ERCC1 and XRCC1 single nucleotide polymorphisms can guide treatment decision in patients with metastatic non-small cell lung cancer

Results from studies in several cancers on single nucleotide polymorphisms (SNPs) suggest that DNA repair capacity may have prognostic implication for disease recurrence, survival, and responses to treatment. This study aimed to evaluate the potential prognostic value of SNPs as biomarkers in patients with metastatic non-small cell lung cancer (mNSCLC) treated with platinum. Analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)-Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters, and survival. The median progression-free survival (PFS) and overall survival (OS) of 145 patients were 5.1 months and 30.9 months, respectively. In the univariate analysis ERCC1 genotype, XRCC1 genotype, and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were significant parameters for OS. In the multivariate analysis ERCC1 genotype, XRCC1 genotype, and ECOG-PS retained their significance. The median OS was 45.2 months for the ERCC1 normal (CC) and heterozygote (CT) genotypes, and 25.5 months for the ERCC1 mutant (TT) genotype. The median OS was 31.4 months for the XRCC1 normal (AA) and heterozygote (AG) genotypes, and 23.1 months for the XRCC1 mutant (GG) genotype. The median OS was 30,7 months for ECOG-PS≤ 1 and 10.2 months for ECOG-PS≥ 2. ERCC1 and XRCC1 genotypes, and ECOG-PS independently predicted OS in mNSCLC patients. Additional studies are needed for the further evaluation of potential prognostic SNPs in mNSCLC. [Med-Science 2020; 9(1.000): 255-60

Association of a synonymous SCN1B variant affecting splicing efficiency with Benign Familial Infantile Epilepsy (BFIE)

Benign Familial Infantile Epilepsy (BFIE) is clinically characterized by clusters of brief partial seizures progressing to secondarily generalized seizures with onset at the age of 3-7 months and with favorable outcome. PRRT2 mutations are the most common cause of BFIE, and found in about 80% of BFIE families. In this study, we analyzed a large multiplex BFIE family by linkage and whole exome sequencing (WES) analyses. Genome-wide linkage analysis revealed significant evidence for linkage in the chromosomal region 19p12-q13 (LOD score 3.48). Mutation screening of positional candidate genes identified a synonymous SCN1B variant (c.492T>C, p.Tyr164Tyr) affecting splicing by the removal of a splicing silencer sequence, shown by in silico analysis, as the most likely causative mutation. In addition, the PRRT2 frameshift mutation (c.649dupC/p.Arg217Profs*8) was observed, showing incomplete, but high segregation with the phenotype. In vitro splicing assay of SCN1B expression confirmed the in silico findings showing a splicing imbalance between wild type and mutant exons. Herein, the involvement of the SCN1B gene in the etiology of BFIE, contributing to the disease phenotype as a modifier or part of an oligogenic predisposition, is shown for the first time. (C) 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved

Plasma treated-double layer electrospun fiber mats from thermoplastic polyurethane and gelatin for wound healing applications

Conventional wound treatment options provide a barrier against exogenous microbial penetration but cannot simultaneously provide an antibacterial characteristic and promote healing. However, bioactive dressings can accelerate wound healing and have an antibacterial effect in addition to being able to cover and protect lesions. In this study, double-layer thermoplastic polyurethane (TPU)-gelatin fibrous dressings that mimic the epidermis and dermis layers of the skin were fabricated via electrospinning technique. As a bioactive agent, Hypericum perforatum oil (HPO) was utilized to impart antibacterial and therapeutic properties to the dressings. Tannic acid was also used in fiber mat formulations as a cross-linking agent. Oxygen plasma treatment was applied as a surface activation technique to improve adhesion of TPU and gelation layers. The fiber structure of the mats was revealed by a scanning electron microscopy (SEM) study. Fourier transform infrared (FTIR) spectroscopy was used to demonstrate HPO loading onto the mats. The water vapor transmission rate (WVTR) and fluid absorbency of the mats were compared with some commercial dressings. According to these results, it can be suggested that the mats can be used for moderate to high exudative wounds. All dressings, even the control sample showed antibacterial features against both Staphylococcus aureus and Escherichia coli bacteria due to the tannic acid. In vitro wound healing assays were carried out on the plasma-treated sample and it was observed that the sample did not negatively affect the migration and proliferation abilities of the cells which are necessary for wound healing. Overall results indicated that the plasma-treated fibrous mat would be a good candidate as a wound dressing material having an antibacterial character

Comparison of the efficacy of sunitinib and pazopanib in patients with advanced non-clear renal cell carcinoma

Non-clear cell renal cell carcinoma (non-ccRCC) is a highly heterogeneous disease group, accounting for approximately 25% of all RCC cases. Due to its rarity and especially heterogeneity, phase III trial data is limited and treatment options generally follow those of clear cell RCC. In the literature, there exists a number of studies with sunitinib, cabozantinib, and everolimus, but data on the efficacy of pazopanib are limited. Our aim in this study was to compare the efficacy of pazopanib and sunitinib, in a multicenter retrospective cohort of non-ccRCC patients. Our study included patients diagnosed with non-ccRCC who received pazopanib or sunitinib treatment as first-line therapy from 22 tertiary hospitals. We compared the progression-free survival (PFS), overall survival (OS), and response rates of pazopanib and sunitinib treatments. Additionally, we investigated prognostic factors in non-ccRCC. PFS and response rates of sunitinib and pazopanib were found to be similar, while a numerical difference was observed in OS. Being 65 years and older, being in the intermediate or poor risk group according to the International Metastatic Renal Cell Carcinoma Database Consortium, having liver metastases, presence of a sarcomatoid component, and having de novo metastatic disease were found to be significantly associated with shorter PFS. Pazopanib treatment appears to have similar efficacy in the treatment of non-ccRCC compared to sunitinib. Though randomized controlled trials are lacking and will probably be never be available, we suggest that pazopanib could be a preferred agent like sunitinib and cabozantinib