Download or read book Identification and Characterization of Novel Genetic Alterations in the Progression of Hepatocellular Carcinoma written by 劉銘 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 Identification and Characterization of Novel Genetic Alterations in the Progression of Hepatocellular Carcinoma written by Ming Liu and published by Open Dissertation Press. This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Identification and Characterization of Novel Genetic Alterations in the Progression of Hepatocellular Carcinoma" by Ming, Liu, 劉銘, 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: Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally believed that accumulation of irreversible alterations in critical oncogenes and tumor suppressor genes during the long-term inflammation finally leads to the hepatocellular pathogenesis. Although under intensive investigation, the molecular pathogenesis of HCC still remains to be further elucidated. In this study, we aimed to identify novel genetic alterations critical to the pathogenesis of HCC, especially in hot regions with recurrent chromosomal instability. Amplification of broad regions of 8q is one of the most frequent genetic alterations in HCC, suggesting the existence of oncogenes in addition to MYC at 8q24. By screening the publicly available microarray database and clinical samples, we found frequent amplification and overexpression of Serum and Glucocorticoid Kinase 3 (SGK3) in clinical HCC specimens, and SGK3 genomic activation was significantly associated with poor outcome of HCC patients. Functional assays revealed that SGK3 could increase G1/S cell cycle progression, cell survival, clonogenicity, anchorage-independent growth, and tumor formation in nude mice. We provided evidences that SGK3 could promote HCC growth and survival through inactivating GSK3-β and BAD respectively. We also found that expression of SGK3, which like AKT is activated by PI3K/PDK1, has more significance than overexpression of AKT in predicting poor outcome of HCC patients. Our findings suggested the existence of an AKT-independent SGK3 pathway, which may function in parallel with AKT pathway in the pathogenesis of HCC. In addition to large chromosomal alterations, small changes in nucleotides may also make substantial contributions to carcinogenesis. Recent advances in high-throughput deep sequencing technology have provided a powerful tool to understand the whole cancer transcriptome and identify novel genetic alterations related to cancer progression. In this study, we identified a high proportion of allele imbalance in genes related to cellular stress response by sequencing the whole transcriptome of 3 paired HCC tissues. A novel nucleotide variation which resulted in a R438H amino acid change was identified in the coding region of the gene Oxidative Stress Induced Growth Inhibitor 1 (OSGIN1), and the variant 438H form of OSGIN1 was found to be specifically retained in the tumor tissues in a cohort of HCC patients. OSGIN1 was found to be closely associated with chemotherapeutic reagents and exhibited strong tumor suppressive function in HCC by directly inducing cell apoptosis. The wild type OSGIN1 was found to have stronger tumor suppressive function than the variant allele, and this might be due to their different ability to localize to mitochondria. The significantly decreased basal apoptotic index in HCC patients carrying OSGIN1 variant allele and their poor prognosis further suggested that the specific retention of 438H OSGIN1 might be important in HCC progression. In summary, we found a frequently amplified oncogenic SGK3 signaling pathway, as well as the allele-specific imbalance of tumor suppressive OSGIN1 in the pathogenesis of HCC. Further characterization of their mechanisms in hepatocarcinogenesis may help provide novel prognostic biomarkers and therapeutic targets in HCC treatment. DOI: 10.5353/th_b5177316

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

Download or read book Identification and Characterization of Molecular Targets in Hepatocellular Carcinoma written by Vinay Kumar and published by Frontiers Media SA. This book was released on 2023-07-21 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt: the field of oncology and is the most common form of liver cancer. In some cases, HCC can be treated through surgery and ablations but can be extended to a full transplant. Risk factors for HCC have been elucidated in previous years, linking hepatitis viruses, diabetes, and alcohol-dependent conditions to the pathogenesis of HCC. Given the prevalence of HCC in global populations (currently >800,000 new cases per year, and rising), there is a requirement to identify molecular targets in HCC and develop new therapeutic strategies to manage and treat HCCs. New technologies and techniques, including gene sequencing, bioinformatics, and liquid biopsy, have helped identify molecular and genetic players involved in the development of HCC. As such, a comprehensive genetic/immune signature of HCC would be invaluable in the development of new therapeutics and treatment strategies, as well as early identification and management of HCC. There are currently various trials that implement a combination of already approved drugs to better the prognosis of patients suffering from HCC. There is, however, still room for improvement, and as our understanding of the various factors involved in HCC improves, so will the prognosis of patients suffering from HCC globally. This Research Topic aims to highlight the molecular and genetic targets that lead to the progression of Hepatocellular Carcinoma. We welcome Original Research, Reviews, and other article types.

Download or read book Identification and Characterization of Novel Tumor associated Genes in Liver Cancer written by 洪偉翔 and published by . This book was released on 2010 with total page 98 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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.

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

Download or read book Identification and Characterization of Two Oncogenes Spock1 and Azin1 in Hepatocellular Carcinoma written by Yan Li and published by Open Dissertation Press. This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Identification and Characterization of Two Oncogenes SPOCK1 and AZIN1 in Hepatocellular Carcinoma" by Yan, Li, 李妍, 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: Hepatocellular carcinoma (HCC), which constitutes 75%-80% of primary liver cancer, is one of the most common malignancies worldwide. Hepatocarcinogenesis is a complicated and slow process accumulating multiple genetic and epigenetic alterations. In spite of its prolonged pre-malignant stage, HCC is usually diagnosed late and of high aggressiveness. A better understanding of the genetic and epigenetic changes during HCC development and progression is of great importance to early diagnosis and treatment of HCC. Gain of chromosome 1q21 is one of most frequent genetic alteration in HCC and chromodomain helicase DNA binding protein 1-like (CHD1L) was recently identified to be responsible for this amplification. As a family member of SNF-2 like transcription factors, CHD1L plays an important role in HCC development via regulation of various downstream targets. In this study, a novel oncogene, sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1), was identified as a CHD1L target. CHD1L protein directly bound to the promoter region (nt -1662 to +34) of SPOCK1 and activated its transcription. Clinically, overexpression of SPOCK1 was detected in 60% of human HCC samples and was significantly associated with advanced clinical stage (P=0.020), shorter overall survival (P=0.011) and poorer disease-free survival of patients (P=0.039). Functionally, the ectopic expression of SPOCK1 in HCC cells conferred strong tumorigenic ability, while shRNA-mediated SPOCK1 silencing abolished this effect. Further study showed that the SPOCK1-enhanced cell survival could be attributed to its anti-apoptotic effects. SPOCK1 could suppress HCC cell apoptosis through the activation of AKT and subsequent inhibition of the (cytochrome c)-(caspase-9)-(caspase-3) pathway. In addition to its tumorigenic roles, the overexpression of SPOCK1 in HCC cells conferred strong metastatic ability via MMP9-mediated extracellular matrix remodeling. In addition to genetic alterations, epigenetic changes also get increasing attentions due to their profound effects on gene activity and expression. A-to-I RNA editing is a post-transcriptional epigenetic modification which converts a site-selective adenosine nucleotide into inosine. The importance of RNA editing has long been underestimated because most of RNA editing modifications occur in a subtle way. The next-generation sequencing provides enough depth to unravel this mystery. The transcriptome sequencing data obtained from this study identified an A-to-I RNA editing at codon 367 (Ser→Gly) of antizyme inhibitor 1 (AZIN1). A high modification rate of AZIN1 was found to be prevalent in HCC specimens and closely associated with HCC pathogenesis. Adenosine deaminase acting on RNA-1 (ADAR1), but not ADAR2 or ADAR3, was responsible for AZIN1 RNA editing. This recoding editing event conferred "gain-of-function" phenotypes as manifested by augmented tumorigenic capabilities and higher aggressive potentials. Compared with wild-type AZIN1 protein, the edited form possessed stronger affinity to antizyme. As a result, edited AZIN1 demonstrated higher protein stability and ensuing neutralization of the antizyme-mediated degradation of ODC and CCND1 oncoproteins. The rescued ODC and CCND1 robustly accelerated cell proliferation thereby promoting HCC development. In conclusion, two novel molecular mechanisms, (CHD1L)-(SPOCK1)-(AKT) and (ADAR1)-(edited A

Download or read book Identification and Characterization of Key Genes Involved in the Development and Progression of Hepatocellular Carcinoma written by Sze-hang Lau (Ph. D., Billy) and published by . This book was released on 2007 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Identification and Characterization of TROP 2 as a Novel Tumor Suppressor Gene in Hepatocellular Carcinoma written by 冼子君 and published by . This book was released on 2018 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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:

Download or read book Experimental Hepatocarcinogenesis written by M.B. Roberfroid and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 305 pages. Available in PDF, EPUB and Kindle. Book excerpt: The meeting on experimental hepatocarcinogenesis which took place in Spa, Belgium at the end of May 1987 was the Second European Meeting. About 100 scientists, mostly from Europe but also from the United States, met there for three days in a very friendly atmosphere to exchange knowledge and ideas on experimental and human liver carcinogenesis. The main topics discussed during the meeting included general reviews on hepatocarcinogenesis, experimental models of hepa tocarcinogenesis, biology of hepatocarcinogenesis, and in vitro studies in hepatocarcinogenesis. They are all covered by the various chapters of this proceedings volume, which reflects the present state of knowledge in this important field of cancer research. The final aim of that research is to understand the basic mechanisms of carcinogenesis. The liver offers a parti cularly interesting tool to reach such a goal. Indeed, its biochemistry, its morphology, and its physiology are very diverse, but relatively well known. Various protocols have been developed to produce hepatocellular carcinomas or other malignant tumors. Their appearance is most often preceded by phenotypically altered foci and nodules which have been isolated and characterized. The major cell populations of normal, neoplastic, and malignant livers have been cultivated.

Download or read book The Liver written by Irwin M. Arias and published by John Wiley & Sons. This book was released on 2020-03-09 with total page 1156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.

Download or read book Immunotherapy of Hepatocellular Carcinoma written by Tim F. Greten and published by Springer. This book was released on 2018-08-22 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.

Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Download or read book Biomedical Index to PHS supported Research written by and published by . This book was released on 1995 with total page 1216 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Childhood Acute Lymphoblastic Leukemia written by Ajay Vora and published by Springer. This book was released on 2017-04-21 with total page 345 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive and up-to-date review of all aspects of childhood Acute Lymphoblastic Leukemia, from basic biology to supportive care. It offers new insights into the genetic pre-disposition to the condition and discusses how response to early therapy and its basic biology are utilized to develop new prognostic stratification systems and target therapy. Readers will learn about current treatment and outcomes, such as immunotherapy and targeted therapy approaches. Supportive care and management of the condition in resource poor countries are also discussed in detail. This is an indispensable guide for research and laboratory scientists, pediatric hematologists as well as specialist nurses involved in the care of childhood leukemia.