Download or read book Investigation of Tumor Suppressive Role of Chromosome 9 in Esophageal Squamous Cell Carcinoma written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Xvii, 144 leaves : ill. (some col.) ; 30 cm.
Download or read book Role of Dnajb6 in Esophageal Squamous Cell Carcinoma written by Zhuoyou Yu 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, "Role of DNAJB6 in Esophageal Squamous Cell Carcinoma" by Zhuoyou, Yu, 余卓由, 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: Esophageal cancer (EC), which is geographically diverse, has only a 10.7% five-year survival rate. One of the histologic forms, esophageal squamous cell carcinoma (ESCC), in Hong Kong accounts for 81.5% of the total EC cases and its five-year survival rate is only 14%, due to its high frequency of metastasis. In our previous studies, functional complementation study of chromosome 9 defects led to the discovery of a novel tumor suppressor gene, Deleted in Esophageal Cancer 1 (DEC1), mapping to 9q32. DEC1 was shown to reduce tumorigenicity in a mouse model and its expression was shown to be associated with lymph node metastasis, early onset of ESCC, and familial ESCC development in a tissue microarray (TMA) study. Moreover, DNAJ (Hsp40) homologue subfamily B member 6 (DNAJB6), a molecular co-chaperone protein and the focus of the current study, was identified as a DEC1-interacting protein through a yeast two-hybrid screening. The interaction was further confirmed by the GST pull-down assay and co-localization studies. Using a TMA constructed with ESCC tissues from Hong Kong, the clinical relevance of DNAJB6 expression was demonstrated. In the present study, the role of DNAJB6 in ESCC was investigated using cell line-based in vivo and in vitro studies. DNAJB6 was shown to be down-regulated in ESCC cell lines. The two isoforms of DNAJB6 have distinct subcellular localizations, with DNAJB6a mainly localized to the nucleus and DNAJB6b diffused throughout the cell. Existence of a functional nuclear localization signal peptide and a functional nuclear export signal peptide was verified in DNAJB6a and DNAJB6b, respectively. In vitro evidence of possible DNAJB6a truncation was found. In vivo subcutaneous nude mice tumorigenicity assays showed that over-expression of DNAJB6a, but not DNAJB6b, suppresses tumor growth at the primary site, while DNAJB6a silencing enhances tumor growth. The suppressive effect of DNAJB6a depends on nuclear localization of the protein and the HPD tripeptide motif in the N-terminal J domain. In vitro function studies show that DNAJB6a over-expression impairs cell proliferation by suppressing G1/S transition. AKT1 phosphorylation is down-regulated in DNAJB6a over-expressed cells, leading to up-regulation of p27KIP1 protein expression and down-regulation of cyclin E1 protein expression, the G1/S transition promoter, in an AKT1-dependent manner. DNAJB6a silencing results in the opposite effect. Over-expression of DNAJB6b, but not DNAJB6a, instead suppresses lung colonization in an experimental metastasis assay, and prolongs survival of the mice. Silencing of DNAJB6a in immortalized normal esophageal epithelial cells initially induces a senescence-like phenotype with greatly reduced proliferation possibly due to oncogenic stress from up-regulation of AKT1 phosphorylation and cyclin E1 protein expression, but promotes EMT-like molecular alterations by up-regulating STAT3 phosphorylation and TWIST1 protein expression and resumes proliferation after prolonged culture. In summary, these results suggest that DNAJB6 plays a critical role in ESCC initiation, development, and metastasis and provides valuable insight into the understanding of ESCC tumorigenesis and metastasis. This suggests its usefulness as a biomarker candidate for detecting early ESCC tumor initiation. DOI: 10.5353/th_b5177324 Subjects: Esophagus - Cancer - Genetic aspects
Download or read book Identification and Functional Analysis of Candidate Tumor Suppressor Genes in Chromosome 9 in Esophageal Squamous Cell Carcinoma ESCC written by Chun-lam Wong and published by . This book was released on 2010 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification and Functional Analysis of Candidate Tumor Suppressor Genes in Chromosome 9 in Esophageal Squamous Cell Carcinoma Escc written by Chun-Lam Wong 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 Functional Analysis of Candidate Tumor Suppressor Genes in Chromosome 9 in Esophageal Squamous Cell Carcinoma (ESCC)" by Chun-lam, Wong, 黃俊霖, 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_b4520421 Subjects: Antioncogenes Esophagus - Cancer - Genetic aspects
Download or read book Tumor Suppressive Role of Chromosomes 11 13 and 14 in Esophageal Squamous Cell Carcinoma Studied by Functional Complementation written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: HKUST Call Number: Thesis BIOL 2005 Ko.
Download or read book Identification and Characterization of Cancer Related Genes in Esophageal Squamous Cell Carcinoma written by Li Fu 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 Cancer-related Genes in Esophageal Squamous Cell Carcinoma" by Li, Fu, 付利, 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 cancer-related genes in esophageal squamous cell carcinoma Submitted by Fu Li For the degree of Doctor of Philosophy at The University of Hong Kong in June 2007 Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer death worldwide and the fourth most common malignancies in China. Previous studies have shown that ESCC is a lethal disease caused by a combination of environmental and genetic risk factors. However, the genetic steps involved in carcinogenesis of ESCC are still unclear. This study aims to identify more ESCC-related genes and to characterize their roles in the tumorigenesis of ESCC. Deletion of chromosome 3p is common in ESCC, suggesting the existence of one or more tumor suppressor genes (TSGs) at this region. Single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG), was applied to investigate loss of heterozygosity (LOH) on 3p in 100 primary ESCC cases with 386 SNP markers. The accuracy of LOH frequency detected by SMSG was further validated by quantitative real-time PCR in five selected SNP loci and the results demonstrated that SMSG is a reliable tool for LOH screening. Four minimal deleted regions (MDRs) at 3p26.3, 3p22, i3p21.3 and 3p14.2 were identified. Absent and down-regulated expression of candidate TSGs from MDRs and other frequent LOH loci, including CHL1, APG7L, PCAF, RBMS3, PLCD1 and CACNA2D3, were detected in primary ESCC tumors and ESCC cell lines. Deletions of MDR-1, 2 and 4 correlated with both advanced tumor stage and poor differentiation in ESCC further strengthened the clinical relevance to these deleted regions. A potential TSG located at 3p22, Phospholipase C-δ1 (PLCD1), was subsequently characterized. Absent expression of PLCD1 was detected in 26/50 (52%) primary ESCCs and 4/9 (44.4%) ESCC cell lines, which was significantly associated with DNA- copy-number loss and promoter hypermethylation (P The majority of ESCC patients presented with advanced/metastatic disease upon diagnosis let us to identify new biomarkers for molecular tumor staging and prognostic evaluation. Differentially expressed proteins among different stages of primary ESCCs and their paired nontumorous tissues were compared by proteomics-based technology. Among 18 differentially expressed proteins, the expression levels of alpha-actinin 4 ii(ACTN4) and 67 kDa laminin receptor (67LR) progressively increased from stage I to III. Clinicopathological correlation study using TMA revealed that ACTN4 overexpression was significantly associated with advanced clinical stage and lymph node metastasis while 67LR overexpression was significantly correlated with advanced clinical stage. In summary, this study provided evidence that more ESCC-associated 3p
Download or read book Identification and Characterization of Tumor Suppressor Gene and Cancer Stemness Gene in Esophageal Squamous Cell Carcinoma written by Liyi Zhang 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 Tumor Suppressor Gene and Cancer Stemness Gene in Esophageal Squamous Cell Carcinoma" by Liyi, Zhang, 張麗儀, 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: Esophageal squamous cell carcinoma (ESCC), the major histological subtype of esophageal cancer, is one of the most common malignancies with poor prognosis in the world. Despite continued development of diagnosis and treatment, ESCC remains the sixth leading cause of cancer death worldwide. Current treatment regimens in ESCC are often characterized by ineffectiveness and poor selectivity. Therapeutic methods directed at cancer-associated genes or cancer stem cells (CSCs) may be effective approaches to cure this deadly cancer. Therefore, this study aims to identify specific ESCC-related genes and cancer stemness genes which help us to develop new targeted agents to achieving objective, long-lasting therapeutic responses in ESCC. To obtain an accurate overview of genetic changes occurring in ESCC patients, our group performed microarray-based mRNA expression profiling and high-throughout transcriptome sequencing (RNA-Seq) to compare differentially expressed genes between ESCC tumors and their corresponding non-tumorous tissues. Prostate stem cell antigen (PSCA) was considered to be a candidate of primary interest due to significantly reduced expression in both microarray and RNA-Seq data. In this study, we examined the role of PSCA on the pathogenesis of esophageal cancer. Our results showed that PSCA was frequently down-regulated in ESCC. Its expression was negatively regulated by transcription factor SOX5. Also, we provided evidence that down-regulation of PSCA was associated with poor clinical outcomes of patients with ESCC. Both in vitro and in vivo assays revealed that PSCA could arrest cell cycle progression and promote differentiation. To further elucidate the mechanism involved in biological function of PSCA, we performed co-immunoprecipitation and mass spectroscopy to identify proteins that associate with PSCA. This study found that RB1CC1, a key signaling node to regulate cellular proliferation and differentiation, interacted specifically with PSCA both in vitro and in vivo. Binding of PSCA and RB1CC1 in cytoplasm resulted in stabilization and translocation of RB1CC1 into nucleus and then further regulates the crucial cell cycle and differentiation genes. Furthermore, in order to identify the cancer stemness genes specifically expressed in CSCs of ESCC, we utilized gene expression analysis to profile 34 stemness-associated genes in ESCC specimens. Developmental pluripotency associated 4 (DPPA4), a well known pluripotent marker of stem cell, was considered as the best candidate. Our following histopathological study demonstrated that DPPA4 rigorously marked the rare CSCs, in contrast to core stemness factors (OCT4 and SOX2) and previous reported CSC markers (CD90 and CD44), which expressed in a large population of cancer cells. Moreover, the expression of DPPA4 was also found to have prognostic value in ESCC, as the appearance of DPPA4+ cells was significantly associated with poor differentiation, advanced stage and higher incidences of lymph node metastasis. Finally, our functional studies showed that ESCC cells expressing exogenous DPPA4 conferred an enhanced ability to initiate tumor, self-renew, resist chemotherapy and metastasize through lymphatic system. In summary, this study provide evidence indicating that novel tumor suppressor gene PSCA and cancer stemness gene DPPA4 may contribute to the development and pr
Download or read book Oncogene Activation in Esophageal Cancer written by Alan G. Casson and published by R. G. Landes. This book was released on 1992 with total page 112 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oesophageal cancer is a particulary virulent gastrointestinal malignancy with poor prognosis. Changing patterns for this cancer have recently been observed in developed countries, and recently a 10% yearly increase in the rate of occurrence for primary adenocarcinoma of the oesophagus in North America was found, which exceeds that of any other malignancy. New techniques in molecular genetics have permitted the study of a number of human solid tumours at both the NDA and RNA levels, contributing significantly to our understanding of the multistep process of tumour development. This book reviews underlying molecular genetic events associated with the development of oesophageal cancer. The book also emphasizes the relationship of these events to other etiologic factors and premalignant conditions (such as Barrett's oesophagus).
Download or read book Investigation of Candidate Tumor Suppressor Gene Latent Transforming Growth Factor Beta Binding Protein 2 LTBP 2 in Esophageal Squamous Cell Carcinoma written by Ho Kin Chan and published by . This book was released on 2009 with total page 119 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book New Research on Esophageal Cancer written by Henry K. Kinner and published by Nova Publishers. This book was released on 2007 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: Esophageal cancer is a malignant tumour of the esophagus, the muscular tube that transports food from the mouth to the stomach. Esophageal cancer occurs most often in men over 50 years old. There are two main types of esophageal cancer, squamous cell carcinoma and adenocarcinoma. These two types are distinguished by the way they look under the microscope. Squamous cell cancer is associated with smoking and alcohol consumption. The incidence of this disease in the United States has remained relatively constant, while the incidence of adenocarcinoma of the esophagus has risen dramatically. Barrett's esophagus, a complication of gastroesophageal reflux disease (GERD), is a risk factor for the development of adenocarcinoma of the esophagus. Risk factors for adenocarcinoma of the esophagus include male gender, obesity, western diet, and smoking. This book presents new advances in this field of cancer research.
Download or read book Human Skin Cancers written by Miroslav Blumenberg and published by BoD – Books on Demand. This book was released on 2018-05-02 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human skin cancers, the most common type of tumors, represent a significant health burden. The deadliest is unquestionably melanoma. Half of melanomas have an activating mutation in the BRAF gene, prompting development of novel drugs, vemurafenib and dabrafenib, specifically targeting mutated BRAF. Trametinib and cobimetinib, which block MEK, a BRAF effector protein, have been used in combination with BRAF inhibitors. A promising new melanoma treatment is immunotherapy, approach that boosts patient's own immune system to attack cancer. Pembrolizumab and nivolumab inhibit PD-1, whereas Ipilimumab targets CTLA-4, another immunity check point, to boost the immune response. Here we focus on pathways, mechanisms, targets and treatments of human skin cancers, with particular emphasis on the new developments in the research on melanomas.
Download or read book How Tobacco Smoke Causes Disease written by United States. Public Health Service. Office of the Surgeon General and published by . This book was released on 2010 with total page 728 pages. Available in PDF, EPUB and Kindle. Book excerpt: This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
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.
Download or read book Journal of the National Cancer Institute written by and published by . This book was released on 2001-05 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book MicroRNAs in Diseases and Disorders written by Philip V Peplow and published by Royal Society of Chemistry. This book was released on 2019-05-07 with total page 500 pages. Available in PDF, EPUB and Kindle. Book excerpt: From pathology to treatment, MicroRNAs in Diseases and Disorders highlights the role of microRNAs (miRNAs) in the development and progression of a variety of diseases, including cancer, neurological disease, endocrine disease and autoimmune disease, and underscores the utilization of miRNA targets in the treatment of these conditions. Providing a comprehensive account, this book also includes the identification of miRNAs as diagnostic and prognostic biomarkers for disease, as well as evaluates translational value from clinical trials using synthesized and functionalized miRNA mimics and inhibitors. With a global contribution list and chapters from leading experts across the field, MicroRNAs in Diseases and Disorders is an invaluable reference to miRNA researchers and health professionals in a variety of disease areas in government, academia and industry. The book will also appeal to pharmaceutical and medicinal chemists with an interest in miRNA targeting therapeutics, as well as to advanced students in chemical biology and drug discovery.
Download or read book WHO Classification of Tumours of the Digestive System written by F. T. Bosman and published by International Agency for Research on Cancer. This book was released on 2010-10-15 with total page 424 pages. Available in PDF, EPUB and Kindle. Book excerpt: "The WHO Classification of Tumours of the Digestive System presented in this book reflects the views of a Working Group that convened for an Editorial and Consensus Conference at the International Agency for Research on Cancer (IARC), Lyon, December 10-12, 2009"--P. [5].
Download or read book Molecular Pathology of Gastroenterological Cancer written by Eiichi Tahara and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: Twenty years have passed since I became a professor in the First Department of Pathology, Hiroshima University School of Medicine. It is my great pleas ure that Molecular Pathology o[ Gastroenterological Cancer-Application to Clinical Practice has been published by Springer-Verlag Tokyo to commemo rate the 20th anniversary of my professorship. Seeing the academic achievements of our department during these 20 years, I am confident that we could establish a department of oncology to research the pathogenesis of human cancer through systemic application of a variety of molecular techniques. We have demonstrated that the develop me nt and progression of esophageal, gastric, and colon cancer require mul tiple alterations affecting DNA mismatch repair genes, oncogenes, and tumorsuppressor genes, and that common and uncommon genetic changes exist for esophageal, gastric, and colorectal carcinomas. In addition to these genetic changes, the majority of gastrointestinal cancers express telomerase activity, with overexpression of telomerase RNA, indicating a powerful addi tional tool for early detection of gastrointestinal cancer. By transferring these basic observations to the clinic, we now are able to make accurate cancer diagnoses, thus determing the grade of malignancy and patient prognosis. We also can identify patients at high risk for developing cancer and create new therapeutic approaches. In fact, we have routinely implemented a new molecular diagnosis strategy at the Hiroshima City Medi cal Association Clinical Laboratory since August 1993.
