de Oliveira, S. Moss; Alves, Domingos; Martins, J. S. Sá
The idea of this review is to connect the different models of evolution to those of biological ageing through Darwin's theory. We start with the Eigen model of quasispecies for microevolution, then introduce the Bak-Sneppen model for macroevolution and, finally, present the Penna model for biological ageing and some of its most important results. We also explore the concept of coevolution using this model.
Alberto A. Antunes
Full Text Available OBJECTIVE: To assess the influence of age in pathological findings and clinical evolution of prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Five hundred and fifty-six patients operated on between 1991 and 2000 were selected. Patients were divided into age groups of between 10 and 49 years, 50 to 59 years, 60 to 69 years and 70 to 83 years. RESULTS: Patients having less than 60 years of age presented clinical stage (p = 0.001, PSA (p = 0.013 and biopsy Gleason score (p = 0.013 more favorable than older patients. Age groups did not show any relationship between either postoperative Gleason score or pathological stage or risk of non-confined organ disease and involvement of seminal vesicles. After a mean follow-up of 58.3 months, 149 (27% patients presented recurrence. Patients aged between 40 and 59 years presented a disease-free survival rate significantly higher when compared to patients aged between 60 and 83 years (p = 0.022. However, when controlled with clinical stage, PSA, Gleason score and percentage of positive fragments, there was no relationship between age and biochemical recurrence risk (p = 0.426. CONCLUSIONS: Even though younger patients presented more favorable preoperative characteristics, postoperative pathological findings and biochemical recurrence rates did not differ between studied age groups.
Pedersen, Jacob K; Engholm, Gerda; Skytthe, Axel
studies of cancer epidemiology and minimized the challenges often faced in many countries, such as uncertain identification of the study base, age misreporting, and low validity of the cancer diagnoses. However, methodological challenges still remain to be addressed, especially in cancer epidemiology...... studies among the elderly and the oldest-old. For example, a characteristic pattern for many cancer types is that the incidence increases up to a maximum at about ages 75-90 years and is then followed by a decline or a leveling off at the oldest ages. It has been suggested that the oldest individuals may...... be asymptomatic, or even insusceptible to cancer. An alternative interpretation is that this pattern is an artifact due to lower diagnostic intensity among the elderly and oldest-old caused by higher levels of co-morbidities in this age group. Currently, the available cancer epidemiology data are not able...
In the late 19th century, the evolutionary approach to the problem of ageing was initiated by August Weismann, who argued that natural selection was more important for ageing than any physiological mechanism. In the mid-twentieth century, J. B. S. Haldane, P. B. Medawar and G. C. Williams informally argued that the force ...
the following courses: From year 1: Responsible Conduct of Research Ecology and Evolution : Principles of Population Genetics I 10 Ecology and...Statistical Methods and their Applications The Ecology and Evolution : Fundamentals of Molecular Evolution course from year 1, and Intro to Statistical...AWARD NUMBER: DoD Award W81XWH-13-1-0451 TITLE: The Genomic Evolution of Prostate Cancer PRINCIPAL INVESTIGATOR: David VanderWeele, M.D
Sprouffske, Kathleen; Merlo, Lauren M.F.; Gerrish, Philip J.; Maley, Carlo C.; Sniegowski, Paul D.
Cancer initiation, progression, and the emergence of therapeutic resistance are evolutionary phenomena of clonal somatic cell populations. Studies in microbial experimental evolution and the theoretical work inspired by such studies are yielding deep insights into the evolutionary dynamics of clonal populations, yet there has been little explicit consideration of the relevance of this rapidly growing field to cancer biology. Here, we examine how the understanding of mutation, selection, and spatial structure in clonal populations that is emerging from experimental evolution may be applicable to cancer. Along the way, we discuss some significant ways in which cancer differs from the model systems used in experimental evolution. Despite these differences, we argue that enhanced prediction and control of cancer may be possible using ideas developed in the context of experimental evolution, and we point out some prospects for future research at the interface between these traditionally separate areas. PMID:22975007
Stearns Stephen C
Full Text Available Abstract Background Aging refers to a decline in reproduction and survival with increasing age. According to evolutionary theory, aging evolves because selection late in life is weak and mutations exist whose deleterious effects manifest only late in life. Whether the assumptions behind this theory are fulfilled in all organisms, and whether all organisms age, has not been clear. We tested the generality of this theory by experimental evolution with Caulobacter crescentus, a bacterium whose asymmetric division allows mother and daughter to be distinguished. Results We evolved three populations for 2000 generations in the laboratory under conditions where selection was strong early in life, but very weak later in life. All populations evolved faster growth rates, mostly by decreasing the age at first division. Evolutionary changes in aging were inconsistent. The predominant response was the unexpected evolution of slower aging, revealing the limits of theoretical predictions if mutations have unanticipated phenotypic effects. However, we also observed the spread of a mutation causing earlier aging of mothers whose negative effect was reset in the daughters. Conclusion Our results confirm that late-acting deleterious mutations do occur in bacteria and that they can invade populations when selection late in life is weak. They suggest that very few organisms – perhaps none- can avoid the accumulation of such mutations over evolutionary time, and thus that aging is probably a fundamental property of all cellular organisms.
For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses ...
Junji Moriya; Tohru Minamino
Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD) among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging o...
For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyper-plastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366
The purpose of this monograph is to describe recent developments in mathematical modeling and mathematical analysis of certain problems arising from cell biology. Cancer cells and their growth via several stages are of particular interest. To describe these events, multi-scale models are applied, involving continuously distributed environment variables and several components related to particles. Hybrid simulations are also carried out, using discretization of environment variables and the Monte Carlo method for the principal particle variables. Rigorous mathematical foundations are the bases of these tools. The monograph is composed of four chapters. The first three chapters are concerned with modeling, while the last one is devoted to mathematical analysis. The first chapter deals with molecular dynamics occurring at the early stage of cancer invasion. A pathway network model based on a biological scenario is constructed, and then its mathematical structures are determined. In the second chapter mathematica...
Mascolo, Giuseppe; Mascolo, Maria Cristina; Vitale, Alessandro; Marino, Ottavio
The microstructure evolution of lime putty upon aging was investigated by slaking quicklime (CaO) with an excess of water for 3, 12, 24, 36, 48 and 66 months. The as-obtained lime putties were characterized in the water retention and in the particle size distribution using the static laser scattering (SLS). The same lime putties, dehydrated by lyophilization, were also investigated in the pore size distribution by mercury intrusion porosimetry, in the surface area by the BET method and, finally, in particle morphology by scanning electron microscopy (SEM). The effect of the extended exposure of quicklime to water confirms a shape change from prismatic crystals of portlandite, Ca(OH) 2, into platelike ones. Simultaneously a growth of larger hexagonal crystals at the expense of the smallest ones (Ostwald ripening) favours a secondary precipitation of submicrometer platelike crystals of portlandite. The shape change and the broader particles size distribution of portlandite crystals upon aging seem to contribute to a better plasticity of lime putty.
Boddy, Amy M.; Gatenby, Robert A.; Brown, Joel S.; Maley, Carlo C.
Somatic evolution during cancer progression and therapy results in tumor cells that exhibit a wide range of phenotypes including rapid proliferation and quiescence. Evolutionary life history theory may help us understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly while those with slow life histories show less fecundity and invest more resources in survival. Life history theory also provides an evolutionary framework for phenotypic plasticity with potential implications for understanding ‘cancer stem cells’. Life history theory suggests that different therapy dosing schedules could select for fast or slow life history cell phenotypes, with important clinical consequences. PMID:24213474
Gladyshev, G P
Life in the Universe emerges and develops under certain conditions in accordance with the general laws of nature, in particular, in accordance with the law of temporal hierarchies, the second law of thermodynamics and the principle of stability of matter. Biological evolution and organism's aging are accompanied by a change in the chemical and supramolecular compositions of living bodies. As shown by the author in 1977 these well-known changes have the thermodynamic nature (origin). Phenomenological hierarchical thermodynamics of near-equilibrium quasi-closed systems allows us to explain and predict the evolutionary transformation in the living world. From a viewpoint of power-consuming substance of biological objects the phenomenon of life, first, is the struggle for power-consuming chemicals. The accumulation of this substance in biological systems is associated with the aspiration of the specific Gibbs function of formation of supramolecular structures of living organisms to a minimum. The development of classical science opens up new horizons to explore the real world and contributes to the success of gerontology and geriatrics. This paper is a brief review containing new results.
Newburger, D. E.
Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.
Muss, Hyman B
In the U.S., cancer is a disease of aging. The average 65-year-old patient has an anticipated life expectancy of 20 years, and clinicians should take this into account when making breast cancer management decisions...
Muss, Hyman B
In the U.S., cancer is a disease of aging. The average 65-year-old patient has an anticipated life expectancy of 20 years, and clinicians should take this into account when making breast cancer management decisions...
Bravo, Ignacio G; Félez-Sánchez, Marta
Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.
Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 8 ... Research News Volume 3 Issue 8 August 1998 pp 67-72 ... Evolution and Behaviour Laboratory, Animal Behaviour Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P. O. Bangalore 560 064, India; 403 Shriji Palace, ...
Sep 4, 2009 ... Cancer and ageing are often said to be diseases of development. During the past fifty years, the genetic components of cancer and ageing have been intensely investigated since development, itself, was seen to be an epiphenomenon of the genome. However, as we have learned more about the ...
Navarrete-Reyes, Ana Patricia; Soto-Pérez-de-Celis, Enrique; Hurria, Arti
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.
Full Text Available Cells of different organs at different ages have an intrinsic set of kinetics that dictates their behavior. Transformation into cancer cells will inherit these kinetics that determine initial cell and tumor population progression dynamics. Subject to genetic mutation and epigenetic alterations, cancer cell kinetics can change, and favorable alterations that increase cellular fitness will manifest themselves and accelerate tumor progression. We set out to investigate the emerging intratumoral heterogeneity and to determine the evolutionary trajectories of the combination of cell-intrinsic kinetics that yield aggressive tumor growth. We develop a cellular automaton model that tracks the temporal evolution of the malignant subpopulation of so-called cancer stem cells(CSC, as these cells are exclusively able to initiate and sustain tumors. We explore orthogonal cell traits, including cell migration to facilitate invasion, spontaneous cell death due to genetic drift after accumulation of irreversible deleterious mutations, symmetric cancer stem cell division that increases the cancer stem cell pool, and telomere length and erosion as a mitotic counter for inherited non-stem cancer cell proliferation potential. Our study suggests that cell proliferation potential is the strongest modulator of tumor growth. Early increase in proliferation potential yields larger populations of non-stem cancer cells(CC that compete with CSC and thus inhibit CSC division while a reduction in proliferation potential loosens such inhibition and facilitates frequent CSC division. The sub-population of cancer stem cells in itself becomes highly heterogeneous dictating population level dynamics that vary from long-term dormancy to aggressive progression. Our study suggests that the clonal diversity that is captured in single tumor biopsy samples represents only a small proportion of the total number of phenotypes.
Oxman, T E; Silberfarb, P M
The greatest risk factor for cancer is ageing, yet little is known about the epidemiology and treatment of psychiatric disorders in the aged cancer population. This is particularly true for the group over 75 years of age. Four important areas of psychiatric treatment relevant to the aged cancer patient are: illness behaviour, cognitive disorders, depression and psychosocial adaptation. Within these areas the following four conclusions can be made: (a) Symptom presentation and health promoting practices are two important aspects of illness behaviour that affect the detection and prevention of cancer in the aged. (b) It is likely that there will be an increased co-occurrence of dementia and cancer, raising important issues of treatment and informed consent. (c) There appears to be evidence that depression in cancer patients does not increase with age. (d) Similar to depression, despite widely differing methods and age cutoffs, the results of several studies have shown that psychosocial adaptation to cancer is maintained with age. With respect to psychiatric treatment, no patient should be denied full use of appropriate therapy on grounds of old age alone, and more attention should be given to the systematic detection and evaluation of reversible cognitive disorders.
Naylor, R.M.; Deursen, J.M.A. van
Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs
Maklakov, Alexei A; Bonduriansky, Russell; Brooks, Robert C
Life-history (LH) theory predicts that selection will optimize the trade-off between reproduction and somatic maintenance. Reproductive ageing and finite life span are direct consequences of such optimization. Sexual selection and conflict profoundly affect the reproductive strategies of the sexes and thus can play an important role in the evolution of life span and ageing. In theory, sexual selection can favor the evolution of either faster or slower ageing, but the evidence is equivocal. We used a novel selection experiment to investigate the potential of sexual selection to influence the adaptive evolution of age-specific LH traits. We selected replicate populations of the seed beetle Callosobruchus maculatus for age at reproduction ("Young" and "Old") either with or without sexual selection. We found that LH selection resulted in the evolution of age-specific reproduction and mortality but these changes were largely unaffected by sexual selection. Sexual selection depressed net reproductive performance and failed to promote adaptation. Nonetheless, the evolution of several traits differed between males and females. These data challenge the importance of current sexual selection in promoting rapid adaptation to environmental change but support the hypothesis that sex differences in LH-a historical signature of sexual selection-are key in shaping trait responses to novel selection.
Jamal-Hanjani, Mariam; Wilson, Gareth A.; McGranahan, Nicholas
Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine...... as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .)....
Kubczak, Małgorzata; Rogalińska, Małgorzata
Since late 90s of last century the new age of directed therapy began using mainly biological constructs produced in rodents called monoclonal antibodies. The side effects of monoclonal antibodies were a challenge for pharmaceutical companies to improve the biological properties of these biological drugs. The humanization of monoclonal constructs was an idea to improve monoclonal antibodies next generation activity cancer cell reduction in humans. Moreover for some other patients sensitive for monoclonal antibodies therapy could also potentially induce immunological differences that might imply on human health. The new idea related to monoclonal antibodies was to design a small molecule constructs of nanoantibodies with ability to enter into cells. Such small molecules could find their targets inside human cells, even in nuclei leading to differences in cancer cells expression. The existing knowledge on monoclonal antibodies as well as directed activity of nanoantibodies could improve anticancer treatment efficancy of diseases.
Zwoinska, Martyna K; Maklakov, Alexei A; Kawecki, Tadeusz J; Hollis, Brian
Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories. © 2016 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.
... conditions for tumor induction, promotion and progression. The pineal gland, via its hormone melatonin, has been shown by numerous laboratories to inhibit the proliferation of both human and animal models of breast cancer...
Gladyshev, G P
Briefly discusses the history of the search of thermodynamic approach to explain the origin of life, evolution and aging of living beings. The origin of life is the result of requirement by the quasi-equilibrium hierarchical thermodynamics, in particular, the supramolecular thermodynamics. The evolution and aging of living beings is accompanied with changes of chemical and supramolecular compositions of living bodies, as well as with changes in the composition and structure of all hierarchies of the living world. The thermodynamic principle of substance stability predicts the existence of a single genetic code in our universe. The thermodynamic theory optimizes physiology and medicine and recommends antiaging diets and medicines. Hierarchical thermodynamics forms the design diversity of culture and art. The thermodynamic theory of origin of life, evolution and aging is the development of Clausius-Gibbs thermodynamics. Hierarchical thermodynamics is the mirror of Darwin-Wallace's-theory.
Full Text Available Lung cancer treatment has altered from conventional chemotherapy to targeted treatment, which now has been turned to the immunotherapy. Translational research has played an irreplaceable role during this progression which graphic evolution has witnessed. The evolution has gone through forest plot, KM-curve, waterfall plot, spider plot and timeline-area, showing us the refining concept and gradual process of lung cancer treatment undergoing from community towards individual. Even though the latest immunotherapy is getting increasingly hot, the result isn’t quite expected. Meanwhile, the limitations of conventional treatment still exist which require further research. This article will primarily illustrate the development of translational research of lung cancer via the aspect of curve evolution and analysis some abortive clinical trials in lung cancer surgery for inspiring the next graphic style and lung cancer treatment.
Wensink, Maarten Jan
The evolution of ageing is a field flush with misconceptions, misunderstandings, and hiatuses. In this thesis I address the most important misunderstanding and misconceptions, and develop new theory to fill the gaps. This work directly leads to the restatement of the central question in the
Coffey, D S
Environment determines the risk of both prostate and breast cancer, and this risk can vary >10-fold. In contrast, no risk exists for human seminal vesicle cancer demonstrating tissue specificity. There is also species specificity, because there is no risk for prostate cancer in any other aging mammal except the dog. A study of evolution indicates that the prostate and breast appeared at the same time 65 million years ago with the development of mammals. All male mammals have a prostate; however, the seminal vesicles are variable and are determined by the diet so that species primarily eating meat do not have seminal vesicles. The exception is the human, who has seminal vesicles and consumes meat, although this is a recent dietary change. Human lineage departed from other higher primates 8 million years ago. The closest existing primate to humans is the bonobo (pigmy chimpanzee), which does not eat meat but exists primarily on a high fruit and fresh vegetable diet. Homo sapiens evolved only about 150,000 years ago, and only in the last 10% of that time (10 to 15 thousand years ago) did humans and dogs dramatically alter their diets. This is the time when humans domesticated the dog, bred animals, grew crops, and cooked, processed, and stored meats and vegetables. All current epidemiologic evidence and suggestions for preventing prostate and breast cancer in humans indicates that we should return to the original diets under which our ancestors evolved. The recent development of the Western-type diet is associated with breast and prostate cancer throughout the world. It is believed that the exposure to and metabolism of estrogens, and the dietary intake of phytoestrogens, combined with fat intake, obesity, and burned food processing may all be related to hormonal carcinogenesis and oxidative DNA damage. An explanatory model is proposed.
Blagosklonny, Mikhail V
Common cancer is an age-related disease. Slow aging is associated with reduced and delayed carcinogenesis. Calorie restriction (CR), the most studied anti-aging intervention, prevents cancer by slowing down the aging process. Evidence is emerging that CR decelerates aging by deactivating MTOR (Target of Rapamycin). Rapamycin and other rapalogs suppress cellular senescence, slow down aging and postpone age-related diseases including cancer. At the same time, rapalogs are approved for certain cancer treatments. Can cancer prevention be explained by direct targeting of cancer cells? Or does rapamycin prevent cancer indirectly through slowing down the aging process? Increasing evidence points to the latter scenario.
Full Text Available Characterizing age from handwriting (HW has important applications, as it is key to distinguishing normal HW evolution with age from abnormal HW change, potentially triggered by neurodegenerative decline. We propose, in this work, an original approach for online HW style characterization based on a two-level clustering scheme. The first level generates writer-independent word clusters from raw spatial-dynamic HW information. At the second level, each writer’s words are converted into a Bag of Prototype Words that is augmented by an interword stability measure. This two-level HW style representation is input to an unsupervised learning technique, aiming at uncovering HW style categories and their correlation with age. To assess the effectiveness of our approach, we propose information theoretic measures to quantify the gain on age information from each clustering layer. We have carried out extensive experiments on a large public online HW database, augmented by HW samples acquired at Broca Hospital in Paris from people mostly between 60 and 85 years old. Unlike previous works claiming that there is only one pattern of HW change with age, our study reveals three major aging HW styles, one specific to aged people and the two others shared by other age groups.
Korolev, Kirill S; Xavier, Joao B; Gore, Jeff
The fight against cancer has drawn researchers from a wide variety of disciplines, ranging from molecular biology to physics, but the perspective of an ecological theorist has been mostly overlooked. By thinking about the cells that make up a tumour as an endangered species, cancer vulnerabilities become more apparent. Studies in conservation biology and microbial experiments indicate that extinction is a complex phenomenon, which is often driven by the interaction of ecological and evolutionary processes. Recent advances in cancer research have shown that tumours, like species striving for survival, harbour intricate population dynamics, which suggests the possibility to exploit the ecology of tumours for treatment.
Kennedy, Scott R; Loeb, Lawrence A; Herr, Alan J
The somatic mutation theory of aging posits that the accumulation of mutations in the genetic material of somatic cells as a function of time results in a decrease in cellular function. In particular, the accumulation of random mutations may inactivate genes that are important for the functioning of the somatic cells of various organ systems of the adult, result in a decrease in organ function. When the organ function decreases below a critical level, death occurs. A significant amount of research has shown that somatic mutations play an important role in aging and a number of age related pathologies. In this review, we explore evidence for increases in somatic nuclear mutation burden with age and the consequences for aging, cancer, and neurodegeneration. We then review evidence for increases in mitochondrial mutation burden and the consequences for dysfunction in the disease processes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
His, Mathilde; Le Guélennec, Marine; Mesrine, Sylvie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Dossus, Laure
Although adult obesity has been associated with poor breast cancer survival, data on adiposity at different periods in life and its lifelong evolution are scarce. Our aims were to assess the associations between breast cancer survival and body size during childhood, puberty and early adulthood and body size trajectories from childhood to adulthood. Self-assessed body size at age 8, at puberty, at age 20-25 and at age 35-40 and trajectories of body size of 4,662 breast cancer survivors from the prospective E3N cohort were studied in relation to risk of death from any cause, death from breast cancer and second invasive cancer event using multivariate Cox regression models. Four trajectories of body size were identified (T1 "moderate increase," T2 "stable/low increase," T3 "increase at puberty" and T4 "constantly high"). Compared with stable body size, an increase in body size during adult life was associated with an increased risk of death from any cause (HR T1 vs. T2 = 1.27; 95% CI = 1.01-1.60) and an increased risk of second invasive cancer event (HR T1 vs. T2 = 1.25; 95% CI = 1.06-1.47). Silhouettes at various ages were not associated with survival. Our results suggest that the evolution of body size from childhood to adulthood has a long-term influence on breast cancer survival. Although these results need to be confirmed, this work sheds light on the need to combine lifelong approaches to current BMI to better identify breast cancer survivors who are at higher risk of recurrence or second primary cancer, or of death. © 2017 UICC.
Verduzca Rodríguez, L A; Palet Guzmán, J A; Aguirre González, H; González Puebla, E
A retrospective study of 182 cases of invasive squamous cell carcinoma of the uterine cervix and 133 cases cases of in situ carcinoma, based on histological classification studies and their relation with mean age, during 1985-1994, is reported in a second level Hospital in Rio Blanco, Veracruz, Mexico. The mean age of invasive cervix carcinoma is 50.2 years and the mean age is not the same in the different clinical stages, stage I 45.1 years; stage II 48.6 years; stage III 54.9 years and stage IV 57.4 years. This finding maybe has clinical importance. The mean age of in situ carcinoma is 43.9 years, late when compare with other series in the literature. Plan some considerations about mass screening cervical cancer program in Mexico.
Castelli, Germana; Pelosi, Elvira; Testa, Ugo
Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV) infection (frequent in Asia and Africa)...
micr- oRNA-mediated inactivation of LRP1B, a modulator of the extracellular environment of thyroid cancer cells. Oncogene 2011; 30: 1302–17. 28 Lawrence...node metastases obtained at the time of prostatectomy and seminal vesicle regions involved through direct extension were included for two cases each...white (apex) to black (base), with purple (seminal vesicles ) and red (lymph node metastasis) indicating extraprostatic regions. Left panels specify
mutational landscape of lethal castration-resistant prostate cancer. Nature 2012; 487: 239–43. 12 Kumar A, White TA, MacKenzie AP et al. Exome...patient’s muta- tional landscape and expression signature. The recent rise of sequencing of PCa genomes has significantly increased our understanding...We demon- strate that fixation of prostates with PAXgene results in preservation of high quality DNA and RNA with preserved tissue architecture and
CONTRACTING ORGANIZATION: Memorial Sloan Kettering Institute for Cancer Research New York, NY 10065 REPORT DATE: October 2016 TYPE OF REPORT...of mitochondrial aconitase, is an early change in carcinogenesis in the prostate. This change in metabolism is detectable by magnetic resonance. The... mitochondrial aconitase (m-Acon) activity. This has been associated with zinc-induced inhibition of m-Acon in the peripheral epithelial cells. Activation of m
Full Text Available Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC and intrahepatic cholangiocarcinoma (iCCA. Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV infection (frequent in Asia and Africa, hepatitis C virus (HCV, chronic alcohol abuse, or metabolic syndrome (frequent in Western countries. In cirrhosis, hepatocarcinogenesis is a multi-step process where pre-cancerous dysplastic macronodules transform progressively into HCC. The patterns of genomic alterations observed in these tumors were recently identified and were instrumental for the identification of potential targeted therapies that could improve patient care. Liver cancer stem cells are a small subset of undifferentiated liver tumor cells, responsible for cancer initiation, metastasis, relapse and chemoresistance, enriched and isolated according to immunophenotypic and functional properties: cell surface proteins (CD133, CD90, CD44, EpCAM, OV-6, CD13, CD24, DLK1, α2δ1, ICAM-1 and CD47; the functional markers corresponding to side population, high aldehyde dehydrogenase (ALDH activity and autofluorescence. The identification and definition of liver cancer stem cells requires both immunophenotypic and functional properties.
Full Text Available Elizabeth A Jones, Yuanyuan Cheng, Katherine BelovFaculty of Veterinary Science, University of Sydney, NSW, AustraliaAbstract: Three transmissible cancers are known to have emerged naturally in the wild: canine transmissible venereal tumor (CTVT; Tasmanian devil facial tumor disease (DFTD; and a recently discovered leukemia-like cancer in soft-shell clams (Mya arenaria. These cancers have all acquired the ability to pass between individuals. DFTD emerged approximately 20 years ago and has decimated the Tasmanian devil population. CTVT arose over 10,000 years ago in an ancient breed of dog. The clam cancer is believed to have evolved at least 40 years ago. In this manuscript, we review CTVT and DFTD, the two transmissible mammalian cancers, and provide an overview of the leukemia-like cancer of clams. We showcase how genetics and genomics have enhanced our understanding of the unique biology, origins, and evolutionary histories of these rare cancers.Keywords: transmissible cancer, devil facial tumor disease, DFTD, canine transmissible venereal tumor, origin, evolution
Zheng, Yinan; Joyce, Brian T; Colicino, Elena; Liu, Lei; Zhang, Wei; Dai, Qi; Shrubsole, Martha J; Kibbe, Warren A; Gao, Tao; Zhang, Zhou; Jafari, Nadereh; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A; Hou, Lifang
Biological measures of aging are important for understanding the health of an aging population, with epigenetics particularly promising. Previous studies found that tumor tissue is epigenetically older than its donors are chronologically. We examined whether blood Δage (the discrepancy between epigenetic and chronological ages) can predict cancer incidence or mortality, thus assessing its potential as a cancer biomarker. In a prospective cohort, Δage and its rate of change over time were calculated in 834 blood leukocyte samples collected from 442 participants free of cancer at blood draw. About 3-5 years before cancer onset or death, Δage was associated with cancer risks in a dose-responsive manner (P = 0.02) and a one-year increase in Δage was associated with cancer incidence (HR: 1.06, 95% CI: 1.02-1.10) and mortality (HR: 1.17, 95% CI: 1.07-1.28). Participants with smaller Δage and decelerated epigenetic aging over time had the lowest risks of cancer incidence (P = 0.003) and mortality (P = 0.02). Δage was associated with cancer incidence in a 'J-shaped' manner for subjects examined pre-2003, and with cancer mortality in a time-varying manner. We conclude that blood epigenetic age may mirror epigenetic abnormalities related to cancer development, potentially serving as a minimally invasive biomarker for cancer early detection.
Yates, Lucy R; Knappskog, Stian; Wedge, David; Farmery, James H R; Gonzalez, Santiago; Martincorena, Inigo; Alexandrov, Ludmil B; Van Loo, Peter; Haugland, Hans Kristian; Lilleng, Peer Kaare; Gundem, Gunes; Gerstung, Moritz; Pappaemmanuil, Elli; Gazinska, Patrycja; Bhosle, Shriram G; Jones, David; Raine, Keiran; Mudie, Laura; Latimer, Calli; Sawyer, Elinor; Desmedt, Christine; Sotiriou, Christos; Stratton, Michael R; Sieuwerts, Anieta M; Lynch, Andy G; Martens, John W; Richardson, Andrea L; Tutt, Andrew; Lønning, Per Eystein; Campbell, Peter J
Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Talukder, Asoke K.; Agarwal, Mahima; Buetow, Kenneth H.; Denèfle, Patrice P.
It is difficult for existing methods to quantify, and track the constant evolution of cancers due to high heterogeneity of mutations. However, structural variations associated with nucleotide number changes show repeatable patterns in localized regions of the genome. Here we introduce SPKMG, which generalizes nucleotide number based properties of genes, in statistical terms, at the genome-wide scale. It is measured from the normalized amount of aligned NGS reads in exonic regions of a gene. SPKMG values are calculated within OncoTrack. SPKMG values being continuous numeric variables provide a statistical metric to track DNA level changes. We show that SPKMG measures of cancer DNA show a normative pattern at the genome-wide scale. The analysis leads to the discovery of core cancer genes and also provides novel dynamic insights into the stage of cancer, including cancer development, progression, and metastasis. This technique will allow exome data to also be used for quantitative LOH/CNV analysis for tracking tumour progression and evolution with a higher efficiency.
Tang, Chunlei; Zhou, Li; Plasek, Joseph; Rozenblum, Ronen; Bates, David
Our goal was to identify and track the evolution of the topics discussed in free-text comments on a cancer institution's social media page. We utilized the Latent Dirichlet Allocation model to extract ten topics from free-text comments on a cancer research institution's Facebook™ page between January 1, 2009, and June 30, 2014. We calculated Pearson correlation coefficients between the comment categories to demonstrate topic intensity evolution. A total of 4,335 comments were included in this study, from which ten topics were identified: greetings (17.3%), comments about the cancer institution (16.7%), blessings (10.9%), time (10.7%), treatment (9.3%), expressions of optimism (7.9%), tumor (7.5%), father figure (6.3%), and other family members & friends (8.2%), leaving 5.1% of comments unclassified. The comment distributions reveal an overall increasing trend during the study period. We discovered a strong positive correlation between greetings and other family members & friends (r=0.88; p<0.001), a positive correlation between blessings and the cancer institution (r=0.65; p<0.05), and a negative correlation between blessings and greetings (r=-0.70; p<0.05). A cancer institution's social media platform can provide emotional support to patients and family members. Topic analysis may help institutions better identify and support the needs (emotional, instrumental, and social) of their community and influence their social media strategy.
Bozic, Ivana; Gerold, Jeffrey M.; Nowak, Martin A.
The vast majority of mutations in the exome of cancer cells are passengers, which do not affect the reproductive rate of the cell. Passengers can provide important information about the evolutionary history of an individual cancer, and serve as a molecular clock. Passengers can also become targets for immunotherapy or confer resistance to treatment. We study the stochastic expansion of a population of cancer cells describing the growth of primary tumors or metastatic lesions. We first analyze the process by looking forward in time and calculate the fixation probabilities and frequencies of successive passenger mutations ordered by their time of appearance. We compute the likelihood of specific evolutionary trees, thereby informing the phylogenetic reconstruction of cancer evolution in individual patients. Next, we derive results looking backward in time: for a given subclonal mutation we estimate the number of cancer cells that were present at the time when that mutation arose. We derive exact formulas for the expected numbers of subclonal mutations of any frequency. Fitting this formula to cancer sequencing data leads to an estimate for the ratio of birth and death rates of cancer cells during the early stages of clonal expansion. PMID:26828429
Rebbeck, Clare A; Thomas, Rachael; Breen, Matthew; Leroi, Armand M; Burt, Austin
Canine transmissible venereal tumor (CTVT) is an infectious disease of dogs. Remarkably, the infectious agent is the cancerous cell itself. To investigate its origin and spread, we collected 37 tumor samples from four continents and determined their evolutionary relationships using microsatellite length differences and microarray-based comparative genomic hybridization (aCGH). The different tumors show very little microsatellite variation, and the pattern of variation that does exist is consistent with a purely asexual mode of transmission. Approximately one quarter of the loci scored by aCGH show copy number variation relative to normal dogs, again with little variation among different tumor samples. Sequence analysis of the RPPH1 gene indicates an origin from either dogs or wolves, and microsatellite analysis indicates that the tumor is more than 6000 years old, and perhaps originated when dogs were first domesticated. By contrast, the common ancestor of extant tumors lived within the last few hundred years, long after the first tumor. The genetic and genomic patterns we observe are typical of those expected of asexual pathogens, and the extended time since first origin may explain the many remarkable adaptations that have enabled this mammalian cell lineage to live as a unicellular pathogen.
Pelosi, Elvira; Castelli, Germana
Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-driven genetically-engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer have clarified the mechanisms through which various mutated genes act in neoplasia induction and progression and have led to identifying the possible cellular origin of these neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for the development of personalized medicine strategies. The studies of the purification and characterization of pancreatic cancer stem cells have suggested that a minority cell population is responsible for initiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contribute to the identification and clinical development of more efficacious drug treatments. PMID:29156578
Elvira Pelosi; Germana Castelli; Ugo Testa
Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of <10%. PDAC arises from different types of non-invasive precursor lesions: intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The dev...
Mellemkjær, Lene; Christensen, Jane; Frederiksen, Kirsten Skovsgaard
Women diagnosed with breast cancer at young age have been shown to be at higher risk of developing a new primary cancer than women diagnosed at older ages, but little is known about whether adjustment for calendar year of breast cancer diagnosis, length of follow-up, and/or breast cancer treatment...
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. |
Full Text Available Stochastic genetic and epigenetic events have been fundamental in contributing to the development of manifold life-forms, past and present. The development of malignant cell clones and the role of stochasticity as a driving force in cancer cell evolution complements, in a perverse way evidence for the role of chance in normal cellular development and evolution. Stochastic events at multiple levels of cellular control and implementation represent a primary driving force and an ultimate filter through which evolutionary innovation occurs. Stochasticity provides the opportunity for a random assortment of disparate genetic and epigenetic events, in some instances resulting in altered metabolic and developmental capabilities of sufficient stability and uniqueness to contribute to deterministic sequelae that promote the viability and procreation of cells under stress. Cellular evolution has so far resulted in a “survival of a (sic fittest”, often dependent mechanistically on and determined by stochastic events. The implications of this are mirrored in the evolution of malignant change, to some extent as a variant of “reverse engineering” of dedifferentiation. Efforts to reduce the incidence of malignant change will have to take in to account its random nature and further the understanding of this feature.
Full Text Available Biological measures of aging are important for understanding the health of an aging population, with epigenetics particularly promising. Previous studies found that tumor tissue is epigenetically older than its donors are chronologically. We examined whether blood Δage (the discrepancy between epigenetic and chronological ages can predict cancer incidence or mortality, thus assessing its potential as a cancer biomarker. In a prospective cohort, Δage and its rate of change over time were calculated in 834 blood leukocyte samples collected from 442 participants free of cancer at blood draw. About 3–5 years before cancer onset or death, Δage was associated with cancer risks in a dose-responsive manner (P = 0.02 and a one-year increase in Δage was associated with cancer incidence (HR: 1.06, 95% CI: 1.02–1.10 and mortality (HR: 1.17, 95% CI: 1.07–1.28. Participants with smaller Δage and decelerated epigenetic aging over time had the lowest risks of cancer incidence (P = 0.003 and mortality (P = 0.02. Δage was associated with cancer incidence in a ‘J-shaped’ manner for subjects examined pre-2003, and with cancer mortality in a time-varying manner. We conclude that blood epigenetic age may mirror epigenetic abnormalities related to cancer development, potentially serving as a minimally invasive biomarker for cancer early detection.
Kudryavtseva, Anna V; Krasnov, George S; Dmitriev, Alexey A; Alekseev, Boris Y; Kardymon, Olga L; Sadritdinova, Asiya F; Fedorova, Maria S; Pokrovsky, Anatoly V; Melnikova, Nataliya V; Kaprin, Andrey D; Moskalev, Alexey A; Snezhkina, Anastasiya V
Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.
Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Moadel, Alyson; Kaur, Gurpreet; Levitt, Joshua; Girda, Eugenia; Goldfinger, Mendel; Goldberg, Gary L; Einstein, Mark H
Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, Page of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. II.
Noorda, E. M.; Somers, R.; van Leeuwen, F. E.; Vulsma, T.; Behrendt, H.
The aim of this study was to assess the long-term effects of cancer treatments on adult height and age at menarche in survivors of various types of childhood cancer. 285 childhood cancer survivors (161 men and 124 women), at least 18 years old and having been off treatment for at least 5 years, were
Gosain, Rahul; Pollock, YaoYao; Jain, Dharamvir
Aging poses an unique opportunity to study cancer biology and treatment in older adults. Breast cancer is often studied in young women; however, much investigation remains to be done on breast cancer in our expanding elderly population. Diagnostic and management strategies applicable to younger patients cannot be empirically used to manage older breast cancer patients. Lack of evidence-based data continues to be the major impediment toward delivery of personalized cancer care to elderly breast cancer patients. This article reviews the relevant literature on management of curable breast cancer in the elderly, the role of geriatric assessment, complex treatment decision making within the context of patient's expected life expectancy, comorbidities, physical function, socioeconomic status, barriers to health care delivery, goals of treatment, and therapy-related side effects. Continuing efforts for enrolling elderly breast cancer patients in contemporary clinical trials, and thus improving age-appropriate care, are emphasized.
Vostakolaei, F.A.; Broeders, M.J.M.; Rostami, N.; Dijck, J.A. van; Feuth, T.; Kiemeney, L.A.L.M.; Verbeek, A.L.M.
Background. Tumour characteristics are the most important prognostic factors in breast cancer. Patient-related factors such as young age at diagnosis, obesity, and smoking behaviour may also modify disease outcome. Due to the absence of a unique definition for "young age breast cancer" and the
Kimberly M. Arnold; Flynn, Nicole J.; Sims-Mourtada, Jennifer
Obesity rates within the United States are on the rise. Obesity is a known risk factor for various diseases, including cancer. Numerous studies have linked obesity to the incidence and treatment outcomes of breast cancer. However, the risk of obesity may vary between breast cancer subtypes and different racial or age groups. In this article, we review the literature regarding the impact of obesity on incidence and response for different subtypes of breast cancer within different population gr...
Lynch, H T; Albano, W A; Layton, M A; Kimberling, W.J.; Lynch, J. F.
Hereditary breast cancer shows a distinctive natural history characterised by an earlier age of onset, excess bilaterality, vertical transmission, heterogeneous tumour associations, and improved survival when compared to its sporadic counterpart. To date, very little attention has been given to interrelationships between breast cancer risk factors and genetics. In the general population, early age of first term pregnancy has been generally accepted as protective against breast cancer. In addi...
Henderson, Tara O; Ness, Kirsten K; Cohen, Harvey Jay
There are almost 14-million cancer survivors in the United States and the population is growing. Almost two-thirds of these survivors are age 65 or older. Given this, it is imperative to understand the impact of cancer and its therapies on the aging process. Childhood cancer survivors, diagnosed with cancer at age 21 or younger, particularly females, have rates of frailty similar to rates in older adults. This phenomenon appears to start early, suggesting an aging phenotype. Frailty among childhood cancer survivors increases risk for chronic disease and mortality. Adults diagnosed with cancer are faced with the effects of cancer and its therapies compounded by the issues of multiple morbidities that occur with the typical aging process. Intervention studies to date have focused on smoking cessation, diet, and exercise, as well as improving rates of late effects surveillance in childhood cancer survivors. No intervention studies have specifically addressed the issue of frailty or multiple morbidities in cancer survivors. Concerted efforts must continue to create and disseminate survivorship care plans to all cancer survivors.
Blagosklonny, Mikhail V
Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are involved in both cancer and aging). In cancer, intrinsic and acquired resistance, tumor heterogeneity, adaptation, and genetic instability of cancer cells all hinder cancer-directed therapy. But for anti-aging applications, these hurdles are irrelevant. For example, since anti-aging interventions should be aimed at normal postmitotic cells, no selection for resistance is expected. At low doses, certain agents may decelerate aging and age-related diseases. Importantly, deceleration of aging can in turn postpone cancer, which is an age-related disease.
Lin, Qiong; Wagner, Wolfgang
Aging is associated with highly reproducible DNA methylation (DNAm) changes, which may contribute to higher prevalence of malignant diseases in the elderly. In this study, we analyzed epigenetic aging signatures in 5,621 DNAm profiles of 25 cancer types from The Cancer Genome Atlas (TCGA). Overall, age-associated DNAm patterns hardly reflect chronological age of cancer patients, but they are coherently modified in a non-stochastic manner, particularly at CpGs that become hypermethylated upon aging in non-malignant tissues. This coordinated regulation in epigenetic aging signatures can therefore be used for aberrant epigenetic age-predictions, which facilitate disease stratification. For example, in acute myeloid leukemia (AML) higher epigenetic age-predictions are associated with increased incidence of mutations in RUNX1, WT1, and IDH2, whereas mutations in TET2, TP53, and PML-PARA translocation are more frequent in younger age-predictions. Furthermore, epigenetic aging signatures correlate with overall survival in several types of cancer (such as lower grade glioma, glioblastoma multiforme, esophageal carcinoma, chromophobe renal cell carcinoma, cutaneous melanoma, lung squamous cell carcinoma, and neuroendocrine neoplasms). In conclusion, age-associated DNAm patterns in cancer are not related to chronological age of the patient, but they are coordinately regulated, particularly at CpGs that become hypermethylated in normal aging. Furthermore, the apparent epigenetic age-predictions correlate with clinical parameters and overall survival in several types of cancer, indicating that regulation of DNAm patterns in age-associated CpGs is relevant for cancer development.
Full Text Available Aging is associated with highly reproducible DNA methylation (DNAm changes, which may contribute to higher prevalence of malignant diseases in the elderly. In this study, we analyzed epigenetic aging signatures in 5,621 DNAm profiles of 25 cancer types from The Cancer Genome Atlas (TCGA. Overall, age-associated DNAm patterns hardly reflect chronological age of cancer patients, but they are coherently modified in a non-stochastic manner, particularly at CpGs that become hypermethylated upon aging in non-malignant tissues. This coordinated regulation in epigenetic aging signatures can therefore be used for aberrant epigenetic age-predictions, which facilitate disease stratification. For example, in acute myeloid leukemia (AML higher epigenetic age-predictions are associated with increased incidence of mutations in RUNX1, WT1, and IDH2, whereas mutations in TET2, TP53, and PML-PARA translocation are more frequent in younger age-predictions. Furthermore, epigenetic aging signatures correlate with overall survival in several types of cancer (such as lower grade glioma, glioblastoma multiforme, esophageal carcinoma, chromophobe renal cell carcinoma, cutaneous melanoma, lung squamous cell carcinoma, and neuroendocrine neoplasms. In conclusion, age-associated DNAm patterns in cancer are not related to chronological age of the patient, but they are coordinately regulated, particularly at CpGs that become hypermethylated in normal aging. Furthermore, the apparent epigenetic age-predictions correlate with clinical parameters and overall survival in several types of cancer, indicating that regulation of DNAm patterns in age-associated CpGs is relevant for cancer development.
Liu, Li; Chang, Yung; Yang, Tao; Noren, David P; Long, Byron; Kornblau, Steven; Qutub, Amina; Ye, Jieping
Despite wide applications of high-throughput biotechnologies in cancer research, many biomarkers discovered by exploring large-scale omics data do not provide satisfactory performance when used to predict cancer treatment outcomes. This problem is partly due to the overlooking of functional implications of molecular markers. Here, we present a novel computational method that uses evolutionary conservation as prior knowledge to discover bona fide biomarkers. Evolutionary selection at the molecular level is nature's test on functional consequences of genetic elements. By prioritizing genes that show significant statistical association and high functional impact, our new method reduces the chances of including spurious markers in the predictive model. When applied to predicting therapeutic responses for patients with acute myeloid leukemia and to predicting metastasis for patients with prostate cancers, the new method gave rise to evolution-informed models that enjoyed low complexity and high accuracy. The identified genetic markers also have significant implications in tumor progression and embrace potential drug targets. Because evolutionary conservation can be estimated as a gene-specific, position-specific, or allele-specific parameter on the nucleotide level and on the protein level, this new method can be extended to apply to miscellaneous "omics" data to accelerate biomarker discoveries.
Sexual selection theory models evolution of sexual signals and preferences using simple life histories. However, life-history models predict that males benefit from increasing sexual investment approaching old age, producing age-dependent sexual traits. Age-dependent traits require time and energy to grow, and will not fully mature before individuals enter mating competition. Early evolutionary stages pose several problems for these traits. Age-dependent traits suffer from strong viability selection and gain little benefit from mate choice when rare. Few males will grow large traits, and they will rarely encounter choosy females. The evolutionary origins of age-dependent traits therefore remain unclear. I used numerical simulations to analyze evolution of preferences, condition (viability) and traits in an age-structured population. Traits in the model depended on age and condition (“good genes”) in a population with no genetic drift. I asked (1) if age-dependent indicator traits and their preferences can originate depending on the strength of selection and the size of the trait; (2) which mode of development (age-dependent versus age-independent) eventually predominates when both modes occur in the population; and (3) if age-independent traits can invade a population with age-dependent traits. Age-dependent traits evolve under weaker selection and at smaller sizes than age-independent traits. This result held in isolation and when the types co-occur. Evolution of age-independent traits depends only on trait size, whereas evolution of age-dependent traits depends on both strength of selection and growth rate. Invasion of age-independence into populations with established traits followed a similar pattern with age-dependence predominating at small trait sizes. I suggest that reduced adult mortality facilitates sexual selection by favoring the evolution of age-dependent sexual signals under weak selection. PMID:24392289
With the continuing shift of cancer care to community-based care the necessity to develop programs that will enable the family to meet patients' needs for support and assistance is of paramount importance...
With the continuing shift of cancer care to community-based care the necessity to develop programs that will enable the family to meet patients' needs for support and assistance is of paramount importance...
Levi, Fabio; Randimbison, Lalao; Blanc-Moya, Rafael; La Vecchia, Carlo
Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.
Patrick M Loerch
Full Text Available Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4. However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.
, there is need to define the epidemiological pattern of breast cancer patients in the Niger delta; assessing their age distribution and histological types towards improved health care planning. OBJECTIVE: To determine the pattern of ...
Ojha, Rohit P; Jackson, Bradford E; Tota, Joseph E; Offutt-Powell, Tabatha N; Hudson, Melissa M; Gurney, James G
Pediatric and young adult (PAYA) cancer survivors may have an earlier onset of chronic diseases compared with the general population. We compared the age at cervical cancer diagnosis between PAYA cancer survivors and females in the general US population. We used longitudinal data from 9 population-based registries of the Surveillance, Epidemiology, and End Results program collected between 1973 and 2010. PAYA cancer survivors were females diagnosed with any cancer before age 30 years, survived at least 5 years post-diagnosis, and were subsequently diagnosed with invasive cervical cancer (n=46). The general US population comprised females who were diagnosed with invasive cervical cancer as the primary malignancy (n=26,956). We estimated the difference in median age at diagnosis (ß₅₀) and bootstrap 95% confidence limits (CL) of invasive cervical cancer after adjustment for year of diagnosis and race. The median age at diagnosis of invasive cervical cancer was 33 years for female PAYA cancer survivors and 40 years for females in the general US population (ß50=-7.0, 95% CL: -11, -3.2). Similar differences were observed across subgroups of stage and histologic subtype of invasive cervical cancer. Our results suggest that PAYA cancer survivors are diagnosed with invasive cervical cancer at a substantially younger age compared with females without a prior cancer diagnosis in the general US population. This issue warrants further study, and could have implications for determining age at initiation or frequency of cervical cancer screening if younger age at diagnosis is attributable to an underlying biological phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.
Chaisson, Lola Judith
In this enthralling and illuminating book, Eric Chaisson, author of the classic work Cosmic Dawn, synthesizes current scientific thinking regarding the origin and evolution of the universe. How did everything around us-the air, the land, the sea, and the stars-come to be? What is the source of order, form, and structure characterizing all material things? Drawing on recent breakthroughs in astrophysics and biochemistry, Chaisson explores the development of the most microscopic and the most immense aspects of our universe, including the idea that all objects-from quarks and quas
Full Text Available Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.. In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine. We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.
Arruebo, Manuel [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Vilaboa, Nuria [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046 (Spain); Sáez-Gutierrez, Berta; Lambea, Julio; Tres, Alejandro [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); Servicio de Oncología Médica, Hospital Clínico Universitario Lozano Blesa, Avda. San Juan Bosco 50009, Zaragoza (Spain); Instituto Aragonés de Ciencias de la Salud (I-CS), Avda. Gómez Laguna, 25, Zaragoza 50009 (Spain); Valladares, Mónica [Lonza Biologics Porriño, A relva s/n, Porriño (Pontevedra) 36410 (Spain); González-Fernández, África, E-mail: email@example.com [Immunology Department, Biomedical Research Center (CINBIO), University of Vigo, Campus Lagoas Marcosende, Vigo (Pontevedra) 36310 (Spain)
Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.
Pesenti, Sébastien; Blondel, Benjamin; Peltier, Emilie; Viehweger, Elke; Pomero, Vincent; Authier, Guillaume; Fuentes, Stéphane; Jouve, Jean-Luc
AIM To describe, using gait analysis, the development of spinal motion in the growing child. METHODS Thirty-six healthy children aged from 3 to 16 years old were included in this study for a gait analysis (9 m-walk). Various kinematic parameters were recorded and analyzed such as thoracic angle (TA), lumbar angle (LA) and sagittal vertical axis (SVA). The kinetic parameters were the net reaction moments (N.m/kg) at the thoracolumbar and lumbosacral junctions. RESULTS TA and LA curves were not statistically correlated to the age (respectively, P = 0.32 and P = 0.41). SVA increased significantly with age (P < 0.001). Moments in sagittal plane at the lumbosacral junction were statistically correlated to the age (P = 0.003), underlining the fact that sagittal mechanical constraints at the lumbosacral junction increase with age. Moments in transversal plane at the thoracolumbar and lumbosacral junctions were statistically correlated to the age (P = 0.0002 and P = 0.0006), revealing that transversal mechanical constraints decrease with age. CONCLUSION The kinetic analysis showed that during growth, a decrease of torsional constraint occurs while an increase of sagittal constraint is observed. These changes in spine biomechanics are related to the crucial role of the trunk for bipedalism acquisition, allowing stabilization despite lower limbs immaturity. With the acquisition of mature gait, the spine will mainly undergo constraints in the sagittal plane. PMID:28361018
Kawasaki, Takeshi; Tanaka, Hajime
When a liquid is rapidly quenched to a temperature below the glass-transition point, it is driven out of equilibrium; it then slowly relaxes to a (quasi)equilibrium state. This slow relaxation process is called aging. By definition, any glasses are inevitably in the process of aging and actually slowly evolving with time. Thus the study of aging phenomena is of fundamental importance for understanding not only the nonequilibrium nature of the glass transition, but also the stability of glassy materials. Here we consider aging after a rather shallow quench, for which a system is still able to reach (metastable) equilibrium. By using polydisperse colloidal liquids as a model, we show the validity of dynamical scaling that there is only one relevant length scale not only for a quasiequilibrium supercooled state but also for a nonequilibrium process of aging, which is reminiscent of dynamical critical phenomena. Our finding indicates that the aging toward (metastable) equilibrium may be regarded as the growth process of critical-like fluctuations of static order associated with low-free-energy configurations, further suggesting that this ordering is the origin of cooperative slow dynamics in the systems studied. The generality of this statement for other glass-forming systems remains for a future study.
Savard, Josée; Ivers, Hans
This population-based longitudinal study assessed the prevalence, incidence and evolution of fear of cancer recurrence (FCR) and its relationship with some cancer characteristics in a large sample of patients with mixed cancer sites over an 18-month period. A total of 962 patients scheduled to undergo surgery for cancer completed the severity subscale of the Fear of Cancer Recurrence Inventory at the peri-operative period and 2, 6, 10, 14, and 18 months later. Results indicated that FCR levels were highest at baseline, significantly decreased at the 2-month evaluation and then remained stable throughout the remainder of the study. Between 44.0% and 56.1% of the patients reported a clinical level of FCR during the study, with the highest proportion found at baseline. A relationship was obtained between greater FCR and some indices of poorer prognosis (i.e., diagnosis of head and neck cancer, more advanced cancer, cancer recurrence), as well as with the administration of adjuvant treatment, particularly chemotherapy. Patients with clinical FCR at baseline continued to display clinical levels at all subsequent time points. The incidence rate of clinical levels of FCR was 51.7% overall. FCR is a highly prevalent and persistent condition. More efforts should be devoted to developing effective treatments for patients with clinical levels of FCR. Early interventions appear particularly relevant in order to prevent the problem from becoming chronic, although patients' acceptability and the efficacy of this approach remain to be demonstrated. Copyright © 2013 Elsevier Inc. All rights reserved.
McLaughlin, W. I.
A systems analysis of the future evolution of man can be conducted by analyzing the biological material of the galaxy into three subsystems: man, intelligent machines, and intelligent extraterrestrial organisms. A binomial interpretation is applied to this system wherein each of the subsystems is assigned a designation of success or failure. For man the two alternatives are, respectively, 'decline' or 'flourish', for machine they are 'become intelligent' or 'stay dumb', while for extraterrestrial intelligence the dichotomy is that of 'existence' or 'nonexistence'. The choices for each of three subsystems yield a total of eight possible states for the system. The relative lack of integration between brain components makes man a weak evolutionary contestant compared to machines. It is judged that machines should become dominant on earth within 100 years, probably by means of continuing development of existing man-machine systems. Advanced forms of extraterrestrial intelligence may exist but are too difficult to observe. The prospects for communication with extraterrestrial intelligence are reviewed.
Mclaughlin, W. I.
A systems analysis of the future evolution of man can be conducted by analyzing the biological material of the galaxy into three subsystems: man, intelligent machines, and intelligent extraterrestrial organisms. A binomial interpretation is applied to this system wherein each of the subsystems is assigned a designation of success or failure. For man the two alternatives are, respectively, 'decline' or 'flourish', for machine they are 'become intelligent' or 'stay dumb', while for extraterrestrial intelligence the dichotomy is that of 'existence' or 'nonexistence'. The choices for each of three subsystems yield a total of eight possible states for the system. The relative lack of integration between brain components makes man a weak evolutionary contestant compared to machines. It is judged that machines should become dominant on earth within 100 years, probably by means of continuing development of existing man-machine systems. Advanced forms of extraterrestrial intelligence may exist but are too difficult to observe. The prospects for communication with extraterrestrial intelligence are reviewed.
. 1. Ageing as an epigenetic disease. There is now substantial evidence that many components of the normal ageing syndrome are due to the accumulation of errors in DNA methylation (see Fraga and Esteller 2007). Some of the first evidence ...
Ayvaci, Mehmet U S; Alagoz, Oguzhan; Chhatwal, Jagpreet; Munoz del Rio, Alejandro; Sickles, Edward A; Nassif, Houssam; Kerlikowske, Karla; Burnside, Elizabeth S
Increasing focus on potentially unnecessary diagnosis and treatment of certain breast cancers prompted our investigation of whether clinical and mammographic features predictive of invasive breast cancer versus ductal carcinoma in situ (DCIS) differ by age. We analyzed 1,475 malignant breast biopsies, 1,063 invasive and 412 DCIS, from 35,871 prospectively collected consecutive diagnostic mammograms interpreted at University of California, San Francisco between 1/6/1997 and 6/29/2007. We constructed three logistic regression models to predict the probability of invasive cancer versus DCIS for the following groups: women ≥ 65 (older group), women 50-64 (middle age group), and women group). We identified significant predictors and measured the performance in all models using area under the receiver operating characteristic curve (AUC). The models for older and the middle age groups performed significantly better than the model for younger group (AUC = 0.848 vs, 0.778; p = 0.049 and AUC = 0.851 vs, 0.778; p = 0.022, respectively). Palpability and principal mammographic finding were significant predictors in distinguishing invasive from DCIS in all age groups. Family history of breast cancer, mass shape and mass margins were significant positive predictors of invasive cancer in the older group whereas calcification distribution was a negative predictor of invasive cancer (i.e. predicted DCIS). In the middle age group--mass margins, and in the younger group--mass size were positive predictors of invasive cancer. Clinical and mammographic finding features predict invasive breast cancer versus DCIS better in older women than younger women. Specific predictive variables differ based on age.
Flores, Lisa C; Ortiz, Melanie; Dube, Sara; Hubbard, Gene B; Lee, Shuko; Salmon, Adam; Zhang, Yiqiang; Ikeno, Yuji
The Free Radical or Oxidative Stress Theory of Aging is one of the most popular theories in aging research and has been extensively studied over the past several decades. However, recent evidence using transgenic/knockout mice that overexpress or down-regulate antioxidant enzymes challenge the veracity of this theory since the animals show no increase or decrease in lifespan. These results seriously call into question the role of oxidative damage/stress in the aging process in mammals. Therefore, the theory requires significant modifications if we are to understand the relationship between aging and the regulation of oxidative stress. Our laboratory has been examining the impacts of thioredoxins (Trxs), in the cytosol and mitochondria, on aging and age-related diseases. Our data from mice that are either up-regulating or down-regulating Trx in different cellular compartments, that is, the cytosol or mitochondria, could shed some light on the role of oxidative stress and its pathophysiological effects. The results generated from our lab and others may indicate that: 1) changes in oxidative stress and the redox state in the cytosol, mitochondria or nucleus might play different roles in the aging process; 2) the role of oxidative stress and redox state could have different pathophysiological consequences in different tissues/cells, for example, mitotic vs. post-mitotic; 3) oxidative stress could have different pathophysiological impacts in young and old animals; and 4) the pathophysiological roles of oxidative stress and redox state could be controlled through changes in redox-sensitive signaling, which could have more diverse effects on pathophysiology than the accumulation of oxidative damage to various molecules. To critically test the role of oxidative stress on aging and age-related diseases, further study is required using animal models that regulate oxidative stress levels differently in each cellular compartment, each tissue/organ, and/or at different stages
The percentage of elderly people with associated age-related health deterioration, including cancer, has been increasing for decades. Among age-related diseases, the incidence of cancer has grown substantially, in part because of the overlap of some molecular pathways between cancer and aging. Studies with model organisms suggest that aging and age-related conditions are manipulable processes that can be modified by both genetic and environmental factors, including dietary habits. Variations in genetic backgrounds likely lead to differential responses to dietary changes and account for some of the inconsistencies found in the literature. The intricacies of the aging process, coupled with the interrelational role of bioactive food components on gene expression, make this review a complex undertaking. Nevertheless, intriguing evidence suggests that dietary habits can manipulate the aging process and/or its consequences and potentially may have unprecedented health benefits. The present review focuses on 4 cellular events: telomerase activity, bioenergetics, DNA repair, and oxidative stress. These processes are linked to both aging and cancer risk, and their alteration in animal models by selected food components is evident. © 2016 American Society for Nutrition.
Mar 2, 1991 ... months for patients aged 55 - 64 years (P= 0,08; Cox model). The median survival improves again to 24,6 months ... in the very old (aged 75 - 84 years) (P = 0,52; Cox model). The more favourable prognosis in the elderly ... po Box 667, Pretoria, 0001 RSA. Accepted 18 Ocr 1990. tic breast cancer seen in ...
J.-O. Andressoo (Jaan-Olle)
textabstractIt is widely although not uniformly accepted that ageing is caused by time-dependent accumulation of damage. A side effect of ageing is an increased risk of developing a disease, such as cancer. Yet, the primary molecular target of damage accumulation has remained obscure. A clue has
The data on 217 elderly (aged ≥ 65 years) and 209 middleaged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more ...
Abstract. The issue of the illicit use and trafficking in drugs has been of great concern to mankind for ages. Over the years, the world has developed a consensus on the need to adopt a global approach to the problem. This paper attempts to review the various legal instruments adopted at the international level for the ...
Owusu, Cynthia; Berger, Nathan A
Cancer care at the extremes of life, in the young and the old, is characterized by unique issues associated with pediatrics and geriatric medicine, accentuated by the special vulnerabilities of these groups. In response to these needs, the field of pediatric oncology has been well honed to deal with the special problems associated with juvenile cancer patients. While most adult oncologists consider themselves well prepared to deal with older cancer patients, the current expansion of the geriatric population – their variable levels of fitness, frailty and vulnerability, the fact that cancer is primarily a disease of older adults, the significant expansion of agents and approaches to treat cancer, as well as their resultant toxicities and complications – has led to the development of specialized geriatric oncologists. Moreover, the special characteristics and needs of these patients have led to the evolution of new guidelines for evaluation, management and the conduct of research in older patients with cancer. PMID:25642321
Full Text Available Telomeres are progressively eroded during repeated rounds of cell division due to the end replication problem but also undergo additional more substantial stochastic shortening events. In most cases, shortened telomeres induce a cell-cycle arrest or trigger apoptosis, although for those cells that bypass such signals during tumour progression, a critical length threshold is reached at which telomere dysfunction may ensue. Dysfunction of the telomere nucleoprotein complex can expose free chromosome ends to the DNA double-strand break (DSB repair machinery, leading to telomere fusion with both telomeric and non-telomeric loci. The consequences of telomere fusions in promoting genome instability have long been appreciated through the breakage–fusion–bridge (BFB cycle mechanism, although recent studies using high-throughput sequencing technologies have uncovered evidence of involvement in a wider spectrum of genomic rearrangements including chromothripsis. A critical step in cancer progression is the transition of a clone to immortality, through the stabilisation of the telomere repeat array. This can be achieved via the reactivation of telomerase, or the induction of the alternative lengthening of telomeres (ALT pathway. Whilst telomere dysfunction may promote genome instability and tumour progression, by limiting the replicative potential of a cell and enforcing senescence, telomere shortening can act as a tumour suppressor mechanism. However, the burden of senescent cells has also been implicated as a driver of ageing and age-related pathology, and in the promotion of cancer through inflammatory signalling. Considering the critical role of telomere length in governing cancer biology, we review questions related to the prognostic value of studying the dynamics of telomere shortening and fusion, and discuss mechanisms and consequences of telomere-induced genome rearrangements.
Bhikhari P. Tharu
Full Text Available Background The objective of this study was to analyze the time trend for lung cancer mortality in the population of the USA by 5 years based on most recent available data namely to 2010. The knowledge of the mortality rates in the temporal trends is necessary to understand cancer burden.Methods Bayesian Age-Period-Cohort model was fitted using Poisson regression with histogram smoothing prior to decompose mortality rates based on age at death, period at death, and birth-cohort.Results Mortality rates from lung cancer increased more rapidly from age 52 years. It ended up to 325 deaths annually for 82 years on average. The mortality of younger cohorts was lower than older cohorts. The risk of lung cancer was lowered from period 1993 to recent periods.Conclusions The fitted Bayesian Age-Period-Cohort model with histogram smoothing prior is capable of explaining mortality rate of lung cancer. The reduction in carcinogens in cigarettes and increase in smoking cessation from around 1960 might led to decreasing trend of lung cancer mortality after calendar period 1993.
Previously, anatomists considered paranasal sinuses as a mysterious region of the human skull. Historically, paranasal sinuses were first identified by ancient Egyptians and later, by Greek physicians. After a long period of no remarkable improvement in the understanding of anatomy during the Middle Ages, anatomists of the Renaissance period-Leonardo da Vinci and Vesalius-made their own contribution. Nathaniel Highmore's name is also associated with the anatomy of paranasal sinuses as he was first to describe the maxillary sinus. PMID:24386595
McClure, Melissa; Bailey, J.; Beck, T.; Boogert, A.; Brown, W.; Caselli, P.; Chiar, J.; Egami, E.; Fraser, H.; Garrod, R.; Gordon, K.; Ioppolo, S.; Jimenez-Serra, I.; Jorgensen, J.; Kristensen, L.; Linnartz, H.; McCoustra, M.; Murillo, N.; Noble, J.; Oberg, K.; Palumbo, M.; Pendleton, Y.; Pontoppidan, K.; Van Dishoeck, E.; Viti, S.
Icy grain mantles are the main reservoir for volatile elements in star-forming regions across the Universe, as well as the formation site of pre-biotic complex organic molecules (COMs) seen in our Solar System. We propose to trace the evolution of pristine and complex ice chemistry in a representative low-mass star-forming region through observations of a: pre-stellar core, Class 0 protostar, Class I protostar, and protoplanetary disk. Comparing high spectral resolution (R 1500-3000) and sensitivity (S/N 100-300) observations from 3 to 15 um to template spectra, we will map the spatial distribution of ices down to 20-50 AU in these targets to identify when, and at what visual extinction, the formation of each ice species begins. Such high-resolution spectra will allow us to search for new COMs, as well as distinguish between different ice morphologies,thermal histories, and mixing environments. The analysis of these data will result in science products beneficial to Cycle 2 proposers. A newly updated public laboratory ice database will provide feature identifications for all of the expected ices, while a chemical model fit to the observed ice abundances will be released publically as a grid, with varied metallicity and UV fields to simulate other environments. We will create improved algorithms to extract NIRCAM WFSS spectra in crowded fields with extended sources as well as optimize the defringing of MIRI LRS spectra in order to recover broad spectral features. We anticipate that these resources will be particularly useful for astrochemistry and spectroscopy of fainter, extended targets like star forming regions of the SMC/LMC or more distant galaxies.
Full Text Available Background & aim: Breast, cervical, and colorectal cancers are the leading causes of mortality among women, the incidence rate of which has an upward trend with advancing age. Although cost-effective, easy, and available screening programs can help control these types of cancer in their early stages, it seems that cancer screening programs have not been implemented effectively. In this study, we investigated the rate of cancer screening practice in middle-aged women and explained the influential factors. Methods: This cross-sectional study with a sequential mixed method approach was conducted on 483 middle-age women selected through cluster random sampling in Yazd, Iran. Data were obtained by a research made questionnaire and analyzed with descriptive statistics and performing Pearson product-moment correlation, Student’s t-test, and One-way ANOVA tests, using SPSS version 16. In the second phase of the study, qualitative, semi-structured interviews were performed and data were analyzed through content analysis. Results: The majority of the subjects had never been screened for cancer through mammogram (87.7%, Pap test (64.2%, or fecal occult blood test (FOBT (89.8%. Educational level, employment status, perceived adequacy of income, perceived health status, and the number of children were significantly associated with breast and colon cancer screening practice. Qualitative data showed that lack of knowledge, the cost of screening exams, lack of financial independence, negligence of spouse, fear of cancer, embarrassment, and belief in destiny were the main reasons for non-adherence to cancer screening tests. In addition, knowledge and observing cancer in acquaintances and relatives were the main motivators of cancer screening. Conclusion: Middle-aged housewives, as well as women with low educational level and income were the most vulnerable groups, who did not adhere to cancer screening. Planning and management of cancer preventive programs and
Adsersen, Mathilde; Thygesen, Lau Caspar; Jensen, Anders Bonde
/units. Patients with brain cancer were more often admitted to hospices, whereas patients with prostate cancer were more often admitted to hospital-based palliative care teams/units. CONCLUSION: It is unlikely that the variations in relation to sex, age and cancer diagnoses can be fully explained by differences...... to investigate whether cancer patients' admittance to SPC in Denmark varied in relation to sex, age and diagnosis, and whether the patterns differed by type of institution (hospital-based palliative care team/unit, hospice, or both). METHODS: This was a register-based study of adult patients living in Denmark...... who died from cancer in 2010-2012. Data sources were the Danish Palliative Care Database, Danish Register of Causes of Death and Danish Cancer Registry. The associations between the explanatory variables (sex, age, diagnosis) and admittance to SPC were investigated using logistic regression. RESULTS...
Riquet, M; Legras, A; Pricopi, C; Badia, A; Arame, A; Dujon, A; Foucault, C; Le Pimpec Barthes, F; Fabre, E
Management of non-small cell lung cancer (NSCLC) is getting better and results on long-term survival have improved. We reviewed the modifications observed in surgery over a 32-year time period. Data of 6105 patients who underwent surgery from 1979 to 2010 were analyzed over three equal time-periods: gender, age, type of surgery, histology, pTNM, tobacco addiction, comorbidity and time periods. Age, number of females and high-risk patients with comorbidity (including the history of a previous cancer) increased with time periods. Number of exploratory thoracotomy (7.7 % to 1.6 %) and pneumonectomy (48 % to 18 %) decreased. Number of wedge resection (0.5 % to 6 %) and lobectomy (42 % to 64 %) increased. Rates of the other types of resection were unchanged. Neoadjuvant treatments accounted for more than 20 % of patients in the last time period. Postoperative mortality (4 %) did not vary but non-lethal complication rates increased (16.9 % to 27.7 %). Global 5-year survival rates dramatically increased with time going from 37.4 % to 49.8 % (P<10(-6)). Survival improvement was observed in the different components of the pTNM and whatever the type of treatment. However, survival was affected by increasing age and multiplication of comorbidities but without impairing the general better outcome trend. NSCLC itself, its diagnostic and therapeutic management, and patient's characteristics evolved with time. Survival improved in most studied prognosis factors. Time period factor was of paramount importance and might be included in research dealing with NSCLC. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Iacobuzio-Donahue, Christine A
Pancreatic cancer is a disease caused by the accumulation of genetic alterations in specific genes. Elucidation of the human genome sequence, in conjunction with technical advances in the ability to perform whole exome sequencing, have provided new insight into the mutational spectra characteristic of this lethal tumour type. Most recently, exomic sequencing has been used to clarify the clonal evolution of pancreatic cancer as well as provide time estimates of pancreatic carcinogenesis, indicating that a long window of opportunity may exist for early detection of this disease while in the curative stage. Moving forward, these mutational analyses indicate potential targets for personalised diagnostic and therapeutic intervention as well as the optimal timing for intervention based on the natural history of pancreatic carcinogenesis and progression. PMID:21749982
Wensink, Maarten Jan; Caswell, Hal; Baudisch, Annette
The evolution of senescence is often explained by arguing that, in nature, few individuals survive to be old and hence it is evolutionarily unimportant what happens to organisms when they are old. A corollary to this idea is that extrinsically imposed mortality, because it reduces the chance of surviving to be old, favors the evolution of senescence. We show that these ideas, although widespread, are incorrect. Selection leading to senescence does not depend directly on survival to old age, b...
together. Phylogenetic analysis For phylogenetic analysis , we selected 21,285 variant sites with no missing information for all samples ( read ...AWARD NUMBER: W81XWH-15-1-0243 TITLE: Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution 5b. GRANT NUMBER 5c. PROGRAM
van Weert, J.C.M.; Bolle, S.; Muusses, L.D.; Stephanidis, C.; Antona, M.
This study investigates age and age-related differences in Internet usage of 952 cancer patients treated with chemotherapy. Older patients (> 65 years) reported significantly less Internet usage to find treatment-related information than younger ones (< 65 years). Still, 40.1% of the older patients
Cerella, Claudia; Grandjenette, Cindy; Dicato, Mario; Diederich, Marc
Cancer and aging are two similar processes representing the final outcome of timedependent accumulation of various irreversible dysfunctions, mainly caused by stress-induced DNA and cellular damages. Apoptosis and senescence are two types of cellular response to damages that are altered in both cancer and aging, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the ability of the cells to trigger apoptosis and senescence. In contrast, in aging tissues, there is an increased accumulation of senescent cells, and the nature of apoptosis deregulation varies depending on the tissue. Thus, the prevailing model suggests that apoptosis and cellular senescence function as two essential tumor-suppressor mechanisms, ensuring the health of the individual during early and reproductive stages of life, but become detrimental and promote aging later in life. The recent discovery that various anticancer agents, including canonical inducers of apoptosis, act also as inducers of cellular senescence indicates that pro-senescence strategies may have applications in cancer prevention therapy. Therefore, dissection of the mechanisms mediating the delicate balance between apoptosis and cellular senescence will be beneficial in the therapeutic exploitation of both processes in the development of future anticancer and anti-aging strategies, including minimizing the side effects of such strategies. Here, we provide an overview of the roles of apoptosis and cellular senescence in cancer and aging.
Full Text Available The world population is ageing, with the proportion of older people (65+ years expected to reach 21% in 2050 and to exceed the number of younger people (aged 15 or less for the first time in history. Because cancer is particularly a chronic disease of older people, a large increase in the number of elderly patients with cancer is anticipated. The estimated number of new cancer cases worldwide among people over 65 is expected to grow from about 6 million in 2008 to more than 11 million during the coming decade. By 2030, individuals over 65 are expected to account for 70% of all cancer patients in the Western world.Along with the increase in oncology patients, the number of older people caring for their ill spouses or other relatives is also growing, with the ensuing toll on these caregivers causing major concern, especially in western countries.In different societies the characteristics of family caregiver stressors, cultural norms concerning care giving, and the availability of support have a huge impact on those providing care. Any study of older caregivers of older cancer patients requires an integrative evaluation of ageing that takes into account cultural, social, psychological, and behavioral variables.This review proposes a critical discussion of the multidimensionality of the caregiving and of the impact that age, culture and gender have on it.
Kozielski, Jerzy; Kaczmarczyk, Grzegorz; Porębska, Irena; Szmygin-Milanowska, Katarzyna; Gołecki, Marcin
In the paper clinical cases of individuals diagnosed with lung cancer below the age of 40 years have been analyzed. 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. 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.
Romero-Vargas, M E; Flores-Cortés, M; Valera, Z; Gómez-Bravo, M A; Barrera-Pulido, L; Pareja-Ciuró, F; Serrano Díez-Canedo, J; García, I; Bernardos, A
To investigate the incidence, time of appearance, treatment, and evolution of tumors appearing in liver transplant recipients at our hospital. We undertook a retrospective analysis of our series of liver transplants between 1990 and 2005. Patients who died during the immediate postoperative period were excluded. Of the 515 patients, 25 died during the immediate postoperative period and therefore had no occasion to develop neoplasms. Of the remaining 490, 32 developed cancers (6.5%). The average age was 55.4 +/- 7.17 years. The reasons for transplant were alcoholic cirrhosis (n = 15), hepatitis C virus (2), hepatitis B virus (n = 1), alcoholic and viral cirrhosis (n = 7), primary biliary cirrhosis (n = 1), and cryptogenic cirrhosis (n = 1). Four patients developed multiple neoplasms. Most of the tumors were cutaneous: nine basal cell and six squamous cell carcinomas. Other locations were the lung, urothelium, stomach, thyroid, and brain. Eight patients presented metastasis at the time of diagnosis. The average tumor-free period was 3.36 years. Nine patients died as a result of the tumor. Patients with a liver transplant have a high risk of developing cancers as a result of the immunosuppression treatment, which is lifelong. Nevertheless, other factors can be involved, such as infection by cytomegalovirus or the original diagnosis leading to transplantation. The risk for developing cancers is significantly greater than in the general population, with a higher tendency to recurrence and later development of second neoplasms.
Full Text Available Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1. The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics.
Cheng, Feixiong; Liu, Chuang; Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming
Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics.
Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming
Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260
Mukhtar, Rita A; Wong, Jasmine M; Esserman, Laura J
The problem of overdiagnosis and overtreatment has been highlighted in breast cancer and many other cancer types, most notably prostate cancer. Addressing this problem presents an opportunity to continue the evolution of breast cancer care. Advances in technology, such as molecular subtyping, have increased the understanding of breast cancer biology and the range of associated behavior, and have provided tools that allow greater personalization of treatment. This article identifies 3 areas of breast cancer care where opportunity currently exists to refine management strategies and help decrease overtreatment and overdiagnosis: the use of adjuvant-external beam radiation in invasive breast cancer, the application of aggressive treatment for all ductal carcinoma in situ, and the authors' approach to breast cancer screening. Personalizing treatment based on patient and tumor characteristics holds promise for minimizing harms and maximizing benefits. This approach will allow continual improvement and ultimately result in providing the right treatment for each patient. Copyright © 2015 by the National Comprehensive Cancer Network.
Kraan, P.M. van der; Berg, W.B. van den
Ageing is the main risk factor of primary osteoarthritis (OA) and OA is the disease most strongly correlated with ageing. Both in humans and other animals OA development appears to be not strictly time-dependent but to hold pace with ageing processes. A characteristic of OA is deviant behaviour of
Phillips, Karon L; Smith, Matthew Lee; Ahn, SangNam; Ory, Marcia G; Hochhalter, Angie K
This study examined (a) differences in rates of initiating colorectal cancer screening across age groups, and (b) factors associated with initiation of colorectal cancer screening among persons age 50-75. Data from 1,699 adults age 50-75 were analyzed from a random sample of households in an eight-county region surrounding the Brazos Valley in Texas. Bivariate descriptive analyses were performed. Logistic regression was employed to assess relationships between demographic, health status, and healthcare utilization variables and having initiated colorectal cancer examination. Having more than a high school education (OR = 1.48, p = 0.002), having insurance (OR = 1.76, p = 0.007), being obese (OR = 1.58, p = 0.015), and having a routine health check-up within the past 2 years (OR = 3.39, p < 0.001) were associated with an increased likelihood of having a colorectal cancer examination. The findings suggest that routine interactions with health care providers may encourage persons to initiate colorectal cancer screening according to guidelines.
Wu, Chung-I; Wang, Hurng-Yi; Ling, Shaoping; Lu, Xuemei
Although tumorigenesis has been accepted as an evolutionary process ( 20 , 102 ), many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in multicellular organisms ( 20 , 29 ). In this review, selection is analyzed in two stages of cancer evolution: Stage I is the evolution between tumors and normal tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas (TCGA) data show a low degree of convergent evolution in Stage I, where genetic changes are not extensively shared among cases. An equally important, albeit much less highlighted, discovery using TCGA data is that there is almost no net selection in cancer evolution. Both positive and negative selection are evident but they neatly cancel each other out, rendering total selection ineffective in the absence of recombination. The efficacy of selection is even lower in Stage II, where neutral (non-Darwinian) evolution is increasingly supported by high-density sampling studies ( 81 , 123 ). Because natural selection is not a strong deterministic force, cancers usually evolve divergently even in similar tissue environments.
Jackaman, Connie; Tomay, Federica; Duong, Lelinh; Abdol Razak, Norbaini Bintu; Pixley, Fiona J; Metharom, Pat; Nelson, Delia J
Impaired immune function has been implicated in the declining health and higher incidence of cancer in the elderly. However, age-related changes to immunity are not completely understood. Neutrophils and macrophages represent the first line of defence yet their ability to phagocytose pathogens decrease with aging. Cytotoxic T lymphocytes are critical in eliminating tumors, but T cell function is also compromised with aging. T cell responses can be regulated by macrophages and may depend on the functional phenotype macrophages adopt in response to microenvironmental signals. This can range from pro-inflammatory, anti-tumorigenic M1 to anti-inflammatory, pro-tumorigenic M2 macrophages. Macrophages in healthy elderly adipose and hepatic tissue exhibit a more pro-inflammatory M1 phenotype compared to young hosts whilst immunosuppressive M2 macrophages increase in elderly lymphoid tissues, lung and muscle. These M2-like macrophages demonstrate altered responses to stimuli. Recent studies suggest that neutrophils also regulate T cell function and, like macrophages, neutrophil function is modulated with aging. It is possible that age-modified tissue-specific macrophages and neutrophils contribute to chronic low-grade inflammation that is associated with dysregulated macrophage-mediated immunosuppression, which together are responsible for development of multiple pathologies, including cancer. This review discusses recent advances in macrophage and neutrophil biology in healthy aging and cancer. Copyright © 2017 Elsevier B.V. All rights reserved.
Gadaud, Pascal; Caccuri, Vincenzo; Bertheau, Denis [Institut Pprime, Dept. Phys. Mech. Mat., UPR CNRS 3346, ENSMA, Université de Poitiers, 1 av. Clément Ader, Téléport 2, 86961 Futuroscope – Chasseneuil (France); Carr, James [HMXIF, Materials Science Centre, The University of Manchester, M13 9PL (United Kingdom); Milhet, Xavier, E-mail: firstname.lastname@example.org [Institut Pprime, Dept. Phys. Mech. Mat., UPR CNRS 3346, ENSMA, Université de Poitiers, 1 av. Clément Ader, Téléport 2, 86961 Futuroscope – Chasseneuil (France)
Silver pastes sintering is a potential candidate for die bonding in power electronic modules. The joints, obtained by sintering, exhibit a significant pore fraction thus reducing the density of the material compared to bulk silver. This was shown to alter drastically the mechanical properties (Young's modulus, yield strength and ultimate tensile stress) at room temperature. While careful analysis of the microstructure has been reported for the as-sintered material, little is known about its quantitative evolution (pores and grains) during thermal ageing. To address this issue, sintered bulk specimens and sintered joints were aged either under isothermal conditions (125 °C up to 1500 h) or under thermal cycling (between −40 °C/+125 °C with 30 min dwell time at each temperature for 2400 cycles). Under these conditions, it is shown that the density of the material does not change but the sub-micron porosity evolves towards a broader size distribution, consistent with Oswald ripening. It is also shown that only the step at 125 °C during the non-isothermal ageing is responsible for the microstructure evolution: isothermal ageing at high temperature can be regarded as a useful tool to perform accelerated ageing tests. Tensile properties are investigated as both a function of ageing time and a function of density. It is shown that the elastic properties do not evolve with the ageing time unlike the plastic properties. This is discussed as a function of the material microstructure evolution.
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.
Sinha, Sonam; Shukla, Samriddhi; Khan, Sajid; Farhan, Mohammad; Kamal, Mohammad Amjad; Meeran, Syed Musthapa
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.
Full Text Available BACKGROUND: Cancer of the oral cavity is one of the commonest cancers among males. AIMS: To assess the aetiological factors, patient characteristics, treatment and the outcome in young patients with oral cancer. SETTINGS AND DESIGN: A retrospective descriptive study of patients under the age of 35 years with cancer of the oral cavity treated between 1982-1996, with the last follow-up till 2001, using the tumour registry data of Regional Cancer Centre (RCC, Trivandrum, Kerala, India. SUBJECT AND METHOD: The detailed clinical, treatment and follow-up data were obtained from the computerised records of RCC and recorded on a preset proforma. This was analysed with emphasis on age, sex, risk factors, site, histology, clinical extent and treatment methods and survival in the study group. STATISTICAL ANALYSIS: The survival analysis was carried by Kaplan-Meier method and the difference in survival was analysed using log-rank test. RESULTS: Out of 264 patients analysed, tongue was the commonest site identified in 136 (52% patients followed by buccal mucosa in 69 (26% patients. A male female ratio of 2.3:1 was observed with a significantly higher male preponderance in buccal mucosa (4.3:1. Prior exposure to tobacco or alcohol was noted in 59.4% patients, with more habituÃ©s in buccal mucosa cancer. Histological confirmation was present only in 83.7% patients and among them most were squamous cell carcinoma (85.9%. Radiotherapy, surgery or combined modalities of treatment were employed for majority of patients. The 5-year survival was 57.3%. T stage of the tumour was found to be significant in predicting disease free survival (P=0.03. CONCLUSIONS: The importance of early detection for clinical down staging is stressed. There is a need to investigate the aetiology of intra oral cancers in younger patients since a significant proportion (almost 40% of these patients do not have associated risk factors for cancer.
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.
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.
Full Text Available Aging can significantly modify the dielectric, piezoelectric, and ferroelectric performance of ferroelectrics. However, little attention has been paid to the aging effect during ferroelectric-ferroelectric phase transitions that is essentially correlated with real applications. In this letter, the authors report the aging effect evolution between two ferroelectric phases in an acceptor-doped piezoceramics. The results show that aging-induced double hysteresis loops were exhibited in different ferroelectric phases, but disappeared during ferroelectric-ferroelectric phase transitions, suggesting the mechanism that the intrinsic restoring force for the reversible switching of domains caused by the alignment of defect dipoles was weakened due to ferroelectric dipole reorientation.
Full Text Available The combination of high rates of reclaimed asphalt pavement (RAP and warm mix asphalt (WMA technologies is still ambiguous in terms of durability. With the aim of clarifying this issue, a study comparing a hot mix asphalt with a WMA prepared using the foaming process technology. Both mixes contain 50% of RAP and are submitted to a laboratory ageing procedure. The long term related performance of the mixtures is compared by means of complex modulus and fatigue testing. Penetration and ring and ball tests are undertaken on the recovered bitumens, as well as the ageing evolution, characterised by the Fourier Transform Infrared analysis. Finally, the Apparent Molecular Weight Distribution (AMWD of the binders is calculated from rheological measurements using the δ-method. Results show a relation between ageing evolution and mechanical performance. After ageing, the overall tendencies are similar for both processes.
Tunia Gil Hernández
Full Text Available This article analyzes the historical evolution of the Cuban medical publications over time, from its appearance in print to the digital age. Reference is made to the first forms of scientific communication in the world, the advent of printing in America and the historical and social events that favored the birth and development of printed publications on the island of Cuba, as well as its development in the digital age.
Andrew McGuire; Brown, James A. L.; Carmel Malone; Ray McLaughlin; Michael J. Kerin
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, ...
Warner, Erica T; Colditz, Graham A; Palmer, Julie R; Partridge, Ann H; Rosner, Bernard A; Tamimi, Rulla M
We examined the relationship between reproductive factors and risk of premenopausal breast cancer among women less than age 40 compared with older premenopausal women. We documented 374 incident cases of breast cancer diagnosed before age 40, and 2,533 cases diagnosed at age 40 and older among premenopausal women in the Nurses' Health Study cohorts. Biennial questionnaires were used to determine age at menarche, age at first birth, parity, breastfeeding, and other reproductive factors. Multivariate relative risks (RR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models within age at diagnosis groups. Tumors in younger women were significantly more likely to be higher grade, larger size, and hormone receptor negative than were tumors in older premenopausal women (p breast cancer. First birth at age 30 or older increased breast cancer risk in both age groups (age breast cancer decreased with each additional year of age at menarche in both age groups (age breast cancer before and after age 40, we found that younger women were more likely to develop tumors with less favorable prognostic characteristics. However, associations between reproductive factors and risk of breast cancer were similar regardless of age at diagnosis of premenopausal breast cancer.
Ory, Marcia G.; Anderson, Lynda A.; Friedman, Daniela B.; Pulczinski, Jairus C.; Eugene, Nola; Satariano, William A.
As part of setting the stage for this supplement to the American Journal of Preventive Medicine, a life-course perspective is presented to assist in understanding the importance of cancer prevention for adults in midlife, a period roughly spanning 20 years between ages 45 and 64 years. Drawing on disciplinary perspectives from the social sciences and public health, several life-course themes are delineated in this article: how specific life transitions present unique opportunities for interventions to inform policy and practice that can improve population health outcomes; how interventions can be focused on those at particular life stages or on the entire life course; and how the onset and progression of chronic conditions such as cancer are dependent on a complex interplay of critical and sensitive periods, and trajectory and accumulation processes. A translational research framework is applied to help promote the movement of applied public health interventions for cancer prevention into practice. Also explored are differences that can affect people at midlife relative to other age cohorts. Specifically, cancer-related risks and care networks are examined, with examples of public health strategies that can be applied to cancer prevention and control. As a conclusion, select methodologic issues and next steps for advancing research and practice are identified. PMID:24512925
Papadopoulos, Fotios C; Pantziaras, Ioannis; Lagiou, Pagona; Brandt, Lena; Ekselius, Lisa; Ekbom, Anders
The objective of this study was to investigate breast cancer occurrence among women treated for anorexia nervosa (AN), with emphasis on age at the onset of this disorder. We conducted a register-based retrospective cohort with a total of 6009 women with at least one admission with an AN diagnosis during the period 1973-2003 in Sweden. During a mean follow-up of 13.4 years, information on 80 057 women-years was generated. The standardized incidence ratio (SIR)--the ratio of observed-to-expected number of cases--was used as the measure of relative risk. Overall, 16 women developed breast cancer versus 25.5 expected cases [SIR: 0.6, 95% confidence interval (CI): 0.4-0.9]. Among women who were first admitted for AN between the age of 10 and 24 years, four developed breast cancer versus 11.3 expected (SIR: 0.4, 95% CI: 0.1-0.9). In this group of women with early onset AN, only one parous woman developed breast cancer versus 6.3 expected (SIR: 0.2, 95% CI: 0-0.9). Among women first hospitalized for AN between the age of 25 and 40 years, 12 developed breast cancer, whereas the expected number was 14.2, a nonsignificant deficit. Our results suggest that early onset AN may play an important role in the development of breast cancer, possibly because of the extreme restriction of energy intake at a crucial period for mammary gland development. Late onset AN is likely to play a relatively less important role.
Deng, Wei; Long, Long; Li, Ji-Lin; Zheng, Dan; Yu, Jia-Hua; Zhang, Chun-Yan; Li, Ke-Zhi; Liu, Hai-Zhou; Huang, Tian-Ren
The incidence and mortality rates of liver and nasopharyngeal cancer in Guangxi province of China have always been among the highest in the world, and cancer is one of the major diseases that pose a threat to the health of residents in Guangxi. However, no systematic study has been performed to evaluate the time trends in the structure of cancer-related deaths and cancer mortality. In this study, we reveal sex, age and geography differences of cancers mortality between three death surveys (1971 to 1973, 1990 to 1992, and 2004 to 2005). The results show that the standardized mortality rate of cancer in Guangxi residents has risen from 43.3/100,000 to 84.2/100,000, the share of cancer deaths in all-cause deaths has increased from 13.3% to 20.7%, and cancer has become the second most common cause of death. The five major cancers, liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and colorectal cancer, account for 60% of all the cancer deaths. Cancers with growing mortality rates over the past 30 years include lung cancer, colorectal cancer, liver cancer and female breast cancer, of which lung cancer is associated with the sharpest rise in mortality, with a more than 600% rise in both men and women. Cancer death in Guangxi residents occurs mainly in the elderly population above 45 years of age, especially in people over the age of 65. The areas with the highest mortality rates for liver cancer and nasopharyngeal cancer, which feature regional high incidences, include Chongzuo and Wuzhou. Therefore, for major cancers such as liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and female breast cancer in Guangxi, we can select high-risk age groups as the target population for cancer prevention and control efforts in high-prevalence areas in a bid to achieve the ultimate goal of lowering cancer mortality in Guangxi.
Levine, Jennifer M; Kelvin, Joanne Frankel; Quinn, Gwendolyn P; Gracia, Clarisa R
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. © 2015 American Cancer Society.
Pustilnik, Simon; Kniazev, Alexei; Lyamina, Yulia; Tepliakova, Arina
The nearby Lynx-Cancer void is a good laboratory to study the effect of very rarefied environment on the evolution of the least massive dwarf galaxies. A recently compiled sample of this void's galaxies includes about one hundred objects with MB in the range -12 to -18 mag. Good quality images are available in the SDSS database for ˜80% of the sample. Their u, g, r, i, z photometry allows one to derive galaxy stellar mass (and, incorporating HI data, gas mass-fraction) and ages of visible stellar populations, and hence, the epoch of their formation (first SF episode). We present the first photometric results of the ongoing study of the Lynx-Cancer void.
Vacek, Pamela M; Skelly, Joan M; Geller, Berta M
Although the benefit of screening mammography for women over 69 has not been established, it is generally agreed that screening recommendations for older women should be individualized based on health status and breast cancer risk. However, statistical models to assess breast cancer risk have not been previously evaluated in this age group. In this study, the original Gail model and three more recent models that include mammographic breast density as a risk factor were applied to a cohort of 19,779 Vermont women aged 70 and older. Women were followed for an average of 7.1 years and 821 developed breast cancer. The predictive accuracy of each risk model was measured by its c-statistic and associations between individual risk factors and breast cancer risk were assessed by Cox regression. C-statistics were 0.54 (95% CI = 0.52-0.56) for the Gail model, 0.54 (95% CI = 0.51-0.56) for the Tice modification of the Gail model, 0.55 (95% CI = 0.53-0.58) for a model developed by Barlow and 0.55 (95% CI = 0.53-0.58) for a Vermont model. These results indicate that the models are not useful for assessing risk in women aged 70 and older. Several risk factors in the models were not significantly associated with outcome in the cohort, while others were significantly related to outcome but had smaller relative risks than estimated by the models. Age-related attenuation of the effects of some risk factors makes the prediction of breast cancer in older women particularly difficult.
Sabaawy, Hatem E
The efficacy of targeted therapies in leukemias and solid tumors depends upon the accurate detection and sustained targeting of initial and evolving driver mutations and/or aberrations in cancer cells. Tumor clonal evolution of the diverse populations of cancer cells during cancer progression contributes to the longitudinal variations of clonal, morphological, anatomical, and molecular heterogeneity of tumors. Moreover, drug-resistant subclones present at initiation of therapy or emerging as a result of targeted therapies represent major challenges for achieving success of personalized therapies in providing meaningful improvement in cancer survival rates. Here, I briefly portray tumor cell clonal evolution at the cellular and molecular levels, and present the multiple types of genetic heterogeneity in tumors, with a focus on their impact on the implementation of personalized or precision cancer medicine.
Wensink, Maarten J; Caswell, Hal; Baudisch, Annette
The evolution of senescence is often explained by arguing that, in nature, few individuals survive to be old and hence it is evolutionarily unimportant what happens to organisms when they are old. A corollary to this idea is that extrinsically imposed mortality, because it reduces the chance of surviving to be old, favors the evolution of senescence. We show that these ideas, although widespread, are incorrect. Selection leading to senescence does not depend directly on survival to old age, but on the shape of the stable age distribution, and we discuss the implications of this important distinction. We show that the selection gradient on mortality declines with age even in the hypothetical case of zero mortality, when survivorship does not decline. Changing the survivorship function by imposing age independent mortality has no affect on the selection gradients. A similar result exists for optimization models: age independent mortality does not change the optimal result. We propose an alternative, brief explanation for the decline of selection gradients, and hence the evolution of senescence.
... in Young Women Cancer and Men Cancer and Women Cancer Prevention in the Workplace Cancer Prevention Starts in Childhood Cancer, the Flu, and You Cervical Cancer Awareness Colorectal Cancer Awareness Gynecologic Cancer Awareness Health Disparities in Cancer Improving Health and Quality of ...
Meier-Abt, Fabienne; Bentires-Alj, Mohamed
Pregnancy at an early age has a strong protective effect against breast cancer in humans and rodents. Postulated mechanisms underlying this phenomenon include alterations in the relative dynamics of hormone and growth factor-initiated cell fate-determining signaling pathways within the hierarchically organized mammary gland epithelium. Recent studies in epithelial cell subpopulations isolated from mouse and human mammary glands have shown that early pregnancy decreases the proportion of hormone receptor-positive cells and causes pronounced changes in gene expression as well as decreased proliferation in stem/progenitor cells. The changes include downregulation of Wnt and transforming growth factor β (TGFβ) signaling. These new findings highlight the importance of cell-cell interactions within the mammary gland epithelium in modulating cancer risk and provide potential targets for breast cancer prevention strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.
Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.
The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells ...... [discovery data: hazard ratio (HR), 4.70, 95% confidence interval (CI), 1.04–21.37; validation data: HR, 1.59, 95% CI, 1.05–2.42]. These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution.......The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells...
Strickertsson, Jesper A B; Madsen, Claus Desler; Rasmussen, Lene Juel
The commensal floras that inhabit the gastrointestinal tract play critical roles in immune responses, energy metabolism, and even cancer prevention. Pathogenic and out of place commensal bacteria, can however have detrimental effects on the host, by introducing genomic instability and mitochondri...... infections impact DNA repair and damage, and the consequence on the mitochondrial and nuclear genomes. We argue that in the gastrointestinal tract, these mechanisms can contribute to tumorigenesis as well as cellular aging of the digestive system....... dysfunction, which are hallmarks of both aging and cancer. Helicobacter pylori and Enterococcus faecalis are bacteria of the gastrointestinal tract that have been demonstrated to affect these two hallmarks. These, and other bacteria, have been shown to decrease the transcription and translation of essential...
Lasry, Audrey; Ben-Neriah, Yinon
Senescent cells, albeit not proliferating, are metabolically and transcriptionally active, thereby capable of affecting their microenvironment, notably via the production of inflammatory mediators. These mediators maintain and propagate the senescence process to neighboring cells, and then recruit immune cells for clearing senescent cells. Among the inflammatory cues are molecules with pronounced tumor-controlling properties, both growth and invasion factors and inhibitory factors, working directly or via recruited immune cells. These senescence-inflammatory effects also prevail within tumors, mediated by the senescent tumor cells and the senescent tumor stroma. Here, we review the course and impact of senescence-associated inflammatory responses in aging and cancer. We propose that controlling senescence-associated inflammation by targeting specific inflammatory mediators may have a beneficial therapeutic effect in treatment of cancer and aging-related diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.
Hantman, Shira; Solomon, Zahava
The current study aims to determine whether elderly Holocaust survivors are affected differently from non-survivors by the adversity of aging and cancer. Holocaust survivors and non-survivors suffering from cancer, were assessed tapping PTSD, psychiatric symptomatology, psychosocial adjustment to illness and coping with the aftermath of the Holocaust. Findings indicate a significant difference between survivors and non-survivors in post-traumatic symptoms and their intensity, survivors endorsing significantly more PTSD symptoms. Survivors were classified into 3 sub-groups, namely "Victims," "Fighters," and "Those who made it". "Victims" reported the highest percentage of persons who met PTSD, psychiatric symptomatology and difficulty coping with the problems of old age. The diversity of responses points to heterogeneity of long-term adaptation and adjustment among Holocaust survivors and similar response to subsequent adversity.
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.
McGranahan, Nicholas; Favero, Francesco; de Bruin, Elza C.
during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal “actionable” mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D......), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K (phosphatidylinositol 3-kinase)–AKT–mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations...
Hasnine, M.; Tolla, B.; Vahora, N.
This paper explores the effects of aging on the mechanical behavior, microstructure evolution and IMC formation on different surface finishes of two high temperature solders, Sn-5 wt.% Ag and Sn-5 wt.% Sb. High temperature aging showed significant degradation of Sn-5 wt.% Ag solder hardness (34%) while aging has little effect on Sn-5 wt.% Sb solder. Sn-5 wt.% Ag experienced rapid grain growth as well as the coarsening of particles during aging. Sn-5 wt.% Sb showed a stable microstructure due to solid solution strengthening and the stable nature of SnSb precipitates. The increase of intermetallic compound (IMC) thickness during aging follows a parabolic relationship with time. Regression analysis (time exponent, n) indicated that IMC growth kinetics is controlled by a diffusion mechanism. The results have important implications in the selection of high temperature solders used in high temperature applications.
Xiao-Min Hu; Jun Zhang; Haihong Chen
Vaccination is one of the effective ways for protecting susceptible individuals from infectious diseases. Different age groups of population have different vulnerability to the disease and different contact frequencies. In order to achieve the maximum effects, the distribution of vaccine doses to the groups of individuals needs to be optimized. In this paper, a differential evolution (DE) algorithm is proposed to address the problem. The performance of the proposed algorithm has been tested b...
Blagosklonny, Mikhail V
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.
Full Text Available The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx], a prospective study of patients with primary non-small cell lung cancer (NSCLC, aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.
Liu, Li; Chang, Yung; Yang, Tao; Noren, David P; Long, Byron; Kornblau, Steven; Qutub, Amina; Ye, Jieping
Abstract Despite wide applications of high?throughput biotechnologies in cancer research, many biomarkers discovered by exploring large?scale omics data do not provide satisfactory performance when used to predict cancer treatment outcomes. This problem is partly due to the overlooking of functional implications of molecular markers. Here, we present a novel computational method that uses evolutionary conservation as prior knowledge to discover bona fide biomarkers. Evolutionary selection at ...
Ostrow, Sheli L.; Barshir, Ruth; DeGregori, James; Yeger-Lotem, Esti; Hershberg, Ruth
Cancer is an evolutionary process in which cells acquire new transformative, proliferative and metastatic capabilities. A full understanding of cancer requires learning the dynamics of the cancer evolutionary process. We present here a large-scale analysis of the dynamics of this evolutionary process within tumors, with a focus on breast cancer. We show that the cancer evolutionary process differs greatly from organismal (germline) evolution. Organismal evolution is dominated by purifying selection (that removes mutations that are harmful to fitness). In contrast, in the cancer evolutionary process the dominance of purifying selection is much reduced, allowing for a much easier detection of the signals of positive selection (adaptation). We further show that, as a group, genes that are globally expressed across human tissues show a very strong signal of positive selection within tumors. Indeed, known cancer genes are enriched for global expression patterns. Yet, positive selection is prevalent even on globally expressed genes that have not yet been associated with cancer, suggesting that globally expressed genes are enriched for yet undiscovered cancer related functions. We find that the increased positive selection on globally expressed genes within tumors is not due to their expression in the tissue relevant to the cancer. Rather, such increased adaptation is likely due to globally expressed genes being enriched in important housekeeping and essential functions. Thus, our results suggest that tumor adaptation is most often mediated through somatic changes to those genes that are important for the most basic cellular functions. Together, our analysis reveals the uniqueness of the cancer evolutionary process and the particular importance of globally expressed genes in driving cancer initiation and progression. PMID:24603726
Liu, Liyu; Austin, Robert
The growth and spreading of cancer in host organisms is an evolutionary process. Cells accumulate mutations that help them adapt to changing environments and to obtain survival fitness. However, all cancer--promoting mutations do not occur at once. Cancer cells face selective environmental pressures that drive their evolution in stages. In traditional cancer studies, environmental stress is usually homogenous in space and difficult to change in time. Here, we propose a microfluidic chip employing embedded dynamic traps to generate dynamic heterogeneous microenvironments for cancer cells in evolution studies. Based on polydimethylsiloxane (PDMS) flexible diaphragms, these traps are able to enclose and shield cancer cells or expose them to external environmental stress. Digital controls for each trap determine the nutrition, antibiotics, CO2/O2 conditions, and temperatures to which trapped cells are subjected. Thus, the stress applied to cells can be varied in intensity and duration in each trap independently. The chip can also output cells from specific traps for sequencing and other biological analysis. Hence our design simultaneously monitors and analyzes cell evolution behaviors under dynamic stresses.
Lemaître, Jean-François; Berger, Vérane; Bonenfant, Christophe; Douhard, Mathieu; Gamelon, Marlène; Plard, Floriane; Gaillard, Jean-Michel
Empirical evidence for declines in fitness components (survival and reproductive performance) with age has recently accumulated in wild populations, highlighting that the process of senescence is nearly ubiquitous in the living world. Senescence patterns are highly variable among species and current evolutionary theories of ageing propose that such variation can be accounted for by differences in allocation to growth and reproduction during early life. Here, we compiled 26 studies of free-ranging vertebrate populations that explicitly tested for a trade-off between performance in early and late life. Our review brings overall support for the presence of early-late life trade-offs, suggesting that the limitation of available resources leads individuals to trade somatic maintenance later in life for high allocation to reproduction early in life. We discuss our results in the light of two closely related theories of ageing-the disposable soma and the antagonistic pleiotropy theories-and propose that the principle of energy allocation roots the ageing process in the evolution of life-history strategies. Finally, we outline research topics that should be investigated in future studies, including the importance of natal environmental conditions in the study of trade-offs between early- and late-life performance and the evolution of sex-differences in ageing patterns. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Ye, Dong-Qing; Zheng, Xiao-Tian; Xu, Xiao-Qing; Wang, Yun-He; Duan, Chang-Qing; Liu, Yan-Lin
The evolution of volatile sulfur compounds (VSCs) in Cabernet Sauvignon wines from seven regions of China during maturation in oak barrels was investigated. The barrels were made of different wood grains (fine and medium) and toasting levels (light and medium). Twelve VSCs were quantified by GC/FPD, with dimethyl sulfide (DMS) and methionol exceeding their sensory thresholds. Most VSCs tended to decline during the aging, while DMS was found to increase. After one year aging, the levels of DMS, 2-methyltetrahy-drothiophen-3-one and sulfur-containing esters were lower in the wines aged in oak barrels than in stainless steel tanks. The wood grain and toasting level of oak barrels significantly influenced the concentration of S-methyl thioacetate and 2-methyltetrahy-drothiophen-3-one. This study reported the evolution of VSCs in wines during oak barrel aging for the first time and evaluated the influence of barrel types, which would provide wine-makers with references in making proposals about wine aging. Copyright © 2016 Elsevier Ltd. All rights reserved.
Rodier, Francis; Kim, Sahn-ho; Nijjar, Tarlochan; Yaswen, Paul; Campisi, Judith
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.
evolution by NGS, we first developed high throughput single cell sequencing (SCS) pipeline on whole exome and trascriptome and updated the pipeline after systematically reviewed the existed single cell whole genome amplification (WGA) and whole transcriptome amplification methods. Using SCS pipeline we...
Fortner, J G; MacLean, B J; Kim, D K; Howland, W S; Turnbull, A D; Goldiner, P; Carlon, G; Beattie, E J
During the past decade, one of the major changes in the field of oncology has been in the surgical approach to primary and secondary cancer of the liver. As a result of data and experience gained in liver transplantation programs and with the application of vascular surgical principles, resectability rates have been increased. The present rate of 32% has been achieved with an overall 30-day operative mortality rate of 9%. More sophisticated intraoperative and postoperative supports have been essential in achieving these results. The median operating time is now 4 3/4 hours in length. Complications are minimal. The median postoperative hospital stay is now 13 days. During the past decade, 436 patients with liver tumors were treated by the authors. It has become apparent in this experience and in that reported by others that an increasing number of patients with primary liver cancer or metastatic cancer in the liver can be cured by surgery with minimal operative risk. Adjuvant chemotherapy may increase the salvage rate. Current therapeutic results are best evaluated after staging of the liver disease: Stage I (no involvement of margins of resection, hepatic vascular structures or bile ducts; all gross disease removed): 85% three-year survival estimate, using the Kaplan-Meier method, for individuals with primary liver cancer; 71% for those with metastatic colorectal cancer. Stages II and III (regional or extrahepatic spread): 22% three-year survival for individuals with primary liver cancer but no survivors at two years with metastatic colorectal cancer. These data permit better selection of patients who are most likely to benefit from surgery.
Shokhirev, Maxim Nikolaievich; Johnson, Adiv Adam
The evolutionary theories of aging are useful for gaining insights into the complex mechanisms underlying senescence. Classical theories argue that high levels of extrinsic mortality should select for the evolution of shorter lifespans and earlier peak fertility. Non-classical theories, in contrast, posit that an increase in extrinsic mortality could select for the evolution of longer lifespans. Although numerous studies support the classical paradigm, recent data challenge classical predictions, finding that high extrinsic mortality can select for the evolution of longer lifespans. To further elucidate the role of extrinsic mortality in the evolution of aging, we implemented a stochastic, agent-based, computational model. We used a simulated annealing optimization approach to predict which model parameters predispose populations to evolve longer or shorter lifespans in response to increased levels of predation. We report that longer lifespans evolved in the presence of rising predation if the cost of mating is relatively high and if energy is available in excess. Conversely, we found that dramatically shorter lifespans evolved when mating costs were relatively low and food was relatively scarce. We also analyzed the effects of increased predation on various parameters related to density dependence and energy allocation. Longer and shorter lifespans were accompanied by increased and decreased investments of energy into somatic maintenance, respectively. Similarly, earlier and later maturation ages were accompanied by increased and decreased energetic investments into early fecundity, respectively. Higher predation significantly decreased the total population size, enlarged the shared resource pool, and redistributed energy reserves for mature individuals. These results both corroborate and refine classical predictions, demonstrating a population-level trade-off between longevity and fecundity and identifying conditions that produce both classical and non
Maxim Nikolaievich Shokhirev
Full Text Available The evolutionary theories of aging are useful for gaining insights into the complex mechanisms underlying senescence. Classical theories argue that high levels of extrinsic mortality should select for the evolution of shorter lifespans and earlier peak fertility. Non-classical theories, in contrast, posit that an increase in extrinsic mortality could select for the evolution of longer lifespans. Although numerous studies support the classical paradigm, recent data challenge classical predictions, finding that high extrinsic mortality can select for the evolution of longer lifespans. To further elucidate the role of extrinsic mortality in the evolution of aging, we implemented a stochastic, agent-based, computational model. We used a simulated annealing optimization approach to predict which model parameters predispose populations to evolve longer or shorter lifespans in response to increased levels of predation. We report that longer lifespans evolved in the presence of rising predation if the cost of mating is relatively high and if energy is available in excess. Conversely, we found that dramatically shorter lifespans evolved when mating costs were relatively low and food was relatively scarce. We also analyzed the effects of increased predation on various parameters related to density dependence and energy allocation. Longer and shorter lifespans were accompanied by increased and decreased investments of energy into somatic maintenance, respectively. Similarly, earlier and later maturation ages were accompanied by increased and decreased energetic investments into early fecundity, respectively. Higher predation significantly decreased the total population size, enlarged the shared resource pool, and redistributed energy reserves for mature individuals. These results both corroborate and refine classical predictions, demonstrating a population-level trade-off between longevity and fecundity and identifying conditions that produce both
Thomas, Paul D; Kahn, Michael
Long-lived somatic stem cells regenerate adult tissues throughout our lifetime. However, with aging, there is a significant deterioration in the function of stem and progenitor cells, which contribute to diseases of aging. The decision for a long-lived somatic stem cell to become activated and subsequently to undergo either a symmetric or an asymmetric division is a critical cellular decision process. The decision to preferentially divide symmetrically or asymmetrically may be the major fundamental intrinsic difference between normal somatic stem cells and cancer stem cells. Based upon work done primarily in our laboratory over the past 15 years, this article provides a perspective on the critical role of somatic stem cells in aging. In particular, we discuss the importance of symmetric versus asymmetric divisions in somatic stem cells and the role of the differential usage of the highly similar Kat3 coactivators, CREB-binding protein (CBP) and p300, in stem cells. We describe and propose a more complete model for the biological mechanism and roles of these two coactivators, their evolution, and unique roles and importance in stem cell biology. Finally, we discuss the potential to pharmacologically manipulate Kat3 coactivator interactions in endogenous stem cells (both normal and cancer stem cells) to potentially ameliorate the aging process and common diseases of aging.
Perrier, Lionel; Borella, Laurent; Philip, Thierry
In this article we have reviewed the cost of cancer in France, based on a literature review. The cost of the treatment of cancer is estimated to be 10 thousand million euros for 75,000 lives saved annually. The increasing number of economic evaluations of cancer use both a macro economic approach, based on DRG data, and a micro economic approach, based on cost result analysis. These cost studies provide the elements for a decision aid in the context of social demands, budget constraints and the evolution towards a DRG's prospective payment system which characterises present organisation of health care in France.
Full Text Available Human epidermal growth factor receptor 2 (HER2 is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15%–20% of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin a “humanized” monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.
Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke
Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence....
Adsersen, Mathilde; Thygesen, Lau Caspar; Jensen, Anders Bonde
BACKGROUND: Specialised palliative care (SPC) takes place in specialised services for patients with complex symptoms and problems. Little is known about what determines the admission of patients to SPC and whether there are differences in relation to institution type. The aims of the study were...... to investigate whether cancer patients' admittance to SPC in Denmark varied in relation to sex, age and diagnosis, and whether the patterns differed by type of institution (hospital-based palliative care team/unit, hospice, or both). METHODS: This was a register-based study of adult patients living in Denmark...... who died from cancer in 2010-2012. Data sources were the Danish Palliative Care Database, Danish Register of Causes of Death and Danish Cancer Registry. The associations between the explanatory variables (sex, age, diagnosis) and admittance to SPC were investigated using logistic regression. RESULTS...
Full Text Available The main scope of this work is to describe the microstructure evolution of single-crystal (SX superalloy RenÃ© N4 during creep and static aging at high temperatures, in function of time, stress and temperature. During creep at high temperatures, SX microstructure evolves from a dense and ordered distribution of cuboidal Î³â² particles to a configuration characterized by alternate rafts of Î³â² phase and Î³ matrix, through a process known as rafting. The microstructural evolution of superalloys is very important to derive models able to predict service conditions of a component through microstructural analysis. In this work two microstructural parameters were identified and analyzed for RenÃ© N4: matrix channels width w along the  lattice direction and periodicity width Î», given by the sum of w and the width of the Î³â² precipitates along . Both parameters were measured on some creep-damaged and some statically aged specimens, as well as on the virgin material to analyze their trends in function of time, temperature and stress. In particular, the parameter ÎÎ» looks independent of both the stress level and the microstructural morphology and could be used in future works to develop microstructural evolution model of RenÃ© N4 in function of service time and temperature. Keywords: Single-crystal, Superalloy, Microstructure, RenÃ© N4
Oliveira, Luis M. C.
Port Wine ageing process is very important to produce the most appreciated and expensive wines from the class. The process takes decades to accomplish and involves particular techniques which are taken inside refrigerated cellars. Different wines pass through such process to produce 10 year, 20 year, 30 year and 40 year Ports. There are no documented data about color or turbidity evolution during the ageing process. We decided to verify the states of color and spectral turbidity of different aged Gold white port wine. The acquired results show a spectral evolution on transmition and scattered radiation along with color modification which are a close and direct consequence of adopted corrective measures. In measuring the four samples, we have used our spectronephelometer with optical fiber tips to illuminate sample and to acquire transmitted or scattered radiation. Transmition results were calibrated with a standard spectrophotometer at our laboratory, and scattered spectra were measured considering a system calibration with ISO12103 standard dust. We are aware that the four samples were harvested in different years, but the wine type is the same and the ageing process does not differ from one sample to another.
Cardenal, Violeta; Cerezo, M Victoria; Martínez, Joaquina; Ortiz-Tallo, Margarita; José Blanca, M
This study had a twofold goal: to define differences in psychological aspects between cancer patients and a control group and to explore the predictive value of such aspects for the evolution of the disease two years later. Firstly, personality, anxiety, anger and depression were assessed in both groups. Results of t-analyses revealed significant group differences. In personality, cancer patients had higher levels of neuroticism and lower levels of extraversion, agreeableness and conscientiousness than the control group. In emotional variables, cancer patients had higher levels of anxiety and some aspects of anger, but there were no group differences in depression levels. Secondly, applying a quasi-prospective design, the predictive value of personality, emotions and coping styles for the evolution of cancer (favourable or unfavourable) was explored using generalized linear models and logistic regression. A four-predictor logistic model was fitted: Anger Expression-In, Resignation, Self-blame and Conscientiousness, indicating that the higher Anger Expression-in, Resignation, and Self-blame scores together with a lower Conscientiousness score, the more likely it is for patients' cancer to evolve unfavourably. These results indicate the crucial role of psychological aspects for the evolution of the disease and the need to include such aspects in the design of clinical interventions.
Clavel-Chapelon, Françoise; Gerber, Mariette
Studies yielding results on risk factors stratified by age at diagnosis or menopausal status were reviewed to better understand the role of hormonal factors and to determine whether reproductive events influence breast cancer risk differently according to age at diagnosis of breast cancer. Through a Medline/Pubmed search, 26 articles providing risk estimates by age at diagnosis of breast cancer or by menopausal status were analysed. A decrease of about 9% of breast cancer risk was found for e...
Ivan B. Djordjevic
Full Text Available Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i Markovian classical model, (ii Markovian-like quantum model, and (iii hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage Markov chain-like models of aging, which
Lande, Russell; Engen, Steinar; Sæther, Bernt-Erik
We analyze the stochastic demography and evolution of a density-dependent age- (or stage-) structured population in a fluctuating environment. A positive linear combination of age classes (e.g., weighted by body mass) is assumed to act as the single variable of population size, [Formula: see text], exerting density dependence on age-specific vital rates through an increasing function of population size. The environment fluctuates in a stationary distribution with no autocorrelation. We show by analysis and simulation of age structure, under assumptions often met by vertebrate populations, that the stochastic dynamics of population size can be accurately approximated by a univariate model governed by three key demographic parameters: the intrinsic rate of increase and carrying capacity in the average environment, [Formula: see text] and [Formula: see text], and the environmental variance in population growth rate, [Formula: see text] Allowing these parameters to be genetically variable and to evolve, but assuming that a fourth parameter, [Formula: see text], measuring the nonlinearity of density dependence, remains constant, the expected evolution maximizes [Formula: see text] This shows that the magnitude of environmental stochasticity governs the classical trade-off between selection for higher [Formula: see text] versus higher [Formula: see text] However, selection also acts to decrease [Formula: see text], so the simple life-history trade-off between [Formula: see text]- and [Formula: see text]-selection may be obscured by additional trade-offs between them and [Formula: see text] Under the classical logistic model of population growth with linear density dependence ([Formula: see text]), life-history evolution in a fluctuating environment tends to maximize the average population size. Published under the PNAS license.
Djordjevic, Ivan B
Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i) Markovian classical model, (ii) Markovian-like quantum model, and (iii) hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage) Markov chain-like models of aging, which are mutually
Noreen, Faiza; Röösli, Martin; Gaj, Pawel; Pietrzak, Jakub; Weis, Stefan; Urfer, Patric; Regula, Jaroslaw; Schär, Primo; Truninger, Kaspar
Aberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa. We measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided. Of 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥ 2 years) and hormonal replacement therapy (HRT age ≥ 50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥ 20 years) and individuals with a body mass index (BMI) of 25 kg/m(2) and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P cancer-related genes, whereas smoking (P colonic epithelium and thereby impacts the evolution of cancer methylomes. © The Author 2014. Published by Oxford University Press.
Dr S Bapat
Nov 8, 2015 ... Most therapies fail to consider differential drug sensitivities of various cells in a tumor. (Tumor Cell Heterogeneity). • Drug refractory behaviour of tumor cells may arise due to either –. - Intrinsic drug resistance mechanisms (Molecular Heterogeneity). - Cell dormancy / reversible quiescence (Cancer stem ...
Full Text Available Breast cancer is one of the most common cancers among the population of the Western world. Diagnostic methods include mammography, ultrasound, and magnetic resonance; meanwhile, nuclear medicine techniques have a secondary role, being useful in regional assessment and therapy followup. Optical imaging is a very promising imaging technique that uses near-infrared light to assess optical properties of tissues and is expected to play an important role in breast cancer detection. Optical breast imaging can be performed by intrinsic breast tissue contrast alone (hemoglobin, water, and lipid content or with the use of exogenous fluorescent probes that target specific molecules for breast cancer. Major advantages of optical imaging are that it does not use any radioactive components, very high sensitivity, relatively inexpensive, easily accessible, and the potential to be combined in a multimodal approach with other technologies such as mammography, ultrasound, MRI, and positron emission tomography. Moreover, optical imaging agents could, potentially, be used as “theranostics,” combining the process of diagnosis and therapy.
Ferko, Nicole; Postma, Maarten; Gallivan, Steve; Kruzikas, Denise; Drummond, Michael
This paper reviews the history of modelling for cervical cancer vaccination. We provide an interpretation and summary of conclusions pertaining to the usefulness of different models, the predicted epidemiological impact of vaccination and the cost-effectiveness of adolescent, catch-up and
Vincent, Mark D
Heritable genomic variation and natural selection have long been acknowledged as striking parallels between evolution and cancer. The logical conclusion, that cancer really is a form of speciation, has seldom been expounded directly. My purpose is to reexamine the "cancer as species" thesis in the light of current attitudes to asexual speciation, and modern analyses of species definitions. The chief obstacles to accepting this thesis have been the asexual nature of cancer cell reproduction, the instability of the malignant genotype and phenotype, and our conditioning that speciation is an extremely rare and imperceptibly gradualistic process. However, these are not absolute barriers to the acceptance of cancers as bona fide species. Furthermore, although ongoing clonal evolution of extant cancers also results in a series of secondary speciation events, the initial emergence of a cancer requires a level of taxonomic reclassification even beyond the concept of speciation (i.e., phylogenation), and which is almost certain to provide a rich source of novel drug targets. The implications of the "cancer as species" idea may be as important for biology as for oncology, providing as it does an endless supply of observable if accelerated examples of a phenomenon once regarded as rare. From the perspective of cancer treatment, speciation guarantees the existence of causal molecular mechanisms which may have been neglected as exploitable targets for rational therapy; in particular, the mediators of metazoan life seem to have substantial overlap with components commonly deranged in cancer cells. However, the intractability of the drug resistance problem, residing as it does in the inherent plasticity of the genome, is traceable back to, and inseparable from, the very origins and nature of life.
L'alcoolisme chronique était retrouvé chez 8 patients, 3 patients étaient tabagiques et l'association alcoolisme-tabac dans 3 cas. Deux patients avaient un antécédent d'ulcère gastrique, et 1 patient un antécédent d'ingestion de caustique. Aucun antécédent familial de cancer , de gastrite chronique ou de gastrectomie ...
Archer, C.R.; Duffy, E.; Hosken, D.J.; Mokkonen, M.; Okada, K.; Oku, K.; Sharma, M.D.; Hunt, J.
1. Variation in the strength of age-dependent natural selection shapes differences in ageing rates across species and populations. Likewise, sexual selection can promote divergent patterns of senescence across the sexes. However, the effects of these processes on the evolution of ageing have largely
van der Aa, Maaike A.; de Kok, Inge M.C.M.; Siesling, Sabine; van Ballegooijen, Marjolein; Coebergh, Jan Willem W.
Recommendations for the age to initiate cervical cancer screening should be directed towards maximum detection of early cervical cancer. However, the screening programme should do more good than harm. The aim of this analysis was to determine whether the target age for cervical cancer screening
Tsoi, Kelvin K F; Hirai, Hoyee W; Chan, Felix C H; Griffiths, Sian; Sung, Joseph J Y
China is facing the challenges of an expanding ageing population and the impact of rapid urbanization, cancer rates are subsequently increasing. This study focuses on the changes of the ageing population and projects the incidence of common ageing-related cancers in the urban regions in China up to 2030. Cancer incidence data and population statistics in China were extracted from the International Agency for Research on Cancer. Due to improving longevity in China, continuous and remarkable increasing trends for the lung, colorectal and prostate cancers are expected. The rate of expanding ageing population was taken into account when predicting the trend of cancer incidence; the estimations of ageing-related cancers were more factual and significant than using the conventional approach of age standardization. The incidence rates of lung, colorectal and prostate cancers will continue to rise in the future decades due to the rise of ageing population. Lifestyle modification such as cutting tobacco smoking rates and promoting healthier diets as well as cancer screening programs should be a health system priority in order to decrease the growing burden of cancer-related mortality and morbidity.
Hurria, Arti; Jones, Lee; Muss, Hyman B
An accumulating body of evidence supports the hypothesis that cancer and/or cancer treatment is associated with accelerated aging. The majority of these data come from the pediatric literature; however, a smaller yet growing body of literature points toward similar findings in the geriatric population. This is a key survivorship issue the growing number of older adults with cancer face, along with the short- and long-term impact of cancer therapy on the aging process. This article will review clinical and biologic markers of aging in older adults with cancer, use cardiovascular disease as a model of accelerated aging, and discuss potential interventions to decrease the risk.
Flink, Dina M; Kondapalli, Laxmi A; Kellar-Guenther, Yvonne
The Fertility Attitudes and Cancer Treatment Study (FACTS) aims at better understanding the reasons and priorities of young adult cancer patients making decisions for fertility preservation (FP). Identifying the factors that center around a patient's fertility decisions will support the development of educational tools for providers and improve clinical care to meet patients' reproductive needs. An exploratory qualitative study was conducted of 27 newly diagnosed male and female cancer patients who had presented for an oncofertility consultation. Interviews lasted ∼30 minutes and were transcribed verbatim. A thematic analysis was conducted to explore the factors driving decisions for future fertility. Themes were grouped to address the following topics: reasons for/against FP, patient priorities, informational needs, support, wellness, and satisfaction with information. Strength of the theme was determined by examining the frequency of a response. Patients who chose FP versus those who did not choose FP and men versus women proved to be more similar than different in their reasoning, priorities, and informational needs for FP decisions. Patients who chose FP identified a "concern for future fertility" as a top reason to do so and "parenthood" as a top priority. For those who did not choose FP, "cancer treatment" was identified as their top priority. For patients identifying financial barriers, 50% of them were able to overcome this to pursue FP. Reproductive-aged patients diagnosed with a new cancer should be referred to a reproductive specialist and provided the opportunity to come to a fertility decision on their own before initiating cancer treatment.
Full Text Available Genetic sequencing of malignancies has become increasingly important to uncover therapeutic targets and capture the tumor’s dynamic changes to drug sensitivity and resistance through genomic evolution. In lung cancers, the current standard of tissue biopsy at the time of diagnosis and progression is not always feasible or practical and may underestimate intratumoral heterogeneity. Technological advances in genetic sequencing have enabled the use of circulating tumor DNA (ctDNA analysis to obtain information on both targetable mutations and capturing real-time Darwinian evolution of tumor clones and drug resistance mechanisms under selective therapeutic pressure. The ability to analyze ctDNA from plasma, CSF, or urine enables a comprehensive view of cancers as systemic diseases and captures intratumoral heterogeneity. Here, we describe these recent advances in the setting of lung cancers and advocate for further research and the incorporation of ctDNA analysis in clinical trials of targeted therapies. By capturing genomic evolution in a noninvasive manner, liquid biopsy for ctDNA analysis could accelerate therapeutic discovery and deliver the next leap forward in precision medicine for patients with lung cancers and other solid tumors.
Ribnikar, D; Ribeiro, J M; Pinto, D; Sousa, B; Pinto, A C; Gomes, E; Moser, E C; Cardoso, M J; Cardoso, F
Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Womenmanagement strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient's comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in
He, Ting; Mullins, C Daniel
Prostate cancer mortality rates have decreased over recent decades, but racial disparities in prostate cancer survival still present as a serious challenge. These disparities may be impacted by age; in fact, African-American men younger than age 65 have prostate cancer mortality rates nearly three times greater than that of White men. Therefore, a systematic literature review was conducted in Medline and EMBASE databases focusing on articles comparing survival and mortality rates for prostate cancer patients across age and race. Articles included were based on the following criteria: (1) included African-American and White prostate cancer patients residing in the US; (2) measured racial disparities across distinct age categories with at least one category below and one above age 65; and (3) addressed racial disparities in terms of overall survival or mortality. Twenty eight articles compared survival and mortality disparities between African-American and White prostate cancer patients across different age categories. Of the 28 articles, 19 articles (68%) showed disparities decreased with age, 8 articles (29%) showed disparities constant with age, and 1 article (3%) showed disparities increased with age. More often the survival and mortality gap between African-American and White prostate cancer patients decreases with age. Additional studies are needed to elucidate other factors that may influence racial disparities in prostate cancer patients. These results provide insight into the racial disparities in prostate cancer and suggest more resources should be directed towards decreasing the disparity gap in younger prostate cancer patients.
Myers Virtue, Shannon; Manne, Sharon L; Ozga, Melissa; Kissane, David W; Rubin, Stephen; Heckman, Carolyn; Rosenblum, Norm; Graff, John J
The study aimed to characterize cancer-related concerns among women with a new diagnosis of gynecological cancer from a developmental life stage perspective. The study compared the degree of cancer-related concern between young women (45 years or younger), middle age women (46-64 years), and older women (65 years or older). Data from women (N = 243) with a condition diagnosed as primary gynecological cancer who were participating in a randomized control trial were analyzed. Women completed a measure that assessed the degree of concern in 12 cancer-related domains (physical functioning, cancer treatment, emotional functioning, sexual functioning, disease progression/death, own well-being, partner well-being, relationship with spouse/partner, body image, relationship with others, employment, and finances). Multivariate comparisons were made between the 3 age groups on the cancer-related concerns. There were age group differences in overall cancer-related concern and specific cancer-related domains. Young women reported the greatest cancer-related concern (P < 0.001). They reported greater concern over emotional functioning (P < 0.001) and sexual functioning (P < 0.001) compared to the middle- and older-age groups. Older women reported less concern over the impact of cancer on finances (P = 007). There were no differences between age groups in concern over physical impairment, cancer treatment, disease progression/death, own well-being, partner well-being, relationship with spouse/partner, body image, and relationship with others. Age may play an important role in the impact of a gynecological cancer diagnosis in domains of functioning, specifically emotional functioning, sexual functioning, and finances. Other cancer-related areas may represent more universal degree of impact. Professionals may benefit from considering the impact of cancer from a developmental life stage perspective.
Myers Virtue, Shannon; Manne, Sharon L.; Ozga, Melissa; Kissane, David; Rubin, Stephen; Heckman, Carolyn; Rosenblum, Norm; Graff, John J.
Objective The study aimed to characterize cancer-related concerns among women newly diagnosed with gynecological cancer from a developmental life stage perspective. The study compared degree of cancer-related concern between young women (≤ 45 years), middle age women (46–64 years), and older women (≥ 65 years). Methods/Materials Data from women (N =243) diagnosed with primary gynecological cancer who were participating in a randomized control trial were analyzed. Women completed a measure that assessed degree of concern in twelve cancer-related domains (physical functioning, cancer treatment, emotional functioning, sexual functioning, disease progression/death, own well-being, partner well-being, relationship with spouse/partner, body image, relationship with others, employment, and finances). Multivariate comparisons were made between the three age groups on the cancer-related concerns. Results There were age group differences in overall cancer-related concern and specific cancer-related domains. Young women reported the greatest cancer-related concern (p < .001). They reported greater concern over emotional functioning (p < .001) and sexual functioning (p < .001) compared to the middle and older age groups. Older women reported less concern over the impact of cancer on finances (p = 007). There were no differences between age groups in concern over physical impairment, cancer treatment, disease progression/death, own well-being, partner well-being, relationship with spouse/partner, body image, and relationship with others. Conclusions Age may play an important role in the impact of a gynecological cancer diagnosis in domains of functioning, specifically emotional functioning, sexual functioning, and finances. Other cancer-related areas may represent more universal degree of impact. Professionals may benefit form considering the impact of cancer from a developmental life stage perspective. PMID:24346489
Mina, Marco; Raynaud, Franck; Tavernari, Daniele; Battistello, Elena; Sungalee, Stephanie; Saghafinia, Sadegh; Laessle, Titouan; Sanchez-Vega, Francisco; Schultz, Nikolaus; Oricchio, Elisa; Ciriello, Giovanni
Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available The aim of this study is to analyze the evolution with age of the prostatic dimensions in German shepherd dogs. For the veterinarians, these results could help to recognize more easily a pathological state of the German shepherd dog’s prostate, only by an ultrasound examination. After examining 22 German shepherd dogs, for dogs of 2 to 5 years old, we obtained a mean prostatic volume of 16.239 cmc, for dogs between 6 and 10 years old the mean prostatic volume was 37.712 cmc and for dogs older than 10 years, the mean prostatic volume was 40.327 cmc. In conclusion, regarding the results, it can be affirmed that in German shepherd dogs, prostate dimensions are increasing with age.
Shiovitz, S.; Korde, L. A.
A hereditary predisposition to breast cancer significantly influences screening and follow-up recommendations for high-risk women. However, in patients with a suggestive personal and/or family history, a specific predisposing gene is identified in highly penetrant genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11), which confer up to an 80% lifetime risk of breast cancer. An additional 2%–3% of cases are due to a mutation in a rare, moderate-penetrance gene (e.g. CHEK2, BRIP1, ATM, and PALB2), each associated with a twofold increase in risk. Prediction models suggest that there are unlikely to be additional yet to be identified high-penetrance genes. Investigation of common, low-penetrance alleles contributing to risk in a polygenic fashion has yielded a small number of suggestive single-nucleotide polymorphisms (SNPs), but the contributive risk of an individual SNP is quite small. Mutation testing is currently recommended for individual genes in the appropriate clinical setting where there is a high index of suspicion for a specific mutated gene or syndrome. Next-generation sequencing offers a new venue for risk assessment. At the present time, there are clear clinical guidelines for individuals with a mutation in a high-penetrance gene. Otherwise, standard models are used to predict an individual's lifetime risk by clinical and family history rather than genomic information. PMID:25605744
Pirone, Jason R; D'Arcy, Monica; Stewart, Delisha A; Hines, William C; Johnson, Melissa; Gould, Michael N; Yaswen, Paul; Jerry, D Joseph; Smith Schneider, Sallie; Troester, Melissa A
Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women's breast cancer may be more aggressive. Although, several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors is poorly understood. Characterizing age-related patterns of gene expression in normal breast tissues may provide insights on etiology of distinct breast cancer subtypes that arise from these tissues. To identify age-related changes in normal breast tissue, 96 tissue specimens from patients with reduction mammoplasty, ages 14 to 70 years, were assayed by gene expression microarray. Significant associations between gene expression levels and age were identified for 802 probes (481 increased, 321 decreased with increasing age). Enriched functions included "aging of cells," "shape change," and "chemotaxis," and enriched pathways included Wnt/beta-catenin signaling, Ephrin receptor signaling, and JAK/Stat signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival. The hazard rates of young-like tumors mirrored that of high-grade tumors in the Surveillance, Epidemiology, and End Results Program, providing a biologic link between normal aging and age-related tumor aggressiveness. These data show that studies of normal tissue gene expression can yield important insights about the pathways and biologic pressures that are relevant during tumor etiology and progression. 2012 AACR
Amaro, Adriana; Chiara, Silvana; Pfeffer, Ulrich
Colorectal cancer is characterized by exquisite genomic instability either in the form of microsatellite instability or chromosomal instability. Microsatellite instability is the result of mutation of mismatch repair genes or their silencing through promoter methylation as a consequence of the CpG island methylator phenotype. The molecular causes of chromosomal instability are less well characterized. Genomic instability and field cancerization lead to a high degree of intratumoral heterogeneity and determine the formation of cancer stem cells and epithelial-mesenchymal transition mediated by the TGF-β and APC pathways. Recent analyses using integrated genomics reveal different phases of colorectal cancer evolution. An initial phase of genomic instability that yields many clones with different mutations (big bang) is followed by an important, previously not detected phase of cancer evolution that consists in the stabilization of several clones and a relatively flat outgrowth. The big bang model can best explain the coexistence of several stable clones and is compatible with the fact that the analysis of the bulk of the primary tumor yields prognostic information.
Ujvari, Beata; Pearse, Anne-Maree; Peck, Sarah; Harmsen, Collette; Taylor, Robyn; Pyecroft, Stephen; Madsen, Thomas; Papenfuss, Anthony T.; Belov, Katherine
The emergence of Devil Facial Tumour Disease (DFTD), a highly contagious cancer, is driving Tasmanian devils (Sarcophilus harrisii) to extinction. The cancer is a genetically and chromosomally stable clonal cell line which is transmitted by biting during social interactions. In the present study, we explore the Devil Facial Tumour (DFT) epigenome and the genes involved in DNA methylation homeostasis. We show that tumour cells have similar levels of methylation to peripheral nerves, the tissue from which DFTD originated. We did not observe any strain or region-specific epimutations. However, we revealed a significant increase in hypomethylation in DFT samples over time (p nerves (p < 0.005). Instead, we believe that loss of methylation is owing to active demethylation, supported by the temporal increase in MBD2 and MBD4 (p < 0.001). The implications of these changes on disease phenotypes need to be explored. Our work shows that DFTD should not be treated as a static entity, but rather as an evolving parasite with epigenetic plasticity. Understanding the role of epimutations in the evolution of this parasitic cancer will provide unique insights into the role of epigenetic plasticity in cancer evolution and progression in traditional cancers that arise and die with their hosts. PMID:23135679
Schneider, Uwe, E-mail: email@example.com [Institute of Physics, Science Faculty, University of Zürich, Zürich 8057, Switzerland and Radiotherapy Hirslanden, Uwe Schneider Institute of Radiotherapy, Witellikerstr. 40, Zürich 8032 (Switzerland); Walsh, Linda [Institute of Physics, Science Faculty, University of Zürich, Zürich 8057, Switzerland and BfS - Federal Office for Radiation Protection, Radiation Protection and Health, Neuherberg 85764 (Germany)
Purpose: Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Methods: Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. Results: It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin’s disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. Conclusions: The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages
Parakh, Sagun; Gan, Hui K; Parslow, Adam C; Burvenich, Ingrid J G; Burgess, Antony W; Scott, Andrew M
The development of HER2-directed monoclonal antibodies and tyrosine kinase inhibitors have provided benefits to cancer patients, as well as produced many insights into the biology of the ErbB receptor family. Current therapies based on ErbB family members have resulted in improved overall survival with associated improvements in quality of life for the cancer patients that respond to treatment. Compared to monotherapy using either two antibodies to block the HER2 receptor blockade or combinatorial approaches with HER2 antibodies and standard therapies has provided additional benefits. Despite the therapeutic success of existing HER2 therapies, personalising treatment and overcoming resistance to these therapies remains a significant challenge. The heterogeneous intra-tumoural HER2 expression and lack of fully predictive and prognostic biomarkers remain significant barriers to improving the use of HER2 antibodies. Imaging modalities using radiolabelled pertuzumab and trastuzumab allow quantitative assessment of intra-tumoural HER2 expression, HER2 antibody saturation and the success of different drug delivery systems to be assessed. Molecular imaging with HER2 antibodies has the potential to be a non-invasive, predictive and prognostic technique capable of influencing therapeutic decisions, predicting response and failure of treatments as well as providing insights into receptor recycling and signalling. Similarly, conjugating HER2 antibodies with novel toxic payloads or combining HER2 antibodies with cellular immunotherapy provide exciting new opportunities for the management of tumours overexpressing HER2. Future research will lead to higher therapeutic responses, lower toxicities and providing insight into the mechanisms of resistance to HER2-targeted treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.
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
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
Siriwardena, Bogahawatte Samarakoon Mudiyanselage Samadarani; Rasnayaka, Rasnayaka Mudiynaselage Sumudu Geethika Kumari; Masood, Yaghma; Masood, Mohd; Kumarasiri, Pallegoda Vithanage Ranjith; Tilakaratne, Wanninayake Mudiyanselage
The high incidence rates for oral cancer (excluding lip) are especially found in the South and South-East Asia. Therefore, the aim of the present study was to investigate the relationship between sex, age, site, and metastasis of a large sample with oral squamous cell carcinoma (OSCC). A total of 989 OSCC treated with neck dissection were selected. All the relevant data were recorded from biopsy request forms. The patients were divided into seven groups, and there were nine different oral sites. The male-to-female ratio of the sample was 4:1. Most of the patients were aged between 30 and 60 years. Of the 989 patients, approximately 40% patients had metastasis. Age age groups, but it was not statistically significant. Palate cancers had more than 14 times higher chance of metastasis, followed by maxilla (4.6 times) and tongue (2.8 times). The present study provides important information on the metastatic potential of OSCC in different oral sites, and identifies high-risk age groups for metastasis. This will be helpful in planning neck treatment for OSCC. © 2015 Wiley Publishing Asia Pty Ltd.
Full Text Available
Cancer is a disease of aging . Currently 50% of all malignancies occur in individuals 65 and over and by the year 2030 older individuals will account for 70% of all neoplasms.
With the aging of the population the management of cancer in the older person with chemotherapy is beoming increasingly common. This treatment may be safe and effective if some appropriate measures are taken, including, an assessment of the physiologic age of each patient, modification of doses according to the renal function, use of meyelopoietic growth factors prophylactically in presence of moderately toxic chemotherapy, and provision of an adequate caregiver. Cure, prolongation of survival, and symptom palliation are universal goals of medical treatment. Prolongation of active life expectancy should be added to the treatment goal of the older aged person .
Brooks, Robert C; Garratt, Michael G
Males and females in many species differ in how they age and how long they live. These differences have motivated much research, concerning both their evolution and the underlying mechanisms that cause them. We review how differences in male and female life histories have evolved to shape patterns of aging and some of the mechanisms and pathways involved. We pay particular attention to three areas where considerable potential for synergy between mechanistic and evolutionary research exists: (1) the role of estrogens, androgens, the growth hormone/insulin-like growth factor 1 pathway, and the mechanistic target of rapamycin signaling pathway in sex-dependent growth and reproduction; (2) sexual conflict over mating rate and fertility, and how mate presence or mating can become an avenue for males and females to directly affect each other's life span; and (3) the link between dietary restriction and aging, and the emerging understanding that only the restriction of certain nutrients is involved and that this is linked to reproduction. We suggest that ideas about life histories, sex-dependent selection, and sexual conflict can inform and be informed by the ever more refined and complex understanding of the mechanisms that cause aging. © 2016 New York Academy of Sciences.
Powers, Mike; Pan, Jianbiao; Silk, Julie; Hyland, Patrick
Au over Ni on Cu is a widely used printed circuit board (PCB) surface finish, under bump metallization (UBM), and component lead metallization. It is generally accepted that less than 3 wt.% Au in Sn-Pb solder joints inhibits formation of detrimental intermetallic compounds (IMC). However, the critical limit for Au content in Pb-free solder joints is not well established. Three surface-mount package platforms, one with a matte Sn surface finish and the others with Ni/Au finish, were soldered to Ni/Au-finished PCB using Sn-3.0Ag-0.5Cu (SAC305) solder, in a realistic manufacturing setting. The assembled boards were divided into three groups: one without any thermal treatment, one subjected to isothermal aging at 125°C for 30 days, and the third group aged at 125°C for 56 days. Representative solder joints were cross-sectioned and analyzed using scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDX) to investigate the evolution of the solder joint morphology as a function of Au content and isothermal aging. It was found that, if Cu is available to dissolve in the solder joint, the migration of AuSn4 from the bulk to the interface as a result of thermal aging is mitigated.
Hemminki, Kari; Mousavi, Seyed Mohsen; Sundquist, Jan; Brandt, Andreas
Age-specific incidence rates for breast cancer in low-risk and high-risk ethnic populations differ by age at which the incidence maximum is reached. The results show that in many immigrant groups the diagnostic age is earlier than that in natives of Sweden, suggesting that true biological factors underlie the differences. These factors may explain much of the international variation in breast cancer incidence. Identifying these factors should advance understanding of breast cancer etiology an...
Sansone, Pasquale; Berishaj, Marjan; Rajasekhar, Vinagolu K; Ceccarelli, Claudio; Chang, Qing; Strillacci, Antonio; Savini, Claudia; Shapiro, Lauren; Bowman, Robert L; Mastroleo, Chiara; De Carolis, Sabrina; Daly, Laura; Benito-Martin, Alberto; Perna, Fabiana; Fabbri, Nicola; Healey, John H; Spisni, Enzo; Cricca, Monica; Lyden, David; Bonafé, Massimiliano; Bromberg, Jacqueline
The hypothesis that microvesicle-mediated miRNA transfer converts noncancer stem cells into cancer stem cells (CSC) leading to therapy resistance remains poorly investigated. Here we provide direct evidence supporting this hypothesis, by demonstrating how microvesicles derived from cancer-associated fibroblasts (CAF) transfer miR-221 to promote hormonal therapy resistance (HTR) in models of luminal breast cancer. We determined that CAF-derived microvesicles horizontally transferred miR-221 to tumor cells and, in combination with hormone therapy, activated an ER(lo)/Notch(hi) feed-forward loop responsible for the generation of CD133(hi) CSCs. Importantly, microvesicles from patients with HTR metastatic disease expressed high levels of miR-221. We further determined that the IL6-pStat3 pathway promoted the biogenesis of onco-miR-221(hi) CAF microvesicles and established stromal CSC niches in experimental and patient-derived breast cancer models. Coinjection of patient-derived CAFs from bone metastases led to de novo HTR tumors, which was reversed with IL6R blockade. Finally, we generated patient-derived xenograft (PDX) models from patient-derived HTR bone metastases and analyzed tumor cells, stroma, and microvesicles. Murine and human CAFs were enriched in HTR tumors expressing high levels of CD133(hi) cells. Depletion of murine CAFs from PDX restored sensitivity to HT, with a concurrent reduction of CD133(hi) CSCs. Conversely, in models of CD133(neg), HT-sensitive cancer cells, both murine and human CAFs promoted de novo HT resistance via the generation of CD133(hi) CSCs that expressed low levels of estrogen receptor alpha. Overall, our results illuminate how microvesicle-mediated horizontal transfer of genetic material from host stromal cells to cancer cells triggers the evolution of therapy-resistant metastases, with potentially broad implications for their control. Cancer Res; 77(8); 1927-41. ©2017 AACR. ©2017 American Association for Cancer Research.
Forman, D; Pike, M C; Davey, G; Dawson, S; Baker, K; Chilvers, C E D; Oliver, R T D; Coupland, C A C
Abstract Objective : To determine the risk of testicular cancer associated with undescended testis, inguinal hernia, age at puberty, marital status, infertility, vasectomy, and amount of exercise. Design...
Full Text Available Background: The burden of cancer is growing globally and is one of the top leading causes of death. Information on cancer patterns is essential for effective planning of cancer control interventions. Aims and Objectives: The present cross sectional study aims to explore the patterns and trends of the cancer incidences in the western regions of Tamil Nadu, India including Coimbatore, Erode, Tiruppur, Salem, Namakkal and Nilgiris. Materials and Methods: A sum of 14392 cancer cases were recorded from the hospital based cancer registries of Coimbatore district. The cancer cases were segregated district-wise for specific cancer sites and the age-standardized incident rates were calculated for different age groups. Results: Coimbatore district recorded the highest number of incidences among all districts. Among all age-groups the adults aged 50-74 carry the highest burden of cancer. Among men, head and neck and gastrointestinal cancers are predominant while among women, breast and gynecological cancers are high. The age-standardized incidence rates were found to be higher in Coimbatore and least in Salem. Conclusion: Through this study, it is observed that Coimbatore district is under major threat and needs further investigation of risk factors for implementing optimized treatment and prevention strategies for reducing the adverse effects of cancer.
When we are looking for intelligent life outside the Earth, there is a fundamental question: Assuming that life has formed on an extraterrestrial planet, will it also develop toward intelligence? As this is hotly debated, we will now describe the development of life on Earth in more detail in order to show that there are good reasons why evolution should culminate in intelligent beings.
Stout, Dietrich; Toth, Nicholas; Schick, Kathy; Chaminade, Thierry
Archaeological and palaeontological evidence from the Early Stone Age (ESA) documents parallel trends of brain expansion and technological elaboration in human evolution over a period of more than 2Myr. However, the relationship between these defining trends remains controversial and poorly understood. Here, we present results from a positron emission tomography study of functional brain activation during experimental ESA (Oldowan and Acheulean) toolmaking by expert subjects. Together with a previous study of Oldowan toolmaking by novices, these results document increased demands for effective visuomotor coordination and hierarchical action organization in more advanced toolmaking. This includes an increased activation of ventral premotor and inferior parietal elements of the parietofrontal praxis circuits in both the hemispheres and of the right hemisphere homologue of Broca's area. The observed patterns of activation and of overlap with language circuits suggest that toolmaking and language share a basis in more general human capacities for complex, goal-directed action. The results are consistent with coevolutionary hypotheses linking the emergence of language, toolmaking, population-level functional lateralization and association cortex expansion in human evolution.
Calsina, Angel; Ripoll, Jordi
We investigate the evolution of the age (or size) at sex-reversal in a model of sequential hermaphroditism, by means of the function-valued adaptive dynamics. The trait is the probability law of the age at sex-reversal considered as a random variable. Our analysis starts with the ecological model which was first introduced and analyzed by Calsina and Ripoll (Math Biosci 208(2), 393-418, 2007). The structure of the population is extended to a genotype class and a new model for an invading/mutant population is introduced. The invasion fitness functional is derived from the ecological setting, and it turns out to be controlled by a formula of Shaw-Mohler type. The problem of finding evolutionarily stable strategies is solved by means of infinite-dimensional linear optimization. We have found that these strategies correspond to sex-reversal at a single particular age (or size) even if the set of feasible strategies is considerably broader and allows for a probabilistic sex-reversal. Several examples, including in addition the population-dynamical stability, are illustrated. For a special case, we can show that an unbeatable size at sex-reversal must be larger than 69.3% of the expected size at death.
Aktipis, C. Athena; Kwan, Virginia S. Y.; Johnson, Kathryn A.; Neuberg, Steven L.; Maley, Carlo C.
Cancer therapy selects for cancer cells resistant to treatment, a process that is fundamentally evolutionary. To what extent, however, is the evolutionary perspective employed in research on therapeutic resistance and relapse? We analyzed 6,228 papers on therapeutic resistance and/or relapse in cancers and found that the use of evolution terms in abstracts has remained at about 1% since the 1980s. However, detailed coding of 22 recent papers revealed a higher proportion of papers using evolutionary methods or evolutionary theory, although this number is still less than 10%. Despite the fact that relapse and therapeutic resistance is essentially an evolutionary process, it appears that this framework has not permeated research. This represents an unrealized opportunity for advances in research on therapeutic resistance. PMID:22125594
Full Text Available The discovery of small molecules targeted to specific oncogenic pathways has revolutionized anti-cancer therapy. However, such therapy often fails due to the evolution of acquired resistance. One long-standing question in clinical cancer research is the identification of optimum therapeutic administration strategies so that the risk of resistance is minimized. In this paper, we investigate optimal drug dosing schedules to prevent, or at least delay, the emergence of resistance. We design and analyze a stochastic mathematical model describing the evolutionary dynamics of a tumor cell population during therapy. We consider drug resistance emerging due to a single (epigenetic alteration and calculate the probability of resistance arising during specific dosing strategies. We then optimize treatment protocols such that the risk of resistance is minimal while considering drug toxicity and side effects as constraints. Our methodology can be used to identify optimum drug administration schedules to avoid resistance conferred by one (epigenetic alteration for any cancer and treatment type.
Levine, Marc S; Yee, Judy
Colorectal cancer screening is thought to be an effective tool with which to reduce the mortality from colorectal cancer through early detection and removal of colonic adenomas and early colon cancers. In this article, we review the history, evolution, and current status of imaging tests of the colon-including single-contrast barium enema, double-contrast barium enema, computed tomographic (CT) colonography, and magnetic resonance (MR) colonography-for colorectal cancer screening. Despite its documented value in the detection of colonic polyps, the double-contrast barium enema has largely disappeared as a screening test because it is widely perceived as a labor-intensive, time-consuming, and technically demanding procedure. In the past decade, the barium enema has been supplanted by CT colonography as the major imaging test in colorectal cancer screening in the United States, with MR colonography emerging as another viable option in Europe. Although MR colonography does not require ionizing radiation, the radiation dose for CT colonography has decreased substantially, and regular screening with this technique has a high benefit-to-risk ratio. In recent years, CT colonography has been validated as an effective tool for use in colorectal cancer screening that is increasingly being disseminated.
Serial comprehensive geriatric assessment in elderly head and neck cancer patients undergoing curative radiotherapy identifies evolution of multidimensional health problems and is indicative of quality of life.
Pottel, L; Lycke, M; Boterberg, T; Pottel, H; Goethals, L; Duprez, F; Van Den Noortgate, N; De Neve, W; Rottey, S; Geldhof, K; Buyse, V; Kargar-Samani, K; Ghekiere, V; Debruyne, P R
Head and neck (H&N) cancer is mainly a cancer of the elderly; however, the implementation of comprehensive geriatric assessment (CGA) to quantify functional age in these patients has not yet been studied. We evaluated the diagnostic performance of screening tools [Vulnerable Elders Survey-13 (VES-13), G8 and the Combined Screening Tool 'VES-13 + (17-G8)' or CST], the feasibility of serial CGA, and correlations with health-related quality of life evolution [HRQOL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ)-C30 and -HN35] during therapy in hundred patients, aged ≥65 years, with primary H&N cancer undergoing curative radio(chemo)therapy. Respectively 36.8%, 69.0%, 62.1% and 71.3% were defined vulnerable according to VES-13, G8, CST and CGA at week 0, mostly due to presence of severe grade co-morbidities, difficulties in community functioning and nutritional problems. At week 4, significantly more patients were identified vulnerable due to nutritional, functional and emotional deterioration. The CST did not achieve the predefined proportion necessary for validation. Vulnerable patients reported lower function and higher symptom HRQOL scores as compared with fit patients. A comparable deterioration in HRQOL was observed in both groups through therapy. In conclusion, G8 remains the screening tool of choice. Serial CGA identifies the evolution of multidimensional health problems and HRQOL conditions during therapy with potential to guide individualised supportive care. © 2014 John Wiley & Sons Ltd.
Rebolj, Matejka; van Ballegooijen, Marjolein; Lynge, Elsebeth
OBJECTIVE: To determine the incidence of cervical cancer after several negative cervical smear tests at different ages. DESIGN: Prospective observational study of incidence of cervical cancer after the third consecutive negative result based on individual level data in a national registry...... of histopathology and cytopathology (PALGA). SETTING: Netherlands, national data. Population 218,847 women aged 45-54 and 445,382 aged 30-44 at the time of the third negative smear test. MAIN OUTCOME MEASURES: 10 year cumulative incidence of interval cervical cancer. RESULTS: 105 women developed cervical cancer...... within 2 595,964 woman years at risk after the third negative result at age 30-44 and 42 within 1,278,532 woman years at risk after age 45-54. During follow-up, both age groups had similar levels of screening. After 10 years of follow-up, the cumulative incidence rate of cervical cancer was similar: 41...
ni ketut alit armini
Full Text Available Introduction: Cervical cancer as the most common cause of morbidity and mortality around the world. The worse cervical cancer prevention program might lead to delayed treatment of cancer. Furthermore patient who suffered cervical cancer in women of childbearing age. Method: The study design was descriptive cross sectional approach correlation. The population were women of childbearing age who involved the region of Puskesmas Kenjeran Surabaya. The number of sample were 64 respondents who taken by using simple random sampling. The independent variables were factor of personal and self efficacy. The dependent variable was the primary and secondary prevention of cervical cancer. The data was analyzed by using statistic tests Spearmans’s rho to know correlation of independent variable with prevention measures of cervical cancer. Result: The result of relationship between the personal factors and cervical cancer prevention showed value p=0.025 (r=0.280. The relationship between self efficacy with prevention of cervical cancer in women of childbearing age showed value p=0.094 (r=0.211. Conclusion: Personal factors associated with prevention of cervical cancer in women of childbearing age. Self efficacy had no relationship with prevention of cervical cancer in women of childbearing age. The further study was recommended to develop health promotion model factors to increase the prevention of cervical cancer.
Alberto Caballero Vázquez; Ana Dolores Romero Ortiz; Jose Manuel González de Vega San Román; Raimundo García del Moral; Bernardino Alcázar Navarrete
Background: Changes in lung cancer has been characterized by the increase of cases among women and the increase in adenocarcinomas among other histological subtypes. Methods: Descriptive analysis of cases diagnosed with lung cancer in Hospital Virgen de las Nieves (Spain) from 1990 to 2010, based on five variables (age, sex, smoking, histology and pathological anatomy). The study establishes associations between these variables and compares the results with the literature. Results: 2,026 pati...
Vos, Janet; de Bock, G.H.; Teixeira, N.; van der Kolk, D.M.; Jansen, Liesbeth; Mourits, M.J.E.; Oosterwijk, J.C.
Background: Risk estimates for proven non-carriers in BRCA mutation families are inconsistent for breast cancer and lacking for ovarian cancer. We aimed to assess the age-related risks for breast and ovarian cancer for proven non-carriers in these families. Methods: A consecutive cohort study
Overbeek, L.I.H.; Hoogerbrugge, N.; Krieken, J.H.J.M. van; Nagengast, F.M.; Ruers, T.J.M.; Ligtenberg, M.J.L.; Hermens, R.P.M.G.
PURPOSE: This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. METHODS: Patients who were recently diagnosed with colorectal cancer at a young age or
Aunan, Jan R; Cho, William C; Søreide, Kjetil
Aging is the inevitable time-dependent decline in physiological organ function and is a major risk factor for cancer development. Due to advances in health care, hygiene control and food availability, life expectancy is increasing and the population in most developed countries is shifting to an increasing proportion of people at a cancer susceptible age. Mechanisms of aging are also found to occur in carcinogenesis, albeit with shared or divergent end-results. It is now clear that aging and cancer development either share or diverge in several disease mechanisms. Such mechanisms include the role of genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, decreased nutrient sensing and altered metabolism, but also cellular senescence and stem cell function. Cancer cells and aged cells are also fundamentally opposite, as cancer cells can be thought of as hyperactive cells with advantageous mutations, rapid cell division and increased energy consumption, while aged cells are hypoactive with accumulated disadvantageous mutations, cell division inability and a decreased ability for energy production and consumption. Nonetheless, aging and cancer are tightly interconnected and many of the same strategies and drugs may be used to target both, while in other cases antagonistic pleiotrophy come into effect and inhibition of one can be the activation of the other. Cancer can be considered an aging disease, though the shared mechanisms underpinning the two processes remain unclear. Better understanding of the shared and divergent pathways of aging and cancer is needed.
Aunan, Jan R.; Cho, William C; Søreide, Kjetil
Aging is the inevitable time-dependent decline in physiological organ function and is a major risk factor for cancer development. Due to advances in health care, hygiene control and food availability, life expectancy is increasing and the population in most developed countries is shifting to an increasing proportion of people at a cancer susceptible age. Mechanisms of aging are also found to occur in carcinogenesis, albeit with shared or divergent end-results. It is now clear that aging and cancer development either share or diverge in several disease mechanisms. Such mechanisms include the role of genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, decreased nutrient sensing and altered metabolism, but also cellular senescence and stem cell function. Cancer cells and aged cells are also fundamentally opposite, as cancer cells can be thought of as hyperactive cells with advantageous mutations, rapid cell division and increased energy consumption, while aged cells are hypoactive with accumulated disadvantageous mutations, cell division inability and a decreased ability for energy production and consumption. Nonetheless, aging and cancer are tightly interconnected and many of the same strategies and drugs may be used to target both, while in other cases antagonistic pleiotrophy come into effect and inhibition of one can be the activation of the other. Cancer can be considered an aging disease, though the shared mechanisms underpinning the two processes remain unclear. Better understanding of the shared and divergent pathways of aging and cancer is needed. PMID:28966806
Liu, Yifang; Lee, Chi-Guhn [Department of Mechanical and Industrial Engineering, University of Toronto, 5 King' s College Road, Toronto, Ontario M5S 3G8 (Canada); Chan, Timothy C. Y., E-mail: firstname.lastname@example.org [Department of Mechanical and Industrial Engineering, University of Toronto, 5 King' s College Road, Toronto, Ontario M5S 3G8, Canada and Techna Institute for the Advancement of Technology for Health, 124-100 College Street Toronto, Ontario M5G 1P5 (Canada); Cho, Young-Bin [Department of Radiation Physics, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University of Avenue, Toronto, Ontario M5T 2M9, Canada and Department of Radiation Oncology, University of Toronto, 148-150 College Street, Toronto, Ontario M5S 3S2 (Canada); Islam, Mohammad K. [Department of Radiation Physics, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University of Avenue, Toronto, Ontario M5T 2M9 (Canada); Department of Radiation Oncology, University of Toronto, 148-150 College Street, Toronto, Ontario M5S 3S2 (Canada); Techna Institute for the Advancement of Technology for Health, 124-100 College Street, Toronto, Ontario M5G 1P5 (Canada)
Purpose: To develop mathematical models to predict the evolution of tumor geometry in cervical cancer undergoing radiation therapy. Methods: The authors develop two mathematical models to estimate tumor geometry change: a Markov model and an isomorphic shrinkage model. The Markov model describes tumor evolution by investigating the change in state (either tumor or nontumor) of voxels on the tumor surface. It assumes that the evolution follows a Markov process. Transition probabilities are obtained using maximum likelihood estimation and depend on the states of neighboring voxels. The isomorphic shrinkage model describes tumor shrinkage or growth in terms of layers of voxels on the tumor surface, instead of modeling individual voxels. The two proposed models were applied to data from 29 cervical cancer patients treated at Princess Margaret Cancer Centre and then compared to a constant volume approach. Model performance was measured using sensitivity and specificity. Results: The Markov model outperformed both the isomorphic shrinkage and constant volume models in terms of the trade-off between sensitivity (target coverage) and specificity (normal tissue sparing). Generally, the Markov model achieved a few percentage points in improvement in either sensitivity or specificity compared to the other models. The isomorphic shrinkage model was comparable to the Markov approach under certain parameter settings. Convex tumor shapes were easier to predict. Conclusions: By modeling tumor geometry change at the voxel level using a probabilistic model, improvements in target coverage and normal tissue sparing are possible. Our Markov model is flexible and has tunable parameters to adjust model performance to meet a range of criteria. Such a model may support the development of an adaptive paradigm for radiation therapy of cervical cancer.
Liu, Yifang; Chan, Timothy C Y; Lee, Chi-Guhn; Cho, Young-Bin; Islam, Mohammad K
To develop mathematical models to predict the evolution of tumor geometry in cervical cancer undergoing radiation therapy. The authors develop two mathematical models to estimate tumor geometry change: a Markov model and an isomorphic shrinkage model. The Markov model describes tumor evolution by investigating the change in state (either tumor or nontumor) of voxels on the tumor surface. It assumes that the evolution follows a Markov process. Transition probabilities are obtained using maximum likelihood estimation and depend on the states of neighboring voxels. The isomorphic shrinkage model describes tumor shrinkage or growth in terms of layers of voxels on the tumor surface, instead of modeling individual voxels. The two proposed models were applied to data from 29 cervical cancer patients treated at Princess Margaret Cancer Centre and then compared to a constant volume approach. Model performance was measured using sensitivity and specificity. The Markov model outperformed both the isomorphic shrinkage and constant volume models in terms of the trade-off between sensitivity (target coverage) and specificity (normal tissue sparing). Generally, the Markov model achieved a few percentage points in improvement in either sensitivity or specificity compared to the other models. The isomorphic shrinkage model was comparable to the Markov approach under certain parameter settings. Convex tumor shapes were easier to predict. By modeling tumor geometry change at the voxel level using a probabilistic model, improvements in target coverage and normal tissue sparing are possible. Our Markov model is flexible and has tunable parameters to adjust model performance to meet a range of criteria. Such a model may support the development of an adaptive paradigm for radiation therapy of cervical cancer.
Chakrabarti, Shaon; Michor, Franziska
The identification of optimal drug administration schedules to battle the emergence of resistance is a major challenge in cancer research. The existence of a multitude of resistance mechanisms necessitates administering drugs in combination, significantly complicating the endeavor of predicting the evolutionary dynamics of cancers and optimal intervention strategies. A thorough understanding of the important determinants of cancer evolution under combination therapies is therefore crucial for correctly predicting treatment outcomes. Here we developed the first computational strategy to explore pharmacokinetic and drug interaction effects in evolutionary models of cancer progression, a crucial step towards making clinically relevant predictions. We found that incorporating these phenomena into our multiscale stochastic modeling framework significantly changes the optimum drug administration schedules identified, often predicting nonintuitive strategies for combination therapies. We applied our approach to an ongoing phase Ib clinical trial (TATTON) administering AZD9291 and selumetinib to EGFR-mutant lung cancer patients. Our results suggest that the schedules used in the three trial arms have almost identical efficacies, but slight modifications in the dosing frequencies of the two drugs can significantly increase tumor cell eradication. Interestingly, we also predict that drug concentrations lower than the MTD are as efficacious, suggesting that lowering the total amount of drug administered could lower toxicities while not compromising on the effectiveness of the drugs. Our approach highlights the fact that quantitative knowledge of pharmacokinetic, drug interaction, and evolutionary processes is essential for identifying best intervention strategies. Our method is applicable to diverse cancer and treatment types and allows for a rational design of clinical trials. Cancer Res; 77(14); 3908-21. ©2017 AACR. ©2017 American Association for Cancer Research.
Lebel, Sophie; Beattie, Sara; Arès, Isabelle; Bielajew, Catherine
Fear of cancer recurrence (FCR) is a frequently cited and unmet need of cancer survivors. While the relation between age and FCR is well documented, the mechanisms that may explain this phenomenon remain to be investigated. This study examined four possible mechanisms of the relation between age and FCR: motherhood, severity of the cancer (defined as cancer stage and chemotherapy), anxiety, and illness intrusiveness. 3,239 women with breast cancer (mean time since diagnosis: 6.6 years) completed the Concerns About Recurrence Scale (CARS), the State Trait Anxiety Inventory (STAI), and the Illness Intrusiveness Ratings Scale (IIRS) within a larger web-based study. Women were divided into four groups based on their current age: 65. Multivariate analyses were performed with age category and motherhood as the independent variables and the CARS subscales as the dependent variables, controlling for age of children and relevant covariates. Severity of the cancer, anxiety, and illness intrusiveness were simultaneously tested as mediators of the relation between age and FCR. Results indicated that age category was related to FCR, F = 10.37, p cancer was not. Younger age was associated with more FCR among breast cancer patients, regardless of motherhood status. Our findings suggest new, potentially valuable ways of managing FCR by helping affected people to reduce anxiety and illness intrusiveness. PsycINFO Database Record (c) 2013 APA, all rights reserved.
Objective: To determine the relationship between the age at diagnosis and established prognostic factors of breast cancers in Calabar, Nigeria. Attempts made to assess the prognostic value of age at presentation. Design: Retrospective study of invasive breast cancer seen in Calabar over a seventeen year period.
Santos, Sabrina da Silva; Melo,Leticia Rodrigues; Koifman,Rosalina Jorge; Koifman, Sergio
Many countries have reported an increase in breast cancer incidence in young women. The current study's objective was to explore breast cancer distribution in women less than 50 years of age in Brazil. A descriptive study on breast cancer incidence (selected cities) and mortality (Brazil and selected cities) in 2002-2004 was carried out, and the results were compared with those from other countries. The study also analyzed the trend in hospital morbidity and incidence rates for breast cancer....
Angulo, J C; Viñas, M A; Gimbernat, H; Fata, F Ramón de; Granados, R; Luján, M
We researched the usefulness of optimizing prostate cancer (PC) screening in our community using baseline PSA readings in men between 40-49 years of age. A retrospective study was performed that analyzed baseline PSA in the fifth decade of life and its ability to predict the development of PC in a population of Madrid (Spain). An ROC curve was created and a cutoff was proposed. We compared the evolution of PSA from baseline in patients with consecutive readings using the Friedman test. We established baseline PSA ranges with different risks of developing cancer and assessed the diagnostic utility of the annual PSA velocity (PSAV) in this population. Some 4,304 men aged 40-49 years underwent opportunistic screening over the course of 17 years, with at least one serum PSA reading (6,001 readings) and a mean follow-up of 57.1±36.8 months. Of these, 768 underwent biopsy of some organ, and 104 underwent prostate biopsy. Fourteen patients (.33%) were diagnosed with prostate cancer. The median baseline PSA was .74 (.01-58.5) ng/mL for patients without PC and 4.21 (.76-47.4) ng/mL for those with PC. The median time from the reading to diagnosis was 26.8 (1.5-143.8) months. The optimal cutoff for detecting PC was 1.9ng/mL (sensitivity, 92.86%; specificity, 92.54%; PPV, 3.9%; NPV, 99.97%), and the area under the curve was 92.8%. In terms of the repeated reading, the evolution of the PSA showed no statistically significant differences between the patients without cancer (p=.56) and those with cancer (P=.64). However, a PSAV value >.3ng/mL/year revealed high specificity for detecting cancer in this population. A baseline PSA level ≥1.9ng/mL in Spanish men aged 40-49 years predicted the development of PC. This value could therefore be of use for opportunistic screening at an early age. An appropriate follow-up adapted to the risk of this population needs to be defined, but an annual PSAV ≥.3ng/mL/year appears of use for reaching an early diagnosis. Copyright © 2015 AEU
Skulachev, Vladimir P.
A concept is presented considering aging of living organisms as a final step of their ontogenetic program. It is assumed that such an aging program was invented by biological evolution to facilitate the evolutionary process. Indications are summarized suggesting that controlled production of toxic forms of oxygen (so called reactive oxygen species) by respiring intracellular organelles (mitochondria) is an obligatory component of the aging program. First results of a research project devoted to an attempt to interrupt aging program by antioxidants specifically addressed to mitochondria have been described. Within the framework of the project, antioxidants of a new type (SkQ) were synthesized. SkQs are composed of (i) plastoquinone (an antioxidant moiety), (ii) a penetrating cation, and (iii) a decane or pentane linker. Using planar bilayer phospholipid membranes, we selected SkQ derivatives of the highest penetrability, namely plastoquinonyl decyl triphenylphosphonium (SkQ1), plastoquinonyl decyl rhodamine 19 (SkQR1), and methylplastoquinonyl decyl triphenylphosphonium (SkQ3). Anti- and prooxidant properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested in isolated mitochondria. Micromolar concentrations of cationic quinones are found to be very strong prooxidants, but in the lower (sub-micromolar) concentrations they display antioxidant activity which decreases in the series SkQ1 = SkQR1 > SkQ3 > MitoQ. Thus, the window between the anti- and prooxidant effects is the smallest for MitoQ and the largest for SkQ1 and SkQR1. SkQ1 is rapidly reduced by complex III of the mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Extremely low concentrations of SkQ1 and SkQR1 completely arrest the H2O2-induced apoptosis in human fibroblasts and HeLa cells (for SkQ1, C 1/2 = 8 · 10-9M). Higher concentrations of SkQ1 are required to block necrosis initiated by reactive oxygen species (ROS). In mice, SkQ1
Full Text Available Deleterious mutations appearing in a population increase in frequency until stopped by natural selection. The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load. Here I develop the comparable concept of a damage load, which is caused by harmful non-heritable changes to the phenotype. A damage load also ensues when the increase of damage is opposed by selection. The presence of a damage load favors the evolution of asymmetrical transmission of damage by a mother to her daughters. The asymmetry is beneficial because it increases fitness variance, but it also leads to aging or senescence. A mathematical model based on microbes reveals that a cell lineage dividing symmetrically is immortal if lifetime damage rates do not exceed a threshold. The evolution of asymmetry allows the lineage to persist above the threshold, but the lineage becomes mortal. In microbes with low genomic mutation rates, it is likely that the damage load is much greater than the mutational load. In metazoans with higher genomic mutation rates, the damage and the mutational load could be of the same magnitude. A fit of the model to experimental data shows that Escherichia coli cells experience a damage rate that is below the threshold and are immortal under the conditions examined. The model estimates the asymmetry level of E. coli to be low but sufficient for persisting at higher damage rates. The model also predicts that increasing asymmetry results in diminishing fitness returns, which may explain why the bacterium has not evolved higher asymmetry.
Verhoog, L. C.; Brekelmans, C. T.; Seynaeve, C.; Meijers-Heijboer, E. J.; Klijn, J. G.
BRCA1/2 mutation carriers diagnosed with breast cancer have a strongly elevated life-time risk of developing a contralateral tumour. We studied the contralateral breast cancer risk in 164 patients from 83 families with a proven BRCA1 mutation in relation to the age at diagnosis of the first primary
Tidwell, Tia R.; Søreide, Kjetil; Hagland, Hanne R.
Medical advances made over the last century have increased our lifespan, but age-related diseases are a fundamental health burden worldwide. Aging is therefore a major risk factor for cardiovascular disease, cancer, diabetes, obesity, and neurodegenerative diseases, all increasing in prevalence. However, huge inter-individual variations in aging and disease risk exist, which cannot be explained by chronological age, but rather physiological age decline initiated even at young age due to lifes...
Vlaeminck-Guillem, Virginie; Ruffion, Alain; André, Jean; Devonec, Marian; Paparel, Philippe
The prostate cancer 3 (PCA3) gene was discovered in 1999, on the basis of differential expression between cancer and noncancerous prostate tissue. Including the first study published in 2003, 11 clinical studies have evaluated its utility for the diagnosis of prostate cancer by measuring the number of PCA3 RNA copies in urine enriched with prostate cells. Although the sensitivity of the PCA3 test was less than that of serum prostate-specific antigen (PSA), its specificity appeared to be much better, particularly in patients with a previous negative biopsy. Recent studies also have suggested that this test could be used to predict cancer prognosis. 2010 Elsevier Inc. All rights reserved.
Agranat, Sivan; Baris, Hagit; Kedar, Inbal; Shochat, Mordechai; Rizel, Shulamith; Perry, Shlomit; Margel, David; Sulkes, Aaron; Yerushalmi, Rinat
Data on genetic anticipation in breast cancer are sparse. We sought to evaluate age at diagnosis of breast cancer in daughters with a BRCA mutation and their mothers. A review of all carriers of the BRCA mutation diagnosed with breast cancer at the Genetics Institute of a tertiary medical center in 2000-2013 yielded 80 women who could be paired with a mother with breast cancer who was either a carrier of the BRCA mutation or an obligate carrier according to pedigree analysis. Age at diagnosis, type of mutation (BRCA1, BRCA2), year of birth, and ethnicity were recorded. Paired t-test was used to analyze differences in age at cancer diagnosis between groups and subgroups. Mean age at diagnosis of breast cancer was 50.74 years (range 22-88) in the mothers and 43.85 years (range 24-75) in the daughters. The difference was statistically significant (p age of 50 years, there was no significant difference in mean age at diagnosis between mothers and daughters (~42 years for both). Daughters who carry a BRCA mutation are diagnosed with breast cancer at an earlier age than their carrier mothers, with the exception of pairs in which the mother was diagnosed before the age of 50 years. Future breast-screening guidelines may need to target specific subpopulations of BRCA mutation carriers. © 2016 Wiley Periodicals, Inc.
Full Text Available Advanced glycation end products (AGEs are produced in an irreversible non-enzymatic reaction of carbohydrates and proteins. Patients with diabetes mellitus (DM are known to have elevated AGE levels, which is viewed as a risk factor of diabetes-related complications. In a clinical setting, it has been shown that patients with oral cancer in conjunction with DM have a higher likelihood of cancer metastasis and lower cancer survival rates. AGE-RAGE (a receptor of AGEs is also correlated with metastasis and angiogenesis. Recent studies have suggested that the malignancy of cancer may be enhanced by glyceraldehyde-derived AGEs; however, the underlying mechanism remains unclear. This study examined the apparently close correlation between AGE-RAGE and the malignancy of SAS oral cancer cell line. In this study, AGEs increased ERK phosphorylation, enhanced cell migration, and promoted the expression of RAGE, MMP2, and MMP9. Using PD98059, RAGE antibody, and RAGE RNAi to block RAGE pathway resulted in the inhibition of ERK phosphorylation. Cell migration, MMP2 and MMP9 expression were also reduced by this treatment. Our findings demonstrate the importance of AGE-RAGE with regard to the malignancy of oral cancer, and help to explain the poor prognosis of DM subjects with oral cancer.
Ambatipudi, Srikant; Horvath, Steve; Perrier, Flavie; Cuenin, Cyrille; Hernandez-Vargas, Hector; Le Calvez-Kelm, Florence; Durand, Geoffroy; Byrnes, Graham; Ferrari, Pietro; Bouaoun, Liacine; Sklias, Athena; Chajes, Véronique; Overvad, Kim; Severi, Gianluca; Baglietto, Laura; Clavel-Chapelon, Françoise; Kaaks, Rudolf; Barrdahl, Myrto; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Naska, Androniki; Masala, Giovanna; Agnoli, Claudia; Polidoro, Silvia; Tumino, Rosario; Panico, Salvatore; Dollé, Martijn; Peeters, Petra H M; Onland-Moret, N Charlotte; Sandanger, Torkjel M; Nøst, Therese H; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Rodriguez-Barranco, Miguel; Huerta Castaño, José María; Barricarte, Aurelio; Fernández, Ander Matheu; Travis, Ruth C; Vineis, Paolo; Muller, David C; Riboli, Elio; Gunter, Marc; Romieu, Isabelle; Herceg, Zdenko
A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007-1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007-1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020-1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03-1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility. Copyright © 2017 Elsevier Ltd. All rights reserved.
Rosalina Jorge Koifman
Full Text Available Antecedents of familial aggregation of breast and ovarian cancer are observed in only 5-8% of all breast cancer cases. Nevertheless, this variable displays one of the highest risk ratios associated to breast cancer outcome. Despite recent identification of genetic mutations associated with familial aggregation of these tumors, mainly at BRCA1 and BRCA2 genes, knowledge on the interaction between environmental agents in these families remains quite unclear. In this paper we ascertained the correlation among ages of the onset of breast/ovarian cancer in 260 Brazilian families with those cancer aggregation. Further we estimated the median age of the onset of breast cancer among four generations. We observed that the higher the number of family cancer cases, the highest is the correlation of ages for the onset of breast cancer. We also observed a 8-10 year decline in the mean age-of-onset of breast/ovarian cancer from one generation to another in the studied families. If these results could be confirmed elsewhere, we believe that the hypothesis of interaction between environmental risks factors in families indeed showing breast/ovarian cancer aggregation is reinforced.
Brocks, David; Assenov, Yassen; Minner, Sarah
Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent epigenetic alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity in DNA methylation and copy-number patterns can be explained...... by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, and lymph node metastases within five cases of prostate cancer, we demonstrate that both DNA methylation and copy-number heterogeneity consistently reflect the life history of the tumors....... Furthermore, we show cases of genetic or epigenetic convergent evolution and highlight the diversity in the evolutionary origins and aberration spectrum between tumor and metastatic subclones. Importantly, DNA methylation can complement genetic data by serving as a proxy for activity at regulatory domains...
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
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
Götz, Joachim; Salcher, Bernhard
Kettle holes are very common features in proglacial environments. Myriads of small, often circular shaped lakes are indicative of dead ice slowly melting out after the collapse of glaciers and subsequent burial of glaciofluvial sediments. Many of these lakes transformed into mires during the Postglacial and the Holocene. Still, little is known about the mechanisms leading to mire formation in such environments. We aim to analyse the shape and the postglacial history of infilling and peat accumulation of a typical dead ice kettle using 2D resistivity surveying, core-drilling, 14C dating and palynologic analyses. The kettle hole mire is located within a small kame delta deposit just south of the LGM extend of the Salzach Piedmont glacier (Austria/Germany). Today, the mire is a spot of exceptional high biodiversity and under protection. Sediment core samples extracted in the deepest (c. 10-14 m) and central part of the kettle directly overly lacustrine fine sediments and yielded young ages covering the subatlantic period only. Young ages are in agreement with palynologic results comprising e.g. pollen of secale (rye) and juglans (walnut). However, these deposits are situated beneath a massive water body (10 m), only covered by a thin floating mat. A second, more distally situated drill core indicates the thinning of this water body at the expense of peat deposits covering the Late Glacial to Middle Holocene. Multiple 2D resistivity data support drilling information and enabled us to reconstruct the shape of the basin. The transition from lacustrine sediments to the water body above is characterised by a sharp increase in resistivity. Furthermore, the resistivity pattern within the entire kettle indicates an increase towards the centre, most probably as a result of the changing nutrient content. The postglacial evolution of the mire is in agreement with the concept of "floating mat terrestrialisation", representing a horizontal growth of the floating mat from the edges
Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown. Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis.
Jesse M Hunter
Full Text Available Key pathological hallmarks of Alzheimer's disease (AD, including amyloid plaques, cerebral amyloid angiopathy (CAA and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1 nonagenarians with AD and a high amyloid plaque load; 2 nonagenarians with no dementia and a high amyloid plaque load; 3 nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND group (average age 71 years with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular "dysfunction" compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD.
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
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
Bertrand, Kimberly A; Tamimi, Rulla M; Scott, Christopher G; Jensen, Matthew R; Pankratz, V; Visscher, Daniel; Norman, Aaron; Couch, Fergus; Shepherd, John; Fan, Bo; Chen, Yunn-Yi; Ma, Lin; Beck, Andrew H; Cummings, Steven R; Kerlikowske, Karla; Vachon, Celine M
Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models. Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (ages, with a two-fold increased risk for high (>51%) versus average density (11-25%). Women ages ages 55-64 and ≥ 65 years (P(age-interaction) = 0.02). Among all ages, MD had a stronger association with large (>2.1 cm) versus small tumors and positive versus negative lymph node status (P's ages breast cancer than ER-positive tumors compared to women ages 55-64 and ≥ 65 years (P(age-interaction) = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group. MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women.
Johnson, Nichola; Dudbridge, Frank; Orr, Nick
. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence......INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ..., associated with age at menarche in controls (Ptrend = 0.005) but not cases (Ptrend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (Phet = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women...
Butt, Salma; Harlid, Sophia; Borgquist, Signe; Ivarsson, Malin; Landberg, Göran; Dillner, Joakim; Carlson, Joyce; Manjer, Jonas
Recent studies have identified several single-nucleotide polymorphisms (SNPs) associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk. The Malmö Diet and Cancer Study (MDCS) included 17 035 female participants, from which 728 incident breast cancer cases were matched to 1448 controls. The associations between 14 SNPs and breast cancer risk were investigated in different strata of parity and age at first childbirth. A logistic regression analysis for the per allele risk, adjusted for potential confounders yielded odds ratios (OR) with 95% confidence intervals (CI). Six of the previously identified SNPs showed a statistically significant association with breast cancer risk: rs2981582 (FGFR2), rs3803662 (TNRC9), rs12443621 (TNRC9), rs889312 (MAP3K1), rs3817198 (LSP1) and rs2107425 (H19). We could not find any statistically significant interaction between the effects of tested SNPs and parity/age at first childbirth on breast cancer risk after adjusting for multiple comparisons. The results of this study are in agreement with previous studies of null interactions between tested SNPs and parity/age at first childbirth with regard to breast cancer risk.
Full Text Available Abstract Background Recent studies have identified several single-nucleotide polymorphisms (SNPs associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk. Methods The Malmö Diet and Cancer Study (MDCS included 17 035 female participants, from which 728 incident breast cancer cases were matched to 1448 controls. The associations between 14 SNPs and breast cancer risk were investigated in different strata of parity and age at first childbirth. A logistic regression analysis for the per allele risk, adjusted for potential confounders yielded odds ratios (OR with 95% confidence intervals (CI. Results Six of the previously identified SNPs showed a statistically significant association with breast cancer risk: rs2981582 (FGFR2, rs3803662 (TNRC9, rs12443621 (TNRC9, rs889312 (MAP3K1, rs3817198 (LSP1 and rs2107425 (H19. We could not find any statistically significant interaction between the effects of tested SNPs and parity/age at first childbirth on breast cancer risk after adjusting for multiple comparisons. Conclusions The results of this study are in agreement with previous studies of null interactions between tested SNPs and parity/age at first childbirth with regard to breast cancer risk.
Ziner, Kim Wagler; Sledge, George W; Bell, Cynthia J; Johns, Shelley; Miller, Kathy D; Champion, Victoria L
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. Cross-sectional survey. Two university cancer centers and one cooperative group in the midwestern United States. 1,128 long-term survivors. 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. Fear of recurrence, breast cancer survivor self-efficacy, and age at diagnosis. 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. 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. 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 recurrence to reduce psychological distress in survivorship follow-up care are warranted.
Hanson, Heidi A.; Smith, Ken R.; Stroup, Antoinette M.; Harrell, C. Janna
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
Liedtke, Cornelia; Rody, Achim; Gluz, Oleg; Baumann, Kristin; Beyer, Daniel; Kohls, Eva-Beatrice; Lausen, Kerstin; Hanker, Lars; Holtrich, Uwe; Becker, Sven; Karn, Thomas
Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40 datasets were compiled and homogenized. Breast cancer subgroups were defined based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was calculated as recurrence-free survival or distant metastasis-free survival if recurrence-free survival was not available. Young age at diagnosis is associated with higher frequency of triple negative and HER2 subtypes and lower frequency of luminal A breast cancers. The 5-year event-free survival rates of patients aged less than 40, between 40 and 50, and >50 years were 54.3 ± 3.5, 68.5 ± 1.9, and 70.4 ± 1.3 %, respectively. When controlling for breast cancer subtype, we found that age breast cancer. The effect was modest in luminal tumors and not found in HER2 subtype. Both subtypes and age retained their significances in multivariate analysis. Association of age at diagnosis with molecular breast cancer subtype contributes to its important role as prognostic factor among patients with breast cancer. Still, within the group of triple negative breast cancer, young age <40 years has a significant prognostic value which was retained in multivariate analysis.
Fribbens, C; Garcia Murillas, I; Beaney, M; Hrebien, S; O'Leary, B; Kilburn, L; Howarth, K; Epstein, M; Green, E; Rosenfeld, N; Ring, A; Johnston, S; Turner, N
Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to the first-line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Eighty-three patients on the first-line AI therapy for metastatic breast cancer were enrolled in a prospective study. Plasma samples were collected every 3 months to disease progression and ctDNA analysed by digital droplet PCR and enhanced tagged-amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by sequencing were tracked back through samples before progression to study the evolution of mutations on therapy. The frequency of novel mutations was validated in an independent cohort of available baseline plasma samples in the Study of Faslodex versus Exemestane with or without Arimidex (SoFEA) trial, which enrolled patients with prior sensitivity to AI. Of the 39 patients who progressed on the first-line AI, 56.4% (22/39) had ESR1 mutations detectable at progression, which were polyclonal in 40.9% (9/22) patients. In serial tracking, ESR1 mutations were detectable median 6.7 months (95% confidence interval 3.7-NA) before clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2% (13/18) patients. Mutations in RAS genes were identified in 15.4% (6/39) of progressing patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in 21.2% (24/113) patients although there was no evidence that KRAS mutation status was prognostic for progression free or overall survival. Cancers progressing on the first-line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic
Creina S Stockley
Creina S StockleyThe Australian Wine Research Institute, Adelaide, South Australia, AustraliaAbstract: Population aging is associated with the increased incidence cancer and of degenerative diseases. Population aging is occurring on a global scale, with faster aging projected for the coming decades than has occurred in the past. Globally, the population aged 60 years and over is projected to nearly triple by 2050, while the population aged 80 years and over is projected to experience a more t...
Jacobs, P A; Maloney, V; Cooke, R; Crolla, J A; Ashworth, A; Swerdlow, A J
.... In blood samples from 565 men with breast cancer and 54 control men from the England and Wales general population, 80 cell nuclei per sample were scored for presence of X and Y chromosomes using...
With the continuing shift of cancer care to community-based care the necessity to develop programs that enable the family to meet patients' needs for support and assistance is of paramount importance...
Bertrand, Kimberly A; Scott, Christopher G; Tamimi, Rulla M; Jensen, Matthew R; Pankratz, V Shane; Norman, Aaron D; Visscher, Daniel W; Couch, Fergus J; Shepherd, John; Chen, Yunn-Yi; Fan, Bo; Wu, Fang-Fang; Ma, Lin; Beck, Andrew H; Cummings, Steven R; Kerlikowske, Karla; Vachon, Celine M
Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)-negative status among women ages breast cancer subtypes. Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression. DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; P(trend) ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (P(trend) age. DA and NDA are important to consider when developing age- and subtype-specific risk models. ©2015 American Association for Cancer Research.
Molinié, Florence; Delacour-Billon, Solenne; Tretarre, Brigitte; Delafosse, Patricia; Seradour, Brigitte; Colonna, Marc
Objective A decrease in advanced breast cancer incidence is considered an early indicator of breast cancer mortality reduction in a screening programme. We describe trends in breast cancer incidence according to tumour size and age in three French administrative areas, where an organized screening programme was implemented during the 1990s. Methods Our study included all 28,092 invasive breast cancers diagnosed from 2000 to 2010 in women living in three areas (Hérault, Isère, Loire-Atlantique). Age, year of diagnosis, and size of tumour at diagnosis was provided by the three area cancer registries. Poisson regression models were fitted to estimate changes in incidence over time, after adjustment for age and administrative area. Results From 2000 to 2010, the incidence rate of large (tumour size >20 mm) breast cancer linearly decreased in women aged 50-74 (target age of the screening programme) from 108.4 to 84.1/100,000 (annual percent change = -1.9%, p trend in incidence of large tumour size breast cancer in the target age of the screening programme is demonstrated for the first time in France. The overall 20.9% linear decrease over 11 years in these three areas is encouraging and should be closely monitored and extended to other areas of France, where the screening programme was generally implemented only in 2004.
Thomé, B; Esbensen, B A; Dykes, A-K
Little is known about how older people with cancer experience their life situation. To increase the understanding of how illness is experienced in older people with cancer, the aim of this study was to investigate the meaning of living with cancer in old age. The hermeneutic phenomenological method...... as described by van Manen and referred to as 'phenomenology of praxis' was used. Ten persons (seven women and three men) aged 75 and over, who had a diagnosis of cancer and who had just completed cancer treatment, were interviewed in their own homes. The analysis revealed a life world affected to varying...... degrees by the cancer disease. The lived experiences across the interviews were revealed in four overarching essential themes: transition into a more or less disintegrated existence, sudden awareness of the finiteness of life, redefinition of one's role in life for good and for bad, meeting disease...
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.
Bogusz, Renata; Humeniuk, Ewa; Walecka, Irena; Bojar, Iwona
Women aged 50-69 are the most likely to develop breast cancer. Knowledge about breast tumours as well as regular examination are two of the key factors which reduce the risk of the disease, and increase both the success of treatment and chances of survival. The aim of the paper was to assess knowledge about risk factors, symptoms, screening, early diagnosis and breast cancer treatment among women in perimenopausal age. 400 women aged 45-60, residing in the Lublin region of eastern Poland participated in the research. The primary research tool was a questionnaire with 35 questions checking knowledge about symptoms, screening and early diagnosis, as well as breast cancer treatment. Particulars were also part of the questionnaire. Over 50% of women obtained average results with regard to general knowledge, 40% obtained high results and 6% low results. Subjective assessment of the women's knowledge was statistically significantly (pbreast cancer early diagnosis and therapy. Over a half of the women in perimenopausal age had average general knowledge, while only 40% - high. Over half of the women in perimenopausal age had average general knowledge, while only 40% - high. Subjective assessment of knowledge differed statistically significantly from the objective assessment. Women with higher education and living in rural areas displayed a higher level of general knowledge about breast cancer. The study did not identified any relationship between level of knowledge about breast cancer and age, financial situation or health of women in perimenopausal age.
Kadhel, Philippe; Multigner, Luc
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. © 2014 Wiley Periodicals, Inc.
Tsai, Hsiu-Pei; Huang, Shiang-Fu; Li, Chien-Fan; Chien, Huei-Tzu; Chen, Shin-Cheh
The lower breast cancer incidence in Asian populations compared with Western populations has been speculated to be caused by environmental and genetic variation. Early-onset breast cancer occupies a considerable proportion of breast cancers in Asian populations, but the reason for this is unclear. We aimed to examine miRNA expression profiles in different age-onset groups and pathological subtypes in Asian breast cancer. At the first stage, 10 samples (tumor: n = 6, normal tissue: n = 4) were analyzed with an Agilent microRNA 470 probe microarray. Candidate miRNAs with expression levels that were significantly altered in breast cancer samples or selected from a literature review were further validated by quantitative real-time PCR (qPCR) of 145 breast cancer samples at the second stage of the process. Correlations between clinicopathological parameters of breast cancer patients from different age groups and candidate miRNA expression were elucidated. In the present study, the tumor subtypes were significantly different in each age group, and an onset age below 40 had poor disease-free and overall survival rates. For all breast cancer patients, miR-335 and miR-145 were down-regulated, and miR-21, miR-200a, miR-200c, and miR-141 were up-regulated. In very young patients (age cancer. Differential miRNA expressions between normal and tumor tissues were observed in different age groups and tumor subtypes. Evolutionarily conserved miRNA clusters, which initiate malignancy transformation, were up-regulated in the breast cancers of very young patients. None of the significantly altered miRNAs were observed in postmenopausal patients.
Melanin provides a crucial filter for solar UV radiation and its genetically determined variation influences both skin pigmentation and risk of cancer. Genetic evidence suggests that the acquisition of a highly stable melanocortin 1 receptor allele promoting black pigmentation arose around the time of savannah colonization by hominins at some 1–2 Ma. The adaptive significance of dark skin is generally believed to be protection from UV damage but the pathologies that might have had a deleterious impact on survival and/or reproductive fitness, though much debated, are uncertain. Here, I suggest that data on age-associated cancer incidence and lethality in albinos living at low latitudes in both Africa and Central America support the contention that skin cancer could have provided a potent selective force for the emergence of black skin in early hominins. PMID:24573849
Isaacowitz, Derek M; Harris, Julia A
Older adults fixate less on negative parts of skin cancer videos than younger adults, leading them to feel better (Isaacowitz & Choi, 2012). We extended this paradigm to middle-aged adults (ages 35-59, n = 63), whose fixation patterns were measured as they viewed skin cancer videos; mood and behavior were also assessed. Middle-aged adults looked even less at the videos than the other age groups, especially at the negative clips. They also reported the best moods but relatively low levels of learning and positive skin cancer behavior. In some cases, middle-aged adults may show larger "age-related positivity effects" than older adults. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Marti, R.; Gascoin, S.; Houet, T.; Ribière, O.; Laffly, D.; Condom, T.; Monnier, S.; Schmutz, M.; Camerlynck, C.; Tihay, J. P.; Soubeyroux, J. M.; René, P.
Little is known about the fluctuations of the Pyrenean glaciers. In this study, we reconstructed the evolution of Ossoue Glacier (42°46' N, 0.45 km2), which is located in the central Pyrenees, from the Little Ice Age (LIA) onwards. To do so, length, area, thickness, and mass changes in the glacier were generated from historical data sets, topographical surveys, glaciological measurements (2001-2013), a ground penetrating radar (GPR) survey (2006), and stereoscopic satellite images (2013). The glacier has receded considerably since the end of the LIA, losing 40 % of its length and 60 % of its area. Three periods of marked ice depletion were identified: 1850-1890, 1928-1950, and 1983-2013, as well as two short periods of stabilization: 1890-1894, 1905-1913, and a longer period of slight growth: 1950-1983; these agree with other Pyrenean glacier reconstructions (Maladeta, Coronas, Taillon glaciers). Pyrenean and Alpine glaciers exhibit similar multidecadal variations during the 20th century, with a stable period detected at the end of the 1970s and periods of ice depletion during the 1940s and since the 1980s. Ossoue Glacier fluctuations generally concur with climatic data (air temperature, precipitation, North Atlantic Oscillation, Atlantic Multidecadal Oscillation). Geodetic mass balance over 1983-2013 was -1.04 ± 0.06 w.e.a-1 (-31.3 ± 1.9 m w.e.), whereas glaciological mass balance was -1.45 ± 0.85 m w.e. a-1 (-17.3 ± 2.9 m w.e.) over 2001-2013, resulting in a doubling of the ablation rate in the last decade. In 2013 the maximum ice thickness was 59 ± 10.3 m. Assuming that the current ablation rate remains constant, Ossoue Glacier will disappear midway through the 21st century.
Full Text Available Little is known about the fluctuations of the Pyrenean glaciers. In this study, we reconstructed the evolution of Ossoue Glacier (42°46' N, 0.45 km2, which is located in the central Pyrenees, from the Little Ice Age (LIA onwards. To do so, length, area, thickness, and mass changes in the glacier were generated from historical data sets, topographical surveys, glaciological measurements (2001–2013, a ground penetrating radar (GPR survey (2006, and stereoscopic satellite images (2013. The glacier has receded considerably since the end of the LIA, losing 40 % of its length and 60 % of its area. Three periods of marked ice depletion were identified: 1850–1890, 1928–1950, and 1983–2013, as well as two short periods of stabilization: 1890–1894, 1905–1913, and a longer period of slight growth: 1950–1983; these agree with other Pyrenean glacier reconstructions (Maladeta, Coronas, Taillon glaciers. Pyrenean and Alpine glaciers exhibit similar multidecadal variations during the 20th century, with a stable period detected at the end of the 1970s and periods of ice depletion during the 1940s and since the 1980s. Ossoue Glacier fluctuations generally concur with climatic data (air temperature, precipitation, North Atlantic Oscillation, Atlantic Multidecadal Oscillation. Geodetic mass balance over 1983–2013 was −1.04 ± 0.06 w.e.a−1 (−31.3 ± 1.9 m w.e., whereas glaciological mass balance was −1.45 ± 0.85 m w.e. a−1 (−17.3 ± 2.9 m w.e. over 2001–2013, resulting in a doubling of the ablation rate in the last decade. In 2013 the maximum ice thickness was 59 ± 10.3 m. Assuming that the current ablation rate remains constant, Ossoue Glacier will disappear midway through the 21st century.
Faguet, Guy B
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. © 2014 UICC.
Full Text Available 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.
Waldmann, A; Raspe, H; Katalinic, A
The question whether persons at familial or hereditary risk differ in terms of absolute, relative, or cumulative risk for colorectal cancer or not is of importance for the estimation of the potential of early detection of colorectal cancer in persons with familial or hereditary risks. Based on the results of a systematic literature search on absolute, relative, and cumulative risks of familial and hereditary disposition for colorectal cancer as well as actual German tumour incidence data, projections were conducted. The absolute risk for colorectal cancer in familial risk persons identified by means of a questionnaire is increased by a factor of 2 - 4 depending on the age at questioning, the age of the family member at cancer diagnosis and number of family members with colorectal cancer. Their absolute colorectal cancer risk equals that of persons without this risk who are 10 to 15 years older. Persons with hereditary risk show an increase in risk by a factor of 8 - 80. Persons aged 40 to 45 years with a familial risk constellation show a risk for colorectal cancer that equals the risk of 55- to 59-year-old persons from the general population. Therefore, the legal right for screening colonoscopy should be extended to the persons at risk aged 40 to 45 years. Persons suspected for hereditary risk should have a genetic counselling and, in case of germ mutation, a colonoscopic surveillance according to the actual guidelines. Copyright Georg Thieme Verlag KG Stuttgart . New York.
Aims/Objective: To determine the distribution of bowel cancer with special emphasis on age, sex and site. Methods: One hundred and sixty cases of histologically confirmed large bowel cancers at Jos University Teaching Hospital between January 1991 – December 2000 were reviewed. The records were collected from the ...
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.
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
Jessica M. Dolle; Janet R. Daling; Emily White; Louise A. Brinton; David R. Doody; Peggy L. Porter; Kathleen E. Malone
.... We undertook this study to assess the risk for triple-negative breast cancer among women 45 years of age and younger in relation to demographic/lifestyle factors, reproductive history, and oral contraceptive use...
Tryggvadóttir, Laufey; Tulinius, Hrafn; Eyfjord, Jórunn E; Sigurvinsson, Trausti
An increasing number of studies indicates that the strength and even direction of association between breast cancer and established risk factors differ according to the woman's age when she develops the disease...
Madsen, Claus Desler; Espersen, Maiken Lise Marcker; Singh, Keshav K
of the mitochondrial genome contributes to the development of age- and tumor-related pathological conditions. The mechanisms described encompass altered production of mitochondrial ROS, altered regulation of the nuclear epigenome, affected initiation of apoptosis, and a limiting effect on the production......Mitochondrial dysfunction has been implicated in premature aging, age-related diseases, and tumor initiation and progression. Alterations of the mitochondrial genome accumulate both in aging tissue and tumors. This paper describes our contemporary view of mechanisms by which alterations...
Wada, Saho; Shimizu, Ken; Inoguchi, Hironobu; Shimoda, Haruki; Yoshiuchi, Kazuhiro; Akechi, Tatsuo; Uchida, Megumi; Ogawa, Asao; Fujisawa, Daisuke; Inoue, Shinichirou; Uchitomi, Yosuke; Matsushima, Eisuke
There is controversy around the association between depressive symptoms and age in adult cancer patients. The aim of this study was to evaluate the following hypotheses: 1) cancer patients' depressive symptoms decrease with age, and 2) in individuals aged 65 years or older, depressive symptoms increase because of the effect of somatic symptoms. We retrospectively analyzed a database of 356 cancer patients who were consecutively recruited in a previous multicenter cross-sectional study. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9), and correlations with age and other factors were assessed by hierarchical multivariate regression analysis. Age was entered as the dependent variable in the first step, patient characteristics and cancer-related variables were entered in the second step, and somatic symptoms were entered in the last step. We analyzed this model for both the total sample and the subpopulation aged 65 years or older. In the total sample, the PHQ-9 score was significantly associated with lower age, fatigue, and shortness of breath (adjusted R(2) 14.2%). In the subpopulation aged 65 years or older, no factor was associated with the PHQ-9 score (adjusted R(2) 7.3%). The finding that depressive symptoms in cancer patients decreased with age was concordant with our first hypothesis, but the second hypothesis was not supported. Younger cancer patients were vulnerable to depressive symptoms and should be monitored carefully. Further studies using more representative samples are needed to examine in detail the association between depressive symptoms and age in older cancer patients. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
Krastan B Blagoev
Full Text Available Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1 do mutations in the target/pathway confer resistance? (2 Are these mutations pre-existing? (3 What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC. We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices. We analyzed published data and our own data to calculate rates of growth (g and regression (d, decay of tumors in patients with CRC correlating these results with the detection of circulating MT-KRAS DNA. Additionally we estimated mathematically the caloric burden of such tumors using data on mitotic and apoptotic indices. We conclude outgrowth of cells harboring intrinsic or acquired MT-KRAS cannot explain resistance to anti-EGFR (epidermal growth factor receptor antibodies. Rates of tumor growth with panitumumab are unaffected by presence/absence of MT-KRAS. While MT-KRAS cells may be resistant to anti-EGFR antibodies, WT-KRAS cells also rapidly bypass this blockade suggesting inherent resistance mechanisms are responsible and a neutral evolution model is most appropriate. Using the above clinical data on tumor doubling times and mitotic and apoptotic indices we estimated the caloric intake required to support tumor growth and suggest it may explain in part cancer-associated cachexia.
Brandizzi, Daniel; Gandolfo, Mariana; Velazco, María Lucia; Cabrini, Rómulo Luis; Lanfranchi, Hector Eduardo
Oral Squamous Cell Carcinoma has a low survival rate, 34 to 66% five-year survival after initial diagnosis, due to late diagnosis. The aim of the present study was to examine the clinical features and evolution of oral cancer in the University of Buenos Aires. 274 patients with primary oral carcinoma, over the 1992-2000 period were included in the study. The survival rate of this population was 80% at 12 months, 60% at 24 months, 46% at 36 months, 40% at 48 months, and 39% at 60 months (5 years). The tumor localizations with worse prognosis were floor of mouth and tongue, with survival rates of 19% and 27% respectively. Sixty-five percent of the oral carcinomas evaluated were diagnosed at advanced stages (III and IV). The patients under study exhibited the lowest survival rate described for oral cancer (34% five-year survival after initial diagnosis). The population included in this study can be considered representative of the Argentine population. This bad prognosis would be mainly due to the large number of oral cancer cases that were diagnosed at advanced stages.
Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne-Vibeke
Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer...... progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each...
Pan, Jie; Zhao, Jun; Jiang, Ning
Objective: The immune compromised patients after treatment of oral cancer may have a chance of infection by drug-resistant opportunistic microbes. We investigated the occurrence of opportunistic microorganisms in aged individuals receiving follow-up examinations after treatment of oral cancer in China. Material and Methods: These patients were used as test group and the respective age grouped healthy individuals as control group. In this study, the oral cavity microorganisms such as bact...
Agustina, Edelyn; Dodd, Rachael H; Waller, Jo; Vrinten, Charlotte
Cancer is still widely feared and often associated with death. Fatalistic beliefs adversely affect help-seeking for cancer symptoms and engagement in cancer prevention. This study aims to understand middle-aged and older adults' first association with the word "cancer" and their relationship with sociodemographic factors, cancer fear, and cancer information avoidance. We conducted a cross-sectional survey of 1464 community-based adults aged 50 to 70 living in England in April 2015. First associations with cancer were measured qualitatively and analysed using content analysis. We used binary logistic regression to analyse associations between the most common first association of cancer and sociodemographic characteristics, cancer fear, and cancer information avoidance. Cancer was most commonly associated with "death" (26%). Respondents with lower levels of education, living in the Midlands or North of England where cancer mortality is higher, or with close friends or family members with a cancer history, were more likely to associate cancer with death. Cancer fear was significantly associated with death associations, but cancer information avoidance was not. Despite improved cancer outcomes, middle-aged and older adults often associate cancer with death. Further efforts to decrease fatalistic associations in this age group may be needed. © 2017 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.
Vogel, Jeffery E; Chu, Carrie; McCullough, Meghan; Anderson, Erica; Losken, Albert; Carlson, Grant W
Breast cancer in women under 40 years of age is rare, accounting for approximately 5% of cases. The disease tends to be more aggressive in younger women. Younger age has been shown to be an independent predictive of breast reconstruction after total mastectomy. Treatment by total mastectomy and reconstruction is examined in relation to patient age. A retrospective review of all breast cancer patients treated by total mastectomy and reconstruction between 2005 and 2009 was performed by querying a prospective database. A total of 671 patients underwent total mastectomy and reconstruction; of them, 106 (16%) aged mastectomy (P mastectomy.
Yu, Elizabeth A; Weaver, David R
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.
Schonberg, Mara A; Li, Vicky W; Eliassen, A Heather; Davis, Roger B; LaCroix, Andrea Z; McCarthy, Ellen P; Rosner, Bernard A; Chlebowski, Rowan T; Rohan, Thomas E; Hankinson, Susan E; Marcantonio, Edward R; Ngo, Long H
The Breast Cancer Risk Assessment Tool (BCRAT, "Gail model") is commonly used for breast cancer prediction; however, it has not been validated for women age 75 years and older. We used Nurses' Health Study (NHS) data beginning in 2004 and Women's Health Initiative (WHI) data beginning in 2005 to compare BCRAT's performance among women age 75 years and older with that in women age 55 to 74 years in predicting five-year breast cancer incidence. BCRAT risk factors include: age, race/ethnicity, age at menarche, age at first birth, family history, history of benign breast biopsy, and atypia. We examined BCRAT's calibration by age by comparing expected/observed (E/O) ratios of breast cancer incidence. We examined discrimination by computing c-statistics for the model by age. All statistical tests were two-sided. Seventy-three thousand seventy-two NHS and 97 081 WHI women participated. NHS participants were more likely to be non-Hispanic white (96.2% vs 84.7% in WHI, P breast cancer (1.8% vs 2.0%, P = .02). E/O ratios by age in NHS were 1.16 (95% confidence interval [CI] = 1.09 to 1.23, age 57-74 years) and 1.31 (95% CI = 1.18 to 1.45, age ≥ 75 years, P = .02), and in WHI 1.03 (95% CI = 0.97 to 1.09, age 55-74 years) and 1.10 (95% CI = 1.00 to 1.21, age ≥ 75 years, P = .21). E/O ratio 95% confidence intervals crossed one among women age 75 years and older when samples were limited to women who underwent mammography and were without significant illness. C-statistics ranged between 0.56 and 0.58 in both cohorts regardless of age. BCRAT accurately predicted breast cancer for women age 75 years and older who underwent mammography and were without significant illness but had modest discrimination. Models that consider individual competing risks of non-breast cancer death may improve breast cancer risk prediction for older women. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: email@example.com.
Isaacowitz, Derek M.; Harris, Julia
Older adults fixate less on negative parts of skin cancer videos than younger adults, leading them to feel better (Isaacowitz & Choi, 2012). We extended this paradigm to middle-aged adults (ages 35–59, n=63), whose fixation patterns were measured as they viewed skin cancer videos; mood and behavior were also assessed. Middle-aged adults looked even less at the videos than the other age groups, especially at the negative clips. They also reported the best moods, but relatively low levels of le...
Lorenzi, Tommaso; Chisholm, Rebecca H; Clairambault, Jean
A thorough understanding of the ecological and evolutionary mechanisms that drive the phenotypic evolution of neoplastic cells is a timely and key challenge for the cancer research community. In this respect, mathematical modelling can complement experimental cancer research by offering alternative means of understanding the results of in vitro and in vivo experiments, and by allowing for a quick and easy exploration of a variety of biological scenarios through in silico studies. To elucidate the roles of phenotypic plasticity and selection pressures in tumour relapse, we present here a phenotype-structured model of evolutionary dynamics in a cancer cell population which is exposed to the action of a cytotoxic drug. The analytical tractability of our model allows us to investigate how the phenotype distribution, the level of phenotypic heterogeneity, and the size of the cell population are shaped by the strength of natural selection, the rate of random epimutations, the intensity of the competition for limited resources between cells, and the drug dose in use. Our analytical results clarify the conditions for the successful adaptation of cancer cells faced with environmental changes. Furthermore, the results of our analyses demonstrate that the same cell population exposed to different concentrations of the same cytotoxic drug can take different evolutionary trajectories, which culminate in the selection of phenotypic variants characterised by different levels of drug tolerance. This suggests that the response of cancer cells to cytotoxic agents is more complex than a simple binary outcome, i.e., extinction of sensitive cells and selection of highly resistant cells. Also, our mathematical results formalise the idea that the use of cytotoxic agents at high doses can act as a double-edged sword by promoting the outgrowth of drug resistant cellular clones. Overall, our theoretical work offers a formal basis for the development of anti-cancer therapeutic protocols that
Gonzalez, Llilians Calvo; Ghadaouia, Sabrina; Martinez, Aurélie; Rodier, Francis
Normal and cancer cells facing their demise following exposure to radio-chemotherapy can actively participate in choosing their subsequent fate. These programmed cell fate decisions include true cell death (apoptosis-necroptosis) and therapy-induced cellular senescence (TIS), a permanent "proliferative arrest" commonly portrayed as premature cellular aging. Despite a permanent loss of proliferative potential, senescent cells remain viable and are highly bioactive at the microenvironment level, resulting in a prolonged impact on tissue architecture and functions. Cellular senescence is primarily documented as a tumor suppression mechanism that prevents cellular transformation. In the context of normal tissues, cellular senescence also plays important roles in tissue repair, but contributes to age-associated tissue dysfunction when senescent cells accumulate. Theoretically, in multi-step cancer progression models, cancer cells have already bypassed cellular senescence during their immortalization step (see hallmarks of cancer). It is then perhaps surprising to find that cancer cells often retain the ability to undergo TIS, or premature aging. This occurs because cellular senescence results from multiple signalling pathways, some retained in cancer cells, aiming to prevent cell cycle progression in damaged cells. Since senescent cancer cells persist after therapy and secrete an array of cytokines and growth factors that can modulate the tumor microenvironment, these cells may have beneficial and detrimental effects regarding immune modulation and survival of remaining proliferation-competent cancer cells. Similarly, while normal cells undergoing senescence are believed to remain indefinitely growth arrested, whether this is true for senescent cancer cells remains unclear, raising the possibility that these cells may represent a reservoir for cancer recurrence after treatment. This review discusses our current knowledge on cancer cell senescence and highlight questions
Aging is the progressive accumulation in an organism of diverse, deleterious changes with time that increase the chance of disease and death. The basic chemical process underlying aging was first advanced by the free radical theory of aging (FRTA) in 1954: the reaction of active free radicals, normally produced in the organisms, with cellular constituents initiates the changes associated with aging. The involvement of free radicals in aging is related to their key role in the origin and evolution of life. The initial low acceptance of the FRTA by the scientific community, its slow growth, manifested by meetings and occasional papers based on the theory, prompted this account of the intermittent growth of acceptance of the theory over the past nearly 55 years.
Partridge, Ann H; Hughes, Melissa E; Warner, Erica T; Ottesen, Rebecca A; Wong, Yu-Ning; Edge, Stephen B; Theriault, Richard L; Blayney, Douglas W; Niland, Joyce C; Winer, Eric P; Weeks, Jane C; Tamimi, Rulla M
Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes. We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer-specific survival. A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors. The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers. © 2016 by American Society of Clinical Oncology.
Semple, John; Metcalfe, Kelly A; Lubinski, Jan; Huzarski, Tomasz; Gronwald, Jacek; Armel, Susan; Lynch, Henry T; Karlan, Beth; Foulkes, William; Singer, Christian F; Neuhausen, Susan L; Eng, Charis; Iqbal, Javaid; Narod, Steven A
The purpose of this study is to estimate the age-specific annual risks of breast cancer in a woman with a germline BRCA mutation and an affected first-degree relative according to the age of breast cancer diagnosis in the relative. Women with BRCA mutations with no previous diagnosis of breast cancer and with one first-degree relative with breast cancer were followed for breast cancers for a mean of 5.9 years (minimum 2 years). Age-specific annual breast cancer risks were calculated, according to the age of breast cancer diagnosis in the proband and the first-degree relative. 1114 cancer-free women with a BRCA mutation with a single first-degree relative with breast cancer were eligible for the study. 122 women (11.0 %) were diagnosed with incident breast cancer. The annual risk of breast cancer was 2.0 % for women with BRCA1 mutations and was 1.6 % for women with BRCA2 mutations. The age of breast cancer diagnosis in the first-degree relative did not affect the annual breast cancer risks for BRCA1 mutation carriers. For BRCA2 mutation carriers, the annual breast cancer risk was 4.5 % for women with a first-degree relative diagnosed with breast cancer under the age of 30 years and was 0.7 % for women with a relative diagnosed over the age of 60. Among women with BRCA2 mutations, a family history of early-onset breast cancer is a risk factor for developing breast cancer. Risk assessment for healthy BRCA2 mutation carriers should consider the ages of breast cancers diagnosed in first-degree relatives.
van den Broek, Alexandra J; van 't Veer, Laura J; Hooning, Maartje J; Cornelissen, Sten; Broeks, Annegien; Rutgers, Emiel J; Smit, Vincent T H B M; Cornelisse, Cees J; van Beek, Mike; Janssen-Heijnen, Maryska L; Seynaeve, Caroline; Westenend, Pieter J; Jobsen, Jan J; Siesling, Sabine; Tollenaar, Rob A E M; van Leeuwen, Flora E; Schmidt, Marjanka K
To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations. A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses. After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 [95% CI, 2.41 to 4.55; P Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively. Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling. © 2015 by American Society of Clinical Oncology.
Eilati, Erfan; Pan, Lurui; Bahr, Janice M.; Hales, Dale Buchanan
Chronic inflammation has been linked to cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory lipid and one of the downstream products of 2 isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. Ovarian cancer is the most lethal gynecological malignancy and mainly occurs in older women. The factors that contribute to the correlation of age and ovarian cancer are unknown. The purpose of this study was to examine the expression of COX enzymes and PGE2 levels in ovaries and correlate them to ovarian cancer and aging. White Leghorn hens aged 1, 1.5, 2, 2.5, 3 and 3.5 years were used. The incidence of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 protein and mRNA expression and PGE2 concentrations in ovaries were measured using Western blot, quantitative real-time PCR and ELISA, respectively. Our results indicated an increase in ovarian cancer incidence and expression of both COX enzymes in ovaries of older hens. In correlation with ovarian cancer incidence and COX enzymes expression, PGE2 concentrations were elevated with age. Ovaries with tumor had elevated COX-1 expression and PGE2 concentration compared to normal ovaries. Our findings suggest that the up-regulation of COX enzymes with age is the main contributing factor in the age associated increase in PGE2. Furthermore, elevated PGE2 in ovaries of hens concomitant with age suggests its important role in early stages of ovarian carcinogenesis. These finding may provide the basis for clinical trials utilizing COX specific inhibitors or dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer. PMID:23089186
Lafata, Jennifer Elston; Salloum, Ramzi G; Fishman, Paul A; Ritzwoller, Debra Pearson; O'Keeffe-Rosetti, Maureen C; Hornbrook, Mark C
We compare breast and colorectal cancer survivors' annual receipt of preventive care and office visits to that of age- and gender-matched cancer-free controls. Automated data, including tumor registries, were used to identify insured individuals aged 50+ at the time of breast or colorectal cancer diagnosis between 2000 and 2008 as well as cancer-free controls receiving care from four integrated delivery systems. Those with metastatic or un-staged disease, or a prior cancer diagnosis were excluded. Annual visits to primary care, oncology, and surgery as well as receipt of mammography, colorectal cancer, Papanicolaou, bone densitometry, and cholesterol screening were observed for 5 years. We used generalized estimating equations that accounted for repeated observations over time per person to test annual service use differences by cancer survivor/cancer-free control status and whether survivor/cancer-free status associations were moderated by patient age breast and 1530 colorectal cancer survivors were identified, representing 12,923 and 5103 patient-years of follow-up, respectively. Compared to cancer-free controls, breast and colorectal cancer survivors were equally or more likely to use all types of office visits and to receive cancer screenings and bone densitometry testing. Both breast and colorectal cancer survivors were less likely than cancer-free controls to receive cholesterol testing, regardless of age, year of diagnosis, or use of primary care. Programs targeting cancer survivors may benefit from addressing a broad range of primary preventive care needs, including recommended cardiovascular disease screening.
Thomé, B; Esbensen, B A; Dykes, A-K
Little is known about how older people with cancer experience their life situation. To increase the understanding of how illness is experienced in older people with cancer, the aim of this study was to investigate the meaning of living with cancer in old age. The hermeneutic phenomenological method...... as described by van Manen and referred to as 'phenomenology of praxis' was used. Ten persons (seven women and three men) aged 75 and over, who had a diagnosis of cancer and who had just completed cancer treatment, were interviewed in their own homes. The analysis revealed a life world affected to varying...... person's thoughts about death. Thus, it is important to encourage the old person to describe her/his illness experience to increase understanding about what is meaningful for her/him....
Leyla Bulatovna Djansugurova
Full Text Available Aging associates with a variety of pathological conditions such as cancer, cardiovascular, neurodegenerative, autoimmune diseases, and metabolic disorders. The oncogenic alterations overlap frequently with the genes linked to aging. Here, we show that several aging related genes may serve as the genetic risk factors for cervical and esophagus cancers. In our study, we analyzed samples obtained from 115 patients with esophageal and 207 patients with cervical cancer. The control groups were selected to match the ethnicity and age of cancer patients. We examined the genes involved in the processes of xenobiotics detoxification (GSTM1 and GSTT1, DNA repair (XRCC1 and XRCC3, and cell cycle regulation and apoptosis (CCND1 and TP53. Our study revealed that deletions of GSTT1 and GSTM1 genes or the distinct point mutations of XRCC1 gene are associated with cervical and esophageal cancers. These results will lead to development of screening for detection of individuals susceptible to esophageal and cervical cancers. Introduction of the screening programs will allow the early and effective preventive measures that will reduce cancer incidence and mortality in Kazakhstan.
Full Text Available Mitochondrial dysfunction has been implicated in premature aging, age-related diseases, and tumor initiation and progression. Alterations of the mitochondrial genome accumulate both in aging tissue and tumors. This paper describes our contemporary view of mechanisms by which alterations of the mitochondrial genome contributes to the development of age- and tumor-related pathological conditions. The mechanisms described encompass altered production of mitochondrial ROS, altered regulation of the nuclear epigenome, affected initiation of apoptosis, and a limiting effect on the production of ribonucleotides and deoxyribonucleotides.
Falandry, Claire; Bonnefoy, Marc; Freyer, Gilles; Gilson, Eric
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.
Molleman, F.; Zwaan, B J; Brakefield, P M; Carey, J.R.
Information on the life span of organisms in the field is essential for elucidating the evolution of life span and aging. We present mark-recapture data (>30 000 marked individuals, >4000 recaptured at least once) on forty-seven species of fruit-feeding butterflies in a tropical forest in Uganda. The data reveal adult life spans in the field for several species that are significantly longer than previously recorded in Lepidoptera (butterflies and moths). Longevity records for species of which...
Blacher, Pierre; Timothy J. Huggins; Bourke, Andrew F. G.
Eusocial insects provide special opportunities to elucidate the evolution of ageing as queens have apparently evaded costs of reproduction and reversed the fecundity?longevity trade-off generally observed in non-social organisms. But how reproduction affects longevity in eusocial insects has rarely been tested experimentally. In this study, we took advantage of the reproductive plasticity of workers to test the causal role of reproduction in determining longevity in eusocial insects. Using th...
Lokate, Mariëtte; Stellato, Rebecca K; Veldhuis, Wouter B; Peeters, Petra H M; van Gils, Carla H
High mammographic density is a strong breast cancer risk factor. Density normally declines with aging. We investigated whether the level of decline in mammographic density is related to breast cancer risk using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Prospect cohort. This cohort was recruited among participants of a population-based breast cancer screening program in the Netherlands between 1993 and 1997. We examined whether age-related changes in mammographic density were different for 533 cases and 1,367 controls who were 49-69 years of age at the time of recruitment into the cohort. We used mixed models with linear and quadratic terms for age and interaction terms between age terms and case status. The percent mammographic density at the first available mammogram was higher for cases than for controls (25.2% vs. 22.5%) (P = 0.003). The average decline in density over 10 years was 11% in both cases and controls (P = 0.56). When studying changes among 4 categories of density, we saw some indication that large changes may influence breast cancer risk. Although no difference was seen in the average decline, we cannot exclude that large changes may influence breast cancer risk.
Full Text Available Abstract Background Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia. Methods International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC model was used to estimate the period effect (adjusted for age and cohort effects for mortality from lung cancer. Results The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns. Conclusion Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries.
Full Text Available Julia M Sidorova,1,* Raymond J Monnat Jr,1,2,* 1Department of Pathology, 2Department of Genome Sciences, University of Washington, Seattle, WA, USA *The authors contributed equally to this review Abstract: DNA helicases use the energy of ATP hydrolysis to disrupt DNA base pairing and displace proteins from DNA in order to facilitate replication, recombination, transcription, and repair. This article focuses on the human RECQ helicases, five DNA-dependent helicases that play key roles in cellular physiology and disease. Loss of function of three RECQ helicases causes the cancer predisposition syndromes Bloom syndrome, Werner syndrome, and Rothmund–Thomson and related syndromes. We summarize recent work on these syndromes and proteins and discuss disease pathogenesis in light of RECQ helicase biochemical activities and in vivo functions. Keywords: ATP-dependent DNA helicase, Bloom syndrome, Werner syndrome, Rothmund–Thomson syndrome, DNA replication, DNA repair, genetic instability, cancer predisposition syndrome
Objective To correct cervical cancer mortality rates for death cause certification problems in Belgium and to describe the corrected trends (1954-1997) using Bayesian models. Method Cervical cancer (cervix uteri (CVX), corpus uteri (CRP), not otherwise specified (NOS) uterus cancer and other very rare uterus cancer (OTH) mortality data were extracted from the WHO mortality database together with population data for Belgium and the Netherlands. Different ICD (International Classification of Diseases) were used over time for death cause certification. In the Netherlands, the proportion of not-otherwise specified uterine cancer deaths was small over large periods and therefore internal reallocation could be used to estimate the corrected rates cervical cancer mortality. In Belgium, the proportion of improperly defined uterus deaths was high. Therefore, the age-specific proportions of uterus cancer deaths that are probably of cervical origin for the Netherlands was applied to Belgian uterus cancer deaths to estimate the corrected number of cervix cancer deaths (corCVX). A Bayesian loglinear Poisson-regression model was performed to disentangle the separate effects of age, period and cohort. Results The corrected age standardized mortality rate (ASMR) decreased regularly from 9.2/100 000 in the mid 1950s to 2.5/100,000 in the late 1990s. Inclusion of age, period and cohort into the models were required to obtain an adequate fit. Cervical cancer mortality increases with age, declines over calendar period and varied irregularly by cohort. Conclusion Mortality increased with ageing and declined over time in most age-groups, but varied irregularly by birth cohort. In global, with some discrete exceptions, mortality decreased for successive generations up to the cohorts born in the 1930s. This decline stopped for cohorts born in the 1940s and thereafter. For the youngest cohorts, even a tendency of increasing risk of dying from cervical cancer could be observed, reflecting
Li, Xilan; An, Yuan; Jin, Jiang; Zhu, Zhi; Hao, Linlin; Liu, Lu; Shi, Yongquan; Fan, Daiming; Ji, Tianhai; Yang, Chaoyong James
Metastasis, the capability of tumor cells to spread and grow at distant sites, is the primary factor in cancer mortality. Because metastasis in sentinel lymph nodes suggests the original spread of tumors from a primary site, the detection of lymph node involvement with cancer serves as an important prognostic and treatment parameter. Here we have developed a panel of DNA aptamers specifically binding to colon cancer cell SW620 derived from metastatic site lymph node, with high affinity after 14 rounds of selection by the cell-SELEX (systematic evolution of ligands by exponential enrichment) method. The binding affinities of selected aptamers were evaluated by flow cytometry. Aptamer XL-33 with the best binding affinity (0.7 nM) and its truncated sequence XL-33-1 with 45 nt showed excellent selectivity for recognizing target cell SW620. The binding entity of the selected aptamer has been preliminarily determined as a membrane protein on the cell surface. Tissue imaging results showed that XL-33-1 was highly specific to the metastatic tumor tissue or lymph node tissue with corresponding cancer metastasis and displayed an 81.7% detection rate against colon cancer tissue with metastasis in regional lymph nodes. These results suggest that XL-33-1 has great potential to become a molecular imaging agent for early detection of lymph node tissue with colon cancer metastasis. More importantly, this study clearly demonstrates that DNA ligands selectively recognizing metastatic cancer cells can be readily generated by metastatic-cell-based SELEX for potential applications in metastatic cancer diagnosis and treatment.
de Bruin, Elza C; McGranahan, Nicholas; Mitter, Richard; Salm, Max; Wedge, David C; Yates, Lucy; Jamal-Hanjani, Mariam; Shafi, Seema; Murugaesu, Nirupa; Rowan, Andrew J; Grönroos, Eva; Muhammad, Madiha A; Horswell, Stuart; Gerlinger, Marco; Varela, Ignacio; Jones, David; Marshall, John; Voet, Thierry; Van Loo, Peter; Rassl, Doris M; Rintoul, Robert C; Janes, Sam M; Lee, Siow-Ming; Forster, Martin; Ahmad, Tanya; Lawrence, David; Falzon, Mary; Capitanio, Arrigo; Harkins, Timothy T; Lee, Clarence C; Tom, Warren; Teefe, Enock; Chen, Shann-Ching; Begum, Sharmin; Rabinowitz, Adam; Phillimore, Benjamin; Spencer-Dene, Bradley; Stamp, Gordon; Szallasi, Zoltan; Matthews, Nik; Stewart, Aengus; Campbell, Peter; Swanton, Charles
Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC. Copyright © 2014, American Association for the Advancement of Science.
Maule, M; Malavassi, J L; Richiardi, L
Testicular cancer is one of the most rapidly increasing tumour types but its aetiology is still largely unexplained. Cryptorchidism and familial testicular cancer, established risk factors, explain less than 10% of all cases. Among investigated post-natal factors, early puberty was suggested as a potential risk factor but the topic has been poorly investigated. We undertook a meta-analysis of the effect of age at puberty on testicular cancer risk, attempting at enhancing the homogeneity in the definition of the exposure among studies to obtain valid pooled estimates. Search strategies were conducted in PubMed on December 2011. All markers of puberty onset (age at voice change, age when started shaving and reported age at onset) were considered. We re-categorized age at puberty from all studies into a common three-level variable: younger than peers, same age as peers, older than peers. A total of 391 references were retrieved, of which 12 met the inclusion criteria. Later puberty appeared to be protective. In particular late vs. same age at start shaving gave an OR of 0.84 (95% CI: 0.75-0.95, five studies); late vs. same age at voice change gave an OR of 0.87 (95% CI: 0.75-1.01, five studies); and later age than peers at reported onset of puberty gave an OR of 0.81 (95% CI: 0.73-0.89, eight studies). Early puberty showed no effect on testicular cancer risk. This meta-analysis has found consistent evidence of a decreased risk of testicular cancer in association with later puberty, suggesting that post-natal factors may contribute to testicular cancer risk. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.
Ng, Charlotte K Y; Cooke, Susanna L; Howe, Kevin; Newman, Scott; Xian, Jian; Temple, Jillian; Batty, Elizabeth M; Pole, Jessica C M; Langdon, Simon P; Edwards, Paul A W; Brenton, James D
High-grade serous ovarian carcinoma (HGSOC) is characterized by genomic instability, ubiquitous TP53 loss, and frequent development of platinum resistance. Loss of homologous recombination (HR) is a mutator phenotype present in 50% of HGSOCs and confers hypersensitivity to platinum treatment. We asked which other mutator phenotypes are present in HGSOC and how they drive the emergence of platinum resistance. We performed whole-genome paired-end sequencing on a model of two HGSOC cases, each consisting of a pair of cell lines established before and after clinical resistance emerged, to describe their structural variants (SVs) and to infer their ancestral genomes as the SVs present within each pair. The first case (PEO1/PEO4), with HR deficiency, acquired translocations and small deletions through its early evolution, but a revertant BRCA2 mutation restoring HR function in the resistant lineage re-stabilized its genome and reduced platinum sensitivity. The second case (PEO14/PEO23) had 216 tandem duplications and did not show evidence of HR or mismatch repair deficiency. By comparing the cell lines to the tissues from which they originated, we showed that the tandem duplicator mutator phenotype arose early in progression in vivo and persisted throughout evolution in vivo and in vitro, which may have enabled continual evolution. From the analysis of SNP array data from 454 HGSOC cases in The Cancer Genome Atlas series, we estimate that 12.8% of cases show patterns of aberrations similar to the tandem duplicator, and this phenotype is mutually exclusive with BRCA1/2 carrier mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The products of proto-oncogene play critical roles in the development or maintenance of multicellular societies in animals via strict regulatory systems. When these regulatory systems are disrupted, proto-oncogenes can become oncogenes, and thereby induce cell transformation and carcinogenesis. To understand the molecular basis for development of the regulatory system of proto-oncogenes during evolution, we screened for ancestral proto-oncogenes from the unicellular choanoflagellate Monosiga ovata (M. ovata) by monitoring their transforming ability in mammalian cells; consequently, we isolated a Pak gene ortholog, which encodes a serine/threonine kinase as a 'primitive oncogene'. We also cloned Pak orthologs from fungi and the multicellular sponge Ephydatia fluviatilis, and compared their regulatory features with that of M. ovata Pak (MoPak). MoPak is constitutively active and induces cell transformation in mammalian cells. In contrast, Pak orthologs from multicellular animals are strictly regulated. Analyses of Pak mutants revealed that structural alterations in the auto-inhibitory domain (AID) are responsible for the enhanced kinase activity and the oncogenic activity of MoPak. Furthermore, we show that Rho family GTPases-mediated regulatory system of Pak kinase is conserved throughout the evolution from unicellular to multicellular animals, but the MoPak is more sensitive to the Rho family GTPases-mediated activation than multicellular Pak. These results show that maturation of AID function was required for the development of the strict regulatory system of the Pak proto-oncogene, and support the potential link between the development of the regulatory system of proto-oncogenes and the evolution of multicellularity. Further analysis of oncogenic functions of proto-oncogene orthologs in the unicellular genes would provide some insights into the mechanisms of the destruction of multicellular society in cancer.
C. He (Chunyan); D.I. Chasman (Daniel); H. Dreyfus (Hélène); S.J. Hwang; R. Ruiter (Rikje); S. Sanna (Serena); J.E. Buring (Julie); L. Fernández-Rhodes (Lindsay); N. Franceschini (Nora); S.E. Hankinson (Susan); A. Hofman (Albert); K.L. Lunetta (Kathryn); D. Palmieri (Dario); E. Porcu (Eleonora); F. Rivadeneira Ramirez (Fernando); L.M. Rose (Lynda); G.L. Splansky (Greta); L. Stolk (Lisette); A.G. Uitterlinden (André); S.J. Chanock (Stephen); L. Crisponi (Laura); E.W. Demerath (Ellen); J. Murabito (Joanne); P.M. Ridker (Paul); B.H.Ch. Stricker (Bruno); D. Hunter (David)
textabstractIntroduction: 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
Bol, Nadine; Smets, Ellen M. A.; Burgers, Jacobus A.; Samii, Suzy M.; de Haes, Hanneke C. J. M.; van Weert, Julia C. M.
This study proposes and tests a model to provide a more comprehensive understanding of the contribution of chronological age versus age-related ability and motivation factors in explaining recall of online cancer information among older patients (n = 197). Results revealed that recall is not a
Alberto Caballero Vázquez
Full Text Available Background: Changes in lung cancer has been characterized by the increase of cases among women and the increase in adenocarcinomas among other histological subtypes. Methods: Descriptive analysis of cases diagnosed with lung cancer in Hospital Virgen de las Nieves (Spain from 1990 to 2010, based on five variables (age, sex, smoking, histology and pathological anatomy. The study establishes associations between these variables and compares the results with the literature. Results: 2,026 patients were diagnosed with lung cancer in this period; 1,838 were males (90.7% and 188 women (9.3%; 1,892 patients (93.4% were smokers or ex-smokers and 134 (6.6% had never smoked; the most frequent non-small cell histology types were squamous cell carcinoma and adenocarcinoma and it was the most frequent neoplasia in women and were associated with a lower tobacco consumption. Conclusion: The large majority of lung cancer cases is associated with a history of smoking tobacco and there are histopathological differences according to gender and cumulative tobacco smoke load.
Ahmad, Saheem; Khan, Hamda; Siddiqui, Zeba; Khan, Mohd Yasir; Rehman, Shahnawaz; Shahab, Uzma; Godovikova, Tatyana; Silnikov, Vladimir; Moinuddin
Impaired awareness of glycation biology in cancer initiation and progression is one of the fundamental reasons for its meticulous investigation of the molecules involved in signalling pathway. Glycation of biological macromolecules results in the progression of advanced glycation end-products (AGEs) that proliferates the process of carcinogenesis by activation of transcription factors and release of cytokines. The receptor for advanced glycation end-products (RAGEs) with the binding of its different ligands like; AGEs, HMGB1 and S100 activate the signalling arrays. The activation of downstream signalling pathway ultimately leads to the pathophysiological conditions of diabetes, ageing, neurological disorders and cancers as well as a result of the activation of transcription factors which is discussed in the main body text of this review. However, there might be a likelihood of the positive effect of the HMGB1 and S100 proteins in cancer. Still, some untouched mechanisms might be responsible for the establishment of the function of AGE-RAGE or AGE-sRAGE axis activation that leads to the friend-foe association with the cancers. The levels of RAGE and s-RAGE may be a useful biomarker of ligand-RAGE pathway activation and cancer. Thus, the possibility of providing a potential complement to carcinogenesis is very high which might be an interesting target for therapeutic interventions. This article is an insightful assessment on AGE, RAGE and s-RAGE for its possible role in cancer onset and progression. The novel therapeutic targets for cancer prevention or inhibition are also explained in brief in relation to AGE and RAGE. Copyright © 2017 Elsevier Ltd. All rights reserved.
Honda, G D; Bernstein, L; Ross, R K; Greenland, S; Gerkins, V; Henderson, B E
A population-based case-control study was conducted in men aged 60 or less to assess the risk of prostate cancer associated with vasectomy and other factors. Data were obtained from 216 case-control pairs by telephone interviews; this number represented 55% of all eligible cases. The matched pairs relative risk (RR) for vasectomy in ever married men was 1.4 with a 95% confidence interval (CI) of 0.9-2.3. There was a positive association between the number of years since vasectomy and prostate cancer risk (1-sided P = 0.01). Early age at first sexual intercourse was associated with increased prostate cancer risk (age less than 17 vs. 21+, RR = 2.3, 95% CI = 1.3, 4.0) but there were no consistent associations with number of sexual partners or frequency of sexual intercourse. Cigarette smoking was also associated with increased risk of prostate cancer (RR = 1.9, 95% CI = 1.2, 3.0) and there was a positive dose-response relationship with years of smoking (1-sided P = 0.001). We discuss the possible implication of the low response rate on each of these findings. To determine whether the association with vasectomy might have a hormonal basis, we compared levels of testosterone (T) and testosterone binding globulin-binding capacity (TeBG-bc) in 33 of the vasectomized control men with levels in 33 non-vasectomized controls of the same age, weight and height. T levels were higher in vasectomized than in non-vasectomized controls (1-sided P = 0.06). The ratio of T to TeBG-bc (an index of bioavailable T) was 13.5% higher in vasectomized men (1-sided P = 0.03).
Full Text Available Michael F Leitzmann1, Sabine Rohrmann21Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany; 2Institute of Social and Preventive Medicine, University of Zurich, Zurich, SwitzerlandAbstract: At present, only three risk factors for prostate cancer have been firmly established; these are all nonmodifiable: age, race, and a positive family history of prostate cancer. However, numerous modifiable factors have also been implicated in the development of prostate cancer. In the current review, we summarize the epidemiologic data for age, location, and selected behavioral factors in relation to the onset of prostate cancer. Although the available data are not entirely consistent, possible preventative behavioral factors include increased physical activity, intakes of tomatoes, cruciferous vegetables, and soy. Factors that may enhance prostate cancer risk include frequent consumption of dairy products and, possibly, meat. By comparison, alcohol probably exerts no important influence on prostate cancer development. Similarly, dietary supplements are unlikely to protect against the onset of prostate cancer in healthy men. Several factors, such as smoking and obesity, show a weak association with prostate cancer incidence but a positive relation with prostate cancer mortality. Other factors, such as fish intake, also appear to be unassociated with incident prostate cancer but show an inverse relation with fatal prostate cancer. Such heterogeneity in the relationship between behavioral factors and nonadvanced, advanced, or fatal prostate cancers helps shed light on the carcinogenetic process because it discerns the impact of exposure on early and late stages of prostate cancer development. Inconsistent associations between behavioral factors and prostate cancer risk seen in previous studies may in part be due to uncontrolled detection bias because of current widespread use of prostate-specific antigen
Esbensen, Bente Appel; Swane, Christine E; Hallberg, Ingalill Rahm
elderly people in dealing with issues arising after cancer is diagnosed. Design: A descriptive phenomenological method was used to investigate the phenomenon "the lived experience of being given a cancer diagnosis in old age". Participants: In total, 16 persons (aged 65+, mean age 76, range 68...... that the essential meaning of the lived experience was "Illness as a turning point marking old age". This main essence was represented overall by three essences: "Illness means losing control", "Disturbing the family balance" and "Life and death suddenly apparent". These three essences were manifested through seven...... constituents: growing old in the context of illness, becoming a patient with cancer, everyday life being controlled by bodily limitations, managing family reactions, becoming conscious about dying and death through illness experience and retaining hope, and enjoying life. Conclusion: It is important...
Rostgaard, K; Vaeth, M; Holst, H
The Nordic countries have experienced a steady increase in breast cancer incidence throughout the past 35 years. We analysed the incidence in Denmark, Finland, Norway and Sweden during the period 1958 to 1992 using age-period-cohort models and taking the systematic mammography screening...... in breast cancer incidence seen in the Nordic countries. The widespread practice of neglecting the period effects in age-period-cohort analysis of time trends in breast cancer incidence therefore probably needs reconsideration. A key finding was that Danish women born in the 20th century seem to have been...... into account. Assuming the age dependency of the incidence pattern in old age to be common for the Nordic countries, an internal comparison could be made among the four countries of the cohort effects and the period effects. The study indicated that the period effects have been of importance for the increase...
Rojo Álvaro, Jorge; Bermejo Fraile, Begoña; Menéndez Torre, Edelmiro; Ardanaz, Eva; Guevara, Marcela; Anda Apiñániz, Emma
The latest published studies show an increased incidence of thyroid cancer worldwide. The aim of this study was to analyze the changes in the incidence of thyroid cancer in Navarra and its clinical presentation regarding sex, histological subtype and size over the last 25 years. Thyroid cancer incidence rates were calculated on the basis of data from the Cancer Registry of Navarra during 1986-2010. Clinical data were obtained from the historical cohort of the Hospital Registry of Cancer of Navarra, which includes all the new cases of differentiated thyroid carcinoma diagnosed and treated in the public health network of this Community in that period. The overall incidence of thyroid cancer in Navarra increased over the last 25 years, with an increase in the adjusted rate in men from 2.24 (1986-1990) to 5.85 (2006-2010) per 100,000 population/year (P<.001) and in women from 9.05 to 14.04, respectively (P<.001). This increase occurs only in papillary carcinoma. The clinical characteristics of 739 patients with differentiated thyroid cancer were studied. The mean age at diagnosis increased over the years and the predominance of women (about 80%) remains stable. Mean tumor size decreased over the five-year periods from 30.9 to 22.5mm (P<.001), the proportion of microcarcinomas (T1a) increased from 8.8% to 30% (P<.001) and, despite this increase, there were no statistical differences in the TNM stage at diagnosis during the study period. The distribution of histological variants of papillary and follicular carcinoma did not change over 25 years. During the period studied, the incidence of thyroid cancer increased in Navarra in both sexes. The increase occurred only in papillary carcinoma, without changes in the distribution of his histological variants. The increase in the proportion of T1a tumors is remarkable, but the TNM stage distribution was maintained. These results suggest an increase in the diagnosis of thyroid microcarcinomas due to changes in clinical practice
Coate, Linda E.; Shepherd, Frances A.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world. Despite significant progress in early stage disease, survival rates for advanced disease remain low. Maintenance therapy is a treatment strategy that has been investigated extensively in NSCLC and has been the subject of considerable recent debate. Options for maintenance include continuing the initial combination chemotherapy regimen, continuing only single agent chemotherapy (‘continuation maintenance’) or introducing a new agent (‘switch’ maintenance therapy). Therapies that have been studied in this setting in randomized trials to date include chemotherapy, molecularly targeted agents and immunotherapy approaches. Following the development of multiple new agents that show activity in NSCLC, and have a tolerable side-effect profile, there has been increasing interest in utilizing them to maintain response to initial therapy after treatment with platinum-based doublets. Despite considerable controversy, it has become an acceptable treatment paradigm. Here, we briefly outline the evolution of this treatment paradigm and examine which subgroups of patients are most likely to benefit. PMID:21904577
OBJECTIVE--To determine the risk of testicular cancer associated with undescended testis, inguinal hernia, age at puberty, marital status, infertility, vasectomy, and amount of exercise. DESIGN--A population based case-control study with a questionnaire administered by an interviewer and with relevant supplementary data extracted from general practitioners' notes. SETTING--Nine health regions within England and Wales. SUBJECTS--794 men, aged 15-49 years, with a testicular germ cell tumour dia...
To determine the risk of testicular cancer associated with undescended testis, inguinal hernia, age at puberty, marital status, infertility, vasectomy, and amount of exercise. A population based case-control study with a questionnaire administered by an interviewer and with relevant supplementary data extracted from general practitioners' notes. Nine health regions within England and Wales. 794 men, aged 15-49 years, with a testicular germ cell tumour diagnosed between 1 January 1984 and 1 January 1987; each had an age matched (within one year) control selected from the list of their general practitioner. There was a significant association of testicular cancer with undescended testis (odds ratio 3.82; 95% confidence interval 2.24 to 6.52) and inguinal hernia (1.91; 1.12 to 3.23). The excess risk associated with undescended testis was eliminated in men who had had an orchidopexy before the age of 10 years. There were positive associations with early age at voice breaking, early age at starting to shave, and infertility. There was a significant association with a sedentary lifestyle and a moderate protective effect of exercise. There was no association with vasectomy. This study confirms previous reports that developmental urogenital abnormalities result in an increased risk of testicular cancer. The trend to perform orchidopexy at younger ages may reduce the risk associated with undescended testis. The increased risks associated with early age at puberty and low amounts of exercise may be related to effects of exposure to endogenous hormones. Changes in both of these factors may partly contribute to the increasing rates of testicular cancer observed in the past few decades.
Herget, Kimberly A; Patel, Darshan P; Hanson, Heidi A; Sweeney, Carol; Lowrance, William T
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. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Gusti Ayu Triara Dewi
Full Text Available The number of cases of breast cancer is increasing every year and it’s a serious health problem in the world, including in Indonesia. Breast cancer is type of cancer that is most dominant in Indonesia. High estrogen exposure is one of factor that can increase the risk of breast cancer in women. This study was conducted to determine the relationship of estrogen exposure through the use of hormonal contraceptives and age of menarche with breast cancer incidence in women. Type of this study is observational analytic and use case control design. All of women breast cancer patients of Dr. Soetomo Hospital in 2013 were the population of case. All of woman non breast cancer patients who done breast examination at Dr Soetomo Hospital in 2013 were the population of control. The number of respondents in this study were 90 respondents were drawn from population using simple random sampling method. The variables studied were the use of hormonal contraceptives and age of menarche. The results of the analysis used binary logistic regression (α = 5% indicated that the use of hormonal contraceptives (p = 0,028; OR = 3,266 and age of menarche (p =0,031; OR = 3,492 has an significant correlation with incidence of breast cancer in women at Dr. Soetomo Hospital in 2013. It is expected that the community can be more accurate in determining the duration of hormonal contraception usage and avoid lifestyle can accelerate the occurrence of menarche. Keywords: breast cancer, risk factor, hormonal contraceptives, age of menarche, estrogen
Mäkelä, Jyrki Tapani; Klintrup, Kai Hans; Rautio, Tero Tapani
The purpose of this study was to identify the clinical factors and tumor characteristics that predict the outcome of colorectal cancer patients aged >80 years. The data of 186 patients aged >80 years with colorectal cancer were collected from a computer database, and the variables were analyzed by both uni- and multivariate analyses. The 30-day mortality was 4% and the 90-day mortality 10%. The 1-year survival was 76%, and 27 (61%) of the 44 deaths were unrelated to cancer. The overall 5-year survival was 36%, the median survival 38 months, and the cancer-specific survival 40%. The recurrence rate after radical surgery was 22% and it was not affected by age. Kaplan-Meier estimates indicated that age, number of underlying diseases, radical operation, Union for International Cancer Control stage of the tumor, tumor size, number of lymph nodes involved, venous invasion, and recurrent disease were significant predictors of survival, but in the Cox regression model, only radical operation and venous invasion were independent prognostic factors for survival. After good surgical selection, low early mortality and acceptable long-term survival can be achieved even in the oldest old patients with colorectal cancer. However, low early mortality seems to underestimate the effects of surgery during the first postoperative year.
Full Text Available Abstract Background Modeling the relationship between age and mortality for breast cancer patients may have important prognostic and therapeutic implications. Methods Data from 9 registries of the Surveillance, Epidemiology, and End Results Program (SEER of the United States were used. This study employed proportional hazards to model mortality in women with T1-2 breast cancers. The residuals of the model were used to examine the effect of age on mortality. This procedure was applied to node-negative (N0 and node-positive (N+ patients. All causes mortality and breast cancer specific mortality were evaluated. Results The relationship between age and mortality is biphasic. For both N0 and N+ patients among the T1-2 group, the analysis suggested two age components. One component is linear and corresponds to a natural increase of mortality with each year of age. The other component is quasi-quadratic and is centered around age 50. This component contributes to an increased risk of mortality as age increases beyond 50. It suggests a hormonally related process: the farther from menopause in either direction, the more prognosis is adversely influenced by the quasi-quadratic component. There is a complex relationship between hormone receptor status and other prognostic factors, like age. Conclusion The present analysis confirms the findings of many epidemiological and clinical trials that the relationship between age and mortality is biphasic. Compared with older patients, young women experience an abnormally high risk of death. Among elderly patients, the risk of death from breast cancer does not decrease with increasing age. These facts are important in the discussion of options for adjuvant treatment with breast cancer patients.
Tai, Patricia; Cserni, Gábor; Van De Steene, Jan; Vlastos, Georges; Voordeckers, Mia; Royce, Melanie; Lee, Sang-Joon; Vinh-Hung, Vincent; Storme, Guy
Background Modeling the relationship between age and mortality for breast cancer patients may have important prognostic and therapeutic implications. Methods Data from 9 registries of the Surveillance, Epidemiology, and End Results Program (SEER) of the United States were used. This study employed proportional hazards to model mortality in women with T1-2 breast cancers. The residuals of the model were used to examine the effect of age on mortality. This procedure was applied to node-negative (N0) and node-positive (N+) patients. All causes mortality and breast cancer specific mortality were evaluated. Results The relationship between age and mortality is biphasic. For both N0 and N+ patients among the T1-2 group, the analysis suggested two age components. One component is linear and corresponds to a natural increase of mortality with each year of age. The other component is quasi-quadratic and is centered around age 50. This component contributes to an increased risk of mortality as age increases beyond 50. It suggests a hormonally related process: the farther from menopause in either direction, the more prognosis is adversely influenced by the quasi-quadratic component. There is a complex relationship between hormone receptor status and other prognostic factors, like age. Conclusion The present analysis confirms the findings of many epidemiological and clinical trials that the relationship between age and mortality is biphasic. Compared with older patients, young women experience an abnormally high risk of death. Among elderly patients, the risk of death from breast cancer does not decrease with increasing age. These facts are important in the discussion of options for adjuvant treatment with breast cancer patients. PMID:16212670
Kikuchi, Shoichi; Takeshita, Takashi; Shibata, Hiroshi; Hase, Kazuo; Clark, Orlo H
We have made a cross-sectional investigation of men in the Japanese military for the presence of thyroid abnormalities and thyroid cancer to document the prevalence of thyroid disease in these persons. Six thousand, four hundred and twenty-two Japanese military men and women were screened for thyroid disease by history, physical examination and ultrasound examination. Among them, 6,182 were men 50 years of age, 47 were women 50 years of age, and 149 were men 40 years of age and 44 were women 40 years of age. Among the 50 years old men, thyroid nodules were found in 924 men (14.9%): Nineteen individuals (0.31%) had thyroid cancers ranging from 1 mm to 30 mm in diameter (12.5 mm in mean), pathological TNM staging revealed 7 cases of stage I, 2 cases of stage II and 9 cases of stage III. There was a significant increase in thyroid nodules in 50 years old men compared to that in 40 year old men, but there was no significant difference between men and women (p>0.05). Our data document that the detection rate of thyroid cancer in 50 years old men was 0.31%, and the rate of thyroid nodules increased with age in men, but the frequency of thyroid nodules were similar in men and women of the same age.
Mitrasing, Ingrid Saroda
The evolution of Acehnese kingship is examined against the background of its relations with European traders and the tradingports in the region of the Malacca Straits. There are two defining moments in the history of Aceh: first the arrival of the Portuguese in Malacca in 1511 which gave impetus to
Caggiano, A.; Pepe, M.; Koenders, E.A.B.; Martinelli, E.; Etse, G.J.
Heat production induced by the hydration reaction and the resulting temperature evolution in the early phases of setting and hardening processes are critical phenomena, often leading to premature cracking of concrete members. However, the interest for simulating such phenomena is also related to the
Jacob, J.; Dyment, J.; Yatheesh, V.
analyze the past plate kinematic evolution of the Wharton Basin by two-plate (India-Australia) and three-plate (India-Australia-Antarctica) reconstructions. Despite the diffuse plate boundaries within the Indo-Australian plate for the last 20 Ma, we obtain...
Hillen, Marij A; Gutheil, Caitlin M; Smets, Ellen M A; Hansen, Moritz; Kungel, Terrence M; Strout, Tania D; Han, Paul K J
People who have cancer increasingly seek second opinions. Yet, we know little about what motivates patients to seek them and how beneficial they are. Uncertainty-experienced by patients or communicated by physician and patient-may be crucial throughout the second opinion process. This study sought to investigate (1) how uncertainty influences men with prostate cancer to seek second opinions and (2) how second opinions may affect these patients' sense of uncertainty and subsequent experiences with their care. A qualitative study using semi-structured interviews was performed. Men with localized or advanced prostate cancer (n=23) were interviewed by telephone about their motivations and experiences with seeking second opinions and the uncertainties they experienced. Analysis was performed using the constant comparative method. Patients sought second opinions because they were uncertain about receiving too little or biased information, experienced insufficient support in coming to a treatment decision, or because physicians expressed different levels of uncertainty than they did ("unshared uncertainty"). Uncertainty was reduced by the second opinion process for most patients, whereas for others, it increased or was sustained. This evolution depended on the way uncertainty was addressed during the second opinion consultation. Second opinions may be a useful tool for some but not all patients. They should be used judiciously and not be viewed as a solution for current limitations to health-care organization. An important yet challenging task for physicians is to focus less on information per se and more on how to assist patients manage irreducible uncertainty. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.
Simpson Andrew J
Full Text Available Abstract Background Cancer/testis (CT genes are normally expressed only in germ cells, but can be activated in the cancer state. This unusual property, together with the finding that many CT proteins elicit an antigenic response in cancer patients, has established a role for this class of genes as targets in immunotherapy regimes. Many families of CT genes have been identified in the human genome, but their biological function for the most part remains unclear. While it has been shown that some CT genes are under diversifying selection, this question has not been addressed before for the class as a whole. Results To shed more light on this interesting group of genes, we exploited the generation of a draft chimpanzee (Pan troglodytes genomic sequence to examine CT genes in an organism that is closely related to human, and generated a high-quality, manually curated set of human:chimpanzee CT gene alignments. We find that the chimpanzee genome contains homologues to most of the human CT families, and that the genes are located on the same chromosome and at a similar copy number to those in human. Comparison of putative human:chimpanzee orthologues indicates that CT genes located on chromosome X are diverging faster and are undergoing stronger diversifying selection than those on the autosomes or than a set of control genes on either chromosome X or autosomes. Conclusion Given their high level of diversifying selection, we suggest that CT genes are primarily responsible for the observed rapid evolution of protein-coding genes on the X chromosome.
Menapace, Ilaria; Masad, Eyad
This paper presents findings on the evolution of the surface microstructure of two asphalt binders, one unmodified and one polymer modified, directly exposed to aging agents with increasing durations. The aging is performed using an accelerated weathering tester, where ultraviolet radiation, oxygen and an increased temperature are applied to the asphalt binder surface. Ultraviolet and dark cycles, which simulated the succession of day and night, alternated during the aging process, and also the temperature varied, which corresponded to typical summer day and night temperatures registered in the state of Qatar. Direct aging of an exposed binder surface is more effective in showing microstructural modifications than previously applied protocols, which involved the heat treatment of binders previously aged with standardized methods. With the new protocol, any molecular rearrangements in the binder surface after aging induced by the heat treatment is prevented. Optical photos show the rippling and degradation of the binder surface due to aging. Microstructure images obtained by means of atomic force microscopy show gradual alteration of the surface due to aging. The original relatively flat microstructure was substituted with a profoundly different microstructure, which significantly protrudes from the surface, and is characterized by various shapes, such as rods, round structures and finally 'flower' or 'leaf' structures. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.
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
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.
Perna, Laura; Zhang, Yan; Mons, Ute; Holleczek, Bernd; Saum, Kai-Uwe; Brenner, Hermann
Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand such observations by investigating whether different concepts of the epigenetic clocks in a population-based cohort are associated with cancer, cardiovascular, and all-cause mortality. DNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Δage) was calculated. A case-cohort design and weighted proportional Cox hazard models were used to estimate associations of Δage with cancer, cardiovascular, and all-cause mortality. Hazard ratios for Δage (per 5 years) calculated using the epigenetic clock developed by Horvath were 1.23 (95 % CI 1.10-1.38) for all-cause mortality, 1.22 (95 % CI 1.03-1.45) for cancer mortality, and 1.19 (95 % CI 0.98-1.43) for cardiovascular mortality after adjustment for batch effects, age, sex, educational level, history of chronic diseases, hypertension, smoking status, body mass index, and leucocyte distribution. Associations were similar but weaker for Δage calculated using the epigenetic clock developed by Hannum. These results show that age acceleration in terms of the difference between age predicted by DNA methylation and chronological age is an independent predictor of all-cause and cause-specific mortality and may be useful as a general marker of healthy aging.
Bennai, F.; Issaadi, N.; Abahri, K.; Belarbi, R.; Tahakourt, A.
The incorporation of plant crops in construction materials offers very good hygrothermal performance to the building, ensuring substantial environmental and ecological benefits. This paper focuses on studying the evolution of hygrothermal properties of hemp concrete over age (7, 30 and 60 days). The analysis is done with respect to two main hygric and thermal properties, respectively: sorption isotherms, water vapor permeability, thermal conductivity and heat capacity. In fact, most of these parameters are very susceptible to change function of the age of the material. This influence of the aging is mainly due to the evolution of the microstructure with the binder hydration over time and the creation of new hydrates which can reduces the porosity of the material and consequently modify its properties. All the tested hemp concrete samples presented high moisture storage capacity and high-water vapor permeability whatever the age of such hygroscopic material. These hygric parameters increase significantly for high relative humidity requiring more consideration of such variability during the modeling of coupled heat and mass transfer within the material. By the same, the thermal conductivity and heat capacity tests highlighted the impact of the temperature and hygric state of the studied material.
Richardson, Richard B
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
Zu, Hongliang; Wang, Huiling; Li, Chunfeng; Kang, Yue; Xue, Yingwei
The prognostic value of age on patients with gastric cancer is not well defined. The aim of this retrospective study is to analyze the impact of age on survival in patients with gastric cancer. A total of 1800 patients with gastric carcinoma, who had undergone gastrectomy between 1997-2007 years were included. They were divided into six different age groups (21-30, 31-40, 41-50, 51- 60, 61-70 and 71-80 years). We reviewed patient's clinico-pathological characteristics and the prognosis with special reference to their ages. Among the six age groups, the younger patients have more female-dominated patients and poorly differentiated carcinoma, whereas the older patients have a higher incidence of large tumors (≥5 cm) and more patients with stage T3. Moreover, there were more liver metastases in the older age groups. Univariate analysis showed that there were significant differences in 5-year survival rates among the six age groups. Multivariate analysis confirmed age, tumor size, pT stage, pN stage and curability were independent prognostic factors. There are several distinctive properties related to age of patients with gastric cancer, the older patients have more aggressive features and poorer prognosis than the younger patients.
Carpenter, Kristen M; Eisenberg, Stacy; Weltfreid, Sharone; Low, Carissa A; Beran, Tammy; Stanton, Annette L
This study evaluated associations of cancer-related cognitive processing with BRCA1/2 mutation carrier status, personal cancer history, age, and election of prophylactic surgery in women at high risk for breast cancer. In a 2 (BRCA1/2 mutation carrier status) × 2 (personal cancer history) matched-control design, with age as an additional predictor, participants (N = 115) completed a computerized cancer Stroop task. Dependent variables were response latency to cancer-related stimuli (reaction time [RT]) and cancer-related cognitive interference (cancer RT minus neutral RT). RT and interference were tested as predictors of prophylactic surgery in the subsequent four years. RT for cancer-related words was significantly slower than other word groups, indicating biased processing specific to cancer-related stimuli. Participants with a cancer history evidenced longer RT to cancer-related words than those without a history; moreover, a significant Cancer History × Age interaction indicated that, among participants with a cancer history, the typical advantage associated with younger age on Stroop tasks was absent. BRCA mutation carriers demonstrated more cancer-related cognitive interference than noncarriers. Again, the typical Stroop age advantage was absent among carriers. Exploratory analyses indicated that BRCA+ status and greater cognitive interference predicted greater likelihood of undergoing prophylactic surgery. Post hoc tests suggest that cancer-related distress does not account for these relationships. In the genetic testing context, younger women with a personal cancer history or who are BRCA1/2 mutation carriers might be particularly vulnerable to biases in cancer-related cognitive processing. Biased processing was associated marginally with greater likelihood of prophylactic surgery. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Harden, Janet K; Northouse, Laurel L; Mood, Darlene W
Prostate cancer is a significant cause of morbidity and mortality in men in all adult life stages. Normative developmental tasks of aging combined with disease-related stressors may negatively affect adjustment to prostate cancer and, consequently, affect the quality of life of both the man and his spouse. The purpose of this study was to examine the experiences of men with prostate cancer and their partners according to their life cycle cohort: 50-64 (late middle age), 65-74 (young-old), and 75-84 (old-old). Qualitative interviews with 15 couples were used to provide information about the dyad's experiences with prostate cancer. Interview data were analyzed to identify preliminary coding schemas, which were subsequently refined and modified into themes. Three major themes were identified from the data. Across all age groups, prostate cancer had a significant effect on: (1) couples' daily lives, (2) their dyadic and family relationships, and (3) their developmental stage. There were also differences in age groups. Couples in the late middle age group reported greater disappointment and anger at their inability to reach life goals and establish financial security. Couples in the young-old group made more spontaneous comments about being satisfied with their life than the couples in the other 2 groups. Couples in the old-old group reported slower recovery from the illness than the younger couples. Results indicate that although prostate cancer may have some universal effects on couples, it also may have differential effects by age cohort. Hence, targeted interventions by age cohort may be warranted.
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.
Rafiemanesh, Hosein; Salehiniya, Hamid; Lotfi, Zahra
Breast cancer is the most common cancer and the first cause of cancer death in women worldwide, with infiltrating duct carcinoma as the most common morphology. This study aimed to investigate trend of breast cancer incidence by age groups and histological changes in Iranian women between 2003 and 2008. This is analytic study, carried out based on re-analysis of the Cancer Registry Center report of health deputy for women's breast cancer in Iran during a 6-year period (2003-2008). Statistical analysis for incidence time trends and morphology change percentage carried out joinpoint regression analysis using the software Joinpoint Regression Program. A total of 36,340 cases were reported for Iranian women in the six years. Analytical trend showed an increasing incidence trend with significant annual percentage change (APC) of 15.2 (CI: 11.6 to 18.8). The lowest and highest significant increased trend were related to age groups of 40 to 44 years and above 85 years, respectively; with APCs of 13.0 and 25.1, respectively. Of total cases, 78.7% of cases were infiltrating duct carcinoma, decreasing from 82.0% in 2003 to 76.6% in 2008, which was significant with an APC equal to -1.76 (CI:-2.7 to -0.8). The incidence trend of breast cancer is rising in Iranian women. The highest incidence was observed in the age groups 45-65 and 80-85. In conclusion, to reduce breast cancer incidence and its burden, preventive and screening programs for breast cancer, especially in young women, are recommended in Iran.
Liu, Yen-Lin; Lo, Wei-Cheng; Chiang, Chun-Ju; Yang, Ya-Wen; Lu, Meng-Yao; Hsu, Wen-Ming; Ho, Wan-Ling; Li, Meng-Ju; Miser, James S; Lin, Dong-Tsamn; Lai, Mei-Shu
Studies have found lower risk of childhood cancer among Asian children. We aim to characterize the recent incidence and incidence-trend of childhood cancer in Taiwan after the National Health Insurance program was launched in March 1995. Data were extracted from the Taiwan Cancer Registry, a population-based database established in 1979. Cases diagnosed at age 0-14 from 1996 to 2010 were analyzed and categorized according to the International Classification of Childhood Cancer, Third Edition (ICCC-3). In total, 8032 childhood cancer cases were included, with a microscopic verification rate of 93.9%. The overall age-standardized rate (ASR) of incidence adjusted to the 2000 World Standard Population is 125.0 cases/million, with a male-to-female ratio of 1.3. The top five cancer types (ICCC-3 subgroup[s]; ASR per million) are acute lymphoblastic leukemia (Ia, 30.3), acute myeloid leukemia (Ib; 9.4), non-Hodgkin lymphoma (IIb,c,e, 9.0), extracranial germ cell tumor (Xb,c; 8.3), and neuroblastoma (IVa; 7.8). The median age of diagnosis was 6 years for both genders. During the study period, the ASR of childhood cancer has been increasing at a rate of 1.2% per year (95% confidence interval, 0.6-1.7%). In contrast to Western countries, China, Japan, and Taiwan have lower incidence of childhood cancer; however, Taiwan's incidence rates of childhood germ cell tumors and hepatic tumors are higher. In conclusion, this population-based study reveals that the incidence rate of childhood cancer in Taiwan is rising consistently. The high incidence of germ cell tumors warrants further investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.
Hemminki, Kari; Sundquist, Jan; Brandt, Andreas
Background. Age-specific incidence rates for breast cancer in low-risk and high-risk ethnic populations differ by age at which the incidence maximum is reached: around 50 years in low-risk populations and over 60 years in high-risk populations. The interpretation of these differences remains unsettled, one line primarily referring to biological differences, the second one to cohort effects of rapidly increasing rates in young populations, and the third one to incomplete registration of cancer in the elderly. Methods. The nationwide Family-Cancer Database was used to analyze standardized incidence ratios (SIRs) and age at diagnosis of breast cancer in female immigrants to Sweden by their region of origin compared with women native to Sweden matched on birth year and other relevant factors. Results. We showed first that the SIRs for breast cancer were lower in many immigrant groups compared with natives of Sweden; women from Turkey had the lowest SIR of 0.45, followed by those from Chile (0.54) and Southeast Asia (0.57). Women from nine regions showed an earlier mean age at diagnosis than their matched Swedish controls, the largest differences being 5.5 years for women from Turkey, 5.1 years for those from Asian Arab and “Other African” countries, 4.3 years for those from Iran, and 4.0 years for those from Iraq. Conclusions. The results show that in many immigrant groups, the diagnostic age is earlier (Sweden (>50 years), suggesting that true biological factors underlie the differences. These factors may explain much of the international variation in breast cancer incidence. Identifying these factors should advance understanding of breast cancer etiology and prevention. PMID:21266400
Hornbrook, Mark C; Goshen, Ran; Choman, Eran; O'Keeffe-Rosetti, Maureen; Kinar, Yaron; Liles, Elizabeth G; Rust, Kristal C
Machine learning tools identify patients with blood counts indicating greater likelihood of colorectal cancer and warranting colonoscopy referral. To validate a machine learning colorectal cancer detection model on a US community-based insured adult population. Eligible colorectal cancer cases (439 females, 461 males) with complete blood counts before diagnosis were identified from Kaiser Permanente Northwest Region's Tumor Registry. Control patients (n = 9108) were randomly selected from KPNW's population who had no cancers, received at ≥1 blood count, had continuous enrollment from 180 days prior to the blood count through 24 months after the count, and were aged 40-89. For each control, one blood count was randomly selected as the pseudo-colorectal cancer diagnosis date for matching to cases, and assigned a "calendar year" based on the count date. For each calendar year, 18 controls were randomly selected to match the general enrollment's 10-year age groups and lengths of continuous enrollment. Prediction performance was evaluated by area under the curve, specificity, and odds ratios. Area under the receiver operating characteristics curve for detecting colorectal cancer was 0.80 ± 0.01. At 99% specificity, the odds ratio for association of a high-risk detection score with colorectal cancer was 34.7 (95% CI 28.9-40.4). The detection model had the highest accuracy in identifying right-sided colorectal cancers. ColonFlag® identifies individuals with tenfold higher risk of undiagnosed colorectal cancer at curable stages (0/I/II), flags colorectal tumors 180-360 days prior to usual clinical diagnosis, and is more accurate at identifying right-sided (compared to left-sided) colorectal cancers.
Liu, Lihua; Zhang, Juanjuan; Wu, Anna H.; Pike, Malcolm C.; Deapen, Dennis
Racial/ethnic disparities in breast cancer incidence may contain important evidence for understanding and control of the disease. Monitoring the incidence trends of breast cancer by race/ethnicity allows identification of high risk groups and development of targeted prevention programs. Using population-based cancer registry data from the Los Angeles Cancer Surveillance Program, we examined the invasive female breast cancer incidence trends among the diverse racial/ethnic populations in Los Angeles County, California, from 1972 to 2007. Age-adjusted incidence rates (AAIR) and age-specific incidence rates (ASIR) were calculated and examined respectively for non-Hispanic (NH) white, black, Hispanic, Chinese, Filipina, Japanese, and Korean women by calendar year and time period. Rising trends of AAIR were found in all racial/ethnic groups during the 1980s and 1990s. The breast cancer risk increased more substantially in Japanese and Filipinas than in Chinese and Koreans. During 2000–2007, the trends of AAIR declined significantly among NH white women and slightly in blacks, remained unchanged for Hispanics, and continued to rise significantly among all Asian subgroups. The patterns of ASIR by race/ethnicity changed dramatically over time. By 2000–2007, younger Hispanic women had the lowest breast cancer risk, replacing the Chinese and Koreans who formerly had the lowest risk. Rapidly increasing breast cancer incidence trends among Asian-Americans underline the importance of behavioral and lifestyle changes as a result of acculturation on the development of the disease. The unique trends of breast cancer incidence by race/ethnicity suggest the need for targeted breast cancer control programs for different racial/ethnic populations. PMID:21351091
Савченко, Светлана Викторовна
The evolution of the information society in transition "knowledge society" in the era of globalization Tendencies and prospects of development of information society in the era of globalization, explored ways of information society in the developed world and the conditions of its own models of development of the information society; revealed the characteristic features of the models of the information society - western and eastern; the main tendencies of the transition process in the informat...
Gleadow, Roslyn; Honeydew, Melissa; Ford, Allie; Isaac, Bronwyn; Abbott, Kirsti
In this paper we describe how digital technologies can be used to enhance collaboration and student engagement in a large, multicampus undergraduate science unit. Four innovations developed and implemented over a period of eight years are described: use of electronic whiteboards, on-line discussion forums, social media and blogs. In showing the intermediate steps in the evolution of the use of digital and communication technologies, we demonstrate that to be effective, good educational principles are paramount.
Abdollahi, Mahbubeh; Hajizadeh, Ebrahim; Baghestani, Ahmad Reza; Haghighat, Shahpar
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.
Liu, Q; Liu, B; Ding, G R
Objective: To investigate the clinical data of patients with hepatocellular carcinoma in Ningxia Hui Autonomous Region through questionnaire survey, explore the association between the risk factors of liver cancer and the onset age of disease in this area and provide evidence for prevention and treatment of liver diseases. Methods: A retrospectively analysis was conducted in 250 patients with primary hepatocellular carcinoma by using their clinical data collected through questionnaire survey to understand the relationship between gender, smoking, alcohol use, hypertension, diabetes mellitus, hyperlipidemia, family history of liver cancer, liver cirrhosis, HBV infection, eating fish history and other factors and the incidence of hepatocellular carcinoma by univariate and logistic multivariate regression models. Results: Univariate regression analysis showed that hypertension, diabetes mellitus, hyperlipidemia and family history of liver cancer, HBV infection, cirrhosis, smoking, eating fish history were risk factors for the early onset of liver cancer, t=4.150, Pliver cancer onset vary with area diet pattern alcohol use did not influenced the age of liver cancer onset, but smoking and HBV infection were the independent risk factors for early onset of liver cancer. It is necessary to strengthen the HBV infection prevention and control and advise people to quit smoking.
Maini Philip K
Full Text Available Abstract Background The transition from premalignant to invasive tumour growth is a prolonged multistep process governed by phenotypic adaptation to changing microenvironmental selection pressures. Cancer prevention strategies are required to interrupt or delay somatic evolution of the malignant invasive phenotype. Empirical studies have consistently demonstrated that increased physical activity is highly effective in reducing the risk of breast cancer but the mechanism is unknown. Results Here we propose the hypothesis that exercise-induced transient systemic acidosis will alter the in situ tumour microenvironment and delay tumour adaptation to regional hypoxia and acidosis in the later stages of carcinogenesis. We test this hypothesis using a hybrid cellular automaton approach. This model has been previously applied to somatic evolution on epithelial surfaces and demonstrated three phases of somatic evolution, with cancer cells escaping in turn from the constraints of limited space, nutrient supply and waste removal. In this paper we extend the model to test our hypothesis that transient systemic acidosis is sufficient to arrest, or at least delay, transition from in situ to invasive cancer. Conclusions Model simulations demonstrate that repeated episodes of transient systemic acidosis will interrupt critical evolutionary steps in the later stages of carcinogenesis resulting in substantial delay in the evolution to the invasive phenotype. Our results suggest transient systemic acidosis may mediate the observed reduction in cancer risk associated with increased physical activity. Reviewers This article was reviewed by Natalia Komarova (nominated by Marek Kimmel, Heiko Enderling (nominated by Marek Kimmel, Mark Little (nominated by Marek Kimmel and Yang Kuang.
Creina S Stockley
Full Text Available Creina S StockleyThe Australian Wine Research Institute, Adelaide, South Australia, AustraliaAbstract: Population aging is associated with the increased incidence cancer and of degenerative diseases. Population aging is occurring on a global scale, with faster aging projected for the coming decades than has occurred in the past. Globally, the population aged 60 years and over is projected to nearly triple by 2050, while the population aged 80 years and over is projected to experience a more than fivefold increase. Increased numbers of older individuals may have implications for associated expenditure on income support, housing and health services, although a healthy, independent older population can also form a valued social resource, for example in providing care for others, sharing skills and knowledge, and engaging in volunteer activities. Simple dietary measures such as moderate wine consumption to supplement a healthy exercise and nutrition routine, or as an adjunct to prescription medicines when appropriate, are thus needed to maintain an aging population. The role of wine in cancer and the degenerative diseases of aging is thus discussed.Keywords: population aging, wine, degenerative disease, cancer
Talley, Costellia H; Williams, Karen Patricia
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. Copyright © 2015 Elsevier Inc. All rights reserved.
Pan, Jie; Zhao, Jun; Jiang, Ning
The immune compromised patients after treatment of oral cancer may have a chance of infection by drug-resistant opportunistic microbes. We investigated the occurrence of opportunistic microorganisms in aged individuals receiving follow-up examinations after treatment of oral cancer in China. These patients were used as test group and the respective age grouped healthy individuals as control group. In this study, the oral cavity microorganisms such as bacteria and yeast were taken for the analysis. After the screening of representative microorganisms, their aptitude of pervasiveness against drugs was studied. Here, we used antimicrobial agents which are common in clinical practice. We also performed studies to investigate the presence of toxin genes in methicillin-resistant S. aureus (MRSA). The results indicate that the prevalence of drug-resistant microbes was more pronounced in oral cancer patients after initial treatment above 70 years old. The oxacillin resistance of S. aureus isolate confirms that the prevalence of MRSA is increasing in accordance to age-factor and immune compromise in elderly patients. This study reveals the occurrence of drug-resistant opportunistic microorganisms in oral cavity after treatment for oral cancer in aged individuals. Special attention should be directed to MRSA during the treatment of oral cancer, and to realize the fact of immune compromise in elderly patients.
Harrison, Sheree A; Hayes, Sandra C; Newman, Beth
Physical activity has become a focus of cancer recovery research because it has the potential to reduce treatment-related burden and to optimize health-related quality of life (HRQoL). However, the potential for physical activity to influence recovery may be age dependent. This article describes physical activity levels and HRQoL among younger and older women after surgery for breast cancer and explores the correlates of physical inactivity. A population-based sample of breast cancer patients (n = 287) diagnosed in South-East Queensland, Australia, were assessed once every 3 months, from 6 to 18 months postsurgery. The Functional Assessment of Cancer Therapy-Breast questionnaire and items from the Behavioral Risk Factor Surveillance System questionnaire were used to measure HRQoL and physical activity, respectively. Physical activity was assigned MET values and categorized as age stratification (or=3 MET x h x wk of physical activity reported a higher HRQoL at 18 months compared with their more sedentary counterparts (P age, being overweight or obese, and restricting use of the treated side at 6 months postsurgery increased the likelihood of sedentary behavior (odds ratio >or= 3, P Age influences the potential to observe HRQoL benefits related to physical activity participation. These results also provide relevant information for the design of exercise interventions for breast cancer survivors and highlight that some groups of women are at greater risk of long-term sedentary behavior.
Molleman, F; Zwaan, B J; Brakefield, P M; Carey, J R
Information on the life span of organisms in the field is essential for elucidating the evolution of life span and aging. We present mark-recapture data (>30,000 marked individuals, >4000 recaptured at least once) on 47 species of fruit-feeding butterflies in a tropical forest in Uganda. The data reveal adult life spans in the field for several species that are significantly longer than previously recorded in Lepidoptera (butterflies and moths). Longevity records for species of which more than 100 individuals were recaptured ranged from 67 (Bicyclus auricruda) to 293 days (Euphaedra medon). In contrast to the majority of Lepidoptera which are short-lived, these all show exceptionally long life spans, and may thus help to better identify factors that affect aging, particularly when combined with information on temporal patterns in reproduction, strategies to avoid predation, and nutritional ecology. These key traits are readily measurable in butterflies and thus studies on fruit-feeding butterflies have much potential for gaining insight into the evolution of life span and aging, especially given the tradition of field-research on butterflies.
Fraile, Julia M; Campos-Iglesias, Diana; Freije, José M P
Proteases play key roles in the execution and regulation of most if not all biological functions, and alterations in their activity, expression, or location are associated with multiple pathological conditions, including cancer and aging. In this regard, the use of RNA interference-based approaches to specifically target the expression of individual proteases constitutes an invaluable tool to identify enzymes involved in central aspects of these processes and to explore their potential as targets of therapeutic interventions. Here we describe simple protocols to optimize and monitor the specific silencing of cancer- and aging-related proteases.
Choi, Kyoung Joon; Yoo, Seung Chang; Kim, Taeho [School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Banyeon-ri, Eonyang-eup, Ulju-gun, Ulsan 689-798 (Korea, Republic of); Bahn, Chi Bum [School of Mechanical Engineering, Pusan National University (PNU), Busandaehak-ro 63, Beon-gil, Geumjeong-gu, Busan 609-735 (Korea, Republic of); Kim, Ji Hyun, E-mail: firstname.lastname@example.org [School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Banyeon-ri, Eonyang-eup, Ulju-gun, Ulsan 689-798 (Korea, Republic of)
From the earlier study which characterized the region of a fusion boundary between a low-alloy steel (LAS) and a Ni-based weld metal of as-welded and aged samples at 450 °C for a 30-y-equivalent time, it was observed in the microstructure that the aging treatment induced the formation and growth of Cr precipitates in the fusion boundary region because of the thermodynamic driving force. Now, this research extends the text matrix and continues the previous study by compiling all the test data, with an additional aging heat treatment conducted at 400 °C for 15- and 30-y-equivalent times (6450 and 12,911 h, respectively). The results for the extended test matrix primarily represent the common features of and disparities in the effects of thermal aging on the aged samples at two different heat-treatment temperatures (400 and 450 °C). Although no difference was expected between the samples, because the heat treatment conditions simulate thermal aging effects during the same service time of 30 y, the sample aged at 450 °C exhibited slightly more severe effects of thermal aging than the sample aged at 400 °C. Nevertheless, the trends for these effects are similar and the simulation of thermal aging effects for a light-water reactor appears to be reliable. However, according to a simulation of the same degree of thermal aging effects, it appears that the activation energy for Cr diffusion should be larger than the numerical value used in this study.
Choi, Kyoung Joon; Yoo, Seung Chang; Kim, Taeho; Bahn, Chi Bum; Kim, Ji Hyun
From the earlier study which characterized the region of a fusion boundary between a low-alloy steel (LAS) and a Ni-based weld metal of as-welded and aged samples at 450 °C for a 30-y-equivalent time, it was observed in the microstructure that the aging treatment induced the formation and growth of Cr precipitates in the fusion boundary region because of the thermodynamic driving force. Now, this research extends the text matrix and continues the previous study by compiling all the test data, with an additional aging heat treatment conducted at 400 °C for 15- and 30-y-equivalent times (6450 and 12,911 h, respectively). The results for the extended test matrix primarily represent the common features of and disparities in the effects of thermal aging on the aged samples at two different heat-treatment temperatures (400 and 450 °C). Although no difference was expected between the samples, because the heat treatment conditions simulate thermal aging effects during the same service time of 30 y, the sample aged at 450 °C exhibited slightly more severe effects of thermal aging than the sample aged at 400 °C. Nevertheless, the trends for these effects are similar and the simulation of thermal aging effects for a light-water reactor appears to be reliable. However, according to a simulation of the same degree of thermal aging effects, it appears that the activation energy for Cr diffusion should be larger than the numerical value used in this study.
Ozkan, Murat; Cakiroglu, Murat; Kocaman, Orhan; Kurt, Mevlut; Yilmaz, Bulent; Can, Guray; Korkmaz, Ugur; Dandil, Emre; Eksi, Ziya
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 (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; 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
Keith M. Bellizzi
Full Text Available Understanding the post-treatment physical and mental function of older adults from ethnic/racial minority backgrounds with cancer is a critical step to determine the services required to serve this growing population. The double jeopardy hypothesis suggests being a minority and old could have compounding effects on health. This population-based study examined the physical and mental function of older adults by age (mean age = 75.7, SD = 6.1, ethnicity/race, and cancer (breast, prostate, colorectal, and gynecologic as well as interaction effects between age, ethnicity/race and HRQOL. There was evidence of a significant age by ethnicity/race interaction in physical function for breast, prostate and all sites combined, but the interaction became non-significant (for breast and all sites combined when comorbidity was entered into the model. The interaction persisted in the prostate cancer group after controlling for comorbidity, such that African Americans and Asian Americans in the 75–79 age group report lower physical health than non-Hispanic Whites and Hispanic Whites in this age group. The presence of double jeopardy in the breast and all sites combined group can be explained by a differential comorbid burden among the older (75–79 minority group, but the interaction found in prostate cancer survivors does not reflect this differential comorbid burden.
Ekwueme, Donatus U; Trogdon, Justin G; Khavjou, Olga A; Guy, Gery P
No study has quantified productivity losses associated with breast cancer in younger women aged 18-44 years. This study estimated productivity costs, including work and home productivity losses, among younger women who reported ever receiving a breast cancer diagnosis. A two-part regression model and 2000-2010 National Health Interview Survey data were used to estimate the number of work and home productivity days missed because of breast cancer, adjusted for socioeconomic characteristics and comorbidities. Estimates for younger women were compared with those for women aged 45-64 years. Data were analyzed in 2013-2014. Per capita, younger women with breast cancer had annual losses of $2,293 (95% CI=$1,069, $3,518) from missed work and $442 (95% CI=$161, $723) from missed home productivity. Total annual breast cancer-associated productivity costs for younger women were $344 million (95% CI=$154 million, $535 million). Older women with breast cancer had lower per capita work loss productivity costs of $1,407 (95% CI=$899, $1,915) but higher total work loss productivity costs estimated at $1,072 million (95% CI=$685 million, $1,460 million) than younger women. Younger women with a history of breast cancer face a disproportionate share of work and home productivity losses. Although older women have lower per capita costs, total productivity costs were higher for older women because the number of older women with breast cancer is higher. The results underscore the importance of continued efforts by the public health community to promote and support the unique needs of younger breast cancer survivors. Published by Elsevier Inc.
Full Text Available BACKGROUND: Western breast cancer survivors have an increased risk of osteoporosis and bone fracture. Breast cancer occurs 10 to 20 years earlier in Asian women than in Western women. We investigated if younger Asian women with breast cancer also have increased risk of fracture. METHODS: We used the universal insurance claims data from 2000 to 2003 to identify 22,076 patients with breast cancer and 88,304 women without cancer, frequency matched with age and index date (the date for a health care visit. The incidence of fracture in both cohorts and the hazard ratios (HRs of fracture in the cancer cohort were estimated by the end of 2009. RESULTS: The incidence of all types of fracture was higher in the breast cancer cohort than in the comparison cohort (46.72 vs. 42.52 per 10,000 person-years, with adjusted HRs (aHRs of 1.18 (95% confidence intervals [CI], 1.03-1.35 for hip fractures, 1.12 (95% CI, 0.98-1.28 for forearm fractures and 1.24 (95% CI, 1.04-1.48 for vertebral fractures. The aHRs were significant in both non-traumatic fractures (1.29; 95% CI, 1.11-1.51 and traumatic fractures (1.12; 95% CI, 1.01-1.23. The age-specific aHR was higher for younger breast cancer patients, and was significant for <50 years old patients in both traumatic (aHR 1.35; 95% CI 1.08-1.68 and non-traumatic (aHR, 1.72; 95% CI, 1.21-2.44 fractures. CONCLUSION: This study suggests that Asian women with breast cancer might have an increased risk of fracture.
Full Text Available Over the past 30 years, policy makers and professionals who provide services to older adults with chronic conditions and impairments have placed greater emphasis on conceptualizing aging in place as an attainable and worthwhile goal. Little is known, however, of the changes in how this concept has evolved in aging research. To track trends in aging in place, we examined scholarly articles published from 1980 to 2010 that included the concept in eleven academic gerontology journals. We report an increase in the absolute number and proportion of aging-in-place manuscripts published during this period, with marked growth in the 2000s. Topics related to the environment and services were the most commonly examined during 2000–2010 (35% and 31%, resp., with a substantial increase in manuscripts pertaining to technology and health/functioning. This underscores the increase in diversity of topics that surround the concept of aging-in-place literature in gerontological research.
Adams, Peter D.; Jasper, Heinrich; Rudolph, K. Lenhard
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
I. Soerjomataram (Isabelle); E. Pukkala (Eero); H. Brenner (Hermann); J.W.W. Coebergh (Jan Willem)
textabstractBackground: Breast cancer incidence continuous to increase. We examined at population level the association between the relative excess risk of breast cancer and previous age of mother at first birth. Method: Incidence of breast cancer in 34 industrialized countries was obtained from the
Yiu, Raymond; Qiu, Hongming; Lee, Suk-Hwan; García-Aguilar, Julio
The proportion of colorectal cancers located proximal to the splenic flexure increases with age. Colorectal cancers of the microsatellite instability phenotype are preferentially located in the proximal colon. We investigated the location of colorectal cancer with this phenotype in different age groups to determine whether different molecular mechanisms could account for the changes in distribution of colorectal cancers. A representative sample of 230 colorectal cancers from three age groups (87 years) was selected from a subset of The Upper Midwest Oncology Medical Registries database. Microsatellite instability was determined by polymerase chain reaction using a panel of five microsatellite markers. The presence of new microsatellite alleles at two or more loci was scored as microsatellite instability. Tumors were otherwise considered microsatellite stable. MLH1 and MSH2 expression was determined by immunohistochemistry. Methylation of the MLH1 gene promotor was determined by methylation-specific polymerase chain reaction assay. The proportion of tumors of the microsatellite instability phenotype was 21 percent in the young group, 15 percent in the middle group, and 33 percent in the old group. More tumors of the microsatellite instability phenotype were proximal compared with microsatellite-stable tumors in all three age groups, but the differences were significant only for the old group. Tumors of the microsatellite instability phenotype in the older group were associated with MLH1 inactivation (24/29 or 83 percent), MLH1 promoter methylation (18/29 or 62 percent), and proximal location (25/29 or 86 percent), while tumors in the young group were associated with MSH2 inactivation (8/18 or 44 percent) and distal location (11/18 or 62 percent). The age-related proximal shift of colorectal cancers is associated with the microsatellite instability phenotype, MLH1 inactivation, and MLH1 promoter hypermethylation.
Bentzon, N.; During, M.; Rasmussen, B.B.
Estrogen receptor (ER) status is considered as an important prognostic factor as well as a predictive factor for endocrine responsiveness in breast cancer. We analyzed the distribution of ER status across age and estimated variations in the prognostic impact of ER status related to patients' age...... and time since diagnosis. Overall, 26,944 patients with primary breast cancer diagnosed from 1989 to 2004 were included. The proportion of ER positive tumors increased over age from 51 to 82%. In multivariate analysis of overall survival, ER positive status was found to be a significantly positive...... prognostic factor over all age groups. This effect was limited to the first 5 years after diagnosis, RR: 2.08 (95% CI: 1.95-2.22, p
Hlusko, Leslea J
An organism's anatomy is the result of millions of years of interplay between DNA sequence, developmental processes, the environment, and evolutionary forces. The anatomical sciences are consequently highly integrative and interdisciplinary. That said, reaching across all of the relevant disciplines can be a daunting task because scientific publications are produced today at an astounding rate. This manuscript brings together insights from the quantitative genetic analysis of dental variation into the study of human evolutionary odontology within the context of genomics, genetic modularity, and phenomics. It primarily advocates the use of quantitative genetics to not only identify QTLs, but also to assess the patterns of genetic covariance that underlie phenotypic covariance, thereby enabling us to conceptualize phenotypic variation as a reflection of the underlying genetic mechanisms. By highlighting three phenotypes of importance within the study of human evolution (patterning of the dental arcade, enamel thickness, and taurodontism), it is demonstrated how an integrated consideration of quantitative genetics, genomic analyses, and paleontology can bring us to more detailed hypotheses about the evolution of the hominid clade. Copyright © 2015 Elsevier GmbH. All rights reserved.
Wellisch, David K; Ormseth, Sarah R; Aréchiga, Adam E
This study longitudinally profiled anxiety and depressive symptoms of daughters of patients with breast cancer and examined the mother׳s survival status, the daughter׳s age at the time of mother׳s diagnosis, and the style of family communication about breast cancer as moderators of change in symptomatology across participants׳ first 3 appointments at the University of California, Los Angeles Revlon Breast Center High Risk Clinic. We evaluated the effects of hypothesized predictors on change in anxiety and depressive symptoms, 3 (symptomatology at first, second, and third clinic visits) × 2 (mother survived or died) × 2 (<20 or ≥20y old at diagnosis) × 2 (open or closed family communication) repeated-measures analyses of variance were employed. There was a main effect for time of diagnosis on state anxiety, demonstrating a significant reduction in anxiety across clinic visits overall (p < 0.001). There were also significant 3-way interactions. For state anxiety, mother׳s survival status moderated the time of diagnosis × age at diagnosis and time of diagnosis × family communication interaction effects. For daughters whose mothers died, decreased anxiety was observed in those who were younger at the time of diagnosis (p = 0.001). For daughters whose mothers survived, anxiety was decreased for those with closed family communication styles (p = 0.001). The time of diagnosis × mother׳s survival × age at diagnosis interaction was also significant for depressive symptoms (p = 0.001). Among daughters whose mothers died, those who were younger showed decreases in symptoms (p = 0.004). These daughters appeared to benefit from the high-risk program as demonstrated by decreased symptomatology, particularly daughters whose mothers died who were younger at the time of diagnosis. Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.
Carrasco-Garcia, Estefania; Moreno, Manuel; Moreno-Cugnon, Leire; Matheu, Ander
Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Perneger Thomas V
Full Text Available Abstract Background The aim of this study was to identify factors associated with cancer screening practices and with general attitudes toward cancer screening in a general population. Methods Mailed survey of 30–60 year old residents of Geneva, Switzerland, that included questions about screening for five cancers (breast, cervix uteri, prostate, colon, skin in the past 3 years, attitudes toward screening, health care use, preventive behaviours and socio-demographic characteristics. Cancer screening practice was dichotomised as having done at least one screening test in the past 3 years versus none. Results The survey response rate was 49.3% (2301/4670. More women than men had had at least one cancer screening test in the past 3 years (83.2% vs 34.5%, p Conclusion Attitudes play an important role in cancer screening practices among middle-aged adults in the general population, independent of demographic variables (age and sex that determine in part screening recommendations. Negative attitudes were the most frequent among men and the most socio-economically disadvantaged. The moderate participation rate raises the possibility of selection bias.
Sabrina da Silva Santos
Full Text Available Many countries have reported an increase in breast cancer incidence in young women. The current study's objective was to explore breast cancer distribution in women less than 50 years of age in Brazil. A descriptive study on breast cancer incidence (selected cities and mortality (Brazil and selected cities in 2002-2004 was carried out, and the results were compared with those from other countries. The study also analyzed the trend in hospital morbidity and incidence rates for breast cancer. Porto Alegre (Rio Grande do Sul State showed the highest incidence rates (17.9 and 165.5/100,000 in the 15-39 and 40-49-year age strata, respectively. Regarding mortality, Belo Horizonte (Minas Gerais State showed the highest rate in the 15-39-year group and Porto Alegre in the 40-49-year group (2.8 and 25.5/100,000. Hospital admissions and incidence rates for breast cancer suggest a change in epidemiological distribution. The results reveal an epidemiological pattern of breast cancer in young Brazilian women with regional distribution characteristics.
McCuaig, Jeanna M; Armel, Susan R; Novokmet, Ana; Ginsburg, Ophira M; Demsky, Rochelle; Narod, Steven A; Malkin, David
It is well known that early-onset breast cancer may be due to an inherited predisposition. When evaluating women diagnosed with breast cancer under age 30, two important syndromes are typically considered: Hereditary Breast and Ovarian Cancer Syndrome and Li-Fraumeni syndrome. Many women are offered genetic testing for mutations in the BRCA1 and BRCA2 genes; however, few are offered genetic testing for mutations in the TP53 gene. There is a concern that overly restrictive testing of TP53 may fail to recognize families with Li-Fraumeni syndrome. We reviewed the genetic test results and family histories of all women with early-onset breast cancer who had genetic testing of the TP53 gene at the Toronto Hospital for Sick Children. Of the 28 women tested, six (33.3 %) had a mutation in the TP53 gene; a mutation was found in 7.7 % of women who did not meet current criteria for Li-Fraumeni syndrome. By reviewing similar data published between 2000 and 2011, we estimate that 5-8 % of women diagnosed with early-onset breast cancer, and who have a negative family history, may have a mutation in the TP53 gene. Given the potential benefits versus harms of this testing, we discuss the option of simultaneous testing of all three genes (BRCA1, BRCA2, and TP53) for women diagnosed with breast cancer before age 30.
Fuss, Jill O.; Cooper, Priscilla K.
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 , 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 . 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
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.
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 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
Wong, Jonathan [University of Hawaii, John A. Burns School of Medicine, Honolulu, Hawaii (United States); Xu, Beibei [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Moores Cancer Center, University of California San Diego, La Jolla, California (United States); Yeung, Heidi N.; Roeland, Eric J. [Moores Cancer Center, University of California San Diego, La Jolla, California (United States); Division of Palliative Medicine, Department of Internal Medicine, University of California San Diego, La Jolla, California (United States); Martinez, Maria Elena [Moores Cancer Center, University of California San Diego, La Jolla, California (United States); Department of Family and Preventive Medicine, University of California San Diego, La Jolla, California (United States); Le, Quynh-Thu [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Mell, Loren K. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Moores Cancer Center, University of California San Diego, La Jolla, California (United States); Murphy, James D., E-mail: email@example.com [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Moores Cancer Center, University of California San Diego, La Jolla, California (United States)
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
Lach, Timothy G.; Byun, Thak Sang; Leonard, Keith J.
Mechanical testing and microstructural characterization were performed on short-term thermally aged cast austenitic stainless steels (CASS) to understand the severity and mechanisms of thermal-aging degradation experienced during extended operation of light water reactor (LWR) coolant systems. Four CASS materials – CF3, CF3M, CF8, and CF8M – were thermally aged for 1500 hours at 290 °C, 330 °C, 360 °C, and 400 °C. All four alloys experienced insignificant change in strength and ductility properties but a significant reduction in absorbed impact energy. The primary microstructural and compositional changes during thermal aging were spinodal decomposition of the δ-ferrite into α/ α`, precipitation of G-phase in the δ-ferrite, segregation of solute to the austenite/ ferrite interphase boundary, and growth of M23C6 carbides on the austenite/ferrite interphase boundary. These changes were shown to be highly dependent on chemical composition, particularly the concentration of C and Mo, and aging temperature. A comprehensive model is being developed to correlate the microstructural evolution with mechanical behavior and simulation for predictive evaluations of LWR coolant system components.
Esteva, Magdalena; Ruiz, Amador; Ramos, Maria; Casamitjana, Monserrat; Sánchez-Calavera, María A; González-Luján, Luis; Pita-Fernández, Salvador; Leiva, Alfonso; Pértega-Díaz, Sonia; Costa-Alcaraz, Ana M; Macià, Francesc; Espí, Alejandro; Segura, Josep M; Lafita, Sergio; Novella, Maria T; Yus, Carmen; Oliván, Barbara; Cabeza, Elena; Seoane-Pillado, Teresa; López-Calviño, Beatriz; Llobera, Joan
The gap in survival between older and younger European cancer patients is getting wider. It is possible that cancer in the elderly is being managed or treated differently than in their younger counterparts. This study aims to explore age disparities with respect to the clinical characteristics of the tumour, diagnostic pathway and treatment of colorectal cancer patients. We conducted a multicenter cross sectional study in 5 Spanish regions. Consecutive incident cases of CRC were identified from pathology services. From patient interviews, hospital and primary care clinical records, we collected data on symptoms, stage, doctors investigations, time duration to diagnosis/treatment, quality of care and treatment. 777 symptomatic cases, 154 were older than 80 years. Stage was similar by age group. General symptoms were more frequent in the eldest and abdominal symptoms in the youngest. No differences were found regarding perception of symptom seriousness and symptom disclosure between age groups as no longer duration to diagnosis or treatment was observed in the oldest groups. In primary care, only ultrasound is more frequently ordered in those 80 years had a significantly higher proportion of iron testing and abdominal XR requested in hospital. We observed a high resection rate independently of age but less adjuvant chemotherapy in Stage III colon cancer, and of radiotherapy in stage II and III rectal cancer as age increases. There are no relevant age disparities in the CRC diagnosis process with similar stage, duration to diagnosis, investigations and surgery. However, further improvements have to be made with respect to adjuvant therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available AIM: Cervical cancer is the most frequently seen genital system cancer in women after endometrium adenocarcinoma. Because cervical is an easy reach organ, early diagnosis can be done due to Papanicolau (Pap smear in the cancer cases of this organ and prognosis ameliorates considerably. In this ailment there are two peaks. The first one is around the ages 35-39, the second one is around the ages 60-64. The aim of the study is to scan cervical cancer among the women between the ages of 35-40 in the district of Kisecik health office. METHOD: This study is a definitional, society based sectional study performed among the women between the ages of 35- 40 in the district of Kisecik in Hatay. 187 women between the ages of 35- 40 were enrolled to the study; 10 out of 187 women who were single were not included to the study. The study was completed after enrolling 150 women out of 177. Cervical smear samples were taken from the participants; and these samples were evaluated in a pathology laboratory according to the Bethesda 2001 scale. RESULTS: The avarage age of the participants was 37.55±1.77. After the evaluation of the cervical smears in the pathology laboratory, the results were normal for 73 participants (%48.7. 36 participants (%24.0 had non specific inflamation, 20 participants (%13.3 had bacterial vaginosis, 19 participants (%12.7 had seconder reactive changes to the inflamation and 2 participants (%1.3 was reported to be ASC-US. CONCLUSION: By the help of cheap and easily applied Pap smear test, society based scanning programmes can be performed frequently and thus; servical lesions may be detected in early phases. Furthermore through education, the level of information about cervical cancer should be raised and consciousness should be created. [TAF Prev Med Bull 2010; 9(5.000: 471-474
Johnson, Leah R; Mangel, Marc
The disposable soma theory of aging was developed to explore how differences in lifespans and aging rates could be linked to life history trade-offs. Although generally applied for multicellular organisms, it is also useful for exploring life history strategies of single-celled organisms such as bacteria. Motivated by recent research of aging in E. coli, we explore the effects of aging on the fitness of simple single-celled organisms. Starting from the Euler-Lotka equation, we propose a mathematical model to explore how a finite reproductive lifespan affects fitness and resource allocation in simple organisms. This model provides quantitative predictions that have the potential for direct comparison with experiment, providing an opportunity to test the disposable soma theory more directly.
Maslow, Bat-Sheva L; Morse, Christopher B; Schanne, Allison; Loren, Alison; Domchek, Susan M; Gracia, Clarisa R
Few data on contraceptive choices in women with cancer exist. Contraception is challenging for women with cancer, particularly those with breast cancer, who are limited to nonhormonal methods. This study characterized contraceptive use during cancer treatment in a group of reproductive-aged women with a recent cancer diagnosis and assessed the impact of contraceptive counseling on the methods they selected. Cross-sectional, survey study of reproductive-aged women at a large tertiary care health system with a recent cancer diagnosis. A total of 107 women completed the survey. Eighty-two women reported 101 contraceptive choices. Twenty-seven percent (27/101) of all methods selected were Tier I/II, and 35% (35/101) were Tier III/IV. Only 4 used an intrauterine device (IUD). Among women reporting sexual activity after diagnosis, 19 (27%) of 71 reported using Tier I/II methods, 21 (30%) of 71 reported using Tier III/IV methods, 16 (23%) of 71 reported abstinence and 10 (14%) of 71 reported using no method. Factors significantly associated with Tier I/II use in the multivariable model included not having a college degree [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.05-0.92, p=.038], intercourse during treatment (OR 5.92, 95% CI 1.48-23.66, p=.012) and non-breast cancer (OR 3.60, 95% CI 1.03-12.64, p=.046). Report of contraceptive counseling was positively associated with Tier I/II contraceptive use during cancer treatment (OR 6.92, 95% CI 1.14-42.11, p=.036). Reproductive-aged women diagnosed with cancer underutilized Tier I/II contraceptive agents, especially IUDs. Contraceptive counseling by physicians increases contraceptive use, particularly methods most effective at preventing pregnancy. The study uniquely described the contraceptive practices of over 100 women with cancer. The study sample commonly reported abstinence and use of contraceptive methods with high failure rates. Our data suggest that contraceptive counseling from a health care provider may
Roswall, Nina; Larsen, Signe B.; Friis, Søren
Purpose: Micronutrients may protect against prostate cancer. However, few studies have had high-quality assessment of both dietary and supplemental consumption of micronutrients, rendering possible different source-specific effects difficult to discern. This study evaluates associations between...... intake of vitamin C, E, folate, and beta-carotene and prostate cancer risk, focusing on possible different effects of dietary, supplemental, or total intake and on potential effect modification by alcohol intake and BMI. Methods: Danish prospective cohort study of 26,856 men aged 50-64 years...... was inversely associated with prostate cancer risk, notably on a continuous scale [HR 0.88 (95 % CI 0.79-0.98) per 100 µg increase/day]. The risk reduction was largely confined to non-aggressive tumors [HR 0.71 (0.55-0.93) per 100 µg increase/day]. No influence on prostate cancer risk was observed for dietary...
I. S. Stilidi
Full Text Available Background. Colorectal cancer is highly prevalent in Russia, especially among the elderly patients. We analyzed the influence of age on anxiety level and cognitive function on patients with colorectal cancer.Materials and methods. In the period 2012–2015 we analyzed pre-operatively the level of anxiety (HADS scale and cognitive disfunction (MoCA test in 244 patients who underwent radical colorectal resection.Results. Patients younger than 60 constituted 34 %, 60–74 years – 31 %, 75 years and older – 35 %. We were able to show a correlation between age and anxiety level according to HADS. The same trend was found according to MoCA test.Conclusion. Oncopsychologist shall develop individualized treatment plan according to anxiety and cognitive levels in patients with colorectal cancer.
Stevens, Richard J; Roddam, Andrew W; Spencer, Elizabeth A; Pirie, Kirstin L; Reeves, Gillian K; Green, Jane; Beral, Valerie
Risk factors for pancreatic cancer, other than smoking and diabetes, are not well-established, especially for women. In a cohort of 1.3 million middle-aged women, followed for 9.2 million person-years for cancer incidence and 11.5 million person-years for mortality, there were 1,338 incident pancreatic cancer cases and 1,710 deaths from the disease. Using proportional hazards models, we calculated adjusted relative risks (RRs) and 95% confidence intervals (CIs) by smoking, height, body mass index (BMI), alcohol consumption, physical activity and history of diabetes. Pancreatic cancer incidence was greater in current than never smokers (RR 2.39, CI 2.10-2.73), the risk increasing with the number of cigarettes smoked. The incidence of pancreatic cancer also increased with increasing BMI (RR 1.34, CI 1.13-1.57 for BMI >or= 30 vs. 22.5-25 kg/m(2)), and with a history of diabetes (RR 1.58, CI 1.22-2.03, with vs. without such a history). These factors were also associated with increased mortality from pancreatic cancer. Height, alcohol consumption and physical activity showed little or no association with pancreatic cancer risk. (c) 2008 Wiley-Liss, Inc.
Rosenberg, Philip S; Check, David P; Anderson, William F
Age-period-cohort (APC) analysis can inform registry-based studies of cancer incidence and mortality, but concerns about statistical identifiability and interpretability, as well as the learning curves of statistical software packages, have limited its uptake. We implemented a panel of easy-to-interpret estimable APC functions and corresponding Wald tests in R code that can be accessed through a user-friendly Web tool. Input data for the Web tool consist of age-specific numbers of events and person-years over time, in the form of a rate matrix of paired columns. Output functions include model-based estimators of cross-sectional and longitudinal age-specific rates, period and cohort rate ratios that incorporate the overall annual percentage change (net drift), and estimators of the age-specific annual percentage change (local drifts). The Web tool includes built-in examples for teaching and demonstration. User data can be input from a Microsoft Excel worksheet or by uploading a comma-separated-value file. Model outputs can be saved in a variety of formats, including R and Excel. APC methodology can now be carried out through a freely available user-friendly Web tool. The tool can be accessed at http://analysistools.nci.nih.gov/apc/. The Web tool can help cancer surveillance researchers make important discoveries about emerging cancer trends and patterns. ©2014 American Association for Cancer Research.
Wolde, B. ten; Kuiper, M.; Wilt, J.H.W. de; Strobbe, L.J.A.
INTRODUCTION: Consensus about surgical treatment options for breast cancer in elderly patients remains elusive due to exclusion from clinical trials. Fear of complications due to increased age often is an important factor in the choice of treatment and might result in different treatment of the
Baccaro, Luiz Francisco, E-mail: firstname.lastname@example.org [Department of Gynecology, State University of Campinas, Rua Alexander Fleming, 101, Cidade Universitária Zeferino Vaz, Campinas, São Paulo 13.083-881 (Brazil); Conde, Délio Marques [Breast Clinic, Hospital for Maternal and Child Healthcare, Goiânia, Goiás 74.125-120 (Brazil); Costa-Paiva, Lúcia; Machado, Vanessa de Souza Santos; Pinto-Neto, Aarão Mendes [Department of Gynecology, State University of Campinas, Campinas, São Paulo 13.083-881 (Brazil)
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.
Luiz Francisco Baccaro
Full Text Available 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.
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…
When cells produce energy, they also form reactive oxygen molecules capable of damaging proteins and DNA. Normally, these molecules are neutralized by a protein called superoxide dismutase, or SOD. However, as a cell ages, oxidative damage accumulates. The increase in oxidative cellular damage as people age may provide a mechanistic connection between aging and carcinogenesis.
Smith, R A
In the hope of resolving underlying policy questions related to the value of breast cancer screening with mammography for women younger than 50 years of age, the National Institutes of Health and the National Cancer Institute in 1997 jointly sponsored a consensus conference on the subject. While the panel concluded that the data were insufficient to endorse mammography for this age group apart from individual choice, the conclusion was not the "consensus" sought by many of those with strong opinions on both sides of this issue, and the debate raged on. Prior to the 1997 conference, and since, meta-analyses of trial data and assessments of service screening programs have indicated that breast cancer screening with mammography for women between 40 and 49 meets recommended levels of performance compared with performance in women 50 years and older, especially if programs achieve high quality and screen at 12-to-18 month intervals. Because the detectable preclinical phase is shorter in younger women who develop breast cancer compared with that in women 50 years of age or older, a key component of any screening program for those younger than 50 is an appropriate screening interval. Many of the screening programs that had historically been developed for women in their forties--and whose disappointing results contributed to the confusion and controversy about the efficacy of mammography in younger women--had a 24-month screening interval, which was not found to be of significant benefit for early detection of breast cancer in this age group. While a new emphasis of this controversy has focused on the balance of benefits and harms in women ages 40 to 49, women of all ages need to be fully informed about the benefits and limitations of breast cancer screening--more specifically, what to expect at the time of screening, and what to expect from screening. There are differences in the performance and effectiveness of mammography in different age groups of women aged 40 and
Full Text Available Education and training research for business environment has become an important subject to debate in nowadays, because it allows the design of scenarios that contribute to economic and social development. In this paper, we propose to analyse the evolution of business educational models, in terms of new forms of learning: e-learning and MOOC. It will also be analysed the impact of educational methods in the virtual environment in the classic educational system. Last but not least there will be outlined the perspectives and opportunities of business education in the context of educational reform at European and global level. In this regard, it will be drawn the direction and position of Romania towards the reorganization of business education model.
Full Text Available The paper is a brief notice of a series of WORKS covering the topic of Ukraine’s economy international specialization, Ukraine’s evolution since the pre-state period in its history, formation of the first states within the territory of Ukraine (the Scythian culture, Greek states within Ukraine, the tribal Antes Alliance and Huts Empire, the origin of Slavs and the Ukrainian people, the period from the foundation of Kyiv through liquidation of Kyiv Principality, the Cossack Era in the history of Ukraine, the Ukrainian People’s Republic, declaration of Ukraine’s independence, Famine-Genocide, and the place and role of Ukraine’s international specialization as part of the USSR
Mateus, N; de Freitas, V
For three years, the evolution of the three major anthocyanidin monoglucosides (malvidin 3-glucoside, malvidin 3-acetylglucoside, and malvidin 3-coumaroylglucoside) and their anthocyanin-pyruvic acid adducts was monitored in Port wines stored in oak barrels. The degradation reactions of all pigments followed first-order kinetics in all the wines studied. The degradation rate constants of the anthocyanin-pyruvic acid adducts were much lower than those of the anthocyanidin monoglucosides. The results of both anthocyanins and pyruvic acid adducts show that acylation on the sugar moiety of all the pigments decreased their stability in wine. The levels of malvidin 3-glucoside-pyruvic acid adduct and its acylated forms increased right after wine fortification with wine spirit before starting to decrease around 100 days. The initial formation of anthocyanin-pyruvic acid adducts was concurrent with the degradation of anthocyanidin monoglucosides.
Olivieri, Fabiola; Rippo, Maria Rita; Monsurrò, Vladia; Salvioli, Stefano; Capri, Miriam; Procopio, Antonio Domenico; Franceschi, Claudio
Epidemiological and experimental data demonstrate a strong correlation between age-related chronic inflammation (inflamm-aging) and cancer development. However, a comprehensive approach is needed to clarify the underlying molecular mechanisms. Chronic inflammation has mainly been attributed to continuous immune cells activation, but the cellular senescence process, which may involve acquisition of a senescence-associated secretory phenotype (SASP), can be another important contributor, especially in the elderly. MicroRNAs (miRs), a class of molecules involved in gene expression regulation, are emerging as modulators of some pathways, including NF-κB, mTOR, sirtuins, TGF-β and Wnt, that may be related to inflammation, cellular senescence and age-related diseases, cancer included. Interestingly, cancer development is largely avoided or delayed in centenarians, where changes in some miRs are found in plasma and leukocytes. We identified miRs that can be considered as senescence-associated (SA-miRs), inflammation-associated (inflamma-miRs) and cancer-associated (onco-miRs). Here we review recent findings concerning three of them, miR-21, -126 and -146a, which target mRNAs belonging to the NF-κB pathway; we discuss their ability to link cellular senescence, inflamm-aging and cancer and their changes in centenarians, and provide an update on the possibility of using miRs to block accumulation of senescent cells to prevent formation of a microenvironment favoring cancer development and progression. Copyright © 2013 Elsevier B.V. All rights reserved.
Halmos, G. B.; Bras, L.; Siesling, S.; van der Laan, B.F.A.M.; Langendijk, Johannes A.; van Dijk, Boukje A.C.
Objectives: To explore the incidence and treatment pattern of head and neck cancer in different age groups. Design: Cohort study. Setting: Netherlands Cancer Registry. Participants: All new primary head and neck cancer cases diagnosed between 2010 and 2014 were included and categorised into
Wong, Jonathan; Xu, Beibei; Yeung, Heidi N; Roeland, Eric J; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K; Murphy, James D
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. 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. 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 Ppalliative 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 of life. Copyright © 2014 Elsevier Inc. All rights reserved.
Fidler, Miranda M; Gupta, Sumit; Soerjomataram, Isabelle; Ferlay, Jacques; Steliarova-Foucher, Eva; Bray, Freddie
To date, the burden of cancer among young adults has rarely been studied in depth. Our aim was to describe the scale and profile of cancer incidence and mortality worldwide among 20-39 year-olds, highlighting major patterns by age, sex, development level, and geographical region. We did a population-based study to quantify the burden of young adult cancers worldwide. We defined young adult cancers as those occurring between the ages of 20 and 39 years because these individuals will have passed puberty and adolescence, but not yet experienced the effects of hormonal decline, immune response deterioration, or organ dysfunction associated with chronic health conditions. Global, regional, and country-specific (n=184) data estimates of the number of new cancer cases and cancer-associated deaths that occurred in 2012 among young adults were extracted in four 5-year bands from the International Agency for Research on Cancer's GLOBOCAN 2012 for all cancers combined and for 27 major types as defined by the International Classification of Disease, tenth revision. We report the number of new cancer cases and cancer-associated deaths overall and by sex alongside corresponding age-standardised rates (ASR) per 100 000 people per year. We also present results using four levels of the Human Development Index (HDI; low [least developed], medium, high, and very high [most developed]), which is a composite indicator for socioeconomic development comprising life expectancy, education, and gross national income. 975 396 new cancer cases and 358 392 cancer-associated deaths occurred among young adults worldwide in 2012, which equated to an ASR of 43·3 new cancer cases per 100 000 people per year and 15·9 cancer-associated deaths per 100 000 people per year. The burden was disproportionally greater among women and the most common cancer types overall in terms of new cases were female breast cancer, cervical cancer, thyroid cancer, leukaemia, and colorectal cancer; in terms of
of the concept of tumors as caricatures of tissue renewal. Thus, recent molecular classification of breast cancer based on genome wide expression analysis operates with different subtypes with specific reference to the normal luminal epithelial and myoepithelial/basal lineages in the breast. Apparently some...... tumors are lineage restricted and others differentiate more broadly as if they have preserved some stem-like properties. This holds promise for the existence of a stem cell hierarchy, the understanding of which may prove to be instrumental in further dissecting the histogenesis of breast cancer evolution...... tumor progression is still very much required. Complete knowledge of the primary cell of origin of breast cancer and the mechanisms that influence differentiation programs during tumor initiation, promotion and progression may be crucial for the development of novel non-toxic therapies that influence...
Braen, Bernard B.
This report evaluates the Young Mothers' Educational Development Program sponsored by the State University of New York, for pregnant girls between the ages of 16 and 21. The program provided needed services in the areas of obstetrics, pediatrics, education, social work, nursing, and psychology. The girls were Black, Caucasian, and Indian.…
de Haas, G.J.L.M.
In this thesis the results of a petrological, geochemical and isotopic study of five coronitic gabbros (hyperites) from the Arendal-Nelaug area, Bamble Sector, South Norway, are presented. The scope of this study was 1) to determine the age of these gabbros, 2) to study their magmatic and chemical
Moreno-Arribas, M V; Gómez-Cordovés, C; Martín-Álvarez, P J
A comparative study was conducted on nine batches of wine, from the same initial wine, subjected to malolactic fermentation and ageing in barrels, under different technological conditions: Malolactic fermentation in barrel or in tank, with or without wine clarification, ageing with or without lees and stirring or no stirring of the lees. Samples were taken of the initial wine, of the wine at the end of malolactic fermentation, of the wines after clarifying treatments, and after 3, 6, 9, 12 and 14 months of ageing in the barrel, making a total of 48 wines. As a result of the anthocyanin analysis of all the wines studied, a total of 21 different anthocyanin compounds were detected, which can be classified into four groups: simple glucosides, acetyl glucosides, cinnamoyl glucosides and pyroanthocyanins. During MLF, it was shown that the effect of the container used seems to be more important than the metabolic activity of the bacteria responsible for the process. From application of the LSD test, significant differences were found in the concentrations of all the anthocyanin compounds identified due to ageing time and significant differences were also revealed for most anthocyanin compounds in relation to the manufacturing method, especially the presence or absence of lees. Copyright © 2007 Elsevier Ltd. All rights reserved.
Richter, Diana; Ernst, Jochen; Lehmann, Claudia; Koch, Uwe; Mehnert, Anja; Friedrich, Michael
While psychosocial distress and supportive care needs of young adult cancer patients have been increasingly studied, little knowledge exists about preferences for communicating bad news. We aimed to analyze patients' communication preferences against their actual experiences with regard to doctor-patient interactions. We surveyed a total of 270 cancer patients with different tumor entities. 3 age groups (young, middle-aged, and elderly) were compared concerning their communication preferences (MPP; Measure of Patients' Preferences questionnaire) and the impact on distress (National Comprehensive Cancer Network Distress Thermometer). We found no age differences of communication preferences and the content of bad news. A significant difference was found in the dimension 'professional expertise/patient orientation (p children' (odds ratio (OR) 0.296; 95% confidence interval (CI) 0.155, 0.563), tumor staging (OR 1.737, 95% CI 1.028, 2.936), and insufficient 'privacy' (OR 0.987; 95% CI 0.978, 0.997) and 'clarity' (OR 1.013; 95% CI 1.002, 1.025) on distress. Communication preferences related to breaking bad news depend less on age differences than on other variables. Future studies should investigate the long-term impact of ineffective patient-physician communication, taking into account unmet patient preferences in different age groups. © 2015 S. Karger GmbH, Freiburg.
Land, L H; Dalton, S O; Jensen, M-B
Prevalence of comorbidity at breast cancer diagnosis increases with age and is likely to influence the likelihood of receiving treatment according to guidelines. The aim of this study was to examine the effect of breast cancer treatment on mortality, taking age at diagnosis and comorbidity...
Bentzon, Niels; Düring, Maria; Rasmussen, Birgitte Bruun
Estrogen receptor (ER) status is considered as an important prognostic factor as well as a predictive factor for endocrine responsiveness in breast cancer. We analyzed the distribution of ER status across age and estimated variations in the prognostic impact of ER status related to patients' age...... and time since diagnosis. Overall, 26,944 patients with primary breast cancer diagnosed from 1989 to 2004 were included. The proportion of ER positive tumors increased over age from 51 to 82%. In multivariate analysis of overall survival, ER positive status was found to be a significantly positive...... unchanged in patients who did not receive adjuvant systemic therapy (n = 6,272). Thus, positive ER status does not confer a negative impact on survival in young women as has been previously reported. The inferior prognosis for ER negative patients during the first 5 years after diagnosis changes...
Kim, Jun Woo; Jang, Mi Jung; Kim, Sun Mi; Yun, Bo La; Lee, Jong Yoon; Kim, Eun Kyu; Kang, Eun Young; Park, So Yeon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)
To evaluate the clinicopathological and imaging features of mammography, ultrasonography, and magnetic resonance imaging (MRI) for breast cancer in Korean women under 40 years of age according to molecular subtypes. We included 183 breast cancers in 176 consecutive women under 40 years old who had been diagnosed with breast cancer between January 2012 and November 2014. The patients' clinical and pathologic records were available as electronic medical records. A retrospective review of the pre-operative imaging studies was performed with 177 mammographies, 183 ultrasonographies, and 178 MRIs. Eighty-six percent (158/183) of lesions were symptomatic, with masses (147/183) as the most common presentation. Eighty percent (22/25) of the asymptomatic lesions were diagnosed via screening ultrasonography. The luminal A subtype was the most common (n = 79, 43%), human epidermal growth factor receptor 2-enriched subtype showed indistinct margins on mammography (p = 0.006), the triple negative subtype depicted a posterior enhancement on ultrasonography (p < 0.001) and rim enhancement on MRI (p < 0.001). Breast cancers in Korean women under 40 years of age are commonly presented with a palpable mass, and luminal A is the most common molecular subtype. In our study, the imaging and pathologic characteristics of breast cancer in younger women were similar to those previously reported for older patients.
Therkildsen, Christina; Ladelund, Steen; Smith-Hansen, Lars
increased IRRs were identified for 13 cancer types with differences related to gender, age and disease-predisposing gene. The different cancer types showed variable peak age incidence rates (IRs) with the highest IRs for ovarian cancer at age 30-49 years, for endometrial cancer, breast cancer, renal cell...... cancer and brain tumours at age 50-69 years, and for urothelial cancer, small bowel cancer, gastric cancer, pancreatic cancer and skin tumours after age 70. CONCLUSIONS: The broad spectrum of tumour types that develop at an increased incidence defines Lynch syndrome as a multi-tumour syndrome....... The variable incidences in relation to age, gender and gene suggest a need for individualised surveillance.British Journal of Cancer advance online publication 24 October 2017; doi:10.1038/bjc.2017.348 www.bjcancer.com....
Maida J Sewitch
Full Text Available Colorectal cancer screening is underutilized, resulting in preventable morbidity and mortality. In the present study, age-related and other disparities associated with physicians’ delivery of colorectal cancer screening recommendations were examined. The present cross-sectional study included 43 physicians and 618 of their patients, aged 50 to 80 years, without past or present colorectal cancer. Of the 285 screen-eligible patients, 45% received a recommendation. Multivariate analyses revealed that, compared with younger nonde-pressed patients, older depressed patients were less likely to receive fecal occult blood test recommendations, compared with no recommendation (OR=0.31, 95% CI 0.09 to 1.02, as well as less likely to receive colonoscopy recommendations, compared with no recommendation (OR=0.14; 95% CI 0.03 to 0.66. Comorbidity and marital status were associated with delivery of fecal occult blood test and colonoscopy recommendations, respectively, compared with no recommendation. In summary, patient age and other characteristics appeared to influence physicians’ delivery of colorectal cancer screening and choice of modality.
Checka, Cristina M; Chun, Jennifer E; Schnabel, Freya R; Lee, Jiyon; Toth, Hildegard
Breast density is increasingly recognized as an independent risk factor for the development of breast cancer, because it has been shown to be associated with a four- to sixfold increase in a woman's risk of malignant breast disease. Increased breast density as identified on mammography is also known to decrease the diagnostic sensitivity of the examination, which is of great concern to women at increased risk for breast cancer. Dense tissue has generally been associated with younger age and premenopausal status, with the assumption that breast density gradually decreases after menopause. However, the actual proportion of older women with dense breasts is unknown. The purpose of this study was to examine the relationship between age and breast density, particularly focusing on postmenopausal women. All screening mammograms completed at the New York University Langone Medical Center in 2008 were retrospectively reviewed. Analysis of variance and descriptive analyses were used to evaluate the relationship between patient age and breast density. A total of 7007 screening mammograms were performed. The median age of our cohort was 57 years. Within each subgroup categorized by decade of age, there was a normal distribution among the categories of breast density. There was a significant inverse relationship between age and breast density (p breasts. This percentage decreased to 57% of women in their 50s. However, 44% of women in their 60s and 36% of women in their 70s had dense breasts as characterized on their screening mammograms. In general, we found an inverse relationship between patient age and mammographic breast density. However, there were outliers at the extremes of age. A meaningful proportion of young women had predominantly fatty breasts and a subset of older women had extremely dense breasts. Increased density renders mammography a less sensitive tool for early detection. Breast density should be considered when evaluating the potential benefit of extended
Anderson, Chelsea; Sandler, Dale P; Weinberg, Clarice R; Houck, Kevin; Chunduri, Minal; Hodgson, M Elizabeth; Sabatino, Susan A; White, Mary C; Rodriguez, Juan L; Nichols, Hazel B
The aim of this study was to identify demographic and treatment-related factors associated with health-promoting behavior changes after a breast cancer diagnosis. Changes in health behaviors were also evaluated according to weight, exercise, diet and alcohol consumption patterns before breast cancer diagnosis. We examined self-reported behavior changes among 1415 women diagnosed with breast cancer in the NIEHS Sister Study cohort. Women reported changes in exercising, eating healthy foods, maintaining a healthy body weight, drinking alcohol, smoking, getting enough sleep, spending time with family and friends, and participating in breast cancer awareness events. On average, women were 3.7 years from their breast cancer diagnosis. Overall, 20-36% reported positive changes in exercise, eating healthy foods, maintaining a healthy weight, or alcohol consumption. However, 17% exercised less. With each 5-year increase in diagnosis age, women were 11-16% less likely to report positive change in each of these behaviors (OR = 0.84-0.89; p cancer survivorship guideline-supported behaviors after diagnosis. Positive changes were more common among younger women or those who underwent chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.
Coffey, K; Beral, V; Green, J; Reeves, G; Barnes, I
Anal cancer incidence increases with age and is higher in women than men. Risk factors in this group other than high-risk human papillomavirus infection are unclear. In all, 1.3 million women were recruited in 1996-2001 and followed for incident anal cancer. Cox regression models were used to calculate relative risks (RRs) for anal cancer by various potential risk factors. Five hundred and seventeen incident anal cancers were registered over 13 years of follow-up. The largest RR was associated with a history of cervical intraepithelial neoplasia grade 3 (CIN 3; RR=4.03, 95% CI 2.59-6.28). Other factors associated with significantly increased risks in multivariate analyses were: ever smoking (RR=1.49, 1.24-1.80); previous use of oral contraceptives (RR=1.51, 1.24-1.83); nulliparity (RR=1.61, 1.24-2.07); tubal ligation (RR=1.39, 1.13-1.70) and not living with a partner (RR=1.82, 1.40-2.38). The association with smoking was significantly greater for squamous cell carcinoma than adenocarcinoma of the anus (RR 1.66 vs 0.89, P for heterogeneity=0.04). History of CIN 3, smoking, past oral contraceptive use, nulliparity, tubal ligation and not living with a partner are risk factors for anal cancer in women. There was a significant increase in risk associated with smoking for squamous cell anal cancers but not adenocarcinomas.
Banegas, Matthew P; Dickerson, John F; Kent, Erin E; de Moor, Janet S; Virgo, Katherine S; Guy, Gery P; Ekwueme, Donatus U; Zheng, Zhiyuan; Nutt, Stephanie; Pace, Loyce; Varga, Alexandra; Waiwaiole, Lisa; Schneider, Jennifer; Robin Yabroff, K
With increasing cancer care costs and greater patient cost-sharing in the USA, understanding access to medical care among cancer survivors is imperative. This study aims to identify financial, psychosocial, and cancer-related barriers to the receipt of medical care, tests, or treatments deemed necessary by the doctor or patient for cancer among cancer survivors age medical care, including sociodemographic, financial hardship, debt amount, caregiver status, and cancer-related variables. Approximately 28% of cancer survivors were within 1 year, and 43% between 1 and 5 years, since their last treatment at the time of survey. Nearly 9% of cancer survivors reported not receiving necessary medical care. Compared to survivors without financial hardship, the likelihood of not receiving necessary medical care significantly increased as the amount of debt increased among those with financial hardship (RR Financial hardship w/medical bills were significantly more likely to not receive necessary medical care. We identified key financial and insurance risk factors that may serve as significant barriers to the receipt of necessary medical care among cancer survivors age medical care either they or their doctors deemed necessary. However, identifying potentially modifiable barriers to receipt of necessary medical cancer care among cancer survivors age care and reducing cancer disparities.
Lennartz-Sassinek, Sabine; Main, Ian G.; Danku Zsuzsa (1984-) (fizikus); Kun Ferenc (1966-) (fizikus)
Damage growth in composite materials is a complex process which is of interest in many fields of science and engineering. We consider this problem in a fiber bundle model where fibers undergo an aging process due to the accumulation of damage driven by the locally acting stress in a chemically active environment. By subjecting the bundle to a constant external load, fibers fail either when the load on them exceeds their individual intrinsic strength or when the accumulated internal damage exc...
Full Text Available In this work, we evaluate the physic-chemical characteristics and volatile compounds during the second fermentation and aging of typical Brazilian sparkling wines. For this purpose, second fermentations were conducted by the traditional method using a base wine elaborated with Pinot Noir, Chardonnay and Riesling Italic, and fermented with S. cerevisiae vr. bayanus EC1118 strain. Samples were collected from 0 to 360 days, and evaluated with respect to the basic physic-chemical characteristics, yeast population, and the concentration of volatile compounds. The results showed that the second fermentation, other than an increment in the alcohol concentration leads to a small increase in volatile acidity, where total acidity decreased during fermentation, and increase again during aging. Yeast population declined rapidly after fermentation, but autolysis initiated just after 9 month of aging. Based on the concentration of volatile compounds, three profiles could be defined: (1 a fermentation profile defined by higher concentrations of acetates and lower concentrations of ethylates and fatty acids; (2 a post-fermentation profile with intermediary concentrations of acetates, and increased concentrations of fatty acids, and their ethyl esters; and (3 a mature profile with higher concentrations of diethyl succinate, fusel alcohols, volatile fatty acids, and their ethyl esters, and lower concentrations of acetates.
Full Text Available Abstract Background Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea. Methods Histologically confirmed breast cancer cases (n = 1,011 and controls (n = 1,011 with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR and 95% confidence interval (95% CI were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration. Results The risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025. The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged Conclusion These findings suggest that older paternal age increases the risk of breast cancer in their female offspring.
Gilbert, J W; Wolpin, B; Clancy, T; Wang, J; Mamon, H; Shinagare, A B; Jagannathan, J; Rosenthal, M
Diagnostic imaging plays a critical role in the initial diagnosis and therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the concept of 'borderline resectable' pancreatic cancer has emerged to describe a distinct subset of patients existing along the spectrum from resectable to locally advanced disease for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship of the primary tumor with surrounding vasculature. This review traces the conceptual evolution of borderline resectability from a radiological perspective, including the debates over the key imaging criteria that define the thresholds between resectable, borderline resectable, and locally advanced or metastatic disease. This review also addresses the data supporting neoadjuvant therapy in this population and discusses current imaging practices before and during treatment. A growing body of evidence suggests that the borderline resectable group of patients may particularly benefit from neoadjuvant therapy to increase the likelihood of an ultimately margin-negative (R0) resection. Unfortunately, anatomic and imaging criteria to define borderline resectability are not yet universally agreed upon, with several classification systems proposed in the literature and considerable variance in institution-by-institution practice. As a result of this lack of consensus, as well as overall small patient numbers and lack of established clinical trials dedicated to borderline resectable patients, accurate evidence-based diagnostic categorization and treatment selection for this subset of patients remains a significant challenge. Clinicians and radiologists alike should be cognizant of evolving imaging criteria for borderline resectability given their profound implications for treatment strategy, follow-up recommendations, and prognosis.
Jehn, C F; Flath, B; Strux, A; Krebs, M; Possinger, K; Pezzutto, A; Lüftner, D
Depression and anxiety are the core disorders causing emotional distress in patients (pts) with metastatic breast cancer. The aim of our study was to screen metastatic breast cancer outpatients for anxiety and depression, and to investigate the influence of age, Karnofsky Performance Status (KPS), cancer activity, and inflammation as represented by IL-6 levels on these two mood disorders. Pts treated with chemotherapy for metastatic breast cancer (n = 70) were assessed using the Hospital Anxiety and Depression Scale (HADS) for symptoms (scores 0-21) and caseness (score ≥11) of clinical depression and anxiety. Blood samples for IL-6 concentrations were collected at 10:00 a.m. A total of 22 (31.4 %) pts were diagnosed with caseness of clinical depression and 23 (32.9 %) pts with clinical anxiety, while 12 pts were diagnosed positive for both mood disorders. Depression and anxiety were positively but moderately correlated (Spearman's r (2) = 0.24, p < 0.001). IL-6 was significantly correlated with symptoms of depression (r (2) = 0.42, p < 0.001) and to a lesser extent to symptoms of anxiety (r (2) = 0.16, p = 0.001). In addition, IL-6 was positively associated with tumor progression (p < 0.001). Multiple linear regression analysis showed that tumor progression (standardized b = 0.226, p = 0.047), symptoms of anxiety (b = 0.292, p = 0.016), and IL-6 (b = 0.314, p = 0.007) were independently associated with clinical depression, whereas anxiety was linked to tumor progression (b = 0.238, p = 0.030), symptoms of depression (b = 0.407, p < 0.001) and age (b = -0.381, p < 0.001), but not to IL-6 (b = 0.168, p = 0.134). Even though a positive correlation between depression and anxiety exists, clinical parameters like age, cancer activity, KPS, and IL-6 do influence depression and anxiety differently. Unlike clinical depression, anxiety is not associated with increased IL-6 levels, however, shows a reciprocal correlation with age.
Zhang, Meiying; Zhuang, Guanglei; Sun, Xiangjun; Shen, Yanying; Wang, Wenjing; Li, Qing; Di, Wen
Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. We attempted to gain insight into the potential contribution of ovarian cancer genomic instability resulted from TP53 mutation to the aberrant expression of multidrug resistance gene MDR1. TP53 mutation status was assessed by performing nucleotide sequencing and immunohistochemistry. Ovarian cancer cell DNA ploidy was determined using Feulgen-stained smears or flow cytometry. DNA copy number was analyzed by performing fluorescence in situ hybridization (FISH). In addition to performing nucleotide sequencing for 5 cases of ovarian cancer, TP53 mutations were analyzed via immunohistochemical staining for P53. Both intensive P53 immunohistochemical staining and complete absence of signal were associated with the occurrence of TP53 mutations. HE staining and the quantification of DNA content indicated a significantly higher proportion of polyploidy and aneuploidy cells in the TP53 mutant group than in the wild-type group (p ovarian cancer patients, multivariate logistic analysis identified late FIGO (International Federation of Gynecology and Obstetrics) stage, serous histotype, G3 grade and TP53 mutation as independent risk factors for ovarian cancer recurrence. In relapse patients, the proportion of chemoresistant cases in the TP53 wild-type group was significantly lower than in the mutant group (63.6% vs. 91.8%, p 6 MDR1 copies and chromosome 7 amplication in the TP53 mutant group than in the wild-type group [11.7 ± 2.3% vs. 3.0 ± 0.7% and 2.1 ± 0.7% vs. 0.3 ± 0.05%, (p ovarian cancer chemoresistance and recurrence. Our findings lay the foundation for the development of promising chemotherapeutic approaches to treat aggressive and recurrent ovarian cancer.
Unlu, Ozan; Kiyak, Dilara; Caka, Canan; Yagmur, Merve; Yavas, Huseyin G; Erdogan, Fadime; Sener, Nazli; Oguz, Bahar; Babacan, Taner; Altundag, Kadri
Although there are studies that investigate different risk factors and clinicopathological features of breast cancer in women at different age groups and menopausal status, there is a need for studies with larger study populations due to controversial findings. We conducted this study to identify demographic parameters in breast cancer patients and histopathological features of the tumors for different age groups and compare them to demonstrate significant differences, if any. 3325 women diagnosed with breast cancer in Hacettepe University Oncology Hospital Outpatient Clinic between January 1994 and March 2014 were included in this study. Postmenopausal women who were older than 65 were found to have higher number of children, higher rates of oral contraceptive use, greater age at menarche, and have higher rates of first full-time pregnancy before the age of 30. On the other hand, higher rates of grade 3 tumors, advanced lymph node stage, lymphovascular invasion, and triple negative breast cancers were more frequently seen in premenopausal women below the age of 35. Since earlier age at the time of diagnosis is associated with bad prognosis, early diagnosis of breast cancer gains importance in younger women. Implementing targeted screening programs of breast cancer for younger women may become a need in the future. Meanwhile, well-education on risks of breast cancer and regular self-examination for early diagnosis need to be emphasized for the prevention of breast cancer and related diseases in young ages.
Sonia Alejandra Pou
Full Text Available Abstract: The world faces an aging population that implies a large number of people affected with chronic diseases. Argentina has reached an advanced stage of demographic transition and presents a comparatively high rate of cancer mortality within Latin America. The objectives of this study were to examine cancer mortality trends in the province of Córdoba, Argentina, between 1986 and 2011, and to analyze the differences attributable to risk variations and demographic changes. Longitudinal series of age-standardized mortality rates for overall, breast and prostate cancers were modeled by Joinpoint regression to estimate the annual percent change. The Bashir & Estève method was used to split crude mortality rate variation into three components: mortality risk, population age structure and population size. A decreasing cancer age-standardized mortality rates trend was observed (1986-2011 annual percent change: -1.4, 95%CI: -1.6, -1.2 in men; -0.8, 95%CI: -1.0, -0.6 in women, with a significant shift in 1996. There were positive crude mortality rate net changes for overall female cancer, breast and prostate cancers, which were primarily attributable to demographic changes. Inversely, overall male cancer crude mortality rate showed a 9.15% decrease, mostly due to mortality risk. Despite favorable age-standardized mortality rates trends, the influence of population aging reinforces the challenge to control cancer in populations with an increasingly aged demographic structure.
Nigrelli, Guido; Lucchesi, Stefania; Bertotto, Stefania; Fioraso, Gianfranco; Chiarle, Marta
In this work, we analyze climate variability and glacier evolution for a study area in the Northwestern Italian Alps from the Little Ice Age (LIA) to the 2010s. In this area, glacier retreat has been almost continuous since the end of the LIA, and many glaciers are now extinct. We compared glaciological and climatic data in order to evaluate the sensitivity of glaciers to temperature and precipitation trends. We found that temperatures show significant warming trends, while precipitation shows no clear signal. After the 1980s, the total number of positive trends in temperature increased, particularly minimum temperature. The latter does not seem to be the only cause of glacier shrinkage but rather on acceleration of an ongoing trend documented since the end of the LIA. In some rare cases, the effects of warming trends on glacier dynamics have been accentuated by a concomitant decrease in precipitation. We hope that this study will contribute to increase the knowledge of the relationships between climate variation and glacier evolution in the Greater Alpine Region.
Manjelievskaia, Janna; Brown, Derek; McGlynn, Katherine A; Anderson, William; Shriver, Craig D; Zhu, Kangmin
Treatment options for patients with young-onset colon cancer remain to be defined and their effects on prognosis are unclear. To investigate receipt of adjuvant chemotherapy by age category (18-49, 50-64, and 65-75 years) and assess whether age differences in chemotherapy matched survival gains among patients diagnosed as having colon cancer in an equal-access health care system. This cohort study was based on linked and consolidated data from the US Department of Defense's Central Cancer Registry and Military Heath System medical claims databases. There were 3143 patients aged 18 to 75 years with histologically confirmed primary colon adenocarcinoma diagnosed between 1998 and 2007. This study was conducted from December 2015 to August 2016. Patients who underwent surgery and postoperative systemic chemotherapy. The primary outcome measure of the study was overall survival of patients who only received surgery and those who received both surgery and postoperative systemic chemotherapy. Of the 3143 patients, 1841 were men (58.6%). Young (18-49 years) and middle-aged (50-64 years) patients were 2 to 8 times more likely to receive postoperative systemic chemotherapy compared with older patients (65-75 years) across all tumor stages. Middle-aged patients with stage I (odds ratio, 5.04; 95% CI, 2.30-11.05) and stage II (odds ratio, 2.42; 95% CI, 1.58-3.72) disease were more likely to receive postoperative chemotherapy compared with older patients. Both groups were more likely to receive multiagent chemotherapy than were older patients (patients aged 18-49 years: odds ratio, 2.48; 95% CI, 1.42-4.32 and patients aged 50-64 years: odds ratio, 2.66; 95% CI, 1.70-4.18). Among patients who received surgery and postoperative systemic chemotherapy, no significant differences were observed in survival among age groups (the 95% CIs of hazard ratios included 1 for young and middle-aged patients compared with older patients for all tumor stages). In an equal-access health care
Rinaldi, Carmela; Malara, Natalia Maria; D’Angelo, Rosalia; Sidoti, Antonina; Leotta, Attilio; Lio, Santo; Caparello, Basilio; Ruggeri, Alessia; Mollace, Vincenzo; Amato, Aldo
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
Avis, Nancy E; Levine, Beverly; Naughton, Michelle J; Case, L Douglas; Naftalis, Elizabeth; Van Zee, Kimberly J
Younger women being treated for breast cancer consistently show greater depression shortly after diagnosis than older women. In this longitudinal study, we examine whether these age differences persist over the first 26 months following diagnosis and identify factors related to change in depressive symptoms. A total of 653 women within 8 months of a first time breast cancer diagnosis completed questionnaires at baseline and three additional timepoints (6, 12, and 18 months after baseline) on contextual/patient characteristics, symptoms, and psychosocial variables. Chart reviews provided cancer and treatment-related data. The primary outcome was depressive symptomatology assessed by the Beck Depression Inventory. Among women younger than age 65, depressive symptoms were highest soon after diagnosis and significantly decreased over time. Depressive symptoms remained stable and low for women aged 65 and older. Age was no longer significantly related to depressive symptoms in multivariable analyses controlling for a wide range of covariates. The primary factors related to levels of and declines in depressive symptomatology were the ability to pay for basics; completing chemotherapy with doxorubicin; and decreases in pain, vasomotor symptoms, illness intrusiveness, and passive coping. Increased sense of meaning/peace and social support were related to decreased depression. Interventions to reduce symptoms and illness intrusiveness, improve a sense of meaning and peace, and increase social support, may help reduce depression and such interventions may be especially relevant for younger women.
Van Pottelbergh, Gijs; Bartholomeeusen, Stephaan; Buntinx, Frank; Degryse, Jan
The prevalence of chronic kidney disease (CKD) is high, especially among older patients. In order to identify risk factors for the evolution towards end-stage renal disease (ESRD), a cohort of patients ≥ 50 years of age for whom at least four serum creatinine measurements were available were selected from a primary care-based database. The slope of changes in estimated glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease formula) was calculated, and ESRD was defined as eGFR HR = 0.47 or 0.41 for patients 65-79 years and HR = 0.26 or 0.32 for patients ≥ 80 years compared with patients aged 50-64 years). Females (HR = 1.48) and patients with diabetes (HR = 1.20), hypertension (HR = 1.25), high total cholesterol (HR = 1.28) or high low-density lipoprotein (LDL) cholesterol (HR = 1.39) were at higher risk for ESRD. Baseline eGFR, diabetes, high cholesterol, high LDL, hypertension and female gender are independent risk factors for developing ESRD. Older age at baseline predicts a lower risk.
G. P. Stiller
Full Text Available An extensive observational data set, consisting of more than 106 SF6 vertical profiles from MIPAS measurements distributed over the whole globe has been condensed into monthly zonal means of mean age of air for the period September 2002 to January 2010, binned at 10° latitude and 1–2 km altitude. The data were analysed with respect to their temporal variation by fitting a regression model consisting of a constant and a linear increase term, 2 proxies for the QBO variation, sinusoidal terms for the seasonal and semi-annual variation and overtones for the correction of the shapes to the observed data set. The impact of subsidence of mesospheric SF6-depleted air and in-mixing into non-polar latitudes on mid-latitudinal absolute age of air and its linear increase was assessed and found to be small.
The linear increase of mean age of stratospheric air was found to be positive and partly larger than the trend derived by Engel et al. (2009 for most of the Northern mid-latitudes, the middle stratosphere in the tropics, and parts of the Southern mid-latitudes, as well as for the Southern polar upper stratosphere. Multi-year decrease of age of air was found for the lowermost and the upper stratospheric tropics, for parts of Southern mid-latitudes, and for the Northern polar regions. Analysis of the amplitudes and phases of the seasonal variation shed light on the coupling of stratospheric regions to each other. In particular, the Northern mid-latitude stratosphere is well coupled to the tropics, while the Northern lowermost mid-latitudinal stratosphere is decoupled, confirming the separation of the shallow branch of the Brewer-Dobson circulation from the deep branch. We suggest an overall increased tropical upwelling, together with weakening of mixing barriers, especially in the Northern Hemisphere, as a hypothetical model to explain the observed pattern of linear multi-year increase/decrease, and amplitudes
Polyak, Victor; Hill, Carol; Asmerom, Yemane
The age and evolution of the Grand Canyon have been subjects of great interest and debate since its discovery. We found that cave mammillaries (water table indicator speleothems) from nine sites in the Grand Canyon showed uranium-lead dating evidence for an old western Grand Canyon on the assumption that groundwater table decline rates are equivalent to incision rates. Samples in the western Grand Canyon yielded apparent water table decline rates of 55 to 123 meters per million years over the past 17 million years, in contrast to eastern Grand Canyon samples that yielded much faster rates (166 to 411 meters per million years). Chronology and inferred incision data indicate that the Grand Canyon evolved via headward erosion from west to east, together with late-stage ( approximately 3.7 million years ago) accelerated incision in the eastern block.
Myers, Elizabeth A; Feingold, Daniel L; Forde, Kenneth A; Arnell, Tracey; Jang, Joon Ho; Whelan, Richard L
AIM: To investigate the epidemiological characteristics of colorectal cancer (CRC) in patients under 50 years of age across two institutions. METHODS: Records of patients under age 50 years of age who had CRC surgery over a 16 year period were assessed at two institutions. The following documents where reviewed: admission notes, operative notes, and discharge summaries. The main study variables included: age, presenting symptoms, family history, tumor location, operation, stage/differentiation of disease, and post operative complications. Stage of disease was classified according to the American Joint Committee on Cancer TNM staging system: tumor depth; node status; and metastases. RESULTS: CRC was found in 180 patients under age 50 years (87 females, 93 males; mean age 41.4 ± 6.2 years). Young patients accounted for 11.2% of cases during a 6 year period for which the full data set was available. Eight percent had a 1st degree and 12% a 2nd degree family CRC history. Almost all patients (94%) were symptomatic at diagnosis; common symptoms included: bleeding (59%), obstruction (9%), and abdominal/rectal pain (35%). Evaluation was often delayed and bleeding frequently attributed to hemorrhoids. Advanced stage CRC (Stage 3 or 4) was noted in 53% of patients. Most tumors were distal to the splenic flexure (77%) and 39% involved the rectum. Most patients (95%) had segmental resections; 6 patients had subtotal/total colectomy. Poorly differentiated tumors were noted in 12% and mucinous lesions in 19% of patients of which most had Stage 3 or 4 disease. Twenty-two patients (13%) developed recurrence and/or progression of disease to date. Three patients (ages 42, 42 and 49 years) went on to develop metachronous primary colon cancers within 3 to 4 years of their initial resection. CONCLUSION: CRC was common in young patients with no family history. Young patients with symptoms merit a timely evaluation to avoid presentation with late stage CRC. PMID:24039357
Geary, David C
Traits that facilitate competition for reproductive resources or that influence mate choice generally have a heightened sensitivity to stressors. They have evolved to signal resilience to infectious disease and nutritional and social stressors, and they are compromised by exposure to man-made toxins. Although these traits can differ from one species or sex to the next, an understanding of the dynamics of competition and choice can in theory be used to generate a priori predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species. I provide a review of these dynamics and illustrate associated vulnerabilities in nonhuman species. The age- and sex-specific vulnerability of such traits is then illustrated for stressor-related disruptions of boys' and girls' physical growth and play behavior, as well as for aspects of boys' and girls' and men's and women's personality, language, and spatial abilities. There is much that remains to be determined, but enough is now known to reframe trait sensitivity in ways that will allow scientists and practitioners to better identify and understand vulnerable human traits, and eventually ameliorate or prevent their expression. © The Author(s) 2016.
Diouf, Ibrahima; Charles, Marie Aline; Ducimetière, Pierre; Basdevant, Arnaud; Eschwege, Evelyne; Heude, Barbara
Background A rapid increase in the prevalence of obesity has been reported in France since 1990. We investigated the impact of birth cohort on the changes in obesity prevalence after taking into account age and survey period. Methods We analyzed data from four national surveys in 1997, 2000, 2003 and 2006. For each survey, self-reported data on weight and height were recorded on mailed questionnaires sent to a sample of 20 000 households, representative of the French population. Obesity was defined according to WHO criteria, BMI ≥ 30 kg/m2. We modeled the prevalence of obesity using logistic regression with age, cohort and period as explanatory variables. As these variables are linearly dependent, only nonlinear effects can be estimated uniquely and interpreted, after including specific chosen constraints in the models. Results There was a progressive increase in the prevalence of obesity between 1997 and 2006, attributable either to a period or to a cohort effect. There was a substantial departure from a linear trend for the cohort effect only, which appeared to be stronger in women: there was an acceleration in the prevalence of obesity with birth cohort for individuals born after the mid-1960s, in both sexes. Conclusions Our results are consistent with previous studies in other countries. Compared with older generations, men and women born in the late 1960s may have been subject to early exposures that increased their lifelong susceptibility to obesity. PMID:20375843
Bruce N. Ames
Full Text Available 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.
Hannum, Susan M; Clegg Smith, Katherine; Coa, Kisha; Klassen, Ann C
This article evaluates how older cancer patients describe cancer survivorship and incorporate the cancer experience into long-term evaluations of health. From a series of 53 qualitative interviews with adults with histories of breast and prostate cancers and non-Hodgkin's lymphoma, we analyzed age-related discussions among those 65 and older (n = 21). Emergent themes revealed the: (1) historical conceptualization of cancer, (2) changed perspective following diagnosis, (3) cancer in the context of a long biography, (4) cancer in the context of the aging body and decline, and (5) meaning of time remaining and quality of life. One important suggestion from our work, relevant to all clinicians regardless of specialty or role, is to incorporate goals for the future into individualized survivor care plans for older survivors.
Silva, Susana N; Moita, Rita; Azevedo, Ana Paula; Gouveia, Rita; Manita, Isabel; Pina, Julieta Esperança; Rueff, José; Gaspar, Jorge
Recent evidence that some DNA-repair functions are haploinsufficient adds weight to the notion that variants in DNA-repair genes constitute part of the spectrum of defects contributing to cancer risk. X-ray repair cross-complementing group 1 gene (XRCC1) is involved in base excision repair (BER) pathway, acting on spontaneous and induced DNA damage. This gene encodes for a scaffolding protein that brings together different proteins involved in the repair process. Among the non-synonymous polymorphisms in XRCC1 gene, codons 194 and 399 lead to amino acid changes at evolutionary conserved regions, and seem to alter the efficiency of the protein. A hospital based case-control study was carried out in a Caucasian Portuguese population (241 cancer patients and 457 controls matched for sex and age) in order to evaluate the potential modifying role of the XRCC1 polymorphisms on the individual susceptibility to breast cancer. Our data did not reveal a positive association between the polymorphisms individually and breast cancer, or with the combination of the different genotypic associations. However, after stratification to the menopausal status, it was observed that carriers of the Gln/Gln genotype of the R399Q polymorphism with a menopausal age above 55 years are at increased risk for breast cancer (OR=4.074; CI=1.562-10.626; P=0.004). Concerning the Arg194Trp polymorphism, after stratification by menopausal status, it was observed that heterozygous individuals (Arg/Trp) with a menopausal age between 45 and 54 are at increased risk for breast cancer (adjusted OR=1.964; CI=1.174-3.288; P=0.01) as well as carriers of the variant allele (Arg/Trp+Trp/Trp) (adjusted OR=1.932; CI=1.156-3.228; P=0.012). Our results suggest that menopausal age together with Arg194Trp and Arg399Gln XRCC1 gene polymorphisms might be involved in individual susceptibility to breast cancer.
Puig-Vives, Montse; Osca-Gelis, Gemma; Camprubí-Font, Carla; Vilardell, M Loreto; Izquierdo, Angel; Marcos-Gragera, Rafael
The aim of this study was to determine the tumor stage, the proportion of cases and the age specific rate of breast cancer (BC) cases according to detection method. Cases of women aged 50 to 69 years diagnosed with BC in the Girona province during 1999-2006 were extracted from the population-based Girona Cancer Registry (n=1,254). BC was classified by detection method: screen-detected cancer, interval cancer and others. Proportion of cases and age-specific incidence were calculated according to detection method. During the period 2002-2006, the proportion of screen-detected cancers, interval cancers and other cancers were 42.2%, 5.8% and 52.2%, respectively. After implementation of the early detection of breast cancer program (PDPCM), the incidence of screen-detected cases raised; thereafter, interval cancers also increased and the rate of other cancers decreased. In the Girona province during the fully implemented PDPCM period (2002-2006), interval cancers represented a low proportion (5.8%) of women diagnosed with BC at 50 to 69 years old. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
Cancer in adolescence raises unique challenges for all involved. In healthy populations, the transition from childhood to adulthood is seen as a normal phase of the human life course focused primarily on the process of identity formation. For young people diagnosed with cancer, there are specific, negative impacts to consider. In this paper, the impact on intimacy, body image, and sexuality are discussed and the need for innovative supportive solutions highlighted. Based on a presentation given at the ISSM conference in Washington, DC, the paper describes the challenges in providing effective supportive care in relation to sexuality in young people surviving cancer. Discussion of key issues involved when developing psychosexual interventions for this age group. A scan of available evidence was combined with examples of recent service and research developments. The limited amount of available research belies the complexity of providing effective supportive care in relation to sexuality for young people both during and after cancer. As the number of long-term survivors of cancer during childhood and adolescence increases, there will be increasing demand for attention to be paid to the supportive care needs of this population; including issues of relationships and sexuality. Two examples of novel interventions are presented. Services provided for cancer survivors must consider the unique challenges facing different age groups. For young people diagnosed during adolescence and young adulthood there is a need to enhance the evidence base, and to apply this evidence in practice contexts. Locating the need for further developments within a Complex Intervention Framework may assist in the development of interventions that can be developed and tested in a logical, step-wise fashion. © 2013 International Society for Sexual Medicine.
Olsson, Mariann; Nilsson, Marie; Fugl-Meyer, Kerstin; Petersson, Lena-Marie; Wennman-Larsen, Agneta; Kjeldgård, Linnea; Alexanderson, Kristina
To explore, among women of working age, satisfaction with life as a whole and with different life domains, and its associations with social and health variables, shortly after breast cancer surgery. This cross-sectional study included 605 women, aged 20-63 years, who had had breast cancer surgery with no distant metastasis, pre-surgical chemotherapy, or previous breast cancer. Associations between LiSat-11 and demographic and social factors as well as health- and treatment-related variables were analysed by multivariable logistic regression. Compared with Swedish reference levels, the women were, after breast cancer surgery, less satisfied with life, particularly sexual life. Women working shortly after breast cancer surgery were more often satisfied with life in provision domains compared with the reference population. Although most included variables showed associations with satisfaction, after adjustment for all significantly associated variables, only six variables-having children, being in work, having emotional and informational social support, and having good physical and emotional functioning-were positively associated with satisfaction with life as a whole. The odds ratios for satisfaction were higher in most life domains if the woman had social support and good emotional and cognitive functioning. One month after breast cancer surgery, satisfaction with different life domains was associated primarily with social support and health-related functioning. However, this soon after surgery, treatment-related variables showed no significant associations with life satisfaction. These results are useful for planning interventions to enhance e.g. social support and emotional as well as cognitive functioning.
Kerri M. Winters-Stone
Full Text Available Currently there are more than 13.7 million cancer survivors living in the U.S., and that figure is projected to increase by 31% in the next decade, adding another 4 million cancer survivors into the healthcare system. Cancer is largely a disease of aging, and the aging of the population will sharply raise the proportion of older cancer survivors, many of whom will be long-term survivors (5+ years post diagnosis. This review will address the potential utility of exercise to address three health problems that are of particular concern for the aging cancer survivor and the healthcare system, i.e., disability, falls, and cardiovascular disease, because the development of these age-related problems may be accelerated by cancer treatment. While there are many different modes of exercise that each produce specific adaptations, Tai Ji Quan may be a particularly suitable strategy to mitigate the development of age- and cancer-treatment-related problems. Based on studies in older adults without cancer, Tai Ji Quan produces musculoskeletal and cardiometabolic adaptations and is more easily performed by older adults due to its low energy cost and slower movement patterns. Since cancer survivors are mostly older, inactive, and often physically limited by the lingering side effects of treatment, they need to engage in safe, practical, and effective modes of exercise. The dearth of published controlled trials examining the efficacy of Tai Ji Quan to mitigate cancer-treatment-related musculoskeletal and cardiovascular side effects points to ample research opportunities to explore the application of this non-Western exercise modality to improve long-term outcomes for aging cancer survivors.
Bellavita, Rita; Scricciolo, Melissa; Bini, Vittorio; Arcidiacono, Fabio; Montesi, Giampaolo; Lancellotta, Valentina; Zucchetti, Claudio; Lupattelli, Marco; Palumbo, Isabella; Aristei, Cynthia
To demonstrate that radiotherapy (RT) is a valid alternative to surgery in men ≤70 years old with localized prostate cancer. From 1988 to 2009, 214 patients with T1-2 N0 M0 prostate cancer were treated with RT. The effects of patient- and treatment-related risk factors on toxicity were investigated. Median follow-up was 105 months (range 14.2-180). The 5-, 10-, and 15-year biochemical relapse-free survival for all 214 patients was 80%, 61.9%, and 57.5%, respectively. In bivariate analysis, age (≤65 vs 65-70 years) was not a significant factor for biochemical relapse, while radiation dose was (p = 0.05) in multivariate analysis. Cancer-specific survival rates at 5, 10, and 15 years were 98.4%, 93.2%, and 69.7%, respectively. Median overall survival (OS) was 167 months (95% confidence interval 147.3-186.7). The OS rates at 5, 10, and 15 years were 91.8%, 75.8%, and 42.5%, respectively. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 105 (49%) and 98 patients (45.8%), respectively, with only 2 cases of grade III GI toxicity. Late GU and GI toxicities occurred in 17 (7.9%) and 20 (9.3%) patients, respectively, with 1 grade III GI toxicity and 2 grade III GU toxicities. Risk factors for late toxicity were age and RT dose and technique, which were unrelated to acute toxicity. Age ≤70 years does not consistently confer a negative prognosis for localized prostate cancer. Radiotherapy appears to be a viable alternative to surgery, offering excellent long-term cancer control.
Chan, Sarah; Harris, John
Animals, in the age of biotechnology, are the subjects of a myriad of scientific procedures, interventions, and modifications. They are created, altered, and experimented upon--often with highly beneficial outcomes for humans in terms of knowledge gained and applied, yet not without concern also for the effects upon the experimental subjects themselves: consideration of the use of animals in research remains an intensely debated topic. Concerns for animal welfare in scientific research have, however, been primarily directed at harm to and suffering of animal subjects and their prevention. Little attention has been paid to the benefits research might potentially produce for animals themselves and the interests that some animals may therefore have in the furtherance of particular avenues of science.
da Silva Ferreira, Antonio Cesar; Barbe, Jean-Christophe; Bertrand, Alain
In Port wine, isomers of glycerol and acetaldehyde acetals have been found at total contents ranging from 9.4 to 175.3 mg/L. During oxidative aging, the concentrations of the 5-hydroxy-2-methyl-1,3-dioxane and 4-hydroxymethyl-2-methyl-1,3-dioxolane isomers increased with time showing a linear correlation (r > 0.95). The flavor threshold for the mixture of the four isomers was evaluated in wine at 100 mg/L. Thus, it is expected that they contribute to "old Port wine" aroma in wines older than 30 years. Experiments with model solutions and wine clearly demonstrated that SO(2) combines with acetaldehyde and blocks the acetalization reaction.
Full Text Available Introduction: In an average Polish person aged 35–44, more than 16 teeth have or had been affected by dental caries. Of that number, almost half of the teeth have already been extracted. Oral health behaviours contribute to this civilization disease in 50%. Such poor oral health status limits the ability of the affected people to take many social and professional roles. Objectives: To evaluate current oral health behaviours and their trends among 35–44 year old Polish people during the period of recent 30 years. Material and Methods: The data were obtained from the International Collaborative Studies conducted in 1978 and 1988 at the Nofer Institute of Occupational Medicine, Łódź, Poland, under the auspices of the World Health Organization (WHO as well as from 3 stages of the study on Nationwide Monitoring of Oral Health Status and Its Conditioning performed in 1998, 2002 and 2010. The researchers evaluated oral health behaviours and oral health condition of 5425 subjects. Results: Despite a noticeable improvement, poor oral health behaviours are observed in 30%–40% of the adults. In the analysed period, the number of people brushing their teeth at least twice a day increased by more than 10% and the number of people using dental floss increased by 38%. Only 60% of the adults visited a dentist at least once a year. Reduced accessibility of state-run, free-of-charge dental care has caused that over 58% of Poles paid for their dental services. Every 3rd person of working age has not visited a dentist for longer than 2.5 half years, primarily due to behavioural and financial reasons. Oral health behaviours of Polish people are among the poorest in Europe. Conclusions: Despite a noticeable improvement of the behaviours, gap between the Poles and citizens of other highly developed countries is around 20 years. A health promotion programme including oral health issues, if implemented in workplaces, might considerably reduce this gap.
Godtman, Rebecka Arnsrud; Carlsson, Sigrid; Holmberg, Erik; Stranne, Johan; Hugosson, Jonas
We investigated the effect of age and number of screens on the risk of prostate cancer diagnosis. Since 1995 the Göteborg randomized population based prostate cancer screening trial has invited men biennially for prostate specific antigen testing, until the upper age limit of 70 years. Men with a prostate specific antigen above the threshold of 2.5 ng/ml were recommended further evaluation including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born between 1930 and 1943 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3 to 9 invitations). The cumulative incidence of prostate cancer was calculated using standard methods. Of the 3,488 (38%) complete attendees 667 were diagnosed with prostate cancer (followup 1995 to June 30, 2014). At age 70 years there was no significant difference in prostate cancer risk among those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of prostate cancer diagnosis increased dramatically with age, and was 7.9% at age 60, 15% at age 65 and 21% at age 70 for men who had been screened 4 or more times. There was no clear association between risk of prostate cancer and the number of screens. Starting screening at an early age appears to advance the time of prostate cancer diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with prostate cancer. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Full Text Available Introduction: gastric cancer (GC is the fourth leading cause of cancer death in Spain after lung, colorectal, breast and prostate tumours. Surgery remains the only potentially curative treatment in localized gastric cancer. Objective: the aim of our study is to evaluate and compare the clinical and surgical aspects, development of postoperative complications and outcomes of patients over 75 years old compared with younger patients in our centre. Material and methods: comparative retrospective study, from March 2003 to June 2011. We diagnosed 166 cases of GC, 109 (65 % underwent curative surgery. Two groups were settled: group M: ≥ 75 years (41 patients and group m: < 75 years (68 patients. We analyzed age, sex, comorbidities, tumour location, clinical stage, perioperative chemotherapy, surgical technique, postoperative complications, recurrence and mortality from cancer. Results: a more frequent presence of cardiovascular comorbidities and a greater postoperative mortality by medical causes were the only significant differences between both groups. Also, a lower proportion of patients in group M received preoperative chemotherapy and underwent D1 lymphadenectomy. However, the rate of local and systemic recurrence and overall survival were similar in both groups. Conclusions: age should not be considered a contraindication for curative surgery on GC. The general condition and comorbidities are more important to contraindicate surgical treatment.
Lewis, F M; Zahlis, E H; Shands, M E; Sinsheimer, J A; Hammond, M A
Although there are significant numbers of single women with breast cancer who are rearing children, there is no known study of their own or their school-aged children's adjustment to the illness. The purposes of this study are: 1) to describe the adjustment of single women to early stage breast cancer; 2) to contrast their responses to a comparable sample of married/partnered women; 3) and to document the psychosocial functioning of school-aged children when their single mother has breast cancer. Results obtained from questionnaire data from 22 single and 101 married/partnered women revealed that single women had significantly higher rates of depression; reported significantly higher numbers of illness-related pressures on their family; had a significantly higher proportion of young children scoring in the abnormal range on measures of self-worth and social acceptance; and reported lower quality in parenting their children. Interviews with single women revealed that many were burdened by feelings of self-deprecation because of their breast cancer, and many felt alone with the disease through the initial diagnosis period, during treatments, and through recovery. Evidence from this pilot study suggests that single women need early and immediate linkage into an informational and educational network and a viable adult support network.
Lee, Eunice E.; Eun, Young; Lee, Shin-Young; Nandy, Karabi
Cervical cancer screening rates among older Korean American (KA) women are much lower than the rates for younger KA women, even though the overall cancer screening rates in the population continue to have one of the lowest Papanicolaou (Pap) test adherence rates compared with non-Hispanic White women. Variables based on the Health Belief Model related to cervical cancer screening were compared by age group among KA women. A telephone survey was conducted with 189 KA women living in the midwestern United States. Perceived barriers to having a Pap test predicted the outcome variable of having had Pap tests in the preceding 3 years in older KA women who were 65 or older, but not in younger women who were between 40 and 64 years old. Having physical examinations without symptoms in the preceding 2 years predicted the outcome variable in both age groups. Intervention strategies for all KA women should focus on encouraging them to receive routine physical examinations. In addition, attempts should be made to reduce perception of barriers in older KA women to improve their cervical cancer screening behaviors. PMID:22477716
Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith
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.
Maynard, Scott; Schurman, Shepherd H; Harboe, Charlotte
Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack DNA...... recently, BER was shown to also exist in the mitochondria. Here, we review the association of BER of oxidative DNA damage with aging, cancer and other diseases....... readily, generating a variety of DNA lesions, such as oxidized bases and strand breaks. If not properly removed, DNA damage can be potentially devastating to normal cell physiology, leading to mutagenesis and/or cell death, especially in the case of cytotoxic lesions that block the progression of DNA...
Full Text Available The generally accepted mechanism of metformin’s effect is stimulation of adenosine monophosphate (AMP-activated protein kinase (AMPK. AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin’s beneficial effects. It may help to identify new targets for treatment of diabetes and metabolic syndrome. Moreover, metformin is now attracting the attention of researchers in fields other than diabetes, as it has been shown to have anti-cancer, immunoregulatory and anti-aging effects. The aim of this review is to describe the potential anti-cancer and anti-aging properties of metformin and discuss the possible underlying mechanisms.
Stahlman, Shauna; Oetting, Alexis
In the U.S. general population, incidence of colorectal cancer appears to be increasing in younger age groups since the mid-1980s. The objective of this report was to better understand the time-varying elements (age, period, and birth cohort effects) in the epidemiology of colorectal cancer among the active component of the U.S. Armed Forces. During 1997-2016, there were 1,108 incident cases of colorectal cancer among service members aged 20-59 years, corresponding to an overall incidence rate of 4.3 per 100,000 person-years (p-yrs). Rates were particularly high among men (4.4 per 100,000 p-yrs) and non- Hispanic black service members (5.3 per 100,000 p-yrs). Overall crude incidence of colorectal cancer increased in an exponential fashion with increasing age groups until the oldest age group (55-59 years), in which the increase was attenuated. No birth cohort or period effects were identified in the age-period-cohort analysis. This finding could be due to limited power, selection bias, better screening practices in the Military Health System (MHS) compared with the general population, or true lack of effects. Continued population-based screening for colorectal cancer in the MHS is recommended to maintain low and decreasing incidence in the U.S. Armed Forces.
Baburin, Aleksei; Aareleid, Tiiu; Padrik, Peeter; Valvere, Vahur; Innos, Kaire
Survival from breast cancer (BC) in Estonia has been consistently among the lowest in Europe. The aim of this study was to examine most recent trends in BC survival in Estonia by age and stage. The trends in overall BC incidence and mortality are also shown in the paper. Estonian Cancer Registry data on all cases of BC, diagnosed in women in Estonia during 1995-2007 (n = 7424) and followed up for vital status through 2009, were used to estimate relative survival ratios (RSR). Period hybrid approach was used to obtain the most recent estimates (2005-2009). Stage was classified as localized, local/regional spread or distant. BC incidence continued to rise throughout the study period, but mortality has been in steady decline since 2000. The distribution of patients shifted towards older age and earlier stage at diagnosis. Overall age-standardized five-year RSR increased from 63% in 1995-1999 to 74% in 2005-2009. Younger age groups experienced a more rapid improvement compared to women over 60. Significant survival increase was observed for both localized and locally/regionally spread BC with five-year RSRs reaching 96% and 70% in 2005-2009, respectively; the latest five-year RSR for distant BC was 11%. Survival for T4 tumors was poor and large age difference was seen for locally/regionally spread BC. Considerable improvement in BC survival was observed over the study period. Women under 60 benefited most from both earlier diagnosis and treatment advances of locally/regionally spread cancers. However, the survival gap with more developed countries persists. Further increase in survival, but also decline in BC mortality in Estonia could be achieved by facilitating early diagnosis in all age groups, but particularly among women over 60. Investigations should continue to clarify the underlying mechanisms of the stage-specific survival deficit in Estonia.
Li, Yi; Tiwari, Ram C; Zou, Zhaohui
The annual percent change (APC) has been used as a measure to describe the trend in the age-adjusted cancer incidence or mortality rate over relatively short time intervals. The yearly data on these age-adjusted rates are available from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The traditional methods to estimate the APC is to fit a linear regression of logarithm of age-adjusted rates on time using the least squares method or the weighted least squares method, and use the estimate of the slope parameter to define the APC as the percent change in the rates between two consecutive years. For comparing the APC for two regions, one uses a t-test which assumes that the two datasets on the logarithm of the age-adjusted rates are independent and normally distributed with a common variance. Two modifications of this test, when there is an overlap between the two regions or between the time intervals for the two datasets have been recently developed. The first modification relaxes the assumption of the independence of the two datasets but still assumes the common variance. The second modification relaxes the assumption of the common variance also, but assumes that the variances of the age-adjusted rates are obtained using Poisson distributions for the mortality or incidence counts. In this paper, a unified approach to the problem of estimating the APC is undertaken by modeling the counts to follow an age-stratified Poisson regression model, and by deriving a corrected Z -test for testing the equality of two APCs. A simulation study is carried out to assess the performance of the test and an application of the test to compare the trends, for a selected number of cancer sites, for two overlapping regions and with varied degree of overlapping time intervals is presented. (c) 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Al Zaabi, Muna; Al Muqbali, Shaikha; Al Sayadi, Thekra; Al Ameeri, Suhaila; Coetsee, Karin; Balayah, Zuhur; Ortashi, Osman
Cervical cancer is the second most common cancer in women worldwide, with about 500,000 new cases and 270,000 deaths each year. Globally, it is estimated that over one million women currently have cervical cancer, most of whom have not been diagnosed, or have no access to treatment that could cure them or prolong their lives. In the United Arab Emirates (UAE) cervical cancer is the third most common cancer in women. A population-based cross-sectional retrospective survey of cervical smear abnormalities was conducted in the Emirate of Abu Dhabi, UAE, from January 2013 to December 2013 by collecting consecutive liquid-based cytology samples from the Department of Pathology at the SKMC Hospital in Abu Dhabi city. The total number of women screened for cervical cancer for the year 2013 at SKMC was 4,593, with 225 (4.89%) abnormal smears. The majority of the abnormal smear results were atypical squamous cells of undetermined significance (ASCUS) 114 (2.48%). This study showed 60% increase in the rate of abnormal cervical smears in the UAE over the last 10 years. In this study the highest incidence of high grade abnormalities were seen in women above the age of 61 years (1.73%), this might be due to the fact that this group of women missed the chance of screening of cervical cancer earlier in their lives or could be explained by the well-known second peak of HPV infection seen in many prevalence studies. We conclude that the rate of abnormal cervical smear in the screened Abu Dhabi women is not different from the rate in developed countries. A notable increase in both low and high grade abnormalities has occurred within the last decade.
Beeken, Rebecca J; Wilson, Rose; McDonald, Laura; Wardle, Jane
Obesity is associated with an increased cancer incidence and mortality and therefore cancer screening is particularly important for obese individuals. However, some US studies find lower screening uptake in this group. This study explored whether rates of breast and colorectal screening in England are lower for obese than healthy weight individuals. Data were from the English Longitudinal Study of Ageing (ELSA). We analysed data from adults who were eligible to have been invited to the UK national screening programmes for breast or colorectal cancer (CRC) in the last five years, and had been given the screening module in Wave 5 of ELSA (N = 1804 for CRC screening, N = 2401 for breast cancer screening). Weight and height were measured by a nurse at Wave 4 (two years earlier). Logistic regression was used to calculate the odds of breast and CRC screening (ever) for participants in higher weight categories (Body Mass Index [BMI] ≥ 25) compared with healthy weight individuals (BMI <25), controlling for socio-demographic variables. Of ELSA participants, 63% reported CRC screening, and 92% of the women reported breast cancer screening. Obesity was associated with lower CRC screening, but effects were strongest for class III obesity (BMI ≥40) (45% screened; OR = 0.48, 95% CI = 0.32-0.93, P = .029). There was no association between weight status and breast cancer screening. Severe obesity appears to be a deterrent to CRC screening but not breast cancer screening. Targeted interventions may be required to promote CRC screening uptake in this group, which already has a heightened risk as a consequence of weight. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Inhibition of delta133p53 may be a novel approach for cell senescence-mediated anti-proliferative therapy, including anti-cancer treatments. In addition, enhanced expression of delta 133p53 can extend the replicative lifespan of normal human cells. Therefore, this technology may provide a new method in the field of regenerative medicine for aging-related degenerative disease as well as cancer therapeutics. The National Cancer Institute seeks parties to co-develop or license a new method for inhibiting aging-related degenerative disease and cancer.
Meza, Rafael; Jeon, Jihyoun; Moolgavkar, Suresh H.; Luebeck, E. Georg
The observation that the age-specific incidence curve of many carcinomas is approximately linear on a double logarithmic plot has led to much speculation regarding the number and nature of the critical events involved in carcinogenesis. By a consideration of colorectal and pancreatic cancers in the Surveillance Epidemiology and End Results (SEER) registry we show that the log-log model provides a poor description of the data, and that a much better description is provided by a multistage mode...
Full Text Available Purpose: To determine the impact of age and gender on the clinicopathological characteristics of histologically confirmed bladder cancer in India. Materials and Methods: From January 2001 to June 2008, records of patients with bladder cancer were evaluated for age and gender at presentation, clinical symptoms, cystoscopic finding, history of smoking, and histopathological characteristics. A total of 561 patients were identified from the computer-based hospital information system and the case files of patients. Results: A total of 97% of the patients presented with painless hematuria. The mean age was 60.2 ± 4.4 years old (range: 18-90 years old and the male to female ratio was 8.6:1. Transitional cell carcinoma (TCC was the most common histological variety, which was present in 97.71% (470 of 481 of the patients. A total of 26% of the patients had muscle invasive disease at the time of presentation. However, 34.5% (166 of 481 of the patients did not show any evidence of detrusor muscle in their biopsy specimen. In patients with nonmuscle-invasive bladder carcinoma, 55% had p Ta while 45% had p T1. Overall, 44.7% (215 of 481 of the patients had low-grade disease. Among patients younger than 60 years old, low-grade (51.0% vs. 38.1%; P = 0.006 and low-stage (77.1% vs. 70.8%; P = 0.119 disease were more prevalent than in patients older than 60 years old. The incidence of smoking was much higher among males compared with females (74% vs. 22%. Conclusion: TCC is the predominant cancer, with significant male preponderance among Indian patients. Younger-aged patients have low-grade disease. Hematuria is the most common presentation and greater awareness is needed not to overlook bladder cancer.
Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan
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.
Full Text Available Abstract Background U.S. cancer screening guidelines communicate important information regarding the ages for which screening tests are appropriate. Little attention has been given to whether breast, colorectal and prostate cancer screening test use is responsive to guideline age information regarding the age of screening initiation. Methods The 2006 Behavioral Risk Factor Social Survey and the 2003 National Health Interview Surveys were used to compute breast, colorectal and prostate cancer screening test rates by single year of age. Graphical and logistic regression analyses were used to compare screening rates for individuals close to and on either side of the guideline recommended screening initiation ages. Results We identified large discrete shifts in the use of screening tests precisely at the ages where guidelines recommend that screening begin. Mammography screening in the last year increased from 22% [95% CI = 20, 25] at age 39 to 36% [95% CI = 33, 39] at age 40 and 47% [95% CI = 44, 51] at age 41. Adherence to the colorectal cancer screening guidelines within the last year increased from 18% [95% CI = 15, 22] at age 49 to 19% [95% CI = 15, 23] at age 50 and 34% [95% CI = 28, 39] at age 51. Prostate specific antigen screening in the last year increased from 28% [95% CI = 25, 31] at age 49 to 33% [95% CI = 29, 36] and 42% [95% CI = 38, 46] at ages 50 and 51. These results are robust to multivariate analyses that adjust for age, sex, income, education, marital status and health insurance status. Conclusion The results from this study suggest that cancer screening test utilization is consistent with guideline age information regarding the age of screening initiation. Screening test and adherence rates increased by approximately 100% at the breast and colorectal cancer guideline recommended ages compared to only a 50% increase in the screening test rate for prostate cancer screening. Since information regarding the age of cancer screening
Scerri, Eleanor M L
The North African Middle Stone Age (NAMSA, ∼300-24 thousand years ago, or ka) features what may be the oldest fossils of our species as well as extremely early examples of technological regionalization and 'symbolic' material culture (d'Errico, Vanhaeren, Barton, Bouzouggar, Mienis, Richter, Hublin, McPherron, Louzouet, & Klein, ; Scerri, ; Richter, Grün, Joannes-Boyau, Steele, Amani, Rué, Fernandes, Raynal, Geraads, Ben-Ncer Hublin, McPherron, ). The geographic situation of North Africa and an increased understanding of the wet-dry climatic pulses of the Sahara Desert also show that North Africa played a strategic role in continental-scale evolutionary processes by modulating human dispersal and demographic structure (Drake, Blench, Armitage, Bristow, & White, ; Blome, Cohen, Tryon, Brooks, & Russell, ). However, current understanding of the NAMSA remains patchy and subject to a bewildering array of industrial nomenclatures that mask underlying variability. These issues are compounded by a geographic research bias skewed toward non-desert regions. As a result, it has been difficult to test long-established narratives of behavioral and evolutionary change in North Africa and to resolve debates on their wider significance. In order to evaluate existing data and identify future research directions, this paper provides a critical overview of the component elements of the NAMSA and shows that the timing of many key behaviors has close parallels with others in sub-Saharan Africa and Southwest Asia. © 2017 Wiley Periodicals, Inc.
Müller, Patrick; Rehfeld, Kathrin; Schmicker, Marlen; Hökelmann, Anita; Dordevic, Milos; Lessmann, Volkmar; Brigadski, Tanja; Kaufmann, Jörn; Müller, Notger G
From animal research, it is known that combining physical activity with sensory enrichment has stronger and longer-lasting effects on the brain than either treatment alone. For humans dancing has been suggested to be analogous to such combined training. Here we assessed whether a newly designed dance training program that stresses the constant learning of new movement patterns is superior in terms of neuroplasticity to conventional fitness activities with repetitive exercises and whether extending the training duration has additional benefits. Twenty-two healthy seniors (63-80 years) who had been randomly assigned to either a dance or a sport group completed the entire 18-month study. MRI, BDNF and neuropsychological tests were performed at baseline and after 6 and 18 months of intervention. After 6 months, we found a significant increase in gray matter volume in the left precentral gyrus in the dancers compared to controls. This neuroplasticity effect may have been mediated by the increased BDNF plasma levels observed in the dancers. Regarding cognitive measures, both groups showed significant improvements in attention after 6 months and in verbal memory after 18 months. In addition, volume increases in the parahippocampal region were observed in the dancers after 18 months. The results of our study suggest that participating in a long-term dance program that requires constant cognitive and motor learning is superior to engaging in repetitive physical exercises in inducing neuroplasticity in the brains of seniors. Therefore, dance is highly promising in its potential to counteract age-related gray matter decline.
Gobbi, P G; Valentino, F; Berardi, E; Tronconi, C; Brugnatelli, S; Luinetti, O; Moratti, R; Corazza, G R
The aim of this study was to verify through relative survival (an estimate of cancer-specific survival) the true prognostic factors of colorectal cancer. The study involved 506 patients who underwent locally radical resection. All the clinical, histological and laboratory parameters were prognostically analysed for both overall and relative survival. This latter was calculated from the expected survival of the general population with identical age, sex and calendar years of observation. Univariate and multivariate analyses were applied to the proportional hazards model. Liver metastases, age, lymph node involvement and depth of bowel wall involvement were independent prognosticators of both overall and relative survival, whereas carcinoembryonic antigen (CEA) was predictive only of relative survival. Increasing age was unfavourably related to overall survival, but mildly protective with regard to relative survival. Three out of the five prognostic factors identified are the cornerstones of the current staging systems, and were confirmed as adequate by the analysis of relative survival. The results regarding age explain the conflicting findings so far obtained from studies considering overall survival only and advise against the adoption of absolute age limits in therapeutic protocols. Moreover, the prechemotherapy CEA level showed a high clinical value. PMID:18026187
Akinfolarin, Adepiti Clement; Olusegun, Ajenifuja Kayode; Omoladun, Okunola; Omoniyi-Esan, G O; Onwundiegu, Uche
To characterize the age and pattern of Pap smear abnormalities in a major teaching hospital in Southwestern Nigeria. This is a review of medical records of patients that came for cervical cancer screening. The Pap smear results of women between May 2013 and April 2015 were retrieved. A total of 2048 Pap smear results were retrieved during the study period and analyzed with Statistical Package for Social Sciences (SPSS) version 20. A total of 252 (12.3%) samples were excluded from the analysis. The mean age of the women was 45.77 ± 9.9 years and the mode was 50 years. Normal Pap smear result was reported in 728 (40.6%) women. Only 20 women has had more than one more than one Pap smear done. The most common abnormality was inflammatory smear result as this was reported in 613 (29.9%) women. Atypical squamous cell of undetermined significance, low-grade squamous intraepithelial lesion (LGSIL), and high-grade squamous intraepithelial lesion (HGSIL) were reported in 117 (5.7%), 209 (10.2%), and 111 (5.4%) women, respectively. Atypical glandular cell and squamous cell carcinoma were reported in 12 (6.0%) and 3 (1.0%), respectively. There is a high incidence of abnormal Pap smear in this environment and women start cervical cancer screening late in their reproductive life, past the age at which cervical premalignant lesions peak. This may be a contributing factor to the high burden of cervical cancer in developing countries.
Full Text Available Abstract Objectives To examine the association between time of smoking initiation and both the independent and joint effects of active and passive tobacco smoke exposure and the risk of breast cancer in a sample of Ontario women. Methods Data from two large population-based case-control studies conducted among Ontario women aged 25–75 years were combined for analysis (n = 12,768. Results Women who had ever smoked and were exposed to passive smoke had a significant increased risk of breast cancer (OR 1.13, 95%CI 1.01–1.25. A significant increased risk was also observed among women who initiated smoking: at age 26 or older (OR 1.26, 95%CI 1.03–1.55; more than five years from menarche (OR 1.26, 95%CI 1.12–1.42; and, after their first live birth (OR 1.25, 95%CI 1.02–1.52. Conclusion The results suggest that women who initiate smoking at an older age are at an increased risk of breast cancer.
Lee, JungSun; Oh, Minkyung
The influence of parity and time interval between age at first pregnancy (AFP) and age at diagnosis on breast cancer survival is not established in the same way as their influence on breast cancer risk. We aimed to investigate the association of time interval or parity with prognosis in pre- and postmenopausal women in Korea. We conducted a retrospective study of 29,167 women with breast cancer through the Korean Breast Cancer Registry from 1993-2009. Information on reproductive factors, including breastfeeding, AFP, and parity were collected from a routine questionnaire. Conditional logistic regression was used to estimate the associations between menopausal status and overall mortality (OM) and breast-cancer-specific mortality (BCSM), adjusting for treatment and stage. High parity (≥5) increased the hazard ratios (HR) of BCSM (HR = 1.33, 95% confidence interval (CI): 0.83-2.11, p breast cancer diagnosis and AFP reduced the HRs of BCSM (HR = 0.97, 95% CI: 0.96-0.98, p = 0.001) and OM (HR = 0.98, 95% CI: 0.97-0.98, p breast cancer prognosis in both pre- and postmenopausal women. The time intervals between reproductive events had different effects on breast cancer outcomes depending on menopausal status.
Russell, Michael; Berardi, Philip; Gong, Wei; Riabowol, Karl
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 (p21WAF1, 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.
Blacher, Pierre; Huggins, Timothy J; Bourke, Andrew F G
Eusocial insects provide special opportunities to elucidate the evolution of ageing as queens have apparently evaded costs of reproduction and reversed the fecundity-longevity trade-off generally observed in non-social organisms. But how reproduction affects longevity in eusocial insects has rarely been tested experimentally. In this study, we took advantage of the reproductive plasticity of workers to test the causal role of reproduction in determining longevity in eusocial insects. Using the eusocial bumblebee Bombus terrestris, we found that, in whole colonies, in which workers could freely 'choose' whether to become reproductive, workers' level of ovarian activation was significantly positively associated with longevity and ovary-active workers significantly outlived ovary-inactive workers. By contrast, when reproductivity was experimentally induced in randomly selected workers, thereby decoupling it from other traits, workers' level of ovarian activation was significantly negatively associated with longevity and ovary-active workers were significantly less long-lived than ovary-inactive workers. These findings show that workers experience costs of reproduction and suggest that intrinsically high-quality individuals can overcome these costs. They also raise the possibility that eusocial insect queens exhibit condition-dependent longevity and hence call into question whether eusociality entails a truly reversed fecundity-longevity trade-off involving a fundamental remodelling of conserved genetic and endocrine networks underpinning ageing. © 2017 The Authors.
Huggins, Timothy J.
Eusocial insects provide special opportunities to elucidate the evolution of ageing as queens have apparently evaded costs of reproduction and reversed the fecundity–longevity trade-off generally observed in non-social organisms. But how reproduction affects longevity in eusocial insects has rarely been tested experimentally. In this study, we took advantage of the reproductive plasticity of workers to test the causal role of reproduction in determining longevity in eusocial insects. Using the eusocial bumblebee Bombus terrestris, we found that, in whole colonies, in which workers could freely ‘choose’ whether to become reproductive, workers' level of ovarian activation was significantly positively associated with longevity and ovary-active workers significantly outlived ovary-inactive workers. By contrast, when reproductivity was experimentally induced in randomly selected workers, thereby decoupling it from other traits, workers' level of ovarian activation was significantly negatively associated with longevity and ovary-active workers were significantly less long-lived than ovary-inactive workers. These findings show that workers experience costs of reproduction and suggest that intrinsically high-quality individuals can overcome these costs. They also raise the possibility that eusocial insect queens exhibit condition-dependent longevity and hence call into question whether eusociality entails a truly reversed fecundity–longevity trade-off involving a fundamental remodelling of conserved genetic and endocrine networks underpinning ageing. PMID:28701554
Kinlen, Leo J
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.
Boer, R; de Koning, H J; van Oortmarssen, G J; van der Maas, P J
The aim of this study was to determine the best upper age limit for a breast cancer screening programme. We used a model-based study using optimistic and pessimistic assumptions, concerning improvement of prognosis due to screen-detection and duration of the period of mammographic detectability, resulting in upper and lower limits for favourable and unfavourable effects. Under pessimistic assumptions, the balance between positive and negative effects of screening remains favourable up to an age of around 80 years. Under optimistic assumptions, this balance never becomes clearly negative with increase of the upper age limit of a screening programme. When including the costs in the analysis, the balance between effects and costs of increasing the upper age limit from 69 to 75 years is likely to be at least as favourable as intensifying a screening programme within the age group 50-69 years. A further increase leads to a markedly less favourable balance. Competing causes of death do not lead to missing net benefit for women up to at least age 80 years, but the disproportional rise of negative effects of screening with age in older women leads to a lower cost-effectiveness ratio than intensifying screening at ages 50-69 years.
Giannakeas, Vasily; Narod, Steven A
Preventive breast surgery is offered to unaffected BRCA mutation carriers to prevent breast cancer incidence and mortality. The clinical benefit of preventive mastectomy can be measured in several ways, including extension of life expectancy (mean years of life gained) and by estimating the probability of surviving until age 80. We sought to estimate the expected benefit of a preventive mastectomy at various ages, using these indices of mortality, by simulating hypothetical cohorts of women. The age-specific annual risks of developing breast cancer were used to estimate the actuarial risk of developing breast cancer by age 80 for women with a BRCA1 or BRCA2 mutation. The probability of developing breast cancer before age 80 was then modified to include competing causes of death, including from ovarian cancer. The mortality rate from breast cancer after a diagnosis of breast cancer was set at 2% annually for the first 10 years and then 1% annually for years ten to twenty. The incidence rate and mortality rate from ovarian cancer were based on published literature. We assumed that preventive mastectomy was associated with complete protection against subsequent breast cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) until age 80, according to the age at mastectomy. The actuarial risk of developing breast cancer until age 80 was estimated to be 70.8%. The actual risk (incorporating competing risks) was 64.0%. The probability of being alive at age 80 by having a mastectomy at age 25 increased by 8.7% (from 42.7 to 51.3%). The estimated benefit declined with age at mastectomy; for surgery done at age 50 the improvement in survival to age 80 was much more modest (2.8% at age 80, from 42.7 to 45.5%). Among BRCA mutation carriers, the mortality benefit of preventive mastectomy at age 25 is substantial, but the expected benefit declines rapidly with increasing age at surgery.
Kharazmi, Elham; Chen, Tianhui; Narod, Steven; Sundquist, Kristina; Hemminki, Kari
The objective of this nationwide prospective cohort study is to find out the risk of breast cancer (BC) in relatives of patients with multiple BCs by laterality and age at diagnosis of first BC. Having family history of single (HR 1.8; 95 % CI 1.8-1.9) or multiple (HR 2.7; 95 % CI 2.6-2.9) BC was associated with higher risk of BC. Those with an FDR with contralateral BC at any age had the highest risk of familial cancer except at age risk (HR 9.7; 95 % CI 6.0-15.6). The familial risk of BC in these families decreased as the subject's and FDRs' age at diagnosis of first BC increased. The HR was still significantly increased (2.2) for old individuals (>60) having a FDR with contralateral BC at an advanced age (≥80). Despite the common belief that later onset breast cancer is more associated with sporadic breast cancer, our data suggest that breast cancer at any age in the family is associated with some increase in the familial risk, though that risk decreases as the age of onset increases. Contralateral and multiple ipsilateral breast cancers might be associated with distinct shared familial risk factors. Our results have implication for genetic counseling and urge gene identification studies.
Li, Jing; Hong, Wenxue
The feature extraction and feature selection are the important issues in pattern recognition. Based on the geometric algebra representation of vector, a new feature extraction method using blade coefficient of geometric algebra was proposed in this study. At the same time, an improved differential evolution (DE) feature selection method was proposed to solve the elevated high dimension issue. The simple linear discriminant analysis was used as the classifier. The result of the 10-fold cross-validation (10 CV) classification of public breast cancer biomedical dataset was more than 96% and proved superior to that of the original features and traditional feature extraction method.
Land, L H; Dalton, S O; Jensen, M-B; Ewertz, M
Prevalence of comorbidity at breast cancer diagnosis increases with age and is likely to influence the likelihood of receiving treatment according to guidelines. The aim of this study was to examine the effect of breast cancer treatment on mortality, taking age at diagnosis and comorbidity into account. Four nationwide population registries in Denmark: the Danish Civil Registration System, the Danish Breast Cancer Cooperative Group, the Danish National Patient Register, and the Danish Register of Causes of Death provided information on 62 591 women diagnosed with early-stage breast cancer, 1990-2008, of whom data on treatment were available for 39 943. Comorbidity was measured using the Charlson Comorbidity Index. Adjuvant treatment were categorised as none, chemotherapy, endocrine therapy, and unknown. Multivariable Cox modelling assessed the effect of comorbidity on breast cancer-specific mortality and other cause mortality according to treatment, adjusting for age at diagnosis and other clinical prognostic factors. The impact of comorbidity on mortality was most pronounced in patients aged 50-79 years. Patients receiving chemotherapy with mild to moderate comorbidity had HR 0.99 (95% confidence interval (CI); 0.82-1.19) and 1.06 (95% CI; 0.77-1.46) for breast cancer-specific mortality, respectively, compared with patients without comorbidity. Comorbidity at breast cancer diagnosis is an independent adverse prognostic factor for death after breast cancer. We identified a subgroup of patients with mild to moderate comorbidity receiving chemotherapy who had similar breast cancer mortality as patients with no comorbidity.
Săbău, Gavril; Negulescu, Elena
. On the other hand, the chemical variability of the monazite grains enables separation of discrete populations, which cluster in ternary chemical plots (LREE - Y+Nd+MREE - U+Th+Ca, LREE - Nd+MREE - Y) and display similar chondrite-normalized lanthanide patterns, quantitatively evaluated by ratios such as (La/Nd)CN, (Nd/Gd)CN, (Gd/Y)CN, (U/Th)CN, (Y/Y*)CN, and (Eu/Eu*)CN. The correspondence between age and chemical clusters endorses their geological relevance and make a case for geunuine tectonothermal events. Distinct compositional domains corresponding to well-defined age clusters have been identified in gneissic rocks of the Leaota Massif, South Carpathians, highlighting the lower Paleozoic evolution of a crustal fragment detached during the Cambrian from northern Gondwana. Relict ages of Panafrican affinity of around 530 Ma are heavily overprinted by Lower Ordovician crustal thickening followed by tectonic relaxation coeval with granitization (around 470 Ma), followed in turn by high-pressure metamorphism at the Ordovician-Silurian boundary (Negulescu et al., 2015) and final tectonic stacking associated to Variscan docking to Laurussia + Avalonia, reflected in a high-pressure overprint at 350-325 Ma. References Kelly N. M., Harley S. L., Möller A. et al. (2012) Chemical Geology 322-323, 192-208 Montel J.-M., Foret S., Veschambre M., Nicollet C., Provost A. (1996) Chemical Geology 131, 37-53 Săbău G., Negulescu E. (2013) GSTF International Journal of Geological Sciences 1/ 1, 20-29 Negulescu E., Săbău G., Massonne H.-J. (2015) EGU2015-6663
Kulminski, Alexander M; Culminskaya, Irina; Arbeev, Konstantin G; Ukraintseva, Svetlana V; Arbeeva, Liubov; Yashin, Anatoli I
Decades of studies of candidate genes show their complex role in aging-related traits. We focus on apolipoprotein E e2/3/4 polymorphism and ages at onset of cardiovascular diseases (CVD) and cancer in the parental and offspring generations of the Framingham Heart Study participants to gain insights on the role of age and gender across generations in genetic trade-offs. The analyses show that the apolipoprotein E e4 allele carriers live longer lives without cancer than the non-e4 allele carriers in each generation. The role of the e4 allele in onset of CVD is age- and generation-specific, constit