by Yam Hin Fai. / "June 1998." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 118-151). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstract in Chinese.

1. Study on improving the diagnostic accuracy of treatment-naive nasopharyngeal carcinoma. / 2. Study on diagnostic accuracy of EBV-DNA on recurrent nasopharyngeal carcinoma. / 3. Studies on EBV-DNA as a screening tool for nasopharyngeal carcinoma. Part 1. To define the detection rate of NPC and the false-positive rate of IgA-VCA in an IgA-VCA-based screening problem, and to define the specificity of IgA-EA in IgA-VCA-positive screenees. Part 2. To define the specificity of EBV-DNA in IgA-VCA-positive screenees. Part 3. To define the sensitivity of IgA-EA, and EBV-DNA in IgA-positive NPC patients. / 4. Studies on pre-therapy prognostication of nasopharyngeal carcinoma Study Part 1. Objective. To assess the role of EBV-DNA in pre-therapy prognostication of early-stage NPC. / Background. The specific association between nasopharyngeal carcinoma (NPC) and the Epstein-Barr virus (EBV) had been exploited to develop a spectrum of EBV-antibodies-based blood markers. Among these markers, the Immunoglobulin A antibody against the viral capsid antigen (IgA-VCA) of the EBV has been the most popularly employed marker to assist diagnosis of NPC. There is however a relative paucity of data on the application of blood markers for screening, for detection of relapse, and for prognostification of patient cohorts managed in present-day therapy oncology protocols. Peripheral blood EBV-DNA, measured by quantitative polymerase chain reaction assay, is a newly-developed marker, and represents a prototype model of a nuclei acid-based, as opposed to antibody-based, EBV tumor marker for NPC. The present thesis describes the translation of this basic scientific advance into clinical applications, through several prospective and retrospective studies that address the diagnosis of treatment-naive NPC, the detection of recurrent NPC, the screening of individuals at risk of NPC, the pre-therapy prognostication for NPC to guide for choice of therapy. The role of integration of conventional markers and EBV-DNA in clinical applications was also examined. / Study Part 2. Objectives. To assess whether incorporation of EBV-DNA data to TNM staging improves prognostic discrimination of patients subsets within individual cancer stage, to assess if EBV-DNA is an independent prognostic factor for survival after ontological therapy. (Abstract shortened by UMI.) / Leung Sing-fai. / "February 2005." / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3695. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

(1) MRI is shown to be an accurate test for detecting NPC and one which has the potential to be used in screening to (a) screen out normal patients who do not require endoscopie biopsy; and (b) identify small tumours that would be missed on endoscopy. / (2) At diagnosis staging NPC by MRI reveals that oropharyngeal and maxillary sinus invasion are markers of more advanced disease than reflected in current staging system. Tumour involvement of the preclival/prevertebral region, skull base and retropharyngeal nodes are more common than previously recognised by computed tomography, while parapharyngeal tumour invasion is less common. The latter resuits from the superior ability of MRI to differentiate primary tumours with true parapharyngeal invasion from those contained within the nasopharynx which are causing bowing of the wall or lie adjacent to a retropharyngeal node. / (3) Post treatment complications were detected by MRI in over 50% of patients. Neural damage, especially to the temporal lobes and 12th cranial nerves, was the most frequent complication (48%), followed by osteoradionecrosis (20%) involving the mandible, upper cervical spine and skull base, the latter including destruction of the roof of the nasopharynx. Malignant tumours and unusual benign masses (6%) showed radiological features useful in the differential diagnosis from NPC recurrence. Malignant tumours were mainly squamous cell carcinomas or sarcomas showing a predilection for the maxillary region, tongue and external auditory canal. The unusual benign masses were found in the nasopharynx/sphenoid sinus. / (4) Finally functional MRI using DWI and 1H-MRS are feasible in the technically challenging region of the head and neck. Choline ratios and ADC values of NPC are established. The successful demonstration of differences between the biomarkers of NPC and those of lymphoma and squamous cell carcinoma, show that functional MRI is a new tool for the evaluation of NPC, opening up the possibility that these biomarkers can be used for monitoring NPC treatment response in the future. / Magnetic resonance imaging (MRI) provides excellent anatomical detail and functional information about cancer. This thesis explores the role of MRI in the assessment of nasopharyngeal carcinoma (NPC) from detection through to the long term complications of radiotherapy treatment. / Ann D King. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3468. / Thesis (M.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 180-191). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English only. / School code: 1307.

Chan Wing Yan Michael. / "August 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 168-200). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

膀胱尿路上皮腫瘤發病率在泌尿道腫瘤中排第二位，它具有高複發性的特點。目前，有創性尿道膀胱鏡檢查是診斷的金標準。儘管先後有很多血液或尿液中的分子被先後用於診斷膀胱癌的診斷研究，但到目前為止尚未有任何一種方法可以取代膀胱鏡檢查。有證據表明在膀胱上皮腫瘤組織中有很多異常表達的microRNA，但是內在機制的有關研究相對缺乏。在本研究中，我們利用在尿液上清中異常表達的microRNA來評估它們在膀胱癌診斷中的價值。而且，我們揭示了其潛在的調控機理。通過microRNA基因芯片，我們結合并對比來自膀胱腫瘤病人和正常對照患者的9個尿液上清樣本，以及4對腫瘤組織及臨近正常黏膜上皮中microRNA的表達，初步篩選出10個異常的microRNA。然後我們使用定量RT-PCR的方法在另外獨立的18對腫瘤組織和正常黏膜中進一步驗證芯片結果。最後我們就6個被帥選出來的microRNA在71例的膀胱癌患者和正常對照組的尿液上清中進行檢測並評估其診斷效能。我們發現，miR-125b和miR-99a的表達在膀胱癌患者的尿液上清中明顯下調。另外，它們下調程度與腫瘤的病理分級相關。結合miR-125b和miR-99b兩者作為診斷膀胱癌的指標，靈敏度達86.7%，特異度達81.1%，同時有陽性預測值達91.8%。當作為腫瘤分級指標，miR-125b具有81.4%的敏感度，87.0%的特異度，陽性預測值達93.4%。膀胱腫瘤切除之後，和術前比較，兩個microRNA的表達水平再度上升。我們將miR-99轉染到三個膀胱腫瘤細胞株中（T24，UMUC3和J82）。我們發現miR-99a對UMUC3細胞具有輕微的抗增殖功能。同時，miR-99a在3個細胞株中顯示均顯示具有抗遷移和抗侵襲能力。為尋找miR-99a的目標mRNA，我們結合數據庫算法預測，在Western blot中驗證到miR-99a能顯著下調VLDLR蛋白。隨後我們將帶有VLDLR的3'UTR質粒轉染進入細胞中并證實VLDLR mRNA是miR-99a直接作用的目標。另外，當VLDLR siRNA被轉入3個細胞株之後，我們觀察到相似的抗遷移和抗侵襲的現象。最後我們發現N-cadherin是該通路中的下游抑制遷移和侵襲的分子。本項研究證實研究尿液上清中的microRNA是可行的。MiR-125b和miR-99a是膀胱腫瘤的診斷和分級的有效指標。此外，miR-99a能夠通過和VLDLR mRNA直接結合從而抑制膀胱腫瘤遷移和侵襲功能。 / Urothelial carcinoma of the bladder (UCB) is the second most common malignancy in the urological system with high recurrence rate. Current gold standard examination for diagnosis is urethrocystoscopy, which is an invasive procedure. Although numerous molecular markers in blood or urine have been proposed as diagnostic biomarkers for bladder cancer, none of them could replace urethrocystoscopy in clinical practice. There are accumulating evidences suggesting microRNA dysregulation might be related to the pathogenesis of UCB. However, the exact functions of these microRNAs in UCB remain unknown. In this thesis, the role of selected microRNAs in urine supernatant was investigated in the diagnosis of UCB and also the carcinogenesis of UCB. / In brief, a high-throughput microarray was carried out on nine supernatants of urine from UCB and normal subjects, and also four pairs of tissue from UCB and normal mucosa. Ten microRNA candidates were then identified. Quantitative RT-PCR was used to validate these microRNAs on a set of 18 pairs of tumor tissue and normal mucosa. Eventually, six potential candidate microRNAs were selected and then validated as diagnostic tools on the samples of urine supernatants from 71 patients (50 of known UCB and 21 of normal subjects). The expression levels of these selected microRNAs were further evaluated in the urine supernatants of 20 patients after tumors resections. MiR-125b and miR-99a were the two most significantly down-regulated microRNAs in the urine supernatants of patients with UCB. Moreover, the degree of down-regulation was associated with the pathological grade of the tumor. A combined index of miR-125b and miR-99a in urine supernatant had a sensitivity of 86.7%, specificity of 81.1%, and a positive predicted value of 91.8% for diagnosing UCB. When used to discriminate high-grade from low-grade UCB, miR-125b alone had a sensitivity of 81.4%, specificity of 87.0% and PPV of 93.4%. After transurethral resections, the expression levels of both microRNAs were significantly increased compared to pre-operative levels. / In further studies on the role of microRNAs on the development of UCB, miR-99a was selected for further studies. The precursor of miR-99a was temporally transfected into 3 bladder cancer cell lines: T24, UMUC3 and J82. The proliferation ability was noticed to be suppressed mildly in UMUC3, but not the other. Meanwhile, migration and invasion abilities were inhibited by miR-99a in the all 3 cell lines. Potential targets of miR-99a were predicted from several prediction databases. Subsequently, in Western Blot study, the protein level of very low density lipoprotein receptor (VLDLR) was showed to be down-regulated by miR-99a. Thereafter, a plasmid constructed with 3’UTR of VLDLR was transfected into cytoplasm, which confirmed VLDLR mRNA was a direct target of miR-99a. All 3 cells lines showed the same effect on suppression of migration and invasion after knockdown of VLDLR. N-cadherin was identified as a down-stream molecule responsible for the migration and invasion suppression in this pathway. / This study confirmed microRNA expression in urine supernatants was a feasible approach for the assessment of biomarkers, and miR-125b and miR-99a showed promising results in the diagnosis and grading of UCB. Furthermore, we showed that miR-99a suppressed tumor migration and invasion by directly targeting VLDLR. / Detailed summary in vernacular field only. / Zhang, Dingzuan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 107-131). / Abstract and appendix also in Chinese. / Abstract --- p.I / 摘要 --- p.III / Acknowledgments --- p.V / Abbreviations --- p.VII / List of figures --- p.IX / List of Tables --- p.XI / Content --- p.XII / Chapter Chapter I: --- General Introduction / Chapter 1.1 --- Bladder cancer --- p.1 / Chapter 1.1.1 --- The incidence of bladder cancer / Chapter 1.1.2 --- The burden of bladder cancer to the health care system / Chapter 1.1.3 --- Risk factors for bladder cancer / Chapter 1.1.4 --- Pathology grading system in bladder cancer / Chapter 1.1.5 --- Current diagnostic methods and treatment for bladder cancer / Chapter 1.2 --- Biomarkers for bladder cancer --- p.7 / Chapter 1.2.1 --- The advantages of biomarkers in blood and urine for the diagnosis of bladder cancer / Chapter 1.2.2 --- Biomarkers in blood for bladder cancer / Chapter 1.2.3 --- Biomarkers in the urine for bladder cancer / Chapter 1.2.4 --- Current concerning problems with biomarkers / Chapter 1.3 --- MicroRNAs and bladder cancer --- p.11 / Chapter 1.3.1 --- Post-trancriptional function of microRNAs / Chapter 1.3.2 --- The function of microRNAs in tumor / Chapter 1.3.3 --- Prospects of detecting microRNA in cell-free fluid in tumor / Chapter 1.4 --- MicroRNA target identification --- p.15 / Chapter 1.4.1 --- Prediction of microRNA target / Chapter 1.4.2 --- Validation of microRNA target / Chapter 1.4.3 --- Validation of direct interaction between microRNA and target RNA / Chapter 1.4.4 --- Validation of direct binding of microRNA and mRNA in vivo / Chapter 1.5 --- Migration and invasion of bladder cancer --- p.19 / Chapter 1.5.1 --- The biological process of migration in bladder cancer / Chapter 1.5.2 --- Epithelial to mesenchymal transition in bladder cancer / Chapter 1.6 --- Objectives of this study --- p.21 / Chapter Chapter II --- MicroRNAs in urine supernatant: potential useful markers for bladder cancer screening / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- Materials and methods --- p.26 / Chapter 2.2.1 --- Ethics Statement / Chapter 2.2.2 --- Patients and samples / Chapter 2.2.3 --- RNA extraction / Chapter 2.2.4 --- MicroRNA microarray / Chapter 2.2.5 --- Quantitative real-time polymerase chain reaction (RT-PCR) / Chapter 2.2.6 --- Statistical methods / Chapter 2.3 --- Results --- p.31 / Chapter 2.3.1 --- MicroRNA screening by microRNA microarray / Chapter 2.3.2 --- Independent validation of the ten selected microRNAs by qRT-PCR on tissue / Chapter 2.3.3 --- Verification of the six validated microRNAs in urine supernatants as tumor markers / Chapter 2.3.4 --- MiR-125b and miR-99a in urine supernatants were useful for the diagnosis of bladder cancer / Chapter 2. --- 3.5 MiR-125b and miR-99a were two highly correlated microRNAs / Chapter 2.3.6 --- Expression levels of miR-125b and miR-99a increased after tumor resection / Chapter 2.4 --- Discussion --- p.47 / Chapter Chapter III: --- MiR-99a suppresses migration and invasion in bladder cancer by targeting VLDLR / Chapter 3.1 --- Introduction --- p.53 / Chapter 3.2 --- Materials and methods --- p.56 / Chapter 3.2.1 --- Human tissue samples and bladder cancer cell lines / Chapter 3.2.2 --- RNA extraction and Polymerase Chain Reaction / Chapter 3.2.3 --- MicroRNA and plasmid transfection / Chapter 3.2.4 --- Western Immunoblotting / Chapter 3.2.5 --- Agarose gel electrophoresis / Chapter 3.2.6 --- Luciferase assay / Chapter 3.2.7 --- MTT proliferation assay / Chapter 3.2.8 --- Apoptosis assay / Chapter 3.2.9 --- Cell cycle analysis / Chapter 3.2.10 --- Cell migration Assay / Chapter 3.1.11 --- Cell invasion assay: / Chapter 3.2.12 --- Statistical methods: / Chapter 3.3 --- Results --- p.67 / Chapter 3.3.1 --- MiR-99a was significantly down-regulated in bladder cancer / Chapter 3.3.2 --- Precursor microRNA was successfully transfected into bladder cancer cell lines / Chapter 3.3.3 --- MiR-99a had little effect on cell proliferation / Chapter 3.3.4 --- MiR-99a had little effect on cell apoptosis and cell cycle / Chapter 3.3.5 --- Over-expression of miR-99a suppressed cell migration in bladder cancer / Chapter 3.3.6 --- Over-expression of miR-99a also suppressed invasion ability in bladder cancer / Chapter 3.3.7 --- Target prediction for miR-99a using 8 target prediction databases / Chapter 3.3.8 --- Protein level of VLDLR was down-regulated by miR-99a in bladder cancer / Chapter 3.3.9 --- VLDLR was a direct target of miR-99a / Chapter 3.3.10 --- VLDLR mRNA was not down-regulated correspondingly by miR-99a / Chapter 3.3.11 --- MiR-99a suppressed down-stream protein of VLDLR in Reelin pathway / Chapter 3.3.12 --- Knockdown of VLDLR also suppressed cell migration and invasion / Chapter 3.3.13 --- N-cadherin was the down-stream protein responsible for the suppression of migration and invasion in miR-99a/VLDLR pathway / Chapter 3.4 --- Discussion --- p.93 / Chapter Chapter IV: --- Conclusion and prospective --- p.101 / Appendix --- p.105 / Reference --- p.107

INTRODUÇÃO: O diagnóstico do câncer de próstata em pacientes com níveis séricos do antígeno prostático específico persistentemente elevados após biópsia prostática negativa representa um grande desafio para urologistas e patologistas. A baixa especificidade do antígeno prostático específico e a baixa sensibilidade da biópsia prostática guiada por ultra-som são os maiores obstáculos observados na prática clínica. Apesar do uso de diversos métodos para prever a presença de câncer na glândula, nenhum deles tem precisão absoluta, obrigando os pacientes a realizar novas biópsias. Neste contexto, a descoberta de novos marcadores diagnósticos para o câncer da próstata tornase necessária. OBJETIVO: Avaliar o valor diagnóstico da expressão de seis genes no tecido prostático de pacientes com câncer de próstata clinicamente localizado. MÉTODOS: O estudo consistiu na análise de 50 pacientes com diagnóstico de câncer da próstata, submetidos à prostatectomia radical por doença localizada. A seleção dos genes foi baseada em um estudo prévio que utilizou a tecnologia de microarray (Agilent Technologies 44k whole human genome, two-color) em pacientes com câncer de próstata, divididos de acordo com as características clínico-patológicas. Entre os 4.147 genes com expressão diferenciada entre os casos de câncer de próstata, seis genes (PSMA, TMEFF2, GREB1, TH1L, IgH3 e PGC) foram selecionados. Estes genes foram então testados quanto a seu valor diagnóstico no câncer da próstata através da técnica de reação em cadeia da polimerase quantitativa com transcriptase reversa. Na primeira etapa do estudo, amostras de tecido maligno de 33 pacientes com câncer de próstata foram avaliadas. O grupo controle foi composto de nove pacientes com hiperplasia benigna da próstata. Na segunda etapa do estudo foram analisadas amostras de tecido benigno dos demais 17 pacientes com câncer da próstata. O mesmo grupo controle foi utilizado para comparação. RESULTADOS: A análise demonstrou que o PSMA estava super-expresso (em média nove vezes) e o PGC sub-expresso (em média de 1,3 x 10-4 vezes) no tecido neoplásico de todos os casos de câncer quando comparados com os casos de hiperplasia benigna. Os demais genes demonstraram um padrão de expressão variado, não permitindo a diferenciação entre os tecidos malignos e benignos. Quando estes resultados foram testados no tecido prostático benigno dos pacientes com câncer, o PGC manteve o mesmo padrão de expressão em todos os casos e o PSMA, apresentou-se super-expresso em 88% dos pacientes (média de 12 vezes), em relação aos casos de hiperplasia benigna. CONCLUSÃO: A combinação da super-expressão do PSMA e sub-expressão do PGC no tecido prostático pode representar uma evidência objetiva de presença de Cap. Análises clínicas prospectivas adicionais são necessárias para confirmar estes resultados / Introduction and objective: Prostate cancer (PCa) diagnosis in men with persistently increased PSA after a negative initial prostate biopsy has become a great challenge for urologists and pathologists. Despite the use of several methods to increase the sensitivity of prostate biopsy, the false-negative rates remain substantial, leading many patients to undergo repeated procedures. We analyzed the diagnostic value of six genes in the prostatic tissue of patients with clinically localized PCa, in order to predict the presence of cancer. Methods: The study was comprised by 50 patients with clinically localized PCa who underwent radical prostatectomy. Gene selection was based on a microarray analysis of patients with PCa. Among the 4,147 genes with different expressions between two groups, six genes (PSMA, TMEFF2, GREB1, TH1L, IgH3 and PGC) were selected. These genes were tested for its cancer diagnostic role using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method. In the first part of the study, malignant tissue samples from 33 patients were analyzed, and in the second part we analyzed benign tissue samples of the other 17 patients with PCa. The control group was comprised of prostatic tissue samples of patients with benign prostatic hyperplasia (BPH). Results: The analysis of malignant prostatic tissue by qRTPCR showed that PSMA was over-expressed (mean nine times) and PGC was under-expressed (mean 1.3 x 10-4 times) in all cases when compared to BPH. The other four tested genes showed a variable expression pattern not allowing a differentiation between benign and malignant cases. When we tested these results in the benign prostate tissues from patients with PCa, PGC maintained the expression pattern, and PSMA, despite over-expression in most cases (mean 12 times), two cases (12%) presented under-expression. Conclusions: PGC under-expression and PSMA over-expression in the tissue may represent an objective evidence of prostate cancer and constitute a powerful adjunctive method in patients with negative prostate biopsy. Further prospective clinical analyses are necessary to confirm theses results

No description available.

Lee, Kar Ho Francis. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 148-163). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Background: Although rare relative to adult cancers, cancer is still the leading cause of disease-related death in children in developed countries, including Canada. Few studies have specifically examined the epidemiology and public health significance of diagnosis and treatment delays in childhood cancer. This study aimed to investigate the nature of delays in care for children and adolescents with cancer in Canada and to assess the potential impact of such delays on clinical outcomes. / Study Design: I conducted a prospective cohort study to investigate the delays of cancer symptoms reporting, diagnosis, and treatment in children between 0-19 years of age in Canada. This study used a database from Health Canada's Treatment and Outcomes component of the Canadian Childhood Cancer Surveillance and Control Program. / Methodology: Patients were identified from 17 paediatric cancer centres across Canada. Subjects included in this study were residents of Canada, aged less than 20 years, diagnosed with a malignant tumour and had information on date of first symptoms, diagnosis, treatment and outcome available. Descriptive statistics and regression techniques (linear, logistic and Cox regression) were used as appropriate. I measured the individual impact of patient and provider delays on disease severity and prognosis by using judicious control for potential confounding mechanisms and mediating factors. / Study Findings and Significance: By measuring various types of delays in Canada, I found that varying lengths of patient and referral delay, across age groups, types of cancers, and Canadian settings, are the main contributors to diagnosis, HCS and overall delay. Factors relating to the patients, the parents, healthcare and the cancer may all exert different influences on different segments of cancer care. I also found a negative association between diagnosis delay and disease severity for lymphoma and CNS tumour patients. Furthermore, I found that diagnosis and physician delay had a negative effect, while patient delay had a positive effect, on survival for patients diagnosed with CNS tumours. The information provided from this study may form the basis for new effective policies aimed at eliminating obstacles in cancer the diagnostic and care trajectories for Canadian children with cancer and for improving their prognosis.

No description available.