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Book Identification and Characterization of a Novel Tumor Suppressor Gene  Delected in Liver Cancer 2   Dlc2

Download or read book Identification and Characterization of a Novel Tumor Suppressor Gene Delected in Liver Cancer 2 Dlc2 written by Ho-Yin Thomas Leung and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Identification and Characterization of a Novel Tumor Suppressor Gene, Delected in Liver Cancer 2, (DLC2)" by Ho-yin, Thomas, Leung, 梁浩然, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Identification and characterization of a novel tumor suppressor gene, deleted in liver cancer 2, (DLC2)" Submitted by Leung Ho Yin, Thomas for the degree of Doctor of Philosophy at The University of Hong Kong in December 2005 The deleted in liver cancer 2 (DLC2) gene, located at chromosome 13q12.3, is a recently identified tumor suppressor gene. The DLC2 gene has striking homology to another tumor suppressor gene, DLC1, located at chromosome 8p22-8p21.3. The DLC2 gene is frequently underexpressed in human hepatocellular carcinoma and its chromosomal region shows frequent deletion. DLC2 encodes a novel RhoGTPase-activating protein (RhoGAP) specific for small RhoGTPases, RhoA and Cdc42. With bioinformatic analysis, we have identified four different isoforms of DLC2, which we named DLC2α, β, γ and δ. Three of the isoforms contain the RhoGAP domain, namely, DLC2α, β and γ. Ectopic expression of these three isoforms in mouse fibroblasts showed cytoplasmic localization. Interestingly, overexpression of these isoforms suppressed the lysophosphatidic acid-induced stress fiber formation in mouse fibroblasts and changed the morphology of the transfected cells from angular and spindle to round. Furthermore, the RhoA pull-down assay demonstrated a remarkable reduction in RhoA activity in the DLC2 transiently transfected cells. In contrast, cells transfected with inactive DLC2 GAP-mutant remained unchanged in cell morphology, actin stress fiber formation, and RhoA activity. HepG2 hepatoma cells stably transfected with the DLC2γ isoform also changed to a round morphology, as in mouse fibroblasts. Significantly, these DLC2γ stable transfectants showed marked suppression in cell proliferation, cell cycle progression, cell motility and transformation, and there was a remarkable reduction in in vivo RhoA activity in these cells. These results suggest that DLC2 exhibits its tumor suppressor functions in vivo as a GTPase activating protein specific for RhoA, exerting its effects in suppression of cytoskeleton reorganization, cell growth, cell migration and transformation. (An abstract of 260 words) DOI: 10.5353/th_b3644505 Subjects: Antioncogenes Liver - Cancer - Genetic aspects

Book Identification and Characterization of a Novel Tumor Suppressor Gene  Delected in Liver Cancer 2   DLC2

Download or read book Identification and Characterization of a Novel Tumor Suppressor Gene Delected in Liver Cancer 2 DLC2 written by Ho-yin Leung (Ph.D., Thomas) and published by . This book was released on 2005 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Characterization of Novel Tumor Suppressor Genes  DLC 1 and DLC 2  in Hepatocellular Carcinoma

Download or read book Characterization of Novel Tumor Suppressor Genes DLC 1 and DLC 2 in Hepatocellular Carcinoma written by Chun-Ming Wong and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Characterization of Novel Tumor Suppressor Genes, DLC-1 and DLC-2, in Hepatocellular Carcinoma" by Chun-ming, Wong, 黃俊銘, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Characterization of Novel Tumor Suppressor Genes, DLC-1 and DLC-2, in Hepatocellular Carcinoma Submitted by Wong Chun-Ming For the degree of Doctor of Philosophy at the University of Hong Kong in December 2003 Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Although the risk factors are well known, the underlying molecular mechanisms contributing to hepatocarcinogenesis are far from clear. Deletions of chromosomal materials are the most frequent genetic alteration found in HCC. Allelic losses in HCC show a non-random pattern, and chromosomes 8p and 13q are two of the most susceptible chromosomal arms. However, critical regions of loss and putative suppressor genes on 8p and 13q have not been firmly identified. Our experimental data indicated that allelic losses on chromosomes 8p and 13q were frequent in HCC and were associated with aggressive tumor phenotypes. In addition, our results showed recurrent losses on the sub-chromosomal regions 8p21.3-22 and 13q12.3. Such recurrent losses suggest the presence of putative tumor suppressor genes, loss of which may be important to HCC development and progression. In search of candidate tumor suppressor genes in these regions, we identified a novel gene DLC-2 (deleted in liver cancer 2) at 13q12.3. DLC-2 shared a high sequence homology with putative tumor suppressor gene DLC-1 at 8p21.3-22. Both DLC-1 and DLC-2 are GTPase activating proteins that activate the intrinsic GTPase activity of RhoA and Cdc42 and switch them off by converting the active GTP-bound state to the inactive GDP-bound state. Several lines of evidence suggest that aberrant activation of Rho proteins is oncogenic. Thus, it is not surprising that DLC-1 and DLC-2 may function as a tumor suppressor. Although we rarely found somatic mutations in the RhoGAP domain of DLC-1 or DLC-2 mRNA, deletion of DLC-1 or DLC-2 locus as revealed by loss of heterozygosity analysis was frequent in human HCC. In addition, DLC-1 and DLC-2 were significantly underexpressed at mRNA levels in primary HCC, suggesting that loss of DLC-1 and DLC-2 functions as a result of downregulated mRNA expression might contribute to hepatocarcinogenesis. Furthermore, DLC-1 promoter methylation was found in 6 (24%) of 25 primary HCCs and in hepatoma cell lines showing loss of DLC-1 mRNA expression. Our results indicated that both genetic and epigenetic alterations play an important role in inactivation of the DLC-1 gene in hepatocarcinogenesis. We also characterized the tumor suppression function of DLC-1 and DLC-2. We noticed that colony formation was significantly inhibited by transient transfection of DLC-1 cDNA into hepatoma cell lines with no DLC-1 expression. Furthermore, stable expression of DLC-1 mRNA successfully suppressed the proliferation, mitogen- independent growth, and anchorage-independent growth capabilities of SMMC-7721 cells. On the other hand, expression of the GAP domain of DLC-2 in mouse fibroblasts sufficiently repressed Ras signaling and Ras-induced cellular transformation. Overall, our findings suggest that DLC-1 and DLC-2 play an important role in hepatocarcinogenesis. An abstract of 439 words DOI: 10.5353/th_b2776853 Subjects: Liver - Cancer - Genetic aspects Antioncogenes

Book Hepatocellular Carcinoma

Download or read book Hepatocellular Carcinoma written by Yujin Hoshida and published by Springer. This book was released on 2019-08-05 with total page 366 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive overview of the current limitations and unmet needs in Hepatocellular Carcinoma (HCC) diagnosis, treatment, and prevention. It also provides newly emerging concepts, approaches, and technologies to address challenges. Topics covered include changing landscape of HCC etiologies in association with health disparities, framework of clinical management algorithm, new and experimental modalities of HCC diagnosis and prognostication, multidisciplinary treatment options including rapidly evolving molecular targeted therapies and immune therapies, multi-omics molecular characterization, and clinically relevant experimental models. The book is intended to assist collaboration between the diverse disciplines and facilitate forward and reverse translation between basic and clinical research by providing a comprehensive overview of relevant areas, covering epidemiological trend and population-level patient management strategies, new diagnostic and prognostic tools, recent advances in the standard care and novel therapeutic approaches, and new concepts in pathogenesis and experimental approaches and tools, by experts and opinion leaders in their respective fields. By thoroughly and concisely covering whole aspects of HCC care, Hepatocellular Carcinoma serves as a valuable reference for multidisciplinary readers, and promotes the development of personalized precision care strategies that lead to substantial improvement of disease burden and patient prognosis in HCC.

Book Systems Biology of Cancer

Download or read book Systems Biology of Cancer written by Sam Thiagalingam and published by Cambridge University Press. This book was released on 2015-04-09 with total page 597 pages. Available in PDF, EPUB and Kindle. Book excerpt: An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.

Book Index Medicus

Download or read book Index Medicus written by and published by . This book was released on 2004 with total page 2520 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

Book Heat Shock Proteins in Cancer

    Book Details:
  • Author : Stuart K. Calderwood
  • Publisher : Springer Science & Business Media
  • Release : 2007-09-09
  • ISBN : 1402064012
  • Pages : 399 pages

Download or read book Heat Shock Proteins in Cancer written by Stuart K. Calderwood and published by Springer Science & Business Media. This book was released on 2007-09-09 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.

Book Signal Transduction in Cancer

    Book Details:
  • Author : David A. Frank
  • Publisher : Springer Science & Business Media
  • Release : 2002-12-31
  • ISBN : 1402073402
  • Pages : 358 pages

Download or read book Signal Transduction in Cancer written by David A. Frank and published by Springer Science & Business Media. This book was released on 2002-12-31 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

Book Cumulated Index Medicus

Download or read book Cumulated Index Medicus written by and published by . This book was released on 2000 with total page 1844 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Comparative Oncology

Download or read book Comparative Oncology written by Alecsandru Ioan Baba and published by . This book was released on 2007 with total page 787 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Leong s Manual of Diagnostic Antibodies for Immunohistology

Download or read book Leong s Manual of Diagnostic Antibodies for Immunohistology written by Runjan Chetty and published by Cambridge University Press. This book was released on 2016-11-28 with total page 525 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing a unique A-Z guide to antibodies for immunohistology, this is an indispensable source for pathologists to ensure the correct application of immunohistochemistry in daily practice. Each entry includes commercial sources, clones, descriptions of stained proteins/epitopes, the full staining spectrum of normal and tumor tissues, staining pattern and cellular localization, the range of conditions of immunoreactivity, and pitfalls of the antibody's immunoprofile, giving pathologists a truly thorough quick-reference guide to sources, preparation and applications of specific antibodies. Appendices provide useful quick-reference tables of antibody panels for differential diagnoses, as well as summaries of diagnostic applications. Expanded from previous editions with over forty new entries, this handbook for diagnostic, therapeutic, prognostic and research applications of antibodies is an essential desktop book for practicing pathologists as well as researchers, residents and trainees.

Book Clinical Gynecology

    Book Details:
  • Author : Eric J. Bieber
  • Publisher : Cambridge University Press
  • Release : 2015-04-23
  • ISBN : 1107040396
  • Pages : 1127 pages

Download or read book Clinical Gynecology written by Eric J. Bieber and published by Cambridge University Press. This book was released on 2015-04-23 with total page 1127 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written with the busy practice in mind, this book delivers clinically focused, evidence-based gynecology guidance in a quick-reference format. It explores etiology, screening, tests, diagnosis, and treatment for a full range of gynecologic health issues. The coverage includes the full range of gynecologic malignancies, reproductive endocrinology and infertility, infectious diseases, urogynecologic problems, gynecologic concerns in children and adolescents, and surgical interventions including minimally invasive surgical procedures. Information is easy to find and absorb owing to the extensive use of full-color diagrams, algorithms, and illustrations. The new edition has been expanded to include aspects of gynecology important in international and resource-poor settings.