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To isolate novel molecular targets for treatment of testicular germ cell tumor (TGCT), we performed genome-wide expression profile analysis of testicular seminomas using a cDNA microarray. We here report identification of NACHT, leucine-rich repeat and PYD containing 7 (NALP7), that was significantly transactivated in testicular seminomas. Subsequent semi-quantitative RT-PCR and northern blot analyses confirmed an approximately 3.3-kb transcript that was expressed exclusively in testis, although the expression level of this gene in normal testis was much lower than in tumor cells, suggesting an important role of this gene in germcell proliferation. Immunohistochemical analysis using anti-NALP7 polyclonal antibody detected the endogenous NALP7 protein in the cytoplasm of embryonal carcinoma cells and testicular seminoma tissues. Transfection of small interfering RNA (siRNA) for NALP7 significantly reduced the NALP7 expression and resulted in growth suppression of testicular germ-cell tumors. These findings imply that NALP7 may play a crucial role in cell proliferation, as well as testicular tumorigenesis, and it appears to be a promising candidate for development of targeted therapy for TGCTs. (Cancer Sci 2004; 95: 949–954)

There is only one report on cytological findings of oncocytic variant of chromophobe renal cell carcinoma (RCC). In this article, we report a new case with focus on cytological, and ultrastructural findings. A 60-year-old Japanese man was found to have a right renal tumor on medical checkup. In imprint cytological materials, the smears consisted of slightly discohesive clusters and isolated tumor cells with granular green colored cytoplasm on Papanicolaou staining. Nuclei were generally round and centrally located in the cytoplasm, but nuclear irregularity or perinuclear halo was absent. Ultrastructurally, the tumor was full of mitochondria with tubulovesicular cristae. Fluorescence in situ hybridization study using histological material showed multiple chromosomal losses including chromosomes 7, 10, 13, and 17. This finding supports the hypothesis that this variant may ultrastructurally show the nature of chromophobe RCC rather than renal oncocytoma.

In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for development of novel treatments of renal cell carcinoma (RCC), we previously analyzed genome-wide gene expression profiles of clear-cell types of RCC by cDNA microarray. Among the transcativated genes, we herein focused on functional significance of TMEM22 (transmembrane protein 22), a transmembrane protein, in cell growth of RCC. Northern blot and semi-quantitative RT-PCR analyses confirmed up-regulation of TMEM22 in a great majority of RCC clinical samples and cell lines examined. Immunocytochemical analysis validated its localization at the plasma membrane. We found an interaction between TMEM22 and RAB37 (Ras-related protein Rab-37), which was also up-regulated in RCC cells. Interestingly, knockdown of either of TMEM22 or RAB37 expression by specific siRNA caused significant reduction of cancer cell growth. Our results imply that the TMEM22/RAB37 complex is likely to play a crucial role in growth of RCC and that inhibition of the TMEM22/RAB37 expression or their interaction should be novel therapeutic targets for RCC.

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Laser absorption spectroscopy is suitable for the direct determination of the absolute values of non-emissive radical densities. Using frequency-variable infrared diode lasers, we have measured for the first time the SiH3 radical density in silane plasma. This paper reviews the recent progress in the measurements of neutral non-emissive radicals SiHm (m=0-3) in silane plasma by laser absorption spectroscopy.

In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes. We identified 257 genes that were commonly up-regulated and 721 genes that were down-regulated in RCCs. None of top 24 up-regulated genes that showed most significant differences in informative RCC-cases were included in previous reports describing expression profiles of RCC using RNAs isolated from bulk tissues. These findings suggest that it is important to purify as much as possible the populations of cancerous and normal epithelial cells obtained from surgical specimens. Among the significantly-transactivated genes, we focused on Semaphorin 5B (SEMA5B) and knocked-down its expression in RCC cells by small-interfering RNA (siRNA). Effective down-regulation of its expression levels in RCC cells significantly attenuated RCC cell viability. In conclusion, our data should be helpful for a better understanding of the tumorigenesis of RCC and should contribute to the development of diagnostic tumor markers and molecular-targeting therapy for patients with RCC.