Upregulated wnt-11 and mir-21 expression trigger epithelial mesenchymal transition in aggressive prostate cancer cells

Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells’ behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa

AMPK Is the Crucial Target for the CDK4/6 Inhibitors Mediated Therapeutic Responses in PANC-1 and MIA PaCa-2 Pancreatic Cancer Cell Lines

The survival rate of pancreatic ductal adenocarcinoma (PDAC) patients is short, and PDAC is a cancer type that ranks fourth in the statistics regarding death due to cancer. Mutation in the KRAS gene, which plays a role in pancreatic cancer development, activates the PI3K/AKT/mTOR signaling pathway. The activity of the AMPK as a cellular energy sensor is one of the fundamental mechanisms that can induce effective therapeutic responses against CDK4/6 inhibitors via adjusting the cellular and tumor microenvironment stress management. The phosphorylation of AMPKα at the different phosphorylation residues such as Thr172 and Ser 377 causes metabolic differentiation in the cells following CDK4/6 inhibitor treatment in accordance with an increased cell cycle arrest and senescence under the control of different cellular players. In this study, we examined the competencies of the CDK4/6 inhibitors LY2835219 and PD-0332991 on the mechanism of cell survival and death based on AMPK signaling. Both CDK4/6 inhibitors LY2835219 and PD-0332991 modulated different molecular players on the PI3K/AKT/mTOR and AMPK signaling axis in different ways to reduce cell survival in a cell type dependent manner. These drugs are potential inducers of apoptosis and senescence that can alter the therapeutic efficacy cells

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Retention of vacuum-assisted closure device sponge leading to a perianal abscess and fistula

PubMedID: 24612666[No abstract available

Detection of MSI in circulating cell-free DNA from colorectal cancer patients

52nd Conference of the European-Society-of-Human-Genetics (ESHG) -- JUN 15-18, 2019 -- Gothenburg, SWEDENWOS: 000489313905078…European Soc Human Gene

Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma

PubMedID: 31101189Background: Scarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT)for localized hepatocellular carcinoma (HCC)patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC. Method: Between January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38)vs OLT (n = 28)for localized HCC were compared using a prospectively maintained database. Results: A total of 66 patients (with a median age of 62)who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P =.45)and perioperative mortality rates (7.9% vs 10.7%, P =.2)were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P =.0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P =.0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P =.034). However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P =.63). Based on logistic regression analysis, number of tumors (P =.034, odds ratio: 2.1)and “resection”-type surgery (P =.008, odds ratio: 20.2)were independently associated with recurrence. Conclusion: Compared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality. © 2019 Elsevier Inc

Chromosome aberration and sister chromatid exchange in workers of the iron and steel factory of Iskenderun, Turkey

WOS: 000179021800003PubMed ID: 12395403The aim of this study was to investigate, by using chromosome aberration (CA) and sister chromatid exchange (SCE) tests, whether or not the workers employed in the iskenderun (Turkey) iron and steel factory have any genotoxic risk. The CA and the SCE were investigated in 48 males employed in a coke ovens unit and 8 males employed in a product side unit of the factory and in control groups. The frequency of CA was higher while the frequency of the SCE was not in all the smoker-nonsmoker workers than in smoker-nonsmoker control groups. In addition, there was no significant decrease in the RI, while the MI was significantly lower than in the controls. (C) 2002 Wiley-Liss, Inc

The genotoxic risk of underground coal miners from Turkey

PubMedID: 16337427A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining. © 2005 Elsevier B.V. All rights reserved.2003/7-47We are grateful to Osman Balamir, manager of the Armutçuk Coal Mining Institution, for his contribution to the study. The authors would like to thank health technicians of the Armutçuk Coal Mining Institution for collecting blood samples. This research was financially supported by the Research Fund of Kahramanmaras Sutcu Imam University (Grant 2003/7-47)