Cheol-Yong Yoon | PubMed Health

PubMed2007

Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase.

Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ASS, which enables tumor cells to recycle citrulline to arginine. Thus, we examined the expression levels of ASS in various cancer cells and found that it is low in renal cell carcinoma (RCC) cells, rendering the cells highly sensitive to arginine deprivation by ADI treatment. Immunohistochemical analysis revealed that in biopsy specimens from RCC patients (n = 98), the expression of ASS is highly demonstrated in the epithelium of normal proximal tubule but not seen in tumor cells. Furthermore, RCC cells treated with ADI showed remarkable growth retardation in a dose dependent manner. ADI also exerted in vivo antiproliferative effect on the allografted renal cell carcinoma (RENCA) tumor cells and prolonged the survival of tumor-bearing mice. Histological examination of the tumors revealed that tumor angiogenesis and vascular endothelial growth factor (VEGF) expression were significantly diminished by ADI administration. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of RCC in ways of inhibitions of arginine availability and neovascularization.

Adult↗

PubMed2005

Prostate cancer and the genomic revolution: Advances using microarray analyses.

The emerging technology of microarray analysis allows the establishment of molecular portraits of prostate cancer and the discovery of novel genes involved in the carcinogenesis process. Many novel genes have already been identified using this technique, and functional analyses of these genes are currently being tested. The combination of microarray analysis with other recently developed high-throughput techniques, such as proteomics, tissue arrays, and gene promoter-methylation, especially using tissue microdissection methods, will provide us with more comprehensive insights into how prostate cancer develops and responds to gene-targeted therapies. Animal models of prostate cancer are being characterized by high throughput techniques to better define the similarities and differences between those models and the human disease, and to determine whether particular models may be useful for specific targeted therapies in pre-clinical studies. Although profiling of mRNA expression provides important information of gene expression, the development of proteomic technologies will allow for an even more precise global insight into cellular signaling and structural alterations during prostate carcinogenesis. Not only will the "omic" revolution change basic science, but it will lead to a new era of molecular medicine.

Animals↗