Download or read book Mouse Models for Prostate Cancer Initiation and Progression written by Minjung Kim and published by . This book was released on 2001 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Developing Improved Mouse Models of Prostate Cancer written by Gretchen Kathleen Hubbard and published by . This book was released on 2013 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetically modified rodent models provide a platform to dissect the complex and multifactorial mechanisms of prostate cancer initiation and progression. Existing mouse models based on MYC overexpression, including Lo-MYC and Hi-MYC strains, show distinct features of prostatic intraepithelial neoplasia (PIN) and adenocarcinoma that are quite similar to those observed in humans. However, the cancers that emerge in these models rarely progress to metastasis. Evidence is mounting that multiple molecular changes, including loss of tumor suppressor PTEN and MYC overexpression, cooperate to promote human prostate carcinogenesis. To better understand the pathobiology of this disease, we have modeled multiple genetic changes associated with prostate carcinogenesis by combining conditional loss of Pten and concomitant activation of MYC within prostate luminal epithelial cells. A triple transgenic mouse model in which the androgen independent Hoxb13 promoter drives MYC expression concurrent with conditional loss of Pten (Hoxb13-Myc/Hoxb13-Cre/Pten-l-) was generated. To date, tissues from thirty triply transgenic (Myc+, Cre+, Pten-/-) mice (referred to as BMTs) have been examined for disease progression and by immunohistochemical analyses. By two months of age, BMTs have developed high-grade PIN lesions and have lost expression of the key tumor suppressor Nkx3.1. By four months of age, these mice have developed adenocarcinoma that has metastasized lymph nodes (20/20), liver (13/20), and lung (11/20), mimicking the progression of human prostate cancer. Expression of several key markers including Cytokeratin 18 (CK18), Cytokeratin 8 (CK8), FoxA1, focal AR expression, and loss of p63 in the primary and metastatic tumors provides strong evidence that these tumors are adenocarcinomas of prostate origin. Comparative Genomic Hybridization (CGH) analyses using DNA from primary and metastatic lesions of four different mice were performed. Over 250 DNA copy number (DCN) changes were identified, indicating that genomic instability accompanied disease progression, in parallel with human prostate cancer. This innovative mouse model provides a powerful platform in which the molecular events underlying the progression from PIN through highly penetrant lethal metastatic disease can be systematically analyzed.
Download or read book Animal Models for the Study of Human Disease written by Ann-Christin Gaupel and published by Elsevier Inc. Chapters. This book was released on 2013-05-29 with total page 59 pages. Available in PDF, EPUB and Kindle. Book excerpt: In humans, the natural history of prostate cancer spans 30–40 years, which makes it a difficult disease to model in rodents. Furthermore, the molecular pathology of prostate cancer responsible for tumor initiation and progression is complex and often redundant. The sequential changes in oncogene and tumor suppressor gene expression during prostate cancer progression have not been fully delineated. Despite these issues, there are model systems, including carefully designed orthotopic xenograft models, that provide robust platforms for drug evaluation and studying the effects of diet and environmental stress on prostate carcinogenesis. Comprehensive transgenic and knockout models have also been developed that recapitulate individual steps in tumor initiation and metastatic progression and highlight the importance of the tumor microenvironment. While very few of the transgenic and knockout systems recapitulate the entire natural history of prostate cancer, individual model systems provide valuable genetic insight into the biological consequences of disrupting prostate homeostasis.
Download or read book A Mouse Model for Prostate Cancer written by and published by . This book was released on 2001 with total page 26 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mouse models of carcinogenesis have provided significant insights into the molecular mechanisms of tumor suppressor gene function. Our goal is to develop mouse models that recapitulate early stages of prostate carcinoma. Using such models we have demonstrated that the Nkx3.1 homeobox gene represents a prostate-specific tumor suppressor that undergoes epigenetic inactivation through loss of protein expression. Loss-of-function of Nkx3.1 in mice results in histopathological defects that resembles prostate cancer initiation in humans, and cooperates with loss-of-function of the Pten tumor suppressor gene in cancer progression. Furthermore, our findings suggest that the molecular mechanisms that mediate this cooperativity include the synergistic activation of Akt (protein kinase B), a key modulator of cell growth and survival. We propose that interactions between tissue-specific regulators such as Nkx3.1 and broad-spectrum tumor suppressors such as Pten underlie the distinct phenotypes of different cancers.
Download or read book Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15 Lipoxygenase 1 written by and published by . This book was released on 2008 with total page 7 pages. Available in PDF, EPUB and Kindle. Book excerpt: To gain better mechanistic insight of the role of Fifteen lipoxygenase-1 (15-LO-1) in prostate cancer (PCa), we recently developed a novel C57BL/6 transgenic mouse called 15-LO-1 in the Mouse Prostate (FLiMP). These mice, which conditionally express prostatic human 15-LO-1, display mouse prostatic intraepithelial neoplasia (mPIN) by week 20, but do not progress to cancer when on normal diet. Therefore, FLiMP mice provide an excellent model to study the experimental paradigm of PCa initiation, highlighting their usefulness in evaluating early proactive intervention strategies in PCa. In year 1, we have studied the effect of n-6 linoleic acid (LA) in diet on the onset of PIN in prostates of FLiMP+/+ mice and studies with n-3 Stearidonic acid (SDA) in diet is ongoing. We observed that, (a) wild type (WT) mice did not exhibit any prostate-specific phenotypic changes regardless of their diet, (b) FLiMP+/+ mice fed a diet high LA diet exhibited more aggressive PIN, with PIN-like changes observed in as early as 10 weeks compared to FLiMP+/+ mice fed a normal diet (PIN observed by week 20), and (c) the severity of these mPIN-like changes in the LA-diet fed mice are similar to those seen at 35 weeks or later in the FLiMP+/+ group which were on normal diet. This preliminary observation suggests the bad effects of excessive n-6 LA diet consumption in the progression of PCa.
Download or read book Genetic Variation in the Androgen Receptor Impacts Prostate Cancer Initiation and Progression in the Humanized AR Mouse written by Megan A. Albertelli and published by . This book was released on 2006 with total page 438 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Development of a Mouse Model for Prostate Cancer Imaging and Study of Disease Progression written by and published by . This book was released on 2007 with total page 9 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate carcinogenesis is a multi-step process resulting in the transformation of prostatic epithelial cells into invasive carcinoma and metastasis. In recent years, mouse models have emerged that recapitulate salient features of prostate carcinogenesis found in human disease. These models illuminate the molecular events that result in transformation and disease progression. In addition, mouse models can be used to identify molecular targets and test chemotherapeutic agents that may alter the course of disease. We have generated a new mouse model to further delineate targets that may halt cancer progression and lead to regression of disease. Crossing the TRAMP mouse with the PSCA-TVA transgenic mouse has resulted in the TRAMP-TVA mouse that is destined to develop prostate cancer and expresses the avian viral receptor, TVA, on prostate cancer cells. This new transgenic mouse should enable specific gene transfer of imaging genes and small hairpin nuclear RNAs (shRNAs) resulting in knockdown of specific targets. TRAMP-TVA mice demonstrate PIN lesions at 8 weeks and develop adenocarcinoma at 6-15 months. We have been able to demonstrate PSCA-driven expression of the TVA viral receptor in these lesions. Intraperitoneal injection of virus containing the luciferase gene results in luminescence signal in the prostate. Further development of this model will enable the effect of target gene knockdown via RNA interference to be monitored non-invasively in mice. This approach will facilitate high throughput analysis of potential shRNA targets.ta.
Download or read book Molecular Biology of Prostate Cancer written by Manfred Wirth and published by Walter de Gruyter. This book was released on 2013-05-22 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mouse Models of Prostate Cancer Progression and Bone Metastasis written by Srinivas Nandana and published by . This book was released on 2010 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Prostate Cancer written by Donald J. Tindall and published by Springer Science & Business Media. This book was released on 2013-05-09 with total page 575 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate Cancer provides an up-to-date review of the biochemistry, molecular biology, and genetic changes in prostate cells that are the driving forces in the initiation and progression of cancer. It includes an overview by experts in the field of cell-cell interactions, including stem cells, reactive Stromal cells and membrane lipid rafts that are instrumental in the initiation and progression of prostate cancer.
Download or read book ABC of Obesity written by Naveed Sattar and published by John Wiley & Sons. This book was released on 2009-04-08 with total page 64 pages. Available in PDF, EPUB and Kindle. Book excerpt: Obesity is a hugely expensive and increasing problem worldwide,leading to disability, reproductive problems, depression andaccelerated metabolic and vascular diseases in a large proportionof men, women and children. The ABC of Obesity is a newguide which will aid its effective management, addressing issuessuch as dieting, exercise, self esteem, drug treatment and surgery.Recent evidence is used to highlight frequent problems, successfultreatment options, and the most common causes. Written by leading experts, this is a widely accessible text andan indispensable guide for all general practitioners, juniordoctors, nurses, and other healthcare professionals who areinvolved in the treatment and research of this commoncondition.
Download or read book Defeating Prostate Cancer written by National Cancer Institute (U.S.). Prostate Cancer Progress Review Group and published by . This book was released on 1998 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Bioluminescent Mouse Models of Prostate Cancer Progression and Therapy written by Robert Ulf Svensson and published by . This book was released on 2010 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: However, longitudinal BLI from 12-40 weeks reveals a plateau in bioluminescence signal that is correlated with a halt in cellular proliferation as evidenced by Ki67 staining at necropsy. In contrast to other studies, prostate cancer never progressed beyond a high grade prostatic intraepithelial neoplasm (HGPIN). Furthermore, we demonstrate for the first time that cancer progression is accompanied by increased inflammation, characterized by enhanced recruitment of myeloid derived suppressor cells (MDSCs). We further demonstrate the utility of B6-Luc mice in monitoring response to prostate cancer therapy. Relatively few established risk factors for prostate cancer have been identified. Obesity has been linked to increased mortality rates in prostate cancer patients. Using B6-Luc mice we demonstrate that obesity induced a prostatic inflammatory response characterized by increased expression of IL-6 and IL-1[beta]. However, the effects of obesity on prostate cancer progression were inconclusive due to the small number of animals enrolled in the study. Taken together, we have developed novel model systems that will enable the mechanistic basis of prostate cancer progression and response to therapy to be evaluated in the appropriate experimental context.
Download or read book Mouse Models of Human Cancer written by Eric C. Holland and published by John Wiley & Sons. This book was released on 2004-08-27 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mice have become the species of choice for modeling the complex interactions between tumor cells and the host environment. Mouse genetics are easily manipulated, and a growing array of technology exists for this purpose. Mouse models allow investigators to better understand causal relationships between specific genetic alterations and tumors, utilize new imaging techniques, and test novel therapies. Recent developments along these lines show great promise for the development of new anti-cancer treatments. Mouse Models of Human Cancer provides researchers and students with a complete resource on the subject, systematically presenting the principles, methodologies, applications, and challenges associated with this exciting field. Offering a survey of the latest research and a description of future areas of interest, this text: Presents real experimental data Describes organ site-specific mouse models Clearly identifies suitable models for further drug testing Critically analyzes current methodologies and their limitations Features numerous recognizable expert contributors Lists key Web sites, reagents, and companies From mouse handling and genetic engineering to preclinical trials, Mouse Models of Human Cancer is a comprehensive guide to using these models and relating them to human disease. Its uniform presentation describes organ-specific models in clinical, imaging, and molecular terms, and lays out the relevant genetics, experimental approaches, histological comparisons with human disease, and conclusions. Combining stellar chapter authors, rich illustrations, and clear, up-to-date coverage, Mouse Models of Human Cancer is an invaluable resource for advanced students and cutting-edge researchers.
Download or read book The Role of Nkx3 1 in the Initiation and Progression of Prostate Cancer written by Sydika Amari McKissic and published by . This book was released on 2012 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Using Mouse Model to Investigate the Cell Origins for Prostate Epithelial Differentiation and Cancer Initiation written by Tsai-Ling Lu and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Humanizing the Mouse Androgen Receptor to Study Polymorphisms and Mutations in Prostate Cancer written by and published by . This book was released on 2005 with total page 70 pages. Available in PDF, EPUB and Kindle. Book excerpt: Androgen receptor (AR) is a critical component in prostrate oncogenesis. AR alleles varying in length of the Nterminal glutamine (Q) tract carry distinct disease risks. Mutation of AR in tumors may influence androgen independence and resistance to treatment. Difficulties studying cancer initiation and progression are partly overcome with transgenic mouse tumor models. However, the mouse AR N-terminus differs significantly from human.
