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  1. Age distribution types of bladder cancers and their relationship with opium consumption and smoking

    PubMed Central

    Aliramaji, Arsalan; Kaseean, Aliakbar; Yousefnia Pasha, Yousef Reza; Shafi, Hamid; Kamali, Sekineh; Safari, Mohsen; Moudi, Emaduddin

    2015-01-01

    Background: Recognition of the predisposing factors of bladder cancer is very important and provides possible prevention measures. The aim of this study was to investigate the types, distribution of bladder tumors and their relationship with opium consumption and smoking in patients who referred to Shahid Beheshti Hospital, Babol, Iran. Methods: In this case-control study, all patients diagnosed with bladder cancer who underwent surgery during 2001-2012 were enrolled. The subjects of the control group were selected among the patients who underwent ERCP (endoscopic retrograde cholangiopancreatography) for gallstone and had no tumors and genitourinary problems. Data regarding demographic, pathology reports and tumor type, smoking status, history of opium consumption and its duration were collected. Patients and controls were compared using t-test and chi-square test. SPSS software Version 20 was used for analysis. Results: In this study, 175 patients with an average age of 63.30±15.29 years and 175 age- matched controls were studied. A significant association was observed between smoking and opium consumption with bladder cancer (P=0.001 for both). Conclusion: The results of this study showed that opium consumption and smoking are associated with bladder cancer PMID:26221505

  2. Age and Cancer Risk

    PubMed Central

    White, Mary C.; Holman, Dawn M.; Boehm, Jennifer E.; Peipins, Lucy A.; Grossman, Melissa; Henley, S. Jane

    2015-01-01

    This article challenges the idea that cancer cannot be prevented among older adults by examining different aspects of the relationship between age and cancer. Although the sequential patterns of aging cannot be changed, several age-related factors that contribute to disease risk can be. For most adults, age is coincidentally associated with preventable chronic conditions, avoidable exposures, and modifiable risk behaviors that are causally associated with cancer. Midlife is a period of life when the prevalence of multiple cancer risk factors is high and incidence rates begin to increase for many types of cancer. However, current evidence suggests that for most adults, cancer does not have to be an inevitable consequence of growing older. Interventions that support healthy environments, help people manage chronic conditions, and promote healthy behaviors may help people make a healthier transition from midlife to older age and reduce the likelihood of developing cancer. Because the number of adults reaching older ages is increasing rapidly, the number of new cancer cases will also increase if current incidence rates remain unchanged. Thus, the need to translate the available research into practice to promote cancer prevention, especially for adults at midlife, has never been greater. PMID:24512933

  3. Types of Breast Cancers

    MedlinePlus

    ... the key statistics about breast cancer? Types of breast cancers Breast cancer can be separated into different types ... than invasive ductal carcinoma. Less common types of breast cancer Inflammatory breast cancer This uncommon type of invasive ...

  4. Aging, cancer, and cancer vaccines

    PubMed Central

    2012-01-01

    World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people [1]. Most cancers are age-related diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be diagnosed in elderly patients by 2020 [2]. Further, cancer-related mortality increases with age: 70% of all malignancy-related deaths are registered in people aged 65 years or older [3]. Here we introduce the microscopic aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence. Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present be recommended in association to a stronger cancer prevention and conventional therapies (surgery, chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality associated to cancer progression. PMID:22510392

  5. Aging and Cancer Vaccines

    PubMed Central

    Gravekamp, Claudia; Chandra, Dinesh

    2014-01-01

    Cancer vaccination is less effective at old than at young age, due to T cell unresponsiveness. This is caused by age-related changes of the immune system. Major immune defects at older age are lack of naïve T cells, impaired activation pathways of T cells and antigen-presenting cells (APC), and age-related changes in the tumor microenvironment (TME). Also innate immune responses are affected by aging, but this seems less abundant than adaptive immune responses. In this review we compared various cancer vaccine studies at young and old age, demonstrating the importance of both innate and adaptive immune responses for cancer immunotherapy. Moreover, we found suggestive evidence that innate immune responses could help improve adaptive immune responses through cancer vaccination in old age. PMID:24579737

  6. Cell Senescence: Aging and Cancer

    ScienceCinema

    Campisi, Judith

    2013-05-29

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  7. Cell Senescence: Aging and Cancer

    SciTech Connect

    Campisi, Judith

    2008-01-01

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  8. CANCER VACCINES IN OLD AGE

    PubMed Central

    Gravekamp, Claudia

    2007-01-01

    The incidence of cancer has increased over the last decade, mainly due to an increase in the elderly population. Vaccine therapy for cancer is less toxic than chemotherapy or radiation and could be, therefore, especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T cell unresponsiveness, a phenomenon also observed in cancer patients per se. This review summarizes the current knowledge of T cell unresponsiveness in cancer patients and elderly, the results of cancer vaccination in preclinical models and in clinical trials, and recent data of cancer vaccination at young and old age in preclinical models. Finally, experimental approaches will be proposed how to make cancer vaccines more effective at older age. PMID:17197144

  9. Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: a cohort study using metformin as the comparator

    PubMed Central

    Chen, Yu-Ching; Kok, Victor C; Chien, Ching-Hsuan; Horng, Jorng-Tzong; Tsai, Jeffrey J P

    2015-01-01

    Introduction Accumulating evidence suggests that metformin reduces incident cancer development. Few cohort studies have evaluated the risk of subsequent cancer development in diabetic cohorts receiving antidiabetic monotherapy. We conducted a population-based study in patients with new-onset type 2 diabetes treated with antidiabetic monotherapy. Methods We identified a cohort of patients with type 2 diabetics aged ≥30 years receiving hypoglycemic monotherapy (n=7,325) from the 1998–2007 Longitudinal Health Insurance Dataset. Patients were grouped according to the antidiabetic therapy they received into metformin (n=2,223), sulfonylurea (n=3,965), glitazone (n=53), meglitinide (n=128), acarbose (n=150), and insulin (n=806) groups. Patients with preexisting cancer were excluded. All patients were followed up until cancer development, dropout, death, or until December 31, 2008. Cox’s model was used to estimate multivariable hazard ratios (HRs) adjusted for age, sex, Charlson comorbidity index, smoking-related comorbidities, alcohol use disorders, morbid obesity, pancreatitis, hypertension, monthly income, and urbanization level. The log-rank test was used to compare cumulative cancer incidence. Two-sided P-values <0.05 were required to reject the null hypothesis. Results The overall median follow-up duration was 2.5 years (interquartile range, 3.6 years). Totally, 367 and 124 cancers developed in the sulfonylurea and metformin groups, respectively, representing an adjusted HR of 1.36 (95% confidence interval [CI], 1.11–1.67; P<0.005). No significant differences were observed between other groups. Increased adjusted HRs were observed for colorectal cancer (adjusted HR, 1.94; 95% CI, 1.15–3.27; P<0.05) and lung cancer (adjusted HR, 1.76; 95% CI, 1.00–3.07; P<0.05). Conclusion Metformin monotherapy may be associated with a reduction in the risk for cancer development compared with sulfonylurea monotherapy. Moreover, the use of an average defined daily dose of

  10. Trends in the Incidence of In Situ and Invasive Cervical Cancer by Age Group and Histological Type in Korea from 1993 to 2009

    PubMed Central

    Oh, Chang-Mo; Jung, Kyu-Won; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Jun, Jae Kwan; Park, Sang-yoon

    2013-01-01

    Objective Our study aims to describe changes in carcinoma in situ (CIS) and invasive cervical carcinoma (ICC) in Korean women diagnosed between 1993 and 2009. Methods All cases of CIS and invasive cervical carcinoma diagnosed from 1993 to 2009 in the Korean National Cancer Incidence database were analyzed. Age-standardized rates (ASRs) and annual percent changes (APCs) in incidence rates were compared according to age and histological type. Additionally, we used Korea National Health and Nutrition Examination Survey (KNHANES) to know the association between screening rate for cervical cancer and incidence rate of cervical cancer. Results Between 1993 and 2009, 72,240 cases of ICC were reported in Korea. Total incidence rate of ICC was 14.7 per 100,000 females. ASRs of ICC declined 3.8% per year, from 19.3 per 100,000 in 1993 to 10.5 per 100,000 in 2009. Although the overall incidence rate of adenocarcinoma remained stable, invasive squamous cell carcinoma showed a decreasing trend (APC −4.2%). For women aged 60–79 years, ASRs for squamous cell carcinoma increased from 1993 to 2001, and decreased from 2001 to 2009 (APC: −4.6%). Total 62,300 cases of CIS were diagnosed from 1993 to 2009. Total incidence rate of CIS was 12.2 per 100,000 females. ASRs of CIS increased 5.7% per year, from 7.5 per 100,000 in 1993 to 19.0 per 100,000 in 2009. Adenocarcinoma in situ increased 13.2% per year. There was a strong positive correlation between screening rate for cervical cancer and incidence rate for CIS (p-value = 0.03) whereas screening rate showed a strong negative correlation with incidence rate for squamous ICC (p-value = 0.04). Conclusions The increasing trend in CIS, coupled with a decreasing trend in ICC, suggests the important role of cervix cancer screening. The incidence of adenocarcinoma showed a plateau, but the incidence of adenocarcinoma in situ showed an increasing trend. PMID:23977194

  11. Types of Cancer Teens Get

    MedlinePlus

    ... symptoms and how these cancers can be treated. Osteosarcoma Osteosarcoma (pronounced: os-tee-oh-sahr-KOH-muh) is the most common type of bone cancer. In teens, it can sometimes appear during their ...

  12. Types of Cancer Research

    Cancer.gov

    An infographic from the National Cancer Institute (NCI) describing the four broad categories of cancer research: basic research, clinical research, population-based research, and translational research.

  13. Aging, Cellular Senescence, and Cancer

    PubMed Central

    Campisi, Judith

    2014-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyper-plastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  14. Aging, cellular senescence, and cancer.

    PubMed

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  15. Genome instability, cancer and aging

    PubMed Central

    Maslov, Alexander Y.; Vijg, Jan

    2015-01-01

    DNA damage-driven genome instability underlies the diversity of life forms generated by the evolutionary process but is detrimental to the somatic cells of individual organisms. The cellular response to DNA damage can be roughly divided in two parts. First, when damage is severe, programmed cell death may occur or, alternatively, temporary or permanent cell cycle arrest. This protects against cancer but can have negative effects on the long term, e.g., by depleting stem cell reservoirs. Second, damage can be repaired through one or more of the many sophisticated genome maintenance pathways. However, erroneous DNA repair and incomplete restoration of chromatin after damage is resolved, produce mutations and epimutations, respectively, both of which have been shown to accumulate with age. An increased burden of mutations and/or epimutations in aged tissues increases cancer risk and adversely affects gene transcriptional regulation, leading to progressive decline in organ function. Cellular degeneration and uncontrolled cell proliferation are both major hallmarks of aging. Despite the fact that one seems to exclude the other, they both may be driven by a common mechanism. Here, we review age related changes in the mammalian genome and their possible functional consequences, with special emphasis on genome instability in stem/progenitor cells. PMID:19344750

  16. Telomeres in cancer and ageing

    PubMed Central

    Donate, Luis E.; Blasco, Maria A.

    2011-01-01

    Telomeres protect the chromosome ends from unscheduled DNA repair and degradation. Telomeres are heterochromatic domains composed of repetitive DNA (TTAGGG repeats) bound to an array of specialized proteins. The length of telomere repeats and the integrity of telomere-binding proteins are both important for telomere protection. Furthermore, telomere length and integrity are regulated by a number of epigenetic modifications, thus pointing to higher order control of telomere function. In this regard, we have recently discovered that telomeres are transcribed generating long, non-coding RNAs, which remain associated with the telomeric chromatin and are likely to have important roles in telomere regulation. In the past, we showed that telomere length and the catalytic component of telomerase, Tert, are critical determinants for the mobilization of stem cells. These effects of telomerase and telomere length on stem cell behaviour anticipate the premature ageing and cancer phenotypes of telomerase mutant mice. Recently, we have demonstrated the anti-ageing activity of telomerase by forcing telomerase expression in mice with augmented cancer resistance. Shelterin is the major protein complex bound to mammalian telomeres; however, its potential relevance for cancer and ageing remained unaddressed to date. To this end, we have generated mice conditionally deleted for the shelterin proteins TRF1, TPP1 and Rap1. The study of these mice demonstrates that telomere dysfunction, even if telomeres are of a normal length, is sufficient to produce premature tissue degeneration, acquisition of chromosomal aberrations and initiation of neoplastic lesions. These new mouse models, together with the telomerase-deficient mouse model, are valuable tools for understanding human pathologies produced by telomere dysfunction. PMID:21115533

  17. DNA methylation age of human tissues and cell types

    PubMed Central

    2013-01-01

    Background It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. Results I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. Conclusions I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research. PMID:24138928

  18. Is cancer vaccination feasible at older age?

    PubMed Central

    Gravekamp, Claudia; Jahangir, Arthee

    2014-01-01

    Age-related defects of the immune system are responsible for T cell unresponsiveness to cancer vaccination at older age. Major immune defects at older age are lack of naïve T cells, impaired activation pathways of T cells and antigen-presenting cells (APC), and age-related changes in the tumor microenvironment (TME). This raises the question whether cancer vaccination is feasible at older age. We compared various cancer vaccine studies at young and old age, thereby focusing on the importance of both innate and adaptive immune responses for cancer immunotherapy. These analyses suggest that creating an immune-stimulating environment with help of the innate immune system may improve T cell responses in cancer vaccination at older age. PMID:24509231

  19. Age and cancer risk: a potentially modifiable relationship.

    PubMed

    White, Mary C; Holman, Dawn M; Boehm, Jennifer E; Peipins, Lucy A; Grossman, Melissa; Henley, S Jane

    2014-03-01

    This article challenges the idea that cancer cannot be prevented among older adults by examining different aspects of the relationship between age and cancer. Although the sequential patterns of aging cannot be changed, several age-related factors that contribute to disease risk can be. For most adults, age is coincidentally associated with preventable chronic conditions, avoidable exposures, and modifiable risk behaviors that are causally associated with cancer. Midlife is a period of life when the prevalence of multiple cancer risk factors is high and incidence rates begin to increase for many types of cancer. However, current evidence suggests that for most adults, cancer does not have to be an inevitable consequence of growing older. Interventions that support healthy environments, help people manage chronic conditions, and promote healthy behaviors may help people make a healthier transition from midlife to older age and reduce the likelihood of developing cancer. Because the number of adults reaching older ages is increasing rapidly, the number of new cancer cases will also increase if current incidence rates remain unchanged. Thus, the need to translate the available research into practice to promote cancer prevention, especially for adults at midlife, has never been greater. PMID:24512933

  20. Cancer and Aging: A Complex Biological Association.

    PubMed

    Navarrete-Reyes, Ana Patricia; Soto-Pérez-de-Celis, Enrique; Hurria, Arti

    2016-01-01

    Cancer is one of the leading causes of death in both developing and developed countries. It is also a particularly significant health problem in older populations since half of all malignancies occur in patients aged 70 years or older. Cancer is a disease of aging, and as such there is a strong biological association between the mechanisms of aging and carcinogenesis. During the past few decades, mechanisms of aging exerting pro- and anti-oncogenic effects have been described, and the role of these mechanisms in cancer treatment and prognosis is currently being investigated. In this review we describe the different theories of aging and the evidence on the biological link between these mechanisms and carcinogenesis. Additionally, we review the implications of the biology of aging on the treatment and prognosis of older adults with cancer, and the opportunities for translational research into biomarkers of aging in this patient population. PMID:27028173

  1. Telomerase at the intersection of cancer and aging

    PubMed Central

    de Jesus, Bruno Bernardes; Blasco, Maria A.

    2014-01-01

    Although cancer and aging have been studied as independent diseases, mounting evidence suggest that cancer is an aging-associated disease and that cancer and aging share many molecular pathways. In particular, recent studies validated telomerase activation as a potential therapeutic target for age-related diseases, and at the same time, abnormal telomerase expression and telomerase mutations have been associated with many different types of human tumors. Here, we revisit the connection of telomerase to cancer and aging in light of recent findings supporting a role for telomerase not only in telomere elongation, but also in metabolic fitness and Wnt activation. Understanding the physiological impact of telomerase regulation is fundamental considering the therapeutic strategies that are being developed involving telomerase modulation. PMID:23876621

  2. Aging: Balancing regeneration and cancer

    SciTech Connect

    Beausejour, Christian M.; Campisi, Judith

    2006-08-24

    The proliferation of cells must balance the longevity assured by tissue renewal against the risk of developing cancer. The tumor-suppressor protein p16{sup INK4a} seems to act at the pivot of this delicate equilibrium.

  3. Lung cancer in patients under the age of 40 years

    PubMed Central

    Kaczmarczyk, Grzegorz; Porębska, Irena; Szmygin-Milanowska, Katarzyna; Gołecki, Marcin

    2012-01-01

    Aim of the study In the paper clinical cases of individuals diagnosed with lung cancer below the age of 40 years have been analyzed. Material and methods The analysis included: sex, age, clinical symptoms found before and at the moment of diagnosis, character of changes visible in radiological imaging, time that passed from the first symptoms to reporting to a doctor and to establishing a diagnosis, type of diagnostic method used in establishing the final diagnosis, histopathologic type of cancer, degree of cancer progression. Results The results have been compared with a peer group who had been diagnosed 20 years earlier. Currently 7% of patients were diagnosed at the age of 25 or younger, whereas in the previous cohort patients in this age constituted 2%. The predominant pathological type was adenocarcinoma (currently 33%, previously 4%) in contrast to the earlier group in which 57% of patients had small cell lung cancer (57%). The incidence is equally distributed between both sexes, although there is an evident increase in female lung cancer cases. In the majority of patients the clinical presentation is a peripheral mass on chest X-ray. 20% of patients present pleural effusion on diagnosis. Patients reported the following complaints: breathlessness, chest pain, weight loss and fatigue. The majority of cases were diagnosed in advanced stages on the basis of a bronchoscopy acquired specimen. Time course from symptoms to diagnosis tends to be shorter than 20 years ago. PMID:23788919

  4. Regulation of Senescence in Cancer and Aging

    PubMed Central

    Kong, Yahui; Cui, Hang; Ramkumar, Charusheila; Zhang, Hong

    2011-01-01

    Senescence is regarded as a physiological response of cells to stress, including telomere dysfunction, aberrant oncogenic activation, DNA damage, and oxidative stress. This stress response has an antagonistically pleiotropic effect to organisms: beneficial as a tumor suppressor, but detrimental by contributing to aging. The emergence of senescence as an effective tumor suppression mechanism is highlighted by recent demonstration that senescence prevents proliferation of cells at risk of neoplastic transformation. Consequently, induction of senescence is recognized as a potential treatment of cancer. Substantial evidence also suggests that senescence plays an important role in aging, particularly in aging of stem cells. In this paper, we will discuss the molecular regulation of senescence its role in cancer and aging. The potential utility of senescence in cancer therapeutics will also be discussed. PMID:21423549

  5. Telomeres, lifestyle, cancer, and aging

    PubMed Central

    Shammas, Masood A.

    2012-01-01

    Purpose of review There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening. Recent findings Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases. Summary Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging. PMID:21102320

  6. [Epidemiologic aspects of the histologic types of lung cancer].

    PubMed

    Wilde, J; Matthäi, C; Wilde, J

    1990-01-01

    An epidemiological study was performed in the county of Erfurt including all lung cancer patients of the years 1963, 1968, and 1972 to 1977, together 2,585 males and 358 females. The following results were found: 1. The incidence of lung cancer increased significantly from 1963 to 1977. 2. About 60% of all lung cancer patients were younger than 70 years. 3. In male patients squamous cell carcinomas prevailed with 44.8%. Small cell cancers came up to 34.6% and adenocarcinomas to 10.1%. Large cell cancers reached 10.5%. These types in female patients had a proportion to each other like 26.9%: 30.8%: 30.4%: 11.9%. The proportion of adenocarcinomas increased significantly during 1963 to 1977. 4. We found a non significant age relation of histological types. The adenocarcinoma and the small cell cancers dropped with rising age. 5. The classification of histological types and the conditions of detection of lung cancers did not change in the study interval. Therefore the altering of patterns of histological types, especially the increase of adenocarcinomas was attached to the beginning of cigarette smoking in younger ages and the increasing proportion of filter tipped brands as well to a variation of exposition against professional cancerogens. 6. Patients with adenocarcinomas have the highest survival rate after 5 years: 8.1%. Squamous cell lung cancer patients have a 5 year survival rate of 6.8%. Patients with small cell cancers and large cell cancers ranged at 2.7% or 2.6%. 7. Peripheral tumors of each histological type will be detected earlier by fluorographic screening than central carcinomas. Therefore the 5 year survival rates of peripheral cancers always are more favourable than that of central cancers. 8. For the problems in exact typing and staging we propose an internationally adjusted definition of tumor localization as a third parameter for prognosis. PMID:2171236

  7. DAMPs, ageing, and cancer: The 'DAMP Hypothesis'.

    PubMed

    Huang, Jin; Xie, Yangchun; Sun, Xiaofang; Zeh, Herbert J; Kang, Rui; Lotze, Michael T; Tang, Daolin

    2015-11-01

    Ageing is a complex and multifactorial process characterized by the accumulation of many forms of damage at the molecular, cellular, and tissue level with advancing age. Ageing increases the risk of the onset of chronic inflammation-associated diseases such as cancer, diabetes, stroke, and neurodegenerative disease. In particular, ageing and cancer share some common origins and hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury, reprogrammed metabolism, and degradation system impairment (including within the ubiquitin-proteasome system and the autophagic machinery). Recent advances indicate that damage-associated molecular pattern molecules (DAMPs) such as high mobility group box 1, histones, S100, and heat shock proteins play location-dependent roles inside and outside the cell. These provide interaction platforms at molecular levels linked to common hallmarks of ageing and cancer. They can act as inducers, sensors, and mediators of stress through individual plasma membrane receptors, intracellular recognition receptors (e.g., advanced glycosylation end product-specific receptors, AIM2-like receptors, RIG-I-like receptors, and NOD1-like receptors, and toll-like receptors), or following endocytic uptake. Thus, the DAMP Hypothesis is novel and complements other theories that explain the features of ageing. DAMPs represent ideal biomarkers of ageing and provide an attractive target for interventions in ageing and age-associated diseases. PMID:25446804

  8. Age-related somatic mutations in the cancer genome

    PubMed Central

    Milholland, Brandon; Auton, Adam; Suh, Yousin; Vijg, Jan

    2015-01-01

    Aging is associated with an increased risk of cancer, possibly in part because of an age-related increase in mutations in normal tissues. Due to their extremely low abundance, somatic mutations in normal tissues frequently escape detection. Tumors, as clonal expansions of single cells, can provide information about the somatic mutations present in these cells prior to tumorigenesis. Here, we used data from The Cancer Genome Atlas (TCGA), to systematically study the frequency and spectrum of somatic mutations in a total of 6,969 patients and 34 different tumor types as a function of the age of the patient. After using linear modeling to control for the age structure of different tumor types, we found that the number of identified somatic mutations increases exponentially with age. Using additional data from the literature, we found that accumulation of somatic mutations is associated with cell division rate, cancer risk and cigarette smoking, with the latter also associated with a distinct spectrum of mutations. Our results confirm that aging is associated with the accumulation of somatic mutations, and strongly suggest that the level of genome instability of normal cells, modified by both endogenous and environmental factors, is the main risk factor for cancer. PMID:26384365

  9. Opioid therapy in non-cancer chronic pain patients: Trends and efficacy in different types of pain, patients age and gender

    PubMed Central

    AlMakadma, Yasin S.; Simpson, Karen

    2013-01-01

    Background: In both developing and developed countries, chronic pain remains a real issue and a true disease that affects up to 42% of the population in some areas. Opioids are widely used for the management of chronic pain with variations in prescribing practices, indications and observed efficacy. Aim: to analyze trends in opioids prescribing and patient response in chronic non-cancer pain conditions. Methods: Retrospective study of 1500 casenotes of patients suffering variable non-cancer chronic pain conditions. Detailed review of those cases who were managed using opioids. Statistical analysis using “SOFA” software set. Results: The prevalence of opioids prescribing in patients suffering this condition was thus around 35% (n=526). Women older than 50 years were more likely than men to have a chronic pain condition and to be given opioid therapy for 1 year or more. Opioid efficacy on neuropathic and mixed types of pain was found to be significant with relatively low rate of drop-out and limited side-effects that are not life threatening. Overall, patients stopped or changed their opioid medication due to inefficacy in only 12.7% of cases. Conclusions: The simple fact of having pain is itself a source of self-reported disability regardless of the actual physiological or pathological mechanism. Policy makers should be aware of the huge impact of chronic pain disease and of its serious effects on social and economical well-being. In developing countries, chronic pain could represent a real challenge for all parties. Multimodal management, including opioids, appears crucial for the approach of this disease. PMID:24015132

  10. [Specific types of bladder cancer].

    PubMed

    Bertz, S; Hartmann, A; Knüchel-Clarke, R; Gaisa, N T

    2016-02-01

    Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review. PMID:26782034

  11. Cancer and aging. An evolving panorama.

    PubMed

    Balducci, L; Extermann, M

    2000-02-01

    This article illustrates how the nosology of cancer evolves with the patient's age. If the current trends are maintained, 70% of all neoplasms will occur in persons aged 65 years and over by the year 2020, leading to increased cancer-related morbidity among older persons. Cancer control in the older person involves chemoprevention, early diagnosis, and timely and effective treatment that entails both antineoplastic therapy and symptom management. These interventions must be individualized based on a multidimensional assessment that can predict life expectancy and treatment complications and that may evaluate the quality of life of the older person. This article suggests a number of interventions that may improve cancer control in the aged. Public education is needed to illustrate the benefits of health maintenance and early detection of cancer even among older individuals, to create realistic expectations, and to heighten awareness of early symptoms and signs of cancer. Professional education is needed to train students and practitioners in the evaluation and management of the older person. Of special interest is the current initiative of the Hartford Foundation offering combined fellowships in oncology and geriatrics and incorporating principles of geriatric medicine in medical specialty training. Prudent pharmacologic principles must be followed in managing older persons with cytotoxic chemotherapy. These principles include adjusting the dose according to the patient's renal function, using epoietin to maintain hemoglobin levels of 12 g/dL or more, and using hemopoietic growth factors in persons aged 70 years and older receiving cytotoxic chemotherapy of moderate toxicity (e.g., CHOP). To assure uniformity of data, a cooperative oncology group should formulate a geriatric package outlining a common plan for evaluating function and comorbidity. This article also suggests several important areas of research items: Molecular interactions of age and cancer Host

  12. Body Type Attractiveness Preferences of the Aged.

    ERIC Educational Resources Information Center

    Portnoy, Enid J.

    A study explored the relationship between body types and four attraction dimensions (physical, social, task, and communication) as perceived by older adults (mean age 68). Subjects, 35 males and 73 females in private residences and senior citizen centers, were shown three same-sex body silhouettes representing the older ectomorph, mesomorph, and…

  13. ANOVA like analysis of cancer death age

    NASA Astrophysics Data System (ADS)

    Areia, Aníbal; Mexia, João T.

    2016-06-01

    We use ANOVA to study the influence of year, sex, country and location on the average cancer death age. The data used was from the World Health Organization (WHO) files for 1999, 2003, 2007 and 2011. The locations considered were: kidney, leukaemia, melanoma of skin and oesophagus and the countries: Portugal, Norway, Greece and Romania.

  14. Incorporating Biomarkers Into Cancer and Aging Research

    PubMed Central

    Hubbard, Joleen M.; Cohen, Harvey J.; Muss, Hyman B.

    2014-01-01

    The challenge in treating the older adult with cancer is accurately accounting for and adapting management to the heterogeneity in health status of the individual patient. Many oncologists recognize that chronological age alone should not be the determinant when deciding on a treatment regimen. Easily measurable markers that provide an assessment of functional age would be ideal to assess frailty, which may predispose the patient to complications from cancer treatment, including increased toxicity, functional decline, decreased quality of life, and poorer survival. Several categories of potential markers, including chronic inflammatory markers, markers of cellular senescence, and imaging to assess muscle mass to detect sarcopenia, may provide insight into the likelihood of treatment-related complications. This article discusses candidate markers and strategies to evaluate these markers in cancer treatment trials, with the aim of developing a method to assess risk of oncologic outcomes and guide management decisions for both the physician and patient. PMID:25071114

  15. Aging properties of Kodak type 101 emulsions

    NASA Technical Reports Server (NTRS)

    Dohne, B.; Feldman, U.; Neupert, W.

    1984-01-01

    Aging tests for several batches of Kodak type 101 emulsion show that storage conditions significantly influence how well the film will maintain its sensitometric properties, with sensitivity and density increasing to a maximum during this period. Any further aging may result in higher fog levels and sensitivity loss. It is noted that storage in an environment free of photographically active compounds allows film property optimization, and that film batches with different sensitivities age differently. Emulsions with maximum 1700-A sensitivity are 2.5 times faster than those at the low end of the sensitivity scale. These sensitive emulsions exhibit significantly accelerated changes in aging properties. Their use in space applications requires careful consideration of time and temperature profiles, encouraging the use of less sensitive emulsions when the controllability of these factors is limited.

  16. Type 2 diabetes mellitus, glycemic control, and cancer risk.

    PubMed

    Onitilo, Adedayo A; Stankowski, Rachel V; Berg, Richard L; Engel, Jessica M; Glurich, Ingrid; Williams, Gail M; Doi, Suhail A

    2014-03-01

    Type 2 diabetes mellitus is characterized by prolonged hyperinsulinemia, insulin resistance, and progressive hyperglycemia. Disease management relies on glycemic control through diet, exercise, and pharmacological intervention. The goal of the present study was to examine the effects of glycemic control and the use of glucose-lowering medication on the risk of breast, prostate, and colon cancer. Patients diagnosed with type 2 diabetes mellitus (N=9486) between 1 January 1995 and 31 December 2009 were identified and data on glycemic control (hemoglobin A1c, glucose), glucose-lowering medication use (insulin, metformin, sulfonylurea), age, BMI, date of diabetes diagnosis, insurance status, comorbidities, smoking history, location of residence, and cancer diagnoses were electronically abstracted. Cox proportional hazards regression modeling was used to examine the relationship between glycemic control, including medication use, and cancer risk. The results varied by cancer type and medication exposure. There was no association between glycemic control and breast or colon cancer; however, prostate cancer risk was significantly higher with better glycemic control (hemoglobin A1c ≤ 7.0%). Insulin use was associated with increased colon cancer incidence in women, but not with colon cancer in men or breast or prostate cancer risk. Metformin exposure was associated with reduced breast and prostate cancer incidence, but had no association with colon cancer risk. Sulfonylurea exposure was not associated with risk of any type of cancer. The data reported here support hyperinsulinemia, rather than hyperglycemia, as a major diabetes-related factor associated with increased risk of breast and colon cancer. In contrast, hyperglycemia appears to be protective in the case of prostate cancer. PMID:23962874

  17. DNA Methylation in Cancer and Aging.

    PubMed

    Klutstein, Michael; Nejman, Deborah; Greenfield, Razi; Cedar, Howard

    2016-06-15

    DNA methylation is known to be abnormal in all forms of cancer, but it is not really understood how this occurs and what is its role in tumorigenesis. In this review, we take a wide view of this problem by analyzing the strategies involved in setting up normal DNA methylation patterns and understanding how this stable epigenetic mark works to prevent gene activation during development. Aberrant DNA methylation in cancer can be generated either prior to or following cell transformation through mutations. Increasing evidence suggests, however, that most methylation changes are generated in a programmed manner and occur in a subpopulation of tissue cells during normal aging, probably predisposing them for tumorigenesis. It is likely that this methylation contributes to the tumor state by inhibiting the plasticity of cell differentiation processes. Cancer Res; 76(12); 3446-50. ©2016 AACR. PMID:27256564

  18. Epigenetic linkage of aging, cancer and nutrition

    PubMed Central

    Daniel, Michael; Tollefsbol, Trygve O.

    2015-01-01

    Epigenetic mechanisms play a pivotal role in the expression of genes and can be influenced by both the quality and quantity of diet. Dietary compounds such as sulforaphane (SFN) found in cruciferous vegetables and epigallocatechin-3-gallate (EGCG) in green tea exhibit the ability to affect various epigenetic mechanisms such as DNA methyltransferase (DNMT) inhibition, histone modifications via histone deacetylase (HDAC), histone acetyltransferase (HAT) inhibition, or noncoding RNA expression. Regulation of these epigenetic mechanisms has been shown to have notable influences on the formation and progression of various neoplasms. We have shown that an epigenetic diet can influence both cellular longevity and carcinogenesis through the modulation of certain key genes that encode telomerase and p16. Caloric restriction (CR) can also play a crucial role in aging and cancer. Reductions in caloric intake have been shown to increase both the life- and health-span in a variety of animal models. Moreover, restriction of glucose has been demonstrated to decrease the incidence of age-related diseases such as cancer and diabetes. A diet rich in compounds such as genistein, SFN and EGCG can positively modulate the epigenome and lead to many health benefits. Also, reducing the quantity of calories and glucose in the diet can confer an increased health-span, including reduced cancer incidence. PMID:25568452

  19. Types of Cancer Treatment: Hormone Therapy

    Cancer.gov

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  20. Co-Managing Patients with Type 1 Diabetes and Cancer.

    PubMed

    Best, Conor J; Thosani, Sonali; Ortiz, Marjorie; Levesque, Celia; Varghese, Sigi S; Lavis, Victor R

    2016-08-01

    The life expectancy of people with type 1 diabetes is improving and now approaches that of those without diabetes. As this population ages, a growing number will be diagnosed with and treated for cancer. Cancer treatments can drastically affect insulin requirement and glycemic control through multiple mechanisms including high doses of glucocorticoids and targeted therapies that directly interfere with cellular pathways involved in the action of insulin. Patients with cancer frequently also have alterations in gastrointestinal motility or appetite and require supplemental enteral or parenteral nutrition. Few studies have evaluated these patients directly, but data on patients with and without diabetes suggest that glycemic control may play a larger role in cancer outcomes than is often recognized. Collaboration between the treating oncologist and diabetologist allows people with diabetes to receive the most effective therapies for their cancers without undue risk of hypoglycemia or adverse outcomes due to hyperglycemia. PMID:27319323

  1. The Intricate Interplay between Mechanisms Underlying Aging and Cancer

    PubMed Central

    Piano, Amanda; Titorenko, Vladimir I.

    2015-01-01

    Age is the major risk factor in the incidence of cancer, a hyperplastic disease associated with aging. Here, we discuss the complex interplay between mechanisms underlying aging and cancer as a reciprocal relationship. This relationship progresses with organismal age, follows the history of cell proliferation and senescence, is driven by common or antagonistic causes underlying aging and cancer in an age-dependent fashion, and is maintained via age-related convergent and divergent mechanisms. We summarize our knowledge of these mechanisms, outline the most important unanswered questions and suggest directions for future research. PMID:25657853

  2. Cancer and Aging: General Principles, Biology, and Geriatric Assessment.

    PubMed

    Li, Daneng; de Glas, Nienke A; Hurria, Arti

    2016-02-01

    Cancer is a disease of aging as older adults are much more likely to develop cancer compared with their younger counterparts. Understanding the biology of cancer and aging remains complex, and numerous theories regarding the relationship between the two have been proposed. Cancer treatment decisions in older patients are particularly challenging, because the evidence is scarce and the risk of toxicity increases with age. Determination of biologic age is essential due to heterogeneity of functional status, comorbidity, and physiologic reserves between patients of the same chronologic age. PMID:26614857

  3. Prognostic Typing in Breast Cancer

    PubMed Central

    Hartveit, F.

    1971-01-01

    Infiltrating breast carcinomas in which recurrence takes place 10 years or more after operation are reported to contain tumour cells of characteristic morphology. The cytological features of these tumour cells form the basis of the system of classification described here. Three cytological types are recognized, prognosis being best in type III. Typing is carried out on specimens stained with haematoxylin and eosin. The results of typing were reproducible in over 90% of cases and independent of the histology of the lesion. Correlation to survival time was shown in a total of 222 cases. ImagesFIG. 1 PMID:4107964

  4. Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance.

    PubMed

    van Spaendonck-Zwarts, Karin Y; Badeloe, Sadhanna; Oosting, Sjoukje F; Hovenga, Sjoerd; Semmelink, Harry J F; van Moorselaar, R Jeroen A; van Waesberghe, Jan Hein; Mensenkamp, Arjen R; Menko, Fred H

    2012-03-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation carriers starting at the age of 20 years. However, recently an 18-year-old woman from a Dutch family with HLRCC presented with metastatic renal cancer. We describe the patient and family data, evaluate current evidence on renal cancer risk and surveillance in HLRCC and consider the advantages and disadvantages of starting surveillance for renal cancer in childhood. We also discuss the targeted therapies administered to our patient. PMID:22086304

  5. Online CME Series Can Nutrition Simultaneously Affect Cancer and Aging? | Division of Cancer Prevention

    Cancer.gov

    Aging is considered by some scientists to be a normal physiological process, while others believe it is a disease. Increased cancer risk in the elderly raises the question regarding the common pathways for cancer and aging. Undeniably, nutrition plays an important role in both cases and this webinar will explore whether nutrition can simultaneously affect cancer and aging. |

  6. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kamakura, T.; Haraguchi, Y.; Saku, M.; Sugimachi, K.

    1995-01-01

    The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types. PMID:7640228

  7. Ferrocifen type anti cancer drugs.

    PubMed

    Jaouen, Gérard; Vessières, Anne; Top, Siden

    2015-12-21

    Despite current developments in therapeutics focusing on biotechnologically-oriented species, the unflagging utility of small molecules or peptides in medicine is still producing strong results. In 2014 for example, of the 41 new medicines authorized for sale, 33 belonged to the category of small molecules, while in 2013 they represented 24 of 27, according to the FDA. This can be explained as the result of recent forays into new or long-neglected areas of chemistry. Medicinal organometallic chemistry can provide us with an antimalarial against resistant parasitic strains, as attested by the phase II clinical development of ferroquine, with a new framework for conceptual advances based on three-dimensional space-filling, and with redox or indeed catalytic intracellular properties. In this context, bioferrocene species with antiproliferative potential have for several years been the subject of sustained effort, based on some initial successes and on the nature of ferrocene as a stable aromatic, with low toxicity, low cost, and possessing reversible redox properties. We show here the different antitumoral approaches offered by ferrocifen derivatives, originally simple derivatives of tamoxifen, which over the course of their development have proved to possess remarkable structural and mechanistic diversity. These entities act via various targets, some of which have been identified, that are triggered according to the concentration of the products. They also act according to the nature of the cancer cells and their functionality, by mechanistic pathways that can operate either synergistically or not, in successive, concomitant or sequential ways, depending for example on newly identified signaling pathways inducing senescence or apoptosis. Here we present a first attempt to rationalize the behavior of these entities with various anticancer targets. PMID:26486993

  8. Age Differences in Types of Interpersonal Tensions

    ERIC Educational Resources Information Center

    Cichy, Kelly E.; Fingerman, Karen L.; Lefkowitz, Eva S.

    2007-01-01

    This study examined age differences in topics that generate interpersonal tensions as well as relationship level characteristics that may account for variability in the content of interpersonal tensions. Participants aged 13 to 99 years (N = 184) diagramed their close and problematic social networks, and then provided open-ended descriptions of…

  9. Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium.

    PubMed

    Setiawan, Veronica Wendy; Pike, Malcolm C; Karageorgi, Stalo; Deming, Sandra L; Anderson, Kristin; Bernstein, Leslie; Brinton, Louise A; Cai, Hui; Cerhan, James R; Cozen, Wendy; Chen, Chu; Doherty, Jennifer; Freudenheim, Jo L; Goodman, Marc T; Hankinson, Susan E; Lacey, James V; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Lurie, Galina; Mack, Thomas; Matsuno, Rayna K; McCann, Susan; Moysich, Kirsten B; Olson, Sara H; Rastogi, Radhai; Rebbeck, Timothy R; Risch, Harvey; Robien, Kim; Schairer, Catherine; Shu, Xiao-Ou; Spurdle, Amanda B; Strom, Brian L; Thompson, Pamela J; Ursin, Giske; Webb, Penelope M; Weiss, Noel S; Wentzensen, Nicolas; Xiang, Yong-Bing; Yang, Hannah P; Yu, Herbert; Horn-Ross, Pamela L; De Vivo, Immaculata

    2012-08-15

    Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P(trend) < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. PMID:22831825

  10. Anthropometric measures at different ages and endometrial cancer risk

    PubMed Central

    Maso, L Dal; Tavani, A; Zucchetto, A; Montella, M; Ferraroni, M; Negri, E; Polesel, J; Decarli, A; Talamini, R; La Vecchia, C; Franceschi, S

    2011-01-01

    Background: Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain. Ethods: M A case–control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models. Results: The OR for BMI >30 at diagnosis compared with 20 to <25 kg m−2 was 4.08 (95% CI: 2.90–5.74). The association for BMI was monotonic with a possible steeper increase for BMI above 28. Conversely, waist-to-hip ratio (WHR) showed a bell shaped curve with increased OR (2.10; 95% CI: 1.43–3.09) in the intermediate tertile only. After stratification by BMI at diagnosis, history of weight loss and BMI at age 30 did not influence endometrial cancer risk. History of obesity in middle age had a weak and not significant adverse effect among obese women (OR=1.60; 95% CI: 0.52–4.96). Conclusion: The predominant importance of recent weight compared to lifetime history, justifies encouraging weight reduction in women at any age. PMID:21386846

  11. Selective anti-cancer agents as anti-aging drugs

    PubMed Central

    Blagosklonny, Mikhail V

    2013-01-01

    Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are involved in both cancer and aging). In cancer, intrinsic and acquired resistance, tumor heterogeneity, adaptation, and genetic instability of cancer cells all hinder cancer-directed therapy. But for anti-aging applications, these hurdles are irrelevant. For example, since anti-aging interventions should be aimed at normal postmitotic cells, no selection for resistance is expected. At low doses, certain agents may decelerate aging and age-related diseases. Importantly, deceleration of aging can in turn postpone cancer, which is an age-related disease. PMID:24345884

  12. Blood Type Influences Pancreatic Cancer Risk | Division of Cancer Prevention

    Cancer.gov

    A variation in the gene that determines ABO blood type influences the risk of pancreatic cancer, according to the results of the first genome-wide association study (GWAS) for this highly lethal disease. The genetic variation, a single nucleotide polymorphism (SNP), was discovered in a region of chromosome 9 that harbors the gene that determines blood type, the researchers reported August 2 online in Nature Genetics. |

  13. Impact of age on epidermal growth factor receptor mutation in lung cancer.

    PubMed

    Ueno, Tsuyoshi; Toyooka, Shinichi; Suda, Kenichi; Soh, Junichi; Yatabe, Yasushi; Miyoshi, Shinichiro; Matsuo, Keitaro; Mitsudomi, Tetsuya

    2012-12-01

    Aging is one of the best, but rarely referred, risk factors for various types of cancer including lung cancer, because age could be a surrogate for accumulation of genetic events in cancers. Smoking inversely associates with the presence of epidermal growth factor receptor (EGFR) mutation in lung cancer, but its strong confounding with age and sex makes it difficult to evaluate sole impact of age. To clarify an impact of age on EGFR mutation, we conducted a cross-sectional study based on data of 1262 lung cancer patients. The associations between EGFR mutation and age, considering sex, smoking and histology, were evaluated using logistic regression models. In multivariate analysis, we found a significant increase of EGFR mutation prevalence by increase of age (p-trend=0.0004). Consistent trend was observed among never-smoking females (p-trend=0.011) and never-smoking males also showed similar trend although not significant. These were consistently observed when we limit the subject to those with adenocarcinoma. In conclusion, age independently associates with EGFR mutation among lung cancer. Positive association between EGFR mutation and age among never-smokers regardless of sex might indicate that EGFR mutation occurs cumulatively by unidentified internal/external factors other than smoking. PMID:23036155

  14. Burden of cancer associated with type 2 diabetes mellitus in Japan, 2010-2030.

    PubMed

    Saito, Eiko; Charvat, Hadrien; Goto, Atsushi; Matsuda, Tomohiro; Noda, Mitsuhiko; Sasazuki, Shizuka; Inoue, Manami

    2016-04-01

    Diabetes mellitus constitutes a major disease burden globally, and the prevalence of diabetes continues to increase worldwide. We aimed to estimate the burden of cancer associated with type 2 diabetes mellitus in Japan between 2010 and 2030. In this study, we estimated the population attributable fraction of cancer risk associated with type 2 diabetes in 2010 and 2030 using the prevalence estimates of type 2 diabetes in Japan from 1990 to 2030, summary hazard ratios of diabetes and cancer risk from a pooled analysis of eight large-scale Japanese cohort studies, observed incidence/mortality of cancer in 2010 and predicted incidence/mortality for 2030 derived from the age-period-cohort model. Our results showed that between 2010 and 2030, the total numbers of cancer incidence and mortality were predicted to increase by 38.9% and 10.5% in adults aged above 20 years, respectively. In the number of excess incident cancer cases associated with type 2 diabetes, an increase of 26.5% in men and 53.2% in women is expected between 2010 and 2030. The age-specific analysis showed that the population attributable fraction of cancer will increase in adults aged >60 years over time, but will not change in adults aged 20-59 years. In conclusion, this study suggests a modest but steady increase in cancers associated with type 2 diabetes. PMID:27079439

  15. AGE metabolites: a biomarker linked to cancer disparity?

    PubMed

    Foster, Dion; Spruill, Laura; Walter, Katherine R; Nogueira, Lourdes M; Fedarovich, Hleb; Turner, Ryan Y; Ahmed, Mahtabuddin; Salley, Judith D; Ford, Marvella E; Findlay, Victoria J; Turner, David P

    2014-10-01

    Socioeconomic and environmental influences are established factors promoting cancer disparity, but the contribution of biologic factors is not clear. We report a mechanistic link between carbohydrate-derived metabolites and cancer that may provide a biologic consequence of established factors of cancer disparity. Glycation is the nonenzymatic glycosylation of carbohydrates to macromolecules, which produces reactive metabolites called advanced glycation end products (AGE). A sedentary lifestyle and poor diet all promote disease and the AGE accumulation pool in our bodies and also increase cancer risk. We examined AGE metabolites in clinical specimens of African American and European American patients with prostate cancer and found a higher AGE concentration in these specimens among African American patients when compared with European American patients. Elevated AGE levels corresponded with expression of the receptor for AGE (RAGE or AGER). We show that AGE-mediated increases in cancer-associated processes are dependent upon RAGE. Aberrant AGE accumulation may represent a metabolic susceptibility difference that contributes to cancer disparity. PMID:25053712

  16. AGE metabolites: A biomarker linked to cancer disparity?

    PubMed Central

    Foster, Dion; Spruill, Laura; Walter, Katherine R.; Nogueira, Lourdes M.; Fedarovich, Hleb; Turner, Ryan Y.; Ahmed, Mahtabuddin; Salley, Judith D.; Ford, Marvella E.; Findlay, Victoria J.; Turner, David P.

    2014-01-01

    Socioeconomic and environmental influences are established factors promoting cancer disparity but the contribution of biological factors is not clear. We report a mechanistic link between carbohydrate derived metabolites and cancer which may provide a biological consequence of established factors of cancer disparity. Glycation is the non-enzymatic glycosylation of carbohydrates to macromolecules which produces reactive metabolites called advanced glycation end products (AGEs). A sedentary lifestyle and poor diet all promote disease and the AGE accumulation pool in our bodies and also increase cancer risk. We examined AGE metabolites in clinical specimens of African American and European American prostate cancer patients and found a higher AGE concentration in these specimens among African American patients when compared to European American patients. Elevated AGE levels corresponded with expression of the receptor for AGE (RAGE or AGER). We show that AGE mediated increases in cancer associated processes is dependent upon RAGE. Aberrant AGE accumulation may represent a metabolic susceptibility difference that contributes to cancer disparity. PMID:25053712

  17. Cancer Strikes Out!/Definitions/ Glossary/ Common Types

    MedlinePlus

    ... Cover Story: Leukemia/Lymphoma Cancer Strikes Out!/ Definitions/ Glossary/ Common Types Past Issues / Summer 2008 Table of ... stage and the type of cancer. Leukemia-Lymphoma Glossary B-cell: A white blood cell that comes ...

  18. Laser irradiation for central-type lung cancer

    NASA Astrophysics Data System (ADS)

    Sun, Kai

    1993-03-01

    Based on laser irradiation experiments on isolated lung specimens of animals done in 1989, 8 patients with central type lung cancer were treated with Nd:YAG laser irradiation via fiberoptic bronchoscope from January 1990 to August 1991 in our hospital. The patients recruited were all diagnosed by fiberoptic bronchoscopy and histology as having central type bronchopulmonary cancer without distal metastasis. All patients were male with a mean age of 64 (range 57 - 72). Of 8 patients, 4 had squamous cell carcinoma, 3 adenocarcinoma, and 1 undifferentiated small cell carcinoma, all being stage TUM 3. After laser treatment, 6 cases had a result of significant response and 2 had minor response. Among 6 cases of atelectasis, 4 were completely cured or partially improved and 4 recovered from their hemoptysis. The subjective symptoms in all cases remitted. A combined chemotherapy was carried out accompanying laser therapy for all, 6 of whom had a shrink of focus over 25%. Six cases were re-examined with fiberoptic bronchoscopy, showing a distinct reduction of the tumor. Four cases expectorated black charring tissues and residual tumorous tissues persistently as an outcome. Two typical cases are reported, the characteristics, indications, techniques, and side effects of laser therapy are analyzed and factors affecting efficacy discussed, indicating that the technique has such advantages as easy operation, accurate orientation, and safe outcome. The procedure is really an effective one for treating central type lung cancer in intermediate or late stage.

  19. Preparing for an epidemic: cancer care in an aging population.

    PubMed

    Shih, Ya-Chen Tina; Hurria, Arti

    2014-01-01

    The Institute of Medicine's (IOM) Committee on Improving the Quality of Cancer Care: Addressing the Challenges of an Aging Population was charged with evaluating and proposing recommendations on how to improve the quality of cancer care, with a specific focus on the aging population. Based on their findings, the IOM committee recently released a report highlighting their 10 recommendations for improving the quality of cancer care. Based on those recommendations, this article highlights ways to improve evidence-based care and addresses rising costs in health care for older adults with cancer. The IOM highlighted three recommendations to address the current research gaps in providing evidence-based care in older adults with cancer, which included (1) studying populations which match the age and health-risk profile of the population with the disease, (2) legislative incentives for companies to include patients that are older or with multiple morbidities in new cancer drug trials, and (3) expansion of research that contributes to the depth and breadth of data available for assessing interventions. The recommendations also highlighted the need to maintain affordable and accessible care for older adults with cancer, with an emphasis on finding creative solutions within both the care delivery system and payment models in order to balance costs while preserving quality of care. The implementation of the IOM's recommendations will be a key step in moving closer to the goal of providing accessible, affordable, evidence-based, high-quality care to all patients with cancer. PMID:24857069

  20. What Are the Most Common Types of Childhood Cancers?

    MedlinePlus

    ... see Brain and Spinal Cord Tumors in Children . Neuroblastoma Neuroblastoma starts in early forms of nerve cells found ... or fetus. About 6% of childhood cancers are neuroblastomas. This type of cancer develops in infants and ...

  1. Opportunities for Cancer Prevention Among Adults Aged 45 to 64

    PubMed Central

    Zonderman, Alan B.; Ejiogu, Ngozi; Norbeck, Jennifer; Evans, Michele K.

    2015-01-01

    Despite the advances in cancer medicine and the resultant 20% decline in cancer death rates for Americans since 1991, there remain distinct cancer health disparities among African Americans, Hispanics, Native Americans, and the those living in poverty. Minorities and the poor continue to bear the disproportionate burden of cancer especially in terms of stage at diagnosis, incidence and mortality. Cancer health disparities are persistent reminders that state-of-the art cancer prevention, diagnosis, and treatment are not equally effective for and accessible to all Americans. The cancer prevention model must take into account the phenotype of accelerated aging associated with health disparities as well as the important interplay of biological and sociocultural factors that lead to disparate health outcomes. The building blocks of this prevention model will include: interdisciplinary prevention modalities that encourage partnerships across medical and nonmedical entities, community-based participatory research, development of ethnically and racially diverse research cohorts, and full actualization of the prevention benefits outlined in the 2010 Patient Protection and Affordable Care Act. However, the most essential facet should be a thoughtful integration of cancer prevention and screening into prevention, screening, and disease management activities for hypertension and diabetes mellitus since these chronic medical illnesses have a substantial prevalence in populations at risk for cancer disparities and cause considerable comorbidity and likely complicate effective treatment and contribute to disproportionate cancer death rates. PMID:24512936

  2. Modeling age-specific cancer incidences using logistic growth equations: implications for data collection.

    PubMed

    Shen, Xing-Rong; Feng, Rui; Chai, Jing; Cheng, Jing; Wang, De-Bin

    2014-01-01

    Large scale secular registry or surveillance systems have been accumulating vast data that allow mathematical modeling of cancer incidence and mortality rates. Most contemporary models in this regard use time series and APC (age-period-cohort) methods and focus primarily on predicting or analyzing cancer epidemiology with little attention being paid to implications for designing cancer registry, surveillance or evaluation initiatives. This research models age-specific cancer incidence rates using logistic growth equations and explores their performance under different scenarios of data completeness in the hope of deriving clues for reshaping relevant data collection. The study used China Cancer Registry Report 2012 as the data source. It employed 3-parameter logistic growth equations and modeled the age-specific incidence rates of all and the top 10 cancers presented in the registry report. The study performed 3 types of modeling, namely full age-span by fitting, multiple 5-year- segment fitting and single-segment fitting. Measurement of model performance adopted adjusted goodness of fit that combines sum of squred residuals and relative errors. Both model simulation and performance evalation utilized self-developed algorithms programed using C# languade and MS Visual Studio 2008. For models built upon full age-span data, predicted age-specific cancer incidence rates fitted very well with observed values for most (except cervical and breast) cancers with estimated goodness of fit (Rs) being over 0.96. When a given cancer is concerned, the R valuae of the logistic growth model derived using observed data from urban residents was greater than or at least equal to that of the same model built on data from rural people. For models based on multiple-5-year-segment data, the Rs remained fairly high (over 0.89) until 3-fourths of the data segments were excluded. For models using a fixed length single-segment of observed data, the older the age covered by the corresponding

  3. Breast cancer racial differences before age 40--implications for screening.

    PubMed Central

    Johnson, Edwin T.

    2002-01-01

    BACKGROUND: Most authorities advocate mammogram screening for breast cancer beginning at age 40 based on the age-specific distribution and incidence of breast cancer in the general population. This policy has been bolstered by studies that demonstrate that, for the general population, mammography in the 40-49 age bracket reduces mortality. However, it also has been reported that African-American breast cancer patients are diagnosed more often than white patients below the age of 40. Young African-American women are also more likely to have advanced disease at the time of diagnosis with predictably higher mortality. The purpose of this investigation is to explore the question, whether a subset of African-American women, age 30-39, by virtue of increased vulnerability, would benefit from early mammogram screening. STUDY DESIGN: The age-specific distribution (age 30-84) of African-American and white breast cancer patients in five State cancer registries were compared. Prognostic indicators (tumor size and nodal status) in two of the five registries in African-American and white breast cancer cases below the age of 40 were compared. Age-specific incidence in the 30-39 age group and the relative populations of black and white women in the United States were noted in the Surveillance Epidemiology and End Report (SEER) (1994-1998) and The U.S. Census 2000. RESULTS: The differences of age-specific distribution and age-specific incidence of African-American and white breast cancer patients were found to be significant. More than 10% of African-American women with breast cancer were diagnosed before age 40 compared to 5% of white patients. The incidence of breast cancer (SEER Report 1994-1998) in the 30-39-age bracket for African-American and white women was 48.9 and 40.2 at the 95% confidence level, while the proportion of African-American and white women reported by the Census Bureau was not too dissimilar, 15.8% and 14.6% respectively. Prognostic indicators (tumor size

  4. Q-Type Factor Analysis of Healthy Aged Men.

    ERIC Educational Resources Information Center

    Kleban, Morton H.

    Q-type factor analysis was used to re-analyze baseline data collected in 1957, on 47 men aged 65-91. Q-type analysis is the use of factor methods to study persons rather than tests. Although 550 variables were originally studied involving psychiatry, medicine, cerebral metabolism and chemistry, personality, audiometry, dichotic and diotic memory,…

  5. Analysis of the Potent Prognostic Factors in Luminal-Type Breast Cancer

    PubMed Central

    Kim, Han-Sung; Park, Inseok; Cho, Hyun Jin; Yang, Keunho; Bae, Byung Noe; Kim, Ki Whan; Han, Sehwan; Kim, Hong-Joo; Kim, Young-Duck

    2012-01-01

    Purpose Luminal-type breast cancer has a good prognosis compared to other types, such as human epidermal growth factor receptor 2 and triple negative types. Luminal-type breast cancer is classified into luminal A and B, according to the proliferation index. We investigated the clinicopathological factors that affect the prognosis of the luminal-type subgroups. Methods We reviewed the medical records and the pathologic reports of 159 luminal-type breast cancer patients who were treated between February 2005 and November 2007. We divided luminal-type breast cancer into luminal A and B, according to Ki-67 (cutoff value, 14%) and analyzed the clinicopathologic factors, such as age at diagnosis, intensity score of estrogen receptor and progesterone receptor, histologic grade, and Bcl-2. Moreover, we compared the disease-free survival (DFS) of each group. Results In the univariate analysis, age (p=0.004), tumor size (p=0.010), lymph node metastasis (p=0.001), and Bcl-2 (p=0.002) were statistically significant factors in luminal-type breast cancer. In the multivariate analysis, lymph node (p=0.049) and Bcl-2 (p=0.034) were significant relevant factors in luminal-type breast cancer. In the subgroup analysis, the increased Bcl-2 (cutoff value, 33%) was related with a longer DFS in the luminal B group (p=0.004). Conclusion In our study, luminal A breast cancer showed a longer DFS than luminal B breast cancer, further, Bcl-2 may be a potent prognostic factor in luminal-type breast cancer. PMID:23346168

  6. Breast cancer screening among women of child-bearing age.

    PubMed

    Munyaradzi, Daphne; January, James; Maradzika, Julita

    2014-01-01

    We explored behavioral factors that contributed to late presentation of breast cancer. A cross-sectional survey of 120 women of child-bearing age was employed, and data were collected using interviewer-administered questionnaires addressing predisposing, enabling, and reinforcing factors associated with breast cancer screening. A total of 53.5% knew what breast cancer screening was; breast self-exam was the most commonly known form of screening, although only 7.5% practiced it. Lack of awareness (p =.004) and the knowledge of someone who previously had breast cancer (p =.0004) were prominent predictors for breast cancer screening, leading to either delay in or early presentation of the condition, respectively. PMID:24875862

  7. Universality of aging: family caregivers for elderly cancer patients

    PubMed Central

    Baider, Lea; Surbone, Antonella

    2014-01-01

    The world population is aging, with the proportion of older people (65+ years) expected to reach 21% in 2050 and to exceed the number of younger people (aged 15 or less) for the first time in history. Because cancer is particularly a chronic disease of older people, a large increase in the number of elderly patients with cancer is anticipated. The estimated number of new cancer cases worldwide among people over 65 is expected to grow from about 6 million in 2008 to more than 11 million during the coming decade. By 2030, individuals over 65 are expected to account for 70% of all cancer patients in the Western world. Along with the increase in oncology patients, the number of older people caring for their ill spouses or other relatives is also growing, with the ensuing toll on these caregivers causing major concern, especially in western countries. In different societies the characteristics of family caregiver stressors, cultural norms concerning caregiving, and the availability of support have a huge impact on those providing care. Any study of older caregivers of older cancer patients requires an integrative evaluation of aging that takes into account cultural, social, psychological, and behavioral variables. This review proposes a critical discussion of the multidimensionality of the caregiving and of the impact that age, culture, and gender have on it. PMID:25076927

  8. Pattern of malignancies in children <15 years of age reported in Hadhramout Cancer Registry, Yemen between 2002 and 2014

    PubMed Central

    Jawass, Mazin A.; Al-Ezzi, Jalil I.; Gouth, Hanan S. Bin; Bahwal, Saleh A.; Bamatraf, Fawzia F.; Ba’amer, Abubakir A.

    2016-01-01

    Objectives: To describe the patterns of childhood cancers in Hadhramout Sector, Yemen between January 2002 and December 2014. Methods: This descriptive retrospective study was based on secondary data from Hadhramout Cancer Registry, Hadhramout, Yemen. All Yemeni children under age of 15 years, who were diagnosed with cancer were included. The International Childhood Cancer Classification system was used to categorize cancer types. Results: A total of 406 childhood cancers of both gender <15 years of age were reported. These represented 8.5% of all cases registered. The mean age was 7.34 ± 4.18 years. There were 240 males (59.1%) and 166 females (40.9%) with a male to female ratio of 1.4:1. Calculated incidence of cancer in children in this population is 1.9 per 100,000. The predominant age group was 5-9 years (35%) followed by 10-14 years (33.7%), and 0-4 years group (31%). The most common group of malignancies were hematological malignancies accounting for 47% of cases, followed by nervous system malignancies (15%). The most frequently reported cancer types were lymphoma (24%), leukemia (23%), carcinoma (13.1%), and central nervous system (CNS) tumors (11.6%). Conclusions: There is a lower frequency of childhood cancer in Hadhramout Sector when compared with developed countries. The most common cancers among children were lymphoma, leukemia, carcinoma, and CNS tumors. PMID:27146613

  9. Aging Impacts Transcriptome but not Genome of Hormone-dependentBreast Cancers

    SciTech Connect

    Yau, Christina; Fedele, Vita; Roydasgupta, Ritu; Fridlyand, Jane; Hubbard, Alan; Gray, Joe W.; Chew, Karen; Dairkee, Shanaz H.; Moore, DanH.; Schittulli, Francesco; Tommasi, Stefania; Paradiso, Angelo; Albertson, Donna G.; Benz, Christopher C.

    2007-10-09

    Age is one of the most important risk factors for human malignancies, including breast cancer; in addition, age-at-diagnosis has been shown to be an independent indicator of breast cancer prognosis. However, except for inherited forms of breast cancer, there is little genetic or epigenetic understanding of the biological basis linking aging with sporadic breast cancer incidence and its clinical behavior.

  10. p53 as an intervention target for cancer and aging

    PubMed Central

    Hasty, Paul; Christy, Barbara A.

    2013-01-01

    p53 is well known for suppressing tumors but could also affect other aging processes not associated with tumor suppression. As a transcription factor, p53 responds to a variety of stresses to either induce apoptosis (cell death) or cell cycle arrest (cell preservation) to suppress tumor development. Yet, the effect p53 has on the non-cancer aspects of aging is complicated and not well understood. On one side, p53 could induce cellular senescence or apoptosis to suppress cancer but as an unintended consequence enhance the aging process especially if these responses diminish stem and progenitor cell populations. But on the flip side, p53 could reduce growth and growth-related stress to enable cell survival and ultimately delay the aging process. A better understanding of diverse functions of p53 is essential to elucidate its influences on the aging process and the possibility of targeting p53 or p53 transcriptional targets to treat cancer and ameliorate general aging. PMID:24124625

  11. Type of Cancer Treatment: Targeted Therapy

    Cancer.gov

    Information about the role that targeted therapies play in cancer treatment. Includes how targeted therapies work against cancer, who receives targeted therapies, common side effects, and what to expect when having targeted therapies.

  12. Aging. Aging-induced type I interferon signaling at the choroid plexus negatively affects brain function

    PubMed Central

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M.; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2016-01-01

    Age-associated cognitive decline is affected by factors produced inside and outside the brain. We found in aged mice and humans, that the choroid plexus (CP), an epithelial interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent expression profile, often associated with anti-viral responses. This signature was induced by brain-derived signals present in the cerebrospinal fluid of aged mice. Blocking IFN-I signaling within the brain of cognitively-impaired aged mice, using IFN-I receptor neutralizing antibody, led to partial restoration of cognitive function and hippocampal neurogenesis, and reestablished IFN-II-dependent CP activity, lost in aging. Our data identify an aging-induced IFN-I signature at the CP, and demonstrate its negative influence on brain function, thereby suggesting a potential target for therapeutic intervention for age-related cognitive decline. PMID:25147279

  13. Aggressive thyroid cancer in low-risk age population

    SciTech Connect

    Rosen, I.B.; Bowden, J.; Luk, S.C.; Simpson, J.A.

    1987-12-01

    Seventy-eight patients under the age of 40 (low-risk patients) who had undergone surgical treatment for well-differentiated thyroid carcinoma were referred from 1979 to 1986 to our hospital for adjuvant therapy. A subgroup of 37 patients, 14 with apparent aggressive cancer, was studied. This study group consisted of 27 female and 10 male patients with mixed papillary and follicular cancer, who ranged in age from 11 to 40 years. Nodal disease occurred in 27 (73%) patients and invasiveness in 30 (81%) patients and involved multiple areas in 9 (24%) patients. Recurrence occurred in 14 (38%) patients and visceral metastases occurred in eight (22%) patients. All patients underwent appropriate surgery, but microscopic residual disease was seen in 15 patients and gross residual disease in seven patients, so that 31 patients underwent iodine-131 therapy, and 17 of these patients also underwent external radiation therapy. Three patients died of their disease, whereas 24 (65%) patients are free of disease and 9 (24%) patients are alive with disease. An additional 7 (19%) patients were initially seen in the fifth to seventh decade after decades of neglected thyroid disease, which culminated in residual cancer and death. Although low-risk categorization for thyroid cancer appears valid, its rigid application in support of conservative treatment may lead to inadequate primary treatment and underdiagnosis of cancer in thyroid nodule disease in the low-risk age population.

  14. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development.

    PubMed

    Podolskiy, Dmitriy I; Lobanov, Alexei V; Kryukov, Gregory V; Gladyshev, Vadim N

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  15. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development

    PubMed Central

    Podolskiy, Dmitriy I.; Lobanov, Alexei V.; Kryukov, Gregory V.; Gladyshev, Vadim N.

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  16. Aging, tumor suppression and cancer: High-wire act!

    SciTech Connect

    Campisi, Judith

    2004-08-15

    Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropy--protecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms.

  17. Study Suggests Type 2 Diabetes-Cancer Link

    MedlinePlus

    ... gov/news/fullstory_159814.html Study Suggests Type 2 Diabetes-Cancer Link It hints at -- but doesn' ... decade before -- and three months following -- a type 2 diabetes diagnosis, new research suggests. Although it's not ...

  18. How type of excuse defense, mock juror age, and defendant age affect mock jurors' decisions.

    PubMed

    Higgins, Pamela L; Heath, Wendy P; Grannemann, Bruce D

    2007-08-01

    The authors investigated the effects of mock juror age (younger vs. older), defendant age (22 vs. 65), and type of excuse defense used by defendants (a highly self-inflicted condition, Cocaine Dependency Disorder, vs. a less self-inflicted condition, Posttraumatic Stress Disorder) on mock juror decisions. Ninety-six younger and 96 older adults read a scenario and answered a questionnaire. Results indicated that the defendant using the highly self-inflicted excuse was more likely to receive a guilty verdict and a longer sentence than was the defendant using the less self-inflicted excuse. Older jurors were more certain of their verdicts and saw the defendant as more responsible for his condition than did younger jurors. Defendant age did not affect juror decisions. In addition, excuse type and juror age affected the jurors' perceptions of the victim's responsibility for the attack. The authors discuss the potential influence of juror age on perceptions of defendant responsibility. PMID:17955749

  19. Role of cancer stem cells in age-related rise in colorectal cancer

    PubMed Central

    Nangia-Makker, Pratima; Yu, Yingjie; Majumdar, Adhip PN

    2015-01-01

    Colorectal cancer (CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells (CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of (1) CSC; (2) epigenetic and genetic mechanisms giving rise to CSCs; (3) markers of CSC; (4) characteristics; and (5) age-related increase in CSC in the colonic crypt. PMID:26600965

  20. The Age Related Properties of Solar Type Stars

    NASA Technical Reports Server (NTRS)

    Soderblom, David

    1999-01-01

    The studies of lithium in solar-type stars in clusters of a wide range of ages has provided critical information on a tracer of convective processes, especially among very young stars. Our most recent work has been on a pre-main sequence cluster (NGC 2264) that took place after this grant expired, but was founded on it. The spread seen in Li in Zero-Age Main Sequence clusters like the Pleiades is huge and possibly related to rotation. No clear spread in seen in NGC 2264, so it does not have its origins in the conditions of formation but is instead a result of processes occurring during PMS evolution. Our observations of M67 were particularly interesting because this cluster is the same age as the Sun, i.e.,very old. Clear evidence was seen for a spread in Li there too, indicating that the spread seen in very young stars perpetuates itself into old age.

  1. Contraceptive Practices Among Female Cancer Survivors of Reproductive Age

    PubMed Central

    Dominick, Sally A.; McLean, Mamie R.; Whitcomb, Brian W.; Gorman, Jessica R.; Mersereau, Jennifer E.; Bouknight, Janet M.; Su, H. Irene

    2015-01-01

    Objective To compare rates of contraception between reproductive-aged cancer survivors and women in the general U.S. population. Among survivors, the study examined factors associated with use of contraception and emergency contraception. Methods This study analyzed enrollment data from an ongoing national prospective cohort study on reproductive health after cancer entitled the Fertility Information Research Study. We compared current contraceptive use in survivors with that of the general population ascertained by the 2006–2010 National Survey for Family Growth. Log-binomial regression models estimated relative risks for characteristics associated with use of contraception, World Health Organization tiers I–II (sterilization and hormonal) contraceptive methods, and emergency contraception in survivors. Results Data from 295 survivors (mean age 31.6 ± 5.7 years, range 20–44 years) enrolled in this prospective study (85% response rate) were examined. Age-adjusted rates of using tiers I–II contraceptive methods were lower in survivors than the general population (34% [28.8–40.0] compared with 53% [51.5–54.5], P<.01). Only 56% of survivors reported receiving family planning services (counseling, prescription or procedure related to birth control) since cancer diagnosis. In adjusted analysis, receipt of family planning services was associated with both increased use of tiers I–II contraceptive methods (relative risk 1.3, 95% confidence interval [CI] 1.1–1.5) and accessing emergency contraception (relative risk 5.0, 95% CI 1.6–16.3) in survivors. Conclusion Lower rates of using Tiers I–II contraceptive methods were found in reproductive-aged cancer survivors compared to the general population of U.S. women. Exposure to family planning services across the cancer care continuum may improve contraception utilization among these women. Clinical Trial Registration ClinicalTrials.gov, www.clinicaltrials.gov, NCT01843140. PMID:26181090

  2. The intersection of cancer and aging: establishing the need for breast cancer rehabilitation.

    PubMed

    Schmitz, Kathryn H; Cappola, Anne R; Stricker, Carrie T; Sweeney, Carol; Norman, Sandra A

    2007-05-01

    The increasing success of treatments for common cancers has resulted in growing awareness of the unique health care needs of cancer survivors. Cancer treatments can be toxic and have long-lasting effects on health, potentially accelerating the aging process and producing associated declines in physical function. In this synthesis of the literature, we critically examine the strength of existing evidence that breast cancer diagnosis and treatment are associated with a disproportionate decline in physical function compared with the effects of living without cancer for the same number of years. There is some observational epidemiologic evidence that women treated for breast cancer report greater declines in physical function than their peers. Discerning the factors associated with such declines and their clinical significance remains to be addressed. Physiologic, psychological, and behavioral changes associated with both aging and cancer treatment are reviewed. Parallels are proposed between existing preventive and rehabilitative programs and possibilities for similar interventions aimed at preventing, reversing, or halting declines in physical function in cancer survivors. Finally, a program of research is proposed to evaluate whether there is some subset of breast cancer survivors for whom prevention or rehabilitation of functional status declines is needed, as well as development of targeted, mechanistically driven interventions. PMID:17507607

  3. Premature aging and cancer in nucleotide excision repair-disorders

    PubMed Central

    Diderich, K.; Alanazi, M.; Hoeijmakers, J.H.J.

    2014-01-01

    During past decades the major impact of DNA damage on cancer as ‘disease of the genes’ has become abundantly apparent. In addition to cancer recent years have also uncovered a very strong association of DNA damage with many features of (premature) aging. The notion that DNA repair systems not only protect against cancer but equally against too fast aging has become evident from a systematic, integral analysis of a variety of mouse mutants carrying defects in e.g. transcription-coupled repair with or without an additional impairment of global genome nucleotide excision repair and the corresponding segmental premature aging syndromes in man. A striking correlation between the degree of the DNA repair deficiency and the acceleration of specific progeroid symptoms has been discovered for those repair systems that primarily protect from the cytotoxic and cytostatic effects of DNA damage. These observations are explained from the perspective of nucleotide excision repair mouse mutant and human syndromes. However, similar principles likely apply to other DNA repair pathways including interstrand crosslink repair and double strand break repair and genome maintenance systems in general, supporting the notion that DNA damage constitutes an important intermediate in the process of aging. PMID:21680258

  4. Types of Cancer Associated with Transplant Recipients

    MedlinePlus

    ... cancer can be transmitted through deceased and living donor organ, cell and tissue transplantation. Treatment of donor related ... 2000. First Report of the United Network for Organ Sharing Transplant Tumor Registry: Donors with a History of Cancer. Transplantation 80:883- ...

  5. Detectable clonal mosaicism and its relationship to aging and cancer

    PubMed Central

    Jacobs, Kevin B; Yeager, Meredith; Zhou, Weiyin; Wacholder, Sholom; Wang, Zhaoming; Rodriguez-Santiago, Benjamin; Hutchinson, Amy; Deng, Xiang; Liu, Chenwei; Horner, Marie-Josephe; Cullen, Michael; Epstein, Caroline G; Burdett, Laurie; Dean, Michael C; Chatterjee, Nilanjan; Sampson, Joshua; Chung, Charles C; Kovaks, Joseph; Gapstur, Susan M; Stevens, Victoria L; Teras, Lauren T; Gaudet, Mia M; Albanes, Demetrius; Weinstein, Stephanie J; Virtamo, Jarmo; Taylor, Philip R; Freedman, Neal D; Abnet, Christian C; Goldstein, Alisa M; Hu, Nan; Yu, Kai; Yuan, Jian-Min; Liao, Linda; Ding, Ti; Qiao, You-Lin; Gao, Yu-Tang; Koh, Woon-Puay; Xiang, Yong-Bing; Tang, Ze-Zhong; Fan, Jin-Hu; Aldrich, Melinda C; Amos, Christopher; Blot, William J; Bock, Cathryn H; Gillanders, Elizabeth M; Harris, Curtis C; Haiman, Christopher A; Henderson, Brian E; Kolonel, Laurence N; Le Marchand, Loic; McNeill, Lorna H; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret R; Wiencke, John K; Wrensch, Margaret; Wu, Xifeng; Zanetti, Krista A; Ziegler, Regina G; Figueroa, Jonine D; Garcia-Closas, Montserrat; Malats, Nuria; Marenne, Gaelle; Prokunina-Olsson, Ludmila; Baris, Dalsu; Schwenn, Molly; Johnson, Alison; Landi, Maria Teresa; Goldin, Lynn; Consonni, Dario; Bertazzi, Pier Alberto; Rotunno, Melissa; Rajaraman, Preetha; Andersson, Ulrika; Freeman, Laura E Beane; Berg, Christine D; Buring, Julie E; Butler, Mary A; Carreon, Tania; Feychting, Maria; Ahlbom, Anders; Gaziano, J Michael; Giles, Graham G; Hallmans, Goran; Hankinson, Susan E; Hartge, Patricia; Henriksson, Roger; Inskip, Peter D; Johansen, Christoffer; Landgren, Annelie; McKean-Cowdin, Roberta; Michaud, Dominique S; Melin, Beatrice S; Peters, Ulrike; Ruder, Avima M; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Visvanathan, Kala; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Silverman, Debra T; Kogevinas, Manolis; Gonzalez, Juan R; Villa, Olaya; Li, Donghui; Duell, Eric J; Risch, Harvey A; Olson, Sara H; Kooperberg, Charles; Wolpin, Brian M; Jiao, Li; Hassan, Manal; Wheeler, William; Arslan, Alan A; Bas Bueno-de-Mesquita, H; Fuchs, Charles S; Gallinger, Steven; Gross, Myron D; Holly, Elizabeth A; Klein, Alison P; LaCroix, Andrea; Mandelson, Margaret T; Petersen, Gloria; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Canzian, Federico; Chang, Kenneth; Cotterchio, Michelle; Giovannucci, Edward L; Goggins, Michael; Bolton, Judith A Hoffman; Jenab, Mazda; Khaw, Kay-Tee; Krogh, Vittorio; Kurtz, Robert C; McWilliams, Robert R; Mendelsohn, Julie B; Rabe, Kari G; Riboli, Elio; Tjønneland, Anne; Tobias, Geoffrey S; Trichopoulos, Dimitrios; Elena, Joanne W; Yu, Herbert; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael Z; Kraft, Peter; Schumacher, Fredrick; Stram, Daniel; Savage, Sharon A; Mirabello, Lisa; Andrulis, Irene L; Wunder, Jay S; García, Ana Patiño; Sierrasesúmaga, Luis; Barkauskas, Donald A; Gorlick, Richard G; Purdue, Mark; Chow, Wong-Ho; Moore, Lee E; Schwartz, Kendra L; Davis, Faith G; Hsing, Ann W; Berndt, Sonja I; Black, Amanda; Wentzensen, Nicolas; Brinton, Louise A; Lissowska, Jolanta; Peplonska, Beata; McGlynn, Katherine A; Cook, Michael B; Graubard, Barry I; Kratz, Christian P; Greene, Mark H; Erickson, Ralph L; Hunter, David J; Thomas, Gilles; Hoover, Robert N; Real, Francisco X; Fraumeni, Joseph F; Caporaso, Neil E; Tucker, Margaret; Rothman, Nathaniel; Pérez-Jurado, Luis A; Chanock, Stephen J

    2012-01-01

    In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of size >2 Mb were observed in autosomes of 517 individuals (0.89%) with abnormal cell proportions between 7% and 95%. In cancer-free individuals, the frequency increased with age; 0.23% under 50 and 1.91% between 75 and 79 (p=4.8×10−8). Mosaic abnormalities were more frequent in individuals with solid-tumors (0.97% versus 0.74% in cancer-free individuals, OR=1.25, p=0.016), with a stronger association for cases who had DNA collected prior to diagnosis or treatment (OR=1.45, p=0.0005). Detectable clonal mosaicism was common in individuals for whom DNA was collected at least one year prior to diagnosis of leukemia compared to cancer-free individuals (OR=35.4, p=3.8×10−11). These findings underscore the importance of the role and time-dependent nature of somatic events in the etiology of cancer and other late-onset diseases. PMID:22561519

  6. Exercise enhances wound healing and prevents cancer progression during aging by targeting macrophage polarity.

    PubMed

    Goh, Jorming; Ladiges, Warren C

    2014-07-01

    Physical activity, which can include regular and repetitive exercise training, has been shown to decrease the incidence of age-related diseases. Aging is characterized by aberrant immune responses, including impaired wound healing and increased cancer risk. The behavior and polarized phenotype of tissue macrophages are distinct between young and old organisms. The balance of M1 and M2 macrophages is altered in the aged tissue microenvironment, with a tilt towards an M2-dominant macrophage population, as well as its associated signaling pathways. These M2-type responses may result in unresolved inflammation and create an environment that impairs wound healing and is favorable for cancer growth. We discuss the concept that exercise training can improve the regulation of macrophage polarization and normalize the inflammatory process, and thereby exert anticancer effects and enhance wound healing in older humans. PMID:24932991

  7. Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types.

    PubMed

    Park, Solip; Lehner, Ben

    2015-07-01

    Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another. PMID:26227665

  8. Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types

    PubMed Central

    Park, Solip; Lehner, Ben

    2015-01-01

    Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another. PMID:26227665

  9. Oncofertility for gynecologic and non-gynecologic cancers: fertility sparing in young women of reproductive age.

    PubMed

    Dursun, Polat; Doğan, N Utku; Ayhan, Ali

    2014-12-01

    About ten percent of all female cancer survivors is younger than 40 years of age. For these young women the primary goal is to ensure the highest possibility of cure and to maintain the reproductive functions as well. Oncofertility is a new concept including both oncology and reproductive medicine. By this recently defined concept young women will have maximal chance to make an optimal decision without any significant impact and delay in oncologic outcome. Oncofertility concept could be applied for genital cancer as well as non-genital cancer of reproductive age. Currently sperm and embryo banking are the standard methods used for young patients with cancer whose future fertility is under risk. In contrary oocyte banking, ovarian tissue cryopreservation are all controversial procedures and still accepted as experimental by many authors although American Society of Reproductive Medicine (ASRM) consideres oocyte cryopreservation "no longer experimental". For genital cancers procedures for oncofertility depends on the type of the cancer and the treatment of choice. In this review the current data and concepts regarding oncofertility concept including the gynecologic oncologic perspective is reviewed. PMID:25090914

  10. Interrelation between Western type cancers and non-Western type cancers as regards their risk variations in time and space. VI. Chronological transition of various cancer risks of the world from 1975 to 1985.

    PubMed

    Kodama, M; Kodama, T

    1993-01-01

    We comparatively investigated the age-adjusted incidence rates (AAIRs) of overall cancers of the world between 1975 and 1985 to see whether or not any consistent change is in progress in the risk for cancer in general on a world scale. Results obtained are summarized as follows: 1) the total male population of the world, but not the total female population, experienced a significant rise in AAIR for cancers of all sites during the above 10 years. 2) In the comparison study of geographical subgroups, the above integral cancer risk significantly increased with time in the male population of Canada, USA-White, USA-Black, European continent (EC)-West, EC-others and Great Britain, and also in the female populations of both USA-Black and Great Britain. In other geographical subgroups the cancer risks for 1985 were also higher than those for 1975, but the differences were not statistically significant. 3) The above increase of cancer risk in general was accounted for by a surplus in weight of the increasing contribution of Western-type cancers over the decreasing contribution of non-Western type cancers to the integral cancer risk of a population. 4) Japan was found to be an exceptional case in that the risk for liver cancer (a non-Western type cancer) increased 3 to 8 fold from 1975 to 1985 in both male and female populations of Japan. Evidence was presented to suggest that the above increase of liver cancer incidence could be related to the persistence of social tension following the first oil crisis in 1973. In summary, the chronological transition patterns of cancer risk in Japan as well as in other parts of the world support our interpretation that social tension linked to the economic recession plays a crucial role in the production of recent changes of cancer risk in the world. PMID:8135476

  11. Types of Cancer Associated with Transplant Recipients

    MedlinePlus

    ... normal population. Cancer due to suppression of the immune system Transplant recipients have an increased risk of developing ... growth of white blood cells in the body's immune system. There are several treatment options that will require ...

  12. A survey of cancer and occupation in young and middle aged men. II. Non-respiratory cancers.

    PubMed Central

    Coggon, D; Pannett, B; Osmond, C; Acheson, E D

    1986-01-01

    In a search for clues to previously unrecognised industrial carcinogens the occupational and smoking histories of young and middle aged men with different types of cancer have been compared. The study population comprised men aged 18-54 and resident in the counties of Cleveland, Humberside, and Cheshire (including the Wirral). Within this population 2942 patients in whom cancers were first diagnosed during the period 1975-80 were identified retrospectively from hospital and cancer registration records. Lifetime occupational and smoking histories were then sought from these subjects (or if they had died by proxy from their next of kin), using a postal questionnaire. The overall response rate was 52.1%. Analysis of limited occupational data obtained from the hospital notes of 89% of the patients suggests that no serious bias arose from the incomplete response to the questionnaire. The present paper describes the findings for non-respiratory cancers. Some tumours did not occur with sufficient frequency to warrant formal statistical analysis. Nevertheless, examination of the histories of patients with these cancers showed several interesting occupational clusters. In particular, five out of 29 patients with acute myeloid leukaemia had worked in electrical trades. The more common cancers were studied by statistical techniques. A large number of possible occupational associations were examined, and some will probably have achieved conventional levels of statistical significance by chance. The results should therefore be interpreted with caution, taking into account evidence from other studies and the biological plausibility of suggested hazards. Among the more interesting findings were an excess of bladder cancer in lorry drivers (RR=1.6, CI 1.0-2.4) and in men employed in the manufacture of vegetable and animal oils and fats (RR = 4.8, CI 1.8-12.9). PMID:3718882

  13. Infertility in reproductive-age female cancer survivors.

    PubMed

    Levine, Jennifer M; Kelvin, Joanne Frankel; Quinn, Gwendolyn P; Gracia, Clarisa R

    2015-05-15

    Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program. PMID:25649243

  14. Aging and the Dendritic Cell System: Implications for Cancer

    PubMed Central

    Shurin, Michael R.; Shurin, Galina V.; Chatta, Gurkamal S.

    2007-01-01

    The immune system shows a decline in responsiveness to antigens both with aging, as well as in the presence of tumors. The malfunction of the immune system with age can be attributed to developmental and functional alterations in several cell populations. Previous studies have shown defects in humoral responses and abnormalities in T cell function in aged individuals, but have not distinguished between abnormalities in antigen presentation and intrinsic T cell or B cell defects in aged individuals. Dendritic cells (DC) play a pivotal role in regulating immune responses by presenting antigens to naïve T lymphocytes, modulating Th1/Th2/Treg balance, producing numerous regulatory cytokines and chemokines, and modifying survival of immune effectors. DC are receiving increased attention due to their involvement in the immunobiology of tolerance and autoimmunity, as well as their potential role as biological adjuvants in tumor vaccines. Recent advances in the molecular and cell biology of different DC populations allow for addressing the issue of DC and aging both in rodents and humans. Since DC play a crucial role in initiating and regulating immune responses, it is reasonable to hypothesize that they are directly involved in altered antitumor immunity in aging. However, the results of studies focusing on DC in the elderly are conflicting. The present review summarizes the available human and experimental animal data on quantitative and qualitative alterations of DC in aging and discusses the potential role of the DC system in the increased incidence of cancer in the elderly. PMID:17446082

  15. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  16. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  17. Breast Cancer Subtypes in Patients Aged 70 Years and Older.

    PubMed

    Königsberg, Robert; Pfeiler, Georg; Hammerschmid, Nicole; Holub, Oliver; Glössmann, Kerstin; Larcher-Senn, Julian; Dittrich, Christian

    2016-05-27

    Recurrence and survival pattern in breast cancer (bc) patients (pts) ≥ 70 years subcategorized according to subtype and age are still an area of uncertainty. Tumor characteristics, patient demographics, therapies applied, and recurrence pattern were compared between luminal A (LA), luminal B (LB), Her2/neu overexpressing (Her+) and triple-negative (TN) bc subtypes and the age subcategories 70-74, 75-79, ≥80 years. Based on univariate Cox-regression-analyses distant-disease-free-survival (DDFS) differed significantly for bc subtypes (p = 0.0002), notably for Her+ vs. LA (p = 0.0014), TN vs. LA (p < 0.001), and TN vs. LB (p = 0.0086). Not age, but Her+ and TN represented prognostic factors for DDFS. PMID:27215407

  18. CancerNet: a database for decoding multilevel molecular interactions across diverse cancer types.

    PubMed

    Meng, X; Wang, J; Yuan, C; Li, X; Zhou, Y; Hofestädt, R; Chen, M

    2015-01-01

    Protein-protein interactions (PPIs) and microRNA (miRNA)-target interactions are important for deciphering the mechanisms of tumorigenesis. However, current PPI databases do not support cancer-specific analysis. Also, no available databases can be used to retrieve cancer-associated miRNA-target interactions. As the pathogenesis of human cancers is affected by several miRNAs rather than a single miRNA, it is needed to uncover miRNA synergism in a systems level. Here for each cancer type, we constructed a miRNA-miRNA functionally synergistic network based on the functions of miRNA targets and their topological features in that cancer PPI network. And for the first time, we report the cancer-specific database CancerNet (http://bis.zju.edu.cn/CancerNet), which contains information about PPIs, miRNA-target interactions and functionally synergistic miRNA-miRNA pairs across 33 human cancer types. In addition, PPI information across 33 main normal tissues and cell types are included. Flexible query methods are allowed to retrieve cancer molecular interactions. Network viewer can be used to visualize interactions that users are interested in. Enrichment analysis tool was designed to detect significantly overrepresented Gene Ontology categories of miRNA targets. Thus, CancerNet serves as a comprehensive platform for assessing the roles of proteins and miRNAs, as well as their interactions across human cancers. PMID:26690544

  19. Cancer and aging: The importance of telomeres in genome maintenance

    SciTech Connect

    Rodier, Francis; Kim, Sahn-ho; Nijjar, Tarlochan; Yaswen, Paul; Campisi, Judith

    2004-10-01

    Telomeres are the specialized DNA-protein structures that cap the ends of linear chromosomes, thereby protecting them from degradation and fusion by cellular DNA repair processes. In vertebrate cells, telomeres consist of several kilobase pairs of DNA having the sequence TTAGGG, a few hundred base pairs of single-stranded DNA at the 3' end of the telomeric DNA tract, and a host of proteins that organize the telomeric double and single stranded DNA into a protective structure. Functional telomeres are essential for maintaining the integrity and stability of genomes. When combined with loss of cell cycle checkpoint controls, telomere dysfunction can lead to genomic instability, a common cause and hallmark of cancer. Consequently, normal mammalian cells respond to dysfunctional telomeres by undergoing apoptosis (programmed cell death) or cellular senescence (permanent cell cycle arrest), two cellular tumor suppressor mechanisms. These tumor suppressor mechanisms are potent suppressors of cancer, but recent evidence suggests that they can antagonistically also contribute to aging phenotypes. Here, we review what is known about the structure and function of telomeres in mammalian cells, particularly human cells, and how telomere dysfunction may arise and contribute to cancer and aging phenotypes.

  20. Identification of neutral tumor evolution across cancer types.

    PubMed

    Williams, Marc J; Werner, Benjamin; Barnes, Chris P; Graham, Trevor A; Sottoriva, Andrea

    2016-03-01

    Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power law fits with high precision 323 of 904 cancers from 14 types and from different cohorts. In malignancies identified as evolving neutrally, all clonal selection seemingly occurred before the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intratumoral heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intratumoral heterogeneity. PMID:26780609

  1. The Association between Type 2 Diabetes Mellitus and Women Cancer: The Epidemiological Evidences and Putative Mechanisms

    PubMed Central

    2015-01-01

    Type 2 diabetes mellitus (T2DM), a chronic disease increasing rapidly worldwide, is well established as an important risk factor for various types of cancer. Although many factors impact the development of T2DM and cancer including sex, age, ethnicity, obesity, diet, physical activity levels, and environmental exposure, many epidemiological and experimental studies are gradually contributing to knowledge regarding the interrelationship between DM and cancer. The insulin resistance, hyperinsulinemia, and chronic inflammation associated with diabetes mellitus are all associated strongly with cancer. The changes in bioavailable ovarian steroid hormone that occur in diabetes mellitus (the increasing levels of estrogen and androgen and the decreasing level of progesterone) are also considered potentially carcinogenic conditions for the breast, endometrium, and ovaries in women. In addition, the interaction among insulin, insulin-like growth factors (IGFs), and ovarian steroid hormones, such as estrogen and progesterone, could act synergistically during cancer development. Here, we review the cancer-related mechanisms in T2DM, the epidemiological evidence linking T2DM and cancers in women, and the role of antidiabetic medication in these cancers. PMID:25866823

  2. Cancer versus FM radio polarization types.

    PubMed

    Hallberg, Örjan

    2016-07-01

    In 2002, a detailed analysis of skin melanoma in 289 Swedish municipalities showed a strong association with the number of horizontally polarized main FM transmitters covering a municipality. Basic antenna theory says that body-resonance and standing waves cannot appear above a metal spring mattress unless the electric field is horizontally polarized. To test the hypothesis that body-resonant radiation can cause increased cancer risk in other European countries, I collected and analysed reported data from 24 countries, among which six were using vertical polarization. The results showed a strong association between cancer risk and the use of horizontally polarized FM broadcasting radiation, whereas vertical polarization seemed to cause no health effects. This information should form the basis for initiating relevant corrective actions by responsible authorities. PMID:26954356

  3. ABO blood types and cancer risk—A cohort study of 339,432 subjects in Taiwan

    PubMed Central

    Sun, Wenjie; Wen, Chi-Pang; Lin, Jie; Wen, Christopher; Pu, Xia; Huang, Maosheng; Tsai, Min Kuang; Tsao, Chwen Keng; Wu, Xifeng; Chow, Wong-Ho

    2016-01-01

    Background The associations of laboratory-based ABO phenotypes with cancer risks and mortality have not been systematically determined. Methods The study subjects were 339,432 healthy individuals with laboratory-based blood types from a Taiwan cohort. Results Compared to blood type O, blood type A was significantly associated with an elevated risk of stomach cancer incidence (Hazard Ratio [HR], 1.38 [95% CI, 1.11–1.72]) and mortality (HR, 1.38 [95% CI, 1.02–1.86]) compared with blood type O, after adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and body mass index. Non-O blood types were associated with an elevated risk of pancreatic cancer, with blood type B reaching statistical significance for incidence (HR, 1.59 [95% CI, 1.02–2.48]) and mortality (HR, 1.63 [95% CI, 1.02–2.60]). In contrast, kidney cancer risk was inversely associated with blood type AB (HR, 0.41 [95% CI, 0.18–0.93]) compared to type O. Conclusion Cancer risks vary in people with different ABO blood types, with elevated risks of stomach cancer associated with blood type A and pancreatic cancer associated with non-O blood types (A, B, and AB). PMID:25600007

  4. Rosiglitazone Use and the Risk of Bladder Cancer in Patients With Type 2 Diabetes

    PubMed Central

    Han, Eugene; Jang, Suk-Yong; Kim, Gyuri; Lee, Yong-ho; Choe, Eun Yeong; Nam, Chung Mo; Kang, Eun Seok

    2016-01-01

    Abstract Patients with diabetes have a higher incidence of bladder cancer; however, the association between thiazolidinedione use and bladder cancer risk has been controversial. We aimed to investigate whether pioglitazone or rosiglitazone use is associated with bladder cancer risk in patients with type 2 diabetes mellitus. This nationwide nested case-control study used data set obtained from the Korean National Health Insurance Service National Sample Cohort 2002 to 2013. Among the 47,738 patients with incident diabetes, 85 cases of newly diagnosed bladder cancer and 850 controls (1:10 matched by age, sex, index year, and diabetes diagnosis year) were recruited. Type 2 diabetes mellitus and bladder cancer were diagnosed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision code. More cases of bladder cancer were diagnosed in men (81.2%), and the stratified age peaked at 70 to 79 years old. Exclusive rosiglitazone use raised the incidence of bladder cancer (odds ratio [OR] = 3.07, 95% confidence interval [CI ] = 1.48–6.37). The risk of bladder cancer started to increase after less than 3 months use (OR = 3.30, 95% CI = 1.02–10.70) and peaked at 3 to 12 months of rosiglitazone use (OR = 4.48, 95% CI = 1.51–13.31). Patients were first exposed to exclusive rosiglitazone within 1 year (OR = 11.74, 95% CI = 2.46–56.12) and those who had consistently used it for 1 year (OR = 4.48 95% CI = 1.51–13.31), had higher risks of bladder cancer compared with nonthiazolidinedione users. Neither pioglitazone use nor exclusive pioglitazone use were associated with an increased incidence of bladder cancer. Rosiglitazone use is associated with an increased risk of incident bladder cancer independent of age and sex in patients with type 2 diabetes mellitus. The highest odds of bladder cancer in rosiglitazone users was seen in those with <1 year of exposure. PMID:26871835

  5. Rosiglitazone Use and the Risk of Bladder Cancer in Patients With Type 2 Diabetes.

    PubMed

    Han, Eugene; Jang, Suk-Yong; Kim, Gyuri; Lee, Yong-Ho; Choe, Eun Yeong; Nam, Chung Mo; Kang, Eun Seok

    2016-02-01

    Patients with diabetes have a higher incidence of bladder cancer; however, the association between thiazolidinedione use and bladder cancer risk has been controversial. We aimed to investigate whether pioglitazone or rosiglitazone use is associated with bladder cancer risk in patients with type 2 diabetes mellitus.This nationwide nested case-control study used data set obtained from the Korean National Health Insurance Service National Sample Cohort 2002 to 2013. Among the 47,738 patients with incident diabetes, 85 cases of newly diagnosed bladder cancer and 850 controls (1:10 matched by age, sex, index year, and diabetes diagnosis year) were recruited. Type 2 diabetes mellitus and bladder cancer were diagnosed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision code.More cases of bladder cancer were diagnosed in men (81.2%), and the stratified age peaked at 70 to 79 years old. Exclusive rosiglitazone use raised the incidence of bladder cancer (odds ratio [OR] = 3.07, 95% confidence interval [CI ] = 1.48-6.37). The risk of bladder cancer started to increase after less than 3 months use (OR = 3.30, 95% CI = 1.02-10.70) and peaked at 3 to 12 months of rosiglitazone use (OR = 4.48, 95% CI = 1.51-13.31). Patients were first exposed to exclusive rosiglitazone within 1 year (OR = 11.74, 95% CI = 2.46-56.12) and those who had consistently used it for 1 year (OR = 4.48 95% CI = 1.51-13.31), had higher risks of bladder cancer compared with nonthiazolidinedione users. Neither pioglitazone use nor exclusive pioglitazone use were associated with an increased incidence of bladder cancer.Rosiglitazone use is associated with an increased risk of incident bladder cancer independent of age and sex in patients with type 2 diabetes mellitus. The highest odds of bladder cancer in rosiglitazone users was seen in those with <1 year of exposure. PMID:26871835

  6. Cytotoxicity of dietary flavonoids on different human cancer types

    PubMed Central

    Sak, Katrin

    2014-01-01

    Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment. PMID:25125885

  7. Type 3 Deiodinase: Role in Cancer Growth, Stemness, and Metabolism

    PubMed Central

    Ciavardelli, Domenico; Bellomo, Maria; Crescimanno, Caterina; Vella, Veronica

    2014-01-01

    Deiodinases are selenoenzymes that catalyze thyroid hormones (THs) activation (type 1 and type 2, D1 and D2, respectively) or inactivation (type 3, D3). THs are essential for proper body development and cellular differentiation. Their intra- and extra-cellular concentrations are tightly regulated by deiodinases with a pre-receptorial control thus generating active or inactive form of THs. Changes in deiodinases expression are anatomically and temporally regulated and influence the downstream TH signaling. D3 overexpression is a feature of proliferative tissues such as embryo or cancer tissues. The enhanced TH degradation by D3 induces a local hypothyroidism, thus inhibiting THs transcriptional activity. Of note, overexpression of D3 is a feature of several highly proliferative cancers. In this paper, we review recent advances in the role of D3 in cancer growth, stemness, and metabolic phenotype. In particular, we focus on the main signaling pathways that result in the overexpression of D3 in cancer cells and are known to be relevant to cancer development, progression, and recurrence. We also discuss the potential role of D3 in cancer stem cells metabolic phenotype, an emerging topic in cancer research. PMID:25566187

  8. STAT Signaling in Different Breast Cancer Sub-types

    PubMed Central

    Furth, Priscilla A.

    2013-01-01

    This review summarizes information on expression of Signal Transducer and Activator of Transcription (STAT)s 1, 2, 3, 4, 5a/b and 6 in cancer cells from different human breast cancer sub-types. STAT proteins, especially STATs 1,3 and 5a/b are expressed in some but not all cancers from all of the different major breast cancer sub-types. However, well-designed studies comparing expression patterns at the protein level in cancer and surrounding stromal cells are still needed to fully examine links with prognosis and therapeutic response. Moreover, it is not yet known if distinct expression patterns of STAT proteins could have dissimilar impacts in different sub-types, especially between the luminal A and B ER+ sub-types and the different TNBC sub-types. Recent data indicating that STAT5 can be activated secondary to a therapeutic intervention and mediate resistance suggests that expression patterns should not only be examined in pre-treatment but also post-treatment samples from different sub-types. PMID:23562422

  9. Metformin use and young age lung cancer: A case series report

    PubMed Central

    DENG, BO; WANG, YI; XIE, DONG; STODDARD, SHAWN M.; YANG, PING

    2016-01-01

    Metformin, a widely-prescribed antihyperglycemic drug for the treatment of diabetes mellitus type 2 (DM-II), has been demonstrated to be antineoplastic in vivo and in vitro. However, various preclinical and epidemiological studies investigating the effects of metformin on lung cancer have obtained inconclusive results. The aim of the present study was to retrospectively investigate the effects of metformin, for the treatment of diabetes mellitus type 2 (DM-II), on the onset of lung cancer. In the present study, the pathological features of ten consecutive young age lung cancer cases, aged between 15 and 45 years old at the time of diagnosis and exhibiting existing primary DM, were investigated using the Mayo Clinic Lung Cancer Cohort database. Amongst this cohort, there were 2 cases of DM type 1 (DM-I) and 8 cases of DM-II. Of these patients, two exhibiting adenocarcinoma and DM-II had not been administered metformin; however, 1 patient exhibiting lymphoma and 4 patients with pulmonary neuroendocrine tumors (NETs) had been administered metformin at least 12 months prior to lung cancer diagnosis. The remaining 3 patients exhibiting NETs and DM-II had been treated with insulin therapy. The present study hypothesized that the high proportion of NETs observed in the cases of metformin-treated DM-II was unlikely to be a random event. It was suggested that metformin treatment was not effective in the prevention of pulmonary NETs, and that metformin may instead induce the occurrence of NETs via as yet unknown signaling pathways. The present hypothesis may potentially serve as a novel indicator for the requirement to monitor young patients with diabetes, who are being treated with metformin, for the occurrence of pulmonary NETs. PMID:27073573

  10. Data on the distribution of cancer incidence and death across age and sex groups visualized using multilevel spie charts.

    PubMed

    Feitelson, Dror G

    2016-04-01

    Cancer incidence and death statistics are typically recorded for multiple age and sex brackets, leading to large data tables which are difficult to digest. Effective visualizations of this data would allow practitioners, policy makers, and the general public to comprehend the data more readily and act on it appropriately. We introduce multilevel spie charts to create a combined visualization of cancer incidence and death statistics. Spie charts combine multiple pie charts, where the base pie chart (representing the general population) is used to set the angles of slices, and the superimposed ones use variable radii to portray the cancer data. Spie charts of cancer incidence and death statistics from Israel for 2009-2011 are used as an illustration. These charts clearly show various patterns of how cancer incidence and death distribute across age and sex groups, illustrating (1) absolute numbers and (2) rates per 100,000 population for different age and sex brackets. In addition, drawing separate charts for different cancer types illustrates relative mortality, both (3) across cancer types and (4) mortality relative to incidence. Naturally, this graphical depiction can be used for other diseases as well. PMID:26560991

  11. Radiation and Smoking Effects on Lung Cancer Incidence by Histological Types Among Atomic Bomb Survivors

    PubMed Central

    Egawa, Hiromi; Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori; Mabuchi, Kiyohiko

    2014-01-01

    While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1–4.6) for small-cell carcinoma, 0.75 (0.3–1.3) for adenocarcinoma, and 0.27 (0–1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses. PMID:22862780

  12. Radiation and smoking effects on lung cancer incidence by histological types among atomic bomb survivors.

    PubMed

    Egawa, Hiromi; Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori; Mabuchi, Kiyohiko

    2012-09-01

    While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1-4.6) for small-cell carcinoma, 0.75 (0.3-1.3) for adenocarcinoma, and 0.27 (0-1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses. PMID:22862780

  13. Urinary markers of nucleic acid oxidation and cancer in type 2 diabetes

    PubMed Central

    Broedbaek, Kasper; Siersma, Volkert; Henriksen, Trine; Weimann, Allan; Petersen, Morten; Andersen, Jon T.; Jimenez-Solem, Espen; Hansen, Lars J.; Henriksen, Jan Erik; Bonnema, Steen J.; de Fine Olivarius, Niels; Friis, Søren; Poulsen, Henrik E.

    2014-01-01

    Aims/hypothesis We investigated whether urinary markers of nucleic acid oxidation are associated with an increased risk of cancer in type 2 diabetes patients. Methods Urine samples from 1381 newly diagnosed diabetes patients were assayed for the oxidatively modified guanine nucleosides 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Cox proportional hazards regression was used to examine the relationship between the urinary markers and cancer incidence. Results The crude analyses showed an association between overall cancer and urinary excretion of the RNA oxidation marker 8-oxoGuo (unadjusted hazard ratio for cancer per natural log increase in 8-oxoGuo 1.35 [95% CI, 1.01–1.81]), however, in the adjusted analyses, no significant associations between 8-oxodG or 8-oxoGuo and overall cancer were found. For site-specific cancers 8-oxodG was associated with breast cancer in the crude analyses (unadjusted hazard ratio for breast cancer per natural log increase in 8-oxodG was 2.37 [95% CI, 1.07–5.26]), although the association was attenuated in the adjusted analyses (sex- and age-adjusted hazard ratio 2.15 [95% CI, 0.92–5.02] and multivariate adjusted hazard ratio1.98 [95% CI, 0.95–4.10]). Conclusions Urinary excretion of the nucleic acid oxidation markers 8-oxodG and 8-oxoGuo at the time of diagnosis was not associated with cancer overall in type 2 diabetes patients. For site-specific cancers, risk elevations were seen for breast cancer (8-oxodG). These findings should be examined in future and larger studies. PMID:25498965

  14. Breast cancer under age 40: a different approach.

    PubMed

    Ribnikar, D; Ribeiro, J M; Pinto, D; Sousa, B; Pinto, A C; Gomes, E; Moser, E C; Cardoso, M J; Cardoso, F

    2015-04-01

    Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Women<40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age<40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC<40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative

  15. Hypothesis: cell signalling influences age-related risk of colorectal cancer.

    PubMed

    Bordonaro, Michael; Lazarova, Darina L

    2015-01-01

    We propose that ageing is linked to colonic carcinogenesis through crosstalk between Wnt activity and signalling pathways related to ageing and senescence: progerin, klotho and mTOR. Mutations in the Wnt signalling pathway are responsible for the majority of colorectal cancers (CRCs); however, hyperactivation of Wnt signalling by butyrate, a breakdown product of dietary fibre, induces CRC cell apoptosis. This effect of butyrate may in part explain the protective action of fibre against CRC. Hutchinson-Gilford progeria syndrome is a premature ageing disorder caused by accumulation of the progerin protein; however, healthy individuals also produce progerin in the course of their normal ageing. Progerin activates expression of the Wnt inhibitors HES1 and TLE1. Thus, we hypothesize that with age, the increasing expression of progerin suppresses butyrate-mediated Wnt hyperactivation and apoptosis, leading to increased CRC risk. Wild-type klotho contributes to a significantly increased lifespan; however, Klotho gene variants differ significantly between newborns and elderly. Klotho inhibits basal Wnt signalling activity; thus, the protein may function as a tumour suppressor for CRC. However, similar to progerin, klotho variants associated with lifespan differences may repress butyrate-mediated Wnt hyperactivation, and thus increase the risk of CRC. Finally, mTOR signalling has also been linked to human ageing, and crosstalk between Wnt and mTOR signalling may influence colonic tumourigenesis. Understanding how progerin, klotho and mTOR link ageing with colonic neoplastic development may lead to novel preventive and therapeutic strategies against CRC associated with age. PMID:25388238

  16. Ink4-Arf locus in cancer and aging.

    PubMed

    Sherr, Charles J

    2012-01-01

    Three tumor suppressor genes at the small (<50 kb) INK4-ARF (CDKN2A/B) locus on human chromosome 9p21 coordinate a signaling network that depends on the activities of the retinoblastoma (RB) protein and the p53 transcription factor. Disruption of this circuitry, frequently by codeletion of INK4-ARF, is a hallmark of cancer, begging the question of why the intimate genetic linkage of these tumor suppressor genes has been maintained in mammals despite the risk of their coinactivation. The INK4-ARF locus is not highly expressed under normal physiologic conditions in young mammals, but its induction becomes more pronounced as animals age. Notably, INK4-ARF is actively silenced en bloc in embryonic, fetal, and adult stem cells but becomes poised to respond to oncogenic stress signals as stem cells lose their self-renewal capacity and differentiate, thereby providing a potent barrier to tumor formation. Epigenetic remodeling of the locus as a whole provides a mechanism for coordinating the activities of RB and p53. A hypothesis is that the INK4-ARF locus may have evolved to physiologically restrict the self-renewal capacities and numbers of stem and progenitor cells with the attendant consequence of limiting tissue regenerative capacity, particularly as animals age. Deletion of INK4-ARF contributes to the aberrant self-renewal capacity of tumor cells and occurs frequently in many forms of human cancer. PMID:22960768

  17. A survey of cancer and occupation in young and middle aged men. I. Cancers of the respiratory tract.

    PubMed Central

    Coggon, D; Pannett, B; Osmond, C; Acheson, E D

    1986-01-01

    In a search for clues to previously industrial carcinogens the occupational and smoking histories of young and middle aged men with different types of cancer were compared. The study population comprised men aged 18-54 and resident in the counties of Cleveland, Humberside, and Cheshire (including the Wirral). From hospital and cancer registration records 2942 members of the study population in whom cancers were diagnosed during the period 1975-80 were identified retrospectively. The occupational and smoking histories of these patients were sought by a postal questionnaire addressed either to the patients themselves or, if they had died, to their next of kin. The overall response rate to the questionnaire was 52.1%. Additionally, limited occupational information was obtained for 89% of cases from their hospital notes. Analysis of these data suggests that no serious bias arose as a consequence of the incomplete response to the questionnaire. This paper concentrates on the results for cancers of the respiratory tract and mesothelioma. Mesothelioma was found to cluster in laggers, electricians, and shipyard workers, and nasal carcinoma in woodworkers. Carcinomas of the larynx and of the bronchus were examined by formal statistical techniques, each being compared with a control group made up of all other cancers combined. Several interesting occupational and industrial associations were shown, in particular, an excess of bronchial carcinoma in the leather industry (RR = 2.6, CI 1.2-6.0), in building labourers (RR = 1.7, CI 1.0-2.9) and other construction workers (RR = 1.8, CI 1.0-3.0), in bakers and pastry cooks (RR = 3.6, CI 1.3-10.4). and in cooks (RR = 2.5, CI 1.2-5.1). In addition, a small cluster of lung tumours was observed in men who had worked as dental mechanics. PMID:3707871

  18. The influence of hormone therapies on type I and II endometrial cancer: A nationwide cohort study.

    PubMed

    Mørch, Lina S; Kjaer, Susanne K; Keiding, Niels; Løkkegaard, Ellen; Lidegaard, Øjvind

    2016-03-15

    The influence of hormone therapy (HT) on risk for endometrial cancer is still casting which type of HT the clinicians recommend. It is unrevealed if HT has a differential influence on Type I versus Type II endometrial tumors, and little is known about the influence of, e.g., different routes of administration and about the influence of tibolone. We followed all Danish women aged 50-79 years without previous cancer or hysterectomy (n = 914,595) during 1995-2009. From the National Prescription Register, we computed HT exposures as time-dependent covariates. Incident endometrial cancers (n = 6,202) were identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1.92-9.52), nonconjugated estrogen: 2.00 (1.87-2.13), long cycle combined therapy: 2.89 (2.27-3.67), cyclic combined therapy: 2.06 (1.88-2.27), tibolone 3.56 (2.94-4.32), transdermal estrogen: 2.77 (2.12-3.62) and vaginal estrogen: 1.96 (1.77-2.17), but not with continuous combined therapy: 1.02 (0.87-1.20). In contrast, the risk of Type II tumors appeared decreased with continuous combined therapy: 0.45 (0.20-1.01), and estrogen therapy implied a nonsignificantly altered risk of 1.43 (0.85-2.41). Our findings support that continuous combined therapy is risk free for Type I tumors, while all other hormone therapies increase risk. In contrast, Type II endometrial cancer was less convincingly associated with hormone use, and continuous combined therapy appeared to decrease the risk. PMID:26421912

  19. New perspectives on type I IFNs in cancer.

    PubMed

    Gajewski, Thomas F; Corrales, Leticia

    2015-04-01

    Although type I IFNs were initially described based on their anti-viral properties, it was quickly realized that these cytokines had anti-proliferative and anti-cancer activities. These observations ultimately led to the clinical development and utility of IFN-α2b for the treatment of patients with melanoma, renal cell carcinoma, and chronic myelogenous leukemia, among others. However, the mechanism of action of type I IFNs in vivo was never fully elucidated, and the pleiotropic effects of IFNs on multiple cell types had made it challenging to decipher. Advancement of genetically engineered mouse models has provided new tools for interrogating these mechanisms. Recent evidence has indicated that spontaneous innate immune sensing of cancers that leads to adaptive immune responses is dependent on host type I IFN production and signaling. The major innate immune receptor pathway that leads to type I IFN production in response to a growing tumor appears to be the STING pathway of cytosolic DNA sensing. STING agonists drive type I IFN production and are impressively therapeutic in mouse tumor models. Targeting low doses of type I IFNs to the tumor microenvironment also promotes anti-tumor activity via host adaptive immunity that is T cell-dependent. However, high doses of intratumoral type I IFNs largely function via an anti-angiogenic effect. Understanding these mechanistic details should enable improved clinical manipulation of the type I IFN system in cancer. PMID:25630967

  20. Borrmann Type 4 Advanced Gastric Cancer: Focus on the Development of Scirrhous Gastric Cancer

    PubMed Central

    Jung, Kyoungwon; Park, Moo In; Kim, Sung Eun; Park, Seun Ja

    2016-01-01

    Early diagnosis of Borrmann type 4 advanced gastric cancer (AGC) is very important for improving the prognosis of AGC patients. Because there is no definite mass in most cases of Borrmann type 4 AGC, its accurate diagnosis via endoscopy requires an understanding of its pathogenesis and developmental process. Moreover, many people confuse linitis plastica (LP) type gastric cancer (GC), scirrhous GC, and Borrmann type 4 AGC. To distinguish each of these cancers, knowledge of their endoscopic and pathological differences is necessary, especially for LP type GCs in the developmental stage. In conclusion, diagnosis of pre-stage or latent LP type GC before progression to typical LP type GC requires the detection of IIc-like lesions in the fundic gland area. It is also crucial to identify any abnormalities such as sclerosis of the gastric wall and hypertrophy of the mucosal folds during endoscopy. PMID:27456608

  1. Middle-Aged More Often Diagnosed with Late-Stage Lung Cancer

    MedlinePlus

    ... Middle-Aged More Often Diagnosed With Late-Stage Lung Cancer British study highlights the need for better early ... more likely to be diagnosed with late-stage lung cancer than those who are slightly older, a new ...

  2. Targeting mitochondria for cancer treatment - two types of mitochondrial dysfunction.

    PubMed

    Pokorný, Jiří; Pokorný, Jan; Kobilková, Jitka; Jandová, Anna; Vrba, Jan; Vrba, Jan

    2014-01-01

    Two basic types of cancers were identified – those with the mitochondrial dysfunction in cancer cells (the Warburg effect) or in fibroblasts supplying energy rich metabolites to a cancer cell with functional mitochondria (the reverse Warburg effect). Inner membrane potential of the functional and dysfunctional mitochondria measured by fluorescent dyes (e.g. by Rhodamine 123) displays low and high values (apparent potential), respectively, which is in contrast to the level of oxidative metabolism. Mitochondrial dysfunction (full function) results in reduced (high) oxidative metabolism, low (high) real membrane potential, a simple layer (two layers) of transported protons around mitochondria, and high (low) damping of microtubule electric polar vibrations. Crucial modifications are caused by ordered water layer (exclusion zone). For the high oxidative metabolism one proton layer is at the mitochondrial membrane and the other at the outer rim of the ordered water layer. High and low damping of electric polar vibrations results in decreased and increased electromagnetic activity in cancer cells with the normal and the reverse Warburg effect, respectively. Due to nonlinear properties the electromagnetic frequency spectra of cancer cells and transformed fibroblasts are shifted in directions corresponding to their power deviations resulting in disturbances of interactions and escape from tissue control. The cancer cells and fibroblasts of the reverse Warburg effect tumors display frequency shifts in mutually opposite directions resulting in early generalization. High oxidative metabolism conditions high aggressiveness. Mitochondrial dysfunction, a gate to malignancy along the cancer transformation pathway, forms a narrow neck which could be convenient for cancer treatment. PMID:25626329

  3. Cancer type-specific epigenetic changes: gastric cancer.

    PubMed

    Calcagno, Danielle Queiroz; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodriguez

    2015-01-01

    Gastric cancer (GC) remains a major cause of mortality despite declining rate in the world. Epigenetic alterations contribute significantly to the development and progression of gastric tumors. Epigenetic refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches have emerged. This chapter summarizes the main epigenomic mechanisms described recently involved in gastric carcinogenesis, focusing on the roles that aberrant DNA methylation, histone modifications (histone acetylation and methylation), and miRNAs (oncogenic and tumor suppressor function of miRNA) play in the onset and progression of gastric tumors. Clinical implications of these epigenetic alterations in GC are also discussed. PMID:25421656

  4. Opposite phenotypes of cancer and aging arise from alternative regulation of common signaling pathways.

    PubMed

    Ukraintseva, Svetlana V; Yashin, Anatoly I

    2003-12-01

    Phenotypic features of malignant and senescent cells are in many instances opposite. Cancer cells do not "age"; their metabolic, proliferative, and growth characteristics are opposite to those observed with cellular aging (both replicative and functional). In many such characteristics cancer cells resemble embryonic cells. One can say that cancer manifests itself as a local, uncontrolled "rejuvenation" in an organism. Available evidence from human and animal studies suggests that the opposite phenotypic features of aging and cancer arise from the opposite regulation of genes participating in apoptosis/growth arrest or growth signal transduction pathways in cells. This fact may be applicable in the development of new anti-aging treatments. Genes that are contrarily regulated in cancer and aging cells (e.g., proto-oncogenes or tumor suppressors) could be candidate targets for anti-aging interventions. Their "cancer-like" regulation, if strictly controlled, might help to rejuvenate the human organism. PMID:15033776

  5. Cancer Snapshots: Facts and statistics for each cancer type or topic

    Cancer.gov

    Snapshots provide key information on disease incidence and mortality, NCI funding trends, relevant research activities, and recent scientific advances related to specific types of cancer and on special populations and scientific topics.

  6. Effects of post-mortem aging time and type of aging on palatability of low marbled beef loins.

    PubMed

    Lepper-Blilie, A N; Berg, E P; Buchanan, D S; Berg, P T

    2016-02-01

    The study objective was to evaluate the effect of post-mortem aging period (14 to 49days), dry vs. wet (D vs W) type of aging on the palatability of bone-in (BI) beef short loins (n=96) and boneless (BL) strip loins (n=96) possessing United States Department of Agriculture marbling scores between Slight and Small. Warner-Bratzler shear force (WBSF) scores decreased linearly over time (P=0.0001). WBSF was not influenced by aging method or loin type. Aged flavor was higher for DBL than for DBI with WBL and WBI intermediate. Dry aging strip loins increase aged flavor yet did not improve beefy flavor compared to wet aging. Based on objective data and panelist's scores for tenderness, juiciness and aged flavor, a boneless, 28days wet aged strip steak, cooked to 71°C would provide the best combination of eating satisfaction and value. PMID:26551359

  7. Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at-onset of familial breast cancer.

    PubMed

    Lee, Haiping; Geng, Cuizhi; Cheng, Meng; Lee, Zheng; Guo, Zhanjun

    2016-09-01

    Single nucleotide polymorphisms (SNPs) are accumulated frequently in the mitochondrial displacement loop (D-loop) in various types of cancer, and their association with cancer risk and disease outcome has been extensively identified. We have identified specific risk-associated SNP for familial breast cancer patients previously. In this study, we investigated the association between age-at-onset and the SNPs in familial breast cancer patients. The SNP sites of nucleotides 16 311 T/C were identified for their association with age-at-onset using the log-rank test. The age-at-onset of the patients with the minor allele C genotype was significantly earlier than that of patients carrying the T genotype at the site 16 311 (p = 0.032). Accordingly, the genetic polymorphisms in the mitochondrial D-loop are predictive markers for age-at-onset in familial breast cancer patients, which may help to identify familial breast cancer patient subgroups at high risk of early onset. PMID:27158866

  8. Association between the CYP11 family and six cancer types

    PubMed Central

    FAN, ZIWEI; WANG, ZHEN; CHEN, WEIRAN; CAO, ZHIWEI; LI, YIXUE

    2016-01-01

    Cytochromes P450 (CYPs) are a major source of variability in pharmacokinetics and drug response. CYPs utilize a variety of small and large molecules as substrates in enzymatic reactions. The CYP genes may be divided into two groups: Endogenous CYPs (CYP family 7–51) and xenobiotic CYPs (CYP family 1–4). The aim of the present study was to investigate whether endogenous CYPs exhibit similar gene expression and mutations in various cancer types. The gene expression profiles and somatic mutations exhibited in colon adenocarcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, lung squamous cell carcinoma, prostate adenocarcinoma and uterine corpus endometrial carcinoma were analyzed using data obtained from The Cancer Genome Atlas. The expression of CYP11A1 was significantly downregulated in all six cancer types. In addition, CYP11B1 and CYP11B2 exhibited the highest number of mutations among endogenous CYPs in all samples. As the CYP11 family is important for steroid biosynthesis, and previous studies have demonstrated that steroid hormones are associated with certain cancers, these results indicate a common role of the CYP11 family in various cancer types. PMID:27347096

  9. What Makes You Stronger: Age and Cohort Differences in Personal Growth after Cancer

    PubMed Central

    Pudrovska, Tetyana

    2012-01-01

    Using two waves of the National Survey of Midlife Development in the United States, I compare changes in personal growth over a 10-year period among cancer survivors and individuals without cancer. Moreover, I examine joint effects of age and cohort on personal growth after a cancer diagnosis. The theoretical framework of this study integrates impairment, resilience, and thriving perspectives. Findings reveal that, although personal growth declines with age for all individuals regardless of cohort and cancer status, cancer slows the decline in personal growth with age in 1940s, 1950s, and 1960s birth cohorts, yet accelerates the age-related decline in the 1920s cohort. I argue that a sociological perspective can enhance our understanding of the interplay of developmental and socio-cultural influences on psychological adjustment to cancer. Seemingly idiosyncratic psychological reactions to cancer partly reflect macro-level processes represented by cohort differences. PMID:20943589

  10. Cancer among patients with type 2 diabetes mellitus: A population-based cohort study in northeastern Italy.

    PubMed

    Gini, Andrea; Bidoli, Ettore; Zanier, Loris; Clagnan, Elena; Zanette, Giorgio; Gobbato, Michele; De Paoli, Paolo; Serraino, Diego

    2016-04-01

    Diabetes mellitus (DM) is associated with an elevated risk of cancer. The aim of this study was to assess cancer risk and survival in individuals with type 2 DM (T2DM) in Friuli Venezia Giulia, Italy. A retrospective population-based cohort study of 32,247 T2DM patients aged 40-84 years was conducted through a record linkage of local healthcare databases and cancer registry for the period 2002-2009. Standardized incidence ratios (SIRs) with 95% confidence intervals (95%CIs) and 5-year survival probabilities after T2DM and cancer diagnosis were computed. The SIRs for all cancers (n=2069) was 1.28 (95%CI: 1.23-1.34). The highest SIRs were observed for cancers of the liver, female genital organs, small intestine, and pancreas. After 3 years from T2DM diagnosis, a reduced risk of prostate cancer (SIR=0.73, 95%CI: 0.54-0.96) was found in men aged 65-74 years, and a higher risk for breast cancer (SIR=1.24, 95%CI: 1.00-1.52) was found among T2DM female patients. The overall 5-year survival after T2DM was 88.7%. Furthermore, T2DM appeared to have a negative effect on survival of women with breast cancer. This population-based study confirmed that T2DM patients are at increased risk of several cancers, and of premature death in women with breast cancer. PMID:26851751

  11. Variation in the Association Between Colorectal Cancer Susceptibility Loci and Colorectal Polyps by Polyp Type

    PubMed Central

    Burnett-Hartman, Andrea N.; Newcomb, Polly A.; Hutter, Carolyn M.; Peters, Ulrike; Passarelli, Michael N.; Schwartz, Malaika R.; Upton, Melissa P.; Zhu, Lee-Ching; Potter, John D.; Makar, Karen W.

    2014-01-01

    We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24–79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs. Polytomous logistic regression models were used to estimate odds ratios and 95% confidence intervals for associations between polyps and the colorectal cancer risk allele for each SNP under a log-additive model. Analyses included 781 controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases with both polyp types. The following SNPs were associated with advanced adenomas: rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced adenomas and for serrated polyps overall, only rs961253 was statistically significant (P < 0.05). These associations were in the same directions as those in prior colorectal cancer GWAS. No SNP was significantly associated with hyperplastic polyps, and only rs6983267 was significantly associated with sessile serrated polyps, but this association was opposite of that found in colorectal cancer GWAS. Our results suggest that the association between colorectal cancer susceptibility SNPs and colorectal polyps varies by polyp type. PMID:24875374

  12. Signatures of accelerated somatic evolution in gene promoters in multiple cancer types

    PubMed Central

    Smith, Kyle S.; Yadav, Vinod K.; Pedersen, Brent S.; Shaknovich, Rita; Geraci, Mark W.; Pollard, Katherine S.; De, Subhajyoti

    2015-01-01

    Cancer-associated somatic mutations outside protein-coding regions remain largely unexplored. Analyses of the TERT locus have indicated that non-coding regulatory mutations can be more frequent than previously suspected and play important roles in oncogenesis. Using a computational method called SASE-hunter, developed here, we identified a novel signature of accelerated somatic evolution (SASE) marked by a significant excess of somatic mutations localized in a genomic locus, and prioritized those loci that carried the signature in multiple cancer patients. Interestingly, even when an affected locus carried the signature in multiple individuals, the mutations contributing to SASE themselves were rarely recurrent at the base-pair resolution. In a pan-cancer analysis of 906 samples from 12 tumor types, we detected SASE in the promoters of several genes, including known cancer genes such as MYC, BCL2, RBM5 and WWOX. Nucleotide substitution patterns consistent with oxidative DNA damage and local somatic hypermutation appeared to contribute to this signature in selected gene promoters (e.g. MYC). SASEs in selected cancer gene promoters were associated with over-expression, and also correlated with the age of onset of cancer, aggressiveness of the disease and survival. Taken together, our work detects a hitherto under-appreciated and clinically important class of regulatory changes in cancer genomes. PMID:25934800

  13. Molecular Detection and Typing of Human Papillomaviruses in Paraffin-Embedded Cervical Cancer and Pre-Cancer Tissue Specimens

    PubMed Central

    Mahmoodi, Pezhman; Motamedi, Hossein; Seyfi Abad Shapouri, Masoud Reza; Bahrami Shehni, Mahjabin; Kargar, Mohammad

    2016-01-01

    Background: Cervical cancer is one of the important reasons of mortality among females. Prevention, early diagnosis and immediate treatment can affect the rate of mortality in this cancer and several epidemiological studies have shown a strong relationship between human papilloma viruses (HPVs) and cervical cancer. Objectives: The present study was conducted to survey HPV infections in a women population with cervical cancer and cervical dysplasia/metaplasia in southwest of Iran. Materials and Methods: 72 paraffin-embedded cervical biopsies which had been previously archived from women with cervical cancer and cervical dysplasia were examined by polymerase chain reaction (PCR). Afterward, the detected HPV strains were typed by restriction fragment length polymorphism (RFLP) analysis of PCR amplicons. Results: 60 out of 72 samples had necessary requirements and HPV DNA was detected in 43.3% of these samples. Most HPV positive samples belonged to women aged from 48 to 63 years. On the other hand, HPV infection among patients with squamous cell carcinoma (SCC) was 48.78% and in women with dysplasia/metaplasia was 26.66%. The most prevalent type of the human papilloma virus was HPV16 (100%). Conclusions: Knowing the most prevalent type of the human papilloma viruses circulating in the population (HPV16) can be applied in the future screening and managing programs of this major disease and also in vaccination against the prevalent types of the virus. Meanwhile, it seems that more studies should be performed to determine the role of different risk factors involved in development of the disease, especially those related with social behaviors and traditions with respect to different areas. PMID:27366309

  14. Regional variations in cancer survival: Impact of tumour stage, socioeconomic status, comorbidity and type of treatment in Norway.

    PubMed

    Skyrud, Katrine Damgaard; Bray, Freddie; Eriksen, Morten Tandberg; Nilssen, Yngvar; Møller, Bjørn

    2016-05-01

    Cancer survival varies by place of residence, but it remains uncertain whether this reflects differences in tumour, patient and treatment characteristics (including tumour stage, indicators of socioeconomic status (SES), comorbidity and information on received surgery and radiotherapy) or possibly regional differences in the quality of delivered health care. National population-based data from the Cancer Registry of Norway were used to identify cancer patients diagnosed in 2002-2011 (n = 258,675). We investigated survival from any type of cancer (all cancer sites combined), as well as for the six most common cancers. The effect of adjusting for prognostic factors on regional variations in cancer survival was examined by calculating the mean deviation, defined by the mean absolute deviation of the relative excess risks across health services regions. For prostate cancer, the mean deviation across regions was 1.78 when adjusting for age and sex only, but decreased to 1.27 after further adjustment for tumour stage. For breast cancer, the corresponding mean deviations were 1.34 and 1.27. Additional adjustment for other prognostic factors did not materially change the regional variation in any of the other sites. Adjustment for tumour stage explained most of the regional variations in prostate cancer survival, but had little impact for other sites. Unexplained regional variations after adjusting for tumour stage, SES indicators, comorbidity and type of treatment in Norway may be related to regional inequalities in the quality of cancer care. PMID:26679150

  15. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate recorded before age 5; (2) A church record of birth or baptism recorded before age 5; or (3) Notification of registration of birth made before age 5. (b) Other evidence of age. If an individual cannot obtain...

  16. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate recorded before age 5; (2) A church record of birth or baptism recorded before age 5; or (3) Notification of registration of birth made before age 5. (b) Other evidence of age. If an individual cannot obtain...

  17. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate recorded before age 5; (2) A church record of birth or baptism recorded before age 5; or (3) Notification of registration of birth made before age 5. (b) Other evidence of age. If an individual cannot obtain...

  18. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate recorded before age 5; (2) A church record of birth or baptism recorded before age 5; or (3) Notification of registration of birth made before age 5. (b) Other evidence of age. If an individual cannot obtain...

  19. Increasing Age and Treatment Modality Are Predictors for Subsequent Diagnosis of Bladder Cancer Following Prostate Cancer Diagnosis

    SciTech Connect

    Singh, Anurag K.; Mashtare, Terry L.; McCloskey, Susan A.; Seixas-Mikelus, Stefanie A.; Kim, Hyung L.; May, Kilian Salerno

    2010-11-15

    Purpose: To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. Methods and Materials: The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. Results: In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. Conclusions: Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

  20. Childhood cancer incidence patterns by race, sex and age for 2000-2006: a report from the South African National Cancer Registry.

    PubMed

    Erdmann, Friederike; Kielkowski, Danuta; Schonfeld, Sara J; Kellett, Patricia; Stanulla, Martin; Dickens, Caroline; Kaatsch, Peter; Singh, Elvira; Schüz, Joachim

    2015-06-01

    Higher childhood cancer incidence rates are generally reported for high income countries although high quality information on descriptive patterns of childhood cancer incidence for low or middle income countries is limited, particularly in Sub-Saharan Africa. There is a need to quantify global differences by cancer types, and to investigate whether they reflect true incidence differences or can be attributed to under-diagnosis or under-reporting. For the first time, we describe childhood cancer data reported to the pathology report-based National Cancer Registry of South Africa in 2000-2006 and compare our results to incidence data from Germany, a high income country. The overall age-standardized incidence rate (ASR) for South Africa in 2000-2006 was 45.7 per million children. We observed substantial differences by cancer types within South Africa by racial group; ASRs tended to be 3-4-fold higher in South African Whites compared to Blacks. ASRs among both Black and White South Africans were generally lower than those from Germany with the greatest differences observed between the Black population in South Africa and Germany, although there was marked variation between cancer types. Age-specific rates were particularly low comparing South African Whites and Blacks with German infants. Overall, patterns across South African population groups and in comparison to Germans were similar for boys and girls. Genetic and environmental reasons may probably explain rather a small proportion of the observed differences. More research is needed to understand the extent to which under-ascertainment and under-diagnosis of childhood cancers drives differences in observed rates. PMID:25363616

  1. Identification of neutral tumor evolution across cancer types

    PubMed Central

    Barnes, Chris P; Graham, Trevor A; Sottoriva, Andrea

    2016-01-01

    Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power-law fits with high precision 323 of 904 cancers from 14 types, selected from different cohorts. In malignancies identified as neutral, all clonal selection occurred prior to the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intra-tumor heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intra-tumor heterogeneity. PMID:26780609

  2. Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO)

    PubMed Central

    Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

    2014-01-01

    While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 controls who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17–1.45) for all histological types combined, 1.26 (95% CI: 1.10–1.44) for adenocarcinoma, 1.41 (95% CI: 0.99–1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89–2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62–5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for non-small cell lung cancers (OR=2.11, 95% CI: 1.11–4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. PMID:24615328

  3. [Treatment of type four gastric cancer in our institution].

    PubMed

    Ito, Masahiro; Takayama, Tomoyoshi; Matsumoto, Sohei; Wakatsuki, Kohei; Tanaka, Tetsuya; Migita, Kazuhiro; Kunishige, Tomohiro; Nakade, Hiroshi; Nakajima, Yoshiyuki

    2014-11-01

    Since 2011, we have performed routine staging laparoscopy on 7 patients presenting with type 4 gastric cancer at our department. After staging laparoscopy, the patients received neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS). After the completion of 2 courses of chemotherapy, radical gastrectomy with D2 gastrectomy or greater was performed, followed by postoperative adjuvant chemotherapy with S-1 for 1 year. In the present study, we evaluate the outcomes of the treatment strategies for the type 4 gastric cancer patients treated at our institution. Staging laparoscopy and peritoneal lavage cytology revealed that none of the patients had peritoneal metastasis, while peritoneal cytology detected carcinoma cells in 3 patients. Grade 3 or greater neutropenia developed in 3 patients, and Grade 3 or greater nonhematological toxicity developed in 3 patients after neoadjuvant chemotherapy. The disease control rate was 100% and all patients underwent radical gastrectomy. Of the 3 patients who had positive peritoneal cytology on staging laparoscopy, 2 patients had no peritoneal cancer cells at the time of gastrectomy. Six patients underwent R0 surgery after DCS chemotherapy, and the response rate was 57.1%. The median survival time was 540 days. Four patients experienced peritoneal recurrence, and 1 developed lymph node recurrence. Our therapeutic strategy for type 4 gastric cancer contributed to prolonged survival; however, it is necessary to develop better strategies that can prevent or control the peritoneal recurrence. PMID:25731483

  4. Lung cancer in women and type of dwelling in relation to radon exposure

    SciTech Connect

    Svensson, C.; Pershagen, G.; Klominek, J.

    1989-04-01

    A case-control study based on interviews with 210 incident female lung cancer patients, 209 age-matched population controls, and 191 hospital controls was carried out in Stockholm county, Sweden. Radon measurements made in a sample of 303 dwellings, in which the study subjects had lived, showed that dwellings with ground contact had an average concentration of approximately 160 Bqm-3, twice the average concentration of other dwellings. A cumulated radon exposure index was calculated for each subject based on data from the interviews and the measurements. For the total group of lung cancer a relative risk (RR), adjusted for smoking, age, and degree of urbanization, of 1.8 (95% confidence interval: 1.2-2.9) and 1.7 (0.9-3.3) associated with ''intermediate'' and ''high'' exposure to radon was found. There was also a significant trend to a positive dose-response relationship (Ptrend = 0.03). For small cell cancer the corresponding figures for RRs were 1.9 (0.6-4.5) and 4.7 (1.5-14.2), respectively (Ptrend = 0.01). There seemed to be a positive interaction between radon exposure and smoking in relation to lung cancer. The findings indicate that domestic radon may be of importance for the induction of lung cancer, particularly for some histological types.

  5. Fatigue and quality of life in women treated for various types of gynaecological cancers: a cross-sectional study

    PubMed Central

    Sekse, Ragnhild Johanne Tveit; Hufthammer, Karl Ove; Vika, Margrethe Elin

    2015-01-01

    Aims and objectives To examine the prevalence of cancer-related fatigue in women treated for various types of gynaecological cancers and, for these cancers, to assess fatigue in relation to distress, health-related quality of life, demography and treatment characteristics. Background Advances in treatment of cancer have improved the likelihood of survival. Consequently, there are a growing number of patients who become survivors after cancer and who face side effects even years after treatment. One of the most frequently reported side effects across all types and stages of the disease is cancer-related fatigue. Design A descriptive cross-sectional study. Methods One hundred and twenty women treated for gynaecological cancers who were participants in an intervention study were included. Fatigue, psychological distress, health-related QoL and demographics were assessed by questionnaires. Disease and treatment characteristics were extracted from medical records. Results Cancer-related fatigue was reported in 53% of the women treated for gynaecological cancers, with a higher proportion in the group of cervical cancer, followed by ovarian cancer. Younger participants reported fatigue more frequently than older participants. When adjusting for age, the type of cancer a woman experiences was shown to have little impact on her risk of experiencing fatigue. The participants with fatigue reported higher levels of anxiety and depression than participants without fatigue. There was a relationship between fatigue and quality of life as measured by SF-36 domains. Conclusion The findings underscore the importance of screening for fatigue, patient education and symptom management. This should be included in a standard procedure during treatment and follow-up. Both somatic and psychological aspects of fatigue should be emphasised. Relevance to clinical practice The findings imply the need for health personnel to have focus on fatigue during the entire cancer trajectory of women

  6. Effects of Age on the Detection and Management of Breast Cancer

    PubMed Central

    McGuire, Andrew; Brown, James A. L.; Malone, Carmel; McLaughlin, Ray; Kerin, Michael J.

    2015-01-01

    Currently, breast cancer affects approximately 12% of women worldwide. While the incidence of breast cancer rises with age, a younger age at diagnosis is linked to increased mortality. We discuss age related factors affecting breast cancer diagnosis, management and treatment, exploring key concepts and identifying critical areas requiring further research. We examine age as a factor in breast cancer diagnosis and treatment relating it to factors such as genetic status, breast cancer subtype, hormone factors and nodal status. We examine the effects of age as seen through the adoption of population wide breast cancer screening programs. Assessing the incidence rates of each breast cancer subtype, in the context of age, we examine the observed correlations. We explore how age affects patient’s prognosis, exploring the effects of age on stage and subtype incidence. Finally we discuss the future of breast cancer diagnosis and treatment, examining the potential of emerging tests and technologies (such as microRNA) and how novel research findings are being translated into clinically relevant practices. PMID:26010605

  7. Functional Outcomes by Age for Inpatient Cancer Rehabilitation: A Retrospective Chart Review

    PubMed Central

    Hunter, Elizabeth G.; Baltisberger, Julie

    2013-01-01

    Cancer-related impairments result in disabilities similar to those typically encountered in inpatient rehabilitation settings; however, the use of rehabilitation services by cancer survivors is low. This is particularly important for older adults as they are at higher risk for cancer. This retrospective study collected data from medical records from 215 charts of patients admitted to an inpatient physical rehabilitation hospital, within a 5-year period, with a primary diagnosis of cancer. Mean age was 61 years (SD = 15.7) for 109 (51%) females and 106 (49%) males. Regardless of age, patients achieved significant functional improvement, as shown by their FIM scores (t = 23.06, p < .0001), from admission to discharge. The results have several important implications related to cancer survivorship among older adults. With a push toward aging in place, maintaining optimal physical functioning is crucial. Physical rehabilitation benefited the functional outcomes of this group of cancer survivors regardless of age. PMID:23908563

  8. Widely Used Type 2 Diabetes Drug May Reduce Cancer Death Risk

    MedlinePlus

    ... Used Type 2 Diabetes Drug May Reduce Cancer Death Risk Older women taking metformin saw a boost ... a risk factor for cancer and cancer-related death, and metformin therapy, compared to other diabetes medications, ...

  9. NFKB1: a suppressor of inflammation, ageing and cancer.

    PubMed

    Cartwright, Tyrell; Perkins, Neil D; L Wilson, Caroline

    2016-05-01

    The pleiotropic consequences of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) pathway activation result from the combinatorial effects of the five subunits that form the homo- and heterodimeric NF-κB complexes. Although biochemical and gene knockout studies have demonstrated overlapping and distinct functions for these proteins, much is still not known about the mechanisms determining context-dependent functions, the formation of different dimer complexes and transcriptional control in response to diverse stimuli. Here we discuss recent results that reveal that the nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1) (p105/p50) subunit is an important regulator of NF-κB activity in vivo. These effects are not restricted to being a dimer partner for other NF-κB subunits. Rather p50 homodimers have a critical role as suppressors of the NF-κB response, while the p105 precursor has a variety of NF-κB-independent functions. The importance of Nfkb1 function can be seen in mouse models, where Nfkb1(-/-) mice display increased inflammation and susceptibility to certain forms of DNA damage, leading to cancer, and a rapid ageing phenotype. In humans, low expression of Kip1 ubiquitination-promoting complex 1 (KPC1), a ubiquitin ligase required for p105 to p50 processing, was shown to correlate with a reduction in p50 and glioblastoma incidence. Therefore, while the majority of research in this field has focused on the upstream signalling pathways leading to NF-κB activation or the function of other NF-κB subunits, such as RelA (p65), these data demonstrate a critical role for NFKB1, potentially revealing new strategies for targeting this pathway in inflammatory diseases and cancer. PMID:26663363

  10. Different patterns in the prognostic value of age for bladder cancer-specific survival depending on tumor stages

    PubMed Central

    Feng, Huan; Zhang, Wei; Li, Jiajun; Lu, Xiaozhe

    2015-01-01

    To compare the pathological features and long-term survival of bladder cancer (BCa) in young patients with elderly counterparts. Using the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 93115 patients with non-metastatic bladder cancer diagnosed between 1988 and 2003. Patients were categorized into young (50 years and under) and elderly groups (over 50 years of age). The overall and five-year bladder cancer specific survival (BCSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in primary site, pathologic grading, histologic type, AJCC stage (p<0.001). The overall and 5-year cancer specific survival rates were 88.1% and 90.8% in young group, 64.8% and 81.3% in elderly group, which had significant difference in both univariate and multivariate analysis (p<0.001). Further analysis showed this significant difference existed across all the AJCC stage patients. The study findings show different patterns in the prognostic value of age for determining BCSS, depending on the tumor stages. Compared with elderly patients, young patients with bladder cancer surgery appear to have unique characteristics and a higher overall and cancer specific survival rate. PMID:26269768

  11. Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis

    SciTech Connect

    Russell, Michael; Berardi, Philip; Gong Wei; Riabowol, Karl . E-mail: karl@ucalgary.ca

    2006-04-15

    The INhibitor of Growth (ING) family of plant homeodomain (PHD) proteins induce apoptosis and regulate gene expression through stress-inducible binding of phospholipids with subsequent nuclear and nucleolar localization. Relocalization occurs concomitantly with interaction with a subset of nuclear proteins, including PCNA, p53 and several regulators of acetylation such as the p300/CBP and PCAF histone acetyltransferases (HATs), as well as the histone deacetylases HDAC1 and hSir2. These interactions alter the localized state of chromatin compaction, subsequently affecting the expression of subsets of genes, including those associated with the stress response (Hsp70), apoptosis (Bax, MDM2) and cell cycle regulation (p21{sup WAF1}, cyclin B) in a cell- and tissue-specific manner. The expression levels and subcellular localization of ING proteins are altered in a significant number of human cancer types, while the expression of ING isoforms changes during cellular aging, suggesting that ING proteins may play a role in linking cellular transformation and replicative senescence. The variety of functions attributed to ING proteins suggest that this tumor suppressor serves to link the disparate processes of cell cycle regulation, cell suicide and cellular aging through epigenetic regulation of gene expression. This review examines recent findings in the ING field with a focus on the functions of protein-protein interactions involving ING family members and the mechanisms by which these interactions facilitate the various roles that ING proteins play in tumorigenesis, apoptosis and senescence.

  12. Prostate Cancer-Associated Membrane Type 1-Matrix Metalloproteinase

    PubMed Central

    Bonfil, R. Daniel; Dong, Zhong; Trindade Filho, J. Carlos; Sabbota, Aaron; Osenkowski, Pamela; Nabha, Sanaa; Yamamoto, Hamilto; Chinni, Sreenivasa R.; Zhao, Huiren; Mobashery, Shahriar; Vessella, Robert L.; Fridman, Rafael; Cher, Michael L.

    2007-01-01

    Membrane type 1-matrix metalloproteinase (MT1-MMP) is a major mediator of collagen I degradation. In human samples, we show that prostate cancer cells in skeletal metastases consistently express abundant MT1-MMP protein. Because prostate cancer bone metastasis requires remodeling of the collagen-rich bone matrix, we investigated the role of cancer cell-derived MT1-MMP in an experimental model of tumor-bone interaction. MT1-MMP-deficient LNCaP human prostate cancer cells were stably transfected with human wild-type MT1-MMP (MT1wt). Furthermore, endogenous MT1-MMP was down-regulated by small interfering RNA in DU145 human prostate cancer cells. Intratibial tumor injection in severe combined immunodeficient mice was used to simulate intraosseous growth of metastatic tumors. LNCaP-MT1wt cells produced larger osseous tumors than Neo control cells and induced osteolysis, whereas DU145 MT1-MMP-silenced transfectants induced osteogenic changes. In vitro assays showed that MT1wt overexpression enhanced collagen I degradation, whereas MT1-MMP-silencing did the opposite, suggesting that tumor-derived MT1-MMP may contribute directly to bone remodeling. LNCaP-MT1wt-derived conditioned medium stimulated in vitro multinucleated osteoclast formation. This effect was inhibited by osteoprotegerin, a decoy receptor for receptor activator of nuclear factor κB ligand, and by 4-[4-(methanesulfonamido) phenoxy] phenylsulfonyl methylthiirane, an MT1-MMP inhibitor. Our findings are consistent with the hypothesis that prostate cancer-associated MT1-MMP plays a direct and/or indirect role in bone matrix degradation, thus favoring intraosseous tumor expansion. PMID:17525276

  13. Age-period-cohort analysis on the cancer mortality in rural China: 1990–2010

    PubMed Central

    2014-01-01

    Background Cancer has become a global health problem. China still suffers continuous increasing cancer mortality. To study the trend of cancer mortality in rural China, this paper established an Age-Period-Cohort model to discuss the age effect, period effect and cohort effect on cancer mortality in rural China. Methods The data were collected from the “China Health Statistical Yearbook” from 1990 to 2010. Collected data were analyzed by Age-Period-Cohort model and Intrinsic Estimation method. Results The age effect on the total cancer mortality represented a V trend. Compared with Group 0–4, Group 5–9 showed 71.87% lower cancer mortality risk. Compared with Group 5–9, Group 75–79 showed 38 times higher cancer mortality risk. The period effect on the total cancer mortality risk weakened firstly but then increased. It increased by 35.70% from 1990 to 2010, showing an annual average growth of 1.79%. The cohort effect on the total cancer mortality risk weakened by totally 84.94% from 1906–1910 to 2005–2010. Three “deterioration periods” and three “improvement periods” were witnessed during this period. The malignant cancer mortality varied similarly with the total cancer mortality, while benign cancer mortality and other cancer mortality represented different variation laws. Conclusions Although the total cancer mortality risk is increasing at an accelerated rate, cancer mortality risk in recent born year is decreasing, indicating very important impact of social change on the cancer mortality in rural China. PMID:24383432

  14. Cervical cancer: is herpes simplex virus type II a cofactor?

    PubMed Central

    Jones, C

    1995-01-01

    In many ways, cervical cancer behaves as a sexually transmitted disease. The major risk factors are multiple sexual partners and early onset of sexual activity. Although high-risk types of human papillomaviruses (HPV) play an important role in the development of nearly all cases of cervical cancer, other sexually transmitted infectious agents may be cofactors. Herpes simplex virus type 2 (HSV-2) is transmitted primarily by sexual contact and therefore has been implicated as a risk factor. Several independent studies suggest that HSV-2 infections correlate with a higher than normal incidence of cervical cancer. In contrast, other epidemiological studies have concluded that infection with HSV-2 is not a major risk factor. Two separate transforming domains have been identified within the HSV-2 genome, but continued viral gene expression apparently is not necessary for neoplastic transformation. HSV infections lead to unscheduled cellular DNA synthesis, chromosomal amplifications, and mutations. These observations suggest that HSV-2 is not a typical DNA tumor virus. It is hypothesized that persistent or abortive infections induce permanent genetic alterations that interfere with differentiation of cervical epithelium and subsequently induce abnormal proliferation. Thus, HSV-2 may be a cofactor in some but not all cases of cervical cancer. PMID:8665469

  15. Reproductive aging-associated common genetic variants and the risk of breast cancer

    PubMed Central

    2012-01-01

    Introduction A younger age at menarche and an older age at menopause are well established risk factors for breast cancer. Recent genome-wide association studies have identified several novel genetic loci associated with these two traits. However, the association between these loci and breast cancer risk is unknown. Methods In this study, we investigated 19 and 17 newly identified single nucleotide polymorphisms (SNPs) from the ReproGen Consortium that have been associated with age at menarche and age at natural menopause, respectively, and assessed their associations with breast cancer risk in 6 population-based studies among up to 3,683 breast cancer cases and 34,174 controls in white women of European ancestry. In addition, we used these SNPs to calculate genetic risk scores (GRSs) based on their associations with each trait. Results After adjusting for age and potential population stratification, two age at menarche associated SNPs (rs1079866 and rs7821178) and one age at natural menopause associated SNP (rs2517388) were associated with breast cancer risk (p values, 0.003, 0.009 and 0.023, respectively). The odds ratios for breast cancer corresponding to per-risk-allele were 1.14 (95% CI, 1.05 to 1.24), 1.08 (95% CI, 1.02 to 1.15) and 1.10 (95% CI, 1.01 to 1.20), respectively, and were in the direction predicted by their associations with age at menarche or age at natural menopause. These associations did not appear to be attenuated by further controlling for self-reported age at menarche, age at natural menopause, or known breast cancer susceptibility loci. Although we did not observe a statistically significant association between any GRS for reproductive aging and breast cancer risk, the 4th and 5th highest quintiles of the younger age at menarche GRS had odds ratios of 1.14 (95% CI, 1.01 to 1.28) and 1.13 (95% CI, 1.00 to 1.27), respectively, compared to the lowest quintile. Conclusions Our study suggests that three genetic variants, independent of their

  16. Characterization of Age Differences in Error Types in a Multitrial Spatial Learning Task

    ERIC Educational Resources Information Center

    Krueger, Lacy E.

    2013-01-01

    Although increased age is associated with greater errors in spatial memory tasks, it is unclear if there are age differences in error types. To investigate this, 334 participants (ages 22-88) completed a task in which they remembered object locations across multiple study-test trials. Far and close error types were categorized based on the spatial…

  17. Perceived Fashionability of a Garment as Inferred from the Age and Body Type of the Wearer.

    ERIC Educational Resources Information Center

    Clayton, Ruth; And Others

    1987-01-01

    Ninety college-aged females rated the fashionability of six garments worn by nine models representing three age levels and three body types. Results show respondents used age and body type cues as well as fashion detail to judge garment fashionability. (Author/CH)

  18. MicroRNA-Based Linkage between Aging and Cancer: from Epigenetics View Point.

    PubMed

    Saeidimehr, Saeid; Ebrahimi, Ammar; Saki, Najmaldin; Goodarzi, Parisa; Rahim, Fakher

    2016-01-01

    Ageing is a complex process and a broad spectrum of physical, psychological, and social changes over time. Accompanying diseases and disabilities, which can interfere with cancer treatment and recovery, occur in old ages. MicroRNAs (miRNAs) are a set of small non-coding RNAs, which have considerable roles in post-transcriptional regulation at gene expression level. In this review, we attempted to summarize the current knowledge of miRNAs functions in ageing, with mainly focuses on malignancies and all underlying genetic, molecular and epigenetics mechanisms. The evidences indicated the complex and dynamic nature of miRNA-based linkage of ageing and cancer at genomics and epigenomics levels which might be generally crucial for understanding the mechanisms of age-related cancer and ageing. Recently in the field of cancer and ageing, scientists claimed that uric acid can be used to regulate reactive oxygen species (ROS), leading to cancer and ageing prevention; these findings highlight the role of miRNA-based inhibition of the SLC2A9 antioxidant pathway in cancer, as a novel way to kill malignant cells, while a patient is fighting with cancer. PMID:27540517

  19. MicroRNA-Based Linkage between Aging and Cancer: from Epigenetics View Point

    PubMed Central

    Saeidimehr, Saeid; Ebrahimi, Ammar; Saki, Najmaldin; Goodarzi, Parisa; Rahim, Fakher

    2016-01-01

    Ageing is a complex process and a broad spectrum of physical, psychological, and social changes over time. Accompanying diseases and disabilities, which can interfere with cancer treatment and recovery, occur in old ages. MicroRNAs (miRNAs) are a set of small non-coding RNAs, which have considerable roles in post-transcriptional regulation at gene expression level. In this review, we attempted to summarize the current knowledge of miRNAs functions in ageing, with mainly focuses on malignancies and all underlying genetic, molecular and epigenetics mechanisms. The evidences indicated the complex and dynamic nature of miRNA-based linkage of ageing and cancer at genomics and epigenomics levels which might be generally crucial for understanding the mechanisms of age-related cancer and ageing. Recently in the field of cancer and ageing, scientists claimed that uric acid can be used to regulate reactive oxygen species (ROS), leading to cancer and ageing prevention; these findings highlight the role of miRNA-based inhibition of the SLC2A9 antioxidant pathway in cancer, as a novel way to kill malignant cells, while a patient is fighting with cancer. PMID:27540517

  20. Colorectal Cancer Screening Based on Age and Gender

    PubMed Central

    Wong, Martin C.S.; Ching, Jessica Y.L.; Chan, Victor C.W.; Lam, Thomas Y.T.; Luk, Arthur K.C.; Wong, Sunny H.; Ng, Siew C.; Ng, Simon S.M.; Wu, Justin C.Y.; Chan, Francis K.L.; Sung, Joseph J.Y.

    2016-01-01

    Abstract We evaluated whether age- and gender-based colorectal cancer screening is cost-effective. Recent studies in the United States identified age and gender as 2 important variables predicting advanced proximal neoplasia, and that women aged <60 to 70 years were more suited for sigmoidoscopy screening due to their low risk of proximal neoplasia. Yet, quantitative assessment of the incremental benefits, risks, and cost remains to be performed. Primary care screening practice (2008–2015). A Markov modeling was constructed using data from a screening cohort. The following strategies were compared according to the Incremental Cost Effectiveness Ratio (ICER) for 1 life-year saved: flexible sigmoidoscopy (FS) 5 yearly; colonoscopy 10 yearly; FS for each woman at 50- and 55-year old followed by colonoscopy at 60- and 70-year old; FS for each woman at 50-, 55-, 60-, and 65-year old followed by colonoscopy at 70-year old; FS for each woman at 50-, 55-, 60-, 65-, and 70-year old. All male subjects received colonoscopy at 50-, 60-, and 70-year old under strategies 3 to 5. From a hypothetical population of 100,000 asymptomatic subjects, strategy 2 could save the largest number of life-years (4226 vs 2268 to 3841 by other strategies). When compared with no screening, strategy 5 had the lowest ICER (US$42,515), followed by strategy 3 (US$43,517), strategy 2 (US$43,739), strategy 4 (US$47,710), and strategy 1 (US$56,510). Strategy 2 leads to the highest number of bleeding and perforations, and required a prohibitive number of colonoscopy procedures. Strategy 5 remains the most cost-effective when assessed with a wide range of deterministic sensitivity analyses around the base case. From the cost effectiveness analysis, FS for women and colonoscopy for men represent an economically favorable screening strategy. These findings could inform physicians and policy-makers in triaging eligible subjects for risk-based screening, especially in countries with limited colonoscopic

  1. Breast cancer and age in Black and White women in South East England.

    PubMed

    Jack, Ruth H; Davies, Elizabeth A; Møller, Henrik

    2012-03-01

    Black women have lower age-standardized breast cancer incidence rates than White women in the United Kingdom. However, little is known about such differences in risk in separate age groups. Records on female residents of South East England diagnosed with breast cancer between 1998 and 2003 were extracted from the Thames Cancer Registry database. Age-specific incidence rates were calculated for each 5-year age group using 2001 Census population data for White, Black Caribbean and Black African women. Black Caribbean and Black African breast cancer patients were younger than both the White patients and those with no ethnicity recorded. Black Caribbean and Black African women in the population also had a younger age profile than White women. The computed age-specific incidence rates in women aged under 50 were similar in the different ethnic groups, whereas in women aged 50 and over White women had higher rates. The younger age of Black Caribbean and Black African breast cancer patients in South East England reflects the younger age of these populations, rather than an increased risk of disease at younger ages. PMID:21445965

  2. Use of Q-Type Factor Analysis with the Aged.

    ERIC Educational Resources Information Center

    Kleban, Morton H.; And Others

    This paper explores Q-Factor Analysis as a method of organizing data on a large array of variables to describe a group of aged Ss. Forty-seven males, specially selected for their good health (Mean Age: 71.5; SD: 4.8) were measured on 550 biological and behavioral variables. A Q-Factor Analysis was calculated, using a S by variable matrix, which is…

  3. Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

    SciTech Connect

    Mendelsohn, M.L.; Pierce, P.A.

    1997-09-04

    Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.

  4. Implications of Type1/2 Diabetes Mellitus in Breast Cancer Development: A General Female Population-based Cohort Study

    PubMed Central

    Liaw, Yung-Po; Ko, Pei-Chieh; Jan, Shiou-Rung; Huang, Jing-Yang; Nfor, Oswald Ndi; Lung, Chia-Chi; Chiang, Yi-Chen; Yeh, Liang-Tsai; Chou, Ming-Chih; Tsai, Horng-Der; Hsiao, Yi-Hsuan

    2015-01-01

    Aim: The current study assessed the potential impact of diabetes type 1 and type 2 for female breast cancer risk. Materials and Methods: The health information and medical record of the entire adult female residents in Taiwan were retrieved from Taiwan's National Health Insurance Research Database. Multivariate Cox proportional hazard regression models and descriptive statistics were used to identify potential correlations between type 1/2 diabetes and breast cancer. In addition, this study statistically assessed the possible association of diabetes and breast cancer risk with age, insurance amount (quality of care), and regions. Results: The diabetic status of the entire adult female population was assessed between 2001 and 2003. Of 10,827,079 adult females, 4,738 (0.04%) were diagnosed with type 1 and 830,546 (7.7%) with type 2 diabetes, and 9, 991,795 (92.3%) were free of diabetes. From 2004 to 2010, a total of 57,283 cases of breast cancer were detected, with an average breast cancer incidence rate of 0.53% in the generation population. The actual breast cancer incidence rate was 0.30% (14 of 4,738) in patients with type 1 diabetes, 1.10% (9,105 of 830,546) in patients with type 2 diabetes, and 0.48% (48,164 of 9,991,795) in patients free of diabetes. The breast cancer incidence rate is significantly higher (p < 0.001) in patients with type 2 diabetes than that in patients with type 1 diabetes and in patients free of diabetes. After adjusting for the covariates of age, insurance cost, and region, hazard ratios (HRs) for the association between breast cancer risk and types 1 and 2 DM were 1.01 (CI = 0.60-1.71) and 1.13 (CI = 1.10-1.16), respectively. Women with type 2 diabetes were at a significantly higher risk for development of breast cancer compared with those free of diabetes, but there appeared to have no significant increase in risk for those with type 1 diabetes. Our study also revealed that age, insurance amount (quality of care), and region are

  5. Cancer Basics

    MedlinePlus

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  6. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  7. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  8. 20 CFR 404.716 - Type of evidence of age to be given.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DISABILITY INSURANCE (1950- ) Evidence Evidence of Age, Marriage, and Death § 404.716 Type of evidence of age...; insurance policies; a marriage record; a passport; an employment record; a delayed birth certificate,...

  9. 20 CFR 404.716 - Type of evidence of age to be given.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DISABILITY INSURANCE (1950- ) Evidence Evidence of Age, Marriage, and Death § 404.716 Type of evidence of age...; insurance policies; a marriage record; a passport; an employment record; a delayed birth certificate,...

  10. Knowledge about hereditary cancer of women with family histories of breast, colorectal, or both types of cancer.

    PubMed

    Campacci, N; de Lima, J O; Ramadan, L; Palmero, E I

    2015-03-01

    Usually, the mass media do not address hereditary cancer and their risk factors, nor are these topics discussed at the community level. We used an informative guide on cancer and hereditary cancer, followed by a questionnaire on these topics to investigate the relevant knowledge among women at high risk for hereditary breast and/or colorectal cancer from a population-based cohort. The cohort was composed of 81 Brazilian women with positive family histories of breast and/or colorectal cancer. Strauss and Corbin's Grounded Theory was used for qualitative analysis. The average age of the cohort was 49.9 years old. Three participants (3.9%) were illiterate, 45 (59.2%) had attended elementary school, 14 (18.4%) had secondary school, and 14 (18.4%) held higher education degrees. A total of 47 (54.3%) volunteers were unable to fully understand the information provided in the guide because they did not know the meaning of words such as metastasis, malignant, hereditary, sporadic, or oncogenetics. Notwithstanding, the acceptance of the educational tool utilized was satisfactory, and it enhanced the volunteers' interest in a better understanding of cancer and heredity. Thereby, we concluded that the low knowledge of this important subject and the unawareness about fundamental terms required for the comprehension of this specific type of neoplasm made us believe that the use of the informative guide can provide a great value when used previously to the genetic counseling consultations. Besides, educational tools of easy understanding should be part of everyday clinical practice, from primary to specialized patient care. PMID:24792524

  11. Blood Telomere Length Attrition and Cancer Development in the Normative Aging Study Cohort

    PubMed Central

    Hou, Lifang; Joyce, Brian Thomas; Gao, Tao; Liu, Lei; Zheng, Yinan; Penedo, Frank J.; Liu, Siran; Zhang, Wei; Bergan, Raymond; Dai, Qi; Vokonas, Pantel; Hoxha, Mirjam; Schwartz, Joel; Baccarelli, Andrea

    2015-01-01

    Background Accelerated telomere shortening may cause cancer via chromosomal instability, making it a potentially useful biomarker. However, publications on blood telomere length (BTL) and cancer are inconsistent. We prospectively examined BTL measures over time and cancer incidence. Methods We included 792 Normative Aging Study participants with 1–4 BTL measurements from 1999 to 2012. We used linear mixed-effects models to examine BTL attrition by cancer status (relative to increasing age and decreasing years pre-diagnosis), Cox models for time-dependent associations, and logistic regression for cancer incidence stratified by years between BTL measurement and diagnosis. Findings Age-related BTL attrition was faster in cancer cases pre-diagnosis than in cancer-free participants (pdifference = 0.017); all participants had similar age-adjusted BTL 8–14 years pre-diagnosis, followed by decelerated attrition in cancer cases resulting in longer BTL three (p = 0.003) and four (p = 0.012) years pre-diagnosis. Longer time-dependent BTL was associated with prostate cancer (HR = 1.79, p = 0.03), and longer BTL measured ≤ 4 years pre-diagnosis with any (OR = 3.27, p < 0.001) and prostate cancers (OR = 6.87, p < 0.001). Interpretation Age-related BTL attrition was faster in cancer cases but their age-adjusted BTL attrition began decelerating as diagnosis approached. This may explain prior inconsistencies and help develop BTL as a cancer detection biomarker. PMID:26288820

  12. Age at exposure to ionising radiation and cancer mortality among Hanford workers: follow up through 1994

    PubMed Central

    Wing, S; Richardson, D

    2005-01-01

    Background: Studies of workers at the plutonium production factory in Hanford, WA have led to conflicting conclusions about the role of age at exposure as a modifier of associations between ionising radiation and cancer. Aims: To evaluate the influence of age at exposure on radiation risk estimates in an updated follow up of Hanford workers. Methods: A cohort of 26 389 workers hired between 1944 and 1978 was followed through 1994 to ascertain vital status and causes of death. External radiation dose estimates were derived from personal dosimeters. Poisson regression was used to estimate associations between mortality and cumulative external radiation dose at all ages, and in specific age ranges. Results: A total of 8153 deaths were identified, 2265 of which included cancer as an underlying or contributory cause. Estimates of the excess relative risk per Sievert (ERR/Sv) for cumulative radiation doses at all ages combined were negative for all cause and leukaemia and positive for all cancer and lung cancer. Cumulative doses accrued at ages below 35, 35–44, and 45–54 showed little association with mortality. For cumulative dose accrued at ages 55 and above (10 year lag), the estimated ERR/Sv for all cancers was 3.24 (90% CI: 0.80 to 6.17), primarily due to an association with lung cancer (ERR/Sv: 9.05, 90% CI: 2.96 to 17.92). Conclusions: Associations between radiation and cancer mortality in this cohort are primarily a function of doses at older ages and deaths from lung cancer. The association of older age radiation exposures and cancer mortality is similar to observations from several other occupational studies. PMID:15961623

  13. Treating cancer with embryonic stem cells: rationale comes from aging studies.

    PubMed

    Ukraintseva, Svetlana V; Yashin, Anatoly I

    2005-01-01

    In an earlier poster paper (1) we proposed that cancer can be viewed not only as a fatal disease but also as a local aberrant, rejuvenation, in an organism, and this fact can be useful for developing new anti-aging and anti-cancer treatments. In this paper we provide additional evidence from human and experimental animal studies in support of this view. First, we discuss cancer genes as candidate targets for anti-aging interventions. We review examples in which the life of experimental animals has been prolonged in situations of increased activity of proto-oncogenes - or decreased activity of tumor suppressors - in normal (non-cancerous) cells in vivo. Studies of genetic polymorphisms revealed similar effects on longevity in humans. Second, we discuss the possibility of treating cancer with embryonic stem cells. The fact that cancer cells do not, age, means that these cells overcome aging host cells. However, cancer cells can be suppressed by young and quickly proliferating non-cancer cells, such as embryonic stem cells. The grafting of these cells in the tumor environment could be a prospective non-toxic anti-cancer treatment. We discuss recent evidence in support of this view. PMID:15569600

  14. Sex, Race, and Age Disparities in the Improvement of Survival for Gastrointestinal Cancer over Time

    PubMed Central

    Wan, Jue-feng; Yang, Li-feng; Shen, Yun-zhu; Jia, Hui-xun; Zhu, Ji; Li, Gui-chao; Zhang, Zhen

    2016-01-01

    There have been notable improvements in survival over the past 2 decades for gastrointestinal (GI) cancer. However, the degree of improvement by age, race, and sex remains unclear. We analyzed data from 9 population-based cancer registries included in the SEER program of the National Cancer Institute (SEER 9) in 1990 to 2009 (n = 288,337). The degree of survival improvement over time by age, race, and sex was longitudinally measured. From 1990 to 2009, improvements in survival were greater for younger age groups. For patients aged 20 to 49 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.74 (95% CI, 0.66–0.83), 0.49 (95% CI, 0.37–0.64), 0.69 (95% CI, 0.65–0.76), 0.62 (95% CI, 0.54–0.69), and 0.56 (95% CI, 0.42–0.76), for cancer of the stomach, small intestine, colon, rectum and anus, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. Compared with African Americans, whites experienced greater improvement in small intestinal and anal cancer survival. Female anal cancer and regional anal cancer patients experienced no improvement. Our data suggest that different improvement in survival in age, sex and race exists. PMID:27406065

  15. Predicting Fear of Breast Cancer Recurrence and Self-Efficacy in Survivors by Age at Diagnosis

    PubMed Central

    Ziner, Kim Wagler; Sledge, George W.; Bell, Cynthia J.; Johns, Shelley; Miller, Kathy D.; Champion, Victoria L.

    2016-01-01

    Purpose/Objectives To determine the effect that age at diagnosis has on fear of breast cancer recurrence and to identify the predictors of fear of recurrence using self-efficacy as a mediator. Design Cross-sectional survey. Setting Two university cancer centers and one cooperative group in the midwestern United States. Sample 1,128 long-term survivors. Methods Survivors were eligible if they were aged 18–45 years (younger group) or 55–70 years (older group) at cancer diagnosis, had received chemotherapy, and were three to eight years postdiagnosis. Fear of recurrence was compared between younger and older groups. Multiple regression analyses were used to test variables’ prediction of fear of recurrence and breast cancer survivor self-efficacy, as well as breast cancer survivor self-efficacy mediation effects. Main Research Variables Fear of recurrence, breast cancer survivor self-efficacy, and age at diagnosis. Findings Survivors diagnosed at a younger age had significantly higher fear of recurrence, as well as health, role, womanhood, death, and parenting worries. Perceived risk of recurrence, trait anxiety, and breast cancer reminders explained significant variance in fear of recurrence and breast cancer survivor self-efficacy. Breast cancer survivor self-efficacy partially mediated the effects of variables on fear of recurrence. Conclusions The findings suggest that breast cancer survivor self-efficacy may have a protective effect for survivors who are younger at diagnosis and have higher perceived risk of recurrence, higher trait anxiety, and more breast cancer reminders. Oncology nurses already use the skills required to support self-efficacy. Additional research is needed to define and test breast cancer survivor self-efficacy interventions. Implications for Nursing Oncology nurses are in a key role to assess fear of recurrence and provide self-efficacy interventions to reduce it in breast cancer survivors. Strategies to efficiently address fear of

  16. Chromosomal abnormalities are associated with aging and cancer

    Cancer.gov

    Two new studies have found that large structural abnormalities in chromosomes, some of which have been associated with increased risk of cancer, can be detected in a small fraction of people without a prior history of cancer. The studies found that these

  17. The Age Specific Incidence Anomaly Suggests that Cancers Originate During Development

    NASA Astrophysics Data System (ADS)

    Brody, James P.

    The accumulation of genetic alterations causes cancers. Since this accumulation takes time, the incidence of most cancers is thought to increase exponentially with age. However, careful measurements of the age-specific incidence show that the specific incidence for many forms of cancer rises with age to a maximum, and then decreases. This decrease in the age-specific incidence with age is an anomaly. Understanding this anomaly should lead to a better understanding of how tumors develop and grow. Here we derive the shape of the age-specific incidence, showing that it should follow the shape of a Weibull distribution. Measurements indicate that the age-specific incidence for colon cancer does indeed follow a Weibull distribution. This analysis leads to the interpretation that for colon cancer two subpopulations exist in the general population: a susceptible population and an immune population. Colon tumors will only occur in the susceptible population. This analysis is consistent with the developmental origins of disease hypothesis and generalizable to many other common forms of cancer.

  18. The Age Specific Incidence Anomaly Suggests that Cancers Originate During Development

    NASA Astrophysics Data System (ADS)

    Brody, James P.

    2014-05-01

    The accumulation of genetic alterations causes cancers. Since this accumulation takes time, the incidence of most cancers is thought to increase exponentially with age. However, careful measurements of the age-specific incidence show that the specific incidence for many forms of cancer rises with age to a maximum, and then decreases. This decrease in the age-specific incidence with age is an anomaly. Understanding this anomaly should lead to a better understanding of how tumors develop and grow. Here we derive the shape of the age-specific incidence, showing that it should follow the shape of a Weibull distribution. Measurements indicate that the age-specific incidence for colon cancer does indeed follow a Weibull distribution. This analysis leads to the interpretation that for colon cancer two subpopulations exist in the general population: a susceptible population and an immune population. Colon tumors will only occur in the susceptible population. This analysis is consistent with the developmental origins of disease hypothesis and generalizable to many other common forms of cancer.

  19. Does Cancer Reduce Labor Market Entry? Evidence for Prime-Age Females

    PubMed Central

    Moran, John R.; Short, Pamela Farley

    2014-01-01

    Existing studies of the labor market status of cancer survivors have focused on the extent to which cancer disrupts the employment of individuals who were working when diagnosed with cancer. We examine how surviving cancer affects labor market entry and usual hours of work among females age 28-54 who were not working when first diagnosed. We find that prime-age females have employment rates two to six years after diagnosis that are 12 percentage points lower than otherwise similar women who were initially out of the labor force, full-time employment rates that are 10 percentage points lower, and usual hours of work that are 5 hours per week lower. These estimates are somewhat larger than estimates for prime-age women employed at the time of diagnosis and highlight the importance of considering non-working females when assessing the economic and psychosocial burden of cancer. PMID:24243912

  20. Fatigued Breast Cancer Survivors: The Role of Sleep Quality, Depressed Mood, Stage, and Age

    PubMed Central

    Banthia, Rajni; Malcarne, Vanessa L.; Ko, Celine M.; Varni, James W.; Sadler, Georgia Robins

    2015-01-01

    Cancer-related fatigue is associated with lower health-related quality of life and the majority of breast cancer survivors experience persistent fatigue after finishing treatment. The present study examined age, cancer stage, sleep quality, and depressed mood as predictors of five dimensions of fatigue in seventy fatigued breast cancer survivors who no longer evidenced any signs of cancer and were finished with treatment. Discriminant function analyses were used to predict fatigue subgroup membership (higher, lower) from age, stage, mood, and sleep for five subtypes: General, Mental, Emotional, and Physical Fatigue, and Vigor. Significant discriminant functions were found for all subtypes. Findings suggest that age, staging, mood, and sleep are all important predictors, but there are differential relationships when subtypes of fatigue are considered. Given current limitations in treating fatigue directly, interventions targeting mood and sleep should be considered as alternate approaches to reduce fatigue. PMID:20205039

  1. Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types

    PubMed Central

    Wang, Cheng; Gu, Yayun; Zhang, Kai; Xie, Kaipeng; Zhu, Meng; Dai, Ningbin; Jiang, Yue; Guo, Xuejiang; Liu, Mingxi; Dai, Juncheng; Wu, Linxiang; Jin, Guangfu; Ma, Hongxia; Jiang, Tao; Yin, Rong; Xia, Yankai; Liu, Li; Wang, Shouyu; Shen, Bin; Huo, Ran; Wang, Qianghu; Xu, Lin; Yang, Liuqing; Huang, Xingxu; Shen, Hongbing; Sha, Jiahao; Hu, Zhibin

    2016-01-01

    Cancer-testis (CT) genes represent the similarity between the processes of spermatogenesis and tumorigenesis. It is possible that their selective expression pattern can help identify driver genes in cancer. In this study, we integrate transcriptomics data from multiple databases and systematically identify 876 new CT genes in 19 cancer types. We explore their relationship with testis-specific regulatory elements. We propose that extremely highly expressed CT genes (EECTGs) are potential drivers activated through epigenetic mechanisms. We find mutually exclusive associations between EECTGs and somatic mutations in mutated genes, such as PIK3CA in breast cancer. We also provide evidence that promoter demethylation and close non-coding RNAs (namely, CT-ncRNAs) may be two mechanisms to reactivate EECTG gene expression. We show that the meiosis-related EECTG (MEIOB) and its nearby CT-ncRNA have a role in tumorigenesis in lung adenocarcinoma. Our findings provide methods for identifying epigenetic-driver genes of cancer, which could serve as targets of future cancer therapies. PMID:26813108

  2. Incidence of lung cancer by histological type among asbestos cement workers in Denmark.

    PubMed Central

    Raffn, E; Lynge, E; Korsgaard, B

    1993-01-01

    OBJECTIVE--A significant twofold increased risk of lung cancer was found among 8000 men employed in the Danish asbestos cement industry between 1928 and 1984. The histological pattern of 104 lung cancer cases was studied with the aim of evaluating a relation between specific morphological types, duration of employment, and time since first employment. METHODS--Age, sex, and calendar time specific incidence of morphological subtypes of lung cancer (adenocarcinoma, squamous cell carcinoma, anaplastic carcinoma, and unspecified malignant tumour) for all Danish men were computed from 1943 to 1984, from data routinely collected by the Danish Cancer Registry. Person-years of observation were counted from 15 years after the date of first employment until date of diagnosis of cancer, death, emigration, or the end of follow up on 31 December 1984. Expected numbers of cases were computed by applying person-years at risk to the appropriate incidence rates. Observed numbers were distributed accordingly and the relative risk calculated. RESULTS--The relative risk for adenocarcinoma was 3.31 (observed (O) 24, expected (E) 7.26), for squamous cell carcinoma 1.67 (O, 37, E, 22.12), for anaplastic carcinoma 1.58 (O, 23, E, 14.53), and for unspecified malignant tumour 1.57 (O, 18, E, 11.46). An increased risk by duration of employment and time since first employment was most pronounced for adenocarcinoma. CONCLUSION--The link between adenocarcinoma and asbestos was confirmed in this, the first study of risk of lung cancer by histological category based on incident cancer cases for a whole population during a 50 year period. PMID:8431397

  3. Association Between Maternal Diabetes in Utero and Age at Offspring's Diagnosis of Type 2 Diabetes

    PubMed Central

    Pettitt, David J.; Lawrence, Jean M.; Beyer, Jennifer; Hillier, Teresa A.; Liese, Angela D.; Mayer-Davis, Beth; Loots, Beth; Imperatore, Giuseppina; Liu, Lenna; Dolan, Lawrence M.; Linder, Barbara; Dabelea, Dana

    2008-01-01

    OBJECTIVE—The purpose of this study was to examine age of diabetes diagnosis in youth who have a parent with diabetes by diabetes type and whether the parent's diabetes was diagnosed before or after the youth's birth. RESEARCH DESIGN AND METHODS—The cohort comprised SEARCH for Diabetes in Youth Study participants (diabetes diagnosis 2001–2005) with a diabetic parent. SEARCH is a multicenter survey of youth with diabetes diagnosed before age 20 years. RESULTS—Youth with type 2 diabetes were more likely to have a parent with either type 1 or type 2 diabetes (mother 39.3%; father 21.2%) than youth with type 1 diabetes (5.3 and 6.7%, respectively, P < 0.001 for each). Type 2 diabetes was diagnosed 1.68 years earlier among those exposed to diabetes in utero (n = 174) than among those whose mothers’ diabetes was diagnosed later (P = 0.018, controlled for maternal diagnosis age, paternal diabetes, sex, and race/ethnicity). Age at diagnosis of type 1 diabetes for 269 youth with and without in utero exposure did not differ significantly (difference 0.96 year, P = 0.403 after adjustment). Controlled for the father's age of diagnosis, father's diabetes before the child's birth was not associated with age at diagnosis (P = 0.078 for type 1 diabetes; P = 0.140 for type 2 diabetes). CONCLUSIONS—Type 2 diabetes was diagnosed at younger ages among those exposed to hyperglycemia in utero. Among youth with type 1 diabetes, the effect of the intrauterine exposure was not significant when controlled for mother's age of diagnosis. This study helps explain why other studies have found higher age-specific rates of type 2 diabetes among offspring of women with diabetes. PMID:18694977

  4. A new type of accelerator for charged particle cancer therapy

    NASA Astrophysics Data System (ADS)

    Edgecock, Rob

    2013-04-01

    Non-scaling Fixed Field Alternating Gradient accelerators (ns-FFAGs) show great potential for the acceleration of protons and light ions for the treatment of certain cancers. They have unique features as they combine techniques from the existing types of accelerators, cyclotrons and synchrotrons, and hence look to have advantages over both for this application. However, these unique features meant that it was necessary to build one of these accelerators to show that it works and to undertake a detailed conceptual design of a medical machine. Both of these have now been done. This paper will describe the concepts of this type of accelerator, show results from the proof-of-principle machine (EMMA) and described the medical machine (PAMELA).

  5. Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer

    PubMed Central

    Öhlund, D; Lundin, C; Ardnor, B; Öman, M; Naredi, P; Sund, M

    2009-01-01

    Background: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients. Methods: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques. Results: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival. Conclusion: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context. PMID:19491897

  6. Recent progress in genetics of aging, senescence and longevity: focusing on cancer-related genes

    PubMed Central

    Berman, Albert E.; Leontieva, Olga V.; Natarajan, Venkatesh; McCubrey, James A.; Demidenko, Zoya N.; Nikiforov, Mikhail A.

    2012-01-01

    It is widely believed that aging results from the accumulation of molecular damage, including damage of DNA and mitochondria and accumulation of molecular garbage both inside and outside of the cell. Recently, this paradigm is being replaced by the “hyperfunction theory”, which postulates that aging is caused by activation of signal transduction pathways such as TOR (Target of Rapamycin). These pathways consist of different enzymes, mostly kinases, but also phosphatases, deacetylases, GTPases, and some other molecules that cause overactivation of normal cellular functions. Overactivation of these sensory signal transduction pathways can cause cellular senescence, age-related diseases, including cancer, and shorten life span. Here we review some of the numerous very recent publications on the role of signal transduction molecules in aging and age-related diseases. As was emphasized by the author of the “hyperfunction model”, many (or actually all) of them also play roles in cancer. So these “participants” in pro-aging signaling pathways are actually very well acquainted to cancer researchers. A cancer-related journal such as Oncotarget is the perfect place for publication of such experimental studies, reviews and perspectives, as it can bridge the gap between cancer and aging researchers. PMID:23455653

  7. Safety symbol comprehension: effects of symbol type, familiarity, and age.

    PubMed

    Hancock, Holly E; Rogers, Wendy A; Schroeder, Derek; Fisk, Arthur D

    2004-01-01

    A new procedure for evaluating symbol comprehension, the phrase generation procedure, was assessed with 52 younger and 52 older adults. Participants generated as many phrases as came to mind when viewing 40 different safety symbols (hazard alerting, mandatory action, prohibition, and information symbols). Symbol familiarity was also assessed. Comprehension rates for both groups were lower than the 85% level recommended by the American National Standards Institute. Moreover, older participants' comprehension was significantly worse than younger participants', and the older adults also generated significantly fewer phrases. Generally, prohibition symbols were comprehended best and hazard alerting symbols worst. In addition, symbol familiarity was positively correlated with symbol comprehension. These findings indicate that important safety information depicted on signs and household products may be misunderstood if presented in symbolic form. Furthermore, certain types of symbols may be better understood (e.g., prohibition symbols) than other types (e.g., hazard alerting symbols) by both younger and older individuals. These findings signify the utility of the phrase generation procedure as a method for evaluating symbol comprehension, particularly when it is not possible or desirable to provide contextual information. Actual or potential applications of this research include using the phrase generation approach to identify poorly comprehended symbols, including identification of critical confusions that may arise when processing symbolic information. PMID:15359669

  8. The Marble Types of Thassos Island through the Ages

    NASA Astrophysics Data System (ADS)

    Laskaridis, Kostas; Patronis, Michael; Papatrechas, Christos; Schouenborg, Björn

    2013-04-01

    The first references to the "white whole-grain" marble of Thassos Island, Greece, date back to the 6th century BC when stones were quarried at Alyki peninsula and at Fanari and Vathy capes. Since that time, Thassos marble was exported to Samothraki and other neighbouring islands, Asia Minor coastal cities, Southern Greece and Rome. In ancient times, there were two principal types of marble quarries in Thassos: (a) those producing material for the construction of temples and for the creation of various art pieces, i.e. ornamental stones, and (b) those for extraction of rough blocks for export. This paper aims at describing the Thassos marble, the geological setting in brief, its historic use and future supply possibilities and other reasons why it is a time-enduring ornamental stone. The aesthetical characteristics and the physical mechanical properties of its two main types (i.e. calcitic and dolomitic) are described and evaluated. The relevant results justify the wide application range and the continuous use of Thassos marble from ancient to present times and confirm the ability of this stone to survive over time. Keywords: Thassos, Marble, Ornamental Stones, Physical Mechanical Properties, Historic use

  9. Coming of age: the artificial pancreas for type 1 diabetes.

    PubMed

    Thabit, Hood; Hovorka, Roman

    2016-09-01

    The artificial pancreas (closed-loop system) addresses the unmet clinical need for improved glucose control whilst reducing the burden of diabetes self-care in type 1 diabetes. Glucose-responsive insulin delivery above and below a preset insulin amount informed by sensor glucose readings differentiates closed-loop systems from conventional, threshold-suspend and predictive-suspend insulin pump therapy. Insulin requirements in type 1 diabetes can vary between one-third-threefold on a daily basis. Closed-loop systems accommodate these variations and mitigate the risk of hypoglycaemia associated with tight glucose control. In this review we focus on the progress being made in the development and evaluation of closed-loop systems in outpatient settings. Randomised transitional studies have shown feasibility and efficacy of closed-loop systems under supervision or remote monitoring. Closed-loop application during free-living, unsupervised conditions by children, adolescents and adults compared with sensor-augmented pumps have shown improved glucose outcomes, reduced hypoglycaemia and positive user acceptance. Innovative approaches to enhance closed-loop performance are discussed and we also present the outlook and strategies used to ease clinical adoption of closed-loop systems. PMID:27364997

  10. Factors Associated With Cancer Worry Among People Aged 50 or Older, Spain, 2012–2014

    PubMed Central

    Sotos, Joseba Rabanales; Herráez, María José Simarro; Rosa, Monchi Campos; López, Jaime López-Torres; Ortiz, María Pilar Sánchez

    2015-01-01

    Introduction Cancer worry varies among patients and may influence their participation in preventive activities. We tested whether sociodemographic characteristics, lifestyle, locus of control, comorbidity, and perceived health status were associated with the level of cancer worry among adults aged 50 or older. Methods We conducted an observational cross-sectional study of 666 adults in Spain aged 50 or older. Participants were selected by simple random sampling and asked to visit their designated health center for a personal interview. The study variables were level of cancer worry (measured by Cancer Worry Scale [CWS]), sociodemographic characteristics, lifestyle, personal history or family history of cancer, comorbidity, self-perceived health, locus of control, and social support. Results More than half of participants, 58.1%, were women; mean age was 60.5 years (standard deviation [SD], 6.8 y). Measurement of the frequency and severity of cancer worry (possible scale of 6–24 points) yielded a mean CWS score of 9.3 (95% confidence interval, 9.0–9.5); 31.9% of participants reported being concerned about cancer. Scores were higher among women (9.7 [SD, 3.3]) than men (8.7 [SD, 2.7]) (P < .001) and among participants in rural settings (10.0 [SD, 3.4]) than in urban settings (9.0 [SD, 3.0]) (P < .001). Multiple linear regression showed a greater degree of cancer worry among people with personal or family history of cancer, more health problems, worse self-perceived health, and lower social support. Conclusion Cancer worry is frequent among older adults, and the level of such concern is related not only to personal characteristics but also to lifestyle and health status. Further research is required to understand how contextual factors can influence cancer worry and how such concern changes behavior patterns related to cancer prevention activities. PMID:26704444

  11. The trends in histological types of lung cancer during 1980-1988, Guangzhou, China.

    PubMed

    Cha, Q; Chen, Y; Du, Y

    1997-07-01

    Five thousand five hundred and forty six cases of all lung cancer patients who died during 1980-1988 in Guangzhou, China were investigated retrospectively with a standardized 31-item questionnaire administered to their next of kin. The data of 1093 lung cancer patients(20%, 1093/5546) who had a histological record was analyzed to investigate the changes in histological types and the possible etiologic causes. The difference between the lung cancer deaths with and without histological record is not significant in age, location (peripheral or central) of tumour and status of occupation (P > 0.05), but the difference in sex is significant (P < 0.01). We analyzed the data of 1093 cases by sex and by 3-year period. There had been a shift in the histology pattern with an increase in the percentage of adenocarcinoma (P = 0.0011) and a decrease in percentage of squamous cell carcinoma (P = 0.0027) in males, inversely, there has been an absolute and a relative decrease of percentage in adenocarcinoma in females (P = 0.0028). The percentage of smokers, age of starting to smoke and type of tobacco smoking were nearly constant in both sexes during the studied periods. The pack-years of smoking decreased in males (P = 0.0396), and seemed increase in females (P = 0.1576, no significance). The analysis of occupation and dietary habits among 5546 cases were performed. The proportion of housewives decreased with time (P < 0.001) while the percentage of chemists in females increased (P < 0.001) with time. The dietary habits are changing with an increase in roast food intake for males (P = 0.0055) and in vegetable intake for males (P < 0.0001), females (P < 0.0001), and for patients with lung squamous cell carcinoma and adenocarcinoma in both sexes (P < 0.001). Perhaps the changes in pack-years of smoking may be responsible for the percentage change of lung cancer histological types observed in our study. The role that changes in dietary habits and status of occupations play in the

  12. Inclusive fitness effects can select for cancer suppression into old age

    PubMed Central

    Brown, Joel S.; Aktipis, C. Athena

    2015-01-01

    Natural selection can favour health at youth or middle age (high reproductive value) over health at old age (low reproductive value). This means, all else being equal, selection for cancer suppression should dramatically drop after reproductive age. However, in species with significant parental investment, the capacity to enhance inclusive fitness may increase the reproductive value of older individuals or even those past reproductive age. Variation in parental investment levels could therefore contribute to variation in cancer susceptibility across species. In this article, we describe a simple model and framework for the evolution of cancer suppression with varying levels of parental investment and use this model to make testable predictions about variation in cancer suppression across species. This model can be extended to show that selection for cancer suppression is stronger in species with cooperative breeding systems and intergenerational transfers. We consider three cases that can select for cancer suppression into old age: (i) extended parental care that increases the survivorship of their offspring, (ii) grandparents contributing to higher fecundity of their children and (iii) cooperative breeding where helpers forgo reproduction or even survivorship to assist parents in having higher fecundity. PMID:26056358

  13. Relationship of oral cancer with age, sex, site distribution and habits.

    PubMed

    Patel, Mandakini Mansukh; Pandya, Amrish N

    2004-04-01

    Many studies are carried out regarding age incidence, tobacco smoking and sites of oral cancer, but in Gujarat tobacco chewing in form of Gutkha is more common than smoking and start during preteen years. Tobacco chewing causing chronic inflammation, submucous fibrosis and oral cancer. This study was conducted on 504 patients to find out if there is increasing incidence of oral cancer in lower age group and its relation with sex as well which site was commonly affected. There was statistically significant increase in oral cancer in lower age group, and anatomically anterior part of oral cavity showed involvement in 61.32% of cases. Though males were affected more but female cases were 25%. So tobacco chewing has got detrimental effect on oral cavity. PMID:16295466

  14. Targeted therapy for hereditary cancer syndromes: neurofibromatosis type 1, neurofibromatosis type 2, and Gorlin syndrome.

    PubMed

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Hereditary cancer syndromes are well known in the oncology community, typically affecting children, adolescents, and young adults and thereby resulting in great cumulative morbidity and mortality. These syndromes often lag behind their de novo counterparts in the development of approved novel treatment options due to their rarity in the general population. Recent work has allowed the identification of molecular aberrations and associated targeted therapies that may effectively treat these conditions. In this review, we seek to characterize some of the involved aberrations and associated targeted therapies for several germline malignancies, including neurofibromatosis types 1 and 2, and Gorlin syndrome. Though patients with hereditary cancer syndromes may be too rare to effectively include in large clinical trials, by understanding the pathophysiology of these diseases, clinicians can attain insights into the use of targeted therapies in their own practice when treating affected individuals. PMID:25549703

  15. Bayesian Ages for Early-type Stars from Isochrones Including Rotation, and a Possible Old Age for the Hyades

    NASA Astrophysics Data System (ADS)

    Brandt, Timothy D.; Huang, Chelsea X.

    2015-07-01

    We combine recently computed models of stellar evolution using a new treatment of rotation with a Bayesian statistical framework to constrain the ages and other properties of early-type stars. We find good agreement for early-type stars and clusters with known young ages, including β Pictoris, the Pleiades, and the Ursa Majoris moving group. However, we derive a substantially older age for the Hyades open cluster (750 ± 100 Myr compared to 625 ± 50 Myr). This older age results from both the increase in main-sequence lifetime with stellar rotation and from the fact that rotating models near the main-sequence turnoff are more luminous, overlapping with slightly more massive (and shorter-lived) nonrotating ones. Our method uses a large grid of nonrotating models to interpolate between a much sparser rotating grid, and also includes a detailed calculation of synthetic magnitudes as a function of orientation. We provide a web interface at http://www.bayesianstellarparameters.info, where the results of our analysis may be downloaded for individual early-type (B-V≲ 0.25) Hipparcos stars. The web interface accepts user-supplied parameters for a Gaussian metallicity prior and returns posterior probability distributions on mass, age, and orientation.

  16. Advanced BrainAGE in older adults with type 2 diabetes mellitus.

    PubMed

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The "Brain Age Gap Estimation" (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM

  17. [Experimental evidence on the role of different types unsaturated fats in the diet on ageing].

    PubMed

    González-Alonso, Adrian; Pérez-López, Patricia; Varela-López, Alfonso; Ramírez-Tortosa, M Carmen; Battino, Maurizio; Quiles, José L

    2015-01-01

    Nutrition has been largely related to the physiological ageing process. Several nutrients, such as certain types of dietary fat and various antioxidants have been shown to have positive effects on age-related diseases. The type of dietary fat affects mitochondrial structure and function, as well as its susceptibility to oxidative stress, all factors involved in ageing. The present review aims to summarise the studies conducted by our research group in the past 10 years, using virgin olive oil, sunflower oil, or fish oil as a source of unsaturated fat diet relative to a rat model of ageing. PMID:26210544

  18. The p53 network: Cellular and systemic DNA damage responses in aging and cancer

    PubMed Central

    Reinhardt, H. Christian; Schumacher, Björn

    2014-01-01

    Genome instability contributes to cancer development and accelerates age-related pathologies as evidenced by a variety of congenital cancer susceptibility and progeroid syndromes that are caused by defects in genome maintenance mechanisms. DNA damage response pathways that are mediated through the tumor suppressor p53 play an important role in the cell intrinsic responses to genome instability, including a transient cell cycle arrest, senescence and apoptosis. Both senescence and apoptosis are powerful tumor suppressive pathways preventing the uncontrolled proliferation of transformed cells. However, both pathways can potentially deplete stem and progenitor cell pools, thus promoting tissue degeneration and organ failure, which are both hallmarks of aging. p53 signaling is also involved in mediating non-cell autonomous interactions with the innate immune system and in the systemic adjustments during the aging process. The network of p53 target genes thus functions as an important regulator of cancer prevention and the physiology of aging. PMID:22265392

  19. Identifying Fracture Types and Relative Ages Using Fluid Inclusion Stratigraphy

    SciTech Connect

    Dilley, Lorie M.; Norman, David; Owens, Lara

    2008-06-30

    Enhanced Geothermal Systems (EGS) are designed to recover heat from the subsurface by mechanically creating fractures in subsurface rocks. Understanding the life cycle of a fracture in a geothermal system is fundamental to the development of techniques for creating fractures. Recognizing the stage of a fracture, whether it is currently open and transmitting fluids; if it recently has closed; or if it is an ancient fracture would assist in targeting areas for further fracture stimulation. Identifying dense fracture areas as well as large open fractures from small fracture systems will also assist in fracture stimulation selection. Geothermal systems are constantly generating fractures, and fluids and gases passing through rocks in these systems leave small fluid and gas samples trapped in healed microfractures. Fluid inclusions trapped in minerals as the fractures heal are characteristic of the fluids that formed them, and this signature can be seen in fluid inclusion gas analysis. Our hypothesis is that fractures over their life cycle have different chemical signatures that we can see in fluid inclusion gas analysis and by using the new method of fluid inclusion stratigraphy (FIS) the different stages of fractures, along with an estimate of fracture size can be identified during the well drilling process. We have shown with this study that it is possible to identify fracture locations using FIS and that different fractures have different chemical signatures however that signature is somewhat dependent upon rock type. Open, active fractures correlate with increase concentrations of CO2, N2, Ar, and to a lesser extent H2O. These fractures would be targets for further enhancement. The usefulness of this method is that it is low cost alternative to current well logging techniques and can be done as a well is being drilled.

  20. Relationship between vascularity, age and survival in non-small-cell lung cancer.

    PubMed Central

    Chandrachud, L. M.; Pendleton, N.; Chisholm, D. M.; Horan, M. A.; Schor, A. M.

    1997-01-01

    Lung tumours in the elderly show reduced growth potential; impaired angiogenesis may contribute to this phenomenon. Recent studies have suggested that the angiogenic potential of a tumour may be inferred by the vascularity measured in histological sections. The purpose of this study has been to determine whether vascularity is related to age, survival or other clinical parameters in resected non-small-cell lung cancer (NSCLC). A group of 88 consecutive patients with a follow-up period of at least 5 years was selected. The group exhibited a wide age range (37-78 years) and similar survival characteristics to those of the general NSCLC population. Tumour sections were stained with a pan-endothelial antibody (vWF) and vascularity was quantitated, without knowledge of the clinical details, by three methods: highest microvascular density; average microvascular density; and average microvascular volume. The results were analysed by non-parametric statistical tests. A correlation was found between all three methods of quantitation. Vascularity was not associated with age, sex, tumour type, stage, volume, size (TNM-T) nodal status (TNM-N) or survival. However, survival time was generally longer for patients with higher vascularity, reaching borderline significance (P = 0.06) for the average microvascular density values. Higher tumour volume (P = 0.02) and stage (P = 0.05) were associated with lower survival times. Using multivariate survival analysis, tumour volume was the only factor related to survival. We conclude that vascularity is not associated with age and has no significant prognostic value in NSCLC. Images Figure 1 PMID:9374385

  1. Age at diagnosis of female breast cancer in Oman: Issues and implications

    PubMed Central

    Mehdi, Itrat; Monem, Essam Abdul; Al Bahrani, Bassim Jaffar; Al Kharusi, Suad; Nada, Ayman Mohammad; Al Lawati, Jawad; Al Lawati, Najla

    2014-01-01

    Introduction: Female breast cancer (BC) is the most frequent malignancy diagnosed globally, about 23% of the diagnosed cancers. BC incidence varies geographically, highest in Western Europe and lowest in Africa. BC in females is strongly correlated to age, the highest incidence rate amongst older women reinforcing the importance of hormonal status. BC in young females has an aggressive phenotype. There is a shared observation amongst practicing oncologists that BC in Middle East and the developing world presents at an earlier age. Aim and Objective: The aims of this study are to evaluate the age at presentation of female BC in Oman, and to compare our data with international and regional published data. It discusses the impact of young age Breast Cancer. Materials and Methods: All diagnosed female BC cases registered from 1996-2010 all over the country, were retrieved from the National Cancer Registry, Ministry of Health. BC cases were analyzed with respect to age at presentation. The data were compared with regional and international data. Results: A total of 14,109 cancer cases were recorded during the period of study. BC was the leading malignancy as 1,294 cases (9.1%). Female BC patients were 1,230; denoting 19.2% of all female cancers. 53.5% of female BC presented below 50 years of age. Male BC constituted 5% of total, with 67% of male BC occurring over 50 years of age. Compared with data from Oman, the highest rates in UK and other Western countries are above 50 years of age. These rates are four to 10 times higher than local in different age groups. Interestingly, these rates increase with increasing age in UK from 40-45 to up to 85+, keep on increasing and go up to four times higher with higher age. This phenomenon, of increasing incidence rates with age, is not observed in our local population. Discussion: BC is significantly correlated to age as reported from Western population. BC is reported at a younger age from developing and Arab World, which need to

  2. Inflamma-miRs in Aging and Breast Cancer: Are They Reliable Players?

    PubMed Central

    Cătană, Cristina Sorina; Calin, George A.; Berindan-Neagoe, Ioana

    2015-01-01

    Human aging is characterized by chronic low-grade inflammation known as “inflammaging.” Persistent low-level inflammation also plays a key role in all stages of breast cancer since “inflammaging” is the potential link between cancer and aging through NF-kB pathways highly influenced by specific miRs. Micro-RNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at a posttranscriptional level. Inflamma-miRs have been implicated in the regulation of immune and inflammatory responses. Their abnormal expression contributes to the chronic pro-inflammatory status documented in normal aging and major age-related diseases (ARDs), inflammaging being a significant mortality risk factor in both cases. Nevertheless, the correct diagnosis of inflammaging is difficult to make and its hidden contribution to negative health outcomes remains unknown. This methodological work flow was aimed at defining crucial unanswered questions about inflammaging that can be used to clarify aging-related miRNAs in serum and cell lines as well as their targets, thus confirming their role in aging and breast cancer tumorigenesis. Moreover, we aim to highlight the links between the pro-inflammatory mechanism underlying the cancer and aging processes and the precise function of certain miRNAs in cellular senescence (CS). In addition, miRNAs and cancer genes represent the basis for new therapeutic findings indicating that both cancer and ARDs genes are possible candidates involved in CS and vice versa. Our goal is to obtain a focused review that could facilitate future approaches in the investigation of the mechanisms by which miRNAs control the aging process by acting as efficient ARDs inflammatory biomarkers. An understanding of the sources and modulation of inflamma-miRs along with the identification of their specific target genes could enhance their therapeutic potential. PMID:26697428

  3. Age-Dependent Metastatic Spread and Survival: Cancer of Unknown Primary as a Model

    PubMed Central

    Hemminki, Kari; Pavlidis, Nicholas; Tsilidis, Konstantinos K.; Sundquist, Kristina; Ji, Jianguang

    2016-01-01

    In order to describe a novel approach for the clinical study of metastases, we provide here age-specific incidence and survival data for cancer of unknown primary (CUP). Metastases in various organs are found at CUP diagnosis, which have implications for prognosis, and we hypothesize similar prognostic implications for metastases found at diagnosis of primary cancers. We identified 33,224 CUP patients from the Swedish Cancer Registry and calculated incidence rates (IRs) for CUP development. Cox proportional hazards regression models were performed to estimate hazard ratios (HRs) for relative survival in CUP patients compared to the general population. In age-group specific analyses, a maximal IR was reached at age 85–89 years, followed by a marked decline to age 90+ (7-fold in men and 3-fold in women). The overall HR for relative survival declined systematically by age. CUP may be applied as an epidemiological age-incidence model for cancer metastases providing evidence in line with autopsy data that the metastatic potential, as shown by the incidence of CUP, appears to weaken markedly at age 85 years, depending on metastatic locations. The relative death rates were highest among young patients, which was probably entirely due to the low death rates in young background population. PMID:27009354

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

    PubMed

    Shi, Rong-Liang; Qu, Ning; Liao, Tian; Wei, Wen-Jun; Wang, Yu-Long; Ji, Qing-Hai

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Radiation risk models for all solid cancers other than those types of cancer requiring individual assessments after a nuclear accident.

    PubMed

    Walsh, Linda; Zhang, Wei

    2016-03-01

    In the assessment of health risks after nuclear accidents, some health consequences require special attention. For example, in their 2013 report on health risk assessment after the Fukushima nuclear accident, the World Health Organisation (WHO) panel of experts considered risks of breast cancer, thyroid cancer and leukaemia. For these specific cancer types, use was made of already published excess relative risk (ERR) and excess absolute risk (EAR) models for radiation-related cancer incidence fitted to the epidemiological data from the Japanese A-bomb Life Span Study (LSS). However, it was also considered important to assess all other types of solid cancer together and the WHO, in their above-mentioned report, stated "No model to calculate the risk for all other solid cancer excluding breast and thyroid cancer risks is available from the LSS data". Applying the LSS models for all solid cancers along with the models for the specific sites means that some cancers have an overlap in the risk evaluations. Thus, calculating the total solid cancer risk plus the breast cancer risk plus the thyroid cancer risk can overestimate the total risk by several per cent. Therefore, the purpose of this paper was to publish the required models for all other solid cancers, i.e. all solid cancers other than those types of cancer requiring special attention after a nuclear accident. The new models presented here have been fitted to the same LSS data set from which the risks provided by the WHO were derived. Although it is known already that the EAR and ERR effect modifications by sex are statistically significant for the outcome "all solid cancer", it is shown here that sex modification is not statistically significant for the outcome "all solid cancer other than thyroid and breast cancer". It is also shown here that the sex-averaged solid cancer risks with and without the sex modification are very similar once breast and thyroid cancers are factored out. Some other notable model

  7. Characterisation of Familial Colorectal Cancer Type X, Lynch syndrome, and non-familial colorectal cancer

    PubMed Central

    Shiovitz, S; Copeland, W K; Passarelli, M N; Burnett-Hartman, A N; Grady, W M; Potter, J D; Gallinger, S; Buchanan, D D; Rosty, C; Win, A K; Jenkins, M; Thibodeau, S N; Haile, R; Baron, J A; Marchand, L L; Newcomb, P A; Lindor, N M

    2014-01-01

    Background: Familial Colorectal Cancer Type X (FCCTX) is defined as individuals with colorectal cancer (CRC) who families meet Amsterdam Criteria-1 (AC1), but whose tumours are DNA-mismatch-repair-proficient, unlike Lynch syndrome (LS). FCCTX does not have an increased risk of extra-colonic cancers. This analysis compares epidemiologic and clinicopathologic features among FCCTX, LS, and ‘non-familial' (non-AC1) CRC cases. Methods: From the Colon Cancer Family Registry, FCCTX (n=173), LS (n=303), and non-AC1 (n=9603) CRC cases were identified. Questionnaire-based epidemiologic information and CRC pathologic features were compared across case groups using polytomous logistic regression. Results: Compared with LS, FCCTX cases were less likely to be current (vs never) smokers; have a proximal subsite (vs rectal) tumour; or have mucinous histology, poor differentiation, or tumour-infiltrating lymphocytes. There were no observed differences in co-morbidities or medication usage. Conclusions: FCCTX were less likely to be current tobacco users; other exposures were similar between these groups. Histopathologic differences highly suggestive of LS CRCs do not appear to be shared by FCCTX. PMID:24918813

  8. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    NASA Astrophysics Data System (ADS)

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-05-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

  9. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    PubMed Central

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-01-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer. PMID:27198045

  10. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes.

    PubMed

    Ashkani, Jahanshah; Naidoo, Kevin J

    2016-01-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer. PMID:27198045

  11. Natural history of age-related lobular involution and impact on breast cancer risk.

    PubMed

    Radisky, Derek C; Visscher, Daniel W; Frank, Ryan D; Vierkant, Robert A; Winham, Stacey; Stallings-Mann, Melody; Hoskin, Tanya L; Nassar, Aziza; Vachon, Celine M; Denison, Lori A; Hartmann, Lynn C; Frost, Marlene H; Degnim, Amy C

    2016-02-01

    Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk. PMID:26846985

  12. Most Patients with Colorectal Tumors at Young Age Do Not Visit a Cancer Genetics Clinic

    PubMed Central

    Overbeek, Lucia I. H.; Hoogerbrugge, Nicoline; van Krieken, Joannes H. J. M.; Nagengast, Fokko M.; Ruers, Theo J. M.; Ligtenberg, Marjolijn J. L.

    2008-01-01

    Purpose This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. Methods Patients who were recently diagnosed with colorectal cancer at a young age or multiple cancers associated with Lynch syndrome, hereditary nonpolyposis colorectal cancer, (N = 119) were selected from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. In a retrospective analysis, we examined whether these patients visited a cancer genetics clinic and identified determinants for referral to such a clinic. Factors of patients, professional practice, and hospital setting were explored with logistic regression modeling. Results Thirty-six (30 percent) patients visited a cancer genetics clinic. Seventy percent of patients whom the surgeon referred to a cancer genetics clinic decided to visit such a clinic. Analysis of determinants showed that patients with whom the surgeon discussed referral and that were treated in a teaching hospital were more likely to visit a cancer genetics clinic. Conclusion The referral process is not optimally carried out. To deliver optimal care for patients suspected of hereditary colorectal cancer, this process must be improved with interventions focusing on patient referral by surgeons and raising awareness in nonteaching hospitals. PMID:18536968

  13. Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

    PubMed Central

    Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. PMID:24599168

  14. Impact of Comorbidity and Age on Determinants Therapeutic Strategies in Advanced Pancreatic Head Cancer Patients With Obstructive Jaundices

    PubMed Central

    Chen, Yu-Guang; Pan, Hsueh-Hsing; Dai, Ming-Shen; Lin, Chin; Lu, Chieh-Sheng; Su, Sui-Lung; Chang, Ping-Ying; Huang, Tzu-Chuan; Chen, Jia-Hong; Wu, Yi-Ying; Chen, Yeu-Chin; Ho, Ching Liang

    2015-01-01

    Abstract The current retrospective study aimed to investigate the relationship between prognostic factors and overall survival (OS) in patients with advanced pancreatic head cancers who initially presented with obstructive jaundice. Furthermore, the impact of age and comorbidities on therapeutic strategies in such patients was evaluated. A total of 79 advanced pancreatic head cancer patients who were treated at our institution between January 2006 and November 2013 were reviewed. We analyzed OS risk factors including sex, age, laboratory characteristics, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index Scores (CCIS), and therapeutic strategies using Cox proportional hazards regression models. There was no difference in the OS of patients according to the type biliary drainage procedure they underwent. Other related factors, such as better performance status, lower CCIS, and receiving chemotherapy significantly correlated with survival in multivariate analyses. There was a significant survival benefit in systemic chemotherapy compared to best supportive care (BSC) or local radiotherapy. However, no survival benefit was found in elderly patients (age >70 years) undergoing systemic therapy compared to younger patients, except in those elderly patients with CCIS ≤ 1. In advanced pancreatic head cancer patients with obstructive jaundice, systemic therapy and adequate biliary drainage were still the most effective procedures for improving OS in the general population. However, in elderly patients with relatively higher CCIS, BSC with adequate biliary drainage was palliative and no less effective than systemic/local therapies. PMID:26252308

  15. Geochronology of type Santacrucian (Middle Tertiary) Land Mammal Age, Patagonia, Argentina

    SciTech Connect

    Marshall, L.G.; Drake, R.E.; Curtis, G.H.; Butler, R.F.; Flanagan, K.M.; Naeser, C.W.

    1986-07-01

    Mammal-bearing lacustrine and tuffaceous sediments from three localities of the Santa Cruz Formation, type fauna of the Santacrucian Land Mammal Age, in Patagonia, southern Argentina, are calibrated by radioisotope dating with the aid of magnetostratigraphy. The strata range from about 17.6 Ma to perhaps 16.0 Ma, and are thus of late-early Miocene age. The Santacrucian Land Mammal Age ranges from about 18.0 Ma to about 15.0 Ma.

  16. Obesity as an Important Risk Factor for Certain Types of Cancer

    PubMed Central

    Davoodi, Sayed Hossain; Malek-Shahabi, Talieh; Malekshahi-Moghadam, Ali; Shahbazi, Roghieh; Esmaeili, Saeideh

    2013-01-01

    Cancer could be described as the uncontrolled and unrestricted growth of malignant cells in any place of the body. It is a multifactorial disease which either heredity or environmental factors (such as nutrition, physical inactivity, alcohol, obesity, exposure to sun, environmental pollutants, infections) chip in incidence of cancer. In recent years, several researchers have focused on obesity as a potent cancer risk factor. Scientificevidences have suggested that obesity has associated with increased risk for a plenty of different types of cancer. The evidences are the most consistent for endometrial cancer, breast cancer between the postmenopausal women, and renal cell cancer. More contradictoryresults have reported about the colorectal, prostate, and pancreatic cancer. Although numerous studies have done according to the obesity and cancer relation or joint, but the molecular mechanisms in which obesity could increase the risks of cancer, have been poorly understood. PMID:25250133

  17. Searching for the Kinkeepers: Historian Gender, Age, and Type 2 Diabetes Family History

    ERIC Educational Resources Information Center

    Giordimaina, Alicia M.; Sheldon, Jane P.; Kiedrowski, Lesli A.; Jayaratne, Toby Epstein

    2015-01-01

    Kinkeepers facilitate family communication and may be key to family medical history collection and dissemination. Middle-aged women are frequently kinkeepers. Using type 2 diabetes (T2DM) as a model, we explored whether the predicted gender and age effects of kinkeeping can be extended to family medical historians. Through a U.S. telephone survey,…

  18. A theory of the cancer age-specific incidence data based on extreme value distributions

    NASA Astrophysics Data System (ADS)

    Soto-Ortiz, Luis; Brody, James P.

    2012-03-01

    The incidence of cancers varies with age, if normalized this is called the age-specific incidence. A mathematical model that describes this variation should provide a better understanding of how cancers develop. We suggest that the age-specific incidence should follow an extreme value distribution, based on three widely accepted assumptions: (1) a tumor develops from a single cell, (2) many potential tumor progenitor cells exist in a tissue, and (3) cancer is diagnosed when the first of these many potential tumor cells develops into a tumor. We tested this by comparing the predicted distribution to the age-specific incidence data for colon and prostate carcinomas collected by the Surveillance, Epidemiology and End Results network of 17 cancer registries. We found that colon carcinoma age-specific incidence data is consistent with an extreme value distribution, while prostate carcinomas age-specific incidence data generally follows the distribution. This model indicates that both colon and prostate carcinomas only occur in a subset of the population (22% for prostate and 13.5% for colon.) Because of their very general nature, extreme value distributions might be applicable to understanding other chronic human diseases.

  19. Defining a Valid Age Cutoff in Staging of Well-Differentiated Thyroid Cancer

    PubMed Central

    Nixon, Iain J.; Kuk, Deborah; Wreesmann, Volkert; Morris, Luc; Palmer, Frank L.; Ganly, Ian; Patel, Snehal G.; Singh, Bhuvanesh; Tuttle, R. Michael; Shaha, Ashok R.; Gönen, Mithat; Shah, Jatin P.

    2016-01-01

    Background Age 45 years is used as a cutoff in the staging of well-differentiated thyroid cancer (WDTC) as it represents the median age of most datasets. The aim of this study was to determine a statistically optimized age threshold using a large dataset of patients treated at a comprehensive cancer center. Methods Overall, 1807 patients with a median follow-up of 109 months were included in the study. Recursive partitioning was used to determine which American Joint Committee on Cancer (AJCC) variables were most predictive of disease-specific death, and whether a different cutoff for age would be found. From the resulting tree, a new age cutoff was picked and patients were restaged using this new cutoff. Results The 10-year disease-specific survival (DSS) by Union for International Cancer Control (AJCC/UICC) stage was 99.6, 100, 96, and 81 % for stages I–IV, respectively. Using recursive partitioning, the presence of distant metastasis was the most powerful predictor of DSS. For M0 patients, age was the next most powerful predictor, with a cutoff of 56 years. For M1 patients, a cutoff at 54 years was most predictive. Having reviewed the analysis, age 55 years was selected as a more robust age cutoff than 45 years. The 10-year DSS by new stage (using age 55 years as the cutoff) was 99.2, 98, 100, and 74 % for stages I–IV, respectively. Conclusion A change in age cutoff in the AJCC/UICC staging for WDTC to 55 years would improve the accuracy of the system and appropriately prevent low-risk patients being overstaged and overtreated. PMID:26215199

  20. Impact of Age and Comorbidity on Non–Small-Cell Lung Cancer Treatment in Older Veterans

    PubMed Central

    Wang, Sunny; Wong, Melisa L.; Hamilton, Nathan; Davoren, J. Ben; Jahan, Thierry M.; Walter, Louise C.

    2012-01-01

    Purpose Because comorbidity affects cancer treatment outcomes, guidelines recommend considering comorbidity when making treatment decisions in older patients with lung cancer. Yet, it is unclear whether treatment is targeted to healthier older adults who might reasonably benefit. Patients and Methods Receipt of first-line guideline-recommended treatment was assessed for 20,511 veterans age ≥ 65 years with non–small-cell lung cancer (NSCLC) in the Veterans Affairs (VA) Central Cancer Registry from 2003 to 2008. Patients were stratified by age (65 to 74, 75 to 84, ≥ 85 years), Charlson comorbidity index score (0, 1 to 3, ≥ 4), and American Joint Committee on Cancer stage (I to II, IIIA to IIIB, IIIB with malignant effusion to IV). Comorbidity and patient characteristics were obtained from VA claims and registry data. Multivariate analysis identified predictors of receipt of guideline-recommended treatment. Results In all, 51% of patients with local, 35% with regional, and 27% with metastatic disease received guideline-recommended treatment. Treatment rates decreased more with advancing age than with worsening comorbidity for all stages, such that older patients with no comorbidity had lower rates than younger patients with severe comorbidity. For example, 50% of patients with local disease age 75 to 84 years with no comorbidity received surgery compared with 57% of patients age 65 to 74 years with severe comorbidity (P < .001). In multivariate analysis, age and histology remained strong negative predictors of treatment for all stages, whereas comorbidity and nonclinical factors had a minor effect. Conclusion Advancing age is a much stronger negative predictor of treatment receipt among older veterans with NSCLC than comorbidity. Individualized decisions that go beyond age and include comorbidity are needed to better target NSCLC treatments to older patients who may reasonably benefit. PMID:22454424

  1. Targeting C-Type Lectin Receptors for Cancer Immunity

    PubMed Central

    Yan, Huimin; Kamiya, Tomomori; Suabjakyong, Papawee; Tsuji, Noriko M.

    2015-01-01

    C-type lectin receptors (CLRs) are a large family of soluble and trans-membrane pattern recognition receptors that are widely and primarily expressed on myeloid cells. CLRs are important for cell–cell communication and host defense against pathogens through the recognition of specific carbohydrate structures. Similar to a family of Toll-like receptors, CLRs signaling are involved in the various steps for initiation of innate immune responses and promote secretion of soluble factors such as cytokines and interferons. Moreover, CLRs contribute to endocytosis and antigen presentation, thereby fine-tune adaptive immune responses. In addition, there may also be a direct activation of acquired immunity. On the other hand, glycans, such as mannose structures, Lewis-type antigens, or GalNAc are components of tumor antigens and ligate CLRs, leading to immunoregulation. Therefore, agonists or antagonists of CLRs signaling are potential therapeutic reagents for cancer immunotherapy. We aim to overview the current knowledge of CLRs signaling and the application of their ligands on tumor-associating immune response. PMID:26379663

  2. Does the Breast Cancer Age at Diagnosis Differ by Ethnicity? A Study on Immigrants to Sweden

    PubMed Central

    Hemminki, Kari; Sundquist, Jan; Brandt, Andreas

    2011-01-01

    Background. Age-specific incidence rates for breast cancer in low-risk and high-risk ethnic populations differ by age at which the incidence maximum is reached: around 50 years in low-risk populations and over 60 years in high-risk populations. The interpretation of these differences remains unsettled, one line primarily referring to biological differences, the second one to cohort effects of rapidly increasing rates in young populations, and the third one to incomplete registration of cancer in the elderly. Methods. The nationwide Family-Cancer Database was used to analyze standardized incidence ratios (SIRs) and age at diagnosis of breast cancer in female immigrants to Sweden by their region of origin compared with women native to Sweden matched on birth year and other relevant factors. Results. We showed first that the SIRs for breast cancer were lower in many immigrant groups compared with natives of Sweden; women from Turkey had the lowest SIR of 0.45, followed by those from Chile (0.54) and Southeast Asia (0.57). Women from nine regions showed an earlier mean age at diagnosis than their matched Swedish controls, the largest differences being 5.5 years for women from Turkey, 5.1 years for those from Asian Arab and “Other African” countries, 4.3 years for those from Iran, and 4.0 years for those from Iraq. Conclusions. The results show that in many immigrant groups, the diagnostic age is earlier (<50 years) than in natives of Sweden (>50 years), suggesting that true biological factors underlie the differences. These factors may explain much of the international variation in breast cancer incidence. Identifying these factors should advance understanding of breast cancer etiology and prevention. PMID:21266400

  3. Cell type-specific properties and environment shape tissue specificity of cancer genes

    PubMed Central

    Schaefer, Martin H.; Serrano, Luis

    2016-01-01

    One of the biggest mysteries in cancer research remains why mutations in certain genes cause cancer only at specific sites in the human body. The poor correlation between the expression level of a cancer gene and the tissues in which it causes malignant transformations raises the question of which factors determine the tissue-specific effects of a mutation. Here, we explore why some cancer genes are associated only with few different cancer types (i.e., are specific), while others are found mutated in a large number of different types of cancer (i.e., are general). We do so by contrasting cellular functions of specific-cancer genes with those of general ones to identify properties that determine where in the body a gene mutation is causing malignant transformations. We identified different groups of cancer genes that did not behave as expected (i.e., DNA repair genes being tissue specific, immune response genes showing a bimodal specificity function or strong association of generally expressed genes to particular cancers). Analysis of these three groups demonstrates the importance of environmental impact for understanding why certain cancer genes are only involved in the development of some cancer types but are rarely found mutated in other types of cancer. PMID:26856619

  4. Cell type-specific properties and environment shape tissue specificity of cancer genes.

    PubMed

    Schaefer, Martin H; Serrano, Luis

    2016-01-01

    One of the biggest mysteries in cancer research remains why mutations in certain genes cause cancer only at specific sites in the human body. The poor correlation between the expression level of a cancer gene and the tissues in which it causes malignant transformations raises the question of which factors determine the tissue-specific effects of a mutation. Here, we explore why some cancer genes are associated only with few different cancer types (i.e., are specific), while others are found mutated in a large number of different types of cancer (i.e., are general). We do so by contrasting cellular functions of specific-cancer genes with those of general ones to identify properties that determine where in the body a gene mutation is causing malignant transformations. We identified different groups of cancer genes that did not behave as expected (i.e., DNA repair genes being tissue specific, immune response genes showing a bimodal specificity function or strong association of generally expressed genes to particular cancers). Analysis of these three groups demonstrates the importance of environmental impact for understanding why certain cancer genes are only involved in the development of some cancer types but are rarely found mutated in other types of cancer. PMID:26856619

  5. Treatment Options for Testicular Cancer, by Type and Stage

    MedlinePlus

    ... it does, radiation or chemo can still usually cure the cancer. Doctors are less likely to advise surveillance if ... usually removed surgically, which may result in a cure. If cancer is found in the tumors removed, further chemo ( ...

  6. Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer.

    PubMed

    Adams, Peter D; Jasper, Heinrich; Rudolph, K Lenhard

    2015-06-01

    Aging is characterized by a decrease in genome integrity, impaired organ maintenance, and an increased risk of cancer, which coincide with clonal dominance of expanded mutant stem and progenitor cell populations in aging tissues, such as the intestinal epithelium, the hematopoietic system, and the male germline. Here we discuss possible explanations for age-associated increases in the initiation and/or progression of mutant stem/progenitor clones and highlight the roles of stem cell quiescence, replication-associated DNA damage, telomere shortening, epigenetic alterations, and metabolic challenges as determinants of stem cell mutations and clonal dominance in aging. PMID:26046760

  7. Incidence and Mortality Risks of Cancer in Patients with Type 2 Diabetes: A Retrospective Study in Shanghai, China

    PubMed Central

    Gu, Yunjuan; Hou, Xuhong; Zheng, Ying; Wang, Chunfang; Zhang, Lei; Li, Jie; Huang, Zhezhou; Han, Ming; Bao, Yuqian; Zhong, Weijian; Jia, Weiping; Cui, Shiwei

    2016-01-01

    Background: Evidence from epidemiologic investigation indicates that people with type 2 diabetes (T2DM) are at a significantly higher risk of many types of cancer and mortality. The aim of this study was to investigate the incidence and mortality risks of cancer in patients with T2DM compared with the general population in Shanghai, China. Methods: Based on the Shanghai Diabetes Registry (SDR) database linking to the Shanghai Cancer Registry and Surveillance System (SCRSS), a total of 12,276 T2DM patients without cancer were defined and followed up from 1 December 2001 to 31 July 2011. Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) with 95% confidence interval (CI) were calculated using the whole gender and age-matched general population of Shanghai as a reference during the same period. Results: The overall cancer risk was found higher in both males and females T2DM patients, with the SIR of 3.14 (95% CI 2.73–3.56) and 4.29 (95% CI 3.64–4.94), respectively. The overall mortality risk of cancer also significantly increased with the SMR of 2.27 (95% CI 1.86–2.68) and 1.86 (95% CI 1.46–2.26), respectively. Pancreatic cancer was with the highest SIR and SMR in both genders. Conclusions: Compared with the general population, patients with T2DM were associated with higher incidence and mortality risks of cancer, especially pancreatic cancer. PMID:27271648

  8. Should all colorectal cancer patients over age 60 be screened for prostate cancer?

    PubMed

    Aizer, Ayal A; D'Amico, Anthony V

    2013-10-01

    Two large, randomized studies have demonstrated a prostate cancer-specific survival benefit to prostate cancer screening using the prostate-specific antigen (PSA) assay. Yet, the US Preventive Services Task Force recently recommended against PSA-based screening for prostate cancer, claiming it results in more harm than good, given concerns regarding overtreatment. The purpose of this article is to characterize the patients with colorectal cancer who are most likely to benefit from PSA-based screening for prostate cancer. Because the survival benefit due to PSA-based screening does not manifest until 7 years after screening is initiated, we conclude that PSA screening is most appropriate for men with a remaining life expectancy of at least 10 years. Accordingly, younger men with stage I-II colorectal cancers at diagnosis (or stage III colorectal cancer that has not recurred 5 years after treatment) who have no or minimal comorbidities and who are at increased risk for either a diagnosis of prostate cancer or mortality secondary to prostate cancer (patients who have a positive family history or are African-American, respectively) are most likely to experience more good outcomes than harmful ones as a result of undergoing PSA-based screening. PMID:24367864

  9. Socioeconomic factors, immigration status, and cancer screening among Mexican American women aged 75 and older

    PubMed Central

    Reyes-Ortiz, Carlos A.; Markides, Kyriakos S.

    2011-01-01

    To explore the association between socioeconomic factors and acculturation with cancer screening methods, we analyzed data from the Hispanic Established Population for the Epidemiologic Study of the Elderly, on 1,272 women aged 75 and older residing in the United States in 2004-2005. We found that lower Pap smear or mammography uses were associated with older age, lower education, and having public health insurance compared to private. Other factors associated with mammography use were depressive symptoms, cognition and functional limitations. In sum, socioeconomic factors and health insurance coverage determine cancer screening utilization in very old Mexican American women but not acculturation. PMID:21058091

  10. For Working-Age Cancer Survivors, Medical Debt And Bankruptcy Create Financial Hardships.

    PubMed

    Banegas, Matthew P; Guy, Gery P; de Moor, Janet S; Ekwueme, Donatus U; Virgo, Katherine S; Kent, Erin E; Nutt, Stephanie; Zheng, Zhiyuan; Rechis, Ruth; Yabroff, K Robin

    2016-01-01

    The rising medical costs associated with cancer have led to considerable financial hardship for patients and their families in the United States. Using data from the LIVESTRONG 2012 survey of 4,719 cancer survivors ages 18-64, we examined the proportions of survivors who reported going into debt or filing for bankruptcy as a result of cancer, as well as the amount of debt incurred. Approximately one-third of the survivors had gone into debt, and 3 percent had filed for bankruptcy. Of those who had gone into debt, 55 percent incurred obligations of $10,000 or more. Cancer survivors who were younger, had lower incomes, and had public health insurance were more likely to go into debt or file for bankruptcy, compared to those who were older, had higher incomes, and had private insurance, respectively. Future longitudinal population-based studies are needed to improve understanding of financial hardship among US working-age cancer survivors throughout the cancer care trajectory and, ultimately, to help stakeholders develop evidence-based interventions and policies to reduce the financial hardship of cancer. PMID:26733701

  11. Late age at first full term birth is strongly associated with lobular breast cancer

    PubMed Central

    Newcomb, PA; Trentham-Dietz, A; Hampton, JM; Egan, KM; Titus-Ernstoff, L; Andersen, S Warren; Greenberg, ER; Willett, WC

    2010-01-01

    Background Late age at first full-term birth (AFB) and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades. Methods We conducted a population-based case-control study to examine associations between parity, AFB, and specific histological subtypes of breast cancer. Women with breast cancer (N=21,266) were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control women (N=26,677) were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of ductal, lobular, and mixed ductal-lobular breast cancer diagnosis in association with AFB and nulliparity. Results AFB ≥ 30 years of age was associated with a 2.4-fold increase in risk of lobular breast cancer compared to AFB < 20 years (OR 2.4; 95%CI 1.9–2.9). The association was less pronounced for ductal breast cancer (OR 1.3; 95% CI, 1.2–1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared to women with AFB <20 years, but the association was stronger for lobular (OR 1.72, 95% CI 1.34–2.20) than for ductal (OR 1.19, 95% CI 1.08–1.31) subtypes (P=0.004). The adverse effects of later AFB was stronger with obesity (P=0.03) in lobular, but not ductal, breast cancer. Conclusion Stronger associations observed for late AFB and nulliparity suggests that these preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer. PMID:21509772

  12. Age and School-Type Differences in Children's Beliefs about School Performance

    ERIC Educational Resources Information Center

    Malmberg, Lars-Erik; Wanner, Brigitte; Little, Todd D.

    2008-01-01

    Age and school-type differences (primary school and three types of secondary school) in self-related beliefs about ability, effort, and difficulty were investigated in a study of 1723 Berlin youth. Consistent with selective ability-stratified schooling, multi-group structural equation models revealed: (1) mean-level belief differences reflecting…

  13. Skin cancer risk perceptions: A comparison across ethnicity, age, education, gender, and income

    PubMed Central

    Buster, Kesha J.; You, Zhiying; Fouad, Mona; Elmets, Craig

    2013-01-01

    Background Studies of non-cutaneous and cutaneous malignancies support the hypothesis that poor risk-perception status contributes to health disparity. Objective We evaluated skin cancer risk perceptions across race and other demographic markers using the Health Information National Trends Survey (HINTS) and compared them to discover differences in perception that may contribute to the disparities in skin cancer diagnosis and treatment. Methods Respondents with no prior history of skin cancer were randomly selected to answer questions assessing perceived risk and knowledge of preventive strategies of skin cancer. Logistic regression was performed to identify associations between perceptions of skin cancer and demographic variables including self-described race, age, sex, education, income, and health insurance status. Results Blacks, the elderly, and people with less education perceived themselves as at lower risk of developing skin cancer. They, along with Hispanics, were also more likely to believe that one cannot lower their skin cancer risk and that there are so many different recommendations on how to prevent skin cancer that it makes it difficult to know which ones to follow. Lower education also correlated with greater reluctance to have a skin exam. Limitations HINTS is a cross-sectional instrument, thus it only provides a snapshot of skin cancer perceptions. Conclusion Uncertainty and altered perceptions are more common in the skin cancer risk perceptions of ethnic minorities, the elderly, and those with less education. These are the same groups that are subject to disparities in skin cancer outcomes. Educational programs directed at these demographic groups may help to reduce the skin cancer-related health disparities. PMID:21875760

  14. One-carbon metabolism: An aging-cancer crossroad for the gerosuppressant metformin

    PubMed Central

    Menendez, Javier A.; Joven, Jorge

    2012-01-01

    The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK. If an aging-related decline in the AMPK sensitivity to cellular stress is a crucial event for mTOR-driven aging and aging-related diseases, including cancer, unraveling new proximal causes through which AMPK activation endows its gerosuppressive effects may offer not only a better understanding of metformin function but also the likely possibility of repositioning our existing gerosuppressant drugs. Here we provide our perspective on recent findings suggesting that de novo biosynthesis of purine nucleotides, which is based on the metabolism of one-carbon compounds, is a new target for metformin's actions at the crossroads of aging and cancer. PMID:23525940

  15. Dietary risk factors in intestinal and diffuse types of stomach cancer: a multicenter case-control study in Poland.

    PubMed

    Boeing, H; Jedrychowski, W; Wahrendorf, J; Popiela, T; Tobiasz-Adamczyk, B; Kulig, A

    1991-07-01

    A hospital-based, multicenter, case-control study has been performed in Poland covering 741 incident stomach-cancer cases (520 males and 221 females) and the same number of controls. All stomach-cancer diagnoses were evaluated for histologic type according to the Lauren criteria. Fifty-one percent were of the intestinal type, 35 percent of the diffuse type, and 8.5 percent of the mixed type. The frequency of consumption of individual food items and several food groups was analyzed and the association of various foods with stomach cancer risk was evaluated after controlling for sex, age, occupation, education, and residency. Increased consumption of sausages was related significantly to gastric cancer risk, whereas increased consumption of cheese products, nonwhite bread, vegetables, and fruit was associated with decreased risk. A particularly strong decrease in risk was associated with consumption of radishes and onions. When consumption of fruits and vegetables, sausages, nonwhite bread, and cheese were introduced simultaneously in a multivariate model, independent effects were found only for fruit and vegetables, sausages, and nonwhite bread. The use of table salt, the frequency of eating hot meals, and an irregular eating pattern were also associated with increased risk, while additional consumption of fruit between meals showed reduced risk. If a reduction in vegetable and fruit consumption took place after marriage, an increased risk for stomach cancer was found, whereas augmented consumption of these food items after marriage decreased the risk. Separate risk models were calculated for stomach cancer of the intestinal and diffuse types, but both histologic varieties showed the same pattern of associations with dietary risk factors. PMID:1873452

  16. Usefulness of Photodynamic Diagnosis and Therapy using Talaporfin Sodium for an Advanced-aged Patient with Inoperable Gastric Cancer (a secondary publication)

    PubMed Central

    Oinuma, Takeshi

    2014-01-01

    Background and aims: In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of elderly people being treated for cancer is increasing concomitantly. However, with the increase in age, the numbers of prior complications also increase. This is especially so in the advanced-aged patients, defined in Japan as those over the age of 85. Such complications may be too high risk for radical surgery and a less invasive treatment is warranted. Photodynamic therapy (PDT) is a noninvasive treatment approved by the Japanese National Health Insurance for the treatment of early stage superficial type esophageal and gastric cancers, early stage uterine cervical cancers and dysplasia, and early and advanced lung cancer. We report herein on the efficacy of palliative PDT using talaporfin sodium (Laserphyrin®) for a case of inoperable gastric cancer. Material and methods: The patient was an 87-year-old-man, a diabetic with histories of diabetic nephropathy, cerebral infarction and myocardial infarction. This patient was first diagnosed as having gastric cancer in 2007 but surgery and chemotherapy were contraindicated due to his poor physical status and poor renal function, respectively, owing to the anticipated side effects. The patient was referred to our institution after hearing of PDT in 2009. He was treated with 1 course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with photodynamic diagnosis (PDD) during the period from September, 2009 to June, 2011. Results: The massive gastric cancer located in the cardia was successfully treated with 4 PDT sessions without any serious complications; therefore the patient was able to orally ingest food until his death due to natural causes other than the cancer, in October, 2011. Conclusion: Talaporfin sodium PDT is safe and effective treatment for advanced-aged patients suffering from inoperable gastric cancer. PMID

  17. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  18. Prospective Predictors of Mental Health after the Development of Breast Cancer in Middle-Aged Women

    ERIC Educational Resources Information Center

    Wade, Tracey D.; Lee, Christina

    2005-01-01

    This paper investigated the prospective predictors of mental health after breast cancer diagnosis among mid-aged Australian women (initially aged 45-50 years). Two waves of data collected 2 years apart from a longitudinal population-based survey of 12,177 women identified a group of 63 women who reported onset of BC between T1 (T1) and Time 2…

  19. Structured additive regression modeling of age of menarche and menopause in a breast cancer screening program.

    PubMed

    Duarte, Elisa; de Sousa, Bruno; Cadarso-Suarez, Carmen; Rodrigues, Vitor; Kneib, Thomas

    2014-05-01

    Breast cancer risk is believed to be associated with several reproductive factors, such as early menarche and late menopause. This study is based on the registries of the first time a woman enters the screening program, and presents a spatio-temporal analysis of the variables age of menarche and age of menopause along with other reproductive and socioeconomic factors. The database was provided by the Portuguese Cancer League (LPCC), a private nonprofit organization dealing with multiple issues related to oncology of which the Breast Cancer Screening Program is one of its main activities. The registry consists of 259,652 records of women who entered the screening program for the first time between 1990 and 2007 (45-69-year age group). Structured Additive Regression (STAR) models were used to explore spatial and temporal correlations with a wide range of covariates. These models are flexible enough to deal with a variety of complex datasets, allowing us to reveal possible relationships among the variables considered in this study. The analysis shows that early menarche occurs in younger women and in municipalities located in the interior of central Portugal. Women living in inland municipalities register later ages for menopause, and those born in central Portugal after 1933 show a decreasing trend in the age of menopause. Younger ages of menarche and late menopause are observed in municipalities with a higher purchasing power index. The analysis performed in this study portrays the time evolution of the age of menarche and age of menopause and their spatial characterization, adding to the identification of factors that could be of the utmost importance in future breast cancer incidence research. PMID:24615881

  20. Does cancer survivors' health-related quality of life depend on cancer type? Findings from a large French national sample 2 years after cancer diagnosis.

    PubMed

    Le Corroller-Soriano, A-G; Bouhnik, A-D; Preau, M; Malavolti, L; Julian-Reynier, C; Auquier, P; Moatti, J-P

    2011-01-01

    We investigated whether health-related quality of life (HRQL) depends on cancer type, after adjustment for demographic and medical variables. A French national population-based survey was conducted between November and December 2004 to assess surviving cancer patients' HRQL 2 years after diagnosis. HRQL was measured by the 36-Item Short Form Survey scale. The sample included 3900 persons. All cancer diagnoses were entered in the study. We demonstrated that medical and treatment variables have an impact on patients' physical HRQL but not on mental HRQL. Cancer type impacted on physical HRQL, with those suffering from upper aerodigestive tract /lung cancers and haematological malignancies being affected to a greater degree. Disturbing side effects impacted both HRQL domains. Socio-demographic variables had statistically significant effects but not clinically meaningful ones. Socio-economic variables led to potentially clinically meaningful differences for cancer patients' HRQL and represented a socio-economic gradient in HRQL among cancer survivors. From our results, we may assert that cancer survivors, 2 years after cancer diagnosis, share a similar pattern of psychological morbidity, independent of cancer type. Patients disproportionately affected by cancer, such as those with lower educational levels and income, need to be identified and targeted and interventions which address their unique needs and concerns need to be developed. PMID:20345457

  1. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.

    PubMed

    Plikus, Maksim V; Van Spyk, Elyse N; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S; Andersen, Bogi

    2015-06-01

    Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model

  2. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity

    PubMed Central

    Plikus, Maksim V.; Van Spyk, Elyse Noelani; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S.; Andersen, Bogi

    2015-01-01

    Historically work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as liver, fat and muscle. In recent years, skin is emerging as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging and carcinogenesis. Morphologically skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration -- the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell-type specific circadian mutants. Also, due to the accessibility of the skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar UV radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. The skin also provides opportunities to interrogate clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model for investigating the

  3. DNA methylation of oxidative stress genes and cancer risk in the Normative Aging Study

    PubMed Central

    Gao, Tao; Joyce, Brian Thomas; Liu, Lei; Zheng, Yinan; Dai, Qi; Zhang, Zhou; Zhang, Wei; Shrubsole, Martha J; Tao, Meng-Hua; Schwartz, Joel; Baccarelli, Andrea; Hou, Lifang

    2016-01-01

    Oxidative stress (OS) is a primary mechanism of carcinogenesis, and methylation of genes related to it may play a role in cancer development. In this study, we examined the prospective association between blood DNA methylation of four oxidative stress genes and cancer incidence. Our study population included a total of 582 participants in the Normative Aging Study (NAS) who had blood drawn during 1-4 visits from 1999-2012 (mean follow up 9.0 years). Promoter DNA methylation of CRAT, iNOS, OGG1 and GCR in blood leukocytes was measured using pyrosequencing. We used Cox regression models to examine prospective associations between cancer incidence and both methylation at the baseline visit and methylation rate of changes over time. Baseline OGG1 methylation was associated with higher risk of all-cancer (HR: 1.43, 95% CI: 1.15-1.78) and prostate cancer (HR: 1.52, 95% CI: 1.03-2.25) incidence. Compared with participants remaining cancer-free, those who eventually developed cancer had significantly accelerated CRAT methylation (p = 0.04) and decelerated iNOS methylation (p<0.01) over time prior to cancer diagnosis. Accelerated CRAT methylation was associated with higher all-cancer incidence (HR: 3.88, 95% CI: 1.06-14.30), whereas accelerated iNOS methylation was associated with lower all-cancer incidence (HR: 0.08, 95% CI 0.02-0.38). Our results suggest that methylation and its dynamic change over time in OS-related genes, including OGG1, CRAT and iNOS, may play an important role in carcinogenesis. These results can potentially facilitate the development of early detection biomarkers and new treatments for a variety of cancers. PMID:27186424

  4. Standard errors of non-standardised and age-standardised relative survival of cancer patients

    PubMed Central

    Jansen, L; Hakulinen, T; Brenner, H

    2012-01-01

    Background: Relative survival estimates cancer survival in the absence of other causes of death. Previous work has shown that standard errors of non-standardised relative survival may be substantially overestimated by the conventionally used method. However, evidence was restricted to non-standardised relative survival estimates using Hakulinen's method. Here, we provide a more comprehensive evaluation of the accuracy of standard errors including age-standardised survival and estimation by the Ederer II method. Methods: Five- and ten-year non-standardised and age-standardised relative survival was estimated for patients diagnosed with 25 common forms of cancer in Finland in 1989–1993, using data from the nationwide Finnish Cancer Registry. Standard errors of mutually comparable non-standardised and age-standardised relative survival were computed by the conventionally used method and compared with bootstrap standard errors. Results: When using Hakulinen's method, standard errors of non-standardised relative survival were overestimated by up to 28%. In contrast, standard errors of age-standardised relative survival were accurately estimated. When using the Ederer II method, deviations of the standard errors of non-standardised and age-standardised relative survival were generally small to negligible. Conclusion: In most cases, overestimations of standard errors are effectively overcome by age standardisation and by using Ederer II rather than Hakulinen's method. PMID:22173672

  5. The role of telomere dynamics in aging and cancer

    NASA Astrophysics Data System (ADS)

    Blagoev, Krastan; Goodwin, Edwin

    2006-03-01

    Telomere length changes are far more dynamic than previously thought. In addition to a gradual loss of ˜100 base pairs per telomere in each cell division, losses as well as gains may occur within a single cell cycle. We are investigating how telomere exchange, extension, and deletion affect the proliferative potential of telomerase-negative somatic cells. Experimental techniques are being devised to detect dynamic telomere processes and quantify both the frequency and length changes of each. In parallel, a ``dynamic telomere model'' is being used that incorporates telomere dynamics to study how the telomere size distribution evolves with time. This is an essential step towards understanding the role that telomere dynamics play in the normal aging of tissues and organisms. The model casts light on relationships not otherwise easily explained by a deterministic ``mitotic clock,'' or to what extent the shortest initial telomere determines the onset of senescence. We also expect to identify biomarkers that will correlate with aging better than average telomere length and to shed light on the transition to unlimited growth found in telomerase-negative tumor cells having the ALT (alternative lengthening of telomeres) phenotype, and to evaluate strategies to suppress the growth of these tumors.

  6. Alzheimer's Disease as Subcellular `Cancer' --- The Scale-Invariant Principles Underlying the Mechanisms of Aging ---

    NASA Astrophysics Data System (ADS)

    Murase, M.

    1996-01-01

    Alzheimer's disease (AD) is characterized by the slow onset of neurodegeneration leading to dementia in many elderly people. The pathological hallmarks of AD are: the extracellular β-amyloid deposition in the senile plaques; the β-amyloid deposition in cerebral blood vessel walls especially in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D); the intracellular neurofibrillary tangle formation composed of paired helical filaments (PHF), the principal component of which is a hyperphosphorylated form of the microtubule-binding protein, tau; and neurological dysfuction and neuronal cell death in limited regions and pathways of the central nervous system. Note that β-amyloid is a truncated form of a cell surface integral membrane glycoprotein: amyloid precursor protein (APP). Despite these hallmarks, the pathogenesis of AD has been poorly understood. In the present paper, a theory of aging is proposed to give a coherent account of the origins and causes of neurodegeneration common to the diverse neurodegenerative disorders such as AD and prion (proteinaceous infectious particles) diseases in comparison with the pathogenesis of cancers. Surprisingly, the self-aggregation of denatured proteins -- such as β-amyloid, PHF and prions -- responsible for neuronal cell death resembles, in many respects, the development (or the clonal evolution) of malignant cells at the expense of the entire organism harboring them. Although neurodegenerative disorders and cancers apparently differe in pathology, they nevertheless seem to follow the same priciples regardless of the level and scale of the biological organization. It is the general principles of heritable variations and natural selection as well as the general principles of self-organization that operate, not only on different molecules, but also at different hierarchical levels and scales of the biological organizaiton, independent of the details of diseases. Traditionally, natural selection, along

  7. Cardiovascular medication after cancer at a young age in Finland: A nationwide registry linkage study.

    PubMed

    Kero, A E; Madanat-Harjuoja, L M; Järvelä, L S; Malila, N; Matomäki, J; Lähteenmäki, P M

    2016-08-01

    Despite improved survival rates, childhood and young adult (YA) cancer survivors face elevated risks for life-threatening morbidities, especially cardiovascular complications. Our nationwide Finnish registry study investigated the purchases of cardiovascular medication from 1993 to 2011 in patients diagnosed with cancer aged below 35 years (N = 8,197) between 1993 and 2004 compared to siblings (N = 29,974) via linkage to the drug purchase registry. The cumulative incidence for purchasing cardiovascular medications was higher in childhood and YA cancer patients compared to siblings with a rising trend over time. After childhood cancer, the highest hazard ratio (HR) was found for purchasing anticoagulants (HR 19.8, 95% CI 8.5-45.9). The HRs for any cardiovascular medication (HR 7.2, 95% CI 5.1-10.1) and cardiac medication (HR 4.8, 95% CI 3.3-6.9) were markedly elevated after childhood cancer as well. Regarding YA cancer patients, the respective HRs were 2.5 (95% CI 2.0-3.2) for anticoagulants, HR 1.7 (95% CI 1.5-1.9) for any cardiovascular medication and HR 1.5 (95% CI 1.3-1.7) for cardiac medication. Among cancer patients, highest HRs for cardiovascular medication were observed after childhood acute lymphoblastic leukemia (ALL) and bone tumors (HR 10.2, 95% CI 6.8-15.5 and HR 7.4, 95% CI 4.0-13.7) and YA ALL and acute myeloid leukemia (HR 5.1, 95% CI 3.5-7.1 and HR 2.8, 95% CI 1.8-4.0). Our study demonstrated increased HRs for purchasing cardiovascular medication after early-onset cancer compared to siblings reflecting elevated cardiovascular morbidity. Thus, the implementation of long-term cardiovascular disease screening is imperative to prevent, detect and adequately treat cardiovascular late effects after cancer at a young age. PMID:26610262

  8. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease

    PubMed Central

    Lisanti, Camilla L.; Tanowitz, Herbert B.; Howell, Anthony; Martinez-Outschoorn, Ubaldo E.; Sotgia, Federica; Lisanti, Michael P.

    2015-01-01

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of “stemness”, independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point – a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known “side-effect”, which could be harnessed instead as a “therapeutic effect”. Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally

  9. Biological, Clinical, and Psychosocial Correlates at the Interface of Cancer and Aging Research

    PubMed Central

    Dale, William; Mohile, Supriya G.; Eldadah, Basil A.; Trimble, Edward L.; Schilsky, Richard L.; Cohen, Harvey J.; Muss, Hyman B.; Schmader, Kenneth E.; Ferrell, Betty; Extermann, Martine; Nayfield, Susan G.

    2012-01-01

    In September 2010, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, conducted the first of three planned conferences to discuss research methodology to generate the highest quality research in older adults with cancer and then disseminate these findings among those working in the fields of cancer and aging. Conference speakers discussed the current level of research evidence in geriatric oncology, outlined the current knowledge gaps, and put forth principles for research designs and strategies that would address these gaps within the next 10 years. It was agreed that future oncology research trials that enroll older adults should include: 1) improved standardized geriatric assessment of older oncology patients, 2) substantially enhanced biological assessment of older oncology patients, 3) specific trials for the most vulnerable and/or those older than 75 years, and 4) research infrastructure that specifically targets older adults and substantially strengthened geriatrics and oncology research collaborations. This initial conference laid the foundation for the next two meetings, which will address the research designs and collaborations needed to enhance therapeutic and intervention trials in older adults with cancer. PMID:22457474

  10. Metformin may reduce oral cancer risk in patients with type 2 diabetes

    PubMed Central

    Tseng, Chin-Hsiao

    2016-01-01

    Background Whether metformin use may affect the risk of oral cancer required further investigation. Methods The reimbursement database of the National Health Insurance in Taiwan was used. Patients with type 2 diabetes mellitus at an onset age of 25-74 years during 1999-2005 and newly treated with either metformin (n = 288198, “ever users of metformin”) or other antidiabetic drugs (n = 16263, “never users of metformin”) were followed for at least 6 months for oral cancer until December 31, 2011. The treatment effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression adjusted for propensity score (PS) or incorporated with the inverse probability of treatment weighting (IPTW) using PS. Results The respective numbers of incident oral cancer in ever users and never users were 1273 (0.44%) and 119 (0.73%), with respective incidences of 92.7 and 163.6 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) suggested a significantly lower risk [0.584 (0.483-0.707) for PS-adjusted model, and 0.562 (0.465-0.678) for IPTW model]. In tertile analyses, the PS-adjusted hazard ratios (95% confidence intervals) for the first (<21.5 months), second (21.5-45.9 months) and third (>45.9 months) tertile of cumulative duration were 1.403 (1.152-1.708), 0.557 (0.453-0.684) and 0.152 (0.119-0.194), respectively; and were 1.244 (1.024-1.511), 0.526 (0.429-0.645) and 0.138 (0.108-0.176), respectively, for IPTW. Conclusions Metformin may significantly reduce the risk of oral cancer, especially when the cumulative duration is more than 21.5 months. PMID:26683519

  11. Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer

    PubMed Central

    Rebbeck, Timothy R.; Mitra, Nandita; Wan, Fei; Sinilnikova, Olga M.; Healey, Sue; McGuffog, Lesley; Mazoyer, Sylvie; Chenevix-Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.; Nathanson, Katherine L.

    2015-01-01

    ), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69–3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44–0.60; P = 6 × 10−17). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41–0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations. PMID:25849179

  12. Low-Temperature Aging Characteristics of Type 316L Stainless Steel Welds: Dependence on Solidification Mode

    NASA Astrophysics Data System (ADS)

    Abe, Hiroshi; Watanabe, Yutaka

    2008-06-01

    Thermal aging embrittlement of light water reactor (LWR) components made of stainless steel cast has been recognized as a potential degradation issue, and careful attention has been paid to it. Although welds of austenitic stainless steels have γ-δ duplex microstructure, which is similar to that of the stainless steel cast, examination of the thermal aging characteristics of the stainless steel welds is very limited. In this investigation, two types of type 316L stainless steel weld metal with different solidification modes were prepared using two kinds of filler metals having tailored Ni equivalent and Cr equivalent. Differences between the two weld metals in the morphology of microstructure, in the composition of δ-ferrite, and in hardening behaviors with isothermal aging at 335 °C have been investigated. The hardness of the ferrite phase has increased with aging time, while the hardness of austenite phase has stayed the same. The mottled aspect has been observed in δ-ferrite of aged samples by transmission electron microscopy (TEM) observation. These characteristics suggest that spinodal decomposition has occurred in δ-ferrite by aging at 335 °C. The age-hardening rate of δ-ferrite was faster for the primary austenite solidification mode (AF mode) sample than the primary ferrite solidification mode (FA mode) sample in the initial stage of the aging up to 2000 hours. It has been suggested that the solidification mode can affect the kinetics of spinodal decomposition.

  13. Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer

    Cancer.gov

    Treatment with the multitargeted agent vandetanib (Caprelsa) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial.

  14. Human Papillomavirus Type-Specific Prevalence in the Cervical Cancer Screening Population of Czech Women

    PubMed Central

    Tachezy, Ruth; Smahelova, Jana; Kaspirkova, Jana; Salakova, Martina

    2013-01-01

    Background Infection with high-risk human papillomavirus (HPV)types has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice. Objectives The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV. Methods Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2) and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB). Results Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393) of women were positive for any HPV type by BS-RLB, 18.2% (254/1393) by HR HC2, and 22.3% (310/1393) by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%). HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years. Conclusions Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future. PMID:24265750

  15. Middle-Aged More Often Diagnosed with Late-Stage Lung Cancer

    MedlinePlus

    ... Middle-Aged More Often Diagnosed With Late-Stage Lung Cancer British study highlights the need for better early detection, researchers say To use the sharing features on this page, please enable JavaScript. (*this news item will not ...

  16. Age Differences in Understandings of Disease Causality: AIDS, Colds, and Cancer.

    ERIC Educational Resources Information Center

    Sigelman, Carol; And Others

    1993-01-01

    Asked 9, 11, and 13 year olds and college students about risk factors for AIDS, colds, and cancer. Found that knowledge of risk factors became more accurate with age; knowledge of risk factors was largely independent of knowledge of nonrisk factors; and knowledge about 1 disease was largely independent of knowledge about another. (MDM)

  17. Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia.

    PubMed

    Argilés, Josep M; Busquets, Sílvia; Felipe, Antonio; López-Soriano, Francisco J

    2005-05-01

    The aim of the present review is to summarize and evaluate the different mechanisms and catabolic mediators involved in cancer cachexia and ageing sarcopenia since they may represent targets for future promising clinical investigations. Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. In fact, many patients who die with advanced cancer suffer from cachexia. The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis. Unfortunately, at the clinical level, cachexia is not treated until the patient suffers from a considerable weight loss and wasting. At this point, the cachectic syndrome is almost irreversible. The cachectic state is often associated with the presence and growth of the tumour and leads to a malnutrition status due to the induction of anorexia. In recent years, age-related diseases and disabilities have become of major health interest and importance. This holds particularly for muscle wasting, also known as sarcopenia, that decreases the quality of life of the geriatric population, increasing morbidity and decreasing life expectancy. The cachectic factors (associated with both depletion of fat stores and muscular tissue) can be divided into two categories: of tumour origin and humoural factors. In conclusion, more research should be devoted to the understanding of muscle wasting mediators, both in cancer and ageing, in particular the identification of common mediators may prove as a good therapeutic strategies for both prevention and treatment of wasting both in disease and during healthy ageing. PMID:15743680

  18. Comprehension of a Colon Cancer Pamphlet among American Adults at Least 50 Years of Age

    ERIC Educational Resources Information Center

    Liu, Chiung-ju

    2010-01-01

    Objective: The purpose of this study was to identify determinants of comprehension of an educational pamphlet on colon cancer, by adults at least 50 years of age living in the United States. Design: Data were analysed from the "2003 National Assessment of Adult Literacy" survey. The survey was designed to assess functional English literacy, which…

  19. Family Support, Age, and Emotional States of Terminally Ill Cancer Patients.

    ERIC Educational Resources Information Center

    Wu, Kitty K. Y.

    1991-01-01

    Explored emotional states of dying patients, age, and family support. Findings from 26 terminally ill female cancer patients revealed that younger patients expressed more bargaining and complaints than older patients who revealed more depression and acceptance. Patients with immediate family support expressed less depression and more fears than…

  20. Barriers to Cervical Cancer Screening among Middle-aged and Older Rural Appalachian Women

    PubMed Central

    Studts, Christina R.; Tarasenko, Yelena N.; Schoenberg, Nancy E.

    2012-01-01

    Although cervical cancer rates in the United States have declined sharply in recent decades, certain groups of women remain at elevated risk, including middle-aged and older women in central Appalachia. Cross-sectional baseline data from a community-based randomized controlled trial were examined to identify barriers to cervical cancer screening. Questionnaires assessing barriers were administered to 345 Appalachian women aged 40-64, years when Pap testing declines and cervical cancer rates increase. Consistent with the PRECEDE/PROCEED framework, participants identified barriers included predisposing, enabling, and reinforcing factors. Descriptive and bivariate analyses are reported, identifying (a) the most frequently endorsed barriers to screening, and (b) significant associations of barriers with sociodemographic characteristics in the sample. Recommendations are provided to decrease these barriers and, ultimately, improve rates of Pap tests among this traditionally underserved and disproportionately affected group. PMID:23179390

  1. Age and Prostate-Specific Antigen Level Prior to Diagnosis Predict Risk of Death from Prostate Cancer

    PubMed Central

    MacKintosh, F. Roy; Sprenkle, Preston C.; Walter, Louise C.; Rawson, Lori; Karnes, R. Jeffrey; Morrell, Christopher H.; Kattan, Michael W.; Nawaf, Cayce B.; Neville, Thomas B.

    2016-01-01

    A single early prostate-specific antigen (PSA) level has been correlated with a higher likelihood of prostate cancer diagnosis and death in younger men. PSA testing in older men has been considered of limited utility. We evaluated prostate cancer death in relation to age and PSA level immediately prior to prostate cancer diagnosis. Using the Veterans Affairs database, we identified 230,081 men aged 50–89 years diagnosed with prostate cancer and at least one prior PSA test between 1999 and 2009. Prostate cancer-specific death over time was calculated for patients stratified by age group (e.g., 50–59 years, through 80–89 years) and PSA range at diagnosis (10 ranges) using Kaplan–Meier methods. Risk of 10-year prostate cancer mortality across age and PSA was compared using log-rank tests with a Bonferroni adjustment for multiple testing. 10.5% of men diagnosed with prostate cancer died of cancer during the 10-year study period (mean follow-up = 3.7 years). Higher PSA values prior to diagnosis predict a higher risk of death in all age groups (p < 0.0001). Within the same PSA range, older age groups are at increased risk for death from prostate cancer (p < 0.0001). For PSA of 7–10 ng/mL, cancer-specific death, 10 years after diagnosis, increased from 7% for age 50–59 years to 51% for age 80–89 years. Men older than 70 years are more likely to die of prostate cancer at any PSA level than younger men, suggesting prostate cancer remains a significant problem among older men (even those aged 80+) and deserves additional study. PMID:27446803

  2. PROXIMAL GUT MUCOSAL EPITHELIAL HOMEOSTASIS IN AGED IL-1 TYPE I RECEPTOR KNOCKOUT MICE AFTER STARVATION

    PubMed Central

    Song, Juquan; Wolf, Steven E.; Wu, Xiao-Wu; Finnerty, Celeste C.; Herndon, David N.; Jeschke, Marc G.

    2010-01-01

    Background Previous studies have shown that starvation induces small bowel atrophy, and that atrophy diminishes with aging. In this experiment, we assessed whether starvation-induced atrophy of proximal gut mucosa is associated with the Interleukin-1 receptor (IL-1R) signaling pathway in aged mice. Materials and Methods Thirty 26-month-old IL-1R knockout mice and age-matched wild-type C57BL/6 mice were randomly divided into two groups: ad libitum fed and fasted. Mice were euthanized 12 or 48 hours after starvation. The proximal small bowel was harvested for morphologic analysis. Gut epithelial cell proliferation was detected using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), and apoptosis was identified using terminal deoxyuridine nick-end labeling (TUNEL) staining. Results Aged IL-1R knockout mice were larger than aged-matched wild-type mice (p<0.05). Proximal gut mucosal height and mucosal cell number were not different between aged IL-1R knockout and wild-type groups. The apoptosis index in gut epithelial cells was higher in fed IL-1R knockout versus wild-type mice (p<0.05), while no significant difference in cell proliferation between both groups. Mucosal atrophy was induced in both aged IL-1R knockout and wild-type groups by starvation (p<0.05), however, aged IL-1R knockout mice experienced greater losses in proximal gut weight, mucosal length, and corresponding cell number than did wild-type mice at the 12-hour time point (p<0.05). The apoptosis index in gut epithelial cells significantly increased in both groups after starvation (p<0.05). Starvation decreased cell proliferation in IL-1R knockout mice (p<0.05), but not in wild-type mice. Conclusions The response in aged IL-1R knockout mice differs from wild-type mice in that starvation increases atrophy and is associated with decreased cell proliferation rather than increased apoptosis. PMID:20605606

  3. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model

    PubMed Central

    Park, Se Eun; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID:26894429

  4. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

    PubMed

    Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID:26894429

  5. Promoter Methylation Status of Breast Cancer Susceptibility Gene 1 and 17 Beta Hydroxysteroid Dehydrogenase Type 1 Gene in Sporadic Breast Cancer Patients

    PubMed Central

    Hosny, Marwa M.; Sabek, Nagwan A.; El-Abaseri, Taghrid B.; Hassan, Fathalla M.; Farrag, Sherif H.

    2016-01-01

    Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17βHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation-specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17βHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (p < 0.001). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype “luminal A” (p = 0.048, p = 0.042, p = 0.007, and p = 0.049, resp.). Methylation of BRCA1 and 17βHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17βHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies. PMID:27413552

  6. Alcohol consumption and risk of prostate cancer in middle-aged men.

    PubMed

    Schoonen, W Marieke; Salinas, Claudia A; Kiemeney, Lambertus A L M; Stanford, Janet L

    2005-01-01

    Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal milieu and contains chemical substances such as flavonoids (red wine), which may alter tumor cell growth. Data from a population-based case-control study in King County, WA, were utilized to evaluate the association of alcohol consumption with prostate cancer in middle-aged men. A total of 753 newly diagnosed prostate cancer cases, 40-64 years of age, participated in the study. Seven hundred three control subjects, frequency matched to cases by age, were selected through random digit dialing. All participants completed an in-person interview on lifetime alcohol consumption and other risk factors for prostate cancer. Logistic regression models were used to estimate odds ratios (OR) and assess significance (95% confidence intervals [CI]). All tests of statistical significance were two-sided. No clear association with prostate cancer risk was seen for overall alcohol consumption. Each additional glass of red wine consumed per week showed a statistically significant 6% decrease in relative risk (OR = 0.94; 95% CI = 0.90-0.98), and there was evidence for a decline in risk estimates across increasing categories of red wine intake (trend p = 0.02). No clear associations were seen for consumption of beer or liquor. Our present study suggests that consumption of beer or liquor is not associated with prostate cancer. There may be, however, a reduced relative risk associated with increasing level of red wine consumption. Further research is needed to evaluate the potential negative association between red wine intake and prostate cancer risk. PMID:15386436

  7. Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate Cancer

    SciTech Connect

    Kang, Josephine; Chen Minghui; Zhang Yuanye; Moran, Brian J.; Dosoretz, Daniel E.; Katin, Michael J.; Braccioforte, Michelle H.; Salenius, Sharon A.; D'Amico, Anthony V.

    2012-03-01

    Purpose: It has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 to 10; however, whether this association holds for both Type 1 and 2 DM is unknown. In this study we evaluated whether DM Type 1, 2, or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease. Methods and Materials: Between 1991 and 2010, a total of 15,330 men diagnosed with PCa and treated with radiation therapy were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether Type 1 or 2 DM was associated with odds of GS 7 or GS 8 to 10 compared with 6 or lower PCa, adjusting for African American race, age, prostate-specific antigen (PSA) level, and digital rectal examination findings. Results: Men with Type 1 DM (adjusted odds ratio [AOR], 2.05; 95% confidence interval [CI], 1.28-3.27; p = 0.003) or Type 2 DM (AOR, 1.58; 95% CI, 1.26-1.99; p < 0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared with nondiabetic men. However this was not true for GS 7, for which these respective results were AOR, 1.30; 95% CI, 0.93-1.82; p = 0.12 and AOR, 1.13; 95% CI, 0.98-1.32; p = 0.10. Conclusion: Type 1 and 2 DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, men who are diagnosed with Type I DM with GS 7 or lower should be considered for additional workup to rule out occult high-grade disease.

  8. Age-specific prevalence of HPV16/18 genotypes in cervical cancer: A systematic review and meta-analysis.

    PubMed

    Hammer, Anne; Rositch, Anne; Qeadan, Fares; Gravitt, Patti E; Blaakaer, Jan

    2016-06-15

    The prevalence of HPV16/18 in cervical cancer has been reported to decline with age in some papers. However, whether this decline in proportion of cancers positive for HPV16/18 is consistently observed across studies remains to be elucidated. Thus, the aim of this study was to identify papers reporting data on age-specific prevalence of HPV16/18 in cervical cancer and to summarize the results. We employed MEDLINE and Embase for a systematic literature search and thereby identified a total of 644 papers published in the period 1999-2015, of which 15 papers, reporting cross-sectional data, were included for review (11,526 cervical cancers). The prevalence of HPV16/18 in cervical cancer declined significantly with age (ρ = -0.83, p = 0.04) from 74.8% (95% CI 67.6-80.8) in women aged 30-39 years to 56.8% (95% CI 43.9-68.8) in women aged ≥70 years. As the HPV16/18 positive cancers are prevented in fully vaccinated cohorts, the age-specific epidemiology of cervical cancer is anticipated to change, with a shift in peak incidence rate to older ages. It will be important for integrated vaccination and screening strategies to consider predicted change in the age-specific epidemiology of cervical cancer. PMID:26661889

  9. Psychosocial Adjustment in School-age Girls With a Family History of Breast Cancer

    PubMed Central

    Bradbury, Angela R.; Patrick-Miller, Linda; Schwartz, Lisa; Egleston, Brian; Sands, Colleen Burke; Chung, Wendy K.; Glendon, Gord; McDonald, Jasmine A.; Moore, Cynthia; Rauch, Paula; Tuchman, Lisa; Andrulis, Irene L.; Buys, Saundra S.; Frost, Caren J.; Keegan, Theresa H.M.; Knight, Julia A.; Terry, Mary Beth; John, Esther M.; Daly, Mary B.

    2016-01-01

    OBJECTIVE Understanding how young girls respond to growing up with breast cancer family histories is critical given expansion of genetic testing and breast cancer messaging. We examined the impact of breast cancer family history on psychosocial adjustment and health behaviors among >800 girls in the multicenter LEGACY Girls Study. METHODS Girls aged 6 to 13 years with a family history of breast cancer or familial BRCA1/2 mutation (BCFH+), peers without a family history (BCFH−), and their biological mothers completed assessments of psychosocial adjustment (maternal report for 6- to 13-year-olds, self-report for 10- to 13-year-olds), breast cancer–specific distress, perceived risk of breast cancer, and health behaviors (10- to 13-year-olds). RESULTS BCFH+ girls had better general psychosocial adjustment than BCFH− peers by maternal report. Psychosocial adjustment and health behaviors did not differ significantly by self-report among 10- to 13-year-old girls. BCFH+ girls reported higher breast cancer–specific distress (P = .001) and were more likely to report themselves at increased breast cancer risk than BCFH− peers (38.4% vs 13.7%, P < .001), although many girls were unsure of their risk. In multivariable analyses, higher daughter anxiety was associated with higher maternal anxiety and poorer family communication. Higher daughter breast cancer–specific distress was associated with higher maternal breast cancer-specific distress. CONCLUSIONS Although growing up in a family at risk for breast cancer does not negatively affect general psychosocial adjustment among preadolescent girls, those from breast cancer risk families experience greater breast cancer–specific distress. Interventions to address daughter and mother breast cancer concerns and responses to genetic or familial risk might improve psychosocial outcomes of teen daughters. PMID:26482668

  10. Age and metallicity gradients in early-type galaxies: a dwarf-to-giant sequence

    NASA Astrophysics Data System (ADS)

    Koleva, Mina; Prugniel, Philippe; de Rijcke, Sven; Zeilinger, Werner W.

    2011-11-01

    We studied the stellar populations of 40 early-type galaxies using medium-resolution long-slit spectroscopy along their major axes (and along the minor axis for two of them). The sample, including elliptical and lenticular galaxies as well as dwarf galaxies, is combined with other previously published data in order to discuss the systematics of the radial gradients of age and metallicity over a large mass range, from 107 M⊙ to 1012 M⊙ (-9.2 > MB > -22.4 mag). The well-known mass-metallicity relation is continuous throughout the whole mass range, in the sense that more massive galaxies are more metal-rich. The age-mass relation is consistent with the idea of downsizing: smaller galaxies have more extended star formation histories than more massive ones. The transition-type dwarfs (intermediate between dwarf irregular and dwarf elliptical galaxies) deviate from this relation having younger mean age, and the low-mass dwarf spheroidals have older ages, marking a discontinuity in the relation, possibly due to selection effects. In all mass regimes, the mean metallicity gradients are approximately -0.2 and the mean age gradients +0.1 dex per decade of radius. The individual gradients are widely spread: -0.1 < ∇Age < 0.4 and -0.54 < ∇[Fe/H] < +0.2. We do not find evidence for a correlation between the metallicity gradient and luminosity, velocity dispersion, central age or age gradient. Likewise, we do not find a correlation between the age gradient and any other parameter in bright early-type galaxies. In faint early-types with MB≳-17 mag, on the other hand, we find a strong correlation between the age gradient and luminosity: the age gradient becomes more positive for fainter galaxies. Together with the observed downsizing phenomenon this indicates that, as time passes, star formation persists in dwarf galaxies and becomes more centrally concentrated. However, this prolonged central star formation is not reflected in the metallicity profiles of the dwarfs in

  11. Antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes mellitus

    PubMed Central

    Lee, Young-Min; Gweon, Oh-Cheon; Seo, Yeong-Ju; Im, Jieun; Kang, Min-Jung; Kim, Myo-Jeong

    2009-01-01

    Hyperglycemia in the diabetic state increases oxidative stress and antioxidant therapy can be strongly correlated with decreased risks for diabetic complications. The purpose of this study is to determine antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes. The antioxidant activity of garlic and aged black garlic was measured as the activity in scavenging free radicals by the trolox equivalent antioxidant capacity (TEAC) assay. Three week-old db/db mice were fed AIN-93G diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Hepatic levels of lipid peroxides and activities of antioxidant enzymes were measured. TEAC values of garlic and aged black garlic were 13.3 ± 0.5 and 59.2 ± 0.8 µmol/g wet weight, respectively. Consumption of aged black garlic significantly decreased hepatic thiobarbituric acid reactive substances (TBARS) level compared with the garlic group which showed lower TBARS level than control group (p<0.05). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of garlic and aged black garlic group were significantly elevated compared to the control group. Catalase (CAT) activity of aged black garlic group was increased compared with the control group. These results show that aged black garlic exerts stronger antioxidant activity than garlic in vitro and in vivo, suggesting garlic and aged black garlic, to a greater extent, could be useful in preventing diabetic complications. PMID:20016716

  12. Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.

    PubMed

    Marsh, Timothy; Wong, Irene; Sceneay, Jaclyn; Barakat, Amey; Qin, Yuanbo; Sjödin, Andreas; Alspach, Elise; Nilsson, Björn; Stewart, Sheila A; McAllister, Sandra S

    2016-05-15

    Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs. Cancer Res; 76(10); 2932-43. ©2016 AACR. PMID:27197230

  13. Loss of antigenicity with tissue age in breast cancer.

    PubMed

    Combs, Susan E; Han, Gang; Mani, Nikita; Beruti, Susan; Nerenberg, Michael; Rimm, David L

    2016-03-01

    Archived tumor specimens, particularly those collected by large cooperative groups and trials, provide a wealth of material for post hoc clinical investigation. As these tissues are rigorously collected and preserved for many decades, subsequent use of the specimens to answer clinical questions must rely on the assumption that expression and detection of target biomarkers are not degraded with time. To test this assumption, we measured the expression of estrogen receptor (ER), human epidermal growth receptor 2 (HER2), and Ki67 in human breast carcinoma using quantitative immunofluorescence (QIF) in a series of formalin-fixed paraffin-embedded (FFPE) tissues from 1295 individual patients preserved for 7 to 53 years in four cohorts on tissue microarrays. Protein expression was measured using the automated quantitative analysis method for QIF. Change in quantitative protein expression over time was estimated in positive cases using both Pearson's correlation and a polynomial regression analysis with a random effects model. The average signal decreased with preservation time for all biomarkers measured. For ER and HER2, there was an average of 10% signal loss after 9.9 years and 8.5 years, respectively, compared with the most recent tissue. Detection of Ki67 expression was lost more rapidly, with 10% signal loss in just 4.5 years. Overall, these results demonstrate the need for adjustment of tissue age when studying FFPE biospecimens. The rate of antigenicity loss is biomarker specific and should be considered as an important variable for studies using archived tissues. PMID:26568292

  14. Discovering Distinct Functional Modules of Specific Cancer Types Using Protein-Protein Interaction Networks

    PubMed Central

    Shen, Ru; Wang, Xiaosheng; Guda, Chittibabu

    2015-01-01

    Background. The molecular profiles exhibited in different cancer types are very different; hence, discovering distinct functional modules associated with specific cancer types is very important to understand the distinct functions associated with them. Protein-protein interaction networks carry vital information about molecular interactions in cellular systems, and identification of functional modules (subgraphs) in these networks is one of the most important applications of biological network analysis. Results. In this study, we developed a new graph theory based method to identify distinct functional modules from nine different cancer protein-protein interaction networks. The method is composed of three major steps: (i) extracting modules from protein-protein interaction networks using network clustering algorithms; (ii) identifying distinct subgraphs from the derived modules; and (iii) identifying distinct subgraph patterns from distinct subgraphs. The subgraph patterns were evaluated using experimentally determined cancer-specific protein-protein interaction data from the Ingenuity knowledgebase, to identify distinct functional modules that are specific to each cancer type. Conclusion. We identified cancer-type specific subgraph patterns that may represent the functional modules involved in the molecular pathogenesis of different cancer types. Our method can serve as an effective tool to discover cancer-type specific functional modules from large protein-protein interaction networks. PMID:26495282

  15. The Relationship between Type D Personality and Suicidality in Low-Income, Middle-Aged Adults

    PubMed Central

    Yoon, Dae Hyun; Kim, Seog Ju; Lee, Jong-Ha; Kim, Pyo-Min; Park, Doo-Heum; Ryu, Seung Ho; Yu, Jaehak

    2015-01-01

    Objective Low-income adults are considered to be a group at high risk for suicide. We sought to examine the effect of type D personality and other socio-demographic factors on suicidality in low-income, middle-aged Koreans. Methods In total, 306 low-income, middle-aged Koreans [age: 49.16±5.24 (40-59) years, 156 males, 150 females] were enrolled from the Korean National Basic Livelihood Security System. Socio-demographic data, including employment status, income, health, marital status, and educational attainment, were gathered. Beck's 19-item Scale for Suicidal Ideation (SSI) was applied to evaluate suicidality, and the DS14 was used to assess type D personality. Results Unemployment (p<0.01) and absence of spouse (p=0.03) predicted higher SSI scores independent of other socioeconomic factors. All type D personality scores [i.e., negative affectivity (NA), social inhibition (SI), and total score] predicted higher SSI scores independent of all socioeconomic factors (all, p<0.001). Subjects with type D personality had higher SSI scores (p<0.001), and the association between suicidality and socio-demographic factors (employment or physical health) could be found only in subjects without type D personality. Conclusion Type D personality was a risk factor for suicide in low-income Koreans, independently from socio-economic factors. In addition, the socio-demographic factors were less prominently associated with suicidality in those with type D personality. PMID:25670941

  16. Biochemical typing of pathological prion protein in aging cattle with BSE

    PubMed Central

    Tester, Seraina; Juillerat, Valerie; Doherr, Marcus G; Haase, Bianca; Polak, Miroslaw; Ehrensperger, Felix; Leeb, Tosso; Zurbriggen, Andreas; Seuberlich, Torsten

    2009-01-01

    Background The broad enforcement of active surveillance for bovine spongiform encephalopathy (BSE) in 2000 led to the discovery of previously unnoticed, atypical BSE phenotypes in aged cattle that differed from classical BSE (C-type) in biochemical properties of the pathological prion protein. Depending on the molecular mass and the degree of glycosylation of its proteinase K resistant core fragment (PrPres), mainly determined in samples derived from the medulla oblongata, these atypical cases are currently classified into low (L)-type or high (H)-type BSE. In the present study we address the question to what extent such atypical BSE cases are part of the BSE epidemic in Switzerland. Results To this end we analyzed the biochemical PrPres type by Western blot in a total of 33 BSE cases in cattle with a minimum age of eight years, targeting up to ten different brain regions. Our work confirmed H-type BSE in a zebu but classified all other cases as C-type BSE; indicating a very low incidence of H- and L-type BSE in Switzerland. It was documented for the first time that the biochemical PrPres type was consistent across different brain regions of aging animals with C-type and H-type BSE, i.e. independent of the neuroanatomical structure investigated. Conclusion Taken together this study provides further characteristics of the BSE epidemic in Switzerland and generates new baseline data for the definition of C- and H-type BSE phenotypes, thereby underpinning the notion that they indeed represent distinct prion disease entities. PMID:19470160

  17. Aging, muscle fiber type, and contractile function in sprint-trained athletes.

    PubMed

    Korhonen, Marko T; Cristea, Alexander; Alén, Markku; Häkkinen, Keijo; Sipilä, Sarianna; Mero, Antti; Viitasalo, Jukka T; Larsson, Lars; Suominen, Harri

    2006-09-01

    Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters (n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity (V(o)) were determined in 144 single skinned fibers from younger (18-33 yr, n = 8) and older (53-77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced (P < 0.001). With age there was an increased MHC I (P < 0.01) and reduced MHC IIx isoform content (P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. V(o) of fibers expressing type I MHC was lower (P < 0.05) in older than in younger subjects, but there was no difference in V(o) of type IIa MHC fibers. An aging-related decline of maximal isometric force (P < 0.001) and normalized rate of force development (P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II (P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower V(o) of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle. PMID:16690791

  18. Impact of Glucose-Lowering Agents on the Risk of Cancer in Type 2 Diabetic Patients. The Barcelona Case-Control Study

    PubMed Central

    Simó, Rafael; Plana-Ripoll, Oleguer; Puente, Diana; Morros, Rosa; Mundet, Xavier; Vilca, Luz M.; Hernández, Cristina; Fuentes, Inmaculada; Procupet, Adriana; Tabernero, Josep M.; Violán, Concepción

    2013-01-01

    Background The aim of the present study is to evaluate the impact of glucose-lowering agents in the risk of cancer in a large type 2 diabetic population. Methods A nested case-control study was conducted within a defined cohort (275,164 type 2 diabetic patients attending 16 Primary Health Care Centers of Barcelona). Cases (n = 1,040) comprised those subjects with any cancer diagnosed between 2008 and 2010, registered at the Cancer Registry of Hospital Vall d'Hebron (Barcelona). Three control subjects for each case (n = 3,120) were matched by age, sex, diabetes duration, and geographical area. The treatments analyzed (within 3 years prior to cancer diagnosis) were: insulin glargine, insulin detemir, human insulin, fast-acting insulin and analogues, metformin, sulfonylureas, repaglinide, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and alpha glucosidase inhibitors. Conditional logistic regressions were used to calculate the risk of cancer associated with the use of each drug adjusted by age, BMI, dose and duration of treatment, alcohol use, smoking habit, and diabetes duration. Results No differences were observed between case and control subjects for the proportion, dose or duration of exposure to each treatment. None of the types of insulin and oral agents analyzed showed a significant increase in the risk of cancer. Moreover, no cancer risk was observed when glargine was used alone or in combination with metformin. Conclusions Our results suggest that diabetes treatment does not influence the risk of cancer associated with type 2 diabetes. Therefore, an eventual increase of cancer should not be a reason for biasing the selection of any glucose-lowering treatment in type 2 diabetic population. PMID:24278227

  19. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer.

    PubMed

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    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. PMID:26975491

  20. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer

    PubMed Central

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    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. PMID:26975491

  1. Cost-Effectiveness of HPV Vaccination and Cervical Cancer Screening in Women over Age 30 in the United States

    PubMed Central

    Kim, Jane J.; Ortendahl, Jesse; Goldie, Sue J.

    2009-01-01

    Background Women over the age of 30 are the main beneficiaries of improved cervical cancer screening with human papillomavirus (HPV) DNA testing. The role of vaccination against HPV types 16 and 18, recommended routinely in pre-adolescent girls, is unclear in this age group. Objective To assess the health and economic outcomes of HPV vaccination in older women participating in the U.S. screening program. Design Cost-effectiveness analysis with an empirically-calibrated model. Data Sources Published literature. Target Population U.S. women, ages 35–45. Time Horizon Lifetime. Perspective Societal. Interventions HPV vaccination added to screening strategies that differ by test (cytology, HPV DNA testing), frequency, and start age, versus screening alone. Outcome Measures Incremental cost-effectiveness ratios (2006 U.S. dollars per quality-adjusted life year (QALY) gained). Results of Base-Case Analysis In the context of annual or biennial screening, HPV vaccination of women ages 35–45 ranged from $116,950 to $272,350 per QALY using cytology with HPV DNA testing for triage of equivocal results, and from $193,690 to $381,590 per QALY using combination cytology and HPV DNA testing, depending on age and screening frequency. Results of Sensitivity Analysis Probabilistic sensitivity analysis revealed that the probability of HPV vaccination being cost-effective for women ages 35–45 was 0% when screening occurred annually or biennially, and <5% when screening occurred triennially, at thresholds considered good value for money. Limitations Uncertainty in the natural history of disease and vaccine efficacy in older women. Conclusions Given currently available information, the effectiveness of HPV vaccination of screened women over age 30 appears, on average, to be small. Compared with current screening that uses sensitive HPV DNA testing, HPV vaccination in this older population is associated with cost-effectiveness ratios that are less attractive than well

  2. Ages, chemistry, and type 1A supernovae: Clues to the formation of the galactic stellar halo

    NASA Technical Reports Server (NTRS)

    Smecker-Hane, Tammy A.; Wyse, Rosemary F. G.

    1993-01-01

    We endeavor to resolve two conflicting constraints on the duration of the formation of the Galactic stellar halo - 2-3 Gyr age differences in halo stars, and the time scale inferred from the observed constant values of chemical element abundance ratios characteristic of enrichment by Type II supernovae - by investigating the time scale for the onset of Type Ia supernovae (SNIa) in the currently favored progenitor model - mergers of carbon and oxygen white dwarfs (CO WDs).

  3. Reconstruction of Genome-Scale Active Metabolic Networks for 69 Human Cell Types and 16 Cancer Types Using INIT

    PubMed Central

    Mardinoglu, Adil; Pornputtapong, Natapol; Nookaew, Intawat; Nielsen, Jens

    2012-01-01

    Development of high throughput analytical methods has given physicians the potential access to extensive and patient-specific data sets, such as gene sequences, gene expression profiles or metabolite footprints. This opens for a new approach in health care, which is both personalized and based on system-level analysis. Genome-scale metabolic networks provide a mechanistic description of the relationships between different genes, which is valuable for the analysis and interpretation of large experimental data-sets. Here we describe the generation of genome-scale active metabolic networks for 69 different cell types and 16 cancer types using the INIT (Integrative Network Inference for Tissues) algorithm. The INIT algorithm uses cell type specific information about protein abundances contained in the Human Proteome Atlas as the main source of evidence. The generated models constitute the first step towards establishing a Human Metabolic Atlas, which will be a comprehensive description (accessible online) of the metabolism of different human cell types, and will allow for tissue-level and organism-level simulations in order to achieve a better understanding of complex diseases. A comparative analysis between the active metabolic networks of cancer types and healthy cell types allowed for identification of cancer-specific metabolic features that constitute generic potential drug targets for cancer treatment. PMID:22615553

  4. Prognostic significance and optimal cutoff of age in medullary thyroid cancer

    PubMed Central

    Wang, Yu-long; Li, Duan-shu; Wang, Yu; Huang, Cai-ping; Ji, Qing-hai

    2016-01-01

    Age has been found to correlate with the prognosis for medullary thyroid cancer (MTC). This study was conducted to investigate whether age can predict long-term unfavorable prognosis and evaluate its predictive accuracy associated with TNM staging, using data of patients diagnosed with MTC between 2000 and 2010 from Surveillance, Epidemiology and End Results database. The relationship between the patients’ age at diagnosis and cancer-specific survival (CSS) was evaluated using multivariate Cox regression analysis. Age stratifications were combined into a nomogram model to predict the CSS of MTC. The X-tile program determined 49 and 69 as optimal age cutoff values for CSS. On multivariate analysis, independent factors for survival were age (50–69 years, HR 2.853, 95% CI 1.631–4.991; ≥70 years, HR 5.804, 95% CI 2.91–11.555), race (white, HR 0.344, 95% CI 0.188–0.630), T (T3/4, HR 3.931, 95% CI 2.093–7.381), N (N1a, HR 3.269, 95% CI 1.386–7.710) and M (M1, HR 3.998, 95% CI 2.419–6.606). The C-index for CSS prediction with TNM, age (cutoff of 45)/sex/race/TNM and age (cutoff of 49 and 69)/sex/race/TNM were 0.832 (95% CI 0.763–0.901), 0.863 (95% CI 0.799–0.928), and 0.876 (95% CI 0.817–0.935), respectively. Subgroup multivariate analyses also showed that age significantly increased the risk for CSS in females, non-Hispanic white patients, and those with stage IV MTC. In conclusion, CSS was independently associated with ages between 49 and 69 years, which might be applied for risk stratification in MTC patients. PMID:26910117

  5. Type-Specific Cell Line Models for Type-Specific Ovarian Cancer Research

    PubMed Central

    Anglesio, Michael S.; Wiegand, Kimberly C.; Melnyk, Nataliya; Chow, Christine; Salamanca, Clara; Prentice, Leah M.; Senz, Janine; Yang, Winnie; Spillman, Monique A.; Cochrane, Dawn R.; Shumansky, Karey; Shah, Sohrab P.; Kalloger, Steve E.; Huntsman, David G.

    2013-01-01

    Background Ovarian carcinomas consist of at least five distinct diseases: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of origin. Molecular characteristics have become the new standard for clinical pathology, however development of tailored type-specific therapies is hampered by a failure of basic research to recognize that model systems used to study these diseases must also be stratified. Unrelated model systems do offer value for study of biochemical processes but specific cellular context needs to be applied to assess relevant therapeutic strategies. Methods We have focused on the identification of clear cell carcinoma cell line models. A panel of 32 “ovarian cancer” cell lines has been classified into histotypes using a combination of mutation profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All cell lines were identity verified using STR analysis. Results Many described ovarian clear cell lines have characteristic mutations (including ARID1A and PIK3CA) and an overall molecular/immuno-profile typical of primary tumors. Mutations in TP53 were present in the majority of high-grade serous cell lines. Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also support copy number changes in typical biomarkers such at MET and HNF1B and a lack of any recurrent expressed re-arrangements. Conclusions: As with primary ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a general immuno-profile serve well for establishing histotype of ovarian cancer cell We describe specific biomarkers and molecular features to re-classify generic “ovarian carcinoma” cell lines into type specific categories. Our data supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and questions the use of SKOV3 and A

  6. DNA repair: Dynamic defenders against cancer and aging

    SciTech Connect

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet (UV

  7. Maternal Age at Birth and Childhood Type 1 Diabetes: A Pooled Analysis of 30 Observational Studies

    PubMed Central

    Cardwell, Chris R.; Stene, Lars C.; Joner, Geir; Bulsara, Max K.; Cinek, Ondrej; Rosenbauer, Joachim; Ludvigsson, Johnny; Jané, Mireia; Svensson, Jannet; Goldacre, Michael J.; Waldhoer, Thomas; Jarosz-Chobot, Przemysława; Gimeno, Suely G.A.; Chuang, Lee-Ming; Parslow, Roger C.; Wadsworth, Emma J.K.; Chetwynd, Amanda; Pozzilli, Paolo; Brigis, Girts; Urbonaitė, Brone; Šipetić, Sandra; Schober, Edith; Devoti, Gabriele; Ionescu-Tirgoviste, Constantin; de Beaufort, Carine E.; Stoyanov, Denka; Buschard, Karsten; Patterson, Chris C.

    2010-01-01

    OBJECTIVE The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2–9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age. PMID:19875616

  8. Streptococcus pneumoniae pharyngeal colonization in school-age children and adolescents with cancer.

    PubMed

    Principi, Nicola; Preti, Valentina; Gaspari, Stefania; Colombini, Antonella; Zecca, Marco; Terranova, Leonardo; Cefalo, Maria Giuseppina; Ierardi, Valentina; Pelucchi, Claudio; Esposito, Susanna

    2016-02-01

    Patients with cancer, particularly those with hematologic malignancies, are at an increased risk of invasive pneumococcal disease (IPD) and they are included in the list of subjects for whom pneumococcal vaccination is recommended. The main aim of this study was to evaluate Streptococcus pneumoniae colonization in school-aged children and adolescents with cancer to determine the potential protective efficacy of 13-valent pneumococcal conjugate vaccine (PCV13). An oropharyngeal swab was obtained from 277 patients (age range 6-17 years) with cancer during routine clinical visits and analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in 52 patients (18.8%), including 47/235 (20.0%) with hematologic malignancies and 5/42 (11.9%) with solid tumors. Colonization declined significantly with an increase in age (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.16-0.71, and OR 0.30, 95% CI 0.11-0.82 in children aged 10-14 and ≥15 years, respectively, as compared to those <10 years). Carriage was more common among patients with leukemia or lymphoma than in children with solid tumors. Co-trimoxazole prophylaxis was significantly associated with reduced pneumococcal carriage (OR 0.41, 95% CI 0.19-0.89). A total of 15/58 (25.9%) and 26/216 (12.0%) children were colonized by PCV13 serotypes among cancer patients previously vaccinated and not vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7), respectively. In conclusion, this study indicates that children and adolescents with cancer are frequently colonized by S. pneumoniae. Because most of the carried serotypes are included in PCV13, this vaccine is presently the best solution to reduce the risk of IPD in these patients. PMID:26367101

  9. [Cancer of the larynx in patients under 40 years of age].

    PubMed

    Kozuch-Gdak, W; Peszyński, J; Boguszewska, D

    1990-01-01

    440 patients with the plano-epithelial laryngeal cancer were radically treated by radiotherapy in Oncologic Department ZOZ in Lublin during the years 1976-1985. Among them were 23 (5.2%) "young" patients, aged below 40. In this group 10 patients (43%) revealed the first grade of clinical stage of the disease, whereas in remaining material there were 25% of cases in the first grade. The therapeutic effects in "young" group were the same as in the rest of cases. The percentage of "young" cancer patients became greater during the time: in 1976-80-4.1%, in 1981-85-6.1%. PMID:2255555

  10. Comprehensive identification of mutational cancer driver genes across 12 tumor types

    PubMed Central

    Tamborero, David; Gonzalez-Perez, Abel; Perez-Llamas, Christian; Deu-Pons, Jordi; Kandoth, Cyriac; Reimand, Jüri; Lawrence, Michael S.; Getz, Gad; Bader, Gary D.; Ding, Li; Lopez-Bigas, Nuria

    2013-01-01

    With the ability to fully sequence tumor genomes/exomes, the quest for cancer driver genes can now be undertaken in an unbiased manner. However, obtaining a complete catalog of cancer genes is difficult due to the heterogeneous molecular nature of the disease and the limitations of available computational methods. Here we show that the combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes. We provide a list of 291 high-confidence cancer driver genes acting on 3,205 tumors from 12 different cancer types. Among those genes, some have not been previously identified as cancer drivers and 16 have clear preference to sustain mutations in one specific tumor type. The novel driver candidates complement our current picture of the emergence of these diseases. In summary, the catalog of driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis. PMID:24084849

  11. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population.

    PubMed

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M; Narendran, Parth

    2015-11-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population - the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  12. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

    PubMed Central

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

    2015-01-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  13. Factors associated with cervical cancer screening amongst women of reproductive age from Yucatan, Mexico.

    PubMed

    Conde-Ferraez, Laura; Suarez Allen, Rosa Etelvina; Carrillo Martinez, Jorge Ramiro; Ayora-Talavera, Guadalupe; Gonzalez-Losa, Maria Del Refugio

    2012-01-01

    This study aimed to analyse the participation of women of reproductive age in a cancer screening program, and survey reasons for non-screening in a region from Mexico with high cervical cancer mortality. A total of 281 obstetric patients from a previous HPV study in a social security hospital during 2008-2009 were included. Reasons for not participating in the screening were directly asked. HPV positive patients were invited to participate in an informative workshop, and they filled in a knowledge questionnaire. The women ranged in age from 14-47 years; 123 (43.8%) had never participated in screening, of which 97 (78.9%) had their first sexual intercourse 2 to 10 years ago, resulting in 25% HPV positive. Screening history was strongly associated with 2 or more gestations (OR= 10.07, p=0.00) and older age (OR=6.69 p=0.00). When 197 women were contacted and interviewed, reasons referred for non-screening were ignorance, lack of interest or time, recent sexual onset, shame and fear. More than 50% of the workshop participants showed knowledge of HPV, while 38.9% and 25% knew about Pap smear and cervical cancer. A high percentage of women of reproductive age have never had a Pap smear. Promoting the screening program in medical facilities seems to be important in this population. New approaches to inform vulnerable individuals on the benefits of screening need to be implemented, especially for young women. PMID:23167409

  14. The Effects of Age, Years of Experience, and Type of Experience in the Teacher Selection Process

    ERIC Educational Resources Information Center

    Vail, David Scott

    2010-01-01

    Paper screening in the pre-selection process of hiring teachers has been the focus in an ongoing series of similar studies starting with Allison in 1981. There have been many independent variables, including, but not limited to, age, gender, ethnic background, years of experience, type of experience, and grade point average, introduced into the…

  15. Age-based computer-aided diagnosis approach for pancreatic cancer on endoscopic ultrasound images

    PubMed Central

    Ozkan, Murat; Cakiroglu, Murat; Kocaman, Orhan; Kurt, Mevlut; Yilmaz, Bulent; Can, Guray; Korkmaz, Ugur; Dandil, Emre; Eksi, Ziya

    2016-01-01

    Aim: The aim was to develop a high-performance computer-aided diagnosis (CAD) system with image processing and pattern recognition in diagnosing pancreatic cancer by using endosonography images. Materials and Methods: On the images, regions of interest (ROI) of three groups of patients (<40, 40-60 and >60) were extracted by experts; features were obtained from images using three different techniques and were trained separately for each age group with an Artificial Neural Network (ANN) to diagnose cancer. The study was conducted on endosonography images of 202 patients with pancreatic cancer and 130 noncancer patients. Results: 122 features were identified from the 332 endosonography images obtained in the study, and the 20 most appropriate features were selected by using the relief method. Images classified under three age groups (in years; <40, 40-60 and >60) were tested via 200 random tests and the following ratios were obtained in the classification: accuracy: 92%, 88.5%, and 91.7%, respectively; sensitivity: 87.5%, 85.7%, and 93.3%, respectively; and specificity: 94.1%, 91.7%, and 88.9%, respectively. When all the age groups were assessed together, the following values were obtained: accuracy: 87.5%, sensitivity: 83.3%, and specificity: 93.3%. Conclusions: It was observed that the CAD system developed in the study performed better in diagnosing pancreatic cancer images based on classification by patient age compared to diagnosis without classification. Therefore, it is imperative to take patient age into consideration to ensure higher performance. PMID:27080608

  16. Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance

    PubMed Central

    Tseng, Chin-Hsiao

    2015-01-01

    Purpose To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus. Methods A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40–64, 65–74 and ≥75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1–2.9 years, 3–4.9 years and ≥5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively. Results The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3–2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1–2.9 years, 3–4.9 years and ≥5 years was 1.5 (0.8–2.7), 1.6 (1.0–2.4), 1.6 (1.1–2.4) and 1.7 (1.3–2

  17. Glycative stress from advanced glycation end products (AGEs) and dicarbonyls: An emerging biological factor in cancer onset and progression.

    PubMed

    Lin, Jer-An; Wu, Chi-Hao; Lu, Chi-Cheng; Hsia, Shih-Min; Yen, Gow-Chin

    2016-08-01

    In recent years, glycative stress from exogenous or endogenous advanced glycation end products (AGEs) and highly reactive dicarbonyls has gained great attention for its putative effects on cancer development. AGEs are a group of compounds formed from the complex chemical reaction of reducing sugars with compounds containing an amino group. AGEs bind to and activate the receptor for AGEs (RAGE), which is a predominant modulator of inflammation-associated cancer, and AGEs induce reactive oxygen species that are an important regulator of the hallmarks of cancer. Dicarbonyls, which are formed during glycolysis, lipid oxidation, or protein degradation, include glyoxal, methylglyoxal, and 3-deoxyglucosone and are regarded as major precursors of AGEs. These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins, or DNA. Carbonylative damage then leads to many lesions, some of which are implicated in the pathogenesis of cancer. In this review, studies regarding the effects of AGEs and dicarbonyls on cancer onset or progression are systematically discussed, and the utilization of AGE inhibitors and dicarbonyl scavengers in cancer therapy are noted. PMID:26774083

  18. Technology Use in Transition-Age Patients With Type 1 Diabetes: Reality and Promises.

    PubMed

    Los, Evan; Ulrich, Jenae; Guttmann-Bauman, Ines

    2016-05-01

    Youth with chronic illnesses have the greatest risk for a decline in their health management during transition-age. Because of this demonstrated and well-known issue, research has focused on how to improve the transition of care process. Despite the increasing number of technological devices on the market and the advances in telemedicine modalities available to patients with type 1 diabetes (T1D), the utilization of technology is still suboptimal among patients of transition-age (ages 13-25). This article reviews the available resources, patterns of use in transition-age youth, and explores opportunities to advance technology use in transitioning patients with T1D from pediatric to adult care. PMID:26892506

  19. Clinicopathological characteristics and prognosis of breast cancer patients with type 2 diabetes mellitus

    PubMed Central

    HE, DE; BAI, JING-WEN; LIU, JING; DU, CAI-WEN; HUANG, WEN-HE; ZHANG, GUO-JUN

    2015-01-01

    Type 2 diabetes mellitus (T2DM) can increase the risk of several common cancers, including breast cancer (BC). The purpose of the present study was to investigate the clinicopathological features and prognosis of BC patients with or without T2DM. Seventy-eight patients were diagnosed with T2DM prior to the diagnosis of BC in the Cancer Hospital of Shantou University Medical College (Shantou, China) between 2002 and 2008. A total of 300 BC patients without T2DM were randomly selected as study controls during the same period. The clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) rates of these two groups were compared. Fifty-five BC patients and 133 control patients with T2DM were >50 years old (70.5 and 44.3%, respectively). There were more T2DM BC patients with body mass index (BMI) ≥25 kg/m2 (46.2 vs. 23.3%) and these patients had a higher rate of lymph node involvement (67.9 vs. 55.0%). The DFS of the two groups was 32.1 vs. 22.3%. The OS of the two groups was 24.4 vs. 13.7%. Following adjustment for BMI, tumor-node metastasis stage and stratification of age, the relapse risk of T2DM BC patients was >2-fold higher than that of the control group in the estrogen receptor/progesterone receptor (ER/PR)-positive patients. In Her-2-negative BC patients, the relapse risk of T2DM patients was 2.237-fold higher than that of the non-T2DM patients. In conclusion, T2DM BC patients were significantly older and more likely to be overweight, and had more lymph nodes involvement. T2DM was associated with poor prognosis in ER/PR positive or Her-2-negative BC patients. PMID:26137275

  20. Chronological age and breed-type effects on carcass characteristics and palatability of bull beef.

    PubMed

    Riley, R R; Smith, G C; Cross, H R; Savell, J W; Long, C R; Cartwright, T C

    1986-01-01

    Bulls (n = 115) of four slaughter ages (9, 12, 15 or 18 months) and of 15 genotypes were studied. In this analysis, each bullock was assigned to one of four breed groups-British and British crosses, Brahman and Brahman crosses. Jersey and Jersey crosses or Holstein and Holstein crosses. Slaughter age had an (P < 0·01) effect on marbling score, longissimus muscle area, fat thickness and yield grade while breed group had an (P < 0·01) effect on marbling score and quality grade. In general, British and British cross bullocks produced carcasses with the thickest subcutaneous fat, the highest marbling score and the highest USDA quality grade while Jersey and Jersey cross bullocks yielded carcasses with the lowest weight, smallest longissimus muscle area and the lowest USDA quality grade of the four breed-type groups. Increases in chronological age (from 9 to 18 months) were generally associated with a decrease in USDA maturity score, and increases in marbling score, USDA quality grade, longissimus muscle area, subcutaneous fat thickness and USDA yield grade. Shear force values decreased as bulls matured from 9 to 18 months of age. The meat from Brahman-type bulls had higher shear force values (P < 0·01) than that from bulls of the other breed groups. Steaks from British-type carcasses received the highest numerical ratings for sustained juiciness and flavor while steaks from the Brahman-type carcasses were assigned the lowest numerical ratings for juiciness. Breed-type had a greater effect on tenderness of bull beef than did chronological age. PMID:22055275

  1. Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations

    PubMed Central

    Yang, Fan; Petsalaki, Evangelia; Rolland, Thomas; Hill, David E.; Vidal, Marc; Roth, Frederick P.

    2015-01-01

    Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level. PMID:25794154

  2. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types.

    PubMed

    Cheng, Feixiong; Liu, Chuang; Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

    2015-09-01

    Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

  3. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

    PubMed Central

    Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

    2015-01-01

    Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

  4. Assessment of skeletal and dental ages of children and adolescents with type 1 diabetes mellitus.

    PubMed

    Bezerra, Ilana Sanamaika Queiroga; Topolski, Francielle; França, Suzana Nesi; Brücker, Márcia Rejane; Fernandes, Ângela

    2015-01-01

    The present study aimed to assess the skeletal and dental ages of type 1 diabetes mellitus (T1DM) patients. Therefore, panoramic and hand-wrist radiographs of 82 patients, aged between 5 and 15 years, were collected and divided into case and control groups. The case group consisted of 41 panoramic and 41 hand-wrist radiographs of T1DM patients, whereas the control group consisted of 41 panoramic and 41 hand-wrist radiographs of patients without T1DM. Skeletal age was assessed according to the method of Greulich and Pyle (1999), whereas dental age was assessed according to the method of Nolla (1960). Chi-square tests revealed no statistically significant differences between skeletal and dental ages between the case and control groups (p > 0.05). However, in the case group, the skeletal age of females was greater than that of age-matched males (p = 0.005). Considering that skeletal and dental growth of the case and control groups were closely related, clinical interventions involving orthodontics and dentomaxillofacial orthopedics should be equally performed both for healthy and specific patient groups, such as those with T1DM. PMID:25627889

  5. Study shows colon and rectal tumors constitute a single type of cancer

    Cancer.gov

    The pattern of genomic alterations in colon and rectal tissues is the same regardless of anatomic location or origin within the colon or the rectum, leading researchers to conclude that these two cancer types can be grouped as one, according to The Cancer

  6. Age-dependent Characteristics in Women with Breast Cancer: Mastectomy and Reconstructive Trends at an Urban Academic Institution.

    PubMed

    Rodby, Katherine A; Robinson, Emilie; Danielson, Kirstie K; Quinn, Karina P; Antony, Anuja K

    2016-03-01

    Breast reconstruction is an important aspect of treatment after breast cancer. Postmastectomy reconstruction bears a significant impact on a woman's postsurgical confidence, sexuality, and overall well-being. Previous studies have inferred that women under age 40 years have unique characteristics that distinguish them from an older cohort. Identifying age-dependent trends will assist with counseling women on mastectomy and reconstruction. To identify age-dependent trends, 100 consecutive women were sampled from a prospectively maintained breast reconstruction database at an urban academic institution from June 2010 through June 2013. Women were placed into two cohorts <40 and ≥40 as well cohorts by decade (20s, 30s, 40s, 50s, and 60s). Statistical trends were reported as odds of risk per year of increasing age using logistic regression; linear regression, χ(2), and Fischer's exact were used to compare <40 and ≥40 and split cohorts for comparison. Comorbidities, tumor staging, oncologic treatment including chemotherapy and radiation, disease characteristics and genetics, and mastectomy, reconstructive and symmetry procedures were evaluated. Statistical analysis was performed using SAS software. In 100 patients of the sample study cohort, 151 reconstructions were performed. Increasing age was associated with one or more comorbidities [odds ratio (OR) = 1.07, P = 0.005], whereas younger age was associated with metastatic disease (OR = 0.88, P = 0.006), chemotherapy (OR = 0.94, P = 0.01), and radiation (OR = 0.94, P = 0.006); split cohorts demonstrated similar trends (P < 0.005). Mastectomy and reconstructive characteristics associated with younger age included bilateral mastectomy (OR = 0.94, P = 0.004), tissue expander (versus autologous flap) (OR = 0.94, P = 0.009), extra high implant type (OR = 0.94, P = 0.049), whereas increasing use of autologous flaps and contralateral mastopexy symmetry procedures (OR = 1.09, P = 0.02) were associated with an aging cohort

  7. Tai Ji Quan for the aging cancer survivor: Mitigating the accelerated development of disability, falls, and cardiovascular disease from cancer treatment

    PubMed Central

    Winters-Stone, Kerri

    2014-01-01

    Currently there are more than 13.7 million cancer survivors living in the U.S., and that figure is projected to increase by 31% in the next decade, adding another 4 million cancer survivors into the healthcare system. Cancer is largely a disease of aging, and the aging of the population will sharply raise the proportion of older cancer survivors, many of whom will be long-term survivors (5+ years post diagnosis). This review will address the potential utility of exercise to address three health problems that are of particular concern for the aging cancer survivor and the healthcare system, i.e., disability, falls, and cardiovascular disease, because the development of these age-related problems may be accelerated by cancer treatment. While there are many different modes of exercise that each produce specific adaptations, Tai Ji Quan may be a particularly suitable strategy to mitigate the development of age- and cancer-treatment-related problems. Based on studies in older adults without cancer, Tai Ji Quan produces musculoskeletal and cardiometabolic adaptations and is more easily performed by older adults due to its low energy cost and slower movement patterns. Since cancer survivors are mostly older, inactive, and often physically limited by the lingering side effects of treatment, they need to engage in safe, practical, and effective modes of exercise. The dearth of published controlled trials examining the efficacy of Tai Ji Quan to mitigate cancer-treatment-related musculoskeletal and cardiovascular side effects points to ample research opportunities to explore the application of this non-Western exercise modality to improve long-term outcomes for aging cancer survivors. PMID:25285233

  8. Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type and HER-2 transgenic FVB/N female mice.

    PubMed

    Panchenko, Andrey V; Popovich, Irina G; Trashkov, Alexandr P; Egormin, Peter A; Yurova, Maria N; Tyndyk, Margarita L; Gubareva, Ekaterina A; Artyukin, Ilia N; Vasiliev, Andrey G; Khaitsev, Nikolai V; Zabezhinski, Mark A; Anisimov, Vladimir N

    2016-04-01

    FVB/N wild type and transgenic HER-2/neu FVB/N female mice breed at N.N. Petrov Research Institute of Oncology were under observation until natural death without any special treatment. Age-related dynamics of body weight, food consumption and parameters of carbohydrate and lipid metabolism, level of nitric oxide, malonic dialdehyde, catalase, Cu, Zn-superoxide dismutase, vascular endothelial growth factor were studied in both mice strains. The parameters of life span and tumor pathology were studied as well. Cancer-prone transgenic HER-2/neu mice developed in 100 % multiple mammary adenocarcinomas and died before the age of 1 year. Forty tree percent of long-lived wild type mice survived the age of 2 years and 19 %-800 days. The total tumor incidence in wild type mice was 34 %. The age-associated changes in the level of serum IGF-1, glucose and insulin started much earlier in transgene HER-2/neu mice as compared with wild type FVB/N mice. It was suggested that transgenic HER-2/neu involves in initiation of malignization of mammary epithelial cells but also in acceleration of age-related hormonal and metabolic changes in turn promoting mammary carcinogenesis. PMID:26423570

  9. A Population-based Study of Age Inequalities in Access to Palliative Care Among Cancer Patients

    PubMed Central

    Burge, Frederick I.; Lawson, Beverley J.; Johnston, Grace M.; Grunfeld, Eva

    2013-01-01

    Background Inequalities in access to palliative care programs (PCP) by age have been shown to exist in Canada and elsewhere. Few studies have been able to provide greater insight by simultaneously adjusting for multiple demographic, health service, and socio-cultural indicators. Objective To re-examine the relationship between age and registration to specialized community-based PCP programs among cancer patients and identify the multiple indicators contributing to these inequalities. Methods This retrospective, population-based study was a secondary data analysis of linked individual level information extracted from 6 administrative health databases and contextual (neighborhood level) data from provincial and census information. Subjects included all adults who died due to cancer between 1998 and 2003 living within 2 District Health Authorities in the province of Nova Scotia, Canada. The relationship between registration in a PCP and age was examined using hierarchical nonlinear regression modeling techniques. Identification of potential patient and ecologic contributing indicators was guided by Andersen’s conceptual model of health service utilization. Results Overall, 66% of 7511 subjects were registered with a PCP. Older subjects were significantly less likely than those <65 years of age to be registered with a PCP, in particular those aged 85 years and older (adjusted odds ratio: 0.4; 95% confidence interval: 0.3–0.5). Distance to the closest cancer center had a major impact on registration. Conclusions Age continues to be a significant predictor of PCP registration in Nova Scotia even after controlling for the confounding effects of many new demographic, health service, and ecologic indicators. PMID:19300309

  10. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer

    PubMed Central

    Bernardes de Jesus, Bruno; Vera, Elsa; Schneeberger, Kerstin; Tejera, Agueda M; Ayuso, Eduard; Bosch, Fatima; Blasco, Maria A

    2012-01-01

    A major goal in aging research is to improve health during aging. In the case of mice, genetic manipulations that shorten or lengthen telomeres result, respectively, in decreased or increased longevity. Based on this, we have tested the effects of a telomerase gene therapy in adult (1 year of age) and old (2 years of age) mice. Treatment of 1- and 2-year old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging. Importantly, telomerase-treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors. Finally, telomerase-treated mice, both at 1-year and at 2-year of age, had an increase in median lifespan of 24 and 13%, respectively. These beneficial effects were not observed with a catalytically inactive TERT, demonstrating that they require telomerase activity. Together, these results constitute a proof-of-principle of a role of TERT in delaying physiological aging and extending longevity in normal mice through a telomerase-based treatment, and demonstrate the feasibility of anti-aging gene therapy. PMID:22585399

  11. The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes

    PubMed Central

    Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

    2016-01-01

    As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies. PMID:26949191

  12. The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes.

    PubMed

    Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

    2016-01-01

    As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies. PMID:26949191

  13. Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer.

    PubMed

    Ishikawa, Hideki; Saeki, Tomoko; Otani, Toru; Suzuki, Takaichiro; Shimozuma, Kojiro; Nishino, Hoyoku; Fukuda, Sanae; Morimoto, Kanehisa

    2006-03-01

    Aged garlic extract (AGE) has manifold biological activities including immunomodulative and antioxidative effects. It is used as a major component of nonprescription tonics and cold-prevention medicines or dietary supplements. Advanced-cancer patients decline in immune functions and quality of life (QOL). The study's subjects were patients with inoperable colorectal, liver, or pancreatic cancer. In a randomized double-blind trial, AGE was administered to one group and a placebo was administered to another for 6 mo. The primary endpoint was a QOL questionnaire based on the Functional Assessment of Cancer Therapy (FACT). The subendpoints were changes in the natural-killer (NK) cell activity the salivary cortisol level from before and after administering AGE. Out of 55 patients invited to participate in the trial, 50 (91%) consented to enroll. They consisted of 42 patients with liver cancer (84%), 7 patients with pancreatic cancer (14%), and 1 patient with colon cancer (2%). Drug compliance was relatively good in both the AGE and placebo groups. Although no difference was observed in QOL, both the number of NK cells and the NK cell activity increased significantly in the AGE group. No adverse effect was observed in either group. The study showed that administering AGE to patients with advanced cancer of the digestive system improved NK cell activity, but caused no improvement in QOL. PMID:16484572

  14. Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older

    SciTech Connect

    Miyamoto, David T.; Mamon, Harvey J.

    2010-07-15

    Purpose: To review the outcomes and tolerability of full-dose chemoradiation in elderly patients aged 75 years or older with localized pancreatic cancer. Methods and Materials: We retrospectively reviewed patients aged 75 years or older with nonmetastatic pancreatic cancer treated with chemoradiation therapy at two institutions from 2002 to 2007. Patients were analyzed for treatment toxicity, local recurrences, distant metastases, and survival. Results: A total of 42 patients with a median age of 78 years (range, 75-90 years) who received chemoradiation therapy for pancreatic cancer were identified. Of the patients, 24 had locally advanced disease treated with definitive chemoradiation, and 18 had disease treated with surgery and chemoradiation. Before chemoradiotherapy, the mean Eastern Cooperative Oncology Group performance status was 1.0 {+-} 0.8, and the mean 6-month weight loss was 5.3 {+-} 3.8 kg. The mean radiation dose delivered was 48.1 {+-} 9.2 Gy. All patients received fluoropyrimidine-based chemotherapy concurrently with radiotherapy. In all, 8 patients (19%) were hospitalized, 7 (17%) had an emergency room visit, 15 (36%) required a radiation treatment break, 3 (7%) required a chemotherapy break, 9 (21%) did not complete therapy, and 22 (49%) had at least one of these adverse events. The most common toxicities were nausea, pain, and failure to thrive. Median overall survival was 8.6 months (95% confidence interval, 7.2-13.1) in patients who received definitive chemoradiation therapy and 20.6 months (95% confidence interval, 9.5-{infinity}) in patients who underwent resection and chemoradiation therapy. Conclusions: In this dataset of very elderly patients with pancreatic cancer and good Eastern Cooperative Oncology Group performance status, outcomes after chemoradiotherapy were similar to those among historic controls for patients with locally advanced and resected pancreatic cancer, although many patients experienced substantial treatment

  15. DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and aging.

    PubMed

    Mostoslavsky, Raul

    2008-01-01

    For many years organismal aging and cancer were viewed as separate entities. Recent studies however have suggested that these two seemingly disparate biological processes may in fact share common biochemical pathways. One area of emerging convergence involves the intersection of pathways known to mediate DNA repair with pathways previously implicated in insulin signaling. Recent evidence suggests that the sirtuin family of proteins act as central mediators of this molecular crosstalk. The coordination of DNA repair with overall energy balance may be essential for reducing the risk of developing cancer as well as for determining the rate at which we age. This review will summarize our current knowledge on how the maintenance of genomic integrity and insulin signaling intersect, the potential regulation of sirtuins in this crosstalk, and how this coordinated regulation may have important implication for both tumor-free and overall survival. PMID:18508709

  16. Prevalence of aging population in the Middle East and its implications on cancer incidence and care

    PubMed Central

    Hajjar, R. R.; Atli, T.; Al-Mandhari, Z.; Oudrhiri, M.; Balducci, L.; Silbermann, M.

    2013-01-01

    The Middle Eastern population is aging rapidly, and as aging is the main risk factor for cancer, the incidence and prevalence of that disease are increasing among all the populations in the region. These developments represent huge challenges to national and community-based health services. At the current state of affairs, most Middle Eastern countries require the cooperation of international agencies in order to cope with such new challenges to their health systems. The focus and emphasis in facing these changing circumstances lie in the education and training of professionals, mainly physicians and nurses, at the primary, secondary and tertiary levels of health services. It is imperative that these training initiatives include clinical practice, with priority given to the creation of multidisciplinary teams both at the cancer centers and for home-based services. PMID:24001758

  17. Cancer Survivorship Issues: Life After Treatment and Implications for an Aging Population

    PubMed Central

    Rowland, Julia H.; Bellizzi, Keith M.

    2014-01-01

    The US population of cancer survivors age ≥ 65 years will continue to grow rapidly over the next few decades. This growth will be driven largely by the aging of the national population. With the diffusion of earlier detection and more effective therapies, the majority of these individuals can expect to live long term after diagnosis. This often vulnerable group of survivors poses significant challenges for both researchers and clinicians with regard to how best to document and address its unique health care needs. In this article, we briefly review the long-term and late-occurring effects of cancer and its treatment in older survivors, review information on current patterns of post-treatment care and the evolving guidelines for this care, and discuss opportunities for future research. PMID:25071099

  18. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    SciTech Connect

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  19. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation

    PubMed Central

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2016-01-01

    Summary Cellular senescence suppresses cancer by arresting cells at risk of malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation and branching morphogenesis. Furthermore, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts – the ability to alter epithelial differentiation – that might also explain the loss of tissue function and organization that is a hallmark of aging. PMID:15657080

  20. Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component

    PubMed Central

    Hwang, Chung-Su; Ahn, Sangjeong; Lee, Bong-Eun; Lee, So-Jeong; Kim, Ahrong; Choi, Chang In; Kim, Dae Hwan; Jeon, Tae-Yong; Kim, Gwang Ha; Song, Geum Am; Park, Do Youn

    2016-01-01

    AIM: To predict the rate of lymph node (LN) metastasis in diffuse- and mixed-type early gastric cancers (EGC) for guidelines of the treatment. METHODS: We reviewed 550 cases of EGC with diffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type (diffuse > intestinal type), mixed-predominantly intestinal type (intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components. RESULTS: LN metastasis was observed in 12.9% (71/550) of early gastric cancers cases [15/288 mucosal EGCs (5.2%) and 56/262 submucosal EGCs (21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis (20.2%) than cases of pure diffuse type (9.3%) and predominantly intestinal type (12.2%) histology. We measured the dimensions of each component (intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not. CONCLUSION: We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment. PMID:27099445

  1. Stage III Colon Cancer: The Individualized Strategy of Adjuvant Chemotherapy for Aged Under and Over 70

    PubMed Central

    Lu, Chieh-Sheng; Chang, Ping-Ying; Chen, Yu-Guang; Chen, Jia-Hong; Wu, Yi-Ying; Ho, Ching-Liang

    2015-01-01

    Background The aim of this study was to examine the specific chemoregimens selected for adjuvant therapy in the patients with stage III colon cancer. We investigated the trends in chemotherapeutic prescribing patterns and looked for adequate therapeutic setting for these patients. Methods 288 patients presenting with stage III colon cancer and undergoing adjuvant therapies after curative surgery for more than 3-month were enrolled between January 2006 and December 2011. Demographic characteristics and therapeutic factors were analyzed, including age, gender, histological grade, tumor sizes, tumor location, pathologic stage, performance status, serum carcinoembryonic antigen, regimens selection, interval from the operation to the start of adjuvant therapy and prolonged adjuvant therapy. Kaplan– Meier methods were utilized for drawing survival curves and Cox model was used to analyze survival, prognostic factors. Results The analysis showed that the patients aged under 70 received more intensive therapies than those aged over 70 (P<0.001). Later, advanced analysis in therapeutic factors was conducted between the patients aged under 70 and those over 70. In the patients aged under 70, significant differences in 4-year overall survival (OS) were noted between UFUR (oral tegafur-uracil plus leucovorin) groups and FOLFOX (5-FU plus oxaliplatin) [65.6% versus (vs) 89.8%, relative risk (RR) 3.780, 95% confidence interval (CI) 1.263–11.315, P = 0.017]. There were also differences in 4-year OS between these patients with and without oxaliplatin-contained regimens (92.1% vs 83.4%, respectively, RR 0.385, 95% CI 0.157–0.946, P = 0.037). In addition, the patients who received intravenous or combined therapy also had higher 4-year OS than those only received oral regimens (92.1% vs 76.6%, P = 0.077), though the finding did not reach statistical significance. In contrast to the survival benefits of above therapeutic settings for the patients aged under 70, there was less

  2. Prostate cancer and consistency of reporting sexual histories in men over age 50.

    PubMed

    Dennis, L K; Ritchie, J M; Resnick, M I

    2005-01-01

    We conducted an in-person interview to examine the reliability of reported sexual histories among men over age 50 y with and without prostate cancer. Marriage and cohabitation were used as memory cues to recall sexual activity. High correlations on test-retest for questions evaluating sexual histories suggest reliable answers for most factors, and specifically for age at first sexual activity, and lifetime number of sexual partners. Low correlations were seen for ill-defined and socially undesirable items. These data suggest that men consistently report most measures of sexual activity when using marriage and cohabitation as memory cues to recall sexual histories. PMID:15983628

  3. Patterns and functional implications of rare germline variants across 12 cancer types

    PubMed Central

    Lu, Charles; Xie, Mingchao; Wendl, Michael C.; Wang, Jiayin; McLellan, Michael D.; Leiserson, Mark D. M.; Huang, Kuan-lin; Wyczalkowski, Matthew A.; Jayasinghe, Reyka; Banerjee, Tapahsama; Ning, Jie; Tripathi, Piyush; Zhang, Qunyuan; Niu, Beifang; Ye, Kai; Schmidt, Heather K.; Fulton, Robert S.; McMichael, Joshua F.; Batra, Prag; Kandoth, Cyriac; Bharadwaj, Maheetha; Koboldt, Daniel C.; Miller, Christopher A.; Kanchi, Krishna L.; Eldred, James M.; Larson, David E.; Welch, John S.; You, Ming; Ozenberger, Bradley A.; Govindan, Ramaswamy; Walter, Matthew J.; Ellis, Matthew J.; Mardis, Elaine R.; Graubert, Timothy A.; Dipersio, John F.; Ley, Timothy J.; Wilson, Richard K.; Goodfellow, Paul J.; Raphael, Benjamin J.; Chen, Feng; Johnson, Kimberly J.; Parvin, Jeffrey D.; Ding, Li

    2015-01-01

    Large-scale cancer sequencing data enable discovery of rare germline cancer susceptibility variants. Here we systematically analyse 4,034 cases from The Cancer Genome Atlas cancer cases representing 12 cancer types. We find that the frequency of rare germline truncations in 114 cancer-susceptibility-associated genes varies widely, from 4% (acute myeloid leukaemia (AML)) to 19% (ovarian cancer), with a notably high frequency of 11% in stomach cancer. Burden testing identifies 13 cancer genes with significant enrichment of rare truncations, some associated with specific cancers (for example, RAD51C, PALB2 and MSH6 in AML, stomach and endometrial cancers, respectively). Significant, tumour-specific loss of heterozygosity occurs in nine genes (ATM, BAP1, BRCA1/2, BRIP1, FANCM, PALB2 and RAD51C/D). Moreover, our homology-directed repair assay of 68 BRCA1 rare missense variants supports the utility of allelic enrichment analysis for characterizing variants of unknown significance. The scale of this analysis and the somatic-germline integration enable the detection of rare variants that may affect individual susceptibility to tumour development, a critical step toward precision medicine. PMID:26689913

  4. Patterns and functional implications of rare germline variants across 12 cancer types.

    PubMed

    Lu, Charles; Xie, Mingchao; Wendl, Michael C; Wang, Jiayin; McLellan, Michael D; Leiserson, Mark D M; Huang, Kuan-Lin; Wyczalkowski, Matthew A; Jayasinghe, Reyka; Banerjee, Tapahsama; Ning, Jie; Tripathi, Piyush; Zhang, Qunyuan; Niu, Beifang; Ye, Kai; Schmidt, Heather K; Fulton, Robert S; McMichael, Joshua F; Batra, Prag; Kandoth, Cyriac; Bharadwaj, Maheetha; Koboldt, Daniel C; Miller, Christopher A; Kanchi, Krishna L; Eldred, James M; Larson, David E; Welch, John S; You, Ming; Ozenberger, Bradley A; Govindan, Ramaswamy; Walter, Matthew J; Ellis, Matthew J; Mardis, Elaine R; Graubert, Timothy A; Dipersio, John F; Ley, Timothy J; Wilson, Richard K; Goodfellow, Paul J; Raphael, Benjamin J; Chen, Feng; Johnson, Kimberly J; Parvin, Jeffrey D; Ding, Li

    2015-01-01

    Large-scale cancer sequencing data enable discovery of rare germline cancer susceptibility variants. Here we systematically analyse 4,034 cases from The Cancer Genome Atlas cancer cases representing 12 cancer types. We find that the frequency of rare germline truncations in 114 cancer-susceptibility-associated genes varies widely, from 4% (acute myeloid leukaemia (AML)) to 19% (ovarian cancer), with a notably high frequency of 11% in stomach cancer. Burden testing identifies 13 cancer genes with significant enrichment of rare truncations, some associated with specific cancers (for example, RAD51C, PALB2 and MSH6 in AML, stomach and endometrial cancers, respectively). Significant, tumour-specific loss of heterozygosity occurs in nine genes (ATM, BAP1, BRCA1/2, BRIP1, FANCM, PALB2 and RAD51C/D). Moreover, our homology-directed repair assay of 68 BRCA1 rare missense variants supports the utility of allelic enrichment analysis for characterizing variants of unknown significance. The scale of this analysis and the somatic-germline integration enable the detection of rare variants that may affect individual susceptibility to tumour development, a critical step toward precision medicine. PMID:26689913

  5. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging

    NASA Astrophysics Data System (ADS)

    Kaczanowski, Szymon

    2016-06-01

    Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging.

  6. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging.

    PubMed

    Kaczanowski, Szymon

    2016-01-01

    Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging

  7. Body Fatness at Young Ages and Risk of Breast Cancer Throughout Life

    PubMed Central

    Baer, Heather J.; Tworoger, Shelley S.; Hankinson, Susan E.; Willett, Walter C.

    2010-01-01

    Body fatness at young ages may be related to breast cancer risk independently of adult adiposity. The authors conducted a prospective analysis among 188,860 women (7,582 breast cancer cases) in the Nurses’ Health Study (1988–2004) and Nurses’ Health Study II (1989–2005) who recalled their body fatness at ages 5, 10, and 20 years using a 9-level pictogram (level 1: most lean; level 9: most overweight). Body fatness at young ages was inversely associated with risk of both premenopausal and postmenopausal breast cancer (per 1-unit increase in adolescent body fatness, relative risk (RR) = 0.88 and RR = 0.91, respectively; Ptrend < 0.0001). Among all women, the RR for adolescent body fatness of level 6.5 or higher versus level 1 was 0.57 (per 1-unit increase, RR = 0.90; Ptrend < 0.0001) and was unaffected by adjustment for current body mass index. The association was stronger for women with birth weights under 8.5 pounds (<3.9 kg) than for women with birth weights of 8.5 pounds or more (≥3.9 kg) (per 1-unit increase, RR = 0.89 and RR = 0.94, respectively; Pinteraction = 0.04) and stronger for estrogen receptor-negative tumors than for estrogen receptor-positive tumors (per 1-unit increase, RR = 0.86 and RR = 0.92, respectively; Pheterogeneity = 0.03). Body fatness at young ages has a strong and independent inverse relation to breast cancer risk throughout life. PMID:20460303

  8. Attitudes and practices for smoking cessation counseling by provider type and patient age.

    PubMed

    Kviz, F J; Clark, M A; Prohaska, T R; Slezak, J A; Crittenden, K S; Freels, S; Campbell, R T

    1995-03-01

    Attitudes and self-reported practices for smoking cessation counseling among 145 providers at a health maintenance organization were compared among two provider groups, physicians/nurse practitioners and registered/licensed practical nurses, and across three patient age groups, < 50, 50-64, and > or = 65. Smoking cessation attitudes did not differ by provider type but they did differ by patient age, especially among the registered/licensed practical nurses, whose attitudes were least favorable for the oldest smokers (> or = 65). While smoking cessation practices did not differ by patient age, they did differ by provider type. Self-reported performance of the 4 As of smoking cessation practice (Ask, Advise, Assist, Arrange) was more frequent among the physicians/nurse practitioners than among the registered/licensed practical nurses. However, among both groups, asking and advising practices were reported more often than were assisting and arranging. In all cases, different attitudes were correlated with different practice behaviors for the two provider groups. Also, there were more significant correlations between age-specific attitudes and practices among the registered/licensed practical nurses than among the physicians/nurse practitioners. This was true especially regarding the oldest patients. The findings suggest a need for provider education, especially among registered/licensed practical nurses, about the benefits of smoking cessation for patients of all ages and the potential effectiveness of provider-based intervention strategies that are targeted toward specific age groups. The findings also suggest that assisting and arranging practices in particular need improvement among all types of providers. PMID:7597023

  9. Clinical Trial Participation and Time to Treatment Among Adolescents and Young Adults With Cancer: Does Age at Diagnosis or Insurance Make a Difference?

    PubMed Central

    Parsons, Helen M.; Harlan, Linda C.; Seibel, Nita L.; Stevens, Jennifer L.; Keegan, Theresa H.M.

    2011-01-01

    Purpose Because adolescent and young adult (AYA) patients with cancer have experienced variable improvement in survival over the past two decades, enhancing the quality and timeliness of cancer care in this population has emerged as a priority area. To identify current trends in AYA care, we examined patterns of clinical trial participation, time to treatment, and provider characteristics in a population-based sample of AYA patients with cancer. Methods Using the National Cancer Institute Patterns of Care Study, we used multivariate logistic regression to evaluate demographic and provider characteristics associated with clinical trial enrollment and time to treatment among 1,358 AYA patients with cancer (age 15 to 39 years) identified through the Surveillance, Epidemiology, and End Results Program. Results In our study, 14% of patients age 15 to 39 years had enrolled onto a clinical trial; participation varied by type of cancer, with the highest participation in those diagnosed with acute lymphoblastic leukemia (37%) and sarcoma (32%). Multivariate analyses demonstrated that uninsured, older patients and those treated by nonpediatric oncologists were less likely to enroll onto clinical trials. Median time from pathologic confirmation to first treatment was 3 days, but this varied by race/ethnicity and cancer site. In multivariate analyses, advanced cancer stage and outpatient treatment alone were associated with longer time from pathologic confirmation to treatment. Conclusion Our study identified factors associated with low clinical trial participation in AYA patients with cancer. These findings support the continued need to improve access to clinical trials and innovative treatments for this population, which may ultimately translate into improved survival. PMID:21931022

  10. Effect of Age and Race Upon Quality of Life of Young Breast Cancer Survivors

    PubMed Central

    Morrow, P.K.; Broxson, A.C.; Munsell, M.F.; Basen-Enquist, K.; Rosenblum, C.K.; Schover, L.R.; Nguyen, L.H.; Hsu, L.; Castillo, L.; Hahn, K.M.E.; Litton, J.K.; Mattair, D.M.; Hortobagyi, G.N.

    2014-01-01

    Background Given their early age of diagnosis, young breast cancer (BC) survivors face issues that differ widely from their older counterparts. Patients and Methods We mailed a survey to 2209 patients who were ≤45 years at time of BC diagnosis. Each survey was comprised of: the Quality of Life in Adult Cancer Survivors instrument, Menopause Symptom Scale, and questions aimed at obtaining pertinent background information. Results 1090 patients completed the survey. Mean age at time of diagnosis was 39.5 years; median years from diagnosis was 6.6 years. Distress related to vaginal dryness (p=0.0002) and pain from intercourse (p=0.0014) was significantly higher in patients who were <5 years from diagnosis, compared to those >10 years from diagnosis. In the area of financial problems, black women had greater distress than white women (p=0.0010). Compared to white women, Hispanic women had worse family distress scores (p=0.0028) and summary cancer specific scores (p=0.0076). Patients >10 years from diagnosis had poorer sexual interest (p=0.003) than women who were closer to diagnosis. Women ≥40 years at diagnosis had significantly lower sexual interest (p=0.0016) than women <40 years. Stage and neoadjuvant chemotherapy did not have a significant effect on QOL. Conclusion Even in comparison to stage and neoadjuvant chemotherapy, race, age at diagnosis, and time from diagnosis have significant long term effects on QOL following BC treatment. PMID:24461458

  11. Sirtuins and the Estrogen Receptor as Regulators of the Mammalian Mitochondrial UPR in Cancer and Aging.

    PubMed

    Germain, D

    2016-01-01

    By being both the source of ATP and the mediator of apoptosis, the mitochondria are key regulators of cellular life and death. Not surprisingly alterations in the biology of the mitochondria have implications in a wide array of diseases including cancer and age-related diseases such as neurodegeneration. To protect the mitochondria against damage the mitochondrial unfolded protein response (UPR(mt)) orchestrates several pathways, including the protein quality controls, the antioxidant machinery, oxidative phosphorylation, mitophagy, and mitochondrial biogenesis. While several reports have implicated an array of transcription factors in the UPR(mt), most of the focus has been on studies of Caenorhabditis elegans, which led to the identification of ATFS-1, for which the mammalian homolog remains unknown. Meanwhile, there are studies which link the UPR(mt) to sirtuins and transcription factors of the Foxo family in both C. elegans and mammalian cells but those have been largely overlooked. This review aims at emphasizing the potential importance of these studies by building on the large body of literature supporting the key role of the sirtuins in the maintenance of the integrity of the mitochondria in both cancer and aging. Further, the estrogen receptor alpha (ERα) and beta (ERβ) are known to confer protection against mitochondrial stress, and at least ERα has been linked to the UPR(mt). Considering the difference in gender longevity, this chapter also includes a discussion of the link between the ERα and ERβ and the mitochondria in cancer and aging. PMID:27037754

  12. Do Variants Associated with Susceptibility to Pancreatic Cancer and Type 2 Diabetes Reciprocally Affect Risk?

    PubMed Central

    Wu, Lang; Rabe, Kari G.; Petersen, Gloria M.

    2015-01-01

    Objectives Although type 2 diabetes mellitus is a known risk factor for pancreatic cancer, the existence of shared genetic susceptibility is largely unknown. We evaluated whether any reported genetic risk variants of either disease found by genome-wide association studies reciprocally confer susceptibility. Methods Data that were generated in previous genome-wide association studies (GENEVA Type 2 Diabetes; PanScan) were obtained through the National Institutes of Health database of Genotypes and Phenotypes (dbGaP). Using the PanScan datasets, we tested for association of 38 variants within 37 genomic regions known to be susceptibility factors for type 2 diabetes. We further examined whether type 2 diabetes variants predispose to pancreatic cancer risk stratified by diabetes status. Correspondingly, we examined the association of fourteen pancreatic cancer susceptibility variants within eight genomic regions in the GENEVA Type 2 Diabetes dataset. Results Four plausible associations of diabetes variants and pancreatic cancer risk were detected at a significance threshold of p = 0.05, and one pancreatic cancer susceptibility variant was associated with diabetes risk at threshold of p = 0.05, but none remained significant after correction for multiple comparisons. Conclusion Currently identified GWAS susceptibility variants are unlikely to explain the potential shared genetic etiology between Type 2 diabetes and pancreatic cancer. PMID:25658847

  13. Mitochondrial Lon protease at the crossroads of oxidative stress, ageing and cancer.

    PubMed

    Pinti, Marcello; Gibellini, Lara; Liu, Yongzhang; Xu, Shan; Lu, Bin; Cossarizza, Andrea

    2015-12-01

    Lon protease is a nuclear DNA-encoded mitochondrial enzyme highly conserved throughout evolution, involved in the degradation of damaged and oxidized proteins of the mitochondrial matrix, in the correct folding of proteins imported in mitochondria, and in the maintenance of mitochondrial DNA. Lon expression is induced by various stimuli, including hypoxia and reactive oxygen species, and provides protection against cell stress. Lon down-regulation is associated with ageing and with cell senescence, while up-regulation is observed in tumour cells, and is correlated with a more aggressive phenotype of cancer. Lon up-regulation contributes to metabolic reprogramming observed in cancer, favours the switch from a respiratory to a glycolytic metabolism, helping cancer cell survival in the tumour microenvironment, and contributes to epithelial to mesenchymal transition. Silencing of Lon, or pharmacological inhibition of its activity, causes cell death in various cancer cells. Thus, Lon can be included in the growing class of proteins that are not responsible for oncogenic transformation, but that are essential for survival and proliferation of cancer cells, and that can be considered as a new target for development of anticancer drugs. PMID:26363553

  14. TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer.

    PubMed

    Steurer, Stefan; Mayer, Pascale Sophia; Adam, Meike; Krohn, Antje; Koop, Christina; Ospina-Klinck, Daniel; Tehrani, Ali Attarchi; Simon, Ronald; Tennstedt, Pierre; Graefen, Markus; Wittmer, Corinna; Brors, Benedikt; Plass, Christoph; Korbel, Jan; Weischenfeldt, Joachim; Sauter, Guido; Huland, Hartwig; Tsourlakis, Maria Christina; Minner, Sarah; Schlomm, Thorsten

    2014-12-01

    Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes-such as transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11,152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2-ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3+4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non-androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients. PMID:25015038

  15. Mosaic aging

    PubMed Central

    Walker, Lary C.; Herndon, James G.

    2010-01-01

    Summary Although all multicellular organisms undergo structural and functional deterioration with age, senescence is not a uniform process. Rather, each organism experiences a constellation of changes that reflect the heterogeneous effects of age on molecules, cells, organs and systems, an idiosyncratic pattern that we refer to as mosaic aging. Varying genetic, epigenetic and environmental factors (local and extrinsic) contribute to the aging phenotype in a given individual, and these agents influence the type and rate of functional decline, as well as the likelihood of developing age-associated afflictions such as cardiovascular disease, arthritis, cancer, and neurodegenerative disorders. Identifying key factors that drive aging, clarifying their activities in different systems, and in particular understanding how they interact will enhance our comprehension of the aging process, and could yield insights into the permissive role that senescence plays in the emergence of acute and chronic diseases of the elderly. PMID:20110150

  16. Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types

    PubMed Central

    Soeldner, Robert; Egorov, Mark; Guenther, Rolf; Dehler, Silvia; Morys-Wortmann, Corinna; Moch, Holger; Henco, Karsten; Schraml, Peter

    2016-01-01

    Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC) as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs) which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers. PMID:27537329

  17. Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.

    PubMed

    Beleut, Manfred; Soeldner, Robert; Egorov, Mark; Guenther, Rolf; Dehler, Silvia; Morys-Wortmann, Corinna; Moch, Holger; Henco, Karsten; Schraml, Peter

    2016-01-01

    Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC) as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs) which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers. PMID:27537329

  18. Is cancer a good way to die? A population-based survey among middle-aged and older adults in the United Kingdom

    PubMed Central

    Vrinten, Charlotte; Wardle, Jane

    2016-01-01

    Objectives Despite improved outcomes, cancer remains widely feared, often because of its association with a long and protracted death as opposed to the quick death that people associate with that other common cause of adult mortality: heart disease. Former editor-in-chief of the BMJ Richard Smith's view that ‘cancer is the best way to die’ therefore attracted much criticism. We examined middle-aged and older adults' agreement with this view and compared their attitudes towards dying from cancer versus heart disease in terms of which was a good death. Methods This study was part of an online survey (February 2015) in a United Kingdom (UK) population sample of 50- to 70-year olds (n = 391), with sampling quotas for gender and education. Five characteristics of ‘a good death’ were selected from the end-of-life literature. Respondents were asked to rate the importance of each characteristic for their own death to ensure their relevance to a population sample and the likelihood of each for death from cancer and heart disease. We also asked whether they agreed with Smith's view. Results At least 95% of respondents considered the selected five characteristics important for their own death. Death from cancer was rated as more likely to provide control over what happens (p < 0.001), control over pain and other symptoms (p < 0.01), time to settle affairs (p < 0.001), and time to say goodbye to loved ones (p < 0.001) compared with death from heart disease, but there were no differences in expectation of living independently until death (p > 0.05). Almost half (40%) agreed that cancer is ‘the best way to die’, with no differences by age (p = 0.40), gender (p = 0.85), or education (p = 0.27). Conclusion Despite the media commotion, a surprisingly high proportion of middle-aged and older adults viewed cancer as ‘the best way to die’ and rated cancer death as better than heart disease. Given that one in two of us are likely to be diagnosed with

  19. Age-Adjusted PSA Levels in Prostate Cancer Prediction: Updated Results of the Tyrol Prostate Cancer Early Detection Program

    PubMed Central

    Heidegger, Isabel; Fritz, Josef; Klocker, Helmut; Pichler, Renate

    2015-01-01

    Objective To reduce the number of unnecessary biopsies in patients with benign prostatic disease, however, without missing significant PCa the present study re-evaluates the age-dependent PSA cut-offs in the Tyrol Prostate Cancer (PCa) early detection program. Patients and Methods The study population included 2225 patients who underwent prostate biopsy due to elevated PSA levels at our department. We divided our patient collective into four age groups: ≤49 years (n = 178), 50-59 years (n = 597), 60-69 years (n = 962) and ≥70 years (n = 488). We simulated different scenarios for PSA cut-off values between 1.25 and 6 ng/mL and fPSA% between 15 and 21% for all four age groups and calculated sensitivity, specificity, confidence intervals and predictive values. Results PCa was detected in 1218 men (54.7%). We found that in combination with free PSA ≤21% the following PSA cut-offs had the best cancer specificity: 1.75 ng/ml for men ≤49 years and 50-59 years, 2.25 ng/ml for men aged 60-69 years and 3.25 ng/ml for men ≥70 years. Using these adjusted PSA cut-off values all significant tumors are recognized in all age groups, yet the number of biopsies is reduced. Overall, one biopsy is avoided in 13 to 14 men (number needed to screen = 13.3, reduction of biopsies = 7.5%) when decision regarding biopsy is done according to the “new” cut-off values instead of the “old” ones. For the different age groups the number needed to screen to avoid one biopsy varied between 9.2 (≤49 years) and 17.4 (50-59 years). Conclusion With “new”, fine-tuned PSA cut-offs we detect all relevant PCa with a significant reduction of biopsies compared to the “old” cut-off values. Optimization of age-specific PSA cut-offs is one step towards a smarter strategy in the Tyrol PCa Early Detection Program. PMID:26218594

  20. Pleiotropy and pathway analyses of genetic variants associated with both type 2 diabetes and prostate cancer

    PubMed Central

    Raynor, LA; Pankow, James S; Rasmussen-Torvik, Laura J; Tang, Weihong; Prizment, Anna; Couper, David J

    2013-01-01

    Aims: Epidemiological evidence shows that diabetes is associated with a reduced risk of prostate cancer. The objective of this study was to identify genes that may contribute to both type 2 diabetes and prostate cancer outcomes and the biological pathways these diseases may share. Methods: The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities that included a baseline examination in 1987-89 and three follow-up exams at three year intervals. Participants were 45-64 years old at baseline. We conducted a genomewide association (GWA) study of incident type 2 diabetes in males, summarized variation across genetic loci into a polygenic risk score, and determined if that diabetes risk score was also associated with incident prostate cancer in the same study population. Secondarily we conducted a separate GWA study of prostate cancer, performed a pathway analysis of both type 2 diabetes and prostate cancer, and qualitatively determined if any of the biochemical pathways identified were shared between the two outcomes. Results: We found that the polygenic risk score for type 2 diabetes was not statistically significantly associated with prostate cancer. The pathway analysis also found no overlap between pathways associated with type 2 diabetes and prostate cancer. However, it did find that the growth hormone signaling pathway was statistically significantly associated with type 2 diabetes (p=0.0001). Conclusion: The inability of this study to find an association between type 2 diabetes polygenic risk scores with prostate cancer or biological pathways in common suggests that shared genetic variants may not contribute significantly to explaining shared etiology. PMID:23565322

  1. Impact of two types of image processing on cancer detection in mammography

    NASA Astrophysics Data System (ADS)

    Warren, Lucy M.; Halling-Brown, Mark D.; Looney, Padraig T.; Dance, David R.; Wilkinson, Louise; Wallis, Matthew G.; Given-Wilson, Rosalind M.; Cooke, Julie; McAvinchey, Rita; Young, Kenneth C.

    2016-03-01

    The impact of image processing on cancer detection is still a concern to radiologists and physicists. This work aims to evaluate the effect of two types of image processing on cancer detection in mammography. An observer study was performed in which six radiologists inspected 349 cases (a mixture of normal cases, benign lesions and cancers) processed with two types of image processing. The observers marked areas they were suspicious were cancers. JAFROC analysis was performed to determine if there was a significant difference in cancer detection between the two types of image processing. Cancer detection was significantly better with the standard setting image processing (flavor A) compared with one that provides enhanced image contrast (flavor B), p = 0.036. The image processing was applied to images of the CDMAM test object, which were then analysed using CDCOM. The threshold gold thickness measured with the CDMAM test object was thinner using flavor A than flavor B image processing. Since Flavor A was found to be superior in both the observer study and the measurements using the CDMAM phantom, this may indicate that measurements using the CDMAM correlate with change in cancer detection with different types of image processing.

  2. Impact of Age and Comorbidity on Cervical and Breast Cancer Literacy of African Americans, Latina, and Arab women

    PubMed Central

    Talley, Costellia H.; Williams, Karen Patricia

    2015-01-01

    Background Appropriate and timely screening can significantly reduce breast and cervical cancer morbidity and mortality. Racial/ethnic minorities and immigrant populations have lower screening rates and delays in follow-up after abnormal tests. Purpose In this study, we examined the relationship between age, comorbidity, breast and cervical cancer literacy in a sample of African American, Latina, and Arab women (N=371) from Detroit, Michigan. Methods Age-adjusted Charlson Comorbidity Index (ACC) was used characterize the impact of age and comorbidity has on breast and cervical cancer literacy; Breast Cancer Literacy Assessment Tool was used to assess breast cancer literacy; Cervical Cancer Literacy Assessment Tool was used to assess cervical cancer literacy. ANOVA was used to assess the relationship between ACC, breast and cervical cancer screening and group differences. Results There was a statistically significant difference between breast cancer literacy (Breast-CLAT total scores) scores (F(2,367)= 17.31, p= < 0.01). ACC had a greater impact on breast cancer literacy for African American F(2,214) =11, p = <0.01. PMID:26333609

  3. Dynapenic Obesity and Prevalence of Type 2 Diabetes in Middle-Aged Japanese Men

    PubMed Central

    Kawakami, Ryoko; Sawada, Susumu S.; Lee, I-Min; Matsushita, Munehiro; Gando, Yuko; Okamoto, Takashi; Tsukamoto, Koji; Higuchi, Mitsuru; Miyachi, Motohiko; Blair, Steven N.

    2015-01-01

    Background The independent and combined associations of muscle strength and obesity on the prevalence of type 2 diabetes in Japanese men remain unclear. Methods Hand grip strength was cross-sectionally evaluated between 2011 and 2013 to assess muscle strength in 5039 male workers aged 40 to 64 years. Weight and height were measured, and overweight/obesity was defined as a body mass index ≥25 kg/m2. The prevalence of type 2 diabetes, defined as fasting plasma glucose ≥126 mg/dL and/or hemoglobin A1c ≥6.5% and/or self-reported physician-diagnosed diabetes, was evaluated. Odds ratios (OR) and 95% confidence intervals (95% CI) for the prevalence of type 2 diabetes were obtained using a logistic regression model. Results In total, 611 participants had type 2 diabetes, and 1763 participants were overweight/obese. After adjustment for covariates, we found an inverse association between muscle strength and the prevalence of type 2 diabetes (P for trend <0.01). In addition, when the analyses were stratified by obesity status, the multivariable-adjusted OR per 2-standard-deviation increase in muscle strength was 0.64 (95% CI, 0.49–0.83) in the overweight/obese group, compared to a weaker relationship in the normal-weight group (OR 0.79 per 2-standard-deviation increase; 95% CI, 0.60–1.06). Conclusions Dynapenia, an age-related decrease in muscle strength, is associated with increased prevalence of type 2 diabetes, and this relationship is stronger in overweight/obese middle-aged Japanese men than in normal-weight men. PMID:26256772

  4. Parental age and Neurofibromatosis Type 1: a report from the NF1 Patient Registry Initiative.

    PubMed

    Liu, Qian; Zoellner, Nancy; Gutmann, David H; Johnson, Kimberly J

    2015-06-01

    One of the potential etiologies for non-familial Neurofibromatosis Type 1 (NF1) is increasing parental age. We sought to evaluate recent evidence for parental age effects in NF1 in a large study. Individuals with NF1 and a comparison group from the U.S. general population born between 1994 and 2012 were ascertained from the NF1 Patient Registry Initiative (NPRI) and the National Center for Vital Statistics, respectively. Multiple linear regression analysis was employed to identify differences between familial NF1, non-familial NF1, and U.S. population subjects in the mean parental ages at the time of the birth of offspring in each group. In addition, we also evaluated the effect of parental age on NF1 offspring with and without a pediatric brain tumor history. A total of 313 subjects from the NPRI (including 99 brain tumor cases) matched by birth year at a 1:3 ratio to U.S. general population births (n = 939) were included. Compared to the U.S. general population and familial NF1 cases, the mean paternal age for non-familial NF1 cases was 4.34 years (95% CI 3.23-5.46, p ≤ 0.0001) and 3.39 years (95% CI 1.57-5.20, p ≤ 0.0001) older, respectively, after adjusting for birth year. A similar pattern was observed for maternal age. There were no statistically significant differences in the mean maternal or paternal ages between NF1 offspring with and without a pediatric brain tumor. In conclusion, these data support a parental age effect for non-familial NF1 cases, but not for pediatric brain tumors in NF1. PMID:25523354

  5. The Effect of Types of Postsecondary Education on Drinking: Does Age of Enrollment Matter?

    PubMed Central

    Thompson, Kara; Stockwell, Tim; Leadbeater, Bonnie; Homel, Jacqueline

    2016-01-01

    Using longitudinal data from early adolescence through young adulthood, this study examined the association between different types of postsecondary education (PSE), age of enrollment in PSE, and the trajectory of alcohol use for Canadian young adults (N = 521). Trajectories of alcohol use were compared across young adults at 2-year colleges, 4-year universities, transfer programs (started at a 2-year college and transferred to a 4-year university), and terminal high school graduates. While initial findings revealed significant differences in the drinking trajectories of 2-year college students and 4-year university students, all differences were accounted for by variability in the age of enrollment. Overall, there were few differences in heavy drinking across types of institutions, but younger students increased their alcohol use more than older students following enrollment. However, young adults who do not attend PSE may be at greatest risk for heavy drinking over time. PMID:27308184

  6. The Age Conundrum: A Scoping Review of Younger Age or Adolescent and Young Adult as a Risk Factor for Clinical Distress, Depression, or Anxiety in Cancer.

    PubMed

    Lang, Michael J; David, Victoria; Giese-Davis, Janine

    2015-12-01

    This scoping review was conducted to understand the extent, range, and nature of current research on adolescents and young adults (AYA) with cancer and distress, depression, and anxiety (DDA). This information is necessary to find and aggregate valuable data on the AYA population embedded in generalized studies of DDA. Keyword searches of six relevant electronic databases identified 2156 articles, with 316 selected for abstract review and 40 for full text review. Full-text reviews and data extraction resulted in 34 studies being included, which ranged widely in design, sample size, age-range categorization, analysis methods, DDA measurement tool, overall study rigor, and quality of evidence. Studies very seldom reported using theory to guide their age categorization, with only four studies giving any rationale for their age-group definitions. All 34 studies found a significant association between at least one DDA construct and the younger age group relative to the older age groups at some point along the cancer trajectory. However, age as an independent risk factor for DDA is still unclear, as the relationship could be confounded by other age-related factors. Despite the wide range of definitions and effect sizes in the studies included in this review, one thing is clear: adolescents and young adults, however defined, are a distinct group within the cancer population with an elevated risk of DDA. Widespread adoption of a standard AYA age-range definition will be essential to any future meta-analytical psycho-oncology research in this population. PMID:26697266

  7. Suppression of murine type-C RNA virogenes by type-specific oncornavirus vaccines: prospects for prevention of cancer.

    PubMed Central

    Huebner, R J; Gilden, R V; Lane, W T; Toni, R; Trimmer, R W; Hill, P R

    1976-01-01

    Immunization of crossbred and F1 mice with combined killed and live Gross leukemia virus AKR type-C viral vaccines suppressed endogeneous N-type AKR virus up to 10,000-fold for significant periods during early life. Since several previous studies in the same and similar crossbred systems revealed direct correlations between low and high levels of type-C virus early in life with low and high incidences of leukemia and other cancers later in life, we believe that prospects for suppression of spontaneous neoplasms are good; however, 8-14 months will be required to achieve the final results. Should cancers be prevented by serotype-specific vaccines, such evidence would provide conclusive proof of endogenous viral etiology. PMID:174116

  8. Prostaglandin E2/cyclooxygenase pathway in human skeletal muscle: influence of muscle fiber type and age.

    PubMed

    Liu, Sophia Z; Jemiolo, Bozena; Lavin, Kaleen M; Lester, Bridget E; Trappe, Scott W; Trappe, Todd A

    2016-03-01

    Prostaglandin E2 (PGE2) produced by the cyclooxygenase (COX) pathway regulates skeletal muscle protein turnover and exercise training adaptations. The purpose of this study was twofold: 1) define the PGE2/COX pathway enzymes and receptors in human skeletal muscle, with a focus on type I and II muscle fibers; and 2) examine the influence of aging on this pathway. Muscle biopsies were obtained from the soleus (primarily type I fibers) and vastus lateralis (proportionally more type II fibers than soleus) of young men and women (n = 8; 26 ± 2 yr), and from the vastus lateralis of young (n = 8; 25 ± 1 yr) and old (n = 12; 79 ± 2 yr) men and women. PGE2/COX pathway proteins [COX enzymes (COX-1 and COX-2), PGE2 synthases (cPGES, mPGES-1, and mPGES-2), and PGE2 receptors (EP1, EP2, EP3, and EP4)] were quantified via Western blot. COX-1, cPGES, mPGES-2, and all four PGE2 receptors were detected in all skeletal muscle samples examined. COX-1 (P < 0.1) and mPGES-2 were ∼20% higher, while EP3 was 99% higher and EP4 57% lower in soleus compared with vastus lateralis (P < 0.05). Aging did not change the level of skeletal muscle COX-1, while cPGES increased 45% and EP1 (P < 0.1), EP3, and EP4 decreased ∼33% (P < 0.05). In summary, PGE2 production capacity and receptor levels are different in human skeletal muscles with markedly different type I and II muscle fiber composition. In aging skeletal muscle, PGE2 production capacity is elevated and receptor levels are downregulated. These findings have implications for understanding the regulation of skeletal muscle adaptations to exercise and aging by the PGE2/COX pathway and related inhibitors. PMID:26607246

  9. Age and Sex Influence Cystatin C in Adolescents With and Without Type 1 Diabetes

    PubMed Central

    Maahs, David M.; Prentice, Nicole; McFann, Kim; Snell-Bergeon, Janet K.; Jalal, Diana; Bishop, Franziska K.; Aragon, Brittany; Wadwa, R. Paul

    2011-01-01

    OBJECTIVE To compare serum cystatin C levels, a novel biomarker of renal function, in adolescents with and without type 1 diabetes and to determine what factors affect cystatin C levels. RESEARCH DESIGN AND METHODS Cystatin C was measured in youth 12–19 years of age with (n = 259, diabetes duration 9 ± 3 years, HbA1c 8.9 ± 1.6%) and without diabetes (n = 78). Data were compared by diabetes status, and linear regression was used to determine factors affecting cystatin C. RESULTS Cystatin C (0.698 ± 0.083 vs. 0.688 ± 0.127 mg/L, P = 0.40) was similar by diabetes status. In multiple linear regression, cystatin C was associated with age and serum creatinine in nondiabetic subjects and sex, age, and serum creatinine in subjects with diabetes (P < 0.05). CONCLUSIONS These data suggest sex differences and age-related changes in cystatin C in adolescents with type 1 diabetes. An understanding of these changes is needed to determine the potential role of cystatin C as a marker of renal function in this population. PMID:21926294

  10. Age-related anabolic resistance after endurance-type exercise in healthy humans

    PubMed Central

    Durham, William J.; Casperson, Shanon L.; Dillon, Edgar L.; Keske, Michelle A.; Paddon-Jones, Douglas; Sanford, Arthur P.; Hickner, Robert C.; Grady, James J.; Sheffield-Moore, Melinda

    2010-01-01

    Age-related skeletal muscle loss is thought to stem from suboptimal nutrition and resistance to anabolic stimuli. Impaired microcirculatory (nutritive) blood flow may contribute to anabolic resistance by reducing delivery of amino acids to skeletal muscle. In this study, we employed contrast-enhanced ultrasound, microdialysis sampling of skeletal muscle interstitium, and stable isotope methodology, to assess hemodynamic and metabolic responses of older individuals to endurance type (walking) exercise during controlled amino acid provision. We hypothesized that older individuals would exhibit reduced microcirculatory blood flow, interstitial amino acid concentrations, and amino acid transport when compared with younger controls. We report for the first time that aging induces anabolic resistance following endurance exercise, manifested as reduced (by ∼40%) efficiency of muscle protein synthesis. Despite lower (by ∼40–45%) microcirculatory flow in the older than in the younger participants, circulating and interstitial amino acid concentrations and phenylalanine transport into skeletal muscle were all equal or higher in older individuals than in the young, comprehensively refuting our hypothesis that amino acid availability limits postexercise anabolism in older individuals. Our data point to alternative mediators of age-related anabolic resistance and importantly suggest correction of these impairments may reduce requirements for, and increase the efficacy of, dietary protein in older individuals. Durham, W. J., Casperson, S. L., Dillon, E. L., Keske, M. A., Paddon-Jones, D., Sanford, A. P., Hickner, R. C., Grady, J. J., Sheffield-Moore, M. Age-related anabolic resistance after endurance-type exercise in healthy humans. PMID:20547663

  11. Analysis of plasma microRNA expression profiles revealed different cancer susceptibility in healthy young adult smokers and middle-aged smokers

    PubMed Central

    Shi, Bing; Gao, Hongmin; Zhang, Tianyang; Cui, Qinghua

    2016-01-01

    Cigarette smoking is a world-wide habit and an important risk factor for cancer. It was known that cigarette smoking can change the expression of circulating microRNAs (miRNAs) in healthy middle-aged adults. However, it remains unclear whether cigarette smoking can change the levels of circulating miRNAs in young healthy smokers and whether there are differences in cancer susceptibility for the two cases. In this study, the miRNA expression profiles of 28 smokers and 12 non-smokers were determined by Agilent human MicroRNA array. We further performed bioinformatics analysis for the differentially expressed miRNAs. The result showed that 35 miRNAs were differentially expressed. Among them, 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in smokers. Functional enrichment analysis showed that the deregulated miRNAs are related to immune system and hormones regulation. Strikingly, the up-regulated miRNAs are mostly associated with hematologic cancers, such as lymphoma, leukemia. As a comparison, the up-regulated plasma miRNAs in middle-aged smokers are mostly associated with solid cancers, such as hepatocellular carcinoma and lung cancer, suggesting that smoking could have different influences on young adults and middle-aged adults. In a conclusion, we identified the circulating miRNAs deregulated by cigarette smoking and revealed that the age-dependent deregulated miRNAs tend to be mainly involved in different types of human cancers. PMID:26943588

  12. Bromodomain Coactivators in Cancer, Obesity, Type 2 Diabetes, and Inflammation

    PubMed Central

    Denis, Gerald V.

    2011-01-01

    Double bromodomain proteins bind to acetylated lysines in histones, bringing associated histone modification and nucleosome remodeling activity to chromatin. The ability of bromodomain regulators to alter chromatin status and control gene expression has long been appreciated to be important in the development of certain human cancers. However, bromodomain proteins have now been found also to be critical, non-redundant players in diverse, non-malignant phenotypes, directing transcriptional programs that control adipogenesis, energy metabolism and inflammation. The fact that such different processes are functionally linked by the same molecular machinery suggests a common epigenetic basis to understand and interpret the origins of several important co-morbidities, such as asthma or cancer that occurs in obesity, and complex inflammatory diseases like cardiovascular disease, systemic lupus erythematosus, rheumatoid arthritis and insulin resistance that may be built on a common pro-inflammatory foundation. PMID:21189220

  13. Age-rotation relationship for late-type main-sequence stars

    NASA Technical Reports Server (NTRS)

    Rengarajan, T. N.

    1984-01-01

    With advancing spectral type and increasing age, late main-sequence stars exhibit monotonic decrease in rotational velocity. It is of great interest to extend the rotation-age relationship to stars of later spectral type. In recent times it has become possible to measure directly the rotational periods from the photometric modulation by Ca II H and K line emission. There have also been successful attempts to relate the chromospheric activity as manifested through Ca II H and K lines to the rotation period, and it was shown that the fraction of total stellar luminosity in Ca II H and K lines, corrected for photospheric contribution, is a function of a single parameter related to P and B-V. In the present investigation, this rotation-activity relation is utilized to infer the rotation periods as a function of spectral type. The period versus B-V plot is employed as a basis to infer that the rotational period of main-sequence stars is a single-valued function of mass (B-V color) and age.

  14. Detection of erythrocytes influenced by aging and type 2 diabetes using atomic force microscope

    SciTech Connect

    Jin, Hua; Xing, Xiaobo; Zhao, Hongxia; Chen, Yong; Huang, Xun; Ma, Shuyuan; Ye, Hongyan; Cai, Jiye

    2010-01-22

    The pathophysiological changes of erythrocytes are detected at the molecular scale, which is important to reveal the onset of diseases. Type 2 diabetes is an age-related metabolic disorder with high prevalence in elderly (or old) people. Up to now, there are no treatments to cure diabetes. Therefore, early detection and the ability to monitor the progression of type 2 diabetes are very important for developing effective therapies. Type 2 diabetes is associated with high blood glucose in the context of insulin resistance and relative insulin deficiency. These abnormalities may disturb the architecture and functions of erythrocytes at molecular scale. In this study, the aging- and diabetes-induced changes in morphological and biomechanical properties of erythrocytes are clearly characterized at nanometer scale using atomic force microscope (AFM). The structural information and mechanical properties of the cell surface membranes of erythrocytes are very important indicators for determining the healthy, diseased or aging status. So, AFM may potentially be developed into a powerful tool in diagnosing diseases.

  15. Colorectal Cancer Screening in US Seniors Ages 76-84 Years.

    PubMed

    Klabunde, Carrie N; Shapiro, Jean A; Kobrin, Sarah; Nadel, Marion R; Zapka, Jane M

    2015-08-01

    The US Preventive Services Task Force recommends patient-physician discussions about the appropriateness of colorectal cancer (CRC) screening among adults ages 76-84 years who have never been screened. In this study, we used data from the 2010 National Health Interview Survey to examine patterns of CRC screening and provider recommendation among seniors ages 76-84 years, and made some comparisons to younger adults. Nationally-representative samples of 1379 adults ages 76-84 years and 8797 adults ages 50-75 years responded to questions about CRC screening status, receipt of provider recommendation, and discussion of test options; 22.7% (95% CI 20.1-25.3) of seniors ages 76-84 had never been tested for CRC and therefore were not up-to-date with guidelines; 3.9% (95% CI 2.0-7.6) of these individuals reported a recent provider recommendation for screening. In multivariate analyses, the likelihood of never having been tested was significantly greater for seniors of other/multiple race or Hispanic ethnicity; with high school or less education; without private health insurance coverage; who had ≤ 1 doctor visit in the past year; without recent screening for breast, cervical, or prostate cancer; with no or unknown CRC family history; or with ≤ 1 chronic disease. Among the minority of respondents ages 50-75 and 76-84 reporting a provider recommendation, 73.2% indicated that the provider recommended particular tests, which was overwhelmingly colonoscopy (≥ 89 %). Nearly one-quarter of adults 76-84 have never been screened for CRC, and rates of provider recommendation in this group are very low. Greater attention to informed CRC screening discussions with screening-eligible seniors is needed. PMID:25716518

  16. Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

    PubMed Central

    Murotomi, Kazutoshi; Umeno, Aya; Yasunaga, Mayu; Shichiri, Mototada; Ishida, Noriko; Abe, Hiroko; Yoshida, Yasukazu; Nakajima, Yoshihiro

    2014-01-01

    Tsumura Suzuki Obese Diabetes (TSOD) mouse, a model of obese type 2 diabetes, older than around 11 weeks of age develops diabetic phenotypes. Previous studies have indicated that the development of diabetes is partly due to three loci associated with body weight and glucose homeostasis. However, little is known about the initial events triggering the development of the diabetic phenotypes in TSOD mouse. Here, we investigated the alteration of diabetes-related parameters, including the levels of blood glucose and inflammatory cytokines, and the oxidative stress status, in young TSOD mice. TSOD mice at 5 weeks of age showed increases in body weight and plasma total cholesterol level, but not hyperglycemia or impaired glucose tolerance, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were not detected in TSOD mice at 5 weeks of age. However, plasma total hydroxyoctadecadienoic acid (tHODE), a biomarker of oxidative stress, was increased in TSOD mice relative to TSNO mice at same age. The results demonstrated that young TSOD mice are exposed to oxidative stress before developing the diabetic phenotypes, and suggested that oxidative stress is an initial event triggering the development of diabetes in TSOD mice. PMID:25411529

  17. Mortality of breast cancer in Taiwan, 1971-2010: temporal changes and an age-period-cohort analysis.

    PubMed

    Ho, M-L; Hsiao, Y-H; Su, S-Y; Chou, M-C; Liaw, Y-P

    2015-01-01

    The current paper describes the age, period and cohort effects on breast cancer mortality in Taiwan. Female breast cancer mortality data were collected from the Taiwan death registries for 1971-2010. The annual percentage changes, age- standardised mortality rates (ASMR) and age-period-cohort model were calculated. The mortality rates increased with advancing age groups when fixing the period. The percentage change in the breast cancer mortality rate increased from 54.79% at aged 20-44 years, to 149.78% in those aged 45-64 years (between 1971-75 and 2006-10). The mortality rates in the 45-64 age group increased steadily from 1971 to 1975 and 2006-10. The 1951 birth cohorts (actual birth cohort; 1947-55) showed peak mortalities in both the 50-54 and 45-49 age groups. We found that the 1951 birth cohorts had the greatest mortality risk from breast cancer. This might be attributed to the DDT that was used in large amounts to prevent deaths from malaria in Taiwan. However, future researches require DDT data to evaluate the association between breast cancer and DDT use. PMID:25020211

  18. AB044. AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation

    PubMed Central

    Bao, Jiming; Bao, Yawei; Zhao, Shanchao; He, Minyi; Luo, Haihua; Ren, Zhonglu; Lv, Yongjie; Hong, Yingqia

    2016-01-01

    Objective Metabolomic research has revealed that metabolites play an important role in prostate cancer development and progression. Previous studies have suggested that prostate cancer cell proliferation is induced by advanced glycation end products (AGEs) exposure, but the mechanism of this induction remains unknown. This study aim to investigate the molecular mechanisms underlying the proliferative response of prostate cancer cell to the interaction of AGEs and the receptor for advanced glycation end products (RAGE). Methods To investigate this mechanism, we used Western blotting to evaluate the responses of the retinoblastoma (Rb), p-Rb and PI3K/Akt pathway to AGEs stimulation. We also examined the effect of knocking down Rb and blocking the PI3K/Akt pathway on AGEs induced PC-3 cell proliferation. Results Our results indicated that AGE-RAGE interaction enhanced Rb phosphorylation and subsequently decreased total Rb levels. Bioinformatics analysis further indicated a negative correlation between RAGE and RB1 expression in prostate cancer tissue. Furthermore, we observed that AGEs stimulation activated the PI3K/Akt signaling pathway and that blocking PI3K/Akt signaling abrogated AGEs-induced cell proliferation. Conclusions We report, for the first time, that AGE-RAGE interaction enhances prostate cancer cell proliferation by phosphorylation of Rb via the PI3K/Akt signaling pathway.

  19. Colorectal cancer screening awareness and intentions among low income, sociodemographically diverse adults under age 50.

    PubMed

    Emmons, Karen; Puleo, Elaine; McNeill, Lorna H; Bennett, Gary; Chan, Sophia; Syngal, Sapna

    2008-12-01

    Colorectal cancer (CRC) screening rates in the US are suboptimal, particularly among lower income and racial/ethnically diverse groups. If specific populations have limited awareness of screening when they reach age 50, there may be delays in screening adoption. This study investigated sociodemographic and social contextual factors associated with awareness of CRC and intentions to be screened at age 50 among 692 low income, racial, and ethnic minority adults living in low income housing. The majority of respondents (62%) were between ages 30 and 49, and 94% had some form of health insurance (e.g., Medicaid). About 70% reported having heard about CRC screening; 66% reported intentions to be screened at age 50. In multivariable analyses, screening awareness was associated with age and education. Immigrants who had English as a second language had lower awareness. Females tended to have higher awareness if they had private insurance; there were no differences among males. Multivariable analyses found that screening intentions were higher among men, those with more role responsibilities, more role conflicts, and higher levels of social cohesion. It is important to identify opportunities for maximizing screening uptake among those who become age-eligible for screening if we are to make a significant impact on CRC disparities. PMID:18478340

  20. Vulva cancer

    MedlinePlus

    ... Cancer - perineum; Cancer - vulvar; Genital warts - vulvar cancer; HPV - vulvar cancer ... is rare. Risk factors include: Human papilloma virus (HPV, or genital warts ) infection in women under age ...

  1. Lifestyle and reproductive risk factors associated with anal cancer in women aged over 50 years

    PubMed Central

    Coffey, K; Beral, V; Green, J; Reeves, G; Barnes, I

    2015-01-01

    Background: Anal cancer incidence increases with age and is higher in women than men. Risk factors in this group other than high-risk human papillomavirus infection are unclear. Methods: In all, 1.3 million women were recruited in 1996–2001 and followed for incident anal cancer. Cox regression models were used to calculate relative risks (RRs) for anal cancer by various potential risk factors. Results: Five hundred and seventeen incident anal cancers were registered over 13 years of follow-up. The largest RR was associated with a history of cervical intraepithelial neoplasia grade 3 (CIN 3; RR=4.03, 95% CI 2.59–6.28). Other factors associated with significantly increased risks in multivariate analyses were: ever smoking (RR=1.49, 1.24–1.80); previous use of oral contraceptives (RR=1.51, 1.24–1.83); nulliparity (RR=1.61, 1.24–2.07); tubal ligation (RR=1.39, 1.13–1.70) and not living with a partner (RR=1.82, 1.40–2.38). The association with smoking was significantly greater for squamous cell carcinoma than adenocarcinoma of the anus (RR 1.66 vs 0.89, P for heterogeneity=0.04). Conclusions: History of CIN 3, smoking, past oral contraceptive use, nulliparity, tubal ligation and not living with a partner are risk factors for anal cancer in women. There was a significant increase in risk associated with smoking for squamous cell anal cancers but not adenocarcinomas. PMID:25867258

  2. Energy metabolism and metabolic sensors in stem cells: the metabostem crossroads of aging and cancer.

    PubMed

    Menendez, Javier A; Joven, Jorge

    2014-01-01

    We are as old as our adult stem cells are; therefore, stem cell exhaustion is considered a hallmark of aging. Our tumors are as aggressive as the number of cancer stem cells (CSCs) they bear because CSCs can survive treatments with hormones, radiation, chemotherapy, and molecularly targeted drugs, thus increasing the difficulty of curing cancer. Not surprisingly, interest in stem cell research has never been greater among members of the public, politicians, and scientists. But how can we slow the rate at which our adult stem cells decline over our lifetime, reducing the regenerative potential of tissues, while efficiently eliminating the aberrant, life-threatening activity of "selfish", immortal, and migrating CSCs? Frustrated by the gene-centric limitations of conventional approaches to aging diseases, our group and other groups have begun to appreciate that bioenergetic metabolism, i.e., the production of fuel & building blocks for growth and division, and autophagy/mitophagy, i.e., the quality-control, self-cannibalistic system responsible for "cleaning house" and "recycling the trash", can govern the genetic and epigenetic networks that facilitate stem cell behaviors. Indeed, it is reasonable to suggest the existence of a "metabostem" infrastructure that operates as a shared hallmark of aging and cancer, thus making it physiologically plausible to maintain or even increase the functionality of adult stem cells while reducing the incidence of cancer and extending the lifespan. This "metabostemness" property could lead to the discovery of new drugs that reprogram cell metabotypes to increase the structural and functional integrity of adult stem cells and positively influence their lineage determination, while preventing the development and aberrant function of stem cells in cancer tissues. While it is obvious that the antifungal antibiotic rapamycin, the polyphenol resveratrol, and the biguanide metformin already belong to this new family of metabostemness

  3. DNA repair diseases: What do they tell us about cancer and aging?

    PubMed Central

    Menck, Carlos FM; Munford, Veridiana

    2014-01-01

    The discovery of DNA repair defects in human syndromes, initially in xeroderma pigmentosum (XP) but later in many others, led to striking observations on the association of molecular defects and patients’ clinical phenotypes. For example, patients with syndromes resulting from defective nucleotide excision repair (NER) or translesion synthesis (TLS) present high levels of skin cancer in areas exposed to sunlight. However, some defects in NER also lead to more severe symptoms, such as developmental and neurological impairment and signs of premature aging. Skin cancer in XP patients is clearly associated with increased mutagenesis and genomic instability, reflecting the defective repair of DNA lesions. By analogy, more severe symptoms observed in NER-defective patients have also been associated with defective repair, likely involving cell death after transcription blockage of damaged templates. Endogenously induced DNA lesions, particularly through oxidative stress, have been identified as responsible for these severe pathologies. However, this association is not that clear and alternative explanations have been proposed. Despite high levels of exposure to intense sunlight, patients from tropical countries receive little attention or care, which likely also reflects the lack of understanding of how DNA damage causes cancer and premature aging. PMID:24764756

  4. [Metastatic non-small cell lung cancer: Systemic treatment of patients aged 70 and over].

    PubMed

    Quoix, Elisabeth; Ducoloné, Alain; Mennecier, Bertrand; Fraisse, Philippe

    2011-04-01

    Patients aged 70 and over represent the third of the population of patients with lung cancer. There has been for a long time a certain nihilism regarding the treatment of elderly patients with advanced lung cancer as well from medical doctors but also from families and patients themselves with the false belief of an indolent course of the disease in elderly patients. As a result, clinical trials devoted to elderly patients were quite scarce until the end of the last decade. Nevertheless, an important trial was published in 1999 with the comparison of vinorelbine as a single agent versus best supportive care only in patients aged 70 and over with an advanced non-small cell lung cancer. The survival benefit with vinorelbine was important. Then two trials were published comparing monotherapy with either vinorelbine or gemcitabine to the doublet vinorelbine and gemcitabine without convincing results. As a consequence, the ASCO 2004 recommendations were to treat elderly patients with a monotherapy (gemcitabine or vinorelbine). Recently an IFCT trial was presented at the plenary session of the ASCO 2010. A carboplatin (every 4weeks)+weekly paclitaxel doublet was compared to a vinorelbine or gemcitabine (choice of the center). The survival benefit was of such magnitude that the paradigm of treatment of elderly patients PS 0-2 with advanced NSCLC should be modified in favor of the tested doublet. There should be a reappraisal of the geriatric indexes recommended by the oncogeriatricians regarding their exact prognostic or predictive role. PMID:21388776

  5. Optical Coherence Tomography Angiography of Type 2 Neovascularization in Age-Related Macular Degeneration.

    PubMed

    Souied, Eric H; El Ameen, Ala; Semoun, Oudy; Miere, Alexandra; Querques, Giuseppe; Cohen, Salomon Yves

    2016-01-01

    Well-defined choroidal neovascularization, known as type 2 neovascularization (NV) or classic NV, is the least representative phenotype of exudative age-related macular degeneration. Clinical aspects of type 2 NV have been widely described in the literature, and to date fluorescein angiography remains the gold standard for imaging age-related macular degeneration at initial presentation. Optical coherence tomography angiography (OCT-A) can be used to image vessels based on flow characteristics without any dye injection. Type 2 NV can be visualized using OCT-A with very typical patterns. A neovascular membrane appears as either a medusa-shaped complex or a glomerulus-shaped lesion in the outer retina and the choriocapillaris layer. Furthermore, in the choriocapillaris layer, the external borders of the lesion appear as a dark ring in most cases, and one or more central feeder vessels that extend deeply into the more profound choroidal layers are visible. Identification of type 2 NV is easily feasible for any clinician using OCT-A, especially in areas where there are normally no vessels, like in subretinal space, if the interpretation rules are respected. PMID:27023798

  6. Accelerated age-related olfactory decline among type 1 Usher patients

    PubMed Central

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

    2016-01-01

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

  7. Accelerated age-related olfactory decline among type 1 Usher patients.

    PubMed

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D

    2016-01-01

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin' Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

  8. The challenge of cancer in middle-income countries with an ageing population: Mexico as a case study.

    PubMed

    Aggarwal, Ajay; Unger-Saldaña, Karla; Lewison, Grant; Sullivan, Richard

    2015-01-01

    Mexico is undergoing rapid population ageing as a result of its epidemiological transition. This study explores the interface between this rapid population ageing and the burden of cancer. The number of new cancer cases is expected to increase by nearly 75% by 2030 (107,000 additional cases per annum), with 60% of cases in the elderly (aged ≥ 65). A review of the literature was supplemented by a bibliometric analysis of Mexico's cancer research output. Cancer incidence projections for selected sites were estimated with Globocan software. Data were obtained from recent national census, surveys, and cancer death registrations. The elderly, especially women and those living in rural areas, face high levels of poverty, have low rates of educational attainment, and many are not covered by health insurance schemes. Out of pocket payments and private health care usage remain high, despite the implementation of Seguro Popular that was designed to achieve financial protection for the lowest income groups. A number of cancers that predominate in elderly persons are not covered by the scheme and individuals face catastrophic expenditure in seeking treatment. There is limited research output in those cancer sites that have a high burden in the elderly Mexican population, especially research that focuses on outcomes. The elderly population in Mexico is vulnerable to the effects of the rising cancer burden and faces challenges in accessing high quality cancer care. Based on our evidence, we recommend that geriatric oncology should be an urgent public policy priority for Mexico. PMID:26015805

  9. The challenge of cancer in middle-income countries with an ageing population: Mexico as a case study

    PubMed Central

    Aggarwal, Ajay; Unger-Saldaña, Karla; Lewison, Grant; Sullivan, Richard

    2015-01-01

    Mexico is undergoing rapid population ageing as a result of its epidemiological transition. This study explores the interface between this rapid population ageing and the burden of cancer. The number of new cancer cases is expected to increase by nearly 75% by 2030 (107,000 additional cases per annum), with 60% of cases in the elderly (aged ≥ 65). A review of the literature was supplemented by a bibliometric analysis of Mexico’s cancer research output. Cancer incidence projections for selected sites were estimated with Globocan software. Data were obtained from recent national census, surveys, and cancer death registrations. The elderly, especially women and those living in rural areas, face high levels of poverty, have low rates of educational attainment, and many are not covered by health insurance schemes. Out of pocket payments and private health care usage remain high, despite the implementation of Seguro Popular that was designed to achieve financial protection for the lowest income groups. A number of cancers that predominate in elderly persons are not covered by the scheme and individuals face catastrophic expenditure in seeking treatment. There is limited research output in those cancer sites that have a high burden in the elderly Mexican population, especially research that focuses on outcomes. The elderly population in Mexico is vulnerable to the effects of the rising cancer burden and faces challenges in accessing high quality cancer care. Based on our evidence, we recommend that geriatric oncology should be an urgent public policy priority for Mexico. PMID:26015805

  10. Incidental Diagnosis of Bladder Cancer in a 17-year-old Patient.

    PubMed

    Facio, Fernando Nestor; Facio, Maria Fernanda W; Spessoto, Luis Cesar F; Gatti, Marcio; Ferraz Arruda, Pedro F; Ferraz Arruda, Jose G; Gabriotti, Luis Francisco B; Polotto, Pedro Paulo Silva L

    2015-07-01

    Bladder cancer is the fourth most common type of cancer among males and the ninth most common cause of cancer death. Bladder cancer can occur at any age. This paper reports the incidental diagnosis of bladder cancer in a 17-year-old female patient. Data on bladder cancer at this age are uncommon in the literature. PMID:26793515

  11. T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin.

    PubMed

    Dziegielewska, Barbara; Casarez, Eli V; Yang, Wesley Z; Gray, Lloyd S; Dziegielewski, Jaroslaw; Slack-Davis, Jill K

    2016-03-01

    Ovarian cancer is the deadliest gynecologic cancer, due in large part to the diagnosis of advanced stage disease, the development of platinum resistance, and inadequate treatment alternatives. Recent studies by our group and others have shown that T-type calcium (Ca(2+)) channels play a reinforcing role in cancer cell proliferation, cell-cycle progression, and apoptosis evasion. Therefore, we investigated whether T-type Ca(2+) channels affect ovarian tumor growth and response to platinum agents. Inhibition of T-type Ca(2+) channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer cells with a simultaneous increase in apoptosis, which was accompanied by decreased expression of the antiapoptotic gene survivin (BIRC5). Analysis of intracellular signaling revealed mibefradil reduced AKT phosphorylation, increased the levels and nuclear retention of FOXO transcription factors that repress BIRC5 expression, and decreased the expression of FOXM1, which promotes BIRC5 expression. Combining carboplatin with mibefradil synergistically increased apoptosis in vitro. Importantly, mibefradil rendered platinum-resistant ovarian tumors sensitive to carboplatin in a mouse model of peritoneal metastasis. Together, the data provide rationale for future use of T-type channel antagonists together with platinum agents for the treatment of ovarian cancer. Mol Cancer Ther; 15(3); 460-70. ©2016 AACR. PMID:26832797

  12. Breakpoint Analysis of Transcriptional and Genomic Profiles Uncovers Novel Gene Fusions Spanning Multiple Human Cancer Types

    PubMed Central

    Giacomini, Craig P.; Sun, Steven; Varma, Sushama; Shain, A. Hunter; Giacomini, Marilyn M.; Balagtas, Jay; Sweeney, Robert T.; Lai, Everett; Del Vecchio, Catherine A.; Forster, Andrew D.; Clarke, Nicole; Montgomery, Kelli D.; Zhu, Shirley; Wong, Albert J.; van de Rijn, Matt; West, Robert B.; Pollack, Jonathan R.

    2013-01-01

    Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a “breakpoint analysis” pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1), SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2), RAF1 kinase in pancreatic cancer (ATG7/RAF1) and anaplastic astrocytoma (BCL6/RAF1), EWSR1 in melanoma (EWSR1/CREM), CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/CDK6), and CLTC in breast cancer (CLTC/VMP1). Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases), with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis. PMID:23637631

  13. A Population-Based Cohort Study of All-Cause and Site-Specific Cancer Incidence Among Patients With Type 1 Diabetes Mellitus in Taiwan

    PubMed Central

    Hsu, Pei-Chun; Lin, Wei-Hung; Kuo, Te-Hui; Lee, Hui-Mei; Kuo, Chieh; Li, Chung-Yi

    2015-01-01

    Background The relationship between type 1 diabetes mellitus (T1DM) and cancer incidence remains unclear. We sought to assess the all-cause and site-specific cancer incidence in patients with T1DM. Methods A retrospective cohort study design was employed, in which 14 619 patients with T1DM were retrieved from Taiwan’s National Health Insurance medical claims between 2000 and 2007. The study subjects were followed to the end of 2008, and cancer incidence was assessed. We calculated age-, sex-, and calendar year-standardized incidence ratios (SIRs) of all-cause cancer incidence and site-specific neoplasm incidence, with reference to the general population. Results Seven hundred and sixty patients were identified for all-cause cancer over 86 610 person-years, representing an incidence rate of 87.75 cases per 10 000 person-years. The incidence rate was higher in males than in female patients (109.86 vs 69.75 cases per 10 000 person-years). T1DM was associated with a significantly increased SIR of all-cause cancer (1.13; 95% confidence interval [CI], 1.05–1.22). The sex-specific SIR was significantly elevated in female patients (1.19; 95% CI, 1.07–1.33), but the SIR for male patients was insignificantly elevated (1.09; 95% CI, 0.99–1.20). Pancreatic cancer showed the greatest increase in SIR among both male and female patients with T1DM. Male patients experienced significantly increased SIRs for kidney, rectum, liver, and colon neoplasm, and significantly increased SIRs were noted for ovarian, bladder, and colon cancer in female patients. Conclusions T1DM was associated with a 13% increase in risk of all-cause cancer incidence. Patients with T1DM should be advised to undergo cancer screening for certain types of cancer. PMID:26212724

  14. Effects of Type of Health Insurance Coverage on Colorectal Cancer Survival in Puerto Rico: A Population-Based Study

    PubMed Central

    Ortiz-Ortiz, Karen J.; Ramírez-García, Roberto; Cruz-Correa, Marcia; Ríos-González, Moraima Y.; Ortiz, Ana Patricia

    2014-01-01

    Colorectal cancer represents a major health problem and an important economic burden in Puerto Rico. In the 1990's, the Commonwealth of Puerto Rico implemented a health care reform through the privatization of the public health system. The goal was to ensure access to health services, eliminate disparities for medically indigent citizens and provide special coverage for high-risk conditions such as cancer. This study estimates the 5-year relative survival rate of colorectal cancer and the relative excess risk of death in Puerto Rico for 2004–2005, by type of health insurance coverage; Government Health Plan vs. Non-Government Health Plan. Colorectal cancer in advanced stages was more common in Government Health Plan patients compared with Non-Government Health Plan patients (44.29% vs. 40.24 had regional extent and 13.58% versus 10.42% had distant involvement, respectively). Government Health Plan patients in the 50–64 (RR = 6.59; CI: 2.85–15.24) and ≥65 (RR = 2.4; CI: 1.72–4.04) age-groups had the greater excess risk of death compared with Non-Government Health Plan patients. Further studies evaluating the interplay of access to health services and the barriers affecting the Government Health Plan population are warranted. PMID:24796444

  15. Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

    PubMed Central

    Kirzin, Sylvain; Marisa, Laetitia; Guimbaud, Rosine; De Reynies, Aurélien; Legrain, Michèle; Laurent-Puig, Pierre; Cordelier, Pierre; Pradère, Bernard; Bonnet, Delphine; Meggetto, Fabienne; Portier, Guillaume; Brousset, Pierre; Selves, Janick

    2014-01-01

    Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45–60 years were excluded to help define “young” and “old” groups. Thirty-nine cases of sporadic EOCRC (patients≤45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013). Genetic studies also showed the absence of BRAF mutations (p = 0.022) and the methylator phenotype (p = 0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways

  16. Age, Race and Regional Disparities in Colorectal Cancer Incidence Rates in Georgia between 2000 and 2012

    PubMed Central

    Yoo, Wonsuk; De, Subhendu; Wilkins, Thad; Smith, Selina A.; Blumenthal, Daniel

    2016-01-01

    Colorectal cancer (CRC) incidence rates and mortality have been decreasing in the United States. Currently, states in the South have the smallest reduction in CRC mortality. The trends of CRC incidence rates in Georgia in comparison to the United States have not been investigated. We analyzed age-adjusted incidence rates of CRC in Georgia and the United States from 2000 to 2012 using data from SEER 18 registries. Age-adjusted incidence rates (95% CI) were calculated as cases per 100,000 to the 2000 US Standard population. CRC incidence rates were calculated for groupings based on age at time of diagnosis, race, sex, and geographic location within Georgia. Incidence rates were higher in males compared to females in Georgia. In Georgians age 50–64, incidence rates were higher compared to the US, while those ages 65+ displayed lower incidence rates. Black Georgians age 50–64 generally exhibited higher incidence rates of CRC and lower rates of decrease in incidence compared to other races in Georgia. Asian/Pacific Islander females age 50–64 in Georgia exhibited an increasing trend in incidence rate. Whites and blacks Georgians age 50–64 displayed higher incidence rates compared to the US, while Asian/Pacific Islanders displayed lower incidence rates. Greater incidence rates of CRC in rural and Greater Georgia were seen across all races when compared to overall rates in Georgia. Efforts should be made to address disparities in Georgia based on race and geographic location. Increased screening by colonoscopy or fecal occult blood testing, reduction of risk factors and promotion of healthy lifestyles can reduce CRC incidence rates. PMID:27042701

  17. Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis

    PubMed Central

    Xu, Hanxiao; Tian, Yijun; Yuan, Xun; Liu, Yu; Wu, Hua; Liu, Qian; Wu, Gen Sheng; Wu, Kongming

    2016-01-01

    Cluster of differentiation 44 (CD44) is a transmembrane glycoprotein that serves as the receptor for the extracellular matrix component hyaluronic acid. CD44 has been reported to play key roles in cell proliferation, motility, and survival, but its role in breast cancer remains controversial. In this study, we conducted a meta-analysis. A total of 23 published Gene Expression Omnibus databases were included to evaluate the association between CD44 mRNA expression and clinicopathological characteristics or prognosis of the patients with breast cancer. Our analysis revealed that CD44 expression was associated with clinicopathological features, including the histological grade, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor-2 status. Higher levels of CD44 expression were observed in the basal subtype of breast cancer both at the mRNA and protein levels (odds ratio [OR] =2.08, 95% confidence interval [CI]: 1.72–2.52; OR =2.11, 95% CI: 1.67–2.68). Patients with CD44 overexpression exhibited significantly worse overall survival (hazard ratio =1.27; 95% CI: 1.04–1.55). Whole gene profile analysis revealed that CD44 expression was enriched in basal-type breast cancer and correlated with epithelial–mesenchymal transition and cancer stem cell gene profiles. In summary, our analyses indicated that CD44 potentially might be a prognostic marker for breast cancer and thus can serve as a therapeutic target for basal-type breast cancer. PMID:26855592

  18. Battling regional (stage III) lung cancer: bumpy road of a cancer survivor in the immunotherapy age.

    PubMed

    Hao, Zhonglin; Biddinger, Paul; Schroeder, Carsten; Tariq, Khurram

    2016-01-01

    A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles. Despite not being eligible for a durvalumab trial because of lack of PD-L1 expression, she had a meaningful response to nivolumab. Once every 2 weeks, infusion of nivolumab resulted in rapid tumour shrinkage in multiple areas. In the next few months, she experienced a variety of side effects, some of which were potentially life-threatening. She had disease progression 9 months into treatment. PMID:27389724

  19. Probing Radial age/metallicity degeneracy in early-type galaxies

    NASA Astrophysics Data System (ADS)

    Silva, David R.; Elston, Richard

    1994-06-01

    It has been generally concluded that the optical broad band color and line index gradients observed in early-type galaxies are driven by metallicity. Yet, this conclusion remains uncertain due to the age/metallicity degeneracy inherent in most optical data. Furthermore, optical broad-band colors are susceptible to reddening in the presence of dust. Near-infrared colors, on the other hand, are significantly less age sensitive than optical colors in old stellar populations and are much less affected by dust. In principle, the combination of optical and near-IR data should provide less ambivalent age and metallicity discrimination than using optical or near-IR data alone. To investigate this possibility, near-IR images of early-type galaxies with significant U-R gradients have been measured. Comparison of the optical and near-IR results leads to the primary conclusion that broad-band optical and near-IR gradients are not tracing metallicity in concert but are affected by different astrophysical parameters. Three general possibilites are discussed: reddening, radial age gradients, and differing metallicity sensitivities. Proving the absence or presence of significant reddening is difficult from broad-band colors alone. In the absence of reddening, the optical color gradients would suggest that age decreases wit radius, leading to somewhat contrived evolution scenarios. Alternatively, it is proposed that the optical color gradients may be tracing light element (e.g. CNO) abundances while the near-IR gradients are tracing Fe- peak element abundances. This scenario leads to the conclusion that many of these galaxies have enhanced nuclear (light/FE) ratios, consistent with the recently published studies of nuclear line indices in these galaxies. Given the quality of the current available data, these hypotheses remain somewhat unconstrained. Nevertheless, this study reinforces the necessity of obtaining data over a long spectral baseline to properly interpret the ensemble

  20. Age-time patterns of radiogenic cancer risk: their nature and likely explanations.

    PubMed

    Pierce, Donald A

    2002-09-01

    It is important for both radiation protection and scientific reasons to understand the age-time patterns of radiation cancer risk. This is surprisingly difficult even for acute exposures and much more so for prolonged exposures. I shall provide current information on this for solid cancers among atomic-bomb survivors, pointing out some of the difficulties in description and interpretation. I shall then take up some stochastic considerations regarding accumulation of mutations, which may help in dealing with these difficulties. These considerations are highly idealised, and their consequences should mainly be used only for guidance rather than as a primary basis for descriptive analyses. They are particularly suitable for this because they provide insights fairly independent of parameter values in the stochastic models involved. PMID:12400964

  1. Cancer Strikes Out!/Definitions/ Glossary/ Common Types

    MedlinePlus

    ... have an indolent (slow-growing) course or an aggressive (fast-growing) course. These subtypes behave and respond ... non-Hodgkin's lymphoma, which can be divided into aggressive (fast-growing) and indolent (slow-growing) types and ...

  2. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression.

    PubMed

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

    2016-05-01

    Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2. PMID:27121132

  3. Designing exercise clinical trials for older adults with cancer: Recommendations from 2015 Cancer and Aging Research Group NCI U13 Meeting.

    PubMed

    Kilari, Deepak; Soto-Perez-de-Celis, Enrique; Mohile, Supriya Gupta; Alibhai, Shabbir M H; Presley, Carolyn J; Wildes, Tanya M; Klepin, Heidi D; Demark-Wahnefried, Wendy; Jatoi, Amina; Harrison, Robert; Won, Elizabeth; Mustian, Karen M

    2016-07-01

    Cancer and its treatment can lead to a myriad of adverse events and negatively impact quality of life of older cancer patients and survivors. Unmet physical activity needs vary across the cancer continuum and remain an important yet understudied area of research in this population. Exercise interventions have been shown to be effective in treating both the physical and psychological declines associated with cancer and its treatment, with a potential to improve cancer-related outcomes. Despite the current evidence, exercise is clearly underutilized due to several barriers and knowledge gaps in existing trials that include appropriate population identification, design, and outcome measures selection. The benefits of regular exercise in both the primary and secondary prevention of chronic conditions are well established in the non-cancer population. In older cancer patients and survivors, further research is needed before exercise gains widespread acceptance. The Cancer and Aging Research Group convened experts in exercise, aging and cancer to evaluate current scientific evidence and knowledge gaps in geriatric exercise oncology. This report summarizes these findings and provides future research directions. PMID:27197916

  4. Designing exercise clinical trials for older adults with cancer: Recommendations from 2015 Cancer and Aging Research Group NCI U13 Meeting

    PubMed Central

    Kilari, Deepak; Soto-Perez-de-Celis, Enrique; Mohile, Supriya Gupta; Alibhai, Shabbir M.H.; Presley, Carolyn J.; Wildes, Tanya M.; Klepin, Heidi D.; Demark-Wahnefried, Wendy; Jatoi, Amina; Harrison, Robert; Won, Elizabeth; Mustian, Karen M.

    2016-01-01

    Cancer and its treatment can lead to a myriad of adverse events and negatively impact quality of life of older cancer patients and survivors. Unmet physical activity needs vary across the cancer continuum and remain an important yet understudied area of research in this population. Exercise interventions have been shown to be effective in treating both the physical and psychological declines associated with cancer and its treatment, with a potential to improve cancer-related outcomes. Despite the current evidence, exercise is clearly underutilized due to several barriers and knowledge gaps in existing trials that include appropriate population identification, design, and outcome measures selection. The benefits of regular exercise in both the primary and secondary prevention of chronic conditions are well established in the non-cancer population. In older cancer patients and survivors, further research is needed before exercise gains widespread acceptance. The Cancer and Aging Research Group convened experts in exercise, aging and cancer to evaluate current scientific evidence and knowledge gaps in geriatric exercise oncology. This report summarizes these findings and provides future research directions. PMID:27197916

  5. Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics

    PubMed Central

    Gilroy, Kathryn L.; Terry, Anne; Naseer, Asif; de Ridder, Jeroen; Wang, Weiwei; Carpenter, Eric; Mason, Andrew; Wong, Gane K-S.; Kilbey, Anna; Neil, James C.

    2016-01-01

    Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types. PMID:27097319

  6. Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics.

    PubMed

    Gilroy, Kathryn L; Terry, Anne; Naseer, Asif; de Ridder, Jeroen; Allahyar, Amin; Wang, Weiwei; Carpenter, Eric; Mason, Andrew; Wong, Gane K-S; Cameron, Ewan R; Kilbey, Anna; Neil, James C

    2016-01-01

    Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types. PMID:27097319

  7. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.

    PubMed

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a 'common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  8. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types

    PubMed Central

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P.; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a ‘common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  9. Prediction of Female Breast Cancer Incidence among the Aging Society in Kanagawa, Japan

    PubMed Central

    Katayama, Kayoko

    2016-01-01

    Owing to the increasing number of elderly “baby boomers” in Japan, the number of cancer patients is also expected to increase. Approximately 2 million baby boomers from nearby local areas are residing in metropolitan areas; hence, the geographical distribution of cancer patients will probably markedly change. We assessed the expected number of breast cancer (BC) patients in different regions (urban, outer city, town, rural) using estimates of the nation’s population and Kanagawa Cancer Registry data. To estimate future BC incidence for each region, we multiplied the 2010 rate by the predicted female population for each region according to age group. The incidence cases of BC in those aged ≥65 years is expected to increase in all areas; in particular, compared to rates in 2010, the BC incidence in urban areas was predicted to increase by 82.6% in 2035 and 102.2% in 2040. Although the incidence in all BC cases in urban areas showed an increasing trend, until peaking in 2040 (increasing 31.2% from 2010), the number of BC patients would continue to decrease in other areas. The number of BC patients per capita BC specialist was 64.3 patients in 2010; this value would increase from 59.3 in 2010 to 77.7 in 2040 in urban areas, but would decrease in other areas. Our findings suggest that the number of elderly BC patients is expected to increase rapidly in urban areas and that the demand for BC treatment would increase in the elderly population in urban areas. PMID:27532126

  10. Human papillomavirus types 16 and 18 and the prognosis of patients with stage I cervical cancer

    PubMed Central

    de Araújo Catão Zampronha, Rossana; Freitas-Junior, Ruffo; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi; Barbaresco, Aline Almeida; Adad, Sheila Jorge; de Oliveira, Amaurillo Monteiro; Rassi, Amanda B.; Oton, Glória Jabur Bittar

    2013-01-01

    OBJECTIVE: This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis. METHODS: A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival. RESULTS: The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p = 0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p = 0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18. CONCLUSION: In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy. PMID:23778490

  11. Neurocognitive Functioning in Preschool-age Children with Type 1 Diabetes Mellitus

    PubMed Central

    Patiño-Fernández, Anna Maria; Delamater, Alan M.; Applegate, E. Brooks; Brady, Erika; Eidson, Margaret; Nemery, Robin; Gonzalez-Mendoza, Luis; Richton, Samuel

    2010-01-01

    Neurocognitive functioning may be compromised in children with type 1 diabetes mellitus (T1DM). The factor most consistently implicated in the long-term neurocognitive functioning of children with T1DM is age of onset. The pediatric literature suggests that glycemic extremes may have an effect on the neurocognitive functioning of children, but findings are mixed. The purpose of this study was to compare the neurocognitive functioning of young children with T1DM diagnosed before six years of age and healthy children (i.e., without chronic illness). Additionally, in the children with T1DM, we examined the relationship between their neurocognitive functioning and glycemic control. Sixty eight (36 with T1DM and 32 without chronic illness) preschool-age children (M age = 4.4yrs) were recruited and administered a battery of instruments to measure cognitive, language, and fine motor skills. Children with T1DM performed similarly to the healthy controls and both groups' skills fell in the average range. Among children with diabetes, poor glycemic control (higher HbA1c) was related to lower general cognitive abilities (r = -.44, p < .04), slower fine motor speed (r = -.64, p < .02), and lower receptive language scores (r = -.39, p < .04). Such findings indicate that young children with T1DM already demonstrate some negative neurocognitive effects in association with chronic hyperglycemia. PMID:20456084

  12. Colorectal cancer in aged patients. Toward the routine treatment through laparoscopic surgical approach

    PubMed Central

    VECCHIO, R.; MARCHESE, S.; FAMOSO, F.; LA CORTE, F.; MARLETTA, S.; LEANZA, G.; ZANGHÌ, G.; LEANZA, V.; INTAGLIATA, E.

    2015-01-01

    Aim Colorectal cancer is one of the most common malignancies in general population. The incidence seems to be higher in older age. Surgery remains the treatment of choice and laparoscopic approach offers numerous benefits. We report our personal experience in elderly patients operated on for colorectal cancer with laparoscopic resection. Patients and methods From January 2003 to September 2013, out of 160 patients aged 65 years or older and operated with minimally invasive techniques, 30 cases affected by colorectal cancer and operated on with laparoscopic approach were analyzed in this study. Results Male/female ratio was 1.35 and mean age 72 years. Constipation, weight loss, anemia and rectal bleeding were the most commonly reported symptoms. Lesions involved descending-sigmoid colon in 53% of cases, rectum in 37% and ascending colon in 10%. Among laparoscopic colorectal operations laparoscopic left colectomy was the most frequently performed, followed by right colectomy, abdominoperineal resection and Hartmann procedure. Operative times ranged from 3 to 5 hours depending on surgical procedure performed. Mean hospital stay was 6 days (range 4–9). Conversion to open approach occurred only in a case of laparoscopic right colectomy (3%) for uncontrolled bleeding. A single case of mortality was reported. In two cases (7%) anastomotic leakage was observed, conservatively treated in one patient and requiring reoperation in the other one. Conclusions Laparoscopic colorectal surgery is feasible and effective for malignancies in elderly population offering several advantages including immunologic and oncologic ones. However an experienced surgical team is essential in reducing risks and complications. PMID:25827663

  13. HDL Cholesterol and Cancer Risk Among Patients With Type 2 Diabetes

    PubMed Central

    Zhao, Wenhui; Guan, Jing; Horswell, Ronald; Li, Weiqin; Wang, Yujie; Wu, Xiaocheng

    2014-01-01

    OBJECTIVE To investigate the relationship between HDL cholesterol (HDL-C) and cancer risk among type 2 diabetic patients. RESEARCH DESIGN AND METHODS We performed a retrospective cohort study of 14,169 men and 23,176 women with type 2 diabetes. Cox proportional hazards regression models were used to estimate the association of various levels of HDL cholesterol (HDL-C) with cancer risk. RESULTS During a mean follow-up period of 6.4 years, 3,711 type 2 diabetic patients had a cancer diagnosis. A significant inverse association between HDL-C and the risk of cancer was found among men and women. The multivariable-adjusted hazard ratios (HRs) of cancer at various levels of HDL-C at baseline (<30, 30–39.9, 40–49.9, 50–59.9, 60–69.9, 70–79.9, and ≥80 mg/dL) were 1.00, 0.87, 0.95, 1.01, 0.61, 0.45, and 0.37, respectively, in men (Ptrend = 0.027) and 1.00, 0.98, 0.88, 0.85, 0.84, 0.86, and 0.84, respectively, in women (Ptrend = 0.025). When stratified by race, BMI, smoking status, or medication use, the inverse association was still present. With an updated mean of HDL-C used in the analysis, the inverse association of HDL-C with cancer risk did not change. The inverse association substantially attenuated after excluding patients who died of or were diagnosed with cancer during the first 2 years of follow-up. CONCLUSIONS The study suggests an inverse association of HDL-C with cancer risk among men and women with type 2 diabetes, whereas the effect of HDL-C was partially mediated by reverse causation. PMID:25216507

  14. Clinical Experience of Bronchoscopy-Guided Radiofrequency Ablation for Peripheral-Type Lung Cancer

    PubMed Central

    Koizumi, Tomonobu; Kobayashi, Takashi; Tanabe, Tsuyoshi; Tsushima, Kenji; Yasuo, Masanori

    2013-01-01

    We have developed a new internal cooled electrode for radiofrequency ablation (RFA) (Japan Application no. 2006-88228) suitable for forceps channel bronchoscopy. Here, we present our clinical experience with bronchoscopy-guided RFA under computed tomography (CT) monitoring for patients with peripheral-type non-small-cell lung cancer (NSCLC). Bronchoscopy-guided RFA was performed in two patients (80 and 70 years old) with NSCLC, who had no lymph node involvement and distant metastases (T1N0M0), but not indicated for surgery because of other complications, such as advanced age, poor pulmonary function, and refusal of thoracic surgery. The locations of the tumors were right S2 and left S3, respectively. Although the tumors showed ground-glass opacity (GGO) with solid components in both cases, radiographic findings changed to reduced mass-like shadow and remained stable for 4 and 3.5 years after bronchoscopy-guided RFA. As the former case developed progressive disease on chest CT, bronchoscopy-guided RFA was repeated in the same lesion, resulting in no change for the subsequent 1 year. There were no adverse reactions during the procedures. Thus, bronchoscopy-guided RFA is a safe and feasible procedure that represents a potentially useful therapeutic tool in local control in medically inoperable patients with stage I NSCLC. PMID:24106625

  15. The generation and maintenance of visual mental images: evidence from image type and aging.

    PubMed

    De Beni, Rossana; Pazzaglia, Francesca; Gardini, Simona

    2007-04-01

    Imagery is a multi-componential process involving different mental operations. This paper addresses whether separate processes underlie the generation, maintenance and transformation of mental images or whether these cognitive processes rely on the same mental functions. We also examine the influence of age on these mental operations for independence of components. In Experiment 1, younger (22 years) and older (69 years) adults generated and maintained general, specific, contextual and autobiographical visual mental images evoked in response to concrete nouns. The older adults had longer generation times, but there was no difference between the two groups on maintenance. Both groups had shortest generation and maintenance times for general images, whereas only the older adults took longest in generating autobiographical images. In Experiment 2, the total maintenance time and number of transformations for each type of image were compared in another group of younger and older adults. General images were less transformed and more subject to decay for both groups. The older people maintained the autobiographical mental images for longest compared to other image types. In conclusion, image generation, maintenance and transformation seem to be differently affected by type of image and aging, supporting a model of their cognitive segregation. PMID:17074426

  16. Sex, age, race and intervention type in clinical studies of HIV cure: a systematic review.

    PubMed

    Johnston, Rowena E; Heitzeg, Mary M

    2015-01-01

    This systematic review was undertaken to determine the extent to which adult subjects representing sex (female), race (nonwhite), and age (>50 years) categories are included in clinical studies of HIV curative interventions and thus, by extension, the potential for data to be analyzed that may shed light on the influence of such demographic variables on safety and/or efficacy. English-language publications retrieved from PubMed and from references of retrieved papers describing clinical studies of curative interventions were read and demographic, recruitment year, and intervention-type details were noted. Variables of interest included participation by sex, age, and race; changes in participation rates by recruitment year; and differences in participation by intervention type. Of 151 publications, 23% reported full demographic data of study enrollees, and only 6% reported conducting efficacy analyses by demographic variables. Included studies recruited participants from 1991 to 2011. No study conducted safety analyses by demographic variables. The representation of women, older people, and nonwhites did not reflect national or international burdens of HIV infection. Participation of demographic subgroups differed by intervention type and study location. Rates of participation of demographic groups of interest did not vary with time. Limited data suggest efficacy, particularly of early therapy initiation followed by treatment interruption, may vary by demographic variables, in this case sex. More data are needed to determine associations between demographic characteristics and safety/efficacy of curative interventions. Studies should be powered to conduct such analyses and cure-relevant measures should be standardized. PMID:25313793

  17. Sex, Age, Race and Intervention Type in Clinical Studies of HIV Cure: A Systematic Review

    PubMed Central

    Heitzeg, Mary M.

    2015-01-01

    Abstract This systematic review was undertaken to determine the extent to which adult subjects representing sex (female), race (nonwhite), and age (>50 years) categories are included in clinical studies of HIV curative interventions and thus, by extension, the potential for data to be analyzed that may shed light on the influence of such demographic variables on safety and/or efficacy. English-language publications retrieved from PubMed and from references of retrieved papers describing clinical studies of curative interventions were read and demographic, recruitment year, and intervention-type details were noted. Variables of interest included participation by sex, age, and race; changes in participation rates by recruitment year; and differences in participation by intervention type. Of 151 publications, 23% reported full demographic data of study enrollees, and only 6% reported conducting efficacy analyses by demographic variables. Included studies recruited participants from 1991 to 2011. No study conducted safety analyses by demographic variables. The representation of women, older people, and nonwhites did not reflect national or international burdens of HIV infection. Participation of demographic subgroups differed by intervention type and study location. Rates of participation of demographic groups of interest did not vary with time. Limited data suggest efficacy, particularly of early therapy initiation followed by treatment interruption, may vary by demographic variables, in this case sex. More data are needed to determine associations between demographic characteristics and safety/efficacy of curative interventions. Studies should be powered to conduct such analyses and cure-relevant measures should be standardized. PMID:25313793

  18. Effects of subprimal type, quality grade, and aging time on display color of ground beef patties.

    PubMed

    Garner, C M; Unruh, J A; Hunt, M C; Boyle, E A E; Houser, T A

    2014-10-01

    A factorial design was used to evaluate the effects of two subprimal types (chuck roll and knuckle), two quality grades (Premium Choice and Select), and three vacuum-storage aging times before processing (7, 21, and 42d) ground beef patty display color attributes. Patties from chuck roll and Premium Choice subprimals had brighter red visual color scores, less discoloration, and higher L*, a*, b*, and chroma values than those from knuckle and Select subprimals, respectively. With an increased display time, patties became darker red, more discolored, and had decreased L*, a*, b*, and chroma values. Therefore, aging Premium Choice chuck rolls for less time (fewer than 21d) could maximize display color life. PMID:24880976

  19. Challenges in Recruiting Aging Women Holocaust Survivors to a Case Control Study of Breast Cancer.

    PubMed

    Vin-Raviv, Neomi; Dekel, Rachel; Barchana, Micha; Linn, Shai; Keinan-Boker, Lital

    2015-01-01

    Older adults are underrepresented in medical research for many reasons, including recruitment difficulties. Recruitment of older adults for research studies is often a time-consuming process and can be more challenging when the study involves older adults with unique exposures to traumatic events and from minority groups. The current article provides a brief overview of (a) challenges encountered while recruiting aging women Holocaust survivors for a case control study and (b) strategies used for meeting those challenges. The case group comprised women Holocaust survivors who were recently diagnosed with breast cancer and the control group comprised healthy women from a Holocaust-survivor community in Israel. PMID:26020580

  20. Risk of Developing Second Cancer From Neutron Dose in Proton Therapy as Function of Field Characteristics, Organ, and Patient Age

    SciTech Connect

    Zacharatou Jarlskog, Christina; Paganetti, Harald

    2008-09-01

    Purpose: To estimate the risk of a second malignancy after treatment of a primary brain cancer using passive scattered proton beam therapy. The focus was on the cancer risk caused by neutrons outside the treatment volume and the dependency on the patient's age. Methods and Materials: Organ-specific neutron-equivalent doses previously calculated for eight different proton therapy brain fields were considered. Organ-specific models were applied to assess the risk of developing solid cancers and leukemia. Results: The main contributors (>80%) to the neutron-induced risk are neutrons generated in the treatment head. Treatment volume can influence the risk by up to a factor of {approx}2. Young patients are subject to significantly greater risks than are adult patients because of the geometric differences and age dependency of the risk models. Breast cancer should be the main concern for females. For males, the risks of lung cancer, leukemia, and thyroid cancer were significant for pediatric patients. In contrast, leukemia was the leading risk for an adult. Most lifetime risks were <1% (70-Gy treatment). The only exceptions were breast, thyroid, and lung cancer for females. For female thyroid cancer, the treatment risk can exceed the baseline risk. Conclusion: The risk of developing a second malignancy from neutrons from proton beam therapy of a brain lesion is small (i.e., presumably outweighed by the therapeutic benefit) but not negligible (i.e., potentially greater than the baseline risk). The patient's age at treatment plays a major role.

  1. Cancer risk according to type and location of ATM mutation in ataxia-telangiectasia families.

    PubMed

    Cavaciuti, E; Laugé, A; Janin, N; Ossian, K; Hall, J; Stoppa-Lyonnet, D; Andrieu, N

    2005-01-01

    Epidemiological studies have indicated that ataxia-telangiectasia (AT) heterozygotes in AT families have an increased risk of cancer, particularly of breast cancer (BC). However, in BC case-control studies, no significant differences were found in the frequency of ATM mutations between patients and controls. In such studies missense mutations were found more frequently than truncating mutations, suggesting that the cancer risk depends on mutation type. To investigate this possibility, we assessed the risk of BC according to the type and position of the ATM truncating mutation in extended AT families. DNA or RNA that had been isolated from blood or buccal cells of AT children and their relatives was screened for ATM germ-line mutations using restriction endonuclease fingerprinting, the protein truncation test, fluorescence-assisted mismatch analysis, and direct sequencing. The standardized incidence ratio of cancer associated with ATM heterozygosity status and type of mutation was estimated. We tested for genotype-phenotype correlations by simulations, permuting mutations among parental branches. No significant difference was found in the relative risk of breast cancer or any other type of cancer based on mutation type. However, the occurrence of BC may be associated with truncating mutations in certain binding domains of the ATM protein (e.g., P53/BRCA1, beta-adaptin, and FAT domains; P = 0.006). In this limited sample set, the presence of missense or truncating ATM mutations was not associated with different cancer risks. The risk of BC appeared to be associated with the alteration of binding domains rather than with the length of the predicted ATM protein. PMID:15390180

  2. Biology of the Mi-2/NuRD Complex in SLAC (Stemness, Longevity/Ageing, and Cancer)

    PubMed Central

    Zhang, Yue

    2011-01-01

    The dynamic chromatin activities of Mi-2/Nucleosome Remodeling and Histone deacetylation (Mi-2/NuRD) complexes in mammals are at the basis of current research on stemness, longevity/ageing, and cancer (4-2-1/SLAC), and have been widely studied over the past decade in mammals and the elegant model organism, Caenorhabditis elegans. Interestingly, a common emergent theme from these studies is that of distinct coregulator-recruited Mi-2/NuRD complexes largely orchestrating the 4-2-1/SLAC within a unique paradigm by maintaining genome stability via DNA repair and controlling three types of transcriptional programs in concert in a number of cellular, tissue, and organism contexts. Thus, the core Mi-2/NuRD complex plays a central role in 4-2-1/SLAC. The plasticity and robustness of 4-2-1/SLAC can be interpreted as modulation of specific coregulator(s) within cell-specific, tissue-specific, stage-specific, or organism-specific niches during stress induction, ie, a functional module and its networking, thereby conferring differential responses to different environmental cues. According to “Occam’s razor”, a simple theory is preferable to a complex one, so this simplified notion might be useful for exploring 4-2-1/SLAC with a holistic view. This thought could also be valuable in forming strategies for future research, and could open up avenues for cancer prevention and antiageing strategies. PMID:21523247

  3. Multi-omics approach to infer cancer therapeutic targets on chromosome 20q across tumor types

    PubMed Central

    Snijders, Antoine M; Mao, Jian-Hua

    2016-01-01

    The identification of good targets is a critical step for the development of targeted therapies for cancer treatment. Here, we used a multi-omics approach to delineate potential targets on chromosome 20q, which frequently shows a complex pattern of DNA copy number amplification in many human cancers suggesting the presence of multiple driver genes. By comparing the amounts of individual mRNAs in cancer from 11 different human tissues with those in their corresponding normal tissues, we identified 18 genes that were robustly elevated across human cancers. Moreover, we found that higher expression levels of a majority of these genes were associated with poor prognosis in many human cancer types. Using DNA copy number and expression data for all 18 genes obtained from The Cancer Genome Atlas project, we discovered that amplification is a major mechanism driving overexpression of these 18 genes in the majority of human cancers. Our integrated analysis suggests that 18 genes on chromosome 20q might serve as novel potential molecular targets for targeted cancer therapy.

  4. mDia1 regulates breast cancer invasion by controlling membrane type 1-matrix metalloproteinase localization

    PubMed Central

    Kim, Daehwan; Jung, Jangho; You, Eunae; Ko, Panseon; Oh, Somi; Rhee, Sangmyung

    2016-01-01

    Mammalian diaphanous-related formin 1 (mDia1) expression has been linked with progression of malignant cancers in various tissues. However, the precise molecular mechanism underlying mDia1-mediated invasion in cancer cells has not been fully elucidated. In this study, we found that mDia1 is upregulated in invasive breast cancer cells. Knockdown of mDia1 in invasive breast cancer profoundly reduced invasive activity by controlling cellular localization of membrane type 1-matrix metalloproteinase (MT1-MMP) through interaction with microtubule tracks. Gene silencing and ectopic expression of the active form of mDia1 showed that mDia1 plays a key role in the intracellular trafficking of MT1-MMP to the plasma membrane through microtubules. We also demonstrated that highly invasive breast cancer cells possessed invasive activity in a 3D culture system, which was significantly reduced upon silencing mDia1 or MT1-MMP. Furthermore, mDia1-deficient cells cultured in 3D matrix showed impaired expression of the cancer stem cell marker genes, CD44 and CD133. Collectively, our findings suggest that regulation of cellular trafficking and microtubule-mediated localization of MT1-MMP by mDia1 is likely important in breast cancer invasion through the expression of cancer stem cell genes. PMID:26893363

  5. Ethnic differences in the relationships between diabetes, early age adiposity and mortality among breast cancer survivors: the Breast Cancer Health Disparities Study.

    PubMed

    Connor, Avonne E; Visvanathan, Kala; Baumgartner, Kathy B; Baumgartner, Richard N; Boone, Stephanie D; Hines, Lisa M; Wolff, Roger K; John, Esther M; Slattery, Martha L

    2016-05-01

    The contribution of type 2 diabetes and obesity on mortality in breast cancer (BC) patients has not been well studied among Hispanic women, in whom these exposures are highly prevalent. In a multi-center population-based study, we examined the associations between diabetes, multiple obesity measures, and mortality in 1180 Hispanic and 1298 non-Hispanic white (NHW) women who were diagnosed with incident invasive BC from the San Francisco Bay Area, New Mexico, Utah, Colorado, and Arizona. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards regression models. The median follow-up time from BC diagnosis to death was 10.8 years. In ethnic-stratified results, the association for BC-specific mortality among Hispanics was significantly increased (HR 1.85 95 % CI 1.11, 3.09), but the ethnic interaction was not statistically significant. In contrast, obesity at age 30 increased BC-specific mortality risk in NHW women (HR 2.33 95 % CI 1.36, 3.97) but not Hispanics (p-interaction = 0.045). Although there were no ethnic differences for all-cause mortality, diabetes, obesity at age 30, and post-diagnostic waist-hip ratio were significantly associated with all-cause mortality in all women. This study provides evidence that diabetes and adiposity, both modifiable, are prognostic factors among Hispanic and NHW BC patients. PMID:27116186

  6. Neoadjuvant vs. adjuvant treatment of Siewert type II gastroesophageal junction cancer: an analysis of data from the surveillance, epidemiology, and end results (SEER) registry

    PubMed Central

    Miccio, Joseph A.; Oladeru, Oluwadamilola T.; Yang, Jie; Xue, Yaqi; Choi, Minsig; Zhang, Yue; Yoon, Hannah; Ryu, Samuel

    2016-01-01

    Background Cancer of the gastroesophageal junction (GEJ) has been rising in incidence in recent years. The role of radiation therapy (RT) in the treatment of GEJ cancer remains unclear, as the largest prospective trials advocating for either adjuvant or neoadjuvant chemoradiotherapy (CRT) combine GEJ cancer with either gastric or esophageal cancer. The aim of the present study is to examine the association of neoadjuvant versus adjuvant treatment with overall and disease-specific survival (DSS) for patients with surgically resected cancer of the true GEJ (Siewert type II). Methods The surveillance, epidemiology, and end results (SEER) registry database (2001–2011) was queried for cases of surgically resected Siewert type II GEJ cancer. A total of 1,497 patients with resectable GEJ cancer were identified, with 746 receiving adjuvant RT and 751 receiving neoadjuvant RT. Retrospective analysis was performed with the endpoints of overall and DSS. Results Using cox regression and controlling for independent covariates (age, sex, race, stage, grade, histology, and year of diagnosis), we showed that adjuvant RT was associated with a significantly lower death risk [hazard ratio (HR), 0.84; 95% confidence interval 0.73–0.97; P value=0.0168] and significantly lower disease-specific death risk (HR, 0.84; 95% confidence interval, 0.72–0.97; P value=0.0211) as compared to neoadjuvant RT. Conclusions This analysis of SEER data showed that adjuvant RT was associated with a survival benefit as compared to neoadjuvant RT for the treatment of Siewert type II GEJ cancer. We suggest future prospective studies to compare outcomes of adjuvant versus neoadjuvant treatment for true GEJ cancer. PMID:27284473

  7. Diagnostic yield of targeted next generation sequencing in various cancer types: an information-theoretic approach.

    PubMed

    Hagemann, Ian S; O'Neill, Patrick K; Erill, Ivan; Pfeifer, John D

    2015-09-01

    The information-theoretic concept of Shannon entropy can be used to quantify the information provided by a diagnostic test. We hypothesized that in tumor types with stereotyped mutational profiles, the results of NGS testing would yield lower average information than in tumors with more diverse mutations. To test this hypothesis, we estimated the entropy of NGS testing in various cancer types, using results obtained from clinical sequencing. A set of 238 tumors were subjected to clinical targeted NGS across all exons of 27 genes. There were 120 actionable variants in 109 cases, occurring in the genes KRAS, EGFR, PTEN, PIK3CA, KIT, BRAF, NRAS, IDH1, and JAK2. Sequencing results for each tumor were modeled as a dichotomized genotype (actionable mutation detected or not detected) for each of the 27 genes. Based upon the entropy of these genotypes, sequencing was most informative for colorectal cancer (3.235 bits of information/case) followed by high grade glioma (2.938 bits), lung cancer (2.197 bits), pancreatic cancer (1.339 bits), and sarcoma/STTs (1.289 bits). In the most informative cancer types, the information content of NGS was similar to surgical pathology examination (modeled at approximately 2-3 bits). Entropy provides a novel measure of utility for laboratory testing in general and for NGS in particular. This metric is, however, purely analytical and does not capture the relative clinical significance of the identified variants, which may also differ across tumor types. PMID:26227479

  8. Variation of benefits and harms of breast cancer screening with age.

    PubMed

    Harris, R

    1997-01-01

    The critical issue in deciding whether to recommend breast cancer screening for women in their forties is to determine whether potential benefits are substantially greater than potential harms. Recent evidence from randomized clinical trials makes it likely that, after 10-12 years of follow-up, there is a real benefit from screening women ages 40-49, on the order of a 15-20% reduction in the relative risk of breast cancer death. This relative risk reduction translates into an absolute risk reduction of 1-2 women whose lives are extended from screening 1,000 women in their forties annually for 10 years (i.e., about one life extended per 5,000 mammograms). The absolute benefit of screening increases with age. Evidence about potential harms is less well established, but it is compelling that there are 15-40 times as many false positive as true positive mammograms (depending on the patient's age), and that at least some of the women with false positive mammograms have ongoing psychological distress as a result. Some 30% of all women who are screened annually during their forties will have at least one false positive mammogram and this probability likely decreases with advancing age. If the balance between benefits and harms is judged to be a "close call" for women in their forties, a blanket recommendation for all is inappropriate. Instead, each woman in her forties should be helped to understand the pros and cons of screening, to clarify her own values, and to consider with her primary care physician what decision would be best for her. PMID:9709290

  9. Limited significance of curative surgery in Borrmann type IV gastric cancer.

    PubMed

    Kim, Eun Young; Yoo, Han Mo; Song, Kyo Young; Park, Cho Hyun

    2016-07-01

    Borrmann type IV advanced gastric cancer has a poor prognosis. Although surgical resection remains the only hope for a cure, the role of curative surgery is questionable in this type of cancer. This study defined the role of curative surgery in the prognosis of type IV gastric cancer. We analyzed 168 patients with Borrmann type IV undergoing surgery at Seoul St. Mary's Hospital from 1989 to 2010. We categorized the patients into curative (R0) and non-curative (R1, R2, and non-resection) groups. The curative and non-curative groups comprised 88 and 80 patients, respectively. The preoperative predictive value of Borrmann type IV was 50.5, and 8.9 % of the patients had microscopic resection margin involvement. The 3- to 5-year overall survival (OS) of patients in the curative group was significantly higher than that of in the non-curative group (p < 0.001). However, in a multivariate analysis, curability was not a significant predictor of survival (p = 0.187). In the curative group, the most frequent recurrence site was the peritoneum (85.7 %). Most recurrences occurred within 2 years. The role of surgery for Borrmann type IV is quite limited. Such cases have a poor prognosis even after curative surgery. In addition, microscopic resection margin involvement is frequent in type IV cancer because it is difficult to diagnose preoperatively. Therefore, multimodal diagnostic tools and treatment strategies should be developed for Borrmann type IV gastric cancer. PMID:27251378

  10. Aging among Persons with Intellectual Disability in Israel in Relation to Type of Residence, Age, and Etiology

    ERIC Educational Resources Information Center

    Lifshitz, Hefziba; Merrick, Joav

    2004-01-01

    This study was conducted to compare aging phenomena of persons with intellectual and developmental disability (ID) aged 40 years and older living in community residence (N=65) with those living with their families (N=43) in Jerusalem, Israel. All 108 persons and care givers were interviewed to ascertain health problems, sensory impairment,…

  11. Ages and Metallicities of Early-Type Void Galaxies from Line Strength Measurements

    NASA Astrophysics Data System (ADS)

    Wegner, Gary; Grogin, Norman A.

    2008-07-01

    We present spectroscopic observations of 26 galaxies of type E and S0, based on their blue morphologies, located in voids by the study of Grogin & Geller in 1999. Measurements of redshift, velocity dispersion, and four Lick line indices, Mg b , Fe5270, Fe5335, and Hβ with their errors are given for all of these galaxies, along with Hβ, [O III], Hα, and [N II] emission line strengths for a subset of these objects. These sources are brighter than M* for low-density regions and tend to be bluer than their counterpart early-type objects in high-density regions. Using the models of Thomas et al., developed in 2003, gives metal abundances and ages with a median α enhancement, [α/Fe] = +0.13, and median metal abundance, [Z/H] = +0.22, values comparable to those found for E and S0 galaxies in clusters, but with a wider spread in [Z/H] toward low values. If the emission line subsample is interpreted as younger, the proportion of young objects is higher than for early types in higher-density regions. There is a significant incidence of sources in the sample with emission lines in their spectra (46% with Hβ and [O III] and 69% with Hα or [N II]) as well as shells and rings in their morphologies (19%). The diagnostic log [{N\\,\\mathsc{ii}}]/ H\\alpha, log [{O\\,\\mathsc{iii}}]/ H\\beta diagram places 10 of 12 emission line galaxies in or near the star-forming and liner region and two among the Seyferts. The Hα fluxes indicate star-formation rates of 0.2-1.0 M sun yr-1. The percentage of these early-type void galaxies undergoing star formation appears to be higher compared to their cluster counterparts and the range of ages wider.

  12. In Silico Identification of OncomiRs in Different Cancer Types

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Malay; Bandyopadhyay, Sanghamitra

    2012-03-01

    The diagnosis, prognosis and therapeutics of various kinds of cancers are challenging domains of research. Current landmark of cancer research at the molecular level mainly focuses on the regulation of genes for studying cancer pathways. Recent investigations highlight that there is a significant association of a class of short RNAs in the progression of different types of cancer. In this paper, the involvement of microRNAs (miRNAs), a type of small endogenous RNAs, is explored in two categories of cancers in human, one tumor-based and another non-tumorous. A new approach of in silico identification of the miRNAs that might be associated with these cancer types is proposed. The oncomiRs, miRNAs associated with cancer, are identified by analyzing the differentially co-expressed miRNAs and further exploring how they cooperate with each other. Extensive computational analysis on miRNA expression profiles for the discovery of novel oncomiRs is pursued. The results are found to be promising by going deep into the regulatory information available on oncogenes from the up-to-date literature. Some of the miRNAs as oncogenic are identified by the approach like hsa-miR-186 and hsa-miR-154 for leukemia and prostate cancer, respectively, which are not included in standard databases. However, some of the emerging studies give evidences to these findings. Statistical and biological studies, on the other hand, strengthen the effectiveness of the proposed method in futuristic investigations for the exploration of undiscovered oncomiRs. On the whole, these analyses provide insight into the discovery of miRNA markers.

  13. Self-Perceptions of Age among 292 Chemotherapy-Treated Cancer Patients: Exploring Associations with Symptoms and Survival

    PubMed Central

    Lim, Ming Y.; Stephens, Elisabeth K.; Novotny, Paul; Price, Katharine; Salayi, Marcia; Roeker, Lindsey; Peethambaram, Prema; Jatoi, Aminah

    2013-01-01

    Background A growing literature suggests that older individuals who report feeling younger than their actual chronological age enjoy better health and survival. The purpose of this study was to explore similar associations in patients with cancer. Methods Chemotherapy-treated cancer patients completed a previously-validated questionnaire item on their self-perception of age. Concurrent patient-reported number of symptoms and pain severity were recorded. In addition, baseline and longitudinal data captured demographics and vital status, respectively. Results Among 292 patients, 185 (63%) reported that they perceived themselves as younger than their actual age, 45 as older (15%), 56 (19%) as the same age (unable to be determined in 6). The mean actual chronological age (standard deviation) among those who perceived themselves as younger, older, or the same age were 63 years (11), 54 (12), and 60 (10); (p< 0.0001). An inverse relationship was observed between self-perceived age and actual age (odds ratio 1.05 with 95% confidence interval of 1.02, 1.07; p=0.0001) but, otherwise, no statistically significant relationships were observed with gender, cancer curability potential, number of symptoms, or pain severity. Improved survival was associated with fewer symptoms and the potential for curing the cancer but not with patients’ age perceptions. Qualitative themes such as positive thinking, staying engaged with life, the importance of family, and maintaining a sense of humor emerged among those who felt younger. Conclusion A substantial percentage of patients with cancer -- particularly older ones -- report feeling younger than their actual age; this perception appears to have no relevance to symptoms or survival. PMID:23795225

  14. Age at diagnosis predicts deterioration in glycaemic control among children and adolescents with type 1 diabetes

    PubMed Central

    Clements, Mark A; Lind, Marcus; Raman, Sripriya; Patton, Susana R; Lipska, Kasia J; Fridlington, Amanda G; Tang, Fengming; Jones, Phil G; Wu, Yue; Spertus, John A; Kosiborod, Mikhail

    2014-01-01

    Background Poor glycemic control early in the course of type 1 diabetes mellitus (T1DM) increases the risk for microvascular complications. However, predictors of deteriorating control after diagnosis have not been described, making it difficult to identify high-risk patients and proactively provide aggressive interventions. Objective We examined whether diagnostic age, gender, and race were associated with deteriorating glycemic control during the first 5 years after diagnosis. Participants 2218 pediatric patients with T1DM. Methods We conducted a longitudinal cohort study of pediatric patients with T1DM from the Midwest USA, 1993–2009, evaluating within-patient glycated hemoglobin (HbA1c) trajectories constructed from all available HbA1c values within 5 years of diagnosis. Results 52.6% of patients were male; 86.1% were non-Hispanic Caucasian. The mean diagnostic age was 9.0±4.1 years. The mean number of HbA1c values/year/participant was 2.4±0.9. HbA1c trajectories differed markedly across age groups, with older patients experiencing greater deterioration than their younger counterparts (p<0.001). HbA1c trajectories, stratified by age, varied markedly by race (p for race×diagnostic age <0.001). Non-Hispanic African-American patients experienced higher initial HbA1c (8.7% vs 7.6% (71.6 vs 59.6 mmol/mol); p<0.001), and greater deterioration in HbA1c than non-Hispanic Caucasian patients across diagnostic ages (rise of 2.04% vs 0.99% per year (22.3 vs 10.8 mmol/mol/year); p<0.0001). Conclusions Older diagnostic age and black race are major risk factors for deterioration in glycemic control early in the course of T1DM. These findings can inform efforts to explore the reasons behind these differences and develop preventive interventions for high-risk patients. PMID:25452876

  15. Comparative analysis of somatic copy-number alterations across different human cancer types reveals two distinct classes of breakpoint hotspots

    PubMed Central

    Li, Yudong; Zhang, Li; Ball, Robyn L.; Liang, Xinle; Li, Jianrong; Lin, Zhenguo; Liang, Han

    2012-01-01

    Somatic copy-number alterations (SCNAs) play a crucial role in the development of human cancer. However, it is not well understood what evolutionary mechanisms contribute to the global patterns of SCNAs in cancer genomes. Taking advantage of data recently available through The Cancer Genome Atlas, we performed a systematic analysis on genome-wide SCNA breakpoint data for eight cancer types. First, we observed a high degree of overall similarity among the SCNA breakpoint landscapes of different cancer types. Then, we compiled 19 genomic features and evaluated their effects on the observed SCNA patterns. We found that evolutionary indel and substitution rates between species (i.e. humans and chimpanzees) consistently show the strongest correlations with breakpoint frequency among all the surveyed features; whereas the effects of some features are quite cancer-type dependent. Focusing on SCNA breakpoint hotspots, we found that cancer-type-specific breakpoint hotspots and common hotspots show distinct patterns. Cancer-type-specific hotspots are enriched with known cancer genes but are poorly predicted from genomic features; whereas common hotspots show the opposite patterns. This contrast suggests that explaining high-frequency SCNAs in cancer may require different evolutionary models: positive selection driven by cancer genes, and non-adaptive evolution related to an intrinsically unstable genomic context. Our results not only present a systematic view of the effects of genetic factors on genome-wide SCNA patterns, but also provide deep insights into the evolutionary process of SCNAs in cancer. PMID:22899649

  16. Persistence analysis in a Kolmogorov-type model for cancer-immune system competition

    NASA Astrophysics Data System (ADS)

    Bianca, C.; Pappalardo, F.; Pennisi, M.; Ragusa, M. A.

    2013-10-01

    This paper is concerned with analytical investigations on the competition between cancer cells and immune system cells. Specifically the role of the B-cells and T-cells in the evolution of cancer cells is taken into account. The mathematical model is a Kolmogorov-type system of three evolution equations where the growth rate of the cells is described by logistic law and the response of B-cells and T-cells is modeled according to Holling type-II function. The stability analysis of equilibrium points is performed and the persistence of the model is proved.

  17. Efficacy of quadrivalent human papillomavirus (types 6, 11, 16 and 18) vaccine (GARDASIL) in Japanese women aged 18-26 years.

    PubMed

    Yoshikawa, Hiroyuki; Ebihara, Keiko; Tanaka, Yoshiyuki; Noda, Kiichiro

    2013-04-01

    A randomized double-blind placebo-controlled phase II trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types most frequently associated with cervical cancer (types 16/18) and genital warts (types 6/11) in Japanese women aged 18-26 years. Participants were randomly assigned to either quadrivalent HPV (types 6/11/16/18) L1 virus-like particle vaccine (GARDASIL) (n = 509) or placebo (n = 512). Participants underwent regular gynecological examinations, cervicovaginal sampling for HPV DNA, testing for serum neutralizing antibodies to HPV and Papanicolau testing. The primary end-point was the combined incidence of persistent infection with HPV types 6, 11, 16 or 18 and cervical or external genital disease (i.e. cervical intraepithelial neoplasia, cervical cancer or external genital lesions related to HPV 6, 11, 16 or 18. Primary analyses were done per protocol. Combined incidence of persistent infection or disease with HPV 6, 11, 16 or 18 fell by 87.6% (95% confidence interval [CI], 59.2-97.6; P < 0.001), with HPV 6 or 11 by 73.1% (95% CI, -1.1-97.3; P = 0.0756) and with HPV 16 or 18 by 94.5% (95% CI, 65.2-99.9; P < 0.001) in those assigned vaccine compared with those assigned placebo. The median duration of follow up after month 7 in subjects was 23 months. In addition, the vaccine was well tolerated in Japanese women aged 18-26 years. Quadrivalent HPV vaccine could significantly reduce the acquisition of infection and clinical disease caused by HPV types 6, 11, 16 and 18. PMID:23331518

  18. Aging.

    PubMed

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  19. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  20. Tolerability of Combined Modality Therapy for Rectal Cancer in Elderly Patients Aged 75 Years and Older

    SciTech Connect

    Margalit, Danielle N.; Mamon, Harvey J.; Ryan, David P.; Blaszkowsky, Lawrence S.; Clark, Jeffrey; Willett, Christopher G.; Hong, Theodore S.

    2011-12-01

    Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham and Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability. Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed {>=}4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0). Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of

  1. Predictors of Surgery Types after Neoadjuvant Therapy for Advanced Stage Breast Cancer: Analysis from Florida Population-Based Cancer Registry (1996–2009)

    PubMed Central

    Al-Azhri, Jamila; Koru-Sengul, Tulay; Miao, Feng; Saclarides, Constantine; Byrne, Margaret M.; Avisar, Eli

    2015-01-01

    PURPOSE Despite the established guidelines for breast cancer treatment, there is still variability in surgical treatment after neoadjuvant therapy (NT) for women with large breast tumors. Our objective was to identify predictors of the type of surgical treatment: mastectomy versus breast-conserving surgery (BCS) in women with T3/T4 breast cancer who received NT. METHODS Population-based Florida Cancer Data System Registry, Florida’s Agency for Health Care Administration, and US census from 1996 to 2009 were linked for women diagnosed with T3/T4 breast cancer and received NT followed by either BCS or mastectomy. Analysis of multiple variables, such as sociodemographic characteristics (race, ethnicity, socioeconomic status, age, marital status, and urban/rural residency), tumor’s characteristics (estrogen/progesterone receptor status, histology, grade, SEER stage, and regional nodes positivity), treatment facilities (hospital volume and teaching status), patients’ comorbidities, and type of NT, was performed. RESULTS Of 1,056 patients treated with NT for T3/T4 breast cancer, 107 (10%) had BCS and 949 (90%) had mastectomy. After adjusting with extensive covariables, Hispanic patients (adjusted odds ratio (aOR) = [3.50], 95% confidence interval (CI): 1.38–8.84, P = 0.008) were more likely to have mastectomy than BCS. Compared to localized SEER stage, regional stage with direct extension (aOR = [3.24], 95% CI: 1.60–6.54, P = 0.001), regional stage with direct extension and nodes (aOR = [4.35], 95% CI: 1.72–11.03, P = 0.002), and distant stage (aOR = [4.44], 95% CI: 1.81–10.88, P = 0.001) were significantly more likely to have mastectomy than BCS. Compared to patients who received both chemotherapy and hormonal therapy, patients who received hormonal NT only (aOR = [0.29], 95% CI: 0.12–0.68, P = 0.004) were less likely to receive mastectomy. CONCLUSION Our study suggests that Hispanic ethnicity, advanced SEER stage, and type of NT are significant

  2. Incidence and Mortality Trends in German Women with Breast Cancer Using Age, Period and Cohort 1999 to 2008

    PubMed Central

    Berkemeyer, Shoma; Lemke, Dorothea; Hense, Hans Werner

    2016-01-01

    Longitudinal analysis investigates period (P), often as years. Additional scales of time are age (A) and birth cohort (C) Aim of our study was to use ecological APC analysis for women breast cancer incidence and mortality in Germany. Nation-wide new cases and deaths were obtained from Robert Koch Institute and female population from federal statistics, 1999–2008. Data was stratified into ten 5-years age-groups starting 20–24 years, ten birth cohorts starting 1939–43, and two calendar periods 1999–2003 and 2004–2008. Annual incidence and mortality were calculated: cases to 100,000 women per year. Data was analyzed using glm and apc packages of R. Breast cancer incidence and mortality increased with age. Secular rise in breast cancer incidence and decline in mortality was observed for period1999-2008. Breast cancer incidence and mortality declined with cohorts; cohorts 1950s showed highest incidence and mortality. Age-cohort best explained incidence and mortality followed by age-period-cohort with overall declining trends. Declining age-cohort mortality could be probable. Declining age-cohort incidence would require future biological explanations or rendered statistical artefact. Cohorts 1949–1958 could be unique in having highest incidence and mortality in recent time or future period associations could emerge relatively stronger to cohort to provide additional explanation of temporal change over cohorts. PMID:26933878

  3. Age- and Sex-Specific Trends in Lung Cancer Mortality over 62 Years in a Nation with a Low Effort in Cancer Prevention

    PubMed Central

    John, Ulrich; Hanke, Monika

    2016-01-01

    Background: A decrease in lung cancer mortality among females below 50 years of age has been reported for countries with significant tobacco control efforts. The aim of this study was to describe the lung cancer deaths, including the mortality rates and proportions among total deaths, for females and males by age at death in a country with a high smoking prevalence (Germany) over a time period of 62 years. Methods: The vital statistics data were analyzed using a joinpoint regression analysis stratified by age and sex. An age-period-cohort analysis was used to estimate the potential effects of sex and school education on mortality. Results: After an increase, lung cancer mortality among women aged 35–44 years remained stable from 1989 to 2009 and decreased by 10.8% per year from 2009 to 2013. Conclusions: Lung cancer mortality among females aged 35–44 years has decreased. The potential reasons include an increase in the number of never smokers, following significant increases in school education since 1950, particularly among females. PMID:27023582

  4. The influence of gender and gender typicality on autobiographical memory across event types and age groups.

    PubMed

    Grysman, Azriel; Fivush, Robyn; Merrill, Natalie A; Graci, Matthew

    2016-08-01

    Gender differences in autobiographical memory emerge in some data collection paradigms and not others. The present study included an extensive analysis of gender differences in autobiographical narratives. Data were collected from 196 participants, evenly split by gender and by age group (emerging adults, ages 18-29, and young adults, ages 30-40). Each participant reported four narratives, including an event that had occurred in the last 2 years, a high point, a low point, and a self-defining memory. Additionally, all participants completed self-report measures of masculine and feminine gender typicality. The narratives were coded along six dimensions-namely coherence, connectedness, agency, affect, factual elaboration, and interpretive elaboration. The results indicated that females expressed more affect, connection, and factual elaboration than males across all narratives, and that feminine typicality predicted increased connectedness in narratives. Masculine typicality predicted higher agency, lower connectedness, and lower affect, but only for some narratives and not others. These findings support an approach that views autobiographical reminiscing as a feminine-typed activity and that identifies gender differences as being linked to categorical gender, but also to one's feminine gender typicality, whereas the influences of masculine gender typicality were more context-dependent. We suggest that implicit gendered socialization and more explicit gender typicality each contribute to gendered autobiographies. PMID:27068433

  5. Different Perspectives on Technology Acceptance: The Role of Technology Type and Age

    NASA Astrophysics Data System (ADS)

    Arning, Katrin; Ziefle, Martina

    Although eHealth technologies offer an enormous potential to improve healthcare, the knowledge about key determinants of acceptance for eHealth technology is restricted. While the underlying technology of eHealth technologies and Information and Communication technology (ICT) is quite similar, utilization contexts and using motives are quite different. In order to explore the role of technology type on acceptance, we contrasted central application characteristics of both technology types using the scenario technique. A questionnaire was administered (n = 104) measuring individual variables (age, gender) and attitudes regarding an eHealth application (blood sugar meter) in contrast to an ICT device (Personal Digital Assistant, PDA). Older users basically approved the utilization of health-related technologies and perceived lower usability barriers. In addition, we identified main utilization motives of eHealth technology and technology-specific acceptance patterns, especially regarding issues of data safety in the eHealth context. Effects of age and gender in acceptance ratings suggest a differential perspective on eHealth acceptance. Finally, practical interventions were derived in order to support eHealth device design and to promote acceptance of eHealth technology.

  6. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    PubMed

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M; Mahmoudi, Morteza; De Rooij, Felix W M; Sijbrands, Eric; Peppelenbosch, Maikel P; Rezaee, Farhad

    2015-10-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

  7. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci

    PubMed Central

    Coetzee, Simon G.; Shen, Howard C.; Hazelett, Dennis J.; Lawrenson, Kate; Kuchenbaecker, Karoline; Tyrer, Jonathan; Rhie, Suhn K.; Levanon, Keren; Karst, Alison; Drapkin, Ronny; Ramus, Susan J.; Couch, Fergus J.; Offit, Kenneth; Chenevix-Trench, Georgia; Monteiro, Alvaro N.A.; Antoniou, Antonis; Freedman, Matthew; Coetzee, Gerhard A.; Pharoah, Paul D.P.; Noushmehr, Houtan; Gayther, Simon A.

    2015-01-01

    Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10−30), OSECs (P = 2.4 × 10−23) and HMECs (P = 6.7 × 10−15) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer. PMID:25804953

  8. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.

    PubMed

    Hoadley, Katherine A; Yau, Christina; Wolf, Denise M; Cherniack, Andrew D; Tamborero, David; Ng, Sam; Leiserson, Max D M; Niu, Beifang; McLellan, Michael D; Uzunangelov, Vladislav; Zhang, Jiashan; Kandoth, Cyriac; Akbani, Rehan; Shen, Hui; Omberg, Larsson; Chu, Andy; Margolin, Adam A; Van't Veer, Laura J; Lopez-Bigas, Nuria; Laird, Peter W; Raphael, Benjamin J; Ding, Li; Robertson, A Gordon; Byers, Lauren A; Mills, Gordon B; Weinstein, John N; Van Waes, Carter; Chen, Zhong; Collisson, Eric A; Benz, Christopher C; Perou, Charles M; Stuart, Joshua M

    2014-08-14

    Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies. PMID:25109877

  9. Delivery strategies and potential targets for siRNA in major cancer types.

    PubMed

    Lee, So Jin; Kim, Min Ju; Kwon, Ick Chan; Roberts, Thomas M

    2016-09-01

    Small interfering RNA (siRNA) has gained attention as a potential therapeutic reagent due to its ability to inhibit specific genes in many genetic diseases. For many years, studies of siRNA have progressively advanced toward novel treatment strategies against cancer. Cancer is caused by various mutations in hundreds of genes including both proto-oncogenes and tumor suppressor genes. In order to develop siRNAs as therapeutic agents for cancer treatment, delivery strategies for siRNA must be carefully designed and potential gene targets carefully selected for optimal anti-cancer effects. In this review, various modifications and delivery strategies for siRNA delivery are discussed. In addition, we present current thinking on target gene selection in major tumor types. PMID:27259398

  10. Type II transmembrane serine proteases as potential targets for cancer therapy.

    PubMed

    Murray, Andrew S; Varela, Fausto A; List, Karin

    2016-09-01

    Carcinogenesis is accompanied by increased protein and activity levels of extracellular cell-surface proteases that are capable of modifying the tumor microenvironment by directly cleaving the extracellular matrix, as well as activating growth factors and proinflammatory mediators involved in proliferation and invasion of cancer cells, and recruitment of inflammatory cells. These complex processes ultimately potentiate neoplastic progression leading to local tumor cell invasion, entry into the vasculature, and metastasis to distal sites. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression. In this review the knowledge collected over the past two decades about the molecular mechanisms underlying the pro-cancerous properties of selected TTSPs will be summarized. Furthermore, we will discuss how these insights may facilitate the translation into clinical settings in the future by specifically targeting TTSPs as part of novel cancer treatment regimens. PMID:27078673

  11. Type II transmembrane serine proteases as potential targets for cancer therapy

    PubMed Central

    Murray, Andrew S.; Varela, Fausto A.

    2016-01-01

    Carcinogenesis is accompanied by increased protein and activity levels of extracellular cell-surface proteases that are capable of modifying the tumor micro-environment by directly cleaving the extracellular matrix, as well as activating growth factors and proinflammatory mediators involved in proliferation and invasion of cancer cells, and recruitment of inflammatory cells. These complex processes ultimately potentiate neoplastic progression leading to local tumor cell invasion, entry into the vasculature, and metastasis to distal sites. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression. In this review the knowledge collected over the past two decades about the molecular mechanisms underlying the pro-cancerous properties of selected TTSPs will be summarized. Furthermore, we will discuss how these insights may facilitate the translation into clinical settings in the future by specifically targeting TTSPs as part of novel cancer treatment regimens. PMID:27078673

  12. Aging and Physical Function in Type 2 Diabetes: 8 Years of an Intensive Lifestyle Intervention

    PubMed Central

    Bray, George A.; Chen, Shyh-Huei; Clark, Jeanne M.; Evans, Mary; Hill, James O.; Jakicic, John M.; Johnson, Karen C.; Neiberg, Rebecca; Ip, Edward H.

    2015-01-01

    Background. Compared with adults without type 2 diabetes mellitus, those with the disease experience more limitations in their physical functioning (PF). Look AHEAD is a large multicenter trial that examined the effects of an intensive lifestyle intervention (ILI) for weight loss on cardiovascular outcomes compared with diabetes support and education (DSE). Although the current study compared treatment differences between ILI and DSE on PF, the primary goal was to examine whether this effect was moderated by age and history of cardiovascular disease at enrollment. Methods. Overweight or obese adults with type 2 diabetes mellitus (n = 5,145) were randomly assigned to either ILI or DSE. The mean (±SD) age and % females in ILI was 58.9 years (±6.9) and 59.8%; it was 58.6 years (6.8) and 59.5% in DSE. Analysis in 4,998 participants assessed the differential rates of decline in PF across a period of 8 years for the ILI and DSE groups. Results. ILI resulted in improved PF compared with DSE after 1 year (p < .0001) and was maintained across time. Within the ILI, older adults experienced greater improvements than younger adults (p < .0001). By year 2, persons in ILI with preexisting cardiovascular disease were no different in PF than in DSE participants with preexisting cardiovascular disease. Conclusion. With the exception of persons who had a history of cardiovascular disease, ILI slowed the decline in PF with type 2 diabetes mellitus despite weight regain, an effect that was stronger for older than younger participants and could translate into reductions in falls and disability. PMID:24986062

  13. General and Gender Characteristics of Type 2 Diabetes Mellitus Among the Younger and Older Age Groups

    PubMed Central

    Al-Mukhtar, Samir Burhanaldin; Fadhil, Nabeel Najib; Hanna, Bassam Edward

    2012-01-01

    Objectives To study the characteristics of cardiovascular risk factors in regard to age (before and after 60) and gender. Many reports refer to the higher prevalence of cardiovascular risk factors among the younger type 2 diabetics in comparison with the older population. Methods The study included 462 randomly recruited type 2 diabetic subjects (above and below 60 years) attending Al-Zahrawi Private Hospital in Mosul City-Iraq, during the period from June to August 2011. They were analyzed in regard to age, duration of diabetes, smoking, socioeconomic status, anthropometric indices, blood pressure, fasting plasma glucose, glycated hemoglobin A1c and serum lipids. Data were analyzed using chi-square and unpaired Z test. Results Duration of diabetes, diastolic blood pressure, glycated hemoglobin A1c, fasting plasma glucose, serum lipids, number of hypercholesterolemic patients, number of patients having unfavorable total cholesterol/HDL ratio (≥5) and positive family history of coronary heart disease were all significantly higher in the younger diabetics. In addition, younger diabetic females were distinguished by a larger number of hypertensive patients, higher level of systolic blood pressure, higher means of body mass index, total cholesterol and LDL, and larger number of patients having low HDL-C (<1 mmol/L). The younger diabetic males were distinct by a larger number of smokers, number of smoked cigarettes/day, and longer duration of smoking. All parameters ranged between p<0.05 and p<0.005. Conclusion Cardiovascular risk factors were significantly higher among younger type 2 diabetics (<60 years), particularly females. PMID:23074547

  14. Skeletal muscle lipid content and oxidative activity in relation to muscle fiber type in aging and metabolic syndrome.

    PubMed

    Gueugneau, Marine; Coudy-Gandilhon, Cécile; Théron, Laëtitia; Meunier, Bruno; Barboiron, Christiane; Combaret, Lydie; Taillandier, Daniel; Polge, Cécile; Attaix, Didier; Picard, Brigitte; Verney, Julien; Roche, Frédéric; Féasson, Léonard; Barthélémy, Jean-Claude; Béchet, Daniel

    2015-05-01

    One of the most noticeable effects of aging is the reduction in skeletal muscle mass and strength (sarcopenia). The metabolic syndrome (MS) is also prevalent in old subjects, but its relevance to skeletal muscle characteristics has poorly been investigated. Immunohistochemical studies were performed with muscle biopsies from young (22 years) and old (73 years) men with and without MS to reveal age-dependent and MS-associated modifications of fiber-type characteristics. Atrophy of type II fibers and altered fiber shape characterized muscle aging in lean healthy men. In contrast, increased cross-sectional area of the most abundant type I and type IIA fibers, and reduced cytochrome c oxidase content in all fiber types, characterized MS. Aging and particularly MS were associated with accumulation of intramyocellular lipid droplets. Although lipids mostly accumulated in type I fibers, matrix-assisted laser desorption/ionization-mass spectrometry imaging of intramyocellular lipids did not distinguish fiber types, but clearly separated young, old, and MS subjects. In conclusion, our study suggests that MS in the elderly persons is associated with alterations in skeletal muscle at a fiber-type specific level. Overall, these fiber type-specific modifications may be important both for the age-related loss of muscle mass and strength and for the increased prevalence of MS in elderly subjects. PMID:24939997

  15. Botulinum neurotoxin type A inhibits synaptic vesicle 2 expression in breast cancer cell lines

    PubMed Central

    Bandala, C; Cortés-Algara, AL; Mejía-Barradas, CM; Ilizaliturri-Flores, I; Dominguez-Rubio, R; Bazán-Méndez, CI; Floriano-Sánchez, E; Luna-Arias, JP; Anaya-Ruiz, M; Lara-Padilla, E

    2015-01-01

    Aim: It is known that botulinum neurotoxin type A (BoNTA) improves some kinds of cancer (e.g. prostate) and that synaptic vesicle glycoprotein 2 (SV2) is the molecular target of this neurotoxin. Besides having potential therapeutic value, this glycoprotein has recently been proposed as a molecular marker for several types of cancer. Although the mechanisms of cancer development and the improvement found with botulinum treatment are not well understood, the formation of the botulinum-SV2 complex may influence the presence and distribution of SV2 and the function of vesicles. To date, there are no reports on the possible effect of botulinum on breast cancer of unknown causes, which have a great impact on women’s health. Thus we determined the presence of SV2 in three breast cancer cell lines and the alterations found with botulinum application. Materials and methods: With and without adding 10 units of botulinum, SV2 protein expression was determined by optical densitometry in T47D, MDA-MB-231 and MDA-MB-453 cell lines and the distribution of SV2 was observed with immunochemistry (hematoxylin staining). Results: The SV2 protein was abundant in the cancer cells herein tested, and maximally so in T47D. In all three cancer cell lines botulinum diminished SV2 expression, which was found mostly in the cell periphery. Conclusion: SV2 could be a molecular marker in breast cancer. Its expression and distribution is regulated by botulinum, suggesting an interesting control mechanism for SV2 expression and a possible alternative therapy. Further studies are needed in this sense. PMID:26339411

  16. Metformin and lung cancer risk of patients with type 2 diabetes mellitus: A meta-analysis

    PubMed Central

    ZHU, NING; ZHANG, YUANYUAN; GONG, YI; HE, JIAN; CHEN, XIAODONG

    2015-01-01

    The association between metformin and the lung cancer risk of patients with type 2 diabetes mellitus (T2DM) remains controversial. Therefore, the present meta-analysis on epidemiological studies was performed to explore this issue. A comprehensive literature search was conducted for all the potential studies addressing metformin use and lung cancer risk by utilizing Pubmed, CBM and ISI Web of Science using the Mesh terms: ‘Metformin,’ or ‘biguanides’ and ‘lung cancer,’ or ‘neoplasms’. The reference lists were also inspected. Eight observational studies, including 17,997 lung cancer patients, were eventually selected, which contained seven case-control and one cohort study. Compared to other antidiabetic agents, metformin was significantly associated with the 16% reduction of lung cancer risk in type 2 diabetic patients [relative risk (RR)=0.84; 95% confidence interval (95% CI), 0.73-0.97]. In the sensitivity analysis by separately excluding the study with a high weight or lower quality, the results did not materially change. Subsequently, subgroup analysis was performed on the type of study design, unadjusted or adjusted hazard ratio, quality of enrolled studies, duration of treatment, country and control drugs. The magnitude of lung cancer risk reduction was strengthened when compared to sulfonylureas (RR=0.79; 95% CI, 0.83-0.9), without significant heterogeneity (Q-value=2.98, P=0.085). In conclusion, the present analysis supported that the use of metformin significantly decreased the risk of lung cancer among patients with T2DM. However, further studies are required to confirm these findings. PMID:26075077

  17. The Coexistence of Common Pulmonary Diseases on the Histologic Type of Lung Cancer in Both Genders in Taiwan

    PubMed Central

    Jian, Zhi-Hong; Lung, Chia-Chi; Huang, Jing-Yang; Ko, Pei-Chieh; Jan, Shiou-Rung; Ndi Nfor, Oswald; Ku, Wen-Yuan; Ho, Chien-Chang; Pan, Hui-Hsien; Liaw, Yung-Po

    2014-01-01

    Abstract Effects of pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and lung tuberculosis (TB)] on subsequent lung cancer development have been reported. However, whether patients with coexisting pulmonary diseases are at greater risk of developing various histologic types of lung cancer remains elusive. Patients newly diagnosed with lung cancer between 2004 and 2008 were identified from National Health Insurance Research Database (Taiwan). The histologic types of lung cancer were further confirmed using Taiwan Cancer Registry Database. Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB to estimate lung cancer risk by histologic type. During the study period, 32,759 cases of lung cancer were identified from 15,219,024 residents age 20 years and older, who were free from the disease before 2003. Coexisting pulmonary diseases showed stronger association with lung cancer than specific lung disorders. Specifically, among men, the HRs for squamous cell carcinoma (SqCC) were 3.98 (95% CI, 3.22–4.93), 2.68 (95% CI, 2.45–2.93), and 2.57 (95% CI, 2.10–3.13) for individuals with asthma+COPD+TB, asthma+COPD, and COPD+TB, respectively. Among women, the HRs for SqCC were 3.64 (95% CI, 1.88–7.05), 3.35 (95% CI, 1.59–7.07), and 2.21 (95% CI, 1.66–2.94) for individuals with TB, COPD+TB, and asthma+COPD, respectively. Adenocarcinoma HRs for men and women were 2.00 (95% CI, 1.54–2.60) and 2.82 (95% CI, 1.97–4.04) for individuals with asthma+COPD+TB, 2.28 (95% CI, 1.91–2.73) and 2.16 (95% CI, 1.57–2.95) for COPD+TB, and 1.76 (95% CI, 1.04–2.97) and 2.04 (95% CI, 1.02–4.09) for individuals with asthma+TB. Specifically, small cell carcinoma (SmCC) HRs among men were 3.65 (95% CI, 1.97–6.80), 2.20 (95% CI, 1.45–3.36), and 2.14 (95% CI, 1.86–2.47) for those with asthma+TB, asthma+COPD+TB, and asthma+ COPD, respectively. Among women, the HRs of SmCC were 8.97 (95% CI, 3

  18. [Cancer].

    PubMed

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  19. Optimizing eHealth breast cancer interventions: which types of eHealth services are effective?

    PubMed

    Baker, Timothy B; Hawkins, Robert; Pingree, Suzanne; Roberts, Linda J; McDowell, Helene E; Shaw, Bret R; Serlin, Ron; Dillenburg, Lisa; Swoboda, Christopher M; Han, Jeong-Yeob; Stewart, James A; Carmack-Taylor, Cindy L; Salner, Andrew; Schlam, Tanya R; McTavish, Fiona; Gustafson, David H

    2011-03-01

    Little is known about the effective elements of Interactive Cancer Communication Systems (ICCSs). A randomized trial explored which types of services of a multifaceted ICCS benefited patients and the nature of the benefit. Women with breast cancer (N=450) were randomized to different types of ICCS services or to a control condition that provided internet access. The Comprehensive Health Enhancement Support System (CHESS), served as the ICCS. ICCS services providing information and support, but not coaching such as cognitive behavior therapy, produced significant benefits in health information competence and emotional processing. Provision of Information and Support ICCS services significantly benefited women with breast cancer. More complex and interactive services designed to train the user had negligible effects. PMID:21709810

  20. Multifunctional metal rattle-type nanocarriers for MRI-guided photothermal cancer therapy

    NASA Astrophysics Data System (ADS)

    Huang, Yuran; Wei, Tuo; Yu, Jing; Hou, Yanglong; Cai, Kaiyong; Liang, Xing-jie

    2015-03-01

    Numerous nanomaterials have been developed for biomedical application, especially cancer therapy. Visualizing cancer therapy is highly promising now because of the potential ability to realize accurate, localized treatment. In this work, we firstly synthesized metal nanorattles (MNRs), which utilized porous gold shells capable of photothermal therapy to carry multiple superparmagnetic iron oxide nanoparticles (SPIONs) as MR imaging contrast agents inside. As shown in the infrared light, these metal rattle-typed nanostructures were able to convert to heat to kill cells, and inhibit tumor growth. As a carrier for multiple SPIONs, it also performed a good behavior for T2-weighted MR imaging in tumor site. Moreover, the rest of the inner space of the gold shell also introduced potential ability as nanocarriers for other cargos such as chemotherapeutic drugs, which is still under investigation. This metal-rattle-type nanocarriers is highly potential as a novel platforms for cancer therapy in the future.

  1. Palliative chemotherapy in advanced colorectal cancer patients 80 years of age and older

    PubMed Central

    Lai, P.; Sud, S.; Zhang, T.; Asmis, T.; Wheatley-Price, P.

    2016-01-01

    Background Colorectal cancer (crc) has a median diagnostic age of 68 years. Despite significant progress in chemotherapy (ctx) options, few data on outcomes or toxicity from ctx in patients 80 years of age and older are available. We investigated ctx in such patients with metastatic crc (mcrc), hypothesizing high rates of hospitalization and toxicity. Methods A retrospective chart review identified patients 80 years of age and older with mcrc who initiated ctx between 2005–2010 at our institution. Patient demographics and ctx data were collected. Endpoints included rates of hospitalization, ctx discontinuation because of toxicity, and overall survival. Results In 60 patients, ctx was initiated on 88 occasions. Median age in the cohort was 83 years; 52% were men; 72% lived with family; 53% had a modified Charlson comorbidity index of 2 or greater; and 31% were taking 6 or more prescription medications at baseline. At baseline, 33% of the patients were anemic (hemoglobin < 100 g/L), 36% had leukocytosis (white blood cells > 11×109/L), and 48% had renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m2). In 53%, ctx was given as first-line treatment. The initial ctx dose was adjusted in 67%, and capecitabine was the most common chemotherapeutic agent (45%). In 19 instances (22%), the patient was hospitalized during or within 30 days of ctx; in 26 instances (30%), the ctx was discontinued because of toxicity, and in 48 instances (55%), the patient required at least 1 dose reduction, omission, or delay. Median overall survival was 17.8 months (95% confidence interval: 14.3 to 20.8 months). Conclusions In the population 80 years of age and older, ctx for mcrc is feasible; however, most recipients will require dose adjustments, and a significant proportion will be hospitalized or stop ctx because of toxicity. Prospective research incorporating geriatric assessment tools is required to better select these older patients for ctx. PMID:27330342

  2. Circulating microRNAs as biomarkers for early detection of diffuse-type gastric cancer using a mouse model

    PubMed Central

    Rotkrua, P; Shimada, S; Mogushi, K; Akiyama, Y; Tanaka, H; Yuasa, Y

    2013-01-01

    Background: Diffuse-type gastric cancer (DGC) exhibits rapid disease progression and a poor prognosis. There are no effective serum biomarkers for early detection of DGC. We have established an E-cadherin/p53 double conditional knockout (DCKO) mouse line that recapitulates human DGC morphologically and molecularly. In this study we tried to identify circulating microRNAs (miRNAs) as non-invasive biomarkers for DGC diagnosis using DCKO mice. Methods: We performed miRNA microarray and quantitative reverse transcription–PCR analyses of tissue and serum samples from DCKO mice with DGC and age-matched littermate controls. Results: Comparative analyses showed that mouse and human primary gastric cancers have similar miRNA expression patterns. Next, we selected some candidate miRNAs highly expressed in sera and cancer tissues of DCKO mice for further evaluation. TaqMan quantitative RT–PCR analyses indicated that four of them, miR-103, miR-107, miR-194 and miR-210, were significantly upregulated in sera of both early and advanced-stage DGC-bearing mice compared with in corresponding controls. Receiver-operating characteristic curve analyses demonstrated that these four miRNAs can discriminate DGC-positive cases from normal ones with high sensitivity and specificity. Conclusion: These observations suggest that this mouse model of DGC is useful for identifying serum biomarkers, and we found circulating miRNAs that can accurately detect DGC at an early stage. PMID:23385731

  3. News Portrayal of Cancer: Content Analysis of Threat and Efficacy by Cancer Type and Comparison with Incidence and Mortality in Korea.

    PubMed

    Shim, Minsun; Kim, Yong-Chan; Kye, Su Yeon; Park, Keeho

    2016-08-01

    How the news media cover cancer may have profound significance for cancer prevention and control; however, little is known about the actual content of cancer news coverage in Korea. This research thus aimed to examine news portrayal of specific cancer types with respect to threat and efficacy, and to investigate whether news portrayal corresponds to actual cancer statistics. A content analysis of 1,138 cancer news stories was conducted, using a representative sample from 23 news outlets (television, newspapers, and other news media) in Korea over a 5-year period from 2008 to 2012. Cancer incidence and mortality rates were obtained from the Korean Statistical Information Service. Results suggest that threat was most prominent in news stories on pancreatic cancer (with 87% of the articles containing threat information with specific details), followed by liver (80%) and lung cancers (70%), and least in stomach cancer (41%). Efficacy information with details was conveyed most often in articles on colorectal (54%), skin (54%), and liver (50%) cancers, and least in thyroid cancer (17%). In terms of discrepancies between news portrayal and actual statistics, the threat of pancreatic and liver cancers was overreported, whereas the threat of stomach and prostate cancers was underreported. Efficacy information regarding cervical and colorectal cancers was overrepresented in the news relative to cancer statistics; efficacy of lung and thyroid cancers was underreported. Findings provide important implications for medical professionals to understand news information about particular cancers as a basis for public (mis)perception, and to communicate effectively about cancer risk with the public and patients. PMID:27478333

  4. News Portrayal of Cancer: Content Analysis of Threat and Efficacy by Cancer Type and Comparison with Incidence and Mortality in Korea

    PubMed Central

    2016-01-01

    How the news media cover cancer may have profound significance for cancer prevention and control; however, little is known about the actual content of cancer news coverage in Korea. This research thus aimed to examine news portrayal of specific cancer types with respect to threat and efficacy, and to investigate whether news portrayal corresponds to actual cancer statistics. A content analysis of 1,138 cancer news stories was conducted, using a representative sample from 23 news outlets (television, newspapers, and other news media) in Korea over a 5-year period from 2008 to 2012. Cancer incidence and mortality rates were obtained from the Korean Statistical Information Service. Results suggest that threat was most prominent in news stories on pancreatic cancer (with 87% of the articles containing threat information with specific details), followed by liver (80%) and lung cancers (70%), and least in stomach cancer (41%). Efficacy information with details was conveyed most often in articles on colorectal (54%), skin (54%), and liver (50%) cancers, and least in thyroid cancer (17%). In terms of discrepancies between news portrayal and actual statistics, the threat of pancreatic and liver cancers was overreported, whereas the threat of stomach and prostate cancers was underreported. Efficacy information regarding cervical and colorectal cancers was overrepresented in the news relative to cancer statistics; efficacy of lung and thyroid cancers was underreported. Findings provide important implications for medical professionals to understand news information about particular cancers as a basis for public (mis)perception, and to communicate effectively about cancer risk with the public and patients. PMID:27478333

  5. Age Dating Merger Events in Early Type Galaxies via the Detection of AGB Light

    NASA Technical Reports Server (NTRS)

    Bothun, G.

    2005-01-01

    A thorough statistical analysis of the J-H vs. H-K color plane of all detected early type galaxies in the 2MASS catalog with velocities less than 5000 km/s has been performed. This all sky survey is not sensitive to one particular galactic environment and therefore a representative range of early type galaxy environments have been sampled. Virtually all N-body simulation so major mergers produces a central starburst due to rapid collection of gas. This central starburst is of sufficient amplitude to change the stellar population in the central regions of the galaxy. Intermediate age populations are given away by the presence of AGB stars which will drive the central colors redder in H-K relative to the J- H baseline. This color anomaly has a lifetime of 2-5 billion years depending on the amplitude of the initial starburst Employing this technique on the entire 2MASS sample (several hundred galaxies) reveals that the AGB signature occurs less than 1% of the time. This is a straightforward indication that virtually all nearby early type galaxies have not had a major merger occur within the last few billion years.

  6. Increased Physical Activity Associated With Lower Risk of 13 Types of Cancer

    MedlinePlus

    ... and its programs, visit www.nih.gov . NIH…Turning Discovery Into Health ® Reference Moore SC, et al. Leisure-time physical activity and risk of 26 types of cancer in 1.44 million adults. JAMA Internal Medicine. May 16, 2016. DOI:10.1001/jamainternmed. ...

  7. List of gene variants developed for cancer cells from nine tissue types

    Cancer.gov

    NCI scientists have developed a comprehensive list of genetic variants for each of the types of cells that comprise what is known as the NCI-60 cell line collection. This new list adds depth to the most frequently studied human tumor cell lines in cancer

  8. Indirectly estimated absolute lung cancer mortality rates by smoking status and histological type based on a systematic review

    PubMed Central

    2013-01-01

    Background National smoking-specific lung cancer mortality rates are unavailable, and studies presenting estimates are limited, particularly by histology. This hinders interpretation. We attempted to rectify this by deriving estimates indirectly, combining data from national rates and epidemiological studies. Methods We estimated study-specific absolute mortality rates and variances by histology and smoking habit (never/ever/current/former) based on relative risk estimates derived from studies published in the 20th century, coupled with WHO mortality data for age 70–74 for the relevant country and period. Studies with populations grossly unrepresentative nationally were excluded. 70–74 was chosen based on analyses of large cohort studies presenting rates by smoking and age. Variations by sex, period and region were assessed by meta-analysis and meta-regression. Results 148 studies provided estimates (Europe 59, America 54, China 22, other Asia 13), 54 providing estimates by histology (squamous cell carcinoma, adenocarcinoma). For all smoking habits and lung cancer types, mortality rates were higher in males, the excess less evident for never smokers. Never smoker rates were clearly highest in China, and showed some increasing time trend, particularly for adenocarcinoma. Ever smoker rates were higher in parts of Europe and America than in China, with the time trend very clear, especially for adenocarcinoma. Variations by time trend and continent were clear for current smokers (rates being higher in Europe and America than Asia), but less clear for former smokers. Models involving continent and trend explained much variability, but non-linearity was sometimes seen (with rates lower in 1991–99 than 1981–90), and there was regional variation within continent (with rates in Europe often high in UK and low in Scandinavia, and higher in North than South America). Conclusions The indirect method may be questioned, because of variations in definition of smoking and

  9. Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1

    PubMed Central

    Xiao, Qian; Jiang, Yan; Liu, Qingbo; Yue, Jiao; Liu, Chunying; Zhao, Xiaotong; Qiao, Yuemei; Ji, Hongbin; Chen, Jianfeng; Ge, Gaoxiang

    2015-01-01

    Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV α chains form α1α1α2, α3α4α5 and α5α5α6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (α1α1α2), little is known whether minor Col IV (α3α4α5 and α5α5α6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV α5 chain is indispensable in cancer development by using α5(IV)-deficient mouse model. Ablation of α5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial α5(IV) supports cancer cell proliferation, while endothelial α5(IV) is essential for efficient tumor angiogenesis. α5(IV), but not α1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of α5(IV). Constitutively active DDR1 or MEK1 rescued the defects of α5(IV)-ablated cells. Thus, minor Col IV α5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV. PMID:25992553

  10. Cardiopulmonary Function and Age-Related Decline Across the Breast Cancer Survivorship Continuum

    PubMed Central

    Jones, Lee W.; Courneya, Kerry S.; Mackey, John R.; Muss, Hyman B.; Pituskin, Edith N.; Scott, Jessica M.; Hornsby, Whitney E.; Coan, April D.; Herndon, James E.; Douglas, Pamela S.; Haykowsky, Mark

    2012-01-01

    Purpose To evaluate cardiopulmonary function (as measured by peak oxygen consumption [VO2peak]) across the breast cancer continuum and its prognostic significance in women with metastatic disease. Patients and Methods Patients with breast cancer representing four cross-sectional cohorts—that is, (1) before, (2) during, and (3) after adjuvant therapy for nonmetastatic disease, and (4) during therapy in metastatic disease—were studied. A cardiopulmonary exercise test (CPET) with expired gas analysis was used to assess VO2peak. A Cox proportional hazards model was used to estimate the risk of death according to VO2peak category (< 15.4 v ≥ 15.4 mL · kg−1 · min−1) with adjustment for clinical factors. Results A total of 248 women (age, 55 ± 8 years) completed a CPET. Mean VO2peak was 17.8 ± a standard deviation of 4.3 mL · kg−1 · min−1, the equivalent of 27% ± 17% below age-matched healthy sedentary women. For the entire cohort, 32% had a VO2peak less than 15.4 mL · kg−1 · min−1—the VO2peak required for functional independence. VO2peak was significantly different across breast cancer cohorts for relative (mL · kg−1 · min−1) and absolute (L · min−1) VO2peak (P = .017 and P < .001, respectively); VO2peak was lowest in women with metastatic disease. In patients with metastatic disease (n = 52), compared with patients achieving a VO2peak ≤ 1.09 L · min−1, the adjusted hazard ratio for death was 0.32 (95% CI, 0.16 to 0.67, P = .002) for a VO2peak more than 1.09 L · min−1. Conclusion Patients with breast cancer have marked impairment in VO2peak across the entire survivorship continuum. VO2peak may be an independent predictor of survival in metastatic disease. PMID:22614980

  11. What types of early gastric cancer are indicated for endoscopic ultrasonography staging of invasion depth?

    PubMed Central

    Watari, Jiro; Ueyama, Shigemitsu; Tomita, Toshihiko; Ikehara, Hisatomo; Hori, Kazutoshi; Hara, Ken; Yamasaki, Takahisa; Okugawa, Takuya; Kondo, Takashi; Kono, Tomoaki; Tozawa, Katsuyuki; Oshima, Tadayuki; Fukui, Hirokazu; Miwa, Hiroto

    2016-01-01

    AIM To clarify the diagnostic efficacy and limitations of endoscopic ultrasonography (EUS) and the characteristics of early gastric cancers (EGCs) that are indications for EUS-based assessment of cancer invasion depth. METHODS We retrospectively investigated the cases of 153 EGC patients who underwent conventional endoscopy (CE) and EUS (20 MHz) before treatment. RESULTS We found that 13.7% were “inconclusive” cases with low-quality EUS images, including all nine of the cases with protruded (0-I)-type EGCs. There was no significant difference in the diagnostic accuracy between CE and EUS. Two significant independent risk factors for misdiagnosis by EUS were identified-ulcer scarring [UL(+); odds ratio (OR) = 4.49, P = 0.003] and non-indication criteria for endoscopic resection (ER) (OR = 3.02, P = 0.03). In the subgroup analysis, 23.1% of the differentiated-type cancers exhibiting SM massive invasion (SM2) invasion (submucosal invasion ≥ 500 μm) by CE were correctly diagnosed by EUS, and 23.1% of the undifferentiated-type EGCs meeting the expanded-indication criteria for ER were correctly diagnosed by EUS. CONCLUSION There is no need to perform EUS for UL(+) EGCs or 0-I-type EGCs, but EUS may enhance the pretreatment staging of differentiated-type EGCs with SM2 invasion without UL or undifferentiated-type EGCs revealed by CE as meeting the expanded-indication criteria for ER.

  12. Helicobacter pylori hopQ alleles (type I and II) in gastric cancer

    PubMed Central

    LEYLABADLO, HAMED EBRAHIMZADEH; YEKANI, MINA; GHOTASLOU, REZA

    2016-01-01

    The Helicobacter pylori (H. pylori) outer membrane protein (HopQ) of is one of the proteins involved in bacterial adherence to gastric mucosa and has been suggested to have a role in the virulence of H. pylori. The aim of the present study was to determine the association between H. pylori virulence types I and II hopQ genotypes and patients with different gastrointestinal diseases. A polymerase chain reaction-based assay was used to determine the presence of type I and type II hopQ genes in 88 H. pylori strains isolated from H. pylori-infected patients. Of the total 88 H. pylori isolates, type I and type II hopQ alleles were detected in 52 (59.1%) and 36 (40.9%), respectively. A significant association was found between type I hopQ gene and gastric cancer [odds ratio, 2.3; 95% confidence interval (CI), 1.3–4.1] and gastric ulcers (odds ratio, 2.5; 95% CI, 1.4–4.3). A significant association was also identified between the type II hopQ gene and gastric cancer (odds ratio, 2.4; 95% CI, 1.1–3.0). The association between hopQ type I and hopQ type II genotypes and clinical status suggest that these genes may be helpful in the universal prediction of specific disease risks. PMID:27123254

  13. Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

    NASA Technical Reports Server (NTRS)

    Rianon, N.; McCormick, J.; Ambrose, C.; Smith, S. M.; Fisher-Hoch, S.

    2016-01-01

    The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (=50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level =8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations

  14. Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

    SciTech Connect

    Desprez, Pierre-Yves; Campisi, Judith

    2014-08-19

    A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.

  15. Association between Neurofibromatosis Type 1 and Breast Cancer: A Report of Two Cases with a Review of the Literature

    PubMed Central

    Seo, Yoon Nae; Park, Young Mi

    2015-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and is associated with various benign and malignant tumors, including breast cancer. However, an increased risk of breast cancer in NF1 patients has not been widely recognized or accepted. Here, we report two cases of breast cancer in NF1 patients and review the literature on the association between NF1 and breast cancer. PMID:26604930

  16. Prevalence, Type, Distribution, and Severity of Cerebral Palsy in Relation to Gestational Age: A Meta-Analytic Review

    ERIC Educational Resources Information Center

    Himpens, E.; Van den Broeck, C.; Oostra, A.; Calders, P.; Vanhaesebrouck, P.

    2008-01-01

    The aim of this review is to determine the relationship between gestational age (GA) and prevalence, type, distribution, and severity of cerebral palsy (CP). Epidemiological studies with cohorts expressed by GA were assessed. A comprehensive meta-analysis and meta-regression was performed on four fetal age categories. Studies of children with CP…

  17. Formal Reasoning Skills of Secondary School Students as Related to Gender, Age, School Type and Learning Abilities.

    ERIC Educational Resources Information Center

    Shemesh, Michal; Lazarowitz, Reuven

    This study investigated: (1) whether boys and girls master formal reasoning tasks to the same degree at the same age; (2) if the variance of boys' and girls' performance in formal tasks could be predicted by the same cognitive learning abilities; and (3) what are the main and interactional effects of age, sex, and school type on the variance of…

  18. Mössbauer study of two different aged rock types in the Vredefort structure, South Africa

    NASA Astrophysics Data System (ADS)

    Waanders, F. B.; Brink, M. C.; Bisschoff, A. A.

    2005-11-01

    The Vredefort Structure in South Africa was recently inscribed into the list of World Heritage sites as the oldest and largest recognised impact structure on earth. Due to upliftment of more than 30 km of the Archaean basement core and subsequent exposure of the deeply eroded central portion of the crater a unique opportunity exists to study rocks of the crust, especially those that have undergone recrystallization due to various thermal metamorphic events over time. Two rock types occurring in the central uplifted part of the impact structure were studied. One was a typical Archaean iron formation of sedimentary origin. The other rock studied, adjacent to this much older rock, is a homogeneous, medium grained recrystallized norite of immediately pre- or post-impact age, indicating a possible mafic igneous activity related to impact. Microscopy, XRD and Mössbauer analyses were performed on both samples.

  19. Cancer-related PTSD symptoms in a veteran sample: association with age, combat PTSD, and quality of life

    PubMed Central

    Wachen, Jennifer Schuster; Patidar, Seema M.; Mulligan, Elizabeth A.; Naik, Aanand D.; Moye, Jennifer

    2015-01-01

    Objective The diagnosis and treatment of cancer is a potentially traumatic experience that may evoke posttraumatic stress symptoms (PTSS) among survivors. This paper describes the rates of endorsement of cancer-related PTSS along with the relationship of demographic, cancer, and combat variables on PTSS and quality of life. Methods Veterans (N = 166) with head and neck, esophageal, gastric, or colorectal cancers were recruited through tumor registries at two regional Veterans Administration Medical Centers. Standardized scales were used to assess self-report of PTSS, combat, and quality of life. Results Most participants (86%) reported experiencing at least some cancer-related PTSS; 10% scored above a clinical cutoff for probable PTSD. In linear regressions, younger age and current combat PTSS were associated with cancer-related PTSS, whereas disease and treatment characteristics were not; in turn, cancer-related PTSS were negatively associated with physical and social quality of life. Conclusions Individual characteristics and psychosocial factors may play a larger role than disease-related variables in determining how an individual responds to the stress of cancer diagnosis and treatment. Given the rates of reported cancer-related PTSS in this sample, and other non-veteran samples, clinicians should consider screening these following diagnosis and treatment, particularly in younger adults and those with previous trauma histories. PMID:24519893

  20. Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

    PubMed Central

    Zinnanti, William J.; Lazovic, Jelena; Housman, Cathy; LaNoue, Kathryn; O’Callaghan, James P.; Simpson, Ian; Woontner, Michael; Goodman, Stephen I.; Connor, James R.; Jacobs, Russell E.; Cheng, Keith C.

    2007-01-01

    Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I. PMID:17932566