Дисертації з теми "Human primary liver cancer"
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曹德良 and De-liang Cao. "Over-expression of aldose reductase and a novel aldose reductase-like gene in human primary liver cancers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31234616.
Повний текст джерелаCao, De-liang. "Over-expression of aldose reductase and a novel aldose reductase-like gene in human primary liver cancers /." Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17506438.
Повний текст джерелаLadep, Nimzing. "Primary liver cancer : epidemiological and biomarker discovery studies." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/24683.
Повний текст джерелаHubbard, J. G. H. "Primary tamoxifen therapy in human breast cancer." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341491.
Повний текст джерелаClifford, Steven Curtis. "Determinants of chemosensitivity in human primary bladder cancer." Thesis, University of Newcastle Upon Tyne, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239771.
Повний текст джерелаCollier, Jane Davina. "Molecular mechanisms in human hepatocellular carcinoma." Thesis, University of Newcastle Upon Tyne, 1993. http://hdl.handle.net/10443/693.
Повний текст джерелаChan, 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.
Повний текст джерелаAOKI, KUNIO, RYUICHIRO SASAKI, and ZHU-MIN HUANG. "Trends in Mortality from Primary Liver Cancer, Cirrhosis of the Liver, Virus Hepatitis, and Other Liver Diseases 1968-1984 in Japan." Nagoya University School of Medicine, 1987. http://hdl.handle.net/2237/17497.
Повний текст джерелаEasom, Nicholas James Wilson. "Interactions between tumour and natural killer cells in primary and secondary liver cancer." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10042188/.
Повний текст джерелаCunha, Virgínia Filipa Pereira Monteiro da. "Human adipose tissue primary cultures and impact in prostate cancer." Master's thesis, Universidade de Aveiro, 2009. http://hdl.handle.net/10773/8985.
Повний текст джерелаProstate cancer (Pca) is one of the most frequent diagnosed neoplasies and the second cause of cancer-related death in the world, in men. Between others risk factors, obesity has been associated to Pca although the innerent mechanisms to this association remain to be clear. With this work, throuhg in vitro studies, we wish to contribute to the understanding of the impact of white adipose tissue and its sub-fractions (adipocytes and stromal vascular fraction), from visceral and periprostatic anatomic regions, in celular proliferation, apoptosis and invasion of castration sensitivity (LNCaP) and castration resistant (PC-3) prostate cells. With the purpose of obtaining answers directly from humam studies, were performed visceral and periprostatic adipose tissue primary cultures obtained during urologic surgeries (radical prostatectomy and prostatic adenomectomy) (n=16). Adipose tissue was used to make primary organotipical cultures (WAT) and after collagenase digestion adipocytes and SVF primary cultures. Sobrenatants and infranatants of each culture were collect and used as conditioned medium representing adipokines production. LNCaP and PC-3 cell lines were stimulated with these mediums and apoptosis, proliferation and invasion were evaluated, in vitro. This study model represent a potential form for analyze the impact of adipose tissue in tumor cells, allowing to evaluate adipose tissue-tumor interactions. The results show that adipose tissue promotes tumor cells proliferation, that periprostatic adipose tissue increase apoptosis in obese individuals and that SVF subfraction suppresses invasion of PC-3 cells through a direct effect in tumor cells.
O Cancro da próstata (CaP) é uma das neoplasias mais frequentemente diagnosticadas e a segunda causa de morte por cancro no mundo nos homens. Entre outros factores de risco, a obesidade tem sido frequentemente associada a CaP, embora permaneçam por esclarecer os mecanismos subjacentes a esta associação. Com o presente trabalho pretendeu-se através de estudos in vitro, contribuir para a compreensão do impacto do tecido adiposo branco e suas sub-fracções (adipócitos e fracção vascular estromal), com origens anatómicas periprostática e viceral, na proliferação, apoptose, e invasão celular de células de cancro da próstata sensíveis à castração (LNCaP) e resistentes à castração (PC-3). Com o propósito de obter respostas directamente através de estudos em humanos, foram efectuadas culturas primárias de tecido adiposo periprostático e visceral obtido durante cirurgias urológicas (prostatectomia radical e adenomectomia prostática) (n=16). O tecido adiposo foi utilizado para realizar culturas primárias organotípicas (tecido adiposo total fraccionado) e após digestão com colagenase culturas primárias de adipócitos e de células da fracção vascular estromal do tecido adiposo. Foram colhidos sobrenadantes e infranadantes destas culturas de tecido adiposo e utilizados como meios condicionados representativos da produção de adipocinas. As linhas celulares LNCaP e PC-3 foram estimuladas com estes meios e avaliados a apoptose, proliferação celular e invasividade tumoral in vitro. Este modelo de estudo representa um potencial meio para análise do impacto do tecido adiposo nas células tumorais, permitindo avaliar as interacções tecido adiposo-tumor. Os resultados evidenciam que o tecido adiposo promove a proliferação das células tumorais, que o tecido adiposo periprostático aumenta a apoptose em indivíduos obesos e que os SVF suprimem a invasão das PC-3 através de um efeito directo nas células tumorais.
Obara, Akio. "DEPTOR-related mTOR suppression is involved in metformin’s anti-cancer action in human liver cancer cells." Kyoto University, 2015. http://hdl.handle.net/2433/200493.
Повний текст джерелаPang, Wen-chi Roberta, and 彭詠枝. "The role of Pin1 in the pathogenesis of human hepatocellularcarcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B36905847.
Повний текст джерелаpublished_or_final_version
abstract
Medicine
Doctoral
Doctor of Philosophy
Campbell, Andrew M. "Microsphere distribution and radiation dosimetry in human liver following Yttrium-90 microsphere therapy." Thesis, Curtin University, 2000. http://hdl.handle.net/20.500.11937/1742.
Повний текст джерелаNg, Lui, and 吳磊. "Actopaxin: a novel regulator of cell migration and invasion in human hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47752610.
Повний текст джерелаpublished_or_final_version
Surgery
Doctoral
Doctor of Philosophy
Ayres, Reuben Christopher Simon. "In vitro investigation into the role of human intrahepatic biliary epithelial cells as targets in primary biliary cirrhosis." Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296245.
Повний текст джерелаPatitucci, Cecilia. "PPARy, a new player in hepatic metabolic adaptation from mouse model to human liver cancer." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB056/document.
Повний текст джерелаTumorigenesis is influenced by genetic and environmental factors. Overnutrition leads to obesity and fatty liver disease, contributing to increase diabetes incidence worldwide. Diabetes and obesity are independent risk factors for liver cancer development (El-Serag et al., Clin Gastroenterol Hepatol, 2006). This PhD project elucidates the molecular mechanisms linking activated insulin signalling pathway, fatty liver disease and liver cancer development and proposes novel therapeutic strategies. The hepatocytes-specific deletion of tumour suppressor Phosphatase and tensin homolog (PTEN) is a model of steatosis-associated liver cancer (Horie et al., J Clin Invest, 2004). Using this model of activated PI3K/mTOR signalling, our laboratory discovered that the nuclear receptor transcription factor Proliferator-Activated Receptor gamma (PPARγ) is induced in PTEN-null liver. My group demonstrated that in the liver PPARγ contributes to steatosis and aerobic glycolysis. Its activity specifically requires a downstream effector in the PI3K/mTOR pathway, the serine/threonine-specific protein kinase AKT2 (Panasyuk et al., Nat Comm, 2012). Based on these observations, we hypothesized that PPARγ might be an important regulator of pathological growth and development of steatohepatitis-associated liver adenocarcinomas. In my PhD work, I demonstrated that PPARγ expression and activity is essential for liver cancer in PTEN mutants. Moreover, PPARγ is induced in human samples of Hepatocellular Carcinoma (HCC) characterized by poor differentiation accompanied by the activation of PI3K/AKT pathway. We could attribute to PPARγ a specific role in tumour formation as it is required for abnormal liver growth and steatosis in mice at pre-tumoral age. In addition, deletion of PPARγ in PTEN mutants protected animals form liver tumorigenesis placing PPARγ downstream of activated AKT2. Analysing human samples of pre-carcinoma lesions characterized by high steatotic rate, we demonstrated that PPARγ transcript levels are increased in a specific subgroup of adenomas characterized by loss-of-function mutations in the Hepatocyte Nuclear Factor 1α (HNF1α). We identified HNF1α as a novel direct negative regulator of PPARγ transcription. We also revealed HNF1α expression and activity inhibited by AKT2 and thereby inducing PPARγ pro-tumorigenic action. Finally, the sensitivity of PPARγ to natural and exogenous ligands encouraged us to perform treatments to pharmacologically modulate PPARγ activity. Further activation of PPARγ with its synthetic ligand pioglitazione dramatically aggravates liver disease. While PPARγ inhibition by selective antagonist SR2595 allowed to reduce the pre-tumoral and tumoral signs of PTEN-null mice. In sum, our studies in men and mice reveal a novel pro-tumorigenic network of transcription factors HNF1α and PPARγ downstream of activated insulin signalling pathway, suggesting possible strategies for treatment of a subgroup of steatohepatitis-associated liver cancer
Campbell, Andrew M. "Microsphere distribution and radiation dosimetry in human liver following Yttrium-90 microsphere therapy." Curtin University of Technology, School of Applied Science, 2000. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=9972.
Повний текст джерелаwhole liver exposure using external beam radiotherapy. These calculations suggest that preferential deposition of microspheres in the well vascularised periphery of large tumours will lead to a high proportion of the tumour volume receiving a therapeutic dose, with most of the normal liver tissue being spared substantial damage.
Zielinski, Nicholas C., and Grant Skrepek. "Mortality and Cost Outcomes of Emergency Department Visits Associated with Primary or Disseminated Liver Cancer in the United States; 2009." The University of Arizona, 2012. http://hdl.handle.net/10150/614537.
Повний текст джерелаSpecific Aims: To evaluate associations between hospital and patient characteristics and mortality and economic outcomes. Included records were of adult patients age 18 years or older with a diagnosis of primary or disseminated liver cancer. Methods: This study was a retrospective cohort design that utilized emergency department discharge records from the Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) National Emergency Department Sample (NEDS). Generalized linear models were used for analyses to assess outcomes of mortality and total charges. Logistic regression was utilized for mortality; gamma regression with log-link was utilized for charges. Main Results: Overall, 239,895 adult records were included in the study with diagnoses of ICD-9 155.x or 197.7. Total charges for all records were over $8.23 billion in 2009. The average age of the case was 65.07 (±13.8) years with 48.7% being female. Mortality (either in the ED or hospital) was 11.1% (n=26,701). The mean length of stay was 6.47 (±6.05) days. Charges for each record were $42,874.50 (±53,956.34). Increased mortality was associated the most with hospital teaching status and primary payer. Increased charges were associated with hospitals located in the Western region. Conclusions: The differences in clinical outcomes were primarily from different payers and economical outcomes differed greatly by the Western region hospital location. Data taken from the nationally-representative investigation reveals that primary and disseminated liver cancer still remains a clinical high burden-of-illness with an 11.1% mortality rate and total charges approaching $10.3 billion dollars.
Ma, Wei, and 馬威. "Study of the roles of RhoE in human hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/205869.
Повний текст джерелаpublished_or_final_version
Pathology
Doctoral
Doctor of Philosophy
Castven, Darko [Verfasser]. "Patient-derived cancer cells to dissect the molecular basis of treatment response in primary liver cancer: a mechanistic and functional approach / Darko Castven." Mainz : Universitätsbibliothek Mainz, 2019. http://d-nb.info/1198442395/34.
Повний текст джерелаLEE, EUNSUK. "RELATIONSHIPS AMONG DEPRESSIVE SYMPTOMS, SPIRITUAL WELL-BEING, AND QUALITY OF LIFE IN PRIMARY LIVER CANCER PATIENTS IN KOREA." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1333599857.
Повний текст джерелаMastrogiovanni, Gianmarco. "Establishment of new human and mouse liver cancer models and their use to uncover the role of RNF43 and ZNRF3 in liver homeostasis and repair." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273341.
Повний текст джерелаColes, Christopher. "Loss of heterozygosity on chromosome 17 and p53 mutation in primary human breast cancer." Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/19636.
Повний текст джерелаLu, Wenjing, and 鲁文静. "The interaction of mortalin and p53 in human hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46330069.
Повний текст джерелаSchuster, Susanne, and Antje Garten. "Resveratrol Differentially Regulates NAMPT and SIRT1 in Hepatocarcinoma Cells and Primary Human Hepatocytes." Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-142581.
Повний текст джерелаCockbain, Andrew James. "The effect of eicosapentaenoic acid on biomarkers of growth and vascularity of human colorectal cancer liver metastases." Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/5903/.
Повний текст джерелаJor, Wing-yan Irene, and 左穎欣. "Proteomic analysis of the effects of omega-3 fatty acids on human hepatocarcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40204042.
Повний текст джерелаBénay, Cassandre E. "Abnormal expression of proprotein convertases PC56 but not NARC-1 in human colorectal cancer and their liver metastases." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100766.
Повний текст джерелаTung, Kwok-kwan, and 董國焜. "Epigenetic inactivation and tumor suppressive roles of hepatocyte growth factor activator inhibitors(HAIs) in human hepatocellularcarcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B3979376X.
Повний текст джерелаVarandas, Edna Soraia Gregório Ribeiro Varandas. "Low-dose effects of Bisphenol A on human primary vascular endothelial cells and colon cancer cells." Doctoral thesis, ISA/UL, 2014. http://hdl.handle.net/10400.5/7338.
Повний текст джерелаBisphenol A (BPA) is an extensively utilized endocrine disruptor for which human exposure is considered generalized through ingestion. Information regarding BPA effects on vascular and digestive tract tissues is scarce. Therefore, in this work primary Human Umbilical Vein Endothelial Cells (HUVEC) and human colon adenocarcinona cell line HT29 were used to evaluate BPA effects at two distinct low-dose concentrations relevant in terms of human health risk assessment. BPA differentially affects the cell types studied, with more pronounced aneugenic effects, nucleolar disruption and transcriptional deregulation observed in HUVEC. Prolonged BPA exposure affects aging processes in senescent HUVEC. Interaction experiments involving expression of key cancer related genes shows that BPA antagonizes transcriptional effects of the chemotherapeutic agent doxorubicin in HT29. Additionally BPA aneugenic effects are enhanced by co-exposure with Eupatorium cannabinum L. ethanolic extract, a medicinal plant, for which a potent cytotoxic activity against HT29 cells is also demonstrated here. Altogether these results support increasing concerns regarding harmful effects of BPA at low-dose on human health and draw attention to the importance of a deeper understanding of BPA potential interactions with other chemicals.
Qin, Lanfang, and 秦蘭芳. "Signficance of cell cycle regulators in human hepatocellular carcinomaand gene expression induced by cisplatin in hepatoma cell lines." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31242248.
Повний текст джерелаZhu, Meifen, and 朱玫芬. "Mir-23a involves in the anti-cancer effect of CRAE and berberine in human hepatocellular carcinoma cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46944771.
Повний текст джерелаVolkmann, Tina. "The effects of silver nanoparticles on the expression of protein biomarkers of cell stress, apoptosis and inflammation by the human liver cancer cell line, HepG2." University of Western Cape, 2021. http://hdl.handle.net/11394/8429.
Повний текст джерелаNanoscience is the study of phenomena and objects at the nanoscale (around 1-100 nm), socalled nanomaterials. These nanomaterials exhibit novel properties that are often very different to those of the bulk materials used for their synthesis. Hence, nanoparticles are widely commercialised, especially silver nanoparticles (AgNPs) due to their antimicrobial properties and some other useful phenomena. This commercialisation leads to inevitable exposure to the environment and humans, which leads to inhalation, ingestion or dermal uptake of AgNPs by the human body culminating in distribution to several major organs, including the liver. Both chronic and acute exposure to AgNPs have been linked to detrimental effects in both in vitro and in vivo studies. These include oxidative stress, induction of inflammation, DNA damage, cell death and many others.
Chalmers, Claire Ritchie. "The effects of the selective cyclooxygenase-2 inhibitor rofecoxib & hypoxia on human colorectal cancer liver metastases : angiogenesis and prostaglandin metabolism." Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522921.
Повний текст джерелаLechler, Christian [Verfasser], Fabian [Akademischer Betreuer] Geisler, Gabriele [Gutachter] Multhoff, and Fabian [Gutachter] Geisler. "Characterization of tumor initiation and development in a mouse model of primary liver cancer / Christian Lechler ; Gutachter: Gabriele Multhoff, Fabian Geisler ; Betreuer: Fabian Geisler." München : Universitätsbibliothek der TU München, 2020. http://d-nb.info/1226287417/34.
Повний текст джерелаOkoli, Arinze Stanley Medical Sciences Faculty of Medicine UNSW. "Molecular studies of the response of Helicobacter hepaticus to bile, and the effect of Helicobacter bilis on human hepatoma cells." Publisher:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/43379.
Повний текст джерелаKarnosky, Julia [Verfasser], and Christian [Akademischer Betreuer] Schulz. "Association between human papillomavirus and primary lung cancer – a systematic review and pilot study / Julia Karnosky ; Betreuer: Christian Schulz." Regensburg : Universitätsbibliothek Regensburg, 2020. http://d-nb.info/1216703590/34.
Повний текст джерелаLaryea, D., A. Isaksson, Colin W. Wright, R. Larsson, and P. Nygren. "Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumour cell lines and primary cultures of tumour cells from patients." Springer, 2009. http://hdl.handle.net/10454/4533.
Повний текст джерелаThe plant derived indoloquinoline alkaloid cryptolepine was investigated for its cytotoxic properties in 12 human tumour cell lines and in primary cultures of tumour cells from patients. The fluorometric microculture cytotoxicity assay was used to assess cytotoxicity and DNA mocro-array analysis to evaluate gene expression. Cryptolepine mean IC50 in the cell line panel was 0.9 microM compared with 1.0 and 2.8 microM in haemaotological and solid tumour malignancies respectively. Among patient solid tumour samples, those from breast cancer were the most sensitive and essentially as sensitive as haematological malignancies, respectively. Among patient solid tumour samples, those from breast cancer were the most sensitive and essentially as senstive as haematological malignancies. Cryptolepine activity showed highest correlations to topoisomerase II and microtubule targetting drugs. In the cell lines cryptolepine activity was essentially unaffected by established mechanisms of drug resistance. A number of genes were identified as associated with cryptolepine activity. In conclusion, cryptolepine shows interesting in vitro cytotoxic properties and its further evaluation as an anticancer drug seems warranted.
Christie, Leane Michelle. "Factors influencing the impact of primary and secondary prevention strategies for cervical cancer among Queensland women." Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/64067/1/Leane_Christie_Thesis.pdf.
Повний текст джерелаAl-Qahtani, Khalid Hussain. "Detection of human papillomavirus in primary site of oraloropharyngeal cancer and in cervical lymph nodes : correlation with clinico-pathological parameters and prognostic significance." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=83960.
Повний текст джерелаMethods. Retrospective analysis and pathology review of patients with SCCA of the oral cavity at McGill in the last 5 years was performed. Age at diagnosis, risk factors, tumor stage, grade, koilocytosis, treatment, outcome, and presence of HPV by PCR were analysed.
Results. 199 patients included were included in the analyses; 5 years mortality was 18.5%. 146 cases reviewed by pathology revealed 67% koilocytosis. One sample was positive for HPV subtype 35 as determined by PCR. Radiotherapy (p<0,5) and complications from radiotherapy (p<0.5) significantly affected survival.
Conclusions. Many oral SCCA's do not contain HPV 6, 11, 16, 18, 31, 33, 35, 52b, 58 subtypes. Given the high prevelence of koilocytosis, probe for other subtypes should be utilized. Mortality rates and survival are similar to those published in the literature. The presence of koilocytosis, it is not related grade, stage or prognosis. Only radiotherapy and its complications affect survival.
Aarab-Terrisse, Safae. "Impact de l'axe microbiome-thymus sur l'efficacité de la déprivation androgénique et sur le renforcement de l’immuno-surveillance dans le cancer de la prostate Immunodynamics of Explanted Human Tumors for Precision and Personalized Immuno-Oncology Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL025.
Повний текст джерелаAndrogen deprivation therapy (ADT) is the backbone treatment for Prostate cancer (PCa), but most patients will become refractory to castration (CRPC). In addition, immune checkpoint blockade may not be an option for CRPC. Given that advanced cancer patients may exhibit a gut dysbiosis and the pivotal role of the intestinal microbiota composition in dictating the success of chemo-and immuno-therapy, we analyzed the role of the immune system, the impact of the gut microbiota and the inter-relationship between both components in the time to CRPC in PCa patients and in a mouse model of prostate cancer (MyC-CaP cell line). First, using CD4 or CD8 depleting antibodies and athymic nude mice, we demonstrated the key role of T lymphocytes in the time to progression during ADT. Secondly, using cohousing experiments, fecal microbial transplantation and broad spectrum antibiotics, we unveiled the seminal role of the host microbiota in governing tumor growth control during ADT. Third, metagenomics coupled with metabolomics analyses highlighted significant changes associated with ADT, their physiological relevance being currently investigated. Finally, while the development of PCa compromises the thymus integrity despite ADT; healthy microbiota restores thymopoiesis and the emigration of mature lymphocytes associated with effective anticancer immunosurveillance. Altogether, ADT mediates a full blown T cell-dependent anti-PCa cancer efficacy when intestinal dysbiosis is compensated by FMT or immunogenic probiotics
Cox, Julie. "Evaluation of Strategies to Improve In Vitro Mutagenicity Assessment: Alternative Sources of S9 Exogenous Metabolic Activation and the Development of an In Vitro Assay Based on MutaMouse Primary Hepatocytes." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39340.
Повний текст джерелаPedersen, Jenny M. "ATP-Binding-Cassette Transporters in Biliary Efflux and Drug-Induced Liver Injury." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-205355.
Повний текст джерелаL'Hermitte, Antoine. "Rôle de LECT2 dans le microenvironnement immunitaire au cours de la cancérogènese hépatique." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS360/document.
Повний текст джерелаHepatocellular carcinoma (HCC) is the second cause of cancer-rel ated death worldwide. Several studies highlighted the tumor microenvironment (TEM) as a key player in cancer from initiation to progression steps of tumorigenesis. Using relevant HCC mouse models, our team identified the chemokine-like LECT2 as a critical actor of liver TEM in the control of tumor aggressiveness.The aim of my thesis was to address functionally the role of LECT2 in the immune microenvironment during HCC.Using mouse models, we observed that the absence of LECT2 induces a significant accumulation of myeloid cells in the TEM. We showed that these myeloid cells were immature, harbored strong immunosuppressive capabilities on T cells and expressed a transcriptional program sustaining tumor progression. Interestingly, the accumulation of these actors in the microenvironment is associated with the emergence of poorly differentiated tumor nodules expressing epithelial-to-mesenchymal transition / progenitor / metastasis markers.Mechanistically, we demonstrated that LECT2-deficient hepatocytes in the context of β-catenin activation were able to perform EMT like WT hepatocytes do after TGF-β1 challenge. In co-culture experiments, we demonstrated that tumor-infiltrating myeloid cells in the absence of LECT2 have a strong ability to induce hepatocyte EMT.Finally, we analyzed the expression of LECT2 in a vast cohort of HCC liver samples and found that downregulation of LECT2 expression strongly correlates with 1) - the presence of vascular invasion, 2) – histological grade and 3) - the presence of inflammatory infiltrates.Altogether, our data demonstrate that LECT2 acts as a strong regulator of liver tumor aggressiveness through its dual action on hepatocytes and impact on the function of tumor infiltrating myeloid cells. This work identifies LECT2 as a new biomarker for HCC and pave the way to new therapeutic strategies
Essid, Ebtisam [Verfasser]. "Apoptosis induction by Ochratoxin A, LPS, TNF-alpha, H2O2, and uv light in cultured primary rat hepatocytes, in immortalized rat liver cells and in human hepatoma cells and the prevention by Silibinin / Ebtisam Essid." Gießen : Universitätsbibliothek, 2013. http://d-nb.info/1065320140/34.
Повний текст джерелаDegli, Esposti Davide. "Les mécanismes de réponse à l'inflammation chronique dans le foie stéatosique et les conséquences sur l'homéostasie cellulaire et la cancérogénèse." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00652594.
Повний текст джерелаHermetet, Francois. "La dualité de l'apoptose des cellules du cancer du col de l'utérus ou la face de Janus de l'apoptose : un objectif thérapeutique et une implication dans le transfert horizontal d'oncogènes viraux." Thesis, Besançon, 2015. http://www.theses.fr/2015BESA3009/document.
Повний текст джерелаMost of the research strategies aiming at improving anticancer therapies currently target apoptosis. Over the last decades, several natural products derived from herbal medicine or food have been identified as pharmacological agents for cancer cell elimination through apoptosis induction. Among them, isoliquiritigenin (ILG) is a chalcone derivative isolated from liquorice and shallots which exhibits a wide variety of biological functions including antitumor properties.In mammals, apoptotic cells (AC) can either be eliminated after their capture by specialized phagocytes or act as vectors of DNA in a process named horizontal gene transfer (HGT). For instance, AC derived from cervical cancer cells can transfer human papillomavirus (HPV) oncogene sequences to human primary fibroblasts (HPFs) which subsequently acquire transformed cell properties. The molecular mechanisms underlying AC uptake by HPFs, a model of non-professional phagocytes, have not been clearly identified. Characterizing these upstream events appears critical to broaden our understanding of HGT and the ultimate transformation of recipient cells which may subsequently occur.The aims of this work were to (i) study the antitumor effects of ILG on cervical cancer cell lines,(ii) characterize the cellular and molecular mechanisms underlying AC uptake by HPF, (iii) study the cellular events which occur in HPFs following AC engulfment such as phagosome maturation, HGT and acquisition of transformed properties, and (iv) evaluate the tumorigenic properties of AC in vivo.In a first part of this PhD project, we found that ILG exhibits multiple antitumor actions on cervical cancer cells in vitro including anti-proliferative, pro-apoptotic and anti-migration properties. Further studies on apoptosis-related events were conducted in Ca Ski cells (p53wt, HPV16 DNA positive), which are representative of the most frequent cervical carcinoma. The treatment of Ca Ski cells with ILG is associated with increased levels of p53 and p21 proteins, loss of mitochondrial membrane potential, cytochrome c release and caspase-9, -8 and -3 cleavage. These features suggest that ILG-induced apoptosis is dependent on p53 and involve both mitochondrial and death receptor- mediated pathways. The effect of ILG in Ca Ski cells may be partly explained by the decrease of HPV16 E6 oncoprotein expression and the associated raise of p53 levels observed after cell treatment. Our work highlights the potential of ILG as an antitumor agent and provides the opportunity of new treatment. ln the second part of this work, we set up a method based on flow cytometry to quantitatively analyze AC uptake. This original method and microscopy analysis allowed us to show that HPFs act as non-professional phagocytes and are able to engulf subcellular fragments rather than dying whole cells, with lower efficiency and rapidity compared to professional phagocytes as macrophages. Uptake of AC by HPFs depends on time, temperature and the presence of bivalent ions. Morphological analysis and fonctional assays using endocytosis inhibitors revealed a mechanism related to phagocytosis and/or macropinocytosis. The recognition of phosphatidylserine exposed on the surface of AC by their receptor BAIl has emerged as a required event for AC uptake by HPFs
Bellamri, Medjda. "Activation métabolique et génotoxicité des Amines Hétérocycliques Aromatiques (AHA) chez l’Homme." Thesis, Rennes 1, 2016. http://www.theses.fr/2016REN1B033/document.
Повний текст джерелаHeterocyclic aromatic amines (HAA) are environmental and food contaminants, mainly formed during meat and fish cooking, but also in cigarette smoke and exhaust gaz. HAA are mutagenic in bacteria, carcinogenic in rodents and are classified as possible or probable human carcinogens by IARC. Today it is essential to characterize exposure biomarkers i.e. DNA adducts and metabolites, to assess the human risk associated with HAA. The research team has previously demonstrated that 2-amino-9H-pyrido[2,3-b]indole (AαC) form high levels of DNA adducts in human hepatocytes. These levels are greater that those derived from other HAAs. Thus, the aim of this thesis was to better understand the genotoxic potential of AαC in human. We demonstrated that in human hepatocytes, DNA adducts derived from AαC are persistent and formed at doses as low as 1nM. Moreover, we confirmed that CYP1A2 is the major enzyme implicated in the bioactivation of AαC in human liver. We have also characterized the major metabolites derived from AαC formed in human hepatocytes. This study allows, for the first time, the establishment of a correlation between the catalytic activity of CYP1A2, AαC-HN2-O-Gl formation and AαC derived DNA adducts formation. AαC-HN2-O-Gl being reactive toward DNA in vitro, our work reinforces the hypothesis that the UDP-glucuronosyltransferase (UGTs) pathway is a new bioactivation pathway for AαC in human liver. Moreover, we demonstrated the formation of HAA derived DNA adducts, especially those derived from AαC at position C8 of guanine, in activated human T lymphocytes. Taken together, our data lead to the identification of stable metabolites as well as DNA adducts which are potentials AαC exposure biomarkers in human. These biomarkers are essential for a better assessment of the genotoxic risk of AαC in human
Lorz, Axel. "Der Leptinrezeptor im Modell primärer humaner Hepatozyten." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-150410.
Повний текст джерела"Effects of gambogic acid on human hepatoma cells." 2008. http://library.cuhk.edu.hk/record=b5893597.
Повний текст джерелаThesis (M.Phil.)--Chinese University of Hong Kong, 2008.
Includes bibliographical references (leaves 120-133).
Abstracts in English and Chinese.
Acknowledgements --- p.IV
Abstract --- p.V
論文摘要 --- p.VII
Table of Contents --- p.IX
List of Figures --- p.XI
List of Abbreviations --- p.XIII
Chapter 1 Introduction --- p.1
Chapter 1.1 --- Hepatocellular carcinoma (HCC) --- p.1
Chapter 1.1.1 --- Risk factors --- p.1
Chapter 1.1.2 --- Molecular mechanism of HCC --- p.4
Chapter 1.1.3 --- Treatment of HCC --- p.7
Chapter 1.2 --- Gambogic acid (GA) - a compound derived from Tradition Chinese Medicine (TCM) --- p.9
Chapter 1.2.1 --- Traditional Chinese Medicine (TCM) --- p.9
Chapter 1.2.2 --- Gambogic acid --- p.13
Chapter 1.3 --- Molecular mechanism of apoptosis --- p.18
Chapter 1.3.1 --- Overview of apoptosis --- p.18
Chapter 1.3.2 --- Caspases cascade --- p.18
Chapter 1.3.3 --- Bcl-2 family --- p.20
Chapter 1.3.4 --- Mitochondria in apoptosis --- p.23
Chapter 1.4 --- Apoptosis as a strategy for cancer therapies --- p.26
Chapter 1.5 --- Aims of study --- p.29
Chapter Chapter 2 --- Materials and Methods --- p.30
Chapter 2.1 --- Cell culture and treatment --- p.30
Chapter 2.1.1 --- Cell lines used --- p.30
Chapter 2.1.2 --- Gambogic acid (GA) --- p.31
Chapter 2.1.3 --- Chemicals and reagents --- p.31
Chapter 2.1.4 --- Preparation of solutions --- p.32
Chapter 2.1.5 --- Procedures --- p.33
Chapter 2.2 --- Apoptotic detection --- p.35
Chapter 2.2.1 --- Chemicals and reagents --- p.35
Chapter 2.2.2 --- Preparation of solutions --- p.35
Chapter 2.2.3 --- Procedures --- p.37
Chapter 2.3 --- Effects of GA on gene expression in HepG2 --- p.41
Chapter 2.3.1 --- Chemicals and Reagents --- p.41
Chapter 2.3.2 --- Preparation of solutions --- p.41
Chapter 2.3.3 --- Procedures --- p.43
Chapter 2.4 --- Protein expression in GA-induced apoptotic cells --- p.51
Chapter 2.4.1 --- Chemicals and Reagents --- p.51
Chapter 2.4.2 --- Preparation of solution --- p.51
Chapter 2.4.3 --- Procedures --- p.54
Chapter 2.5 --- Caspase cascade study in GA-induced apoptosis --- p.60
Chapter 2.5.1 --- Chemicals and reagents --- p.60
Chapter 2.5.2 --- Procedures --- p.60
Chapter 2.6 --- Downregulation of mRNA using siRNA vector --- p.62
Chapter 2.6.1 --- siRNA expression vector --- p.62
Chapter 2.6.2 --- Chemicals and Reagents --- p.63
Chapter 2.6.3 --- Preparation of solution --- p.63
Chapter 2.6.4 --- Procedures --- p.64
Chapter Chapter 3 --- Results --- p.71
Chapter 3.1 --- GA induces apoptosis in hepatocellular cells --- p.71
Chapter 3.2 --- Effects of gene expression in HCC --- p.80
Chapter 3.3 --- Caspase cascade studies in GA-induced apoptosis --- p.83
Chapter 3.4 --- Caspase 8 activation in GA-treated cells lead to Bid cleavage --- p.89
Chapter 3.5 --- GA induces Bax conformational changes and cytochrome c release --- p.95
Chapter 3.6 --- Levels of protein players involved in apoptosis and cell cycle --- p.101
Chapter Chapter 4 --- Discussion --- p.106
References --- p.120