Search results for "Repair"
showing 10 items of 747 documents
Meta-analysis of mismatch repair polymorphisms within the cogent consortium for colorectal cancer susceptibility
2013
In the last four years, Genome-Wide Association Studies (GWAS) have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC). Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a followup of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimate…
The use of cultured hepatocytes to investigate the metabolism of drugs and mechanisms of drug hepatotoxicity.
2001
Hepatotoxins can be classified as intrinsic when they exert their effects on all individuals in a dose-dependent manner, and as idiosyncratic when their effects are the consequence of an abnormal metabolism of the drug by susceptible individuals (metabolic idiosyncrasy) or of an immune-mediated injury to hepatocytes (allergic hepatitis). Some xenobiotics are electrophilic, and others are biotransformed by the liver into highly reactive metabolites that are usually more toxic than the parent compound. This activation process is the key to many hepatotoxic phenomena. Mitochondria are a frequent target of hepatotoxic drugs, and the alteration of their function has immediate effects on the ene…
Tiratricol neutralizes bacterial endotoxins and reduces lipopolysaccharide-induced TNF-alpha production in the cell.
2008
Contains fulltext : 70610.pdf (Publisher’s version ) (Closed access) The screening of a commercially available library of compounds has proved a successful strategy for the identification of a lead compound in a drug discovery programme. Here, we analysed 880 off-patent drugs, which initially comprised the Prestwick Chemical library, as sources of bacterial endotoxin neutralizers. We identified 3,3',5-triiodo-thyroacetic acid (tiratricol) as a non-antibacterial compound that neutralizes the toxic lipopolysaccharide.
The abdominal wall hernia in cirrhotic patients: A historical challenge
2018
Abstract Background The incidence rate of abdominal wall hernia is 20–40% in cirrhotic patients. A surgical approach was originally performed only if complication signs and symptoms occurred. Several recent studies have demonstrated the usefulness of elective surgery. During recent decades, the indications for surgical timing have changed. Methods Cirrhotic patients with abdominal hernia who underwent surgical operation for abdominal wall hernia repair at the Policlinico “Paolo Giaccone” at Palermo University Hospital between January 2010 and September 2016 were identified in a prospective database, and the data collected were retrospectively reviewed; patients’ medical and surgical records…
The abdominal wall incisional hernia repair in cirrhotic patients
2018
BACKGROUND: The incidence of abdominal wall hernia in cirrhotic patients with ascites is between 20 and 40%. Controversies regarding the treatment modality and surgical timing of abdominal wall incisional hernia repair in cirrhotic patients remain. The study proposed wants to analyze the abdominal incisional hernia repair in cirrhotic patients with ascites performed in a single center to determine post-operative morbidity, mortality and complication rate. PATIENTS AND METHODS: Cirrhotic patients with abdominal incisional hernia that underwent surgical operation for abdominal wall hernia repair at the "Policlinico Paolo Giaccone" at Palermo University Hospital between January 2015 and Decemb…
Inducible Responses and Protective Functions of Mammalian Cells Upon Exposure to UV Light and Ionizing Radiation
1999
In mammalian cells, ultraviolet (UV) light as well as ionizing radiation (IR) transcriptionally activate the early-responsive genes c-fos, c jun,junB and junD. The induction of fos and jun by UV-C is currently understood to occur via activation of the EGF receptor and the Ras, Raf, ERK and JNK cascade leading ultimately to phosphorylation of transcription factors such as Fos and Jun (AP-1). This, finally, gives rise to transcriptional activation of AP-1 dependent target genes. Another gene we have recently demonstrated to be immediate-early inducible upon UV-irradiation encodes the Ras-related small GTPase RhoB. The pathway of rhoB induction appears to be different from fos/jun because (i) …
The three-dimensional structure of Drosophila melanogaster (6–4) photolyase at room temperature
2021
A crystal structure of a photolyase at room temperature confirms the structural information obtained from cryogenic crystallography and paves the way for time-resolved studies of the photolyase at an X-ray free-electron laser.
The nucleotide excision repair protein XPC is essential for bulky DNA adducts to promote interleukin-6 expression via the activation of p38-SAPK
2016
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, and many are potent carcinogens. Benzo[a]pyrene (B[a]P), one of the best-studied PAHs, is metabolized ultimately to the genotoxin anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE triggers stress responses linked to gene expression, cell death and survival. So far, the underlying mechanisms that initiate these signal transduction cascades are unknown. Here we show that BPDE-induced DNA damage is recognized by DNA damage sensor proteins to induce activation of the stress-activated protein kinase (SAPK) p38. Surprisingly, the classical DNA damage response, which involves the kinases ATM and ATR, is not involved in p38-SA…
Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition
2017
AbstractPurpose: Despite advances in multimodal therapy, neuroblastomas with hemizygous deletion in chromosome 11q (20%–30%) undergo consecutive recurrences with poor outcome. We hypothesized that patients with 11q-loss may share a druggable molecular target(s) that can be exploited for a precision medicine strategy to improve treatment outcome.Experimental Design: SNP arrays were combined with next-generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma etiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in v…
Exome Analysis Reveals Genomic Markers Associated with Better Efficacy of Nivolumab in Lung Cancer Patients
2019
Abstract Purpose: Immune checkpoint inhibitors revolutionized the treatment of non-small cell lung cancer (NSCLC). However, only one-quarter of patients benefit from these new therapies. PD-L1 assessment and tumor mutational burden (TMB) are available tools to optimize use of checkpoint inhibitors but novel tools are needed. Exome sequencing could generate many variables but their role in identifying predictors of response is unknown. Experimental Design: We performed somatic and constitutional exome analyses for 77 patients with NSCLC treated with nivolumab. We studied: one-tumor-related characteristics: aneuploidy, CNA clonality, mutational signatures, TMB, mutations in WNT, AKT, MAPK, an…