Molecular Determinants of Radio Resistance in Prostate Cancer

Molecular Determinants of Radio Resistance in Prostate Cancer
Author:
Publisher:
Total Pages: 39
Release: 2003
Genre:
ISBN:

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We are studying the radiation response of prostate tissues in relation to the sensing and repair of DNA breaks. Specific aims relate to determining the interaction of DNA repair proteins in vitro using immunoflorescent confocal microscopy and biochemical DNA rejoining assays under both hypoxic and oxic conditions (given in vivo tumor cell populations). An in vivo program of prostate xenograft radioresponse and patient biopsy studies will determine the level of DNA repair in situ using immunohistochemistry and immunoflorescent markers. Our studies show that DNA repair protein expression is abnormal in malignant% versus normal prostate epithelial cultures, and that particularly the Rad51 protein is defective in localizing to the nucleus following DNA damage. We have accrued 13 patients onto a pre-operative radiotherapy trial and all patients' tumors are p53 wild type based on direct DNA sequencing. Post irradiation immunohistochemistry supports an induction of p53-pathway signaling following 25Gy in 5 fractions of clinical radiotherapy. Current experiments are designed to determine whether DNA protein focal interactions using 2- phtoon microscopy can predict the radioresponse of prostate xenografts and human tumors, in vivo. Our studies support the use of novel molecular based therapies that target NDA repair for prostate cancer therapy.

Molecular Determinants of Radioresponse in Prostate Cancer

Molecular Determinants of Radioresponse in Prostate Cancer
Author:
Publisher:
Total Pages: 72
Release: 2002
Genre:
ISBN:

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The overall hypothesis of this project is that the radiation response of normal and cancerous prostate tissues can be correlated to the appropriate sensing and repair of DNA breaks by repair complexes following exposure to ionizing radiation. Specific aims relate to determining the interaction of DNA repair proteins in vitro using immunofluorescence confocal microscopy and biochemical DNA rejoining assays under both hypoxic and oxic conditions (given in vivo tumor cell populations). An in vivo program of prostate xenograft radioresponse is also being initiated to determine the level of DNA repair in situ using immunohistochemistry and immunofluorescence markers. Our studies show that terminal growth arrest rather than apoptosis is the major death pathway for irradiated prostate cancer cells and that prostate cancer cells have a DNA repair defect when compared to normal prostate epithelial cells. This appears to be related to the expression and intracellular function of the rad51 protein.

Molecular Determinants of Prostate Cancer Progression Across Race-Ethnicity

Molecular Determinants of Prostate Cancer Progression Across Race-Ethnicity
Author:
Publisher:
Total Pages: 19
Release: 2003
Genre:
ISBN:

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This Prostate Cancer Center Initiation grant has been designed to identify genetic and molecular markers of prostate cancer progression within and between racial ethnic groups (African-Americans, Latinos, Whites, Japanese) at substantially distinct underlying risk of prostate cancer. Our Epidemiology Core has obtained signed tissue releases from prostate cancer patients to date identified during follow-up of the Hawaii/Los Angeles Multiethnic Cohort study and has procured 438 tissue samples to date (163 African-Americans, 163 Latinos, 74 Caucasians, and 38 Japanese). These have been processed histopathologically by Project C, which has completed immunohistochemical staining for COX-2, p27, and Caveolin-1 markers with analysis of additional markers ongoing. Project B, studying the androgen receptor (AR) gene in detail, has conducted functional studies to understand non-steroidal activation of AR signaling. Project A, studying the SRD5A2 gene in detail, has characterized a series of the somatic mutations identified in tumors to date using site directed mutagenesis assays.

Molecular Determinants of Prostate Cancer Progression Across Race-Ethnicity. Project A - The Human 5RD5A2 Gene and Prostate Cancer Progression. Project B - Androgen Receptor (AR) Signaling in Prostate Cancer Progression. Project C - Cellular and Molecular Markers of Prostate Cancer Progression Core - Epidemiology Core

Molecular Determinants of Prostate Cancer Progression Across Race-Ethnicity. Project A - The Human 5RD5A2 Gene and Prostate Cancer Progression. Project B - Androgen Receptor (AR) Signaling in Prostate Cancer Progression. Project C - Cellular and Molecular Markers of Prostate Cancer Progression Core - Epidemiology Core
Author:
Publisher:
Total Pages: 39
Release: 2002
Genre:
ISBN:

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This Prostate Cancer Center initiation grant has been designed to identify genetic and molecular markers of prostate cancer progression within and between racial ethnic groups (African-Americans, Latinos, Whites, Japanese) at substantially distinct underlying risk of prostate cancer. Our Epidemiology Core has obtained signed tissue releases from prostate cancer patients to date identified during follow-up of the Hawaii/Los Angeles Multiethnic Cohort study. Two hundred thirty-nine tissue samples have been received and processed histopathologically by Project C, which has begun immunohistochemical staining for COX-2, p27, p2l, p16 and Caveolin-l markers with additional markers to follow. Project B, studying the androgen receptor (AR) gene in detail, has identified 54 sequence variants in 90 samples analyzed to date. Two functional assays were developed this year to better assess these sequence variants. In Project A, studying the SRD5A2 gene in detail, in 87 tumors, the 13 mutations detected to date have been reconstructed by site-directed mutagenesis.

Molecular Targeted Radiosensitizers

Molecular Targeted Radiosensitizers
Author: Henning Willers
Publisher: Springer Nature
Total Pages: 370
Release: 2020-08-10
Genre: Medical
ISBN: 3030497011

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Molecular Targeted Radiosensitizers: Opportunities and Challenges provides the reader with a comprehensive review of key pre-clinical research components required to identify effective radiosensitizing drugs. The book features discussions on the mechanisms and markers of clinical radioresistance, pre-clinical screening of targeted radiosensitizers, 3D radiation biology for studying radiosensitizers, in vivo determinations of local tumor control, genetically engineered mouse models for studying radiosensitizers, targeting the DNA damage response for radiosensitization, targeting tumor metabolism to overcome radioresistance, radiosensitizers in the era of immuno-oncology, and more. Additionally, the book features discussions on high-throughput drug screening, predictive biomarkers, pre-clinical tumor models, and the influence of the tumor microenvironment and the immune system, with a specific focus on the challenges radiation oncologists and medical oncologists currently face in testing radiosensitizers in human cancers. Edited by two acclaimed experts in radiation biology and radiosensitizers, with thirteen chapters contributed by experts, this new volume presents an in-depth look at current developments within a rapidly moving field, with a look at where the field will be heading and providing comprehensive insight into the framework of targeted radiosensitzer development. Essential reading for investigators in cancer research and radiation biology.

Molecular Determinants of Radiation Response

Molecular Determinants of Radiation Response
Author: Theodore L. DeWeese
Publisher: Springer Science & Business Media
Total Pages: 282
Release: 2011-03-23
Genre: Medical
ISBN: 144198044X

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Molecular Determinants of Radiation Response includes chapters by expert authors who detail the present understanding of key DNA damage response pathways and proteins. The chapters include comprehensive discussions on where and how specific alterations in function of these pathways and proteins result in substantive modifications of cellular response to DNA injury. Given the importance of therapies that induce DNA injury in the management of human disease, this book is timely and relevant for basic and translational researchers, as well as clinicians alike.

Molecular Biology of Prostate Cancer

Molecular Biology of Prostate Cancer
Author: Manfred Wirth
Publisher: Walter de Gruyter
Total Pages: 220
Release: 2013-05-22
Genre: Medical
ISBN: 3110807270

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Prostate Cancer

Prostate Cancer
Author: Donald J. Tindall
Publisher: Springer Science & Business Media
Total Pages: 575
Release: 2013-05-09
Genre: Medical
ISBN: 1461468280

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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.

Therapy Resistance in Prostate Cancer

Therapy Resistance in Prostate Cancer
Author: Hisham Bahmad
Publisher: Elsevier
Total Pages: 342
Release: 2023-10-24
Genre: Science
ISBN: 0443160333

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Prostate cancer (PCa) is among the most diagnosed cancers in men worldwide as well as one of the most common causes of cancer-related deaths. Despite the advances in treatment, the disease remains associated with poor survival and resistance to cytotoxic and targeted therapies. Therapy Resistance in Prostate Cancer: Mechanisms and Insights highlights the main mechanisms that are responsible for therapy resistance in PCa allowing researchers and clinicians to have a synopsis of current options and new therapies that can be proposed to overcome this resistance. Understanding the mechanisms responsible for chemotherapy resistance helps researchers all over the world to delve deeper into the pathways behind this resistance and potentially discover new therapeutic targets for PCa. Tackles the topic of resistance from a broader perspective, including, but not limited to, the role of the extracellular matrix and cancer stem cells in therapy resistance Creates understanding on how to develop novel therapies that specifically target CSCs to eliminate the regenerating capacity of the tumor and overcome therapy resistance Helps in identifying novel molecular biomarkers and potential therapeutic targets pertaining to the tumor microenvironment to overcome therapy resistance Provides a general view of the main pathways involved in PCa progression that will aid in understanding the mechanisms responsible for chemotherapy resistance