Utjecaj izloženosti 1,6-heksametilen diizocijanatu (HDI) na vršni ekspiratorni protok u autolakirera u Iranu

The aim of this study was to investigate the effects of occupational exposure to 1,6-hexamethylene diisocyanate (HDI) on peak flowmetry in automobile body paint shop workers in Iran. We studied a population of 43 car painters exposed to HDI at their workplaces. Peak expiratory fl ow was tested for one working week, from the start to the end of each shift. Air was sampled and HDI analysed in parallel, according to the OSHA 42 method. Daily and weekly HDI exposure averages were (0.42±0.1) mg m-3 and (0.13±0.05) mg m-3, respectively. On painting days, 72 % of workers showed more than a 10 % variation in peak expiratory fl ow. Inhalation exposure exceeded the threshold limit value (TLV) ten times over. This strongly suggests that HDI affected the peak fl owmetry in the studied workers.Cilj je ovog ispitivanja bio utvrditi vršni protok u 43 iranska autolakirera profesionalno izložena 1,6-heksametilen diizocijanatu (HDI). Vršni ekspiratorni protok testiran je tjedan dana na početku i kraju svake smjene. Uzorkovanje i mjerenje HDI-ja u zraku radilo se istodobno s testiranjem vršnoga protoka, prema metodi OSHA 42. Prosječna dnevna izloženost radnika HDI-ju iznosila je (0.42±0.1) mg m-3, a tjedna (0.13±0.05) mg m-3. U 72 % radnika vršni ekspiratorni protok tijekom dana varirao je više od 10 %. Radnici su udisali deset puta više razine HDI-ja od graničnih te je moguće da je HDI utjecao na mjerenja plućne funkcije

Periostin is up-regulated in high grade and high stage prostate cancer

BACKGROUND: Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. METHODS: Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93) and a test cohort (n = 325). Metastatic prostate cancers (n = 20), hormone refractory prostate cancers (n = 19) and benign prostatic tissues (n = 38) were also analyzed. RESULTS: In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p < 0.01) and advanced tumour stage (p < 0.05) in the test cohort. Whereas periostin expression was weak or absent in the stroma around normal prostate glands, strong periostin expression in tumour stroma was found in most primary and metastatic prostate cancers. High stromal periostin expression was associated with higher Gleason scores (p < 0.001). There was a relationship between stromal periostin expression and shortened PSA relapse free survival times in the training cohort (p < 0.05). CONCLUSIONS: Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer

Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors.

It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants. The resulting reduction of BET protein levels sensitized cancer cells to BET inhibitors. Conversely, prostate cancer-specific SPOP mutations resulted in impaired degradation of BETs, promoting their resistance to pharmacologic inhibition. These results uncover an oncogenomics paradox, whereby mutations mapping to the same domain evoke opposing drug susceptibilities. Specifically, we provide a molecular rationale for the use of BET inhibitors to treat patients with endometrial but not prostate cancer who harbor SPOP mutations

MAGE-C2/CT10 Protein Expression Is an Independent Predictor of Recurrence in Prostate Cancer

The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity) and castration-resistant prostate cancer (17% positivity; p<0.001). Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015), which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05). MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer

Molecular Analysis of Gene Frequencies of TEM, CTX-M and SHV in Beta-Lactam Antibiotic-Resistant Strains of E. Coli Isolated from Urinary Tract Infections in Yasuj Hospitals

Background & aim: Urinary tract infections is one of the most common infectious diseases which many factors are involved, but bacteria such as E.coli is the most important agent of urinary tract infections. Antibiotic resistance as a major problem in the treatment and control of these infections is considered. The aim of this study was to determine the genes that cause resistance to beta-lactam family of antibiotics on E.coli isolated from urinary tract infections in Yasuj city. Methods: In the present Cross-sectional study which was conducted over a period of seven months in 2013, 123 samples of E.coli were collected from Yasuj hospitals for molecular analysis of TEM, SHV CTX-M genes, causing antibiotic resistance by (PCR) method.Data were analyzed using SPSS statistical test. Results: PCR showed that the gene frequency of TEM (50.94%), SHV (47.16%), CTX-M-9 (35.84%), and CTX-M-10, (32.07%) and the highest and lowest prevalent of genes were related to TEM and CTX-M10 in E.coli isolated from urinary tract infections respectively. Conclusion: According to the high prevalence of resistance to beta-lactam antibiotics, the current study showed that the noted genes play an important role in facilitating the spread of antimicrobial resistance in this region

Continuous low-dose aspirin therapy in robotic-assisted laparoscopic radical prostatectomy does not increase risk of surgical hemorrhage

Abstract Background: Withdrawal of oral antiplatelet therapy (OAT) is a major risk factor for stent thrombosis, myocardial infarction, and cerebral strokes. In order to minimize the risk for thrombotic complications, since 2007 robotic-assisted laparoscopic radical prostatectomy (RARP) has taken place under continuous OAT with aspirin at our institution. In this retrospective study we analyzed the risk for perioperative bleeding and surgical outcome after RARP with OAT. Patients and Methods: All patients who underwent RARP with aspirin OAT at our institution since 2007 were included in this analysis. The OAT group was compared with a group that underwent RARP without OAT, which contained twice the number of patients. Matching of the two groups was performed with regard to the tumor stage and whether a lymph node dissection or nerve-sparing was performed. Results: Thirty-eight patients were assigned to the OAT group and 76 to the control group. A difference in the decrease of postoperative hemoglobin concentration was not detectable between the two groups (mean drop of 2.9±1.4 g/dL and 2.9±1.1 g/dL, respectively; P=.93). RARP was completed in all OAT patients without conversion to open surgery. Two of the 38 patients (5.3%) in the OAT group and none in the control group required blood transfusions (P=.11). Equivalent rates of positive surgical margins for pT2 tumors were detected (16% OAT versus 14% control group; P=1.0). No adverse cardiovascular events occurred in either group during the hospitalization. Conclusions: Continued perioperative OAT with aspirin in RARP is safe, feasible, and not associated with increased blood loss

Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors : a post hoc analysis of ORAL Surveillance

Background: In patients with rheumatoid arthritis (RA), persistent inflammation and increasing disease activity are associated with increased risk of adverse events (AEs).Objectives: To assess relationships between RA disease activity and AEs of interest in patients treated with tofacitinib or tumor necrosis factor inhibitors (TNFi).Design: This was a post hoc analysis of a long-term, postauthorization safety endpoint trial of tofacitinib versus TNFi.Methods: In ORAL Surveillance, 4362 patients aged &gt;= 50 years with active RA despite methotrexate, and &gt;= 1 additional cardiovascular (CV) risk factor, were randomized 1:1:1 to tofacitinib 5 or 10 mg twice daily or TNFi for up to 72 months. Post hoc time-dependent multivariable Cox analysis evaluated the relationships between disease activity [Clinical Disease Activity Index (CDAI)], inflammation [C-reactive protein (CRP)], and AEs of interest. The AEs included major adverse CV events (MACE), malignancies excluding nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), serious infections, herpes zoster (HZ), nonserious infections excluding HZ (NSI), and death.Results: Across treatments, risk for NSI was higher when patients had CDAI-defined active disease versus remission; MACE and VTE risks trended higher, but did not reach significance. Hazard ratios for MACE, malignancies excluding NMSC, VTE, infections, and death rose by 2-9% for each 5-mg/L increment in serum CRP. The interaction terms evaluating the impact of treatment assignment on the relationship between disease activity and AEs were all p &gt; 0.05.Conclusion: In ORAL Surveillance, higher NSI risk was observed in the presence of active RA versus remission. The risk of MACE and VTE directionally increased in active disease versus remission, although statistical power was limited due to small event numbers in these categories. The relationship between active disease and AEs was not impacted by treatment with tofacitinib versus TNFi