ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer. The evaluation of INI1 protein level in samples from 50 patients with diagnosed ccRCC, including three displaying rhabdoid features, showed the INI1 positive staining in rhabdoid cells while the conventional ccRCC cells exhibited reduced INI1 level. This indicated the rhabdoid component of ccRCC as distinct from other known rhabdoid tumors. The reduced INI1 protein level observed in all conventional ccRCC cases used in this study correlated with decreased SMARCB1 gene expression at the transcript level. Consistently, the overexpression of INI1 protein in A498 ccRCC cell line resulted in the elevation of endogenous SMARCB1 transcript level indicating that the INI1-dependent regulatory feedback loop controlling expression of this gene is affected in ccRCC Moreover, the set of INI1 target genes including i.e. CXCL12/CXCR7/CXCR4 chemokine axis was identified to be affected in ccRCC. In summary, we demonstrated that the inactivation of INI1 may be of high importance for ccRCC development and aggressiveness.
ABSTRACT
OBJECTIVE: A new surgical method of treating Peyronie's disease consisting in intracavernosal excision of the plaque is presented. MATERIAL AND METHODS: The operation was performed on 16 men aged from 34 to 65 years (mean 50.2 years). The angle of penile curvature was 30 degrees to 60 degrees. Thirteen (81.25%) had impaired intercourse because of penile deformity and in 3 (18.75%) patients it was prevented by marked penile curvature. The mean quality of life score (QoL) was evaluated as 4.8. The operation consists in incising the corpus cavernosum parallel to the plaque and through this incision removing the plaque from the inside without incising or replacing the underlaying tunica albuginea. RESULTS: Follow-up examinations made after 3, 6 and 12 months revealed normal, painless erection in all the patients. In 2 (12.5%) intercourse was impaired only by persistent penile curvature of over 20 degrees. Mean QoL score -1.1. CONCLUSIONS: In our opinion intracavernosal plaque excision is a simple method, easier to perform and less invasive than the operative methods applied to date. It eliminates the pain, does not result in a shortening of the penis, loss of sensation or erectile dysfunction. It ensures a considerable improvement in the QoL of the patients treated.
