Ref. No: PCT/JP2009/004091, Year: 03/2010
Journal of Urology - J UROL. 01/2010; 183(4).
[Show abstract] [Hide abstract]
ABSTRACT: To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that hypoxia-inducible protein-2 (HIG2) was expressed exclusively in RCCs and fetal kidney. Induction of HIG2 cDNA into COS7 cells led to secretion of the gene product into culture medium and resulted in enhancement of cell growth. Small interfering RNA effectively inhibited expression of HIG2 in human RCC cells that endogenously expressed high levels of the protein and significantly suppressed cell growth. Moreover, addition of polyclonal anti-HIG2 antibody into culture medium induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of HIG2 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor marker for patients with renal carcinomas.
Cancer Research 07/2005; 65(11):4817-26. · 8.65 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: To identify a set of genes related to thermoradiosensitivity of cervical carcinoma and to establish a predictive method.
A total of 19 patients with cervical cancer (1 with Stage IIIA, 11 with Stage IIIB, 5 with Stage IVA, and 2 with Stage IVB) who underwent definitive thermoradiotherapy between May 1995 and August 2001 were included in this study. We compared the expression profiles of 8 thermoradiosensitive and 11 thermoradioresistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23,040 human genes.
We selected 35 genes on the basis of a clustering analysis and confirmed the validity of these genes with a cross-validation test. Some of these genes were already known to be associated with apoptosis (BIK, TEGT, SSI-3), hypoxia-inducible genes (HIF1A, CA12), and tumor cell invasion and metastasis (CTSL, CTSB, PLAU, CD44). We developed a "predictive score" system that could clearly separate the thermoradiosensitive group from the thermoradioresistant group.
These results from the treatment program between May 1995 and August 2001 showed that by using gene-expression profiles we can predict the outcome of thermoradiotherapy for advanced cervical carcinoma. A "predictive score" system was developed that could clearly separate the thermoradiosensitive group from the thermoradioresistant group. These results may eventually lead to the achievement of "personalized therapy" for this disease.
International Journal of Radiation OncologyBiologyPhysics 10/2004; 60(1):237-48. · 4.52 Impact Factor