Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Lucie Bahenská Supervisor: doc. MUDr. Bohuslav Matouš, CSc. Title of diploma thesis: Monitor the parameters of thyroid function with regard to a diagnosis of hypothyroidism in middle aged There was proved an occurence of the thyroid disorders with regard to hypothyreosis in humans in the middle age in the file of 15 412 patients (5753 men, 9659 women). Simultaneously there was calculated an occurence of these disorders in the rate on men vs women. There was a file of all patients examined in VFN during the year 2012 including all patients treating at the department of endocrinology. No significant higher occurence of thyroid disorders at women was found. In the examined file there were 474 TSH analysis indicated by a practitioners like a steering control. There wasn't confirmed a higher incidence of an occurence of the thyroid disorders at women. In the file indicated by practitioners there was changed the value of TSH at 7,2% women and 9,9% men. The reason can be caused by examination the men in the risk group in comparison to women, who are examined without risk factors. There was checked the connection between hypothyreosis and diabetes mellitus and no significant higher occurence...

Ma, Buig Yue Brigette. / Thesis M.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 232-270). / Title from PDF title page (viewed on 18, November, 2016).

No description available.

No description available.

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 170-205).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 5 uppsatser.

Thesis (Ph. D.)--East Tennessee State University, 2002. / Includes bibliographical references. Also available via Internet at the UMI web site.

Background Esophageal carcinoma mainly affects middle aged to elderly males. It ranks the ninth most common cancer world-wide. The main histological types are squamous cell carcinoma and adenocarcinoma. In Hong Kong, esophagus squamous cell carcinoma (ESCC) is by far the more common. BARX2 is a human homeobox gene located at 11q24-q25, encoding a protein of 254 amino acids. Recent researches show that its expression in breast cancer promotes cellular invasion. Objectives The study aimed to test the hypothesis that BARX2 is a prognostic marker in ESCC. BARX2 expression in ESCC was correlated with patient survival and other clinicopathologic parameters in a cohort of patients. Material and Methods Records of ESCC patients were obtained retrospectively from the computerized database of Queen Mary Hospital. ESCC patients, who underwent esophagectomy in the hospital from 1998 to 2005 but without receiving prior chemotherapy or radiotherapy directed to the tumor, were selected. Tumor staging was done according to the 6th edition of AJCC Cancer Staging Manual. Immunohistochemical staining for BARX2 expression was performed on paraffin sections of the primary ESCC tissues sampled in a tissue microarray constructed for research purposes. The pattern of BARX2 expression in nucleus and cell cytoplasm of tumor cells was recorded and the staining intensity scored on a 4-point scale. The scores were statistically analyzed together with the various clinicopathologic parameters. BARX2 expression and patient survival time were analyzed by the log-rank test. Results A total of 78 ESCC patients were recruited. At the time of data analysis, 52 (66.7%) patients were dead. The overall median survival of patients was 14.3 months. BARX2 was found to be mainly expressed in the cytoplasm of tumor cells while non-tumor epithelium showed strong nuclear expression. Patients with high level BARX2 expression had short survival time, though the difference did not reach statistical significance (p=0.075). Within the subgroup of lower T-stage ESCC (T1-3), high level BARX2 expression was significantly associated with shorter survival time (p=0.042). However, differential BARX2 expression did not affect survival time within the group of patients who had advanced stage (T4) disease (p=0.525). In patients who had no regional lymph node metastasis (N0), high level BARX2 expression was associated with shorter survival time (p=0.023). However, when patients had regional lymph node metastases (N1), BARX2 expression did not affect patient survival time (p=0.533). Patients whose ESCC showed moderate differentiation in a three-tier tumor grading system, when accompanied with low level BARX2 expression, had longer survival time (p=0.029). However, BARX2 expression did not affect survival time when ESCC showed either well differentiation (p=0.462) or poor differentiation (p=0.637). Multivariate analysis showed patient age and T-stage to be the only two independent parameters of prognostic significance (p=0.025 and p=0.036 respectively). Conclusions BARX2 expression in ESCC was aberrant and mainly cytoplasmic. It was inversely correlated with patient survival time in early ESCC disease (T1-T3 or N0). BARX2 expression evaluated by immunohistochemistry could be a useful and practical prognostic marker of ESCC in its early stages, when the proper decision on treatment would be critical for the patients. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr Virus (EBV).Early diagnosis of NPC will improve the overall survival. However, traditional EBV markers do not perform well in high-risk individuals or for early detection of NPC. Aberrant promoter hypermethylation of tumor suppressor genes (TSGs) is an important epigenetic change in early tumorigenesis. This study identified a promising panel of methylation markers for early detection of NPC and assessed the clinical usefulness of these markers using nasopharyngeal (NP) brushing and blood specimens. Methylation-sensitive high resolution melting (MS-HRM) assays were carried out to assess the methylation status of a selected panel of four TSGs (RASSF1A, WIF1, DAPK1, RAR2)in biopsies, NP brushings and cell-free plasma from NPC patients. NP brushing and blood samples from high-risk and cancer-free groups were used as controls. The DNA methylation panel showed higher sensitivity and specificity than the EBV DNA markerincell-free plasma for early stage (Iand II) NPC (sensitivity: 64.6% vs. 51.2% and specificity: 96.0% vs. 88.0%, respectively). In combination with plasma EBV DNA, testing for DNA methylation in plasma and NP brushings using the four-gene MS-HRM test significantly increased the detection rate for all stages of NPC(94.1% for stages I-II, 98.4% for stages III-IV) as well as recurrence(93.5%). Aberrant activation of the Wnt signaling pathway is a common mechanism for cell transformation and tumor development in a variety of human cancers. A high frequency of promoter hypermethylation of WIF1was observed in NPC cell lines (100%), primary tumor biopsies(89.7%), NP brushings (80.2%), and cell-free plasma (51.8%),with no significant correlation with NPC stage. Simultaneously, expression of WIF1 was completely silenced in NPC cell lines (HONE1, HK1, HNE1, SUNE1, CNE1, CNE2, and C666),but not in immortalized NP epithelial cells (NP460 and NP69). These together suggested an important role of WIF1 in NPC development. In vitro and in vivo functional assays revealed a tumor suppressive role of WIF1in NPC. Restoration of WIF1expression in NPC cells significantly suppressed anchorage-independent growth, in vivo tumorigenicity, invasion, migration, and angiogenesis of NPC cells. A number of important angiogenesis-related genes were down-regulated by WIF1expression, including IL6,IL8,VEGF165,VEGFA, PDGFB, and MCP1. There is inhibition of the Wnt/β-catenin signaling pathway, manifested as decreased β-catenin expression and TCF/LEF Wnt promoter activity. These data indicated the important regulatory role of Wnt signaling pathway in NPC tumorigenicity, invasion, migration, and angiogenesis, by interacting with the complex signaling network in NPC cells. To conclude, the MS-HRM assay on the selected gene panel in combination with the EBV DNA test, increases the sensitivity for NPC detection at an early stage and detection of recurrence and has great potential to become a non-invasive test for early diagnosis and disease monitoring after treatment. Collectively, results from this study reveal that WIF1is not only a sensitive biomarker, but also a tumor suppressor gene in NPC. Understanding the molecular regulatory role ofWIF1in NPC will facilitate the diagnosis of NPC, and development of novel NPC therapeutic strategy. / published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / toc / Surgery / Master / Master of Philosophy