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Culture Models (culture + models)
Kinds of Culture Models Selected AbstractsThe characterization of functions involved in the establishment and maturation of Klebsiella pneumoniae in vitro biofilm reveals dual roles for surface exopolysaccharidesENVIRONMENTAL MICROBIOLOGY, Issue 3 2008Damien Balestrino Summary The ability to form biofilm is seen as an increasingly important colonization strategy among both pathogenic and environmental Klebsiella pneumoniae strains. The aim of the present study was to identify abiotic surface colonization factors of K. pneumoniae using different models at different phases of biofilm development. A 2200 K. pneumoniae mutant library previously obtained by signature-tagged mutagenesis was screened in static and dynamic culture models to detect clones impaired at early and/or mature stages of biofilm formation. A total of 28 mutants were affected during late phases of biofilm formation, whereas 16 mutants displayed early adhesion defect. These mutants corresponded to genes involved in potential cellular and DNA metabolism pathways and to membrane transport functions. Eight mutants were deficient in capsule or LPS production. Gene disruption and microscopic analyses showed that LPS is involved in initial adhesion on both glass and polyvinyl-chloride and the capsule required for the appropriate initial coverage of substratum and the construction of mature biofilm architecture. These results give new insight into the bacterial factors sequentially associated with the ability to colonize an abiotic surface and reveal the dual roles played by surface exopolysaccharides during K. pneumoniae biofilm formation. [source] The effect of hfq on global gene expression and virulence in Neisseria gonorrhoeaeFEBS JOURNAL, Issue 19 2009Manuela Dietrich Hfq is an RNA chaperone that functions as a pleiotropic regulator for RNA metabolism in bacteria. In several pathogenic bacteria, Hfq contributes indirectly to virulence by binding to riboregulators that modulate the stability or translation efficiency of RNA transcripts. To characterize the role of Hfq in the pathogenicity of Neisseria gonorrhoeae, we generated an N. gonorrhoeae hfq mutant. Infectivity and global changes in gene expression caused by the hfq mutation in N. gonorrhoeae strain MS11 were analyzed. Transcriptional analysis using a custom-made N. gonorrhoeae microarray revealed that 369 ORFs were differentially regulated in the hfq mutant, MS11hfq, in comparison with the wild-type strain (202 were upregulated, and 167 were downregulated). The loss-of-function mutation in hfq led to pleiotropic phenotypic effects, including an altered bacterial growth rate and reduced adherence to epithelial cells. Twitching motility and microcolony formation were not affected. Hfq also appears to play a minor role in inducing the inflammatory response of infected human epithelial cells. Interleukin-8 production was slightly decreased, and activation of c-Jun N-terminal kinase, a mitogen-activated protein kinase, was reduced in MS11hfq- infected epithelial cells in comparison with wild type-infected cells. However, activation of nuclear factor kappa B, extracellular signal-regulated kinase 1/2 and p38 remained unchanged. The data presented suggest that Hfq plays an important role as a post-transcriptional regulator in N. gonorrhoeae strain MS11 but does not contribute significantly to its virulence in cell culture models. [source] Potential and Bottlenecks of Bioreactors in 3D Cell Culture and Tissue ManufacturingADVANCED MATERIALS, Issue 32-33 2009David Wendt Abstract Over the last decade, we have witnessed an increased recognition of the importance of 3D culture models to study various aspects of cell physiology and pathology, as well as to engineer implantable tissues. As compared to well-established 2D cell-culture systems, cell/tissue culture within 3D porous biomaterials has introduced new scientific and technical challenges associated with complex transport phenomena, physical forces, and cell,microenvironment interactions. While bioreactor-based 3D model systems have begun to play a crucial role in addressing fundamental scientific questions, numerous hurdles currently impede the most efficient utilization of these systems. We describe how computational modeling and innovative sensor technologies, in conjunction with well-defined and controlled bioreactor-based 3D culture systems, will be key to gain further insight into cell behavior and the complexity of tissue development. These model systems will lay a solid foundation to further develop, optimize, and effectively streamline the essential bioprocesses to safely and reproducibly produce appropriately scaled tissue grafts for clinical studies. [source] Cell death mechanisms in neurodegenerationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2001K. A. Jellinger Abstract Progressive cell loss in specific neuronal populations often associated with typical cytoskeletal protein aggregations is a pathological hallmark of neurodegenerative disorders, but the nature, time course and molecular causes of cell death and their relation to cytoskeletal pathologies are still unresolved. Apoptosis or alternative pathways of cell death have been discussed in Alzheimer's disease and other neurodegenerative disorders. Apoptotic DNA fragmentation in human brain as a sign of neuronal injury is found too frequent as to account for continous neuron loss in these slowly progressive processes. Morphological studies revealed extremely rare apoptotic neuronal death in Alzheimer's disease but yielded mixed results for Parkinson's disease and other neurodegenerative disorders. Based on recent data in human brain, as well as in animal and cell culture models, a picture is beginning to emerge suggesting that, in addition to apoptosis, other forms of programmed cell death may participate in neurodegeneration. Better understanding of the molecular players will further elucidate the mechanisms of cell death in these disorders and their relations to cytoskeletal abnormalities. Susceptible cell populations in a proapoptotic environment show increased vulnerability towards multiple noxious factors discussed in the pathogenesis of neurodegeneration. In conclusion, although many in vivo and in vitro data are in favor of apoptosis involvement in neurodegenerative processes, there is considerable evidence that very complex events may contribute to neuronal death with possible repair mechanisms, the elucidation of which may prove useful for future prevention and therapy of neurodegenerative disorders. [source] Heparin modulates the growth and adherence and augments the growth-inhibitory action of TNF-, on cultured human keratinocytesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004Ilkka T. Harvima Abstract Previous works suggest the involvement of mast cells in the epithelialization of chronic wounds. Since heparin is a major mediator stored in the secretory granules of mast cells, the purpose of this work was to elucidate the function of heparin in epithelialization using in vitro culture models. For this, low- and high-calcium media in monolayer and epithelium cultures of keratinocytes were used. Also, an assay based on keratinocyte adherence onto plastic surface was used as well. Heparin (0.02,200 ,g/ml) inhibited keratinocyte growth in a non-cytotoxic and dose-dependent manner in low- and high-calcium media, Keratinocyte-SFM® and DMEM, in the absence of growth factors and serum. Also, heparin inhibited the growth of keratinocyte epithelium in the presence of 10% fetal calf serum and DMEM. Instead, in the presence of Keratinocyte-SFM and growth factors, heparin at 2 ,g/ml inhibited the growth by 18% but at higher heparin concentrations the inhibition was reversed to baseline. TNF-, is another preformed mediator in mast cell granules and it inhibited keratinocyte growth in monolayer and epithelium cultures. Interestingly, heparin at 2,20 ,g/ml augmented or even potentiated this growth-inhibitory effect of TNF-,. The association of TNF-, with heparin was shown by demonstrating that TNF-, bound tightly to heparin-Sepharose chromatographic material. However, heparin could not augment TNF-,-induced cell cycle arrest at G0/G1 phase or intercellular adhesion molecule-1 expression in keratinocytes. In the cell adherence assay, heparin at 2 ,g/ml inhibited significantly by 12,13% or 33% the adherence of keratinocytes onto the plastic surface coated with fibronectin or collagen, respectively, but this inhibition was reversed back to baseline at 20 or 200 ,g/ml heparin. Also, heparin affected the cell membrane rather than the protein coat on the plastic surface. In conclusion, heparin not only inhibits or modulates keratinocyte growth and adherence but it also binds and potentiates the growth-inhibitory function of TNF-,. © 2004 Wiley-Liss, Inc. [source] Effect of High Pressure Pasteurization on Bacterial Load and Bioactivity of Echinacea PurpureaJOURNAL OF FOOD SCIENCE, Issue 7 2010Xiu-Min Chen Abstract:, High hydrostatic pressure (HHP) technology was applied to organic Echinacea purpurea (E. purpurea) roots and flowers to determine the feasibility of using this technology for cold herb pasteurization, to produce microbiologically safe and shelf-stable products for the natural health products (NHPs) industry. HHP significantly (P < 0.01) reduced microbial contamination in both roots and flowers without affecting the phytochemical retention of chicoric and chlorogenic acids, and total alkamide contents. The antioxidant activity of E. purpurea methanol-derived extracts, evaluated in both chemical (2,2,-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) [ABTS] and oxygen radical absorption capacity [ORAC] assay) and in cell culture models (RAW264, 7 macrophage, H2O2 -induced intracellular oxidation, and lipopolysaccharide [LPS]-induced nitric oxide production), was not adversely affected by the application of HHP at both 2 and 5 min at 600 mPa. Furthermore, HHP did not affect the capacity of E. purpurea extracts to suppress nitric oxide production in LPS-activated macrophage cells. Therefore, our results show that HHP is an effective pasteurization process treatment to reduce microbial-contamination load while not adversely altering chemical and bioactive function of active constituents present in organic E. purpurea. Practical Application:, Our study reports for the first time, the effectiveness of using high hydrostatic pressure (HHP) technology pressure to pasteurize E. purpurea root and flower, and the comparative retention of bioactive phytochemicals. Therefore, this technique can be used in food and natural health product industries to produce high-quality, microbiologically safe, and shelf-stable products. [source] Transgenic mouse and cell culture models demonstrate a lack of mechanistic connection between endoplasmic reticulum stress and tau dysfunctionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010M.L. Spatara Abstract In vivo aggregation of tau protein is a hallmark of many neurodegenerative disorders, including Alzheimer's disease (AD). Recent evidence has also demonstrated activation of the unfolded protein response (UPR), a cellular response to endoplasmic reticulum (ER) stress, in AD, although the role of the UPR in disease pathogenesis is not known. Here, three model systems were used to determine whether a direct mechanistic link could be demonstrated between tau aggregation and the UPR. The first model system used was SH-SY5Y cells, a neuronal cultured cell line that endogenously expresses tau. In this system, the UPR was activated using chemical stressors, tunicamycin and thapsigargin, but no changes in tau expression levels, solubility, or phosphorylation were observed. In the second model system, wild-type 4R tau and P301L tau, a variant with increased aggregation propensity, were heterologously overexpressed in HEK 293 cells. This overexpression did not activate the UPR. The last model system examined here was the PS19 transgenic mouse model. Although PS19 mice, which express the P301S variant of tau, display severe neurodegeneration and formation of tau aggregates, brain tissue samples did not show any activation of the UPR. Taken together, the results from these three model systems suggest that a direct mechanistic link does not exist between tau aggregation and the UPR. © 2010 Wiley-Liss, Inc. [source] The Campylobacter jejuni stringent response controls specific stress survival and virulence-associated phenotypesMOLECULAR MICROBIOLOGY, Issue 1 2005Erin C. Gaynor Summary Campylobacter jejuni is a highly prevalent food-borne pathogen that causes diarrhoeal disease in humans. A natural zoonotic, it must overcome significant stresses both in vivo and during transmission despite the absence of several traditional stress response genes. Although relatively little is understood about its mechanisms of pathogenesis, its ability to interact with and invade human intestinal epithelial cells closely correlates with virulence. A C. jejuni microarray-based screen revealed that several known virulence genes and several uncharacterized genes, including spoT, were rapidly upregulated during infection of human epithelial cells. spoT and its homologue relA have been shown in other bacteria to regulate the stringent response, an important stress response that to date had not been demonstrated for C. jejuni or any other epsilon-proteobacteria. We have found that C. jejuni mounts a stringent response that is regulated by spoT. Detailed analyses of a C. jejuni,spoT mutant revealed that the stringent response is required for several specific stress, transmission and antibiotic resistance-related phenotypes. These include stationary phase survival, growth and survival under low CO2/high O2 conditions, and rifampicin resistance. A secondary suppressor strain that specifically rescues the low CO2 growth defect of the ,spoT mutant was also isolated. The stringent response additionally proved to be required for the virulence-related phenotypes of adherence, invasion, and intracellular survival in two human epithelial cell culture models of infection; spoT is the first C. jejuni gene shown to participate in longer term survival in epithelial cells. Microarray analyses comparing wild-type to the ,spoT mutant also revealed a strong correlation between gene expression profiles and phenotype differences observed. Together, these data demonstrate a critical role for the C. jejuni stringent response in multiple aspects of C. jejuni biology and pathogenesis and, further, may lend novel insight into unexplored features of the stringent response in other prokaryotic organisms. [source] Models of Parkinson's diseaseMOVEMENT DISORDERS, Issue 7 2003Michael Orth MD Abstract Parkinson's disease (PD) is a heterogenous disease likely to be caused by more than one specific aetiological factor. In rare familial cases of PD with similar clinical features to the idiopathic form of the disease, the underlying genetic cause has been identified. These PD-associated genes have been manipulated to create animal and cell culture models of the disease that have helped to further our understanding of the pathogenesis of PD, particularly concerning causes of the selective loss of dopaminergic neurons at the molecular level. In addition, these models will aid the future development of rational therapeutic strategies. This study briefly reviews toxin-induced models and the genetics of PD. It focuses on recently developed animal models of PD, as well as in vitro approaches to model the disease. © 2003 Movement Disorder Society [source] Protein aggregation in motor neurone disordersNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2003J. D. Wood Toxicity associated with abnormal protein folding and protein aggregation are major hypotheses for neurodegeneration. This article comparatively reviews the experimental and human tissue-based evidence for the involvement of such mechanisms in neuronal death associated with the motor system disorders of X-linked spinobulbar muscular atrophy (SBMA; Kennedy's disease) and amyotrophic lateral sclerosis (ALS), especially disease related to mutations in the superoxide dismutase (SOD1) gene. Evidence from transgenic mouse, Drosophila and cell culture models of SBMA, in common with other trinucleotide repeat expansion disorders, show protein aggregation of the mutated androgen receptor, and intraneuronal accumulation of aggregated protein, to be obligate mechanisms. Strong experimental data link these phenomena with downstream biochemical events involving gene transcription pathways (CREB-binding protein) and interactions with protein chaperone systems. Manipulations of these pathways are already established in experimental systems of trinucleotide repeat disorders as potential beneficial targets for therapeutic activity. In contrast, the evidence for the role of protein aggregation in models of SOD1-linked familial ALS is less clear-cut. Several classes of intraneuronal inclusion body have been described, some of which are invariably present. However, the lack of understanding of the biochemical basis of the most frequent inclusion in sporadic ALS, the ubiquitinated inclusion, has hampered research. The toxicity associated with expression of mutant SOD1 has been intensively studied however. Abnormal protein aggregation and folding is the only one of the four major hypotheses for the mechanism of neuronal degeneration in this disorder currently under investigation (the others comprise oxidative stress, axonal transport and cytoskeletal dysfunctions, and glutamatergic excitotoxicity). Whilst hyaline inclusions, which are strongly immunoreactive to SOD1, are linked to degeneration in SOD1 mutant mouse models, the evidence from human tissue is less consistent and convincing. A role for mutant SOD1 aggregation in the mitochondrial dysfunction associated with ALS, and in potentially toxic interactions with heat shock proteins, both leading to apoptosis, are supported by some experimental data. Direct in vitro data on mutant SOD1 show evidence for spontaneous oligomerization, but the role of such oligomers remains to be elucidated, and therapeutic strategies are less well developed for this familial variant of ALS. [source] Experimental approaches for studying uptake and action of herbal medicinesPHYTOTHERAPY RESEARCH, Issue 3 2007Venil N. Sumantran Abstract In order to gain wider credibility, herbal medicines must go through the rigorous scientific scrutiny to which synthetic drugs are subjected, and this includes investigating their absorption, bioavailability and metabolism. This review describes approaches for determining how active compounds in herbal formulations enter the systemic circulation. To assess how bioactive molecules enter the target organs and cells, specific cell lines and organ culture models can be used, followed by in vitro models to show how they may regulate digestion, energy balance and metabolism. This could lead to a better understanding of how herbal medicines affect digestion and absorption; fundamental questions which should be answered in addition to their mechanism of action. Copyright © 2006 John Wiley & Sons, Ltd. [source] The minotaur proteome: Avoiding cross-species identifications deriving from bovine serum in cell culture modelsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 16 2010Jakob Bunkenborg Abstract Cell culture is a fundamental tool in proteomics where mammalian cells are cultured in vitro using a growth medium often supplemented with 5,15% FBS. Contamination by bovine proteins is difficult to avoid because of adherence to the plastic vessel and the cultured cells. We have generated peptides from bovine serum using four sample preparation methods and analyzed the peptides by high mass accuracy LC-MS/MS. Distinguishing between bovine and human peptides is difficult because of a considerable overlap of identical tryptic peptide sequences. Pitfalls in interpretation, different database search strategies to minimize erroneous identifications and an augmented contaminant database are presented. [source] Cadherin switching dictates the biology of transitional cell carcinoma of the bladder: ex vivo and in vitro studies,THE JOURNAL OF PATHOLOGY, Issue 2 2008RT Bryan Abstract Bladder cancer is the fifth most common malignancy in the UK. Clinically, the most important process in determining prognosis is the development of invasion, initially of the lamina propria and then beyond as these transitional cell carcinomas (TCCs) progress from stage pT1 to stages T2+. Cadherins and catenins are the main mediators of cell,cell interactions in epithelial tissues, and loss of membranous E-cadherin immunoreactivity is strongly correlated with high grade, advanced stage and poor prognosis in bladder cancer and other malignancies. However, the role of P-cadherin is yet to be fully elucidated in bladder TCC. The objectives of this study were to establish how the expression of cadherins and catenins determines clinical and in vitro behaviour in bladder TCC. Utilizing immunohistochemistry, immunofluorescence and western blotting, we demonstrated a significant reduction in the expression of E-cadherin and ,-catenin as grade and stage of bladder TCC progress, accompanied by a significant increase in P-cadherin expression (all p < 0.05, Pearson's ,2 test). Increased P-cadherin expression was also associated with a significantly worse bladder cancer-specific survival (log rank p = 0.008), with Cox regression showing P-cadherin to be an independent prognostic factor. Utilizing a variety of tissue culture models in a range of functional studies, we demonstrated that P-cadherin mediates defective cell,cell adhesion and enhances anchorage-independent growth. The results provide evidence that increased P-cadherin expression promotes a more malignant and invasive phenotype of bladder cancer, and appears to have a novel role late in the disease. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal culturesTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006Jin-shun Qi Deficits in GABAergic inhibitory transmission are a hallmark of temporal lobe epilepsy and have been replicated in animal and tissue culture models of epilepsy. GABAergic inhibition comprises phasic and tonic inhibition that is mediated by synaptic and extrasynaptic GABAA receptors, respectively. We have recently demonstrated that chronic stimulation with cyclothiazide (CTZ) or kainic acid (KA) induces robust epileptiform activity in hippocampal neurons both in vitro and in vivo. Here, we report a downregulation of tonic GABA inhibition after chronic epileptogenic stimulation of rat hippocampal cultures. Chronic pretreatment of hippocampal neurons with CTZ or KA resulted in a marked reduction in GABAergic inhibition, as shown by a significant decrease in whole-cell GABA currents and in the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Interestingly, synaptically localized GABAA receptors remained relatively stable, as evidenced by the unaltered amplitude of mIPSCs, as well as the unchanged punctate immunoreactivity of ,2 subunit-containing postsynaptic GABAA receptors. In contrast, tonic GABA currents, assessed either by a GABAA receptor antagonist bicuculline or a selective extrasynaptic GABAA receptor agonist THIP, were significantly reduced following epileptogenic stimulation. These results reveal a novel form of neural plasticity, that epileptogenic stimulation can selectively downregulate extrasynaptic GABAA receptors while leaving synaptic GABAA receptors unchanged. Thus, in addition to synaptic alteration of GABAergic transmission, regulation of tonic inhibition may also play an important role during epileptogenesis. [source] Laboratory Forum: Experimental Models of Peyronie's Disease.THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009Implications for New Therapies ABSTRACT Introduction., Despite its high prevalence and impact on the quality of life of patients, and that it is an excellent model for the study of fibrotic processes, Peyronie's disease (PD) is an orphan disease in biomedical research. The development of animal and cell culture models has advanced substantially the understanding of its molecular and cellular pathology and the proposal of new therapies. Aim., To review the literature pertaining to the use of these models for the study of PD. Methods., PubMed search conducted from the first report of an animal model for PD. Results., This model, based on the finding that transforming growth factor ,1 (TGF,1) is overexpressed in the PD plaque, consists on the injection of TGF,1 into the tunica albuginea of the rat. This leads to a PD-like plaque retaining many of the histological and biochemical features of human PD. Another rat model, based on the hypothesis that the PD plaque arises from trauma to the penis, causing fibrinogen extravasation that initiates as fibrin a fibrotic response, consists on injection of fibrin into the tunica. The cell culture model is based on the demonstration that myofibroblasts are abundant in the human PD plaque. Conclusions., These models have: (i) clarified the role of microtrauma, myofibroblasts, and oxidative stress in plaque development; (ii) demonstrated that this tissue is under sustained turnover by fibrotic and antifibrotic mechanisms; (iii) showed the interplay of collagenolytic and fibrinolytic systems and their inhibitors; (iv) detected an endogenous antifibrotic process consisting of the expression of inducible nitric oxide synthase that counteracts oxidative stress, collagen synthesis, and myofibroblast generation; (v) characterized the antifibrotic effects of chronic treatment with phosphodiesterase type 5 (PDE5) inhibitors; (vi) discovered the cytogenetic instability of PD cells and alterations in their gene expression; and (vii) detected stem cells in the tunica albuginea with a potential role in fibrosis and ossification. Gonzalez-Cadavid NF, and Rajfer J. Experimental models of peyronie's disease. Implications for new therapies. J Sex Med 2009;6:303,313. [source] T-cadherin loss induces an invasive phenotype in human keratinocytes and squamous cell carcinoma (SCC) cells in vitro and is associated with malignant transformation of cutaneous SCC in vivoBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2010D. Pfaff Summary Background, Cadherins play important roles in controlling keratinocyte growth, differentiation and survival. Atypical glycosylphosphatidylinositol-anchored T-cadherin (T-cad) is highly expressed in the basal keratinocyte layer of skin. The role of T-cad in keratinocyte biology and pathology is unclear. Objectives, To define the role of T-cad in the pathogenesis of cutaneous squamous cell carcinoma (SCC) through gain-of-function and loss-of-function studies in vitro and through examination of T-cad expression patterns in human cutaneous SCC specimens in relation to histological classification of degree of tumour differentiation. Methods,In vitro studies employed lentiviral-mediated overexpression/silencing of T-cad in normal human keratinocyte (HaCaT) and SCC (A431) cell lines, monolayer and multicellular spheroid culture models, cell morphology analyses and assays of random motility and invasion. Immunohistochemistry was performed on skin specimens from patients with actinic keratosis, Bowen disease or SCC. Results,In vitro, silencing of T-cad induced a morphologically elongated and disorganized cell phenotype, increased random motility and markedly enhanced invasive potential. Overexpression of T-cad induced a morphologically spread and compact cell phenotype and blunted invasive potential. In vivo, regional loss of T-cad expression was more frequent and prominent in SCC classified as moderately-to-poorly differentiated than in SCC classified as well differentiated. However, in both categories aberrant and/or absence of T-cad expression was associated with histological features of a potentially more malignant and invasive phenotype of cutaneous SCC. Conclusions, T-cad is a controlling determinant of SCC phenotype and invasive behaviour and its loss is associated with the process of malignant transformation from noninvasive to invasive SCC. [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] | ||||||||||||||||