CCL20/CCR6 expression profile in pancreatic cancer

CCL20 and its receptor CCR6 have been shown to play a role in the onset, development and metastatic spread of various gastrointestinal malignancies. In this study, the expression profile and clinical significance of the CCL20/CCR6 system in distinct benign, pre-malignant and malignant pancreatic tissues was investigated

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

<p>Abstract</p> <p>Background</p> <p>Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition.</p> <p>Methods</p> <p>Expression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies.</p> <p>Results</p> <p>In CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05).</p> <p>Conclusions</p> <p>CXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions.</p

Common ABCB4 and ABCB11 Genotypes Are Associated with Idiopathic Chronic Cholestasis in Adults

INTRODUCTION: Pathogenic mutations in genes encoding the hepatocanalicular transporters ATP8B1, ABCB11 and ABCB4 are causative for progressive cholestatic liver disease in children. In adults, less severe variants such as the common ABCB4 c.711A>T polymorphism have been associated with intrahepatic cholestasis in pregnancy and elevated liver enzymes. Hence, our aim was to study the role of common polymorphisms in adult patients with chronic unexplained cholestasis. METHODS: Screening of outpatients of two university hospitals identified a cohort of 94 patients with chronic cholestasis of unknown origin after thorough exclusion of other causes. Genotyping was performed using TaqMan assays, and frequencies for the ABCB4 rs2109505 (c.711A>T), rs1202283 (c.504T>C), ABCB11 rs2287622 (p.A444V) and rs497692 (c.3084A>G) variants of the study cohort were compared to a cohort of 254 healthy controls. RESULTS: The dominating symptoms of the patients were pruritus and jaundice, though the majority of them did not report symptoms at inclusion. Advanced fibrosis or cirrhosis was present in 11 patients (11.7%) only. Genotyping revealed the presence of the ABCB4 c.711A>T risk variant in 79 patients (84%), a frequency that is significantly (p = 0.037) higher than that in controls (71%). The ABCB11 p.A444V variant was also more frequent in cholestatic patients (p = 0.042). CONCLUSION: The common ABCB4 c.711A>T and ABCB11 p.A444V polymorphisms are more prevalent in adult patients with idiopathic cholestasis than in healthy controls and may therefore represent risk factors for the development of chronic cholestatic liver disease

Penetration of moxifloxacin into liver tissue

Moxifloxacin is considered for treatment of pyogenic liver abscesses as well as antibiotic prophylaxis in the case of hepatobiliary interventions. The aim of this study was to provide data on the pharmacokinetic (PK) profile of moxifloxacin in serum and liver tissue of patients undergoing liver resection due to primary or secondary tumours of the liver. Patients scheduled for liver resection (n=34) received moxifloxacin 400 mg at randomised time intervals prior to surgery. Blood and healthy liver tissue were sampled 1.5-26 h after administration of moxifloxacin. Immediately after centrifugation, plasma was separated, frozen and stored until analysis. In a subgroup of 19 patients, additional plasma specimens were obtained after 2, 4, 8, 12, 24, 36 and 48 h to assess the PK profile. PK parameters of moxifloxacin were calculated applying a two-compartment model. Median (interquartile range) PK parameters were as follows: peak concentration at the end of moxifloxacin infusion (C(max)), 6.0 mg/L (4.8-7.1 mg/L); area under the concentration-time curve extrapolated to infinity (AUC(0-∞)), 51.1 mgh/L (40.3-57.7 mgh/L); elimination half-life, 13.2h (11.0-14.1 h); volume of distribution at steady state (V(ss)), 138.7 L (102.7-168.5 L); and total body clearance (CL), 7.8 L/h (6.9-9.9L/h). Mean tissue concentrations were 9.13 mg/kg after 1.6-2.4 h, 7.62 mg/kg after 2.6-4.9h, 7.48 mg/kg after 5.6-10.0 h and 6.24 mg/kg after 22.9-26.5 h. Mean tissue:serum ratios were 2.9, 3.4, 5.0 and 12.3, respectively. The lowest tissue concentration found in the study at any time point was 2.8 mg/kg. In conclusion, moxifloxacin rapidly penetrates into the liver tissue where its concentration remains high following intravenous administration. Therefore, intravenously applied moxifloxacin might be used for the treatment of bacterial liver infections such as pyogenic liver abscess as well as in pre-operative prophylaxis

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases

AIM: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer (CRC) patients

Effect of triclosan-coated sutures for abdominal wound closure on the incidence of abdominal wound dehiscence: a protocol for an individual participant data meta-analysis

INTRODUCTION: Acute abdominal wound dehiscence (AWD) or burst abdomen is a severe complication after abdominal surgery with an incidence up to 3.8%. Surgical site infection (SSI) is the biggest risk factor for the development of AWD. It is strongly suggested that the use of triclosan-coated sutures (TCS) for wound closure reduces the risk of SSI. We hypothesise that the use of TCS for abdominal wound closure may reduce the risk of AWD. Current randomised controlled trials (RCTs) lack power to investigate this. Therefore, the purpose of this individual participant data meta-analysis is to evaluate the effect of TCS for abdominal wound closure on the incidence of AWD. METHODS AND ANALYSIS: We will conduct a systematic review of Medline, Embase and Cochrane Central Register of Controlled Trials for RCTs investigating the effect of TCS compared with non-coated sutures for abdominal wound closure in adult participants scheduled for open abdominal surgery. Two independent reviewers will assess eligible studies for inclusion and methodological quality. Authors of eligible studies will be invited to collaborate and share individual participant data. The primary outcome will be AWD within 30 days after surgery requiring reoperation. Secondary outcomes include SSI, all-cause reoperations, length of hospital stay and all-cause mortality within 30 days after surgery. Data will be analysed with a one-step approach, followed by a two-step approach. In the one-step approach, treatment effects will be estimated as a risk ratio with corresponding 95% CI in a generalised linear mixed model framework with a log link and binomial distribution assumption. The quality of evidence will be judged using the Grading of Recommendations Assessment Development and Evaluation approach. ETHICS AND DISSEMINATION: The medical ethics committee of the Amsterdam UMC, location AMC in the Netherlands waived the necessity for a formal approval of this study, as this research does not fall under the Medical Research involving Human Subjects Act. Collaborating investigators will deidentify data before sharing. The results will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019121173