Dissertations / Theses on the topic 'Liver cancer'
To see the other types of publications on this topic, follow the link: Liver cancer.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Liver cancer.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Clèries, Soler Ramon. "Geographic Variability in Liver Cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2006. http://hdl.handle.net/10803/4627.
Full textAbstract:
At the beginning of the 21st century, primary liver cancer (PLC) remains the fifth most common malignancy in men worldwide, and the eighth in women. Central Africa and South East of Asia are high risk geographic areas for PLC, whereas developed countries appear to be generally low risk. Infections with hepatitis B (HBV) and C (HCV) viruses are the main risk factors for PLC, accounting for well over 80% of PLC cases detected worldwide. The recently detected increase in both incidence and mortality by PLC in developed countries is strongly related to these viral infections. The evaluation of PLC time trends needs to take into consideration the geographic distribution and effect of these viruses. This thesis presents three studies which the aim to describe PLC incidence and mortality issues in different geographic areas, each addressing several epidemiological and methodological issues. For each study, different statistical methods on the basis of the Bayesian inference have been proposed, evaluated and discussed in order to cope with extra-Poisson variability. The first study, entitled "Meta-analysis of cohort studies of risk of liver cancer death among HBV carriers", evaluates the variability in PLC mortality reported in 11 cohort studies of male HBV carriers, taking into consideration the effects of geographic area and the choice of the general population versus a more comparable group such as HBV-negative workers or blood donors as the comparison group. The statistical methods of this study focuses on mixtures of Poisson distributions. The "stickbreaking" method has been used to estimate the number of components of the mixture of Poisson distributions, and, thus to obtain a pooled relative risk (RR) of death for PLC among male HBV carriers. The pooled RR of death by PLC related to HBV infection was 23.5 (95% Credibility Interval (CRI): 14.9 - 44.5). Studies carried out in high risk areas for PLC (China and Taiwan) showed RRs 2 to 5-fold higher than those of studies carried out in Europe, Japan and the U.S.. In low risk areas for PLC, studies which used workers or blood donors as comparison groups had RRs 1.9-fold higher (95% CRI: 1.2 - 3.1) than studies which used the general population. However, in high risk areas, the ratio of RRs was 5.3-fold (95% CRI: 3.4 - 7.9). This is the first time that a "healthy donor effect" has been quantified in longitudinal studies.
The second study, entitled "Geographic distribution of primary liver cancer in Europe in 2002" evaluates the effect of HBV and HCV seroprevalence in 38 European countries on PLC incidence and mortality. Mixed Poisson models based on Bayesian inference have been used to smooth Standardized Incidence (SIR) and Mortality (SMR) ratios for PLC accounting for the effect of HBV and HCV prevalences. This approach enabled us to both examine the effect of different levels of HBV and HCV, and to identify remaining variability in PLC after accounting for infection rates. Bayesian inference allowed the determination of posterior probabilities for the somoothed SIRs and SMRs (hereafter RRs). The Deviance Information Criterion (DIC) and the "effective number of parameters" (pD) have been used as tools for model choice. The highest mortality and incidence PLC RRs were found in Southern European countries (RR range 0.9-2.4), whereas Northern European countries showed the lowest RRs (RR range: 0.3-0.9). The effect of HBV infection was not found to be statistically significant in the model which accounted for both HBV and HCV prevalence. Countries with a prevalence of HCV higher than 2% (e.g.: Italy and Spain) had a higher risk of incidence and mortality (RR range: 1.28 - 1.78) than countries with HCV prevalence below 1%. Thus, the high risk of PLC detected in Southern Europe appears to be explained, in part, by HCV infection. The high HCV seroprevalence in this area could be associated with exposure 30-50 years ago. There may be an underestimation of PLC incidence and mortality rates in Eastern European countries given the low PLC RRs reported, despite high HBV and HCV seroprevalences observed. The implementation of population-based cancer registries in Eastern European countries is warranted, as well as HCV prevalence studies across Europe, to better determine the distribution of PLC in Europe and its relationship with that virus.
The last study, entitled "Time trends in liver disease in Spain during the period 198397", describes incidence and mortality trends in hepatocellular carcinoma and cholangiocarcinoma as well as mortality trends in liver cirrhosis in Spain. Autoregressive age-period-cohort (APC) models have been used to evaluate the time trends. We found that APC models performed well for those liver diseases with large number of cases, whereas the age-period models did for those liver diseases with low number of cases. We found an increase in incidence and mortality of hepatocellular carcinoma in Spain (annual percent change (APCH) in men's incidence: 6.6%, 95% CRI: 5.8, 8.1: APCH in women's incidence: 4.5%, 95% CRI: 1.4%, 7.3%; APCH in men's mortality: 6.8%, 95% CRI: 5.8%, 8.1%; APCH in women's mortality: 5.1%, 95% CRI: 3.5%, 6.3%), that appear to be related to HCV exposure 30 years ago, as described in other studies of PLC. We also found an increasing trend in cholangiocarcinoma mortality (APCH in men: 17.1%, 95% CRI: 13.5%, 21.2%; APCH in women: 15.0%, 95% CRI: 11.5%, 19.5%) similar to that found in some developed countries, that could be attributed to improvement in diagnosis resulting from better imaging and diagnostic techniques. However, we did not detect a significant increasing trend in cholangiocarcinoma incidence, perhaps due to the low number of cases reported by the Spanish cancer registries. We have observed a decreasing trend in cirrhosis mortality in both sexes during the study period (APCH in men: -3.1%, 95% CRI: -5.1, -1.9%; APCH in women: -2.9%; 95% CRI: -6.2%, -1.3%), although younger cohorts did not show this pattern. This cohort effect suggests the possibility that younger cohorts could be exposed to some additional risk factors besides alcohol consumption. HIV and HCV or HBV co-infection and intravenous drug addiction could explain the increase in liver cirrhosis mortality among younger cohorts.
The flexibility of the Bayesian approach allowed us to cope with extra-Poisson variability in three statistical analyses, applying different models, and addressing relevant methodological aspects specific to each problem. Challenging statistical issues in the framework of Bayesian applied modelling are: i) the selection of prior distributions for model parameters, which is related to convergence of the model; and ii) model selection procedures, and these remain important considerations for future research.
2
Ng, Oi-lin Irene, and 呂愛蓮. "Patho-biological prognostic factors in hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1994. http://hub.hku.hk/bib/B31981537.
Full text
3
黎卓先 and Cheuck-seen Edward Lai. "Resection margin for hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1992. http://hub.hku.hk/bib/B30257529.
Full text
4
Urdzik, Jozef. "Colorectal Cancer Liver Metastases : Effects of Chemotherapy on Liver Parenchyma and Resections." Doctoral thesis, Uppsala universitet, Institutionen för kirurgiska vetenskaper, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-233790.
Full textAbstract:
Current multimodal treatment of colorectal cancer liver metastasis often combines liver resections with preoperative chemotherapy with a 5-year survival of 40-50%. Preoperative chemotherapy includes conversion of initially non-resectable situation and control of micrometastatic disease. Despite its potential advantages also problems with associated steatosis, steatohepatitis and sinusoidal injury has been discussed. Paper I focused on prospective steatosis evaluation prior to resections using proton MR spectroscopy, most sensitive non-invasive method. Proton MR spectroscopy showed high concordance with digital quantification of steatosis and was also able to predict steatohepatitis with 100% sensitivity and 89% specificity without knowing lobular inflammation or hepatocyte ballooning. Paper II focused on portal vein hemodynamics changes in patients treated with oxaliplatin-based treatment and with sinusoidal injury. Magnetic resonance imaging flowmetry demonstrated portal vein dilatation associated with oxaliplatin treatment. Patients with SI showed a tendency towards decreased mean portal flow velocity. Portal vein flow was not changed. This may indicate that SI is associated with an increased resistance to blood flow in the liver parenchyma and stasis in splanchnic system. Paper III attempted to enlighten the effects of FOLFOX treatment on human liver tissue 6 weeks after treatment cessation by quantification of protein expression changes using label-free global proteome analysis. Deep proteome analysis identified 5891 proteins, where machine learning algorithm identified 3% of classifying proteins, associated with changes in DNA replication through upregulation of the minichromosome maintenance complex and with the innate immune response. Significant changes were observed in 1% of proteins, associated with DNA replication and cell cycle entry. Results support the hypothesis that liver has already regenerated from the FOLFOX treatment injury after 6 weeks. Paper IV aimed to identify possible patient, disease and chemotherapy characteristics associated with liver specific and severe general complications in a retrospective single centre cohort composed of 516 consecutive resections. Chemotherapy with more than 4 cycles of oxaliplatin was associated with post-hepatectomy hemorrhage. Underlying liver disease and diabetes mellitus were associated with 90-day mortality. Size of resection, intraoperative blood loss and transfusions were verified as independent predictors of liver specific complications to resections.
5
Poon, Tung-ping Ronnie, and 潘冬平. "Surgical strategies to improve long-term survival after hepatectomy for hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31979634.
Full text
6
Farah, Yasser Abdulhamid Elskay, and L. O. Averyanova. "Technologies for prevention liver cancer in Egypt." Thesis, ХНУРЕ, 2019. http://openarchive.nure.ua/handle/document/8373.
Full textAbstract:
Deaths from liver cancer are common, especially in East Asia and Pacific, South Asia, and parts of Sub-Saharan Africa, largely as a result of infection decades ago. Controlling the risk factors would not only reduce the incidence of liver cancer; it would also reduce the incidence of cirrhosis and its other complications. This paper will discuss the clinical implications of imaging in screening, diagnosis, staging, and follow-up of patients in liver malignancies.
7
Rava', M. "FUNCTIONAL DISSECTION OF ST18 IN LIVER CANCER." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/254403.
Full textAbstract:
The molecular mechanisms and pathways responsible for the progression of hepatocellular carcinoma (HCC) remain to be fully characterized. Among the genetic lesions associated with HCC progression, Shukla et al. (2013) identified insertions of the L1 transposon proximal to the gene encoding the zinc-finger DNA-binding protein ST18 (suppression of tumorigenicity 18) and suggested that this actually functions as an oncogene in HCC. However, functional evidence for a cancer-promoting activity of ST18 and insight into its mode of action are missing. Here, I pursued the functional characterization of ST18 in a mouse model of HCC based on ex vivo transformation and subcutaneous transplantation of embryonic hepatoblasts. ST18 was undetectable in either normal liver or cultured hepatoblasts, but was induced in the subcutaneous tumors. ST18 was also expressed in either chronically or acutely inflamed mouse livers (as assessed in Mdr2-/- or LPS-treated mice) as well as in human Progressive Familial Intrahepatic Cholestasis 2 (PFIC2: a condition associated with chronic inflammation), suggesting its induction by inflammatory stimuli. The knockdown of ST18 delayed tumor formation or, if induced in already formed tumors, led to rapid hemorrhage, pervasive morphological changes in the tumor cells reminiscent of an epithelial-to-mesenchymal transition (EMT) and eventually tumor regression. RNA profiling revealed that ST18 silencing caused expression of EMT-associated genes, among others. Previous studies have linked inflammation to the induction of EMT in other epithelia: we hypothesize that the concomitant activation of ST18 constitutes a safeguard against EMT, inactivation of this control mechanism causing the dramatic phenotypic switch observed in our model. These data warrant further evaluation of the mode of action of ST18 and of its potential value as a therapeutic target in HCC.
8
Fung, Wai-yip. "The characterization of PAK 6 in liver cancer." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B4260980X.
Full text
9
Lilienberg, Elsa. "Biopharmaceutical Evaluation of Intra-arterial Drug-Delivery Systems for Liver Cancer : Investigations in healthy pigs and liver cancer patients." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-267396.
Full textAbstract:
There are currently two types of intra-arterial drug-delivery system (DDS) in clinical use in the palliative treatment of primary liver cancer. The chemotherapeutic drug doxorubicin (DOX) can be formulated into a drug-in-lipiodol emulsion (LIPDOX) or a microparticulate drug-eluting bead system (DEBDOX). To facilitate development of future DDSs, we need to understand the release and local distribution of drug from these DDSs into the complex, in vivo, pathological environment. The overall aim of this project was to assess and improve understanding of the in vivo release of DOX from LIPDOX and DEBDOX and its local disposition in the liver. These processes were investigated in detail in a multisampling-site, healthy pig model and in human patients with liver cancer. The mechanisms involved in DOX disposition were studied by examining potential interactions between DOX and lipiodol and/or cyclosporine A (CsA) in pigs. In this project, the main elimination pathway for DOX and its primary metabolite doxorubicinol (DOXol) was via bile; their extensive canalicular carrier-mediated transport (e.g. ATP-binding cassette transporters ABCB1, ABCC1, ABCC2 and ABCG2) was inhibited by CsA. CsA had no effect on the carbonyl and aldo-keto reductases responsible for the metabolism of DOX into DOXol. LIPDOX released DOX more rapidly and to a greater extent into the circulation than DEBDOX, which had only released 15% of the dose in patients after 24 hrs. The systemic exposure to DOX was lower for DEBDOX than for LIPDOX. Greater fractions of DOXol were formed in blood and bile with LIPDOX than with DEBDOX. This may have been because DOX was more widely distributed into regions with increased metabolic capacity or because of increased intracellular uptake when DOX was delivered in LIPDOX. The excipient lipiodol in the LIPDOX formulation did not interact with transporters, enzymes or membranes that would explain the increased cellular uptake of DOX. In conclusion, the release of DOX from DEBDOX is more controlled in vivo than that from LIPDOX, indicating that DEBDOX is a more robust pharmaceutical product. The formulations for future optimized DDSs should therefore be more similar to DEBDOX than to LIPDOX.
10
Liu, Ming, and 劉銘. "Identification and characterization of novel genetic alterations in the progression of hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196441.
Full textAbstract:
Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally believed that accumulation of irreversible alterations in critical oncogenes and tumor suppressor genes during the long-term inflammation finally leads to the hepatocellular pathogenesis. Although under intensive investigation, the molecular pathogenesis of HCC still remains to be further elucidated.
In this study, we aimed to identify novel genetic alterations critical to the pathogenesis of HCC, especially in hot regions with recurrent chromosomal instability. Amplification of broad regions of 8q is one of the most frequent genetic alterations in HCC, suggesting the existence of oncogenes in addition to MYC at 8q24. By screening the publicly available microarray database and clinical samples, we found frequent amplification and overexpression of Serum and Glucocorticoid Kinase 3 (SGK3) in clinical HCC specimens, and SGK3 genomic activation was significantly associated with poor outcome of HCC patients. Functional assays revealed that SGK3 could increase G1/S cell cycle progression, cell survival, clonogenicity, anchorage-independent growth, and tumor formation in nude mice. We provided evidences that SGK3 could promote HCC growth and survival through inactivating GSK3-β and BAD respectively. We also found that expression of SGK3, which like AKT is activated by PI3K/PDK1, has more significance than overexpression of AKT in predicting poor outcome of HCC patients. Our findings suggested the existence of an AKT-independent SGK3 pathway, which may function in parallel with AKT pathway in the pathogenesis of HCC. In addition to large chromosomal alterations, small changes in nucleotides may also make substantial contributions to carcinogenesis. Recent advances in high-throughput deep sequencing technology have provided a powerful tool to understand the whole cancer transcriptome and identify novel genetic alterations related to cancer progression. In this study, we identified a high proportion of allele imbalance in genes related to cellular stress response by sequencing the whole transcriptome of 3 paired HCC tissues. A novel nucleotide variation which resulted in a R438H amino acid change was identified in the coding region of the gene Oxidative Stress Induced Growth Inhibitor 1 (OSGIN1), and the variant 438H form of OSGIN1 was found to be specifically retained in the tumor tissues in a cohort of HCC patients. OSGIN1 was found to be closely associated with chemotherapeutic reagents and exhibited strong tumor suppressive function in HCC by directly inducing cell apoptosis. The wild type OSGIN1 was found to have stronger tumor suppressive function than the variant allele, and this might be due to their different ability to localize to mitochondria. The significantly decreased basal apoptotic index in HCC patients carrying OSGIN1 variant allele and their poor prognosis further suggested that the specific retention of 438H OSGIN1 might be important in HCC progression.
In summary, we found a frequently amplified oncogenic SGK3 signaling pathway, as well as the allele-specific imbalance of tumor suppressive OSGIN1 in the pathogenesis of HCC. Further characterization of their mechanisms in hepatocarcinogenesis may help provide novel prognostic biomarkers and therapeutic targets in HCC treatment.published_or_final_version
Clinical Oncology
Doctoral
Doctor of Philosophy
11
Pescia, Daniel. "Segmentation of liver tumors on CT images." Thesis, Châtenay-Malabry, Ecole centrale de Paris, 2011. http://www.theses.fr/2011ECAP0002/document.
Full textAbstract:
Cette thèse porte sur la segmentation des tumeurs du foie sur des images tomodensitométriques. Ce sujet présente un intérêt certain pour le domaine médical puisque les médecins pourraient ainsi bénéficier d’une méthode reproductible et fiable pour segmenter de telles lésions. Une segmentation précise des tumeurs du foie permettrait en effet d’aider les médecins lors de l’évaluation des lésions (détection, localisation, quantification), du choix d’un traitement, et de sa planification. Les méthodes développées dans ce cadre doivent faire face à trois principales difficultés scientifiques: (i) la grande variabilité de l’apparence et de la forme des structures recherchées, (ii) leur ressemblance avec les régions environnantes et finalement (iii) la faiblesse du rapport signal sur bruit observé dans les images dans lesquelles on travaille. Ce problème est abordé dans une optique d’application clinique et est résolu en suivant une approche en deux temps commençant par le calcul d’une enveloppe du foie, avant de segmenter les tumeurs présentes à l’intérieur de cette enveloppe. Nous commençons par proposer une approche basée sur des atlas pour le calcul d’une enveloppe des foies pathologiques. Tout d’abord, un outil de traitement d’image a été développé pour calculer une enveloppe autour d’un masque binaire, afin d’essayer d’obtenir une enveloppe du foie à partir d’une estimation du parenchyme sain. Un nouvel atlas statistique a ensuite été introduit, puis utilisé pour la segmentation à travers son recalage difféomorphique avec une image. La segmentation est finalement réalisée en combinant les coûts d’appariement des images avec des a priori spatiaux et d’apparence, le tout en suivant une approche multi échelle basée sur des MRFs. La deuxième étape de notre approche porte sur la segmentation des lésions contenues dans ces enveloppes en combinant des techniques d’apprentissage par ordinateur avec de méthodes basées sur des graphes. Un espace d’attributs approprié est tout d’abord défini en considérant des descripteurs de textures déterminés à travers des filtres de diverses tailles et orientations. Des méthodes avancées d’apprentissage automatique sont ensuite utilisées pour déterminer les attributs pertinents, ainsi que l’hyperplan qui sépare les voxels tumoraux des voxels correspondant à des tissus sains dans cet espace d’attributs. Pour finir, la segmentation est réalisée en minimisant une énergie sous forme de MRF, laquelle combine les probabilités d’appartenance de chaque voxel à une classe, avec celles de ses voisins. Des résultats prometteurs montrent les potentiels de notre méthodeThis thesis is dedicated to 3D segmentation of liver tumors in CT images. This is a task of great clinical interest since it allows physicians benefiting from reproducible and reliable methods for segmenting such lesions. Accurate segmentation would indeed help them during the evaluation of the lesions, the choice of treatment and treatment planning. Such a complex segmentation task should cope with three main scientific challenges: (i) the highly variable shape of the structures being sought, (ii) their similarity of appearance compared with their surrounding medium and finally (iii) the low signal to noise ratio being observed in these images. This problem is addressed in a clinical context through a two step approach, consisting of the segmentation of the entire liver envelope, before segmenting the tumors which are present within the envelope. We begin by proposing an atlas-based approach for computing pathological liver envelopes. Initially images are pre-processed to compute the envelopes that wrap around binary masks in an attempt to obtain liver envelopes from estimated segmentations of healthy liver parenchyma. A new statistical atlas is then introduced and used to segmentation through its diffeomorphic registration to the new image. This segmentation is achieved through the combination of image matching costs as well as spatial and appearance priors using a multiscale approach with MRF. The second step of our approach is dedicated to lesions segmentation contained within the envelopes using a combination of machine learning techniques and graphbased methods. First, an appropriate feature space is considered that involves texture descriptors being determined through filtering using various scales and orientations. Then, state of the art machine learning techniques are used to determine the most relevant features, as well as the hyperplane that separates the feature space of tumoral voxels to the ones corresponding to healthy tissues. Segmentation is then achieved by minimizing an MRF energy that combines class probabilities and neighbor constraints. Promising results demonstrate the potentials of our method
12
Fung, Wai-yip, and 馮偉業. "The characterization of PAK 6 in liver cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B4260980X.
Full text
13
Mook, Olaf Roger Franciscus. "Tumor development of colon cancer in rat liver." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/88454.
Full text
14
Ladep, Nimzing. "Primary liver cancer : epidemiological and biomarker discovery studies." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/24683.
Full textAbstract:
With previous reports indicating changes in mortality, risk factors and management of primary liver cancer (PLC), evaluation of current trends in the incidence and mortality rates was indicated. Late diagnosis has been implicated to be a major contributor to the high fatality rates of PLC. This work aimed at: • studying trends of PLC by subcategories globally in general, and in England and Wales, in particular; • investigating liver-related morbidities of HIV infected patients in an African setting; and • discovering urinary biomarkers of hepatocellular carcinoma. The World Health Organisation (WHO) and Small Area Health Statistics Unit (SAHSU) databases were interrogated respectively, in order to achieve the first aim. The second aim was achieved through utilisation of databases of an African-based HIV treatment programme- AIDS Prevention Initiative in Nigeria (APIN), located in Jos, Nigeria. The European Union-funded Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) case-control study in three West African countries was the platform through which urinary metabolic profiling was accomplished. Proton nuclear magnetic resonance spectroscopy (NMR) and parallel ultra-performance liquid chromatography mass spectrometry (UPLC-MS) were used for biomarker discovery studies. Mortality rates of intrahepatic bile duct carcinoma (IHBD) increased in all countries that were studied. Misclassification of hilar cholangiocarcinoma accounted for only a small increase in the rate of IHBD in England and Wales. With over 90% screening rate for viral hepatitides, the rates of hepatitis B (HBV), hepatitis C (HCV) and HBV/HCV in HIV-infected patients in the APIN programme were 17.8%, 11.3% and 2.5% respectively. There was attenuated immune response as well as significantly lower survival observed in HBV/HIV co-infection, relative to HIV mono-infected patients (p=0.0097). Whereas single urinary metabolites, including acetylcarnitine, N-acetylglutamate, betaine aldehyde, 3'-sialyllactose, methionine among others possessed high discriminatory power to diagnose HCC, a combination of three metabolites: 3'-sialyllactose, methionine and 9-decenoylcarnitine significantly outperformed serum alpha-fetoprotein (AFP) in the diagnosis of HCC in a cirrhosis population (area under the receiver operating characteristic curve; [urinary panel= 0.96] compared to [AFP = 0.64]). This work informs a critical assessment of current control strategies in the prevention of HCC, and potentially assists in the development of more affordable means of early detection of PLC for most affected regions of the world.
15
Webster, Peter John. "Targeting tumour angiogenesis in colorectal cancer liver metastases." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/16824/.
Full textAbstract:
Colorectal cancer liver metastases (CLM) remain a significant cause of cancer-related morbidity and mortality. Central to their survival and growth is the process of tumour angiogenesis. Current clinical anti-angiogenic therapies target vascular endothelial growth factor signalling, but resistance to therapy is problematic. The aim of this study was to identify proteins critical for CLM endothelial cell (CLMEC) survival that could be targeted for the development of new anti-angiogenic therapies. CLMECs and endothelial cells of normal adjacent liver (LECs) were isolated from patients undergoing curative resection. The two cell types were superficially similar, exhibiting markers and functional characteristics expected of endothelial cells. However, a number of differences in protein expression were identified, one of which was the previously unrecognised upregulation of the WEE1 checkpoint-kinase, a target of the small molecule WEE1 inhibitor AZD1775, currently in clinical trials. AZD1775 monotherapy was shown to inhibit proliferation and migration of CLMECs. Investigation of the underlying mechanism suggested induction of double-stranded DNA (DS-DNA) breaks due to a critical nucleotide shortage, which then led to caspase-3 dependent apoptosis. The implication for CLMEC tube formation was striking, with AZD1775 inhibiting branching tube formation by 83%. AZD1775 also had direct anti-cancer activity in a p53-mutated colorectal cancer cell line (HT29). In combination with 5-FU it caused increased caspase-3 dependent apoptosis because of DS-DNA breaks, not premature mitosis, which is thought to be the mechanism of AZD1775 toxicity when used in combination with DNA-damaging agents. Proteomic screening of matched LECs and CLMECs identified a further 157 differentially expressed proteins, including up-regulation of the established endogenous angiogenesis inhibitors thrombospondin-1 and vascular endothelial growth factor receptor-1. The mechanosensitive, Ca2+ permeable ion channel Piezo1 was identified as another potential anti-angiogenic target in CLMECs. Modulation of the Piezo1 channel with the newly discovered Piezo1 activator Yoda1 is demonstrated for the first time in CLMECs and shown to induce phosphorylation of endothelial nitric oxide synthase. This study has identified a number of proteins that are differentially expressed in CLMECs, which could be targeted for the development of anti-angiogenic therapies in the treatment of CLM. AZD1775 has anti-angiogenic activity in CLMECs and Piezo1 represents another target which can be investigated in future studies.
16
Taylor, Ryland James. "The impact of cancer cachexia on the liver." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/9723.
Full textAbstract:
Cancer cachexia is a debilitating condition that occurs in a majority of advanced cancer patients. The fundamental feature of cachexia is the rampant depletion of body weight, most critically that of skeletal muscle. Due to the underlying systemic inflammation and metabolic imbalances observed in cachexia, and given the integral role of liver in maintenance of energy homeostasis and its central role in the acute phase response to inflammation, I explored a key area of research that had been neglected - the role of hepatic metabolism in cancer cachexia. The colon 26 carcinoma was selected for study. My first aim was to comprehensively detail features of cachexia in C26 tumour-bearing mice. Then hepatic gene expression was comprehensive analysed using mRNA transcript and proteomic profiling, along with analysis of impacts to circadian regulatory processes across a 24 hour period and attempted reversal of cachexia using antibody blocking at the IL-6 receptor. Hepatic gene and protein expression profiling revealed alterations to lipid handling pathways. Comparison of hepatic and plasma lipid profiles reflected this imbalance with increased sphingolipid levels and reduced hepatic accumulation of di- and triglycerides. Multi-Omic profiling revealed repression in core hepatic regulation and increases in protein translation and acute phase protein synthesis. Mitochondrial processes responsible for ATP synthesis and NAD+ synthesis/salvage were repressed in cachexia. Additionally, there appeared to be a dysregulation in transcriptional control mediated by RXRα-partnered nuclear receptors. Circadian analysis revealed reduced diurnal cycling within nuclear receptors and metabolic genes. The attempted intervention by blocking the IL-6 receptor did not prevent cachectic weight loss in the mice, but it did highlight avenues of future research into the role of other IL-6 family cytokines in the C26 model of cancer cachexia.
17
Sinha, S. "Detection of structural variations during liver cancer progression." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/265927.
Full textAbstract:
Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world and accounts for the vast majority of all liver cancers. HCC develops in response to various factors including viral infections, aflatoxin, alcohol and metabolic diseases. Recent studies have highlighted substantial differences in the acquired genomic alterations depending on the causative agent. Despite such a mutagen-dependent genetic heterogeneity, HCC is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is not yet clear.
The aim of my PhD project has been to understand how chronic inflammation and fibrosis affect the cancer genome. We mapped the acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters. These HCCs arise as a result of chronic exposure to non-neutralized bile acids that cause the onset of chronic inflammation and develop into cancer in the absence of exogenous direct (viruses) or indirect (alcohol) mutagens. We first studied the mutational landscapes of human and mouse cancer genomes and found a surprisingly low number of somatic point mutations with no impairment of cancer genes. We next studied the acquisition of somatic copy number variations (CNVs) and used well-established approaches for detecting CNVs from SNP arrays and whole genome sequencing data. We also developed a novel method, GeneCNV, for the identification of CNVs from targeted re-sequencing screenings. Overall, we observed the acquisition of massive gene copy number gains and rearrangements in both human and mouse HCCs. Amplifications preferentially occurred at late stages of cancer development and frequently targeted the mitogen-activated protein kinase (MAPK) signalling pathway, in particular, direct regulators of c-Jun NH2-terminal kinases (JNKs). We showed that that pharmacological inhibition of JNK impairs the adenoma-to- carcinoma progression in mouse. This suggests that JNK inhibition may be a useful therapeutic approach to block HCC onset in bile salt export pump (BSEP) deficiency patients waiting for liver transplantation.
Altogether, this study showed that human BSEP-HCCs and mouse Mdr2-KO HCCs acquire a similar genomic signature, thus highlighting the remarkable analogy between human and mouse tumours with similar etiopathogenesis. This genomic signature differs from that of other HCCs profiled so far, which were for the most part virus induced. This demonstrates that HCC in the absence of external agents develops through genomic alterations that can be clearly distinguished from those determined by other etiological factors.
18
Lee, Aimei Yen-Jia. "The glycoprotein Basigin in liver disease." Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/17163.
Full textAbstract:
Basigin (Bsg) is a membrane glycoprotein expressed by many different cell types. Bsg is instrumental in tissue development, extracellular matrix (ECM) remodelling, and has been implicated in numerous cancer types. The liver carries out many important functions and when injured, undergoes ECM remodelling. Persistent liver damage can lead to the development of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Bsg is highly expressed within the liver, and membrane bound Bsg is known to be increased in liver disease and HCC. Bsg may also be solubilised via cleavage from the cell surface or secreted in microparticles (MPs) to exert its actions at distal locations. However, not much is known about soluble Bsg (solBsg) in liver disease and its progression. It is also not known whether the glycan structures on Bsg alter with liver disease, and there is a lack of knowledge about the expression of glycosylation-associated genes in the context of liver disease. Hence this thesis sought to investigate solBsg and glycosylation-associated genes in liver disease. The major findings of this thesis identified significant correlations between solBsg and liver diseases, as well as numerous characteristics of HCC. Further, it has been demonstrated that solBsg has the potential to be utilised as a biomarker in the progression of liver disease and HCC prognosis. The results have also demonstrated that glycosylation-associated genes within the liver are dysregulated in different liver diseases. It was also shown that different cytokines, which are prominent in an inflammatory liver environment, are involved in affecting the transcription of glycosylation-associated genes. Future research into the glycan structures of Bsg as its activities become malignant may enable the development of personalised novel therapies to target specific disease conditions.
19
Ma, Kwai-yee Stephanie, and 馬桂宜. "Identification and characterization of tumorigenic liver cancer stem/progenitor cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557534.
Full textAbstract:
Li Ka Shing Prizes for best PhD theses in the Faculties of Dentistry, Engineering, Medicine and Science, 2006-2007published_or_final_version
abstract
Pathology
Doctoral
Doctor of Philosophy
20
Ma, Kwai-yee Stephanie. "Identification and characterization of tumorigenic liver cancer stem/progenitor cells." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39557534.
Full text
21
Little, Sarah Ann. "Hepatic malignancy neo-adjuvant therapy and surgical management : clinical and in vivo studies /." Available from the University of Aberdeen Library and Historic Collections Digital Resources. Restricted: no access, contains 3rd party material and therfore cannot be made available electronically, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=26220.
Full textAbstract:
Thesis (M.Phil.)--Aberdeen University, 2008.Title from web page (Viewed on July 29, 2009). With: Improvement in perioperative outcome after hepatic resection : analysis of 1,803 consecutive cases over the past decade / W. R. Jarnagan ... et al Ann. Surg. 2002: 236(4), 397-407. With: Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer / Sarah A. Little ... et al. J. Gastrointest. Surg. 2002: 6, 88-94. With: Tumours of the ampulla and bile ducts / S. A. Little ... et al. in: Current diagnosis and management in gastroenterology / S. L. Friedman, K. R. McQuaid, J. H. Grendell (eds). With: Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholanagiocarcinona : implications for adjuvant therapeutic strategies / S. A. Little ... et al. Cancer: 2003: 15, 98(8) 1689-700. With: Hepatocellular carcinoma : current surgical management / S. A. Little Y. Fong. Seminars in oncology 2001: 28, 5 474-486. With: Neoadjuvant treatment of hepatic malignancy : an oncolytic herpes simplex virus expressing 1L-12 effectively treats the parent tumor and protects against recurrence after resection /W.R. Jarnagin ... et al. Cancer gene therapy. 2003: 10: 215-223. With: The neo-adjuvant combination of an oncolytic HSV-1 with external beam radiation has potent additive effects against a nude mouse model of human cholangiocarcinoma / J. S. Zagwer ... et al. Wangelsteen Surgical Forum. 2001: LII, 252-255. With: Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy / W.R. Jarnagin Cancer gene therapy. 2006: 13, 3, 326-34. Includes bibliographical references.
22
朱立新 and Lixin Zhu. "Mechanism of spontaneous rupture of hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31238087.
Full text
23
張飛泉 and Fei-chuen Tzang. "Radiofrequency ablation of hepatocellular carcinoma: identifying prognostic factors in long-term survivaloutcome." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40738711.
Full text
24
龔衍峰 and 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.
Full text
25
Ng, Oi-lin Irene. "Patho-biological prognostic factors in hepatocellular carcinoma." [Hong Kong : University of Hong Kong], 1994. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13762412.
Full text
26
Shen, Minqian. "Roles of estrogen hormones and estrogen receptors on regulation of liver and liver cancer metabolism." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1492612390075921.
Full text
27
Ko, Chi-fat. "Molecular regulations of deleted in liver cancer (DLC) protein family." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B41896889.
Full text
28
Lau, Yuen-ting, and 劉婉婷. "Functional characterization of cancer-associated fibroblasts in the regulation of cancer stem cell-like properties in hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/209516.
Full text
29
Nguyen, Thi Lam Uyen Nguyen Centre for Advanced Macromolecular Design Faculty of Engineering UNSW. "Crosslinked microspheres as drug delivery system for liver cancer." Publisher:University of New South Wales. Centre for Advanced Macromolecular Design, 2008. http://handle.unsw.edu.au/1959.4/41528.
Full textAbstract:
It has been demonstrated that 1,25 dihydroxy vitamin D3 (1,25 (OH)2VD3) can inhibit the proliferation of cancer cells including colorectal and hepatocellular cells which are mainly responsible for liver cancer. However, the use of 1, 25 (OH)2VD3 is hampered due to the development of hypercalcaemia. Current treatment using hepatic arterial delivery of drug solution is inconvenient since repetitive invasive treatments are required. This work aims to tackle this problem by utilizing crosslinked microspheres prepared by suspension polymerization as a carrier to control the release of 1, 25 (OH)2VD3 or hydrophobic drug in general at targeted sites over a long period. Poly(vinyl neodecanoate crosslinked ethyleneglycol dimethacrylate) microspheres in the size range of 35 m were prepared via suspension polymerization. Different parameters in suspension polymerization such as temperature, concentration and crosslinker percentage were studied in details. The effect of stabilizer on the formation of spheres was carefully investigated by using RAFT polymerization to produce various structures of the stabilizer, poly (vinyl pyrrolidone). Core- shell microspheres were also produced to enhance the hydrophilicity of the surface of microspheres. Hydrophobic drugs were loaded to these microspheres after reaction by the evaporation method. These microspheres were then used for drug loading and drug release study. Release study has shown that up to 10% of drug was released after 40 days. Cytotoxicity test reveals the suitability of this polymer for application in biomedical field. The MTT assay of Clofazimine loaded microspheres on the colorectal cancer cell lines HT29 has shown that the cell number was decreased about 50% after drug treatment.
30
Sinha, S. "The role of oncogenes in experimental rat liver cancer." Thesis, Open University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234898.
Full text
31
Weinberg, Brent D. "Intratumoral Chemotherapy for Liver Cancer Using Biodegradable Polymer Implants." Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1176749922.
Full text
32
Kita, Ryuichi. "INFREQUENT ALTERATIONS OF THE p16^ GENE IN LIVER CANCER." Kyoto University, 1998. http://hdl.handle.net/2433/182241.
Full text
33
Schlichtemeier, Steven Marc. "Studies in patients undergoing liver resection for hepatocellular cancer." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14581.
Full textAbstract:
INTRODUCTION Hepatocellular cancer (HCC) is a leading cause of mortality and liver resection is the main treatment in suitable patients with operable HCC. While considerable research has been performed in identifying prognostic factors and molecular markers associated with poorer survival little of this research has originated in Australia. METHODS Clinicopathological and survival data was retrospectively collected from patients who underwent liver resection for HCC at Royal North Shore/North Shore Private Hospitals (North Shore) and Westmead Hospital (Westmead) from 1998 to 2012 (n=125). A survival analysis was performed and prognostic factors were identified. Subgroup prognostic factor and molecular marker research on North Shore patients was also performed using tissue proteomics (n=30) and immunohistochemistry (IHC; n=34, n=30). RESULTS In the combined group of 125 patients the 5-year overall survival rate was 56%. On multivariate analysis, only microvascular invasion (MVI) was independently associated with a poorer prognosis on both overall and disease-free survival. Further analysis revealed that age > 64, serum alpha-fetoprotein (AFP) and tumour size > 50 mm were independent preoperative risk factors for MVI and these were used to create an MVI prediction model (area under the curve (AUC) 0.721 or 0.724 depending of AFP cut-off value). Subgroup proteomic analysis identified a panel of four proteins that were differentially expressed between HCC and adjacent normal liver tissue (AUC 0.954). The decreased expression of one of these proteins -- m/z 9,961 -- correlated significantly with the presence of MVI. Subgroup IHC analysis identified several varied clinicopathological correlations with the panel of selected molecular markers (Ki-67, p53, MSI, CK19, GPC3 and S100A6). DISCUSSION In conclusion, our overall survival rate was comparable to the international literature and MVI was the main independent predictor of poor prognosis in our patients. Though our preoperative MVI prediction model did not achieve a clinically applicable AUC, decreased expression of protein m/z 9,961 significantly correlated with the presence of MVI in the proteomics subgroup. This protein should be identified as it could play an important role in liver carcinogenesis. Finally, the clinicopathological correlations in the IHC subgroup were of varied value and additional work could be considered with larger sample sizes.
34
Liu, Da. "Role of Sphingosine Kinases in Liver Metabolism and Cancer." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29556.
Full textAbstract:
Hepatocellular carcinoma (HCC), a primary liver cancer, ranks the sixth morbidity of all cancers and the fourth cause among all cancer deaths. Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and associated lipid metabolic conditions are emerging as chief risk factors for HCC. Sphingolipids are a family of essential lipids in cells. Of them, ceramide, sphingosine, and sphingosine 1-phosphate (S1P) are well-known signalling molecules regulating cellular metabolism and functions. Sphingolipid homeostasis is determined by sphingosine kinases (SphKs), the enzymes that convert ceramide/sphingosine into S1P. My host laboratory and others have implicated both SphK isoforms in chronic liver diseases. SphK1 has been defined as a tumour-promoting factor. It is highly expressed in multiple cancers, including HCC. My host laboratory and collaborators have found that knockout of SphK1 suppresses the Diethylnitrosamine (DEN)-induced HCC in mice. Meanwhile, I and my colleagues have identified SphK2 as a metabolically protective factor against hepatic insulin resistance in diet-induced obese mice. Mechanistically, SphK2 deficiency results in an inhibition of hepatic insulin signalling.
Extended from previous findings, this Master of Philosophy project aims to 1) test if PF-543, a novel, highly selective SphK1 inhibitor, can suppress DEN-induced HCC in vivo; 2) examine if the liver-specific knockout of Sphk2 can predispose NAFLD progression to NASH in mice. PF-543 has never been tested in any primary cancer models in vivo, although it holds promise to be a new anti-HCC therapy. In addition, liver-specific Sphk2 knockout mouse is a long-coveted tool to achieve a definitive, in-depth understanding of the pathophysiological roles of SphK2. In this project, I found that intraperitoneal injection of PF-543 for 12 weeks significantly reduced tumour number and size and mitigated hepatic inflammation in DEN-induced HCC. Notably, the treatment didn’t result in cytotoxicity in liver cancer cells. Instead, it profoundly suppressed tumour neo-vasculature. In addition, I demonstrated that liver-specific ablation of SphK2 promoted the development of glucose intolerance, insulin resistance, hepatic steatosis, and liver fibrosis in mice on a high-fat, high-cholesterol diet for 12 weeks, indicative of NAFLD progression to NASH.
In conclusion, my study provides the first experimental evidence to demonstrate the anti-HCC effects on PF-543 in vivo, offering a potential therapeutic option for difficult-to-treat HCC. Furthermore, my findings of the metabolically protective roles of SphK2 in NAFLD/NASH generate new knowledge of lipid metabolic causes of chronic liver diseases and provide a novel target for fundamental research and drug development.
35
Budzinska, Magdalena. "Genomic Alterations as Determinants of Liver Injury and Cancer." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23216.
Full textAbstract:
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths and arises after decades of chronic liver disease. We aimed to identify genomic alterations in progressive liver disease by examining non-tumour tissue associated with advanced liver injury. Whole-exome sequencing (WES) was performed on liver tissue (n=32) and analysed with public data from non-tumour tissue adjacent to HCC (n=79) and healthy controls (n=30). No genomic variants could consistently distinguish between different stages of progressive liver injury. However, variants were associated with biological pathways related to the development of liver fibrosis. To account for disease- and patient-dependent variations, whole-genome sequencing and WES were done on sporadic and two familial cohorts of PSC (n=10 and n=19, respectively). This identified two putative causal variants in familial PSC (TPP2 and AHNAK) and six likely disease modifier genes, suggesting a recessive inheritance pattern with other genes potentially contributing to the disease susceptibility. Further, the genomic landscape of familial and sporadic PSC differed, suggesting multiple disease-specific genomic variants exist for PSC. Specific genomic alterations (viral DNA integration) in chronic HBV were studied as a potential pro-oncogenic driver during disease progression. Virus-cell junctions from liver tissues (n=41) and an in vitro HBV model were detected by inverse nested PCR. Our results suggest no significant selection for (or against) integration into specific cellular sites. Thus, most HBV DNA integrations are likely passenger events rather than active drivers of HCC as previously suggested. In conclusion, individual genomic alterations do not appear to drive hepatocarcinogenesis in progressive liver disease. Instead, the combination of alterations affecting important biological pathways plays a role in disease progression. Moreover, putative driver alterations likely occur late during cancer development.
36
Dave, Rajiv Vipool. "Oncolytic vaccinia virus for the treatment of liver cancer." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/6887/.
Full textAbstract:
Aims: Current treatment of colorectal cancer (CRC) liver metastases has a success rate of 50% 5-year survival, and recurrence rates of 50%. There is therefore still a need for a novel treatment modality. We aimed to examine the ability of JX-594 to preferentially replicate in and kill CRLM in vitro and ex vivo, and induce immunemediated tumour cytotoxicity by activation of natural killer (NK) cells. Methods: The Wyeth strain of vaccinia virus has been genetically manipulated to encode for granulocyte macrophage colony stimulating factor (JX-594-GM-CSFfLuc) and green fluorescent protein (JX-594-GM-CSF-GFP) in the disrupted thymidine kinase locus. Viability assays and Enzyme Linked Immunoabsorbent Assay (ELISA) was used to confirm tumour cell killing and production of inflammatory cytokines when CRC cell lines were infected with JX-594. Viral replication in vitro was investigated by plaque assay and using an ex vivo ‘tissue core’ method. Induction of the innate immune response was measured by upregulation of activatory markers on virus-treated-NK cells and monocytes by flow cytometry and anti-tumour cytotoxicity by chromium release. Results: JX-594 can directly lyse CRC cell lines, with greater lysis and replication (up to 250-fold) in cells with upregulated surface EGFR. JX-594 treatment resulted in substantial expression of GM-CSF and induction of inflammatory cytokines within the tumour microenvironment, and inhibition of anti-inflammatory and proangiogenic cytokines. Ex vivo infection of CRLM with JX-594-GFP-GM-CSF resulted in tumour-specific GFP and GM-CSF expression. Treatment of NK cells with JX-594-GM-CSF led to activation, degranulation and increased cytotoxicity against CRC cell targets. This was dependent on the presence of CD14+ve monocytes, which acquired an antigen-presenting phenotype (CD86+veCD11c+veClassIIDR+ve). Conclusions: JX-594 holds promise as a novel treatment modality for disseminated CRC. Direct tumour-specific lysis and transgene expression and the induction of tumour-specific innate immunity means that it may provide a twopronged attack against tumour cells whilst sparing normal tissue.
37
Castilho, Antonia Genevieve. "Identification of liver tumour-initiating cells using a chemoresistantanimal model." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45165415.
Full text
38
AOKI, 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.
Full text
39
Robotin, Monica Cristina. "Liver cancer prevention strategies in high risk Australian populations: challenges and opportunities : Is population-level liver cancer prevention feasible in an Australian setting?" Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/13275.
Full textAbstract:
This thesis sought to ascertain the feasibility of population-level liver cancer prevention in people with chronic hepatitis B (CHB) infection. This followed on from our group’s economic modelling work, showing that improved CHB management delivers better and more cost-effective hepatocellular cancer (HCC) outcomes, compared to HCC screening. Establishing the B Positive program in South West Sydney allowed us to test a primary care-based HCC prevention intervention in a high CHB prevalence area. We found that local General Practitioners (GPs) could accommodate additional appointments for CHB management, but not the local specialist services. Consequently we developed a CHB management algorithm stratifying patients by level of HCC risk, with high-risk patients referred for antiviral treatment and primary care-level management for the rest. As antiviral treatments accounts for 75% of program costs, lowering drug costs is critical to make HCC prevention affordable in low-resource settings. We addressed local health practitioners’ information needs about CHB and offered additional practice support. We established a CHB disease Registry, currently enrolling approximately 25% of our target population, with antiviral treatment uptake 6-fold higher than the national average. This thesis demonstrated that clinical-Public Health collaborations can deliver successful HCC prevention at primary care level, endorsed by the local community.
40
Healey, Andrew James. "The roles of laparoscopic liver resection and hypoxia inducible factor in the pathophysiology of liver cancer." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/9319.
Full textAbstract:
In the last 20 years laparoscopic liver resection has been increasingly practised. However its role in the treatment of liver cancer remains under scrutiny. I performed a pilot study at a specialist HPB unit assessing the results of the laparoscopic resections of one surgeon and comparing them to the results of matched cases on whom he had performed open resection. The resection technique was radiofrequency assisted resection pioneered in this unit. I also analysed the resected tissue to investigate any differential effect on cell characteristics of the 2 operative techniques. Operative time was significantly longer in laparoscopic cases and time to recurrence of R0 resections significantly shorter. Resected tissue demonstrated significantly higher levels of the hypoxia inducible factor-2 and CD10, a recognised poor prognostic marker in primary colorectal tumours. I hypothesised that livers resected laparoscopically are under a relative hypoxia because of the increased intraabdominal pressure associated with the pneumoperitoneum and tumours cells therefore have a positive selection advantage. In the setting of longer resection times this may compromise the oncological result of the surgery causing earlier recurrence. Using a established model of HIF activation, I showed that poor prognostic marker CD10 may be a function of hypoxia inducible regulation. Certainly I was able to replicate data from cervical squamous epithelia demonstrating that both in benign, dysplastic and malignant tissue, HIF expression corresponded to a reduced cell E-cadherin expression that may allow a more malignant potential. I also analysed the effect of RF ablation on circulating tumour cells in palliative irresectable cancers and in the context of both open and laparoscopic liver resection. This showed only a transient rise in both resectional techniques, (open and lap) that would unlikely count for the differential oncological outcome previously demonstrated in the pilot study. In keeping with current international opinion, further work is required to verify the role of laparoscopic liver resection in liver cancer.
41
Thomasset, Sarah Carol. "Cancer chemopreventive properties of anthocyanins in patients with colorectal cancer and colorectal liver metastases." Thesis, University of Leicester, 2009. http://hdl.handle.net/2381/7515.
Full textAbstract:
Anthocyanins, polyphenolic phytochemicals which render fruit and vegetables bright red or blue, possess anticarcinogenic properties in preclinical models of carcinogenesis. The aim of this study was to elucidate whether consumption of mirtocyan, a standardised anthocyanin extract, would cause pharmacodynamic changes consistent with chemoprevention and generate measurable levels of anthocyanins in blood, urine and target tissue. Twenty-five patients with either primary colorectal cancer or colorectal liver metastases received 1.4, 2.8 or 5.6 g of mirtocyan (containing 0.5-2.0 g anthocyanins) daily for 7 days prior to colon/liver resection. Anthocyanin levels were measured by high performance liquid chromatography. Proliferation (Ki-67), apoptosis (caspase-3) and inflammation (COX-2) were measured in colorectal tumour tissue. Effects on the insulin-like growth factor (IGF) axis were evaluated in plasma and markers of oxidative DNA damage were assessed in blood and urine. Consumption of up to 5.6 g of mirtocyan daily was well tolerated. Analysis of colorectal tumour tissue revealed that consumption of mirtocyan was associated with a 7% decrease in proliferation (p=0.003) and a 1.7% increase in apoptosis (0.044). A trend towards a reduction in circulating IGF-1 levels was observed (p=0.168). Mirtocyan anthocyanins and methyl and glucuronide metabolites were identified in plasma, urine and colorectal tissue, but not in liver. Anthocyanin concentrations in biomatrices were approximately dose-dependent. Following consumption of 5.6 g of mirtocyan daily anthocyanin levels in plasma, urine and colorectal tumour tissue were 117 ng/ml, 3 μg/ml and 179 ng/g, respectively. Mirtocyan did not affect levels of COX-2 or markers of oxidative DNA damage. Administration of mirtocyan furnished levels of anthocyanins in colorectal tumour tissue comparable to those capable of mediating chemopreventive effects in vivo. Consumption of only 1.4 g of mirtocyan daily may exert pharmacodynamic effects commensurate with colorectal cancer chemoprevention. These data support further clinical development of anthocyanins as potential colorectal cancer chemopreventive agents.
42
Wang, Clarissa Nicole. "Key processes of family resilience in families with long-term liver cancer survivors in Hong Kong." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42664548.
Full text
43
Chung, Ka-kit, and 鍾家傑. "Significance of thrombospondin 1 (THBS 1) in hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B26627164.
Full text
44
Kok, Tsz-wai, and 郭梓瑋. "Blockade of chemokine (C-X-C motif) receptor 4 for the inhibition of hepatocellular carcinoma metastasis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B4068765X.
Full text
45
Cheung, Ka-yee Cindy, and 張家怡. "Recurrent hepatitis B after liver transplantation and the association with hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/211129.
Full textAbstract:
Liver transplantation (LT) is the most effective treatment for hepatitis B virus (HBV) related liver failure and hepatocellular carcinoma (HCC). Nevertheless, HBV and HCC recurrence rate remains high after LT. Previous studies have shown that HBV reactivation is associated with HCC recurrence and poor prognosis after LT. The main objectives of this study are to investigate the risk factors for HBV and HCC recurrence after LT, the efficacy of antiviral drugs to prevent HBV reactivation and the underlying mechanisms contributing to HBV reactivation.
Firstly, we investigate the risk factor for HBV and HCC recurrence in 551 HBsAg seropositive LT patients, of whom374 had no tumor and 177 had HCC. All patients received indefinite antiviral treatment after LT. The study showed that pre-LT HBV DNA levels and HCC recurrence were significantly associated with HBV reactivation after LT. Younger age, lower Child-Pugh score, beyond UCSF criteria, higher AST level, salvage LT, older donor, HBsAg seropositive at the last follow-up and HBV reactivation after LT were independent risk factors for HCC recurrence. HCC recurrence alone accounts for poor overall survival. The sequence analysis identified drug-resistant mutants as the main contributors to HBV reactivation. In addition, wild-type (antiviral drug-sensitive) HBV reactivation was identified in patients with HCC recurrence.
Secondly, we investigate the efficacy of antiviral drugs monotherapy (Lamivudine or Entecavir) in preventing HBV reactivation. This study showed that patients receiving lamivudine (LAM) experienced significantly greater HBV reactivation and HCC recurrence than those receiving entecavir (ETV). In patients with no tumors, HBV reactivation was found in the LAM groups but not in the ETV groups, due to the appearance of a LAM drug-resistant mutant. In patients with HCC recurrence, HBV reactivation was found in both treatment groups. Wild-type HBV reactivation was identified in 17% (5/29) and 100% (1/1) of HCC patients receiving LAM and ETV respectively. This suggests that, although ETV had higher genetic barriers to HBV drug resistance; it still cannot prevent wild-type HBV reactivation in HCC-recurrent patients.
Thirdly, we investigate the expression of HBV markers in HCC and adjacent non-tumor tissues. Origin of circulating HBV was identified using genetic distance analysis of HBV isolated from different compartments (i.e. HCC and adjacent non-tumor tissues). The study showed that, in some HCC cases, the expressions of HBsAg and HBV replicative efficiency are higher in HCC tissues than in adjacent non-tumor tissues. Moreover, through genetic distance analysis, we demonstrated that HBV reactivation could originate from recurrent HCC. These data suggest that HCC supports HBV replication and that HBV is secreted from recurrent HCC.
Finally, we demonstrate that the up-regulation of drug-specific ABC-transporters is significantly associated with patients with HCC recurrence. In vitro studies also showed that the up-regulation of ABCG2 contributes to antiviral drug-resistant.
Finally, we demonstrate that the up-regulation of drug-specific ABC-transporters is significantly associated with patients with HCC recurrence. In vitro studies also showed that the up-regulation of ABCG2 contributes to antiviral drug-resistant.published_or_final_version
Surgery
Doctoral
Doctor of Philosophy
46
Chan, 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.
Full text
47
Ng, Chi-heng David. "Subcellular localisation of growth suppressor protein deleted in liver cancer 2 (DLC2)." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B32028313.
Full text
48
Blechacz, Boris Roman Alexander. "Genetic approaches to the therapy of hepatocellular carcinoma." Thesis, Open University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.505358.
Full textAbstract:
Hepatocellular carcinoma (HCC) is a devastating malignancy originating from hepatocytes. There is an urgent need for novel therapeutic approaches. Currently explored gene therapy systems have not yet achieved significant survival benefits. The aim of this thesis was the development and evaluation of novel genetic approaches to this malignancy.
49
Fan, Sheung Tat, and 范上達. "Hepatectomy for hepatocellular carcinoma: towards a zero hospital mortality." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B31981653.
Full text
50
曾可澄 and Ho-ching Felice Tsang. "Identification of ankyrin repeats and SOCS box protein 4 (ASB4) as oncogenic biomarker in liver cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40738814.
Full text