Prognostic importance of PD-L1 expression in bladder cancer patients.

BACKGROUND: PD-L1/PD-1 molecules are known as important mediators in immune-escape mechanisms of tumors. PD-L1 is highly expressed in various malignancies, including bladder cancer. However, the prognostic value of PD-L1 in bladder cancer patients remains controversial. AIM: To investigate the prognostic significance of PD-L1 expression in tumor tissues of bladder cancer patients. SUBJECTS AND METHODS: RNA was isolated from FFPE tumor tissues of 48 bladder cancer patients using the monophasic phenol and guanidine isothiocyanate method. Total RNA was converted to cDNA and gene expression levels were analyzed by qRT-PCR. The differential expression levels of the PD-L1 gene between tumor grade and cancer stage groups were analyzed by independent student's t-test and one-way ANOVA. RESULTS: Statistically significantly increased PD-L1 expression was observed in the high-grade tumor group (p < 0.05). No significant difference in PD-L1 expression was found among pTa, pT1, and pT2 groups. In addition, the difference in overall survival was not significantly different between groups. CONCLUSION: The results showed that high PD-L1 expression in bladder cancer was associated with tumor aggressiveness and grade. Despite the inability of the qRT-PCR to show the PD-L1 expression at different locations of tumor tissue, evaluation of PD-L1 mRNA expression by qRT-PCR, which is a highly sensitive and specific assay, appears to be a robust approach. Furthermore, these findings may contribute to a rationale for recommending anti-PD-L1 immunotherapy as an alternative to standard therapy for bladder cancer patients who are most likely to benefit from it.

Association of paraoxonase-1 L55M and Q192R polymorphisms with PCOS risk and potential risk factors for atherosclerosis.

AIM: To examine the PON1-L55M and -Q192R polymorphisms for polycystic ovary syndrome (PCOS) risk in relation with atherosclerosis risk markers. METHODS: Blood samples were collected from 203 women (PCOS [n = 151], control [n = 52]). Genomic DNA was extracted and RFLP method was performed following the amplifications of the target regions. RESULTS: Individuals with 192QR/192RR genotypes had a 2.5-fold increased risk of representing PCOS compared with the individuals with 192QQ genotype. Q192R was more strongly associated with PCOS than previously suggested atherosclerosis risk markers. Q192R status and body mass index values in combination were established to be a significant predictor of PCOS (AUC: 0.655, p = 0.001). CONCLUSION: This is one of the first studies suggesting the use of combination biomarkers to better predict the risk of developing PCOS.

Is neuroglial antigen 2 a potential contributor to cilengitide response in glioblastoma?

BACKGROUND: Determining the expression levels of neuroglial antigen 2 (NG2) in glioma cell lines and to evaluate the potential contribution of NG2 to cilengitide response were aimed. MATERIALS AND METHODS: Endogenous expression level of NG2 was determined using quantitative reverse transcription polymerase chain reaction and immunoblotting. Cilengitide responses of the cells were monitored to determine half maximal inhibitory concentration values. Whether the suppression of NG2 expression alters the response of A172 cells to cilengitide was examined. RESULTS: The effect of cilengitide on inducing apoptosis of the cells was determined by TUNEL staining. High mRNA and protein expression of NG2 was detected in A172 and U-87MG cells, while T98G, M059K and M059J cells demonstrated low levels of NG2. A172, U-87MG and positive control MG-63 were relatively sensitive to cilengitide compared to T98G, M059K and M059J. MG-63, A172 and U-87MG were unexpectedly found to be more susceptible to cilengitide. In addition, NG2 knock-down showed no significant difference in cell death between small interfering RNA (siRNA)-transfected and cilengitide-treated groups. The results showed that cilengitide caused detachment and subsequently initiated apoptosis. Glioma cell lines express variable levels of NG2 and differ in their responses to cilengitide. Although increased numbers of apoptotic cells were found in untransfected cells compared to siRNA-transfected cells upon exposed to cilengitide, the difference was not documented to be significant between two groups. CONCLUSION: It may be proposed that the combination therapy of NG2 suppression and cilengitide treatment showed no considerable effect on glioblastoma compared to cilengitide therapy alone. Response to therapy may be further improved by targeting other factors act in concert in this signaling pathway.

Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats.

Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

Investigation of mucus obtained from different fish species on the acute pain induced with scalpel incision in paw of rats.

No comparative study could be found for the analgesic activity of mucuses from the Oncorhynchus mykiss (OM), Salvelinus fontinalis (SF), Salmo coruhensis (SC), Acipenser gueldenstaedtii (AG), and Acipenser baerii (AB) fish species in the literature. We aimed to investigate the effects of mucuses obtained from the abovementioned fish species on scalpel incision-induced pain in the rat paw and to examine the role of oxidant/antioxidant parameters and COX-2 gene expression in the analgesic activities. Animals were divided into groups: SIC (scalpel incision; SI), SIDS (SI+25 mg/kg diclofenac sodium), SOM (SI+25 mg/kg OM mucus), SFM (SI+25 mg/kg SF mucus), SCM (SI+25 mg/kg SC mucus), SAgM (SI+25 mg/kg AG mucus), SAbM (SI+25 mg/kg AB mucus), and HG (healthy). The paw pain thresholds were measured with a Basile algesimeter before and after diclofenac sodium (DS) or mucus administration, and then the rats were euthanized with thiopental sodium. Oxidant/antioxidant and COX-2 gene expression parameters were measured in paw tissues. OM, SC, AG, and AB fish mucuses could not decrease the SI-induced pain. However, SF fish mucus prevented this pain by 69% after the first hour and by 58.3% after the third hour. DS was shown to suppress pain more weakly than SF, preventing the pain by 62.1% and 50.0% after the first and third hours, respectively. SF mucus and DS significantly inhibited increase of COX-2 gene expression, while other fish mucuses could not. None of the fish mucuses except SF mucus in conjunction with DS could significantly inhibit the increase in oxidant parameters and decrease in antioxidants. SF fish mucus should be comparatively assessed in clinical practice for treatment of postoperative pain.