Characteristics and prognosis of EGFR mutations in small cell lung cancer patients in the NGS era.

PURPOSE: Targeted therapy has not been effective for small cell lung cancer (SCLC) patients. Although some studies have reported on EGFR mutations in SCLC, a systematic investigation into the clinical, immunohistochemical, and molecular characteristics and prognosis of EGFR-mutated SCLCs is lacking. METHODS: Fifty-seven SCLC patients underwent next-generation sequencing technology, with 11 in having EGFR mutations (group A) and 46 without (group B). Immunohistochemistry markers were assessed, and the clinical features and first-line treatment outcomes of both groups were analyzed. RESULTS: Group A consisted primarily of non-smokers (63.6%), females (54.5%), and peripheral-type tumors (54.5%), while group B mainly comprised heavy smokers (71.7%), males (84.8%), and central-type tumors (67.4%). Both groups showed similar immunohistochemistry results and had RB1 and TP53 mutations. When treated with tyrosine kinase inhibitors (TKIs) plus chemotherapy, group A had a higher treatment response rate with overall response and disease control rates of 80% and 100%, respectively, compared to 57.1% and 100% in group B. Group A also had a significantly longer median progression-free survival (8.20 months, 95% CI 6.91-9.49 months) than group B (2.97 months, 95% CI 2.79-3.15), with a significant difference (P = 0.043). Additionally, the median overall survival was significantly longer in group A (16.70 months, 95% CI 1.20-32.21) than in group B (7.37 months, 95% CI 3.85-10.89) (P = 0.016). CONCLUSION: EGFR-mutated SCLCs occurred more frequently in non-smoking females and were linked to prolonged survival, implying a positive prognostic impact. These SCLCs shared immunohistochemical similarities with conventional SCLCs, and both types had prevalent RB1 and TP53 mutations.

Oxidative damage and exocrine dysfunction of ovine fetal pancreas are induced by maternal nutritional restriction

This study investigated oxidative damage and exocrine dysfunction of fetal pancreas caused by maternal nutritional restriction. Eighteen ewes carrying singleton fetus were randomly divided into control group (CG, ad libitum, 0.67 MJ ME/BW0.75/d, n = 6), restricted group 1 (RG1, 0.33 MJ ME/BW0.75/d, n = 6), and restricted group 2 (RG2, 0.18 MJ ME/BW0.75/d, n = 6) at d 90 of pregnancy. Maternal undernutrition was imposed from d 90 to 140 of pregnancy. At 140 d of gestation, fetal blood and pancreas tissue were collected to determine fetal pancreatic extracellular matrix, antioxidant capacity, and indicators of exocrine dysfunction. With the decrease of maternal nutrition, the fetal body weight, pancreatic weight, and DNA content were reduced in RG2 compared with CG, and increased and thickened collagen fibers were observed in RG2. Fetuses in RG2 exhibited increased collagen 3 (COL3) and fibronectin (FN) levels relative to CG, and the COL1:COL3 ratio was lower than that of the CG. For RG1, we found increased COL3 compared with CG. Malondialdehyde, serum amylase, and serum lipase in fetal pancreas in RG2 increased, but the total antioxidant capacity (T-AOC) decreased compared with the CG. The impaired ovine fetal pancreas growth, antioxidant imbalance, and pancreatic exocrine dysfunction are induced by maternal undernutrition during late pregnancy.