Thèses sur le sujet « Hepatocellular Carcinoma HSC »
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龔衍峰 et Hin-fung Tony Kung. « The impact of heat on hepatocellular carcinoma (HCC) ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B4073867X.
Texte intégralKung, Hin-fung Tony. « The impact of heat on hepatocellular carcinoma (HCC) ». Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B4073867X.
Texte intégralWu, Guang. « Role of Notch Signaling in Hepatocellular Carcinoma (HCC) ». Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/18718.
Texte intégralMckiver, Bryan D. « SND1-Targeted Gene Therapy for Hepatocellular Carcinoma ». VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5676.
Texte intégralChan, Chun-Fai. « Study of cancer vaccine candidates for human hepatocellular carcinoma (HCC) / ». View abstract or full-text, 2004. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202004%20CHAN.
Texte intégralTam, Hoy-kam Aegean, et 譚凱琴. « Epigenetic dysregulation of microRNA-9 (miRNA-9) in hepatocellular carcinoma (HCC) ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46455425.
Texte intégralKhan, Maheen. « AEG-1 KNOCKOUT SENSITIZES HEPATOCELLULAR CARCINOMA (HCC) CELLS TO IONIZING RADIATION ». VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5853.
Texte intégralKienlein, Andreas. « Lebertransplantation bei Patienten mit hepatozellulärem Karzinom. Eine retrospektive Studie am Universitätsklinikum Leipzig im Zeitraum von 1994 bis 2010. Charakterisierung des Patientenkollektivs und Analyse von Einflussfaktoren auf Überleben und Outcome ». Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-205991.
Texte intégralShinozuka, Ken. « Effectiveness of Radiofrequency Ablation of Initial Recurrent Hepatocellular Carcinoma after Hepatectomy : Long-Term Results and Prognostic Factors ». Kyoto University, 2018. http://hdl.handle.net/2433/231012.
Texte intégralPeng, Chengyuan. « Diagnosis of Steatosis, Precancerous Lesions and Hepatocellular Carcinoma Using Infrared Microspectroscopy ». Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T032.
Texte intégralHepatocellular carcinoma (HCC) is the sixth most common neoplasm and the second most common cause of death in the world. Hepatocarcinogenesis is a multistep process characterized in patients with chronic liver diseases by a spectrum of hepatic nodules that mark the progression from regenerative nodules to dysplastic lesions followed by HCC. Liver transplantation remains the curative therapeutic option able to treat both the HCC and the underlying liver disease. The issue is that there is no objective and quantifiable marker for quality control of liver graft. Specific biomarkers of early stages of HCC are also an unmet need.In this study, we have evaluated the potential of infrared (IR) microspectroscopy for the diagnosis of steatosis, one of the most important factors affecting the liver allograft function. Vibrational microspectroscopy, such as Fourier transform infrared microspectroscopy (FTIR), allows detecting spectral characteristics associated with different molecular components present in the biological sample, both qualitatively and quantitatively. Our first working hypothesis was that the progression of liver steatosis corresponds not only to the accumulation of lipids but also to dramatic changes in the qualitative composition of tissue. Indeed, a lower grade of steatosis showed a decrease in glycogen content and concomitant increase in lipids in comparison with normal liver. Intermediate steatosis exhibited an increase in glycogen and major changes in lipids, with a significant contribution of esterified fatty acids with elongated carbon chains and unsaturated lipids, and these features were more pronounced in a high grade of steatosis. Furthermore, we have shown, that FTIR approach allows a systemic discrimination of morphological features, leading to a separate investigation of steatotic vesicles and the non-steatotic counterpart of the tissue. This highlighted the fact that dramatic biochemical changes occur in the non-steatotic part of the tissue also despite its normal histological aspect, suggesting that the whole tissue reflects the grade of steatosis. The second part of the thesis focused on hepatocarcinogenesis; a multistep process that is characterized in most cirrhotic livers by the progression from hyperplastic regenerative nodules to low grade dysplastic nodules (LGDN), high grade dysplastic nodules (HGDN) and finally small HCC which corresponds either to vaguely nodular well differentiated HCC so called early HCC or to distinctly nodular moderately differentiated hepatocellular carcinomas. Since the differential diagnosis between precancerous dysplastic nodules and early HCC remains extremely difficult, we addressed the potential of FTIR microspectroscopy for grading cirrhotic nodules. The study was focused on 39 surgical specimens including normal livers as controls, dysplastic nodules, early HCC and the progressed HCC. Profound alterations of the biochemical composition of the pathological liver were demonstrated by FTIR microspectroscopy. Indeed, dramatic changes were observed in lipids, proteins and sugars highlighting the metabolic reprogramming in carcinogenesis. The major changes were observed in the frequency domain 950-1480 cm-1 in which several bands allowed significant discrimination of cirrhotic nodules, dysplastic lesions and HCC. Finally, a significant discrimination between benign, dysplastic nodules and early HCC remained possible using a FTIR microscope equipped with a laboratory-based infrared source that can be easily implemented in hospital environment. In conclusion, our study positions FTIR microspectroscopy as a versatile and powerful approach for investigating liver diseases, such as steatosis, dysplastic lesions and cancer. Further studies on larger series of patients as well as on biopsies will allow confirming the clinical reliability of such spectral signatures. Therefore, we anticipate that FTIR microspectroscopy will open new avenue in clinical diagnosis
Ramanathan, Meera, Michael Shroads, Myunghan Choi, David Wood et Anil Seetharam. « Predictors of intermediate-term survival with destination locoregional therapy of hepatocellular cancer in patients either ineligible or unwilling for liver transplantation ». PIONEER BIOSCIENCE PUBL CO, 2017. http://hdl.handle.net/10150/626078.
Texte intégralReyes, Ryan. « Sorafenib and 2-Deoxyglucose : The Future of Hepatocellular Carcinoma Therapy ». The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461275086.
Texte intégralWang, Ruihua, et 王瑞華. « Blockade of heat shock protein 90 (HSP90) for the treatment of hepatocellular carcinoma (HCC) ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41005776.
Texte intégralWang, Ruihua. « Blockade of heat shock protein 90 (HSP90) for the treatment of hepatocellular carcinoma (HCC) ». Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41005776.
Texte intégralChen, Dong. « Function of Insulin-like Growth Factor Binding Protein 7 (IGFBP7) in Hepatocellular Carcinoma ». VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2821.
Texte intégralPourchet, Aldo Decio. « Développement de virus HSV-1 (virus de l’herpes simplex de type 1) oncolytiques ciblés pour traiter les carcinomes hépatocellulaires ». Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10155/document.
Texte intégralOur long-term purpose is to develop transcriptionally targeted oncolytic vectors, derived from herpes simplex virus type 1 (HSV-1), designed to eradicate hepatocellular carcinomas (HCC). We have identified several HCC-specific promoters, as well as other cancer-specific promoters, that maintain their specificity when expressed from the virus genome. More precisely, we have demonstrated that these promoters are able to drive reporter gene (luciferase) expression from the virus genome in HCC-derived cells, both in cultured cells and in nude mice, but not in fresh human hepatocytes or in the WRL38 hepatocyte-like cells. HSV-1 infection induces, but then inhibits, a cellular antiviral apoptotic response, and the early virus protein US3 is a key actor in inhibiting apoptosis. We have hypothesized that inhibition of US3 expression in hepatocytes should led to early apoptotic death of these cells, therefore precluding virus multiplication and spread. In contrast, expression of US3 in cancer cells is expected to block apoptosis, leading to the achievement of the virus life cycle, cell lysis, and virus spread within the tumours. We report in this communication the construction and properties of two different potentially oncolytic HSV-1 vectors. One of them expresses US3 protein under the control of the HCC-specific promoter ANGPTL3, while the second promoter contains 9 repeats of the hypoxia responsive elements of vascular-endothelial growth factor (VEGF) (9xHRE promoter). Growth curves of these viruses were performed on different HCC cell lines to show their oncolytic properties
Yuan, Ke. « THE CHARACTERIZATION OF HSA-MIR148A IN HEPATOCARCINOGENESIS ». Diss., Temple University Libraries, 2011. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/154268.
Texte intégralPh.D.
Chronic Hepatitis B Virus (HBV) infection is a global health problem because of its connection to acute and chronic liver diseases as well as hepatocellular carcinoma (HCC). There is increasing evidence showing that HBV contributes to HCC due to persistently high levels of trans-activating protein---hepatitis B encoded x antigen (HBxAg). Studies have shown that the HBxAg affects and alters the activity of many different transcription factors and plays an essential role in several cytoplasmic signaling transduction pathways, such as Wnt signaling pathways. One of the upregulated genes, designated URG11, was found transactivated by HBxAg. URG11 could stimulate the ß-catenin promoter and hepatocellular growth and survival which suggest that URG11 may be a regulatory element in the ß-catenin signaling pathways. microRNA148a (miR148a) was identified from two miRNA microarrays as one of the up-regulated miRNAs in cells stably expressing HBxAg or over-expressing URG11. Moreover, the expression of miR148a was also elevated in HBV-mediated HCC patient tissue samples. To study the function of miR148a, HepG2 (hepatoblastoma) and Hep3B (hepatoma) cells stably expressing HBxAg or over-expressing URG11 were transduced by recombinant lentiviruses encoding anti-miR148a. anti-miR148a suppressed cell proliferation, cell cycle progression, cell migration, anchorage independent growth in soft agar and subcutaneous tumor formation in SCID mice. Further, introduction of anti-miR148a increased PTEN protein and mRNA expression, suggesting that PTEN was suppressed by miR148a. In addition, anti-miR148a blocked the stimulation of Akt signaling, resulting in decreased expression of ß-catenin. Thus, miR148a may play a central role in HBxAg/URG11 mediated HCC, and may be an early diagnostic marker and/or therapeutic target associated with this tumor type.
Temple University--Theses
Valmasoni, Michele. « Nuove tecniche e tecnologie per l'aumento di sicurezza ed efficacia nel trattamento chirurgico dell'epatocarcinoma ». Doctoral thesis, Università degli studi di Padova, 2008. http://hdl.handle.net/11577/3425536.
Texte intégralYe, Liangtao [Verfasser], et Enrico de [Akademischer Betreuer] Toni. « Novel targets and therapeutic strategies for the treatment of hepatocellular carcinoma (HCC) / Liangtao Ye ; Betreuer : Enrico de Toni ». München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1211957144/34.
Texte intégralBASELLI, GUIDO ALESSANDRO. « FUNCTIONAL CHARACTERIZATION OF A NOVEL GENETIC VARIANT PREDISPOSING TO ADVANCED FIBROSIS AND HEPATOCELLULAR CARCINOMA DEVELOPMENT IN NONALCOHOLIC FATTY LIVER DISEASE ». Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/718850.
Texte intégralFunctional characterization of a novel genetic variant predisposing to advanced fibrosis and hepatocellular carcinoma development in nonalcoholic fatty liver disease Introduction Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in the Western countries and represent an emerging cause of liver cirrhosis and hepatocellular carcinoma (HCC). Several studies underlined the importance of heritability in modifying the susceptibility and progression of NAFLD. However, the specific determinants of NAFLD heritability remain largely unkonwn. Aims In the hypothesis that rare genetic variants with a strong impact on protein activity account for a fraction of NAFLD missing heritability, the first aim of the current study was to identify by Whole Exome Sequencing (WES) novel rare genetic variants determining an alteration of protein activity associated with advanced stage NAFLD. As we detected an association with a variant in Interferon regulatory protein 3 (IRF3) and hepatocellular carcinoma (HCC) related to NAFLD, we next examined the specific regulation of IRF3 isoforms in patients at risk of NAFLD in relation to liver damage, and tried to understand IRF3 regulation and to model the impact of IRF3 alternative transcripts downregulation by exploiting CRISPR/Cas9 gene editing approach in in vitro models. Finally, we tested the impact of IRF3 pathway inhibition by amlexanox, a TBK1-IRF3 axis inhibitor under study for the treatment of obesity related complications, on the proliferation of hepatoma cells (HepG2). Patients and methods • Variants discovery was performed by WES in 72 Italian NAFLD-HCC patients and 50 healthy individuals. HCC patients were compared to those in the European population (Exome Aggregation Consortium Non-Finnish Europeans, N=33,370). • Validation was performed in NAFLD HCC patients (N=105) and in 211 patients with Advanced fibrosis (N=211), further 270 Italian healthy individuals. Furthermore, a larger database was used to evaluate the European population (genome aggregation consortium, N=64,603). • Transcriptomic analyses were performed on 125 severely obese individuals (Transcriptomic cohort) who underwent to percutaneous liver biopsy performed during bariatric surgery. Bulk RNA-Seq was performed on RNA extracted from flash-frozen liver biopsies. • To evaluate the effect of IRF3-CL a somatic variant in the IRF3-CL specific exon 7 splicing acceptor was introduced. Briefly, a Doxycycline (Therm-Fisher, Waltham, US) inducible Cas9 expressing HepG2 cell line was produced by lentiviral infection exploiting was produced exploiting Edit-R Inducible Lentiviral Cas9 Nuclease vectors (Dharmacon, Lafayette, U.S.A.). Specific guide RNA was designed using CRISPR design tool (http://crispr.mit.edu/) and cloned into an sgRNA expression vector (Addgene #51133) and doxycycline treated cells were transfected with the expression vector. Single cell derived populations were obtained by limiting diluition method and presence of mutations in the specified locus was investigated by T7 nuclease assay (New England Biolabs, Ipswich, US) and further confirmed by Sanger sequencing. Results The rs141490768 SNP in IRF3 resulted enriched in HCCs compared with European population (OR=37.1, p=4.5*10-7). We validated this association in the replication cohort (N=211, p=0.049; OR=5.8; 95% CI = 0.7-21). In the overall series of patients with advanced NAFLD (N=388), the association remained significant (OR=11; 95% CI= 4-24; p=6.16*10-6). The rs141490768 encodes a loss-of-function variant (A418T) in the IRF3 inhibitory isoform IRF3-CL, suggesting that increased IRF3 activity may predispose to NAFLD-HCC. Furthermore, two non-coding transcripts of unknown function (referred as IRF3-NC1 and IRF3-NC2, respectively) also overlap with the rs141490768 locus. Burden test analysis revealed enrichment in rare variants altering specifically IRF3-CL in both our HCC discovery (p=5.69*10-7; OR= 35.5; 95% CI = 11-90) and the patients of our advanced fibrosis cohort with available WES data (OR=6.4; 95% CI= 0.8-24; p=0.04). Transcriptomic analyses revealed high expression levels of IRF3, IRF3-CL, and IRF3-NC1. Moreover, the IRF3-CL mRNA levels were directly correlated with the disease stage, whereas those of IRF3-NC1 were inversely correlated (β=1.3 and -0,77, respectively; p<0.05, both). Immunohistochemical analysis revealed overexpression and hyperactivation of IRF3 according to NAFLD transition to fibrogenic steatohepatitis and HCC. Furthermore, IRF3 was overexpressed in tumor tissue compared with healthy tissue in a cohort of 20 patients of the TCGA database, and in histological samples. In HepG2 hepatoma cells, exposure to free fatty acids triggered IRF3 activation, supporting its involvement in NAFLD pathogenesis. Furthermore, IRF3 was also responsive to proliferation stimuli. To model the impact of IRF3-CL loss of function effect on hepatocyte biology, we developed IRF3-CL+/- HepG2 by CRISPR-Cas9 genome editing. As expected, IRF3-CL+/- HepG2 more sustained IRF3 activation in response to serum. Exposure of HepG2 to amlexanox, alone in combination with sorafenib, was able to impair cell growth rate, but more so in IRF3-CL+/- cells. Conclusion In conclusion, the rs141490768 IRF3 variant was associated with an increased risk to develop advanced NAFLD. Moreover, IRF3 upregulation was associated liver disease severity, in parallel with induction of the inflammatory response, altered lipid metabolism and cell proliferation. Even if further mechanistic studies are required to clarify the complex network of interactions among alternative IRF3 transcripts, our in vitro experiments confirm that IRF3-CL exerts an inhibitory effect on the activation of the main IRF3 isoform, which promotes cell proliferation. Altogether, data suggest that the mechanism underpinning the association of the rs141490768 variant with NAFLD progression to severe fibrosis and HCC is related to facilitation of IRF3 pathway activation. Finally, results support the necessity of further studies to examine the possible role of amlexanox (or other Ikk-epsilon inhibitors) in NAFLD treatment and points out this class of chemicals as good candidates to be further evaluated for the treatment of NAFLD HCC in combination with Sorafenib.
Jariwala, Nidhi H. « Characterization of Staphylococcal nuclease and tudor domain containing protein 1 (SND1) as a molecular target in Hepatocellular carcinoma and Non-alcoholic steatohepatitis ». VCU Scholars Compass, 2017. https://scholarscompass.vcu.edu/etd/5183.
Texte intégralSinha, S. « Detection of structural variations during liver cancer progression ». Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/265927.
Texte intégralLukowski, Sonja [Verfasser], et Rainer [Akademischer Betreuer] Zawatzky. « Wisp1 is associated with hepatitis B related human hepatocellular carcinoma and promotes proliferation or migration of HCC derived cell lines / Sonja Lukowski ; Betreuer : Rainer Zawatzky ». Heidelberg : Universitätsbibliothek Heidelberg, 2013. http://d-nb.info/1177148161/34.
Texte intégralRitorto, Maria Stella [Verfasser]. « Cancer proteomics of mouse serum and liver tissue samples to discover candidate biomarkers for hepatocellular carcinoma (HCC) in c-Myc transgenic mice / Maria Stella Ritorto ». Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover (TIB), 2011. http://d-nb.info/101545996X/34.
Texte intégralHansen, Ryan. « Functional and Structural Analysis of Decellularized Liver Tissue Matrix, with Potential Applications in Cancer Tissue Engineering ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1498650461817088.
Texte intégralRobertson, Chadia L. « Analysis of the Role of Astrocyte Elevated Gene-1 in Normal Liver Physiology and in the Onset and Progression of Hepatocellular Carcinoma ». VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3573.
Texte intégralSalvatore, Veronica <1982>. « Changes in tumor stiffness for early prediction of tumor response to sorafenib : a proof-of-concept study with elastosonography in an animal model of Hepatocellular Carcinoma (HCC) ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3481/1/salvatore_veronica_tesi.pdf.
Texte intégralSalvatore, Veronica <1982>. « Changes in tumor stiffness for early prediction of tumor response to sorafenib : a proof-of-concept study with elastosonography in an animal model of Hepatocellular Carcinoma (HCC) ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3481/.
Texte intégralLang, Hauke. « Hepatozelluläres Karzinom ». Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-137389.
Texte intégralRoth, Alexander David. « Modeling Liver Diseases Using Hepatic Cell Microarrays ». Cleveland State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=csu1544719407531728.
Texte intégralLang, Hauke. « Hepatozelluläres Karzinom ». Karger, 2009. https://tud.qucosa.de/id/qucosa%3A27731.
Texte intégralWang, Bo. « Role of microRNAs in Hepatocarcinogenesis ». The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1329154583.
Texte intégralHillemann, Annett. « Verstärkung des bystander Effektes von Suizidgentherapeutika ». Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät II, 2005. http://dx.doi.org/10.18452/15450.
Texte intégralThis work investigates the application of protein based therapeutic suicide enzyme/prodrug approaches providing novel means for both safe and effective local therapeutic regimes in solid tumors. The concept of the used suicide gene therapy system is based mainly on the transfer of the cell permeable bacterial suicide enzyme cytosine deaminase which specifically convert the inactive, non-toxic prodrug 5-fluorocytosine into the toxic metabolite 5-fluorouracil finally executing the efficient destruction of tumor cells. Employing a novel cell permeable peptide, known as the translocation motif (TLM) of hepatitis B virus (HBV), E.coli cytosine deaminase (bCD) suicide fusion proteins were generated. HBV-TLM fusion proteins formed hexamers (as do parental wt bCD) and retained the specific enzymatic activity of cytosine conversion to uracil also being comparable to parental wtbCD protein. However, only bCD-HBV-TLM fusion proteins, but not HBV-TLM-bCD fusion proteins were found to be taken up to the cytoplasm of target hepatoma cells as demonstrated both by confocal laser scanning microscopy and cell fractionation. Uptake of bCD-HBV-TLM worked both efficiently and rapidly and was found to be independent from the endosomal pathway. Since bCD-HBV-TLM fusion proteins completely retained their suicide enzymatic activity in the course of translocation across the plasma membrane their usage as profound inducers of chemo-sensitivity to 5-fluorocytosine strongly is suggested. Future therapeutic local application of cell permeable bCD-HBV-TLM fusion proteins together with a systemic 5-fluorocytosine prodrug application could result in profound antitumor activities without apparent side effects.
Teng, Kun-Yu Teng. « Molecular mechanisms underlying microRNA-122 mediated suppression of liver inflammation, fibrosis, and carcinogenesis ». The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1511206344798557.
Texte intégralLOCATELLI, LUIGI. « Expression of aVB6 integrin by Pkhd1-defective cholangiocytes links enhanced ductal secretion of Macrophage chemokines to progressive portal fibrosis in Congenital Hepatic Fibrosis ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2013. http://hdl.handle.net/10281/41733.
Texte intégralVerger, Elise. « Microparticules à base d’amidon (SBMP) comme agent théranostique unique pour la radiothérapie sélective interne des tumeurs hépatiques : radiomarquage au gallium-68 et rhénium-188 et étude préliminaire in vivo ». Thesis, Angers, 2016. http://www.theses.fr/2016ANGE0054/document.
Texte intégralThe Hepatocellular Carcinoma has a high incidence worldwide and is associated with a bad prognostic. The existing curative treatments can only be apply in a minority of cases. The selective internal radiation therapy (SIRT) is a palliative treatment that is increasingly used. This technique is define by the selective intratumoral injection of yttrium-90microspheres via intra-arterial infusion. It involves two steps : a pre-therapeutic one for treatment simulation purpose with the injection of serum albumin macroaggregates radiolabeled with 99mTc and the treatment itself. However the characteristics of these two vectors are different and can lead to variations in biodistribution and approximate dosimetry. This works aims to develop a unique radiotheranostic vector for the SIRT: the starch-basedmicroparticles (SBMP), in order to overcome the different currents clinical problems. The optimization of the radiolabeling by the 68Ga and the 188Re in the form of ready-to-use radiolabeling kits allowed to obtain a radiochemical purity > 98 % and > 95 % respectively. A preliminary in vivo study by PET/CT imaging in rat, following the intra-arterial injection of 68Ga-SBMP displayed a specific biodistribution of the microparticles with more than 95 % of the activity found in the liver and mostly in the tumors. The SBMP offer several advantages that answer different current issues and area promising theranostic agent for the SIRT. A presentation of the SIRT, the different microparticles in development and the existing animal models of hepatic tumor will also be developed in this work
« Mitochondrial DNA mutations in hepatocellular carcinoma (HCC) of Chinese patients ». 2004. http://library.cuhk.edu.hk/record=b5892082.
Texte intégralThesis submitted in: December 2003.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2004.
Includes bibliographical references (leaves 138-162).
Abstracts in English and Chinese.
List of abbreviations --- p.i
Abstract (in English) --- p.ii
摘要(中文) --- p.iii
Acknowledgement --- p.iv
Chapter Chapter 1. --- Introduction and Objectives of Study --- p.1
Chapter 1.1 --- Hepatocellular carcinoma in general --- p.2
Chapter 1.1.1 --- "Epidemiology, risk factors" --- p.2
Chapter 1.1.2 --- Pathology and staging --- p.4
Chapter 1.1.3 --- Treatment --- p.6
Chapter 1.1.4 --- Improvement of early detection and treatment of HCC --- p.7
Chapter 1.2 --- General aspects of mitochondria and mitochondrial DNA (mtDNA) --- p.10
Chapter 1.2.1 --- Structure and dynamics of mitochondria --- p.10
Chapter 1.2.1.1 --- General introduction of mitochondria --- p.10
Chapter 1.2.1.2 --- Respiration chain of mitochondria --- p.11
Chapter 1.2.2 --- The mitochondrial genome --- p.14
Chapter 1.2.2.1 --- Strucure --- p.14
Chapter 1.2.2.2 --- Genes for structure proteins --- p.16
Chapter 1.2.2.3 --- Genes for translation --- p.17
Chapter 1.2.2.4 --- Imported proteins and RNAs --- p.17
Chapter 1.2.3 --- Mitochondrial DNA maintenance --- p.19
Chapter 1.2.4 --- Mitochondrial DNA replication --- p.25
Chapter 1.2.5 --- Mitochondrial DNA transcription --- p.30
Chapter 1.2.6 --- Mitochondrial DNA translation --- p.32
Chapter 1.3 --- MtDNA diseases --- p.35
Chapter 1.4 --- MtDNA mutation and HCC --- p.35
Chapter 1.5 --- Aims of the study --- p.39
Chapter Chapter 2. --- Materials and Methods --- p.41
Chapter 2.1 --- Materials --- p.42
Chapter 2.1.1 --- Chemicals --- p.42
Chapter 2.1.2 --- Primers --- p.42
Chapter 2.1.3 --- Enzymes --- p.45
Chapter 2.1.4 --- Cell line --- p.45
Chapter 2.1.5 --- Collection of specimens --- p.46
Chapter 2.2 --- Methodology --- p.47
Chapter 2.2.1 --- "DNA extraction from hcc tissues, cell line Hep3B and PBMCs" --- p.47
Chapter 2.2.1.1 --- DNA extraction from HCC tissues --- p.47
Chapter 2.2.1.2 --- DNA extraction from cell line Hep3B --- p.49
Chapter 2.2.1.3 --- DNA extraction from and PBMCs --- p.50
Chapter 2.2.1.3.1 --- Preparation of PBMCs --- p.50
Chapter 2.2.1.3.2 --- DNA extraction from and PBMCs --- p.51
Chapter 2.2.2 --- Detection of mt whole genome mutation by direct sequencing --- p.51
Chapter 2.2.2.1 --- Design of mtDNA primers --- p.51
Chapter 2.2.2.2 --- PCR amplification of the whole mt genome --- p.51
Chapter 2.2.2.3 --- Direct sequencing of the whole mt genome --- p.52
Chapter 2.2.2.3.1 --- Primer used in sequencing --- p.52
Chapter 2.2.2.3.2 --- Purification of the PCR products of the whole mt genome --- p.53
Chapter 2.2.2.3.3 --- Dye terminator cycle sequencing reaction --- p.53
Chapter 2.2.2.3.4 --- Purification of extension products --- p.54
Chapter 2.2.3 --- Detection of mtDNA control region mutation --- p.55
Chapter 2.2.3.1 --- PCR amplification of D310 in the mtDNA control region --- p.55
Chapter 2.2.3.2 --- Screening of D310 mutation by PFLDA --- p.55
Chapter 2.2.3.2.1 --- Making 8% denatured gel mixture --- p.55
Chapter 2.2.3.2.2 --- Setting up and Pouring the denatured gel --- p.56
Chapter 2.2.3.2.4 --- Preparing and Loading the PCR products --- p.57
Chapter 2.2.3.2.5 --- Electrophoresis --- p.57
Chapter 2.2.3.2.6 --- "Gel fixing, silver staining and color development " --- p.58
Chapter 2.2.3.3 --- Direct sequencing of D310 in the mtDNA control region --- p.59
Chapter 2.2.4 --- Detection of mt DNA coding region mutation --- p.60
Chapter 2.2.4.1 --- PCR amplification of the 5 respiratory chain subunit genes --- p.60
Chapter 2.2.4.2 --- Restriction enzyme digestion of 5 genes in mtDNA coding region --- p.60
Chapter 2.2.4.3 --- Screening of mtDNA coding region mutation by SSCP --- p.61
Chapter 2.2.4.3.1 --- Making 6% 49:1 acrylamide/Bis SSCP gel mixture --- p.61
Chapter 2.2.4.3.2 --- "Setting up the SSCP gel, loading sample, fixing, staining and developing of the gel " --- p.62
Chapter 2.2.4.4 --- Sequencing conformation of the mtDNA coding region mutation --- p.62
Chapter 2.2.5 --- Statistics --- p.63
Chapter 2.2.5.1 --- The chi-square test --- p.63
Chapter 2.2.5.2 --- The Friedman test --- p.63
Chapter 2.2.5.3 --- Wilcoxon signed ranks test --- p.63
Chapter Chapter 3. --- Results --- p.64
Chapter 3.1 --- Detection mt DNA whole genome mutation --- p.65
Chapter 3.1.1 --- Identification of mtDNA whole genome by direct sequencing --- p.65
Chapter 3.2 --- Detection mt DNA D-loop mutation --- p.76
Chapter 3.2.1 --- Screening of C-tract alteration in HCC tissus by PCR fragments length detection assay (PFLDA) --- p.76
Chapter 3.2.2 --- Screening of coding region alteration in HCC tissues by SSCP --- p.77
Chapter 3.2.2.1 --- Identification of C-tract alterations in HCC and non-tumorous tissues by direct sequencing --- p.77
Chapter 3.2.3 --- Identification of C-tract alterations by direct sequencing --- p.82
Chapter 3.2.3.1 --- Identification of C-tract alterations in HCC tissues by direct sequencing --- p.82
Chapter 3.2.3.2 --- Identification of C-tract alteration in PBMC of normal subjects by direct sequencing --- p.82
Chapter 3.2.3.3 --- Identification of C-tract alteration in PBMC of HCC patients by direct sequencing --- p.82
Chapter 3.2.4 --- Statistics of the analysis of C-tract alterations --- p.82
Chapter 3.3 --- Detection mt DNA mutation in the coding region --- p.87
Chapter Chapter 4. --- Discussion --- p.98
Chapter 4.1 --- Detection mtDNA whole genome mutation --- p.99
Chapter 4.2 --- Detection mtDNA D-loop mutation --- p.107
Chapter 4.3 --- Detection mtDNA mutation in the coding region --- p.119
Chapter 4.4 --- Possible mechanisms of mtDNA mutation in HCC carcinogenesis --- p.125
Chapter 4.5 --- Proposals for prospective studies --- p.126
Chapter 4.5.1 --- Function of C7 in D310 --- p.128
Chapter 4.5.2 --- Function changes of mtDNA coding region mutation --- p.130
Chapter 4.5.3 --- Detection of D310 C-tract mutation in patients' plasma --- p.131
Chapter 4.5.4 --- Relationship between nMSl and mtMSI --- p.132
Chapter 4.6 --- Summary --- p.134
References --- p.137
Ku, Chung-Yu, et 辜琮祐. « Studies on Hepatocellular Carcinoma (HCC):I. Liver Fatty Acid-Binding Protein (L-FABP) Promotes Cellular Angiogenesis and Migration in Hepatocellular CarcinomaII. Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway ». Thesis, 2015. http://ndltd.ncl.edu.tw/handle/e2c7f8.
Texte intégral國立臺灣大學
生物化學暨分子生物學研究所
103
Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer and the third most common cause of cancer death worldwide. The progression of HCC relies on the formation of new blood vessels, and VEGF is critical in this process. Liver fatty acid-binding protein (L-FABP) is abundant in hepatocytes and known to be involved in lipid metabolism. Overexpression of L-FABP has been reported in various cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated L-FABP and its association with vascular endothelial growth factors (VEGFs) in 90 HCC patients. We found that L-FABP was highly expressed in their HCC tissues, and its expression level was positively correlated with that of VEGF-A. Additionally, L-FABP significantly promoted tumor growth and metastasis in a xenograft mouse model. We also studied the mechanisms of L-FABP activity in tumorigenesis: L-FABP was found to be associated with VEGFR2 on membrane rafts and subsequently activate the Akt/mTOR/P70S6K/4EBP1 and Src/FAK/cdc42 pathways. This resulted in up-regulation of VEGF-A expression accompanied by an increase in both angiogenic potential and migration activity. Taken together, our results suggest that L-FABP may be a potential target for HCC chemotherapy. Inhibition of VEGFR2 activity has been proposed as an important strategy for the clinical treatment of hepatocellular carcinoma (HCC). In this study, we identified corosolic acid (CA), which exists in the root of Actinidia chinensis (藤梨), as having a significant anti-cancer effect on HCC cells. We found that CA inhibits VEGFR2 kinase activity by directly interacting with the ATP binding pocket. CA down-regulates the VEGFR2/Src/FAK/cdc42 axis, subsequently decreasing F-actin formation and migratory activity of Huh7 cells in vitro. In an in vivo model, CA exhibites an effective dose (5 mg/kg/day) on tumor growth, and we further demonstrate that CA has a synergistic effect with sorafenib within a wide range of concentrations. In conclusion, we elucidate the effects and molecular mechanism for CA on HCC cells and suggest that CA could serve as a therapeutic or adjuvant target for patients with aggressive HCC.
Clifford, Corinne. « A cross sectional analysis of the association between FGF19 tumor expression and serum AFP levels in advanced HCC patients ». Thesis, 2017. https://hdl.handle.net/2144/23745.
Texte intégralWilloughby, Jennifer Lynn Sherman. « Transcription factor LSF : a mitotic regulator in hepatocellular carcinoma cells ». Thesis, 2016. https://hdl.handle.net/2144/20713.
Texte intégral2019-03-04T00:00:00Z
ABURAS, SAMI HUSSEIN ALI. « Role of Circulating Endothelial Progenitors cells (EPC) in patients with hepatocellular Carcinoma treated with Sorafenib ». Doctoral thesis, 2017. http://hdl.handle.net/2158/1077552.
Texte intégralCEENG-SHU, YU, et 余政書. « The Hemodynamics of Hepatocellular Carcinoma(HCC):Analysis in Harmonic and RI values ». Thesis, 2000. http://ndltd.ncl.edu.tw/handle/31882007666119142274.
Texte intégral國立臺灣大學
應用力學研究所
89
In this study,we measure the waveform of the blood velocity in common hepatic artery using Doppler ultrasound. Image processing and fast Fourier transform(FFT) were used to get peak velocity waveform of the normalized amplitude of individual harmonics. The harmonics of velocity waveform and RI etc. were investigated for the hemodynamics of hepatocellular carcinoma (HCC). The subjects studied were divided control group and HCC group. The Hcc group studied were further categorized into varies groups based on theirs age,sex,portal vein thrombosis(PVT),liver cirrhosis,α-fetoprotein(αFP),iodocyanide green(ICG) after 15 minutes and ICG after 20 minutes in turns. Results showed that the first harmonic values in control group were lower than those in HCC group(0.772±0.049 vs. 0.806±0.042,P<0.05). RI values in control group were higher than those in HCC group(0.781±0.026 vs. 0.688±0.040,P<0.01). The second harmonic values decreased with age. The first harmonic values in non-PVT were smaller than that in PVT group(0.790±0.084 vs. 0.842±0.043,p<0.01). The RI values in non-PVT were larger than that in PVT group(0.413±0.058 vs. 0.653±0.098,p<0.01). The first harmonic values in liver cirrhosis group were higher than those in liver non-cirrhosis (0.801±0.079 vs. 0.757±0.067,p<0.05). The first harmonic values in αFP<20 group were smaller than those inαFP>20 group(0.756±0.089 vs. 0.812±0.076,p<0.05). With single t-test statistics showed that velocity harmonics were better than RI,in the classifications of PVT,liver cirrhosis andαFP . However considering multi-variables statistics,RI was better in the classifications of PVT and tumor size.
Wu, Hsiang Yao, et 吳香瑤. « Study Alcohol Metabolism genes in hepatocellular carcinoma (HCC) and its association with prognosis of HCC patients ». Thesis, 2009. http://ndltd.ncl.edu.tw/handle/73396580026258450169.
Texte intégral大同大學
生物工程學系(所)
97
Hepatceullar carcinoma (HCC) is the leading and second cause of death in male and female of Taiwan; respectively, which indicated that HCC is one of the major threats to public health. Several evidences showed that viral factors, alcoholic assumption and drugs abuse led to malignant abnormalities of liver. Among these etiologies, viral factor, such as hepatitis virus B (HBV), caused most of malignant abnormalities of liver diseases in Taiwan, including acute and chronic hepatitis, cirrhosis, and HCC. Since HCC is still a main threat to public health until now, therefore we intended to global survey differential gene expression profile between HCC tumor tissues and its normal counterpart. To address this issue, patients with HCC tumor were enrolled (n=15, tumor size < 5cm) and analyzed transcriptome globally by Affymetrix U133A Chip. Our results showed that the most differential expressed (down-regulation) genes in HCC and its normal counterpart belonged to alcohol metabolism; such as: cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1), alcohol dehydrogenase 1A (class I), alpha polypeptide (ADH1A)、alcohol dehydrogenase 1B (class I), beta polypeptide (ADH1B). In addition, drug metabolism gene- nicotinamide N-methyltransferase (NNMT), iron binding genes-metallothionein (MT) were also found to be down-regulated in HCC tumor tissues. Using real-time PCR and immunohistochemistry, we found that expression of these genes was positively correlated with differentiation status of HCC. For example, over-expression of CYP2E1 was found in well-differentiated HCC tumor tissues; whereas in poor differentiated HCC, the expression of CYP2E1 is down-regulated in tumor tissues. Since the differentiation of tumor is significantly correlated with prognosis of HCC patients, therefore, the expression of these genes will be statistically analyzed with stage, survival rate, and clinical manifestations of HCC patients when the sample size of HCC patients is enlarged. These data will provide us a further insight about pathogenesis of HCC and its clinical relevance.
« Characterization of two ras-superfamily members, RhoC and Rab14, in hepatocellular carcinoma (HCC) ». 2004. http://library.cuhk.edu.hk/record=b5896185.
Texte intégralThesis (M.Phil.)--Chinese University of Hong Kong, 2004.
Includes bibliographical references (leaves 147-157).
Abstracts in English and Chinese.
Abstract --- p.i
Acknowledgements --- p.iv
Abbreviations --- p.v
List of Figures --- p.viii
List of Tables --- p.xi
Contents --- p.xii
Chapter Chapter 1 --- Introduction
Chapter 1.1 --- Hepatocellular carcinoma (HCC) --- p.1
Chapter 1.1.1 --- Background of hepatocellular carcinoma (HCC) --- p.1
Chapter 1.1.2 --- Etiology of HCC --- p.2
Chapter 1.1.3 --- Relationship between HCC and HBV --- p.3
Chapter 1.1.4 --- Differential gene expression under induction of HBx protein by microarray analysis --- p.5
Chapter 1.1.5 --- Confirmation of candidate genes --- p.6
Chapter 1.2 --- Ras-Oncogene --- p.8
Chapter 1.2.1 --- Ras superfamily --- p.8
Chapter 1.2.1.1 --- Rho family --- p.9
Chapter 1.2.1.2 --- Rab family --- p.10
Chapter 1.2.2 --- Functional mechanism of small GTPase --- p.11
Chapter 1.2.3 --- Possible functions of Rho and Rab family members --- p.14
Chapter 1.3 --- RhoC --- p.16
Chapter 1.3.1 --- The genomic and protein structures of RhoC --- p.16
Chapter 1.3.2 --- Relationship between RhoC and tumours --- p.19
Chapter 1.4 --- Rabl4 --- p.20
Chapter 1.4.1 --- The genomic and protein structures of Rabl4 --- p.20
Chapter 1.4.2 --- Relationship between Rabl4 and tumours --- p.23
Chapter 1.5 --- Aims of study --- p.23
Chapter Chapter 2 --- Materials and Methods
Chapter 2.1 --- Materials --- p.25
Chapter 2.1.1 --- Cell lines --- p.25
Chapter 2.1.2 --- Cell culture reagents --- p.26
Chapter 2.1.3 --- Reagents for total RNA isolation --- p.29
Chapter 2.1.4 --- Reagents for reverse transcription polymerase chain reaction (RT-PCR) --- p.30
Chapter 2.1.5 --- Reagents and buffers for Western blot analysis --- p.31
Chapter 2.1.6 --- Vectors for cloning --- p.39
Chapter 2.1.7 --- Reagents for polymerase chain reaction (PCR) --- p.39
Chapter 2.1.8 --- Restriction digestion reagents --- p.42
Chapter 2.1.9 --- Reagents for agarose gel electrophoresis --- p.42
Chapter 2.1.10 --- Ligation reagents --- p.44
Chapter 2.1.11 --- Bacterial culture medium --- p.44
Chapter 2.1.12 --- Dyes and reagents for fluorescent microscope --- p.46
Chapter 2.1.13 --- Reagents for flow cytometry --- p.48
Chapter 2.1.14 --- Detection of apoptosis --- p.48
Chapter 2.2 --- Methods --- p.50
Chapter 2.2.1 --- Identification of gene expression of candidate genes in HCC --- p.50
Chapter 2.2.1.1 --- cDNA preparation --- p.50
Chapter (1) --- Cell culture of HepG2 and WRL-68 cell lines --- p.50
Chapter (2) --- Total RNA isolation --- p.50
Chapter (3) --- First-strand cDNA synthesis --- p.51
Chapter 2.2.1.2 --- RT-PCR of candidate genes --- p.52
Chapter 2.2.1.3 --- Western blotting --- p.53
Chapter (1) --- Cell culture --- p.53
Chapter (2) --- Protein extraction --- p.53
Chapter (3) --- Quantification of proteins --- p.53
Chapter (4) --- Detection of RhoC and Rabl4 protein by western blot analysis --- p.54
Chapter (5) --- Western blotting luminol detection --- p.56
Chapter 2.2.2 --- Cloning protocol --- p.57
Chapter 2.2.2.1 --- Amplification of RhoC and Rabl4 genes --- p.57
Chapter 2.2.2.2 --- Purification of PCR product --- p.58
Chapter 2.2.2.3 --- Restriction enzymes digestion --- p.53
Chapter 2.2.2.4 --- Insert/vector ligation --- p.59
Chapter 2.2.2.5 --- Preparation of chemically competent bacterial cells (E. coli strain DH5a) --- p.60
Chapter 2.2.2.6 --- Transformation of ligation product into chemically competent bacterial cells --- p.61
Chapter 2.2.2.7 --- Small-scale preparation of bacterial plasmid DNA --- p.61
Chapter 2.2.2.8 --- Screening for recombinant clones --- p.62
Chapter 2.2.2.9 --- DNA sequencing of cloned plasmid DNA --- p.63
Chapter 2.2.2.10 --- Midi-scale preparation of recombinant plasmid DNA --- p.64
Chapter 2.2.3 --- Visualization of the subcellular localization patterns --- p.66
Chapter 2.2.3.1 --- Cell culture of AML12 and HepG2 cell lines --- p.66
Chapter 2.2.3.2 --- Transfection of GFP fusion constructs into cells --- p.66
Chapter 2.2.3.3 --- DAPI staining --- p.67
Chapter 2.2.3.4 --- ER-Tracker´ёØ Blue-White DPX staining --- p.68
Chapter 2.2.3.5 --- Subcellular localization study using Epi-fluorescence microscopy --- p.68
Chapter 2.2.4 --- Analysis of cell cycle --- p.69
Chapter 2.2.4.1 --- Transfection of GFP vectors / GFP-tagged proteins into cells --- p.69
Chapter 2.2.4.2 --- Analysis of cell cycle by flow cytometry --- p.69
Chapter 2.2.5 --- Detection of apoptosis --- p.70
Chapter 2.2.5.1 --- Transfection --- p.70
Chapter 2.2.5.2 --- Detection of DNA fragmentation --- p.70
Chapter 2.2.6 --- Reorganization of Actin cytoskeleton by RhoC --- p.71
Chapter 2.2.6.1 --- Transfection of GFP vectors/GFP-tagged proteins into cells --- p.71
Chapter 2.2.6.2 --- Rhodamine phalloidin (RP) staining --- p.71
Chapter 2.2.6.3 --- Epi-fluorescence microscopy --- p.72
Chapter 2.2.7 --- Analysis of cell invasion under induction of RhoC --- p.72
Chapter 2.2.7.1 --- "Sub-cloning of human RhoC gene into a mammalian expression vector, pHM6" --- p.72
Chapter 2.2.7.2 --- Transfection of pHM6-RhoC --- p.73
Chapter 2.2.7.3 --- Cell invasion assay --- p.73
Chapter 2.2.8 --- Analysis of downstream effectors in RhoC-mediated pathway --- p.75
Chapter 2.2.8.1 --- RT-PCR --- p.75
Chapter 2.2.8.2 --- Western blotting --- p.75
Chapter 2.2.9 --- Analysis of role of Rabl4 in membrane trafficking --- p.76
Chapter 2.2.9.1 --- Cloning and transfection --- p.76
Chapter 2.2.9.2 --- Alexa 594 transferrin conjugate staining --- p.76
Chapter 2.2.9.3 --- Epi-fluorescence microscopy --- p.77
Chapter 2.2.10 --- Statistics --- p.77
Chapter Chapter 3 --- Results
Chapter 3.1 --- Expression of RhoC and Rabl4 in hepatoma cells --- p.78
Chapter 3.1.1 --- RT-PCR --- p.78
Chapter 3.1.2 --- Western blotting --- p.81
Chapter 3.2 --- Subcellular localization of RhoC and Rab 14 --- p.85
Chapter 3.3 --- Characterization of RhoC --- p.93
Chapter 3.3.1 --- Cell cycle analysis --- p.93
Chapter 3.3.2 --- Apoptosis --- p.95
Chapter 3.3.3 --- Actin cytoskeleton reorganization --- p.97
Chapter 3.3.4 --- Cell invasion ability --- p.99
Chapter 3.3.5 --- Downstream effectors of RhoC in cytoskeletal reorganization --- p.102
Chapter 3.4 --- Characterization of Rabl4 --- p.107
Chapter 3.4.1 --- Cell cycle analysis --- p.107
Chapter 3.4.2 --- Apoptosis --- p.109
Chapter 3.4.3 --- Roles in intracellular transportation --- p.111
Chapter Chapter 4 --- Discussion
Chapter 4.1 --- Strong expression of RhoC and Rabl4 in hepatoma cells --- p.117
Chapter 4.2 --- Subcellular localization of RhoC and Rabl4 --- p.119
Chapter 4.3 --- The effects of RhoC in normal liver cells --- p.122
Chapter 4.3.1 --- Cell cycle progression by RhoC through regulating of G1 to S phase transition --- p.122
Chapter 4.3.2 --- RhoC shows no apoptotic effect in normal liver cell systems --- p.123
Chapter 4.3.3 --- Formation of actin filaments and stress fibers --- p.124
Chapter 4.3.4 --- Induction of cell invasion in RhoC-expressing cells --- p.125
Chapter 4.3.5 --- Downstream effectors in signaling pathway of RhoC in actin filment reorganization and cell invasion --- p.126
Chapter 4.4 --- The effects of Rabl4 in normal liver cells --- p.132
Chapter 4.4.1 --- Cell proliferation effects of Rabl4 by increasing percentage of cells in S phase for DNA synthesis --- p.132
Chapter 4.4.2 --- Rabl4 has no apoptotic effects --- p.133
Chapter 4.4.3 --- Roles of Rabl4 in vesicular transport --- p.134
Chapter 4.5 --- Conclusion --- p.138
Chapter 4.6 --- Future prospects --- p.140
Appendix --- p.143
References --- p.147
Huang, Shih-Yi, et 黃思怡. « Mechanism analysis on Hepatocellular carcinoma (HCC) recurrence and metastasis : Emphasize on miR-34a ». Thesis, 2009. http://ndltd.ncl.edu.tw/handle/94105548630420832202.
Texte intégral國立陽明大學
微生物及免疫學研究所
97
Hepatocellular carcinoma (HCC) is the leading cause of malignant tumors in Taiwan, and its death rate is also high because of its high probability of recurrence and metastasis. It is very important to find the mechanisms of HCC recurrence and metastasis, and such new knowledge may help us to design new drugs for curing this terribly malignant cancer. We first focused on the level of miR-34a in clinical HCC tissues. We found there is a negative correlation between the expression level of miR-34a and the occurrence of primary HCC recurrence and metastasis. Secondly, we proved that miR-34a has the ability to inhibit the migration of HCC cell lines in vitro and established Mahlavu-34a cell line for in vivo experiment. Finally, we used expression microarray to find the target genes of miR-34a which are also related to HCC recurrence and metastasis. This study will help to develop the effective drugs to cure hepatocellular carcinoma in the future. It will be a gift for those people who suffer from the pain of HCC.
Hsi, Ann, et 徐安. « Expression Profiling and Regulatory Mechanism of Tyrosine Kinases in Human Hepatocellular Carcinoma (HCC) ». Thesis, 2008. http://ndltd.ncl.edu.tw/handle/96529008556475212854.
Texte intégral長庚大學
基礎醫學研究所
96
Up to now, hepatocellular carcinoma (HCC) is still one of the major cancer types in Taiwan. For tumorigenesis, oncogene addiction is an important cause and alteration in the expression level of protein tyrosine kinases (PTKs) is related to many human diseases, including cancer. In human, there are about 90 PTKs and they are involved in many signaling pathways that lead to angiogenesis, cell proliferation, migration, survival and apoptosis. We established a sensitive platform, qRT-PCR, for profiling of PTKs in HCC. Profiling of PTKs in 8 normal and 15 tumor samples revealed that 15 PTKs were up-regulated in HCC and 8 PTKs down-regulated. We found the receptor tyrosine kinase, neurotrophic tyrosine kinase receptor type 3 (NTRK3), and its ligand, neurotrophin 3 (NT3), were significantly down-regulated in tumor samples compared with normal samples. Analysis of 40 HCC samples by immunohistochemistry confirmed that protein level of NTRK3 and NT3 were down-regulated. Epigenetic modification is one of the regulatory mechanisms of gene expression in cancer and bioinformatic analysis predicts that both NTRK3 and NT3 have CpG islands in their promoter region. Here we showed that epigenetic modification might be a regulatory mechanism of NTRK3 and NT3 in HCC.
« Characterization of activating transcription factor 5 in HCC carcinogenesis ». 2007. http://library.cuhk.edu.hk/record=b5893084.
Texte intégralThesis submitted in: August 2006.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2007.
Includes bibliographical references (leaves 114-123).
Abstracts in English and Chinese.
ABSTRACT --- p.I
摘要 --- p.IV
ACKNOWLEDGEMENT --- p.VI
TABLE OF CONTENT --- p.VII
LIST OF TABLES --- p.XII
LIST OF FIGURES --- p.XIII
ABBREVIATIONS --- p.XVI
Chapter CHAPTER 1 --- INTRODUCTION --- p.1
Chapter 1.1 --- Introduction --- p.2
Chapter 1.2 --- Epidemiology --- p.2
Chapter 1.3 --- Etiological factors --- p.6
Chapter 1.3.1 --- Viral Hepatitis Infection --- p.6
Chapter 1.3.1.1 --- Hepatitis B Virus (HBV) --- p.7
Chapter 1.3.1.2 --- Hepatitis C Virus (HCV) --- p.9
Chapter 1.3.2 --- Aflatoxin Exposure --- p.10
Chapter 1.3.3 --- Alcohol Abuse --- p.11
Chapter 1.3.4 --- Liver Cirrhosis --- p.12
Chapter 1.4 --- Genetic alterations in hcc --- p.16
Chapter 1.4.1 --- Chromosomal Gain --- p.16
Chapter 1.4.2 --- Chromosomal Loss --- p.17
Chapter 1.5 --- Discovery of common activating transcription factor 5 (atf5) down-regulations in hcc --- p.19
Chapter 1.5.1 --- Chromosome 19 Aberration in HCC --- p.19
Chapter 1.5.2 --- Discovery of High Frequency of ATF5 Down-regulations --- p.19
Chapter 1.5.3 --- Activating Transcription Factor Family --- p.20
Chapter 1.6 --- Aim of thesis --- p.28
Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.29
Chapter 2.1 --- Materials --- p.30
Chapter 2.1.1 --- Chemicals --- p.30
Chapter 2.1.2 --- Buffers --- p.31
Chapter 2.1.3 --- Cell culture --- p.31
Chapter 2.1.4 --- Nucleic acids --- p.32
Chapter 2.1.5 --- Enzymes --- p.32
Chapter 2.1.6 --- Equipment --- p.32
Chapter 2.1.7 --- Kits --- p.33
Chapter 2.1.8 --- Software and Web Resource --- p.33
Chapter 2.2 --- Dna extraction --- p.34
Chapter 2.2.1 --- Cell Lines --- p.34
Chapter 2.2.2 --- Primary HCC --- p.34
Chapter 2.2.3 --- Lymphocytic DNA --- p.35
Chapter 2.3 --- Rna extraction --- p.36
Chapter 2.4 --- Dna sequencing --- p.38
Chapter 2.4.1 --- Polymerase Chain Reaction (PCR) --- p.38
Chapter 2.4.2 --- Cycle Sequencing --- p.39
Chapter 2.5 --- Dual-labeled fluirescence in situ hybridization (fish) --- p.41
Chapter 2.5.1 --- FISH Probe Preparation --- p.41
Chapter 2.5.1.1 --- Preparation of Human Bacterial Artificial Chromosome (BAC) --- p.41
Chapter 2.5.1.2 --- Nick Translation --- p.41
Chapter 2.5.2 --- FISH --- p.42
Chapter 2.6 --- 5-aza-2'-deoxycytidine & trichostatin a treatment on cell lines --- p.43
Chapter 2.7 --- Bisulfite modificaiton of dna --- p.43
Chapter 2.8 --- Methylation-specific pcr (msp) --- p.44
Chapter 2.9 --- Bisulfite dna sequencing --- p.44
Chapter 2.10 --- Quantitative reverse transcription pcr (qrt-pcr) --- p.46
Chapter 2.11 --- In-vitro and in-vivo functinal examination --- p.49
Chapter 2.11.1 --- ATF5 Transfection --- p.49
Chapter 2.11.2 --- Cell Growth Assay --- p.50
Chapter 2.11.3 --- Xenograft Development --- p.51
Chapter 2.12 --- codelink expression microarray --- p.51
Chapter 2.13 --- Statistical analysis --- p.53
Chapter CHAPTER 3 --- INACTIVATION OF MECHANISMS UNDERLYING ATF5 DOWN-REGULATION --- p.54
Chapter 3.1 --- Introduction --- p.55
Chapter 3.2 --- Materials and methods --- p.58
Chapter 3.2.1 --- Cell Lines --- p.58
Chapter 3.2.2 --- Mutational Analysis --- p.58
Chapter 3.2.3 --- Copy Number Loss --- p.59
Chapter 3.2.4 --- Epigenetic Control --- p.59
Chapter 3.3 --- Results --- p.67
Chapter 3.3.1 --- Sequencing Analysis of A TF5 Gene --- p.67
Chapter 3.3.2 --- FISH Analysis of ATF5 Copy Number --- p.73
Chapter 3.3.3 --- Epigenetic Control of A TF5 Expression --- p.73
Chapter 3.4 --- Discussion --- p.82
Chapter CHAPTER 4 --- FUNCTIONAL EXAMINATION AND INVESTIGATION OF DOWNSTREAM TARGETS MODULATED BY ATF5 --- p.85
Chapter 4.1 --- Introduction --- p.86
Chapter 4.2 --- Materials and methods --- p.88
Chapter 4.2.1 --- Cell Lines --- p.88
Chapter 4.2.2 --- Plasmids and Transfection --- p.88
Chapter 4.2.3 --- Cell Growth Assay --- p.88
Chapter 4.2.4 --- Xenograft Development --- p.88
Chapter 4.2.5 --- CodeLink Expression Microarray --- p.89
Chapter 4.2.6 --- Quantitative RT-PCR --- p.90
Chapter 4.2.7 --- Statistical analysis --- p.90
Chapter 4.3 --- Results --- p.91
Chapter 4.3.1 --- Cell Proliferation --- p.91
Chapter 4.3.1.1 --- In-Vitro Examination --- p.91
Chapter 4.3.1.2 --- In-Vivo Examination --- p.91
Chapter 4.3.2 --- Microarray A nalysis --- p.91
Chapter 4.3.3 --- Correlation of A TF5 with Id-1 Expression --- p.103
Chapter 4.4 --- Discussion --- p.106
Chapter CHAPTER 5 --- PROPOSED FUTURE INVESTIGATIONS --- p.110
Chapter 5.1 --- inactivation mechanisms of atf5 gene --- p.111
Chapter 5.2 --- Molecular pathways modulated by atf5 --- p.112
Chapter CHAPTER 6 --- REFERENCES --- p.114
Huang, Yi, et 黃一. « Systems Biology Approach to Identify MicroRNA -mediated Growth-regulatory Networks in Hepatocellular Carcinoma (HCC) ». Thesis, 2009. http://ndltd.ncl.edu.tw/handle/52697774390139446745.
Texte intégral長庚大學
生物醫學研究所
97
Using transcriptome data to profile the global gene expression has been widely applied to identify genes whose expression pattern is associated with clinical pathological features of tumors which may be used for the diagnosis and prognostic predictions of hepatocellular carcinoma (HCC). Recently, researchers have focused on the expression profiling of microRNAs (miRNAs) to provide more comprehensive results. A significant challenge in the post-genomic era is how to use large-scale and multiple dimensions data to extract and understand the underlying biology of hepatocarcinogenesis. Previous studies indicate that 12-O-Tetradecanoylphorbol-13-acetate (TPA) induce G1 growth arrest in HepG2 cells. Deregulation of growth control mechanism may play a key role in the cancer development. We hypothesize that the genes and miRNAs whose expression altered by TPA treatment may be related to growth control of human hepatoma cells. We proposed that expression level of critical regulatory components in particular networks may be moderately modulated at both transcriptional and translational level during tumorgenesis. In this study, we used a systems biology approach to identify regulatory networks by integrating mRNAs and miRNAs expressions and provide a new dimension of target identification which may be ignored by conventional microarray analysis for mRNAs and miRNAs alone.
LOMBARDO, DANIELE. « Evaluation of CTNNB1, TP53, and hTERT promoter variability in patients with hepatocellular carcinoma ». Doctoral thesis, 2017. http://hdl.handle.net/11570/3116679.
Texte intégral« Functional characterization of novel HBV subgenotypes/mutations associated with increased risk for hepatocellular carcinoma (HCC) ». Thesis, 2009. http://library.cuhk.edu.hk/record=b6074766.
Texte intégralChronic infection of hepatitis B virus (HBV) increases the risk of hepatocellular carcinoma (HCC) by more than 100-fold. However, the underlying molecular mechanism of this process is not fully understood. Several recent studies have shown that A1762T and G1764A mutations of HBV were associated with the aggressiveness of liver disease, in which inactive carriers would develop active hepatitis, and eventually liver cirrhosis and HCC. In Asia, genotypes B and C are the predominant genotypes of HBV infections. Our longitudinal five-year follow-up study of 426 chronic hepatitis B patients in Hong Kong found that the genotype C HBV (normally with A1762T/G1764A mutations) was closely associated with higher risk of HCC than genotype B HBV (non-frequent mutations with A1762T/G1764A).
In this study, systemic site-directed mutagenesis studies, promoter assays, replication capacity assays and overexpression of HBx assays were carried out to demonstrate the molecular mechanisms of these mutations for the increases risk of HCC. Three conclusions were drawn from this study. (1) A1762T and/or G1764A mutations of HBV could reduce BCP activities in a synergistic manner with 1764A contributing more. Reversed T1762A and/or A1764G mutations increase the BCP activities also in a synergistic manner with 1764G contributing more; (2) HBx could increase HBV BCP activity, HBV replication and HBsAg expression. The Lys130Met and Val131Ile mutations of HBx could further increase the above abilities while the A1762T/G1764A double mutations in the BCP region could not affect the interaction of HBx and HBV BCP; (3) The G1677T/A1679C and T1706C mutations could increase the BCP activity; The ectopic expression of HBx could further increase the BCP activity while the mutated HBx (130Met and 131Ile) has less effect on these mutated promoters.
Dong, Qingming.
Adviser: Ming-Liang He.
Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: .
Thesis submitted in: December 2008.
Thesis submitted in: December 2008.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2009.
Includes bibliographical references (leaves 132-154).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts in English and Chinese.
School code: 1307.