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Endogenous Factors (endogenous + factor)
Selected AbstractsRegulation of Mineral and Trace Elements in Human Milk: Exogenous and Endogenous FactorsNUTRITION REVIEWS, Issue 8 2000Bo Lönnerdal Ph.D. Breast-fed infants are dependent on an adequate supply of minerals and trace elements for normal growth and development. For most of these elements, the mammary gland appears to have developed mechanisms to regulate their concentrations, even when the maternal diet varies considerably or maternal conditions are affected by different challenges. For some elements, however, there appears to be little or no such regulation. Increased knowledge about these mechanisms, or their absence, and to what extent they may compensate for adverse maternal conditions, including poor nutrition, will help identify infants and women at risk for deficiencies of these nutrients. [source] The sex of the individual as a factor in allergic contact dermatitisCONTACT DERMATITIS, Issue 2 2004B. S. Modjtahedi Exogenous and endogenous factors have been implicated in allergic contact dermatitis (ACD); this review explores the sex of the individual as a possible endogenous factor. While there is a clinical impression that women are more skin-reactive than men, upon review this hypothesis appears oversimplified. This review explores sex differences in controlled testing of adult ACD, occupational ACD and juvenile ACD. Further, geographical location and socioeconomic and cultural factors in relation to sex differences in allergic contact dermatitis are discussed. We conclude that female sex could be a factor predisposing to allergic contact dermatitis not so much because of possible differences in intrinsic skin characteristics between the sexes, but more because of different exposure patterns. This conclusion has practical consequences regarding product labelling requirements, occupational risk assessment and legislation. [source] Clues to an accurate diagnosis of contact dermatitisDERMATOLOGIC THERAPY, Issue 3 2004Robert L. Rietschel ABSTRACT:, An accurate diagnosis of allergic contact dermatitis can be achieved by a combination of historical, morphologic, and diagnostic steps. Clues in the history and physical examination can point to an irritant as the source of contact dermatitis. While irritants and allergens share many common features both immunologically and clinically, there are grounds for the distinction. Knowledge of occupational factors is necessary to assess the source of contact dermatitis. A common pitfall is the failure to appreciate the role of endogenous factors in the clinical presentation and overall care of the dermatitis patient. A comprehensive assessment of the patient's environment will lead to appropriate patch tests being applied and a correct diagnosis being reached. [source] The effects of social environment on adult neurogenesis in the female prairie voleDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002Christie D. Fowler Abstract In the mammalian brain, adult neurogenesis has been found to occur primarily in the subventricular zone (SVZ) and dentate gyrus of the hippocampus (DG) and to be influenced by both exogenous and endogenous factors. In the present study, we examined the effects of male exposure or social isolation on neurogenesis in adult female prairie voles (Microtus ochrogaster). Newly proliferated cells labeled by a cell proliferation marker, 5-bromo-2,-deoxyuridine (BrdU), were found in the SVZ and DG, as well as in other brain areas, such as the amygdala, hypothalamus, neocortex, and caudate/putamen. Two days of male exposure significantly increased the number of BrdU-labeled cells in the amygdala and hypothalamus in comparison to social isolation. Three weeks later, group differences in BrdU labeling generally persisted in the amygdala, whereas in the hypothalamus, the male-exposed animals had more BrdU-labeled cells than did the female-exposed animals. In the SVZ, 2 days of social isolation increased the number of BrdU-labeled cells compared to female exposure, but this difference was no longer present 3 weeks later. We have also found that the vast majority of the BrdU-labeled cells contained a neuronal marker, indicating neuronal phenotypes. Finally, group differences in the number of cells undergoing apoptosis were subtle and did not seem to account for the observed differences in BrdU labeling. Together, our data indicate that social environment affects neuron proliferation in a stimulus- and site-specific manner in adult female prairie voles. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 115,128, 2002 [source] Progress in the development of new treatments for combined Alzheimer's and Parkinson's diseasesDRUG DEVELOPMENT RESEARCH, Issue 3 2002Eliezer Masliah Abstract Misfolding of synaptic molecules such as amyloid , peptide and ,-synuclein has been proposed to play a key role in the mechanisms of neurodegeneration in Alzheimer's and Parkinson's disease, respectively. Notably, the majority of patients with Alzheimer's disease also have ,-synuclein-immunoreactive Lewy bodies, and a substantial proportion of them develop a form of parkinsonism also known as Lewy body disease, that defies conventional therapies. Thus, factors involved in the pathogenesis of Alzheimer's disease might promote the development of particularly recalcitrant forms of Lewy body disease. We have shown that the amyloid , peptide 1-42, of Alzheimer's disease, promotes the toxic conversion of ,-synuclein and accelerates ,-synuclein-dependent deficits in transgenic mice. Understanding the mechanisms promoting the toxic conversion of ,-synuclein is of critical importance for the design of rationale treatments for Lewy body disease and transgenic models hold the promise for the development of such novel therapies. In this context therapies aimed at: (1) reducing amyloid , peptide 1-42 production, (2) blocking toxic ,-synuclein oligomerization (e.g., ,-synuclein, antioxidants), (3) promoting ,-synuclein protofibril degradation, and (4) protecting neurons (e.g., anti-oxidants, neurotrophic agents) against toxic ,-synuclein aggregates might prove to be significantly useful in the treatment of Lewy body disease. We characterized ,-synuclein, the non-amyloidogenic homologue of ,-synuclein, as an inhibitor of aggregation of ,-synuclein. Our results raise the intriguing possibility that ,-synuclein might be a natural negative regulator of ,-synuclein aggregation, and that a similar class of endogenous factors might modulate the toxic conversion of other molecules involved in neurodegeneration. Such an anti-amyloidogenic property of ,-synuclein in combination with other treatments might also provide a novel strategy for the treatment of neurodegenerative disorders. Drug Dev. Res. 56:282,292, 2002. © 2002 Wiley-Liss, Inc. [source] Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Amelia Fernandez-Martin Abstract CD4+CD25+ regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens. Several models support the idea of the peripheral generation of CD4+CD25+ Treg from CD4+CD25, T cells. Little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+CD25+ Treg. In this study we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg in vivo during the development of experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. The administration of VIP to EAE mice results in the expansion of the CD4+CD25+, Foxp3-expressing T cells in the periphery and the nervous system, which inhibit encephalitogenic T cell activation. In addition to the increase in the number of CD4+CD25+ Treg, VIP induces more efficient suppressors on a per cell basis. The VIP-generated CD4+CD25+ Treg transfer suppression and significantly ameliorate the progression of the disease. [source] Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001Mounira Banasr Abstract Characterizing the mechanisms by which endogenous factors stimulate neurogenesis is of special interest in view of the possible implication of newly generated cells in hippocampal functions or disorders. The aim of this study was to determine whether serotonin (5-HT) and oestradiol (E2) act through a common pathway to increase cell proliferation in the adult dentate gyrus (DG). We also investigated the effects of long-lasting changes in oestrogen levels on cell proliferation. Combining ovariectomy with inhibition of 5-HT synthesis using p -chlorophenylalanine (PCPA) treatment produced approximately the same decreases in the number of bromodeoxyuridine (BrdU) and PSA-NCAM immunolabelled cells in the subgranular layer as ovariectomy alone. Administration of 5-hydroxytryptophan (5-HTP) restored cell proliferation primarily decreased by ovariectomy, whereas oestradiol was unable to reverse this change in ovariectomized rats treated with PCPA. These findings demonstrate that 5-HT mediates oestrogen stimulation of cell proliferation in adult dentate gyrus. However, increase in ovarian hormones during pregnancy has no effect on dentate cell proliferation. This finding suggests that concomitant changes in other factors, such as glucocorticoids, may counterbalance the positive regulation of cell proliferation by 5-HT and oestradiol. Finally, oestrogen may regulate structural plasticity by stimulating PSA-NCAM expression independently of neurogenesis, as shown for instance by the increases in the number of PSA-NCAM labelled cells in pregnants. As 5-HT and oestrogen are involved in mood disorders, our data suggest that the positive regulation of cell proliferation and neuroplasticity by these two factors may contribute to restore hippocampal connectivity in depressive patients. [source] Lipopolysaccharide is a frequent and significant contaminant in microglia-activating factorsGLIA, Issue 1 2008Jonathan R. Weinstein Abstract Lipopolysaccharide (LPS/endotoxin) is a potent immunologic stimulant. Many commercial-grade reagents used in research are not screened for LPS contamination. LPS induces a wide spectrum of proinflammatory responses in microglia, the immune cells of the brain. Recent studies have demonstrated that a broad range of endogenous factors including plasma-derived proteins and bioactive phospholipids can also activate microglia. However, few of these studies have reported either the LPS levels found in the preparations used or the effect of LPS inhibitors such as polymyxin B (PMX) on factor-induced responses. Here, we used the Limulus amoebocyte lysate assay to screen a broad range of commercial- and pharmaceutical-grade proteins, peptides, lipids, and inhibitors commonly used in microglia research for contamination with LPS. We then characterized the ability of PMX to alter a representative set of factor-induced microglial activation parameters including surface antigen expression, metabolic activity/proliferation, and NO/cytokine/chemokine release in both the N9 microglial cell line and primary microglia. Significant levels of LPS contamination were detected in a number of commercial-grade plasma/serum- and nonplasma/serum-derived proteins, phospholipids, and synthetic peptide preparations, but not in pharmaceutical-grade recombinant proteins or pharmacological inhibitors. PMX had a significant inhibitory effect on the microglia-activating potential of a number of commercial-, but not pharmaceutical-grade, protein preparations. Novel PMX-resistant responses to ,2 -macroglobulin and albumin were incidentally observed. Our results indicate that LPS is a frequent and significant contaminant in commercial-grade preparations of previously reported microglia-activating factors. Careful attention to LPS levels and appropriate controls are necessary for future studies in the neuroinflammation field. © 2007 Wiley-Liss, Inc. [source] Environmental control of fine root dynamics in a northern hardwood forestGLOBAL CHANGE BIOLOGY, Issue 5 2003GERALDINE L. TIERNEY Abstract Understanding how exogenous and endogenous factors control the distribution, production and mortality of fine roots is fundamental to assessing the implications of global change, yet our knowledge of control over fine root dynamics remains rudimentary. To improve understanding of these processes, the present study developed regression relationships between environmental variables and fine root dynamics within a northern hardwood forest in New Hampshire, USA, which was experimentally manipulated with a snow removal treatment. Fine roots (< 1 mm diameter) were observed using minirhizotrons for 2 years in sugar maple and yellow birch stands and analyzed in relation to temperature, water and nutrient availability. Fine root dynamics at this site fluctuated seasonally, with growth and mortality peaking during warmer months. Monthly fine root production was strongly associated with mean monthly air temperature and neither soil moisture nor nutrient availability added additional predictive power to this relationship. This relationship exhibited a seasonal temperature hysteresis, which was altered by snow removal treatment. These results suggest that both exogenous and endogenous cues may be important in controlling fine root growth in this system. Proportional fine root mortality was directly associated with mean monthly soil temperature, and proportional fine root mortality during the over-winter interval was strongly related to whether the soil froze. The strong relationship between fine root production and air temperature reported herein contrasts with findings from some hardwood forest sites and indicates that controls on fine root dynamics vary geographically. Future research must more clearly distinguish between endogenous and exogenous control over fine root dynamics in various ecosystems. [source] Allelic heterogeneity of molecular events in human coagulation factor IX in Asian Indians,,HUMAN MUTATION, Issue 5 2007Anubha Mahajan Abstract Mutations in Factor IX gene (F9) cause X-linked recessive bleeding disorder hemophilia B. Here, we characterized molecular events in nine North Indian hemophiliac families identifying four missense mutations (three novel), two nonsense mutations, and a deletion. We have also captured the mutational spectrum of this disease in India based on available reports and established their genotype/phenotype relationships. Indian F9 mutations data indicate the absence of an important germline mutagen in the Indian subcontinent over the last century, and are consistent with previously made conclusions that universal, presumably endogenous factors are predominant in the causation of the spontaneous mutations in F9. We also analyzed the distribution of Ala194Thr polymorphism in 1231 Asian Indians and have established that Ala variant is far more frequent and can certainly be exploited for carrier detection, contrary to earlier reports. © 2007 Wiley-Liss, Inc [source] The Differential Susceptibility of Specific Neuronal Populations: Insights from Huntington's DiseaseIUBMB LIFE, Issue 6 2003Ian Mitchell Abstract Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to show how the mutant protein could interact with associated proteins to form an aggregation product. This could lead to neuronal death by direct actions on caspases, or by raising the levels of intracellular calcium ions and reactive oxygen species above a threshold that cannot be resisted by the protection normally conferred by endogenous factors such as calcium binding proteins, free radical scavengers and trophic factors. The local distributions of vulnerability and protective factors could ultimately dictate the pattern of damage induced by the mutant gene. IUBMB Life, 55: 293-298, 2003 [source] Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2002Gu Kong Abstract Background and Aim: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogenous factors of human tumor progression. However, the clinicopathological and biological significance of the expression of COX-2 and iNOS in pancreatic cancer remains unclear. The objective of this study is to find the possible roles and clinical significance of COX-2 and iNOS expression in pancreatic cancer. Methods: Seventy-two pancreatic adenocarcinoma tissue specimens were obtained through surgical resection. We investigated the immunohistochemical expression of COX-2 and iNOS in respect to variable clinicopathological characteristics, proliferation activity (by Ki-67 expression), apoptosis (by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling stain), and microvessel density (by CD34 expression; angiogenesis). Results: Immunohistochemical investigations demonstrated immunolabeling of tumor cells with the primary antibodies, bovine anti-iNOS and anti-COX-2 antibodies. The COX-2 and iNOS positive rates were 41.7 and 66.7%, respectively. There was significant correlation between positive COX-2 and positive iNOS expression (P = 0.043). The proliferation index (Ki-67 labeling index) was higher in COX-2 positive specimens compared to COX-2 negative specimen (P = 0.015). The apoptotic index of positive iNOS expressions was significantly higher than negative expressions (P < 0.001). The expression of COX-2 and iNOS proteins did not correlate with age, sex, serum bilirubin, CA-19,9, location, size, American Joint Committee on Cancer stage, differentiation, distant metastasis, patient survival, or microvessel density. Conclusions: Although the pattern of positive expression was similar in both enzymes, the effect on tumor progression differed; iNOS expression may play a role in apoptosis of tumor cell, while COX-2 expression may contribute to tumor proliferation. However, COX-2 and iNOS expression is not related to prognosis in patients with pancreatic cancer. © 2002 Blackwell Publishing Asia Pty Ltd [source] Coat condition, housing condition and measurement of faecal cortisol metabolites , a non-invasive study about alopecia in captive rhesus macaques (Macaca mulatta)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2006Hanspeter W. Steinmetz Abstract Background, Previous studies have characterized alopecia in captive rhesus macaques (Macaca mulatta) by a mixed partial to complete alopecia in a bilateral symmetric pattern. Methods, In this study, coat condition assessments were related to exogenous and endogenous factors in captive rhesus macaques under different housing conditions in order to identify disturbances in environmental factors controlling or influencing hair growth. Additionally, the degree of alopecia was investigated in relation to adrenal endocrine function as an indicator of social stress using faecal glucocorticoid measurements. Results, Hair loss was found to vary with season and sex, was most pronounced in adult females during the winter and spring months. Generally, infants were not affected, but alopecia developed during adolescence. However, the housing system, available enclosure space and variations in group size and composition also appeared to influence coat condition. Levels of immunoreactive cortisol metabolites (11-oxoetiocholanolone) in faeces were significantly negatively correlated with alopecia, suggesting a relationship between hypothalamic-pituitary-adrenal (HPA) axis activity and hair loss in captive rhesus macaques. Conclusions, Although the present study demonstrates the influence of the HPA axis on coat condition, it is not known if hair loss is caused by abnormal behaviour or hormonal imbalances of the HPA axis itself. Our data suggest that alopecia in rhesus macaques is a highly complex multicausal disorder. [source] Adenosine deaminase activity, trypsin inhibitory capacity and total antioxidant capacity in psoriasisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2010M Hashemi Abstract Background, Psoriasis is a chronic inflammatory skin disease characterized by pathological skin lesions because of various exogenous and endogenous factors and associated with a number of biochemical and immunological disturbances. Objective, The aim of the present study was to determine the level of adenosine deaminase activity, serum trypsin inhibitory capacity and total antioxidant capacity of plasma in psoriatic patients. Subjects and methods, The study was performed in controls (n = 46) and in psoriatic patients (n = 40). The patients were scored with PASI (psoriasis area and severity index). The serum ADA activity was determined using Aguisti and Galanti method and serum trypsin inhibitory capacity (sTIC) were measured by enzymatic assay. Besides, serum total antioxidant capacity was measured using ferric reducing ability of plasma. Results, The serum ADA activity of the psoriatic patients was found to be significantly higher (P < 0.001) than that of the healthy control. We also found that the trypsin inhibitory capacity was significantly higher in patients than in control group (P < 0.001). Total antioxidant capacity of plasma was significantly lower in psoriatic patients than in healthy controls (P = 0.025). There were no significant correlations among ADA, TAC and TIC. Conclusion, Serum ADA activity and sTIC were increased in psoriatic patients. In parallel, serum total anti-oxidant activity was decreased in these patients. [source] Parkinson's disease: 10 years of progress, 1997,2007,,MOVEMENT DISORDERS, Issue S1 2010Stanley Fahn MD Abstract Many people with Parkinson's disease (PD) and their family members ask their physicians "What is happening in research on Parkinson's disease? Is there anything new?" As the initial speaker at the symposium organized by the Parkinson's Disease Foundation in celebration of its 50th anniversary, I sought to address these questions, focusing on research published between the years 1997 and 2007. I cataloged the advances I considered most important in the field, recognizing my viewpoint is a subjective one and most likely differs from similar listings that others would put together. Space limitation allows me to discuss only a tiny fraction of the remarkable new findings that have been discovered during this 10-year span. Nevertheless, I expect the readers of this summation of advances in the field to be as impressed as I am on the wealth, breadth, and excitement stirring in the field of PD research. Included in this overview are highlights in both laboratory science and clinical science of PD research. In the former category are advances in knowledge on the genetics of PD; potential etiologic and pathogenic causes, especially the better understanding of endogenous factors within dopaminergic neurons; pathologic changes including deposition of alpha-synuclein aggregates; and the consequences of altered alpha-synuclein on the degradation of proteins by both the ubiquitin-proteasomal pathway and the lysosome. Clinical science has also been very active and impressively productive with important clinical advances. In this category are new information on the epidemiology of PD, including awareness of additional factors (besides smoking) that might slow the onset and worsening of PD, such as caffeine and urate; neuroimaging with positron emission tomography and single photon emission tomography; keener awareness of nonmotor features of PD and their impact on quality of life for the persons with PD and their family; recognition of behavioral complications of medications utilized to treat PD, such as impulse control problems; appreciation of the natural history of PD with the increasing impairments as the disease relentlessly worsens over time; the many controlled clinical trials attempting to slow the progression of the disease and to provide new symptomatic therapies; and surgical approaches to alleviate symptoms and progression, including cellular and gene therapy as well as deep brain stimulation. © 2010 Movement Disorder Society [source] Interactions between dispersal, competition, and landscape heterogeneityOIKOS, Issue 7 2007Ace North It is widely acknowledged that space has an important role in population regulation, yet more specific knowledge into how the relevant factors interact attains little consensus. We address this issue via a stochastic, individual based model of population dynamics, in a continuous space continuous time framework. We represent habitat quality as a continuously varying surface over the two-dimensional landscape, and assume that the quality affects either fecundity (rate of propagule production) or probability of propagule establishment. We control the properties of the landscape by two parameters, which we call the patch size (the characteristic length scale in quality variation), and the level of heterogeneity (the characteristic quality difference between poor quality and high quality areas). In addition to such exogenous variability, we also account for endogenous factors causing spatial variation by assuming localised dispersal and competition. We find that heterogeneity has a general positive effect on population density, and hence it is beneficial to improve best quality habitat at the expense of worst quality habitat. With regards to patch size, we find an intermediate optimum, due to a conflict between minimising the loss of propagules to low quality regions and maximising the benefits of heterogeneity. We address the consequences of regional stochasticity by allowing the environmental conditions change in time. The cost of having to continuously track where the favourable conditions have moved to ultimately reduces population size. [source] A Comparative Study of Pediatric Onset Psoriasis with Adult Onset PsoriasisPEDIATRIC DERMATOLOGY, Issue 3 2000Siba P. Raychaudhuri M.D. We report data collected from 223 pediatric onset and 484 adult onset psoriasis patients. In the pediatric onset psoriasis patients (POPPs), prevalence of family history was 68.2% compared to 54% in the adult onset psoriasis patients (AOPPs). Also we noticed that exacerbation of psoriasis induced by precipitating factors such as stress (50.4% in POPPs, 42.7% in AOPPs), pharyngitis (27.9% in POPPs, 12.2% in AOPPs), and trauma (49.6% in POPPs and 38.9% in AOPPs) were more frequent in POPPs. Our data show that the frequency of spontaneous remission in POPPs was 35.3% compared to 24.3% in AOPPs. A disfiguring skin disease in childhood may have profound emotional effects. Childhood psoriasis needs special attention. To achieve a prolonged remission it is essential that children with psoriasis and their parents have an understanding of the exogenous and endogenous factors responsible for the increased morbidity of psoriasis. [source] Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: Altered expression and signal in immune cellsARTHRITIS & RHEUMATISM, Issue 4 2008Mario Delgado Objective Vasoactive intestinal peptide (VIP) has been shown to be one of the endogenous factors involved in the maintenance of immune tolerance. Administration of VIP ameliorates clinical signs in various experimental autoimmune disorders. This study was undertaken to investigate whether the exacerbated inflammatory autoimmune response in rheumatoid arthritis (RA) might result directly from altered expression and/or signaling of VIP receptors in immune cells. Methods The effect of specific agonists of different VIP receptors on collagen-induced arthritis in mice was investigated by clinical and histologic assessment and measurement of cytokine and chemokine production. Expression of VIP receptor type 1 (VPAC1) in synovial cells and monocytes from RA patients was determined by flow cytometry. Potential associations of VPAC1 genetic polymorphisms with RA susceptibility were investigated. Results A VPAC1 agonist was very efficient in the treatment of experimental arthritis, and deficient expression of VPAC1 in immune cells of RA patients was associated with the predominant proinflammatory Th1 milieu found in this disease. Immune cells derived from RA patients were less responsive to VIP signaling than were cells from healthy individuals and showed reduced VIP-mediated immunosuppressive activity, rendering leukocytes and synovial cells more proinflammatory in RA. A significant association between multiple-marker haplotypes of VPAC1 and susceptibility to RA was found, suggesting that the reduced VPAC1 expression in RA-derived immune cells is associated with the described VPAC1 genetic polymorphism. Conclusion These findings are highly relevant to the understanding of RA pathogenesis. They suggest that VIP signaling through VPAC1 is critical to maintaining immune tolerance in RA. In addition, the results indicate that VPAC1 may be a novel therapeutic target in RA. [source] Human prostate cancer risk factors,,§CANCER, Issue S10 2004David G. Bostwick M.D. Abstract Prostate cancer has the highest prevalence of any nonskin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating androgens will develop microscopic prostate cancer if they live long enough. This review is a contemporary and comprehensive, literature-based analysis of the putative risk factors for human prostate cancer, and the results were presented at a multidisciplinary consensus conference held in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate known environmental factors and mechanisms of prostatic carcinogenesis and to identify existing data gaps and future research needs. The review is divided into four sections, including 1) epidemiology (endogenous factors [family history, hormones, race, aging and oxidative stress] and exogenous factors [diet, environmental agents, occupation and other factors, including lifestyle factors]); 2) animal and cell culture models for prediction of human risk (rodent models, transgenic models, mouse reconstitution models, severe combined immunodeficiency syndrome mouse models, canine models, xenograft models, and cell culture models); 3) biomarkers in prostate cancer, most of which have been tested only as predictive factors for patient outcome after treatment rather than as risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The authors conclude that most of the data regarding risk relies, of necessity, on epidemiologic studies, but animal and cell culture models offer promise in confirming some important findings. The current understanding of biomarkers of disease and risk factors is limited. An understanding of the risk factors for prostate cancer has practical importance for public health research and policy, genetic and nutritional education and chemoprevention, and prevention strategies. Cancer 2004. © 2004 American Cancer Society. [source] | |||||||||||||