Since the early CL (< or = 4 days after ovulation) does not regress after injection of PGF2 alpha, this study was designed to determine whether number or affinity of PGF2 alpha receptors was lower in the early as compared with the midstage CL. Heifers were randomly assigned to have ovaries removed on Day 2, 4, 6, or 10 (n = 4 heifers per day; Day 0 = day of ovulation). Plasma progesterone concentrations and the weight and size of the CL increased from Day 2 to 6, indicating normal CL development. Plasma membranes from individual CL were evaluated for PGF2 alpha receptor concentration and affinity by Scatchard analysis. CL from each of the 4 days of the estrous cycle were not different with respect to PGF2 alpha receptor concentration (number per microgram of plasma membrane protein) and affinity. To examine tissue specificity, PGF2 alpha binding was evaluated in 12 organs or tissues. High-affinity PGF2 alpha receptors were found in the CL and adrenal medulla but not in granulosa cells or other tissues. In conclusion, a single class of high-affinity PGF2 alpha receptors was present within the bovine CL by 2 days after ovulation; therefore the reported lack of responsiveness to PGF2 alpha in the early CL was not attributable to a deficiency of high-affinity PGF2 alpha receptors.
Whether ICIs combined with chemotherapy can improve outcomes in EGFR-mutant non-small cell lung cancer (NSCLC) remains uncertain. Patients with EGFR-mutant NSCLC and who progressed on first-line EGFR-TKIs treatment were retrospectively collected. We reviewed the outcome of these patients treated with ICIs or ICIs combined chemotherapy (ICI + C). Total 30 patients were included. The ORR were 9.1% and 25.0% for the ICI and ICI + C groups. The ICI + C group showed the trend of longer progression-free survival and overall survival periods. Patients without the T790M mutation had a significantly longer PFS than did those without this mutation (4.23 [95% CI: 2.75–5.72] vs. 1.70 [95% CI: 0.00–3.51] months, HR:4.45, p = 0.019). ICIs combined with chemotherapy tended to be more effective than ICIs alone in pretreated EGFR-mutant NSCLC. The T790M mutation may be a potential biomarker.
Detection of driver gene mutations is important in advanced NSCLC. The cobas EGFR mutation test is a mutant allele-specific real-time PCR assay with limitation owing to its primer design. Next-generation sequencing-based assay has a higher mutation detection coverage; however, its clinical impact remains unclear. We retrospectively collected the records of stage IV NSCLC patients with wild-type EGFR tested by cobas test. FoundationOne CDx was used for comprehensive genomic profiles. We then evaluated the missed EGFR mutations by the cobas test. We studied 62 patients. The median age was 60 (range: 35–86 years). Most patients were male and 58.1% were smokers. 91.9% were adenocarcinomas. Of the 62 samples, 7 (11.3%) were detected with EGFR mutations by NGS. Among these overlooked EGFR mutations, five were exon 20 insertions, and two were exon 19 deletions. Two patients received EGFR TKIs and showed durable response with PFS 5.9 months and 10.1 months, respectively. Using NGS as the standard, the false-negative rate of the cobas EGFR mutation test was 11.3%—in a population with a high prevalence of EGFR mutations. The most overlooked mutations were exon 20 insertions. A comprehensive EGFR mutation assay can provide significant benefits to patients with NSCLC.
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