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Jan-Gowth Chang

Publications and source records attributed to Jan-Gowth Chang.

49 records · Page 3Linked to original sources
PubMed2002

Expression of hBUB1 in acute myeloid leukemia.

hBUB1 gene is a component of the mitotic checkpoint that monitors proper assembly of the mitotic spindles and the alteration of the hBUB1 gene has been found to be associated with chromosomal instability in some tumor cell lines. We analyzed the coding region of the hBUB1 gene for mutations and its expression in 92 acute myeloid leukemia (AML) specimens and five hematopoietic cell lines. We also used Southern hybridization to analyze the genomic DNA of those cases, which had aberrant transcription to confirm the lesion. A thymine/cytosine polymorphism at 8 bp upstream of the 5' splice acceptor site of exon 10 was observed in Raji cell line and two AML specimens without a resultant change in the expression of hBUB1. Reduced expression and aberrant transcription of the hBUB1 gene, which may affect the control of mitotic checkpoint, were detected in AML specimens by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Our study suggests that the mutation of the hBUB1 gene is a rare event in AML, and further studies are necessary to clarify its role in leukemia.

Acute Disease↗
PubMed2002

Molecular analysis of thiopurine S-methyltransferase alleles in South-east Asian populations.

Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. In Caucasians, four variant TPMT alleles have been detected in over 80% of individuals with low or intermediate TPMT activity. The wild-type allele is designated as TPMT*1 and the mutant alleles are designated TPMT*2 through TPMT*8. The frequency of these alleles in different ethnic groups has not been well defined. In this study, one hundred individuals, from each of the Indonesian, Thai and Philippine populations, together with 249 Taiwanese, were analysed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing methods. The results showed that the allelic frequencies of TPMT*3C were 0.6% for Taiwanese and 1% for Filipino, Thai and Indonesian populations, respectively. One Filipino with a Caucasian parent was found to be heterozygous for the TPMT*2 allele. This study provides the first analysis of the allele frequency distribution of all known TPMT mutations in South-east Asian populations.

Alleles↗
PubMed2002

The correlation between CpG methylation and protein expression of P16 in oral squamous cell carcinomas.

We examined the P16 expression by immunohistochemical stain and detected the methylation by methylation specific polymerase chain reaction (MSP) in 48 primary oral squamous cell carcinoma (SCC) tissues. The results showed that 20/48 (41.7%) of cancerous tissues had CpG methylation around the promoter region, but 8/48 (17%) of the nearby non-cancerous tissues also had CpG methylation, around the promoter region. The results from immunohistochemical studies showed that reduced and heterogeneous expression of P16 were found in the tissues, which had CpG methylation around the promoter region. In conclusion, the methylation of P16 in oral SCC occurs in pre-cancerous and cancerous stage, which results in decreasing or abolishing the P16 expression, which is heterogeneous in the cancer cells.

Adult↗
PubMed2002

Sulfotransferase 1A2*2 is a risk factor for early-onset breast cancer.

The estrogen-signaling pathway plays an important role in the pathophysiology of breast cancer, and the sulfotransferase 1A (SULT1A) family has been found to be both downstream targets of tamoxifen and a risk factor of breast cancer. We have used PCR-RFLP and direct sequencing methods to determine SULT1A2 polymorphisms in 230 Taiwanese breast cancer patients. The results showed that the frequencies of SULT1A2*1 and SULT1A2*2 occurring were 94.8% and 5.2%, respectively. No SULT1A2*3 allele was found in these patients. In comparison with the frequency of healthy controls (96.0% and 4.0% for SULT1A2*1 and SULT1A2*2, respectively), the allelic frequencies of SULT1A2 polymorphisms in these patients were not statistically significant (p=0.398). However, the SULT1A2*2 allele seems to influence the age of onset among early-onset breast cancer patients (p=0.021, OR=2.74, 95%CI=1.13-6.65).

Adolescent↗
PubMedDate not supplied

Polymorphism analysis of CYP3A5 in myeloid leukemia.

The human cytochrome P450 (CYP) metabolizes more than 100 structurally diverse exogenous and endogenous molecules. The CYP3A5 is a major P450 enzyme in the liver and represents 50% of the total hepatic CYP3A content in people expressing CYP3A5. The single nucleotide polymorphisms in CYP3A5*3 and CYP3A5*6 that resulted in the absence of CYP3A5 from tissues were noted in some people. Polymorphisms of potential relevance to leukemia and myelodysplastic syndrome (MDS) have been described for various CYP. The bone marrow and/or peripheral blood from 188 acute myeloid leukemia (AML) patients, 101 chronic myeloid leukemia (CML), 40 MDS, and 270 normal controls were analyzed by a PCR-RFLP assay to evaluate the association of the CYP3A5 polymorphisms with myeloid leukemia. Our data showed that 15/188 (8%), 8/101 (7.9%), and 3/40 (7.5%) of the patients (i.e., 188 AML, 101 CML, 40 MDS) were CYP3A5*1/*1; 88/188 (46.8%), 47/101 (46.5%), and 20/40 (50%) were CYP3A5*1/*3; and 85/188 (45.2%), 46/101 (45.5%), and 17/40 (42.5%) carried the CYP3A5*3/*3 genotype, respectively. CYP3A5*6 was not found in any of the patients' specimens. Similar frequencies of CYP3A5*3 were observed in the leukemic patients and normal controls. Consequently, the finding suggests that the CYP3A5 polymorphism was not associated with the risk of myeloid leukemia.

Acute Disease↗
PubMedDate not supplied

The correlation between CpG methylation on promoter and protein expression of E-cadherin in oral squamous cell carcinoma.

BACKGROUND: Reduction of E-cadherin in most common epithelial tumors relates to metastasis, which results from the silence of E-cadherin by CpG methylation. MATERIALS AND METHODS: We examined the E-cadherin expression by immunohistochemical staining and detected methylation by methylation-specific polymerase chain reaction (MSP) in 48 primary oral SCC tissues. RESULTS: The results showed that 41 out of 48 (85.4%) cancerous tissues and 16 out of 48 (33.3%) nearby non-cancerous tissues had CpG methylation on the promoter region of E-cadherin. In these non-cancerous tissues, 2 out of 16 (12.5%) had no methylation change in their paired cancerous part. Immunohistochemical study showed that a decreased expression pattern was found in the tissue which had CpG methylation on the promoter region, but an over expression island or aberrant expression was also frequently found in these cases. CONCLUSION: The methylation of E-cadherin in oral SCC may occur in the precancerous stage and the process is dynamic, which has no relationship with the aberrant expression of E-cadherin protein.

Adult↗
PubMedDate not supplied

Epigenetic changes of tumor suppressor genes, P15, P16, VHL and P53 in oral cancer.

We performed methylation specific PCR to explore the mechanism of inactivation of tumor suppressor genes P15, P16, P53 and VHL in 48 oral SCC. The frequencies of aberrant methylation on the promoter of the P15, the P16, the P53 and the VHL genes were 0.27 (13/48), 0.42 (20/48), 0.04 (2/48) and none, respectively. Altogether, over 50% of the samples showed the CpG-island methylation modification in at least one of the three tumor suppressor genes, indicating that the frequent inactivation of these genes may be an important step during oral cancer development, and the methylation inactivation of P15 or P16 may occur at pre-cancerous stage.

Adult↗
PubMedDate not supplied

Mutation analysis of CTNNB1 (beta-catenin) and AXIN1, the components of Wnt pathway, in cervical carcinomas.

The components of the Wnt-signaling pathway are mutated in tumors, but the relationship between these components and cervical cancer has not been elucidated. In this study, we used immunohistochemistry, single strand confirmation polymorphism (SSCP) and direct sequencing methods to analyze the mutation and protein expressions of both CTNNB1 and AXIN1 in cervical cancer. Among the 30 tested cervical cancers, no mutation of CTNNB1 but 3 polymorphisms were found. Mutation analysis of AXIN1 revealed that one specimen had a heterozygous mutation at codon 740 (GCC right curved arrow ACC) and six polymorphisms were also found. Immunohistochemistry showed no relationship between the protein expression patterns and mutation of AXIN1 and CTNNB1. Mutations of CTNNB1 may not be a factor, whereas mutations of AXIN1 may play a limited role in tumorigenesis of cervical cancer. In addition, aberrant expression patterns are not mutation related, so that other factors may be responsible for these changes.

Adult↗
PubMedDate not supplied

Promoter CpG methylation of caveolin-1 in sporadic colorectal cancer.

BACKGROUND: Caveolin-1 has been shown to be down-regulated in human colon cancer and involved in colon tumorigenesis. We investigated the mechanism. MATERIALS AND METHODS: Cancerous and nearby non-cancerous tissues of 185 sporadic colorectal cancer samples were enrolled in this study. Methylation-specific PCR was performed to explore the mechanism of regulation of caveolin-1 gene expression. RESULTS: Aberrant promoter methylation in the caveolin-1 gene was 3.8% and 5.9% for cancerous and nearby non-cancerous tissues, respectively. All the cancerous and non-cancerous tissue contained unmethylated promoters in the caveolin-1 gene. The methylation status of caveolin-1 had no clear relationship with age, cell grade, location of tumor or lymph node metastasis. However, female gender showed statistically significant difference (p=0.045). The immunohistochemistry study demonstrated that expression of caveolin-1 correlated with aberrant promoter methylation status in sporadic colorectal cancer tissues. CONCLUSION: Our findings suggested that aberrant promoter methylation of the caveolin-1 gene may occur at the precancerous stage, regulated by gender-related factors and is associated with gene silencing of caveolin-1 in the development of colorectal cancer.

Caveolin 1↗