Transcriptomic analysis of plasma exosomes provides molecular information of response to cabazitaxel treatment in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Prostate cancer is the second most common cancer type and the second most common cancer-related cause of death in men. Cabazitaxel, a next-generation taxane, shows favorable toxicity profile and is effective in docetaxel-resistant tumors. Despite initial responses, in most cases, prostate cancer patients acquire resistance to cabazitaxel. There is a need to identify molecular markers that can monitor and predict treatment response. METHODS: We performed transcriptional exosome profiling (Human Transcriptome Array-HTA 2.0) from the plasma of 19 patients with castration-resistant prostate cancer at baseline and in patients after one cycle of cabazitaxel (C1). The patients were stratified in two groups (responders and nonresponders) according to their clinical response to cabazitaxel. Gene set enrichment analysis and ingenuity pathway analysis platforms were used for gene and pathway analysis. RESULTS: We detected molecular differences in the exosomes from two groups of patients (nonresponders vs. responders) at baseline in pathways related to prostate cancer, oncogenic signaling, cytoskeleton, and immune system. In nonresponders, we found enrichment of cytoskeleton related gene (Stathmin-1 and ITSN1) that have been associated with resistance to cabazitaxel. Monitoring of exosomal transcripts after the first cycle of treatment revealed changes in pathways associated with response to treatment. CONCLUSIONS: Sequential transcriptional profiling of plasma-derived exosomes reveals differential expression of genes that may reflect resistance to cabazitaxel treatment and therapy response.

Evaluation of sleep-related respiratory disorders in patients with multiple sclerosis.

Patients with multiple sclerosis (MS) often report fatigue, poor sleep and complaint of sleep disorders. Neurofilament light chain (NF-L) has been identified as a potential biomarker for disease progression in MS patients. In this study, we aimed to evaluate sleep characteristics in MS patients and its relationship with the level of serum NF-L. In the present study carried out as a prospective and cross-sectional study, 32 relapsing-remitting MS (RRMS) patients and 32 control subjects were included. Epworth Sleepiness Scale and Fatigue Severity Scale tests were applied to the groups and the full night polysomnography was performed. Serum samples were obtained for NF-L analysis. Apnea-hypopnea index (AHI), AHI in rapid eye movement sleep (AHI REM), percentage of NonREM stage 1 (N1) and NonREM stage 3 (N3) values were significantly different in RRMS patients (p < 0.05). There was correlation between AHI and Expanded Disability Status Scale indicating a negative directed moderate relationship (r = - 0.343 p = 0.055). Serum NF-L correlations with sleep efficiency and percentage of NonREM stage 2 (N2) were showed mild significant correlation (r = - 0.342 as - 0.535, p < 0.05). We found that sleep disorders are prevalent in RRMS patients and it has a negative effect on the clinical outcome of disease. In clinical practice, the association of these two diseases should be taken into consideration because sleep disturbances increase the disability of MS disease especially presenting with fatigue.

Is pentraxin 3 level an effective biomarker in disease activity in patients with rheumatoid arthritis?

INTRODUCTION: The aim of the current study was to identify whether serum pentraxin 3 (PTX3) level could be a marker of increased inflammation in rheumatoid arthritis (RA) patients. MATERIAL AND METHODS: The study included 41 patients diagnosed with RA according to the American College of Rheumatology (ACR) 1990 diagnostic criteria. We compared the serum PTX3 levels between RA patients and a healthy control group, the relationship between PTX3 level and disease activity was also examined. RESULTS: A statistically significant difference was determined between the RA patients and controls as regards PTX3, platelets, C-reactive protein, and mean platelet volume results (p = 0.042, p = 0.007, p = 0.017, p < 0.001, respectively). There was no statistically significant difference in terms of PTX3 level between anti-CCP-positive and -negative patients (p = 0.368). No statistically significant difference was determined in respect of PTX3 levels between RA patients with different disease activity scores (p = 0.346). CONCLUSIONS: No relationship was determined between PTX3 and disease activity in RA patients, nor with traditional clinical and biochemical measurements of disease activity. However, the PTX3 levels of the RA patients were found to be high in comparison with the control group. Because, from these results, the role of PTX3 in the pathogenesis of RA cannot be ignored, there is a need for further studies to determine the potential role of PTX3 in RA pathogenesis.

Evaluation of Endometrial Receptivity by Measuring HOXA-10, HOXA-11, and Leukemia Inhibitory Factor Expression in Patients with Polycystic Ovary Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is an important cause of infertility. In women with PCOS have increased rate of spontaneous abortion and reduced rate of conception. HOXA-10 and HOXA-11 are proteinous products of homeobox gene group and play an important role during implantation. AIMS: The aim of this study was to evaluate endometrial receptivity by measuring HOXA-10, HOXA-11, and leukemia inhibitory factor (LIF) gene expressions in women with PCOS. SETTINGS AND DESIGN: A tertiary referral center. MATERIALS AND METHODS: This study was conducted on reproductive age women with abnormal uterine bleeding without sonographically proven anatomical reason. Endometrial sampling procedures were done in proliferative phase using low-pressure endometrial suction device to exclude endometrial pathology. HOXA-10, HOXA-11, and LIF gene expressions were measured from endometrial sampling material. Blood sample was taken to measure serum estradiol level on the day of endometrial sampling. STATISTICAL ANALYSIS USED: Statistical analysis was performed using SPSS software version 17 (SPSS Inc., Chicago, IL, USA). Mann-Whitney U-test was used to compare the variables. RESULTS: A total of 53 patients were included in this study. Study group consisted of 33 patients with PCOS. Gene expressions of HOXA-10, HOXA-11, and LIF were significantly lower in patients with PCOS (P < 0.05). CONCLUSIONS: This study results showed that in patients with PCOS have decreased gene expression of HOXA-10, HOXA-11, and LIF which might contribute PCOS-related infertility.

Polymorphisms in the Growth Differentiation Factor 5 (GDF 5) Gene in Knee Osteoarthritis.

OBJECTIVE: To identify the frequency of the rs143383 SNPin the GDF5 gene, which is located in the 5'-untranslated region of Turkish population with knee osteoarthritis (OA). STUDY DESIGN: Acase-control study. PLACE AND DURATION OF STUDY: Orthopedics and Traumatology Department, Bozok University Medical Faculty, Yozgat, Turkey, from 2012 to 2014. METHODOLOGY: Patients diagnosed with OA(n=94) and patients who did not have joint complaints (n=279) were enrolled in this study. Patients diagnosed with osteoarthritis according to the 1986 American College of Rheumatology osteoarthritis criteria and Kellgren and Lawrence scores were investigated, based on age, gender, and X-ray findings. Blood samples were taken for the identification of GDF5 (rs143383) SNPs by PCR/RFLP, according to a standard protocol. RESULTS: This study included 373 patients. The OAgroup (25.2%; n=94) was characterized by specific genotypes: TT (39.4%; n=37); heterozygotes (TC; 45.7%; n=43); and homozygotes (CC; 14.9%; n=14). The control group (74.8%; n=279) was comprised of TT(26.5%; n=74), TC (54.8%; n=153), and CC (18.6%; n=52) genotypes. An analysis of rs143383 SNP of the GDF5 gene polymorphism revealed that the rs143383 TTgenotype had a higher risk for OA(crude OR=1.798, 95% CI=1.010-2.941, p=0.021). CONCLUSION: This study demonstrated that there is a correlation of +104T/C polymorphism in the 5'-UTR of GDF5 with knee OAin a Turkish population.