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 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 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 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 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 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 Tumor Suppressor Gene and Cancer Stemness Gene in Hepatocellular Carcinoma written by 严倩 and published by . This book was released on 2018 with total page 155 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 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 Characterization of Novel Tumor Suppressor Genes DLC 1 and DLC 2 in Hepatocellular Carcinoma written by Chun-ming Wong (Ph.D.) and published by . This book was released on 2003 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Identification and Characterization of Tumorigenic Liver Cancer Stem Progenitor Cells written by Kwai-Yee Stephanie Ma and published by . 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 tumorigenic liver cancer stem/progenitor cells" by Kwai-yee, Stephanie, Ma, 馬桂宜, 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 Tumorigenic Liver Cancer Stem/Progenitor Cells Submitted by Stephanie Kwai-Yee Ma For the degree of Doctor of Philosophy at The University of Hong Kong July 2007 Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide affecting one million individuals annually. Despite advances in the detection and treatment of the disease, mortality rate remains high because current therapies are limited by the emergence of chemotherapy-resistant cancer cells. Existing chemotherapies against HCC are usually developed against the bulk of the tumor mass, where although they are able to initially shrink the size of the tumor, they fail to eradicate the lesion in full, thus resulting in disease relapse. Recent research efforts in stem cell biology put forth the proposal of a hierarchical "stem cell model of carcinogenesis" which suggests that tumors are organized in a hierarchy of heterogeneous cell populations and that the capability to maintain tumor formation and growth specifically resides in a small population of cells called cancer stem cells (CSCs). The stem cell-like characteristics of these cells and their limited number within the tumor bulk are believed to account for their capability to escape therapies. In this study, we pioneered the identification of an exclusive population of CSCs from human HCC cell lines and xenograft tumors. CD133 expression in cultured cell lines was found to correlate with the ability of the cells to develop tumor in vivo. Functional studies on + - + sorted CD133 and CD133 cells found CD133 cells to be inherently more tumorigenic; showing a greater colony-forming efficiency, higher proliferative output and greater ability to form tumor in vivo. As few as 1000 CD133 cells were sufficient for consistent tumor development in SCID mice while at least 50x as many CD133 cells were necessary to generate a tumor in the same model. Moreover, these cells were found to be endowed with characteristics of stem cells including the preferential expression of "stemness" genes, the ability to self-renew and the ability to differentiate into angiomyogenic-like, non-hepatocyte- like lineages. Further, CD133 was found to be maintained in rare numbers in CD133 induced xenograft tumors and human HCC specimens. In addition, CD133 cells were found to be more resistant to anticancer drugs, doxorubicin and 5-fluorouracil; the molecular mechanism by which was mediated via the PI3K/Akt and Bcl-2 survival pathway. Treatment of CD133 cells with an inhibitor specific to AKT1 particularly reduced the expression of 473 136 survival proteins (P-Akt-Ser, P-Bad-Ser, Bcl-2) normally expressed endogenously. In addition, treatment of unsorted cells with both drugs in culture specifically enriched the CD133 subpopulation. Subsequent investigation by 2D-PAGE technique led to the elucidation of aldehyde dehydrogenase 1A1 (ALDH1A1) as an additional differentially expressed marker useful for HCC CSC identification. ALDH1A1 was exclusively expressed + + + in the CD133 subpopulation. More importantly, CD133 ALDH1A1 cells displayed significant preferential tumorigenic potential in vitro, when compared with their respective + - - - CD133 ALDH1A1 or CD133 ALDH1A1 counterparts. In summary, our findings provide a previously uncharacterized model of liver tumor biology in

Download or read book Traditional and Novel Approaches Towards the Identification and Characterization of the Genes Responsible for Hereditary Colorectal and Breast Cancer written by Marco Agostini and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Identification and Characterization of a Putative Tumor Suppressor Gene Akr7a3 in Hepatocellular Carcinoma written by Kwok-Kei Chow and published by . 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 a Putative Tumor Suppressor Gene AKR7A3 in Hepatocellular Carcinoma" by Kwok-kei, Chow, 鄒國基, 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. DOI: 10.5353/th_b5689303 Subjects: Antioncogenes Liver - Cancer - Genetic aspects

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 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 Cd90 Cancer Stem Cells in Hepatocellular Carcinoma written by Wing-Yuen Ho and published by . 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 CD90⁺ Cancer Stem Cells in Hepatocellular Carcinoma" by Wing-yuen, Ho, 何永源, 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 devastating malignancies worldwide with increasing incidences in both developed and developing countries. Survival rates have not been significantly improved over the past decades in spite of advances in detection and therapies for this disease, suggesting that current treatments may target the wrong cells, and miss the cancer stem cells (CSCs). The cancer stem cell hypothesis presents that tumor formation, proliferation and propagation are driven by a rare subpopulation of chemoresistant CSCs that are not killed by conventional therapies and go on to cause disease relapse. The objective of this study was to identify and characterize CSCs in HCC cell lines and human liver tumor specimens using CD90 as a potential marker. The number of CD90+ cells present in HCC cell lines was found to positively correlate with tumorigenicity potentials. Injection of as few as 2,000 sorted CD90+ cells from HCC cell lines resulted in the formation of tumor nodules in nude mice, whereas no tumors formed for CD90ˉcells in the same model. The tumor xenograft generated by injection of CD90+ cells sorted from previous xenograft in a serial xenotransplantation assay exhibited recapitulation of tumor heterogeneity to original primary tumor and consistent proportion of CD90+ and CD90ˉ cells which demonstrated self-renewal and differentiation capacities of CD90+CSCs. CD45ˉCD90+ cells were detected (0.03%-6.2%) in human liver tumor specimens, but were only present in minute quantities in normal, cirrhotic and non-tumorous tissues. More importantly, CD45ˉCD90+ cells sorted from primary HCC tumor also displayed tumorigenicity, self-renewal and lineage differentiation capacities. CD90+CSCs were found to be more resistant to therapeutic drugs compared to CD90- cells, as reflected by the results of enrichment of the CD90+ CSCs and longer survival rates after chemotherapeutic treatment. The high expression of genes, such as OCT4, MRP3, ABCG2, AKT1, BirC5, BCL2, HA and CD44, in CD90+CSCs may mediate chemoresistance. The majority of CD90+ cells co-expressed CD44, another stem cell marker. Blocking CD44 activities by anti-CD44 antibody increased apoptosis of CD90+ CSCs, sensitized CD90+CSCs to chemotherapeutic drugs in vitro, and decreased tumorigenic and metastatic potentials of CD90+CSCs in vivo, indicating that a therapeutic potential of targeting CD44. However side effects may be problematic due to the endogenous expression of CD44 in healthy tissues and normal lymphocytes. To identify novel gene targets specific to liver CSCs, a sensitive RNA-sequencing (RNA-Seq) technique was used to compare the gene expression profiles between CD90+CSCs sorted from HCC primary tumors and CD90+cells from adjacent non-tumorous tissue (CD90+NTSCs). The up-regulated genes in CD90+CSCs were associated with lipid metabolism, inflammation, and drug resistance. Among the differentially expressed genes, glypican-3 (GPC3) was specifically elevated in CD90+CSCs but not in CD90+NTSCs. Therefore, GPC3 could be a promising gene candidate for HCC therapy as targeting GPC3 should not induce damage to normal liver stem cells. In summary, CD90 is a liver CSCs marker. Identification of CD90+ CSCs in HCC provides new insight into cellular basis of hepatocarcinogenesis, recurrence and metastasis, which opens new avenues for the design of future CSC-targeted therapies. D

Download or read book Identification and Characterization of Stemness related Genes RALYL and S100A10 in the Development and Progression of Hepatocellular Carcinoma written by 王霞 and published by . This book was released on 2019 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: