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Author: Vivek M. Rangnekar
Publisher: Springer Nature
ISBN: 3030805581
Category : Medical
Languages : en
Pages : 329
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Book Description
Par-4 is a naturally occurring tumor suppressor. Studies have indicated that overexpression of Par-4 selectively induces apoptosis in cancer cells while leaving normal, health, cells unaffected. Mechanisms contributing to this cancer-selective action of Par-4 have been associated with PKA activation of intracellular Par-4 in cancer cells or GRP78 expression primarily on the surface of cancer cells. On the other hand, endogenous Par-4 sensitizes cells to the action of a broad range of apoptotic inducers acting via the extrinsic and intrinsic pathways. A number of binding partners of Par-4 have been identified and shown to regulate Par-4 function in cancer and other diseases, such as Alzheimer’s and major depression. Recent studies have recognized a number of natural products, dietary supplements, synthetic molecules and FDA-approved drugs that induce the secretion of Par-4 protein to cause apoptosis in primary or metastatic tumors, one of which is in clinical trials. More than 50 different laboratories worldwide are involved in Par-4 based research of this unique protein that has progressed from the bench to clinical trials. This second, companion volume will provide a comprehensive overview of Par-4’s role in cancer and other diseases. Chapters are written by leading researchers, and will be useful for a broad audience across the scientific community, particularly students and trainees, who are the next generation of scientists and clinicians to participate in new studies and discoveries on Par-4.
Author: Vivek M. Rangnekar
Publisher: Springer Nature
ISBN: 3030805581
Category : Medical
Languages : en
Pages : 329
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Book Description
Par-4 is a naturally occurring tumor suppressor. Studies have indicated that overexpression of Par-4 selectively induces apoptosis in cancer cells while leaving normal, health, cells unaffected. Mechanisms contributing to this cancer-selective action of Par-4 have been associated with PKA activation of intracellular Par-4 in cancer cells or GRP78 expression primarily on the surface of cancer cells. On the other hand, endogenous Par-4 sensitizes cells to the action of a broad range of apoptotic inducers acting via the extrinsic and intrinsic pathways. A number of binding partners of Par-4 have been identified and shown to regulate Par-4 function in cancer and other diseases, such as Alzheimer’s and major depression. Recent studies have recognized a number of natural products, dietary supplements, synthetic molecules and FDA-approved drugs that induce the secretion of Par-4 protein to cause apoptosis in primary or metastatic tumors, one of which is in clinical trials. More than 50 different laboratories worldwide are involved in Par-4 based research of this unique protein that has progressed from the bench to clinical trials. This second, companion volume will provide a comprehensive overview of Par-4’s role in cancer and other diseases. Chapters are written by leading researchers, and will be useful for a broad audience across the scientific community, particularly students and trainees, who are the next generation of scientists and clinicians to participate in new studies and discoveries on Par-4.
Author: Vivek M. Rangnekar
Publisher: Springer Nature
ISBN: 3030735729
Category : Medical
Languages : en
Pages : 328
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Book Description
Par-4 is a tumor suppressor protein first discovered and identified in 1993 by Dr. Vivek Rangnekar’s laboratory in prostate cancer cells undergoing apoptosis. Par-4 (later also known as PAWR) is a naturally occurring tumor suppressor. Studies have indicated that Par-4 selectively induces apoptosis in cancer cells while leaving normal, healthy, cells unaffected. Mechanisms contributing to the cancer-selective action of Par-4 have been associated with protein kinase A activation of intracellular Par-4 in cancer cells or GRP78 expression primarily on the surface of cancer cells. Par-4 is downregulated, inactivated or mutated in diverse cancers. This first of two volumes will be the first on the market on the topic of Par-4, and will provide the opportunity for researchers to discuss the future direction of studies, broaden the scope of research, and contribute a more complete understanding of the molecule’s structural features, key functional domains, regulation and relevant basic and clinical/translational facets.
Author: Nathalia Araujo
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Author: James Sledziona
Publisher:
ISBN:
Category :
Languages : en
Pages : 126
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Book Description
Author: Jeffrey Nguyen
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Cancer is a disease where normal cells proliferate uncontrollably, which can ultimately lead to significant morbidity and death. The aggressiveness and mortality of cancers vary by type: certain cancers respond well to treatment, such as pediatric leukemias, whereas pancreatic cancer and glioblastoma have a high mortality and low five-year survival. In an effort to improve current cancer therapies, I focus on elucidating the function and regulation of prostate apoptosis response-4 (Par-4) in various cancers. Par-4 is a tumor-suppressor that has been shown to induce cancer cell selective apoptosis and to sensitize cancer cells to apoptotic stimuli, such as chemotherapeutics and radiation, and therefore has therapeutic potential. In the first part of this work, I focused on studying the effect of Par-4 on cell migration, invasion, and the epithelial-mesenchymal transition in colon cancer cells. I found that ectopic expression of Par-4 inhibited both cell migration and cell invasion, while knocking down Par-4 promoted cell migration in SW480 and SW620 colon cancer cells. In addition, I found that Par-4 overexpression appeared to induce a mesenchymal-epithelial transition in SW620 cells. In the second part of this work, I sought to identify novel regulators of Par-4 and elucidate the mechanism of regulation. I identified Trim21 as a novel binding partner in colon cancer cells, and show that Trim21 overexpression in the presence of cisplatin downregulates Par-4 in colon and pancreatic cancer cell lines, and show that modulating levels of Trim21 and Par-4 affects the sensitivity of cancer cells to cisplatin. Finally, I demonstrate that Trim21 mRNA levels correlate with survival in pancreatic cancer patients, with lower Trim21 levels correlating with increased overall survival and disease-free survival and high Trim21 levels correlating with reduced disease-free survival. In the third part of this work, I sought to determine whether Par-4 could enhance the effectiveness of chemotherapeutics and small molecule drugs. I chose to focus on glioma due to the lack of effective therapeutics. I show that ectopic Par-4 expression alone is sufficient to reduce cell viability and to induce apoptosis in glioma cell lines, A172 and SNB19. Furthermore, I demonstrate that Par-4 transfected glioma cells are sensitized to 5-fluorouracil and ISC-4. Taken together, the results presented in this dissertation suggest novel roles and regulatory mechanisms of Par-4 in cancer, and provide rationale for its use in cancer treatment; as well as suggesting a novel prognostic marker for pancreatic cancer.
Author: David E. Fisher
Publisher: Springer Science & Business Media
ISBN: 1592592309
Category : Medical
Languages : en
Pages : 441
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Book Description
David Fisher, MD, PhD, and an authoritative panel of academic, cutting-edge researchers review and summarize the current state of the field. Describing the broad roles of tumor suppressors from a perspective based in molecular biology and genetics, the authors detail the major suppressors and the pathways they regulate, including cell cycle progression, stress responses, apoptosis, and responses to DNA damage. Leading-edge and forward-looking, Tumor Suppressor Genes in Human Cancer illuminates what is currently known of tumor suppressor genes and their regulation, work that is already beginning to revolutionize cancer target elucidation, drug discovery, and treatment design.
Author: Joseph Thomas Greene
Publisher:
ISBN:
Category : B cells
Languages : en
Pages : 132
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Book Description
The Eμ-TCL1 mouse is a B cell leukemia model commonly used to test the efficacy of experimental therapeutics and interrogate the functions of oncogenes and tumor suppressors. The CLL-like disease in this mouse shares similar pathology and molecular etiology with the human variant. We therefore hypothesized that overexpression of the human isoform of Par-4 in the B cells of this mouse would impede disease progression through either an anti-proliferative or pro-apoptotic mechanism. Consistent with this hypothesis, results indicated that B cell-specific overexpression of human Par-4 reduced the rate of T Cell Leukemia/Lymphoma 1 (TCL1)-induced leukemogenesis. In addition, B cell-specific knockout of endogenous Par-4 increased the rate of TCL1-induced leukemogenesis. Par-4 activity is regulated through a variety of mechanisms, which seem to give it a pleiotropic property. It is generally thought to act as either an anti-proliferative or pro-apoptotic tumor suppressor. In our study, TCL1 mice overexpressing human Par-4 were found to harbor malignant B cell clones that proliferated at reduced rates when compared to their Par-4 wild-type (WT) littermates. This indicated that Par-4 was reducing the expansion of overexpressing cells; which we found interesting, because Par-4 overexpressing mice null for the TCL1 oncogene exhibited no phenotype when examined in various immune response assays.
Author: Kazuwa Nakao
Publisher: Springer
ISBN: 4431556516
Category : Science
Languages : en
Pages : 330
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Book Description
This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Author: Olivier Micheau
Publisher: Springer
ISBN: 3319568051
Category : Medical
Languages : en
Pages : 320
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Book Description
This volume provides the current understanding of death receptor's/TLR3 signaling regulation in cancer. Death receptors, including TRAIL-R1, TRAIL-R2, Fas and TNF-RI, owing to their ability to trigger apoptosis and to contribute to the elimination of cancer cells by the immune system have been considered, to variable extent, as important therapeutic targets for cancer therapy. But an increasing body of evidence suggests that some of these receptors may also contribute to tumorigenesis, or that new players such as TLR3 may be targeted for cancer therapy due to their ability to behave like death receptors.
Author: Stefan Grimm
Publisher: Springer
ISBN: 144716458X
Category : Science
Languages : en
Pages : 288
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Book Description
This book discusses the emergence of a new class of genes with a specific anticancer activity. These genes, recently defined as “Anticancer Genes”, are reviewed in individual chapters on their mode of action, the specific cell death signals they induce, and the status of attempts to translate them into clinical application. Anticancer Genes provides an overview of this nascent field, its genesis, current state, and prospect. It discusses how Anticancer Genes might lead to the identification of a repertoire of signaling pathways directed against cellular alterations that are specific for tumor cells. With contributions from experts worldwide, Anticancer Genes is an essential guide to this dynamic topic for researchers and students in cancer research, molecular medicine, pharmacology and toxicology and genetics as well as clinicians and clinical researchers interested in the therapeutic potential of this exciting new field.
