Tesis sobre el tema "Liver Cancer Diagnosis"

There are a number of existing staging systems for patients with hepatocellular carcinoma (HCC). Yet, Barcelona Clinic Liver Cancer (BCLC) staging classification is the only one which suggests treatment guidance. Although BCLC staging is widely used in Western countries, it may not fit in the management of HCC patients in Hong Kong as they mostly have different etiologies and have more aggressive treatment strategy when compared with their counterparts in Western countries. It is aimed in this thesis to develop a new prognostic staging system in conjunction with treatment guidelines for HCC patients in Hong Kong. Three thousand eight hundred and fifty six adult HCC patients presented to the Department of Surgery, Queen Mary Hospital between January 1995 and December 2008 were included. The patient data were randomly separated into a training set and a test set for scheme development and performance assessment respectively. Four established prognostic factors which have determinative roles in treatment, namely Eastern Cooperative Oncology Group performance status, Child-Pugh grade, tumor status, and presence of extrahepatic vascular invasion/metastasis, were selected in building the scheme. Cox proportional hazards regression on overall survival was used to derive a relative coefficient for each category of these four factors. Clinical knowledge in addition to the relative coefficients was involved in the proposal of the prognostic stages. Then a classification and regression tree analysis was performed to elicit a set of simple clinical decision rules given the factors. This tree-structured classifier was adjusted with clinical judgment and reconciled with the proposed prognostic staging system for treatment guidelines. This Hong Kong Combined Liver Cancer (HKCLC) prognostic classification scheme stratifies patients to stages I to V with distinct overall survival outcomes. Its performance was compared to BCLC scheme for their discriminatory ability as staging systems and effectiveness of treatment guidelines. The former used receiver operating characteristics (ROC) analysis and concordance index as measures of the ability to distinguish patients with different prognosis for overall survival. HKCLC staging had significantly larger 1-year, 3-year and 5-year area under ROC curve values and higher concordance index vis-a-vis BCLC staging. The latter compared the overall survival of patients who received different treatments. The overall survival of patients with the same BCLC stage and the same HKCLC stage but received HKCLC recommended treatments were compared with those received BCLC recommended treatments by Kaplan-Meier plots and log-rank test. HKCLC treatment guidelines had wider indications for more aggressive treatments than the BCLC treatment schedule, and demonstrated significant survival benefit in our patients.<br>published_or_final_version<br>Surgery<br>Master<br>Master of Philosophy

Includes bibliographical references (leaves 142-168) Aim was the purification and identification of the early primitive ectoderm-like (EPL) cell induction signals within the medium conditioned by the human hepatocellular carcinoma cell line HepG2 and the localisation of the signals that induce EPL cell and primitive ectoderm formation.

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.

The causes of stroke disease in Egypt are considered. The diagnosis of stroke is explained, and the used diagnostic instruments are studied. The prevention liver cancer is explained. The treatment of each of the causes of liver cancer is analyzed.

Bakgrund: I Sverige är cancer en av de främsta dödsorsakerna bland kvinnor. Genom att få ett livshotande besked, som att drabbas av cancer, kan individens livsvärld bli påverkad. Beskedet kan leda till att individen genomgår en kris. Syfte: Syftet med studien var att beskriva hur yngre och medelålders kvinnor lever sitt liv efter en cancerdiagnos. Metod: Studiens metod var beskrivande och genomfördes med kvalitativ innehållsanalys av självbiografier. Självbiografier lästes och meningsenheter togs ut. Meningsenheterna kodades och bildade kategorier som slutade i ett huvudtema. Resultat: Resultatet består av ett huvudtema: Leva i en förändrad livsvärld och sju kategorier, vilka är Trygghet – ovisshet, Glädje – sorg, Nära döden – nära livet, Acceptans – förnekelse, Hantering, Förändrade värderingar och nya insikter om livet, Förändrad framtid. Slutsatser: Kvinnornas livsvärld förändrades på så vis att vardagliga rutiner påverkades. Det uttrycktes en känsla av trygghet i sällskapet av sin familj och sina vänner. Kvinnorna kunde uppleva välbefinnande, trots sin sjukdom vid flertalet tillfällen. Sjukdomen ledde till förändrade värderingar och omprioritering av livet.

Thesis (Ph.D.)--University of Florida, 2004.<br>Typescript. Title from title page of source document. Document formatted into pages; contains 234 pages. Includes Vita. Includes bibliographical references.

Under-acknowledged both clinically and socially as a threat to men’s health, breast cancer in men continues to be a critical health issue, with complex ramifications for those affected. Research exploring men’s breast cancer experiences and their lives beyond the diagnosis remain limited. Hence, this inquiry asks ‘How do men describe breast cancer and their experiences of the illness?’ the aim, to advance understandings about men’s meaning-making of breast cancer and masculinity, and to ‘give voice’ to this under-researched population. Embedded theoretically and methodologically within a critical qualitative health framework, the research has two parts. Part one is a qualitative synthesis of nine existing international studies exploring men’s breast cancer experiences, following Noblit and Hare’s (1988) method for synthesising interpretive qualitative data. The outcomes of this synthesis were used to inform part two: a multi-method phenomenological exploration of men’s breast cancer accounts using verbal and visual data. Thirty-One British men recruited through NHS records, Breast Cancer Care, and social media platforms, used self-authored photographs to illustrate their breast cancer experiences, which they later discussed as part of extended semi-structured interviews. All data were analysed together using Interpretative Phenomenological Analysis (Smith & Osborn, 2003). Integrating and triangulating the findings from the two study phases, the on-going marginalisation of men across the breast cancer trajectory, and how this influences men’s experiences of, and adjustment to the illness, are revealed. Findings from the qualitative synthesis suggest current approaches to breast cancer care and advocacy serve to isolate men, potentially alienating and emasculating them; while patient management practices and informational resources unequivocally marginalise men. Findings from the new inquiry corroborate those from earlier studies, further illuminating the difficulties men encounter and some of their coping strategies. Specifically, three superordinate masculinities were identified: ‘threatened and exposed’, ‘protected and asserted’, and ‘reconsidered and reconfigured’. A schematic representation is presented to show how these interconnected masculinities are encountered, performed and utilised by men from pre-diagnosis through treatment and beyond as they manage, make sense of, and live through breast cancer. How and why men encounter/perform these different masculinities at different points in time across the breast cancer trajectory, and how this aids men’s adjustment to illness, and life beyond the diagnosis, is considered. The findings are expected to have both academic and real-world impact through informing future research, and recommendations for advocacy and intervention for improved future breast cancer care and practices.

I Sverige drabbas nästan ett barn om dagen av cancer. De vanligaste cancerformerna hos barn är leukemi och hjärntumör. De flesta barn insjuknar i en låg ålder. Sjukdomen innebär en lång behandling med svåra biverkningar och orsakar ett avbrott från det dagliga livet med förskola och lek. Detta kan få konsekvenser för deras fysiska och kognitiva utveckling. Den forskning som finns idag är bristfällig gällande barns upplevelser av att leva med cancer. Vårt syfte med studien är därför att beskriva barns upplevelser av sitt dagliga liv ett och ett halvt år efter en cancerdiagnos. Sex stycken avidentifierade intervjuer analyserades enligt Lundman och Hällgren Graneheims (2008) modell för kvalitativ innehållsanalys. I analysen fokuserade vi främst på barnens egna berättelser. Vår studie resulterade i fyra kategorier: Avskärmad från andra barn, Behov av stark känsla av kontroll, Annorlunda samspel i leken, Kroppen är annorlunda, samt nio underkategorier. I diskussionen lyfts vikten av lek, behovet av andra barn, känslan av kontroll samt sjuksköterskans roll för en god vårdrelation fram. Då behandlingstiden är lång med många efterkontroller träffar sjuksköterskan barnen under en längre period. Därför behöver sjuksköterskan som vårdar dessa barn en bättre inblick i hur barnen själva upplever sitt dagliga liv för att på bästa sätt kunna identifiera och tillgodose barnens unika behov. Ett barn som är välinformerat och delaktigt i sin egen vård upplever trygghet.<br>Program: Sjuksköterskeutbildning

Ce travail de thèse a consisté en la synthèse et l’étude de dérivés du macrocycle pyclen (3,6,9,15-tétrazabicyclo[9.3.1]pentadéca-1(15),11,13-triène) pour la complexation de l’90Y3+ et du Gd3+ pour le traitement et le diagnostic du cancer du foie par les techniques respectives de radiothérapie interne et d’IRM. Notre objectif a été de développer des chélates stables et inertes répondant aux critères imposés par le milieu biologique. La lipophilie et la neutralité de ces composés ont également été recherchées en raison des applications visées. Nous avons synthétisé des dérivés du pyclen N-fonctionnalisés par des groupements phosphonate puis développé une série de quatre ligands diversement N-fonctionnalisés par des groupements picolinate et acétate. Ces derniers ont été synthétisés grâce au développement de nouvelles voies de N-fonctionnalisation régiospécifiques. Ces synthèses ont été optimisées et les complexes d’Y3+ et Gd3+ étudiés. Les résultats obtenus nous ont amené à synthétiser un analogue lipophile qui forme avec l’yttrium 90 un excellent chélate pour le traitement du cancer du foie. Enfin, ces études ont mis en évidence le potentiel de certains chélates de Gd3+ à être utilisés comme agents de contraste hépatobiliaires<br>This work consisted in the synthesis and study of Y3+ and Gd3+ pyclen derivatives for liver cancer’s treatment and diagnosis by means of internal radiotherapy and MRI techniques. For these applications, the chelates of interest must fulfill numerous criteria: being thermodynamically stable and kinetically inert but also being lipophilic and neutral. In this work, we have synthesized a pyclen derivative N-functionalized by three phosphonate pendant arms and developed four new pyclen derivatives N-functionalized by either picolinate or acetate moities arranged in various way, thanks to the development of new synthetic pathways leading to regiospecific N-functionalization. These syntheses were optimized and the properties of Y3+ and Gd3+ chelates were studied. The good results we have obtained encouraged us to synthesize a lipophilic analogue which forms with yttrium 90 a very promising chelate, suitable for liver cancer’s internal radiotherapy. The gadolinium(III) chelates also show good properties for a use as a liver-specific MRI contrast agent

Cancer är en sjukdom där antalet drabbade unga vuxna ökar mer än någon annan åldersgrupp. Riskfaktorer är oftast kopplade till människans levnadsvanor och behandling kan bland annat ske genom strålning, operation och läkemedel. Att drabbas av en cancersjukdom för att sedan genomgå behandling kan medföra både fysiska och psykiska besvär. Som ung vuxen kan det innebära förändringar i hela tillvaron, där svårigheterna kan prägla vardagen även efter avslutad behandling.  Syftet med denna litteraturöversikt var därmed att belysa unga vuxnas upplevelser och erfarenheter av att leva med cancer vid diagnos och under behandling. Detta för att få en helhetsbild av deras upplevelser under en längre tid av sjukdomen. Efter granskning av återfunna studier inkluderades slutligen nio artiklar med både kvalitativ och kvantitativ ansats. Med en noggrant genomförd dataanalys identifierades tre huvudteman: psykosociala och emotionella reaktioner, konsekvenser av den förändrade kroppen och relationer. Resultatet strukturerades sedan upp med totalt sju subteman under dessa huvudteman. Av resultatet framkom det att en cancerdiagnos och efterföljande behandling kan påverka de unga vuxna både psykiskt och fysiskt i form av emotionella känslor och kroppsliga förändringar, samt en oro för framtiden. Upplevelserna kan skilja sig från tiden för diagnos till behandling där även åldern hos unga vuxna kan ha en påverkan. Ett starkt stöd uttrycks vara betydelsefullt för välbefinnandet och det krävs därmed att vården breddar kunskaperna för ett givande bemötande gentemot unga vuxna. Sjuksköterskan utgör en betydelsefull roll för att minska lidande och istället arbeta för ökat välbefinnande.

Les métastases hépatiques du cancer colorectal (MHCR) sont fréquentes et sont associées à une mortalité significative. Ces dernières décennies, des progrès thérapeutiques importants ont permis d'en améliorer le pronostic. Plus particulièrement, le rôle des résections hépatiques s'est considérablement élargi dans la maladie métastatique limitée au foie, conduisant à un changement radical dans la prise en charge. Ceci a naturellement eu des répercussions sur l'imagerie, qui doit être très performante au niveau lésionnel, nécessitant des sensibilité et spécificité très élevées. Si les techniques modernes ont permis une amélioration très nette en termes de sensibilité, en particulier grâce aux produits de contraste hépatospécifiques et de l'imagerie pondérée en diffusion, l'amélioration de la spécificité est moins claire et moins bien évaluée. Pourtant, la spécificité est tout aussi importante dans ce contexte, où les erreurs diagnostiques sont coûteuses, avec des chirurgies inutiles en cas de faux positifs, et des résections incomplètes en cas de faux négatifs. Ces deux situations sont accompagnées d'une morbi-mortalité très importante. Le présent travail de thèse va donc explorer de nouvelles pistes dont l'objectif ultime serait d'améliorer la spécificité de l'imagerie des MHCR. La première étude confronte l'apparence des métastases d'origine colorectale en IRM de haute résolution et leur histologie sous-jacente. Cette étude originale démontre que la fibrose tumorale apparait en hypersignal T2 et la nécrose tumorale en hyposignal T2 et hypersignal T1, ce qui va à l'encontre du dogme classique. La seconde étude explore la faisabilité de la fusion d'images IRM/échographie dans l'exploration de lésions hépatiques focales chez des patients ayant un cancer colorectal. Cette étude montre qu'un nombre significatif de lésions ne peuvent être visualisées à l'échographie qu'en utilisant la fusion, ouvrant la voie à une meilleure caractérisation lésionnelle en combinant les atouts de l'échographie et de l'IRM. Enfin, la troisième étude, complétée d'une revue iconographique, analyse le comportement IRM des lésions hépatiques après injection d'un produit de contraste intravasculaire. Elle montre une accumulation progressive du contraste au sein des angiomes, mais pas dans les métastases, conduisant à des apparences très différentes sur la phase tardive. Ceci était aussi observé dans les lésions de petites tailles, ce qui devrait permettre une meilleure spécificité dans les cas difficiles<br>Colorectal cancer liver metastases (CRCLM) are common and result in significant mortality. During the past decades, important therapeutic advances have improved the prognosis signficantly, especially through a marked expansion of the role of hepatic resections in liverlimited metastatic disease, leading to a radical change in management. This was naturally accompanied by an equally radical change in the imaging paradigm, now centered at the lesion level and not at the patient level, requiring very high sensitivity and specificity. While modern techniques have allowed a significant improvement in terms of sensitivity, especially through the use of hepatospecific contrast agents and diffusion imaging, the benefits in term of specificity are less clear, with only few studies focusing on and reporting the specificity of the techniques. However, specificity is equally important in this context, where diagnostic errors are costly, resulting either in unnecessary surgeries in case of false positives or in incomplete resections in case of false negatives. In this setting, our thesis will examine the results of three studies, which objective is to offer possible solutions to better understand the imaging of metastases and improve the specificity of liver imaging of CRCLM. The first study analyzes the association between high resolution MRI appearance of CRCLM and their underlying histology, showing that tumor fibrosis was in hypersignal on T2 Weighted Imaging while tumor necrosis was in hyposignal on T2 Weighted Imaging and hypersignal on T1 Weighted Imaging, which goes against the classical teaching about these lesions. The second study assesses the feasibility of using an MRI/Ultrasound fusion system in the exploration of liver lesions in patients with colorectal cancer. This study shows that more lesions were detected with ultrasound when using the fusion system, suggesting that a fusion system may allow a better characterization of lesions by combining the complementary information of MRI and ultrasound. Finally, the third study and its accompanying pictorial essay, explored the behavior of liver lesions after injection of an intravascular contrast agent. The main finding of this study was that hemangioma were accumulating the contrast over time while metastases were not, a key differentiating feature. This finding was found even in small lesions, often difficult to diagnose, suggesting that using such contrast in the exploration of liver lesions in patients with CRCLM would result in a higher specificity of the method

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug response studies in patient-derived xenograft models of triple-negative breast cancer are also discussed. Taken together, data from these studies highlight LCI’s versatility as a tool for clinical, translational, and basic research applications.

在世界範圍內，肝細胞癌(HCC)是其中一種惡性程度很高並且預後很差的疾病。和其他的癌症一樣，肝癌是一种基因疾病，基因異常的積累在肝癌的生成中扮演著重要的角色。近年來，第二代測序技術（NGS）的迅速發展顯現了前所未見的能力揭示癌癥基因組中分子的複雜性，這為癌癥的生物學，診斷和药物治療提供了一個嶄新的思路。<br>非酒精脂肪性肝炎（NASH）是一種與代謝有關的疾病，在發達國家地區例如美國，歐洲，日本和加拿大，這是其中一種越來越常見的HCC 的病因。在本論文的第一部份，三個NASH 相關的HCC 以及其配對的血DNA 進行了全基因組測序（WGS）。另外還有一個來源于這三個NASH 相關的HCC其中之一的細胞株也進行了全基因組測序。在全部樣品中，測序深度範圍介乎29.1X 到102.2X，序列覆蓋度均大於99%。結果顯示發現的新的單核苷酸變異（SNVs）數量介乎于6,898 至17,129，平均值是11,133。根據這些找到的SNV，隨機選出56 個體細胞SNV 進行Sanger 測序，其中92.9%可以被確認。基因突變譜顯示有頻繁的A:T>G:C 和C：G>A:T 體細胞突變，而C：G>T:A 則在CpG 位點頻繁出現。在眾多的非同義體細胞突變基因中，我們選擇了CTNNB1，PNLIP 和MLL2 這三個基因進行進一步研究，此三個基因都在多於一個病例中發現有突變。在額外的一組44 對NASH 相關HCC及50 對HBV 相關的HCC 的癌變組織和其臨近非腫瘤組織中，我們進一步對這三個基因和TP53 的編碼區域進行了測序，而TP53 是在HBV 相關HCC中被報導有高頻率突變的。在NASH 相關的HCC 中，這些基因都只在腫瘤組織中發現重複出現的錯義突變，在臨近的非腫瘤肝組織沒有發現有突變。在NASH 相關的HCC 中，CTNNB1 的突變率（36.4%）明顯高於在HBV相關的HCC 中的突變率（12.0%，P=0.007）。PNLIP 和MLL2 的突變只在NASH相關的HCC 中發現，其突變率分別為12.1%和7.1%，而在HBV 相關的HCC中，則沒有發現突變。然而，TP53 的突變率在NASH 相關的HCC 及HBV相關的HCC 中差別不明顯（P>0.1）。在功能性研究的實驗中，我们发现在HKCI-10（有PNLIP 突變D396N）細胞株中，PNILP 的活性比在正常肝細胞L02 細胞株（野生型PNLIP）中要低。在永生性肝細胞L02 細胞株中，CTNNB1的突變引起了TOPFLASH 活性的提高以及增加了細胞群落形成的能力。HKCI-10 是一條我們實驗室建立的NASH 相關的肝細胞癌細胞株，在HKCI-10細胞株中，抑制CTNNB1 表達引起了細胞生長和增殖的減少。另外，在DEN誘導肝癌的有代謝失衡的db/db 轉基因鼠中，發現了一個CTNNB1 的突變T41A。據報導，CTNNB1 發生的致癌突變會引起蛋白的穩定並且因此激活經典的Wnt/β-catenin 信號通路，從而引致特定基因的轉錄。對於CTNNB1中最常見的突變S45P(在發現的CTNNB1 突變中占31.3%)，我們做了ChIP-array 實驗，結果顯示，在HKCI-10（CTNNB1 有S45P 突變）中，CTNNB1比在Hep3B 中（野生型CTNNB1）有著更緊密的啟動子結合能力（P<0.001）。Gene ontology 分析結果表明，被S45P 富集的生物過程涉及有RNA 代謝調節，轉錄因子活性和凋亡。MYC，E2F1 和ZFX 被ChIP-PCR 證實是與CTNNB1突變子S45P 有著更緊密結合能力的轉錄因子。<br>在本論文的第二部份，爲了進一步闡明致癌性的CTNNB1 突變S45P在HCC 中的角色，我們研究了一個此前未在HCC 報導過的基因ZFX。ZFX是一個在脊椎動物中高度保守，屬於Zfy 家族的zinc finger 蛋白。有報導指出ZFX 對於胚胎和造血幹細胞的自我更新有著重要的作用。另外亦有文獻報導ZFX 在一系列人類癌癥病例中有過度表達，例如食道癌，胃癌，前列腺癌和神經膠質瘤，並且顯現出致癌基因的特性。在本研究中，qRT-PCR結果提示ZFX 在HCC 腫瘤中的表達明顯高於正常肝組織。ZFX 的表達在51.8%的HCC 腫瘤中明顯高於其配對的鄰近非腫瘤肝組織。功能性研究表明，在MTT 實驗中，細胞的生存力在ZFX 缺失的穩定克隆中明顯減弱（P<0.0001）。在細胞群落形成實驗中，ZFX 缺失的穩定克隆顯示出明顯減弱的群落生長能力（P<0.0001）。在單細胞克隆生成實驗中，ZFX 缺失的HCC穩定克隆展示出數量更少，體積更小的細胞群落。另外，ZFX 基因抑制或者cisplatin 單獨處理均顯示細胞生存力的抑制，其抑制效率分別是24.0%和30.9%。當ZFX 基因抑制合併cisplatin 處理時，細胞生存力的抑制效率顯著地提高至65.2%，這個結果提示ZFX 基因抑制和cisplatin 處理兩者有協同增效作用（P<0.0001）。ZFX 基因的缺失會引起兩個為人熟知的胚胎幹細胞（ESCs）標誌物SOX-2 和NANOG 表達的明顯降低。<br>綜上所述，通過進行全基因測序，本論文的研究結果為NASH 相關的HCC 分子層面上的異常提供了一個高解析度的視覺角度。在NASH 相關的HCC 中，一些可能對於肝細胞癌變有重要作用並且重複出現突變的基因被確定，例如CTNNB1 和PNLIP。CTNNB1 的突變體S45P 的其中一個下游目標基因ZFX，在HCC 中被證實有幹細胞和腫瘤啟動細胞特性。闡明在HCC發展過程中的分子改變以及機制，對於為肝癌病人探索新的治療手段有著重要意義。<br>Hepatocellular Carcinoma (HCC) is one of the most malignant diseases worldwide with poor prognosis. Like other human cancers, HCC is a genetic disease, where accumulation of genetic aberration plays important role in the liver carcinogenesis. The rapid advances in Next Generation Sequencing (NGS) technology in recent years have allowed unprecedented ability to unravel the molecular complexity of the cancer genome, providing new insights into the cancer biology, diagnosis and therapeutic drug development.<br>Non-alcoholic steatohepatitis (NASH), which is related to metabolic disorder, is an increasing common etiological factor of HCC, especially in developed countries such as United States, Europe, Japan and Canada. In first part of this thesis, Whole Genome Sequencing (WGS) was performed on three NASH-associated HCCs and their matched lymphocytic DNA. A cell line developed from one of the three NASH-associated HCCs was also subjected to WGS. The sequencing depth ranged from 29.1X to 102.2X with the coverage >99% shown in all samples. Novel SNVs identified ranged from 6,898 to 17,129 with an average of 11,133. Based on the SNVs found, the validation rate was 92.9% in 56 randomly selected somatic SNVs by Sanger sequencing. Mutational spectrum showed frequent somatic substitution of A:T>G:C and C:G>A:T while C:G>T:A transition exhibited a predominant somatic mutation rate in CpG sites. Among the non-synonymous somatic mutated genes, we selected CTNNB1, PNLIP and MLL2 which were mutated in more than one tumor for further study. In additional cohort of 44 NASH-associated and 50 HBV-associated HCC tumors and adjacent non-tumoral tissues, further sequencing all the coding regions of these three genes and TP53, which has been reported to be highly mutated in HBV-associated HCCs, were carried out. In NASH-associated HCCs, all genes harboured recurrent missense mutations exclusive in tumor but none in adjacent ,non-tumoral liver. The prevalence of CTNNB1 mutations was significantly higher in NASH-associated HCCs (36.4%) when compared to HBV-associated HCCs (12.0%, P=0.007). Mutations of PNLIP and MLL2 were detected only in NASH-associated HCCs with rates of 12.1% and 7.1%, respectively, but none in HBV-associated HCCs. The mutation rate of TP53, however, did not differ much between NASH-associated and HBV-associated HCCs (P>0.1). In functional study, for PNLIP, a loss-of-function in PNLIP activity was found in HKCI-10 harbouring D396N mutation as compared to normal liver cell, L02 with wild-type PNLIP. We demonstrated that CTNNB1 mutants conferred elevated TOPFLASH activity and enhanced colony growth in an immortalized hepatocyte cell line L02. Knockdown of CTNNB1 in HKCI-10, which is a NASH-associated HCC in-house cell line, resulted in inhibition of cell growth and proliferation. Also, a CTNNB1 mutation (T41A) was found in DEN-induced liver cancer of db/db transgenic mouse with metabolic disorder. Since oncogenic mutations of CTNNB1 were reported to be contributed to the stabilization of the protein and hence activate the canonical Wnt/β-catenin signaling pathway, inducing transcription of specific gene sets. We performed ChIP-array focusing on the most common CTNNB1 S45P mutation (accounted for 31.3% of all detected CTNNB1 mutants) in NASH-associated HCCs, the result showed more intense promoter binding affinities in HKCI-10 with CTNNB1 S45P mutation than Hep3B with wild-type CTNNB1 (P<0.001). Gene ontology analysis revealed that S45P mutant enriched the process including RNA metabolic regulation, transcription factor activities and apoptosis. Furthermore, we found that CTNNB1 S45P mutant showed more profound binding affinity to the promoter regions of transcription factors MYC, E2F1 and ZFX by ChIP-PCR.<br>In the second part of the thesis, we aimed to further understand the role of oncogenic CTNNB1 S45P mutant in HCC. Zinc finger protein X-linked (ZFX) gene which is previously undescribed in HCC was studied. ZFX is a zinc finger protein of Zfy family that is highly conserved among vertebrates. It has been reported that ZFX is required for self-renewal of embryonic and hematopoietic stem cells. Also, ZFX is suggested to be overexpressed in a number of human cancers such as esophageal carcinoma, gastric cancer, prostate cancer and glioma, conferring oncogenic characteristics. In this study, qRT-PCR analysis showed a significant higher ZFX expression in HCC tumors compared to normal livers. 51.8% of HCC tumors showed significant up-regulations of ZFX when compared to paired adjacent non-tumoral livers. Functional studies showed significant reduction in in-vitro cell proliferation in HCC by MTT assay (P<0.0001) and colony formation ability by colony formation assay (P<0.0001) in ZFX-deficient stable clones. In single-cell clonogenic assay, ZFX-depleted HCC exhibited fewer and smaller colonies. In addition, while ZFX knockdown or cisplatin treatment alone showed an inhibitory effect on cell viability by 24.0% and 30.9%, respectively, the reduction efficiency of cell viability increased dramatically to 65.2% when combine ZFX-knockdown and cisplatin treatment, indicating a synergistic effect between them (P<0.0001). Also, significant reduced expressions of SOX-2 and NANOG, both well-known embryonic stem cells (ESCs) markers, were observed as a result of ZFX depletion.<br>In summary, findings from this thesis provided high-resolution insight into the molecular aberrations in NASH-associated HCCs by performing WGS. Recurrent mutated genes which may be of great importance in hepatocellular carcinogenesis induced by NASH were identified, such as CTNNB1 and PNLIP. One of the S45P CTNNB1 downstream targets ZFX was demonstrated to confer stemness and tumor-initiating cells (TICs) characteristics in HCC. The understanding of molecular changes and mechanisms underlying HCC development will thus facilitate the exploration of new therapeutic options in patients with this deadly disease.<br>Detailed summary in vernacular field only.<br>Detailed summary in vernacular field only.<br>Detailed summary in vernacular field only.<br>Detailed summary in vernacular field only.<br>Chen, Jiawei.<br>Thesis (Ph.D.) Chinese University of Hong Kong, 2014.<br>Includes bibliographical references (leaves 166-190).<br>Abstracts also in Chinese.

Focal liver lesions are commonly encountered in clinical practice. To be able to differentiate potentially life-threatening lesions from clinically insignificant lesions, and to be able to treat them effectively are the two basic problems of a clinician who comes across such lesions. Percutaneous intervention of the liver with a needle enables a clinician to solve the above two problems in a minimally invasive manner. To date, there is a diversity of needle-related percutaneous interventional procedures that are applicable to the clinical management of patients with liver lesions, such as biopsy of focal lesions, drainage of abscesses, and ablation of tumors. Despite a reasonable safety and efficacy associated with these procedures, there are always grounds of further improvement in techniques and technology of needle-related percutaneous procedures to achieve an even better outcome. It was hypothesized that the application of needle-related interventional radiology to clinical management of focal liver lesions could be facilitated and extended with advancement and refinement in needle-related techniques and technology. This thesis was based on a series of nine studies that aimed to explore the potential of needle-related percutaneous interventions in the clinical management of focal liver lesions and to study the effect of the introduction of innovations in needle-related techniques and technology on such clinical applications. It was concluded that the hypothesis was confirmed.<br>Yu Chun Ho.<br>"April 2006."<br>Adviser: Anil Ahuja.<br>Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5176.<br>Thesis (M.D.)--Chinese University of Hong Kong, 2006.<br>Includes bibliographical references (p. 219-235).<br>Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.<br>Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.<br>School code: 1307.

Aim. In this study, we attempted to identify HCC-specific serum glycoproteins by using glycoproteomic technologies. We targeted at finding glycoforms with aberrant alpha-2,6-sialylation and alpha-1,6-fucosylation in sera of HCC patients. These glycoforms may have potentials to be used as tumor marker(s) in the diagnosis of HCC.<br>Among the validated differential glycoproteins, Hp was the only glycoprotein, glycoforms of which were found to be significantly up-regulated in the HCC group when examining both the sialylated glycoprotein profiles and the fucosylated glycoprotein profiles. This glycoprotein was selected for further investigation. In the independent validation group, increased serum levels of Hp (total), alpha-2,6 sialylated Hp and alpha-1,6 fucosylated Hp was observed in the HCC patients. A unique pattern of Hp glycoforms comprising both hypersialylated fucosylated and hyposialytated fucosylated species was found in the HCC patients. Serum concentrations of these glycoforms were significantly higher in the HCC patients with advanced tumor, suggesting their tumor-specific nature. Besides, we have performed quantitative profiling of N-glycans of serum Hp in the HCC patients, CLD patients and normal subjects, and have attempted to identify HCC-associated N-glycans for HCC diagnosis. Combined used of serum alpha-fetoprotein, serum Hp and its N-glycans, we could achieve 84% sensitivity at 100% and 93% specificities when distinguishing the HCC patients from the CLD patients and from the normal subjects, respectively.<br>Background. Hepatocellular carcinoma (HCC) often arises in patients with coexisting chronic liver disease (CLD). Since alpha-fetoprotein, a conventional biomarker, may also be raised in patients with uncomplicated CLD, the use of alpha-fetoprotein in early detection of HCC is limited. Identification of additional biomarkers may improve early detection. Previous studies have shown that levels of alpha-2,6-sialyltransferase and alpha-1,6-fucosyltransferase change in liver cancer, leading to aberrant glycosylations on some serum proteins.<br>Conclusion. By undertaking glycoproteomic approach, we have identified a panel of potential biomarkers for diagnosis of HCC. These biomarkers were useful for classifying among normal healthy subjects, CLD patients, patients with early HCC and patients with advanced HCC. Some of them were validated with the independent cases. Finally, we have identified a unique pattern of Hp glycoforms comprising both hypersialylated fucosylated and hyposialylated fucosylated species in the HCC patients. Serum Hp and its N-glycans have been shown to have potential values for aiding the diagnosis of HCC.<br>Methodology. There are four parts in this study. The first part is "method development". A method for obtaining quantitative profiles of serum glycoproteins with alpha-2,6-sialylation or alpha-1,6-fucosylation was developed by combined use of lectin affinity chromatography, two-dimensional polyacrylamide gel electrophoresis and enzyme-linked lectin assay. The second part is "biomarker discovery". The quantitative profiles of the serum glycoproteins from 20 HCC patients and 10 CLD patients (control) were compared by bioinformatic approaches to identify potential biomarkers for diagnosis of HCC. The protein identities of the potential targets were obtained by using MALDI-TOF/TOF mass spectrometry. The third part is "validation". An independent set of serum samples from 40 HCC patients, 30 CLD patients and 20 normal subjects was used to evaluate the diagnostic values of the potential biomarkers. The last part of this study was aimed to identify HCC-associated N-glycans on one of potential biomarkers found, and examine their values in diagnosis of HCC.<br>Result. When analyzing alpha-2,6-sialylated glycoproteins, 53 glycoprotein spots were significantly different between the HCC and CLD groups, of which 44 spots belonged to 13 glycoproteins. Bioinformatic analyses revealed that these differential sialoglycoprotein profiles contained valuable information for differentiating the HCC patients from CLD patients, and classifying between early HCC and advanced HCC patients. When analyzing alpha-1,6-fucosylated proteins, 11 glycoprotein spots were significant different between the two study groups, of which 8 spots belonged to 1 glycoprotein. Majority of the protein identities were successfully obtained by MALDI-TOF/TOF mass spectrometry. Among the differential glycoproteins, we have identified a subgroup with a unique pattern of glycosylation. These glycoproteins were characterized by the presence of hypersialylated and fucosylated glycoforms. The differential patterns and the diagnostic values of some of these serum glycoproteins were confirmed in the independent validation group by measuring their serum levels with immunoassays. The results of the logistic regression analyses suggest that complement factor B and haptoglobin (Hp) can be used in combination with alpha-fetoprotein to improve the diagnosis of HCC.<br>Ang, Ling.<br>Adviser: Tereng Chuen Wai Poon.<br>Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0947.<br>Thesis (Ph.D.)--Chinese University of Hong Kong, 2007.<br>Includes bibliographical references (leaves 215-238).<br>Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.<br>Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.<br>Abstract also in Chinese.<br>School code: 1307.

Kan, Hoi Lam.<br>Thesis (M.Phil.)--Chinese University of Hong Kong, 2009.<br>Includes bibliographical references (leaves 103-124).<br>Abstracts in English and Chinese.<br>ABSTRACT --- p.i<br>摘要 --- p.iv<br>ACKNOWLEDGEMENTS --- p.vi<br>TABLE OF CONTENTS --- p.viii<br>LIST OF TABLES --- p.xii<br>LIST OF FIGURES --- p.xiii<br>LIST OF ABBREVIATIONS --- p.xiv<br>PUBLICATION --- p.xvi<br>Chapter SECTION I: --- BACKGROUND --- p.1<br>Chapter Chapter 1: --- Hepatocellular Carcinoma (HCC) --- p.2<br>Chapter 1.1. --- Epidemiology of HCC --- p.3<br>Chapter 1.2. --- Etiology of HCC --- p.3<br>Chapter 1.2.1. --- Cirrhosis --- p.4<br>Chapter 1.2.2. --- Hepatitis virus --- p.4<br>Chapter 1.2.3. --- Plant carcinogens --- p.5<br>Chapter 1.2.4. --- Miscellaneous factors --- p.6<br>Chapter 1.3. --- Clinical presentation of HCC --- p.6<br>Chapter 1.4. --- Existing diagnostic tests for HCC --- p.6<br>Chapter 1.4.1. --- Alpha-fetoprotein (AFP) --- p.7<br>Chapter 1.4.2. --- Imaging --- p.7<br>Chapter 1.5. --- Treatment of HCC --- p.8<br>Chapter 1.5.1. --- Surgical Resection and Transplantation --- p.8<br>Chapter 1.5.2. --- Tumor Ablation or Embolization --- p.8<br>Chapter 1.5.3. --- Chemotherapy and Radiotherapy --- p.9<br>Chapter 1.6. --- Tumor marker development for HCC detection --- p.10<br>Chapter 1.6.1. --- Oncofetal antigens and glycoprotein antigens --- p.11<br>Chapter 1.6.2. --- Enzymes and isoenzymes --- p.12<br>Chapter 1.6.3. --- Growth factors --- p.12<br>Chapter 1.6.4. --- Genetics and epigenetics - mRNA and methylation --- p.13<br>Chapter Chapter 2: --- Hypermethylation of tumor suppressor genes in cancer --- p.14<br>Chapter 2.1. --- Cancer epigenetics --- p.14<br>Chapter 2.2. --- DNA methylation in normal cells --- p.15<br>Chapter 2.3. --- Physiological role of DNA methylation in normal cells --- p.18<br>Chapter 2.4. --- Aberrant DNA methylation in cancer --- p.19<br>Chapter 2.4.1. --- DNA hypomethylation in cancer --- p.20<br>Chapter 2.4.2. --- DNA hypermethylation in cancer --- p.20<br>Chapter 2.5. --- Development of methylation markers in tumor diagnosis --- p.21<br>Chapter 2.5.1. --- Methods for the analysis of DNA methylation markers --- p.22<br>Chapter 2.5.2. --- Detection of tumor-associated methylated DNA in the circulation of cancer patients<br>Chapter 2.6. --- Aim of thesis --- p.27<br>Chapter SECTION II: --- MATERIALS AND METHODS --- p.28<br>Chapter Chapter 3: --- Methods for detecting DNA methylation --- p.29<br>Chapter 3.1. --- Subject recruitment --- p.29<br>Chapter 3.2. --- Sample collection and processing --- p.29<br>Chapter 3.2.1. --- Tumor tissue samples --- p.29<br>Chapter 3.2.2. --- Peripheral blood samples --- p.29<br>Chapter 3.3. --- DNA extraction --- p.30<br>Chapter 3.3.1. --- Plasma samples --- p.30<br>Chapter 3.3.2. --- Blood cells --- p.33<br>Chapter 3.3.3. --- Tumor tissue --- p.33<br>Chapter 3.4. --- Quantitative analysis of methylated DNA using methylation-sensitive restriction enzyme-mediated real-time quantitative PCR (MSRE-qPCR) --- p.34<br>Chapter 3.4.1. --- Methylation-sensitive restriction enzyme-mediated real-time quantitative PCR --- p.34<br>Chapter 3.4.3. --- Real-time PCR primer design --- p.36<br>Chapter 3.4.4. --- Duplex real-time PCR --- p.40<br>Chapter 3.4.5. --- "Real-time detection of GSTP1, SOCS1, A PC, pl6 and ACTB sequences" --- p.41<br>Chapter 3.4.6. --- Statistical analysis of real-time PCR results --- p.41<br>Chapter 3.5. --- "Methylation study of GSTP1, SOCS1, APC, pl6 and ACTB in tumor tissues and blood cells using bisulfite sequencing" --- p.46<br>Chapter 3.5.1. --- Principle of bisulfite modification --- p.46<br>Chapter 3.5.2. --- Bisulfite conversion --- p.47<br>Chapter 3.5.3. --- Sequencing primer design --- p.47<br>Chapter 3.5.4. --- Conventional PCR after bisulfite treatment --- p.49<br>Chapter 3.5.5. --- Cloning and bisulfite genomic sequencing --- p.53<br>Chapter 3.5.6. --- Data acquisition and interpretation --- p.54<br>Chapter SECTION III: --- DEVELOPMENT OF METHYLATION MARKERS IN HCC DETECTION<br>Chapter Chapter 4: --- Evaluation of the real-time PCR assay for quantification of methylated tumor suppressor genes --- p.57<br>Chapter 4.1. --- Development of real-time PCR assays --- p.57<br>Chapter 4.2. --- Methylation analyses by bisulfite sequencing were concordant with the real-time quantification results --- p.61<br>Chapter Chapter 5: --- Clinical application of methylated markers in the detection of hepatocellular carcinoma --- p.69<br>Chapter 5.1. --- Demographics of HCC patients and HB V carriers --- p.69<br>Chapter 5.2. --- Quantitative analysis of hypermethylated tumor suppressor genes in tumor and plasma samples --- p.71<br>Chapter 5.3. --- Effect of cirrhosis on the plasma methylated tumor suppressor gene concentrations --- p.77<br>Chapter 5.4. --- Changes in the concentration of the tumor suppressor genes one month after surgical resection of the cancer --- p.81<br>Chapter 5.5. --- Concurrent use of serum AFP level and plasma methylated markers for HCC diagnosis --- p.84<br>Chapter 5.6. --- Prognostic value of plasma methylated TSGs --- p.86<br>Chapter SECTION IV: --- DISCUSSION --- p.90<br>Chapter Chapter 6: --- Discussion --- p.91<br>Chapter 6.1. --- Tumor and plasma detection of hypermethylated tumor suppressor genes --- p.92<br>Chapter 6.2. --- No effect of cirrhosis on plasma methylated DNA level --- p.94<br>Chapter 6.3. --- Clearance of methylated TSG sequences after tumor resection --- p.95<br>Chapter 6.4. --- Concurrent use of serum AFP level and the presence of methylated markers in the plasma in HCC diagnosis --- p.95<br>Chapter 6.5. --- Prognostic significance of circulating methylated tumor markers --- p.96<br>Chapter SECTION V: --- CONCLUDING REMARKS --- p.98<br>Chapter Chapter 7: --- Conclusions and future perspectives --- p.99<br>REFERENCES --- p.103

Includes bibliographical references (leaves 142-168)<br>x, 168 leaves : ill. (chiefly col.) ; 30 cm.<br>Aim was the purification and identification of the early primitive ectoderm-like (EPL) cell induction signals within the medium conditioned by the human hepatocellular carcinoma cell line HepG2 and the localisation of the signals that induce EPL cell and primitive ectoderm formation.<br>Thesis (Ph.D.)--University of Adelaide, Dept. of Molecular Biosciences (Biochemistry), 2001

碩士<br>臺北醫學大學<br>醫學資訊研究所<br>102<br>Background: Since 1982 the first one causes of death is cancer. And diabetes is also the top 10 of death in Taiwan, it severely impact people`s health, and cause a lot medical resources in Taiwan. And according to statistics in 2012 by Ministry of Health and Welfare (Taiwan) show that liver cancer is the second leading cause of cancer death in Taiwan, about 7,000 patients died of liver cancer. The main reason is the high prevalence of hepatitis B and hepatitis C, lead chronic liver disease develops into liver cancer. Objective: Using neural networks to construct a predict model that Type 2 diabetes after diagnosed conversion to Liver cancer. Methods: By Using National Health Insurance Research Database to identify Liver cancer complicated by diabetes and use of neural network to construct prediction model. Predictive models factors is use of the chi-square test and T test to test the relation between factors and Lever cancer. Results: In this study we include 31,953 males, and 364 people have liver cancer; include 33,767 females, and 157 have liver cancer; totally include 65,356 people, and 521 people have cancer. The disease risk prediction models, was created by neural network, Sensitivity is 0.802, Specificity is 0.773, and Area Under ROC is 0.873. Conclusion: The model create by Alcohol factor are lower accuracy, the reason maybe is that diabetes and Alcoholic liver disease have relation, and alcohol-related factor have relation with Liver cancer, but dabetes didn’t has a direct impact to liver cancer, so cause that alcohol-related factor can’t to predict liver cancer, In future we should be combined with other database, such as personal health database and health record database, which can find more risk factors.

Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e Tecnologia<br>O cancro oral encontra-se entre os 10 cancros mais comuns, com 405,000 novos casos esperados anualmente, a nível mundial. A sua taxa de sobrevivência a cinco anos é de aproximadamente 80% no estadio I, mas desce para 20% no estadio IV. Apesar do progresso na área terapêutica, as suas taxas de incidência e de sobrevivência permanecem preocupantes, principalmente devido ao diagnóstico tardio e a altas taxas de recidiva. As biópsias de tecido continuam a ser o gold standard para o diagnóstico e para a determinação do perfil genético dos tumores. No entanto, para além de não serem de fácil obtenção e de estarem associadas a riscos e a dor para o doente, as biópsias de tecido apenas oferecem uma caracterização momentânea da heterogeneidade tumoral, não consideram a plasticidade fenotípica das células cancerígenas, e não podem ser obtidas repetidamente para a monitorização dos doentes. Dada a necessidade de desenvolver métodos não invasivos para a deteção precoce, o diagnóstico, e a monitorização de doentes oncológicos, as biópsias líquidas surgiram recentemente como uma potencial abordagem na medicina de precisão. As biópsias líquidas consistem na deteção de componentes derivados dos tumores, incluindo DNA tumoral em circulação (do inglês, ctDNA), em biofluidos, como o sangue e a urina, ultrapassando várias limitações impostas pelas biópsias de tecido, uma vez que são minimamente invasivas, fáceis de repetir durante o acompanhamento clínico do doente, e capazes de detetar a heterogeneidade tumoral. No entanto, o impacto clínico das biópsias líquidas no cancro oral ainda é muito limitado quando comparado com outros tipos de cancro, requerendo mais estudos de validação para a sua implementação com sucesso. Deste modo, o principal objetivo deste estudo piloto foi explorar o potencial das biópsias líquidas no diagnóstico e na monitorização de doentes com cancro oral. Em suma, procurámos monitorizar as concentrações de DNA livre em circulação (do inglês, cfDNA) no plasma e na urina durante o acompanhamento clínico de doentes com cancro oral, e avaliar e comparar as caraterísticas mutacionais do ctDNA e dos tecidos tumorais correspondentes por sequenciação de nova geração (do inglês, NGS). Ambas as análises quantitativas e qualitativas do cfDNA foram correlacionadas com as caraterísticas clinicopatológicas dos doentes. Para além disso, como um objetivo secundário, estudámos os perfis genómicos e epigenéticos dos tumores orais pelas técnicas de a-CGH e MS-MLPA. Foi possível obter informações preliminares interessantes relativamente à cinética do cfDNA durante o tratamento dos doentes com cancro oral, nomeadamente, que os níveis de cfDNA no plasma parecem aumentar em resposta ao tratamento. Para além disso, a identificação de mutações específicas do cancro em genes como TP53 e SMAD4 no ctDNA revelou que as biópsias líquidas podem ser uma fonte de informação relativamente ao perfil genético dos tumores e à resposta terapêutica no cancro oral. Adicionalmente, a combinação das técnicas MS-MLPA e a-CGH permitiu encontrar alterações frequentes na variação do número de cópias e na metilação em tumores, e identificar um conjunto de genes associados a vias celulares comumente alteradas na carcinogénese que poderão ter potencial como biomarcadores.<br>Oral cancer ranks within the top 10 most common cancers, with 405,000 new cases being anticipated each year, worldwide. Its five-year survival rate is approximately 80% in stage I but decreases to 20% in stage IV. Despite the improvements made in the therapeutic area, its incidence and survival rates are still concerning, mainly due to late diagnosis and high rates of recurrence. Tissue biopsies are still the gold standard for diagnosis and for the genetic profiling of tumors. However, besides not being easily obtained and implying risk and pain to the patient, tissue biopsies only provide a snapshot of tumor heterogeneity, do not consider the phenotypic plasticity of cancer cells, and cannot be obtained repeatedly for patient follow-up. Given the need to develop non-invasive tools for early detection, diagnosis and monitoring of cancer patients, liquid biopsies have recently emerged as a potential approach in precision medicine. Liquid biopsies consist in the detection of cancer-derived components, including circulating tumor DNA (ctDNA), in biofluids, such as blood and urine, overcoming many limitations presented by tissue biopsies, since they are minimally invasive, easily repeated during patient follow-up, and able to detect tumoral heterogeneity. However, the clinical impact of liquid biopsies in oral cancer is still very limited when compared to other cancers, requiring further validation studies for its successful implementation. In this sense, the main objective of this pilot study was to explore the potential of liquid biopsies for the diagnosis and monitoring of oral cancer patients. In sum, we aimed to monitor plasma and urine cell-free DNA (cfDNA) concentrations before and during the treatment course of oral cancer patients, and to assess and compare mutational characteristics of ctDNA and corresponding tumor tissues by Next Generation Sequencing (NGS). Both quantitative and qualitative analysis of cfDNA were correlated with the patient’s clinicopathological features. Moreover, as a secondary objective, we aimed to establish the genomic and epigenetic profiles of oral tumor tissues by array-Comparative Genomic Hybridization (a-CGH) and Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA). We were able to obtain interesting preliminary data on the kinetics of cfDNA during the treatment course of oral cancer patients, namely that plasma cfDNA levels seem to increase in response to treatment. Moreover, the identification of cancer-specific mutations in genes such as TP53 and SMAD4 in ctDNA revealed that liquid biopsies could be a source of information regarding the tumors’ genetic profile and therapeutic response in oral cancer. Additionally, the combination of the MS-MLPA and a-CGH techniques allowed us to find common CNVs and methylation alterations in oral tumors and to identify a set of genes related to commonly altered cellular pathways in carcinogenesis that could have potential as biomarkers.

Aim: The aim of this project was to research participants’ lived experiences of being diagnosed and treated for lung cancer in the outpatient departments of an acute care hospital, particularly in relation to whether they reported lung cancer related psychosocial distress and secondly to analyse whether the participants felt that they had received appropriate psychosocial care from the hospital staff. Background: Lung cancer is the leading cause of cancer death worldwide with only 12% of people diagnosed surviving for more than five years beyond their diagnosis and few surviving for more than one year (Australian Institute of Health and Welfare 2011). Consequently, receiving a lung cancer diagnosis is a source of high emotional and psychosocial distress, which research suggests, is often not detected or treated by health professionals with appropriate levels of supportive care. More research is needed to identify the barriers that exist in the outpatient setting, particularly from the patients’ perspective, which undermine best practice psychosocial care. Methods: The fundamental position of phenomenological research is that human understanding is only accessible through inner subjectivity and that each person and their understandings are inseparable from the context of their environment. This approach allows open expression and exploration of patients’ lung cancer experience within the health care context. For this study, Heidegger’s hermeneutic phenomenology has been used for its interpretive approach, as it allows the researcher to use theories, knowledge and pre-understanding when interpreting the participants’ subjective experience. Results: A very high level of unrelieved psychosocial distress and concern was expressed by some of the participants with late stage lung cancer and most participants, regardless of stage, reported ongoing fear of recurrence. Some evidence of barriers which prevent supportive care from occurring became apparent. The findings developed during the research included some simple health care approaches that practitioners can adopt in order to help reduce the psychosocial distress of this group of people. These include ensuring continuity of care, improving empathetic communications, early referral and reflection on professional attitudes. It is hoped that this research will improve understanding and empathy for lung cancer patients, so that detection and treatment of psychosocial distress can be improved.<br>Thesis (M. Nurs.Sc.) -- University of Adelaide, School of Nursing, 2015