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These gene expression effects appear to occur specifically in the squamous cell carcinoma (SCC) subtype of stage I NSCLC, while not observed in the non-SCC subtypes.
Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype.
Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype.
A two-phase study (clinical and genomic-based) was conducted to evaluate the effect of timing of chronic obstructive pulmonary disease (COPD) diagnosis on lung cancer outcomes.
The prognostic influence of COPD was investigated in a clinical cohort of 1,986 patients who received surgery for stage I lung cancer; 823 (41.4%) of them also had COPD, including 549 (27.6%) incidental COPD (diagnosed within 6-months of lung cancer diagnosis) and 274 (13.8%) prior COPD (>6 months before lung cancer diagnosis). The genomic variations were analyzed from another cohort of 1,549 patients for association with 384 lung cancer-related single nucleotide polymorphisms (SNPs).
Older age (≥70 years), smokers, and respiratory symptoms were independent predictors of incidental COPD in lung cancer (all P<0.05). Similar to prior COPD, incidental COPD increased postoperative complications and worsened quality-of-life related to dyspnea (both P<0.05). Multivariate Cox regression analysis showed lung cancer survival decreased significantly in incidental COPD (HR, 1.30; 95% CI, 1.02-1.66), but not in prior COPD (HR, 1.15; 95% CI, 0.87-1.52). Among prior COPD, median survival showed a trend for being better in those with fewer exacerbations (0-1
≥2 exacerbation/year; 6.1
4.1 years; P=0.10). The SNP-based analysis identified ADCY2rs52827085 was significantly associated with risk of incidental COPD (OR, 1.76; 95% CI, 1.30-2.38) and NRXN1rs1356888 associated with prior COPD complicated with lung cancer (OR, 1.73; 95% CI, 1.29-2.33).
Different long-term survival and genomic variants were observed between lung cancer patients with incidental and with prior COPD, suggesting timing of COPD diagnosis should be considered in lung cancer clinical management and mechanistic research.
Different long-term survival and genomic variants were observed between lung cancer patients with incidental and with prior COPD, suggesting timing of COPD diagnosis should be considered in lung cancer clinical management and mechanistic research.
Liquid biopsy allows the identification of targetable cancer mutations in a minimally invasive manner. In patients with advanced non-small cell lung cancer (NSCLC), droplet digital PCR (ddPCR) is increasingly used to genotype the epidermal growth factor receptor (
) gene in circulating cell-free DNA (cfDNA). DUB inhibitor However, the sensitivity of this method is still under debate. The aim of this study was to implement and assess the performance of a ddPCR assay for detecting the
T790M mutation in liquid biopsies.
A ddPCR assay was optimized to detect the
T790M mutation in plasma samples from 77 patients with NSCLC in progression.
Our ddPCR assay enabled the detection and quantification of the
T790M mutation at cfDNA allele frequency as low as 0.5%. The mutation was detected in 40 plasma samples, corresponding to a positivity rate of 52%. The number of mutant molecules per mL of plasma ranged from 1 to 6,000. A re-biopsy was analyzed for 12 patients that had a negative plasma test and the mutation was detected in 2 cases. A second liquid biopsy was performed for 6 patients and the mutation was detected in 3 cases.
This study highlights the value of ddPCR to detect and quantify the
T790M mutation in liquid biopsies in a real-world clinical setting. Our results suggest that repeated ddPCR tests in cfDNA may obviate tissue re-biopsy in patients unable to provide a tumor tissue sample suitable for molecular analysis.
This study highlights the value of ddPCR to detect and quantify the EGFR T790M mutation in liquid biopsies in a real-world clinical setting. Our results suggest that repeated ddPCR tests in cfDNA may obviate tissue re-biopsy in patients unable to provide a tumor tissue sample suitable for molecular analysis.The effects of exposure to the environmental toxicant cadmium, in combination with obesity, on the metal content in mouse testis were evaluated. Starting in utero and continuing through to 10 or 24 weeks post-weaning, male mice were exposed to cadmium (0, 0.5 or 5 ppm), and fed either a low (LFD) or high fat diet (HFD) post-weaning. Testicular levels of cadmium and essential metals were determined 10 and 24 weeks post-weaning by ICP-MS. Similar to what has been previously observed in the liver, kidney, heart and brain, significant levels of cadmium accumulated in the testis under all exposure conditions. Additionally, HFD-fed animals accumulated more cadmium than did their LFD-treated counterparts. Both treatments affected essential metal homeostasis in the testis. These findings suggest that cadmium and obesity may compromise the reproductive potential in the male mouse by disrupting essential metal levels.Fish is a rich source of proteins for humans and is widely consumed in various places in the world. This study assessed the levels of twenty trace metals (B, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Sn, Sb, Ba, Hg and Pb) in fish feeds (n = 2), water (n = 27), and edible muscles of Oreochromis mossambicus (n = 20 from 8 ponds) from fish farms and Luvuvhu River (n = 3 from 1 river site) in Vhembe district of Limpopo Province, South Africa. Physicochemical parameters of water in the study area were analysed. Temperature ranged between 21.4-30.47 °C, pH 5.59-7.28, electrical conductivity 608-1216 μS/cm, total dissolved solids 156-675 mg/l, dissolved oxygen 0.28 - 0.56 mg/l, turbidity 3.92-356.7 NTU, respectively. Levels of most trace metals such as Cr (2 μg/l and 1000 μg/kg), Mn (100 μg/l and 500 μg/kg), Fe (10 μg/l and 300 μg/kg), Ni (20 μg/l and 100 μg/kg), As (50 μg/l and 3 μg/kg), Pb (10 μg/l and 300 μg/kg) and Cu (2 μg/l and 2250 μg/kg) in water and O. mossambicus muscles were mostly below the World Health Organization (WHO), Food and Agricultural Organization (FAO)/WHO and European Commission (EC) recommended limit in the collected samples (Tshifulalani site and Duthuni site).
Read More: https://www.selleckchem.com/products/gsk2643943a.html
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