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Book Identification and Characterization of Cancer Related Genes in Esophageal Squamous Cell Carcinoma

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

Book Identification and Characterization of Tumor Suppressor Gene and Cancer Stemness Gene in Esophageal Squamous Cell Carcinoma

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

Book Identification and Characterization of Tumor Suppressive Gene and Microrna in Esophageal Squamous Cell Carcinoma

Download or read book Identification and Characterization of Tumor Suppressive Gene and Microrna in Esophageal Squamous Cell Carcinoma written by Kar-Lok Kong 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 Tumor Suppressive Gene and MicroRNA in Esophageal Squamous Cell Carcinoma" by Kar-lok, Kong, 江家樂, 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_b4645569 Subjects: Small interfering RNA Antioncogenes Esophagus - Cancer - Genetic aspects

Book Identification and Characterization of Tumor Suppressor Gene and Cancer Stemness Gene in Esophageal Squamous Cell Carcinoma

Download or read book Identification and Characterization of Tumor Suppressor Gene and Cancer Stemness Gene in Esophageal Squamous Cell Carcinoma written by 張麗儀 and published by . This book was released on 2015 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Identification and Characterization of Tumor Suppressive Gene and MicroRNA in Esophageal Squamous Cell Carcinoma

Download or read book Identification and Characterization of Tumor Suppressive Gene and MicroRNA in Esophageal Squamous Cell Carcinoma written by Kar-lok Kong and published by . This book was released on 2011 with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Identification and Characterization of Chl1 in Esophageal Squamous Cell Carcinoma

Download or read book Identification and Characterization of Chl1 in Esophageal Squamous Cell Carcinoma written by Cailei Zhu 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 CHL1 in Esophageal Squamous Cell Carcinoma" by Cailei, Zhu, 祝彩磊, 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_b4632955 Subjects: Antioncogenes Esophagus - Cancer - Genetic aspects

Book Identification and Characterization of Esophageal Squamous Cell Carcinoma Cancer Stem Cells and Their Chemoradiation Therapy

Download or read book Identification and Characterization of Esophageal Squamous Cell Carcinoma Cancer Stem Cells and Their Chemoradiation Therapy written by 郭佩芳 and published by . This book was released on 2013 with total page 94 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Identification  Functional Characterization and Clinical Relevance of Neuropilin 2  Nrp2  in Esophageal Squamous Cell Carcinoma

Download or read book Identification Functional Characterization and Clinical Relevance of Neuropilin 2 Nrp2 in Esophageal Squamous Cell Carcinoma written by Tsun-Ming Fung 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, Functional Characterization and Clinical Relevance of Neuropilin-2 (NRP2) in Esophageal Squamous Cell Carcinoma" by Tsun-ming, Fung, 馮俊鳴, 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) is the major histological subtype of esophagus cancer. The disease is particularly prevalent in Asia, and ranks the 8th most common cause of cancer mortality in Hong Kong. The overall prognosis for ESCC is poor in part due to the high incidences of metastasis. Therefore, the identification of valid targets and the development of new therapies are necessary for more effective clinical management of this highly aggressive disease. Here, we performed an integrative transcriptome sequencing (RNA-Seq) analysis on three pairs of patient-derived non-tumor and ESCC clinical samples and successfully identified a number of significantly differentially expressed genes, including neuropilin-2 (NRP2) overexpression. Although NRP2 has been reported to be overexpressed in a number of cancer types, its clinical significance and functional role in ESCC has not been explored to date. Subsequent validation in a larger cohort of clinical samples collected from different cities in China known to be troubled with high prevalence of ESCC (Guangzhou p = 59, poor survival (p = 0.049). Further, secretory NRP2 was also found to be present in ESCC patients' sera, but not in the sera collected from healthy normal individuals (p DOI: 10.5353/th_b5351002

Book CHARACTERIZATION OF ONCOGENIC

Download or read book CHARACTERIZATION OF ONCOGENIC written by Qinghui Hu and published by Open Dissertation Press. This book was released on 2017-01-26 with total page 76 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Characterization of Oncogenic Function of MicroRNA665 in Esophageal Squamous Cell Carcinoma" by Qinghui, Hu, 胡庆慧, 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: Background: Esophageal squamous cell carcinoma (ESCC) has been increasing in incidence, but knowledge of the genetic basis of this disease remains limited. In general, esophageal carcinoma can be divided into two main types: Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). The pathogenesis of esophageal carcinoma still remains unclear, although some risk factors like chronic irritation, or chronic inflammation which may be caused by diseases such as gastroesophageal reflux disease (GERD) or unhealthy lifestyles like smoking have been proved to be related to the carcinogenic process. Diagnosis and treatment for this kind of cancer have continue to develop and evolve, but the 5-year overall survival rate is still relatively low. Therefore, it is clinically important to identify any potential genetic changes which may help us to discover some useful biomarker targets for the further development of more direct and harmless targeted therapy for our esophageal cancer patients. Objectives: In this study, I aimed to identify some potential oncogenic microRNA (miRNA) and to study their clinical meaning in ESCC patients. Methods: Microarray was applied to identify differentially expressed miRNAs in ESCC tumour tissue, compared with corresponding adjacent non-tumour esophageal tissue. One candidate oncogenic miRNA, miR-665, was investigated in the present study. After testing the expression level of miR-665 in ESCC cell lines and patients' samples with RT-PCR, miR-665 stably expressing cells was established using two ESCC cell lines (KYSE30 and KYSE510). Functional characterization was then conducted using in vitro and in vivo assays to examine the effect of miR-665 towards the development of ESCC. Bioinformatic software such as Target Scan was used to generate a list of predicted target genes that may be modulated by miR-665. Results: The high expression of miR-665 has been confirmed in ESCC tissues and cell lines, showing the potential carcinogenic function of miR-665. Ectopic expression of miR-665 also demonstrates its ability to enhance tumour growth and invasion in vitro and in vivo. Bioinformatic analysis of miR-665 predicted targets showed putative binding sites for miR-665 within the 3'UTR region of NLK. Conclusions: This study has identified a novel miRNA and a related gene which might play an important role in the pathogenesis of ESCC, affecting the cancer process and tumour growth. This may help to find potential new biomarker for the future improvement and development of new treatment of ESCC patients. DOI: 10.5353/th_b5108698 Subjects: Esophagus - Cancer - Genetic aspects Small interfering RNA

Book Characterization of Two Candidate Tumor Suppressor Genes

Download or read book Characterization of Two Candidate Tumor Suppressor Genes written by Hau-Yi Paulisally Lo 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, "Characterization of Two Candidate Tumor Suppressor Genes: ADAMTS9 and CRIP2 in Esophageal Squamous Cell Carcinoma" by Hau-yi, Paulisally, Lo, 盧巧兒, 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_b4589498 Subjects: Antioncogenes Esophagus - Cancer - Genetic aspects

Book Identification and Functional Analysis of Candidate Tumor Suppressor Genes in Chromosome 9 in Esophageal Squamous Cell Carcinoma  Escc

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

Book Proteomic Identification and Characterization of Proteins That Are Associated with Malignancy of Esophageal Cancer Cells

Download or read book Proteomic Identification and Characterization of Proteins That Are Associated with Malignancy of Esophageal Cancer Cells written by Zhen Cai 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, "Proteomic Identification and Characterization of Proteins That Are Associated With Malignancy of Esophageal Cancer Cells" by Zhen, Cai, 蔡貞, 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 PROTEOMIC IDENTIFICATION AND CHARACTERIZATION OF PROTEINS THAT ARE ASSOCIATED WITH MALIGNANCY OF ESOPHAGEAL CANCER CELLS Submitted by CAI Zhen for the degree of Doctor of Philosophy at The University of Hong Kong in October 2007 Esophageal squamous cell carcinoma (ESCC), a predominant histological type of esophageal neoplasma, is characterized by poor prognosis and rapid clinical progression, with a high frequency of metastasis and recurrence. Ambiguity in molecular mechanisms of etiopathologenesis and disease progression has made it difficult to identify markers for early diagnosis and specialized drug targets. In this study, a combination of 2DE-based comparative proteomics and biochemical methods was employed to analyze the proteome of different experimental models representing tumorigenic and metastatic processes of ESCC, in an attempt to elucidate malignant progression globally and to identify potential protein molecules that might serve as early diagnostic markers, prognosis indicators or treatment targets. Differentially expressed proteins between immortalized esophageal epithelial NE1 cells and cancerous HKESC-2 cells or between xenografts derived respectively from primary ESCCs and metastatic lymph nodes are thought to be associated with malignant phenotype or special to the metastatic characteristics of ESCC. Much attention had been paid to cytoskeletal and associated proteins, due to their ability to govern cell motility and act as signal integrated platform, characteristics especially important in malignant transformation and progression. Several clusters of altered proteins were identified and the expression changes of interesting proteins were further validated in a panel of esophageal origin cell lines and clinical specimens including paired tumor/non-tumor tissue and concomitant primary ESCCs and metastases. CK8 and CK18 were significantly up-regulated in esophageal malignancies, concomitant with changed expression profiles. With metastasis models, CK8 was further found with an obvious increase in expression with similar pattern changes in metastatic tumor-origin xenografts as compared to their primary ESCC derived counterparts, suggesting that CK8 plays a very important role, through either the expression level or post-translational modifications, in ESCC progression. Elevated expressions of galectin-7 and S100A9 in metastatic disease were also confirmed by Western blotting and IHC. Results of IHC further indicated that the translocation of these two proteins from cytoplasma to the nucleus might have important impacts on metastasis of esophageal malignancies. Maspin is one of the identified proteins found to be down-regulated in both tumorigenic and metastatic models. To test its putative effects in ESCC metastasis process, an EMT model was established with maspin-null esophageal cancerous cell line EC109 to mimic in vitro some aspects of the metastasis process. It was found that the stable introduction of maspin into EC109 cells was able to antagonize EGF-induced EMT in EC109 cells, leading to a decreased ability in colony formation. Results from proteomic analysis showed that a group of glycolytic enzymes were decreased in maspin- transfected cells, indicating lower glycolysis of these cells. We therefore propose that the metastasis-suppressive effect of maspin may be a consequence of the re

Book Characterization of Plant Homeodomain Finger Protein 11  Phf11   a Candidate Tumor Suppressor  in Esophageal Squamous Cell Carcinoma

Download or read book Characterization of Plant Homeodomain Finger Protein 11 Phf11 a Candidate Tumor Suppressor in Esophageal Squamous Cell Carcinoma written by Wai-Ying Cheung 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, "Characterization of Plant Homeodomain Finger Protein 11 (PHF11), a Candidate Tumor Suppressor, in Esophageal Squamous Cell Carcinoma" by Wai-ying, Cheung, 張慧盈, 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) is a common cancer worldwide with a high mortality rate. High occurrence of ESCC is observed in Southeast Asia. Identification and characterization of ESCC important tumor suppressor genes will be highly beneficial to the understanding of the disease and for the early diagnosis and improvement of therapy for the cancer. In our previous microcell-mediated chromosome transfer (MMCT) studies, the transfer of an intact chromosome 13 into the recipient ESCC cell line revealed the tumor suppressive ability and putative tumor suppressive function of chromosome 13 in ESCC. One candidate gene, Plant-Homeodomain Finger Protein 11(PHF11), was identified from the study and selected for further functional studies in this current study. PHF11, located on chromosomal region 13q14, contains two plant homeodomain fingers and is a member of the PHD finger protein family. PHF11was reported to be associated with asthma and atopic diseases, yet no studies of PHF11havebeen reported in cancer to date. This study is the first to report the functional role of PHF11in tumor suppression. In this current study, two isoforms of PHF11, PHF11aand b, were reintroduced into ESCC cell lines by methods of transient tranfection and lentiviral-infection. In vitro studies showed both isoforms have cell proliferation and colony-formation inhibition abilities. In the nude mouse tumorigenicity assay, however, it was revealed that only thePHF11aisoform was tumor suppressive in vivo. No differences in angiogenesis-related factors and apoptosis-related factors were observed in PHF11a-and b-expressing cells. Further studies by Western blotting analysis and flow cytometry analysis showed that PHF11amay play a role in delaying cell cycle progression by the down-regulation of cyclin expression, while the PHF11bmay be functionally inactive, The results of this current study further confirm the tumor suppressive role of PHF11ain ESCC, whereas the PHF11b isoform was unable to suppress tumor formation in vivo. Further study of the PHF11 isoforms to identify their differential functions and interacting partners will provide a better understanding of the mechanism by which PHF11a suppressestumor growth. DOI: 10.5353/th_b5016283 Subjects: Antioncogenes Esophagus - Cancer - Genetic aspects

Book Characterization of Two Candidate Tumor Suppressor Genes

Download or read book Characterization of Two Candidate Tumor Suppressor Genes written by Hau-yi Lo (Paulisally) and published by . This book was released on 2011 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Identification and Characterization of Novel Oncogenes Located in a Homogeneously Staining Region  HSR  of Human Esophageal Squamous Cell Carcinoma  ESCC

Download or read book Identification and Characterization of Novel Oncogenes Located in a Homogeneously Staining Region HSR of Human Esophageal Squamous Cell Carcinoma ESCC written by Di Christina Liu and published by . This book was released on 2013 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: