Biomedical subjects

Shih-Huang Chan

Publications and source records attributed to Shih-Huang Chan.

6 recordsLinked to original sources

PubMed2005

The significance of prohibitin and c-Met/hepatocyte growth factor receptor in the progression of cervical adenocarcinoma.

To examine the importance of prohibitin 1 and c-Met/hepatocyte growth factor receptor (HGFR) expression in human cervical adenocarcinomas, 85 patients (69 with invasive adenocarcinoma [ACA] and 16 with adenocarcinoma in situ [AIS]) were studied using immunohistochemistry. High prohibitin 1 expression was found in 51 (73.9%) of the 69 ACAs and 11 (68.7%) of the 16 AIS lesions. Prohibitin 1 overexpression was significantly higher in ACA and AIS than in adjacent nonneoplastic glandular epithelium (P < .001 for both comparisons). Prohibitin 1 expression was also positively related to tumor size (P = .019) or parametrial involvement (P = .027) in ACA. c-Met was expressed in 21 ACAs (30.4%) and was positively correlated with the Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics) stage classification (P = .007) or nodal metastasis (P = .047). Nodal metastasis (P = .028) and c-Met expression (P = .022) were independent predictors for the overall survival of patients in multivariate analysis using the Cox regression method. Prohibitin 1 activation seems to be an early event, whereas c-Met overexpression may be important for the progression of cervical adenocarcinomas. Evaluation of c-Met expression status may identify a subset of patients with cervical adenocarcinoma who require more intensive treatment.

Adenocarcinoma↗

PubMed2005

Nasopharyngeal carcinoma-susceptibility locus is localized to a 132 kb segment containing HLA-A using high-resolution microsatellite mapping.

Nasopharyngeal carcinoma (NPC) is an epithelial tumor uniquely prevalent in southern Chinese. HLA-A2 is associated with NPC. In a previous study, we showed that the genes associated with susceptibility to NPC are primarily located within the HLA-A locus in Taiwanese NPC patients. However, the pathogenic genes causing NPC susceptibility remain unknown. Here, 8 polymorphic microsatellite markers distributed over a 1 megabase region surrounding the HLA-A locus were subjected to genetic analysis for the NPC-susceptibility locus. Statistical studies of associated alleles detected on each microsatellite locus showed that the NPC- susceptibility genes are most likely located between the D6S510 and D6S211 markers within a 132 kb segment containing the HLA-A locus. These results undoubtedly would facilitate the further positional cloning of the NPC-susceptibility locus, which has been elusive for the past 30 years.

Adult↗

PubMed2005

An ancova approach to normalize microarray data, and its performance to existing methods.

A microarray experiment includes many steps, and each one of them may include systematic variations. To have a sound analysis, the systematic bias must be identified and removed prior to the data being analyzed. Based on the M-A dependency observed by Dudoit et al. (2002), we suggest that, instead of using the lowess normalization, a new normalization method called ANCOVA be used for dealing with genes with replicates. Simulation studies have shown that the performance of the suggested ANCOVA method is superior to any of the available approaches with regards to the Fisher's Z score and concordance rate. We used a microarray data from bladder cancer to illustrate the application of our approach. The edge the ANCOVA method has over the existing normalization approaches is further confirmed through real-time PCR.

Algorithms↗

PubMed2003

Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese.

NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (> or =40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2(+)B46(+) individuals are at greater risk for NPC than A2(-)B46(-) individuals in both the population studied and the > or =40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2(+)B38(+) individuals were at higher risk than A2(-)B38(-) individuals in both the population studied and the > or =40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc = 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus.

Adult↗

PubMed2003

Clinical significance of allelotype profiling for urothelial carcinoma.

OBJECTIVES: To perform a global loss of heterozygosity (LOH) analysis on a cohort of urothelial carcinoma to investigate the clinical implication of specific chromosomal loss. Allelic deletions detected as LOH have been used to study the markers for carcinogenesis. METHODS: We examined the allelic loss on 14 chromosomal regions in a total of 71 cases of urothelial carcinoma. The results were analyzed in relation to biologic indicators of urothelial carcinoma and the clinical outcome with a mean follow-up of 101 months. RESULTS: The incidence of LOH in order of frequency was 9p (54.9%), 9q (49.3%), 13q (40.8%), 14q (40.8%), 10q (39.4%), 17p (39.4%), 8p (38.0%), 21q (36.6%), 11p (31.0%), 18q (23.9%), 4q (21.1%), 3p (16.9%), 6q (14.1%), and 1q (8.5%). Positive association with one of the indicators was observed in 3p, 9p, 9q, 10q, 14q, and 18q. The chromosomes that correlated with two biologic indicators were 4q, 6q, 11p, 17p, and 21q. Univariate analysis found that patients having combined 9p and 14q deleted tumors had particularly poor long-term survival compared with those with other patterns of chromosomal alterations (P = 0.01). In the multivariate model, nonpapillary tumors had a greater risk of recurrence, and stage classification was the only important indicator in predicting patient survival (P = 0.04). CONCLUSIONS: LOH assessment does not provide independent prognostic value compared with stage classification. However, chromosomes 4q, 6q, 9p, 11p, 14q, 17p, and 21q may harbor important tumor suppressor genes involved in the progression of urothelial carcinogenesis.

Adult↗

PubMed2002

Overexpression of c-met as a prognostic indicator for transitional cell carcinoma of the urinary bladder: a comparison with p53 nuclear accumulation.

PURPOSE: The c-met proto-oncogene encodes a receptor tyrosine kinase (Met) and has been shown to play a role in oncogenesis. Given that high titers of hepatocyte growth factor, the specific ligand for Met, are excreted in the urine and tend to reflect disease activity of bladder cancer, we performed this study to examine the clinical significance of Met in human bladder cancer. MATERIALS AND METHODS: We studied the mRNA expression and genomic alteration of c-met in five bladder cancer cell lines. Significance of Met overexpression was then compared with p53 nuclear accumulation (TP53) in primary bladder cancer (n = 142 patients). RESULTS: Expression of c-met mRNA tended to positively correlate with differentiation of cancer cell lines in the absence of point mutation. High expression of Met was found in seven cases (4.9%), low expression in 32 cases (22.5%), and negative expression in 103 cases (72.5%). Expression of Met was positively associated with histologic grade, stage classification, tumor size, and nodular tumor growth (P <.05, respectively); however, it was not related to TP53 status. Factors that predicted disease progression were tumor stage, Met status, and TP53 accumulation (P <.05, respectively). Indicators for poor long-term survival were invasive cancer, multiple tumors, and Met overexpression (P =.0006,.01, and.04, respectively). CONCLUSION: The c-met proto-oncogene plays a more important role in the progression of bladder carcinogenesis than p53. Evaluation of Met expression could identify a subset of bladder cancer patients who may require a more intensive treatment strategy.

Adult↗