Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach

Hereditary non-polyposis colorectal cancer is an autosomal dominant condition due to germline mutations in DNA-mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Here we describe the application of a novel technique for the detection of genomic deletions in MLH1 and MSH2. This method, called multiplex ligation-dependent probe amplification, is a quantitative multiplex PCR approach to determine the relative copy number of each MLH1 and MSH2 exon. Mutation screening of genes was performed in 126 colorectal cancer families selected on the basis of clinical criteria and in addition, for a subset of families, the presence of microsatellite instability (MSI-high) in tumours. Thirty-eight germline mutations were detected in 37 (29.4%) of these kindreds, 31 of which have a predicted pathogenic effect. Among families with MSI-high tumours 65.7% harboured germline gene defects. Genomic deletions accounted for 54.8% of the pathogenic mutations. A complete deletion of the MLH1 gene was detected in two families. The multiplex ligation-dependent probe amplification approach is a rapid method for the detection of genomic deletions in MLH1 and MSH2. In addition, it reveals alterations that might escape detection using conventional diagnostic techniques. Multiplex ligation-dependent probe amplification might be considered as an early step in the molecular diagnosis of hereditary non-polyposis colorectal cancer

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

Abuse of over-the-counter medicines: a pharmacist’s perspective

Sujit S Sansgiry, Archita H Bhansali, Shweta S Bapat, Qingqing Xu Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, TX, USA Abstract: Self-care and self-medication practices are essential components of any health care systems. The use of over-the-counter (OTC) medications is a part of the self-medication process. The popularity of OTC medication use among patients may increase the abuse potential of OTC medications. With pharmacists being as accessible as they are, they are often the first line of contact for patients, and have the opportunity to educate and counsel patients on appropriate OTC medication use. The presence of a pharmacist ensures safe and effective use of OTC medications. Pharmacists can liaise with other health care providers in the management of self-care practices by patients. However, a pharmacist has traditionally been underutilized in this role. This article provides a brief review on OTC medications with abuse potential and the effect of self-medication on OTC medication abuse. This review further describes the barriers faced by pharmacists in OTC medication abuse management, given the increased potential of prescription-to-OTC switch in recent years. In addition, the potential for a behind-the-counter drug category to boost patient–pharmacist interaction was discussed. The current review supports the positive role played by pharmacists in the management of OTC medication abuse. This review adds to the knowledge base of the barriers faced by pharmacists to prevent OTC medication abuse while developing appropriate intervention strategies. By expanding the role of pharmacists, OTC medication abuse may be controlled more effectively, thereby providing better patient medication therapy management and outcomes. Keywords: non-prescription, behind-the-counter, medication, self-medicatio

Removal of migrated metallic prostatic stent by holmium laser

A 90-year-old male with prostatic hyperplasia with a history of ischemic heart disease and right-sided hemiplegia had undergone a Urolume stent placement because of acute urinary retention 9 months earliar. The stent had migrated into the bladder causing dysuria and a poor stream of urine. We fragmented the prostatic stent by Holmium (HO: YAG) laser followed by a laser prostatectomy. After the procedure, the patient voided satisfactorily

Enhanced optical-to-THz conversion efficiency of photoconductive antenna using dielectric nano-layer encapsulation

Photoconductive antennas (PCAs) are among the most conventional devices used for emission as well as detection of terahertz (THz) radiation. However, due to their low optical-to-THz conversion efficiencies, applications of these devices in out-of-laboratory conditions are limited. In this paper, we report several factors of enhancement in THz emission efficiency from conventional PCAs by coating a nanolayer of dielectric (TiO2) on the active area between the electrodes of a semi-insulating GaAs-based device. Extensive experiments were done to showthe effect of thicknesses of the TiO2 layer on the THz power enhancement with different applied optical power and bias voltages. Multiphysics simulations were performed to elucidate the underlying physics behind the enhancement of efficiency of the PCA. Additionally, this layer increases the robustness of the electrode gaps of the PCAs with high electrical insulation as well as protect it from external dust particles. (c) 2018 Author(s)