Science.gov

Sample records for age cancer type

  1. 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 ...

  2. Biology of cancer and aging.

    PubMed

    Holmes, F F; Wilson, J; Blesch, K S; Kaesberg, P R; Miller, R; Sprott, R

    1991-12-01

    The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development.

  3. Immunity, ageing and cancer

    PubMed Central

    Derhovanessian, Evelyna; Solana, Rafael; Larbi, Anis; Pawelec, Graham

    2008-01-01

    Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient. PMID:18816370

  4. Cellular aging and cancer

    PubMed Central

    Hornsby, Peter J.

    2010-01-01

    Aging is manifest in a variety of changes over time, including changes at the cellular level. Cellular aging acts primarily as a tumor suppressor mechanism, but also may enhance cancer development under certain circumstances. One important process of cellular aging is oncogene-induced senescence, which acts as an important anti-cancer mechanism. Cellular senescence resulting from damage caused by activated oncogenes prevents the growth or potentially neoplastic cells. Moreover, cells that have entered senescence appear to be targets for elimination by the innnate immune system. In another aspect of cellular aging, the absence of telomerase activity in normal tissues results in such cells lacking a telomere maintenance mechanism. One consequence is that in aging there is an increase in cells with shortened telomeres. In the presence of active oncogenes that cause expansion of a neoplastic clone, shortening of telomeres leading to telomere dysfunction prevents the indefinite expansion of the clone because the cells enter crisis. Crisis results from fusions and other defects caused by dysfunctional telomeres and is a terminal state of the neoplastic clone. In this way the absence of telomerase in human cells, while one cause of cellular aging, also acts as an anti-cancer mechanism. PMID:20705476

  5. Cell Senescence: Aging and Cancer

    ScienceCinema

    Campisi, Judith

    2016-07-12

    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.

  6. 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.

  7. A gerontologic perspective on cancer and aging.

    PubMed

    Blank, Thomas O; Bellizzi, Keith M

    2008-06-01

    Most people diagnosed with cancer are aged >65 years, and many diagnosed younger live to become older survivors. Geriatric oncology is becoming recognized as a specialty area within oncology. It focuses specifically on the functional impacts of the interplay of aging and cancer, including the role of comorbidities. Nevertheless, to the authors' knowledge, little attention has been given to cancer from a gerontologic and lifespan perspective, especially quality of life and psychologic impact. Research has shown that the amount and type of psychologic impact of cancer is highly variable and that part of that variation is related to age, in that older persons are often less affected in both negative and positive ways. Gerontologic concepts and empiric findings related to physical, psychologic, and social aging processes may serve as partial explanations for that age-related pattern. Important potential contributors include psychologic factors, such as changes in future time perspective and goals, as well as social ones, such as roles and previous experience. The result is a complex interplay of factors that vary across persons but are covaried with age. Empiric findings regarding 1-year to 8-year prostate cancer survivors illustrate the age differences and the differential impacts of age itself and comorbidity. The use of gerontologic concepts to explain the age-related impact of cancer will benefit both research and clinical practice by providing a means to target interventions more effectively by taking into account the psychologic and social changes that often accompany aging. .

  8. [Frequency of cancer at older ages].

    PubMed

    Hill, Catherine; Doyon, Françoise

    2008-05-28

    The dependency between the risk of death and age is analysed, and the contribution of cancer to the overall risk of death is evaluated as a function of age. The frequency of the different cancer sites is described in different age groups. Lastly cancer mortality trends are presented by age. The risk of death from cancer increases markedly with age, but the risk of a death from a cardiovascular disease increases even more rapidly, consequently the importance of cancer as a cause of death decreases with age. In the male population, lung and head and neck cancers are the most frequent cancers before age 65, whereas prostate and colorectal cancers are more frequent at older ages. In the female population, breast and colorectal cancers are the most frequent cancers except for mortality before age 65 where lung cancer is the second killer after breast cancer. The risk of cancer death decreases in recent years for all age groups.

  9. 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 ...

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Size, longevity and cancer: age structure

    PubMed Central

    2016-01-01

    There is significant recent interest in Peto's paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto's paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived because they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not. Because no set of competing risks is generally prevalent, it is instructive to temporarily dispose of competing risks and investigate the pure age dynamics of cancer under the multistage model of carcinogenesis. In addition to augmenting earlier results, I show that in terms of cancer-free lifespan large organisms reap greater benefits from an increase in cellular cancer robustness than smaller organisms. Conversely, a higher cellular cancer robustness renders cancer-free lifespan more resilient to an increase in size. This interaction may be an important driver of the evolution of large, cancer-robust organisms. PMID:27629030

  18. Size, longevity and cancer: age structure.

    PubMed

    Wensink, Maarten J

    2016-09-14

    There is significant recent interest in Peto's paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto's paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived because they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not. Because no set of competing risks is generally prevalent, it is instructive to temporarily dispose of competing risks and investigate the pure age dynamics of cancer under the multistage model of carcinogenesis. In addition to augmenting earlier results, I show that in terms of cancer-free lifespan large organisms reap greater benefits from an increase in cellular cancer robustness than smaller organisms. Conversely, a higher cellular cancer robustness renders cancer-free lifespan more resilient to an increase in size. This interaction may be an important driver of the evolution of large, cancer-robust organisms. PMID:27629030

  19. The common biology of cancer and ageing.

    PubMed

    Finkel, Toren; Serrano, Manuel; Blasco, Maria A

    2007-08-16

    At first glance, cancer and ageing would seem to be unlikely bedfellows. Yet the origins for this improbable union can actually be traced back to a sequence of tragic--and some say unethical--events that unfolded more than half a century ago. Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer.

  20. 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.

  1. 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

  2. [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

  3. 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

  4. 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.

  5. 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…

  6. Inulin-type fructans in healthy aging.

    PubMed

    Tuohy, Kieran M

    2007-11-01

    Worldwide, the population is aging, with estimates of 1 billion people aged 60 y or over within the next 20 y. With aging comes a reduction in overall health and increased morbidity and mortality due to infectious disease. Mortality due to gastrointestinal infections is up to 400 times higher in the elderly compared with younger adults. Recent studies have shown that the gut microbiota changes in old age, with an increased number of bacterial groups represented in the predominant elderly gut microbiota. This change in species "evenness" coincides with parallel changes in immune function, diet, and lifestyle and may contribute to disease susceptibility and severity in old age. The intestinal microbiota may thus be identified as an important target for improving health through reduced disease risk. Here, the application of prebiotics, especially the inulin-type fructans, and synbiotics (prebiotics combined with efficacious probiotic strains) will be discussed in terms of microbiota modulation and impact on disease risk in the aged population. Recent human intervention studies have confirmed the microbiota modulatory capability of the inulin-type fructans in the elderly and there is some evidence for reduced risk of disease. However, there is a need for more and larger human intervention studies to determine the efficacy of prebiotics in the elderly, particularly studies that take advantage of recent high resolution analytical methodologies like metabonomics, to shed light on possible prebiotic mechanisms of action.

  7. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer. PMID:27648033

  8. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer.

  9. Telomere biology: cancer firewall or aging clock?

    PubMed

    Mitteldorf, J J

    2013-09-01

    It has been a decade since the first surprising discovery that longer telomeres in humans are statistically associated with longer life expectancies. Since then, it has been firmly established that telomere shortening imposes an individual fitness cost in a number of mammalian species, including humans. But telomere shortening is easily avoided by application of telomerase, an enzyme which is coded into nearly every eukaryotic genome, but whose expression is suppressed most of the time. This raises the question how the sequestration of telomerase might have evolved. The predominant assumption is that in higher organisms, shortening telomeres provide a firewall against tumor growth. A more straightforward interpretation is that telomere attrition provides an aging clock, reliably programming lifespans. The latter hypothesis is routinely rejected by most biologists because the benefit of programmed lifespan applies only to the community, and in fact the individual pays a substantial fitness cost. There is a long-standing skepticism that the concept of fitness can be applied on a communal level, and of group selection in general. But the cancer hypothesis is problematic as well. Animal studies indicate that there is a net fitness cost in sequestration of telomerase, even when cancer risk is lowered. The hypothesis of protection against cancer has never been tested in animals that actually limit telomerase expression, but only in mice, whose lifespans are not telomerase-limited. And human medical evidence suggests a net aggravation of cancer risk from the sequestration of telomerase, because cells with short telomeres are at high risk of neoplastic transformation, and they also secrete cytokines that exacerbate inflammation globally. The aging clock hypothesis fits well with what is known about ancestral origins of telomerase sequestration, and the prejudices concerning group selection are without merit. If telomeres are an aging clock, then telomerase makes an

  10. Epigenetic linkage of aging, cancer and nutrition.

    PubMed

    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.

  11. 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

  12. 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.

  13. Metformin for aging and cancer prevention

    PubMed Central

    Anisimov, Vladimir N.

    2010-01-01

    Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases life span in nematodes, fruit flies and mice. It is possible that the life-prolonging effect of caloric restriction is due to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both life span extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore metformin seems to decrease cancer risk in diabetic patients. PMID:21084729

  14. The Intricate Interplay between Mechanisms Underlying Aging and Cancer.

    PubMed

    Piano, Amanda; Titorenko, Vladimir I

    2015-02-01

    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.

  15. 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. |

  16. 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. |

  17. Age at Last Birth in Relation to Risk of Endometrial Cancer: Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium

    PubMed Central

    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

    2012-01-01

    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 (Ptrend < 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

  18. 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…

  19. Peroxiredoxins, gerontogenes linking aging to genome instability and cancer

    PubMed Central

    Nyström, Thomas; Yang, Junsheng; Molin, Mikael

    2012-01-01

    Age is the highest risk factor known for a large number of maladies, including cancers. However, it is unclear how aging mechanistically predisposes the organism to such diseases and which gene products are the primary targets of the aging process. Recent studies suggest that peroxiredoxins, antioxidant enzymes preventing tumor development, are targets of age-related deterioration and that bolstering their activity (e.g., by caloric restriction) extends cellular life span. This review focuses on how the peroxiredoxin functions (i.e., as peroxidases, signal transducers, and molecular chaperones) fit with contemporary theories of aging and whether peroxiredoxins could be targeted therapeutically in the treatment of age-associated cancers. PMID:22987634

  20. 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.

  1. Nutrition, aging and cancer: lessons from dietary intervention studies.

    PubMed

    Carruba, Giuseppe; Cocciadiferro, Letizia; Di Cristina, Antonietta; Granata, Orazia M; Dolcemascolo, Cecilia; Campisi, Ildegarda; Zarcone, Maurizio; Cinquegrani, Maria; Traina, Adele

    2016-01-01

    There is convincing epidemiological and clinical evidence that, independent of aging, lifestyle and, notably, nutrition are associated with development or progression of major human cancers, including breast, prostate, colorectal tumors, and an increasingly large collection of diet-related cancers. Mechanisms underlying this association are mostly related to the distinct epigenetic effects of different dietary patterns. In this context, Mediterranean diet has been reported to significantly reduce mortality rates for various chronic illnesses, including cardiovascular diseases, neurodegenerative diseases and cancer. Although many observational studies have supported this evidence, dietary intervention studies using a Mediterranean dietary pattern or its selected food components are still limited and affected by a rather large variability in characteristics of study subjects, type and length of intervention, selected end-points and statistical analysis. Here we review data of two of our intervention studies, the MeDiet study and the DiMeSa project, aimed at assessing the effects of traditional Mediterranean diet and/or its component(s) on a large panel of both plasma and urine biomarkers. Both published and unpublished results are presented and discussed. PMID:27057203

  2. 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.

  3. 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.

  4. Second hand smoke, age of exposure and lung cancer risk

    PubMed Central

    Asomaning, Kofi; Miller, David P.; Liu, Geoffrey; Wain, John C.; Lynch, Thomas J.; Su, Li; Christiani, David C.

    2008-01-01

    Background Exposure to second hand smoke (SHS) has been identified as a risk factor for lung cancer for three decades. It is also known that the lung continues to grow from birth to adulthood, when lung growth stops. We hypothesize that after adjusting for active cigarette smoking, if SHS exposure took place during the period of growth i.e. in the earlier part of life (0 to 25 years of age) the risk of lung cancer is greater compared to an exposure occurring after age 25. Method Second hand smoke exposure was self-reported for three different activities (leisure, work and at home) for this study population of 1669 cases and 1263 controls. We created variables that captured location of exposure and timing of first exposure with respect to a study participant's age (0 - 25, >25 years of age). Multiple logistic regressions were used to study the association between SHS exposure and lung cancer, adjusting for age, gender and active smoking variables. Result For study participants that were exposed to SHS at both activities (work and leisure) and compared to one or no activity, the adjusted odds ratio (AOR) for lung cancer was 1.30(1.08-1.57) when exposure occurred between birth and age 25 and 0.66(0.21-1.57) if exposure occurred after age 25 years. Respective results for nonsmokers were: 1.29 (0.82-2.02) and 0.87 (0.22-3.38), and current and ex smokers combined 1.28 (1.04-1.58) and 0.66 (0.15-2.85). Conclusion All individuals exposed to SHS have a higher risk of risk of lung cancer. Furthermore, this study suggests that subjects first exposed before age 25 have a higher lung cancer risk compared to those for whom first exposure occurred after age 25 years. PMID:18191495

  5. Ages of Late Spectral Type Vega-like Stars.

    PubMed

    Song; Caillault; Barrado Y Navascués D; Stauffer; Randich

    2000-04-10

    We have estimated the ages of eight late-type Vega-like stars by using standard age-dating methods for single late-type stars, e.g., location on the color-magnitude diagram, Li lambda6708 absorption, Ca ii H and K emission, X-ray luminosity, and stellar kinematic population. With the exception of the very unusual pre-main-sequence star system HD 98800, all the late-type Vega-like stars are the same age as the Hyades cluster (600-800 Myr) or older. PMID:10727387

  6. 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 ...

  7. DAMPs, Ageing, and Cancer: The ‘DAMP Hypothesis’

    PubMed Central

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

    2014-01-01

    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. HPV types and cofactors causing cervical cancer in Peru.

    PubMed

    Santos, C; Muñoz, N; Klug, S; Almonte, M; Guerrero, I; Alvarez, M; Velarde, C; Galdos, O; Castillo, M; Walboomers, J; Meijer, C; Caceres, E

    2001-09-28

    We conducted a hospital-based case-control study in Peru of 198 women with histologically confirmed cervical cancer (173 squamous cell carcinomas and 25 cases of adenocarcinoma/adenosquamous carcinoma) and 196 control women. Information on risk factors was obtained by personal interview. Using PCR-based assays on exfoliated cervical cells and biopsy specimens, HPV DNA was detected in 95.3% of women with squamous cell carcinoma and in 92.0% of women with adenocarcinoma/adenosquamous carcinoma compared with 17.7% in control women. The age-adjusted odds ratio was 116.0 (95% Cl = 48.6-276.0) for squamous cell carcinoma and 51.4 (95% Cl = 11.4-232.0) for adenocarcinoma/adenosquamous carcinoma. The commonest types in women with cervical cancer were HPV 16, 18, 31, 52 and 35. The association with the various HPV types was equally strong for the two most common types (HPV 16 and 18) as for the other less common types. In addition to HPV, long-term use of oral contraceptives and smoking were associated with an increased risk. HPV is the main cause of both squamous cell carcinoma and adenocarcinoma in Peruvian women. PMID:11592767

  9. 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

  10. Muscle wasting in cancer and ageing: cachexia versus sarcopenia.

    PubMed

    Argilés, J M; Busquets, S; Felipe, A; López-Soriano, F J

    2006-01-01

    Muscle wasting during cancer and ageing share many common metabolic pathways and mediators. Due to the size of the population involved, both cancer cachexia and ageing sarcopenia 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. 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 strategy for both prevention and treatment of wasting both in disease and during healthy ageing.

  11. US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines

    PubMed Central

    Unger, Elizabeth R.; Thompson, Trevor D.; Lynch, Charles F.; Hernandez, Brenda Y.; Lyu, Christopher W.; Steinau, Martin; Watson, Meg; Wilkinson, Edward J.; Hopenhayn, Claudia; Copeland, Glenn; Cozen, Wendy; Peters, Edward S.; Huang, Youjie; Saber, Maria Sibug; Altekruse, Sean; Goodman, Marc T.

    2015-01-01

    Background: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)–associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. Methods: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. Results: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. Conclusions: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine. PMID:25925419

  12. Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony

    2011-01-01

    In 1889, Dr. Stephen Paget proposed the “seed and soil” hypothesis, which states that cancer cells (the seeds) need the proper microenvironment (the soil) for them to grow, spread and metastasize systemically. In this hypothesis, Dr. Paget rightfully recognized that the tumor microenvironment has an important role to play in cancer progression and metastasis. In this regard, a series of recent studies have elegantly shown that the production of hydrogen peroxide, by both cancer cells and cancer-associated fibroblasts, may provide the necessary “fertilizer,” by driving accelerated aging, DNA damage, inflammation and cancer metabolism, in the tumor microenvironment. By secreting hydrogen peroxide, cancer cells and fibroblasts are mimicking the behavior of immune cells (macrophages/neutrophils), driving local and systemic inflammation, via the innate immune response (NFκB). Thus, we should consider using various therapeutic strategies (such as catalase and/or other antioxidants) to neutralize the production of cancer-associated hydrogen peroxide, thereby preventing tumor-stroma co-evolution and metastasis. The implications of these findings for overcoming chemo-resistance in cancer cells are also discussed in the context of hydrogen peroxide production and cancer metabolism. PMID:21734470

  13. 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,…

  14. Age-Period-Cohort Analysis of Thyroid Cancer Incidence in Korea

    PubMed Central

    Oh, Chang-Mo; Jung, Kyu-Won; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Lee, Jin-Soo

    2015-01-01

    Purpose South Korea has the highest incidence rate of thyroid cancer in the world, and the incidence rate continues to increase. The aim of this study was to determine the age-period-cohort effects on the incidence of thyroid cancer in Korea. Materials and Methods Using the Korean National Cancer registry database, age-standardized incidence rates and annual percent changes (APCs) in thyroid cancer according to sex and histologic type were analyzed between 1997 and 2011. Age-period-cohort models were applied using an intrinsic estimator method according to sex. Results In both men and women, the incidence of thyroid cancer showed a sharp increase from 1997 through 2011. Among the histologic types, papillary carcinoma showed the greatest increase, with APCs of 25.1% (95% confidence interval [CI], 22.7% to 27.5%) in men and 23.7% (95% CI, 21.9% to 25.5%) in women, whereas anaplastic carcinoma did not show a significant increase in either sex. An increase in overall thyroid cancer incidence over time was observed in all birth cohorts. An age-period-cohort model indicated a steeply increasing period effect, which increased prominently from 1997 to 2011 in both men and women. The age effect showed an inverted U-shaped trend. The cohort effect tended to show a slight increase or remain constant from 1952 to 1977, followed by a decrease. Conclusion The period effect can explain the sharp increase in thyroid cancer incidence, strongly suggesting the role of thyroid screening. PMID:25672579

  15. Biological ageing and frailty markers in breast cancer patients

    PubMed Central

    Hatse, Sigrid; Laenen, Annouschka; Kenis, Cindy; Swerts, Evalien; Neven, Patrick; Smeets, Ann; Schöffski, Patrick; Wildiers, Hans

    2015-01-01

    Older cancer patients are a highly heterogeneous population in terms of global health and physiological reserves, and it is often difficult to determine the best treatment. Moreover, clinical tools currently used to assess global health require dedicated time and lack a standardized end score. Circulating markers of biological age and/or fitness could complement or partially substitute the existing screening tools. In this study we explored the relationship of potential ageing/frailty biomarkers with age and clinical frailty. On a population of 82 young and 162 older non-metastatic breast cancer patients, we measured mean leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also developed a new tool to summarize clinical frailty, designated Leuven Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi-continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL-6 levels were associated with chronological age in both groups and with clinical frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1 only correlated with age. Plasma IL-6 should be further explored as frailty biomarker in cancer patients. PMID:25989735

  16. 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

  17. Relationship between exposure to radon and various types of cancer

    SciTech Connect

    Cohen, B.L. )

    1993-11-01

    Correlations are studied between average radon levels in 1600 U.S. counties and mortality rates in them from various types of cancer. By far the strongest correlation is with lung cancer, but the sign of the correlation is negative. When smoking prevalence is included in a multiple regression, the large negative correlation between radon and lung cancer is essentially unaffected.

  18. Type of alcoholic beverage and oral cancer.

    PubMed

    Kabat, G C; Wynder, E L

    1989-02-15

    The effect on oral cancer risk of different types of alcoholic beverage was investigated using data from a hospital-based case-control study. Owing to the small numbers of subjects drinking one beverage exclusively, it was necessary to classify drinkers as consumers of predominantly beer, wine, or hard liquor (i.e., more than 50% of their whiskey equivalents of alcohol derived from a specific beverage). The number of predominantly wine drinkers was too small to permit analysis. Logistic regression was used to obtain estimates of the risk associated with each predominant beverage, with adjustment for other risk factors and confounding variables. In males, the odds ratio for predominantly beer drinkers increased with increasing level of intake, reaching 4.87 (95% confidence interval: 2.51-9.46) in drinkers of 7+ oz. of whiskey equivalents/day. The odds ratio for predominantly hard liquor drinkers showed a similar increase, reaching 5.74 (95% confidence interval: 2.94-11.22) in predominantly hard liquor drinkers consuming 7+ oz. of whiskey equivalents/day, suggesting that the effect of these 2 major types of alcoholic beverage is of similar magnitude. The trends were less clearcut in women due to small numbers of drinkers.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Telomeric Repeat Containing RNA (TERRA): Aging and Cancer.

    PubMed

    Sinha, Sonam; Shukla, Samriddhi; Khan, Sajid; Farhan, Mohammad; Kamal, Mohammad Amjad; Meeran, Syed Musthapa

    2015-01-01

    Telomeric repeat containing RNAs (TERRA) are small RNA molecules synthesized from telomeric regions which were previously considered as silent genomic domains. In normal cells, these RNAs are transcribed in a direction from subtelomeric region towards the chromosome ends, but in case of cancer cells, their expression remains limited or absent. Telomerase is a rate limiting enzyme for cellular senescence, cancer and aging. Most of the studies deal with the manipulation of telomerase enzyme in cancer and aging either by synthetic oligonucleotide or by natural phytochemicals. Here, we collected evidences and discussed intensely about the bio-molecular structure of TERRA, naturally occurring ligands of telomerase, and their genetic and epigenetic regulations in aging associated diseases. Due to their capability to act as naturally occurring ligands of telomerase, these RNAs can overcome the limitations possessed by synthetic oligonucleotides, which are aimed against telomerase. Drugs specifically targeting TERRA molecules could modulate telomerase-mediated telomere lengthening. Thus, targeting TERRA-mediated regulation of telomerase would be a promising therapeutic strategy against cancer and age-associated diseases.

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

    PubMed

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

    2015-11-15

    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.

  5. 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.

  6. 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

  7. 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

  8. [Bladder cancer at an early age in father and son].

    PubMed

    Ovsiannikov, D; Stöhr, R; Hartmann, A; Böttrich, R; Hengstler, J G; Golka, K

    2011-12-01

    Bladder cancer may be caused by external factors like tobacco smoking, but may also be familial. We report on a father and son who developed this tumour at the ages of 45 and 35. Testing various genetic markers including the mismatch repair proteins MLH1, MSH2 and MSH6, whose loss is associated with a higher risk for hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome), did not point to a familial disease. Thus the heavy smoking habits of the two patients must be considered as causal.

  9. Characterization of hearing loss in aged type II diabetics.

    PubMed

    Frisina, Susan T; Mapes, Frances; Kim, SungHee; Frisina, D Robert; Frisina, Robert D

    2006-01-01

    Presbycusis - age-related hearing loss - is the number one communicative disorder and a significant chronic medical condition of the aged. Little is known about how type II diabetes, another prevalent age-related medical condition, and presbycusis interact. The present investigation aimed to comprehensively characterize the nature of hearing impairment in aged type II diabetics. Hearing tests measuring both peripheral (cochlea) and central (brainstem and cortex) auditory processing were utilized. The majority of differences between the hearing abilities of the aged diabetics and their age-matched controls were found in measures of inner ear function. For example, large differences were found in pure-tone audiograms, wideband noise and speech reception thresholds, and otoacoustic emissions. The greatest deficits tended to be at low frequencies. In addition, there was a strong tendency for diabetes to affect the right ear more than the left. One possible interpretation is that as one develops presbycusis, the right ear advantage is lost, and this decline is accelerated by diabetes. In contrast, auditory processing tests that measure both peripheral and central processing showed fewer declines between the elderly diabetics and the control group. Consequences of elevated blood sugar levels as possible underlying physiological mechanisms for the hearing loss are discussed.

  10. 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

  11. 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

  12. 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.

  13. Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk

    PubMed Central

    Brand, Judith S.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Sharp, Stephen J.; Ong, Ken K.; Khaw, Kay-Tee; Ardanaz, Eva; Amiano, Pilar; Boeing, Heiner; Chirlaque, Maria-Dolores; Clavel-Chapelon, Françoise; Crowe, Francesca L.; de Lauzon-Guillain, Blandine; Duell, Eric J.; Fagherazzi, Guy; Franks, Paul W.; Grioni, Sara; Groop, Leif C.; Kaaks, Rudolf; Key, Timothy J.; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez, María-José; Slimani, Nadia; Teucher, Birgit; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; Feskens, Edith J.M.; Langenberg, Claudia; Forouhi, Nita G.; Riboli, Elio; Wareham, Nicholas J.

    2013-01-01

    OBJECTIVE Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04–1.69), 1.09 (0.90–1.31), 0.97 (0.86–1.10), and 0.85 (0.70–1.03) for women with menopause at ages <40, 40–44, 45–49, and ≥55 years, respectively, relative to those with menopause at age 50–54 years. The HR per SD younger age at menopause was 1.08 (1.02–1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01–1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05). CONCLUSIONS Early menopause is associated with a greater risk of type 2 diabetes. PMID:23230098

  14. 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

  15. Prevalence of human papillomavirus types in invasive cervical cancers from seven US cancer registries prior to vaccine introduction

    PubMed Central

    Hopenhayn, Claudia; Christian, Amy; Christian, W. Jay; Watson, Meg; Unger, Elizabeth R.; Lynch, Charles F.; Peters, Edward S.; Wilkinson, Edward J.; Huang, Youjie; Copeland, Glenn; Cozen, Wendy; Saber, Maria Sibug; Goodman, Marc T.; Hernandez, Brenda Y.; Steinau, Martin; Lyu, Christopher; Tucker, Thomas T.; Saraiya, Mona

    2013-01-01

    Objective We conducted a baseline study of human papillomavirus (HPV) type prevalence in invasive cervical cancers (ICC) using data from seven cancer registries (CR) in the US. Cases were diagnosed between 1994 and 2005, before the implementation of the HPV vaccines. Materials and Methods CRs from Florida, Kentucky, Louisiana, Michigan, Hawaii, Iowa and Los Angeles, California identified eligible ICC cases, and obtained sections from representative blocks of archived tumor specimens for DNA extraction. All extracts were assayed by Linear Array and if inadequate or HPV negative, re-tested with INNO-LiPA Genotype test. Clinical and demographic factors were obtained from the CRs and merged with the HPV typing data to analyze factors associated with different types and with HPV negativity. Results A total of 777 ICCs were included in this analysis, with broad geographic, age and race distribution. Overall, HPV was detected in 91% of cases, including 51% HPV16, 16% HPV18 (HPV16 negative), and 24% other oncogenic and rare types. After HPV16 and 18, the most common types were 45, 33, 31, 35 and 52. Older age and non-squamous histology were associated with HPV negative typing. Conclusions This study provides baseline pre-vaccine HPV types for post-vaccine ICC surveillance in the future. HPV16 and/or 18 were found in 67% of ICCs, indicating the potential for vaccines to prevent a significant number of cervical cancers. PMID:24477171

  16. 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 ...

  17. 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

  18. Molecular damage in cancer: an argument for mTOR-driven aging.

    PubMed

    Blagosklonny, Mikhail V

    2011-12-01

    Despite common belief, accumulation of molecular damage does not play a key role in aging. Still, cancer (an age-related disease) is initiated by molecular damage. Cancer and aging share a lot in common including the activation of the TOR pathway. But the role of molecular damage distinguishes cancer and aging. Furthermore, an analysis of the role of both damage and aging in cancer argues against "a decline, caused by accumulation of molecular damage" as a cause of aging. I also discuss how random molecular damage, via rounds of multiplication and selection, brings about non-random hallmarks of cancer.

  19. 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 ...

  20. 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.

  1. 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

  2. Type I and II Endometrial Cancers: Have They Different Risk Factors?

    PubMed Central

    Setiawan, Veronica Wendy; Yang, Hannah P.; Pike, Malcolm C.; McCann, Susan E.; Yu, Herbert; Xiang, Yong-Bing; Wolk, Alicja; Wentzensen, Nicolas; Weiss, Noel S.; Webb, Penelope M.; van den Brandt, Piet A.; van de Vijver, Koen; Thompson, Pamela J.; Strom, Brian L.; Spurdle, Amanda B.; Soslow, Robert A.; Shu, Xiao-ou; Schairer, Catherine; Sacerdote, Carlotta; Rohan, Thomas E.; Robien, Kim; Risch, Harvey A.; Ricceri, Fulvio; Rebbeck, Timothy R.; Rastogi, Radhai; Prescott, Jennifer; Polidoro, Silvia; Park, Yikyung; Olson, Sara H.; Moysich, Kirsten B.; Miller, Anthony B.; McCullough, Marjorie L.; Matsuno, Rayna K.; Magliocco, Anthony M.; Lurie, Galina; Lu, Lingeng; Lissowska, Jolanta; Liang, Xiaolin; Lacey, James V.; Kolonel, Laurence N.; Henderson, Brian E.; Hankinson, Susan E.; Håkansson, Niclas; Goodman, Marc T.; Gaudet, Mia M.; Garcia-Closas, Montserrat; Friedenreich, Christine M.; Freudenheim, Jo L.; Doherty, Jennifer; De Vivo, Immaculata; Courneya, Kerry S.; Cook, Linda S.; Chen, Chu; Cerhan, James R.; Cai, Hui; Brinton, Louise A.; Bernstein, Leslie; Anderson, Kristin E.; Anton-Culver, Hoda; Schouten, Leo J.; Horn-Ross, Pamela L.

    2013-01-01

    Purpose Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and Methods Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Results Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (Pheterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. Conclusion The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed. PMID:23733771

  3. Study Suggests Type 2 Diabetes-Cancer Link

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159814.html Study Suggests Type 2 Diabetes-Cancer Link It hints ... screening tests following a diagnosis of diabetes," said study author Dr. Iliana Lega, of the University of ...

  4. 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

  5. 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

    2015-12-21

    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.

  6. 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

  7. 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.

  8. The association between type 2 diabetes mellitus and women cancer: the epidemiological evidences and putative mechanisms.

    PubMed

    Joung, Kyong Hye; Jeong, Jae-Wook; Ku, Bon Jeong

    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.

  9. 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

  10. 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

  11. Recurrence Interval and Event Age Data for Type A Faults

    USGS Publications Warehouse

    Dawson, Timothy E.; Weldon, Ray J.; Biasi, Glenn P.

    2008-01-01

    This appendix summarizes available recurrence interval, event age, and timing of most recent event data for Type A faults considered in the Earthquake Rate Model 2 (ERM 2) and used in the ERM 2 Appendix C analysis as well as Appendix N (time-dependent probabilities). These data have been compiled into an Excel workbook named Appendix B A-fault event ages_recurrence_V5.0 (herein referred to as the Appendix B workbook). For convenience, the Appendix B workbook is attached to the end of this document as a series of tables. The tables within the Appendix B workbook include site locations, event ages, and recurrence data, and in some cases, the interval of time between earthquakes is also reported. The Appendix B workbook is organized as individual worksheets, with each worksheet named by fault and paleoseismic site. Each worksheet contains the site location in latitude and longitude, as well as information on event ages, and a summary of recurrence data. Because the data has been compiled from different sources with different presentation styles, descriptions of the contents of each worksheet within the Appendix B spreadsheet are summarized.

  12. Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband

    PubMed Central

    Gronwald, J; Cybulski, C; Piesiak, W; Suchy, J; Huzarski, T; Byrski, T; Gorski, B; Debniak, T; Szwiec, M; Wokolowczyk, D; Matuszewski, M; Sun, P; Lubinski, J; Narod, S A

    2009-01-01

    It is important to have accurate knowledge of the range of cancers associated with various CHEK2 mutations, and of the lifetime risks of cancer associated with each. We wished to establish the relationship between family history, mutation type and cancer risk in families with a CHEK2 mutation. We obtained a blood sample and pedigree information from 2012 unselected women with breast cancer, from 2007 men with prostate cancer and from 1934 patients with colon cancer, from hospitals throughout Poland. Genetic testing was carried out for four founder CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to be 22.3%. After adjusting for mutation type, the risk of breast cancer was much higher among relatives of probands with breast cancer than among relatives of patients with prostate or colon cancer (HR=3.6; 95% CI=2.1–6.2; P=0.0001). Similarly, the risk of prostate cancer was higher among relatives of probands with prostate cancer than among relatives of patients with breast or colon cancer (HR=4.4; 95% CI=2.2–8.7; P=0.0001) and the risk of colon cancer was higher among relatives of probands with colon cancer than among relatives of patients with prostate or breast cancer (HR=4.2; 95% CI=2.4–7.8; P=0.0001). These analyses suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on the family history of cancer. PMID:19401704

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Increased methylation variation in epigenetic domains across cancer types.

    PubMed

    Hansen, Kasper Daniel; Timp, Winston; Bravo, Héctor Corrada; Sabunciyan, Sarven; Langmead, Benjamin; McDonald, Oliver G; Wen, Bo; Wu, Hao; Liu, Yun; Diep, Dinh; Briem, Eirikur; Zhang, Kun; Irizarry, Rafael A; Feinberg, Andrew P

    2011-06-26

    Tumor heterogeneity is a major barrier to effective cancer diagnosis and treatment. We recently identified cancer-specific differentially DNA-methylated regions (cDMRs) in colon cancer, which also distinguish normal tissue types from each other, suggesting that these cDMRs might be generalized across cancer types. Here we show stochastic methylation variation of the same cDMRs, distinguishing cancer from normal tissue, in colon, lung, breast, thyroid and Wilms' tumors, with intermediate variation in adenomas. Whole-genome bisulfite sequencing shows these variable cDMRs are related to loss of sharply delimited methylation boundaries at CpG islands. Furthermore, we find hypomethylation of discrete blocks encompassing half the genome, with extreme gene expression variability. Genes associated with the cDMRs and large blocks are involved in mitosis and matrix remodeling, respectively. We suggest a model for cancer involving loss of epigenetic stability of well-defined genomic domains that underlies increased methylation variability in cancer that may contribute to tumor heterogeneity.

  1. Are 20 human papillomavirus types causing cervical cancer?

    PubMed

    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim

    2014-12-01

    In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the α-Papillomaviridae, in particular to the species α5 (HPV51), α6 (HPV56), α7 (HPV18, HPV39, HPV45, HPV59) and α9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58). Less evidence is available for a thirteenth type (HPV68, α7), which is classified as a 2A carcinogen (probably carcinogenic). Moreover, seven other phylogenetically related types (HPV26, HPV53, HPV66, HPV67, HPV68, HPV70 and HPV73) were identified as single HPV infections in certain rare cases of cervical cancer and were considered possibly carcinogenic (2B carcinogens). Recently, Halec et al [7] demonstrated that the molecular signature of HPV-induced carcinogenesis (presence of type-specific spliced E6*| mRNA; increased expression of p16; and decreased expression of cyclin D1, p53 and Rb) was similar in cervical cancers containing single infections with one of the eight afore-mentioned 2A or 2B carcinogens to those in cancers with single infections with group 1 carcinogens. Ninety six percent of cervical cancers are attributable to one of the 13 most common HPV types (groups 1 and 2A). Including the additional seven HPV types (group 2B) added 2.6%, to reach a total of 98.7% of all HPV-positive cervical cancers. From recently updated meta-analyses, it was shown that HPV68, HPV26, HPV66, HPV67, HPV73 and HPV82 were significantly more common in cancer cases than in women with normal cervical cytology, suggesting that for these HPV types, an upgrading of the carcinogen classification could be considered. However, there is no need to include them in HPV screening tests or vaccines, given their rarity in

  2. 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

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

    PubMed

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

    1986-05-01

    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.

  4. 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

  5. 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.

  6. 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

  7. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Types of evidence to prove age. 219.21... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.21 Types of evidence to prove age. (a) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate...

  8. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Types of evidence to prove age. 219.21... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.21 Types of evidence to prove age. (a) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate...

  9. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Types of evidence to prove age. 219.21 Section... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.21 Types of evidence to prove age. (a) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate...

  10. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Types of evidence to prove age. 219.21 Section... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.21 Types of evidence to prove age. (a) Preferred evidence. The best type of evidence to prove a claimant's age is— (1) A birth certificate...

  11. Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis.

    PubMed

    Chen, C; Wang, X; Xiong, X; Liu, Q; Huang, Y; Xu, Q; Hu, J; Ge, G; Ling, K

    2015-08-27

    Most deaths from breast cancer are caused by metastasis, a complex behavior of cancer cells involving migration, invasion, survival and microenvironment manipulation. Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) regulates focal adhesion assembly and its phosphorylation at Y639 is critical for cell migration induced by EGF. However, the role of this lipid kinase in tumor metastasis remains unclear. Here we report that PIPKIγ is vital for breast cancer metastasis. Y639 of PIPKIγ can be phosphorylated by stimulation of EGF and hepatocyte growth factor (HGF), two promoting factors for breast cancer progression. Histological analysis revealed elevated Y639 phosphorylation of PIPKIγ in invasive ductal carcinoma lesions and suggested a positive correlation with tumor grade. Orthotopically transplanted PIPKIγ-depleted breast cancer cells showed substantially reduced growth and metastasis, as well as suppressed expression of multiple genes related to cell migration and microenvironment manipulation. Re-expression of wild-type PIPKIγ in PIPKIγ-depleted cells restored tumor growth and metastasis, reinforcing the importance of PIPKIγ in breast cancer progression. Y639-to-F or a kinase-dead mutant of PIPKIγ could not recover the diminished metastasis in PIPKIγ-depleted cancer cells, suggesting that Y639 phosphorylation and lipid kinase activity are both required for development of metastasis. Further analysis with in vitro assays indicated that depleting PIPKIγ inhibited cell proliferation, MMP9 secretion and cell migration and invasion, lending molecular mechanisms for the eliminated cancer progression. These results suggest that PIPKIγ, downstream of EGF and/or HGF receptor, participates in breast cancer progression from multiple aspects and deserves further studies to explore its potential as a therapeutic target.

  12. 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.

  13. 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

  14. Kernel mixture survival models for identifying cancer subtypes, predicting patient's cancer types and survival probabilities.

    PubMed

    Ando, Tomohiro; Imoto, Seiya; Miyano, Satoru

    2004-01-01

    One important application of microarray gene expression data is to study the relationship between the clinical phenotype of cancer patients and gene expression profiles on the whole-genome scale. The clinical phenotype includes several different types of cancers, survival times, relapse times, drug responses and so on. Under the situation that the subtypes of cancer have not been previously identified or known to exist, we develop a new kernel mixture modeling method that performs simultaneously identification of the subtype of cancer, prediction of the probabilities of both cancer type and patient's survival, and detection of a set of marker genes on which to base a diagnosis. The proposed method is successfully performed on real data analysis and simulation studies.

  15. Variation in the association between colorectal cancer susceptibility loci and colorectal polyps by polyp type.

    PubMed

    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

    2014-07-15

    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.

  16. Age-related cancer mutations associated with clonal hematopoietic expansion

    PubMed Central

    Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D.; Johnson, Kimberly J.; Wendl, Michael C.; McMichael, Joshua F.; Schmidt, Heather K.; Yellapantula, Venkata; Miller, Christopher A.; Ozenberger, Bradley A.; Welch, John S.; Link, Daniel C.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Chen, Feng; Wilson, Richard K.; Ley, Timothy J.; Ding, Li

    2015-01-01

    Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. We analyzed blood-derived sequence data from 2,728 individuals within The Cancer Genome Atlas, and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia/lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant, initiating events that cause clonal hematopoietic expansion. PMID:25326804

  17. Exploring different types of Hatha yoga for patients with cancer.

    PubMed

    Subedi, Sunita

    2014-10-01

    Yoga has been practiced for more than 5,000 years and is based on the collective experiences of yoga practitioners over time. Western countries and sophisticated medical facilities use this practice as a complementary therapy with standard medical treatments. Yoga has been shown to improve quality of life. Several types of yoga potentially can benefit people with cancer, including Hatha yoga. The type of recommended Hatha yoga is dependent on the physical conditions and fitness level of patients. This article explores the impact of different types of Hatha yoga on various cancer-related symptoms in patients with cancer. The article also provides guidelines for healthcare personnel-particularly nurses-to help choose the right kind of Hatha yoga that suits their patients' needs and interests. Additional information is provided on measures and instructions that are essential for healthcare providers to know before recommending any yoga type to their patients. Evidence of the feasibility and potential efficacy of yoga for patients with cancer is provided.

  18. 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

  19. 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

  20. Retrospective study of cancer types in different ethnic groups and genders at Karachi.

    PubMed

    Khaliq, Sheikh Abdul; Naqvi, Syed Baqir; Fatima, Anab

    2013-12-01

    Retrospective study of Cancer types in different ethnic groups & genders determines the pattern of cancers in different ethnic groups & genders during the last eight years reported in Oncology wards of hospitals of Karachi, Pakistan. Every single one male & female case with histologically and cytologically established cancer was enrolled from January 2003 to December 2010. Data for all patients were collected retrospectively by patient's file & charts, which represents the population of Karachi, Interior Sindh & Balochistan. 5134 patients (Male = 2432 / Female = 2702) investigated for their diagnosis of cancer type, ethnicity, age & gender. Classification of malignancy was done according to the International Classification of Disease coding system by W.H.O (ICD-10). The statistical analysis was performed for mean, standard error & proportions for ethnic groups & genders. Proportionately 47.37% males and among which major ethnic groups 17% Sindhi, 17% Immigrant, 4% Baloch, 3% Pukhtoon, ≈ 4% Punjabi, 1% Siraiki, 2% Minorities and 52.62% females, in which 16% Sindhi, 21% Immigrant, 4% Baloch 3% Pukhtoon, 5% Punjabi, 1% Siraiki, 3% Minorities. Mean age of males = 45.75 years, SE ± 0.227 and for females = 44.07, SE ± 0.183. The three most occurring tumors in all cancers of male were found Head & Neck, Adenoma/Carcinoma of Glands & Body cavity membranes, GIT, and females Breast, Head & Neck, Adenoma/Carcinoma of Glands & Body cavity membranes, GIT. The analysis of data indicates Head & Neck is most common cancer among male, in the similar way Breast cancer is the most common malignancy among female.

  1. 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.

  2. 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

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

    PubMed

    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

    2014-10-15

    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 control 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 nonsmall 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.

  4. Diffuse Type Gastric and Lobular Breast Carcinoma in a Familial Gastric Cancer Patient with an E-Cadherin Germline Mutation

    PubMed Central

    Keller, Gisela; Vogelsang, Holger; Becker, Ingrid; Hutter, Jörg; Ott, Katja; Candidus, Sonja; Grundei, Tobias; Becker, Karl-Friedrich; Mueller, James; Siewert, Jörg R.; Höfler, Heinz

    1999-01-01

    E-Cadherin alterations have been reported frequently in sporadic diffuse type gastric and lobular breast carcinomas. Germline mutations of this gene have been identified recently in several gastric cancer families. We analyzed seven patients with a family history of the disease who had diffuse type gastric cancer diagnosed before the age of 45 for germline mutations in CDH1, the gene encoding the E-cadherin protein. We identified a frameshift mutation in exon 3 in one patient with a strong family history of gastric cancer. The same germline mutation was found in the patient’s mother, who had metachronous development of lobular breast and diffuse type gastric carcinomas. Immunohistochemistry for E-cadherin protein expression revealed an abnormal staining pattern in both of these tumors, suggesting complete inactivation of the cell adhesion molecule. Thus, our finding suggests that besides diffuse type gastric cancer, lobular breast carcinomas may be associated with germline CDH1 mutations. PMID:10433926

  5. 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.

  6. [Cancer procoagulant activity in cases of esophageal, stomach and colorectal cancer considering progression degree and histological type of cancer].

    PubMed

    Kozuszko, B; Skrzydlewski, Z; Sulkowska, M; Snarska, J; Kozłowski, M; Skrzydlewska, E; Zalewski, B

    2001-09-01

    The cancer procoagulant activity has been evaluated in homogenates of esophagal, stomach and colorectal cancer tissues and in the blood serum of patients with these neoplasms's. Activity of CP was significantly higher in examined material than in control. The correlation between CP activity and progression degree as well as histological type was affirmed. The higher activity of CP in homogenates as well as in serum was observed in cases with higher degree of clinical progression and smaller activity of this enzyme corresponded with lower degree of the cancer progression. The highest activity of CP was observed in the cases of adenocarcinoma whereas the lowest in cases of squamous cell carcinoma. Higher activity of CP in homogenates of examined tissues correlated with higher activity of this enzyme in the serum. Activity of CP depended on the tissue localisation of the cancer and the highest was in the cases of stomach cancers whereas the lowest was in the cases of esophagal cancer.

  7. 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.

  8. 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

  9. 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.

  10. Personalizing Age of Cancer Screening Cessation Based on Comorbidity: Model estimates of harms and benefits

    PubMed Central

    Lansdorp-Vogelaar, Iris; Gulati, Roman; Mariotto, Angela B; Schechter, Clyde B; de Carvalho, Tiago M; Knudsen, Amy B; van Ravesteyn, Nicolien T; Heijnsdijk, Eveline AM; Pabiniak, Chester; van Ballegooijen, Marjolein; Rutter, Carolyn M; Kuntz, Karen M; Feuer, Eric J; Etzioni, Ruth; de Koning, Harry J; Zauber, Ann G; Mandelblatt, Jeanne S

    2014-01-01

    Background Harms and benefits of cancer screening depend on age and comorbidity, yet reliable estimates are lacking. Objective To estimate the harms and benefits of cancer screening by age and comorbidity to inform decisions about screening cessation. Design Collaborative modeling with seven well-established cancer simulation models and common data on average and comorbidity level-specific life expectancy from SEER-Medicare. Setting US population. Patients US cohorts aged 66–90 years in 2010 with average health or one of four comorbidity levels (linked to specific conditions): none, mild, moderate, or severe. Intervention Mammography, prostate-specific antigen testing, or fecal immunochemical testing. Measurements Lifetime cancer deaths prevented and life-years gained (benefits); false-positive tests and overdiagnosed cancers (harms). For each comorbidity level: the age at which harms and benefits of screening were similar to that for individuals with average health undergoing screening at age 74. Results Screening 1000 women with average life expectancy at age 74 for breast cancer resulted in 79–96 (range across models) false-positives, 0.5–0.8 overdiagnosed cancers, and 0.7–0.9 breast cancer deaths prevented. While absolute numbers of harms and benefits differed across cancer sites, the ages at which to cease screening were highly consistent across models and cancer sites when based on harm-benefit ratios comparable to screening average-health individuals at age 74. For individuals with no, mild, moderate, and severe comorbidities, screening until ages of 76, 74, 72, and 66, respectively, resulted in similar harms and benefits as for average-health individuals. Limitations Comorbidity only influenced life expectancy. Conclusion Comorbidity is an important determinant of harms and benefits of screening. Estimates of screening benefits and harms by comorbidity can inform discussions between providers and their older patients about personalizing decisions

  11. The Use of Metformin and the Incidence of Lung Cancer in Patients With Type 2 Diabetes

    PubMed Central

    Smiechowski, Brielan B.; Azoulay, Laurent; Yin, Hui; Pollak, Michael N.; Suissa, Samy

    2013-01-01

    OBJECTIVE Observational studies have associated metformin use with a decreased risk of lung cancer incidence in patients with type 2 diabetes, but the studies had important methodological shortcomings. The objective of this study was to determine whether metformin use is associated with a decreased risk of lung cancer in patients with type 2 diabetes, while avoiding previous biases. RESEARCH DESIGN AND METHODS Using the U.K. General Practice Research Database, we assembled a cohort of patients newly treated with oral hypoglycemic agents (OHAs) between 1988 and 2009. A nested case–control analysis was conducted, where case subjects with lung cancer occurring during follow-up were matched with up to 10 control subjects for age, sex, calendar time, and duration of follow-up. Conditional logistic regression was used to estimate adjusted rate ratios of lung cancer associated with ever use of metformin, along with measures of duration and cumulative dose. Models were adjusted for potential confounders, which included smoking. RESULTS The cohort included 115,923 new users of OHAs, with 1,061 patients diagnosed with lung cancer during follow-up (rate 2.0/1,000 person-years). Metformin use was not associated with a decreased rate of lung cancer (rate ratio 0.94 [95% CI 0.76–1.17]). No dose-response was observed by number of prescriptions received, cumulative duration of use, and dose. CONCLUSIONS Metformin use is not associated with a decreased risk of lung cancer in patients with type 2 diabetes. The decreased risk reported in other observational studies is likely due to bias from methodological shortcomings. Nonetheless, greater consideration should be given to clarify inconsistencies between experimental models and population studies. PMID:22923670

  12. 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

  13. 20 CFR 219.21 - Types of evidence to prove age.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) 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...

  14. A registry study of the association of patient's residence and age with colorectal cancer survival.

    PubMed

    Sankaranarayanan, Jayashri; Qiu, Fang; Watanabe-Galloway, Shinobu

    2014-04-01

    Because of limited literature from rural states of the United States like Nebraska, we evaluated the association of patient's age, Office of Management and Budget residence-county categories (rural-nonmetro, micropolitan-nonmetro, urban), and significant interactions between confounding-variables with colorectal cancer (CRC) survival. This retrospective 1998-2003 study of 6561 CRC patients from the Nebraska Cancer Registry showed median patient survival in colon and rectal cancer in urban, rural and micropolitan counties were 33, 36, and 46 months and 41, 47, 49 months, respectively. In Cox proportional-hazards analyses, after adjusting for significant demographics (age, race, marital status in colon cancer; age, insurance status in rectal cancer), cancer stage, surgery and radiation treatments; 1) no-chemotherapy urban colon cancer patients had significantly shorter survival (rural vs urban; adjusted hazard ratio, HR: 0.78 or urban vs rural HR: 1.28; micropolitan vs urban, HR: 0.78) and 2) no-surgery urban (vs rural, HR: 1.49); micropolitan (vs rural, HR: 2.01) rectal cancer patients had significantly shorter survival. Colon cancer (≥65 years) and rectal cancer (≥75 years) elderly each versus patients aged 19-64 years old had significantly shorter survival (all p < 0.01). The association of patients' age and treatment/residence-county interactions with CRC survival warrant decision-makers' attention.

  15. 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.

  16. The cancer survival gap between elderly and middle-aged patients in Europe is widening.

    PubMed

    Quaglia, Alberto; Tavilla, Andrea; Shack, Lorraine; Brenner, Hermann; Janssen-Heijnen, Maryska; Allemani, Claudia; Colonna, Marc; Grande, Enrico; Grosclaude, Pascale; Vercelli, Marina

    2009-04-01

    The present study is aimed to compare survival and prognostic changes over time between elderly (70-84 years) and middle-aged cancer patients (55-69 years). We considered seven cancer sites (stomach, colon, breast, cervix and corpus uteri, ovary and prostate) and all cancers combined (but excluding prostate and non-melanoma skin cancers). Five-year relative survival was estimated for cohorts of patients diagnosed in 1988-1999 in a pool of 51 European populations covered by cancer registries. Furthermore, we applied the period-analysis method to more recent incidence data from 32 cancer registries to provide 1- and 5-year relative survival estimates for the period of follow-up 2000-2002. A significant survival improvement was observed from 1988 to 1999 for all cancers combined and for every cancer site, except cervical cancer. However, survival increased at a slower rate in the elderly, so that the gap between younger and older patients widened, particularly for prostate cancer in men and for all considered cancers except cervical cancer in women. For breast and prostate cancers, the increasing gap was likely attributable to a larger use of, respectively, mammographic screening and PSA test in middle-aged with respect to the elderly. In the period analysis of the most recent data, relative survival was much higher in middle-aged patients than in the elderly. The differences were higher for breast and gynaecological cancers, and for prostate cancer. Most of this age gap was due to a very large difference in survival after the 1st year following the diagnosis. Differences were much smaller for conditional 5-year relative survival among patients who had already survived the first year. The increase of survival in elderly men is encouraging but the lesser improvement in women and, in particular, the widening gap for breast cancer suggest that many barriers still delay access to care and that enhanced prevention and clinical management remain major issues.

  17. 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

  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. 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 ...

  2. 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.

  3. 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

  4. FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer.

    PubMed

    Bhartiya, Deepa; Singh, Jarnail

    2015-01-01

    Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers.

  5. p53 mutations associated with aging-related rise in cancer incidence rates.

    PubMed

    Richardson, Richard B

    2013-08-01

    TP53's role as guardian of the genome diminishes with age, as the probability of mutation increases. Previous studies have shown an association between p53 gene mutations and cancer. However, the role of somatic TP53 mutations in the steep rise in cancer rates with aging has not been investigated at a population level. This relationship was quantified using the International Agency for Research on Cancer (IARC) TP53 and GLOBOCAN cancer databases. The power function exponent of the cancer rate was calculated for 5-y age-standardized incidence or mortality rates for up to 25 cancer sites occurring in adults of median age 42 to 72 y. Linear regression analysis of the mean percentage of a cancer's TP53 mutations and the corresponding cancer exponent was conducted for four populations: worldwide, Japan, Western Europe, and the United States. Significant associations (P ≤ 0.05) were found for incidence rates but not mortality rates. Regardless of the population studied, positive associations were found for all cancer sites, with more significant associations for solid tumors, excluding the outlier prostate cancer or sex-related tumors. Worldwide and Japanese populations yielded P values as low as 0.002 and 0.005, respectively. For the United States, a significant association was apparent only when analysis utilized the Surveillance, Epidemiology, and End Results (SEER) database. This study found that TP53 mutations accounts for approximately one-quarter and one-third of the aging-related rise in the worldwide and Japanese incidence of all cancers, respectively. These significant associations between TP53 mutations and the rapid rise in cancer incidence with aging, considered with previously published literature, support a causal role for TP53 according to the Bradford-Hill criteria. However, questions remain concerning the contribution of TP53 mutations to neoplastic development and the role of factors such as genetic instability, obesity, and gene deficiencies other

  6. Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes

    PubMed Central

    Hagberg, K W; McGlynn, K A; Sahasrabuddhe, V V; Jick, S

    2014-01-01

    Background: Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication. Methods: To address this association, we conducted a nested case–control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Results: In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45–1.20) for metformin-only, 1.10 (95% CI=0.66–1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58–1.37) for metformin+other OH, 1.11 (95% CI=0.60–2.05) for metformin+insulin, 0.81 (95% CI=0.23–2.85) for other OH+insulin, and 0.72 (95% CI=0.18–2.84) for insulin-only). Stratification by duration of diabetes did not alter the results. Conclusions: Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin. PMID:25093492

  7. DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative.

    PubMed

    Levine, Morgan E; Hosgood, H Dean; Chen, Brian; Absher, Devin; Assimes, Themistocles; Horvath, Steve

    2015-09-01

    Lung cancer is considered an age-associated disease, whose progression is in part due to accumulation of genomic instability as well as age-related decline in system integrity and function. Thus even among individuals exposed to high levels of genotoxic carcinogens, such as those found in cigarette smoke, lung cancer susceptibility may vary as a function of individual differences in the rate of biological aging. We recently developed a highly accurate candidate biomarker of aging based on DNA methylation (DNAm) levels, which may prove useful in assessing risk of aging-related diseases, such as lung cancer. Using data on 2,029 females from the Women's Health Initiative, we examined whether baseline measures of "intrinsic epigenetic age acceleration" (IEAA) predicted subsequent lung cancer incidence. We observed 43 lung cancer cases over the nearly twenty years of follow-up. Results showed that standardized measures of IEAA were significantly associated with lung cancer incidence (HR: 1.50, P=3.4x10-3). Furthermore, stratified Cox proportional hazard models suggested that the association may be even stronger among older individuals (70 years or above) or those who are current smokers. Overall, our results suggest that IEAA may be a useful biomarker for evaluating lung cancer susceptibility from a biological aging perspective. PMID:26411804

  8. Increased chromosome-type chromosome aberration frequencies as biomarkers of cancer risk in a blackfoot endemic area.

    PubMed

    Liou, S H; Lung, J C; Chen, Y H; Yang, T; Hsieh, L L; Chen, C J; Wu, T N

    1999-04-01

    To examine whether biomarkers such as sister chromatid exchanges (SCEs) and chromosome aberrations (CAs) can predict cancer development, a nested case-control study was performed in a blackfoot endemic area with a known high cancer risk. A cohort of 686 residents was recruited from three villages in the blackfoot endemic area. Personal characteristics were collected, and venous blood was drawn for lymphocyte culture and stored in a refrigerator. The vital status and cancer development were followed using the National Death Registry, Cancer Registry, and Blackfoot Disease Registry. The follow-up period was from August 1991 to July 1995. During this 4-year period, 31 residents developed various types of cancer. Blood culture samples from nine of these subjects were unsuitable for experiments due to improper storage. Finally, a total of 22 cancer cases had cytogenetic samples that could be analyzed. Twenty-two control subjects were selected from those who did not develop cancer in the study period, and these subjects were matched to cases by sex, age, smoking habits, and residential area. The results showed that there was no significant difference in the frequencies of SCE and chromatid-type CAs between the case and control groups. However, the frequencies of chromosome-type CAs, e.g., chromosome-type gaps, chromosome-type breaks, chromosome-type breaks plus exchanges, total chromosome-type aberrations, and total frequencies of CAs in the case group, were significantly higher than those in the control group (P < 0.05). The odds ratio of cancer risk in subjects with more than zero chromosome-type breaks was 5.0 (95% confidence interval = 1.09-22.82) compared to those with zero chromosomal breaks. The odds ratios for more than zero chromosome-type breaks plus exchanges and a frequency of total chromosome-type aberrations of >1.007% were 11.0 and 12.0, respectively (P < 0.05). Subjects with a total CA frequency of >4.023% had a 9-fold increase for cancer risk. These

  9. 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

  10. Perceived Changes in Well-Being: The Role of Chronological Age, Target Age, and Type of Measure

    ERIC Educational Resources Information Center

    Okun, Morris A.; Dittburner, Julie L.; Huff, Barbara P.

    2006-01-01

    The goal of this study is to investigate whether perceived changes in one's well-being from the present to the future are related to chronological age, target age, and type of measure (psychological well-being versus life satisfaction). Young adults (N = 114) rated their current well-being and their future well-being at one of three target ages…

  11. AN AGE-PERIOD-COHORT ANALYSIS OF CANCER INCIDENCE AMONG THE OLDEST OLD

    PubMed Central

    Hanson, Heidi A.; Smith, Ken R.; Stroup, Antoinette M.; Harrell, C. Janna

    2014-01-01

    Separating and understanding the effects of age, period, and cohort on major health conditions in the population over eighty-five, the oldest-old, will lead to better population projections of morbidity and mortality. We used age-period-cohort (APC) analyses to describe the simultaneous effects of age, period and cohort on cancer incidence rates in an attempt to understand the population dynamics underlying their patterns. Data from the Utah Cancer Registry (UCR), the US Census, the National Center for Health Statistics (NCHS) and the National Cancer Institute’s Surveillence Epidemiology and End Results (SEER) program were used to generate age-specific estimates of cancer incidence for ages 65–99 from 1973–2002 for Utah. Our results showed increasing cancer incidence rates up to the 85–89 age group followed by declines for ages 90–99 when not confounded by the distinct influence of period and cohort effects. We found significant period and cohort effects, suggesting the role of environmental mechanisms in cancer incidence trends between the ages of 85 and 100. PMID:25396304

  12. 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,...

  13. Discovery of molecular associations among aging, stem cells, and cancer based on gene expression profiling.

    PubMed

    Wang, Xiaosheng

    2013-04-01

    The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.

  14. Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological studies.

    PubMed

    Gong, Ting-Ting; Wu, Qi-Jun; Vogtmann, Emily; Lin, Bei; Wang, Yong-Lai

    2013-06-15

    Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta-analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T-T.G. and Q-J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random-effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case-control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75-0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case-control studies were 0.89 (95% CI = 0.76-1.03) and 0.84 (95% CI = 0.70-0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta-analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.

  15. Ethical issues for cancer screenings. Five countries--four types of cancer.

    PubMed

    Ustun, Cagatay; Ceber, Esin

    2004-08-01

    In recent years, medical ethics has become an undisputed part of medical studies. Many people believe that modern advances in medical technology--such as the development of dialysis machines, respirators, magnetic resonance imaging, and genetic testing and types of cancer screenings--have created the bioethical dilemmas that confront physicians in the 21st century. Debates over research and screening ethics have until recently revolved around two related questions: the voluntary, informed consent of subjects, and the appropriate relationship between risk and benefit to subjects in the experiment. Every patient has a right to full and accurate information about his or her medical condition. This legal principle arose primarily through court decisions concerning informed consent, but over time, physicians recognized that most patients prefer to learn the truth about their condition and use the information well. To screen is to search for disease in the absence of symptoms or, in other words, to attempt to find disease in someone not thought to have a disease. Examples of screening include routine mammography to detect breast cancer, routine Pap smears to detect cervical cancer and routine prostate specific antigen (PSA) testing to detect prostate cancer. Ethical principles to be followed in cancer screening programs are intended mainly to minimize unnecessary harm to the participating individuals. Numerous ethical questions can be raised about the practice of screening for disease. This paper reviews recommendation for cancer screening from five countries, examine them from an ethical perspective, and make conclusion from this analysis. PMID:15226029

  16. Ethical issues for cancer screenings. Five countries--four types of cancer.

    PubMed

    Ustun, Cagatay; Ceber, Esin

    2004-08-01

    In recent years, medical ethics has become an undisputed part of medical studies. Many people believe that modern advances in medical technology--such as the development of dialysis machines, respirators, magnetic resonance imaging, and genetic testing and types of cancer screenings--have created the bioethical dilemmas that confront physicians in the 21st century. Debates over research and screening ethics have until recently revolved around two related questions: the voluntary, informed consent of subjects, and the appropriate relationship between risk and benefit to subjects in the experiment. Every patient has a right to full and accurate information about his or her medical condition. This legal principle arose primarily through court decisions concerning informed consent, but over time, physicians recognized that most patients prefer to learn the truth about their condition and use the information well. To screen is to search for disease in the absence of symptoms or, in other words, to attempt to find disease in someone not thought to have a disease. Examples of screening include routine mammography to detect breast cancer, routine Pap smears to detect cervical cancer and routine prostate specific antigen (PSA) testing to detect prostate cancer. Ethical principles to be followed in cancer screening programs are intended mainly to minimize unnecessary harm to the participating individuals. Numerous ethical questions can be raised about the practice of screening for disease. This paper reviews recommendation for cancer screening from five countries, examine them from an ethical perspective, and make conclusion from this analysis.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Age at breast cancer diagnosis in populations of african and European ancestry.

    PubMed

    Kadhel, Philippe; Multigner, Luc

    2014-01-01

    Based on US national cancer registry data, age differences at breast cancer diagnosis have been reported between African-American women and European-American women. Such differences between populations of African and European ancestry have not been studied in other countries at a nationwide level. Here, we report and compare descriptive nationwide epidemiological indicators of invasive breast cancer for the populations of European ancestry living in the US and in mainland France and for women of African ancestry living in the US and in the French West Indies (Martinique and Guadeloupe). Based on the available data, we determined age frequency distributions, world age-standardized incidence, and the distribution of expected cases of breast cancer in a standard population of women by age. The age frequency distributions revealed that women of African ancestry were younger at diagnosis than women of European ancestry. By contrast, compared with the US regardless of ancestry and mainland France, the standardized incidences appeared lower, and the largest numbers of expected cases younger, in the French West Indies. The populations with African ancestry were not homogeneous in terms of epidemiologic indicators of age-related breast cancer. These descriptive findings suggest that populations of African ancestry cannot be considered uniform when determining whether it would be appropriate to decrease the age of entry into screening programs for breast cancer.

  2. Sugar-sweetened beverage intake and the risk of type I and type II endometrial cancer among postmenopausal women

    PubMed Central

    Inoue-Choi, Maki; Robien, Kim; Mariani, Andrea; Cerhan, James R.; Anderson, Kristin E.

    2013-01-01

    Background: Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear. Methods: We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women’s Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the SEER Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models. Results: From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for BMI and other cofounders (ptrend=0.0005). Compared to non-drinkers of SSB, the risk was 78% higher (95% CI=1.32-2.40) among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk. Conclusion: Higher intake of SSB and sugars were associated with an increased risk of type I, but not type II, endometrial cancer. Impact: SSB intake may be a risk factor for type I endometrial cancer regardless of other lifestyle factors. PMID:24273064

  3. Enhancing knowledge of colorectal cancer among African Americans: why are we waiting until age 50?

    PubMed

    Powe, Barbara D; Finnie, Ramona; Ko, Jean

    2006-01-01

    Because of low rates of colorectal cancer screening among African Americans, it may be beneficial to begin educating persons about this disease before age 50. Using the Patient/Provider/System Theoretical Model for cancer screening, this study compared knowledge of colorectal cancer, sources of information, and awareness of programs among participants of age 20-29, 30-49, and 50-75 years. The majority (n = 354) were women and African American (mean age = 37 years, mean education = 12th grade). Younger participants tended to know less about the disease, but there were few differences in knowledge between the two older groups. Persons in the 40-49-year age group were more likely to be familiar with the role diet plays in the risk of colorectal cancer. Participants associated the need for screening with the presence of symptoms. Television and radio were listed as the most frequent source of information about cancer. The Internet was the least used. The majority were not familiar with selected national programs and services focused on increasing awareness of cancer. Findings suggest that colorectal cancer-related information should be targeted toward this population before age 50, using multiple sources such as TV/radio, providers, magazines, and cancer-related organizations. An estimated 104,950 colon and 40,340 rectal cancer cases will be diagnosed in 2005 with an estimated 56,290 deaths from the disease (American Cancer Society [ACS], 2005). Despite a stabilization of colorectal cancer (CRC) incidence rates since the 1980s, African American males and females have higher incidence and mortality rates associated with this disease compared to Whites. The 5-year survival rate for CRC among African Americans improved to 54% during the years 1995-2000, but lagged well behind the 64% survival rate for Whites during the same time period. Screening and early detection of CRC followed by effective treatment is crucial to reducing these mortality rates.

  4. Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis

    PubMed Central

    McLeod, Donald S.A.; Jonklaas, Jacqueline; Brierley, James D.; Ain, Kenneth B.; Cooper, David S.; Fein, Henry G.; Haugen, Bryan R.; Ladenson, Paul W.; Magner, James; Ross, Douglas S.; Skarulis, Monica C.; Steward, David L.; Xing, Mingzhao; Litofsky, Danielle R.; Maxon, Harry R.

    2015-01-01

    Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45–50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50–55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003–0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation. PMID:26203804

  5. Disrupting the circadian clock: Gene-specific effects on aging, cancer, and other phenotypes

    PubMed Central

    Yu, Elizabeth A.; Weaver, David R.

    2011-01-01

    The circadian clock imparts 24-hour rhythmicity on gene expression and cellular physiology in virtually all cells. Disruption of the genes necessary for the circadian clock to function has diverse effects, including aging-related phenotypes. Some circadian clock genes have been described as tumor suppressors, while other genes have less clear functions in aging and cancer. In this Review, we highlight a recent study [Dubrovsky et al., Aging 2: 936-944, 2010] and discuss the much larger field examining the relationship between circadian clock genes, circadian rhythmicity, aging-related phenotypes, and cancer. PMID:21566258

  6. Disrupting the circadian clock: gene-specific effects on aging, cancer, and other phenotypes.

    PubMed

    Yu, Elizabeth A; Weaver, David R

    2011-05-01

    The circadian clock imparts 24-hour rhythmicity on gene expression and cellular physiology in virtually all cells. Disruption of the genes necessary for the circadian clock to function has diverse effects, including aging-related phenotypes. Some circadian clock genes have been described as tumor suppressors, while other genes have less clear functions in aging and cancer. In this Review, we highlight a recent study [Dubrovsky et al., Aging 2: 936-944, 2010] and discuss the much larger field examining the relationship between circadian clock genes, circadian rhythmicity, aging-related phenotypes, and cancer.

  7. Age determination of the world's oldest movable metal types through measuring the "meog" using AMS

    NASA Astrophysics Data System (ADS)

    Hong, W.; Lee, S. C.; Park, J. H.; Park, G.; Sung, K. H.; Lee, J. G.; Nam, K. H.

    2015-10-01

    The fabrication year of a set of movable metal types that were thought to be used for printing "Jeungdoga" was investigated. Since the types were made from bronze and did not contain carbon, an organic black ink called "meog" was collected from the type surfaces to quantify their ages. The meog samples were collected from 34 metal types, and 27 ages were obtained. The youngest age was 798 ± 44 yrBP, and the oldest reasonable age was 1166 ± 43 yrBP. The weighted average after eliminating ages with poor statistics was 950 ± 28 yrBP. This age is 300 years older than that of the Jikji (AD 1377), which is a Buddhist document recognized as the world's oldest document printed using metal types, and also older than that of the Gutenberg bible (AD 1450).

  8. Recent decline in prostate cancer incidence in the United States, by age, stage, and Gleason score.

    PubMed

    Herget, Kimberly A; Patel, Darshan P; Hanson, Heidi A; Sweeney, Carol; Lowrance, William T

    2016-01-01

    Prostate cancer incidence is sensitive to screening practices, however the impact of recent screening recommendations from the United States Preventative Services Task Force on prostate cancer incidence by age, stage, race, and Gleason score is unknown. This study described the timing and magnitude of changes in prostate cancer incidence trends in the United States by month of diagnosis, and evaluated trends by age, Gleason score, and stage at diagnosis. We analyzed prostate cancer incidence trends using Surveillance, Epidemiology, and End Results (SEER) program data for men diagnosed with invasive prostate cancer from 2007 through 2012. JoinPoint analysis was used to detect changes in the rate of annual percent change (APC) in prostate cancer incidence for all diagnoses and by age, Gleason score, race, and stage. Prostate cancer incidence declined at an estimated -19.6% APC beginning May 2011. This decline was observed in all age groups. Low-grade tumors (Gleason score ≤6) showed a steeper decline (-29.1% APC) than high-grade tumors (Gleason score 8-10: -10.8% APC). Only stage I/II and stage III tumors saw declines (-24.2% and -16.7% APC, respectively). A sharp decline in prostate cancer incidence began before release of the United States Preventative Services Task Force October 2011 draft and May 2012 final screening recommendation. The greatest change occurred with incidence of low-grade tumors, although there is concern that some high-grade tumors may now go undetected.

  9. A brief history of cancer: age-old milestones underlying our current knowledge database.

    PubMed

    Faguet, Guy B

    2015-05-01

    This mini-review chronicles the history of cancer ranging from cancerous growths discovered in dinosaur fossils, suggestions of cancer in Ancient Egyptian papyri written in 1500-1600 BC, and the first documented case of human cancer 2,700 years ago, to contributions by pioneers beginning with Hippocrates and ending with the originators of radiation and medical oncology. Fanciful notions that soon fell into oblivion are mentioned such as Paracelsus and van Helmont substituting Galen's black bile by mysterious ens or archeus systems. Likewise, unfortunate episodes such as Virchow claiming Remak's hypotheses as his own remind us that human shortcomings can affect otherwise excellent scientists. However, age-old benchmark observations, hypotheses, and practices of historic and scientific interest are underscored, excerpts included, as precursors of recent discoveries that shaped modern medicine. Examples include: Petit's total mastectomy with excision of axillary glands for breast cancer; a now routine practice, Peyrilhe's ichorous matter a cancer-causing factor he tested for transmissibility one century before Rous confirmed the virus-cancer link, Hill's warning of the dangers of tobacco snuff; heralding today's cancer pandemic caused by smoking, Pott reporting scrotum cancer in chimney sweepers; the first proven occupational cancer, Velpeau's remarkable foresight that a yet unknown subcellular element would have to be discovered in order to define the nature of cancer; a view confirmed by cancer genetics two centuries later, ending with Röntgen and the Curies, and Gilman et al. ushering radiation (1896, 1919) and medical oncology (1942), respectively.

  10. A brief history of cancer: age-old milestones underlying our current knowledge database.

    PubMed

    Faguet, Guy B

    2015-05-01

    This mini-review chronicles the history of cancer ranging from cancerous growths discovered in dinosaur fossils, suggestions of cancer in Ancient Egyptian papyri written in 1500-1600 BC, and the first documented case of human cancer 2,700 years ago, to contributions by pioneers beginning with Hippocrates and ending with the originators of radiation and medical oncology. Fanciful notions that soon fell into oblivion are mentioned such as Paracelsus and van Helmont substituting Galen's black bile by mysterious ens or archeus systems. Likewise, unfortunate episodes such as Virchow claiming Remak's hypotheses as his own remind us that human shortcomings can affect otherwise excellent scientists. However, age-old benchmark observations, hypotheses, and practices of historic and scientific interest are underscored, excerpts included, as precursors of recent discoveries that shaped modern medicine. Examples include: Petit's total mastectomy with excision of axillary glands for breast cancer; a now routine practice, Peyrilhe's ichorous matter a cancer-causing factor he tested for transmissibility one century before Rous confirmed the virus-cancer link, Hill's warning of the dangers of tobacco snuff; heralding today's cancer pandemic caused by smoking, Pott reporting scrotum cancer in chimney sweepers; the first proven occupational cancer, Velpeau's remarkable foresight that a yet unknown subcellular element would have to be discovered in order to define the nature of cancer; a view confirmed by cancer genetics two centuries later, ending with Röntgen and the Curies, and Gilman et al. ushering radiation (1896, 1919) and medical oncology (1942), respectively. PMID:25113657

  11. Breast cancer and other neoplasms in women with neurofibromatosis type 1: a retrospective review of cases in the Detroit metropolitan area.

    PubMed

    Wang, X; Levin, A M; Smolinski, S E; Vigneau, F D; Levin, N K; Tainsky, M A

    2012-12-01

    Neurofibromatosis type 1 (NF1) is one of the most common cancer predisposing syndromes with an incidence of 1 in 3,500 worldwide. Certain neoplasms or malignancies are over-represented in individuals with NF1; however, an increased risk of breast cancer has not been widely recognized or accepted. We identified 76 women with NF1 seen in the Henry Ford Health System (HFHS) from 1990 to 2009, and linked them to the Surveillance Epidemiology and End Results (SEER) registry covering the metropolitan Detroit area. Fifty-one women (67%) were under age 50 years at the time of data analysis. Six women developed invasive breast cancer before age 50, and three developed invasive breast cancer after age 50. Using standardized incidence ratios (SIRs) calculated based on the SEER age-adjusted invasive breast cancer incidence rates, our findings demonstrated a statistically significant increase of breast cancer incidence occurring in NF1 women (SIR = 5.2; 95% CI 2.4-9.8), and this relative increase was especially evident among those with breast cancer onset under age 50 (SIR = 8.8; 95% CI 3.2-19.2). These data are consistent with other reports suggesting an increase in breast cancer risk among females with NF1, which indicate that breast cancer screening guidelines should be evaluated for this potentially high-risk group.

  12. Pulsatile Stress in Middle-Aged Patients With Type 1 or Type 2 Diabetes Compared With Nondiabetic Control Subjects

    PubMed Central

    Philips, Jean-Christophe; Marchand, Monique; Scheen, André J.

    2010-01-01

    OBJECTIVE Arterial pulse pressure is considered to be an independent cardiovascular risk factor. We compared pulse pressure during an active orthostatic test in middle-aged patients with type 1 diabetes and with type 2 diabetes and corresponding nondiabetic control subjects. RESEARCH DESIGN AND METHODS Forty patients with type 1 diabetes (mean age 50 years, diabetes duration 23 years, and BMI 23.0 kg/m2) were compared with 40 nonhypertensive patients with type 2 diabetes (respectively, 50 years, 8 years, and 29.7 kg/m2). Patients taking antihypertensive agents or with renal insufficiency were excluded. All patients were evaluated with a continuous noninvasive arterial blood pressure monitoring (Finapres) in standing (1 min), squatting (1 min), and again standing position (1 min). Patients with type 1 or type 2 diabetes were compared with two groups of 40 age-, sex- and BMI-matched healthy subjects. RESULTS Patients with type 1 diabetes and patients with type 2 diabetes showed significantly higher pulse pressure, heart rate, and double product of pulse pressure and heart rate (PP×HR) (type 1: 5,263 vs. 4,121 mmHg/min, P = 0.0004; type 2: 5,359 vs. 4,321 mmHg, P = 0.0023) levels than corresponding control subjects. There were no significant differences between patients with type 1 diabetes and type 2 diabetes regarding pulse pressure (59 vs. 58 mmHg), heart rate (89 vs. 88/min), and PP×HR (5,263 vs. 5,359 mmHg/min). CONCLUSIONS Patients with type 1 diabetes have increased levels of peripheral PP, an indirect marker of arterial stiffness, and PP×HR, an index of pulsatile stress, comparable to those of nonhypertensive patients with type 2 diabetes at similar mean age of 50 years. PMID:20693351

  13. Biology of cancer and aging: a complex association with cellular senescence.

    PubMed

    Falandry, Claire; Bonnefoy, Marc; Freyer, Gilles; Gilson, Eric

    2014-08-20

    Over the last 50 years, major improvements have been made in our understanding of the driving forces, both parallel and opposing, that lead to aging and cancer. Many theories on aging first proposed in the 1950s, including those associated with telomere biology, senescence, and adult stem-cell regulation, have since gained support from cumulative experimental evidence. These views suggest that the accumulation of mutations might be a common driver of both aging and cancer. Moreover, some tumor suppressor pathways lead to aging in line with the theory of antagonist pleiotropy. According to the evolutionary-selected disposable soma theory, aging should affect primarily somatic cells. At the cellular level, both intrinsic and extrinsic pathways regulate aging and senescence. However, increasing lines of evidence support the hypothesis that these driving forces might be regulated by evolutionary-conserved pathways that modulate energy balance. According to the hyperfunction theory, aging is a quasi-program favoring both age-related diseases and cancer that could be inhibited by the regulation of longevity pathways. This review summarizes these hypotheses, as well as the experimental data that have accumulated over the last 60 years linking aging and cancer.

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

    PubMed

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

    2012-12-01

    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.

  15. 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

  16. An age-period-cohort analysis of cancer incidence among the oldest old, Utah 1973-2002.

    PubMed

    Hanson, Heidi A; Smith, Ken R; Stroup, Antoinette M; Harrell, C Janna

    2015-01-01

    We used age-period-cohort (APC) analyses to describe the simultaneous effects of age, period, and cohort on cancer incidence rates in an attempt to understand the population dynamics underlying their patterns among those aged 85+. Data from the Utah Cancer Registry (UCR), the US Census, the National Center for Health Statistics (NCHS), and the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) programme were used to generate age-specific estimates of cancer incidence at ages 65-99 from 1973 to 2002 for Utah. Our results showed increasing cancer incidence rates up to the 85-89 age group followed by declines at ages 90-99 when not confounded by the separate influences of period and cohort effects. We found significant period and cohort effects, suggesting the role of environmental mechanisms in cancer incidence trends between the ages of 85 and 100.

  17. 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

  18. Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?.

    PubMed

    Sharp, Zelton Dave; Curiel, Tyler Jay; Livi, Carolina Becker

    2013-01-01

    Cancer and aging appear to be inexorably linked, yet approaches to ameliorate them in concert are lacking. Although not (easily) feasible in humans, years of preclinical research show that diet and growth factor restriction each successfully address cancer and aging together. Chronic treatment of genetically heterogeneous mice with an enteric formulation of rapamycin (eRapa) extended maximum lifespan of both genders when started in mid or late life. In part, cancer amelioration in treated mice suggested that long-term eRapa, like diet restriction, could be a pharmacological approach feasible for use in the clinic. We review the current understanding of the role of the mechanistic target of rapamycin (mTOR) in cancer and aging. We also discuss the tumor immune surveillance system, and the need for a better understanding of its responses to mTOR inhibitors. We also address the issue of the misperception that rapamycin is a potent immunosuppressant. Finally, we review the current state of mTOR inhibitors in the cancer clinic. Because of the burgeoning elderly population most at risk for cancer, there is a great need for our eRapa findings to be a proof of concept for the development of new and more comprehensive approaches to cancer prevention that are safe and also mitigate other deleterious effects of aging.

  19. 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

  20. 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

  1. Age-related changes in rat hippocampal theta rhythms: a difference between type 1 and type 2 theta.

    PubMed

    Abe, Y; Toyosawa, K

    1999-05-01

    The age-related changes in two types of theta rhythms recorded from the hippocampus in young (4 months-old), mature (12-13 months-old) and aged (22-25 months-old) rats were investigated. The type 1 theta rhythm was measured from hippocampal EEG recorded from walking rats and the type 2 theta was measured from the EEG induced by reticular pontin oralis nucleus (PON) stimulation in urethane anesthetized rats. The peak frequency and the peak power were detected from power spectra calculated on each theta sample by fast Fourier transformation (FFT). No age-related alteration was observed on the peak frequency of type 1 theta rhythm. However, on type 2 theta rhythm, the peak frequency was decreased in the aged rats compared with the young and the mature rats. The type 2 theta rhythm is cholinergic, and therefore this result suggests that age-related deterioration can be clearly observed in the cholinergic system including the hippocampus in rats.

  2. Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes.

    PubMed

    Groen, Bart B L; Hamer, Henrike M; Snijders, Tim; van Kranenburg, Janneau; Frijns, Dionne; Vink, Hans; van Loon, Luc J C

    2014-04-15

    Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function. PMID:24577061

  3. 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

  4. 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

  5. [Breast cancer screening in Austria: Key figures, age limits, screening intervals and evidence].

    PubMed

    Jeitler, Klaus; Semlitsch, Thomas; Posch, Nicole; Siebenhofer, Andrea; Horvath, Karl

    2015-01-01

    In January 2014, the first nationwide quality-assured breast cancer screening program addressing women aged ≥ 40 years was introduced in Austria. As part of the process of developing a patient information leaflet, the Evidence Based Medicine (EBM) Review Center of the Medical University of Graz was charged with the task of assessing the potential benefits and harms of breast cancer screening from the available evidence. Based on these results, key figures were derived for mortality, false-positive and false-negative mammography results, and overdiagnosis, considering Austria-specific incidence rates for breast cancer and breast cancer mortality. Furthermore, the current evidence regarding age limits and screening interval, which were the subjects of controversial public discussions, was analyzed. A systematic search for primary and secondary literature was performed and additional evidence was screened, e. g., evaluation reports of European breast cancer screening programs. On the basis of the available evidence and of the Austrian breast cancer mortality and incidence rates, it can be assumed that - depending on the age group - 1 to 4 breast cancer deaths can be avoided per 1,000 women screened in a structured breast cancer screening program, while the overall mortality remains unchanged. On the other hand, 150 to 200 of these 1,000 women will be affected by false-positive results and 1 to 9 women by overdiagnosis due to the structured breast cancer screening. Therefore, the overall benefit-harm balance is uncertain. If women from 40 to 44 or above 70 years of age are considered, who can also participate in the Austrian screening program, even a negative benefit-harm balance seems possible. However, with the implementation of quality standards in breast cancer screening and the dissemination of a patient information leaflet, an improvement in the medical treatment situation, specifically in terms of informed decision-making, can be expected.

  6. [Breast cancer screening in Austria: Key figures, age limits, screening intervals and evidence].

    PubMed

    Jeitler, Klaus; Semlitsch, Thomas; Posch, Nicole; Siebenhofer, Andrea; Horvath, Karl

    2015-01-01

    In January 2014, the first nationwide quality-assured breast cancer screening program addressing women aged ≥ 40 years was introduced in Austria. As part of the process of developing a patient information leaflet, the Evidence Based Medicine (EBM) Review Center of the Medical University of Graz was charged with the task of assessing the potential benefits and harms of breast cancer screening from the available evidence. Based on these results, key figures were derived for mortality, false-positive and false-negative mammography results, and overdiagnosis, considering Austria-specific incidence rates for breast cancer and breast cancer mortality. Furthermore, the current evidence regarding age limits and screening interval, which were the subjects of controversial public discussions, was analyzed. A systematic search for primary and secondary literature was performed and additional evidence was screened, e. g., evaluation reports of European breast cancer screening programs. On the basis of the available evidence and of the Austrian breast cancer mortality and incidence rates, it can be assumed that - depending on the age group - 1 to 4 breast cancer deaths can be avoided per 1,000 women screened in a structured breast cancer screening program, while the overall mortality remains unchanged. On the other hand, 150 to 200 of these 1,000 women will be affected by false-positive results and 1 to 9 women by overdiagnosis due to the structured breast cancer screening. Therefore, the overall benefit-harm balance is uncertain. If women from 40 to 44 or above 70 years of age are considered, who can also participate in the Austrian screening program, even a negative benefit-harm balance seems possible. However, with the implementation of quality standards in breast cancer screening and the dissemination of a patient information leaflet, an improvement in the medical treatment situation, specifically in terms of informed decision-making, can be expected. PMID:26354136

  7. Elderly cancer patients' psychopathology: a systematic review: aging and mental health.

    PubMed

    Parpa, Efi; Tsilika, Eleni; Gennimata, Vassiliki; Mystakidou, Kyriaki

    2015-01-01

    This review of the literature on elderly cancer patients and their psychiatric disorders was undertaken to determine the extent of the problem. It consists of articles with elderly cancer patients. Keyword terms included "cancer", "elderly", "aging", "geriatric", "psychiatric disorders", "psychiatric symptoms", "psychological problems", "aged >60 years", "sucidal ideation, geriatric, cancer", "suicide geriatric cancer". We conducted searches on the following databases: PubMed; PsychINFO (1980-2013); finally, 102 publications were suitable for the current review. Depression in elderly cancer patients is the most common disorder in elderly cancer patients associated with disability, morbidity and mortality. Anxiety disorders may be less frequent in geriatric patients; however, it seemed to be a major problem in late life. Psychiatric disorders are common in geriatric patients with cancer especially at advanced stages of the disease. In addition, health care professionals can help provide treatment and emotional support. Future research should aim to provide data about the real prevalence and severity of psychiatric disorders in elderly patients with cancer, for the improvement of patients' quality of life and their caregivers.

  8. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history.

    PubMed

    Young, R P; Hopkins, R J; Christmas, T; Black, P N; Metcalf, P; Gamble, G D

    2009-08-01

    Chronic obstructive pulmonary disease (COPD) is a common comorbid disease in lung cancer, estimated to affect 40-70% of lung cancer patients, depending on diagnostic criteria. As smoking exposure is found in 85-90% of those diagnosed with either COPD or lung cancer, coexisting disease could merely reflect a shared smoking exposure. Potential confounding by age, sex and pack-yr smoking history, and/or by the possible effects of lung cancer on spirometry, may result in over-diagnosis of COPD prevalence. In the present study, the prevalence of COPD (pre-bronchodilator Global Initiative for Chronic Obstructive Lung Disease 2+ criteria) in patients diagnosed with lung cancer was 50% compared with 8% in a randomly recruited community control group, matched for age, sex and pack-yr smoking exposure (n = 602, odds ratio 11.6; p<0.0001). In a subgroup analysis of those with lung cancer and lung function measured prior to the diagnosis of lung cancer (n = 127), we found a nonsignificant increase in COPD prevalence following diagnosis (56-61%; p = 0.45). After controlling for important variables, the prevalence of COPD in newly diagnosed lung cancer cases was six-fold greater than in matched smokers; this is much greater than previously reported. We conclude that COPD is both a common and important independent risk factor for lung cancer.

  9. A population-based study comparing HRQoL among breast, prostate, and colorectal cancer survivors to propensity score matched controls, by cancer type, and gender

    PubMed Central

    LeMasters, Traci; Madhavan, Suresh; Sambamoorthi, Usha; Kurian, Sobha

    2016-01-01

    Background Objectives were to compare health-related quality of life (HRQoL) between breast cancer survivors, prostate cancer survivors (PCS), and colorectal cancer survivors (CCS) to matched controls, stratified by short and long-term survivors, by cancer type, and gender. Methods By using the 2009 Behavioral Risk Factor Surveillance System, propensity scores matched three controls to adult survivors >1 year past diagnosis (N = 11,964) on age, gender, race/ethnicity, income, insurance status, and region of the USA Chi-square tests and logistic regression models compared HRQoL outcomes (life satisfaction, activity limitations, sleep quality, emotional support, general, physical, and mental health). Results Although all cancer survivors reported worse general health (p < 0.000) and more activity limitations (p < 0.004) than controls, these disparities decreased among long-term survivors. Short-term PCS and male CCS were more likely to report worse outcomes across additional domains of HRQoL than controls, but PCS were 0.61, 0.63, and 0.70 times less likely to report activity limitations, fair/poor general health, and 1–15 bad physical health days in the past month than male CCS. Breast cancer survivors and female CCS were 2.12 and 3.17, 1.58 and 1.86, and 1.49 and 153, respectively, times more likely to report rarely/never receiving needed emotional support, 1–15 bad mental health days in the past month, and not receiving enough sleep 1–15 days in the past month than PCS and male CCS. Conclusions Cancer survivors experience worse HRQoL than similar individuals without a history of cancer and the severity of affected HRQoL domains differ by time since diagnosis, cancer type, and gender. PMID:23606210

  10. 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

  11. 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

  12. 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

  13. Studies on quantitative analysis and automatic recognition of cell types of lung cancer.

    PubMed

    Chen, Yi-Chen; Hu, Kuang-Hu; Li, Fang-Zhen; Li, Shu-Yu; Su, Wan-Fang; Huang, Zhi-Ying; Hu, Ying-Xiong

    2006-01-01

    Recognition of lung cancer cells is very important to the clinical diagnosis of lung cancer. In this paper we present a novel method to extract the structure characteristics of lung cancer cells and automatically recognize their types. Firstly soft mathematical morphology methods are used to enhance the grayscale image, to improve the definition of images, and to eliminate most of disturbance, noise and information of subordinate images, so the contour of target lung cancer cell and biological shape characteristic parameters can be extracted accurately. Then the minimum distance classifier is introduced to realize the automatic recognition of different types of lung cancer cells. A software system named "CANCER.LUNG" is established to demonstrate the efficiency of this method. The clinical experiments show that this method can accurately and objectively recognize the type of lung cancer cells, which can significantly improve the pathology research on the pathological changes of lung cancer and clinical assistant diagnoses.

  14. 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

  15. 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.

  16. Trends in Lung Cancer Incidence Rates by Histological Type in 1975–2008: A Population-Based Study in Osaka, Japan

    PubMed Central

    Kinoshita, Fukuaki Lee; Ito, Yuri; Nakayama, Tomio

    2016-01-01

    Background Monitoring trends in lung cancer incidence and mortality is important for the evaluation of cancer control activities. We investigated recent trends in age-standardized incidence rates by histological type of lung cancer in Osaka, Japan. Methods Cancer incidence data for 1975–2008 were obtained from the Osaka Cancer Registry. Lung cancer mortality data with population data in Osaka during 1975–2012 were obtained from vital statistics. We examined trends in age-standardized incidence and mortality rates for all histological types and age-standardized incidence rates by histological type and age group using a joinpoint regression model. Results The age-standardized incidence rate of lung cancer levelled off or slightly increased from 1975–2008, with an annual percentage change of 0.3% (95% confidence interval [CI], 0.1%–0.4%) for males and 1.1% (95% CI, 0.9%–1.3%) for females, and the mortality rate decreased by 0.9% (95% CI, 1.2%–0.7%) for males and 0.5% (95% CI, 0.8%–0.3%) for females. The incidence rates of squamous cell carcinoma (SQC) and small cell carcinoma (SMC) significantly decreased for both genders, whereas that of adenocarcinoma (ADC) significantly increased among almost all age groups in both genders. Conclusions The incidence rates of SQC and SMC decreased with the decline in smoking prevalence, which probably explains the change in trends in the incidence rates of lung cancer from the mid-1980s. However, the reason for the increase in ADC remains unclear. Therefore, trends in incidence rates of lung cancer should be carefully monitored, especially for ADC, and the associations between ADC and its possible risk factors should be studied. PMID:27150013

  17. 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.

  18. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    PubMed

    Lau, Yat Ming; Cheung, Tak Hong; Yeo, Winnie; Mo, Frankie; Yu, Mei Yung; Lee, Kun Min; Ho, Wendy C S; Yeung, Apple C M; Law, Priscilla T Y; Chan, Paul K S

    2015-01-01

    High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%), HPV-18 (21.6%), HPV-52 (11.9%), and HPV-58 (9.3%). Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1%) patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90), whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79). However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  19. 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

  20. 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

  1. 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

  2. The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth.

    PubMed

    Feng, Yin-Hsun; Velazquez-Torres, Guermarie; Gully, Christopher; Chen, Jian; Lee, Mong-Hong; Yeung, Sai-Ching Jim

    2011-04-01

    Despite investigations into mechanisms linking type 2 diabetes and cancer, there is a gap in knowledge about pharmacotherapy for diabetes in cancer patients. Epidemiological studies have shown that diabetic cancer patients on different antidiabetic treatments have different survival. The clinically relevant question is whether some antidiabetic pharmacotherapeutic agents promote cancer whereas others inhibit cancer progression. We investigated the hypothesis that various antidiabetic drugs had differential direct impact on cancer cells using four human cell lines (pancreatic cancer: MiaPaCa2, Panc-1; breast cancer: MCF7, HER18). We found that insulin and glucose promoted cancer cell proliferation and contributed to chemoresistance. Metformin and rosiglitazone suppressed cancer cell growth and induced apoptosis. Both drugs affected signalling in the protein kinases B (AKT)/mammalian target of rapamycin pathway; metformin activated adenosine monophosphate (AMP)-activated protein kinase whereas rosiglitazone increased chromosome ten level. Although high insulin and glucose concentrations promoted chemoresistance, the combination of metformin or rosiglitazone with gemcitabine or doxorubicin, resulted in an additional decrease in live cancer cells and increase in apoptosis. In contrast, exenatide did not have direct effect on cancer cells. In conclusion, different types of antidiabetic pharmacotherapy had a differential direct impact on cancer cells. This study provides experimental evidence to support further investigation of metformin and rosiglitazone as first-line therapies for type 2 diabetes in cancer patients. PMID:20455996

  3. Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target

    PubMed Central

    Elkhattouti, Abdelouahid; Hassan, Mohamed; Gomez, Christian R.

    2015-01-01

    Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly. PMID:26284191

  4. 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

  5. Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target.

    PubMed

    Elkhattouti, Abdelouahid; Hassan, Mohamed; Gomez, Christian R

    2015-01-01

    Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly. PMID:26284191

  6. 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

  7. 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.

  8. Persistence of the effect of birth size on dysglycaemia and type 2 diabetes in old age: AGES-Reykjavik Study.

    PubMed

    von Bonsdorff, Mikaela B; Muller, Majon; Aspelund, Thor; Garcia, Melissa; Eiriksdottir, Gudny; Rantanen, Taina; Gunnarsdottir, Ingibjörg; Birgisdottir, Bryndis Eva; Thorsdottir, Inga; Sigurdsson, Gunnar; Gudnason, Vilmundur; Launer, Lenore; Harris, Tamara B

    2013-08-01

    We studied the effect of birth size on glucose and insulin metabolism among old non-diabetic individuals. We also explored the combined effect of birth size and midlife body mass index (BMI) on type 2 diabetes in old age. Our study comprised 1,682 Icelanders whose birth records included anthropometrical data. The same individuals had participated in the prospective population-based Reykjavik Study, where BMI was assessed at a mean age of 47 years, and in the AGES-Reykjavik Study during 2002 to 2006, where fasting glucose, insulin and HbA1c were measured and homeostasis model assessment for the degree of insulin resistance (HOMA-IR) calculated at a mean age of 75.5 years. Type 2 diabetes was determined as having a history of diabetes, using glucose-modifying medication or fasting glucose of >7.0 mmol/l. Of the participants, 249 had prevalent type 2 diabetes in old age. Lower birth weight and body length were associated with higher fasting glucose, insulin, HOMA-IR and HbA1c among old non-diabetic individuals. Higher birth weight and ponderal index at birth decreased the risk for type 2 diabetes in old age, odds ratio (OR), 0.61 [95 % confidence interval (CI), 0.48-0.79] and 0.96 (95 % CI, 0.92-1.00), respectively. Compared with those with high birth weight and low BMI in midlife, the odds of diabetes was almost five-fold for individuals with low birth weight and high BMI (OR, 4.93; 95 % CI, 2.14-11.37). Excessive weight gain in adulthood might be particularly detrimental to the health of old individuals with low birth weight.

  9. 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

  10. [Physiology of sarcopenia. Similarities and differences with neoplasic cachexia (muscle impairments in cancer and ageing)].

    PubMed

    Argilés, Josep M; Busquets, Silvia; López-Soriano, Francisco J; Figueras, Maite

    2006-05-01

    Muscle wasting during cancer and ageing share many common metabolic pathways and mediators. Due to the size of the population involved, both cancer cachexia and ageing sarcopenia 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. 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. More research should be devoted to the understanding of muscle wasting mediators (associated with both depletion of fat stores and muscular tissue), 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.

  11. p53 mutations associated with aging-related rise in cancer incidence rates

    PubMed Central

    Richardson, Richard B

    2013-01-01

    TP53’s role as guardian of the genome diminishes with age, as the probability of mutation increases. Previous studies have shown an association between p53 gene mutations and cancer. However, the role of somatic TP53 mutations in the steep rise in cancer rates with aging has not been investigated at a population level. This relationship was quantified using the International Agency for Research on Cancer (IARC) TP53 and GLOBOCAN cancer databases. The power function exponent of the cancer rate was calculated for 5-y age-standardized incidence or mortality rates for up to 25 cancer sites occurring in adults of median age 42 to 72 y. Linear regression analysis of the mean percentage of a cancer’s TP53 mutations and the corresponding cancer exponent was conducted for four populations: worldwide, Japan, Western Europe, and the United States. Significant associations (P ≤ 0.05) were found for incidence rates but not mortality rates. Regardless of the population studied, positive associations were found for all cancer sites, with more significant associations for solid tumors, excluding the outlier prostate cancer or sex-related tumors. Worldwide and Japanese populations yielded P values as low as 0.002 and 0.005, respectively. For the United States, a significant association was apparent only when analysis utilized the Surveillance, Epidemiology, and End Results (SEER) database. This study found that TP53 mutations accounts for approximately one-quarter and one-third of the aging-related rise in the worldwide and Japanese incidence of all cancers, respectively. These significant associations between TP53 mutations and the rapid rise in cancer incidence with aging, considered with previously published literature, support a causal role for TP53 according to the Bradford-Hill criteria. However, questions remain concerning the contribution of TP53 mutations to neoplastic development and the role of factors such as genetic instability, obesity, and gene deficiencies

  12. Cervical cancer screening among women aged 18-30 years - United States, 2000-2010.

    PubMed

    2013-01-01

    Screening women for cervical cancer can save lives. However, among young women, cervical cancer is relatively rare, and too-frequent screening can lead to high costs and adverse events associated with overtreatment. Before 2012, cervical cancer screening guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Cancer Society (ACS), and U.S. Preventive Services Task Force (USPSTF) differed on age to start and how often to get screened for cervical cancer. In 2012, however, all three organizations recommended that 1) screening by Papanicolau (Pap) test should not be used for women aged <21 years, regardless of initiation of sexual activity, and 2) a screening interval of 3 years should be maintained for women aged 21-30 years. ACS and ACOG explicitly recommend against yearly screening. To assess trends in Pap testing before the new guidelines were introduced, CDC analyzed 2000-2010 data from the Behavioral Risk Factor Surveillance System (BRFSS) for women aged 18-30 years. CDC found that, among women aged 18-21 years, the percentage reporting never having been screened increased from 26.3% in 2000 to 47.5% in 2010, and the proportion reporting having had a Pap test in the past 12 months decreased from 65.0% to 41.5%. Among those aged 22-30 years, the proportion reporting having had a Pap test within the preceding 12 months decreased from 78.1% to 67.0%. These findings showed that Pap testing practices for young women have been moving toward the latest guidelines. However, the data also showed a concerning trend: among women aged 22-30 years, who should be screened every 3 years, the proportion who reported never having had a Pap test increased from 6.6% to 9.0%. More effort is needed to promote acceptance of the latest evidence-based recommendations so that all women receive the maximal benefits of cervical cancer screening.

  13. 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

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

    PubMed

    Schaefer, Martin H; Serrano, Luis

    2016-02-09

    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.

  15. 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

  16. 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 ( ...

  17. Determination of a Change Point in the Age at Diagnosis of Breast Cancer Using a Survival Model.

    PubMed

    Abdollahi, Mahbubeh; Hajizadeh, Ebrahim; Baghestani, Ahmad Reza; Haghighat, Shahpar

    2016-01-01

    Breast cancer, the second cause of cancer-related death after lung cancer and the most common cancer in women after skin cancer, is curable if detected in early stages of clinical presentation. Knowledge as to any age cut-off points which might have significance for prognostic groups is important in screening and treatment planning. Therefore, determining a change-point could improve resource allocation. This study aimed to determine if a change point for survival might exist in the age of breast cancer diagnosis. This study included 568 cases of breast cancer that were registered in Breast Cancer Research Center, Tehran, Iran, during the period 1986-2006 and were followed up to 2012. In the presence of curable cases of breast cancer, a change point in the age of breast cancer diagnosis was estimated using a mixture survival cure model. The data were analyzed using SPSS (versions 20) and R (version 2.15.0) software. The results revealed that a change point in the age of breast cancer diagnosis was at 50 years age. Based on our estimation, 35% of the patients diagnosed with breast cancer at age less than or equal to 50 years of age were cured while the figure was 57% for those diagnosed after 50 years of age. Those in the older age group had better survival compared to their younger counterparts during 12 years of follow up. Our results suggest that it is better to estimate change points in age for cancers which are curable in early stages using survival cure models, and that the cure rate would increase with timely screening for breast cancer.

  18. Age-Period-Cohort Models in Cancer Surveillance Research: Ready for Prime Time?

    PubMed Central

    Rosenberg, Philip S.; Anderson, William F.

    2011-01-01

    Standard descriptive methods for the analysis of cancer surveillance data include canonical plots based on the lexis diagram, directly age-standardized rates (ASR), estimated annual percentage change (EAPC), and joinpoint regression. The age-period-cohort (APC) model has been used less often. Here, we argue that it merits much broader use. Firstly, we describe close connections between estimable functions of the model parameters and standard quantities such as the ASR, EAPC, and joinpoints. Estimable functions have the added value of being fully adjusted for period and cohort effects, and generally more precise. Secondly, the APC model provides the descriptive epidemiologist with powerful new tools, including rigorous statistical methods for comparative analyses and the ability to project the future burden of cancer. We illustrate these principles using invasive female breast cancer incidence in the United States, but these concepts apply equally well to other cancer sites for incidence or mortality. PMID:21610223

  19. 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.

  20. Impaired up-regulation of type II corticosteroid receptors in hippocampus of aged rats.

    PubMed

    Eldridge, J C; Fleenor, D G; Kerr, D S; Landfield, P W

    1989-01-30

    Several recent investigations have reported a decline of rat hippocampal corticosteroid-binding receptors (CSRs) with aging. This decline has been proposed to be an initial cause (through disinhibition) of the elevated adrenal steroid secretion that apparently occurs with aging; however, it could instead be an effect of corticoid elevation (through down-regulation). In order to assess the effects of age on CSR biosynthetic capacity in the absence of down-regulatory influences of endogenous corticoids, as well as to study aging changes in CSR plasticity, we examined the up-regulation of hippocampal CSR that follows adrenalectomy (ADX). The rat hippocampus contains at least two types of CSR binding and differential analysis of types I and II CSR was accomplished by selective displacement of [3H]corticosterone with RU-28362, a specific type II agonist. In young (3 months old) Fischer-344 rat hippocampus, up-regulation of type II binding above 2-day ADX baseline was present by 3-7 days and increased still further by 8-10 days post-ADX; type I CSR density did not change significantly between 1 and 10 days post-ADX. However, in aged (24-26 months old) rats, type II CSR up-regulation did not occur over the 10 day post-ADX period. Thus, the age-related impairment of type II up-regulation may reflect an intrinsic deficit in CSR biosynthesis or lability that is independent of the acute endogenous adrenal steroid environment.

  1. 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

  2. Impact of Age and Comorbidity on Cervical and Breast Cancer Literacy of African Americans, Latina, and Arab Women.

    PubMed

    Talley, Costellia H; Williams, Karen Patricia

    2015-09-01

    This study examines the relationship between age, comorbidity, and breast and cervical cancer literacy in a sample of African American, Latina, and Arab women (N = 371) from Detroit, Michigan. The Age-adjusted Charlson Comorbidity Index (ACC) was used characterize the impact of age and comorbidity on breast and cervical cancer literacy. The relationship between ACC and breast and cervical cancer screening, and group differences, were assessed. There was a statistically significant difference between breast cancer literacy scores. ACC had a greater impact on breast cancer literacy for African Americans.

  3. Parental age at birth and risk of breast cancer in daughters: a prospective study among US women.

    PubMed

    Colditz, G A; Willett, W C; Stampfer, M J; Hennekens, C H; Rosner, B; Speizer, F E

    1991-01-01

    We examined the relation between parental age at birth and risk of breast cancer among daughters in a population of 118,309 US women who were 30 to 55 years of age in 1976 and without prior diagnosis of cancer. During 1,140,239 person-years of follow-up, we documented 1,799 incident cases of breast cancer in this population. After adjusting for established breast cancer risk factors, we observed only a weak and nonsignificant trend in risk of breast cancer with increasing maternal age at birth and no relation for paternal age. After adjusting for other risk factors, the chi trend was 1.10, P = 0.27 for increasing maternal age at birth. Daughters born to mothers 30 to 34 years of age had an age-adjusted relative risk of breast cancer of 1.11 (95% confidence interval: 0.89, 1.37) compared to daughters born to mothers less than 20 years of age. The weak positive trend in risk with increasing maternal age was present among both pre- and postmenopausal women. These findings suggest that there is little or no association between maternal age and risk of breast cancer, and that paternal age is not related to risk of breast cancer.

  4. Predominance of CIN versus MSI in the development of rectal cancer at young age

    PubMed Central

    Fernebro, Eva; Halvarsson, Britta; Baldetorp, Bo; Nilbert, Mef

    2002-01-01

    Background Development of proximal and distal colorectal cancers involve partly different mechanisms associated with the microsatellite instability (MSI) and the chromosomal instability (CIN) pathways. Colorectal cancers in patients under 50 years of age represent about 5% of the total number of tumors and have been associated with an increased frequency of MSI tumors. However, MSI and CIN may play different roles in the development of colon cancer and rectal cancer, and we have specifically investigated their contribution to the development of rectal cancer at young age. Methods Thirty rectal cancers diagnosed before the age of 50 were characterized for DNA-ploidy, MSI, mutations of KRAS and CTNNB1 and immunohistochemical expression of p53, β-catenin and of the mismatch repair (MMR) proteins MLH1 and MSH2. Results DNA aneuploidy was detected in 21/30 tumors, KRAS mutations in 6 tumors, no mutations of CTNNB1 were detected but immunohistochemical staining for β-catenin showed nuclear staining in 6 tumors, and immunohistochemical expression of p53 was detected in 18 tumors. MSI was detected in 3/30 tumors, all of which showed and immunohistochemical loss of staining for the MMR protein MSH2, which strongly indicates a phenotype associated with hereditary nonpolyposis colorectal cancer (HNPCC). Conclusions MSI occurs only in a small fraction of the tumors from young patients with rectal cancer, but when present it strongly indicates an underlying HNPCC-causing mutation, and other mechanisms than HNPCC thus cause rectal cancer in the majority of young patients. PMID:12379157

  5. Diverse Family Types and Out-Of-School Learning Time of Young School Age Children

    PubMed Central

    Ono, Hiromi

    2010-01-01

    =Sources of differentials in out-of-school learning time between children in first marriage biological parent families and children in six nontraditional family types are identified. Analyses of time diaries reveal that children in four of the six nontraditional family types spend fewer minutes learning than do children in first marriage biological parent families. In all four cases, however, the differentials are explained by the presence of siblings age 18+, lower levels of family income, or younger maternal age. PMID:21532970

  6. 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.

  7. [The influence of different types of physical exertions on the mature males' biological age].

    PubMed

    Sirotin, A B; Belozerova, L M; Sergeeva, I G; Zhukov, V N; Kolegova, N G

    2014-01-01

    We studied the biological age according to anthropometric indexes, mental, physical and both the types of working efficiency in 122 males at the age of 50-59 years. All of them were devided into 5 groups: untrained individuals, going in for general physical training, sport veterans, specializing in endurance training, sport plays representatives, weight-lifters. We found out a younger biological age in sport veterans, who were carrying out dynamic exertions.

  8. 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,…

  9. [The availability of particular types of medical social care to persons of elderly and senile age].

    PubMed

    Shigabutdinov, A F

    2012-01-01

    The article presents the results of sociological survey of respondents of elderly and senile age living with their families or in senior centers. The comparative analysis was applied to availability of particular types of medical social care of contingent of interest depending on place of its residence. The age and ability of self-support of respondents were taken into account.

  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. 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

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

    PubMed

    Lamb, Rebecca; Ozsvari, Bela; Lisanti, Camilla L; Tanowitz, Herbert B; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2015-03-10

    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, recent

  13. 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

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

    PubMed

    Menendez, Javier A; Joven, Jorge

    2012-12-01

    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.

  15. 'Cancer doesn't have an age': genetic testing and cancer risk management in BRCA1/2 mutation-positive women aged 18-24.

    PubMed

    Werner-Lin, Allison; Hoskins, Lindsey M; Doyle, Maya H; Greene, Mark H

    2012-11-01

    Increasingly, 18-24-year-old women from hereditary breast/ovarian cancer (HBOC) families are pursuing genetic testing, despite their low absolute risks of breast and ovarian cancer and the fact that evidence-based management options used with older high-risk women are not generally available. Difficult clinical decisions in older carriers take on substantially more complexity and value-laden import in very young carriers. As a result, many of the latter receive highly personal and emotionally charged cancer risk information in a life context where management strategies are not well defined. We analyzed 32 in-depth interviews with BRCA1/2 mutation-positive women aged 18-24 using techniques of grounded theory and interpretive description. Participants described feeling vulnerable to a cancer diagnosis but in a quandary regarding their care because evidence-based approaches to management have not been developed and clinical trials have not been undertaken. Our participants demonstrated a wide range of genetic and health literacy. Inconsistent recommendations, surveillance fatigue, and the unpredictability of their having health insurance coverage for surgical risk-reducing procedures led several to contemplate risk-reducing mastectomy before age 25. Parents remained a primary source of emotional and financial support, slowing age-appropriate independence and complicating patient privacy. Our findings suggest that, for 18-24-year-olds, readiness to autonomously elect genetic testing, to fully understand and act on genetic information, and to confidently make decisions with life-long implications are all evolving processes. We comment on the tensions between informed consent, privacy, and the unique developmental needs of BRCA1/2 mutation-positive women just emerging into their adult years. PMID:22547552

  16. Coverage of common cancer types in UK national newspapers: a content analysis

    PubMed Central

    Konfortion, Julie; Jack, Ruth H; Davies, Elizabeth A

    2014-01-01

    Objective To determine whether recent newspaper coverage of the four most common cancer types relates to their relative burden and national awareness months, and to identify the subject focus during high-coverage periods. Design Content analysis using the Nexis newspaper article database. Setting UK 2011–2012. Outcome measures Annual number and ranking, monthly proportions and subject of articles on breast, lung, bowel and prostate cancers. Results 9178 articles were identified during 2011 and 2012 featuring breast (4237), prostate (1757), lung (1746) and bowel (1438) cancer. Peaks in monthly proportions above the 99% upper confidence limit were identified for each. Breast cancer had the highest coverage of 12% and 17% during its awareness month. Smaller peaks (11%) were identified during Bowel Cancer Awareness month. Prostate cancer received high coverage in relation to the case of the man convicted of the Lockerbie bombing who had been diagnosed with the cancer, and lung cancer in relation to the deaths of celebrities. Breast cancer was covered most often overall and by newspaper category while the lower coverage of other cancer types did not consistently mirror the relative number of new cases each year. The peaks by newspaper category were similar to the overall coverage with few exceptions. Conclusions UK newspaper coverage of common cancer types other than of the breast appears under-represented relative to their population burden. Coverage of breast cancer and bowel cancer appears to be influenced by their awareness months, while that of prostate cancer and lung cancer is influenced by other media stories. Health-promoting public bodies and campaigners could learn from the success of Breast Cancer Awareness Month and work more closely with journalists to ensure that the relevant messages reach wider audiences. PMID:25015469

  17. RACIAL DISPARITIES IN BREAST CANCER SURVIVAL: AN ANALYSIS BY AGE AND STAGE

    PubMed Central

    Deshpande, Anjali D.; Jeffe, Donna B.; Gnerlich, Jennifer; Iqbal, Ayesha Z.; Thummalakunta, Abhishek; Margenthaler, Julie A.

    2011-01-01

    Background Black women often present with advanced-stage breast cancer compared with White women, which may result in the observed higher mortality among Black women. Age-related factors (e.g., comorbidity) also affect mortality. Whether racial disparities in mortality are evident within age and/or stage groups has not been reported, and risk factors for greater mortality among Black women are not well defined. Methods Using the 1988–2003 Surveillance, Epidemiology, and End Results (SEER) Program data, we conducted a retrospective, population-based cohort study to compare overall and stage-specific breast-cancer mortality between Black and White women within each age (<40, 40–49, 50–64, and 65+) and stage (stage 0–IV and unstaged) group at diagnosis. Cox regression models calculated unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CI), the latter controlling for potential confounders of the relationship between race and survival. Results In the 1988–2003 SEER data, 20,424 Black and 204,506 White women were diagnosed with first primary breast cancer. In unadjusted models, Black women were more likely than White women to die from breast cancer (HR: 1.90, 95% CI: 1.83–1.96) and from all causes (HR: 1.52, 95% CI: 1.48–1.55) during follow-up. In models stratified by age and stage, Black women were at increased risk of breast-cancer-specific mortality within each stage group among women <65 years. Conclusion Racial disparities in breast-cancer-specific mortality were predominantly observed within each stage at diagnosis among women <65 years old. This greater mortality risk for Black women was largely not observed among women ≥65 years of age. PMID:19084242

  18. 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

  19. 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

  20. 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

  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. 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.

  3. 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

  4. 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.

  5. Association of Insurance Status and Age With Cervical Cancer Stage at Diagnosis: National Cancer Database, 2000–2007

    PubMed Central

    Cokkinides, Vilma; Virgo, Katherine S.; Bandi, Priti; Saslow, Debbie; Ward, Elizabeth M.

    2012-01-01

    Objectives. We examined the relationship of age at diagnosis and insurance status with stage among cervical cancer patients aged 21 to 85 years. Methods. We selected data on women (n = 69 739) diagnosed with invasive cervical cancer between 2000 and 2007 from the National Cancer Database. We evaluated the association between late stage (stage III/IV) and both insurance and age, with adjustment for race/ethnicity and other sociodemographic and clinical factors. We used multivariable log binomial models to estimate risk ratios (RRs) and 95% confidence intervals (CIs). Results. The proportion of late-stage disease increased with age: from 16.53% (21–34 years) to 42.44% (≥ 70 years). The adjusted relative risk of advanced-stage disease among women aged 50 years and older was 2.2 to 2.5 times that of patients aged 21 to 34 years. Uninsured (RR = 1.44; 95% CI = 1.40, 1.49), Medicaid (RR = 1.37, 95% CI = 1.34, 1.41), younger Medicare (RR = 1.12, 95% CI = 1.06, 1.19), and older Medicare (RR = 1.20, 95% CI = 1.15, 1.26) patients had a higher risk of late-stage disease than did privately insured patients. Conclusions. Screening should be encouraged for women at high risk for advanced-stage disease. PMID:22742058

  6. 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

  7. 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 ...

  8. Cancer in Women over 50 Years of Age: A Focus on Smoking.

    PubMed

    Baccaro, Luiz Francisco; Conde, Délio Marques; Costa-Paiva, Lúcia; de Souza Santos Machado, Vanessa; Pinto-Neto, Aarão Mendes

    2015-01-01

    The increase in life expectancy worldwide has resulted in a greater prevalence of chronic non-communicable diseases. This study aims to evaluate the prevalence and factors associated with the occurrence of cancer among Brazilian women over the age of 50. A cross-sectional study with 622 women over the age of 50 was performed using a population survey. The outcome variable was the occurrence of a malignant tumor in any location. The independent variables were sociodemographic characteristics, self-perception of health, health-related habits and morbidities. Statistical analysis was carried out using the chi-square test and Poisson regression. The mean age of the women was 64.1 years. The prevalence of cancer was 6.8%. The main sites of occurrence of malignant tumors were the breast (31.9%), colorectal (12.7%) and skin (12.7%). In the final statistical model, the only factor associated with cancer was smoking > 15 cigarettes/day either currently or in the past: PR 2.03 (95% CI 1.06-3.89). The results have improved understanding of the prevalence and factors associated with cancer in Brazilian women aged 50 years or more. They should be encouraged to maintain a healthy lifestyle and pay particular attention to modifiable risk factors such as smoking.

  9. 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.

  10. 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…

  11. Influence of Educational Level, Stage, and Histological Type on Survival of Oral Cancer in a Brazilian Population

    PubMed Central

    Dantas, Thinali Sousa; de Barros Silva, Paulo Goberlânio; Sousa, Eric Fernandes; da Cunha, Maria do PSS; de Aguiar, Andréa Silvia Walter; Costa, Fábio Wildson Gurgel; Mota, Mário Rogério Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu

    2016-01-01

    Abstract The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juaçaba Hospital – Cancer Institute of Ceará from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia. PMID:26817864

  12. Roles of the nucleoporin Tpr in cancer and aging.

    PubMed

    Snow, Chelsi J; Paschal, Bryce M

    2014-01-01

    Tpr is a prominent architectural component of the nuclear pore complex that forms the basket-like structure on the nucleoplasmic side of the pore. Tpr, which stands for translocated promoter region, was originally described in the context of oncogenic fusions with the receptor tyrosine kinases Met, TRK, and Raf. Tpr has been since implicated in a variety of nuclear functions, including nuclear transport, chromatin organization, regulation of transcription, and mitosis. More recently, Tpr function has been linked to events including p53 signaling and premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS). Here we provide an overview of the various processes that involve Tpr, and discuss how the levels and localization of a single protein can affect diverse pathways in the cell.

  13. 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

  14. Cancer stem cells in Helicobacter pylori infection and aging: Implications for gastric carcinogenesis

    PubMed Central

    Levi, Edi; Sochacki, Paula; Khoury, Nabiha; Patel, Bhaumik B; Majumdar, Adhip PN

    2014-01-01

    AIM: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells (CSCs) of gastric mucosa in an animal model. METHODS: In this study we investigated the effects of aging and Helicobacter pylori (H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old (young) with 22 mo (aged) old Fischer-344 rats. For human studies, gastric biopsies and resection specimens representing normal mucosa or different stages of H. pylori gastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells. RESULTS: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylori gastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylori gastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia. CONCLUSION: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pylori infection may have additive effects in progression to neoplasia. PMID:25133037

  15. 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.

  16. 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

  17. 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

  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. Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins

    PubMed Central

    Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A.

    2014-01-01

    Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceteddisease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute anew family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of “mechanism-effect” and “effect-mechanism” relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins. PMID:25324469

  20. Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

    PubMed

    Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

    2014-09-01

    Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

  1. [DNA repair--a fundamental factor in ageing and development of cancer].

    PubMed

    Rasmussen, Lene Juel; Stevnsner, Tinna; Bohr, Vilhelm A

    2006-06-12

    Advanced age and increased incidence of many illnesses such as cancer are closely linked. The reasons for such a link are numerous but one important factor is DNA repair. DNA repair pathways in both nuclei and mitochondria ensure that genomic instability is minimised, thus preventing transformation and premature cellular decay. However, overall cellular DNA repair capacity decreases with age; moreover, some individuals are born with defects in repair systems. The resulting lower capacity for repair of DNA damage increases mutation load and changes normal cellular functions such as transcription, thereby contributing to the ageing process as well to the onset of various cancers. DNA repair capacity is an important cellular marker that should be considered as a standard clinical test.

  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

    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.

  4. 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

  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. Oral-facial-digital type 1 syndrome of Papillon-Léage and Psaume.

    PubMed

    Larralde de Luna, M; Raspa, M L; Ibargoyen, J

    1992-03-01

    A female infant was classified as having oral-facial-digital syndrome (OFDS) type 1, with oral (cleft palate, bifid uvula, lingual cleft, numerous hypertrophic frenula), facial (numerous milia on face, scalp, and ears; frontal bossing; hypertelorism; hypoplasia of nasal alar cartilage; micrognathia), and digital (bilateral brachydactyly of hands) symptoms. She also had diffuse, nonscarring alopecia with wiry, dry hair. Results of roentgenographic and ultrasound studies were normal. At her present age of 11 months, her psychomotor development is appropriate for her age.

  7. 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

  8. 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

  9. 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.

  10. Social support sources, types, and generativity: a focus group study of cancer survivors and their caregivers.

    PubMed

    Wong, Alison G; Ki, Ppudah; Maharaj, Artie; Brown, Edna; Davis, Cindy; Apolinsky, Felice

    2014-01-01

    Various research studies have identified the sources and types of support that people with cancer receive; however, few have focused on identifying the specific characteristics of emotional, instrumental, and informational support. In this study, focus groups consisting of Gilda's Club members explored the types of support that people with cancer and their caregivers experienced and valued. Results showed that although men and women with cancer and caregivers identify similar sources of support, they experience different types of support. Results also indicated a desire among participants to help and support others, a concept referred to as generativity. Implications for social workers and health care providers are explored.

  11. Age and sex based genetic locus heterogeneity in type 1 diabetes

    PubMed Central

    Paterson, A.; Petronis, A.

    2000-01-01

    BACKGROUND—Two genome scans for susceptibility loci for type 1 diabetes using large collections of families have recently been reported. Apart from strong linkage in both studies of the HLA region on chromosome 6p, clear consistent evidence for linkage was not observed at any other loci. One possible explanation for this is a high degree of locus heterogeneity in type 1 diabetes, and we hypothesised that the sex of affected offspring, age of diagnosis, and parental origin of shared alleles may be the bases of heterogeneity at some loci.
METHODS—Using data from a genome wide linkage study of 356 affected sib pairs with type 1 diabetes, we performed linkage analyses using parental origin of shared alleles in subgroups based on (1) sex of affected sibs and (2) age of diagnosis.
RESULTS—Among the results obtained, we observed that evidence for linkage to IDDM4 on chromosome 11q13 occurred predominantly from opposite sex, rather than same sex sib pairs. At a locus on chromosome 4q, evidence for linkage was observed in sibs where one was diagnosed above the age of 10 years and the other diagnosed below 10 years of age.
CONCLUSIONS—We show that heterogeneity tests based on age of diagnosis, sex of affected subject, and parental origin of shared alleles may be helpful in reducing locus heterogeneity in type 1 diabetes. If repeated in other samples, these findings may assist in the mapping of susceptibility loci for type 1 diabetes. Similar analyses can be recommended in other complex diseases.


Keywords: type 1 diabetes; age of diagnosis; sex; parental origin of alleles PMID:10699054

  12. Aging-associated changes in L-type calcium channels in the left atria of dogs

    PubMed Central

    GAN, TIAN-YI; QIAO, WEIWEI; XU, GUO-JUN; ZHOU, XIAN-HUI; TANG, BAO-PENG; SONG, JIAN-GUO; LI, YAO-DONG; ZHANG, JIAN; LI, FA-PENG; MAO, TING; JIANG, TAO

    2013-01-01

    Action potential (AP) contours vary considerably between the fibers of normal adult and aged left atria. The underlying ionic and molecular mechanisms that mediate these differences remain unknown. The aim of the present study was to investigate whether the L-type calcium current (ICa.L) and the L-type Ca2+ channel of the left atria may be altered with age to contribute to atrial fibrillation (AF). Two groups of mongrel dogs (normal adults, 2–2.5 years old and older dogs, >8 years old) were used in this study. The inducibility of AF was quantitated using the cumulative window of vulnerability (WOV). A whole-cell patch-clamp was used to record APs and ICa.L in left atrial (LA) cells obtained from the two groups of dogs. Protein and mRNA expression levels of the a1C (Cav1.2) subunit of the L-type calcium channel were assessed using western blotting and quantitative PCR (qPCR), respectively. Although the resting potential, AP amplitude and did not differ with age, the plateau potential was more negative and the APD90 was longer in the aged cells compared with that in normal adult cells. Aged LA cells exhibited lower peak ICa.L current densities than normal adult LA cells (P<0.05). In addition, the Cav1.2 mRNA and protein expression levels in LA cells were decreased in the aged group compared with those in the normal adult group. The lower AP plateau potential and the decreased ICa.L of LA cells in aged dogs may contribute to the slow and discontinuous conduction of the left atria. Furthermore, the reduction of the expression levels of Cav1.2 with age may be the molecular mechanism that mediates the decline in ICa.L with increasing age. PMID:24137290

  13. A Case of Multifocal Skin Metastases from Lung Cancer Presenting with Vasculitic-type Cutaneous Nodule

    PubMed Central

    Babacan, Nalan Akgul; Kiliçkap, Saadettin; Sene, Soner; Kacan, Turgut; Yucel, Birsen; Eren, Mehmet Fuat; Cihan, Sener

    2015-01-01

    Although cutaneous metastasis occurs usually at the terminal stage of the disease, it may be rarely concurrent with the diagnosis and may also present as the first sign of the illness. A 55-year-old male patient presented with vasculitic-type cutaneous nodular lesions and a necrotic distal phalangeal lesion developed over the last month. He was a tradesman and smoked 40 packets year. On physical examination, he was found to have multiple cutaneous lesions on the skin of the face, limbs, neck, scalp, dorsal side, fingers, subungual side, right leg, and feet. A skin lesion punch biopsy was performed and squamous cell carcinoma metastasis was detected. He was diagnosed as having squamous cell lung cancer with bronchoscopic biopsy. Although it is very rare, cutaneous metastases that is concurrent with the diagnosis of lung cancer may be the first sign of the disease. In patients with suspicious skin lesions, the patient's age, smoking history, and other symptoms should be evaluated and a biopsy should be performed. PMID:25814739

  14. Individual radiosensitivity in a breast cancer collective is changed with the patients’ age

    PubMed Central

    Auer, Judith; Keller, Ulrike; Schmidt, Manfred; Ott, Oliver; Fietkau, Rainer; Distel, Luitpold V.

    2014-01-01

    Background Individual radiosensitivity has a crucial impact on radiotherapy related side effects. Our aim was to study a breast cancer collective for its variation of individual radiosensitivity depending on the patients’ age. Materials and methods Peripheral blood samples were obtained from 129 individuals. Individual radiosensitivity in 67 breast cancer patients and 62 healthy individuals was estimated by 3-color fluorescence in situ hybridization. Results Breast cancer patients were distinctly more radiosensitive compared to healthy controls. A subgroup of 9 rather radiosensitive and 9 rather radio-resistant patients was identified. A subgroup of patients aged between 40 and 50 was distinctly more radiosensitive than younger or older patients. Conclusions In the breast cancer collective a distinct resistant and sensitive subgroup is identified, which could be subject for treatment adjustment. Preliminary results indicate that especially in the range of age 40 to 50 patients with an increased radiosensitivity are more frequent and may have an increased risk to suffer from therapy related side effects. PMID:24587784

  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. 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

  17. 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

  18. The importance of preoperative elevated serum levels of CEA and CA15-3 in patients with breast cancer in predicting its histological type.

    PubMed

    Agrawal, A K; Jelen, M; Rudnicki, J; Grzebieniak, Z; Zyśko, D; Kielan, W; Słonina, J; Marek, G

    2010-01-01

    It is not known whether in patients with breast cancer the occurrence of elevated serum tumour markers depends on its histological type. The aim of the study was to assess relationship between breast cancer histological type and the presence of increased serum levels of CEA and CA 15-3. The study population was 428 patients (all women, mean age 52.5 years), treated at The Department of Surgery of Wroclaw Medical University from 2005 to 2008 due to breast cancer. All of them had their preoperative CA 15-3 and CEA serum concentrations measured. According to the TNM system, 21% of patients were in stage I, 32.5% in stage II, 46.5% in stage III of the disease. In patients with ductal type of the cancer the elevated serum levels of CEA and CA 15-3 were observed in 48.7% and 42.2%, in lobular type in 42.4% and 52.5%, and in non-ductal/tubular types in 48.1% and 40.4% (p=N/S). Stepwise logistic regression analyses showed that ductal breast cancer is related to elevated CEA and normal CA 15-3 serum levels. The histological types of breast cancer are not significantly related to elevated serum levels of CEA and/or CA 15-3.

  19. Common drugs and treatments for cancer and age-related diseases: revitalizing answers to NCI's provocative questions

    PubMed Central

    Blagosklonny, Mikhail V.

    2012-01-01

    In 2011, The National Cancer Institute (NCI) has announced 24 provocative questions on cancer. Some of these questions have been already answered in “NCI's provocative questions on cancer: some answers to ignite discussion” (published in Oncotarget, 2011, 2: 1352.) The questions included “Why do many cancer cells die when suddenly deprived of a protein encoded by an oncogene?” “Can we extend patient survival by using approaches that keep tumors static?” “Why are some disseminated cancers cured by chemotherapy alone?” “Can we develop methods to rapidly test interventions for cancer treatment or prevention?” “Can we use our knowledge of aging to enhance prevention or treatment of cancer?” “What is the mechanism by which some drugs commonly and chronically used for other indications protect against cancer?” “How does obesity contribute to cancer risk?” I devoted a single subchapter to each the answer. As expected, the provocative questions were very diverse and numerous. Now I choose and combine, as a single problem, only three last questions, all related to common mechanisms and treatment of age-related diseases including obesity and cancer. Can we use common existing drugs for cancer prevention and treatment? Can we use some targeted “cancer-selective” agents for other diseases and … aging itself. PMID:23565531

  20. An age, period and cohort analysis of pleural cancer mortality in Europe.

    PubMed

    La Vecchia, C; Decarli, A; Peto, J; Levi, F; Tomei, F; Negri, E

    2000-06-01

    Death certification data from pleural cancer in eight European countries providing data to the World Health Organization database over the period 1970-1994 were analysed using a log-linear Poisson model to disentangle the effects of age, birth cohort and period of death. The age effect reached values between 10 and 15/100,000 males at age 80-84 in most countries, except Hungary (6.7), Switzerland (18.0), France (20.6) and the Netherlands (36.5). Cohort effects were steadily and appreciably upwards in all countries up to the generations born in 1940 or 1945, and levelled off for the 1950 cohort, except in Hungary, where persistent rises were observed. Thus, most rises in pleural cancer mortality in Europe were on a cohort of birth basis. Since most pleural cases were asbestos-related mesotheliomas, and since asbestos has an early-stage effect on subsequent mesothelioma risk, exposure early in life is important for determining the subsequent mesothelioma risk of each generation. Consequently, the data indicate that the peak mortality from pleural cancer in most western European countries will be reached in the first decades of the 21st century, i.e. around 2010-2020, when the generations born between 1940 and 1950 will reach the peak age for mesothelioma incidence and mortality. This contrasts with US data, where the peak of pleural cancer incidence has been reached at the end of the 20th century, and reflects a delay in adopting adequate prevention measures since the 1940-1945 generations entered the workforce in the 1960s, when cancer risk from asbestos exposure was already recognized.

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

    PubMed Central

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

    2016-01-01

    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

  2. Different influences of field aging on nickel toxicity to Folsomia candida in two types of soil.

    PubMed

    Liu, Yu-Rong; Li, Jing; He, Ji-Zheng; Ma, Yi-Bing; Zheng, Yuan-Ming

    2015-06-01

    Metal aging in soils has been considered an important factor influencing its availability and toxicity to organisms. In this study, we report the influence of 5 years field aging on the nickel (Ni) toxicity to collembolan Folsomia candida based on two different types of soil from Dezhou (DZ) and Qiyang (QY) counties in China. Acute and chronic toxicity of Ni to F. candida was assessed in both freshly spiked and field aging contaminated soils. We found that 5 years field aging increased the EC50 and 2d-LC50 values of Ni to F. candida in the DZ soil, while little influence on the Ni toxicity was observed in the QY soil. There was no adverse effect of the long-term field aging on the Ni toxicity to the survival of F. candida in the two tested soils. In addition, field aging of the two soils impacted differently the water-soluble Ni concentrations, which were significantly correlated to the juvenile production of F. candida based on a logistic model. Our study highlights different effects of long-term field aging on the Ni toxicity to F. candida between divergent types of soil, and this should be taken into account in future toxicity testing and risk assessment practices.

  3. Clinicopathologic and molecular features associated with patient age in gastric cancer

    PubMed Central

    Seo, Ji Yeon; Jin, Eun Hyo; Jo, Hyun Jin; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung; Jung, Hyun Chae; Lee, Dong Ho

    2015-01-01

    AIM: To compare characteristics and prognosis of gastric cancer based on age. METHODS: A retrospective study was conducted on clinical and molecular data from patients (n = 1658) with confirmed cases of gastric cancer in Seoul National University Bundang Hospital (Seoul, South Korea) from 2003 to 2010 after exclusion of patients diagnosed with lymphoma, gastrointestinal stromal tumor, and metastatic cancer in the stomach. DNA was isolated from tumor and adjacent normal tissue, and a set of five markers was amplified by polymerase chain reaction to assess microsatellite instability (MSI). MSI was categorized as high, low, or stable if ≥ 2, 1, or 0 markers, respectively, had changed. Immunohistochemistry was performed on tissue sections to detect levels of expression of p53, human epidermal growth factor receptor (HER)-2, and epidermal growth factor receptor. Statistical analysis of clinical and molecular data was performed to assess prognosis based on the stratification of patients by age (≤ 45 and > 45 years). RESULTS: Among the 1658 gastric cancer patients, the number of patients with an age ≤ 45 years was 202 (12.2%; 38.9 ± 0.4 years) and the number of patients > 45 years was 1456 (87.8%; 64.1 ± 0.3 years). Analyses revealed that females were predominant in the younger group (P < 0.001). Gastric cancers in the younger patients exhibited more aggressive features and were at a more advanced stage than those in older patients. Precancerous lesions, such as atrophic gastritis and intestinal metaplasia, were observed less frequently in the older than in the younger group (P < 0.001). Molecular characteristics, including overexpression of p53 (P < 0.001), overexpression of HER-2 (P = 0.006), and MSI (P = 0.006), were less frequent in gastric cancer of younger patients. Cancer related mortality was higher in younger patients (P = 0.048), but this difference was not significant after adjusting for the stage of cancer. CONCLUSION: Gastric cancer is distinguishable

  4. 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

  5. Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake.

    PubMed

    Ames, Bruce N

    2010-01-01

    I review three of our research efforts which suggest that optimizing micronutrient intake will in turn optimize metabolism, resulting in decreased DNA damage and less cancer as well as other degenerative diseases of aging. (1) Research on delay of the mitochondrial decay of aging, including release of mutagenic oxidants, by supplementing rats with lipoic acid and acetyl carnitine. (2) The triage theory, which posits that modest micronutrient deficiencies (common in much of the population) accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity. (3) The finding that decreased enzyme binding constants (increased Km) for coenzymes (or substrates) can result from protein deformation and loss of function due to an age-related decline in membrane fluidity, or to polymorphisms or mutation. The loss of enzyme function can be compensated by a high dietary intake of any of the B vitamins, which increases the level of the vitamin-derived coenzyme. This dietary remediation illustrates the importance of understanding the effects of age and polymorphisms on optimal micronutrient requirements. Optimizing micronutrient intake could have a major effect on the prevention of cancer and other degenerative diseases of aging.

  6. Age Dependent Switching Role of Cyclin D1 in Breast Cancer

    PubMed Central

    Rinaldi, Carmela; Malara, Natalia Maria; D’Angelo, Rosalia; Sidoti, Antonina; Leotta, Attilio; Lio, Santo; Caparello, Basilio; Ruggeri, Alessia; Mollace, Vincenzo; Amato, Aldo

    2012-01-01

    Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. The aim of this study was to better understand the molecular dynamics of ductal carcinomas with regard to proliferation and the ageing process. Methods: 130 cases of ductal breast cancer in postmenopausal women, aged 52–96 in 3 age classes were selected. Tumoral tissues preserved in formaldehyde solution and subsequently embedded in paraffin were subjected to analysis Fluorescence in situ Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT- PCR) and immuno-histochemical tests. The molecular variables studied were estimated in relation to the patients’ age. Results: The results obtained suggest that the increment of the levels of cyclin D1 in intra-ductal breast tumors in older woman that we have examined is significantly associated with a lower proliferation rate. Conclusion: Cyclin D1, which characterizes tumor in young women as molecular director involved in strengthening tumoral proliferation mechanisms, may be seen as a potential blocking molecular switch in corresponding tumours in old women. PMID:22231956

  7. 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.

  8. Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases.

    PubMed

    Khatami, Mahin

    2009-01-01

    Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging.

  9. Screening for breast cancer and mortality reduction among women 40-49 years of age.

    PubMed

    Kopans, D B

    1994-07-01

    The recent withdrawal of screening support for women ages 40-49 years is not scientifically supported. The subgroup analyses that have been used severely compromise the statistical power of the trials. None of the trials has the statistical power to be able to provide clear proof of benefit for screening women ages 40-49 years because none of the trials involved sufficient numbers of women in these age groups. Despite having not been designed to evaluate women ages 40-49 years as a separate group, five of the eight randomized, controlled trials have demonstrated mortality reductions for these women that range from 22% to 49%. In addition, data from other nonrandomized trials show that there is no difference in survival for women ages 40-49 years than for women ages 50-59 years. The detection rate for small, early cancers, using modern mammography, is similar for women in both decades. There is no scientific reason to believe that there is a sudden change in detection or cure at age 50 years, or even at menopause. The available data suggest that women ages 40-49 years can benefit from screening, just as can women ages 50-59 years.

  10. 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

  11. 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

  12. 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).

  13. Assessment of Oro-Maxillofacial Trauma According to Gender, Age, Cause and Type of the Injury

    PubMed Central

    Matijević, Marko; Sikora, Miroslav; Leović, Dinko; Mumlek, Ivan; Macan, Darko

    2015-01-01

    Objectives The occurrence and causes of maxillofacial trauma varies in different regions of the world. The aim of this study was to identify the occurrence, types and causes of maxillofacial injuries according to the age and gender differences in patients treated at the Department of Maxillofacial Surgery, University Hospital Center Osijek, between January 2011 and December 2013. Materials and methods A total of 64 patients, 41 males (64.1%) and 23 females (35.9%), aged from 18 to 86 years (mean age 42) participated in the study. Data collected and analyzed included gender, age, cause of injury and the type of maxillofacial injuries. Results The most common cause of injuries in both gender groups was falling down (39% males; 65% females). The second leading cause of injuries in males was interpersonal violence (29%) and in females traffic accident (26%) (p<0.05). The most common type of injury in both gender groups was bone injury (50%; in males zygomatic bones 55%, in females mandible 40%) (p>0.05). The most common causes of injuries in the youngest patients was violence (43%), and in others fall (50-70%; p<0.05). The most common reported type of injury in all age groups was bone injury (more than 50%; p>0.05). The majority of the falls and violence caused bone tissue injuries, and soft tissue and dentalveolar injuries were detected in traffic and sports accidents (p>0.05). Conclusion Falling down was the most common cause of oro-maxillofacial injuries in both men and women and in all three age groups. The leading type of injury was bone injury. The data obtained from this study provide important information for future prevention from injuries.

  14. Calcium signaling and T-type calcium channels in cancer cell cycling

    PubMed Central

    Taylor, James T; Zeng, Xiang-Bin; Pottle, Jonathan E; Lee, Kevin; Wang, Alun R; Yi, Stephenie G; Scruggs, Jennifer A S; Sikka, Suresh S; Li, Ming

    2008-01-01

    Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells, free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear; however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel is minimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers. PMID:18763278

  15. Long-term aging of type 308 stainless steel welds: Effects on properties and microstructure

    SciTech Connect

    Alexander, D.J.; Vitek, J.M.; David, S.A.

    1994-09-01

    Multipass gas tungsten arc welds with type 308 stainless steel filler metal in type 304L base plate have been aged at 400, 475, or 550{degrees}C for times up to 5,000 h. The changes in mechanical properties as a result of these agings have been followed with tensile, impact, and fracture toughness testing, using subsize tensile, half-size Charpy, and 0.45T compact specimens, respectively. The changes in the microstructure were evaluated with optical and transmission electron microscopy. Relatively little change was observed in the tensile properties for any of the aging treatments, but significant embrittlement was observed in the impact and fracture toughness testing. The transition temperatures increased rapidly for aging at 475 or 550{degrees}C, and more slowly for aging at 400{degrees}C. The upper-shelf energies and the fracture toughness showed similar responses, with only a small decrease for 400{degrees}C aging, but much greater and rapid decreases with aging at 475 or 550{degrees}C. Aging at 400 or 475{degrees}C resulted in the spinodal decomposition of the ferrite phase in the weld metal into iron-rich alpha and chromium-enriched alpha prime. In addition, at 475{degrees}C G-phase precipitates formed homogeneously in the ferrite and also at dislocations. At 550{degrees}C carbides formed and grew at the ferrite-austenite interfaces, and some ferrite transformed to sigma phase. These changes must all be considered in determining the effect of aging on the fracture properties.

  16. 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

  17. 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

  18. The statistical geometry of transcriptome divergence in cell-type evolution and cancer.

    PubMed

    Liang, Cong; Forrest, Alistair R R; Wagner, Günter P

    2015-01-01

    In evolution, body plan complexity increases due to an increase in the number of individualized cell types. Yet, there is very little understanding of the mechanisms that produce this form of organismal complexity. One model for the origin of novel cell types is the sister cell-type model. According to this model, each cell type arises together with a sister cell type through specialization from an ancestral cell type. A key prediction of the sister cell-type model is that gene expression profiles of cell types exhibit tree structure. Here we present a statistical model for detecting tree structure in transcriptomic data and apply it to transcriptomes from ENCODE and FANTOM5. We show that transcriptomes of normal cells harbour substantial amounts of hierarchical structure. In contrast, cancer cell lines have less tree structure, suggesting that the emergence of cancer cells follows different principles from that of evolutionary cell-type origination. PMID:25585899

  19. Age-associated repression of type 1 inositol 1, 4, 5-triphosphate receptor impairs muscle regeneration

    PubMed Central

    Lee, Bora; Lee, Seung-Min; Bahn, Young Jae; Lee, Kwang-Pyo; Kang, Moonkyung; Kim, Yeon-Soo; Woo, Sun-Hee; Lim, Jae-Young; Kim, Eunhee; Kwon, Ki-Sun

    2016-01-01

    Skeletal muscle mass and power decrease with age, leading to impairment of mobility and metabolism in the elderly. Ca2+ signaling is crucial for myoblast differentiation as well as muscle contraction through activation of transcription factors and Ca2+-dependent kinases and phosphatases. Ca2+ channels, such as dihydropyridine receptor (DHPR), two-pore channel (TPC) and inositol 1,4,5-triphosphate receptor (ITPR), function to maintain Ca2+ homeostasis in myoblasts. Here, we observed a significant decrease in expression of type 1 IP3 receptor (ITPR1), but not types 2 and 3, in aged mice skeletal muscle and isolated myoblasts, compared with those of young mice. ITPR1 knockdown using shRNA-expressing viruses in C2C12 myoblasts and tibialis anterior muscle of mice inhibited myotube formation and muscle regeneration after injury, respectively, a typical phenotype of aged muscle. This aging phenotype was associated with repression of muscle-specific genes and activation of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. ERK inhibition by U0126 not only induced recovery of myotube formation in old myoblasts but also facilitated muscle regeneration after injury in aged muscle. The conserved decline in ITPR1 expression in aged human skeletal muscle suggests utility as a potential therapeutic target for sarcopenia, which can be treated using ERK inhibition strategies. PMID:27658230

  20. 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

  1. Longitudinal associations between activity and cognition vary by age, activity type, and cognitive domain.

    PubMed

    Bielak, Allison A M; Gerstorf, Denis; Anstey, Kaarin J; Luszcz, Mary A

    2014-12-01

    The demonstration of correlated change is critical to understanding the relationship between activity engagement and cognitive functioning in older adulthood. Changes in activity have been shown to be related to changes in cognition, but little attention has been devoted to how this relationship may vary between specific activity types, cognitive domains, and age groups. Participants initially aged 65-98 years (M = 77.46 years) from the Australian Longitudinal Study of Ageing (n = 1,321) completed measurements of activity (i.e., cognitive, group social, one-on-one social, and physical) and cognition (i.e., perceptual speed, and immediate and delayed episodic memory) at baseline, 2, 8, 11, and 15 years later. Bivariate latent growth curve models covarying for education, sex, and baseline age and medical conditions revealed multiple positive-level relations between activity and cognitive performance, but activity level was not related to later cognitive change. Change in perceptual speed over 15 years was positively associated with change in cognitive activity, and change in immediate episodic memory was positively associated with change in one-on-one social activity. Old-old adults showed a stronger change-change covariance for mentally stimulating activity in relation to perceptual speed than did young-old adults. The differentiation by activity type, cognitive domain, and age contributes to the growing evidence that there is variation in the way cognitive ability at different ages is related to activity.

  2. 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

  3. 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

  4. Breast cancer and ages at first marriage and first birth: a new hypothesis.

    PubMed

    Kinlen, Leo J

    2014-01-01

    The aim of this study was to examine available data on breast cancer and age at first marriage from a new perspective: that is, marriage involves the closest contact and contact effects are relevant to the question of infection, a possibility long considered in this disorder. The large Seven Country Study, carried out in 1964-1968, investigated age at first marriage; its reports were examined carefully for details of possible relevance. Intriguing gaps were noted in the grounds for the conclusion by this study that late age at first birth explained an earlier reported association with late age at marriage, with risks presented by age at first marriage for nulliparous, but not for parous, married women. Only in one centre, Glamorgan Wales, and only for two age groups could risks by combined ages at first marriage and first birth be derived. When both events occurred at age 30 or older, the risk estimate was 7.0 (95% confidence interval: 5.2, 9.1) relative to when both events occurred younger than age 20, whereas the corresponding risk was 1.4 (95% confidence interval: 1.1, 1.8) when age at first birth was 30 or older but marriage was younger than age 30. The above findings are consistent with an effect of age at first marriage, and a basis in contacts or infection is considered plausible. However, other explanations may exist, and this report primarily aims to encourage examination of the subject in other datasets, particularly where intersexual contrasts in infective exposures have probably existed.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  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. 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

  12. Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer

    PubMed Central

    Uccella, S; Mariani, A; Wang, A H; Vierkant, R A; Cliby, W A; Robien, K; Anderson, K E; Cerhan, J R

    2013-01-01

    Background: Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously. Methods: Prospective cohort of 23 356 postmenopausal women with 471 Type I and 71 Type II EC cases. Results: Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ⩽1 cup per month: 95% confidence interval (CI): 0.47–0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50–1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m−2 (RR=0.56; 95% CI: 0.36–0.89). Conclusion: Coffee may protect against Type I EC in obese postmenopausal women. PMID:24022184

  13. Effect of age on drug metabolism in women with breast cancer

    PubMed Central

    Singh, Jasmeet C; Lichtman, Stuart M

    2016-01-01

    Introduction The aging of the population will increase the number of breast cancer patients requiring treatment in both the adjuvant and metastatic setting. Hormones, chemotherapy and targeted drugs all have a role in treatment. Older patients have been underrepresented in clinical trials making evidence-based decisions difficult. The increase in comorbidity and aging, polypharmacy and changes in function make pharmacotherapy decisions more complicated. Knowledge of the issues is critical in the prescribing of effective and safe therapy. There are factors associated with advancing age that can result in pharmacokinetic and pharmacodynamic variations in processing of hormonal agents, chemotherapy and targeted drugs. Areas covered A review of the literature pertaining to pharmacokinetic changes in aging in breast cancer was untaken. Studies are reviewed involving single agents and some combinations. Expert opinion Older patients should be considered for standard therapies. Their specific problems need to be evaluated by geriatric-specific assessment including functional status, end organ dysfunction and polypharmacy. There are few instances for age-related changes in pharmacokinetics and when present are usually not clinically significant. When changes are present, they are often the result of comorbidity, drug interactions and drug scheduling issues. The older patients may be more sensitive to certain toxicities such as cardiac toxicity, neuropathy and myelosuppression. PMID:25940027

  14. 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

  15. 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

  16. Tension-type headache in Parma's adult general population: a focus on age of onset.

    PubMed

    Taga, Arens; Russo, Marco; Manzoni, Gian C; Torelli, Paola

    2015-01-01

    In the present paper, we focus on the age of onset for tension-type headache in a population-based sample in the Parma, distinguishing its different subtypes and considering definite and probable diagnoses. Age of headache onset is a useful clinical feature for differential diagnosis between primary headaches and between primary and secondary headache forms. A total of 904 subjects representative of the Parma's adult general population were interviewed face to face by a physician from the Parma Headache Centre, using a validated questionnaire specially designed for the diagnosis of primary headaches according to the ICHD-II criteria. In the majority of subjects diagnosed with definite tension-type headache, age of onset was 39 years or less, while mean age of onset was 29.7 years (SD 16.3 years, range 5-79 years), the median being 25 years. Both infrequent and frequent episodic definite tension-type headache first occurred in the majority of cases in the second, third and fourth decades. Subjects with chronic definite tension-type headache reported a later onset in life (i.e. fourth, fifth and sixth decades). In our study, mean age of onset for probable tension-type headache was 23.7 years (SD 9.2 years, range 10-40 years) and the median was 22 years. In no case did we find significant gender differences. Our study results are similar to most of those reported in the literature. Further research needs to be done in the Italian epidemiological context, given the lack of literature reports on this topic.

  17. 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.

  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. 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.

  20. 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

  1. 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

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

    PubMed

    Kaczanowski, Szymon

    2016-05-11

    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.

  3. 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

  4. 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

  5. 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

  6. The Molecular Balancing Act of p16INK4a in Cancer and Aging

    PubMed Central

    LaPak, Kyle M.; Burd, Christin E.

    2013-01-01

    Located on chromosome 9p21.3, p16INK4a seems lost amongst a cluster of neighboring tumor suppressor genes. While best known for inhibiting cyclin dependent kinase (CDK) activity, p16INK4a is not a one trick pony. Long term p16INK4a expression pushes cells to enter senescence, an irreversible cell cycle arrest that prevents the growth of would-be cancer cells, but also contributes to aging. Loss of p16INK4a is one of the most frequent events in human tumors and allows pre-cancerous lesions to bypass senescence. Therefore, precise regulation of p16INK4a is essential to tissue homeostasis, maintaining a tight balance between tumor suppression and aging. Here, we outline the pathways required for proper p16INK4a regulation and highlight the critical functions of p16INK4a in cancer, aging and human physiology that make this gene special. PMID:24136988

  7. Nutritional fats and the risk of type 2 diabetes and cancer.

    PubMed

    Stoeckli, R; Keller, U

    2004-12-30

    Dietary factors are important predictors for the risk of diabetes type 2. Increased consumption of fibre-rich foods, fruits and vegetables as well as limited amounts of total and saturated fats are essential elements in the prevention of diabetes type 2. The association between these dietary factors and the appearance of diabetes was not only present in cohort studies but were also major elements in the dietary part of the two large diabetes prevention trials (Finnish Diabetes Prevention Study, Diabetes Prevention Program). There is also strong evidence for a relation between obesity and total fat intake and the incidence of certain types of cancers. There is a significant correlation between total fat intake and the risk of cancer; however, it is much weaker than that of the effect of red meat. Recommendations to decrease red meat intake, particularly processed meat, may decrease the risk of colorectal and prostate cancer and may have beneficial effects on breast cancer as well, although this evidence is less compelling. Overall, recommendations focused on controlling or reducing body weight by regular physical activity and avoidance of excessive energy intake from all sources, particularly from fat and saturated fats, by increasing consumption of fibre-rich carbohydrates, vegetables and fruits are effective in decreasing the risk for type 2 diabetes by more than 50% in high-risk individuals. Similar dietary patterns are likely to diminish the manifestation of certain forms of cancers. These conclusions are in agreement with current recommendations for cancer prevention as propagated by the American Cancer Society.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Undiagnosed Borrmann type II gastric cancer due to necrosis and regenerative epithelium

    PubMed Central

    Hur, Joon; Chang, Jae Hyuck; Kim, Byung Kee; Ko, Hoon Young; Lee, Jong Hwan; Kim, Soo Jeong; Song, Mi Ae; Kim, Tae Ho; Kim, Chang Whan; Han, Sok Won

    2014-01-01

    Endoscopic biopsy is essential to the proper diagnosis and treatment of gastric cancer. Unfortunately, the results of endoscopic biopsy are not always the same as what is expected based on gross endoscopic findings. The results of endoscopic biopsy can be negative for malignancy in Borrmann type IV advanced gastric cancer (AGCa) or gastric lymphoma. However, in the case of type II AGCa, repeated biopsies negative for malignancy have not been reported. A 49-year-old male patient underwent esophagogastroduodenoscopy three times due to large gastric ulcer suspected to be Borrmann type II cancer. However, three repeat endoscopic biopsies with multiple specimens showed necrosis and superficial regenerative epithelium without malignant findings. The patient underwent laparoscopic distal gastrectomy with D2 lymph node dissection. The surgical specimen revealed that the mucosal layer was completely replaced with regenerative epithelium without cancer cells. PMID:25071361

  13. 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

  14. Biomolecular bases of the senescence process and cancer. A new approach to oncological treatment linked to ageing.

    PubMed

    Badiola, Iker; Santaolalla, Francisco; Garcia-Gallastegui, Patricia; Ana, Sánchez-Del Rey; Unda, Fernando; Ibarretxe, Gaskon

    2015-09-01

    Human ageing is associated with a gradual decline in the physiological functions of the body at multiple levels and it is a key risk factor for many diseases, including cancer. Ageing process is intimately related to widespread cellular senescence, characterised by an irreversible loss of proliferative capacity and altered functioning associated with telomere attrition, accumulation of DNA damage and compromised mitochondrial and metabolic function. Tumour and senescent cells may be generated in response to the same stimuli, where either cellular senescence or transformation would constitute two opposite outcomes of the same degenerative process. This paper aims to review the state of knowledge on the biomolecular relationship between cellular senescence, ageing and cancer. Importantly, many of the cell signalling pathways that are found to be altered during both cellular senescence and tumourigenesis are regulated through shared epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs are emerging as pivotal players linking ageing and cancer. These small RNA molecules have generated great interest from the point of view of future clinical therapy for cancer because successful experimental results have been obtained in animal models. Micro-RNA therapies for cancer are already being tested in clinical phase trials. These findings have potential importance in cancer treatment in aged people although further research-based knowledge is needed to convert them into an effective molecular therapies for cancer linked to ageing.

  15. An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving.

    PubMed

    McGrath, K G

    2003-12-01

    Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested. PMID:14639125

  16. An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving.

    PubMed

    McGrath, K G

    2003-12-01

    Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested.

  17. 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

  18. Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes.

    PubMed

    Howson, Joanna M M; Cooper, Jason D; Smyth, Deborah J; Walker, Neil M; Stevens, Helen; She, Jin-Xiong; Eisenbarth, George S; Rewers, Marian; Todd, John A; Akolkar, Beena; Concannon, Patrick; Erlich, Henry A; Julier, Cécile; Morahan, Grant; Nerup, Jørn; Nierras, Concepcion; Pociot, Flemming; Rich, Stephen S

    2012-11-01

    The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10⁻⁶ and 2.5 × 10⁻⁵, respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/2q33.2 was obtained (P = 7.90 × 10⁻⁵). No evidence of differential risk by sex was obtained at any loci (P ≥ 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease. PMID:22891215

  19. 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 ...

  20. Prescriptions of traditional Chinese medicine are specific to cancer types and adjustable to temperature changes.

    PubMed

    Chiu, Pei-Hsun; Hsieh, Hsin-Ying; Wang, Sun-Chong

    2012-01-01

    Targeted cancer therapies, with specific molecular targets, ameliorate the side effect issue of radiation and chemotherapy and also point to the development of personalized medicine. Combination of drugs targeting multiple pathways of carcinogenesis is potentially more fruitful. Traditional Chinese medicine (TCM) has been tailoring herbal mixtures for individualized healthcare for two thousand years. A systematic study of the patterns of TCM formulas and herbs prescribed to cancers is valuable. We analysed a total of 187,230 TCM prescriptions to 30 types of cancer in Taiwan in 2007, a year's worth of collection from the National Health Insurance reimbursement database (Taiwan). We found that a TCM cancer prescription consists on average of two formulas and four herbs. We show that the percentage weights of TCM formulas and herbs in a TCM prescription follow Zipf's law with an exponent around 0.6. TCM prescriptions to benign neoplasms have a larger Zipf's exponent than those to malignant cancers. Furthermore, we show that TCM prescriptions, via weighted combination of formulas and herbs, are specific to not only the malignancy of neoplasms but also the sites of origins of malignant cancers. From the effects of formulas and natures of herbs that were heavily prescribed to cancers, that cancers are a 'warm and stagnant' syndrome in TCM can be proposed, suggesting anti-inflammatory regimens for better prevention and treatment of cancers. We show that TCM incorporated relevant formulas to the prescriptions to cancer patients with a secondary morbidity. We compared TCM prescriptions made in different seasons and identified temperatures as the environmental factor that correlates with changes in TCM prescriptions in Taiwan. Lung cancer patients were among the patients whose prescriptions were adjusted when temperatures drop. The findings of our study provide insight to TCM cancer treatment, helping dialogue between modern western medicine and TCM for better cancer care.

  1. 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

  2. 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.

  3. 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

  4. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe.

    PubMed

    Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf; Powell, Ned; Nowakowski, Andrzej M; Kirschner, Benny; Koiss, Robert; O'Leary, John; Joura, Elmar A; Rosenlund, Mats; Colau, Brigitte; Schledermann, Doris; Kukk, Kersti; Damaskou, Vasileia; Repanti, Maria; Vladareanu, Radu; Kolomiets, Larisa; Savicheva, Alevtina; Shipitsyna, Elena; Ordi, Jaume; Molijn, Anco; Quint, Wim; Raillard, Alice; Rosillon, Dominique; De Souza, Sabrina Collas; Jenkins, David; Holl, Katsiaryna

    2013-02-15

    Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical specimens dated 2001-2008. The pooled prevalence of individual HPV types was estimated using meta-analytic methods. A total of 3,103 women were diagnosed with HG-CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV-positive, respectively. The most common HPV types in women with HG-CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both HG-CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG-CIN and associated with a high median age of HG-CIN, with a narrow age interval between HG-CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45-related cervical lesions.

  5. 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

  6. Resistance and gain-of-resistance phenotypes in cancers harboring wild-type p53

    PubMed Central

    Martinez-Rivera, Michelle; Siddik, Zahid H.

    2012-01-01

    Chemotherapy is the bedrock for the clinical management of cancer, and the tumor suppressor p53 has a central role in this therapeutic modality. This protein facilitates favorable antitumor drug response through a variety of key cellular functions, including cell cycle arrest, senescence, and apoptosis. These functions essentially cease once p53 becomes mutated, as occurs in ~50% of cancers, and some p53 mutants even exhibit gain-of-function effects, which lead to greater drug resistance. However, it is becoming increasingly evident that resistance is also seen in cancers harboring wild-type p53. In this review, we discuss how wild-type p53 is inactivated to render cells resistant to antitumor drugs. This may occur through various mechanisms, including an increase in proteasomal degradation, defects in post-translational modification, and downstream defects in p53 target genes. We also consider evidence that the resistance seen in wild-type p53 cancers can be substantially greater than that seen in mutant p53 cancers, and this poses a far greater challenge for efforts to design strategies that increase drug response in resistant cancers already primed with wild-type p53. Because the mechanisms contributing to this wild-type p53 “gain-of-resistance” phenotype are largely unknown, a concerted research effort is needed to identify the underlying basis for the occurrence of this phenotype and, in parallel, to explore the possibility that the phenotype may be a product of wild-type p53 gain-of-function effects. Such studies are essential to lay the foundation for a rational therapeutic approach in the treatment of resistant wild-type p53 cancers. PMID:22227014

  7. BDNF val66met Polymorphism Affects Aging of Multiple Types of Memory

    PubMed Central

    Kennedy, Kristen M.; Reese, Elizabeth D.; Horn, Marci M.; Sizemore, April N.; Unni, Asha K.; Meerbrey, Michael E.; Kalich, Allan G.; Rodrigue, Karen M.

    2014-01-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age x BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (p < .07) toward poorer associative memory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory – in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). PMID:25264352

  8. Large-scale RNA-Seq Transcriptome Analysis of 4043 Cancers and 548 Normal Tissue Controls across 12 TCGA Cancer Types

    PubMed Central

    Peng, Li; Bian, Xiu Wu; Li, Di Kang; Xu, Chuan; Wang, Guang Ming; Xia, Qing You; Xiong, Qing

    2015-01-01

    The Cancer Genome Atlas (TCGA) has accrued RNA-Seq-based transcriptome data for more than 4000 cancer tissue samples across 12 cancer types, translating these data into biological insights remains a major challenge. We analyzed and compared the transcriptomes of 4043 cancer and 548 normal tissue samples from 21 TCGA cancer types, and created a comprehensive catalog of gene expression alterations for each cancer type. By clustering genes into co-regulated gene sets, we identified seven cross-cancer gene signatures altered across a diverse panel of primary human cancer samples. A 14-gene signature extracted from these seven cross-cancer gene signatures precisely differentiated between cancerous and normal samples, the predictive accuracy of leave-one-out cross-validation (LOOCV) were 92.04%, 96.23%, 91.76%, 90.05%, 88.17%, 94.29%, and 99.10% for BLCA, BRCA, COAD, HNSC, LIHC, LUAD, and LUSC, respectively. A lung cancer-specific gene signature, containing SFTPA1 and SFTPA2 genes, accurately distinguished lung cancer from other cancer samples, the predictive accuracy of LOOCV for TCGA and GSE5364 data were 95.68% and 100%, respectively. These gene signatures provide rich insights into the transcriptional programs that trigger tumorigenesis and metastasis, and many genes in the signature gene panels may be of significant value to the diagnosis and treatment of cancer. PMID:26292924

  9. Eribulin Monotherapy in Patients Aged 70 Years and Older With Metastatic Breast Cancer

    PubMed Central

    Cortes, Javier; Vahdat, Linda T.; Cardoso, Fatima; Twelves, Chris; Wanders, Jantien; Dutcus, Corina E.; Yang, Jay; Seegobin, Seth; O’Shaughnessy, Joyce

    2014-01-01

    Purpose. Following the demonstrated efficacy and safety of eribulin mesylate in heavily pretreated patients with metastatic breast cancer, an exploratory analysis was performed to investigate the effect of age in these patients. Methods. Data were pooled from two single-arm phase II studies and one open-label randomized phase III study in which patients received eribulin mesylate at 1.4 mg/m2 as 2- to 5-minute intravenous infusions on days 1 and 8 of a 21-day cycle. The effect of age on median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), clinical benefit rate (CBR), and incidence of adverse events (AEs) was calculated for four age groups (<50 years, 50–59 years, 60–69 years, ≥70 years). Results. Overall, 827 patients were included in the analysis (<50 years, n = 253; 50–59 years, n = 289; 60–69 years, n = 206; ≥70 years, n = 79). Age had no significant impact on OS (11.8 months, 12.3 months, 11.7 months, and 12.5 months, respectively; p = .82), PFS (3.5 months, 2.9 months, 3.8 months, and 4.0 months, respectively; p = .42), ORR (12.7%, 12.5%, 6.3%, and 10.1%, respectively), or CBR (20.2%, 20.8%, 20.4%, and 21.5%, respectively). Although some AEs had higher incidence in either the youngest or the oldest subgroup, there was no overall effect of age on the incidence of AEs (including neuropathy, neutropenia, and leukopenia). Conclusion. Eribulin monotherapy in these selected older patients with good baseline performance status led to OS, PFS, ORR, CBR, and tolerability similar to those of younger patients with metastatic breast cancer. The benefits and risks of eribulin appear to be similar across age groups. PMID:24682463

  10. Different clinical characteristics in sporadic young-age onset colorectal cancer.

    PubMed

    Lee, Jieun; Kim, In-Ho; Kim, Jin Su; Kim, Sang Woo; Kim, Jun Gi; Oh, Seung Tack; Kang, Won Kyung; Lee, Myung Ah

    2016-09-01

    The incidence of colorectal cancer (CRC) is increasing in young-age patients, but the clinical history is not established. Authors analyzed the clinical characteristics of young-age onset CRC to support basic information for setting treatment policies.Between January 2006 to January 2014, 100 CRC patients diagnosed at the age of 10 to 39 were analyzed. The clinicopathologic characteristics were reviewed based on medical records. Survival outcomes including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were analyzed. This study was conducted as a retrospective, observation study.Among 100 patients, 86 patients were diagnosed as CRC at their thirties. Seventy-nine patients had no familial history of cancer. At initial diagnosis, 59 patients showed the normal CEA level (≤3 ng/mL), and 61 patients were diagnosed as advanced CRC (40% stage III, 21% stage IV). Sixty-four patients had lower location-sigmoid colon, rectosigmoid junction, or rectum. Recurrence rate was 7.9% in stage I to III CRC. Although median OS was not reached, patients with normal CEA level showed better survival outcome (P = 0.013) and patients with perineural invasion showed poorer survival (P = 0.011). The 5-year survival rate of total patient population was estimated as 75%. However, median OS of stage IV patients were 19 months (range 7.9-60.63 months), shorter than historical data of >24 months.Young-age CRC was most commonly diagnosed at their thirties, with no familial history, normal range of CEA and located below sigmoid colon. In young-age onset stage IV CRC, patients showed inferior OS compared to historical data. Based on our data, different surveillance program other than serum CEA level (e.g., sigmoidoscopy) is needed in young-age patient population. PMID:27631240

  11. 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

  12. AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation

    PubMed Central

    Bao, Ji-Ming; He, Min-Yi; Liu, Ya-Wei; Lu, Yong-Jie; Hong, Ying-Qia; Luo, Hai-Hua; Ren, Zhong-Lu; Zhao, Shan-Chao; Jiang, Yong

    2015-01-01

    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 investigated 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). 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. 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. 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. PMID:26175942

  13. 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.

  14. Investigations on the Maillard reaction of dextrins during aging of Pilsner type beer.

    PubMed

    Rakete, Stefan; Klaus, Alexander; Glomb, Marcus A

    2014-10-01

    Although Maillard reaction plays a pivotal role during preparation of food, only few investigations concerning the role of carbohydrate degradation in beer aging have been carried out. The formation of Maillard specific precursor structures and their follow-up products during degradation of low molecular carbohydrate dextrins in the presence of proline and lysine was studied in model incubations and in beer. Twenty-one α-dicarbonyl compounds were identified and quantitated as reactive intermediates. The oxidative formation of 3-deoxypentosone as the precursor of furfural from oligosaccharides was verified. N-Carboxymethylproline and N-formylproline were established as novel proline derived Maillard advanced glycation end products. Formation of N-carboxymethylproline and furfural responded considerably to the presence of oxygen and was positively correlated to aging of Pilsner type beer. The present study delivers an in-depth view on the mechanisms behind the formation of beer relevant aging parameters.

  15. Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types.

    PubMed

    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

    2013-04-01

    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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. [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

  3. [Comparative characteristics of antioxidant status in women with diabetes type 2 of different age groups].

    PubMed

    Ishonina, O G; Mikashinovich, Z I; Olempieva, E V; Kovalenko, T D

    2011-01-01

    The purpose of this study was to evaluate the metabolic processes in women with diabetes mellitus type 2 of different age groups. It is established that hyperglycemia in aged women is characterized by the development of pronounced oxidative stress, which is the result of changes in the primary structure of protein molecules due to non enzymatic glycosylation of amino acid residues in the active sites. It is known that observed depletion of reduced glutathione pool is associated with high risk of genotoxicity, because it correlates with activation of mitochondrial, chromatin dysfunction and fragmentation of the DNA. In addition, hydroperoxides of polyunsaturated fatty acids formation leads to necrosis and apoptosis. It can be assumed that the diabetes mellitus type 2 triggers processes of apoptosis, which leads to the activation of aging programs and increase the mortality of patients. Obviously, the change in the concentration of thiol antioxidants, as well as the change in concentration of LPO molecular products may be one of the criteria for evaluation of aging and the efficiency of the treatment of patients.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Involvement of oxidatively damaged DNA and repair in cancer development and aging

    PubMed Central

    Tudek, Barbara; Winczura, Alicja; Janik, Justyna; Siomek, Agnieszka; Foksinski, Marek; Oliński, Ryszard

    2010-01-01

    DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities. PMID:20589166

  10. 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

  11. Magnetic Resonance in the Detection of Breast Cancers of Different Histological Types

    PubMed Central

    Mayrhofer, Rebecca M.; Ng, Hsiao Piau; Putti, Thomas C.; Kuchel, Philip W.

    2013-01-01

    Breast cancer incidence is increasing worldwide. Early detection is critical for long-term patient survival, as is monitoring responses to chemotherapy for management of the disease. Magnetic resonance imaging and spectroscopy (MRI/MRS) has gained in importance in the last decade for the diagnosis and monitoring of breast cancer therapy. The sensitivity of MRI/MRS for anatomical delineation is very high and the consensus is that MRI is more sensitive in detection than x-ray mammography. Advantages of MRS include delivery of biochemical information about tumor metabolism, which can potentially assist in the staging of cancers and monitoring responses to treatment. The roles of MRS and MRI in screening and monitoring responses to treatment of breast cancer are reviewed here. We rationalize how it is that different histological types of breast cancer are differentially detected and characterized by MR methods. PMID:25114543

  12. 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 ...

  13. 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

  14. Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia's ageing population?

    PubMed

    Scott, David; de Courten, Barbora; Ebeling, Peter R

    2016-10-01

    The incidence of type 2 diabetes is increasing in Australia's older adult population. Sarcopenia, the age-related decline in skeletal muscle mass, quality and function, may make a significant but under-appreciated contribution to increasing the risk of type 2 diabetes. As skeletal muscle is the largest insulin-sensitive tissue in the body, low muscle mass in sarcopenia likely results in reduced capacity for glucose disposal. Age-related declines in muscle quality, including increased mitochondrial dysfunction and fat infiltration, are also implicated in skeletal muscle inflammation and subsequent insulin resistance. Prospective studies have shown that low muscle mass and strength are associated with increased risk of incident type 2 diabetes. Prevalent type 2 diabetes also appears to exacerbate progression of sarcopenia in older adults. Recently developed operational definitions and the inclusion of sarcopenia in the International classification of diseases, 10th revision, clinical modification, provide impetus for clinicians to diagnose and treat sarcopenia in older patients. Simple assessments to diagnose sarcopenia can potentially play a role in primary and secondary prevention of type 2 diabetes in older patients. Lifestyle modification programs for older adults with type 2 diabetes, particularly for those with sarcopenia, should incorporate progressive resistance training, along with adequate intakes of protein and vitamin D, which may improve both functional and metabolic health and prevent undesirable decreases in muscle mass associated with weight loss interventions. As some older adults with type 2 diabetes have a poor response to exercise, clinicians must ensure that lifestyle modification programs are appropriately prescribed, regularly monitored and modified if necessary. PMID:27681976

  15. 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

  16. Particulate Organic Carbon Age Spectra: An Emerging Picture of Variability Related to Discharge and Basin Type

    NASA Astrophysics Data System (ADS)

    Rosenheim, Brad; Galy, Valier; Williams, Elizabeth; Roberts, Brian; Allison, Mead

    2013-04-01

    Applying ramped pyrolysis 14C analysis to particulate organic carbon (POC) constrains on the spectrum of radiocarbon ages in the POC. We summarize a multi-year sampling effort on both the Mississippi Atchafalaya River System (MARS), in which several different discharge regimes were sampled, and the Narayani River in Nepal, for application of this novel technique. The emerging picture from the MARS is one of consistency - discharge plays a role in age spectrum, as does channel type and influence of marine waters. Some variability in the MARS is related to flood provenance, however large river systems such as the MARS are integrative of a range of different lithologies and carbon sources. Age spectra differ between the MARS and monsoon samples in Narayani River, where high incision rates erode old carbonaceous rocks more efficiently during high discharge events. The result of limited sedimentary storage of watershed primary productivity in the Narayani River watershed is substantially wider age spectra than those from the integrative MARS system. It is likely that the Narayani River is less consistent in time than the MARS as contributions of old carbonaceous material likely are driven largely by discharge regime. All Narayani River samples analyzed to date are from different monsoon seasons, but low discharge events are not represented in the dataset. Moving forward, our work will focus on how age spectra change downstream in small mountainous rivers that drain into integrative systems.

  17. Systematic review and meta-analysis of age at menarche and risk of type 2 diabetes.

    PubMed

    Janghorbani, Mohsen; Mansourian, Marjan; Hosseini, Elham

    2014-08-01

    The relation of early menarche with type 2 diabetes mellitus (T2DM) remains inconsistent across studies. The objective of this systematic review and meta-analysis of published population-based observational studies was to assess the association between age at menarche and T2DM risk. We searched online data bases through December 2013 and examined the reference lists of pertinent articles. Summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with a random-effects model. A total of 14 effect estimates from 10 eligible studies (three cross-sectional and seven cohort studies) included 315,428 participants and 22,085 cases of T2DM. Compared with the highest or middle category, women in the lowest category of age at menarche had higher risk of T2DM [summary RR (95 % CI) 1.22 (1.17, 1.28)]. These results were consistent between studies that conducted in the United States and in Europe. The association between age at menarche and T2DM was slightly stronger for cohort than for cross-sectional studies. These findings strongly support an association between younger age at menarche and increased risk of T2DM. Age at menarche may help identify women with increased risk of developing T2DM. PMID:24671509

  18. Meat quality traits in the emu (Dromaius novaehollandiae) as affected by muscle type and animal age.

    PubMed

    Berge, P; Lepetit, J; Renerre, M; Touraille, C

    1997-02-01

    Meat quality traits were determined in the major muscles of the emu (Dromaius novaehollandiae) at different slaughter ages (6, 10, 14, 17 or ≥20 months). A mean ultimate pH value of 5.5 was reached within around 3 h post mortem, but this value was 6.1 in animals that had suffered a preslaughter stress (transportation and fasting). The collagen and pigment contents varied widely among the muscles. The protein and pigment contents increased with animal age, but this effect was perceptible only between 6 and 14 months. The other chemical constituents were little affected by muscle type or animal age. The intense red colour of emu meat, due to a high pigment content, was very sensitive to oxidation, thus limiting the storage of fresh meat under aerobic conditions to short periods of time. Despite a rapid post-mortem tenderization (≤24 h), the residual myofibrillar strength obtained after extended ageing remained intermediate between those reported for chicken and beef. The tenderness of meat, cooked to 60 °C, differed between muscles and decreased with increasing age, thus reflecting the changes occuring in the concentration and in the heat stability of the intramuscular connective tissue.

  19. 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

  20. White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes

    PubMed Central

    Nunley, Karen A.; Ryan, Christopher M.; Orchard, Trevor J.; Aizenstein, Howard J.; Jennings, J. Richard; Ryan, John; Zgibor, Janice C.; Boudreau, Robert M.; Costacou, Tina; Maynard, John D.; Miller, Rachel G.

    2015-01-01

    Objective: Although microvascular complications are common in type 1 diabetes mellitus (T1DM), few studies have quantified the severity, risk factors, and implications of cerebral microvascular damage in these patients. As life expectancy in patients with T1DM increases, patients are exposed to age- and disease-related factors that may contribute to cerebral microvascular disease. Methods: Severity and volume of white matter hyperintensities (WMH) and infarcts were quantified in 97 middle-aged patients with childhood-onset T1DM (mean age and duration: 50 and 41 years, respectively) and 81 non-T1DM adults (mean age: 48 years), concurrent with cognitive and health-related measures. Results: Compared with non-T1DM participants, patients had more severe WMH (Fazekas scores 2 and 3 compared with Fazekas score 1, p < 0.0001) and slower information processing (digit symbol substitution, number correct: 65.7 ± 10.9 and 54.9 ± 13.6; pegboard, seconds: 66.0 ± 9.9 and 88.5 ± 34.2; both p < 0.0001) independent of age, education, or other factors. WMH were associated with slower information processing; adjusting for WMH attenuated the group differences in processing speed (13% for digit symbol, 11% for pegboard, both p ≤ 0.05). Among patients, prevalent neuropathies and smoking tripled the odds of high WMH burden, independent of age or disease duration. Associations between measures of blood pressure or hyperglycemia and WMH were not significant. Conclusions: Clinically relevant WMH are evident earlier among middle-aged patients with childhood-onset T1DM and are related to the slower information processing frequently observed in T1DM. Brain imaging in patients with T1DM who have cognitive difficulties, especially those with neuropathies, may help uncover cerebral microvascular damage. Longitudinal studies are warranted to fully characterize WMH development, risk factors, and long-term effects on cognition. PMID:25904692

  1. The key role of growth hormone — insulin — IGF-1 signaling in aging and cancer

    PubMed Central

    Anisimov, Vladimir N.; Bartke, Andrzej

    2014-01-01

    Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients. PMID:23434537

  2. Enabling transparent and collaborative computational analysis of 12 tumor types within The Cancer Genome Atlas.

    PubMed

    Omberg, Larsson; Ellrott, Kyle; Yuan, Yuan; Kandoth, Cyriac; Wong, Chris; Kellen, Michael R; Friend, Stephen H; Stuart, Josh; Liang, Han; Margolin, Adam A

    2013-10-01

    The Cancer Genome Atlas Pan-Cancer Analysis Working Group collaborated on the Synapse software platform to share and evolve data, results and methodologies while performing integrative analysis of molecular profiling data from 12 tumor types. The group's work serves as a pilot case study that provides (i) a template for future large collaborative studies; (ii) a system to support collaborative projects; and (iii) a public resource of highly curated data, results and automated systems for the evaluation of community-developed models.

  3. The Werner's Syndrome RecQ helicase/exonuclease at the nexus of cancer and aging.

    PubMed

    Chun, Stephen G; Shaeffer, David S; Bryant-Greenwood, Peter K

    2011-03-01

    Werner's Syndrome (WS) or adult-onset progeria is an autosomal recessive disorder of accelerated aging caused by mutations of the DNA RecQ helicase/exonuclease (WRN). WRN is an ATP-dependent helicase with 3' to 5' DNA exonuclease activity that regulates the replicative potential of dividing cells, and WRN loss-of-function mutations promote cellular senescence and neoplastic transformation. These molecular findings translate clinically into adult-onset progeria manifested by premature hair graying, dermal atrophy, cardiovascular disease, and cancer predilection along with a markedly reduced life expectancy. Recently, a patient with WS who developed pancreatic adenocarcinoma was identified in Honolulu suggesting a significant prevalence of loss-of-function WRN mutations in Hawaii's Japanese-American population. Based upon the indigenous Japanese WRN loss-of-function mutation heterozygote rate of 6 per 1,000, we speculate the possibility of approximately 1,200 heterozygotes in Hawaii. Our ongoing studies aim to evaluate Hawaii's true allelic prevalence of WRN loss-of-function mutations in the Japanese-American population, and the role of WRN silencing in sporadic cancers. In summary, WRN plays a nexus-like role in the complex interplay of cellular events that regulate aging, and analysis of WRN polymorphisms in Hawaii's population will generate novel insights to advance care for age-related pathologies.

  4. 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

  5. Diabetes type 2, hypertension and cognitive dysfunction in middle age women.

    PubMed

    Petrova, Marina; Prokopenko, Semen; Pronina, Elena; Mozheyko, Elena

    2010-12-15

    Type 2 diabetes mellitus and hypertension are two widely spread diseases among the adults that are known to be risk factors for vascular disease. They are highly related such that comorbidity is common. The purpose of the present study was to investigate the comorbid effects of type 2 diabetes and hypertension on cognitive decline. One hundred and thirteen patients with type 2 diabetes (women, age 56±7.4 years, diabetes duration 8±6.7 years, hypertension duration 13.4±7.7 years) were assessed for cognitive impairment (CI) in comparison with 27 diabetes patients without hypertension (women, age 53±7.45 years, diabetes duration 4.4±5.6 years), all non-demented at baseline. Patients were screened for cognitive dysfunction with the Mini Mental State Examination (MMSE), a clock-drawing test (CDT) and Frontal Assessment Battery (FAB). We assessed history of DM and hypertension by interview. 87% of women with diabetes and hypertension and 70% of normotensive diabetic patients had cognitive impairment (p=0.0282), of mild and subtle degree. The frequency of alterations in the FAB was higher in subjects with diabetes and hypertension (48%) compared to normotensive diabetic patients (26%) p=0.0402. Our results show that people with diabetes type 2 and hypertension demonstrate greater cognitive changes as compared to normotensive diabetic patients.

  6. 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

  7. 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

  8. Identifying Etiologically Distinct Sub-Types of Cancer: A Demonstration Project Involving Breast Cancer

    PubMed Central

    Begg, Colin B; Orlow, Irene; Zabor, Emily C; Arora, Arshi; Sharma, Ajay; Seshan, Venkatraman E; Bernstein, Jonine L

    2015-01-01

    With the advent of increasingly detailed molecular portraits of tumor specimens, much attention has been directed toward identifying clinically distinct subtypes of cancer. Subtyping of tumors can also be accomplished with the goal of identifying distinct etiologies. We demonstrate the use of new methodologies to identify genes that distinguish etiologically heterogeneous subtypes of breast cancer using data from the case–control Cancer and Steroid Hormone Study. Tumor specimens were evaluated using a breast cancer expression panel of 196 genes. Using a statistical measure that distinguishes the degree of etiologic heterogeneity in tumor subtypes, each gene is ranked on the basis of its ability to distinguish etiologically distinct subtypes. This is accomplished independently using case–control comparisons and by examining the concordance odds ratios in double primaries. The estrogen receptor gene, and others in this pathway with expression levels that correlated strongly with estrogen receptor levels, demonstrate high degrees of etiologic heterogeneity in both methods. Our results are consistent with a growing literature that confirms the distinct etiologies of breast cancers classified on the basis of estrogen receptor expression levels. This proof-of-principle project demonstrates the viability of new strategies to identify genomic features that distinguish subtypes of cancer from an etiologic perspective. PMID:25974664

  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 infections in Mexican women with normal cytology, precancerous lesions, and cervical cancer: type-specific prevalence and HPV coinfections.

    PubMed

    Aguilar-Lemarroy, Adriana; Vallejo-Ruiz, Verónica; Cortés-Gutiérrez, Elva I; Salgado-Bernabé, Manuel Eduardo; Ramos-González, Norma Patricia; Ortega-Cervantes, Laura; Arias-Flores, Rafael; Medina-Díaz, Irma M; Hernández-Garza, Fernando; Santos-López, Gerardo; Piña-Sánchez, Patricia

    2015-05-01

    The prevalence and genotype distribution of human papillomavirus (HPV) provides the basis for designing HPV prevention programs. The prevalence rates of type-specific HPV and coinfections in samples of Mexican women were investigated in 822 women aged 18-87 years. HPV detection was performed using a Linear Array™ genotyping test. HPV infection was found in 12.4% of controls, 46.3% of those with cervical intraepithelial neoplasia 1, and 100% of those with cervical intraepithelial neoplasia 3 or cervical cancer. HPV 16 was the most prevalent type in all diagnosis groups. The HPV types most frequently found in cervical cancers were 16, 18, 45, 52, 58, and 39; HPV types 16, 62, 51, 84, 18, 53, and CP6108 were the most prevalent in control women. Considering HPV-positive samples only, coinfections occurred most often in controls (63%) and were less frequent in those with cervical cancer (26%). The most frequent viral types in coinfections with HPV 16 in control women were HPV 62, 51, and 84; in women with cervical cancers, HPV 18, 39, and 70 were most common. In conclusion, in addition to HPV types 16 and 18, types 45, 39, 58, 52, and 71 were found in cervical cancers in Mexican women (78%); among them, only 65% were attributable to HPV types 16 and 18. Therefore, it is necessary to consider these viral types in the design of new vaccines, and to determine whether certain HPV types coinfecting with HPV 16 in precursor lesions determine tumor progression or regression.

  11. The impact of adjuvant chemotherapy in older breast cancer patients on clinical and biological aging parameters

    PubMed Central

    Brouwers, Barbara; Hatse, Sigrid; Lago, Lissandra Dal; Neven, Patrick; Vuylsteke, Peter; Dalmasso, Bruna; Debrock, Guy; Van Den Bulck, Heidi; Smeets, Ann; Bechter, Oliver; Bailur, Jithendra Kini; Kenis, Cindy; Laenen, Annouschka; Schöffski, Patrick; Pawelec, Graham; Journe, Fabrice; Ghanem, Ghanem-Elias; Wildiers, Hans

    2016-01-01

    Purpose This prospective observational study aimed to evaluate the impact of adjuvant chemotherapy on biological and clinical markers of aging and frailty. Methods Women ≥ 70 years old with early breast cancer were enrolled after surgery and assigned to a chemotherapy (Docetaxel and Cyclophosphamide) group (CTG, n=57) or control group (CG, n=52) depending on their planned adjuvant treatment. Full geriatric assessment (GA) and Quality of Life (QoL) were evaluated at inclusion (T0), after 3 months (T1) and at 1 year (T2). Blood samples were collected to measure leukocyte telomere length (LTL), levels of interleukin-6 (IL-6) and other circulating markers potentially informative for aging and frailty: Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), Insulin-like Growth Factor 1 (IGF-1), Monocyte Chemotactic Protein 1 (MCP-1) and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES). Results LTL decreased significantly but comparably in both groups, whereas IL-6 was unchanged at T2. However, IL-10, TNF-α, IGF-1 and MCP-1 suggested a minor biological aging effect of chemotherapy. Clinical frailty and QoL decreased at T1 in the CTG, but recovered at T2, while remaining stable in the CG. Conclusion Chemotherapy (TC) is unlikely to amplify clinical aging or induce frailty at 1 year. Accordingly, there is no impact on the most established aging biomarkers (LTL, IL-6). PMID:27102154

  12. 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. PMID:27642640

  13. 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.

  14. 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.

  15. Psychological Predictors of Prostate Cancer Screening Behaviors Among Men Over 50 Years of Age in Hamadan: Perceived Threat and Efficacy

    PubMed Central

    Barati, Majid; Amirzargar, Mohammad Ali; Bashirian, Saeed; Kafami, Vahid; Mousali, Amir Abbas; Moeini, Babak

    2016-01-01

    Background Prostate cancer is the fourth most common cancer worldwide and is the second most lethal cancer. Objectives The aim of this study was to investigate psychological predictors of prostate cancer screening behaviors among men over 50 years of age in Hamadan. Materials and Methods This cross-sectional study was carried out on 200 men over 50 years of age in Hamadan, west of Iran. Participants were recruited with a cluster sampling method. The subjects completed a self-administered questionnaire including demographic characteristics, prostate cancer screening behaviors and psychological factors related to prostate cancer. Data was analyzed by SPSS-18 using chi-square, fisher exact test, and logestic regression. Results According to the results, 8.5 and 7.5 percent of participants reported history of digital rectal exam and prostate-specific antigen test, respectively. Also, the subjects reported 18.5%, 49.3% and 50.3% of receivable scores of knowledge, perceived threat, and perceived efficacy of prostate cancer screening behaviors, respectively. There was a significant association between prostate cancer screening behaviors and age groups (P < 0.05). Conclusions The results showed that providing analytical studies in this field helps to surface the hidden aspects of this context and the health care providers and administrators will hopefully consider them in planning for identification of psychological factors, such as barriers and facilitators factors.

  16. 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

  17. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression

    PubMed Central

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

    2016-01-01

    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

  18. 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

  19. Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case-control studies.

    PubMed

    Woolcott, Christy G; Koga, Karin; Conroy, Shannon M; Byrne, Celia; Nagata, Chisato; Ursin, Giske; Vachon, Celine M; Yaffe, Martin J; Pagano, Ian; Maskarinec, Gertraud

    2012-04-01

    Mammographic density is strongly and consistently associated with breast cancer risk. To determine if this association was modified by reproductive factors (parity and age at first birth), data were combined from four case-control studies conducted in the United States and Japan. To overcome the issue of variation in mammographic density assessment among the studies, a single observer re-read all the mammograms using one type of interactive thresholding software. Logistic regression was used to estimate odds ratios (OR) while adjusting for other known breast cancer risk factors. Included were 1,699 breast cancer cases and 2,422 controls, 74% of whom were postmenopausal. A positive association between mammographic density and breast cancer risk was evident in every group defined by parity and age at first birth (OR per doubling of percent mammographic density ranged between 1.20 and 1.39). Nonetheless, the association appeared to be stronger among nulliparous than parous women (OR per doubling of percent mammographic density = 1.39 vs. 1.24; P interaction = 0.054). However, when examined by study location, the effect modification by parity was apparent only in women from Hawaii and when examined by menopausal status, it was apparent in postmenopausal, but not premenopausal, women. Effect modification by parity was not significant in subgroups defined by body mass index or ethnicity. Adjusting for mammographic density did not attenuate the OR for the association between parity and breast cancer risk by more than 16.4%, suggesting that mammographic density explains only a small proportion of the reduction in breast cancer risk associated with parity. In conclusion, this study did not support the hypothesis that parity modifies the breast cancer risk attributed to mammographic density. Even though an effect modification was found in Hawaiian women, no such thing was found in women from the other three locations.

  20. 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

  1. Breast cancer risk associations with birth order and maternal age according to breast-feeding status in infancy

    PubMed Central

    Nichols, Hazel B.; Trentham-Dietz, Amy; Sprague, Brian L.; Hampton, John M.; Titus-Ernstoff, Linda; Newcomb, Polly A.

    2009-01-01

    Background Early life risk factors for breast cancer have been investigated in relation to hormonal, nutritional, infectious, and/or genetic hypotheses. Recently, studies of potential health effects associated with exposure to environmental contaminants in breastmilk have been considered. Methods We analyzed data from a population-based case-control study of female Wisconsin residents. Cases (N=2,016) had an incident diagnosis of invasive breast cancer in 2002−2006 reported to the statewide tumor registry. Controls (N=1,960) of similar ages were randomly selected from driver's license lists. Risk factor information was collected during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated from multivariable logistic regression. Results In multivariable models, maternal age and birth order were not associated with breast cancer risk in the full study population. The odds ratio for breast cancer risk associated with having been breastfed in infancy was 0.83 (95% CI 0.72−0.96). In analyses restricted to breastfed women, maternal age associations with breast cancer were null (p-value=0.2). Increasing maternal age was negatively associated with breast cancer risk among women who were not breastfed; the odds ratio for breast cancer associated with each 5-year increase in maternal age was 0.90 (95% CI 0.82−1.00). Higher birth order was inversely associated with breast cancer risk among breastfed women (OR=0.58; 95% CI 0.39−0.86 for women with ≥3 older siblings compared to first-born women) but not among non-breastfed women (OR=1.13; 95% CI 0.81−1.57). Conclusion These findings suggest that early life risk factor associations for breast cancer may differ according to breastfeeding status in infancy. PMID:18379425

  2. 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.

  3. Breast cancer risk in women who fulfill high-risk criteria: at what age should surveillance start?

    PubMed

    Brandt, Andreas; Lorenzo Bermejo, Justo; Sundquist, Jan; Hemminki, Kari

    2010-05-01

    Family history is a strong predictor of hereditary breast cancer, particularly when it includes cases of early onset or bilateral breast cancers and multiple cases of breast or ovarian cancers. This article provides relative risks and cumulative risks of breast cancer in women whose family history indicates high risk. Specifically, the aim was to determine how many years earlier the high-risk women reach the cumulative risk of women without family history at the age at which screening in average-risk women is initiated. The women of the nation-wide Swedish Family-Cancer Database were classified according to clinical criteria based on family history suggesting high risk for hereditary breast ovarian cancer syndrome. The relative risks of breast cancer were calculated as hazard ratio using Cox regression. Cumulative risks of breast cancer were estimated with a stratified Cox model based on Tsiatis' method. The hazard ratios of breast cancer for the considered criteria ranged from 1.50 to 5.99. The cumulative risks ranged from 1 to 10% by age 50 years. The age to reach the same cumulative risk as women lacking a family history at the age of 50 years ranged between 32.0 and 40.8 years. Relative and cumulative risks of women at high risk of breast cancer associated with different clinical criteria were diverse, which may be helpful in considering when current clinical criteria are revised. According to the present results, current recommendations of starting clinical interventions 10 years earlier in high-risk women, based on expert opinions, appear justified at least for the largest high-risk groups. PMID:19641988

  4. Monoclonal antibodies that demonstrate specificity for several types of human lung cancer.

    PubMed Central

    Cuttitta, F; Rosen, S; Gazdar, A F; Minna, J D

    1981-01-01

    Monoclonal antibodies with selectivity for human lung cancer were produced by immunizing BALB/c mice with an established line of human small cell lung cancer (NCI-H69) and fusing the mouse spleen cells to mouse myeloma line X63-Ag8.653. The resulting hybrid cells were initially screened by immunoautoradiography for production of antibodies that would react with NCI-H69 and another small cell lung cancer line (NCI-H128) but not its autologous B-lymphoblastoid line (NCI-H128BL). Stable monoclonal antibody-producing lines were isolated by repeated cloning. Three independently derived monoclonal antibodies, designated 525A5, 534F8, and 538F12, were found to react with three of the major types of human lung cancer (small cell, adenocarcinoma, and squamous carcinoma). They did not react with bronchioloalveolar and large cell lung cancers, myeloma, lymphomas, leukemias, osteogeneic sarcoma, mesothelioma, hypernephroma, malignant melanoma, simian virus 40-transformed human fetal lung cells, skin fibroblast lines, human B-lymphoblastoid lines, human erythrocytes, and rodent cells. Interestingly, these antibodies also bound to three out of three human neuroblastomas and two out of three breast cancers but failed to react with mouse neuroblastoma and rat pheochromocytoma. The monoclonal antibodies reacted with human small cell lung cancer tumors obtained at autopsy, but had insignificant reactions with normal human lung, liver, spleen, and skeletal muscle. We conclude that monoclonal antibodies have been generated that react with common antigenic determinants expressed on several human lung cancer types, neuroblastoma, and some breast cancers, but are not detectable by our current assays on a variety of other human tumors or normal adult human tissues. Such antibodies are of potential clinical and biological importance. PMID:6270685

  5. 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

  6. 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.

  7. Modelling the ages and metallicities of early-type galaxies in Fundamental Plane space

    NASA Astrophysics Data System (ADS)

    Porter, L. A.; Somerville, R. S.; Primack, J. R.; Croton, D. J.; Covington, M. D.; Graves, G. J.; Faber, S. M.

    2014-12-01

    Recent observations have probed the formation histories of nearby elliptical galaxies by tracking correlations between the stellar population parameters, age and metallicity, and the structural parameters that enter the Fundamental Plane, size Re, and velocity dispersion σ. These studies have found intriguing correlations between these four parameters. In this work, we make use of a semi-analytic model, based on halo merger trees extracted from the Bolshoi cosmological simulation, that predicts the structural properties of spheroid-dominated galaxies based on an analytic model that has been tested and calibrated against an extensive suite of hydrodynamic+N-body binary merger simulations. We predict the Re, σ, luminosity, age, and metallicity of spheroid-dominated galaxies, enabling us to compare directly to observations. Our model predicts a strong correlation between age and σ for early-type galaxies, and no significant correlation between age and radius, in agreement with observations. In addition, we predict a strong correlation between metallicity and σ, and a weak correlation between metallicity and Re, in qualitative agreement with observations. We find that the correlations with σ arise as a result of the strong link between σ and the galaxy's assembly time. Minor mergers produce a large change in radius while leaving σ nearly the same, which explains the weaker trends with radius.

  8. Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis.

    PubMed

    Almaguer-Mederos, L E; Falcón, N S; Almira, Y R; Zaldivar, Y G; Almarales, D C; Góngora, E M; Herrera, M P; Batallán, K E; Armiñán, R R; Manresa, M V; Cruz, G S; Laffita-Mesa, J; Cyuz, T M; Chang, V; Auburger, G; Gispert, S; Pérez, L V

    2010-08-01

    Previous studies have investigated the close association that exists between CAG repeat number and the age at onset in SCA2 = spinocerebellar ataxia type 2. These studies have focused on affected individuals. To further characterize this association and estimate the risk of a carrier developing SCA2 at a particular age as a function of a specific CAG repeat size, we have analyzed a large group of 924 individuals, including 394 presymptomatic and 530 affected individuals with a CAG repeat length of 32-79 units. Using a Kaplan-Meier survival analysis, we obtained cumulative probability curves for disease manifestation at a particular age for each CAG repeat length in the 34-45 range. These curves were significantly different (p < 0.001) and showed small overlap. All these information may be very valuable in predictive-testing programs, in the planning of studies for the identification of other genetic and environmental factors as modifiers of age at onset, and in the design of clinical trials for people at enlarged risk for SCA2. PMID:20095980

  9. Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer

    PubMed Central

    Asakawa, Yukiko; Ohtaka, Masahiko; Maekawa, Shinya; Fukasawa, Mitsuharu; Nakayama, Yasuhiro; Yamaguchi, Tatsuya; Inoue, Taisuke; Uetake, Tomoyoshi; Sakamoto, Minoru; Sato, Tadashi; Kawaguchi, Yoshihiko; Fujii, Hideki; Mochizuki, Kunio; Hada, Masao; Oyama, Toshio; Yasumura, Tomotaka; Omata, Kosaku; Nishiyama, Atsushi; Naito, Keiichi; Hata, Hideo; Haba, Yoshiaki; Miyata, Kazuyuki; Saitoh, Haruhisa; Yamadera, Yoichi; Miura, Kazuo; Kawaoi, Akira; Abe, Tohru; Tsunoda, Hajime; Honda, Yuji; Kurosaki, Masayuki; Enomoto, Nobuyuki

    2015-01-01

    AIM: To study how lymph node metastasis (LNM) risk is stratified in undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations of risk factors. METHODS: Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using clinicopathological factors of patient age, location, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by conventional statistical analysis and data-mining analysis. RESULTS: LNM was positive in 44 of 567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis. In preoperatively evaluable factors excluding LVI, sm and > 2 cm were independent factors. According to the depth and size, cases were categorized into the low-risk group [m and ≤ 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%; and sm and ≤ 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than 28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases even in the moderate- and high-risk groups. CONCLUSION: LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively. Among these factors, LI was the most significantly correlated factor. PMID:25759537

  10. 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.

  11. Interaction of age and foam types used in Clinical Test for Sensory Interaction and Balance (CTSIB).

    PubMed

    Chaikeeree, Nithinun; Saengsirisuwan, Vitoon; Chinsongkram, Butsara; Boonsinsukh, Rumpa

    2015-01-01

    Clinical Test for Sensory Interaction and Balance (CTSIB) is a simplified method for investigating the organization of multiple sensory inputs in postural control. The accuracy of the test is based partly on the foam types. Several types of foam are available, but the validity of these foams on CTSIB and the interaction of age and foam types have not been addressed. In this study, postural sway of young (21.6 ± 3.3 years) and older (53.2 ± 4.9 years) participants were assessed while standing on four types of foam: NeuroCom(®), sponge, Ethylene Vinyl Acetate (EVA), and memory foams. Postural sway during stance on solid floor and foams with eyes open and eyes closed were quantified by root-mean-square (RMS) of center of body mass acceleration in the mediolateral (ML) and anteroposterior (AP) directions using the acceleration-based OPAL system. Physical properties of foams including density, Young's modulus, and indentation force deflection (IFD) were determined. Results demonstrated that RMS-ML in older subjects was larger than younger subjects (p ≤ 0.001), especially when standing on the NeuroCom(®) foam with eyes closed (p = 0.001). There was an interaction of age and foam types as larger differences in RMS-ML were observed between young and older subjects on the NeuroCom(®) and EVA foams, but not the other foams. The sway characteristics were largest when standing on the NeuroCom(®) foam which demonstrated high density and high compliance. Our findings suggested the importance of foam selection in CTSIB on accurate postural sway analysis and balance assessment.

  12. 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

  13. Sm-Nd evidence for the age and origin of a Mississippi Valley Type ore deposit.

    PubMed

    Halliday, A N; Shepherd, T J; Dickin, A P; Chesley, J T

    1990-03-01

    MISSISSIPPI Valley Type (MVT) ore deposits represent the relatively common product of large-scale fluid transport in the continental lithosphere, yet the models for their genesis have been more controversial and unconstrained than those of any other class of giant ore deposit(1,2). Here we show that Sm-Nd isotope data can be used to determine the age and origin of an MVT deposit. Sm-Nd data for fluorites from the North Pennine orefield are difficult to explain unless some of the mineralization is of Mesozoic rather than the traditionally accepted Palaeozoic age. Furthermore, the Nd and Sr isotopie compositions of the fluorites do not support a variety of recent models that include derivation of the components from the mantle, the Lower Palaeozoic basement or the underlying buried granite which served to focus the flow of hydrothermal fluids.

  14. Sm-Nd evidence for the age and origin of a Mississippi Valley Type ore deposit.

    PubMed

    Halliday, A N; Shepherd, T J; Dickin, A P; Chesley, J T

    1990-03-01

    MISSISSIPPI Valley Type (MVT) ore deposits represent the relatively common product of large-scale fluid transport in the continental lithosphere, yet the models for their genesis have been more controversial and unconstrained than those of any other class of giant ore deposit(1,2). Here we show that Sm-Nd isotope data can be used to determine the age and origin of an MVT deposit. Sm-Nd data for fluorites from the North Pennine orefield are difficult to explain unless some of the mineralization is of Mesozoic rather than the traditionally accepted Palaeozoic age. Furthermore, the Nd and Sr isotopie compositions of the fluorites do not support a variety of recent models that include derivation of the components from the mantle, the Lower Palaeozoic basement or the underlying buried granite which served to focus the flow of hydrothermal fluids. PMID:18278025

  15. The Effects of Intensive Nutrition Education on Late Middle-Aged Adults with Type 2 Diabetes

    PubMed Central

    Li, Ye; Xu, Meihong; Fan, Rui; Ma, Xiaotao; Gu, Jiaojiao; Cai, Xiaxia; Liu, Rui; Chen, Qihe; Ren, Jinwei; Mao, Ruixue; Bao, Lei; Zhang, Zhaofeng; Wang, Junbo; Li, Yong

    2016-01-01

    Objective: Many patients with type 2 diabetes find it difficult to maintain good glycemic control. Undesirable glycemic control occurs greatly due to deficiencies of nutritional knowledge and difficulty in obtaining dietary prescriptions. The late middle-aged and elder individuals are the main populations that are affected by type 2 diabetes. The main purpose of this study was to investigate whether intensive nutrition education would make benefits for late middle-aged patients with type 2 diabetes. Method: 196 patients between 50 to 65 years old meeting type 2 diabetes criteria and eligible for the program were included in a single-blinded, 30-day centralized management of an education program in China. Participants in the program were randomly divided into a usual nutrition education group or an intensive nutrition education group. The usual nutrition education group was used as a control group and received only basic health advice and principles of diabetic diets at the beginning and the end of the study. Participants in the intensive nutrition education group were arranged to receive intensive nutritional lectures about diabetes for 30 days. The primary outcomes were the changes in weight, body mass index (BMI), fasting plasma glucose (FPG), 2-h postprandial plasma glucose (PG), glycosylated hemoglobin (HbA1c), total glycerin (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). Results: After 30 days of intervention, FPG, PG, and HbA1c in the treatment group decreased significantly than the control group (p < 0.05). HbA1c reduced significantly by 0.6% in the intervention group. No significant differences in the change of blood lipids were observed between groups. However, TG, TC, and HDL-c made improvements compared with the baseline in the experimental group. Both groups had a reduction in weight and BMI within groups, especially in intensive nutrition education group. However, there was

  16. The effects of age, gender, and crash types on drivers' injury-related health care costs.

    PubMed

    Shen, Sijun; Neyens, David M

    2015-04-01

    There are many studies that evaluate the effects of age, gender, and crash types on crash related injury severity. However, few studies investigate the effects of those crash factors on the crash related health care costs for drivers that are transported to hospital. The purpose of this study is to examine the relationships between drivers' age, gender, and the crash types, as well as other crash characteristics (e.g., not wearing a seatbelt, weather condition, and fatigued driving), on the crash related health care costs. The South Carolina Crash Outcome Data Evaluation System (SC CODES) from 2005 to 2007 was used to construct six separate hierarchical linear regression models based on drivers' age and gender. The results suggest that older drivers have higher health care costs than younger drivers and male drivers tend to have higher health care costs than female drivers in the same age group. Overall, single vehicle crashes had the highest health care costs for all drivers. For males older than 64-years old sideswipe crashes are as costly as single vehicle crashes. In general, not wearing a seatbelt, airbag deployment, and speeding were found to be associated with higher health care costs. Distraction-related crashes are more likely to be associated with lower health care costs in most cases. Furthermore this study highlights the value of considering drivers in subgroups, as some factors have different effects on health care costs in different driver groups. Developing an understanding of longer term outcomes of crashes and their characteristics can lead to improvements in vehicle technology, educational materials, and interventions to reduce crash-related health care costs.

  17. [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

  18. Aged black garlic extract induces inhibition of gastric cancer cell growth in vitro and in vivo.

    PubMed

    Wang, Xin; Jiao, Fei; Wang, Qin-Wen; Wang, Juan; Yang, Ke; Hu, Rong-Rong; Liu, Han-Chen; Wang, Hong-Yang; Wang, Yi-Shan

    2012-01-01

    There is mounting evidence that garlic extracts possess significant anticancer actions. However, no studies have been reported on the effects of aged black garlic extracts (ABGE) on gastric cancer in vitro or in vivo. To examine the potential action of ABGE against gastric cancer, the present study evaluated its effect on the inhibition of cell proliferation and induction of apoptosis in SGC-7901 human gastric cancer cells. Additionally, we performed an in vivo study by inoculating the murine foregastric carcinoma cell line in Kunming mice and treating them with various doses of ABGE (0, 200, 400 and 800 mg/kg, intraperitoneally) for 2 weeks. Dose-dependent apoptosis was detected in ABGE-treated cells in in vitro studies. In tumor-bearing mice, significant antitumor effects of ABGE were observed, such as growth inhibition of inoculated tumors. Further investigation of serum superoxide dismutases, glutathione peroxidase, interleukin-2 and the increased indices of spleen and thymus indicated that the anticancer action of ABGE may be partly due to its antioxidant and immunomodulative effects. PMID:21922142

  19. 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

  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. 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

  2. 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.

  3. Assessing the clinical utility of cancer genomic and proteomic data across tumor types.

    PubMed

    Yuan, Yuan; Van Allen, Eliezer M; Omberg, Larsson; Wagle, Nikhil; Amin-Mansour, Ali; Sokolov, Artem; Byers, Lauren A; Xu, Yanxun; Hess, Kenneth R; Diao, Lixia; Han, Leng; Huang, Xuelin; Lawrence, Michael S; Weinstein, John N; Stuart, Josh M; Mills, Gordon B; Garraway, Levi A; Margolin, Adam A; Getz, Gad; Liang, Han

    2014-07-01

    Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, microRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We find that incorporating molecular data with clinical variables yields statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2-23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Syllable Type Consistency is Related to Age, Social Status, and Reproductive Success in the Tropical Mockingbird.

    PubMed

    Botero, Carlos A; Rossman, Rachel J; Caro, Lina M; Stenzler, Laura M; Lovette, Irby J; De Kort, Selvino R; Vehrencamp, Sandra L

    2009-03-01

    Many animals repeat standardized displays multiple times while attracting a mate or deterring a rival. In such contexts it is possible that the ability to perform each display or signal type in a consistent fashion is under direct selection. Studies on sexual selection on song learning in birds have focused on differences in repertoire size with less attention to the potential importance of being able to perform each song/syllable type with high consistency. We present evidence that tropical mockingbirds decrease the variation between renditions of each syllable type as they grow older (i.e., become more consistent) and that more consistent males in this species tend to have higher dominance status and reproductive success. These findings stress the importance of consistency in the performance of sexual displays and suggest that this parameter may be very relevant even in species that are selected for high vocal diversity (i.e., large repertoires). In addition to signalling dominance status and age, we hypothesize that syllable type consistency may also be an indicator of the integrity of brain function in birds analogous to the tests used for neuropsychological assessment in humans.

  14. 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

  15. Reference frameworks for the health management of measles, breast cancer and diabetes (type II).

    PubMed

    Brand, Helmut; Schröder, Peter; Davies, John K; Escamilla, Ixhel; Hall, Caroline; Hickey, Kieran; Jelastopulu, Eleni; Mechtler, Reli; Yared, Wendy Tse; Volf, Jaroslav; Weihrauch, Birgit

    2006-03-01

    This paper presents reference frameworks which order effective and feasible policies and interventions for the health management of measles, breast cancer and diabetes (type II). These reference frameworks can be used to rapidly appraise regional health policy documents and existing health management systems. Furthermore, the reference frameworks can serve health policy makers for the planning of health management measures.

  16. 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.

  17. The effect of accelerated ageing on performance properties of addition type silicone biomaterials.

    PubMed

    Stathi, K; Tarantili, P A; Polyzois, G

    2010-05-01

    The UV-protection provided to addition type silicone elastomers by various colorants, such as conventional dry earth pigments, as well as the so called "functional or reactive" pigments, was investigated. Moreover, the effect of a UV light absorber and a silica filler was also explored. Under the experimental parameters of this work, the exposure of silicone to UV radiation resulted in some changes of the IR absorbance, thermal decomposition after 400 degrees C, T(g) and tensile properties, whereas the storage modulus of samples was not affected. The obtained spectroscopic data, as well as the results of TGA and storage modulus, were interpreted by assuming that chain scission takes place during aging, whereas the improvement of tensile strength allows the hypothesis of a post-curing process, initiated by UV radiation. Therefore, the increase of T(g) could partly be due to the above reason and, furthermore, to the contribution of a rearrangement of chain fragments within the free volume of the elastomeric material. Regarding the evaluation of various coloring agents used in this work, the obtained results show that dry pigments are more sensitive to accelerated ageing conditions in comparison with functional liquid pigments. Moreover, the hydrophobic character of silicone matrix is enhanced, with the addition of this type pigments because of the vinyl functional silanes groups present in their chemical structure. Finally, it should be noted that the incorporation of silica nanofiller did not seem to prevent the silicone elastomer from degradation upon UV irradiation, but showed a significant reinforcing effect.

  18. Age at menarche and endometrial cancer risk: a dose-response meta-analysis of prospective studies.

    PubMed

    Gong, Ting-Ting; Wang, Yong-Lai; Ma, Xiao-Xin

    2015-09-11

    Evidence between age at menarche and endometrial cancer risk have been controversial. Therefore, we conducted a meta-analysis of prospective studies to analyze the aforementioned association. Relevant studies were identified by searching PubMed and EMBASE databases until the end of June 2015. A random-effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between menarcheal age and endometrial cancer risk. Our meta-analysis included eight prospective studies involving 4553 subjects with endometrial cancer. The summarized RRs of endometrial cancer for menarcheal age were 0.68 (95%CI = 0.58-0.81, I(2) = 41.9%, P = 0.099, n = 8) when comparing women with oldest category of menarcheal age with women with youngest category of menarcheal age. Notably, there was an 4% reduction in risk for per 2 years delay in menarcheal age (summarized RR = 0.96; 95%CI = 0.94-0.98, I(2) = 45.7%, P = 0.101, n = 6). Additionally, significant inverse associations were consistent within all stratified analyses. There was no evidence of publication bias or significant heterogeneity between subgroups detected by meta-regression analyses. Our findings support the hypothesis that late menarcheal age is inversely associated with endometrial cancer risk. Further larger prospective or pooled studies are warranted to fully adjust for potential confounders and distinguish whether the associations differ by histological subtypes of endometrial cancer.

  19. 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. PMID:27621768

  20. The Prognostic Impact of Type 2 Diabetes Mellitus on Early Cervical Cancer in Asia

    PubMed Central

    Kuo, Hung-Yang; Lin, Zhong-Zhe; Kuo, Raymond; Shau, Wen-Yi; Lai, Chiu-Lin; Yang, Yen-Yun; Shao, Yu-Yun; Hsu, Chiun; Cheng, Wen-Fan; Cheng, Ann-Lii

    2015-01-01

    Background. Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC. Patients and Methods. We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I–IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality. Results. A total of 2,946 patients had primary stage I–IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55). Conclusion. In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments. Implications for Practice: Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during

  1. 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

  2. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    PubMed Central

    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

    2015-01-01

    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

  3. 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.

  4. 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

  5. Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

    DOEpatents

    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.

  6. Patient age is related to decision-making, treatment selection, and perceived quality of life in breast cancer survivors

    PubMed Central

    2014-01-01

    Background Patients with breast cancer must choose among a variety of treatment options when first diagnosed. Patient age, independent of extent of disease, is also related to quality of life. This study examined the impact of patient age on treatment selected, factors influencing this selection, and perceived quality of life. Methods A 62-question survey evaluating breast cancer treatment and quality of life was mailed to breast cancer survivors. Responses were stratified by age (<50, 50-65, >65 years) and extent of disease. Results Of the 1,131 surveys mailed, 402 were included for analysis. There were 104, 179, and 119 women aged <50, 50-65, and >65 years, respectively. The median patient age was 58 years, and the average interval from diagnosis to survey participation was 31.5 months. Conclusions Young women were more likely to have undergone aggressive therapies and had better physical functioning than old women. Old patients reported good quality of life and body image. Clinicians should consider patient age when discussing breast cancer treatment options. PMID:25052797

  7. 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

  8. Biopotential signals of breast cancer versus tumor types and proliferation stages.

    PubMed

    Hassan, Ahmed M; El-Shenawee, Magda

    2012-02-01

    Clinical studies have shown compelling data of elevated biopotential signals recorded noninvasively from the breasts of women with breast cancer. While these data are compelling and show a strong potential for use in the noninvasive early detection of breast cancer, there remains significant knowledge gaps which must be addressed before this technology can be routinely used for breast cancer detection. A diffusion-drift model is developed to study the spatial and temporal characteristics of the biopotential signals of breast tumors taking into account the morphology and cell division stages. The electric signals of the most common tumor types-papillary, compact, and comedo-are also considered. The largest biopotential signal is observed from the compact tumor, while the smallest signal is observed from the papillary type. The results also show an increase in the time duration of the generated biopotential signals when cancer cells start their transitions at different time instants. The spatial and temporal variations of the biopotential signals are correlated with the tumor pattern which can have important implications for breast cancer detection. PMID:22463250

  9. 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

  10. The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

    PubMed Central

    Terabe, Masaki; Berzofsky, Jay A.

    2014-01-01

    NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

  11. A cross sectional study of HPV type prevalence according to age and cytology

    PubMed Central

    2013-01-01

    Background A cross sectional study to investigate HPV prevalence according to age and cytology. Methods Women presenting to a gynaecological outpatient clinic for a Pap smear test were included in the study (n=3177). All women had cervical cytology and HPV testing. Results Overall prevalence of any 24 HPV type analysed was 33.1% (95% CI 31.5% to 34.7%) and HPV 16 and HPV 42 were the most frequent (6.7% (95% CI 5.8% to 7.6%), 6.8% (95% CI 5.9% to 7.6%)), in total samples. Multiple HPV infection rate was 12.9% (95% CI 11.8% to 14.1%). High risk HPV (hrHPV) types were present in 27.4% (95% CI 25.8% to 28.9%) of the samples. HPV prevalence was highest among 14 to 19 y.o (46.6% (95% CI 40.7%-52.4%)) and second highest among 30–34 y.o. (39.7%, 95% CI 35.4%–44%). HPV 16 was highest among 20–24 (9.0% (95% CI 6.4%–11.6%)) and second highest among 50 to 54 y.o. (6.3% (95% CI 2.9% to 9.8%). In Low-grade Squamous Intraepithelial Lesions (LgSIL) cytology samples, the most frequently detected hrHPV types were: 16 (14.5% (95% CI 12.1% to 16.9%)), 51 (13.0% (95% CI 10.7% to 15.3%)) and 53 (9.1% (95% CI 7.2% to 11.1%)) and in High-grade Squamous Intraepithelial Lesions (HgSIL) were: HPV 16 (37.2% (95% CI 26.5% to 47.9%)), HPV 51 (17.9% (95% CI 9.4% to 26.5%)) and HPV 18 (12.8% (95% CI 5.4% to 20.2%)). Conclusions In the population studied, HPV 16 and 51 were the most frequent detected hrHPV types. HPV positivity, hrHPV and multiple HPV types infections were higher in young women, while HPV prevalence declined with increasing age and presented two peaks a higher (14–19 y.o.) and a lower one (30–34 y.o.) These results may contribute to the creation of a national screening programme. PMID:23363541

  12. Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer.

    PubMed Central

    Yamashita, J.; Ogawa, M.; Yamashita, S.; Nakashima, Y.; Saishoji, T.; Nomura, K.; Inada, K.; Kawano, I.

    1993-01-01

    Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were

  13. 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.

  14. Cancer and frailty in older adults: a nested case-control study of the Mexican Health and Aging Study

    PubMed Central

    Pérez-Zepeda, Mario Ulises; Cárdenas-Cárdenas, Eduardo; Cesari, Matteo; Navarrete-Reyes, Ana Patricia; Gutiérrez-Robledo, Luis Miguel

    2016-01-01

    Purpose Understanding how the convergence between chronic and complex diseases—such as cancer—and emerging conditions of older adults—such as frailty—takes place would help in halting the path that leads to disability in this age group. The objective of this manuscript is to describe the association between a past medical history of cancer and frailty in Mexican older adults. Methods This is a nested in cohort case-control study of the Mexican Health and Aging Study. Frailty was categorized by developing a 55-item frailty index that was also used to define cases in two ways: incident frailty (incident >0.25 frailty index score) and worsening frailty (negative residuals from a regression between 2001 and 2012 frailty index scores). Exposition was defined as self-report of cancer between 2001 and 2012. Older adults with a cancer history were further divided into recently diagnosed (<10 years) and remotely diagnosed (>10 years from the initial diagnosis). Odds ratios were estimated by fitting a logistic regression adjusted for confounding variables. Results Out of a total of 8022 older adults with a mean age of 70.6 years, the prevalence of a past medical history of cancer was 3.6 % (n = 288). Among these participants, 45.1 % had been diagnosed with cancer more than 10 years previously. A higher risk of incident frailty compared to controls [odds ratio (OR) 1.53 (95 % confidence interval (CI) 1.04–2.26, p = 0.03); adjusted model OR 1.74 (95 % CI 1.15–2.61, p = 0.008)] was found in the group with a recent cancer diagnosis. Also, an inverse association between a remote cancer diagnosis and worsening frailty was found [OR = 0.56 (95 % CI 0.39–0.8), p = 0.002; adjusted model OR 0.61 (95 % CI 0.38–0.99, p = 0.046)]. Conclusions Cancer is associated with a higher frailty index, with a potential relevant role of the time that has elapsed since the cancer diagnosis. Implications for cancer survivors Cancer survivors may be more likely to develop frailty or

  15. The angiotensin II type 1 receptor blocker candesartan suppresses proliferation and fibrosis in gastric cancer.

    PubMed

    Okazaki, Mitsuyoshi; Fushida, Sachio; Harada, Shinichi; Tsukada, Tomoya; Kinoshita, Jun; Oyama, Katsunobu; Tajima, Hidehiro; Ninomiya, Itasu; Fujimura, Takashi; Ohta, Tetsuo

    2014-12-01

    Gastric cancer with peritoneal dissemination has poor clinical prognosis because of the presence of rich stromal fibrosis and acquired drug resistance. Recently, Angiotensin II type I receptor blockers such as candesartan have attracted attention for their potential anti-fibrotic activity. We examined whether candesartan could attenuate tumor proliferation and fibrosis through the interaction between gastric cancer cell line (MKN45) cells and human peritoneal mesothelial cells. Candesartan significantly reduced TGF-β1 expression and epithelial-to-mesenchymal transition-like change, while tumor proliferation and stromal fibrosis were impaired. Targeting the Angiotensin II signaling pathway may therefore be an efficient strategy for treatment of tumor proliferation and fibrosis. PMID:25224569

  16. The inflammatory