KRAS mutations in Non-Small Cell Lung Cancer: translational aspects, current therapies and challenges for future research.

Mutations in the KRAS gene are prominent oncogenic drivers in non-small cell lung cancer (NSCLC), with multiple pathophysiological, clinical and prognostic implications. Although historically considered an "undruggable" target, recent research led to the development of specific KRAS-G12C inhibitors, like sotorasib and adagrasib which are currently approved for clinical use in patients affected by advanced NSCLC. However, the clinical utility of these drugs is often limited by resistance development through several biological mechanisms, including additional KRAS mutations, activation of compensatory pathways and metabolic reprogramming.

Comparison between Three Different Techniques for the Detection of EGFR Mutations in Liquid Biopsies of Patients with Advanced Stage Lung Adenocarcinoma.

Oncogenic mutations in the gene are targets of tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LC) patients, and their search is mandatory to make decisions on treatment strategies. Liquid biopsy of circulating tumour DNA (ctDNA) is increasingly used to detect EGFR mutations, including main activating alterations (exon 19 deletions and exon 21 L858R mutation) and T790M mutation, which is the most common mechanism of acquired resistance to first- and second-generation TKIs. In this study, we prospectively compared three different techniques for mutation detection in liquid biopsies of such patients.

The implementation of a reflex locomotion program according to Vojta produces short-term automatic postural control changes in patients with multiple sclerosis.

Background: Imbalance is common in people with multiple sclerosis.

Objective: To examine the effectiveness of a Vojta locomotion reflex program as short-term automatic postural control in patients with Multiple sclerosis.

Methods: Quasi-experimental controlled trial with a pretest-post-test design.

All Cats are Gray in the Dark: Enrichment/Depletion Approaches for Biomarker Discovery on Felis catus Plasma.

In veterinary medicine, assay performance is often affected by the lack of species-specific diagnostic tools. Reliable biomarkers might be identified by investigating biological fluids of the species of interest, but protein sequence databases are often incomplete and human-specific devices for reducing sample complexity might fail when applied to animal plasma. Here, seven commercial methods based on different capturing agents (anti-human antibodies, affinity ligands, mixture of antibodies and ligands, and combinatorial peptide ligand libraries) are applied to cat plasma and evaluated in terms of yield, identified proteins/ peptides, and relative abundance by high-resolution shotgun proteomics and label-free quantitation.

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry.

Application of a new method for GWAS in a related case/control sample with known pedigree structure: identification of new loci for nephrolithiasis.

In contrast to large GWA studies based on thousands of individuals and large meta-analyses combining GWAS results, we analyzed a small case/control sample for uric acid nephrolithiasis. Our cohort of closely related individuals is derived from a small, genetically isolated village in Sardinia, with well-characterized genealogical data linking the extant population up to the 16(th) century. It is expected that the number of risk alleles involved in complex disorders is smaller in isolated founder populations than in more diverse populations, and the power to detect association with complex traits may be increased when related, homogeneous affected individuals are selected, as they are more likely to be enriched with and share specific risk variants than are unrelated, affected individuals from the general population.

Expression pattern of zygote arrest 1 (ZAR1), maternal antigen that embryo requires (MATER), growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes in ovine oocytes and in vitro-produced preimplantation embryos.

The expression patterns of four maternal effect genes (MEG), namely zygote arrest 1 (ZAR1), maternal antigen that embryo requires (MATER), growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), were determined in ovine oocytes and in vitro-produced preimplantation embryos. The existence of ZAR1 and MATER in ovine species has not been reported previously. Reverse transcription-polymerase chain reaction was performed on germinal vesicle and IVM MII oocytes, as well as in in vitro fertilised and cultured two-, four-, eight- and 12/16-cell embryos, morulae and blastocysts.

Mutation analysis of candidate genes in melanoma-prone families: evidence of different pathogenetic mechanisms at chromosome 9P21.

Putative tumour suppressor genes CDKN2A and CDKN2B (on chromosome 9p21) and CDKN2A-interacting cell growth regulatory genes CDK4 and Id-1 have been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). Mutation analysis of these candidate genes was performed in MM families from southern Italy with three or more affected members or two affected members and one or more relative with histologically diagnosed atypical naevus. Two CDKN2A mutations, Arg24Pro and 1-292 G>A, were observed in two (15%) families; except for CDKN2A and Id-1 polymorphisms, no sequence variations were detected in the remaining genes.