Phase II study of oral platinum drug JM216 as first-line treatment in patients with small-cell long cancer

Purpose: This multicenter phase II trial wets performed to determine tumor efficacy and tolerance of the oral platinum drug JM216 in patients with small-cell lung cancer (SCLC). Patients and Methods: patients with SCLC limited disease unfit for intensive chemotherapy or those with extensive disease received JM216 120 mg/m(2)/d for 5 consecutive days every 3 weeks, Individual dose escalation to 140 mg/m(2)/d was allowed if toxicity was less than or equal to grade 2 according to the National Cancer Institute Common Toxicity Criteria, tumor response was evaluated according to World Health Organization criteria, Results: Twenty-seven patients were assessable for toxicity and 26 for tumor response, Eighty-eight cycles were administered. Common Toxicity Criteria grade 3 and 4 hematologic toxicities were neutropenia in 15.9% and 3.7%, lymphocytopenia in 47.6% and 17.1%, and thrombocytopenia in 19.5% and 10.3% of cycles, respectively. One patient suffered from neutropenic fever Nausea, vomiting, and diarrhea were the most common nonhematologic toxicities. Except For grade 4 diarrhea in one patient, no grade 4 nonhematologic toxicity was observed, No severe neurotoxicity or nephrotoxicity was observed, Tumor response rate was 10 of 26 (38%; 95% confidence interval, 19% to 58%), excluding five unconfirmed partial responses. No complete responses were observed. Median overall time to progression was 110 days (range, 5 to 624 days), Median overall survival time was 210 days (range, 5 to 624 days), Conclusion: Oral JM216 is active in previously untreated patients with SCLC and shows mild toxicities, J Clin Oncol 17:3822-3827, (C) 1999 by American Society of Clinical Oncology

Acute cigarette smoke-induced eQTL affects formyl peptide receptor expression and lung function.

BACKGROUND AND OBJECTIVE:Cigarette smoking is one of the most prevalent causes of preventable deaths worldwide, leading to chronic diseases, including chronic obstructive pulmonary disease (COPD). Cigarette smoke is known to induce significant transcriptional modifications throughout the respiratory tract. However, it is largely unknown how genetic profiles influence the smoking-related transcriptional changes and how changes in gene expression translate into altered alveolar epithelial repair responses. METHODS:We performed a candidate-based acute cigarette smoke-induced eQTL study, investigating the association between SNP and differential gene expression of FPR family members in bronchial epithelial cells isolated 24 h after smoking and after 48 h without smoking. The effects FPR1 on lung epithelial integrity and repair upon damage in the presence and absence of cigarette smoke were studied in CRISPR-Cas9-generated lung epithelial knockout cells. RESULTS:One significant (FDR 2-fold change in gene expression. The minor allele of rs3212855 was associated with significantly higher gene expression of FPR1, FPR2 and FPR3 upon smoking. Importantly, the minor allele of rs3212855 was also associated with lower lung function. Alveolar epithelial FPR1 knockout cells were protected against CSE-induced reduction in repair capacity upon wounding. CONCLUSION:We identified a novel smoking-related inducible eQTL that is associated with a smoke-induced increase in the expression of FPR1, FPR2 and FPR3, and with lowered lung function. in vitro FPR1 down-regulation protects against smoke-induced reduction in lung epithelial repair

ModFetch: A modular system for automating queries to relational databases

Computer Science