DUSP9 / MKP-4 belongs to a subclass of bispecific protein phosphatases, which, by dephosphorylation of MAP kinases (ERK1 / 2, p38 and JNK), negatively regulate the activity of MAP kinase cascades. Hyperactivation of MAP kinase cascades is observed in many different cancer types, including kidney cancer. We have previously found that in human clear cell renal cell carcinoma (ccRCC) DUSP9 is downregulated. In this study, using the semi-quantitative RT-PCR method, we evaluated the expression level of DUSP9 in tumors of patients with different stages of renal cell carcinoma of three histological variants: ccRCC (26 samples), papillary (2 samples) and chromophobic (1 sample). For each tumor 3 distantly located pieces were analyzed. We showed that DUSP9 mRNA level was significantly reduced in all three pieces of each tumor compared with normal tissue. Promoter hypermethylation may be one mechanism of gene repression in cancer. Using the DNA demethylating agent 5-Aza-2'-deoxycytidine and RCC cell lines we showed a correlation between the mRNA level and methylation level of the promoter region of DUSP9 gene. We then analyzed methylation level of DUSP9 promoter in 31 clinical samples of RCC (11 female and 20 male patients). It was increased in 10 out of 11 female RCC. In men, the methylated alleles of DUSP9 were not detected in either tumor or paired normal specimens. The results of our study indicate that DUSP9 transcriptional repression is an early event in kidney carcinogenesis and that DUSP9 expression in RCC can be regulated epigenetically via DNA methylation of the gene promoter, in a sex-related manner. They also indicate the existence of alternative mechanisms of inactivation of the DUSP9 gene in RCC.

Infections caused by multiresistant gram-negative bacteria are one of the major problems in the treatment of cancer patients. Strains with mechanisms of resistance mediated by carbapenemases represent a particular threat since they spread rapidly and are characterized by high frequency of occurrence of multiresistance to antimicrobial agents. Here we show that 14 out of 399 gram-negative bacteria (3,5 %), isolated from clinical specimens of 11 patients with solid tumors (n=581) in a hospital of federal level in January 2015-April 2016 were carbapenem-insusceptible. Among them 3 isolates of Klebsiella pneumonia, 2 Enterobacter cloacae, 2 Pseudomonas aeruginosa and 7 Acinetobacter baumannii. All 14 strains were resistant to a wide range of antimicrobial agents including beta-lactams, aminoglycosides, monobactams and fluoroquinolones. The only antimicrobial agent to which all but one Exloacae strain remained susceptible was colistin. This strain was insusceptible to all 10 antimicrobial agents tested in the study, including tigecycline. We observed two cases of infection of a single patient by 2-3 distinct species of multidrug-resistant gram-negative bacteria. In 79 % of the strains the genes encoding carbapenemases of OXA40/24, KPC, VIM and NDM types were detected. Despite the fact that multidrug-resistant car-bapenem-insusceptible strains of gram-negative bacteria were isolated from a relatively small number of cancer patients, the majority of these strains represent a particular epidemiological and clinical threat.