatic hydrocarbons from petroleum, lubricating oils and greases, alkanes with >or=18 carbons, solvents, and mononuclear aromatic hydrocarbons. Based on a model adjusting for age, ethnicity, education, and respondent status, there was evidence of a two-fold excess risk of prostate cancer among farmers with substantial exposure to pesticides [odds ratio (OR)=2.3, 95% confidence interval (CI) 1.1-5.1], as compared to unexposed farmers. There was some suggestion, based on few subjects, of increased risks among farmers ever exposed to diesel engine emissions (OR=5.7, 95% CI 1.2-26.5). The results for pesticides are particularly noteworthy in the light of findings from previous studies. Suggestions of trends for elevated risks were noted with other agricultural chemicals, but these are largely novel and need

  20. Increased standardized incidence ratio of breast cancer in female electronics workers

    Directory of Open Access Journals (Sweden)

    Lin Yi-Ping

    2007-06-01

    Full Text Available Abstract Background In 1994, a hazardous waste site, polluted by the dumping of solvents from a former electronics factory, was discovered in Taoyuan, Taiwan. This subsequently emerged as a serious case of contamination through chlorinated hydrocarbons with suspected occupational cancer. The objective of this study was to determine if there was any increased risk of breast cancer among female workers in a 23-year follow-up period. Methods A total of 63,982 female workers were retrospectively recruited from the database of the Bureau of Labor Insurance (BLI covering the period 1973–1997; the data were then linked with data, up to 2001, from the National Cancer Registry at the Taiwanese Department of Health, from which standardized incidence ratios (SIRs for different types of cancer were calculated as compared to the general population. Results There were a total of 286 cases of breast cancer, and after adjustment for calendar year and age, the SIR was close to 1. When stratified by the year 1974 (the year in which the regulations on solvent use were promulgated, the SIR of the cohort of workers who were first employed prior to 1974 increased to 1.38 (95% confidence interval, 1.11–1.70. No such trend was discernible for workers employed after 1974. When 10 years of employment was considered, there was a further increase in the SIR for breast cancer, to 1.62. Those workers with breast cancer who were first employed prior to 1974 were employed at a younger age and for a longer period. Previous qualitative studies of interviews with the workers, corroborated by inspection records, showed a short-term high exposure to chlorinated alkanes and alkenes, particularly trichloroethylene before 1974. There were no similar findings on other types of cancer. Conclusion Female workers with exposure to trichloroethylene and/or mixture of solvents, first employed prior to 1974, may have an excess risk of breast cancer.

  1. Thyroid Cancer Risk Is Not Increased in Diabetic Patients

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2012-01-01

    Objective This study evaluated thyroid cancer risk with regards to diabetes status and diabetes duration, and with the use of anti-diabetic drugs including sulfonylurea, metformin, insulin, acarbose, pioglitazone and rosiglitazone, by using a population-based reimbursement database in Taiwan. Methods A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. After excluding patients with type 1 diabetes, 999730 subjects (495673 men and 504057 women) were recruited into the analyses. Logistic regression estimated the odds ratios (OR) and their 95% confidence intervals (CI) for independent variables including age, sex, diabetes status/duration, anti-diabetic drugs, other medications, comorbidities, living regions, occupation and examinations that might potentially lead to the diagnosis of thyroid cancer in various models. Results The diabetic patients had a significantly higher probability of receiving potential detection examinations (6.38% vs. 5.83%, Pdiabetes status was 0.816 (0.652–1.021); and for diabetes duration diabetes was 0.071 (0.010–0.507), 0.450 (0.250–0.813), 0.374 (0.203–0.689) and 1.159 (0.914–1.470), respectively. Among the anti-diabetic agents, only sulfonylurea was significantly associated with thyroid cancer, OR (95% CI): 1.882 (1.202–2.947). The OR (95% CI) for insulin, metformin, acarbose, pioglitazone and rosiglitazone was 1.701 (0.860–3.364), 0.696 (0.419–1.155), 0.581 (0.202–1.674), 0.522 (0.069–3.926) and 0.669 (0.230–1.948), respectively. Furthermore, patients with benign thyroid disease or other cancer, living in Kao-Ping/Eastern regions, or receiving potential detection examinations might have a significantly higher risk; and male sex, hypertension, dyslipidemia, chronic obstructive pulmonary disease, vascular complications or use of statin, aspirin or non-steroidal anti-inflammatory drugs might be associated with a significantly lower risk. Conclusions There is a lack of an overall

  2. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10.

    Science.gov (United States)

    Elwood, J Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000-05 and 2006-10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia.

  3. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10.

    Directory of Open Access Journals (Sweden)

    J Mark Elwood

    Full Text Available New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000-05 and 2006-10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia.

  4. Increased incidence of another cancer in myeloproliferative neoplasms patients at the time of diagnosis.

    Science.gov (United States)

    Pettersson, Helna; Knutsen, Håvar; Holmberg, Erik; Andréasson, Björn

    2015-02-01

    Several studies have reported an increased incidence of coexistent cancer in patients with myeloproliferative neoplasms (MPN), and myelosuppressive treatment has been speculated to be one of the causes. In this study, we have concentrated on malignancies diagnosed before the MPN diagnosis to eliminate the possible influence of MPN treatment. The patients were recruited from the Swedish and Norwegian cancer registries. One thousand seven hundred and 45 patients from the Swedish MPN Quality Registry and 468 patients from the Norwegian National Cancer Registry were included in this study covering a 3-yr period. The results show that primary concurrent cancer is higher among patients with MPN compared to the general population. When pooled together, the Swedish and the Norwegian cohort showed increased prevalence of all types of cancer in general compared with the general population, standard prevalence ratio (SPR) of 1.20 (95% CI 1.07-1.34). Significantly high SPRs were reached for skin malignant melanoma [1.89 (95% CI 1.33-2.62)], prostate cancer [1.39 (95% CI 1.11-1.71)], and hematologic cancer [1.49 (95% CI 1.00-2.12)]. In the polycythemia vera group, the risk of having prior malignant melanoma of the skin was significant, with an SPR of 2.20 (95% CI 1.17-3.77). For patients with essential thrombocythemia and primary myelofibrosis, no significant risks were found. Coexisting cancers have a high impact on the treatment strategies of MPN, as it narrows down the treatment options. Chronic inflammation, as a common denominator of MPN with other cancers, can catalyze each other's existence and progression.

  5. Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks.

    Science.gov (United States)

    Wu, Xuping; Smavadati, Shirin; Nordfjäll, Katarina; Karlsson, Krister; Qvarnström, Fredrik; Simonsson, Martin; Bergqvist, Michael; Gryaznov, Sergei; Ekman, Simon; Paulsson-Karlsson, Ylva

    2012-12-01

    Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1 week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer.

  6. Epidemiological studies of oral cancer.

    Science.gov (United States)

    Pindborg, J J

    1977-06-01

    The FDI has shown considerable interest in the oral cancer and has in recent years arranged three symposia on the subject. The incidence of oral cancer shows marked geographic differences mostly depending upon environmental factors. In the present paper the epidemiology of oral cancer is illustrated by the relative frequency to total number of cancers and incidence rates from a number of countries. Canada has the highest rate of cancer of the vermilion border, which is extremely rare among dark-skinned people. Even within one country differences may be found, a fact which is illustrated by findings from Czechoslovakia and India. In most of the studies dealing with the etiology of oral cancer tobacco usage in its various forms is shown to be the outstanding factor.

  7. Increased risk of colorectal cancer in type 2 diabetes is independent of diet quality.

    Directory of Open Access Journals (Sweden)

    Soghra Jarvandi

    Full Text Available BACKGROUND: Poor diet increases the risk of both colorectal cancer and type 2 diabetes. We investigated the role of diet in the association between diabetes and colorectal cancer. METHODS: We analyzed data from 484,020 individuals, aged 50-71 years who participated in the prospective National Institutes of Health-AARP Diet and Health Study and were cancer free at baseline (1995-1996. History of diabetes was self-reported. Diet quality was measured with the Healthy Eating Index-2005 (HEI-2005, using a self-administered food-frequency questionnaire. Cox regression models were constructed to estimate the hazard ratios (HR and 95% confidence intervals (CI of first primary incident colorectal cancer, overall and by anatomical location. RESULTS: During an average follow-up of 9.2 years, we identified 7,598 new cases of colorectal cancer. After controlling for non-dietary confounders, diabetes was associated with increased risk of colorectal cancer (HR 1.27, 95% CI: 1.18, 1.36. Further adjustment for diet quality did not attenuate this association. Diabetes was associated with a HR of 1.23 (95% CI: 1.07, 1.40 in individuals with good diet (quartile 4 of HEI-2005 and 1.58 (95% CI: 1.34, 1.86 in those with poor diet (quartile 1 of HEI-2005, compared to those with no diabetes and good diet. Moreover, diabetes was associated with a stronger risk of proximal than distal colon cancer (HR: 1.33 vs. HR: 1.20, while poor diet was associated with a weaker risk of proximal colon cancer (HR: 1.18 vs. HR: 1.46. CONCLUSION: Diabetes and poor diet, independently and additively are associated with the increased risk of colorectal cancer.

  8. Increased expression of cyclooxygenase-2 in first-degree relatives of gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    Jin-Ting Zhang; Ming-Wei Wang; Zhen-Long Zhu; Xiao-Hui Huo; Jian-Kun Chu; Dong-Sheng Cui; Liang Qiao; Jun Yu

    2005-01-01

    AIM: To study the expression of cyclooxygenase-2 (COX-2)in human gastric cancer tissues and their paired adjacent mucosa, as well as mucosa from gastric antrum and corpus of the first-degree relatives of the recruited cancer patients.METHODS: The expression of COX-2 mRNA in 38 patients with gastric cancer and their 29 first-degree relatives and 18 healthy controls was assessed by the real time RT-PCR.The expression of COX-2 protein was determined by Western blot.RESULTS: A marked increase in COX-2 mRNA expression was found in 20 of 37 (54%) cancerous tissues compared to their respective paired normal mucosa (P<0.001).Interestingly, increased COX-2 mRNA expression was also found in mucosa of the corpus (6/29) and antrum (13/29)of their first-degree relatives. Increased COX-2 mRNA expression was more frequently observed in the antrum biopsies from cancer patients than in the antrum biopsies from healthy controls (P<0.05). In addition, 3 of 23 (13%)patients with atrophic mucosa and 6 of 35 (17%) patients with intestinal metaplasia showed increased COX-2 mRNA expression. Furthermore, COX-2 expression increased in H pylori-positive tissues, especially in antrum mucosa.CONCLUSION: Increased COX-2 expression is involved in gastric carcinogenesis, and may be necessary for maintenance of the malignant phenotype and contribute to Helicobacterpylori-associated malignant transformation.

  9. Women with Saethre-Chotzen syndrome are at increased risk of breast cancer.

    Science.gov (United States)

    Sahlin, Pelle; Windh, Per; Lauritzen, Claes; Emanuelsson, Monica; Grönberg, Henrik; Stenman, Göran

    2007-07-01

    The Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1. This syndrome has hitherto not been associated with an increased risk of cancer. However, recent studies, using a murine breast tumor model, have shown that Twist may act as a key regulator of metastasis and that the gene is overexpressed in subsets of sporadic human breast cancers. Here, we report a novel association between the Saethre-Chotzen syndrome and breast cancer. In 15 Swedish Saethre-Chotzen families, 15 of 29 (52%) women carriers over the age of 25 had developed breast cancer. At least four patients developed breast cancer before 40 years of age, and five between 40 and 50 years of age. The observed cases with breast cancer (n = 15) are significantly higher than expected (n = 0.89), which gives a standardized incidence ratio (SIR) of 16.80 (95% CI 1.54-32.06). Our finding of a high frequency of breast cancer in women with the Saethre-Chotzen syndrome identifies breast cancer as an important and previously unrecognized symptom characteristic of this syndrome. The results strongly suggest that women carriers of this syndrome would benefit from genetic counseling and enrolment in surveillance programs including yearly mammography. Our results also indicate that the TWIST1 gene may be a novel breast cancer susceptibility gene. Additional studies are, however, necessary to reveal the mechanism by which TWIST1 may predispose to early onset breast cancer in Saethre-Chotzen patients.

  10. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, Anette Tønnes; Lynge, Elsebeth

    2004-01-01

    Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort...... was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases...... were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were...

  11. Vitamin D and cancer: an overview on epidemiological studies.

    Science.gov (United States)

    Ordóñez Mena, José Manuel; Brenner, Hermann

    2014-01-01

    In recent years, a rapidly increasing number of studies have investigated the relationship of vitamin D with total cancer and site-specific cancer obtaining diverse findings. In this chapter we provide an overview of epidemiological studies of vitamin D intake, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels and vitamin D associated polymorphisms in relation to total and site-specific cancer risk. Overall, epidemiological evidence for total cancer is inconclusive. However, a large number of studies support a relationship of vitamin D with colorectal cancer and to a lesser extent with breast cancer. Findings are inconsistent for other cancers including all other gastrointestinal cancers and prostate cancer. Different vitamin D associated polymorphisms were found to be significantly associated to colorectal, breast and prostate cancer risk.

  12. Alcohol intake and cigarette smoking and risk of a contralateral breast cancer: The Women's Environmental Cancer and Radiation Epidemiology Study

    DEFF Research Database (Denmark)

    Knight, J.A.; Bernstein, L.; Largent, J.

    2009-01-01

    Women with primary breast cancer are at increased risk of developing second primary breast cancer. Few studies have evaluated risk factors for the development of asynchronous contralateral breast cancer in women with breast cancer. In the Women's Environmental Cancer and Radiation Epidemiology St...

  13. Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Keya De Mukhopadhyay

    Full Text Available In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

  14. Intakes of red meat, processed meat, and meat mutagens increase lung cancer risk.

    Science.gov (United States)

    Lam, Tram Kim; Cross, Amanda J; Consonni, Dario; Randi, Giorgia; Bagnardi, Vincenzo; Bertazzi, Pier Alberto; Caporaso, Neil E; Sinha, Rashmi; Subar, Amy F; Landi, Maria Teresa

    2009-02-01

    Red and processed meat intake may increase lung cancer risk. However, the epidemiologic evidence is inconsistent and few studies have evaluated the role of meat mutagens formed during high cooking temperatures. We investigated the association of red meat, processed meat, and meat mutagen intake with lung cancer risk in Environment And Genetics in Lung cancer Etiology, a population-based case-control study. Primary lung cancer cases (n = 2,101) were recruited from 13 hospitals within the Lombardy region of Italy examining approximately 80% of the cases from the area. Noncancer population controls (n = 2,120), matched to cases on gender, residence, and age, were randomly selected from the same catchment area. Diet was assessed in 1,903 cases and 2,073 controls and used in conjunction with a meat mutagen database to estimate intake of heterocyclic amines (HCA) and benzo(a)pyrene (BaP). Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for sex-specific tertiles of intake were calculated using unconditional logistic regression. Red and processed meat were positively associated with lung cancer risk (highest-versus-lowest tertile: OR, 1.8; 95% CI, 1.5-2.2; P trend processed meat, and meat mutagens were independently associated with increased risk of lung cancer.

  15. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

  16. Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile.

    Science.gov (United States)

    Liaw, Jane; Marshall, Guillermo; Yuan, Yan; Ferreccio, Catterina; Steinmaus, Craig; Smith, Allan H

    2008-08-01

    Arsenic in drinking water is an established cause of lung, bladder, and skin cancers in adults and may also cause adult kidney and liver cancers. Some evidence for these effects originated from region II of Chile, which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water. In this article, we compare cancer mortality rates under the age of 20 in region II during 1950 to 2000 with those of unexposed region V, dividing subjects into those born before, during, or after the peak exposure period. Mortality from the most common childhood cancers, leukemia and brain cancer, was not increased in the exposed population. However, we found that childhood liver cancer mortality occurred at higher rates than expected. For those exposed as young children, liver cancer mortality between ages 0 and 19 was especially high: the relative risk (RR) for males born during this period was 8.9 [95% confidence interval (95% CI), 1.7-45.8; P = 0.009]; for females, the corresponding RR was 14.1 (95% CI, 1.6-126; P = 0.018); and for males and females pooled, the RR was 10.6 (95% CI, 2.9-39.2; P water during early childhood may result in an increase in childhood liver cancer mortality.

  17. INCREASED RISK OF THROMBOEMBOLISM AS A RESULT OF HIGH THROMBIN PRODUCTION IS ASSOCIATED WITH SHORT ACTIVATED PARTIAL THROMBOPLASTIN TIME IN CANCER PATIENTS ON AND AFTER CHEMOTHERAPY: A PROSPECTIVE STUDY IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Indranil

    2014-06-01

    Full Text Available : To investigate wheather cancer patients during and following chemotherapy with short activated partial thromboplastin times (aPTTs have increased thrombin generation and are at increased risk for thromboembolism, this prospective study was designed. Routine coagulation specimens of such patients were screened for the presence of short or normal aPTT for 5-month period, and, accordingly, 250 specimens were collected. Prothrombin fragment F1+2 (F1+2 was measured to evaluate thrombin activation, and a second aPTT was performed with a different reagent. Clinical history were obtained from medical records after conclusion of sample collection. 6 to12months later, patients were questioned on thromboembolic events during the previous 18 months by questionnaire. F1+2 and the incidence of venous thromboses were elevated significantly in the short aPTT group. Patients with acute bleeding had short aPTTs, but 36% of these also had thromboembolic events during the 18 months proximal to blood collection. These findings were confirmed with the second aPTT reagent. Patients with short aPTTs have increased thrombin generation and are at increased risk for thromboembolism, mainly venous thromboses, despite the fact that a short aPTT can occur in the acute setting of bleeding.

  18. Multicultural media outreach: increasing cancer information coverage in minority communities.

    Science.gov (United States)

    Alexander, James; Kwon, Harry T; Strecher, Rachael; Bartholomew, Jill

    2013-12-01

    Ethnic media can serve as an opportunity for cancer education and outreach to minority communities. The National Cancer Institute developed the Multicultural Media Outreach (MMO) program which utilizes an integrated approach of both traditional and social media to disseminate evidence-based cancer education information for minority communities. The MMO program is the contact point for multicultural media outlets seeking evidence-based cancer information, education materials, minority spokespersons, and news tailored to minority communities affected by cancer health disparities. MMO developed Lifelines®, a cancer education series that addresses cancer prevention, treatment, survivorship, clinical trials, and other cancer-related topics for African American, Hispanic, Asian American, American Indian, and Alaska Native audiences. Lifelines® content is disseminated through traditional media (radio, print, and television) as well as social media (web, Twitter, YouTube, and RSS feed). This article describes the MMO program and lessons learned to date.

  19. Isolated Isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk

    NARCIS (Netherlands)

    Vrieling, A.; Rookus, M.A.; Kampman, E.; Bonfrer, J.M.G.; Korse, C.M.; Doorn, van J.; Lampe, J.W.; Cats, A.; Witteman, B.J.M.; Leeuwen, van F.E.; van't Veer, L.J.; Voskuil, D.W.

    2007-01-01

    Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conduc

  20. HFE H63D mutation frequency shows an increase in Turkish women with breast cancer

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    Guler Emine

    2006-02-01

    Full Text Available Abstract Background The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls. Methods Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP. Results All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176 in the breast cancer patients, and 14% (28/200 in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers (P = 0.02. Conclusion Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios (odds ratio = 2.05 computed in this study suggest that H63D has a positive association with breast cancer.

  1. Metabolic syndrome is associated with increased breast cancer risk: a systematic review with meta-analysis.

    Science.gov (United States)

    Bhandari, Ruchi; Kelley, George A; Hartley, Tara A; Rockett, Ian R H

    2014-01-01

    Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and I (2) statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15-1.87; z = 3.13; p = 0.002; Q = 26.28, p = 0.001; I (2) = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women.

  2. Metabolic Syndrome Is Associated with Increased Breast Cancer Risk: A Systematic Review with Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ruchi Bhandari

    2014-01-01

    Full Text Available Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS. We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL, Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill and qualitatively (funnel plots. Heterogeneity was examined using Q and I2 statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15–1.87; z=3.13; p=0.002; Q=26.28, p=0.001; I2=69.55%. No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women.

  3. Ephrin A2 receptor targeting does not increase adenoviral pancreatic cancer transduction in vivo

    Institute of Scientific and Technical Information of China (English)

    Michael A van Geer; Conny T Bakker; Naoya Koizumi; Hiroyuki Mizuguchi; John G Wesseling; Ronald PJ Oude Elferink; Piter J Bosma

    2009-01-01

    AIM:To generate an adenoviral vector specifically targeting the EphA2 receptor (EphA2R) highly expressed on pancreatic cancer cells in vivo.METHODS:YSA,a small peptide ligand that binds the EphA2R with high affinity,was inserted into the HI loop of the adenovirus serotype 5 fiber knob.To further increase the specificity of this vector,binding sites for native adenoviral receptors,the coxsackie and adenovirus receptor (CAR) and integrin,were ablated from the viral capsid.The ablated retargeted adenoviral vector was produced on 293T cells.Specific targeting of this novel adenoviral vector to pancreatic cancer was investigated on established human pancreatic cancer cell lines.Upon demonstrating specific in vitro targeting,in vivo targeting to subcutaneous growing human pancreatic cancer was tested by intravenous and intraperitoneal administration of the ablated adenoviral vector.RESULTS:Ablation of native cellular binding sites reduced adenoviral transduction at least 100-fold.Insertion of the YSA peptide in the HI loop restored adenoviral transduction of EphA2R-expressing cells but not of cells lacking this receptor.YSA-mediated transduction was inhibited by addition of synthetic YSA peptide.The transduction specificity of the ablated retargeted vector towards human pancreatic cancer cells was enhanced almost 10-fold in vitro.In a subsequent in vivo study in a nude (nu/nu) mouse model however,no increased adenoviral targeting to subcutaneously growing human pancreas cancer nodules was seen upon injection into the tail vein,nor upon injection into the peritoneum.CONCLUSION:Targeting the EphA2 receptor increases specificity of adenoviral transduction of human pancreatic cancer cells in vitro but fails to enhance pancreatic cancer transduction in vivo.

  4. Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Guoyu Yu

    Full Text Available Protease-activated receptor 4 (PAR4, a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2, a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38, western blotting (n=38 and tissue microarrays (n = 66. The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the

  5. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    Energy Technology Data Exchange (ETDEWEB)

    Oommen, Deepu [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom); Yiannakis, Dennis [Plymouth Oncology Centre, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth PL6 8DH (United Kingdom); Jha, Awadhesh N., E-mail: a.jha@plymouth.ac.uk [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom)

    2016-02-15

    Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

  6. Increasing physical activity and exercise in lung cancer: reviewing safety, benefits, and application.

    Science.gov (United States)

    Bade, Brett C; Thomas, D David; Scott, JoAnn B; Silvestri, Gerard A

    2015-06-01

    Lung cancer continues to be a difficult disease frequently diagnosed in late stages with a high mortality and symptom burden. In part because of frequent lung comorbidity, even lung cancer survivors often remain symptomatic and functionally limited. Though targeted therapy continues to increase treatment options for advanced-stage disease, symptom burden remains high with few therapeutic options. In the last several decades, exercise and physical activity have arisen as therapeutic options for obstructive lung disease and lung cancer. To date, exercise has been shown to reduce symptoms, increase exercise tolerance, improve quality of life, and potentially reduce length of stay and postoperative complications. Multiple small trials have been performed in perioperative non-small-cell lung cancer patients, although fewer studies are available for patients with advanced-stage disease. Despite the increased interest in this subject over the last few years, a validated exercise regimen has not been established for perioperative or advanced-stage disease. Clinicians underutilize exercise and pulmonary rehabilitation as a therapy, in part because of the lack of evidence-based consensus as to how and when to implement increasing physical activity. This review summarizes the existing evidence on exercise in lung cancer patients.

  7. Increased radiosensitivity as an indicator of genes conferring breast cancer susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    Varga, D.; Kreienberg, R.; Deissler, H.; Sauer, G. [Dept. of Gynecology and Obstetrics, Univ. of Ulm Medical School (Germany); Vogel, W.; Bender, A.; Surowy, H.; Maier, C. [Dept. of Genetics, Univ. of Ulm Medical School (Germany)

    2007-12-15

    Purpose: This paper briefly summarizes the research on increased radiosensitivity in breast cancer patients measured by the micronucleus test (MNT) and its association to genetic variants in DNA repair genes. More preliminary data are presented on the distribution of chromosomes and chromosome fragments in micronuclei (MN) in order to gain more information on clastogenic and aneugenic effects and better understand the phenotype of increased radiosensitivity. Material and Methods: Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. In four patients with high MN frequency (three cancer patients, one control) and four probands with low MN frequency, the presence of chromosome fragments or whole chromosomes in MN was determined by fluorescence in situ hybridization analysis for chromosomes 1, 7, and 17. Results: An increased MN frequency in breast cancer patients compared to controls has consistently been reported with high significance. Higher MN frequencies were observed in 20-50% of breast cancer patients. Chromosomal fragments of chromosome 17, but not of chromosomes 1 and 7 were more frequent in the probands with high MN frequency than in those with low frequency (p = 0.045). Conclusion: The MNT detects a cellular phenotype common to a portion of sporadic breast cancer patients. This phenotype is very likely to be genetically determined. For the genetic dissection of breast cancer susceptibility this phenotype may turn out to be more efficient than breast cancer itself. Additional parameters which can be measured simultaneously with the MN frequency may be able to further enhance its usefulness. (orig.)

  8. Increasing in activity and plasma concentration of matrix metalloproteinase-9 in metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Morteza Sadeghi1

    2009-01-01

    Full Text Available (Received 30 March, 2009 ; Accepted 22 July, 2009AbstractBackground and purpose: Matrix metalloproteinase are a family of proteolytic enzymes that have specific functions in digestion of cells cohesive extra cellular matrix and also, increasing metastasis behavior of acute human tumors. It has been reported that MMPs in two forms, namely proenzyme and active enzyme in biological samples. It is distinguished that among this family, (MMP-9 Matrix Metalloproteinase-9 has function in both initiation and invasion steps of breast cancer. In our previous study, we reported a correlation between C/T polymorphism at promoter region of this gene and metastasis step of breast cancer.Considering few findings regarding the relationship between the active form of this enzyme and occurrence of cancer, and also the correlation between active form and allelic genotype of persons, in this study we decided to do a parallel study on measurement of active plasma MMP-9 and its relationship with allelic genotype of breast cancer patients.Materials and methods: After analysis of data, we found that concentration of active MMP-9 has a significant difference in breast cancer patients in comparison with control group, as the concentration of active form of this enzyme was less in control group than the breast cancer patients group (0.7 ng and 1.7 ng respectively. Thus, the level of active MMP-9 showed a significant increase in persons with CT and TT genotypes in comparison with CC genotype (1.5 folds.Results: The present data suggest the concentration of active MMP-9 in breast cancer patients has significantly increased in comparison with the control group and the increased in plasma level of this enzyme is related with the existence of T allele at this gene promoter and also in progression of breast cancer in these patients. We can use the active plasma level of this enzyme or the existence of T allele as a diagnostic tool for discriminating subgroups of breast cancer

  9. Silencing of claudin-11 is associated with increased invasiveness of gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Rachana Agarwal

    Full Text Available Claudins are membrane proteins that play critical roles in tight junction (TJ formation and function. Members of the claudin gene family have been demonstrated to be aberrantly regulated, and to participate in the pathogenesis of various human cancers. In the present study, we report that claudin-11 (CLDN11 is silenced in gastric cancer via hypermethylation of its promoter region.Levels of CLDN11 methylation and mRNA expression were measured in primary gastric cancer tissues, noncancerous gastric mucosae, and cell lines of gastric origin using quantitative methylation-specific PCR (qMSP and quantitative reverse transcriptase-PCR (qRT-PCR, respectively. Analyses of paired gastric cancers and adjacent normal gastric tissues revealed hypermethylation of the CLDN11 promoter region in gastric cancers, and this hypermethylation was significantly correlated with downregulation of CLDN11 expression vs. normal tissues. The CLDN11 promoter region was also hypermethylated in all gastric cancer cell lines tested relative to immortalized normal gastric epithelial cells. Moreover, CLDN11 mRNA expression was inversely correlated with its methylation level. Treatment of CLDN11-nonexpressing gastric cancer cells with 5-aza-2'-deoxycytidine restored CLDN11 expression. Moreover, siRNA-mediated knockdown of CLDN11 expression in normal gastric epithelial cells increased their motility and invasiveness.These data suggest that hypermethylation of CLDN11, leading to downregulated expression, contributes to gastric carcinogenesis by increasing cellular motility and invasiveness. A further understanding of the mechanisms underlying the role of claudin proteins in gastric carcinogenesis will likely help in the identification of novel approaches for diagnosis and therapy of gastric cancer.

  10. Increased expression of survivin in gastric cancer patients and in first degree relatives

    OpenAIRE

    J. Yu; Leung, W K; Ebert, M P A; Ng, E K W; Go, M Y Y; Wang, H.B.; Chung, S C S; Malfertheiner, P; Sung, J. J. Y.

    2002-01-01

    Survivin was recently described as an apoptosis inhibitor. Its pathogenic role in gastric cancer is largely unknown. Expression of survivin in gastric cancer and non-cancer first-degree relatives, and its association with apoptosis and cyclo-oxygenase-2 expression was investigated. Fifty gastric cancer, 30 non-cancer first-degree relatives, 20 normal controls and five gastric cancer cell lines were studied. Survivin and cyclo-oxygenase-2 were evaluated by reverse transcriptase-polymerase chai...

  11. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer

    NARCIS (Netherlands)

    M. Weischer (Maren); B.G. Nordestgaard (Børge); P.D.P. Pharoah (Paul); M.K. Bolla (Manjeet); H. Nevanlinna (Heli); L.J. van 't Veer (Laura); M. García-Closas (Montserrat); J.L. Hopper (John); P. Hall (Per); I.L. Andrulis (Irene); P. Devilee (Peter); P.A. Fasching (Peter); H. Anton-Culver (Hoda); D. Lambrechts (Diether); M.J. Hooning (Maartje); A. Cox (Angela); G.G. Giles (Graham); B. Burwinkel (Barbara); A. Lindblom (Annika); F.J. Couch (Fergus); A. Mannermaa (Arto); G.G. Alnæs (Grethe); E.M. John (Esther); T. Dörk (Thilo); H. Flyger (Henrik); A.M. Dunning (Alison); Q. Wang (Qing); T.A. Muranen (Taru); R.R. van Hien (Richard); J.D. Figueroa (Jonine); M.C. Southey (Melissa); K. Czene (Kamila); J.A. Knight (Julia); R.A.E.M. Tollenaar (Rob); M.W. Beckmann (Matthias); A. Ziogas (Argyrios); M.R. Christiaens (Marie Rose); J.M. Collee (Margriet); M.W.R. Reed (Malcolm); G. Severi (Gianluca); F. Marme (Federick); S. Margolin (Sara); J.E. Olson (Janet); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); A. Miron (Alexander); N.V. Bogdanova (Natalia); M. Shah (Mitul); C. Blomqvist (Carl); A. Broeks (Annegien); M.E. Sherman (Mark); K. Phillips (Kelly); J. Li (Jingmei); J. Liu (Jianjun); G. Glendon (Gord); C.M. Seynaeve (Caroline); A.B. Ekici (Arif); K. Leunen; M. Kriege (Mieke); S.S. Cross (Simon); L. Baglietto (Laura); C. Sohn (Christof); X. Wang (Xing); V. Kataja (Vesa); A.L. Børresen-Dale (Anne Lise); A. Meyer (Andreas); D.F. Easton (Douglas); M.K. Schmidt (Marjanka); S.E. Bojesen (Stig)

    2012-01-01

    textabstractPurpose: We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods: From 22 studies participating in the Breast C

  12. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

    Science.gov (United States)

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2016-01-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 μM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl− and the decreased HCO3− concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na–K–2Cl electroneutral cotransporter or Cl−/HCO3− anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  13. Trans-Resveratrol Alters Mammary Promoter Hypermethylation in Women at Increased Risk for Breast Cancer

    Science.gov (United States)

    Zhu, Weizhu; Qin, Wenyi; Zhang, Ke; Rottinghaus, George E.; Chen, Yin-Chieh; Kliethermes, Beth; Sauter, Edward R.

    2012-01-01

    Trans-resveratrol, present in high concentration in the skin of red grapes and red wine, has a dose-dependent antiproliferative effect in vitro, prevents the formation of mammary tumors, and has been touted as a chemopreventive agent. Based upon in vitro studies demonstrating that trans-resveratrol downregulates the expression of 1) DNA methyltransferases and 2) the cancer promoting prostaglandin (PG)E2, we determined if trans-resveratrol had a dose-related effect on DNA methylation and prostaglandin expression in humans. Thirty-nine adult women at increased breast cancer risk were randomized in double-blind fashion to placebo, 5 or 50 mg trans-resveratrol twice daily for 12 wk. Methylation assessment of 4 cancer-related genes (p16, RASSF-1α, APC, CCND2) was performed on mammary ductoscopy specimens. The predominant resveratrol species in serum was the glucuronide metabolite. Total trans-resveratrol and glucuronide metabolite serum levels increased after consuming both trans-resveratrol doses (P < .001 for both). RASSF-1α methylation decreased with increasing levels of serum trans-resveratrol (P = .047). The change in RASSF-1α methylation was directly related to the change in PGE2 (P = .045). This work provides novel insights into the effects of trans-resveratrol on the breast of women at increased breast cancer risk, including a decrease in methylation of the tumor suppressor gene RASSF-1α. Because of the limited sample size, our findings should be validated in a larger study. PMID:22332908

  14. Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression

    Directory of Open Access Journals (Sweden)

    Xiao YF

    2016-07-01

    Full Text Available Yu-Feng Xiao,1 Jian-Mei Li,2 Su-Min Wang,1 Xin Yong,1 Bo Tang,1 Meng-Meng Jie,1 Hui Dong,1 Xiao-Chao Yang,2 Shi-Ming Yang1 1Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2School of Biomedical Engineering, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Gastric cancer is one of the leading causes of tumor-related deaths in the world. Current treatment options do not satisfy doctors and patients, and new therapies are therefore needed. Cerium oxide nanoparticles (CNPs have been studied as a potential therapeutic approach for treating many diseases. However, their effects on human gastric cancer are currently unknown. Therefore, in this study, we aimed to characterize the effects of CNPs on human gastric cancer cell lines (MKN28 and BGC823. Gastric cancer cells were cocultured with different concentrations of CNPs, and proliferation and migration were measured both in vitro and in vivo. We found that CNPs inhibited the migration of gastric cancer cells when applied at different concentrations, but only a relatively high concentration (10 µg/mL of CNPs suppressed proliferation. Furthermore, we found that CNPs increased the expression of DHX15 and its downstream signaling pathways. We therefore provide evidence showing that CNPs may be a promising approach to suppress malignant activity of gastric cancer by increasing the expression of DHX15. Keywords: cerium oxide nanoparticles, gastric cancer, DHX15, p38

  15. Increased prostate cancer risk from vitamin E supplements

    Science.gov (United States)

    Men who took 400 international units of vitamin E daily had more prostate cancers compared to men who took a placebo, according to an updated review of data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The findings showed that, per 1,

  16. Increased cancer mortality in type 2 diabetes (ZODIAC-3)

    NARCIS (Netherlands)

    Ubink-Veltmaat, L. J.; Kleefstra, N.; Kollen, B. J.; Bilo, H. J. G.; Landman, G.

    2008-01-01

    Background: It is unclear whether there is a relationship between type two diabetes and cancer mortality. It also is unclear whether obesity and body mass index (BMI) are associated with cancer in type 2 diabetes patients. Patients and Methods: In 1998, 1,145 patients with type two diabetes mellitus

  17. Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

    Science.gov (United States)

    According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

  18. Utilizing a Narrative Approach to Increasing Intimacy after Prostate Cancer

    Science.gov (United States)

    McCoy, Megan; Stinson, Morgan A.; Bermudez, J. Maria; Gladney, Leslie A.

    2013-01-01

    Attitudes about sexual intimacy are an important aspect of relationship satisfaction, especially for couples dealing with prostate cancer. Prostate cancer can have profound effects on men and their partners, and more research is needed to better understand potential sexual barriers for these couples. Five major themes identified in the literature…

  19. Childhood height increases the risk of prostate cancer mortality

    DEFF Research Database (Denmark)

    Aarestrup, J; Gamborg, M; Cook, M B;

    2015-01-01

    BACKGROUND: Adult body size is positively associated with aggressive and fatal prostate cancers. It is unknown whether these associations originate in early life. Therefore, we investigated if childhood height, body mass index (BMI; kg/m(2)) and growth are associated with prostate cancer-specific......BACKGROUND: Adult body size is positively associated with aggressive and fatal prostate cancers. It is unknown whether these associations originate in early life. Therefore, we investigated if childhood height, body mass index (BMI; kg/m(2)) and growth are associated with prostate cancer......-specific mortality and survival. METHODS: Subjects were 125,208 men from the Copenhagen School Health Records Register, born 1930-1969 with height and weight measurements at ages 7-13years. Linkage to the Danish Cancer Registry and the Register of Causes of Death enabled identification of incident and fatal prostate...

  20. A phase II study of weekly irinotecan in patients with locally advanced or metastatic HER2- negative breast cancer and increased copy numbers of the topoisomerase 1 (TOP1) gene

    DEFF Research Database (Denmark)

    Kümler, Iben; Balslev, Eva; Stenvang, Jan;

    2015-01-01

    and a taxane in the adjuvant setting, treatment options for metastatic breast cancer are limited. Furthermore response rates for the most commonly used drugs range from around 30% to 12% . Thus new treatment options are needed and preferably coupled to biomarkers predictive of response. Irinotecan...... is a topoisomerase 1 inhibitor used for decades for the treatment of colorectal cancer. Four studies have investigated the efficacy of irinotecan monotherapy in breast cancer and all have included non-biomarker selected patients. In these studies response rates for irinotecan ranged from 5%-23% and are thus...... comparable to response rates obtained with drugs commonly used in the metastatic setting. If a predictive biomarker could be identified for irinotecan, response rates might be even higher. METHODS/DESIGN: This multi-centre phase II single arm trial was designed to investigate if patients with metastatic...

  1. A systematic review of interventions to increase breast and cervical cancer screening uptake among Asian women

    Directory of Open Access Journals (Sweden)

    Lu Mingshan

    2012-06-01

    Full Text Available Abstract Background The Asian population is one of the fastest growing ethnic minority groups in western countries. However, cancer screening uptake is consistently lower in this group than in the native-born populations. As a first step towards developing an effective cancer screening intervention program targeting Asian women, we conducted a comprehensive systematic review, without geographic, language or date limitations, to update current knowledge on the effectiveness of existing intervention strategies to enhance breast and cervical screening uptake in Asian women. Methods This study systematically reviewed studies published as of January 2010 to synthesize knowledge about effectiveness of cancer screening interventions targeting Asian women. Fifteen multidisciplinary peer-reviewed and grey literature databases were searched to identify relevant studies. Results The results of our systematic review were reported in accordance with the PRISMA Statement. Of 37 selected intervention studies, only 18 studies included valid outcome measures (i.e. self-reported or recorded receipt of mammograms or Pap smear. 11 of the 18 intervention studies with valid outcome measures used multiple intervention strategies to target individuals in a specific Asian ethnic group. This observed pattern of intervention design supports the hypothesis that employing a combination of multiple strategies is more likely to be successful than single interventions. The effectiveness of community-based or workplace-based group education programs increases when additional supports, such as assistance in scheduling/attending screening and mobile screening services are provided. Combining cultural awareness training for health care professionals with outreach workers who can help healthcare professionals overcome language and cultural barriers is likely to improve cancer screening uptake. Media campaigns and mailed culturally sensitive print materials alone may be ineffective

  2. A systematic review of interventions to increase breast and cervical cancer screening uptake among Asian women

    Science.gov (United States)

    2012-01-01

    Background The Asian population is one of the fastest growing ethnic minority groups in western countries. However, cancer screening uptake is consistently lower in this group than in the native-born populations. As a first step towards developing an effective cancer screening intervention program targeting Asian women, we conducted a comprehensive systematic review, without geographic, language or date limitations, to update current knowledge on the effectiveness of existing intervention strategies to enhance breast and cervical screening uptake in Asian women. Methods This study systematically reviewed studies published as of January 2010 to synthesize knowledge about effectiveness of cancer screening interventions targeting Asian women. Fifteen multidisciplinary peer-reviewed and grey literature databases were searched to identify relevant studies. Results The results of our systematic review were reported in accordance with the PRISMA Statement. Of 37 selected intervention studies, only 18 studies included valid outcome measures (i.e. self-reported or recorded receipt of mammograms or Pap smear). 11 of the 18 intervention studies with valid outcome measures used multiple intervention strategies to target individuals in a specific Asian ethnic group. This observed pattern of intervention design supports the hypothesis that employing a combination of multiple strategies is more likely to be successful than single interventions. The effectiveness of community-based or workplace-based group education programs increases when additional supports, such as assistance in scheduling/attending screening and mobile screening services are provided. Combining cultural awareness training for health care professionals with outreach workers who can help healthcare professionals overcome language and cultural barriers is likely to improve cancer screening uptake. Media campaigns and mailed culturally sensitive print materials alone may be ineffective in increasing screening

  3. [Application of cohort study in cancer prevention and control].

    Science.gov (United States)

    Dai, Min; Bai, Yana; Pu, Hongquan; Cheng, Ning; Li, Haiyan; He, Jie

    2016-03-01

    Cancer control is a long-term work. Cancer research and intervention really need the support of cohort study. In the recent years, more and more cohort studies on cancer control were conducted in China along with the increased ability of scientific research in China. Since 2010, Cancer Hospital, Chinese Academy of Medical Sciences, collaborated with Lanzhou University and the Worker' s Hospital of Jinchuan Group Company Limited, have carried out a large-scale cohort study on cancer, which covered a population of more than 50 000 called " Jinchang cohort". Since 2012, a National Key Public Health Project, "cancer screening in urban China" , has been conducted in Jinchang, which strengthened the Jinchang cohort study. Based on the Jinchang cohort study, historical cohort study, cross-sectional study and prospective cohort study have been conducted, which would provide a lot of evidence for the cancer control in China.

  4. Cancer genetic association studies in the genome-wide age

    OpenAIRE

    Savage, Sharon A

    2008-01-01

    Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case–control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-sca...

  5. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Swisher-McClure, Samuel, E-mail: Swisher-Mcclure@uphs.upenn.edu [Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Leonard Davis Institute of Health Economics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita; Woo, Kaitlin [Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Smaldone, Marc; Uzzo, Robert [Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (United States); Bekelman, Justin E. [Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Leonard Davis Institute of Health Economics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2014-05-01

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.

  6. INCREASE INCOME AND MORTALITY OF COLORRECTAL CANCER IN BRAZIL, 2001-2009

    Directory of Open Access Journals (Sweden)

    Raphael Mendonca GUIMARAES

    2013-03-01

    Full Text Available Context Several international studies have observed a correlation between the improvement of socio-demographic indicators and rates of incidence and mortality from cancer of the colon and rectum. Objective The objective of this study is to estimate the correlation between average per capita income and the rate of colorectal cancer mortality in Brazil between 2001 and 2009. Methods We obtained data on income inequality (Gini index, population with low incomes (½ infer the minimum wage/month, average family income, per capita ICP and mortality from colon cancer and straight between 2001-2009 by DATASUS. A trend analysis was performed using linear regression, and correlation between variables by Pearson's correlation coefficient. Results There was a declining trend in poverty and income inequality, and growth in ICP per capita and median family income and standardized mortality rate for colorectal cancer in Brazil. There was also strong positive correlation between mortality from this site of cancer and inequality (men r = -0.30, P = 0.06, women r = -0.33, P = 0.05 income low income (men r = -0.80, P<0.001, women r = -0.76, P<0.001, median family income (men r = 0.79, P = 0.06, women r = 0.76, P<0.001 and ICP per capita (men r = 0.73, P<0.001, women r = 0.68, P<0.001 throughout the study period. Conclusion The increase of income and reducing inequality may partially explain the increased occurrence of colorectal cancer and this is possibly due to differential access to food recognized as a risk factor, such as red meat and high in fat. It is important therefore to assess the priority of public health programs addressing nutrition in countries of intermediate economy, as is the case of Brazil.

  7. Motivational Interviewing to Increase Physical Activity in Breast Cancer Survivors

    Science.gov (United States)

    2011-05-01

    Reinforce appropriate goals IF clients are having trouble coming up with goals, ASK: © Some women with breast cancer have benefited from these types of...clients are having trouble coming up with goals, ASK: © Some women with breast cancer have benefited from these types of activities. Present menu of...minutes (MINIMAL EFFORT, NO PERSPIRATION) Examples: easy walking, yoga , bowling, shuffleboard, horseshoes, golf, fishing from riverbank Fruits and

  8. Evidence of increased chromosomal abnormalities in French Polynesian thyroid cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Violot, D.; M' kacher, R.; Dossou, J. [UPRES, Laboratory of Radiosensitivity and Radiocarcinogenesis (France); Adjadj, E.; Vathaire, F. de [INSERM, Laboratory of Cancer Epidemiology (France); Parmentier, C. [UPRES, Laboratory of Radiosensitivity and Radiocarcinogenesis (France); Institut Gustave Roussy, Department of Nuclear Medicine, Villejuif (France)

    2005-02-01

    The aim of this study was to evaluate the frequency of chromosomal abnormalities in thyroid cancer patients before and after radioactive iodine administration in order to assess cytogenetic particularity in Polynesian thyroid cancer patients. Chromosomal abnormalities were studied in 30 Polynesian patients with differentiated thyroid cancer, prior to and 4 days after{sup 131}I administration. Unstable chromosomal abnormalities were counted in peripheral blood lymphocytes using a conventional cytogenetic method. Peripheral blood was irradiated in vitro at different doses (0.5, 1 and 2 Gy) in order to establish the dose-response of the lymphocytes. Control groups were composed of 50 European thyroid cancer patients before and after first administration of{sup 131}I, and of ten European healthy donors. In addition, in vitro irradiation assays were performed at different doses (0.5, 1 and 2 Gy). The relative risk of spontaneous dicentrics before any radiation treatment was 2.9 (95% CI 1.7-5.1) times higher among Polynesian thyroid patients than among European thyroid cancer patients. After in vitro irradiation, the rise in frequency of dicentrics was similar in the Polynesian thyroid cancer group and the European thyroid patients and healthy donors. Four days after administration of 3.7 GBq{sup 131}I, the relative risk for a dicentric per cell was 1.3 (95% CI 1.0-1.5) times higher in Polynesian than in European patients. This can be explained by higher{sup 131}I retention in Polynesian compared with European patients. The results obtained revealed an increased frequency of cytogenetic abnormalities in Polynesian thyroid cancer patients compared with European control patients. These preliminary findings are compatible with possible previous environmental aggression and therefore imply a need for further investigations on larger series including, in particular, French Polynesian healthy donors. In addition to French Polynesians, Maori and Hawaiian control groups could be

  9. Hormone Replacement Therapy: An Increased Risk of Recurrence and Mortality for Breast Cancer Patients?

    Science.gov (United States)

    Lupo, Molly; Dains, Joyce E.; Madsen, Lydia T.

    2015-01-01

    Historically, randomized controlled trials (RCTs) have shown an increased risk of recurrence and mortality among women who have used primarily oral HRT after breast cancer. However, many of these studies have had design flaws that may impact the findings. Numerous investigators have concluded that additional RCTs should be performed, but because of ethical issues and logistic challenges, large-scale RCTs are unlikely. Thus, the authors conducted an integrative review investigating recurrence and mortality data among breast cancer survivors who have used hormone replacement therapy (HRT). They recommend a stepwise algorithm for treating vaginal symptoms in breast cancer survivors: (1) start with nonhormonal treatments; (2) progress to a detailed discussion among patients and health-care professionals about the current known risks and benefits of vaginal estrogen; and (3) conclude with mutual decision-making between health-care providers and patients regarding the use of vaginal estrogen treatment. PMID:26705493

  10. Chemoresistance of CD133(+) colon cancer may be related with increased survivin expression.

    Science.gov (United States)

    Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah; Cho, Mee-Yon

    2015-07-31

    CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133(+) colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133(-) cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133(+) and siRNA-induced CD133(-) cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133(+) cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133(+) cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133(+) cells at 96 h after siRNA transfection. From this study, we conclude that CD133(+) cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133(+) colon cancer.

  11. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  12. Refractory cachexia is associated with increased plasma concentrations of fentanyl in cancer patients

    Directory of Open Access Journals (Sweden)

    Suno M

    2015-05-01

    Full Text Available Manabu Suno,1,* Yuriko Endo,1,* Hiroyuki Nishie,2 Makoto Kajizono,3 Toshiaki Sendo,3 Junji Matsuoka4 1Department of Oncology Pharmaceutical Care and Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 3Department of Pharmacy, Okayama University Hospital, 4Faculty of Health Sciences, Okayama University Medical School, Okayama, Japan *These authors contributed equally to this work Background: An appropriate plasma concentration of fentanyl is the key to achieving good pain control in cancer patients. Cachexia, a multifactorial syndrome, is known to affect drug-metabolizing enzymes. However, the fentanyl concentrations in the blood of patients with cachexia have not been analyzed. The aim of this study was to evaluate the influence of cancer cachexia on dose-adjusted plasma fentanyl concentrations in cancer patients.Methods: Blood was collected from 21 Japanese cancer patients treated with a 24-hour transdermal fentanyl patch during the steady state of fentanyl plasma concentration. Plasma fentanyl concentrations were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS, and the levels were adjusted with the dose of fentanyl. Laboratory data were collected, and the cachexia stage was determined, based on study by Fearon et al. Multiple regression analysis was performed to identify the factors that affected fentanyl plasma concentrations.Results: Eight patients were classified as precachexia, nine as cachexia, and four as refractory cachexia, and the median dose-adjusted fentanyl concentrations (ng/mL per mg/kg/day were 27.5, 34.4, and 44.5, respectively. The dose-adjusted fentanyl concentration in patients with refractory cachexia was higher than that in patients with precachexia (Kruskal–Wallis test and post hoc Mann–Whitney U-test, P<0.01. The factors that

  13. Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

    Energy Technology Data Exchange (ETDEWEB)

    Boukheris, Houda [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stovall, Marilyn [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gilbert, Ethel S. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stratton, Kayla L. [Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Smith, Susan A.; Weathers, Rita [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hammond, Sue [Department of Pathology, Ohio State University School of Medicine, Columbus, Ohio (United States); Mertens, Ann C. [Department of Pediatrics, Emory University, Atlanta, Georgia (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Armstrong, Gregory T.; Robison, Leslie L. [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Neglia, Joseph P. [Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Inskip, Peter D., E-mail: inskippe@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-03-01

    Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

  14. Pregnancy-associated breast cancer and increased risk of pregnancy-associated recurrence: a case report

    OpenAIRE

    Schnabel Freya; Billig Jessica; Cimeno Arielle; Chun Jennifer

    2012-01-01

    Abstract Introduction Pregnancy-associated breast cancer refers to breast cancer diagnosed during pregnancy, lactation, or within twelve months postpartum. Recent studies suggest that, when matched for age and stage, the prognosis of pregnancy-associated breast cancer is comparable to non-pregnancy-associated breast cancer. However, the risk for breast cancer recurrence associated with subsequent pregnancies in this population is not clear. Case presentation We describe the case of a Caucasia...

  15. Chemoresistance of CD133{sup +} colon cancer may be related with increased survivin expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Cho, Mee-Yon, E-mail: meeyon@yonsei.ac.kr [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Institute of Genomic Cohort, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of)

    2015-07-31

    CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133{sup +} colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133{sup −} cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133{sup +} and siRNA-induced CD133{sup −} cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133{sup +} cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133{sup +} cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133{sup +} cells at 96 h after siRNA transfection. From this study, we conclude that CD133{sup +} cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133{sup +} colon cancer. - Highlights: • We evaluate the role of CD133 in chemoresistance of colon cancer. • We compared the chemoresistance of CD133{sup +} cells and siRNA-induced CD133{sup −} cells. • CD133 had little to no effect on MDR1, ABCG2 and AKT1 expression. • Survivin expression and chemoresistance were increased in CD133{sup +} colon cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Michalski Christoph W

    2007-12-01

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

  17. EGFR may couple moderate alcohol consumption to increased breast cancer risk

    Directory of Open Access Journals (Sweden)

    Christopher P Mill

    2009-10-01

    Full Text Available Christopher P Mill1, Julia A Chester2, David J Riese II11Purdue University School of Pharmacy, Purdue University Center for Cancer Research, 2Purdue University Department of Psychological Sciences, West Lafayette, IN, USAAbstract: Alcohol consumption is an established risk factor for breast cancer. Nonetheless, the mechanism by which alcohol contributes to breast tumor initiation or progression has yet to be definitively established. Studies using cultured human tumor cell lines have identified signaling molecules that may contribute to the effects of alcohol, including reactive oxygen species and other ethanol metabolites, matrix metalloproteases, the ErbB2/Her2/Neu receptor tyrosine kinase, cytoplasmic protein kinases, adenylate cyclase, E-cadherins, estrogen receptor, and a variety of transcription factors. Emerging data suggest that the epidermal growth factor receptor (EGFR tyrosine kinase may contribute to breast cancer genesis and progression. Here we integrate these findings and propose three mechanisms by which alcohol contributes to breast cancer. A common feature of these mechanisms is increased EGFR signaling. Finally, we discuss how these mechanisms suggest strategies for addressing the risks associated with alcohol consumption.Keywords: alcohol, breast cancer risk factor, EGF receptor, matrix metalloprotease

  18. Normal breast physiology: the reasons hormonal contraceptives and induced abortion increase breast-cancer risk.

    Science.gov (United States)

    Lanfranchi, Angela

    2014-01-01

    A woman gains protection from breast cancer by completing a full-term pregnancy. In utero, her offspring produce hormones that mature 85 percent of the mother's breast tissue into cancer-resistant breast tissue. If the pregnancy ends through an induced abortion or a premature birth before thirty-two weeks, the mother's breasts will have only partially matured, retaining even more cancer-susceptible breast tissue than when the pregnancy began. This increased amount of immature breast tissue will leave the mother with more sites for cancer initiation, thereby increasing her risk of breast cancer. Hormonal contraceptives increase breast-cancer risk by their proliferative effect on breast tissue and their direct carcinogenic effects on DNA. Hormonal contraceptives include estrogen-progestin combination drugs prescribed in any manner of delivery: orally, transdermally, vaginally, or intrauterine. This article provides the detailed physiology and data that elucidate the mechanisms through which induced abortion and hormonal contraceptives increase breast-cancer risk.

  19. Increased risks of third primary cancers of non-breast origin among women with bilateral breast cancer

    NARCIS (Netherlands)

    Kwast, A.B.G.; Liu, L.; Roukema, J.A.; Voogd, A.C.; Jobsen, J.J.; Coebergh, J.W.W.; Soerjomataram, I.; Siesling, S.

    2012-01-01

    Background: This study examined the risk of third cancer of non-breast origin (TNBC) among women with bilateral breast cancer (BBC; either synchronous or metachronous), focussing on the relation with breast cancer treatment. Methods: Risk was assessed, among 8752 Dutch women diagnosed with BBC betw

  20. Increased temperature and entropy production in cancer: the role of anti-inflammatory drugs.

    Science.gov (United States)

    Pitt, Michael A

    2015-02-01

    Some cancers have been shown to have a higher temperature than surrounding normal tissue. This higher temperature is due to heat generated internally in the cancer. The higher temperature of cancer (compared to surrounding tissue) enables a thermodynamic analysis to be carried out. Here I show that there is increased entropy production in cancer compared with surrounding tissue. This is termed excess entropy production. The excess entropy production is expressed in terms of heat flow from the cancer to surrounding tissue and enzymic reactions in the cancer and surrounding tissue. The excess entropy production in cancer drives it away from the stationary state that is characterised by minimum entropy production. Treatments that reduce inflammation (and therefore temperature) should drive a cancer towards the stationary state. Anti-inflammatory agents, such as aspirin, other non-steroidal anti-inflammatory drugs, corticosteroids and also thyroxine analogues have been shown (using various criteria) to reduce the progress of cancer.

  1. 8q24 rs6983267G variant is associated with increased thyroid cancer risk

    Science.gov (United States)

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Echeverry, Guadalupe Polanco; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carvajal Carmona, Luis G.

    2015-01-01

    The G allele of the rs6983267 single nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in thyroid cancer susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3,067 cases and 8,575 controls. We detected significant associations between rs6983267G and thyroid cancer in the British Isles (Odds Ratio, OR= 1.19, 95% confidence interval, CI: 1.11–1.27, P= 4.03 × 10−7), Japan (OR= 1.20, 95% CI: 1.03–1.41, P= 0.022) and a borderline significant association of similar effect direction and size in Colombia (OR= 1.19, 95% CI: 0.99–1.44, P= 0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5,484 cases and 12,594 controls, confirmed the association between rs6983267G and thyroid cancer (P= 1.23 × 10−7, OR= 1.13, 95% CI: 1.07–1.18). Our results therefore support the notion that rs6983267G is a bona fide thyroid cancer risk variant that increases the risk of disease by ~13%. PMID:26290501

  2. Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer

    Directory of Open Access Journals (Sweden)

    Iczkowski Kenneth A

    2005-07-01

    Full Text Available Abstract Background Macrophage migration inhibitory factor (MIF is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. Methods MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. Results Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115 compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158. ELISA diluent reagents that included bovine serum albumin (BSA significantly reduced MIF serum detection (p Conclusion Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer.

  3. Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells

    Directory of Open Access Journals (Sweden)

    Conseiller Emmanuel

    2008-01-01

    Full Text Available Abstract Background Colorectal cancer (CRC is one of the most common causes of cancer death throughout the world. In this work our aim was to study the role of the phosphoserine aminotransferase PSAT1 in colorectal cancer development. Results We first observed that PSAT1 is overexpressed in colon tumors. In addition, we showed that after drug treatment, PSAT1 expression level in hepatic metastases increased in non responder and decreased in responder patients. In experiments using human cell lines, we showed that ectopic PSAT1 overexpression in colon carcinoma SW480 cell line resulted in an increase in its growth rate and survival. In addition, SW480-PSAT1 cells presented a higher tumorigenic potential than SW480 control cells in xenografted mice. Moreover, the SW480-PSAT1 cell line was more resistant to oxaliplatin treatment than the non-transfected SW480 cell line. This resistance resulted from a decrease in the apoptotic response and in the mitotic catastrophes induced by the drug treatment. Conclusion These results show that an enzyme playing a role in the L-serine biosynthesis could be implicated in colon cancer progression and chemoresistance and indicate that PSAT1 represents a new interesting target for CRC therapy.

  4. Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Robert E. Page

    2007-01-01

    Full Text Available Background: Proprotein convertases (PCs are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and angiogenic factors. Although the expression of several PCs is increased in many tumors, their expression in primary ovarian tumors has not been studied in detail. We sought to determine if there was an association between the expression of the ubiquitously expressed PCs, furin, PACE-4, PC-5 and PC-7, and ovarian tumor progression. Methods: We assessed their expression by RT-PCR, Real-time PCR, Western blot, and immunohistochemistry using cells derived from normal human ovarian surface epithelium (HOSE and cancer cell lines as well as ovarian epithelial cancer specimens (45 RT-PCR/Real-time PCR, and 120 archival specimens for Immunohistochemistry. Results: We found that furin expression was restricted to the cancer cell lines. In contrast, PACE-4 and PC-7 showed expression only in normal HOSE cells lines. Furthermore, furin was predominantly expressed in primary tumors from patients who survived for less than five years. The other PCs are either expressed in the group of survivors (PC-7 and PACE4 or expressed in low amounts (PC-5. Conclusions: Our studies point to a clear relationship between furin and ovarian cancer. In addition, these results show that furin exhibits the closest association with ovarian cancer among the ubiquitously expressed PCs, arguing against the redundancy of these proteases. In summary, furin may constitute a marker for ovarian tumor progression and could contribute to predict the outcome of this disease.

  5. Increased STAT1 signaling in endocrine-resistant breast cancer.

    Directory of Open Access Journals (Sweden)

    Rui Huang

    Full Text Available Proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its partially sensitive (MCF-7/LCC1 and fully resistant (MCF-7/LCC9 variants was performed to identify modifiers of endocrine sensitivity in breast cancer. Analysis of the expression of 120 paired phosphorylated and non-phosphorylated epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and several phosphorylated epitopes (phospho-STAT1(Tyr701 and phospho-STAT3(Ser727 were differentially expressed between endocrine resistant and parental controls, confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more effective inhibitor of the endocrine resistant MCF-7/LCC1 and MCF-7/LCC9 lines than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally effective in endocrine-resistant and parental lines. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by quantitative immunofluorescence in invasive breast cancers and matched lymph nodes. When lymph node expression was compared to its paired primary breast cancer expression, there was greater expression of cytoplasmic STAT1 (∼3.1 fold, phospho-STAT3(Ser727 (∼1.8 fold, and STAT5 (∼1.5 fold and nuclear phospho-STAT3(Ser727 (∼1.5 fold in the nodes. Expression levels of STAT1 and STAT3 transcript were analysed in 550 breast cancers from publicly available gene expression datasets (GSE2990, GSE12093, GSE6532. When treatment with tamoxifen was considered, STAT1 gene expression was nearly predictive of distant metastasis-free survival (DMFS, log-rank p = 0.067, while STAT3 gene expression was predictive of DMFS (log-rank p<0.0001. Analysis of STAT1 and STAT3 protein expression in a series of 546 breast cancers also indicated that high expression of STAT3 protein was associated with improved survival (DMFS, p = 0.006. These results suggest

  6. A phase II study of weekly irinotecan in patients with locally advanced or metastatic HER2- negative breast cancer and increased copy numbers of the topoisomerase 1 (TOP1) gene

    DEFF Research Database (Denmark)

    Kümler, Iben; Balslev, Eva; Stenvang, Jan;

    2015-01-01

    comparable to response rates obtained with drugs commonly used in the metastatic setting. If a predictive biomarker could be identified for irinotecan, response rates might be even higher. METHODS/DESIGN: This multi-centre phase II single arm trial was designed to investigate if patients with metastatic...... breast cancer and increased expression of the topoisomerase 1 gene have a high likelihood of obtaining a clinical benefit from treatment with irinotecan. Trial recruitment is two-staged as 19 patients are planned to participate in the first part. If less than 7 patients have clinical benefit the trial...

  7. GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System Cancer: Evidences from 63,876 Subjects.

    Science.gov (United States)

    Wang, Ying; He, Jing; Ma, Tian-Jiao; Lei, Wei; Li, Feng; Shen, Han; Shen, Zhen-Ya

    2016-01-01

    GSTT1 gene plays an important role in detoxification and clearance of reactive oxygen species(ROS). A null variant in this gene has been demonstrated to confer cancer susceptibility. Although many studies have demonstrated the association between GSTT1 null polymorphism and urinary system cancer susceptibility, several publications reported opposite conclusions. For better understanding the effects of this polymorphism on the risk of urinary system cancer, a updated meta-analysis was performed with a total of 26,666 cases and 37,210 controls extracted from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The results suggested that the GSTT1 null genotype was significantly associated with an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22). Furthermore, stratified analyses by the type of cancer, ethnicity, source of control and quality score presented a significantly increased risk associated with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and Indians subgroup, population-based(PB) subgroup, medium quality and low quality subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a potential cancer susceptibility variant. Well-designed and large-cohort studies are needed to confirm the association between GSTT1 null genotype and urinary system cancer risk.

  8. GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System Cancer: Evidences from 63,876 Subjects

    Science.gov (United States)

    Wang, Ying; He, Jing; Ma, Tian-Jiao; Lei, Wei; Li, Feng; Shen, Han; Shen, Zhen-Ya

    2016-01-01

    GSTT1 gene plays an important role in detoxification and clearance of reactive oxygen species(ROS). A null variant in this gene has been demonstrated to confer cancer susceptibility. Although many studies have demonstrated the association between GSTT1 null polymorphism and urinary system cancer susceptibility, several publications reported opposite conclusions. For better understanding the effects of this polymorphism on the risk of urinary system cancer, a updated meta-analysis was performed with a total of 26,666 cases and 37,210 controls extracted from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The results suggested that the GSTT1 null genotype was significantly associated with an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22). Furthermore, stratified analyses by the type of cancer, ethnicity, source of control and quality score presented a significantly increased risk associated with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and Indians subgroup, population-based(PB) subgroup, medium quality and low quality subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a potential cancer susceptibility variant. Well-designed and large-cohort studies are needed to confirm the association between GSTT1 null genotype and urinary system cancer risk.

  9. [Increase in the number of cancer stem cells after exposure to low-LET radiation].

    Science.gov (United States)

    Zamulaeva, I A; Matchuk, O N; Selivanova, E I; Andreev, V G; Lipunov, N M; Makarenko, S A; Zhavoronkov, L P; Saenko, A S

    2014-01-01

    Radioresistance of cancer stem cells (CSCs) is regarded as one of the possible causes of cancer recurrence after radiotherapy. Since the regularities and mechanisms of radiation effects on this population of cells have not been sufficiently studied, the aim of this work is to elucidate the changes in the CSC number after γ-irradiation in stable cultures of tumor cells in vitro and tumor tissue in vivo (in the course of radiation therapy of patients with cancers of the upper respiratory tract). CSCs were identified in the cell lines B16, MCF-7, HeLa by the ability to exclude the fluorescent dye Hoechst 33342 (SP method) 48-72 h after irradiation at the doses of 1-20 Gy and in biopsy material by immunophenotype CD44+CD24(-/low) before and 24 h after irradiation at the total dose of 10 Gy. The essential differences in the response of CSCs and other cancer cells were found after exposure to low-LET radiation. The absolute number of CSCs increased after a single exposure at the doses ranging from 1 to 5-10 Gy in different cell cultures, but a further dose increase maintained the current number of CSCs or decreased it. At the same time, the number of non CSCs significantly decreased with increasing doses of radiation exposure, as expected. Fractionated irradiation in vivo at a total dose of 10 Gy increased the relative amount of CSCs in most patients. The registered changes are an integral indicator of cell death, cell division delay immediately after irradiation, proliferation at a later time, possible dedifferentiation of non CSCs, etc. The exact contribution of each of them to the radiation-induced increase of the CSCs number is of considerable interest and requires further research.

  10. A mechanically-induced colon cancer cell population shows increased metastatic potential

    KAUST Repository

    Tang, Xin

    2014-05-29

    Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher\\'s exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular

  11. Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

    Science.gov (United States)

    Lan, Xiuwen; Li, Sen; Gao, Hongyu; Nanding, Abiyasi; Quan, Lina; Yang, Chunyan; Ding, Shaohua; Xue, Yingwei

    2017-01-01

    Purpose Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients. Patients and methods A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed. Results The positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (Pcancer. Conclusion The increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer.

  12. Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis.

    Science.gov (United States)

    He, Shiyao; Tang, Yu-hong; Zhao, Guobin; Yang, Xiaolong; Wang, Dehou; Zhang, Ye

    2014-03-01

    Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence regarding the association between pioglitazone and bladder cancer risk is confusing. A systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After quality assessment, nine datasets from 10 available studies were included on the basis of inclusion criteria. The incidence of bladder cancer among pioglitazone ever users and never users, pooled from four cohort and one randomized studies, were 84.51 and 66.68 per 100,000 person-years, respectively. Nine studies representing 2,596,856 diabetic patients were recognized as eligible for overall study; the result suggested an increased risk of bladder cancer in patients exposed to pioglitazone. A persistent significance was detected after being adjusted by age, gender, and use of other diabetes medications. Subgroup analyses indicated that the significantly increased incidence of bladder cancer was found in men, but not in women. Additionally, the analyses addressing increasing exposure to pioglitazone observed a dose-response relation between exclusive ever use of pioglitazone and bladder cancer in terms of cumulative duration of use and cumulative dosage. With some limitations, our results suggest an increased risk of bladder cancer in diabetic patients using pioglitazone, especially for men with long-term and high-dose exposure. Additional studies are needed to provide more precise evidences to support our results.

  13. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    DEFF Research Database (Denmark)

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan;

    2010-01-01

    According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C>T...

  14. High body mass index and cancer risk-a Mendelian randomisation study

    DEFF Research Database (Denmark)

    Benn, Marianne; Tybjærg-Hansen, Anne; Smith, George Davey;

    2016-01-01

    108,812 individuals from the general population, we found that observationally high BMI was associated with lower risk of lung and skin cancer overall and with higher risk of breast cancer in postmenopausal women, but not with other types of cancer. BMI increasing alleles were not associated with risk...... of follow-up (range 0-37), 8002 developed non-skin cancer, 3347 non-melanoma skin cancer, 1396 lung cancer, 637 other smoking related cancers, 1203 colon cancer, 159 kidney cancer, 1402 breast cancer, 1062 prostate cancer, and 2804 other cancers. Participants were genotyped for five genetic variants...... associated with BMI. Two Danish general population studies, the Copenhagen General Population and the Copenhagen City Heart Study. In observational analyses, overall risk of non-melanoma skin cancer was 35 % (95 % confidence interval 28-42 %) lower and risk of lung cancer 32 % (19-43 %) lower in individuals...

  15. Silymarin inhibits cervical cancer cell through an increase of phosphatase and tensin homolog.

    Science.gov (United States)

    Yu, Hann-Chin; Chen, Li-Jen; Cheng, Kai-Chun; Li, Ying-Xiao; Yeh, Ching-Hua; Cheng, Juei-Tang

    2012-05-01

    Silymarin is an active constituent contained in the seeds of the milk thistle plant and is widely used as a hepatic protection agent due to its antioxidant-like activity. In the present study we evaluated the potential action of silymarin against cervical cancer and investigated its mechanism of action. Treatment of cervical cancer cells (C-33A) with silymarin resulted in a significant decrease in cell viability. Silymarin induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 3. Silymarin also inhibited the phosphorylation of Akt with an increase in expression of phosphatase and tensin homolog (PTEN). We also observed that silymarin suppressed C-33A cell invasion and wound-healing migration in a concentration-dependent manner. Western-blot analysis showed that silymarin significantly inhibited the expression of matrix metalloproteinase-9 (MMP-9) in C-33A cells. Furthermore, we applied siRNA to lower the PTEN gene, which diminished the anticancer actions of silymarin. Taken together, these results show that silymarin has the potential to suppress the survival, migration and invasion of C-33A cancer cells; thus, it could be developed as a promising agent for the treatment of cervical cancer in the future.

  16. ERBB2 increases metastatic potentials specifically in androgen-insensitive prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Jessica Tome-Garcia

    Full Text Available Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145, it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP. In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines.

  17. Formation of Tumorspheres with Increased Stemness without External Mitogens in a Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Juan Sebastian Yakisich

    2016-01-01

    Full Text Available Like with most solid tumors, the presence of a subpopulation of cancer stem cells (CSCs or cancer stem-like cells (CS-LCs has been associated with chemoresistance and tumor relapse in lung cancer cells. In the absence of serum, CSCs/CS-LCs have the ability to grow as lung tumorspheres (LTSs, and this system is routinely used for isolation and characterization of putative CSCs/CS-LCs. Methods to isolate LTSs are usually performed in serum-free media supplemented with specific additives such as epidermal growth factor and basic fibroblast growth factor. In this study, we report the generation of LTSs without the addition of any external mitogenic stimulation. LTSs generated in this manner demonstrated several traits usually associated with increased stemness such as elevated expression of the stemness-associated marker Sox2 and increased chemoresistance to conventional anticancer drugs. In addition, we report that the FDA-approved drug Digitoxin, at concentration close to its therapeutic level, decreased the viability of LTSs and downregulated Sox2 independent of the PI3K/AKT pathway. The potential use of LTSs generated without the addition of any external mitogenic stimulation to study the role of specific factor(s associated with stemness properties is also discussed.

  18. Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV

    DEFF Research Database (Denmark)

    Garnaes, E; Kiss, K; Andersen, L;

    2015-01-01

    BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis...... for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly significant increase...... in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type.(5.4% per year) during the study period. This was explained by a CONCLUSIONS: The increased number of HPV...

  19. Risk for unemployment of cancer survivors: A Danish cohort study

    DEFF Research Database (Denmark)

    Carlsen, Kathrine; Dalton, Susanne Oksbjerg; Diderichsen, Finn;

    2008-01-01

    AIM: To investigate whether cancer survivors are at an increased risk for unemployment after cancer. MATERIALS AND METHODS: A cohort of 65,510 patients who were part of the workforce in the year before diagnosis and a random sample of 316,925 age and gender-matched controls were followed for up...... to 20 years in a longitudinal register-based cohort study. Demographic, socioeconomic and health-related information were obtained through Danish administrative registers. RESULTS: Cancer survivors had a small but significantly increased risk for unemployment following cancer. Stratified analyses showed...

  20. Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro.

    Science.gov (United States)

    Frajese, Giovanni Vanni; Benvenuto, Monica; Fantini, Massimo; Ambrosin, Elena; Sacchetti, Pamela; Masuelli, Laura; Giganti, Maria Gabriella; Modesti, Andrea; Bei, Roberto

    2016-06-01

    Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.

  1. Perceived risk, anxiety, mammogram uptake and breast self examination of women with a family history of breast cancer: The role of knowing to be at increased risk

    NARCIS (Netherlands)

    Drossaert, C.H.C.; Boer, H.; Seydel, E.R.

    1996-01-01

    Since women with a first-degree relative with breast cancer are at increased risk for breast cancer, it is of special importance that they adhere to early detection programs. In this study, women with (389) and without (3295) a family history of breast cancer were compared with respect to risk perce

  2. Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.

    Science.gov (United States)

    McCarty, M F

    1999-12-01

    Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets

  3. Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality.

    Directory of Open Access Journals (Sweden)

    Kui-Kai Lau

    Full Text Available BACKGROUND AND PURPOSE: Cancer patients are at increased risk of cardiovascular and cerebrovascular events. It is unclear whether cancer confers any additional risk for recurrent stroke or cardiovascular mortality after stroke. METHODS: This was a single center, observational study of 1,105 consecutive Chinese ischemic stroke patients recruited from a large stroke rehabilitation unit based in Hong Kong. We sought to determine whether patients with cancer are at higher risk of recurrent stroke and cardiovascular mortality. RESULTS: Amongst 1,105 patients, 58 patients (5.2% had cancer, of whom 74% were in remission. After a mean follow-up of 76 ± 18 months, 241 patients developed a recurrent stroke: 22 in patients with cancer (38%, annual incidence 13.94%/year, substantially more than those without cancer (21%, 4.65%/year (p<0.01. In a Cox regression model, cancer, age and atrial fibrillation were the 3 independent predictors of recurrent stroke with a hazard ratio (HR of 2.42 (95% confidence interval (CI: 1.54-3.80, 1.01 (1.00-1.03 and 1.35 (1.01-1.82 respectively. Likewise, patients with cancer had a higher cardiovascular mortality compared with those without cancer (4.30%/year vs. 2.35%/year, p = 0.08. In Cox regression analysis, cancer (HR: 2.08, 95% CI: 1.08-4.02, age (HR: 1.04, 95% CI 1.02-1.06, heart failure (HR: 3.06, 95% CI 1.72-5.47 and significant carotid atherosclerosis (HR: 1.55, 95% CI 1.02-2.36 were independent predictors for cardiovascular mortality. CONCLUSIONS: Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality.

  4. Increased rate change over time of a sphincter-saving procedure for lower rectal cancer

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-jian; WANG Jian-ping; WANG Lei; HE Xiao-sheng; ZOU Yi-feng; LIAN Lei; ZHANG Long-juan; LAN Ping

    2008-01-01

    Background Total mesorectal excision(TME)has increased the rate of sphincter-preservation(SP)for more patients with low-lying rectal cancer.Here,we analyze the change of sphincter preserving rates in lower rectal cancer and their related factors.Methods We reviewed retrospectively the medical records of 316 patients with lower rectal cancers,1 to 5 cm from the anorectal line,who had surgical resections from August 1994 to November 2005.The 12-year span was divided into 2 periods:period Ⅰ(August 1994-December 1998)and period Ⅱ(January 1999-November 2005),based on the date (January 1999)when standard total mesorectal excision(TME)was introduced.The patients were divided jnto two groups based on the operation:abdominoperineal resection(APR)or SP surgery.SP rates,leakage and other clinicopathological characteristics were compared between the two time periods and between the two different groups.Results The SP rate increased significantly over the 12 years,from 44.9% in period Ⅰ to 76.2% in period Ⅱ(P=0.000).The factors significantly influencing SP included the distance of the tumor from the anorectal line,gender,time period,circumference of intramural spread and histological differentiation (P<0.05).Significant differences were detected between the two time periods in gender,blood transfusion volume and Dukes'stage(P<0.05).The leakage rate was 2.7% in period Ⅰ and 1.3% in period Ⅱ (P>0.05).Conclusions Over the 12-year period of the study the SP rate in rectal cancers 1-5 cm from the anorectal line has increased significantly while the blood transfusion volume has decreased due to the introduction of TME.However,TME had no effect on operating time and leakage rates.

  5. Estrogen withdrawal, increased breast cancer risk and the KRAS-variant

    Science.gov (United States)

    McVeigh, Terri P; Jung, Song-Yi; Kerin, Michael J; Salzman, David W; Nallur, Sunitha; Nemec, Antonio A; Dookwah, Michelle; Sadofsky, Jackie; Paranjape, Trupti; Kelly, Olivia; Chan, Elcie; Miller, Nicola; Sweeney, Karl J; Zelterman, Daniel; Sweasy, Joann; Pilarski, Robert; Telesca, Donatello; Slack, Frank J; Weidhaas, Joanne B

    2015-01-01

    The KRAS-variant is a biologically functional, microRNA binding site variant, which predicts increased cancer risk especially for women. Because external exposures, such as chemotherapy, differentially impact the effect of this mutation, we evaluated the association of estrogen exposures, breast cancer (BC) risk and tumor biology in women with the KRAS-variant. Women with BC (n = 1712), the subset with the KRAS-variant (n = 286) and KRAS-variant unaffected controls (n = 80) were evaluated, and hormonal exposures, KRAS-variant status, and pathology were compared. The impact of estrogen withdrawal on transformation of isogenic normal breast cell lines with or without the KRAS-variant was studied. Finally, the association and presentation characteristics of the KRAS-variant and multiple primary breast cancer (MPBC) were evaluated. KRAS-variant BC patients were more likely to have ovarian removal pre-BC diagnosis than non-variant BC patients (p = 0.033). In addition, KRAS-variant BC patients also appeared to have a lower estrogen state than KRAS-variant unaffected controls, with a lower BMI (P < 0.001). Finally, hormone replacement therapy (HRT) discontinuation in KRAS-variant patients was associated with a diagnosis of triple negative BC (P < 0.001). Biologically confirming our clinical findings, acute estrogen withdrawal led to oncogenic transformation in KRAS-variant positive isogenic cell lines. Finally, KRAS-variant BC patients had greater than an 11-fold increased risk of presenting with MPBC compared to non-variant patients (45.39% vs 6.78%, OR 11.44 [3.42–37.87], P < 0.001). Thus, estrogen withdrawal and a low estrogen state appear to increase BC risk and to predict aggressive tumor biology in women with the KRAS-variant, who are also significantly more likely to present with multiple primary breast cancer. PMID:25961464

  6. Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages.

    Science.gov (United States)

    Liu, Yueying; Metzinger, Matthew N; Lewellen, Kyle A; Cripps, Stephanie N; Carey, Kyle D; Harper, Elizabeth I; Shi, Zonggao; Tarwater, Laura; Grisoli, Annie; Lee, Eric; Slusarz, Ania; Yang, Jing; Loughran, Elizabeth A; Conley, Kaitlyn; Johnson, Jeff J; Klymenko, Yuliya; Bruney, Lana; Liang, Zhong; Dovichi, Norman J; Cheatham, Bentley; Leevy, W Matthew; Stack, M Sharon

    2015-12-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intraperitoneal metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional mesomimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced intraperitoneal tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histologic analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently affects ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival.

  7. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

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    Hao Jiqing

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

  8. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Science.gov (United States)

    Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

    2009-01-01

    Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

  9. Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium

    DEFF Research Database (Denmark)

    Barrow, Hannah; Guo, Xiuli; Wandall, Hans H

    2011-01-01

    Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells...... to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion....

  10. Arterial Clamping Increases Central Renal Cryoablation Efficacy: An Animal Study

    DEFF Research Database (Denmark)

    Nonboe, Lasse Larsen; Nielsen, Tommy Kjaergaard; Høyer, Søren;

    2017-01-01

    INTRODUCTION: The minimally invasive treatment of small renal masses with cryoablation has become increasingly widespread during the past 15 years. Studies with long-term follow-up are beginning to emerge, showing good oncological control, however, tumors with a central and endophytic location seem...... to possess an increased risk of treatment failure. Such tumors are likely to be subjected to a high volume of blood giving thermal protection to the cancerous cells. Arterial clamping during freezing might reduce this effect but at the same time subject the kidney to ischemia. The aim of this study...... was to evaluate the effect of renal artery clamping during cryoablation in a porcine survival model. METHODS: Ten Danish Landrace pigs (approximately 40 kg) underwent bilateral laparoscopic cryoablation with clamping of the right renal artery during freezing. The cryoablation consisted of a standard double...

  11. The Role of Oral Contraceptive Pills on Increased Risk of Breast Cancer in Iranian Populations: A Meta-analysis

    Science.gov (United States)

    Soroush, Ali; Farshchian, Negin; Komasi, Saeid; Izadi, Neda; Amirifard, Nasrin; Shahmohammadi, Afshar

    2016-01-01

    Background Cancer is one of the main public health issues in the world. Breast cancer is one of the most common types of cancer among women. It is also the second cause of mortality in women. The association between the use of oral contraceptive pills and breast cancer is controversial and a main issue in public health. Some findings have shown that taking these pills does not have a significant effect in increasing the risk of breast cancer, while others have confirmed the carcinogenic effect of these products. These contradictory findings necessitated this meta-analysis, through of all correlated studies in Iran. Methods All published studies were considered from June 2000 until June 2015, using reliable Latin databases like PubMed, Google Scholar, Google search, Scopus, and Science Direct, and Persian database like SID, Irandoc, IranMedex, and Magiran. Finally, 26 papers were selected: 24 studies were case control while two were population based studies. A total of 26 papers with 46,260 participants were assessed since 2001. Results Overall estimate of OR for the effect of oral contraceptive pills on breast cancer is 1.521 (CI = 1.25–1.85), which shows that the intervention group had more chance (52%) compared to the control group (P = 0.001). Using these pills increased the risk of breast cancer up to 1.52 times. Conclusions Because of directly increasing levels of estrogen and the role of estrogen in gaining weight indirectly, oral contraceptive pills can stimulate the occurrence of breast cancer. More studies should be conducted for controlling the period of pill use. PMID:28053965

  12. Increased levels of circulating and tumor-infiltrating granulocytic myeloid cells in colorectal cancer patients

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    Salman M Toor

    2016-12-01

    Full Text Available Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs, have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation with clinical settings. The aim of this study was to investigate levels and phenotype of myeloid cells in peripheral blood and tumor microenvironment of colorectal cancer (CRC patients, compared to blood from healthy donors (HDs and paired, adjacent non-tumor colon tissue. Flow cytometric analysis was performed to examine the expression of different myeloid markers in fresh peripheral blood samples from CRC patients and HDs, and tissue-infiltrating immune cells from CRC patients. We found significantly higher levels of cells expressing myeloid markers and lacking the expression of MHC class II molecule HLA-DR in blood and tumor of CRC patients. Further analysis revealed that these cells were granulocytic and expressed Arginase 1 (ARG1, indicative of their suppressive phenotype. These expanded cells could be neutrophils or granulocytic MDSCs, and we refer to them as granulocytic myeloid cells (GMCs due to the phenotypical and functional overlap between these cell subsets. Interestingly, the expansion of peripheral GMCs correlated with higher stage and histological grade of cancer, thereby suggesting their role in cancer progression. Furthermore, an increase in CD33+CD11b+HLA-DR-CD14-CD15- immature myeloid cells (IMCs was also observed in CRC tumor tissue. Our work shows that GMCs are expanded in circulation and tumor microenvironment of CRC patients, which provides further insights for developing immunotherapeutic approaches targeting these cell subsets to enhance anti-tumor immune and clinical responses.

  13. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

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    Yu, Wei [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Guifang [Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Cai, Xiaojun [Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Yang, Jing, E-mail: yangjingliu@yahoo.com.cn [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-10-01

    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  14. Anastomotic Leak Increases Distant Recurrence and Long-Term Mortality After Curative Resection for Colonic Cancer

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Nordholm-Carstensen, Andreas; Jorgensen, Lars N

    2014-01-01

    OBJECTIVE: To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer. BACKGROUND: There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease recurr...

  15. Diabetes promotes DMH-induced colorectal cancer by increasing the activity of glycolytic enzymes in rats.

    Science.gov (United States)

    Jia, Yanglei; Xu, Gang; Zhou, Wenjing; Wang, Zhenzheng; Meng, Linlin; Zhou, Songnan; Xu, Xia; Yuan, Huiqing; Tian, Keli

    2014-01-01

    The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.

  16. Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer.

    Science.gov (United States)

    Qu, Yiqing; Yang, Yie; Ma, Dedong; Xiao, Wei

    2012-04-01

    Lung cancer is the most common cause of cancer-related deaths in the world. The trefoil factor (TFF) family is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3. TFF protein levels have been found to be related to the development of various types of cancer. However, it is still unclear whether TFF proteins are differentially expressed in the serum of different histological subtypes of lung cancer compared to healthy individuals. In this study, we investigated the levels of TFF proteins in serum and lung tissues of 130 lung cancer patients (58 squamous cell lung carcinoma cases, 43 adenocarcinoma cases and 29 SCLC cases) and 60 healthy individuals. It was found that TFF1 and TFF2 have similar or slightly higher levels in these three subtypes of lung cancer compared to healthy individuals, while TFF3 levels were significantly higher in the examined lung cancer cases compared to healthy individuals. Immunoblot analyses of TFF1, TFF2 and TFF3 indicated that lung cancer tissues and lung cancer cell lines have a higher expression of the TFF3 protein, but not of TFF1 or TFF2 proteins, compared to tissues from healthy individuals or from the normal cell line. Quantitative RT-PCR analysis indicated higher levels of TFF3, but not TFF1 and TFF2, transcripts in lung cancer tissues or cell lines. These results show increased TFF3 levels in serum and lung tissues, suggesting that TFF3 may serve as a promising, easily detected biomarker of lung cancer.

  17. Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer

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    Weiqian Chen

    2016-12-01

    Full Text Available Mechanistic/mammalian target of rapamycin (mTOR has emerged as a new potential therapeutic target for gastric cancer. Rapamycin and rapamycin analogs are undergoing clinical trials and have produced clinical responses in a subgroup of cancer patients. However, monotherapy with rapamycin at safe dosage fails to induce cell apoptosis and tumor regression which has hampered its clinical application. This has led to the exploration of more effective combinatorial regimens to enhance the effectiveness of rapamycin. In our present study, we have investigated the combination of rapamycin and a reactive oxygen species (ROS inducer EF24 in gastric cancer. We show that rapamycin increases intracellular ROS levels and displays selective synergistic antitumor activity with EF24 in gastric cancer cells. This activity was mediated through the activation of c-Jun N terminal kinase and endoplasmic reticulum stress (ER pathways in cancer cells. We also show that inhibiting ROS accumulation reverses ER stress and prevents apoptosis induced by the combination of rapamycin and EF24. These mechanisms were confirmed using human gastric cancer xenografts in immunodeficient mice. Taken together, our work provides a novel therapeutic strategy for the treatment of gastric cancer. The work reveals that ROS generation could be an important target for the development of new combination therapies for cancer treatment.

  18. Cancer Mortality in People Treated with Antidepressants before Cancer Diagnosis: A Population Based Cohort Study.

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    Yuelian Sun

    Full Text Available Depression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis.We conducted a population based cohort study of all adults diagnosed with cancer between January 2003 and December 2010 in Denmark (N = 201,662. We obtained information on cancer from the Danish Cancer Registry, on the day of death from the Danish Civil Registry, and on redeemed antidepressants from the Danish National Prescription Registry. Current users of antidepressants were defined as those who redeemed the latest prescription of antidepressant 0-4 months before cancer diagnosis (irrespective of earlier prescriptions, and former users as those who redeemed the latest prescription five or more months before cancer diagnosis. We estimated an all-cause one-year mortality rate ratio (MRR and a conditional five-year MRR for patients who survived the first year after cancer diagnosis and confidence interval (CI using a Cox proportional hazards regression model. Overall, 33,111 (16.4% patients redeemed at least one antidepressant prescription in the three years before cancer diagnosis of whom 21,851 (10.8% were current users at the time of cancer diagnosis. Current antidepressant users had a 32% higher one-year mortality (MRR = 1.32, 95% CI: 1.29-1.35 and a 22% higher conditional five-year mortality (MRR = 1.22, 95% CI: 1.17-1.26 if patients survived the first year after the cancer diagnosis than patients not redeeming antidepressants. The one-year mortality was particularly high for patients who initiated antidepressant treatment within four months before cancer diagnosis (MRR = 1.54, 95% CI: 1.47-1.61. Former users had no increased cancer mortality.Initiation of antidepressive treatment prior to cancer diagnosis is common and is associated with an increased

  19. Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.

    Science.gov (United States)

    Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng

    2016-07-01

    Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.

  20. Increasing Cervical Cancer Awareness and Screening in Jamaica: Effectiveness of a Theory-Based Educational Intervention

    Directory of Open Access Journals (Sweden)

    Evelyn Coronado Interis

    2015-12-01

    Full Text Available Despite declines in cervical cancer mortality in developed countries, cervical cancer incidence and mortality rates remain high in Jamaica due to low levels of screening. Effective interventions are needed to decrease barriers to preventive behaviors and increase adoption of behaviors and services to improve prospects of survival. We enrolled 225 women attending health facilities in an intervention consisting of a pre-test, educational presentation and post-test. The questionnaires assessed attitudes, knowledge, risk factors, and symptoms of cervical cancer among women. Changes in knowledge and intention to screen were assessed using paired t-tests and tests for correlated proportions. Participants were followed approximately six months post-intervention to determine cervical cancer screening rates. We found statistically significant increases from pre-test to post-test in the percentage of questions correctly answered and in participants’ intention to screen for cervical cancer. The greatest improvements were observed in responses to questions on knowledge, symptoms and prevention, with some items increasing up to 62% from pre-test to post-test. Of the 123 women reached for follow-up, 50 (40.7% screened for cervical cancer. This theory-based education intervention significantly increased knowledge of and intention to screen for cervical cancer, and may be replicated in similar settings to promote awareness and increase screening rates.

  1. Increased expression of cysteine cathepsins in ovarian tissue from chickens with ovarian cancer

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    Ahn Suzie E

    2010-08-01

    Full Text Available Abstract Background Cysteine cathepsins (CTSs are involved in the degradation and remodeling of the extracellular matrix and are associated with cell transformation, differentiation, motility, and adhesion. These functions are also related to cancer cell invasion and metastasis. Chickens spontaneously develop epithelial ovarian cancer and are therefore a good animal model for human ovarian cancer. However, no studies have investigated the expression of CTSs in chickens with ovarian cancer. Methods Cancerous (n = 5 and normal (n = 3 ovaries were collected from 2-to 3-year-old hens, and ovarian tissue samples were collected for study. Ovarian cancers were evaluated with hematoxylin and eosin staining. Reverse transcriptase and quantitative PCR analyses, in situ hybridization analysis were performed to examine the mRNA expression pattern of three CTSs in detail, and protein expression of CTSB was evaluated. Results The CTSB, CTSC, and CTSS genes were highly expressed in cancerous chicken ovaries. Messenger RNAs for the three CTSs were localized to a nodule area, a major characteristic of cancerous ovaries, but the three CTSs showed no specific localization in normal ovaries. Immunoreactive CTSB protein was present in the nodule area of cancerous ovaries. Conclusion Our results suggest that CTSB, CTSC, and CTSS have important functions in the development of epithelial ovarian cancer.

  2. The hamster cheek pouch model for field cancerization studies.

    Science.gov (United States)

    Monti-Hughes, Andrea; Aromando, Romina F; Pérez, Miguel A; Schwint, Amanda E; Itoiz, Maria E

    2015-02-01

    External carcinogens, such as tobacco and alcohol, induce molecular changes in large areas of oral mucosa, which increase the risk of malignant transformation. This condition, known as 'field cancerization', can be detected in biopsy specimens using histochemical techniques, even before histological alterations are identified. The efficacy of these histochemical techniques as biomarkers of early cancerization must be demonstrated in appropriate models. The hamster cheek pouch oral cancer model, universally employed in biological studies and in studies for the prevention and treatment of oral cancer, is also an excellent model of field cancerization. The carcinogen is applied in solution to the surface of the mucosa and induces alterations that recapitulate the stages of cancerization in human oral mucosa. We have demonstrated that the following can be used for the early detection of cancerized tissue: silver staining of nucleolar organizer regions; the Feulgen reaction to stain DNA followed by ploidy analysis; immunohistochemical analysis of fibroblast growth factor-2, immunohistochemical labeling of proliferating cells to demonstrate an increase of epithelial cell proliferation in the absence of inflammation; and changes in markers of angiogenesis (i.e. those indicating vascular endothelial growth factor activity, endothelial cell proliferation and vascular density). The hamster cheek pouch model of oral cancer was also proposed and validated by our group for boron neutron capture therapy studies for the treatment of oral cancer. Clinical trials of this novel treatment modality have been performed and are underway for certain tumor types and localizations. Having demonstrated the efficacy of boron neutron capture therapy to control tumors in the hamster cheek pouch oral cancer model, we adapted the model for the long-term study of field cancerized tissue. We demonstrated the inhibitory effect of boron neutron capture therapy on tumor development in field

  3. Detection of cancer clones in human gastric adenoma by increased DNA-instability and other biomarkers

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    A Sun

    2009-06-01

    Full Text Available An immunohistochemical differential staining of cancerous cells with anti-cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N HCl at 30°C for 20 min (DNA-instability test has been used as a marker of malignancy. The test was applied to bioptic tissues of human gastric polyp assessed histopathologically as foveolar hyperplastic polyp (13 cases, mild (58 cases, moderate (86 cases, and severe (20 cases dysplasia, and adenocarcinomas (14 cases. The serial sections of the same tissues were also subjected to immunohistochemical staining for Ki67, p53, DNA-fragmentation factor (DFF45, and basic fibroblast growth factor (bFGF. The DNA-instability test was positive in 14 (100% adenocarinoma cases, 20 (100% severe dysplasia cases, 52 (60.5% moderate dysplasia cases, and 12 (20.7% mild dysplasia cases, indicating malignancy. All foveolar hyperplastic polyps were negative to the DNA-instability testing. Furthermore, the percentage of glands positive in the DNA-instability test steadily increased in going from mild (10%, to moderate (40%, to severe (100% dysplasia, and adenocarcinoma (100%. All other biological markers tested in the present study showed significantly higher values in the adenoma glands, being positive to DNA-instability testing, irrespective of the dysplasia grade, as compared to those in the adenoma glands that were negative to DNA-instability testing. Furthermore, the former values were comparable to those in adenocarcinoma. These results indicate that cancer cell clones are already present at the adenoma stages showing a positive DNA-instability test, enhanced proliferative activity, p53 mutation, induction of DFF45 and bFGF. These factors allow cancer cell proliferation, producing heterogeneous subclones due to DNA-instability, enhancing their survival by escaping apoptosis, and providing abundant nutrients during the early-stage progression of gastric cancer. Based on these findings, we herein propose the

  4. Metabolic Syndrome Is Associated with Increased Breast Cancer Risk: A Systematic Review with Meta-Analysis

    OpenAIRE

    Ruchi Bhandari; Kelley, George A; Hartley, Tara A.; Rockett, Ian R. H.

    2014-01-01

    Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQu...

  5. Lower Salinomycin Concentration Increases Apoptotic Detachment in High-Density Cancer Cells

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    Sungpil Yoon

    2012-10-01

    Full Text Available The present study identified a novel salinomycin (Sal sensitization mechanism in cancer. We tested whether Sal reduced proliferation in a high-density population by counting attached cell numbers after Sal treatment. Sal reduced proliferation in high-density cell populations. Longer exposure to Sal further reduced proliferation. Sal concentrations of 0.1 and 5 μM had similar sensitization effects, suggesting that Sal toxicity was minimal with longer exposure to a high-density cell population. The results suggest that Sal can be applied at a relatively low concentration for a longer time to overcome drug-resistant solid tumors. The 0.5 μM Sal treatment resulted in fewer attached cells than that of the 5 μM Sal treatment with a longer exposure. The lower Sal concentration mainly increased the number of easily detachable cells on the surface. In particular, 0.5 μM Sal increased cellular detachment of newly produced daughter cells. The easily-detachable cells were undergoing apoptosis. It seems that the 0.5 μM Sal treatment also increased cellular toxicity. These novel findings may contribute to the development of Sal-based therapy for patients with drug-resistant cancer or a high-density solid tumor.

  6. Disruption of circadian rhythm increases the risk of cancer, metabolic syndrome and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Vignesh Shanmugam

    2013-03-01

    Full Text Available Incidents of non-communicable diseases (NCD like cardiovascular diseases, cancer, diabetes, and chronic respiratory disease have increased dramatically and are currently the leading causes of death worldwide. Their rising incidents coincide with the dramatic changes in industrialization and development of societies over the past few hundred years. Therefore, current lifestyle practices should be further explored to uncover novel risk factors for certain cancers (i.e. colon, prostate, and breast cancer, metabolic syndrome (i.e. diabetes and obesity, and cardiovascular disease (i.e. coronary artery disease. This review discusses how a disruption of the “biological clock” or circadian rhythms could be involved in the development of these diseases as circadian rhythms control multiple physiological processes such as wake/sleep cycles, hormonal levels, body temperature, metabolism, and immune system.Several environmental factors that disrupt circadian rhythms can be identified including exposure to artificial light and electromagnetic (EM waves, unbalanced diet and night shift work. The mechanisms of how these “chronodisruptors” are associated with NCDs will be discussed. Furthermore, the involvement of genetic factors in the disturbance of circadian rhythms and predisposition to NCDs will be highlighted.Overall there is strong evidence from animal models and epidemiological studies underlining that circadian disruption is a significant player in several diseases particularly the multifactorial diseases that pose a significant public health challenge in contemporary society. A circadian disruption-based model of cancer, metabolic syndrome and cardiovascular disease etiology can be proposed. But, to fully understand the complex interactions of the different components in the network of disease development due to disruption of circadian rhythms, more investigations are needed to unravel the causal relationship between modern lifestyle

  7. Lung cancer in pregnancy: Report of nine cases from an international collaborative study

    NARCIS (Netherlands)

    Boussios, S.; Han, S.N.; Fruscio, R.; Halaska, M.J.; Ottevanger, P.B.; Peccatori, F.A.; Koubkova, L.; Pavlidis, N.; Amant, F.

    2013-01-01

    OBJECTIVE: Lung cancer is an uncommon diagnosis during pregnancy. The combination of smoking in young women, increased maternal age during pregnancy, and increasing incidence of lung cancer worldwide may cause an increase of pregnancy associated lung cancer. The aim of this study was to describe all

  8. Epidemiologic studies of particulate matter and lung cancer

    Institute of Scientific and Technical Information of China (English)

    Yin-Ge Li; Xiang Gao

    2014-01-01

    Particulate matter (PM) plays an important role in air pollution, especially in China. European and American researchers conducted several cohort-based studies to examine the potential relationship between PM and lung cancer and found a positive association between PM and lung cancer mortality. In contrast, the results regarding PM and lung cancer risk remain inconsistent. Most of the previous studies had limitations such as misclassification of PM exposure and residual confounders, diminishing the impact of their findings. In addition, prospective studies on this topic are very limited in Chinese populations. This is an important problem because China has one of the highest concentrations of PM in the world and has had an increased mortality risk due to lung cancer. In this context, more prospective studies in Chinese populations are warranted to investigate the relationship between PM and lung cancer.

  9. Increased risk of intestinal cancer in Crohn's disease

    DEFF Research Database (Denmark)

    Jess, Tine; Gamborg, Michael; Matzen, Peter

    2005-01-01

    OBJECTIVES: The risk of intestinal malignancy in Crohn's disease (CD) remains uncertain since risk estimates vary worldwide. The global CD population is growing and there is a demand for better knowledge of prognosis of this disease. Hence, the aim of the present study was to conduct a meta...

  10. ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling.

    Science.gov (United States)

    Masuda, Tetsuro; Endo, Motoyoshi; Yamamoto, Yutaka; Odagiri, Haruki; Kadomatsu, Tsuyoshi; Nakamura, Takayuki; Tanoue, Hironori; Ito, Hitoshi; Yugami, Masaki; Miyata, Keishi; Morinaga, Jun; Horiguchi, Haruki; Motokawa, Ikuyo; Terada, Kazutoyo; Morioka, Masaki Suimye; Manabe, Ichiro; Iwase, Hirotaka; Mizuta, Hiroshi; Oike, Yuichi

    2015-03-16

    Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer.

  11. Increased risk of fatal prostate cancer may explain the rise in mortality in The Netherlands

    NARCIS (Netherlands)

    P.N. Post (Piet); H. Straatman (Huub); L.A.L.M. Kiemeney (Bart); J.W.W. Coebergh (Jan Willem)

    1999-01-01

    textabstractBACKGROUND: Several lines of evidence suggest that, as a result of improved diagnostic techniques, the increase in incidence of prostate cancer is due largely to increased detection of subclinical cases. Between 1971 and 1989, a considerable increase in inci

  12. The depletion of interleukin-8 causes cell cycle arrest and increases the efficacy of docetaxel in breast cancer cells.

    Science.gov (United States)

    Shao, Nan; Chen, Liu-Hua; Ye, Run-Yi; Lin, Ying; Wang, Shen-Ming

    2013-02-15

    IL-8 is a multi-functional pro-inflammatory chemokine, which is highly expressed in cancers, such as ER-negative breast cancer. The present study demonstrates the pervasive role of IL-8 in the malignant progression of ER-negative breast cancer. IL-8 siRNA inhibited proliferation and delayed the G1 to S cell cycle progression in MDA-MB-231 and BT549 cells. IL-8 silencing resulted in the upregulation of the CDK inhibitor p27, the downregulation of cyclin D1, and the reduction of phosphorylated-Akt and NF-κB activities. IL-8 depletion also increased the chemosensitivity to docetaxel. These results indicate a role for IL-8 in promoting tumor cell survival and resistance to docetaxel and highlight the potential therapeutic significance of IL-8 depletion in ER-negative breast cancer patients.

  13. Low Recent Protein Intake Predicts Cancer-Related Fatigue and Increased Mortality in Patients with Advanced Tumor Disease Undergoing Chemotherapy.

    Science.gov (United States)

    Stobäus, Nicole; Müller, Manfred J; Küpferling, Susanne; Schulzke, Jörg-Dieter; Norman, Kristina

    2015-01-01

    Cancer patients, in general, suffer from anorexia hence diminished nutritional intake. In a prospective observational study, we investigated the impact of recent energy and protein intake on cancer-related fatigue and 6-month mortality in patients undergoing chemotherapy. Recent protein and energy intake was assessed by 24-h recall in 285 patients. Cancer-related fatigue was determined by Brief Fatigue Inventory, and fat free mass index (FFMI) was assessed with bioelectrical impedance analysis. Symptoms with the validated German version of European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (30 questions) and 6-month mortality was documented. Risk factors of cancer-related fatigue and predictors of mortality were investigated with logistic regression analysis and stepwise Cox regression analysis, respectively. Low protein intake (protein intake emerged as the strongest contributor to cancer-related fatigue followed by nausea/vomiting, insomnia, and age. Reduced protein intake, male sex, number of comorbidities, and FFMI were identified as significant predictors for increased 6-month mortality. In conclusion, a low recent protein intake assessed by 24-h recall is associated with a more than twofold higher risk of cancer-related fatigue and 6-month mortality. Every effort should be taken to assess and guarantee proper nutritional intake in patients undergoing chemotherapy.

  14. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude;

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natur...

  15. Academic detailing to increase colorectal cancer screening by primary care practices in Appalachian Pennsylvania

    Directory of Open Access Journals (Sweden)

    Graybill Marie A

    2011-05-01

    Full Text Available Abstract Background In the United States, colorectal cancer (CRC is the third most frequently diagnosed cancer and second leading cause of cancer death. Screening is a primary method to prevent CRC, yet screening remains low in the U.S. and particularly in Appalachian Pennsylvania, a largely rural area with high rates of poverty, limited health care access, and increased CRC incidence and mortality rates. Receiving a physician recommendation for CRC screening is a primary predictor for patient adherence with screening guidelines. One strategy to disseminate practice-oriented interventions is academic detailing (AD, a method that transfers knowledge or methods to physicians, nurses or office staff through the visit(s of a trained educator. The objective of this study was to determine acceptability and feasibility of AD among primary care practices in rural Appalachian Pennsylvania to increase CRC screening. Methods A multi-site, practice-based, intervention study with pre- and 6-month post-intervention review of randomly selected medical records, pre- and post-intervention surveys, as well as a post-intervention key informant interview was conducted. The primary outcome was the proportion of patients current with CRC screening recommendations and having received a CRC screening within the past year. Four practices received three separate AD visits to review four different learning modules. Results We reviewed 323 records pre-intervention and 301 post-intervention. The prevalence of being current with screening recommendation was 56% in the pre-intervention, and 60% in the post-intervention (p = 0. 29, while the prevalence of having been screened in the past year increased from 17% to 35% (p Conclusions AD appears to be acceptable and feasible for primary care providers in rural Appalachia. A ceiling effect for CRC screening may have been a factor in no change in overall screening rates. While the study was not designed to test the efficacy of AD

  16. Tryptophan degradation in women with breast cancer: a pilot study

    Directory of Open Access Journals (Sweden)

    Schubert Christine M

    2011-05-01

    Full Text Available Abstract Background Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy. Findings Blood samples were collected from women with a recent diagnosis of breast cancer (n = 33 before their first cycle of chemotherapy and after their last cycle of chemotherapy. The comparison group (n = 24 provided a blood sample prior to breast biopsy. Plasma concentrations of tryptophan, kynurenine, and tyrosine were determined. The kynurenine to tryptophan ratio (KYN/TRP was used to estimate indoleamine 2,3-dioxygenase activity. On average, the women with breast cancer had lower levels of tryptophan, elevated levels of kynurenine and tyrosine and an increased KYN/TRP ratio compared to women without breast cancer. There was a statistically significant difference between the two groups in the KYN/TRP ratio (p = 0.036, which remained elevated in women with breast cancer throughout the treatment trajectory. Conclusions The findings of this pilot study suggest that increased tryptophan degradation may occur in women with early-stage breast cancer. Given the multifactorial consequences of increased tryptophan degradation in cancer outcomes and neuropsychiatric symptom manifestation, this biological mechanism deserves broader attention in women with breast cancer.

  17. Increased levels of interleukins 8 and 10 as findings of canine inflammatory mammary cancer.

    Science.gov (United States)

    de Andrés, Paloma Jimena; Illera, Juan Carlos; Cáceres, Sara; Díez, Lucía; Pérez-Alenza, Maria Dolores; Peña, Laura

    2013-04-15

    Inflammatory mammary cancer (IMC) is a distinct form of mammary cancer that affects dogs and women [in humans, IMC is known as inflammatory breast cancer (IBC)], and is characterized by a sudden onset and an aggressive clinical course. Spontaneous canine IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as the best spontaneous animal model for studying IBC, although several aspects remain unstudied. Interleukins (ILs) play an important role in cancer as potential modulators of angiogenesis, leukocyte infiltration and tumor growth. The aims of the present study were to assess serum and tumor levels of several ILs (IL-1α, IL-1β, IL-6, IL-8 and IL-10) by enzyme-immunoassay in dogs bearing benign and malignant mammary tumors, including dogs with IMC, for a better understanding of this disease. Forty-eight dogs were prospectively included. Animals consisted of 7 healthy Beagles used as donors for normal mammary glands (NMG) and serum controls (SCs), 10 dogs with hyperplasias and benign mammary tumors (HBMT), 24 with non-inflammatory malignant mammary tumors (non-IMC MMT) and 7 dogs with clinical and pathological IMC. IL-8 (serum) and IL-10 (serum and tissue homogenate) levels were higher in the dogs with IMC compared with the non-IMC MMT group. ILs were increased with tumor malignancy as follows: in tumor homogenates IL-6 levels were higher in malignant tumors (IMC and non-IMC MMT) versus HBMT and versus NMG and tumor IL-8 was increased in malignant tumors versus NMG; in serum, IL-1α and IL-8 levels were higher in the malignant groups respect to HBMT and SCs; interestingly, IL-10 was elevated only in the serum of IMC animals. To the best of our knowledge, this is the first report that analyzes ILs in IMC and IL-10 in canine mammary tumors. Our results indicate a role for IL-6, IL-8 and IL-10 in canine mammary malignancy and specific differences in ILs content in IMC versus non-IMC MMT that could

  18. Plasma levels of trefoil factors are increased in patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Vestergaard, E.M.; Borregaard, Michael Krabbe; Poulsen, Steen Seier;

    2006-01-01

    Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer....

  19. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Neft, R.E.; Lechner, J.F. [and others

    1995-12-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This {open_quotes}field cancerization{close_quotes} theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in {open_quotes}normal{close_quotes} bronchial epithelial cells.

  20. Pri-miR-34b/c rs4938723 TC heterozygote is associated with increased cancer risks: evidence from published data.

    Science.gov (United States)

    Yi, De-Hui; Wang, Ben-Gang; Zhong, Xin-Ping; Liu, Hao; Liu, Yong-Feng

    2014-12-01

    The promoter region of the microRNA pri-miR-34b/c has a potentially functional polymorphism, rs4938723, located in a typical CpG island. Studies of the association between pri-miR-34b/c rs4938723 polymorphism and risks of various cancers have had inconsistent results. We therefore conducted a meta-analysis of nine studies that included 6,036 cancer patients and 7,490 controls to address this association. Overall, this meta-analysis showed the pri-miR-34b/c rs4938723 TC heterozygote to be significantly associated with increased risk of overall cancers compared with the wild-type TT genotype (P = 0.010, odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02-1.18). In stratified analysis, the TC heterozygote was significantly associated with increased cancers risks in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. The CC genotypes of rs4938723 were also associated with increased hepatocellular cancer risk but associated with decreased colorectal cancer risk in the stratification analysis by a single cancer type. Thus our meta-analysis suggests that the pri-miR-34b/c rs4938723 TC heterozygote contributes to increased overall cancer risks, as well as shown in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. This rs4938723 SNP showed an opposite tendency orientation between the hepatocellular cancer and colorectal cancer risks. Large-sample studies are needed to verify our findings.

  1. Germline variation in NCF4, an innate immunity gene, is associated with an increased risk of colorectal cancer.

    Science.gov (United States)

    Ryan, Bríd M; Zanetti, Krista A; Robles, Ana I; Schetter, Aaron J; Goodman, Julie; Hayes, Richard B; Huang, Wen-Yi; Gunter, Mark J; Yeager, Meredith; Burdette, Laurie; Berndt, Sonja I; Harris, Curtis C

    2014-03-15

    Chronic inflammation has been implicated in the etiology of colorectal adenoma and cancer; however, few key inflammatory genes mediating this relationship have been identified. In this study, we investigated the association of germline variation in innate immunity genes in relation to the risk of colorectal neoplasia. Our study was based on the analysis of samples collected from the prostate, lung, colorectal and ovarian (PLCO) Cancer Screening Trial. We investigated the association between 196 tag single nucleotide polymorphisms (SNPs) in 20 key innate immunity genes with risk of advanced colorectal adenoma and cancer in 719 adenoma cases, 481 cancer cases and 719 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). After Bonferroni correction, the AG/GG genotype of rs5995355, which is upstream of NCF4, was associated with an increased risk of colorectal cancer (OR = 2.43, 95% CI = 1.73-3.39; p immune response. While not definitive, our analyses suggest that the variant allele does not affect expression of NCF4, but rather modulates activity of the NADPH complex. Additional studies on the functional consequences of rs5995355 in NCF4 may help to clarify the mechanistic link between inflammation and colorectal cancer.

  2. Zerumbone inhibits growth of hormone refractory prostate cancer cells by inhibiting JAK2/STAT3 pathway and increases paclitaxel sensitivity.

    Science.gov (United States)

    Jorvig, Jessica E; Chakraborty, Arup

    2015-02-01

    Zerumbone, a phytochemical isolated from Zingiber zerumbet has been shown previously to exhibit antineoplastic activity. But, the effect of zerumbone in prostate cancer has not been evaluated. Prostate cancer is frequently associated with elevated levels of interleukin-6 (IL-6), which exerts its oncogenic effects through activation of Janus kinase 2 (JAK2) followed by activation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Here, we investigated whether the anticancer effects of zerumbone are mediated through inhibition of the JAK2/STAT3 signaling pathway and whether zerumbone can increase the paclitaxel (PTX) sensitivity of prostate cancer cells. Zerumbone exerted significant cytotoxicity of DU145 versus PC3 prostate cancer cells through cell cycle arrest at G0/G1 phase followed by apoptosis. Zerumbone selectively inhibited JAK2 in both DU145 and PC3 cells. However, the biological axis of IL-6/JAK2/STAT3 was inhibited only in DU145 cells as no STAT3 phosphorylation was detected in PC3 cells even after IL-6 stimulation. Other signaling pathways in DU145 cells remained unaffected. The expression of prostate cancer-associated genes, including cyclin D1, IL-6, COX2, and ETV1, was blocked. Zerumbone also synergistically increased the sensitivity to PTX. Further preclinical study might reveal the potential use of zerumbone as a chemotherapeutic agent for hormone refractory prostate cancer where IL-6/JAK2/STAT3 signaling is aberrantly active and may be combined with PTX.

  3. 肝癌家族史与肝癌关系的20年前瞻性队列研究%Family history of liver cancer increases the risk of liver cancer incidence: a 20-year prospective cohort study in Qidong, China

    Institute of Scientific and Technical Information of China (English)

    孙燕; 屠红; 陆培新; 王金兵; 吴燕; 张启南; 钱耕荪; 陈陶阳

    2014-01-01

    Objective To evaluate whether first-degree family history of liver cancer plays a role in liver cancer incidence by prospective evaluation of a patient cohort in Qidong,China over a 20-year period.Methods In May 1992,708 hepatitis B surface antigen (HBsAg) carriers and 730 HBsAg-negadve controls from Qidong city were enrolled for participation in a prospective cohort study ending in November 2012.Follow-up was carried out every 6 to 12 months,and evaluations included serum assays to measure concentrations of alpha fetoprotein (AFP),HBsAg and alanine aminotransferase (ALT),as well as abdominal ultrasound to assess liver disease.The relationship between baseline (study entry) information of patients with first-degree family history of liver cancer and liver cancer incidence during the two decades of study was statistically assessed.Results There were 172 newly diagnosed liver cancer cases in the cohort during 25 753 person-years (py) of follow-up,representing an incidence of 667.88/100 000 py.The incidence rates of liver cancer among participants with or without liver cancer family history were 1 244.36/100 000 py and 509.70/100 000 py respectively,and the between-group difference reached the threshold for statistical significance (P < 0.01,Relative Risk (RR):2.44,95% Confidence Interval (CI):1.80-3.31).The incidence rates of liver cancer among participants who had a sibling with liver cancer and participants who had a parent with liver cancer were not significantly different (P > 0.05),but the liver cancer incidence among participants who had a mother with liver cancer was significantly higher than that of participants who had a father with liver cancer (P < 0.05,RR:1.86,95% CI:1.03-3.36).Among the participants with liver cancer family history,56.52% (39/69) were diagnosed before 50 years old,and this rate was significantly higher than that of participants without a family history of liver cancer (40.78%,42/103,P < 0.05).The incidence rate of liver

  4. Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells

    NARCIS (Netherlands)

    Chatterji, T.; Varkaris, A.S.; Parikh, N.U.; Song, J.H.; Cheng, C.J.; Schweppe, R.E.; Alexander, S.; Davis, J.W.; Troncoso, P.; Friedl, P.H.; Kuang, J.; Lin, S.H.; Gallick, G.E.

    2015-01-01

    To study the role of FAK signaling complexes in promoting metastatic properties of prostate cancer (PCa) cells, we selected stable, highly migratory variants, termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3 and DU145. These variants were not only increased migration

  5. Increasing roughness of the human breast cancer cell membrane through incorporation of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Lara-Cruz C

    2016-10-01

    Full Text Available C Lara-Cruz,1 JE Jiménez-Salazar,1 E Ramón-Gallegos,2 P Damian-Matsumura,1 N Batina3 1Department of Biology of Reproduction, Metropolitan Autonomous University, 2Department of Morphology, National School of Biological Sciences, National Polytechnic Institute, 3Department of Chemistry, Nanotechnology and Molecular Engineering Laboratory, Metropolitan Autonomous University, Mexico City, Mexico Abstract: Gold nanoparticles (AuNPs have been proposed for use in the treatment of different types of cancer, including breast cancer. At present, neither the mechanisms of AuNP interaction with the plasma membrane surface and their delivery and intracellular distribution in cancer cells nor their effect on the plasma membrane so as to allow cell incorporation of larger amounts of AuNPs is known. The objective of this work was to study the interaction of bare 20 nm diameter AuNPs with the plasma membrane of human MCF-7 breast cancer cells, as well as their uptake, intracellular distribution, and induction of changes on the cell surface roughness. The dynamics of intracellular incorporation and the distribution of AuNPs were observed by confocal laser scanning microscopy. Changes in roughness were monitored in synchronized MCF-7 cells by atomic force microscopy high-resolution imaging at 6 hour intervals for 24 hours during a single cell cycle. The results show that bare AuNPs are capable of emitting fluorescence at 626 nm, without the need for a fluorescent biomarker, which allows monitoring their uptake and intracellular distribution until they reach the nucleus. These results are correlated with changes in cell roughness, which significantly increases at 12 hours of incubation with AuNPs, when compared with control cells. The obtained data provide bases to understand molecular processes of the use of AuNPs in the treatment of different diseases, mainly breast cancer. Keywords: gold nanoparticles uptake, MCF-7 cells, membrane roughness, atomic force

  6. IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells.

    Science.gov (United States)

    Long, Jun; Zhang, Xulong; Wen, Mingjie; Kong, Qingli; Lv, Zhe; An, Yunqing; Wei, Xiao-Qing

    2013-01-01

    Interleukin (IL)-35 is a novel heterodimeric cytokine in the IL-12 family and is composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. IL-35 is expressed in T regulatory (Treg) cells and contributes to the immune suppression function of these cells. In contrast, we found that both IL-35 subunits were expressed concurrently in most human cancer cell lines compared to normal cell lines. In addition, we found that TNF-α and IFN-γ stimulation led to increased IL-35 expression in human cancer cells. Furthermore, over-expression of IL-35 in human cancer cells suppressed cell growth in vitro, induced cell cycle arrest at the G1 phase, and mediated robust apoptosis induced by serum starvation, TNF-α, and IFN-γ stimulation through the up-regulation of Fas and concurrent down-regulation of cyclinD1, survivin, and Bcl-2 expression. In conclusion, our results reveal a novel functional role for IL-35 in suppressing cancer activity, inhibiting cancer cell growth, and increasing the apoptosis sensitivity of human cancer cells through the regulation of genes related to the cell cycle and apoptosis. Thus, this research provides new insights into IL-35 function and presents a possible target for the development of novel cancer therapies.

  7. Loneliness May Sabotage Breast Cancer Survival: Study

    Science.gov (United States)

    ... gov/news/fullstory_162498.html Loneliness May Sabotage Breast Cancer Survival: Study Weak social ties linked to higher risk ... 2016 (HealthDay News) -- Loneliness may impede long-term breast cancer survival, a new study suggests. In the years after ...

  8. Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Riyasdeen, Anvarbatcha; Al-Shahrani, Mohammad Hamed; Islam, Mozaffarul

    2016-01-01

    Snake venom possesses various kinds of proteins and neurotoxic polypeptides, which can negatively interfere with the neurotransmitter signaling cascade. This phenomenon occurs mainly due to the blocking of ion channels in the body system. Envenomation prevents or severely interrupts nerve impulses from being transmitted, inhibition of adenosine triphosphate synthesis, and proper functioning of the cardiac muscles. However, some beneficial properties of venoms have also been reported. The aim of this study was to examine the snake venom as an anticancer agent due to its inhibitory effects on cancer progression such as cell motility, cell invasion, and colony formation. In this study, the effect of venoms on phenotypic changes and the change on molecular level in colorectal and breast cancer cell lines were examined. A reduction of 60%–90% in cell motility, colony formation, and cell invasion was observed when these cell lines were treated with different concentrations of snake venom. In addition, the increase in oxidative stress that results in an increase in the number of apoptotic cancer cells was significantly higher in the venom-treated cell lines. Further analysis showed that there was a decrease in the expression of pro-inflammatory cytokines and signaling proteins, strongly suggesting a promising role for snake venom against breast and colorectal cancer cell progression. In conclusion, the snake venoms used in this study showed significant anticancer properties against colorectal and breast cancer cell lines. PMID:27799796

  9. Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels.

    Science.gov (United States)

    Yang, Xinhui; Jiang, Jiangtao; Yang, Xinyan; Han, Jichun; Zheng, Qiusheng

    2016-07-01

    Licochalcone A (LCA) has been reported to significantly inhibit cell proliferation, increase reactive oxygen species (ROS) levels, and induce apoptosis of T24 human bladder cancer cells via mitochondria and endoplasmic reticulum (ER) stress-triggered signaling pathways. Based on these findings, the present study aimed to investigate the mechanisms by which LCA induces apoptosis of T24 cells. Cultured T24 cells were treated with LCA, and cell viability was measured using the sulforhodamine B assay. Apoptosis was detected by flow cytometry with Annexin V/propidium iodide staining, and by fluorescent microscopy with Hoechst 33258 staining. The levels of intracellular free calcium ions were determined using Fluo-3 AM dye marker. Intracellular ROS levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate probe assay. The mitochondrial membrane potential was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazole carbocyanine iodide. Furthermore, the mRNA expression levels of B‑cell lymphoma (Bcl)‑extra large, Bcl‑2‑associated X protein, Bcl‑2‑interacting mediator of cell death, apoptotic protease activating factor‑1 (Apaf‑1), calpain 2, cysteinyl aspartate specific proteinase (caspase)‑3, caspase‑4 and caspase‑9 were determined using reverse transcription semiquantitative and quantitative polymerase chain reaction analyses. Treatment with LCA inhibited proliferation and induced apoptosis of T24 cells, and increased intracellular Ca2+ levels and ROS production. Furthermore, LCA induced mitochondrial dysfunction, decreased mitochondrial membrane potential, and increased the mRNA expression levels of Apaf‑1, caspase‑9 and caspase‑3. Exposure of T24 cells to LCA also triggered calpain 2 and caspase‑4 activation, resulting in apoptosis. These findings indicated that LCA increased intracellular Ca2+ levels, which may be associated with mitochondrial dysfunction. In addition, the ER stress pathway may be

  10. Obesity and cancer: mechanistic insights from transdisciplinary studies.

    Science.gov (United States)

    Allott, Emma H; Hursting, Stephen D

    2015-12-01

    Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe data from observational studies of weight change in humans and from calorie-restriction studies in mouse models that support a potential role for weight loss in counteracting tumor-promoting properties of obesity in breast and prostate cancers. Given that weight loss is challenging to achieve and maintain, we also consider evidence linking treatments for obesity-associated co-morbidities, including metformin, statins and non-steroidal anti-inflammatory drugs, with reduced breast and prostate cancer incidence and mortality. Finally, we highlight several challenges that should be considered when conducting epidemiologic and preclinical research in the area of obesity and cancer, including the measurement of obesity in population-based studies, the timing of obesity and weight change in relation to tumor latency and cancer diagnosis, and the heterogeneous nature of obesity and its associated co-morbidities. Given that obesity is a complex trait, comprised of behavioral, epidemiologic and molecular/metabolic factors, we argue that a transdisciplinary approach is the key to understanding the mechanisms linking obesity and cancer. As such, this review highlights the critical need to integrate evidence from both epidemiologic and preclinical studies to gain insight into both biologic and non-biologic mechanisms contributing to the obesity-cancer link.

  11. Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Al-Asmari AK

    2016-10-01

    Full Text Available Abdulrahman Khazim Al-Asmari,1 Anvarbatcha Riyasdeen,1 Mohammad Hamed Al-Shahrani,2 Mozaffarul Islam1 1Research Center, 2Pediatric Hematology/Oncology and Bone Marrow Transplant Unit, Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia Abstract: Snake venom possesses various kinds of proteins and neurotoxic polypeptides, which can negatively interfere with the neurotransmitter signaling cascade. This phenomenon occurs mainly due to the blocking of ion channels in the body system. Envenomation prevents or severely interrupts nerve impulses from being transmitted, inhibition of adenosine triphosphate synthesis, and proper functioning of the cardiac muscles. However, some beneficial properties of venoms have also been reported. The aim of this study was to examine the snake venom as an anticancer agent due to its inhibitory effects on cancer progression such as cell motility, cell invasion, and colony formation. In this study, the effect of venoms on phenotypic changes and the change on molecular level in colorectal and breast cancer cell lines were examined. A reduction of 60%–90% in cell motility, colony formation, and cell invasion was observed when these cell lines were treated with different concentrations of snake venom. In addition, the increase in oxidative stress that results in an increase in the number of apoptotic cancer cells was significantly higher in the venom-treated cell lines. Further analysis showed that there was a decrease in the expression of pro-inflammatory cytokines and signaling proteins, strongly suggesting a promising role for snake venom against breast and colorectal cancer cell progression. In conclusion, the snake venoms used in this study showed significant anticancer properties against colorectal and breast cancer cell lines. Keywords: colorectal cancer, breast cancer, cell motility, colony formation, oxidative stress, apoptosis, IL-8, IL-6, RhoC, p-Erk1/2

  12. Plasma levels of trefoil factors are increased in patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Vestergaard, Else Marie; Borre, Michael; Poulsen, Steen Seier;

    2006-01-01

    . EXPERIMENTAL DESIGN: In 79 patients with prostate cancer, 23 patients with benign prostatic hyperplasia, and 44 healthy individuals plasma TFF1, TFF2, and TFF3 were determined with ELISAs and compared with clinical stage and prostate-specific antigen (PSA) values. Plasma levels of TFF were compared......PURPOSE: Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer...... with the immunohistochemical expression of TFF and chromogranin A in 30 prostate cancer tissue samples. RESULTS: Patients with advanced prostate cancer had significantly higher plasma concentrations of TFF1, TFF2, and TFF3 (P

  13. Pregnancy after treatment of breast cancer--a population-based study on behalf of Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Kroman, N.; Jensen, M.B.; Wohlfahrt, J.;

    2008-01-01

    at diagnosis, tumour size, nodal status, or pregnancy history before diagnosis of breast cancer. Neither spontaneous abortions nor induced abortions subsequent to breast cancer treatment had a negative impact on prognosis. CONCLUSION: In line with our previous study, but based on more than twice the patient...... material, we found no evidence that a pregnancy after treatment of breast cancer has a negative influence the prognosis Udgivelsesdato: 2008......BACKGROUND: Estrogen is an established growth factor in breast cancer and it has been hypothesized that pregnancy associated estrogens may increase the risk of recurrence of breast cancer. In 1997 we published a population-based Danish study indicating no negative prognostic effect of pregnancy...

  14. Utilization of Increased Airlift Capability (UIAC) Study.

    Science.gov (United States)

    1984-09-01

    equipment and supplies, 129 STON; communications equipment and sup- plies, 120 STON; and personnel services, 102 STON. The major significant observation for...Study has the further advantage to the Army of providing an undeniable, C. fully substantiated methology for cargo selection that will stand the test of

  15. Lifetime Increased Cancer Risk in Mice Following Exposure to Clinical Proton Beam–Generated Neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Gerweck, Leo E., E-mail: lgerweck@mgh.harvard.edu; Huang, Peigen; Lu, Hsiao-Ming; Paganetti, Harald; Zhou, Yenong

    2014-05-01

    Purpose: To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam. Methods and Materials: Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice. Results: Exposure of mice to a dose of 600 Gy of proton beam–generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10. Conclusions: Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.

  16. Increased Levels of NF-kB-Dependent Markers in Cancer-Associated Deep Venous Thrombosis.

    Directory of Open Access Journals (Sweden)

    Grazia Malaponte

    Full Text Available Several studies highlight the role of inflammatory markers in thrombosis as well as in cancer. However, their combined role in cancer-associated deep vein thrombosis (DVT and the molecular mechanisms, involved in its pathophysiology, needs further investigations. In the present study, C-reactive protein, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, interleukin-1 (IL-1β, matrix metalloproteases-9 (MMP-9, vascular endothelial growth factor (VEGF, tissue factor (TF, fibrinogen and soluble P-selectin, were analyzed in plasma and in monocyte samples from 385 cancer patients, of whom 64 were concomitantly affected by DVT (+. All these markers were higher in cancer patients DVT+ than in those DVT-. Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-. Significant correlation between data obtained in plasma and monocyte samples was observed. NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-. To further demonstrate the involvement of NF-kB activation by the above mentioned molecules, we treated monocyte derived from healthy donors with a pool of sera from cancer patients with and without DVT. These set of experiments further suggest the significant role played by some molecules, regulated by NF-kB, and detected in cancer patients with DVT. Our data support the notion that NF-kB may be considered as a therapeutic target for cancer patients, especially those complicated by DVT. Treatment with NF-kB inhibitors may represent a possible strategy to prevent or reduce the risk of DVT in cancer patients.

  17. Risk for Hospitalization With Depression After a Cancer Diagnosis: A Nationwide, Population-Based Study of Cancer Patients in Denmark From 1973 to 2003

    DEFF Research Database (Denmark)

    Dalton, S.O.; Laursen, T.M.; Nylandsted, Lone Ross

    2009-01-01

    ) for depression among cancer survivors relative to the cancer-free population was estimated by Poisson regression analysis with adjustment for age and period and stratified by sex, site of cancer, and extent of disease. Results The risk for depression in the first year after a cancer diagnosis was increased......Purpose As more people survive cancer, it is necessary to understand the long-term impact of cancer. We investigated whether cancer survivors are at increased risk for hospitalization for depression. Methods We linked data on all 5,703,754 persons living in Denmark on January 1, 1973, or born...... for both men and women surviving hormone-related cancers, for women surviving smoking-related cancers, and for men surviving virus- and immune-related cancers. Conclusion This study confirms an increased risk for depression in patients facing a disruptive event like cancer. Early recognition and effective...

  18. Growth suppression and radiosensitivity increase by HMGB1 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Hai-chao WANG; Sai-jun FAN

    2007-01-01

    Aim: HMGB 1 (high-mobility group box-1) is a nuclear protein containing a con- sensus RB (retinoblastoma)-binding LXCXE motif. In this study, we studied the potential association of HMGB 1 and RB and the in vitro and in vivo activities of HMGB 1 in human breast cancer cells. Methods: The protein-protein interaction was determined by immunoprecipitation-Western blotting and glutathione-S-trans- ferase capture assays; cell growth and radiosensitivity were examined by cell counts, MTT assay, and clonogenic assay; cell cycle progression and apoptosis were evaluated using flow cytometry; and the antitumor activity of HMGB 1 was examined with tumor xenografts in nude mice. Results: HMGB 1 was associated with RB via a LXCXE motif-dependent mechanism. HMGB 1 enhanced the ability of RB for E2F and cyclin A transcription repression. The increased expression of HMGB 1 conferred an altered phenotypes characterized by the suppression of cell growth; G12 arrest and apoptosis was induced in MCF-7 cells containing the wild- type retinoblastoma (Rb) gene, but showed no activities in BT-549 cells contain- ing the Rb gene deletion. The HMGB 1-induced apoptosis accompanied by caspase 3 activation and PARP (poly(ADP-ribose)polymerase) cleavage. HMGB 1 elevated the radiosensitivity of breast cancer cells in both the MCF-7 and BT-549 cell lines. The enhanced expression of HMGB 1 caused a suppression of growth of MCF-7 tumor xenografts in nude mice, while LXCXE-defective HMGB 1 completely lost antitumor growth activity. Conclusion: HMGB 1 functions as a tumor suppressor and radiosensitizer in breast cancer. A HMGB 1-RB interaction is critical for the HMGB1-mediated transcriptional repression, cell growth inhibition, G12 cell cycle arrest, apoptosis induction, and tumor growth suppression, but is not required for radiosensitization. Therefore, it may be possible to design new therapies for the treatment of breast cancer that exert their effects by modulating the HMGB 1 and RB regulatory

  19. One Health and cancer: A comparative study of human and canine cancers in Nairobi

    Directory of Open Access Journals (Sweden)

    Nyariaro Kelvin Momanyi

    2016-11-01

    Full Text Available Aim: Recent trends in comparative animal and human research inform us that collaborative research plays a key role in deciphering and solving cancer challenges. Globally, cancer is a devastating diagnosis with an increasing burden in both humans and dogs and ranks as the number three killer among humans in Kenya. This study aimed to provide comparative information on cancers affecting humans and dogs in Nairobi, Kenya. Materials and Methods: Dog data collection was by cancer case finding from five veterinary clinics and two diagnostic laboratories, whereas the human dataset was from the Nairobi Cancer Registry covering the period 2002-2012. The analysis was achieved using IBM SPSS Statistics® v.20 (Dog data and CanReg5 (human data. The human population was estimated from the Kenya National Census, whereas the dog population was estimated from the human using a human:dog ratio of 4.1:1. Results: A total of 15,558 human and 367 dog cancer cases were identified. In humans, females had higher cancer cases 8993 (an age-standardized rate of 179.3 per 100,000 compared to 6565 in males (122.1 per 100,000. This order was reversed in dogs where males had higher cases 198 (14.9 per 100,000 compared to 169 (17.5 per 100,000 in females. The incident cancer cases increased over the 11-year study period in both species. Common cancers affecting both humans and dogs were: Prostate (30.4, 0.8, the respiratory tract (8.3, 1.3, lymphoma (5.6, 1.4, and liver and biliary tract (6.3, 0.5, whereas, in females, they were: Breast (44.5, 3.6, lip, oral cavity, and pharynx (8.8, 0.6, liver and biliary tract (6.5, 1.2, and lymphoma (6.0, 0.6, respectively, per 100,000. Conclusion: The commonality of some of the cancers in both humans and dogs fortifies that it may be possible to use dogs as models and sentinels in studying human cancers in Kenya and Africa. We further infer that developing joint animalhuman cancer registries and integrated cancer surveillance systems may

  20. Increased concentrations of growth factors and activation of the EGFR system in breast cancer

    DEFF Research Database (Denmark)

    Aalund Olsen, Dorte; Bechmann, Troels; Østergaard, Birthe;

    2012-01-01

    In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values.......In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values....

  1. Tbx3 fosters pancreatic cancer growth by increased angiogenesis and activin/nodal-dependent induction of stemness

    Directory of Open Access Journals (Sweden)

    Lukas Perkhofer

    2016-09-01

    Full Text Available Cell fate decisions and pluripotency, but also malignancy depend on networks of key transcriptional regulators. The T-box transcription factor TBX3 has been implicated in the regulation of embryonic stem cell self-renewal and cardiogenesis. We have recently discovered that forced TBX3 expression in embryonic stem cells promotes mesendoderm specification directly by activating key lineage specification factors and indirectly by enhancing paracrine NODAL signalling. Interestingly, aberrant TBX3 expression is associated with breast cancer and melanoma formation. In other cancers, loss of TBX3 expression is associated with a more aggressive phenotype e.g. in gastric and cervical cancer. The precise function of TBX3 in pancreatic ductal adenocarcinoma remains to be determined. In the current study we provide conclusive evidence for TBX3 overexpression in pancreatic cancer samples as compared to healthy tissue. While proliferation remains unaltered, forced TBX3 expression strongly increases migration and invasion, but also angiogenesis in vitro and in vivo. Finally, we describe the TBX3-dependency of cancer stem cells that perpetuate themselves through an autocrine TBX3–ACTIVIN/NODAL signalling loop to sustain stemness. Thus, TBX3 is a new key player among pluripotency-related genes driving cancer formation.

  2. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

    Science.gov (United States)

    Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

    2013-12-31

    While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

  3. Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells

    DEFF Research Database (Denmark)

    Dahl, Malin; Bouchelouche, Pierre; Kramer-Marek, Gabriela

    2011-01-01

    epithelial cells. The aim of this work was to investigate the effect of sarcosine on HER2/neu expression in prostate cancer cell lines LNCaP (androgen dependent), PC-3 and DU145 (both androgen independent). Relative amounts of HER2/neu and androgen receptor (AR) transcripts were determined using RT......Increasing evidence suggests that Human epidermal growth factor receptor 2 (HER2/neu) is involved in progression of prostate cancer. Recently, sarcosine was reported to be highly increased during prostate cancer progression, and exogenous sarcosine induces an invasive phenotype in benign prostate......-qPCR. Total expression of HER2/neu was confirmed by Western blot (WB). HER2/neu protein on the surface of living LNCaP cells was visualized by confocal microscopy using a HER2/neu-specific fluorescent probe. Exposure of LNCaP cells to 50 µM sarcosine for 24 h resulted in a 58% increase of the HER2/neu m...

  4. Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells

    DEFF Research Database (Denmark)

    Dahl, Malin; Bouchelouche, Pierre; Kramer-Marek, Gabriela

    2011-01-01

    epithelial cells. The aim of this work was to investigate the effect of sarcosine on HER2/neu expression in prostate cancer cell lines LNCaP (androgen dependent), PC-3 and DU145 (both androgen independent). Relative amounts of HER2/neu and androgen receptor (AR) transcripts were determined using RT......Increasing evidence suggests that Human epidermal growth factor receptor 2 (HER2/neu) is involved in progression of prostate cancer. Recently, sarcosine was reported to be highly increased during prostate cancer progression, and exogenous sarcosine induces an invasive phenotype in benign prostate......-qPCR. Total expression of HER2/neu was confirmed by Western blot (WB). HER2/neu protein on the surface of living LNCaP cells was visualized by confocal microscopy using a HER2/neu-specific fluorescent probe. Exposure of LNCaP cells to 50 μM sarcosine for 24 h resulted in a 58% increase of the HER2/neu m...

  5. Increased fracture rate in women with breast cancer: a review of the hidden risk

    Directory of Open Access Journals (Sweden)

    Body Jean-Jacques

    2011-08-01

    Full Text Available Abstract Background Women with breast cancer, particularly individuals diagnosed at a relatively early age, have an increased incidence of fractures. Fractures can have serious clinical consequences including the need for major surgery, increased morbidity and mortality, increased cost of disease management, and reduced quality of life for patients. The primary cause of the increased fracture risk appears to be an accelerated decrease in bone mineral density (BMD resulting from the loss of estrogenic signaling that occurs with most treatments for breast cancer, including aromatase inhibitors. However, factors other than BMD levels alone may influence treatment decisions to reduce fracture risk in this setting. Our purpose is to review current evidence for BMD loss and fracture risk during treatment for breast cancer and discuss pharmacologic means to reduce this risk. Results Fracture risk during treatment for breast cancer may be influenced by the rate of BMD loss and the consequent rapid alterations in bone microarchitecture, in addition to the established fracture risk factors in postmenopausal osteoporosis. The rapid decrease in BMD during adjuvant chemoendocrine therapy for breast cancer may necessitate more aggressive pharmacotherapy than is indicated for healthy postmenopausal women who develop osteoporosis. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and other antiresorptive agents to preserve BMD during adjuvant therapy for early breast cancer. In addition, some bisphosphonates (eg, zoledronic acid may also delay disease recurrence in women with hormone-responsive tumors, thereby providing an adjuvant benefit in addition to preserving BMD and potentially preventing fractures. Conclusions It is likely that a combined fracture risk assessment (eg, as in the WHO FRAX algorithm will more accurately identify both women with postmenopausal osteoporosis and women with breast cancer who require

  6. sFas levels increase in response to cisplatin-based chemotherapy in lung cancer patients.

    Science.gov (United States)

    Ulukaya, Engin; Acilan, Ceyda; Yilmaz, Meryem; Yilmaztepe-Oral, Arzu; Ari, Ferda; Zik, Berrin; Ursavas, Ahmet; Tokullugil, Asuman H

    2010-10-01

    The Fas/Fas Ligand (FasL) system and survivin have counteracting roles in cell survival. Therefore, we explored the role of circulating soluble Fas (sFas) and the tissue levels of Fas and survivin with regard to response to chemotherapy in lung cancer patients. Serum samples from 52 lung cancer patients and 54 control subjects (19 benign lung disease and 35 healthy control subjects) were collected prior to and 24 and 48 h after chemotherapy. sFas was statistically significantly higher in the cancer group than that in the control groups (p  0,05). In conclusion, increased sFas may be an indicator of poor outcome in lung cancer patients. However, cisplatin-based chemotherapy may not be effective via neither the Fas/FasL system nor survivin pathway. Indeed, larger sample size is required for further evaluation.

  7. Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

    Science.gov (United States)

    Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

    2012-01-01

    The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

  8. Increased Expression of Serglycin in Specific Carcinomas and Aggressive Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Angeliki Korpetinou

    2015-01-01

    Full Text Available In the present pilot study, we examined the presence of serglycin in lung, breast, prostate, and colon cancer and evaluated its expression in cell lines and tissues. We found that serglycin was expressed and constitutively secreted in culture medium in high levels in more aggressive cancer cells. It is worth noticing that aggressive cancer cells that harbor KRAS or EGFR mutations secreted serglycin constitutively in elevated levels. Furthermore, we detected the transcription of an alternative splice variant of serglycin lacking exon 2 in specific cell lines. In a limited number of tissue samples analyzed, serglycin was detected in normal epithelium but was also expressed in higher levels in advanced grade tumors as shown by immunohistochemistry. Serglycin staining was diffuse, granular, and mainly cytoplasmic. In some cancer cells serglycin also exhibited membrane and/or nuclear immunolocalization. Interestingly, the stromal cells of the reactive tumor stroma were positive for serglycin, suggesting an enhanced biosynthesis for this proteoglycan in activated tumor microenvironment. Our study investigated for first time the distribution of serglycin in normal epithelial and cancerous lesions in most common cancer types. The elevated levels of serglycin in aggressive cancer and stromal cells may suggest a key role for serglycin in disease progression.

  9. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    LENUS (Irish Health Repository)

    Cronin, Patricia A

    2010-05-21

    Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

  10. Histone deacetylase inhibition increases levels of choline kinase alpha and phosphocholine facilitating non-invasive imaging in human cancers

    OpenAIRE

    2011-01-01

    Histone deacetylase (HDAC) inhibitors are currently approved for cutaneous T-cell lymphoma and are in mid-late stage trials for other cancers. The HDAC inhibitors LAQ824 and SAHA increase phosphocholine (PC) levels in human colon cancer cells and tumor xenografts as observed by magnetic resonance spectroscopy (MRS). In this study, we show that belinostat, an HDAC inhibitor with an alternative chemical scaffold, also caused a rise in cellular PC content that was detectable by 1H and 31P MRS in...

  11. Screening and cervical cancer cure: population based cohort study

    OpenAIRE

    Andrae, B.; Andersson, T. M.-L.; Lambert, P C; Kemetli, L.; Silfverdal, L.; Strander, B.; Ryd, W.; Dillner, J.; Tornberg, S.; Sparen, P.

    2012-01-01

    Objective To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. Design Nationwide population based cohort study. Setting Sweden. Participants All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. Main outcome measures Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age...

  12. Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort.

    Science.gov (United States)

    Feigelson, Heather Spencer; Jonas, Carolyn R; Robertson, Andreas S; McCullough, Marjorie L; Thun, Michael J; Calle, Eugenia E

    2003-02-01

    Recent studies suggest that the increased risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake. We examined this question among 66,561 postmenopausal women in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. A total of 1,303 incident cases had accrued during the first 5 years of follow-up. Cox proportional hazards models and stratified analysis were used to examine the relationship between alcohol, dietary and total folate intake, multivitamin use, dietary methionine, and breast cancer. We observed an increasing risk of breast cancer with increasing alcohol consumption (P for trend = 0.01). In the highest category of consumption (15 or more grams of ethanol/day), the risk of breast cancer was 1.26 (95% confidence interval, 1.04-1.53) compared with nonusers. We observed this association with higher alcohol consumption for in situ, localized, and regional disease. We found no association between risk of breast cancer and dietary folate, total folate, multivitamin use, or methionine intake. Furthermore, we found no evidence of an interaction between levels of dietary folate (P for interaction = 0.10) or total folate (P for interaction = 0.61) and alcohol. Nor did we find evidence of an interaction between alcohol consumption and recent or long-term multivitamin use (P for interaction = 0.27). Our results are consistent with a positive association with alcohol but do not support an association with folate or methionine intake or an interaction between folate and alcohol intake on risk of breast cancer.

  13. Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, H; Jensenius, J C; Christensen, Ib Jarle

    2004-01-01

    BACKGROUND: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection...... with colorectal cancer compared with healthy persons. However, similar frequencies of MBL pathway deficiency are observed in patients and healthy persons....... in certain patient groups. It is hypothesized that a deficient MBL pathway might be more frequent among patients with CRC than in healthy individuals. The MBL pathway was therefore evaluated in serum obtained preoperatively from 193 patients with primary CRC and in serum from 150 healthy volunteers. METHODS...

  14. The depletion of Interleukin-8 causes cell cycle arrest and increases the efficacy of docetaxel in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Nan [Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, Liu-Hua [Department of Minimally Invasive Surgery Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Ye, Run-Yi [Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Lin, Ying, E-mail: frostlin@hotmail.com [Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Wang, Shen-Ming, E-mail: shenmingwang@hotmail.com [Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

    2013-02-15

    Highlights: ► IL-8 depletion affects cell cycle distribution. ► Intrinsic IL-8 mediates breast cancer cell migration and invasion. ► IL-8 siRNA down regulates key factors that control survival and metastatic pathway. ► IL-8 depletion reduces integrin β3 expression. ► IL-8 depletion increases the chemosensitivity to docetaxel. -- Abstract: IL-8 is a multi-functional pro-inflammatory chemokine, which is highly expressed in cancers, such as ER-negative breast cancer. The present study demonstrates the pervasive role of IL-8 in the malignant progression of ER-negative breast cancer. IL-8 siRNA inhibited proliferation and delayed the G1 to S cell cycle progression in MDA-MB-231 and BT549 cells. IL-8 silencing resulted in the upregulation of the CDK inhibitor p27, the downregulation of cyclin D1, and the reduction of phosphorylated-Akt and NF-κB activities. IL-8 depletion also increased the chemosensitivity to docetaxel. These results indicate a role for IL-8 in promoting tumor cell survival and resistance to docetaxel and highlight the potential therapeutic significance of IL-8 depletion in ER-negative breast cancer patients.

  15. Increased risk of severe depression in male partners of women with breast cancer

    DEFF Research Database (Denmark)

    Nakaya, Naoki; Saito-Nakaya, Kumi; Bidstrup, Pernille Envold

    2010-01-01

    BACKGROUND:: A few small studies published to date have suggested that major psychosocial problems develop in the partners of cancer patients; however, to the authors' knowledge, no studies to date have addressed their risk for severe depression. In a retrospective cohort study, the risk for hosp......BACKGROUND:: A few small studies published to date have suggested that major psychosocial problems develop in the partners of cancer patients; however, to the authors' knowledge, no studies to date have addressed their risk for severe depression. In a retrospective cohort study, the risk...... for hospitalization with an affective disorder of the male partners of women with breast cancer was investigated, using unbiased, nationwide, population-based information. METHODS:: Followed were 1,162,596 men born between 1925 and 1973 who were aged ≥30 years at study entry, resided in Denmark between 1994 and 2006...

  16. Increasing Early Detection of Prostate Cancer in African American Men Through a Culturally Targeted Print Intervention

    Science.gov (United States)

    2006-03-01

    beliefs, and prior screening behavior among blacks and whites reporting for prostate cancer screening. Urology 1995; 46(3):346-351. (14) Tajfel H...cancer brochure • Appendix 3: Randomized control trial questionnaire • Appendix 4: Letter from Dr. Hall to recruit participants for focus group study...Appendix 5: 3 Focus group questionnaires PRINCIPLE INVESTIGATOR: Hayley Thompson, PhD Assistant Professor Mount Sinai School of

  17. Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer.

    Directory of Open Access Journals (Sweden)

    Yasuko Koma

    Full Text Available BACKGROUND: Red cell distribution width (RDW, one of many routinely examined parameters, shows the heterogeneity in erythrocyte size. We investigated the association of RDW levels with clinical parameters and prognosis of lung cancer patients. METHODS: Clinical and laboratory data from 332 patients with lung cancer in a single institution were retrospectively studied by univariate analysis. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. RESULTS: THE RDW LEVELS WERE DIVIDED INTO TWO GROUPS: high RDW (>=15%, n=73 vs. low RDW, n=259 (<15%. Univariate analysis showed that there were significant associations of high RDW values with cancer stage, performance status, presence of other disease, white blood cell count, hemoglobin, mean corpuscular volume, platelet count, albumin level, C-reactive protein level, and cytokeratin 19 fragment level. Kruskal-Wallis tests revealed an association of RDW values with cancer stage in patients irrespective of comorbidity (patient with/without comorbidity: p<0.0001, patient without comorbidity: p<0.0001. Stages I-IV lung cancer patients with higher RDW values had poorer prognoses than those with lower RDW values (Wilcoxon test: p=0.002. In particular, the survival rates of stage I and II patients (n=141 were lower in the high RDW group (n=19 than in the low RDW group (n=122 (Wilcoxon test: p<0.001. Moreover, multivariate analysis showed higher RDW is a significant prognostic factor (p=0.040. CONCLUSION: RDW is associated with several factors that reflect inflammation and malnutrition in lung cancer patients. Moreover, high levels of RDW are associated with poor survival. RDW might be used as a new and convenient marker to determine a patient's general condition and to predict the mortality risk of lung cancer patients.

  18. A novel genetic polymorphism of inducible nitric oxide synthase is associated with an increased risk of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Jing Shen; Run-Tian Wang; Li-Wei Wang; Yao-Chu Xu; Xin-Ru Wang

    2004-01-01

    AIM: Inducible nitric oxide synthase (iNOS) plays a central role in the pathway of reactive oxygen and nitrogen species metabolism when Helicobacter pylori ( H pylori) infection occurs in humans. iNOS Ser608 Leu allele, a novel genetic polymorphism (C/T) occurring within exon 16 of the iNOS reductase domain, may have a dramatic effect on the enzymatic activity. The aim of this study was to determine whether iNOS C/T polymorphism was associated with increased susceptibility to gastric cancer.METHODS: We conducted a population based case-control study in a high gastric cancer incidence area, Yangzhong,China. Questionnaires from 93 patients with intestinal type gastric cancer (IGC), 50 with gastric cardia cancer (GCC)and 246 healthy controls were obtained between 1997 and1998, and iNOS genotyping was carried out. Odds ratios(ORs), interaction index (γ), and 95% confidence intervals for the combined effects of iNOS genotype and H pylori infection, cigarette smoking or alcohol drinking were estimated.RESULTS: The frequency of (CT+TT) genotypes was higher in cases than in control group (24.48% vs23.17%), but the difference was not statistically significant. After adjusting for age and gender, past cigarette smokers with (CT+TT)genotypes had a significantly increased risk of IGC (OR = 3.62,95% CI: 1.23-10.64), while past alcohol drinkers with(CT+TT) genotypes had a significantly increased risk of GCC (OR = 3.33, 95% CI: 1.14-9.67).H pylori CagA negative subjects with (CT+TT) genotypes had a significantly increased risk of both IGC and GCC (OR = 2.19 and 3.52, respectively).CONCLUSION: iNOS Ser608Leu allele may be a potential determinant of susceptibility to cigarette -alcohol induced gastric cancer, but larger studies are needed to confirm the observations.

  19. The 8q24 rs6983267G variant is associated with increased thyroid cancer risk.

    Science.gov (United States)

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Polanco Echeverry, Guadalupe; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carmona, Luis G Carvajal

    2015-10-01

    The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11-1.27, P=4.03×10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23×10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by ∼13%.

  20. ACCISS study rationale and design: activating collaborative cancer information service support for cervical cancer screening

    Directory of Open Access Journals (Sweden)

    Bullard Emily

    2009-12-01

    Full Text Available Abstract Background High-quality cancer information resources are available but underutilized by the public. Despite greater awareness of the National Cancer Institute's Cancer Information Service among low-income African Americans and Hispanics compared with Caucasians, actual Cancer Information Service usage is lower than expected, paralleling excess cancer-related morbidity and mortality for these subgroups. The proposed research examines how to connect the Cancer Information Service to low-income African-American and Hispanic women and their health care providers. The study will examine whether targeted physician mailing to women scheduled for colposcopy to follow up an abnormal Pap test can increase calls to the Cancer Information Service, enhance appropriate medical follow-up, and improve satisfaction with provider-patient communication. Methods/Design The study will be conducted in two clinics in ethnically diverse low-income communities in Chicago. During the formative phase, patients and providers will provide input regarding materials planned for use in the experimental phase of the study. The experimental phase will use a two-group prospective randomized controlled trial design. African American and Hispanic women with an abnormal Pap test will be randomized to Usual Care (routine colposcopy reminder letter or Intervention (reminder plus provider recommendation to call the Cancer Information Service and sample questions to ask. Primary outcomes will be: 1 calls to the Cancer Information Service; 2 timely medical follow-up, operationalized by whether the patient keeps her colposcopy appointment within six months of the abnormal Pap; and 3 patient satisfaction with provider-patient communication at follow-up. Discussion The study examines the effectiveness of a feasible, sustainable, and culturally sensitive strategy to increase awareness and use of the Cancer Information Service among an underserved population. The goal of linking a

  1. The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2 Is Increased in Human Lung Cancer.

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    Paula Moreno

    Full Text Available Lung cancer is the leading cause of cancer-related deaths worldwide. Overall 5-year survival has shown little improvement over the last decades. Seven in absentia homolog (SIAH proteins are E3 ubiquitin ligases that mediate proteasomal protein degradation by poly-ubiquitination. Even though SIAH proteins play a key role in several biological processes, their role in human cancer remains controversial. The aim of the study was to document SIAH2 expression pattern at different levels (mRNA, protein level and immunohistochemistry in human non-small cell lung cancer (NSCLC samples compared to surrounding healthy tissue from the same patient, and to analyse the association with clinicopathological features.One hundred and fifty-two samples from a patient cohort treated surgically for primary lung cancer were obtained for the study. Genic and protein expression levels of SIAH2 were analysed and compared with clinic-pathologic variables.The present study is the first to analyze the SIAH2 expression pattern at different levels (RNA, protein expression and immunohistochemistry in non-small cell lung cancer (NSCLC. We found that SIAH2 protein expression is significantly enhanced in human lung adenocarcinoma (ADC and squamous cell lung cancer (SCC. Paradoxically, non-significant changes at RNA level were found, suggesting a post-traductional regulatory mechanism. More importantly, an increased correlation between SIAH2 expression and tumor grade was detected, suggesting that this protein could be used as a prognostic biomarker to predict lung cancer progression. Likewise, SIAH2 protein expression showed a strong positive correlation with fluorodeoxyglucose (2-deoxy-2(18Ffluoro-D-glucose uptake in primary NSCLC, which may assist clinicians in stratifying patients at increased overall risk of poor survival. Additionally, we described an inverse correlation between the expression of SIAH2 and the levels of one of its substrates, the serine/threonine kinase

  2. DC electric fields direct breast cancer cell migration, induce EGFR polarization, and increase the intracellular level of calcium ions.

    Science.gov (United States)

    Wu, Dan; Ma, Xiuli; Lin, Francis

    2013-01-01

    Migration of cancer cells leads to invasion of primary tumors to distant organs (i.e., metastasis). Growing number of studies have demonstrated the migration of various cancer cell types directed by applied direct current electric fields (dcEF), i.e., electrotaxis, and suggested its potential implications in metastasis. MDA-MB-231 cell, a human metastatic breast cancer cell line, has been shown to migrate toward the anode of dcEF. Further characterizations of MDA-MB-231 cell electrotaxis and investigation of its underlying signaling mechanisms will lead to a better understanding of electrically guided cancer cell migration and metastasis. Therefore, we quantitatively characterized MDA-MB-231 cell electrotaxis and a few associated signaling events. Using a microfluidic device that can create well-controlled dcEF, we showed the anode-directing migration of MDA-MB-231 cells. In addition, surface staining of epidermal growth factor receptor (EGFR) and confocal microscopy showed the dcEF-induced anodal EGFR polarization in MDA-MB-231 cells. Furthermore, we showed an increase of intracellular calcium ions in MDA-MB-231 cells upon dcEF stimulation. Altogether, our study provided quantitative measurements of electrotactic migration of MDA-MB-231 cells, and demonstrated the electric field-mediated EGFR and calcium signaling events, suggesting their involvement in breast cancer cell electrotaxis.

  3. Increased expression of long intergenic non-coding RNA LINC00152 in gastric cancer and its clinical significance.

    Science.gov (United States)

    Pang, Qianqian; Ge, Jiaxin; Shao, Yongfu; Sun, Weiliang; Song, Haojun; Xia, Tian; Xiao, Bingxiu; Guo, Junming

    2014-06-01

    It has been known that differential expression of long non-coding RNA (lncRNA) plays critical roles in carcinogenesis. However, the significance of lncRNA, especially long intergenic ncRNA (lincRNA, the main type of lncRNA family), in the diagnosis of gastric cancer is largely unknown. The aim of this study was to determine the expression level of LINC00152, a newfound lincRNA, in gastric carcinoma and its clinical association. The expression of LINC00152 in 71 pairs of tumorous and adjacent normal tissues from patients with gastric cancer was detected by quantitative real-time reverse transcription-polymerase chain reaction. And then, the potential associations between its level in gastric cancer tissue and the clinicopathological features were analyzed. Finally, a receiver operating characteristic (ROC) curve was constructed for differentiating patients with gastric cancer from patients with benign gastric diseases. The results showed that the expression level of LINC00152 in gastric carcinoma was significantly increased, compared with matched normal tissue (P=0.045) and normal mucosa from health control (P=0.004), respectively. Levels of LINC00152 in gastric cancer cell lines, BGC-823, MGC-803, and SGC-7901, were significantly higher than those in human normal gastric epithelial cell line GES-1. In addition, high expression of LINC00152 was correlated with invasion (P=0.042). LINC00152 levels in gastric juice from patients with gastric cancer were further found significantly higher than those from normal controls (P=0.002). Moreover, the area under the ROC curve (AUC) was up to 0.645 (95 % CI=0.559-0.740, P=0.003). This study highlights that lincRNA LINC00152 might be a novel biomarker for predicting gastric cancer.

  4. Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer.

    Science.gov (United States)

    Chaux, Alcides; Peskoe, Sarah B; Gonzalez-Roibon, Nilda; Schultz, Luciana; Albadine, Roula; Hicks, Jessica; De Marzo, Angelo M; Platz, Elizabeth A; Netto, George J

    2012-11-01

    PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most frequently lost tumor suppressor genes in human cancers and it has been described in more than two-thirds of patients with advanced/aggressive prostate cancer. Previous studies suggest that, in prostate cancer, genomic PTEN loss is associated with tumor progression and poor prognosis. Thus, we evaluated whether immunohistochemical PTEN expression in prostate cancer glands was associated with higher risk of recurrence, using a nested case-control study that included 451 men who recurred and 451 men who did not recur with clinically localized prostate cancer treated by radical prostatectomy. Recurrence was defined as biochemical recurrence (serum prostate-specific antigen >0.2 ng/ml) or clinical recurrence (local recurrence, systemic metastases, or prostate cancer-related death). Cases and controls were matched on pathological T stage, Gleason score, race/ethnicity, and age at surgery. Odds ratios of recurrence and 95% confidence intervals were estimated using conditional logistic regression to account for the matching factors and to adjust for year of surgery, preoperative prostate-specific antigen concentrations, and status of surgical margins. Men who recurred had a higher proportion of PTEN negative expression (16 vs 11%, P=0.05) and PTEN loss (40 vs 31%, P=0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio=1.67; 95% confidence intervals 1.09, 2.57; P=0.02) when compared with all other men. In summary, in patients with clinically localized prostate cancer treated by prostatectomy, decreased PTEN expression was associated with an increased risk of recurrence, independent of known clinicopathological factors.

  5. Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models

    Science.gov (United States)

    Alamo, Patricia; Gallardo, Alberto; Pavón, Miguel A.; Casanova, Isolda; Trias, Manuel; Mangues, Maria A.; Vázquez, Esther; Villaverde, Antonio; Mangues, Ramon; Céspedes, Maria V.

    2014-01-01

    Mouse colorectal cancer (CRC) models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT). This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT) group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC. PMID:24487410

  6. Tea and cancer prevention: epidemiological studies.

    Science.gov (United States)

    Yuan, Jian-Min; Sun, Canlan; Butler, Lesley M

    2011-08-01

    Experimental studies have consistently shown the inhibitory activities of tea extracts on tumorigenesis in multiple model systems. Epidemiological studies, however, have produced inconclusive results in humans. A comprehensive review was conducted to assess the current knowledge on tea consumption and risk of cancers in humans. In general, consumption of black tea was not associated with lower risk of cancer. High intake of green tea was consistently associated with reduced risk of upper gastrointestinal tract cancers after sufficient control for confounders. Limited data support a protective effect of green tea on lung and hepatocellular carcinogenesis. Although observational studies do not support a beneficial role of tea intake on prostate cancer risk, phase II clinical trials have demonstrated an inhibitory effect of green tea extract against the progression of prostate pre-malignant lesions. Green tea may exert beneficial effects against mammary carcinogenesis in premenopausal women and recurrence of breast cancer. There is no sufficient evidence that supports a protective role of tea intake on the development of cancers of the colorectum, pancreas, urinary tract, glioma, lymphoma, and leukemia. Future prospective observational studies with biomarkers of exposure and phase III clinical trials are required to provide definitive evidence for the hypothesized beneficial effect of tea consumption on cancer formation in humans.

  7. Ensuring quality in studies linking cancer registries and biobanks.

    Science.gov (United States)

    Langseth, Hilde; Luostarinen, Tapio; Bray, Freddie; Dillner, Joakim

    2010-04-01

    The Nordic countries have a long tradition of providing comparable and high quality cancer data through the national population-based cancer registries and the capability to link the diverse large-scale biobanks currently in operation. The joining of these two infrastructural resources can provide a study base for large-scale studies of etiology, treatment and early detection of cancer. Research projects based on combined data from cancer registries and biobanks provides great opportunities, but also presents major challenges. Biorepositories have become an important resource in molecular epidemiology, and the increased interest in performing etiological, clinical and gene-environment-interaction studies, involving information from biological samples linked to population-based cancer registries, warrants a joint evaluation of the quality aspects of the two resources, as well as an assessment of whether the resources can be successfully combined into a high quality study. While the quality of biospecimen handling and analysis is commonly considered in different studies, the logistics of data handling including the linkage of the biobank with the cancer registry is an overlooked aspect of a biobank-based study. It is thus the aim of this paper to describe recommendations on data handling, in particular the linkage of biobank material to cancer registry data and the quality aspects thereof, based on the experience of Nordic collaborative projects combining data from cancer registries and biobanks. We propose a standard documentation with respect to the following topics: the quality control aspects of cancer registration, the identification of cases and controls, the identification and use of data confounders, the stability of serum components, historical storage conditions, aliquoting history, the number of freeze/thaw cycles and available volumes.

  8. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia.

    Science.gov (United States)

    Dockery, Frances; Bulpitt, Christopher J; Agarwal, Sanjiv; Donaldson, Mandy; Rajkumar, Chakravarthi

    2003-02-01

    The role of androgens in cardiovascular disease is uncertain. We aimed to determine the vascular effects of androgen suppression in men with prostate cancer. Arterial stiffness (or 'compliance') was measured in 16 men (71+/-9 years, mean+/-S.D.) prior to, and 3 months after, complete androgen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer. Fifteen control men (70+/-7 years) also had arterial stiffness studies at baseline and 3 months later. Two measures of arterial stiffness were employed: systemic arterial compliance (SAC) was measured by simultaneous recording of aortic flow and carotid artery pressure ('area method'), and pulse wave velocities (PWVs) were recorded with the 'Complior' system. The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits. After 3 months of testosterone suppression, there was a significant fall in SAC, which was not seen in the controls [mean change+/-S.E.M., -0.26+/-0.09 a.c.u. (arbitrary compliance unit) in the cases versus +0.06+/-0.11 in the controls; P =0.03). Central, but not peripheral, PWVs tended to increase in the cases (mean change+/-S.E.M. for aorto-femoral PWV, +0.5+/-0.4 m/s for cases versus -0.3+/-0.3 m/s for controls; P =0.08). After testosterone suppression, fasting insulin levels increased from 6.89+/-4.84 m-units/l to 11.34+/-8.16 m-units/l (mean+/-S.D.), total cholesterol increased from 5.32+/-0.77 mmol/l to 5.71+/-0.82 mmol/l and high-density lipoprotein cholesterol increased from 1.05+/-0.24 mmol/l to 1.26+/-0.36 mmol/l; P change occurred in body-mass index, serum glucose, low-density lipoprotein cholesterol or triacylglycerol (triglyceride) levels. Our results indicate that loss of androgens in men leads to an increase in aortic stiffness and serum insulin levels, and may therefore adversely affect cardiovascular risk.

  9. Utilizing Data from Cancer Patient & Survivor Studies

    Science.gov (United States)

    Utilizing Data from Cancer Patient & Survivor Studies and Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2011 workshop sponsored by the Epidemiology and Genomics Research Program.

  10. Recurrent HOXB13 mutations in the Dutch population do not associate with increased breast cancer risk.

    Science.gov (United States)

    Liu, Jingjing; Prager-van der Smissen, Wendy J C; Schmidt, Marjanka K; Collée, J Margriet; Cornelissen, Sten; Lamping, Roy; Nieuwlaat, Anja; Foekens, John A; Hooning, Maartje J; Verhoef, Senno; van den Ouweland, Ans M W; Hogervorst, Frans B L; Martens, John W M; Hollestelle, Antoinette

    2016-01-01

    The HOXB13 p.G84E mutation has been firmly established as a prostate cancer susceptibility allele. Although HOXB13 also plays a role in breast tumor progression, the association of HOXB13 p.G84E with breast cancer risk is less evident. Therefore, we comprehensively interrogated the entire HOXB13 coding sequence for mutations in 1,250 non-BRCA1/2 familial breast cancer cases and 800 controls. We identified two predicted deleterious missense mutations, p.G84E and p.R217C, that were recurrent among breast cancer cases and further evaluated their association with breast cancer risk in a larger study. Taken together, 4,520 familial non-BRCA1/2 breast cancer cases and 3,127 controls were genotyped including the cases and controls of the whole gene screen. The concordance rate for the genotyping assays compared with Sanger sequencing was 100%. The prostate cancer risk allele p.G84E was identified in 18 (0.56%) of 3,187 cases and 16 (0.70%) of 2,300 controls (OR = 0.81, 95% CI = 0.41-1.59, P = 0.54). Additionally, p.R217C was identified in 10 (0.31%) of 3,208 cases and 2 (0.087%) of 2,288 controls (OR = 3.57, 95% CI = 0.76-33.57, P = 0.14). These results imply that none of the recurrent HOXB13 mutations in the Dutch population are associated with breast cancer risk, although it may be worthwhile to evaluate p.R217C in a larger study.

  11. Occupational exposure to organic dust increases lung cancer risk in the general population

    NARCIS (Netherlands)

    Peters, Susan; Kromhout, Hans; Olsson, Ann C.; Wichmann, Heinz-Erich; Brueske, Irene; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Richiardi, Lorenzo; Mirabelli, Dario; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Joeckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Boffetta, Paolo; Brennan, Paul; Zaridze, David; Cassidy, Adrian; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Fabianova, Eleonora; Forastiere, Francesco; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Stuecker, Isabelle; Dumitru, Rodica Stanescu; Benhamou, Simone; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Pesch, Beate; Straif, Kurt; Bruening, Thomas; Vermeulen, Roel

    2012-01-01

    Background Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk, while exposure to microbial components (eg, endotoxin) has been associated with a decreased

  12. Increased cancer risk in patients referred to hospital with suspected fibromyalgia

    DEFF Research Database (Denmark)

    Dreyer, Lene; Mellemkjaer, Lene; Kendall, Sally;

    2007-01-01

    OBJECTIVE: To analyze whether fibromyalgia (FM) and FM-like symptoms are related to an increased incidence of cancer. METHODS: We identified 1361 patients referred on suspicion of FM in the period 1984-99 from hospital records. Following the American College of Rheumatology (ACR) criteria, patients...

  13. Does night-shift work increase the risk of prostate cancer? a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Rao D

    2015-10-01

    Full Text Available Dapang Rao,1,2 Haifeng Yu,2 Yu Bai,3 Xiangyi Zheng,1 Liping Xie1 1Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Urology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Urology, Yunnan Tumor Hospital and Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China Background: Night-shift work is suggested to be associated with an increased risk of breast cancer, but its association with prostate cancer is still controversial. We examined this association by conducting a systematic review and meta-analysis. Methods: Studies were identified by searching PubMed, EMBASE, Ovid, Web of Science, the Cochrane register, and the China National Knowledge Infrastructure databases through December 25, 2014. Summary relative risks (SRRs with their corresponding 95% confidence intervals (CIs were calculated using a random effects or fixed effects model. Heterogeneity and publication bias were also evaluated. Results: A total of 2,459,845 individuals from eight published studies were included in this meta-analysis. Analysis of all studies suggested that night-shift work was associated with a significantly increased risk of prostate cancer (RR: 1.24, 95% CI: 1.05–1.46; P=0.011. Sensitivity analysis showed that the association remained significant when repeating the analysis after removing one study each time. Dose–response meta-analysis suggested that an increase in night-shift work of 5 years duration was statistically significantly associated with a 2.8% (95% CI: 0.3, 5.4%, P=0.030 increase in the risk of prostate cancer. There was no significant publication bias. Conclusion: Based on a meta-analysis, night-shift work is associated with an increased risk of prostate cancer. Because of the limited number of included studies and the large level of heterogeneity

  14. Shortened telomere length is associated with increased risk of cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hongxia Ma

    Full Text Available BACKGROUND: Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting. METHODS: A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. Heterogeneity among studies and their publication bias were further assessed by the χ(2-based Q statistic test and Egger's test, respectively. RESULTS: The results showed that shorter telomeres were significantly associated with cancer risk (OR = 1.35, 95% CI = 1.14-1.60, compared with longer telomeres. In the stratified analysis by tumor type, the association remained significant in subgroups of bladder cancer (OR = 1.84, 95% CI = 1.38-2.44, lung cancer (OR = 2.39, 95% CI = 1.18-4.88, smoking-related cancers (OR = 2.25, 95% CI = 1.83-2.78, cancers in the digestive system (OR = 1.69, 95% CI = 1.53-1.87 and the urogenital system (OR = 1.73, 95% CI = 1.12-2.67. Furthermore, the results also indicated that the association between the relative telomere length and overall cancer risk was statistically significant in studies of Caucasian subjects, Asian subjects, retrospective designs, hospital-based controls and smaller sample sizes. Funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis (P = 0.532. CONCLUSIONS: The results of this meta-analysis suggest that the presence of shortened telomeres may be a marker for susceptibility to human cancer, but single larger, well-design prospective studies are warranted to confirm these findings.

  15. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

    Directory of Open Access Journals (Sweden)

    Gruber Helen E

    2011-08-01

    Full Text Available Abstract Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA. Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17, interleukin-6 (IL-6, Pro- Matrix metallopeptidase 9 (Pro-MMP9, insulin like growth factor-II (GF-II and macrophage colony stimulating factor (M-CSF in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors

  16. Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Pei-Chen Wang

    2014-02-01

    Full Text Available VCAM-1 (CD106, a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1. In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGFβ1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.

  17. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Huang Wen-bin

    2009-09-01

    Full Text Available Abstract Background Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17 in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Methods Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. Results We found that HSp17 was aberrantly expressed in 43% (30/70 of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. Conclusion HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy.

  18. Tnactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ye-Jiang Zhou; Yu-Xia Xiong; Xiao-Ting Wu; De Shi; Wei Fan; Tong Zhou; Yue-Chun Li; Xiong Huang

    2004-01-01

    AIM: To investigate the expression of PTEN/MMAC1/TEP1and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated.RESULTS: PTEN expression significantly decreased (t= 3.98,P<0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P<0.01)in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t = 1.95,P<0.05) whereas VEGF expression (t = 2.37, P<0.05) and MVD (t = 3.28, P<0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P<0.01),invasion depth (t= 1.95, P<0.05) and age (t= 4.69, P<0.01).MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t = 3.69,P<0.01), and there was a negative correlation between PTEN expression and MVD (γ = -0.363, P<0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P<0.01), lymph node metastasis (t= 2.31, P<0.05) and TNM stage (t= 3.04,P<0.01). MVD in VEGF-positive gastric cancer was significantly higher than that in VEGF-negative gastric cancer (t = 4.62,P<0.01), and there was a positive correlation between VEGF expression of and MVD (γ = 0.512, P<0.05). VEGF expression in PTEN

  19. Effectiveness of Logo Therapy to Reduce Stress and Increase Happiness in Women with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Reyhaneh Shadab Jouposhti

    2016-12-01

    Full Text Available Current research was performed aiming at determining effect of logotherapy on reducing stress and increasing happiness in women with breast cancer. It is of quasi-experimental type with pre-test and post-test and control group. Statistical population included all women with breast cancer in Rash city. Statistical sample included 30 women with breast cancer (15 in case group and 15 in control group who were randomly selected using convenient sampling method and were randomly assigned to case and control groups. For casegroup, 10 sessions (90 min of Logotherapy was provided and control group received no intervention. Subjects in two stages (pretest and posttest were evaluated using perceived stress scale and Oxford’s happiness survey. Data analysis was done using descriptive statistics methods (mean, SD, frequency and percentage as well as inferential statistics (ANCOVA and multivariate analysis of covariance. Data analysis showed that Logotherapy in case group led to increased happiness and reduced perceived stress in women in this group. Thus, it can be stated providing Logotherapy training can help patients to accept and adopt to their disease leading to increasing happiness and reducing stress in women with cancer.

  20. Radiotherapy for breast cancer is not associated with increased risk of cied implantation

    DEFF Research Database (Denmark)

    Johansen, J. B.; Rehammar, J. C.; Jorgensen, O. D.

    2015-01-01

    Introduction: Radiotherapy is an important treatment in early stage breast cancer but it is claimed that radiotherapy causes damage to the cardiac conduction system and increases the risk implantation of CIED (pacemaker or ICD). However, this paradigm is based on smaller series of case reports. Due....... The unadjusted RR was 1.02 (0.76-1.36 95% CI, p=0.91) and the RR adjusted for year, age and time since diagnosis was 1.06 (0.79-1.42 95% CI, p=0.71). There was thus no difference in risk of CIED implantation after radioterapy in left- versus right sided breast cancer. Conclusions: Radiotherapy for breast cancer...

  1. Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients.

    Science.gov (United States)

    Chiou, Yu-Hu; Wong, Ruey-Hong; Chao, Mu-Rong; Chen, Chih-Yi; Liou, Saou-Hsing; Lee, Huei

    2014-10-01

    Occupational exposure to nickel compounds has been associated with lung cancer. The correlation between high nickel levels and increased risk of lung cancer has been previously reported in a case-control study. This study assessed whether nickel exposure increased the occurrence of p53 mutations due to DNA repair inhibition by nickel. A total of 189 lung cancer patients were enrolled to determine nickel levels in tumor-adjacent normal lung tissues and p53 mutation status in lung tumors through atomic absorption spectrometry and direct sequencing, respectively. Nickel levels in p53 mutant patients were significantly higher than those in p53 wild-type patients. When patients were divided into high- and low-nickel subgroups by median nickel level, the high-nickel subgroup of patients had an odds ratio (OR) of 3.25 for p53 mutation risk relative to the low-nickel subgroup patients. The OR for p53 mutation risk of lifetime non-smokers, particularly females, in the high-nickel subgroup was greater than that in the low-nickel subgroup. To determine whether nickel affected DNA repair capacity, we conducted the host cell reactivation assay in A549 and H1975 lung cancer cells and showed that the DNA repair activity was reduced by nickel chloride in a dose-dependent manner. This was associated with elevated production of hydrogen peroxide-induced 8-oxo-deoxyguanosine. Therefore, increased risk of p53 mutation due to defective DNA repair caused by high nickel levels in lung tissues may be one mechanism by which nickel exposure contributes to lung cancer development, especially in lifetime female non-smokers.

  2. Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

    Energy Technology Data Exchange (ETDEWEB)

    Pu, Jun [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Bai, Danna [Department of Cardiology, 323 Hospital of PLA, Xi' an 710054 (China); Yang, Xia [Department of Teaching and Medical Administration, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Lu, Xiaozhao [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Xu, Lijuan, E-mail: 13609296272@163.com [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Lu, Jianguo, E-mail: lujianguo029@yahoo.com.cn [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. Black-Right-Pointing-Pointer Adrenaline activates NF{kappa}B in a dose dependent manner. Black-Right-Pointing-Pointer NF{kappa}B-miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NF{kappa}B dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline-NF{kappa}B-miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

  3. Increasing Cervical Cancer Screening Coverage: A Randomised, Community-Based Clinical Trial

    Science.gov (United States)

    Acera, Amelia; Manresa, Josep Maria; Rodriguez, Diego; Rodriguez, Ana; Bonet, Josep Maria; Trapero-Bertran, Marta; Hidalgo, Pablo; Sànchez, Norman

    2017-01-01

    Background Opportunistic cervical cancer screening can lead to suboptimal screening coverage. Coverage could be increased after a personalised invitation to the target population. We present a community randomized intervention study with three strategies aiming to increase screening coverage. Methods The CRICERVA study is a community-based clinical trial to improve coverage of population-based screening in the Cerdanyola SAP area in Barcelona.A total of 32,858 women residing in the study area, aged 30 to 70 years were evaluated. A total of 15,965 women were identified as having no registration of a cervical cytology in the last 3.5 years within the Public Health data base system. Eligible women were assigned to one of four community randomized intervention groups (IGs): (1) (IG1 N = 4197) personalised invitation letter, (2) (IG2 N = 3601) personalised invitation letter + informative leaflet, (3) (IG3 N = 6088) personalised invitation letter + informative leaflet + personalised phone call and (4) (Control N = 2079) based on spontaneous demand of cervical cancer screening as officially recommended. To evaluate screening coverage, we used heterogeneity tests to compare impact of the interventions and mixed logistic regression models to assess the age effect. We refer a “rescue” visit as the screening visit resulting from the study invitation. Results Among the 13,886 women in the IGs, 2,862 were evaluated as having an adequate screening history after the initial contact; 4,263 were lost to follow-up and 5,341 were identified as having insufficient screening and thus being eligible for a rescue visit. All intervention strategies significantly increased participation to screening compared to the control group. Coverage after the intervention reached 84.1% while the control group reached 64.8%. The final impact of our study was an increase of 20% in the three IGs and of 9% in the control group (p<0.001). Within the intervention arms, age was an important determinant

  4. Increased risk of breast cancer in women with false-positive test

    DEFF Research Database (Denmark)

    von Euler-Chelpin, My; Kuchiki, Megumi; Vejborg, Ilse

    2014-01-01

    of misclassification, i.e. women who were actually false-negatives instead of false-positives. METHOD: We used data from the Copenhagen Mammography Screening Programme, Denmark. The study population was the 295 women, out of 4743 recalled women from a total of 58,003 participants, with a false-positive test during...... the screening period 1991-2005 and who later developed breast cancer. Cancers that developed in the same location as the finding that initially caused the recall was studied in-depth in order to establish whether there had been misclassification. RESULTS: Seventy-two cases were found to be misclassified. When...

  5. Sexual Dysfunction in Breast Cancer: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Mandana Ebrahimi

    2015-02-01

    Full Text Available Background: Sexual dysfunction in breast cancer patients is considered as a common and distressing problem. Considering the increasing number of breast cancer survivors living for longer periods of time with the disease and the importance of their quality of life, we conducted the present study to compare the sexual functioning in breast cancer patients with their healthy counterparts.Methods: In this case-control study, breast cancer patients who completed their treatment protocol and were followed up for at least six months were included. The controls were healthy women with normal clinical breast examinations. All subjects filled-in the Persian version of Female Sexual Function Index questionnaire.Results: A total of 165 subjects including 71 breast cancer patients and 94 healthy women were studied. The frequency of sexual dysfunction in cases and controls was 52.6% and 47.4%, respectively (P = 0.09. There were no significant differences between the two groups regarding domain scores, except for vaginal lubrication (P = 0.045. Logistic regression analysis indicated that significant determinants of sexual dysfunction in breast cancer group was patients' age (OR = 4.0, 95%CI: 1.3 – 11.5, P = 0.01 and age of the spouse (OR= 9.8, 95% CI: 1.8-51.9, P= 0.007, while in controls, only emotional relationship with the husband was the significant predictive factor (OR = 6.3, 95%CI: 1.9 – 20.5, P = 0.002.Conclusions: Our findings indicated that sexual dysfunction is prevalent in Iranian women regardless of their physical health status. The frequency of vaginal dryness in breast cancer patients was significantly higher than controls. Age of the patient and the spouse (>40 were the only significant predictors of sexual dysfunction among women with breast cancer. Preventive strategies, sexual education and access to effective treatment should be planned in supportive care of breast cancer patients.

  6. Increased methylation of lung cancer-associated genes in sputum DNA of former smokers with chronic mucous hypersecretion

    OpenAIRE

    Bruse, Shannon; Petersen, Hans; Weissfeld, Joel; Picchi, Maria; Willink, Randall; Do, Kieu; Siegfried, Jill; Belinsky, Steven A.; Tesfaigzi, Yohannes

    2014-01-01

    Background Chronic mucous hypersecretion (CMH) contributes to COPD exacerbations and increased risk for lung cancer. Because methylation of gene promoters in sputum has been shown to be associated with lung cancer risk, we tested whether such methylation was more common in persons with CMH. Methods Eleven genes commonly silenced by promoter methylation in lung cancer and associated with cancer risk were selected. Methylation specific PCR (MSP) was used to profile the sputum of 900 individuals...

  7. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia.

    Science.gov (United States)

    Petruzzelli, Michele; Schweiger, Martina; Schreiber, Renate; Campos-Olivas, Ramon; Tsoli, Maria; Allen, John; Swarbrick, Michael; Rose-John, Stefan; Rincon, Mercedes; Robertson, Graham; Zechner, Rudolf; Wagner, Erwin F

    2014-09-02

    Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or β-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.

  8. A qualitative evaluation of strategies to increase colorectal cancer screening uptake

    Science.gov (United States)

    Tinmouth, Jill; Ritvo, Paul; McGregor, S. Elizabeth; Claus, Danielle; Pasut, George; Myers, Ronald E.; Guglietti, Crissa; Paszat, Lawrence F.; Hilsden, Robert J.; Rabeneck, Linda

    2011-01-01

    Abstract Objective To obtain data that could be used to optimize the content and design of the targeted, mailed invitations that Ontario’s provincewide colorectal cancer (CRC) screening program plans to use to increase screening uptake; to identify other strategies to increase CRC screening uptake; and to describe the effects of this qualitative work on a subsequent quantitative pilot study. Design Qualitative study using semistructured focus groups. Setting Four different Ontario communities. Participants Six focus groups comprising a total of 62 participants. Methods Six focus groups were conducted in 4 different Ontario communities. For 3 of the communities, participants were recruited from the general population by a private marketing firm, using random-digit dialing, and received a small honorarium for participating. In Sault Ste Marie, participants were convenience samples recruited from a large primary care practice and were not offered compensation. Responses were elicited regarding various strategies for promoting CRC screening. Findings represent all responses observed as well as recommendations to program planners based on focus groups observations. Main findings Key themes identified included the importance of receiving a CRC screening invitation from one’s family physician; a desire for personalized, brief communications; and a preference for succinct information in mailed materials. Strong support was indicated for direct mailing of the CRC screening kit (fecal occult blood test). Our findings substantially influenced the final design and content of the envelope and letter to be mailed in the subsequent quantitative pilot study. Conclusion We report strong support from our focus groups for a succinct, personalized invitation for CRC screening from one’s own family physician. We have also shown that qualitative evaluation can be used to provide decision makers with pertinent and timely knowledge. Our study is highly relevant to other public

  9. Digoxin use after diagnosis of breast cancer and survival: a population-based cohort study.

    Science.gov (United States)

    Karasneh, Reema A; Murray, Liam J; Mc Menamin, Úna C; Hughes, Carmel M; Cardwell, Chris R

    2015-06-01

    Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. These findings, particularly recent observations of increased breast cancer risk, raise questions about the safety of digoxin use in breast cancer patients. Therefore, we investigated whether digoxin use after breast cancer diagnosis increased the risk of breast cancer-specific mortality in breast cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify breast cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and breast cancer-specific and all-cause mortality. In 17,842 breast cancer patients, there were 2219 breast cancer-specific deaths. Digoxin users appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39-2.15) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.91; 95 % CI 0.72-1.14). In this large population-based breast cancer cohort study, there was little evidence of an increase in breast cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in breast cancer patients.

  10. Metformin Increases Overall Survival in Patients with Diabetes Undergoing Surgery for Colorectal Cancer

    DEFF Research Database (Denmark)

    Fransgaard, Tina; Thygesen, Lau Caspar; Gögenur, Ismail

    2015-01-01

    between diabetes and overall survival after resection for CRC. Furthermore, the association between antidiabetic medication and overall survival was examined. METHODS: Patients diagnosed with CRC between January 1, 2003 and December 31, 2012 were identified through the Danish Colorectal Cancer Group......BACKGROUND: Emerging evidence suggests that metformin decreases the risk of developing colorectal cancer in patients with diabetes, but only few studies have examined potential survival benefits after surgery for colorectal cancer (CRC). The purpose of the study was to examine the association......'s National Clinical Database (DCCG). The Danish National Patient Register (NPR) records all hospital contacts in Denmark, and the diagnosis of diabetes was identified by combining NPR data with use of antidiabetic drugs identified through the Danish National Prescription Registry and DCCG. The Kaplan...

  11. Increase in cruciferous vegetable intake in women previously treated for breast cancer participating in a dietary intervention trial.

    Science.gov (United States)

    Thomson, Cynthia A; Rock, Cheryl L; Caan, Bette J; Flatt, Shirley W; Al-Delaimy, Wael A; Newman, Vicky A; Hajek, Richard A; Chilton, Janice A; Pierce, John P

    2007-01-01

    Consumption of cruciferous vegetables has been associated with reduced breast cancer risk mechanistically and in population-based studies, although evidence has been inconsistent. This inconsistency may be related to limitations in quantifying and qualifying cruciferous vegetable exposure using standard instruments for dietary assessment (for example, food-frequency questionnaires, FFQs) or due to low levels of intake demonstrated among U.S. population samples. Cruciferous vegetable intake data are presented from a longitudinal study of a high-vegetable dietary intervention to reduce breast cancer recurrence among breast cancer survivors (n=1,156; 536 intervention and 620 comparison group subjects). Intake was assessed using repeat administration of an FFQ and cross-sectional administration of a cruciferous vegetable-specific FFQ (CVFFQ). Mean intake in the intervention group assessed using the standard FFQ was 37.7 g/day at baseline and increased to 57.1 g/day at 12 mo (P=0.0001) and was sustained through 48 mo. Broccoli and cabbage were the most commonly consumed cruciferous vegetables, regardless of the instrument used to assess intake. Differences in intake by group assignment were shown for raw cruciferous vegetables (30.2 g/day vs. 24.6 g/day, assessed using the CVFFQ), suggesting increased exposure to biologically active, cancer-preventive food constituents. These data suggest that this study population will be the first U.S. population sample to provide ample quantity and variety in cruciferous intake to examine whether these vegetables are protective against breast cancer recurrence.

  12. Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model.

    Science.gov (United States)

    Basel, Matthew T; Balivada, Sivasai; Wang, Hongwang; Shrestha, Tej B; Seo, Gwi Moon; Pyle, Marla; Abayaweera, Gayani; Dani, Raj; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L

    2012-01-01

    Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.

  13. Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi; Pirisi, Lucia [Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC (United States); Creek, Kim E., E-mail: creekk@sccp.sc.edu [Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC (United States)

    2013-09-15

    We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer. - Highlights: • Ski oncoprotein levels increase during progression of HPV16-transformed cells. • Ski and phospho-Ski protein levels are cell cycle dependent. • Ski knock-down in HPV16-transformed keratinocytes inhibited cell proliferation. • Cervical cancer samples overexpress Ski.

  14. Association of the rs1346044 Polymorphism of the Werner Syndrome Gene RECQL2 with Increased Risk and Premature Onset of Breast Cancer.

    Science.gov (United States)

    Zins, Karin; Frech, Barbara; Taubenschuss, Eva; Schneeberger, Christian; Abraham, Dietmar; Schreiber, Martin

    2015-12-10

    Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance of genome stability. Inactivating mutations in RECQL2 lead to Werner syndrome, a rare autosomal disease associated with premature aging and an increased susceptibility to multiple cancer types. We analyzed the association of two coding single-nucleotide polymorphisms in WRN, Cys1367Arg (rs1346044), and Arg834Cys (rs3087425), with the risk, age at onset, and clinical subclasses of breast cancer in a hospital-based case-control study of an Austrian population of 272 breast cancer patients and 254 controls. Here we report that the rare homozygous CC genotype of rs1346044 was associated with an approximately two-fold elevated breast cancer risk. Moreover, patients with the CC genotype exhibited a significantly increased risk of developing breast cancer under the age of 55 in both recessive and log-additive genetic models. CC patients developed breast cancer at a mean age of 55.2 ± 13.3 years and TT patients at 60.2 ± 14.7 years. Consistently, the risk of breast cancer was increased in pre-menopausal patients in the recessive model. These findings suggest that the CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer.

  15. Curcumin AntiCancer Studies in Pancreatic Cancer

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  16. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  17. Study Points to Genetic Subtypes of Esophageal Cancer

    Science.gov (United States)

    A Cancer Currents blog post about a study by The Cancer Genome Atlas Research Network that identified distinct genetic and molecular changes in esophageal cancers that could improve their classification and identify potential new treatments.

  18. NIH study confirms risk factors for male breast cancer

    Science.gov (United States)

    Pooled data from studies of about 2,400 men with breast cancer and 52,000 men without breast cancer confirmed that risk factors for male breast cancer include obesity, a rare genetic condition called Klinefelter syndrome, and gynecomastia.

  19. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development.

    Science.gov (United States)

    Theodoropoulos, George E; Saridakis, Vasilios; Karantanos, Theodoros; Michalopoulos, Nikolaos V; Zagouri, Flora; Kontogianni, Panagiota; Lymperi, Maria; Gazouli, Maria; Zografos, George C

    2012-08-01

    Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 gene polymorphisms have been related to increased susceptibility to cancer development in various organs. 261 patients and 480 health individuals were investigated for genotype and allelic frequencies of a 22-bp nucleotide deletion (-196 to -174del) in the promoter of TLR2 gene as well as two polymorphisms causing amino acid substitutions (Asp299Gly and Thr399Ile) in TLR4 gene. As far as (-196 to -174del) in TLR2 gene is concerned ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls. Considering Asp299Gly replacement of TLR4 gene, Gly carriers (Asp/Gly & Gly/Gly genotype) and Gly allele were overrepresented among the breast cancer cases. The -174 to -196del of TLR2 gene and Asp299Gly of TLR4 gene polymorphisms may confer an increased susceptibility to breast cancer development.

  20. OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cao Lu

    2013-02-01

    Full Text Available Abstract Background OCT4 and BIRC5 are preferentially expressed in human cancer cells and mediate cancer cell survival and tumor maintenance. However, the molecular mechanism that regulates OCT4 and BIRC5 expression is not well characterized. Methods By manipulating OCT4 and BIRC5 expression in hepatocellular carcinoma (HCC cell lines, the regulatory mechanism of OCT4 on BIRC5 and CCND1 were investigated. Results Increasing or decreasing OCT4 expression could enhance or suppress BIRC5 expression, respectively, by regulating the activity of BIRC5 promoter. Because there is no binding site for OCT4 within BIRC5 promoter, the effect of OCT4 on BIRC5 promoter is indirect. An octamer motif for OCT4 in the CCND1 promoter has directly and partly participated in the regulation of CCND1 promoter activity, suggesting that OCT4 also could upregulated the expression of CCND1. Co-suppression of OCT4 and BIRC5 induced cancer cell apoptosis and cell cycle arrest, thereby efficiently inhibiting the proliferative activity of cancer cells and suppressing the growth of HCC xenogrfts in nude mice. Conclusion OCT4 can upregulate BIRC5 and CCND1 expression by increasing their promoter activity. These factors collusively promotes HCC cell proliferation, and co-suppression of OCT4 and BIRC5 is potentially beneficial for HCC treatment.

  1. A Western Dietary Pattern Increases Prostate Cancer Risk: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Fabiani, Roberto; Minelli, Liliana; Bertarelli, Gaia; Bacci, Silvia

    2016-01-01

    Dietary patterns were recently applied to examine the relationship between eating habits and prostate cancer (PC) risk. While the associations between PC risk with the glycemic index and Mediterranean score have been reviewed, no meta-analysis is currently available on dietary patterns defined by “a posteriori” methods. A literature search was carried out (PubMed, Web of Science) to identify studies reporting the relationship between dietary patterns and PC risk. Relevant dietary patterns were selected and the risks estimated were calculated by a random-effect model. Multivariable-adjusted odds ratios (ORs), for a first-percentile increase in dietary pattern score, were combined by a dose-response meta-analysis. Twelve observational studies were included in the meta-analysis which identified a “Healthy pattern” and a “Western pattern”. The Healthy pattern was not related to PC risk (OR = 0.96; 95% confidence interval (CI): 0.88–1.04) while the Western pattern significantly increased it (OR = 1.34; 95% CI: 1.08–1.65). In addition, the “Carbohydrate pattern”, which was analyzed in four articles, was positively associated with a higher PC risk (OR = 1.64; 95% CI: 1.35–2.00). A significant linear trend between the Western (p = 0.011) pattern, the Carbohydrate (p = 0.005) pattern, and the increment of PC risk was observed. The small number of studies included in the meta-analysis suggests that further investigation is necessary to support these findings. PMID:27754328

  2. A Western Dietary Pattern Increases Prostate Cancer Risk: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Roberto Fabiani

    2016-10-01

    Full Text Available Dietary patterns were recently applied to examine the relationship between eating habits and prostate cancer (PC risk. While the associations between PC risk with the glycemic index and Mediterranean score have been reviewed, no meta-analysis is currently available on dietary patterns defined by “a posteriori” methods. A literature search was carried out (PubMed, Web of Science to identify studies reporting the relationship between dietary patterns and PC risk. Relevant dietary patterns were selected and the risks estimated were calculated by a random-effect model. Multivariable-adjusted odds ratios (ORs, for a first-percentile increase in dietary pattern score, were combined by a dose-response meta-analysis. Twelve observational studies were included in the meta-analysis which identified a “Healthy pattern” and a “Western pattern”. The Healthy pattern was not related to PC risk (OR = 0.96; 95% confidence interval (CI: 0.88–1.04 while the Western pattern significantly increased it (OR = 1.34; 95% CI: 1.08–1.65. In addition, the “Carbohydrate pattern”, which was analyzed in four articles, was positively associated with a higher PC risk (OR = 1.64; 95% CI: 1.35–2.00. A significant linear trend between the Western (p = 0.011 pattern, the Carbohydrate (p = 0.005 pattern, and the increment of PC risk was observed. The small number of studies included in the meta-analysis suggests that further investigation is necessary to support these findings.

  3. Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk.

    Science.gov (United States)

    Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

    2016-10-01

    Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7(+/-) mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight.

  4. Obesity and Risk of Thyroid Cancer: Evidence from a Meta-Analysis of 21 Observational Studies

    Science.gov (United States)

    Ma, Jie; Huang, Min; Wang, Li; Ye, Wei; Tong, Yan; Wang, Hanmin

    2015-01-01

    Background Several studies have evaluated the association between obesity and thyroid cancer risk. However, the results remain uncertain. In this study, we conducted a meta-analysis to assess the association between obesity and thyroid cancer risk. Material/Methods Published literature from PubMed, EMBASE, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) were retrieved before 10 August 2014. We included all studies that reported adjusted risk ratios (RRs), hazard ratios (HRs) or odds ratios (ORs), and 95% confidence intervals (CIs) of thyroid cancer risk. Results Thirty-two studies (n=12 620 676) were included in this meta-analysis. Obesity was associated with a significantly increased risk of thyroid cancer (adjusted RR=1.33; 95% CI, 1.24–1.42; I2=25%). In the subgroup analysis by study type, increased risk of thyroid cancer was found in cohort studies and case-control studies. In subgroup analysis by sex, both obese men and women were at significantly greater risk of thyroid cancer than non-obese subjects. When stratified by ethnicity, significantly elevated risk was observed in Caucasians and in Asians. In the age subgroup analysis, both young and old populations showed increased thyroid cancer risk. Subgroup analysis on smoking status showed that increased thyroid cancer risks were found in smokers and in non-smokers. In the histology subgroup analyses, increased risks of papillary thyroid cancer, follicular thyroid cancer, and anaplastic thyroid cancer were observed. However, obesity was associated with decreased risk of medullary thyroid cancer. Conclusions Our results indicate that obesity is associated with an increased thyroid cancer risk, except medullary thyroid cancer. PMID:25612155

  5. MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-02-01

    Full Text Available Background/Aims: MicroRNA-218 (miR-218 is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.

  6. Histone deacetylase inhibition increases levels of choline kinase α and phosphocholine facilitating noninvasive imaging in human cancers.

    Science.gov (United States)

    Beloueche-Babari, Mounia; Arunan, Vaitha; Troy, Helen; te Poele, Robert H; te Fong, Anne-Christine Wong; Jackson, L Elizabeth; Payne, Geoffrey S; Griffiths, John R; Judson, Ian R; Workman, Paul; Leach, Martin O; Chung, Yuen-Li

    2012-02-15

    Histone deacetylase (HDAC) inhibitors are currently approved for cutaneous T-cell lymphoma and are in mid-late stage trials for other cancers. The HDAC inhibitors LAQ824 and SAHA increase phosphocholine (PC) levels in human colon cancer cells and tumor xenografts as observed by magnetic resonance spectroscopy (MRS). In this study, we show that belinostat, an HDAC inhibitor with an alternative chemical scaffold, also caused a rise in cellular PC content that was detectable by (1)H and (31)P MRS in prostate and colon carcinoma cells. In addition, (1)H MRS showed an increase in branched chain amino acid and alanine concentrations. (13)C-choline labeling indicated that the rise in PC resulted from increased de novo synthesis and correlated with an induction of choline kinase α expression. Furthermore, metabolic labeling experiments with (13)C-glucose showed that differential glucose routing favored alanine formation at the expense of lactate production. Additional analysis revealed increases in the choline/water and phosphomonoester (including PC)/total phosphate ratios in vivo. Together, our findings provide mechanistic insights into the impact of HDAC inhibition on cancer cell metabolism and highlight PC as a candidate noninvasive imaging biomarker for monitoring the action of HDAC inhibitors.

  7. Combined effects of obesity and type 2 diabetes contribute to increased breast cancer risk in premenopausal women

    Directory of Open Access Journals (Sweden)

    Al-Attas Omar S

    2009-06-01

    Full Text Available Abstract Background Both obesity and type 2 diabetes are among the risk factors for breast cancer development. Combined effect of these metabolic abnormalities on breast cancer risk however, has not been examined in premenopausal women. We tested this association in type 2 diabetic women, categorized as obese, overweight and normal body weight groups based on BMI. Design and methods A total of 101 subjects were included in this study. Serum levels of IL-6, TNF-α, C reactive protein, leptin, TGF-α, adiponectin and insulin were measured by ELISA. Data were logarithmically transformed for variables not normally distributed. Analysis of variance with post-hoc Bonferroni was applied to compare the data between the groups. Simple and partial correlation coefficients between the variables were determined and a stepwise multiple linear regression analysis was performed to determine the relationships between the variables of interest. Results Significantly increased levels of IL-6, C reactive protein, leptin and significantly decreased levels of adiponectin were found in obese group, while the levels of TNF-α and TGF-α were unaltered. A positive correlation between waist circumference and IL-6 was found in obese group. Similarly, C reactive protein, waist and hip circumferences were linearly correlated with BMI in obese group. Stepwise multiple linear regression analysis revealed several significant predictors for breast cancer risk. Conclusion Obesity and type 2 diabetes, owing to their effects on adipocytokines and inflammatory mediators, contribute to increased breast cancer risk in premenopausal women. This study emphasizes healthy life style and better management of these metabolic disorders to avoid the pathogenesis of breast cancer and of other chronic diseases.

  8. Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisomes proliferate-activated receptor {gamma} activation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunjung; Shin, Soyoung; Lee, Jeeyoung; Lee, So Jung; Kim, Jinkyoung; Yoon, Doyoung; Kim, Yangmee [Konkuk Univ., Seoul (Korea, Republic of); Woo, Eunrhan [Chosun Univ., Gwangju (Korea, Republic of)

    2012-07-15

    Human peroxisomes proliferate-activated receptor gamma (hPPAR{gamma}) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of hPPAR{gamma} and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that hPPAR{gamma} expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of hPPAR{gamma} in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to hPPAR{gamma} activation.

  9. Image-guided diagnosis of prostate cancer can increase detection of tumors

    Science.gov (United States)

    In the largest prospective study to date of image-guided technology for identifying suspicious regions of the prostate to biopsy, researchers compared the ability of this technology to detect high-risk prostate cancer with that of the current standard of

  10. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  11. Cancer and inflammation studies using zebrafish cell lines

    NARCIS (Netherlands)

    He, Shuning

    2010-01-01

    As the zebrafish, Danio rerio, has been increasingly used as an animal model for biomedical research, we aimed to establish zebrafish cell line models for inflammation and cancer studies in this thesis. Several zebrafish cell lines were characterized and their genetic and physiological properties we

  12. Studies on retrospective analysis of leading primary cancers and improvement of cancer treatment method in Korea cancer center hospital

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong In; Lee, Kang Hyun; Choi, Soo Yong; Kim, Ki Wha; Kang, Sung Mok

    2000-12-01

    a. Retrospective studies included cancers of the stomach, breast, bladder, salivary gland, thyroid, esophagus, endometrium and ovary. (1) Study cancers were analyzed about clinical characteristics, prognostic factors influenced on survival time, survival rate, etc. (2) Among 5,305 study patients, 1,405(26.5%) were identified with death, 3,485(65.7%) were alive and 415(7.8%) were not identified. b. Prospective studies included 10 subjects such as bladder cancer, retinoblastoma, malignant patients, gastric cancer, uterine cervix cancer and ovary cancer. We are continuing registering eligible study patients. c. Results for 11 papers were published at the journal. d. We established follow-up system in order to identify the survival for study subjects through National Statistical Office, Government Provincial Office and Cancer Registration System at Korea Cancer Center Hospital. e. At present, we are establishing computerized registration system about case report form for study cancers.

  13. Polymorphism of FGFR4 Gly388Arg does not confer an increased risk to breast cancer development.

    Science.gov (United States)

    Naidu, R; Har, Y C; Taib, N A

    2009-01-01

    The genotype analysis of the Gly and Arg allele at codon 388 of fibroblast growth factor receptor-4 (FGFR4) gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The aim of the present study was to evaluate the association between the FGFR4 Gly388Arg polymorphism and breast cancer risk as well as clinicopathological parameters of the patients. The Gly/Gly, Gly/Arg, Arg/Arg, and Arg allele genotypes were detected in 46.3%, 44.4%, 9.3%, and 53.7% of breast cancer cases, respectively. The distribution of genotype (p = 0.204) and allele (p = 0.086) frequencies of FGFR4 polymorphism were not significantly different between the breast cancer cases and normal individuals. Women who were Arg/ Arg homozygotes (OR = 1.714, 95% CI 0.896-3.278), Gly/Arg heterozygotes (OR = 1.205, 95% CI 0.863-1.683), carriers of Arg allele genotype (OR = 1.269, 95% CI 0.921-1.750), or Arg allele (OR = 1.246, 95% CI 0.970-1.602) were not associated with breast cancer risk. The Arg allele genotype was significantly associated with lymph node metastases (p = 0.001) but not with other clinicopathological parameters. Our findings suggest that the polymorphic variant at codon 388 of FGFR4 gene does not confer increased risk to breast cancer development but it may be a potential genetic marker for tumor prognosis.

  14. Increased Midkine and Estrogen Receptor-β Expression in Human Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Shi-hua Zhang; Guang-feng Zhao; Ya-hong Huang; Kai-hua Lu; Ya-yi Hou

    2009-01-01

    Objective: Midkine (MK), a new member of the heparin-binding growth factor family, has been found recently to have a high expression level in many tumor specimens including lung carcinoma. Estrogens may be involved in lung carcinogenesis, and estrogen receptors, mainly estrogen receptor-β (ER-β), are present and functional in normal lung and tumor cell lines and tissues. In addition, estrogens and growth factors may promote the progression of human non-small cell lung cancer (NSCLC). Previously, we have immunohistochemically demonstrated that MK and ER-β proteins were overexpressed in NSCLC and their expression levels were both significantly negatively correlated with the pathological classification. The purpose of this study was to further verify their expression and its correlation with NSCLC.Methods: Taking NSCLC tissues and their corresponding paraneoplastic and normal lung as research objects, we further examined the expression of MK and ER-β by meas of RT-PCR, in situ hybridization and Western blot analyses at the levels of messenger RNA (mRNA) and protein, respectively.Results: The increased MK and ER-β mRNA expression was found in NSCLC by RT-PCR and in situ hybridization analyses. Furthermore, Western blot analysis also displayed increased expression of MK and ER-β proteins in NSCLC. Finally, their correlation analysis at the levels of mRNA and protein expression in NSCLC demonstrated that MK protein level was significantly correlated to estrogen receptor-β (P0.05, r_s=0.178).Conclusion: All these results in the present study confirmed that MK and ER-β were overexpressed in human NSCLC.

  15. Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells.

    Science.gov (United States)

    Parajuli, Bibek; Fishel, Melissa L; Hurley, Thomas D

    2014-01-23

    Aldehyde dehydrogenase enzymes irreversibly oxidize aldehydes generated from metabolism of amino acids, fatty acids, food, smoke, additives, and xenobiotic drugs. Cyclophosphamide is one such xenobiotic used in cancer therapies. Upon activation, cyclophosphamide forms an intermediate, aldophosphamide, which can be detoxified to carboxyphosphamide by aldehyde dehydrogenases (ALDH), especially ALDH1A1 and ALDH3A1. Consequently, selective inhibition of ALDH3A1 could increase chemosensitivity toward cyclophosphamide in ALDH3A1 expressing tumors. Here, we report detailed kinetics and structural characterization of a highly selective submicromolar inhibitor of ALDH3A1, 1-[(4-fluorophenyl)sulfonyl]-2-methyl-1H-benzimidazole (CB7, IC50 of 0.2 μM). CB7 does not inhibit ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2 activity. Structural, kinetics, and mutagenesis studies show that CB7 binds to the aldehyde binding pocket of ALDH3A1. ALDH3A1-expressing lung adenocarcinoma and glioblastoma cell lines are sensitized toward mafosfamide (MF) treatment in the presence analogues of CB7, whereas primary lung fibroblasts lacking ALDH3A1 expression, are not.

  16. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

    Science.gov (United States)

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2016-09-01

    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice.

  17. [Hypofractionated adjuvant radiotherapy for breast cancer: no signs of increased risk of cardiotoxicity].

    Science.gov (United States)

    Aleman, Berthe M P; van Leeuwen, Floor E

    2015-01-01

    Adjuvant radiotherapy is frequently used in women with breast cancer to improve both local control of the tumour and overall survival. Hypofractionated regimens are increasingly being used as they involve fewer treatment sessions and, in terms of tumour control, the effects of conventionally fractionated and hypofractionated radiotherapy seem to be comparable. However, there is concern regarding increased cardiotoxicity following hypofractionated radiotherapy treatment to the left side. In order to determine if cardiac mortality increases with hypofractionation relative to conventional fractionation, a Canadian research group performed a retrospective analysis in 5334 women with breast cancer treated between 1990-1998 with postoperative radiotherapy to the breast/chest wall only. At 15-year follow-up the authors concluded that cardiac mortality was not statistically different among patients with left-sided breast cancer whether treated with hypofractionated or conventionally fractionated whole breast/chest wall irradiation. This commentary discusses the data presented in the paper, puts them into perspective and describes the clinical implications.

  18. Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Inoue-Yamauchi, Akane, E-mail: ainoyama@research.twmu.ac.jp [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Oda, Hideaki [Department of Pathology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer DRP1 is required for mitochondrial fission in colon cancer cells. Black-Right-Pointing-Pointer DRP1 participates in inhibition of colon cancer cell apoptosis. Black-Right-Pointing-Pointer DRP1 can inhibit apoptosis through the regulation of cytochrome c release. -- Abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116 and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.

  19. Designing for Diffusion: How Can We Increase Uptake of Cancer Communication Innovations?

    Science.gov (United States)

    Dearing, James W.; Kreuter, Matthew W.

    2010-01-01

    Objective The best innovations in cancer communication do not necessarily achieve uptake by researchers, public health and clinical practitioners, and policy makers. This paper describes design activities that can be applied and combined for the purpose of spreading effective cancer communication innovations. Methods A previously developed Push-Pull-Infrastructure Model is used to organize and highlight the types of activities that can be deployed during the design phase of innovations. Scientific literature about the diffusion of innovations, knowledge utilization, marketing, public health, and our experiences in working to spread effective practices, programs, and policies are used for this purpose. Results Attempts to broaden the reach, quicken the uptake, and facilitate the use of cancer communication innovations can apply design activities to increase the likelihood of diffusion. Some simple design activities hold considerable promise for improving dissemination and subsequent diffusion. Conclusion Augmenting current dissemination practices with evidence-based concepts from diffusion science, marketing science, and knowledge utilization hold promise for improving results by eliciting greater market pull. Practice Implications Inventors and change agencies seeking to spread cancer communication innovations can experience more success by explicit consideration of design activities that reflect an expanded version of the Push-Pull-Infrastructure Model. PMID:21067884

  20. Colorectal cancer stem cell and chemoresistant colorectal cancer cell phenotypes and increased sensitivity to Notch pathway inhibitor.

    Science.gov (United States)

    Huang, Rui; Wang, Guiyu; Song, Yanni; Tang, Qingchao; You, Qi; Liu, Zheng; Chen, Yinggang; Zhang, Qian; Li, Jiaying; Muhammand, Shan; Wang, Xishan

    2015-08-01

    Colorectal cancer stem cells (Co-CSCs) are a small subpopulation of tumor cells which have been proposed to be tumor-initiating cells in colorectal cancer (CRC) and to be implicated in resistance to standard chemotherapy. Chemoresistance is a common problem in the clinic. However, the interrelation between Co-CSCs and chemoresistant cells has yet to be elucidated. The present study investigated the Co-CSC phenotype in colonospheres and chemoresistant CRC cell lines and aimed to identify targets for therapy. Colonospheres and chemoresistant CRC cells were found to be enriched with the CSC markers CD133 and CD44, and exhibited similar phenotypes. Furthermore, it was found that Notch signaling may simultaneously regulate Co-CSCs and chemoresistant cells and may represent a novel strategy for targeting this pathway in CRC.

  1. A prospective study of occupation and prostate cancer risk.

    Science.gov (United States)

    Zeegers, Maurice P A; Friesema, Ingrid H M; Goldbohm, R Alexandra; van den Brandt, Piet A

    2004-03-01

    A wide variety of occupations has been associated with prostate cancer in previous retrospective studies. Most attention has been paid to farming, metal working, and the rubber industry. Today, these results cannot be affirmed with confidence, because many associations could be influenced by recall bias, have been inconsistent, or have not been confirmed satisfactory in subsequent studies. This study was conducted to investigate and confirm these important associations in a large prospective cohort study. The authors conducted a prospective cohort study among 58,279 men. In September 1986, the cohort members (55-69 years) completed a self-administered questionnaire on potential cancer risk factors, including job history. Related job codes were clustered in professional groups. These predefined clusters were investigated in 3 time windows: 1) profession ever performed, 2) longest profession ever held, and 3) last profession held at baseline. Follow up for incident prostate cancer was established by linkage to cancer registries until December 1993. A case-cohort approach was used based on 830 cases and 1525 subcohort members. To minimize false-positive results, 99% confidence intervals (99% CI) were calculated. Although moderately decreased prostate cancer risks were found for electricians, farmers, firefighters, woodworkers, textile workers, butchers, salesmen, teachers, and clerical workers, none of the relative risks (RR) were found to be statistically significant. For road transporters, metal workers, and managers, no association with prostate cancer risk was found. Although the RR for railway workers, mechanics, welders, chemists, painters, and cooks was moderately increased, these estimates were not statistically significant. For men who reported to have ever worked in the rubber industry, we found a substantially increased prostate cancer risk, but not statistically significant (RR, 4.18; 99% CI = 0.22-80.45). For policemen, we found a substantial and

  2. Expansion of endothelial surface by an increase of vessel diameter during tumor angiogenesis in experimental hepatocellular and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Eduard Ryschich; Eduard Schmidt; Sasa-Marcel Maksan; Ernst Klar; Jan Schmidt

    2004-01-01

    AIM: A low vessel density is a common feature of malignant tumors. We suggested that the expansion of vessel diameter might reconstitute the oxygen and nutritient's supply in this situation. The aim of the present study was to compare the number and diameter of blood vessels in pancreatic and liver carcinoma with normal tissue.METHODS: Tumor induction of pancreatic (DSL6A) or hepatocellular (Morris-hepatoma) carcinoma was performed in male Lewis (pancreatic cancer) and ACI (hepatoma) rats by an orthotopic inoculation of solid tumor fragments (pancreatic cancer) or tumor cells (hepatoma). Six weeks (pancreatic cancer) or 12 d (hepatoma) after tumor implantation, the tumor microvasculature as well as normal pancreatic or liver blood vessels were investigated by intravital microscopy. The number of perfused blood vessels in tumor and healthy tissue was assessed by computer-assisted image analysis.RESULTS: The vessel density in healthy pancreas (565±89n/mm2) was significantly higher compared to pancreatic cancer (116±36 n/mm2) (P<0.001). Healthy liver showed also a significantly higher vessel density (689±36 n/mm2) compared to liver carcinoma (286±32 n/mm2) (P<0.01). The comparison of diameter frequency showed a significant increase of vessel diameter in both malignant tumors compared to normal tissue (P<0.05).CONCLUSION: The expansion of endothelial cells during tumor angiogenesis is accompanied to a large extent by an increase of vessel diameter rather than by formation of new blood vessels. This may be a possible adaptive mechanism by which experimental pancreatic and hepatocellular cancers expand their endothelial diffusion surface of endothelium to compensate for inadequate neoangiogenesis.

  3. Increased chemosensitivity and radiosensitivity of human breast cancer cell lines treated with novel functionalized single-walled carbon nanotubes

    Science.gov (United States)

    Jia, Yijun; Weng, Ziyi; Wang, Chuanying; Zhu, Mingjie; Lu, Yunshu; Ding, Longlong; Wang, Yongkun; Cheng, Xianhua; Lin, Qing; Wu, Kejin

    2017-01-01

    Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay. The cell surviving fractions were determined by colony forming assay. Cell apoptosis induction was monitored by flow cytometry. Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting. The novel synthesized R-O2-FA-CHI-SWCNTs were able to significantly enhance the chemosensitivity and radiosensitivity of human breast cancer cell lines and the material exhibited its expected function by downregulating the expression of Bcl-2, survivin, HIF-1α, P-gp, MRP-1, RAD51 and Ku80.

  4. Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway.

    Directory of Open Access Journals (Sweden)

    M T Weng

    Full Text Available The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.

  5. Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events

    OpenAIRE

    Gustbée, Emma; Anesten, Charlotte; Markkula, Andrea; Simonsson, Maria; Rose, Carsten; Ingvar, Christian; Jernström, Helena

    2013-01-01

    Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from question...

  6. PTEN insufficiency modulates ER+ breast cancer cell cycle progression and increases cell growth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Chiang KC

    2015-08-01

    Full Text Available Kun-Chun Chiang,1,4 Huang-Yang Chen,1 Shu-Yuan Hsu,2 Jong-Hwei S Pang,3 Shang-Yu Wang,4 Jun-Te Hsu,4 Ta-Sen Yeh,4 Li-Wei Chen,5 Sheng-Fong Kuo,6 Chi-Chin Sun,7 Jim-Ming Lee,1 Chun-Nan Yeh,4 Horng-Heng Juang21Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Keelung, 2Department of Anatomy, 3Graduate Institute of Clinical Medical Sciences, 4Department of General Surgery, 5Department of Gastroenterology, 6Department of Endocrinology and Metabolism, 7Department of Ophthalmology, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, Republic of China Abstract: Phosphatase and tensin homolog (PTEN, a well-known tumor suppressor gene and frequently mutated or lost in breast cancer, possesses the negative regulation function over the PI3K/Akt/mTOR pathway. PTEN insufficiency has been associated with advanced breast cancer and poor prognosis of breast cancer patients. Recently, target therapies aimed at PI3K/Akt/mTOR pathway to treat breast cancer have got popularity. However, the exact effect of PTEN on breast cancer cells is still not well understood. This study demonstrated that PTEN knockdown in MCF-7 cells strengthened the downstream gene expressions, including p-Akt, p-ERK1/2, p-mTOR, p-p70s6k, and p-GSK3ß. PTEN knockdown MCF-7 cells had increased cell growth and Ki-67 expression. Further Western blot demonstrated that p27 was repressed obviously with p21 slightly inhibited and CDK1, 2, 4, 6, cyclin A, and Cdc25C were upregulated in MCF-7 PTEN knockdown cells, leading to the higher growth rate. More importantly, PTEN knockdown MCF-7 cells had higher tumorigenesis and tumor growth in vivo. From our current work, we provided more detailed PTEN-mediated mechanisms to stimulate ER+ breast cancer cell growth. Our result may pave the way for further target therapy development used alone or in combination with other drugs for ER+ breast cancer with PTEN insufficiency.Keywords: PTEN, breast cancer, MCF-7

  7. Toward the identification of communities with increased tobacco-associated cancer burden: Application of spatial modeling techniques

    Directory of Open Access Journals (Sweden)

    Noella A Dietz

    2011-01-01

    Full Text Available Introduction: Smoking-attributable risks for lung, esophageal, and head and neck (H/N cancers range from 54% to 90%. Identifying areas with higher than average cancer risk and smoking rates, then targeting those areas for intervention, is one approach to more rapidly lower the overall tobacco disease burden in a given state. Our research team used spatial modeling techniques to identify areas in Florida with higher than expected tobacco-associated cancer incidence clusters. Materials and Methods: Geocoded tobacco-associated incident cancer data from 1998 to 2002 from the Florida Cancer Data System were used. Tobacco-associated cancers included lung, esophageal, and H/N cancers. SaTScan was used to identify geographic areas that had statistically significant (P<0.10 excess age-adjusted rates of tobacco-associated cancers. The Poisson-based spatial scan statistic was used. Phi correlation coefficients were computed to examine associations among block groups with/without overlapping cancer clusters. The logistic regression was used to assess associations between county-level smoking prevalence rates and being diagnosed within versus outside a cancer cluster. Community-level smoking rates were obtained from the 2002 Florida Behavioral Risk Factor Surveillance System (BRFSS. Analyses were repeated using 2007 BRFSS to examine the consistency of associations. Results: Lung cancer clusters were geographically larger for both squamous cell and adenocarcinoma cases in Florida from 1998 to 2002, than esophageal or H/N clusters. There were very few squamous cell and adenocarcinoma esophageal cancer clusters. H/N cancer mapping showed some squamous cell and a very small amount of adenocarcinoma cancer clusters. Phi correlations were generally weak to moderate in strength. The odds of having an invasive lung cancer cluster increased by 12% per increase in the county-level smoking rate. Results were inconsistent for esophageal and H/N cancers, with some

  8. How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients: Current Paradigm and Future Directions

    Directory of Open Access Journals (Sweden)

    Flora Teoh

    2016-01-01

    Full Text Available Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting in a life-threatening, systemic form. Increased susceptibility to such infections in cancer patients is attributed primarily to chemotherapy-induced depression of innate immune cells and weakened epithelial barriers, which are the body’s first-line defenses against fungal infections. Moreover, classical chemotherapeutic agents also have a detrimental effect on components of the adaptive immune system, which further play important roles in the antifungal response. In this review, we discuss the current paradigm regarding the mechanisms behind the increased risk of systemic candidiasis in cancer patients. We also highlight some recent findings, which suggest that chemotherapy may have more extensive effects beyond the human host, in particular towards C. albicans itself and the bacterial microbiota. The extent to which these additional effects contribute towards the development of candidiasis in chemotherapy-treated patients remains to be investigated.

  9. Rs710521[A] on chromosome 3q28 close to TP63 is associated with increased urinary bladder cancer risk.

    Science.gov (United States)

    Lehmann, Marie-Louise; Selinski, Silvia; Blaszkewicz, Meinolf; Orlich, Michael; Ovsiannikov, Daniel; Moormann, Oliver; Guballa, Christoph; Kress, Alexander; Truss, Michael C; Gerullis, Holger; Otto, Thomas; Barski, Dimitri; Niegisch, Günter; Albers, Peter; Frees, Sebastian; Brenner, Walburgis; Thüroff, Joachim W; Angeli-Greaves, Miriam; Seidel, Thilo; Roth, Gerhard; Dietrich, Holger; Ebbinghaus, Rainer; Prager, Hans M; Bolt, Hermann M; Falkenstein, Michael; Zimmermann, Anna; Klein, Torsten; Reckwitz, Thomas; Roemer, Hermann C; Löhlein, Dietrich; Weistenhöfer, Wobbeke; Schöps, Wolfgang; Beg, Anwer E; Aslam, Muhammad; Bánfi, Gergely; Romics, Imre; Ickstadt, Katja; Schwender, Holger; Winterpacht, Andreas; Hengstler, Jan G; Golka, Klaus

    2010-12-01

    Single nucleotide polymorphism (SNP) rs710521[A], located near TP63 on chromosome 3q28, was identified to be significantly associated with increased bladder cancer risk. To investigate the association of rs710521[A] and bladder cancer by new data and by meta-analysis including all published data, rs710521 was studied in 1,425 bladder cancer cases and 1,740 controls that had not been included in previous studies. Blood samples were collected from 1995 to 2010 in Germany (n = 948/1,258), Hungary (n = 262/65), Venezuela (n = 112/190) and Pakistan (n = 103/227) supplemented by a meta-analysis of 5,695 cases and 40,187 controls. Detection of a A/G substitution (rs710521) on chromosome 3q28, position 191128627 was done via fast real-time polymerase chain reaction (rt-PCR). Rs710521[A] is associated with increased risk in the unadjusted analysis (OR = 1.21; 95% Cl = 1.04-1.40; P = 0.011) and in the recessive model adjusted for age, gender, smoking habits and ethnicity (OR = 1.23; 95% Cl = 1.05-1.44; P = 0.010). No difference between individuals occupationally exposed versus not occupationally exposed to urinary bladder carcinogens was observed concerning the relevance of rs710521[A]. Similarly, rs710521[A] did not confer different susceptibility in smokers and non-smokers. Performing a meta-analysis of 5,695 cases and 40,187 controls including all published studies on rs710521, a convincing association with bladder cancer risk was obtained (OR = 1.18; 95% Cl = 1.12-1.25; P < 0.0001). However, the odds ratio is relatively small.

  10. A pilot study on respiratory and digestive tract cancer among woodworkers.

    Science.gov (United States)

    Esping, B; Axelson, O

    1980-09-01

    Cancer of the nose and paranasal sinuses is a known occupational hazard among workers in the furniture industry. An increased frequency of cancer at other sites has also been suggested to occur among different types of woodworkers in the United States, eg, cancer of the gastrointestinal tract and lung but also lymphatic and hematopoietic malignancies. This case-referent study is of a pilot character and was undertaken for the further elucidation of respiratory and digestive tract cancer among Swedish woodworkers. A four-fold excess of respiratory cancer, other than nasal cancer, was found, particularly in relation to furniture workers, whereas no definite excess of digestive tract cancer was indicated. Further studies seem worthwhile regarding cancer hazard in the woodworking industry.

  11. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

    Science.gov (United States)

    Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

  12. Cancer mortality and wood dust exposure among participants in the American Cancer Society Cancer Prevention Study-II (CPS-II).

    Science.gov (United States)

    Stellman, S D; Demers, P A; Colin, D; Boffetta, P

    1998-09-01

    In 1994, the International Agency for Research on Cancer (IARC) classified wood duct as a human carcinogen, based on very strong evidence of a carcinogenic risk of sino-nasal cancer. Excesses of other cancers, including lung and stomach, have been reported among persons employed in wood industries or occupationally exposed to wood dust, but not as consistently. We investigated such possible associations using the mortality experience of 362,823 men enrolled in the American Cancer Society's Cancer Prevention Study-II in 1982 and followed up for 6 years. Within this group, 45,399 men (12.5%) reported either employment in a wood-related occupation or exposure to wood dust or both. Among woodworkers, a small but significant excess risk was found for all cases of death (RR 1.17 (95% CI 1.11-1.24)) and for total malignancies (RR 1.17 (1.05-1.30)). Among men who reported exposure to wood dust, there was an elevated risk of total mortality (Rr 1.07 (1.03-1.11)), total malignancies (RR 1.08 (1.01-1.15)), and lung cancer (RR 1.17 (1.04-1.31)). Among woodworkers, a significant trend (P = 0.02) of increasing risk of lung cancer with increasing duration of exposure was observed. An unexpected, significantly increased mortality from prostate cancer was observed in both wood-employed and wood-exposed, and a twofold increased risk of fatal brain cancer was seen among the former. Lung cancer mortality was especially high among woodworkers who also reported exposure to asbestos or formaldehyde, and it appears that exposure to these known carcinogens may partly explain the observed increased risks. Excess sino-nasal cancer was not observed, but the number of cases was small.

  13. A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010

    DEFF Research Database (Denmark)

    Garnaes, Emilie; Kiss, Katalin; Andersen, Luise;

    2015-01-01

    The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty...... of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs....... Approximately 10% of HPV-positive tumors was genotyped by amplicon next-generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV-positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being...

  14. No increase in brain cancer rates during period of expanding cell phone use

    Science.gov (United States)

    In a new examination of United States cancer incidence data, investigators at the National Cancer Institute (NCI) reported that incidence trends have remained roughly constant for glioma, the main type of brain cancer hypothesized to be related to cell ph

  15. Society of behavioral medicine supports increasing HPV vaccination uptake: an urgent opportunity for cancer prevention.

    Science.gov (United States)

    Peterson, Caryn E; Dykens, J Andrew; Brewer, Noel T; Buscemi, Joanna; Watson, Karriem; Comer-Hagans, DeLawnia; Ramamonjiarivelo, Zo; Fitzgibbon, Marian

    2016-12-01

    Human papillomavirus (HPV) vaccine coverage remains low in the USA. The Society for Behavioral Medicine (SBM) supports the goals outlined by Healthy People 2020, the President's Cancer Panel, and the National Vaccine Advisory Committee to increase vaccination coverage among both males and females. SBM makes the following recommendations in support of efforts to reduce structural and other barriers to HPV vaccination services in order to increase rates of series completion. We encourage legislators and other policymakers to improve administration authority, insurance coverage, and reimbursement rates to healthcare providers who make the HPV vaccine available to adolescents; provide instrumental support to fund the development of school curricula on HPV vaccination; and increase public awareness that HPV vaccination can prevent cancer. We urge healthcare providers and healthcare systems to increase the strength, quality, and consistency of HPV vaccination recommendations for all eligible patients; to treat HPV vaccination as a routine preventive service; employ culturally appropriate communication strategies in clinical settings to educate eligible patients, parents, and guardians about the importance, effectiveness, and safety of HPV vaccination; and to strengthen and better coordinate the use of electronic medical records and immunization information systems.

  16. Cancer Attributable to Asbestos Exposure in Shipbreaking Workers: A Matched-Cohort Study.

    Directory of Open Access Journals (Sweden)

    Wei-Te Wu

    Full Text Available Long-term follow-up studies of asbestos-related cancer in shipbreaking workers are lacking. This study examines the relationship between cancer incidence and asbestos exposure among former Taiwan shipbreaking workers.A total of 4,427 shipbreaking workers and 22,135 population-based matched controls were successfully followed in this study. The study cohort was linked to the Taiwan Cancer Registry for new cancer cases. The adjusted hazard ratio (aHR for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores (TEP for asbestos.Follow-up generated 109,932 person-years, with 940 deaths and 436 cancer cases, among 4,427 shipbreaking workers from 1985 to 2008. The high asbestos exposure group also had a statistically significant increase in the risk of overall cancer (aHR= 1.71; 95% CI: 1.42-2.05, esophagus cancer (aHR= 2.31; 95% CI: 1.00-5.41, liver and intrahepatic bile duct cancer (aHR= 1.60; 95% CI: 1.08-2.36, and trachea, bronchus, and lung cancer (aHR= 3.08; 95% CI: 1.80-5.25. Mesothelioma cases were found in the high asbestos exposure group. Moreover, overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer were seen in a dose-dependent relationship with asbestos exposure.This study presented the elevated trend of asbestos exposure with cancer incidence for overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer among shipbreaking workers. Those workers previously exposed to asbestos should receive persistent monitoring in order to early detect adverse health outcomes.

  17. VMAT planning study in rectal cancer patients

    OpenAIRE

    Shang, Jun; Kong, Wei; Wang, Yan-Yang; Ding, Zhe; Yan, Gang; Zhe, Hong

    2014-01-01

    Background To compare the dosimetric differences among fixed field intensity-modulated radiation therapy (IMRT), single-arc volumetric-modulated arc therapy (SA-VMAT) and double-arc volumetric-modulated arc therapy (DA-VMAT) plans in rectal cancer. Method Fifteen patients with rectal cancer previously treated with IMRT in our institution were selected for this study. For each patient, three plans were generated with the planning CT scan: one using a fixed beam IMRT, and two plans using the VM...

  18. Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jing Jiang

    Full Text Available INTRODUCTION: Galectin-9 (Gal-9 induces adhesion and aggregation of certain cell types and inhibits the metastasis of tumor cells. T-cell immunoglobulin-and mucin domain-3-containing molecule 3 (TIM-3 plays a pivotal role in immune regulation. The aim of this study is to investigate Gal-9 and TIM-3 alterations in gastric cancer and their prognostic values. METHODS: Gal-9 and Tim-3 expression was evaluated using a tissue microarray immunohistochemistry method in 305 gastric cancers, of which 84 had paired adjacent normal samples. Cell lines SGC-7901, BGC-823, MGC-803, MKN45 and GES-1 were also stained. Correlations were analyzed between expression levels of Gal-9 and Tim-3 protein and tumor parameters or clinical outcomes. RESULTS: Gal-9 and Tim-3 stained positive on tumor cells in 86.2% (263/305, and 60.0% (183/305 patients with gastric cancer, respectively. Gal-9 expression was significantly higher in cancer than in normal mucosa (P<0.001. Reduced Gal-9 expression was associated with lymph-vascular invasion, lymph node metastasis, distant metastasis and worse TNM staging (P = 0.034, P = 0.009, P = 0.002 and P = 0.043, respectively. In contrast, Tim-3 expression was significantly lower in cancer than in control mucosa (P<0.001. Patients with lymph-vascular invasion had higher expression levels of Tim-3 (P<0.001. Moreover, multivariate analysis shows that both high Gal-9 expression and low Tim-3 expression were significantly associated with long overall survival (P = 0.002, P = 0.010, respectively; the combination of Gal-9 and Tim-3 expression was an independent prognostic predictor for patients with gastric cancer (RR: 0.43; 95%CI: 0.20-0.93. H.pylori infection status was not associated with Gal-9 and Tim-3 expression (P = 0.102, P = 0.565. CONCLUSION: The results suggest that expression of Gal-9 and Tim-3 in tumor cells may be a potential, independent prognostic factor for patients with gastric cancer. Gal-9 and TIM-3 may play an important part

  19. Exposure to nitrosamines in thirdhand tobacco smoke increases cancer risk in non-smokers.

    Science.gov (United States)

    Ramírez, Noelia; Özel, Mustafa Z; Lewis, Alastair C; Marcé, Rosa M; Borrull, Francesc; Hamilton, Jacqueline F

    2014-10-01

    In addition to passive inhalation, non-smokers, and especially children, are exposed to residual tobacco smoke gases and particles that are deposited to surfaces and dust, known as thirdhand smoke (THS). However, until now the potential cancer risks of this pathway of exposure have been highly uncertain and not considered in public health policy. In this study, we estimate for the first time the potential cancer risk by age group through non-dietary ingestion and dermal exposure to carcinogen N-nitrosamines and tobacco-specific nitrosamines (TSNAs) measured in house dust samples. Using a highly sensitive and selective analytical approach we have determined the presence of nicotine, eight N-nitrosamines and five tobacco-specific nitrosamines in forty-six settled dust samples from homes occupied by both smokers and non-smokers. Using observations of house dust composition, we have estimated the cancer risk by applying the most recent official toxicological information. Calculated cancer risks through exposure to the observed levels of TSNAs at an early life stage (1 to 6years old) exceeded the upper-bound risk recommended by the USEPA in 77% of smokers' and 64% of non-smokers' homes. The maximum risk from exposure to all nitrosamines measured in a smoker occupied home was one excess cancer case per one thousand population exposed. The results presented here highlight the potentially severe long-term consequences of THS exposure, particularly to children, and give strong evidence of its potential health risk and, therefore, they should be considered when developing future environmental and health policies.

  20. Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability

    Directory of Open Access Journals (Sweden)

    Kong Sun-Young

    2008-10-01

    Full Text Available Abstract Background Elucidating the molecular mechanisms by which tumors become resistant to Herceptin is critical for the treatment of Her2-overexpressed metastatic breast cancer. Methods To further understand Herceptin resistance mechanisms at the molecular level, we used comparative proteome approaches to analyze two human breast cancer cell lines; Her2-positive SK-BR-3 cells and its Herceptin-resistant SK-BR-3 (SK-BR-3 HR cells. Results Heat-shock protein 27 (HSP27 expression was shown to be upregulated in SK-BR-3 HR cells. Suppression of HSP27 by specific siRNA transfection increased the susceptibility of SK-BR-3 HR cells to Herceptin. In the presence of Herceptin, Her2 was downregulated in both cell lines. However, Her2 expression was reduced by a greater amount in SK-BR-3 parent cells than in SK-BR-3 HR cells. Interestingly, co-immunoprecipitation analysis showed that HSP27 can bind to Her2. In the absence of Herceptin, HSP27 expression is suppressed and Her2 expression is reduced, indicating that downregulation of Her2 by Herceptin can be obstructed by the formation of a Her2-HSP27 complex. Conclusion Our present study demonstrates that upregulated HSP27 in human breast cancer cells can reduce Herceptin susceptibility by increasing Her2 protein stability.

  1. Osteoprotegerin regulates cancer cell migration through SDF-1/CXCR4 axis and promotes tumour development by increasing neovascularization.

    Science.gov (United States)

    Benslimane-Ahmim, Zahia; Pereira, Jessica; Lokajczyk, Anna; Dizier, Blandine; Galy-Fauroux, Isabelle; Fischer, Anne-Marie; Heymann, Dominique; Boisson-Vidal, Catherine

    2017-06-01

    We previously reported that OPG is involved in ischemic tissue neovascularization through the secretion of SDF-1 by pretreated-OPG endothelial colony-forming cells (ECFCs). As the vascularization is one of the key factor influencing the tumour growth and cancer cell dissemination, we investigated whether OPG was able to modulate the invasion of human MNNG-HOS osteosarcoma and DU145 prostate cancer cell lines in vitro and in vivo. Cell motility was analysed in vitro by using Boyden chambers. Human GFP-labelled MMNG-HOS cells were inoculated in immunodeficient mice and the tumour nodules formed were then injected with OPG and/or FGF-2, AMD3100 or 0.9% NaCl (control group). Tumour growth was manually followed and angiogenesis was assessed by immunohistochemistry. In vitro, SDF-1 released by OPG-pretreated ECFCs markedly attracted both MNNG-HOS and DU145 cells and induced spontaneous migration of cancer cells. In vivo, tumour volumes were significantly increased in OPG-treated group compared to the control group and OPG potentiated the effect of FGF-2. Concomitantly, OPG alone or combined with FGF-2 increased the number of new vasculature compared to the control group. Interestingly AMD3100, an inhibitor of SDF-1, prevented the in vivo effects of OPG induced by SDF-1 This study provides experimental evidence that OPG promotes tumour development trough SDF-1/CXCR4 axis.

  2. Detection of cancer clones in human colorectal adenoma as revealed by increased DNA instability and other bio-markers

    Directory of Open Access Journals (Sweden)

    Y Jin

    2009-06-01

    Full Text Available An immunohistochemical differential staining of cancerous cells with anti-cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N HCl at 30°C for 20 min (DNA-instability test has been used as a marker for malignancy. The test was applied to bioptic tissues of human colorectal polyps assessed histopathologically as hyperplastic polyp (11 cases, tubular adenoma of mild (68 cases, moderate (102 cases, and severe (46 cases dysplasia, and adenocarcinoma (30 cases. The serial sections of the same tissues were also subjected to immunohistochemical staining for Ki67, p53, DNA-fragmentation factor 45 (DFF45 and vascular endothelial growth factor (VEGF. The DNA-instability test was positive in 30 (100% adenocarcinoma cases, 46 (100% severe dysplasia adenoma cases, 36 (35.29% moderate dysplasia adenoma cases, and 8 (11.76% mild dysplasia adenoma cases, indicating malignancy. All hyperplastic polyps were negative to the DNA-instability test. Furthermore, the percentage of glands positive in the DNAinstability test steadily increased in going from mild (10%, to moderate (35%, to severe (100% dysplasia, and adenocarcinoma (100%. All other biological markers tested in the present study showed significantly higher values in those adenoma glands that werepositive to the DNA-instability test, irrespective of the dysplasia grade, as compared to the markers in the adenoma glands that were negative to DNA instability testing. Furthermore, the former values were comparable to those in adenocarcinoma. The results indicate that cancer cell clones are already present at the adenoma stages showing positivity to DNA instability testing, enhanced proliferative activity, p53 mutation and induction of DFF45 and VEGF, at a time when the degree of morphological atypia are not yet large enough for them to be identified as cancer. These factors promote cancer cell proliferation, produce heterogeneous subclones due to DNA instability, enhance their

  3. Mobile Phone Technology to Increase Genetic Counseling for Women with Ovarian Cancer and Their Families

    Science.gov (United States)

    2015-06-01

    2. What is your race? □ White □ Black or African American □ Other: __________________________ 3. Are you of Hispanic, Latino/a, or of Spanish ...overall study objective is to develop and assess the feasibility and effectiveness of a theory -based intervention aimed to encourage ovarian cancer...meetings which resulted in a preliminary draft of the 7-day text message and video intervention. Following completion of the intervention, we will

  4. Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Sayaka; Otake; Hiroaki; Takeda; Shoichiro; Fujishima; Tadahisa; Fukui; Tomohiko; Orii; Takeshi; Sato; Yu; Sasaki; Shoichi; Nishise; Sumio; Kawata

    2010-01-01

    AIM:To investigate the association between adiponectin levels and risk of colorectal adenoma and cancer (early and advanced).METHODS: A cross-sectional study in a cohort of hospital-based patients was conducted between January 2004 and March 2006 at Yamagata University Hospital. Male subjects, who had colorectal tumors detected by endoscopic examination, were enrolled according to inclusion and exclusion criteria. Based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive c...

  5. A Western Dietary Pattern Increases Prostate Cancer Risk: A Systematic Review and Meta-Analysis

    OpenAIRE

    Roberto Fabiani; Liliana Minelli; Gaia Bertarelli; Silvia Bacci

    2016-01-01

    Dietary patterns were recently applied to examine the relationship between eating habits and prostate cancer (PC) risk. While the associations between PC risk with the glycemic index and Mediterranean score have been reviewed, no meta-analysis is currently available on dietary patterns defined by “a posteriori” methods. A literature search was carried out (PubMed, Web of Science) to identify studies reporting the relationship between dietary patterns and PC risk. Relevant dietary patterns wer...

  6. Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer

    Science.gov (United States)

    Zeng, Chao; Wu, Da; Mu, Zhimin; Chen, Baokun; Xie, Yuancai; Ye, Yiwang; Liu, Jixian

    2016-01-01

    Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced proliferation, colony formation and migration of BEAS-2B cells. An increase in TCF21 expression in response to curcumin was also seen, as revealed by real-time PCR (RT-PCR) and western blot. Analysis using the GEO database (access #GSE21210) indicated that a positive correlation existed between TCF21 levels and lung cancer patient survival. TCF21 overexpression and knockdown was introduced to H1299 cells through lentiviral system, which led to suppression and promotion of tumor growth, respectively. We also demonstrated that DNMT1 expression was downregulated by curcumin. Therefore, curcumin exerts its anti-cancer function by downregulating DNMT1, thereby upregulating TCF21. PMID:27894084

  7. Pharmacological ascorbate and ionizing radiation (IR increase labile iron in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Justin C. Moser

    2014-01-01

    Full Text Available Labile iron, i.e. iron that is weakly bound and is relatively unrestricted in its redox activity, has been implicated in both the pathogenesis as well as treatment of cancer. Two cancer treatments where labile iron may contribute to their mechanism of action are pharmacological ascorbate and ionizing radiation (IR. Pharmacological ascorbate has been shown to have tumor-specific toxic effects due to the formation of hydrogen peroxide. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of hydrogen peroxide; labile iron can also react with hydrogen peroxide. Here we have investigated the magnitude of the labile iron pool in tumor and normal tissue. We also examined the ability of pharmacological ascorbate and IR to change the size of the labile iron pool. Although a significant amount of labile iron was seen in tumors (MIA PaCa-2 cells in athymic nude mice, higher levels were seen in murine tissues that were not susceptible to pharmacological ascorbate. Pharmacological ascorbate and irradiation were shown to increase the labile iron in tumor homogenates from this murine model of pancreatic cancer. As both IR and pharmacological ascorbate may rely on labile iron for their effects on tumor tissues, our data suggest that pharmacological ascorbate could be used as a radio-sensitizing agent for some radio-resistant tumors.

  8. Pharmacological ascorbate and ionizing radiation (IR) increase labile iron in pancreatic cancer.

    Science.gov (United States)

    Moser, Justin C; Rawal, Malvika; Wagner, Brett A; Du, Juan; Cullen, Joseph J; Buettner, Garry R

    2013-01-01

    Labile iron, i.e. iron that is weakly bound and is relatively unrestricted in its redox activity, has been implicated in both the pathogenesis as well as treatment of cancer. Two cancer treatments where labile iron may contribute to their mechanism of action are pharmacological ascorbate and ionizing radiation (IR). Pharmacological ascorbate has been shown to have tumor-specific toxic effects due to the formation of hydrogen peroxide. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of hydrogen peroxide; labile iron can also react with hydrogen peroxide. Here we have investigated the magnitude of the labile iron pool in tumor and normal tissue. We also examined the ability of pharmacological ascorbate and IR to change the size of the labile iron pool. Although a significant amount of labile iron was seen in tumors (MIA PaCa-2 cells in athymic nude mice), higher levels were seen in murine tissues that were not susceptible to pharmacological ascorbate. Pharmacological ascorbate and irradiation were shown to increase the labile iron in tumor homogenates from this murine model of pancreatic cancer. As both IR and pharmacological ascorbate may rely on labile iron for their effects on tumor tissues, our data suggest that pharmacological ascorbate could be used as a radio-sensitizing agent for some radio-resistant tumors.

  9. Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of Observational Studies.

    Directory of Open Access Journals (Sweden)

    Weifeng Shang

    Full Text Available The purpose of this paper is to examine cancer incidence in patients with ANCA-associated vasculitis (AASV derived from population-based cohort studies by means of meta-analysis.Relevant electronic databases were searched for studies characterizing the associated risk of overall malignancy in patients with AASV. Standardized incidence rates (SIRs with 95% confidence intervals (CIs were used to evaluate the strength of association. We tested for publication bias and heterogeneity and stratified for site-specific cancers.Six studies (n = 2,578 were eventually identified, of which six provided the SIR for overall malignancy, five reported the SIR for non-melanoma skin cancer (NMSC, four for leukemia, five for bladder cancer, three for lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer, four for prostate cancer, four for colon cancer and four for breast cancer. Overall, the pooled SIR of cancer in AASV patients was 1.74 (95%CI = 1.37-2.21, with moderate heterogeneity among these studies (I(2 = 65.8%, P = 0.012. In sub-analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47-7.73, 4.89 (95%CI = 2.93-8.16 and 3.84 (95%CI = 2.72-5.42 respectively. There was no significant increase in the risk of kidney cancer (SIR = 2.12, 95%CI = 0.66-6.85, prostate cancer (SIR = 1.45, 95%CI = 0.87-2.42, colon cancer (SIR = 1.26, 95%CI = 0.70-2.27, and breast cancer (SIR = 0.95, 95%CI = 0.50-1.79. Among these site-specific cancers, only NMSC showed moderate heterogeneity (I2 = 55.8%, P = 0.06. No publication bias was found by using the Begg's test and Egger's test.This meta-analysis shows that AASV patients treatment with cyclophosphamide (CYC are at increased risk of late-occurring malignancies, particularly of the NMSC, leukemia and bladder cancer. However, there is no significant association between AASV and kidney cancer, prostate cancer

  10. Monitoring of smoking-induced emphysema with CT in a lung cancer screening setting : Detection of real increase in extent of emphysema

    NARCIS (Netherlands)

    Gietema, Hester A.; Schilham, Arnold M.; van Ginneken, Bram; van Klaveren, Rob J.; Lammers, Jan Willem J.; Prokop, Mathias

    2007-01-01

    Purose: To retrospectively establish the minimum increase in emphysema score (ES) required for detection of real Increased extent of emphysema with 95% confidence by using multi-detector row computed tomography (CT) in a lung cancer screening setting. Materials and Methods The study was a substudy o

  11. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.

    Science.gov (United States)

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M; Vadgama, Jaydutt V

    2014-08-05

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.

  12. Increased risk of male cancer and identification of a potential prostate cancer cluster region in BRCA2

    DEFF Research Database (Denmark)

    Roed Nielsen, Henriette; Petersen, Janne; Therkildsen, Christina;

    2016-01-01

    and prostate cancer with cumulative risks of 12.5% and 18.8%, respectively. Breast cancer developed at a mean age of 59 years, typically as ER/PR positive ductal carcinomas. Prostate cancer developed at a mean age of 68 years, with Gleason scores ≥ 8 in 40% of the tumors. The hazard ratio for BRCA2-associated...

  13. Telomere Length Polymorphisms: A Potential Factor Underlying Increased Risk of Prostate Cancer in African American Men and Familial Prostate Cancer

    Science.gov (United States)

    2008-12-01

    markers to allow specific identification of prostate cancer cells in urine cytology specimens. 10 Role: PI Patrick C. Walsh Prostate Cancer Research...Detection of Prostate Cancer in Urine by Multiplex Immunofluorescence and Telomere FISH – Guiding Clinical Decisions Following Negative Prostate

  14. Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, H; Jensenius, Jens Christian; Christensen, I J

    2004-01-01

    in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference (P=0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). CONCLUSIONS: Overall, the MBL complement activation pathway is significantly increased in patients......BACKGROUND: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection......: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P

  15. Increased Porphyrins in Primary Liver Cancer Mainly Reflect a Parallel Liver Disease

    Directory of Open Access Journals (Sweden)

    Jerzy Kaczynski

    2009-01-01

    Full Text Available Hepatic porphyries have been associated with an increased risk of primary liver cancer (PLC, which on the other hand may cause an increased porphyrin production. To evaluate the role of an underlying liver disorder we analyzed porphyrins in patients with hepatocellular carcinoma (HCC (n=65, cholangiocellular carcinoma (n=3, or suspected PLC, which turned out to be metastases (n=18 or a benign disorder (n=11. None of the patients had a family history of porphyry or clinical signs of porphyry. Increased aminolevulinic acid or porphyrin values were common not only in patients with PLC (43% but also in metastatic (50% and benign (64% liver disorders. The corresponding proportion for HCC patients with liver cirrhosis (55% was higher (P<.05 than in those without cirrhosis (17%. We conclude that symptomatic porphyries are unusual in PLC, whereas elevated urinary and/or faecal porphyrins are common, primarily reflecting a parallel liver disease and not the PLC.

  16. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer

    Directory of Open Access Journals (Sweden)

    Simon L Conti

    2016-01-01

    Full Text Available As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted. Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.

  17. Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal/recto sigmoid cancer

    Institute of Scientific and Technical Information of China (English)

    Eeva Salminen; Salla Palmu; Tero Vahlberg; Peter J. Roberts; Karl-Owe S(o)derstr(o)m

    2005-01-01

    AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinicopathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (>40%) and low (≤40%) expression. Areas of extensive proliferation (>50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P<0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) andpresence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.

  18. Changing Epidemiology of Common Cancers in Southern Iran, 2007-2010: A Cross Sectional Study.

    Directory of Open Access Journals (Sweden)

    Seyed Masoom Masoompour

    Full Text Available We have evaluated the ever changing epidemiology of cancers in Fars province, Iran since the re-establishment of Fars cancer registry. Based on the collected data from all related sources in Fars province from 2007-2010 we calculated the cancer age-standardized rates per 100,000 person-years (ASRs. The results are presented as incidence rates of cases by site according to the International Classification of Diseases for Oncology (ICD-O, sex, age, crude rate, and ASRs. In women the total ASR was 41.70 per 100,000 from 1985-1989 which had increased to 55.50 and 95.46 during 1998-2002 and 2007-2010. The incidence of breast cancer in women during 2007-2010 was about two and four times higher than 1998-2002 and 1985-1989. The incidence of colorectal cancer in women during 2007-2010 was about three and five times higher than 1998-2002 and 1985-1989. In men the total ASR was 62.9 per 100,000 in 1985-1989 that increased to 64.50 and 101.48 during 1998-2002 and 2007-2010. Although stomach cancer was the most common cancer among men during 1985-1989 and 1998-2002, but in recent study bladder cancer was the most common cancer among men in Fars province. The incidence of colorectal cancer in men during 2007-2010 was about three times higher than 1998-2002 and 1985-1989. This study shows growing incidence of cancer in southern Iran. The colorectal cancer in both genders had increased and its pattern is similar to western countries. In men, bladder and prostate cancers had a growing rate and the incidences of these cancers in the present study were greater than stomach cancer.

  19. What gastric cancer proteomic studies show about gastric carcinogenesis?

    Science.gov (United States)

    Leal, Mariana Ferreira; Wisnieski, Fernanda; de Oliveira Gigek, Carolina; do Santos, Leonardo Caires; Calcagno, Danielle Queiroz; Burbano, Rommel Rodriguez; Smith, Marilia Cardoso

    2016-08-01

    Gastric cancer is a complex, heterogeneous, and multistep disease. Over the past decades, several studies have aimed to determine the molecular factors that lead to gastric cancer development and progression. After completing the human genome sequencing, proteomic technologies have presented rapid progress. Differently from the relative static state of genome, the cell proteome is dynamic and changes in pathologic conditions. Proteomic approaches have been used to determine proteome profiles and identify differentially expressed proteins between groups of samples, such as neoplastic and nonneoplastic samples or between samples of different cancer subtypes or stages. Therefore, proteomic technologies are a useful tool toward improving the knowledge of gastric cancer molecular pathogenesis and the understanding of tumor heterogeneity. This review aimed to summarize the proteins or protein families that are frequently identified by using high-throughput screening methods and which thus may have a key role in gastric carcinogenesis. The increased knowledge of gastric carcinogenesis will clearly help in the development of new anticancer treatments. Although the studies are still in their infancy, the reviewed proteins may be useful for gastric cancer diagnosis, prognosis, and patient management.

  20. A Comprehensive Study of Extramural Venous Invasion in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    David McClelland

    Full Text Available Colorectal cancer is a common malignancy and a leading cause of cancer related death. Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease. In colorectal cancer, tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome. Increasing emphasis is now being placed on other factors, especially the presence of extramural venous invasion (EMVI. It is important to understand the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance. This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre, using prospectively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period. Overall, EMVI was reported in 27.9% of colorectal cancer excision specimens. In tumours (n = 1928 that had not received neoadjuvant therapy, the presence of EMVI varied significantly depending on tumour site (χ2 = 12.03, p<0.005, tumour stage (χ2 = 268.188, p<0.001, lymph node stage (χ2 = 294.368, p<0.001 and Dukes' stage (χ2 = 253.753, p<0.001. Multivariate analysis confirmed EMVI as a significant independent prognostic indicator (p<0.001. In conclusion, the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors. This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also understanding the relationship of EMVI with other prognostic factors.

  1. A Cohort Study on Risk Factors of Lung Cancer in Yunnan Tin Miners

    Directory of Open Access Journals (Sweden)

    Yong JIANG

    2013-04-01

    Full Text Available Background and objective Smoking is a major cause of lung cancer. Studies of lung cancer among miners have shown that occupational exposure also played an important role. The aim of this study is to investigate radon, cigarette use and other risk factors of lung cancer in Yunnan tin miners and to provide a scientific basis for the prevention and control of occupational lung cancer. Methods A prospective cohort study was conducted among Yunnan tin miners, the associations between potential risk factors for lung cancer were analyzed by multivariate Cox regression model. Effects of age at first radon exposure and radon exposure rate on lung cancer risk were analyzed. The relationship between cumulative working level month and lung cancer was analyzed according to smoking status. The joint effect of tobacco use and cumulative radon exposure was analyzed based on additive and multiplicative models. Results Increased risk of lung cancer was associated with age at enrollment, tobacco use, prior bronchitis, and cumulative arsenic and radon exposure, while higher education level was associated with decreased lung cancer risk. An inverse effect of radon exposure rate was observed. There was no significant association between lung cancer risk and first radon exposure age. There was a significant additive interaction between tobacco use and radon exposure on lung cancer risk. Conclusion Several risk factors may contribute to the high incidence of lung cancer in Yunnan tin miners. Further studies are warranted to evaluate joint effect of different risk factors.

  2. Risk of cancer in patients with iron deficiency anemia: a nationwide population-based study.

    Directory of Open Access Journals (Sweden)

    Ning Hung

    Full Text Available This study evaluated the risk of cancer among patients with iron deficiency anemia (IDA by using a nationwide population-based data set.Patients newly diagnosed with IDA and without antecedent cancer between 2000 and 2010 were recruited from the Taiwan National Health Insurance Research Database. The standardized incidence ratios (SIRs of cancer types among patients with IDA were calculated.Patients with IDA exhibited an increased overall cancer risk (SIR: 2.15. Subgroup analysis showed that patients of both sexes and in all age groups had an increased SIR. After we excluded patients diagnosed with cancer within the first and first 5 years of IDA diagnosis, the SIRs remained significantly elevated at 1.43 and 1.30, respectively. In addition, the risks of pancreatic (SIR: 2.31, kidney (SIR: 2.23, liver (SIR: 1.94, and bladder cancers (SIR: 1.74 remained significantly increased after exclusion of patients diagnosed with cancer within 5 years after IDA diagnosis.The overall cancer risk was significantly elevated among patients with IDA. After we excluded patients diagnosed with IDA and cancer within 1 and 5 years, the SIRs remained significantly elevated compared with those of the general population. The increased risk of cancer was not confined to gastrointestinal cancer when the SIRs of pancreatic, kidney, liver, and bladder cancers significantly increased after exclusion of patients diagnosed with IDA and cancer within the first 5 years. This finding may be caused by immune activities altered by IDA. Further study is necessary to determine the association between IDA and cancer risk.

  3. Risk of Cancer in Patients with Iron Deficiency Anemia: A Nationwide Population-Based Study

    Science.gov (United States)

    Hu, Yu-Wen; Hu, Li-Yu; Yeh, Chiu-Mei; Teng, Chung-Jen; Kuan, Ai-Seon; Chen, San-Chi; Chen, Tzeng-Ji; Liu, Chia-Jen

    2015-01-01

    Objective This study evaluated the risk of cancer among patients with iron deficiency anemia (IDA) by using a nationwide population-based data set. Method Patients newly diagnosed with IDA and without antecedent cancer between 2000 and 2010 were recruited from the Taiwan National Health Insurance Research Database. The standardized incidence ratios (SIRs) of cancer types among patients with IDA were calculated. Results Patients with IDA exhibited an increased overall cancer risk (SIR: 2.15). Subgroup analysis showed that patients of both sexes and in all age groups had an increased SIR. After we excluded patients diagnosed with cancer within the first and first 5 years of IDA diagnosis, the SIRs remained significantly elevated at 1.43 and 1.30, respectively. In addition, the risks of pancreatic (SIR: 2.31), kidney (SIR: 2.23), liver (SIR: 1.94), and bladder cancers (SIR: 1.74) remained significantly increased after exclusion of patients diagnosed with cancer within 5 years after IDA diagnosis. Conclusion The overall cancer risk was significantly elevated among patients with IDA. After we excluded patients diagnosed with IDA and cancer within 1 and 5 years, the SIRs remained significantly elevated compared with those of the general population. The increased risk of cancer was not confined to gastrointestinal cancer when the SIRs of pancreatic, kidney, liver, and bladder cancers significantly increased after exclusion of patients diagnosed with IDA and cancer within the first 5 years. This finding may be caused by immune activities altered by IDA. Further study is necessary to determine the association between IDA and cancer risk. PMID:25781632

  4. Imaging biomarker roadmap for cancer studies

    Science.gov (United States)

    O’Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; deSouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, John R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    2017-01-01

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use. PMID:27725679

  5. A nationwide study on anastomotic leakage after colonic cancer surgery

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Jorgensen, L N; Andreasen, A H

    2012-01-01

    Aim: Anastomotic leakage (AL) is a major challenge in colorectal cancer surgery due to increased morbidity and mortality. Possible risk factors should be investigated differentially, distinguishing between rectal and colonic surgery in large-scale studies to avoid selection bias and confounding....... Method: The incidence and risk factors associated with AL were analysed in an unselected nation-wide prospective cohort of patient subjected to curative colonic cancer surgery with primary anastomosis and entered into The Danish Colorectal Cancer Group database between May 2001 and December 2008. Results......: AL occurred in 593 (6.4%) of 9333 patients. Laparoscopic surgery (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.05-1.70; P = 0.03); left hemicolectomy (OR, 2.02; 95% CI, 1.50-2.72) or sigmoid colectomy (OR, 1.69; 95% CI, 1.32-2.17; P = 0.01); intraoperative blood loss (OR, 1.04; 95% CI, 1...

  6. Cancer patterns among children of Turkish descent in Germany: A study at the German Childhood Cancer Registry

    Directory of Open Access Journals (Sweden)

    Kaatsch Peter

    2008-05-01

    Full Text Available Abstract Background Cancer risks of migrants might differ from risks of the indigenous population due to differences in socioeconomic status, life style, or genetic factors. The aim of this study was to investigate cancer patterns among children of Turkish descent in Germany. Methods We identified cases with Turkish names (as a proxy of Turkish descent among the 37,259 cases of childhood cancer registered in the German Childhood Cancer Registry (GCCR during 1980–2005. As it is not possible to obtain reference population data for children of Turkish descent, the distribution of cancer diagnoses was compared between cases of Turkish descent and all remaining (mainly German cases in the registry, using proportional cancer incidence ratios (PCIRs. Results The overall distribution of cancer diagnoses was similar in the two groups. The PCIRs in three diagnosis groups were increased for cases of Turkish descent: acute non-lymphocytic leukaemia (PCIR 1.23; CI (95% 1.02–1.47, Hodgkin's disease (1.34; 1.13–1.59 and Non-Hodgkin/Burkitt lymphoma (1.19; 1.02–1.39. Age, sex, and period of diagnosis showed no influence on the distribution of diagnoses. Conclusion No major differences were found in cancer patterns among cases of Turkish descent compared to all other cases in the GCCR. Slightly higher proportions of systemic malignant diseases indicate that analytical studies involving migrants may help investigating the causes of such cancers.

  7. Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.

    2014-01-01

    Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective...... of the study was to explore plasma cytokine concentrations in GCC patients randomized to resistance training or usual care during BEP, in comparison with healthy controls. Design/Setting: This was a randomized controlled trial in GCC patients enrolled from an oncology clinic, including a healthy reference......). Changes in TNF-α correlated with pulmonary toxicity (P BEP display consistently elevated levels of systemic inflammatory markers compared with healthy...

  8. Obesity Contributes to Ovarian Cancer Metastatic Success Through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages

    OpenAIRE

    Liu, Yueying; Matthew N. Metzinger; Lewellen, Kyle A.; Cripps, Stephanie N.; Carey, Kyle D.; Harper, Elizabeth I.; Shi, Zonggao; Tarwater, Laura; Grisoli, Annie; Lee, Eric; Slusarz, Ania; Yang, Jing; Loughran, Elizabeth A.; Conley, Kaitlyn; Johnson, Jeff J.

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intra-peritoneal (i.p.) metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obes...

  9. Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative

    OpenAIRE

    Lee, Tsai-Yu; Liu, Chia-Lin; Chang, Yun-Ching; Nieh, Shin; Lin, Yaoh-Shiang; Jao, Shu-Wen; Chen, Su-Feng; Liu, Tsung-Yun

    2016-01-01

    A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smok...

  10. Self-Sampling for Human Papillomavirus Testing among Non-Attenders Increases Attendance to the Norwegian Cervical Cancer Screening Programme

    DEFF Research Database (Denmark)

    Enerly, Espen; Bonde, Jesper; Schee, Kristina;

    2016-01-01

    Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus (HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance....... To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25-69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited...... alternative for increasing cervical cancer screening coverage in Norway....

  11. Social ties and risk for cancer--a prospective cohort study

    DEFF Research Database (Denmark)

    Bergelt, Corinna; Prescott, Eva; Grønbaek, Morten;

    2009-01-01

    (breast, lung, prostate and colon and rectum) were conducted with the Cox proportional hazards model, with adjustment for a number of well-known risk factors for cancer. RESULTS: While we found no significant association between social ties and risk for cancer in men, women with high social network scores......BACKGROUND: Poor social support and small social networks have been associated with increased risks for conditions such as coronary heart disease as well as with overall mortality. We investigated the association between social ties and risk for cancer. MATERIAL AND METHODS: The study sample...... had an increased risk for lung cancer of borderline significance (HR, 2.16; 95% CI, 1.02-4.60). The risks for breast cancer and colorectal cancers were not significantly increased in the same group of women. DISCUSSION: The results of this study do not support the hypothesis that social network size...

  12. Family history of cancer and the risk of laryngeal cancer: a case-control study from Italy and Switzerland.

    Science.gov (United States)

    Garavello, Werner; Turati, Federica; Bosetti, Cristina; Talamini, Renato; Levi, Fabio; Lucenteforte, Ersilia; Chiesa, Fausto; Franceschi, Silvia; La Vecchia, Carlo; Negri, Eva

    2012-02-01

    Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre case-control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval [CI], 1.5-5.3) in subjects reporting a first-degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4-8.8). As compared to subjects without family history, non-smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9-139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0-2.3) and kidney (OR = 3.8, 95% CI 1.2-12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1).

  13. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  14. The Development of a Communication Tool to Facilitate the Cancer Trial Recruitment Process and Increase Research Literacy among Underrepresented Populations.

    Science.gov (United States)

    Torres, Samantha; de la Riva, Erika E; Tom, Laura S; Clayman, Marla L; Taylor, Chirisse; Dong, Xinqi; Simon, Melissa A

    2015-12-01

    Despite increasing need to boost the recruitment of underrepresented populations into cancer trials and biobanking research, few tools exist for facilitating dialogue between researchers and potential research participants during the recruitment process. In this paper, we describe the initial processes of a user-centered design cycle to develop a standardized research communication tool prototype for enhancing research literacy among individuals from underrepresented populations considering enrollment in cancer research and biobanking studies. We present qualitative feedback and recommendations on the prototype's design and content from potential end users: five clinical trial recruiters and ten potential research participants recruited from an academic medical center. Participants were given the prototype (a set of laminated cards) and were asked to provide feedback about the tool's content, design elements, and word choices during semi-structured, in-person interviews. Results suggest that the prototype was well received by recruiters and patients alike. They favored the simplicity, lay language, and layout of the cards. They also noted areas for improvement, leading to card refinements that included the following: addressing additional topic areas, clarifying research processes, increasing the number of diverse images, and using alternative word choices. Our process for refining user interfaces and iterating content in early phases of design may inform future efforts to develop tools for use in clinical research or biobanking studies to increase research literacy.

  15. Salvianolic acid B reverses multidrug resistance in HCT‑8/VCR human colorectal cancer cells by increasing ROS levels.

    Science.gov (United States)

    Guo, Piaoting; Wang, Songpo; Liang, Wei; Wang, Wenjing; Wang, Huijun; Zhao, Miaomiao; Liu, Xiaowei

    2017-02-01

    Salvianolic acid B (SalB) a water‑soluble phenolic compound, extracted from Salvia miltiorrhiza, has previously been demonstrated to reverse tumor multidrug resistance (MDR), including in colorectal cancer. Reactive oxygen species (ROS) are oxygen radicals generated during aerobic metabolism (superoxide and hydroxyl radicals) and superoxide easily generating free radicals (H2O2). The concept that increased ROS levels can lead to augmented tumor cell‑sensitivity to chemotherapy drugs has become notable. The aim of the present study was to elucidate the role of ROS in mediating the effect of SalB on drug resistance and the correlation with drug resistance‑associated protein, P‑glycoprotein (P‑gp), and apoptosis‑associated proteins, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X (Bax). In the current study, through utilizing the multidrug resistant colorectal cancer cell line, HCT‑8/VCR, it was demonstrate that SalB reversed MDR in HCT‑8/VCR. In addition, SalB significantly increased ROS levels, which may have accelerated the apoptosis of HCT‑8/VCR cells by downregulating Bcl‑2 and increasing Bax protein expression. Furthermore the increased intracellular ROS levels may have inhibited P‑gp expression at the gene and protein levels. In conclusion, the data of the current study demonstrate that SalB reversed MDR in HCT‑8/VCR cells, and the effect is associated with increased ROS levels, which may downregulate P‑gp expression and promote tumor cell apoptosis, which in turn increases the sensitivity of drug‑resistant cells to chemotherapy drugs.

  16. Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer.

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    Kerstin B Meyer

    2008-05-01

    Full Text Available The recent whole-genome scan for breast cancer has revealed the FGFR2 (fibroblast growth factor receptor 2 gene as a locus associated with a small, but highly significant, increase in the risk of developing breast cancer. Using fine-scale genetic mapping of the region, it has been possible to narrow the causative locus to a haplotype of eight strongly linked single nucleotide polymorphisms (SNPs spanning a region of 7.5 kilobases (kb in the second intron of the FGFR2 gene. Here we describe a functional analysis to define the causative SNP, and we propose a model for a disease mechanism. Using gene expression microarray data, we observed a trend of increased FGFR2 expression in the rare homozygotes. This trend was confirmed using real-time (RT PCR, with the difference between the rare and the common homozygotes yielding a Wilcox p-value of 0.028. To elucidate which SNPs might be responsible for this difference, we examined protein-DNA interactions for the eight most strongly disease-associated SNPs in different breast cell lines. We identify two cis-regulatory SNPs that alter binding affinity for transcription factors Oct-1/Runx2 and C/EBPbeta, and we demonstrate that both sites are occupied in vivo. In transient transfection experiments, the two SNPs can synergize giving rise to increased FGFR2 expression. We propose a model in which the Oct-1/Runx2 and C/EBPbeta binding sites in the disease-associated allele are able to lead to an increase in FGFR2 gene expression, thereby increasing the propensity for tumour formation.

  17. Gambogic Acid Lysinate Induces Apoptosis in Breast Cancer MCF-7 Cells by Increasing Reactive Oxygen Species

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    Yong-Zhan Zhen

    2015-01-01

    Full Text Available Gambogic acid (GA inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited. Objectives. To investigate the antitumor activity of gambogic acid lysinate (GAL and its mechanism. Methods. Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot. Results. GAL inhibited the proliferation of MCF-7 cells with IC50 values 1.46 μmol/L comparable with GA (IC50, 1.16 μmol/L. GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3. Conclusions. GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy.

  18. Nutrition and cancer: Review of epidemiological studies and clinical trials

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    Demosthenes Panagiotakos

    2010-07-01

    Full Text Available Risk factors of cancer include unhealthy dietary habits, physical inactivity, smoking, various genetic and environmental factors. Cancer is the second cause of death after cardiovascular diseases with increased incidence; moreover, 80% of gastrointestinal, breast and prostate cancers are attributed to unhealthy eating habits. Many surveys have investigated the role of diet in cancer prevention. Here we summarized current knowledge about dietary factors associated with cancer incidence. There is a strong correlation of the protective effect of fruits and vegetables with colon cancer and the negative effect of red meat and the protective effect of milk on colorectal cancer. High alcohol consumption is related to higher incidence of mouth and esophageal cancers, with hot drinks playing a role in mouth or even gastrointestinal cancers. High fat consumption seems to play a negative role in colorectal cancer, where sugar and salt might be negatively related to stomach cancer. Beyond nutrition, physical inactivity and body fat seems to play an important role in cancer, where there are strong evidence that the first protects against colorectal cancer and the second increases the incidence of breast cancer after menopause. Data for the role of micronutrients, vitamins and minerals lead to the suggestion that dietary supplements should be avoided and all nutritional needs should be covered through a well balanced diet.

  19. A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer.

    Science.gov (United States)

    Shen, Hongbing; Wang, Luo; Spitz, Margaret R; Hong, Waun K; Mao, Li; Wei, Qingyi

    2002-09-01

    DNA repair is central to genomic integrity. Reduced expression of several nucleotide excision repair genes has been demonstrated to be associated with increased risk of lung cancer. Because methylation of gene promoters is one of the major regulatory mechanisms of gene expression and most nucleotide excision repair gene promoters have not been fully characterized, we hypothesized that genetic variants of the genes that are responsible for regulating genomic methylation are associated with increased risk of lung cancer. Recently, we identified a C-->T transition at a novel promoter region of cytosine DNA-methyltransferase-3B (DNMT3B) and found that this polymorphic transition significantly increases the promoter activity. In this hospital-based case-control study of 319 patients with incident lung cancer and 340 healthy controls frequency matched on age (+/-5 years), sex, ethnicity, and smoking status, we genotyped subjects for this DNMT3B promoter polymorphism to determine the association between this genetic variant and risk of lung cancer. Compared with CC homozygotes, CT heterozygotes had a >2-fold increased risk of lung cancer [adjusted odds ratio (OR), 2.13; 95% confidence interval (CI), 1.47-3.08] and TT homozygotes an OR of 1.42 (95% CI, 0.91-2.21). The combined variant genotype (CT + TT) was associated with a nearly 2-fold increased risk (adjusted OR, 1.88; 95% CI, 1.32-2.66). These results suggest that this novel variant of DNMT3B is associated with increased risk of lung cancer and may contribute to identifying individuals genetically susceptible to tobacco-induced cancers. Additional studies on the underlying molecular mechanism of this polymorphism are warranted.

  20. Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer.

    Science.gov (United States)

    Chen, Yi; Pirisi, Lucia; Creek, Kim E

    2013-09-01

    We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer.

  1. DNA aptamers as molecular probes for colorectal cancer study.

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    Kwame Sefah

    Full Text Available BACKGROUND: Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development. METHODOLOGY AND RESULTS: Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh, nor do they recognize most other cancer cell lines tested. CONCLUSION/SIGNIFICANCE: The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers.

  2. CT-Screening for lung cancer does not increase the use of anxiolytic or antidepressant medication

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    Kaerlev Linda

    2012-05-01

    Full Text Available Abstract Background CT screening for lung cancer has recently been shown to reduce lung cancer mortality, but screening may have adverse mental health effects. We calculated risk ratios for prescription of anti-depressive (AD or anxiolytic (AX medication redeemed at Danish pharmacies for participants in The Danish Lung Cancer Screening Trial (DLCST. Methods The DLCST was a randomized clinical trial which comprised 4,104 former or present smokers who were randomized from 12 May 2004 to 20 June 2006 to either CT scan of the chest, lung-function test and filling in questionnaires annually for five years in the period 1 April 2006–31 March 2010 (n = 2,052, or to a control group (n = 2,052 receiving similar procedures except CT scan. We used CT scan intervention group versus control group status as exposure. The follow-up period for use of AD or AX was three years. Baseline data on civil status, socioeconomic status, and co-morbidity as well as outcome data on AD and AX were obtained by linkage to national registries. Results The intervention and the control groups did not differ by age, gender, civil status, socio-economic position, co-morbidity index or former use of AD or AX. The adjusted risk ratio for at least one recipe of AD or AX in the CT intervention group during follow-up was not increased when adjusting for previous use of AD or AX, HR 1.00, 95 % CI (0.90-1.12. Similar results were seen when excluding subjects using AD or AX in a four-month or two-year period before baseline, when analyzing AD and AX separately, or requiring at least two recipes. Conclusions We found no indications that participation in a lung cancer CT-screening program increases the risk of specific adverse mental health outcomes. Trial registration Clinical Trials.gov Protocol Registration System (NCT00496977.

  3. Consumption of dietary fat and meat and risk of ovarian cancer in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Gilsing, A.M.J.; Weijenberg, M.P.; Goldbohm, R.A.; Brandt, P.A. van den; Schouten, L.J.

    2011-01-01

    Background: Evidence that links dietary factors to ovarian cancer is conflicting, but several epidemiologic studies suggested that consumption of dietary fat and meat may increase risk of ovarian cancer. Objective: We studied associations of intakes of total fat and sources and subtypes of fat, fres

  4. The expression of S100P increases and promotes cellular proliferation by increasing nuclear translocation of β-catenin in endometrial cancer.

    Science.gov (United States)

    Guo, Luyan; Chen, Shuqin; Jiang, Hongye; Huang, Jiaming; Jin, Wenyan; Yao, Shuzhong

    2014-01-01

    There is increasing evidence suggesting that S100P has a significant role in cancer, and is associated with poor clinical outcomes. The expression of S100P mRNA and protein in endometrial cancer and normal endometrium tissues was detected by real-time quantitative RT-PCR and immunohistochemistry. Moreover, we reduced the expression of S100P in HEC-1A and Ishikawa endometrial cancer cell lines by siRNA transfection. Based on the reduced S100P mRNA expression, we measured the effects of S100P on cellular proliferation by the cell-counting kit-8. Nuclear β-catenin protein level was detected by western blotting. Cyclin D1 and c-myc mRNA expression regulated by β-catenin was detected by real-time quantitative RT-PCR. We found that the expression of S100P mRNA and protein increased in endometrial cancer tissues compared with the normal endometrium. Local S100P expression progressively increased from pathologic differenciation grade 1 to 3. After reducing the S100P expression, the cellular proliferation ability, nuclear β-catenin protein level, cyclin D1 and c-myc mRNA levels reduced. It indicated that S100P could promote cell proliferation by increasing nuclear translocation of β-catenin. The expression of S100P mRNA and protein in endometrial cancer significantly increased and is associated with pathologic differenciation grade. S100P may promote endometrial cell proliferation by increasing nuclear translocation of β-catenin.

  5. The Heritability of Breast Cancer among women in the Nordic Twin Study of Cancer

    DEFF Research Database (Denmark)

    Möller, Sören; Mucci, Lorelei A; Harris, Jennifer R;

    2016-01-01

    and heritability of breast cancer among 21,054 monozygotic and 30,939 dizygotic female twin pairs from the Nordic Twin Study of Cancer, the largest twin study of cancer in the world. We accounted for left-censoring, right-censoring, as well as the competing risk of death. Results From 1943 through 2010, 3...

  6. High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

    DEFF Research Database (Denmark)

    Rask, Lene; Balslev, Eva; Jørgensen, Stine

    2011-01-01

    Low-risk and high-risk breast cancer patients are stratified primarily according to their lymph node (LN) status and grading. However, some low-risk patients relapse, and some high-risk patients have a favorable clinical outcome, implying a need for better prognostic and predictive tests. Micro...... RNAs are often aberrantly expressed in cancer and microRNA-21 is upregulated in a variety of cancers, including breast cancer. High miR-21 levels have been associated with poor prognosis. To determine the cellular localization of miR-21 and to compare its expression levels with histopathological...... features, we performed in situ hybridization and semi-quantitative assessment of the miR-21 signal on 12 LN negative grade I (assumed low risk), and 12 LN positive grade II (high risk) breast cancers. miR-21 was predominantly seen in cancer associated fibroblast-like cells, with no difference in expression...

  7. Increased risk of carcinoma in situ in patients with testicular germ cell cancer with ultrasonic microlithiasis in the contralateral testicle

    DEFF Research Database (Denmark)

    Holm, Mette; Hoei-Hansen, Christina E; Rajpert-De Meyts, Ewa;

    2003-01-01

    We compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia....

  8. Diabetes and risk of incident cancer: a large population-based cohort study in Israel.

    Science.gov (United States)

    Chodick, Gabriel; Heymann, Anthony D; Rosenmann, Lena; Green, Manfred S; Flash, Shira; Porath, Avi; Kokia, Ehud; Shalev, Varda

    2010-06-01

    Type 2 diabetes mellitus has been associated with an increased risk of a variety of cancers in observational studies, but few have reported the relationship between diabetes and cancer risk in men and women separately. The main goal of this retrospective cohort study was to evaluate the sex-specific risk of incident overall and site-specific cancer among people with DM compared with those without, who had no reported history of cancer at the start of the follow-up in January 2000. During an average of 8 years of follow-up (SD = 2.5), we documented 1,639 and 7,945 incident cases of cancer among 16,721 people with DM and 83,874 free of DM, respectively. In women, DM was associated with an adjusted hazard ratio of 1.96 (95% CI: 1.53-2.50) and 1.41 (95% CI: 1.20-1.66) for cancers of genital organs and digestive organs, respectively. A significantly reduced HR was observed for skin cancer (0.38; 95% CI: 0.22-0.66). In men with DM, there was no significant increase in overall risk of cancer. DM was related with a 47% reduction in the risk of prostate cancer. These findings suggest that the nature of the association between DM and cancer depends on sex and specific cancer site.

  9. Afatinib increases sensitivity to radiation in non-small cell lung cancer cells with acquired EGFR T790M mutation.

    Science.gov (United States)

    Zhang, Shirong; Zheng, Xiaoliang; Huang, Haixiu; Wu, Kan; Wang, Bing; Chen, Xufeng; Ma, Shenglin

    2015-03-20

    Afatinib is a second-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has shown a significant clinical benefit in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the potential therapeutic effects of afatinib combining with other modalities, including ionizing radiation (IR), are not well understood. In this study, we developed a gefitinib-resistant cell subline (PC-9-GR) with a secondary EGFR mutation (T790M) from NSCLC PC-9 cells after chronic exposures to increasing doses of gefitinib. The presence of afatinib significantly increases the cell killing effect of radiation in PC-9-GR cells harboring acquired T790M, but not in H1975 cells with de novo T790M or in H460 cells that express wild-type EGFR. In PC-9-GR cells, afatinib remarkable blocks baseline of EGFR and ERK phosphorylations, and causes delay of IR-induced AKT phosphorylation. Afatinib treatment also leads to increased apoptosis and suppressed DNA damage repair in irradiated PC-9-GR cells, and enhanced tumor growth inhibition when combined with IR in PC-9-GR xenografts. Our findings suggest a potential therapeutic impact of afatinib as a radiation sensitizer in lung cancer cells harboring acquired T790M mutation, providing a rationale for a clinical trial with combination of afatinib and radiation in NSCLCs with EGFR T790M mutation.

  10. Does Extending the Waiting Time of Low-Rectal Cancer Surgery after Neoadjuvant Chemoradiation Increase the Perioperative Complications?

    Science.gov (United States)

    Timudom, Kittinut; Phothong, Natthawut; Akaraviputh, Thawatchai; Chinswangwatanakul, Vitoon; Pongpaibul, Ananya; Petsuksiri, Janjira; Ithimakin, Suthinee

    2016-01-01

    Background. Traditionally, rectal cancer surgery is recommended 6 to 8 weeks after completing neoadjuvant chemoradiation. Extending the waiting time may increase the tumor response rate. However, the perioperative complication rate may increase. The purpose of this study was to determine the association between extending the waiting time of surgery after neoadjuvant chemoradiation and perioperative outcomes. Methods. Sixty patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by radical resection at Siriraj hospital between June 2012 and January 2015 were retrospectively analyzed. Demographic data and perioperative outcomes were compared between the two groups. Results. The two groups were comparable in term of demographic parameters. The mean time interval from neoadjuvant chemoradiation to surgery was 6.4 weeks in Group A and 11.7 weeks in Group B. The perioperative outcomes were not significantly different between Groups A and B. Pathologic examination showed a significantly higher rate of circumferential margin positivity in Group A than in Group B (30% versus 9.3%, resp.; P = 0.04). Conclusions. Extending the waiting to >8 weeks from neoadjuvant chemoradiation to surgery did not increase perioperative complications, whereas the rate of circumferential margin positivity decreased.

  11. Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells.

    Science.gov (United States)

    Chatterji, Tanushree; Varkaris, Andreas S; Parikh, Nila U; Song, Jian H; Cheng, Chien-Jui; Schweppe, Rebecca E; Alexander, Stephanie; Davis, John W; Troncoso, Patricia; Friedl, Peter; Kuang, Jian; Lin, Sue-Hwa; Gallick, Gary E

    2015-04-30

    To study the role of FAK signaling complexes in promoting metastatic properties of prostate cancer (PCa) cells, we selected stable, highly migratory variants, termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3 and DU145. These variants were not only increased migration and invasion in vitro, but were also more metastatic to lymph nodes following intraprostatic injection into nude mice. Both PC3 Mig-3 and DU145 Mig-3 were specifically increased in phosphorylation of FAK Y861. We therefore examined potential alterations in Src family kinases responsible for FAK phosphorylation and determined only Yes expression was increased. Overexpression of Yes in PC3 parental cells and src-/-fyn-/-yes-/- fibroblasts selectively increased FAK Y861 phosphorylation, and increased migration. Knockdown of Yes in PC3 Mig-3 cells decreased migration and decreased lymph node metastasis following orthotopic implantation of into nude mice. In human specimens, Yes expression was increased in lymph node metastases relative to paired primary tumors from the same patient, and increased pFAK Y861 expression in lymph node metastases correlated with poor prognosis. These results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis.

  12. Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy

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    Tan Murly BM

    2009-03-01

    Full Text Available Abstract Background Women at increased (genetic risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this study was to asses: 1 the acceptance of the offer of a standard psychological consultation as part of pre-surgical decision-making in high-risk women, 2 reasons for PM and reasons for postponing it, 3 the need for additional psychological interventions, and factors associated, and 4 the frequency of psychiatric/psychological treatment history. Methods During a 30 months period, women at high risk considering PM were offered a psychological consultation. The content of these, and follow-up, consultations were analyzed. Results Most women (70 out of 73 accepted the psychological consultation, and 81% proceeded with PM. Main reasons for undergoing PM were to reduce anxiety about cancer, and to reduce the cancer risk. Uncertainty about surgery and the need for further information were the reasons given most frequently for postponing PM. Additional psychological support was given to 31% before and 14% after PM. The uptake of additional support was significantly higher in women with a BRCA1/2 mutation. A history of psychiatric/psychological treatment was present in 36%, mainly consisting of depression and grief after death of a mother. Conclusion The uptake-rate of the standard psychological consultation indicates a high level of acceptability of this service for women deciding about PM. Since anxiety is one of the main reasons for considering PM, and depression and grief were present in a third, a standard consultation with a psychologist for high-risk women considering PM may be indicated. This may help them arrive at an informed decision, to detect and manage psychological distress, and to plan psychological support services.

  13. Increased risk of carcinoma in situ in patients with testicular germ cell cancer with ultrasonic microlithiasis in the contralateral testicle

    DEFF Research Database (Denmark)

    Holm, Mette; Hoei-Hansen, Christina E; Rajpert-De Meyts, Ewa;

    2003-01-01

    We compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia.......We compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia....

  14. Food intake in three groups of cancer patients. A prospective study during cancer treatment.

    Science.gov (United States)

    Hulshof, K F; Gooskens, A C; Wedel, M; Bruning, P F

    1987-02-01

    The dietary intake of 105 adult Dutch Caucasian patients (28 women with endometrial or cervical cancer, 50 men with bladder or prostate cancer and 14 men and 13 women with malignant lymphoma) was studied for 19 weeks. Energy and nutrient intakes of all patients were assessed by a dietary history with cross-check over 2 months prior to treatment and by seven 48-h dietary records filled in just before, during and after cancer therapy. No differences were observed between the results obtained with the dietary history and the first 48-h diary. In females treated with abdominal irradiation the mean daily intake of fat, dietary fibre, iron and thiamin decreased during therapy. In men treated with radiotherapy the intake of vegetable protein, polysaccharides, dietary fibre and thiamin also decreased during treatment. This may be partly explained by the observation that many of these patients had spontaneously chosen a 'constipating diet' because of diarrhoea. As compared with the Dutch Recommended Dietary Allowance only the iron intake of the women gave rise to some concern. In our study we did not observe marked changes in dietary intake and nutritional status. In females who underwent irradiation therapy especially, the dietary intake increased after a period of intensive treatment. This demonstrates that food intake of these groups of cancer patients is not consistently reduced by chemotherapy or even abdominal radiotherapy.

  15. A Case-Control Study of Risk Factors for Prostate Cancer in Iran

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    Mahmoud Mahmoudi

    2010-02-01

    Full Text Available Prostate cancer is a major cause of morbidity and mortality in Iran, yet there are few studies examining risk factors specific to the Iranian context. We conducted a case-control study to explore risk factors for prostate cancer in Mazandaran, Iran from 2005 to 2008. The cases were 137 men with clinicopathologically confirmed prostate cancer. Controls were 137 neighborhood and age match men without prostate cancer by PSA and digit examination. Analysis comprised an exploratory stage to identify potential risk factors, defined as variables associated with case status at the P < 0.20 level in conditional logistic regression. A second stage included all potential risk factors in multiple conditional logistic regression analysis, retaining those associated with prostate cancer at the P < 0.05 level. Potential risk factors for prostate cancer in exploratory analysis included family history of prostate cancer, history of other cancer, prostatitis, alcohol consumption, pipe or hookah smoking, walking to work, duration of occupational physical activity, intensity of occupational physical activity, body mass index, and older age. Multivariate analysis found intensity of occupational physical activity, prostatitis, and older age as independent predictors of increased risk for prostate cancer in this Iranian population. Our study confirms several recognized risk factors for prostate cancer, contributes evidence to the discussions of other hypothesized risk factors, and points to potentially new factors. Findings, along with confirmatory studies, can help guide efforts for early detection, treatment, and prevention for this common malignancy that is set to increase in Iran in future decades.

  16. Retrospective cohort study of cancer morbidity in furniture makers exposed to wood dust.

    Science.gov (United States)

    Barthel, E; Dietrich, M

    1989-05-01

    A retrospective cohort study was undertaken to examine the cancer morbidity in a group of 759 furniture makers of the Neubrandenburg District. During the study interval of 1973 to 1984, a total of 40 malignant tumors occurred in the exposed group. Except for bronchial cancer (SIR = 68) and prostate cancer (SIR = 43), all observed tumors were overrepresented in comparison to the incidence of such illnesses in the normal population of the study area. Significantly increased SIRs occurred for malignant melanoma (2 cases, SIR = 952) and for rectal cancer (6 cases, SIR = 239). Malignant tumors of the nose and paranasal sinuses were not observed.

  17. Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids - early effect

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    Makarewicz Jacek

    2010-10-01

    Full Text Available Abstract Introduction Radioiodine (131I therapy is widely accepted as an essential part of therapeutic regimens in many cases of differentiated thyroid cancer. Radiation-induced oxidative damage to macromolecules is a well known phenomenon. Frequently examined process to evaluate oxidative damage to macromolecules is lipid peroxidation (LPO, resulting from oxidative damage to membrane lipids. The aim of the study was to examine serum LPO level in hypothyroid (after total thyroidectomy cancer patients subjected to ablative activities of 131I. Materials and methods The study was carried out in 21 patients (18 females and 3 males, average age 52.4 ± 16.5 years after total thyroidectomy for papillary (17 patients or follicular (4 patients thyroid carcinoma. Hypothyroidism was confirmed by increased TSH blood concentration (BRAHMS, Germany, measured before 131I therapy. Activity of 2.8 - 6.9 GBq of 131I was administered to the patients orally as sodium iodide (OBRI, Poland. Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA, as an index of LPO (LPO-586 kit, Calbiochem, USA, were measured in blood serum just before 131I administration (day "0" and on the days 1-4 after 131I therapy. Sera from 23 euthyroid patients served as controls. Correlations between LPO and TSH or 131I activity were calculated. Results Expectedly, serum LPO level, when measured before 131I therapy, was several times higher (p 131I therapy. LPO did not correlate with TSH concentration. In turn, negative correlation was found between 131I activity and LPO level on the day "2" after radioiodine treatment. Conclusions Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.

  18. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

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    Manuela Oraldi

    2009-01-01

    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  19. Betalains increase vitexin-2-O-xyloside cytotoxicity in CaCo-2 cancer cells.

    Science.gov (United States)

    Farabegoli, F; Scarpa, E S; Frati, A; Serafini, G; Papi, A; Spisni, E; Antonini, E; Benedetti, S; Ninfali, P

    2017-03-01

    Vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L. (BVc) seeds, betaxanthin (R1) and betacyanin (R2) fractions from Beta vulgaris var. rubra L. (BVr) roots were combined and tested for cytotoxicity in CaCo-2 colon cancer cells. XVX was the most cytotoxic molecule, but the combination of XVX with R1 and R2 significantly prolonged its cytotoxicity. Cytotoxicity was mediated by the intrinsic apoptotic pathway, as shown by an increase in Bcl2-like protein 4, cleaved Poly ADP-Ribosyl Polymerase 1 and cleaved Caspase 3 levels with a parallel decrease in anti-apoptotic protein B-cell leukemia/lymphoma 2 levels. R1 and R2, used alone or in combination, reduced oxidative stress triggered by H2O2 in CaCo-2 cells. Betalains dampened cyclooxygenase-2 and interleukin-8 mRNA expression after lipopolysaccharide induction in CaCo-2, showing an anti-inflammatory action. Our results support the use of a cocktail of R1, R2 and XVX as a chemopreventive tool against colon cancer.

  20. Cancer preceding Wegener's granulomatosis: a case-control study

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Sørensen, Inge Juul;

    2009-01-01

    OBJECTIVE: To investigate whether patients with WG have an increased risk of malignancies prior to and/or around the time of the vasculitis diagnosis, as suggested by previous studies. METHODS: A total of 293 WG patients were included in the study. Ten gender- and age-matched controls were selected...... interval (OR 4.0; 95% CI 1.4, 12). CONCLUSIONS: We did not find clear evidence of an increased prevalence of preceding cancer in our WG cohort, indicating that shared risk factors are of minor importance for the excess of malignancies that occur in WG patients after the vasculitis diagnosis. Furthermore...

  1. Bullying increased suicide risk: prospective study of Korean adolescents.

    Science.gov (United States)

    Kim, Young Shin; Leventhal, Bennett L; Koh, Yun-Joo; Boyce, W Thomas

    2009-01-01

    This study examines the independent impact of bullying on suicide risk. Bullying was assessed by peer nomination in a prospective study of 1,655 7th and 8th grade Korean students, and suicide by youth self-report. Odds Ratios (ORs) of bullying for suicidal risks were computed, controlling for other suicide risk factors. Victim-Perpetrators and female Victims at baseline showed increased risk for persistent suicidality (OR: 2.4-9.8). Male Incident Victims exhibited increased risk for suicidal behaviors and ideations (OR = 4.4, 3.6). Female Persistent Perpetrators exhibited increased risks for suicidal behaviors; male Incident Perpetrators had increased risk for suicidal ideations (OR = 2.7, 2.3). Baseline-only male Victim-Perpetrators showed increased risk for suicidal ideations. (OR = 6.4). Bullying independently increased suicide risks.

  2. ROLE OF CARICINOGENS IN ORAL CANCER: A MICRONUCLEUS STUDY

    Directory of Open Access Journals (Sweden)

    Pratheepa Sivasankari. N

    2015-12-01

    Full Text Available Background: The three most common fatal cancers were oral, stomach, lung in men. Tobacco related cancers represented 42% in male and 18.3% in female cancer deaths. Poly cyclic aromatic hydrocarbons (PAH is the carcinogen present in tobacco leads to squamous cell carcinoma of oral cavity. Context and purpose of the study: To study the genotoxicity of tobacco and alcohol on the buccal mucosa of alchoholics, smokers and betel nut chewers which is indicated by increased Micro nuclei. 20 persons having the habit of consuming alcohol and smoking and betel nut chewing were compared with 20 controls. After getting the informed consent the material was collected and stained for MN Assay. Results: MN frequency in alcoholic, smokers, betel nut chewers were found to be significant with the ‘P’ value of <0.05 in our study. Conclusion: The present study has revealed that there is a correlation of significant increased frequency of micro nucleus present in users of (1 alcohol and smoking in combination (2 betel nut chewers as compared to normal counterparts, indicating strong cytogenetic damage which may lead to cancerous proliferation. Tobacco can be considered as a leading carcinogenic agent for causing DNA damage which is indicated by increased micro nucleus. Implication: The present micro nuclear study shows a feasible and economical method which could be used as a screening test in population having the habit of alcohol and smoking or betel nut chewing for identifying the effects of genomic instabilities and to introduce timely interventional strategy in order to treat and control the epidemic.

  3. Gene Expression Correlation for Cancer Diagnosis: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Binbing Ling

    2014-01-01

    Full Text Available Poor prognosis for late-stage, high-grade, and recurrent cancers has been motivating cancer researchers to search for more efficient biomarkers to identify the onset of cancer. Recent advances in constructing and dynamically analyzing biomolecular networks for different types of cancer have provided a promising novel strategy to detect tumorigenesis and metastasis. The observation of different biomolecular networks associated with normal and cancerous states led us to hypothesize that correlations for gene expressions could serve as valid indicators of early cancer development. In this pilot study, we tested our hypothesis by examining whether the mRNA expressions of three randomly selected cancer-related genes PIK3C3, PIM3, and PTEN were correlated during cancer progression and the correlation coefficients could be used for cancer diagnosis. Strong correlations (0.68≤r≤1.0 were observed between PIK3C3 and PIM3 in breast cancer, between PIK3C3 and PTEN in breast and ovary cancers, and between PIM3 and PTEN in breast, kidney, liver, and thyroid cancers during disease progression, implicating that the correlations for cancer network gene expressions could serve as a supplement to current clinical biomarkers, such as cancer antigens, for early cancer diagnosis.

  4. Study Ties Alcohol Abuse to Increased Heart Risks

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_162836.html Study Ties Alcohol Abuse to Increased Heart Risks Association similar to that ... 2009. About 2 percent had been diagnosed with alcohol abuse. The researchers adjusted statistics so they wouldn't ...

  5. CT-Screening for lung cancer does not increase the use of anxiolytic or antidepressant medication

    DEFF Research Database (Denmark)

    Kaerlev, Linda; Iachina, Maria; Pedersen, Jesper Holst

    2012-01-01

    CT screening for lung cancer has recently been shown to reduce lung cancer mortality, but screening may have adverse mental health effects. We calculated risk ratios for prescription of anti-depressive (AD) or anxiolytic (AX) medication redeemed at Danish pharmacies for participants in The Danish...... Lung Cancer Screening Trial (DLCST)....

  6. Could mining be protective against prostate cancer? A study and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Girschik, J.; Glass, D.; Ambrosini, G.L.; Fritschi, L. [Western Australian Institute of Medical Research, Perth, WA (Australia)

    2010-06-15

    Prostate cancer is one of the most commonly diagnosed cancers in Western men and one in three Australian men develops the cancer before the age of 75. Currently, only increasing age, race and family history have been well established as risk factors. A growing number of studies have investigated occupation in relation to prostate cancer but, like other risk factors, no associations have been confirmed. Mining employs a significant proportion of the work force in Western Australia. The aims of this study were to describe the characteristics of miners in the Western Australian Prostate Health Study, investigate mining as a risk factor for prostate cancer, conduct a systematic search of the literature for studies that have investigated mining as an occupational risk factor for prostate cancer and compare and contrast their methodologies and results. Data were obtained from a population-based case-control study conducted from 1 January 2001 to 20 August 2002 at The University of Western Australia. After controlling for age, family history and military service in Vietnam, miners had a statistically significantly reduced risk of prostate cancer (adjusted OR 0.35, 95% CI 0.16 to 0.75). The systematic literature search of studies examining mining and prostate cancer found a reasonably consistent trend of a decreased risk of prostate cancer among miners. None of the published articles discussed their results regarding mining and prostate cancer in detail, and a biological mechanism to support these results has not previously been suggested.

  7. CORRELATION OF BREAST CANCER AND SERUM HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL: A SINGLE CENTRE STUDY

    Directory of Open Access Journals (Sweden)

    Anjali

    2015-12-01

    Full Text Available Breast cancer is the most common site specific cancer in women. Lots of etiological factors have been suggested regarding its causation. The risk is influenced by obesity, parity, exogenous and endogenous hormones, exposure to chemicals and radiation and many more. Various studies suggest that as HDL-C seems to be cardio protective, it is also protective for breast cancer. Serum HDL-C levels are found to be low in breast cancer patients. We studied this hypothesis in local population of Southern Rajasthan and nearby region to see if low serum HDL-C is associated with increased risk of breast cancer. We studied serum HDL-C level in 50 female patients of breast cancer along with their menopausal status and compared it to their respective controls. We found that breast cancer patients had significantly low level of serum HDL-C and presented in advanced stage of cancer. It supports that low serum HDL-C level is associated with increased risk of breast cancer. So one should think about those dietary and lifestyle measures, which maintain high serum HDL-C level so that it might become preventive measure for breast cancer.

  8. Insulin-like growth factor binding protein-2 level is increased in blood of lung cancer patients and associated with poor survival.

    Directory of Open Access Journals (Sweden)

    Chengcheng Guo

    Full Text Available BACKGROUND: We recently showed that IGFBP2 is overexpressed in primary lung cancer tissues. This study aims to determine whether IGFBP2 is elevated in blood samples of lung cancer patients and whether its level is associated with clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: Plasma IGFBP2 levels were determined blindly by enzyme-linked immunosorbent assay in 80 lung cancer patients and 80 case-matched healthy controls for comparison. We analyzed blood samples for IGFBP2 levels from an additional 84 patients with lung cancer and then tested for associations between blood IGFBP2 levels and clinical parameters in all 164 lung cancer patients. All statistical tests were two-sided and differences with p160.9 ng/ml is 15.1 months; whereas median survival time was 128.2 months for the patients whose blood IGFBP2 was ≤ 160.9 ng/ml (p =0.0002. CONCLUSIONS/SIGNIFICANCE: Blood IGFBP2 is significantly increased in lung cancer patients. A high circulating level of IGFBP2 is significantly associated with poor survival, suggesting that blood IGFBP2 levels could be a prognostic biomarker for lung cancer.

  9. BRCA1 polymorphisms and breast cancer epidemiology in the Western New York exposures and breast cancer (WEB) study.

    Science.gov (United States)

    Ricks-Santi, Luisel J; Nie, Jing; Marian, Catalin; Ochs-Balcom, Heather M; Trevisan, Maurizio; Edge, Stephen B; Kanaan, Yasmine; Freudenheim, Jo L; Shields, Peter G

    2013-07-01

    Results of studies for the association of BRCA1 genotypes and haplotypes with sporadic breast cancer have been inconsistent. Therefore, a candidate single nucleotide polymorphism (SNP) approach was used in a breast cancer case-control study to explore genotypes and haplotypes that have the potential to affect protein functions or levels. In a breast cancer case-control study, genotyping of BRCA1 polymorphisms Q356R, D693N, and E1038G was performed on 1,005 cases and 1,765 controls. Unconditional, polytomous logistic regression and χ(2) -tests were used to examine the associations of breast cancer with genotypes and haplotypes. In addition, interactions between genotype and smoking, benign breast disease, family history of breast cancer, body mass index (BMI), alcohol consumption, and hormonal risk factors, hormone receptor status, and breast cancer pathology were calculated also using logistic regression and χ(2) . Although sporadic breast cancer was not associated with BRCA1 genotypes or haplotypes overall or by menopausal status, there was evidence of an interaction between the E1038G BRCA1 genotype, smoking, and BMI among premenopausal women (P for interaction = 0.01 and 0.045, respectively) and between E1038G and D693N BRCA1 genotypes and hormone therapy use among postmenopausal women (P for interaction = 0.01 and 0.02, respectively). There were no other associations found between BRCA1 genotypes and stage, histological grade, or nuclear grade. However, the D693N SNP was associated with the risk of triple negative breast cancer (odds ratio = 2.31 95% confidence interval 1.08-4.93). The BRCA1 variants studied may play a role in the etiology of triple negative breast cancer and may interact with environmental factors such as hormone therapy or smoking and increase sporadic breast cancer risk.

  10. Study protocol of KLIMOP: a cohort study on the wellbeing of older cancer patients in Belgium and the Netherlands

    Directory of Open Access Journals (Sweden)

    Verniest Thessa

    2011-10-01

    Full Text Available Abstract Background Cancer is mainly a disease of older patients. In older cancer patients, additional endpoints such as quality of survival and daily functioning might be considered equally relevant as overall or disease free survival. However, these factors have been understudied using prospective designs focussing on older cancer patients. Therefore, this study will focus on the impact of cancer, ageing, and their interaction on the long-term wellbeing of older cancer patients. Methods/Design This study is an observational cohort study. We aim to recruit 720 cancer patients above 70 years with a new diagnosis of breast, prostate, lung or gastrointestinal cancer and two control groups: one control group of 720 patients above 70 years without a previous diagnosis of cancer and one control group of 720 cancer patients between 50 - 69 years newly diagnosed with breast, prostate, lung or gastrointestinal cancer. Data collection will take place at inclusion, after six months, after one year and every subsequent year until death or end of the study. Data will be collected through personal interviews (consisting of socio-demographic information, general health information, a comprehensive geriatric assessment, quality of life, health locus of control and a loneliness scale, a handgrip test, assessment of medical records, two buccal swabs and a blood sample from cancer patients (at baseline. As an annex study, caregivers of the participants will be recruited as well. Data collection for caregivers will consist of a self-administered questionnaire examining depression, coping, and burden. Discussion This extensive data collection will increase insight on how wellbeing of older cancer patients is affected by cancer (diagnosis and treatment, ageing, and their interaction. Results may provide new insights, which might contribute to the improvement of care for older cancer patients.

  11. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    Directory of Open Access Journals (Sweden)

    Ko SH

    2016-09-01

    Full Text Available Sun-Hye Ko,1,2 Myong Ki Baeg,2,3 Woong Jin Bae,4 Pumsoo Kim,3 Myung-Gyu Choi2 1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 2Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 3Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon, South Korea; 4Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, South Korea Background/aims: Patients being treated for prostate cancer (PCa have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs is unknown. We aimed to investigate the risk of CRNs in PCa patients.Materials and methods: Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1 histological findings of high-grade dysplasia, 2 inclusion of villous features, 3 tumor ≥1 cm in size, or 4 presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis.Results: A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0

  12. Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells

    NARCIS (Netherlands)

    Clinton, GM; Rougeot, C; Derancourt, J; Roger, P; Defrenne, A; Godyna, S; Argraves, WS; Rochefort, H

    1996-01-01

    Ovarian cancers have a high ability to invade the peritoneal cavity and some are stimulated by estrogens, In an attempt to understand the mode of action of estrogens on these cancer cells and to develop new markers, we have characterized estrogen-regulated proteins, This study,vas aimed at identifyi

  13. HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive

    DEFF Research Database (Denmark)

    Olsen, Dorte A; Østergaard, Birthe; Bokmand, Susanne

    2007-01-01

    BACKGROUND: The level of HER-2/neu in breast cancer cells is normally measured by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). It determines whether patients should be treated with trastuzumab (Herceptin). In this study, HER-2 protein in breast cancer tissue...

  14. Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms

    Science.gov (United States)

    Singh, Jagdeep K.; Farnie, Gillian; Bundred, Nigel J.; Simões, Bruno M; Shergill, Amrita; Landberg, Göran; Howell, Sacha; Clarke, Robert B.

    2012-01-01

    Purpose Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are predicted to be responsible for tumour initiation, maintenance and metastases. Interleukin-8 (IL-8) is upregulated in breast cancer and associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. Experimental design CSC activity of metastatic and invasive human breast cancers (n=19) was assessed ex vivo using the mammosphere colony forming assay. Results Metastatic fluid IL-8 level correlated directly with mammosphere formation (r=0.652; P<0.05; n=10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in metastatic and invasive breast cancers (n=17). IL-8 induced activation of EGFR/HER2 and downstream signalling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, PI3K or MEK. Furthermore, lapatinib inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers. Conclusions These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and demonstrate that IL-8/CXCR1/2 signalling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients. PMID:23149820

  15. Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on diet and cancer

    NARCIS (Netherlands)

    Mommers, M.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2006-01-01

    Ovary cancer risk in relation to consumption of dairy products was investigated using a self-administered questionnaire on dietary habits and other risk factors for cancer, which was completed in 1986 by 62 573 postmenopausal women participating in the Netherlands Cohort Study. Follow-up for cancer

  16. RASSF1A promoter methylation is associated with increased risk of thyroid cancer: a meta-analysis

    Science.gov (United States)

    Shou, Feiyan; Xu, Feng; Li, Gang; Zhao, Zhenhua; Mao, Ying; Yang, Fangfang; Wang, Hongming; Guo, Hangyuan

    2017-01-01

    Objective Previous studies have reported that Ras-associated domain family 1A (RASSF1A), the most commonly silenced tumor suppressor via promoter methylation, played vital roles in the development of carcinogenesis. The purpose of this meta-analysis was to determine whether RASSF1A promoter methylation increased the risk of thyroid cancer. Methods PubMed, Embase, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure databases were searched to obtain eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations, using Stata 12.0 software. The methodological quality of included studies was evaluated using Newcastle–Ottawa scale table. Egger’s test and Begg’s test were applied to detect publication biases. TSA 0.9 software was used to calculate the required information size and whether the result was conclusive. Results A total of 10 articles with 12 studies that included 422 thyroid cancer patients, identifying the association of RASSF1A promoter methylation with thyroid cancer risk, were collected in this meta-analysis. Overall, RASSF1A promoter methylation significantly increased the risk of thyroid cancer (total, OR=8.27, CI=4.38–15.62, P<0.05; Caucasian, OR=9.25, CI=3.97–21.56, P<0.05; Asian, OR=7.01, CI=2.68–18.38, P<0.05). In the subgroup analysis based on sample type, a significant association between thyroid cancer group and control group was found (normal tissue, OR=9.55, CI=4.21–21.67, P<0.05; adjacent tissue, OR=6.80, CI=2.49–18.56, P<0.05). The frequency of RASSF1A promoter methylation in follicular thyroid carcinoma was higher than in control group (OR=11.88, CI=5.80–24.32, P<0.05). In addition, the results indicated that the RASSF1A promoter methylation was correlated with papillary thyroid carcinoma in Caucasians and Asians (total, OR=8.07, CI=3.54–18.41, P<0.05; Caucasian, OR=11.35, CI=2.39–53.98, P<0.05; Asian, OR=6.67, CI=2.53–17

  17. RASSF1A promoter methylation is associated with increased risk of thyroid cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Shou FY

    2017-01-01

    Full Text Available Feiyan Shou,1,* Feng Xu,2,* Gang Li,1 Zhenhua Zhao,3 Ying Mao,4 Fangfang Yang,5 Hongming Wang,6 Hangyuan Guo5 1Department of General Practice, 2Department of Breast and Thyroid Surgery, 3Department of Radiology, 4Department of Special Inspection Section, 5Department of Cardiovascular Diseases, 6Department of Acupuncture and Moxibustion, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China *These authors contributed equally to this work Objective: Previous studies have reported that Ras-associated domain family 1A (RASSF1A, the most commonly silenced tumor suppressor via promoter methylation, played vital roles in the development of carcinogenesis. The purpose of this meta-analysis was to determine whether RASSF1A promoter methylation increased the risk of thyroid cancer. Methods: PubMed, Embase, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure databases were searched to obtain eligible studies. The pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the strength of the associations, using Stata 12.0 software. The methodological quality of included studies was evaluated using Newcastle–Ottawa scale table. Egger’s test and Begg’s test were applied to detect publication biases. TSA 0.9 software was used to calculate the required information size and whether the result was conclusive. Results: A total of 10 articles with 12 studies that included 422 thyroid cancer patients, identifying the association of RASSF1A promoter methylation with thyroid cancer risk, were collected in this meta-analysis. Overall, RASSF1A promoter methylation significantly increased the risk of thyroid cancer (total, OR=8.27, CI=4.38–15.62, P<0.05; Caucasian, OR=9.25, CI=3.97–21.56, P<0.05; Asian, OR=7.01, CI=2.68–18.38, P<0.05. In the subgroup analysis based on sample type, a significant association between thyroid cancer group and control group was found (normal tissue, OR=9.55, CI=4.21–21

  18. RNA interference targeting extracellular matrix metalloproteinase inducer (CD147) inhibits growth and increases chemosensitivity in human cervical cancer cells.

    Science.gov (United States)

    Zhang, F; Zeng, Y L; Zhang, X G; Chen, W J; Yang, R; Li, S J

    2013-01-01

    Overexpression of extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN CD147) has been implicated in the growth and survival of malignant cells. However, its presence and role in cervical cancer cells has not been well-studied. In the present study, small interfering RNA (siRNA) was designed and synthesized to breakdown the expression of CD147. The present data demonstrated that 24 and 48 hours after transfecting CD147 siRNA, both the CD147 mRNA and protein expression were significantly inhibited as determined by quantitative real-time polymerase chain reaction (RT-PCR) and immunocytochemistry. Meanwhile, simultaneous silencing of CD147 resulted in distinctly increasing MMP-9, VEGF, and MDR-1. Further studies demonstrated decreased CD147 expression, resulted in G1/S phase transition with flow cytometry analysis, as well as the resistance of the cells to 5-FU. These findings provide further evidence that CD147 may become a promising therapeutic target for human cervical cancer and a potential chemotherapy-sensitizing agent.

  19. microRNA-183 plays as oncogenes by increasing cell proliferation, migration and invasion via targeting protein phosphatase 2A in renal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Mingning, E-mail: lcuzfy@163.com; Liu, Lei, E-mail: leiliulab@163.com; Chen, Lieqian, E-mail: lieqianchen@163.com; Tan, Guobin, E-mail: guobintan@163.com; Liang, Ziji, E-mail: zijilianglab@163.com; Wang, Kangning, E-mail: kangningwanglab@163.com; Liu, Jianjun, E-mail: jianjunliulab@163.com; Chen, Hege, E-mail: hegechen@163.com

    2014-09-12

    Highlights: • miR-183 was up-regulated in renal cancer tissues. • Inhibition of endogenous miR-183 suppressed renal cancer cell growth and metastasis. • miR-183 increased cell growth and metastasis. • miR-183 regulated renal cancer cell growth and metastasis via directly targeting tumor suppressor protein phosphatase 2A. - Abstract: The aim of this study was to investigate the function of miR-183 in renal cancer cells and the mechanisms miR-183 regulates this process. In this study, level of miR-183 in clinical renal cancer specimens was detected by quantitative real-time PCR. miR-183 was up- and down-regulated in two renal cancer cell lines ACHN and A498, respectively, and cell proliferation, Caspase 3/7 activity, colony formation, in vitro migration and invasion were measured; and then the mechanisms of miR-183 regulating was analyzed. We found that miR-183 was up-regulated in renal cancer tissues; inhibition of endogenous miR-183 suppressed in vitro cell proliferation, colony formation, migration, and invasion and stimulated Caspase 3/7 activity; up-regulated miR-183 increased cell growth and metastasis and suppressed Caspase 3/7 activity. We also found that miR-183 directly targeted tumor suppressor, specifically the 3′UTR of three subunits of protein phosphatase 2A (PP2A-Cα, PP2A-Cβ, and PP2A-B56-γ) transcripts, inhibiting their expression and regulated the downstream regulators p21, p27, MMP2/3/7 and TIMP1/2/3/4. These results revealed the oncogenes role of miR-183 in renal cancer cells via direct targeting protein phosphatase 2A.

  20. Diagnostic accuracy and tolerability of contrast enhanced CT colonoscopy in symptomatic patients with increased risk for colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ozsunar, Yelda [Department of Radiology, School of Medicine, Adnan Menderes University, Aydin (Turkey)], E-mail: yozsunar@adu.edu.tr; Coskun, Guelten [Izmir Ataturk Egitim ve Arastirma Hastanesi, Izmir (Turkey); Delibas, Naciye; Uz, Burcin [Department of Radiology, School of Medicine, Adnan Menderes University, Aydin (Turkey); Yuekselen, Vahit [Department of Gastroenterology, School of Medicine, Adnan Menderes University, Aydin (Turkey)

    2009-09-15

    Objective: We compared the accuracy and tolerability of intravenous contrast enhanced spiral computed tomography colonography (CTC) and optical colonoscopy (OC) for the detection of colorectal neoplasia in symptomatic patients for colorectal neoplasia. Methods: A prospective study was performed in 48 patients with symptomatic patients with increased risk for colorectal cancer. Spiral CTC was performed in supine and prone positions after colonic cleansing. The axial, 2D MPR and virtual endoluminal views were analyzed. Results of spiral CTC were compared with OC which was done within 15 days. The psychometric tolerance test was asked to be performed for both CTC and colonoscopy after the procedure. Results: Ten lesions in 9 of 48 patients were found in CTC and confirmed with OC. Two masses and eight polyps, consisted of 1 tubulovillous, 1 tubular, 2 villous adenoma, 4 adenomatous polyp, 4 adenocarcinoma, were identified. Lesion prevalence was 21%. Sensitivity, specificity, accuracy, positive and negative predictive values were found 100%, 87%, 89%, 67% and 100%, respectively. Psychometric tolerance test showed that CTC significantly more comfortable comparing with OC (p = 0.00). CTC was the preferred method in 37% while OC was preferred in 6% of patients. In both techniques, the most unpleasant part was bowel cleansing. Conclusion: Contrast enhanced CTC is a highly accurate method in detecting colorectal lesions. Since the technique was found to be more comfortable and less time consuming compare to OE, it may be preferable in management of symptomatic patients with increased risk for colorectal cancer.

  1. Mortality among offspring of women diagnosed with cancer: a population-based cohort study.

    Science.gov (United States)

    Verkooijen, Helena M; Ang, Joella X; Liu, Jenny; Czene, Kamila; Salim, Agus; Hartman, Mikael

    2013-05-15

    One in five cancers in women is diagnosed prior to and during a woman's fertile years. Our study evaluates mortality risks in offspring of mothers with history of cancer. From the Swedish Multi-generation Register and the Cancer Register, we identified all 174,893 children whose mother had been diagnosed with cancer between 1958 and 2001. We categorized offspring into those born before (>1 year before), around (within 1 year before and after diagnosis) and after (>1 year after) their mother's cancer diagnosis and compared their risks of death (standardized mortality ratios, SMRs) and causes of death to the background population. Overall, offspring of mothers diagnosed with cancer had no increased mortality risk (SMR, 1.00; 95% confidence interval [CI], 0.97-1.03). Increased mortality risks were found in offspring of mothers with tobacco-related cancers (head and neck, thoracic and cervical) (SMR, 1.23; 95% CI, 1.13-1.33), in children born around their mother's diagnosis (SMR, 1.66; 95% CI, 1.25-2.13) and in children born after their mother's hematopoietic cancer diagnosis (SMR, 2.07; 95% CI, 1.10-3.35). Compared to the background population, children born around their mother's diagnosis were more likely to die of congenital and perinatal conditions. Overall, offspring of women diagnosed with cancer were not at increased risk of death, except for certain subgroups. Timing of pregnancy in relation to diagnosis and cancer site modifies mortality risks in the offspring.

  2. The Cervix Cancer Research Network (CCRN: Increasing access to cancer clinical trials in low- and middle-income countries

    Directory of Open Access Journals (Sweden)

    Gita eSuneja

    2015-02-01

    Full Text Available Introduction: The burden of cervical cancer is large and growing in developing countries, due in large part to limited access to screening services and lack of human papillomavirus (HPV vaccination. In spite of modern advances in diagnostic and therapeutic modalities, outcomes from cervical cancer have not markedly improved in recent years. Novel clinical trials are urgently needed to improve outcomes from cervical cancer worldwide. Methods: The Cervix Cancer Research Network (CCRN, a subsidiary of the Gynecologic Cancer InterGroup (GCIG, is a multi-national, multi-institutional consortium of physicians and scientists focused on improving cervical cancer outcomes worldwide by making cancer clinical trials available in low-, middle-, and high-income countries. Standard operating procedures for participation in CCRN include a pre-qualifying questionnaire to evaluate clinical activities and research infrastructure, followed by a site visit. Once a site is approved, they may choose to participate in one of four currently accruing clinical trials.Results: To date, 13 different CCRN site visits have been performed. Of these 13 sites visited, 10 have been approved as CCRN sites including Tata Memorial Hospital, India; Bangalore, India; Trivandrum, India; Ramathibodi, Thailand; Siriaj, Thailand; Pramongkutklao, Thailand; Ho Chi Minh, Vietnam; Blokhin Russian Cancer Research Center; the Hertzen Moscow Cancer Research Institute; and the Russian Scientific Center of Roentgenoradiology. The four currently accruing clinical trials are TACO, OUTBACK, INTERLACE, and SHAPE.Discussion: The CCRN has successfully enrolled 10 sites in developing countries to participate in four randomized clinical trials. The primary objectives are to provide novel therapeutics to regions with the greatest need and to improve the validity and generalizability of clinical trial results by enrolling a diverse sample of patients.

  3. HLA-Cw group 1 ligands for KIR increase susceptibility to invasive cervical cancer.

    Science.gov (United States)

    Martin, Maureen P; Borecki, Ingrid B; Zhang, Zhengyan; Nguyen, Loan; Ma, Duanduan; Gao, Xiaojiang; Qi, Ying; Carrington, Mary; Rader, Janet S

    2010-12-01

    Inherited genetic polymorphisms within immune response genes have been shown to associate with risk of invasive cervical cancer (ICC) and its immediate precursor, cervical intraepithelial neoplasia grade 3. Here, we used the transmission/disequilibrium test to detect disease-liability alleles and investigate haplotype transmission of KIR and HLA class I polymorphisms in a large family-based population of women with cervical cancer and their biological parents (359 trios). The effect of distinct human papillomavirus types was also explored. HLA-Cw group 1 (HLA-Cw alleles with asparagine at position 80), which serves as ligand for certain killer immunoglobulin-like receptors (KIR), was significantly overtransmitted in women with ICC (P = 0.04), and particularly in the subgroup of women infected with high risk HPV16 or 18 subtypes (P = 0.008). These data support the involvement of the HLA-C locus in modulating the risk of cervical neoplasia perhaps through its function as ligands for KIR, but functional studies are essential to confirm this hypothesis.

  4. Increased serum midkine concentration as a possible tumor marker in patients with superficial esophageal cancer.

    Science.gov (United States)

    Shimada, Hideaki; Nabeya, Yoshihiro; Okazumi, Shin-ichi; Matsubara, Hisahiro; Kadomatsu, Kenji; Muramatsu, Takashi; Ikematsu, Shinya; Sakuma, Sadatoshi; Ochiai, Takenori

    2003-01-01

    Midkine, a heparin-binding growth factor, is expressed in numerous cancer tissues and is reportedly elevated in patients with various neoplasms. The aim of this study was to evaluate the clinicopathological significance of serum midkine concentration (S-MK) in patients with superficial esophageal squamous cell carcinoma (SCC). Pretreatment S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 60 patients with primary superficial esophageal squamous cell cancer (SESCC). All patients with SESCC underwent curative resection. The disease was staged according to TNM/UICC guidelines. Serum concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated in the same populations. S-MK in patients with SESCC (388+/-411 pg/ml) was significantly higher than in benign esophageal disease or healthy controls (183+/-73 and 154+/-76 pg/ml, respectively). Using the mean + 2 standard deviations of healthy control S-MK (300 pg/ml) as the cut-off level, 50% of patients with esophageal SESCC were deemed positive. This S-MK positivity rate for detecting SESCC was significantly higher than for other tumor markers. Thus, S-MK may be useful as a tumor marker to detect SESCC.

  5. A COMPARATIVE STUDY OF CAREGIVER BURDEN IN CANCER CERVIX AND CANCER BREAST ILLNESSES

    Directory of Open Access Journals (Sweden)

    Srinivasagopalan, Nappinnai, Solayappan

    2015-07-01

    Full Text Available Background: Caregivers of individuals suffering from cancer illnesses are at risk of having subjected to mental health consequences. There is a paucity of data comparing the caregiver burden of cancer breast and cancer cervix patients. Aim: The aim of the present study is to compare the caregiver burden of cancer breast and cancer cervix patients. To study the association of caregiver burden with demographic factors like age, gender, duration of caregiving etc. Materials & Methods: This Cross sectional study is performed on the key relatives of patients of 31 cancer cervix and 31 cancer breast patients. Burden assessment schedule was used. Results: Our findings suggest burden is more in male caregivers of breast cancer patients. It is not so in caregivers of cancer cervix patients. Whenever the caregiver is closely related to the patients the burden is high in both groups. Whenever the burden scores were high the depression scores were also high. Treatment modalities as a whole correlates with burden scores in caregivers of breast cancer patients but not in cancer cervix patients. Conclusion: Caregivers with breast and cervical cancer patients are vulnerable if the caregiver is male, from low socioeconomical background, more closely related and when the patients received poor treatment modalities.

  6. An interactive portal to empower cancer survivors: a qualitative study on user expectations

    NARCIS (Netherlands)

    Kuijpers, W.; Groen, W.G.; Loos, R.; Oldenburg, H.S.A.; Wouters, M.W.J.M.; Aaronson, N.K.; van Harten, W.H.

    2015-01-01

    Purpose: Portals are increasingly used to improve patient empowerment, but are still uncommon in oncology. In this study, we explored cancer survivors’ and health professionals’ expectations of possible features of an interactive portal. Methods: We conducted three focus groups with breast cancer su

  7. An interactive portal to empower cancer survivors: a qualitative study on user expectations

    NARCIS (Netherlands)

    Kuijpers, Wilma; Groen, Wim G.; Loos, Romy; Oldenburg, Hester S.A.; Wouters, Michel W.J.M.; Aaronson, Neil K.; Harten, van W.H.

    2015-01-01

    Purpose Portals are increasingly used to improve patient empowerment, but are still uncommon in oncology. In this study, we explored cancer survivors’ and health professionals’ expectations of possible features of an interactive portal. Methods We conducted three focus groups with breast cancer sur

  8. Indole-3-carbinol (I3C) increases apoptosis, represses growth of cancer cells, and enhances adenovirus-mediated oncolysis.

    Science.gov (United States)

    Chen, Lan; Cheng, Pei-Hsin; Rao, Xiao-Mei; McMasters, Kelly M; Zhou, Heshan Sam

    2014-09-01

    Epidemiological studies suggest that high intake of cruciferous vegetables is associated with a lower risk of cancer. Experiments have shown that indole-3-carbinol (I3C), a naturally occurring compound derived from cruciferous vegetables, exhibits potent anticarcinogenic properties in a wide range of cancers. In this study, we showed that higher doses of I3C (≥400 μM) induced apoptotic cancer cell death and lower doses of I3C (≤200 μM) repressed cancer cell growth concurrently with suppressed expression of cyclin E and its partner CDK2. Notably, we found that pretreatment with low doses of I3C enhanced Ad-mediated oncolysis and cytotoxicity of human carcinoma cells by synergistic upregulation of apoptosis. Thus, the vegetable compound I3C as a dietary supplement may benefit cancer prevention and improve Ad oncolytic therapies.

  9. Enhanced magnetic resonance imaging and staining of cancer cells using ferrimagnetic H-ferritin nanoparticles with increasing core size

    Directory of Open Access Journals (Sweden)

    Cai Y

    2015-04-01

    Full Text Available Yao Cai,1–3 Changqian Cao,1,2 Xiaoqing He,1 Caiyun Yang,1–3 Lanxiang Tian,1,2 Rixiang Zhu,2 Yongxin Pan1,21France–China Bio-Mineralization and Nano-Structures Laboratory, 2Paleomagnetism and Geochronology Laboratory, Key Laboratory of the Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaPurpose: This study is to demonstrate the nanoscale size effect of ferrimagnetic H-ferritin (M-HFn nanoparticles on magnetic properties, relaxivity, enzyme mimetic activities, and application in magnetic resonance imaging (MRI and immunohistochemical staining of cancer cells.Materials and methods: M-HFn nanoparticles with different sizes of magnetite cores in the range of 2.7–5.3 nm were synthesized through loading different amounts of iron into recombinant human H chain ferritin (HFn shells. Core size, crystallinity, and magnetic properties of those M-HFn nanoparticles were analyzed by transmission electron microscope and low-temperature magnetic measurements. The MDA-MB-231 cancer cells were incubated with synthesized M-HFn nanoparticles for 24 hours in Dulbecco’s Modified Eagle’s Medium. In vitro MRI of cell pellets after M-HFn labeling was performed at 7 T. Iron uptake of cells was analyzed by Prussian blue staining and inductively coupled plasma mass spectrometry. Immunohistochemical staining by using the peroxidase-like activity of M-HFn nanoparticles was carried out on MDA-MB-231 tumor tissue paraffin sections.Results: The saturation magnetization (Ms, relaxivity, and peroxidase-like activity of synthesized M-HFn nanoparticles were monotonously increased with the size of ferrimagnetic cores. The M-HFn nanoparticles with the largest core size of 5.3 nm exhibit the strongest saturation magnetization, the highest peroxidase activity in immunohistochemical staining, and the highest r2 of 321 mM-1 s-1, allowing to

  10. Do children with central venous line (CVL dysfunction have increased risk of symptomatic thromboembolism compared to those without CVL-dysfunction, while on cancer therapy?

    Directory of Open Access Journals (Sweden)

    Halton Jacqueline

    2012-07-01

    Full Text Available Abstract Background Thromboembolism (TE and infection are two common complications of central venous line (CVL. Thrombotic CVL-dysfunction is a common, yet less studied, complication of CVL. Two retrospective studies have reported significant association of CVL-dysfunction and TE. Recent studies indicate association of CVL-related small clot with infection. Infection is the most common cause of non-cancer related mortality in children with cancer. We and others have shown reduced overall survival (OS in children with cancer and CVL-dysfunction compared to those without CVL-dysfunction. Despite these observations, to date there are no prospective studies to evaluate the clinical significance of CVL-dysfunction and it’s impact on the development of TE, infection, or outcome of children with cancer. Study design This is a prospective, analytical cohort study conducted at five tertiary care pediatric oncology centers in Ontario. Children (≤ 18 years of age with non-central nervous system cancers and CVL will be eligible for the study. Primary outcome measure is symptomatic TE and secondary outcomes are infection, recurrence of cancer and death due to any cause. Data will be analyzed using regression analyses. Discussion The overall objective is to delineate the relationship between CVL-dysfunction, infection and TE. The primary aim is to evaluate the role of CVL-dysfunction as a predictor of symptomatic TE in children with cancer. We hypothesize that children with CVL-dysfunction have activation of the coagulation system resulting in an increased risk of symptomatic TE. The secondary aims are to study the impact of CVL-dysfunction on the rate of infection and the survival [OS and event free survival (EFS] of children with cancer. We postulate that patients with CVL-dysfunction have an occult CVL-related clot which acts as a microbial focus with resultant increased risk of infection. Further, CVL-dysfunction by itself or in combination with

  11. Unstaged cancer in the United States: a population-based study

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    Anderson Allison E

    2011-09-01

    Full Text Available Abstract Background The current study examines unstaged disease for 18 cancer sites in the United States according to the influence of age, sex, race, marital status, incidence, and lethality. Methods Analyses are based on 1,040,381 male and 1,011,355 female incident cancer cases diagnosed during 2000 through 2007. Data were collected by population-based cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Results The level of unstaged disease was greater in more lethal cancers (e.g., liver, esophagus, and pancreas compared with less deadly cancers (i.e., colon, urinary bladder, and female breast. Unstaged disease increased with age and is greater among non-married patients. Blacks compared with whites experienced significantly higher levels of unstaged cancers of the stomach, rectum, colon, skin (melanoma, urinary bladder, thyroid, breast, corpus, cervix, and ovaries, but lower levels of unstaged liver, lung and bronchial cancers. Males compared with females experienced significantly lower levels of unstaged cancers of the liver, pancreas, esophagus, and stomach, but significantly higher levels of unstaged lung and bronchial cancer and thyroid cancer. The percent of unstaged cancer significantly decreased over the study period for 15 of the 18 cancer sites. Conclusion Tumor staging directly affects treatment options and survival, so it is recommended that further research focus on why a decrease in unstaged disease did not occur for all of the cancer sites considered from 2000 to 2007, and why there are differential levels of staging between whites and blacks, males and females for several of the cancer sites.

  12. The polymorphism interleukin-8 -251A/T is associated with a significantly increased risk of cancers from a meta-analysis.

    Science.gov (United States)

    Wang, Ziliang; Liu, Yang; Yang, Lina; Yin, Sheng; Zang, Rongyu; Yang, Gong

    2014-07-01

    Emerging evidences show that interleukin-8 (IL-8) has important regulatory functions in tumorigenesis. IL-8 -251A/T is a single nucleotide polymorphism in the promoter region of the IL-8 gene and affects IL-8 production. Analysis of previous studies on the association of -251A/T polymorphism with different cancer types remained to be illustrated. To further assess the effect of -251A/T polymorphism on cancer risks, we performed this meta-analysis, up to November 2013, of 12,917 cases with different cancer types and 17,689 controls from 47 published case-control designed studies. Statistical analyses were performed using STATA 11.0 software. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. ORs with 95 % CIs for IL-8 -251A/T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. Significantly increased risks were found in overall under the models of A allele vs. T allele, AA vs. TT, and AA vs. AT/TT. Significantly elevated risks were observed in breast cancer under the models of A allele vs. T allele, AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT, and in nasopharyngeal carcinoma under the models of AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT. We found that significantly elevated risks were observed in the Asian population and hospital-based studies in all comparison models. Thus, this meta-analysis indicates that IL-8 -251A/T polymorphism is associated with a significantly increased risk of cancers and may provide evidence-based medical certificate to study the cancer susceptibility.

  13. Increased Prevalence of Colorectal Polyp in Acromegaly Patients: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Ali Riza Koksal

    2014-01-01

    Full Text Available An increase in the prevalence of colorectal polyps and cancer is reported in patients with acromegaly. This trial is designed to determine whether there is an increase in the prevalence of colorectal polyps/cancer in Turkish acromegaly patients. Sixty-six patients, who were under follow-up with the diagnosis of acromegaly and underwent total colonoscopic examination, were enrolled in the study. Sixty-five age- and gender-matched patients with nonspecific complaints were selected as control. The mean age of acromegalic patients was 51.5±12.8 years of whom 27 (40.9% were females. In 20 (30.3% of the patients with acromegaly a total of 65 colorectal polyps were detected. Forty-seven (72.3% of the polyps were detected at the rectosigmoid region. In 8 (12.3% of the 65 control patients a total of 17 polyps were found. There was a statistically significant difference between the groups (P=0.018. At the logistic regression analysis we found that the risk for colon polyps increased 3.2-fold in the presence of acromegaly, irrespective of age and gender (OR: 3.191, 95% CI: 1.25–8.13. In conclusion, patients who were followed up with the diagnosis of acromegaly should be taken to the colonoscopic surveillance program and all polyps detected should be excised in order to protect them from colorectal cancer.

  14. Informed conditioning on clinical covariates increases power in case-control association studies.

    Science.gov (United States)

    Zaitlen, Noah; Lindström, Sara; Pasaniuc, Bogdan; Cornelis, Marilyn; Genovese, Giulio; Pollack, Samuela; Barton, Anne; Bickeböller, Heike; Bowden, Donald W; Eyre, Steve; Freedman, Barry I; Friedman, David J; Field, John K; Groop, Leif; Haugen, Aage; Heinrich, Joachim; Henderson, Brian E; Hicks, Pamela J; Hocking, Lynne J; Kolonel, Laurence N; Landi, Maria Teresa; Langefeld, Carl D; Le Marchand, Loic; Meister, Michael; Morgan, Ann W; Raji, Olaide Y; Risch, Angela; Rosenberger, Albert; Scherf, David; Steer, Sophia; Walshaw, Martin; Waters, Kevin M; Wilson, Anthony G; Wordsworth, Paul; Zienolddiny, Shanbeh; Tchetgen, Eric Tchetgen; Haiman, Christopher; Hunter, David J; Plenge, Robert M; Worthington, Jane; Christiani, David C; Schaumberg, Debra A; Chasman, Daniel I; Altshuler, David; Voight, Benjamin; Kraft, Peter; Patterson, Nick; Price, Alkes L

    2012-01-01

    Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low-BMI cases are larger than those estimated from high-BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1 × 10(-9)). The improvement varied across diseases with a 16% median increase in χ(2) test statistics and a

  15. Glycemic load, glycemic index, and pancreatic cancer risk in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Lumey, L.H.; Brants, H.A.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2008-01-01

    Background: Recent studies of pancreatic cancer suggest a role for hyperinsulinemia in carcinogenesis. Because insulin is secreted in response to elevated blood glucose concentrations, dietary factors that increase these concentrations may be important in pancreatic carcinogenesis. Objective: The ob

  16. Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of); Yoon, Sungpil, E-mail: yoons@ncc.re.kr [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

  17. Leptin increases HER2 protein levels through a STAT3-mediated up-regulation of Hsp90 in breast cancer cells.

    Science.gov (United States)

    Giordano, Cinzia; Vizza, Donatella; Panza, Salvatore; Barone, Ines; Bonofiglio, Daniela; Lanzino, Marilena; Sisci, Diego; De Amicis, Francesca; Fuqua, Suzanne A W; Catalano, Stefania; Andò, Sebastiano

    2013-06-01

    Obesity condition confers risks to breast cancer development and progression, and several reports indicate that the adipokine leptin, whose synthesis and plasma levels increase with obesity, might play an important role in modulating breast cancer cell phenotype. Functional crosstalk occurring between leptin and different signaling molecules contribute to breast carcinogenesis. In this study, we show, in different human breast cancer cell lines, that leptin enhanced the expression of a chaperone protein Hsp90 resulting in increased HER2 protein levels. Silencing of Hsp90 gene expression by RNA interference abrogated leptin-mediated HER2 up-regulation. Leptin effects were dependent on JAK2/STAT3 activation, since inhibition of this signaling cascade by AG490 or ectopic expression of a STAT3 dominant negative abrogated leptin-induced HER2 and Hsp90 expressions. Functional experiments showed that leptin treatment significantly up-regulated human Hsp90 promoter activity. This occurred through an enhanced STAT3 transcription factor binding to its specific responsive element located in the Hsp90 promoter region as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Analysis of HER2, Akt and MAPK phosphorylation levels revealed that leptin treatment amplified the responsiveness of breast cancer cells to growth factor stimulation. Furthermore, we found that long-term leptin exposure reduced sensitivity of breast cancer cells to the antiestrogen tamoxifen. In the same experimental conditions, the combined treatment of tamoxifen with the Hsp90 inhibitor 17-AAG completely abrogated leptin-induced anchorage-independent breast cancer cell growth. In conclusion, our results highlight, for the first time, the ability of the adipocyte-secreted factor leptin to modulate Hsp90/HER2 expressions in breast cancer cells providing novel insights into the molecular mechanism linking obesity to breast cancer growth and progression.

  18. Prospective cohort study of comprehensive prevention to gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Qiang Guo; Peng Guan; Hai-Long Shi; Xuan Zhang; Bao-Sen Zhou; Yuan Yuan

    2003-01-01

    AIM: To evaluate the preliminary effects of comprehensive prevention of gastric cancer in Zhuanghe County epidemiologically.METHODS: Stratified sampling and cluster sampling were applied to define the intervention group and the control group. The prospective cohort study was used for evaluating the effect of preventing gastric cancer. The relative risk (RR)and attributable risk percent (AR %) of intervention on gastric cancer death were calculated. Potential years of life lost (PLYY) of the disease was analyzed, and the RR and AR %of PYLL were calculated. Survival analysis was applied among the screened patients.RESULTS: In the first 4 years after intervening, the relative risk (RR) of intervention on death was 0.5059 (95 % CI:0.3462~0.7392,P<0.05) with significance statistically. AR %of the intervention on death was 49.41%. The RR of intervention on cumulative PYLL was 0.6778 (95 % CI:0.5604~0.8198,P<0.05) with statistic significance. AR %of the intervention on cumulative PYLL was 30.32 %. The four-year survival rate of the screened patients was 0.6751(95 % CI: 0.5298~0.9047).CONCLUSION: The initiative intervention results showed that the intervention approach used in the trial was effective, it reduced mortality and increased survival rate, and alleviated the adverse effect of gastric cancer on the health and life of screened population.

  19. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

    LENUS (Irish Health Repository)

    Trompet, Stella

    2009-12-01

    Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

  20. Meat consumption among Black and White men and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

    Science.gov (United States)

    Rodriguez, Carmen; McCullough, Marjorie L; Mondul, Alison M; Jacobs, Eric J; Chao, Ann; Patel, Alpa V; Thun, Michael J; Calle, Eugenia E

    2006-02-01

    Previous epidemiologic studies have suggested that intake of red meat may be associated with increased risk of prostate cancer. Few studies, however, have examined these associations by race. We examined intake of red meat, processed meat, and poultry in relation to incident prostate cancer among Black and White men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle in 1992 to 1993. After excluding men with a history of cancer and incomplete dietary information, 692 Black and 64,856 White men were included in the cohort. During follow-up through August 31, 2001, we documented 85 and 5,028 cases of incident prostate cancer among Black and White men, respectively. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI). No measure of meat consumption was associated with risk of prostate cancer among White men. Among Black men, total red meat intake (processed plus unprocessed red meat) was associated with higher risk of prostate cancer (RR, 2.0; 95% CI, 1.0-4.2 for highest versus lowest quartile; P(trend) = 0.05); this increase in risk was mainly due to risk associated with consumption of cooked processed meats (sausages, bacon, and hot dogs; RR, 2.7; 95% CI, 1.3-5.3 for highest versus lowest quartile; P(trend) = 0.008). This study suggests that high consumption of cooked processed meats may contribute to prostate cancer risk among Black men in the United States.