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 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 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 The Oncogenomics Handbook written by William J. LaRochelle and published by Springer Science & Business Media. This book was released on 2007-11-09 with total page 745 pages. Available in PDF, EPUB and Kindle. Book excerpt: An integrated overview of cancer drug discovery and development from the bench to the clinic, showing with broad strokes and representative examples the drug development process as a network of linked components leading from the discovered target to the ultimate therapeutic product. Following a systems biology approach, the authors explain genomic databases and how to discover oncological targets from them, how then to advance from the gene and transcript to the level of protein biochemistry, how next to move from the chemical realm to that of the living cell and, ultimately, pursue animal modeling and clinical development. Emerging cancer therapeutics including Ritux an, Erbitux, Gleevec Herceptin, Avastin, ABX-EGF, Velcade, Kepivance, Iressa, Tarceva, and Zevalin are addressed. Highlights include cancer genomics, pharmacogenomics, transcriptomics, gene expression analysis, proteomic and enzymatic cancer profiling technologies, and cellular and animal approaches to cancer target validation.
Download or read book Prostate Cancer and Bone Metastasis written by James P. Karr and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: The biology of solid tumor metastasis has been the subject of significant scientific and clinical interest for years and while experimental evidence reveals that metastasis is not solely a random event, very little is known about the biology of metastasis originating from prostate cancer. This is in spite of the fact that the majority of prostate cancer patients die with metastatic lesions to the bone. Progress in understanding this most important aspect of prostate cancer has been hampered by the lack of suitable animal models and an inability to accurately quantify bone metastases and their responses to therapy. Over the past decade, scientists in Japan and the United States have steadily advanced our understanding of the cellular, molecular and immunologic biology of primary and disseminated prostate cancer. It is this body of new information, combined with advances in imaging techniques and prostate cancer tumor markers, that prompted the need for an in-depth assessment of bone metastasis of prostate cancer. Accordingly, on December 12, 1990, a group of basic and clinical investigators from Japan and the United States convened in Gotenba, Japan, to hold the first conference devoted solely to the basic biology and clinical aspects of bone metastases originating from prostate cancer. The cross-fertilization of ideas that was fostered through in-depth discussion of technological advances among various basic and clinical disciplines not only further advanced our understanding of prostate metastases to the bone, but suggested approaches for precise quantitative assessment of these lesions and their treatment.
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 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 Pathogenesis of Osteoblastic Metastasis in Prostate Cancer written by Nanda Kumar Thudi and published by . This book was released on 2009 with total page 268 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Prostate cancer (PCa) is the most commonly diagnosed cancer in men accounting for 25% of the new cases every year in the USA. PCa is the second leading cause of cancer-related deaths due to the development of serious skeletal complications in advanced stages of the disease. Bone metastases in PCa are predominantly osteoblastic characterized by formation of excessive low quality woven bone leading to spinal cord compression, paralysis, pathological fractures and severe pain eventually resulting in a poor quality of life. Therefore, bone metastasis represents a major clinical and research interest to investigate and develop therapeutic strategies. Previously, our lab established a canine PCa cell line (Ace-1) that metastasized to bone and caused mixed osteoblastic and osteolytic lesions in nude mice similar to that observed in human patients. We utilized this animal model to investigate the molecular pathogenesis of bone metastasis. First, we investigated the role of osteolytic activity in the development of bone metastasis by inhibiting bone resorption with the bisphosphosphonate, zoledronic acid. We showed that zoledronic acid significantly inhibited osteolysis in this model, but did not affect the PCa growth, incidence and the osteoblastic phenotype of the metastases. These data demonstrated that PCa bone metastases were independent of osteolysis and that PCa secreted factors that directly regulated bone metastasis. To explore the molecular mechanisms involved in metastasis, we investigated the role of Wnt signaling that plays an important role in oncogenesis and osteogenesis in the progression of prostate cancer growth, and incidence and osteoblastic phenotype of bone metastases. Antagonizing Wnt signaling using Dickkopf-1 (Dkk-1) in our model resulted in increased tumor growth although it significantly decreased new woven bone formation in the metastases. In conclusion, these investigations demonstrated PCa secrete factors that induce bone metastasis. Importantly, Wnt signaling in PCa was important for the induction of the osteoblastic phenotype in bone metastases which was inhibited by Dkk-1. Therefore, investigating the factors responsible for prostate cancer-induced bone induction in bone metastases will be useful to design novel therapeutics.
Download or read book Bone Metastases from Prostate Cancer written by Francesco Bertoldo and published by Springer. This book was released on 2016-11-07 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents up-to-date information on one of the hottest topics in prostate cancer, namely bone metastases. The most recent developments with respect to biology, pathology, diagnosis, and treatment are described, providing readers with an excellent understanding of the mechanisms of metastasis formation, the characteristics of metastases, their aggressiveness, and prognostic factors for treatment response. The coverage includes discussion of all of the best available options (laboratory, radiology, and nuclear medicine) for achieving early diagnosis and both established and novel therapeutic approaches. Detailed information is provided on hormonal manipulations, bone-targeted agents, vaccines, taxanes, and other treatments that are enriching the therapeutic armamentarium. The editors can be considered leaders in the field, with great experience in diagnostic and clinical oncology and research, and the authors are experts in diverse specialties. This ensures a multidisciplinary approach, mirroring the current situation in which treatment in patients with bone metastases is undertaken by a team of specialists and health professionals in a variety of fields.
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 Developing a Hoxb13 based Mouse Model of Lethal Metastatic Prostate Cancer written by Nicole Briceno and published by . This book was released on 2015 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer (PCa) is the second most lethal cancer in men with a five year survival rate of only 30 percent. However, it is from metastases to the lung, bone, and lymph that patients will die, not from the primary prostatic cancer. In order to create treatments for this lethal form, researchers need a reliable model that emulates human progression of the disease. Over the last 15 years, there has been great progress made in genetically engineered mouse models using androgen-driven promoters to force oncogene expression. However, these models are not useful in the study of androgen independent PCa, from which most metastases derive. Additionally, existing models do not develop metastases to bone or lung that are common in human PCa. To improve on existing mouse PCa models, a mouse overexpressing the oncogene MYC with loss of the tumor suppressor PTEN under the control of Hoxb13 regulatory elements, termed BMPC, was developed. This model, which involves breeding together three separate transgenic mouse strains, develops adenocarcinoma by 12 weeks of age with metastases in essentially all cases. However, to be useful as a pre-clinical model additional aspects must be included for imaging along with a simplification of the breeding. The goal of my Master’s thesis project is to genetically simplify the BMPC model, and to add a new functionality in the form of human prostate specific membrane antigen (PSMA) expression. This will be accomplished by expressing the proteins through a single transgene using the “self-cleaving” ability of foot and mouth disease virus-derived 2A peptide proteins. Transgenic mice carrying this multifunctional BAC will be derived and characterized in terms of gene expression and function. This model can be used to study the efficacy of treatments such as targeted nanoparticle delivery, a developing method of clinical cancer treatment.
Download or read book Bone Metastasis and Molecular Mechanisms written by Gurmit Singh and published by Springer Science & Business Media. This book was released on 2013-11-11 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: Patients with advanced breast or prostate cancers usually develop bone metastases. The principal complications resulting from metastatic bone disease are pain, spinal cord compression, pathologic fractures and bone marrow suppression. Improving the management of bone metastases is crucial to quality of life for patients with breast and prostate cancer. Advances in understanding of the molecular mechanisms underlying the pathophysiology of bone metastasis are driving the development of new therapeutic strategies.
Download or read book Characterization of Testosterone Loaded Polydimethylsiloxane Pellets for a Mouse Model of Metastatic Prostate Cancer written by Quinlan, Jr. (John Andrew) and published by . This book was released on 2019 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: Approximately one in six men are affected by prostate cancer, making it the most common cancer among men in the United States. For localized disease, the five-year survival rates are around 99%, however two out of every three patients that progress to metastatic disease will succumb to prostate cancer within five years. Androgens play a significant role in prostate cancer progression and biology and are a therapeutic target to slow metastatic progression. Most mouse models that are used to study prostate cancer do not incorporate changes in androgen level into the system. Here, we produce and characterize a silicone-based pellet loaded with testosterone optimized for use in a mouse model. The pellet provides slow release of bioactive testosterone in vitro and induces no cytotoxicity. Subcutaneously implanted in mice, the pellet provides elevated testosterone levels for two weeks, and surgical removal of the pellet causes serum testosterone levels to drop to castrate levels within two days. Importantly, the pellet induces minimal inflammation as observed histologically, meaning that the pellet can be implemented in a mouse model of metastatic prostate cancer without inducing the release of cytokines and other factors that may alter disease biology.
Download or read book Principles of Bone Biology written by John P. Bilezikian and published by Academic Press. This book was released on 2008-09-29 with total page 2074 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Bone Biology provides the most comprehensive, authoritative reference on the study of bone biology and related diseases. It is the essential resource for anyone involved in the study of bone biology. Bone research in recent years has generated enormous attention, mainly because of the broad public health implications of osteoporosis and related bone disorders. - Provides a "one-stop" shop. There is no need to search through many research journals or books to glean the information one wants...it is all in one source written by the experts in the field - The essential resource for anyone involved in the study of bones and bone diseases - Takes the reader from the basic elements of fundamental research to the most sophisticated concepts in therapeutics - Readers can easily search and locate information quickly as it will be online with this new edition
Download or read book Transgenic Models for Prostate Cancer written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: During phase II of this IDEA Award, our goal was to study genes/pathways implicated in prostate cancer progression using transgenic mouse models. Our efforts focused on creating transgenic models that express 1 of 4 different genes in the mouse prostate. All 4 genes were selected based on studies from our lab and others implicating these genes in human prostate cancer. These include Her-2/neu, cathepsin D, Akt, and Myc. We were successful in generating each of the transgenic mice, and the phenotypes of 3 of them (Cathepsin D, Akt, and Nyc) have been fully characterized. Cathepsin D and Akt mice develop prostatic intraepithelial neoplasia (PIN) only, whereas Myc mice develop PIN that progresses to invasive prostatic adenocarcinoma. In addition, we created transgenic mice expressing the avian retrovirus receptor TVA to permit introduction of multiple transgenes into the prostate in a stepwise manner and to manipulate androgen levels without affecting transgene expression. We documented successful infection with avian retroviruses expressing marker genes (CEP) and are optimizing conditions for transfer of oncogenes. We also generated luciferase transgenic mice, which allow us to visualize the mouse prostate using optimal imaging tools.
Download or read book The Principles of Humane Experimental Technique written by William Moy Stratton Russell and published by Hyperion Books. This book was released on 1992 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt:
