Synthesis and evaluation of radioiodinated estrogens for diagnosis and therapy of male urogenital tumours.

The preparation of 24 estrogens, their estrogen receptor (ER) affinity and studies of radioiodinated estrogen binding to ER-positive male bladder tumor cells (HTB9) are described. The estrogens with the highest affinity were selected using fluorescence anisotropy assays. A 2,2,2-trifluoroethyl group at the 11ß-position caused particularly promising affinity. (Radio)iodination was performed on the 17α-vinyl group. Binding studies on HTB9 cells revealed picomolar affinities of radioconjugates 19 and 31, indicating promising ability for targeting of urogenital tumors.

Novel noninvasive marker of regression of clear cell renal cell carcinoma (ccRCC).

OBJECTIVE: Analyzing protein kinase C (PKC) alpha, iota, and zeta as well as levels of Mxi-2 and Vim3 in regressive clear cell renal carcinomas (ccRCCs) and urine samples. MATERIAL AND METHODS: Fresh samples of ccRCCs (predominantly pT1a/b) with different degrees of regression (<10%, 30%, 50%, and 70%) vs normal renal tissue and oncocytomas were studied by Western blot, using antibodies of different PKC isoforms. Urine samples from these tumors were analyzed by ELISA (PKC isoforms, Mxi-2, and Vim3). RESULTS: With increasing degree of regression beyond 10%, nuclear Mxi-2 and Vim3 were highly overexpressed in fresh tumor samples. In urine samples, Vim3 was significantly overexpressed in oncocytoma and downregulated in RCCs with 70% regression. Western blot analysis shows that PKC alpha and iota levels were significantly increased in fresh tumor tissue samples (tumors with 30% regression). PKC zeta was expressed in normal kidney and significantly increased in oncocytoma but not found in ccRCCs. In patients' urines, Mxi-2 was significantly reduced (regression > 50%), while PKC isoform alpha was significantly increased by advanced regression rate. PKC iota in patients' urine was overexpressed in oncocytoma and reduced in all ccRCC urines. CONCLUSION: Tumor regression in ccRCC tissue shows strong nuclear overexpression of Mxi-2, Vim3, and PKC alpha and iota. In respective urines, PKC alpha was overexpressed; PKC iota was decreased. Mxi-2 and Vim3 decreased with increasing regression rates. These reagents could serve as noninvasive ccRCC markers for regression.

EBV induced loss of sperm quality.

OBJECTIVE: To analyze the presence of Epstein-Barr-virus (EBV) in sperm samples from patients diagnosed with some impairment of the fertility parameters evaluated using seminogram and to observe if there is any difference with the normozoospermic samples. We hypothesize that an EBV infection is responsible for the upregulation of the miRNA 199-3p, which binds to the 3'UTR of endothelin-1 (ET-1). ET-1 is a key factor to produce Vimentin (Vim3), and therefore, it influences the expression of Vim3. Since Vim3 is predominantly detectable in sperms without any structural defects, the newly identified regulation mechanism can be responsible for the loss of sperm quality. MATERIAL AND METHODS: This study was performed from January 2017 to December 2020 and included 27 patients who provided ejaculated samples obtained by masturbation. Ejaculates were evaluated according to the Word Health Organization's criteria. Posteriorly, the samples were sorted according to the seminogram diagnosis and further analyzed using different enzyme-linked absorbed immune assays to determine the level or concentration of Epstein-Barr nuclear antigen (EBNA), ET-1, and Vim3. RESULTS: All sperm samples with the impairment of fertility parameters contained the EBNA and presented a downregulation of ET-1 and Vim3. In addition, sperms located in the swim ups are also partially positive for the EBV virus in different clinical aspects. CONCLUSION: Based on the regulation mechanism here presented, it seems that the EBV induces changes at the miRNA level, which are responsible for the decreasing of sperm quality.