[Biomarkers of prostate cancer sensitivity to the Sendai virus].

Metastatic prostate cancer is often associated with either primary or intractable castration-resistant prostate cancer (CRPC), thus justifying the search for entirely new ways of treatment. Oncolytic viruses are able to selectively induce the death of tumor cells without affecting normal cells. A murine Sendai virus has potential to be used as an oncolytic agent. However, tumors vary in their sensitivity to different viruses, prompting us to attempt to identify corresponding biomarkers that reflect the interaction of cancer cells and the virus. Here, we show that the sensitivity of primary prostatic adenocarcinoma cell lines to Sendai virus strain (SeVM) vary substantially. Using quantitative PCR, we evaluated expression levels of genes that encode RIG-1-like and Toll-like receptors (TLRs) in cell lines and showed that the levels of mRNAs that encode TLR3 and TLR7 correlate with a degree of sensitivity of the cells to Sendai virus. The lines with lower levels of TLR3 and TLR7 expression are more sensitive to the virus.

[Molecular genetic mechanisms of drug resistance in prostate cancer].

The major problem in prostate cancer treatment is the development of drug resistance and especially important, cross-resistance. The mechanisms of drug resistance, which are divided into ligand-dependent (requiring the presence of androgens in the cell) and independent (not requiring the presence of androgens) are reviewed. The mechanisms are mainly represented with mutations of the androgen receptor and expression of aberrant constitutively active splice variants, as well as up-regulation of genes involved in androgens synthesis.

[Downregulation of OGDHL expression is associated with promoter hypermethylation in colorectal cancer].

Cell metabolic reprogramming is one of the cancer hallmarks. Glycolysis activation, along with suppression of oxidative phosphorylation and, to a lower extent, the TCA cycle, occurs in the majority of malignant tumors. A bioinformatics search for the glucose metabolism genes that are differentially expressed in colorectal cancer (CC) was performed using the data of The Cancer Genome Atlas (TCGA) Project. OGDHL for an oxoglutarate dehydrogenase complex subunit, which is involved in the TCA cycle and is indirectly responsible for the induction of apoptosis, was identified as one of the most promising candidates. A quantitative PCR analysis showed, on average, an eightfold downregulation of OGDHL in 50% (15/30) of CC samples. Based on the TCGA data, promoter hypermethylation was assumed to be a major mechanism of OGDHL inactivation. Bisulfite sequencing identified the OGDHL promoter region (+327 ... +767 relative to the transcription start site) that is often methylated in CC samples with downregulated ODGHL expression (80%, 8/10) and is possibly crucial for gene inactivation. Thus, frequent and significant OGDHL downregulation due to hypermethylation of a specific promoter region was demonstrated for CC. The OGDHL promoter methylation pattern was assumed to provide a marker for differential diagnosis of CIMP+ (CpG island methylator phenotype) tumors, which display dense hypermethylation of the promoter region in many genes.

[Infective endocarditis: quality of diagnosis and clinical features]. / Infektsionnyi éndokardit: kachestvo diagnostiki i klinicheskie osobennosti.]

AIM: To review current course of infectious endocarditis (IE), time and quality of the diagnosis, results of hospital treatment. MATERIAL AND METHODS: 30 cases of IE have been analysed (17 males, 13 females, mean age 37.6 +/- 2.3 years. The patients were admitted to hospital in 1997-1998. RESULTS: Late diagnosis registered in many IE cases is explained by low quality of history data and of heart auscultation responsible for late start of conservative treatment. Some specific features of the disease course, visceral lesions, efficacy of the treatment are outlined. CONCLUSION: IE morbidity is still high and prognosis in many cases if unfavourable.