Biomedical subjects

Ka-Fai To

Publications and source records attributed to Ka-Fai To.

57 records · Page 4Linked to original sources

PubMed2002

Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma.

PURPOSE: Aberrant promoter methylation, an alternative mechanism for gene silencing, is frequently detected in gastric cancer. We studied the feasibility of detecting aberrant methylation in serum of gastric cancer patients. EXPERIMENTAL DESIGN: Patients (54) with gastric adenocarcinoma were studied. The tumor and the paired serum were examined for aberrant methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 by methylation-specific PCR. Serum from 30 age-matched noncancer patients was used as control. RESULTS: Promoter methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 were detected in 70.3, 75.9, 18.5, 68.5, and 66.7% of primary tumor. In serum of gastric cancer patients, methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 were detected in 48.1, 57.4, 14.8, 55.6, and 51.9%, respectively. None of the control serum showed aberrant methylation. Aberrant methylation in serum DNA was all accompanied with methylation in the corresponding tumor samples. In general, >60% of serum from cancers with aberrant methylation demonstrated these epigenetic alterations. CONCLUSION: Our findings suggest that aberrant promoter methylation in serum can be detected in a substantial proportion of gastric cancer patients, and this strategy should be evaluated in the screening and surveillance of gastric cancer.

Adenocarcinoma↗

PubMed2002

Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival.

PURPOSE: Tumor hypoxia is known to be associated with resistance to chemotherapy, radiotherapy, and poorer survival. Recently, it is shown that hypoxia induces the expression of hypoxia-inducible factor-1alpha and 2alpha (HIF-1alpha and HIF-2alpha), which then up-regulates the expression of downstream genes such as carbonic anhydrase IX (CA IX) and vascular endothelial growth factor (VEGF). EXPERIMENTAL DESIGN: We examined the expression of HIF-1alpha, HIF-2alpha, CA IX, and VEGF by immunohistochemistry in nasopharyngeal carcinoma (NPC) biopsies from 90 consecutive patients recruited between 1994 and 1997 in a randomized controlled trial of chemoradiation in locally advanced NPC and investigated their relationship with survival. RESULTS: HIF-1alpha was expressed in 52 of 90 (58%), HIF-2alpha in 6 of 89 (7%), CA IX in 51 of 90 (57%), and VEGF in 54 of 90 (60%) of tumors. Tumor HIF-1alpha expression correlated significantly with that of CA IX (P = 0.008) and VEGF (P = 0.003). High tumor HIF-1alpha expression was associated with a trend for poor overall survival (P = 0.06). Tumors with a positive hypoxic profile (defined as high expression of both HIF-1alpha and CA9) were associated with worse progression-free survival (P = 0.04). Tumors with both hypoxic and angiogenic profile (defined as high VEGF expression) were associated with a worse progression-free survival (P = 0.0095). CONCLUSION: Overexpression of HIF-1alpha, CA IX, and VEGF is common in NPC, which is probably related to hypoxia up-regulated expression involving a HIF-dependent pathway, and is associated with poor prognosis. Targeting the hypoxia pathway may be useful in the treatment of NPC.

Adult↗

PubMed2002

Quantitative Epstein-Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China and characterized by a strong association with EBV. We aimed to detect EBV DNA and cancer-related gene promoter hypermethylation in nasopharyngeal (NP) brushing samples and provide a novel noninvasive approach for NPC detection. EXPERIMENTAL DESIGN: Twenty-eight NPC cases and 26 noncancerous subjects were prospectively recruited. NP brushing samples were subjected to quantitative real-time PCR analysis of EBV DNA and methylation-specific PCR analysis of the DAP-kinase, RASSF1A, and p16 genes. RESULTS: EBV DNA quantity in NP brushing samples from NPC patients (median, 8.94 copies/actin) was significantly higher than that of controls (median, 0 copies/actin; P < 0.0001). Twenty-seven of 28 NPC patients had detectable EBV DNA in NP brushes, whereas 25 of 26 controls had undetectable or very low levels of EBV DNA. Elevated EBV DNA level in brushing samples as a tumor marker had a sensitivity of 96.4% and a specificity of 96.2% for NPC detection. Moreover, T(1) disease had a significantly lower EBV DNA level as compared with locally more advanced disease (P = 0.037). In brushing samples of NPC patients, the frequencies of DAP-kinase, RASSF1A, and p16 promoter hypermethylation were 50.0%, 39.3%, and 46.4%, respectively. Seventy-eight percent of cases showed methylation of at least one gene. No aberrant hypermethylation was detected in control samples. CONCLUSIONS: Our study demonstrated the feasibility of detecting multiple molecular tumor markers in NP brushing samples with a high sensitivity and specificity for NPC detection. It offers a powerful yet noninvasive approach for the diagnosis of NPC in high-risk populations.

Adult↗