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Wen-Chang Lin

Publications and source records attributed to Wen-Chang Lin.

7 recordsLinked to original sources

Specific induction of the high-molecular-weight microtubule-associated protein 2 (hmw-MAP2) by betel quid extract in cultured oral keratinocytes: clinical implications in betel quid-associated oral squamous cell carcinoma (OSCC).

Betel quid (BQ) chewing, a popular habit in numerous Asian countries including India and Taiwan, has a strong correlation with an increased risk of oral squamous cell carcinoma (OSCC). While substantial efforts have been made to test the cytotoxic, genotoxic and mutagenic effects of BQ extract and its components, the disease mechanisms underlying BQ-induced oral carcinogenesis remain obscure. Here, we show that a neuronal protein, microtubule-associated protein 2 (MAP2), was induced by BQ extract in cultured normal human oral keratinocytes (NHOKs). Subsequent analyses demonstrated that such induction was more eminent and consistent in the high-molecular-weight isoform of MAP2 (hmw-MAP2) than that in its low-molecular-weight counterpart (lmw-MAP2). Furthermore, we analyzed expression of hmw-MAP2 protein in 88 oral specimens consisting of clinicopathologically pre-malignant (leukoplakia) and malignant (OSCC) lesions, along with their adjacent normal mucosa. Immunohistochemistry revealed that, with the exposure to BQ, the hmw-MAP2 was over-expressed in 41.2% (7/17) of OSCC, 11.2% (1/9) of leukoplakia and none (0/19) of normal mucosa. In contrast, expression of the hmw-MAP2 was barely detected in BQ-free OSCC. These results suggest a significant correlation between expression of the hmw-MAP2 and BQ-associated progression of oral carcinogenesis (P=0.0046). Interestingly, the hmw-MAP2 was found to preferentially express in histopathologically less differentiated OSCC (P=0.014); the percentages of positive staining in poorly, moderately and well differentiated OSCC were 62.5, 21.4 and 7.1%, respectively. However, BQ chewing appeared to have marginal correlation with such propensity. Finally, we show that the majority of hmw-MAP2-positive poorly differentiated lesions were also histopathologically invasive. Taken together, these findings suggest the possibility that the hmw-MAP2 may be a diagnostic marker for BQ-chewing lesions and a potential therapeutic target. To our knowledge, this study has provided the first clinical implication that closely links a cytoskeletal protein to BQ-associated oral cancer.

Areca↗

Dang-Gui-Bu-Xai-Tang modulated the immunity of tumor bearing mice.

Dang-Gui-Bu-Xai-Tang (DGBXT), which includes Radix Angelicae Sinensis and Radix Astragali Membranaceus, is a traditional Chinese medicine used to modulate the lymphocyte activity of cancer patients after chemotherapy and radiotherapy. In the present study, we examined the cytotoxicity of DGBXT on transformed cells and the immunomodulating effects of DGBXT in a tumor-bearing murine model. DGBXT markedly inhibited the growth of the EJ-Ha-ras transformed LZEJ and LZEJ-C2 cells lines. Oral administration of DGBXT for three weeks significantly prevented the tumor development in mice that injected with LZEJ-C2 cells subcutaneously. Moreover, DGBXT effectively increased the population of cytotoxic T lymphocytes (CTLs) and NK cells, and down-regulated activated T helper cells (CD4+/CD25+) in spleen and tumor-draining lymph nodes (TDLN). Furthermore, DGBXT stimulated the production of tumor necrosis factor-alpha in in vitro cultured splenocytes. These results might explain the antitumor effects of DGBXT.

3T3 Cells↗

A complexity reduction algorithm for analysis and annotation of large genomic sequences.

DNA is a universal language encrypted with biological instruction for life. In higher organisms, the genetic information is preserved predominantly in an organized exon/intron structure. When a gene is expressed, the exons are spliced together to form the transcript for protein synthesis. We have developed a complexity reduction algorithm for sequence analysis (CRASA) that enables direct alignment of cDNA sequences to the genome. This method features a progressive data structure in hierarchical orders to facilitate a fast and efficient search mechanism. CRASA implementation was tested with already annotated genomic sequences in two benchmark data sets and compared with 15 annotation programs (10 ab initio and 5 homology-based approaches) against the EST database. By the use of layered noise filters, the complexity of CRASA-matched data was reduced exponentially. The results from the benchmark tests showed that CRASA annotation excelled in both the sensitivity and specificity categories. When CRASA was applied to the analysis of human Chromosomes 21 and 22, an additional 83 potential genes were identified. With its large-scale processing capability, CRASA can be used as a robust tool for genome annotation with high accuracy by matching the EST sequences precisely to the genomic sequences.

Algorithms↗

Protein tyrosine kinase and phosphatase expression profiling in human cancers.

Alterations of protein tyrosine kinase and tyrosine phosphatase are often associated with uncontrolled cell growth and cellular transformation. Because of the large number of tyrosine kinase/phosphatase genes in such gene family, it is essential to use an efficient and simple approach to obtain comprehensive protein tyrosine kinase and protein tyrosine phosphatase expression profiles. Knowledge of such an overall expression pattern of tyrosine kinases/phosphatases in a given cancer cell represents the first step in understanding key components involved in the sequential events of tumor progression. In this article, we described a novel approach by using degenerate PCR primers according to the consensus catalytic motifs in order to amplify protein tyrosin kinase/phosphatase molecules from cancer cells by reverse-transcription polymerase-chain-reaction. An improved profiling approach (RAGE) was also described by utilizing restriction enzyme digestion and electrophoresis for quick and efficient kinase/phosphatase profiling.

Amino Acid Sequence↗

Clinical significance of AXL kinase family in gastric cancer.

BACKGROUND: We have used degenerated PCR primers designed according to the consensus kinase motifs in order to amplify expressed protein tyrosine kinase molecules from human gastric cancers. From such kinase expression profiles, we have identified more than fifty different tyrosine and serine/threonine kinases from two matched pairs of gastric cancer tissue and normal mucosa. In previous studies, we have shown the clinical significance of two tyrosine kinases identified in gastric cancer, tie-1 and mkk4. MATERIALS AND METHODS: In this report, we further investigate the protein expression of the whole axl receptor tyrosine-kinase family (axl/ufo, nyk/mer and sky/rse) by immunohistochemistry and their clinicopathological associations. RESULTS: On examination of 96 patients specimens, expression of the axl kinase family alone showed no statistical significance with respect to the patients' survivaL However, the combination of nyk/mer expression with axl/ufo expression correlated inversely with the patients' prognosis result. CONCLUSION: This finding indicates that a co-operative relationship exists between axllufo and nyk/mer protein kinases and this seems to play an important role in gastric cancer progression and metastasis.

Aged↗

Arg tyrosine kinase expression in human gastric adenocarcinoma is associated with vessel invasion.

BACKGROUND: Gastric cancer is one of the prevalent cancer types in the Far East region. In order to discover new prognostic and diagnostic biomarkers for gastric cancer progression, we have used degenerated PCR primers designed to amplify all expressed protein tyrosine kinase molecules from human cancer tissues. In previous studies, we have shown the clinical significance of arg tyrosine kinases in a colorectal cancer progression model. MATERIALS AND METHODS: We further investigated the protein expression of arg tyrosine kinase by immunohistochemistry and analyzed the clinicopathological association with human cancers. RESULTS AND CONCLUSION: Specimens from 79 patients were examined and this demonstrated that the expression of arg kinase showed no statistically significant correlation with the patients' overall survival. However, higher levels of arg kinase immunoreactivity did show a statistically significant association with vessel invasion in gastric cancer tissues examined. This indicates a potential involvement of arg in gastric cancer invasion and progression.

Adenocarcinoma↗