We tested the hypotheses that the secretion of dimeric inhibin-A from cultured bovine granulosa cells is stimulated by FSH, and that antral cells secrete more inhibin-A than do mural cells. Cells from the antral or mural compartment of follicles were cultured in defined medium in two culture systems, and dimeric inhibin-A was measured by two-site ELISA or by Western immunoblotting. In the first culture system, dimeric inhibin-A secretion declined with time in culture, but was significantly (P<0·05) higher from antral than from mural cells (as was total inhibin-measured by RIA). The secretion of dimeric inhibin-A and inhibin-from antral but not mural cells was responsive to FSH. In the second culture system, dimeric inhibin-A secretion increased with time in culture, and was significantly stimulated by FSH, but FSH responsiveness was dependent on the concentrations of insulin in the culture medium. The major forms of inhibin-A secreted had molecular masses of approximately 58, 62, 103-116 and >116 kDa; the 32 kDa form was barely detectable. These different forms were all stimulated by FSH, but the >116 and 62 kDa forms were most responsive to FSH. We conclude that (i) FSH stimulates dimeric inhibin-A secretion from bovine granulosa cells, (ii) the 62 kDa form of inhibin-A may be more responsive to FSH than the 58 kDa form, and (iii) the spatial differentiation of granulosa cell function within the follicle previously observed for oestradiol secretion was also observed for inhibin-and dimeric inhibin-A secretion.
qd) þ atezolizumab (1200 mg infusion q3w), a control arm of sorafenib (400 mg bid), and an exploratory arm of cabozantinib monotherapy (60 mg qd). 640 patients are planned at $200 sites globally. Randomization is stratified by disease etiology (HBV [with or without HCV], HCV [without HBV], or other), region (Asia, other), and the presence of extrahepatic disease and/or macrovascular invasion (yes, no). OS and progression-free survival are co-primary endpoints and objective response rate is a secondary endpoint. Additional endpoints include safety, pharmacokinetics, and correlation of biomarker analyses with clinical outcomes. Enrollment in COSMIC-312 is ongoing.
Prospective study of pancreatic cancer patients undergoing neoadjuvant or palliative therapy with FOLFIRINOX (5 fluorouracil, oxaliplatin, irinotecan) and colorectal cancer patients under FOLFOX (5 fluorouracil, oxaliplatin) or FOLFIRI (5 fluorouracil, irinotecan) who developed OM grade 2 or 2-3 with the previous cycle. We used the same combination with a higher dose of Prednisolone and Nystatin before considering any CM dose reduction (DR). It consisted of 100 mL of water combined with 30 mg of soluble prednisolone, 6 drops of nystatin and 2.300 mg of salt (1 teaspoon). Patients were educated clearly on how to use it. Primary end-point was the incidence of OM grade 2-3 with the following cycle and secondary end-points were rate of CM DR and the incidence of OM grade 0, 1 and 2 with the next cycle. Results: Thirty-five patients were included. 21 had developed OM grade 2-3 with prior cycle and 14 grade 2. After using this mouthwash, no cases developed grade 2-3 OM and none needed a DR due to OM. Ten patients developed OM grade 2 which recovered quickly to grade 1. Sixteen patients grade 1 OM and the rest no OM (grade 0). Conclusion:This study shows a significant reduction in the rate of OM grade 2-3 in patients using this mixture as mouthwash. Although further evaluation is needed to confirm its final benefits we use this as standard in our institution.
20 to 84 years, 85% (51) men, 91% (55) ps 0-1, 65% (39) smoking, 17% (10) had Barret's esophagus. The diagnosis was made with high videoendoscopy with biopsy in 100%, staging with PET/CT in 77% (46), 73% (44) had positive nodes and 48% (29) had siewert II location. 92% (55) of the tumors corresponded to adenocarcinomas and 35% (21) were tested for her2 of which 24% (5) were positive. The radiotherapy dose was 180 Gy with 41 Gy per session. 98% (59) completed radiotherapy, of which 96% did 3D radiotherapy and 4% (2) IMRT. 92% (55) received carboplatin 2 AUC and paclitaxel weekly. 58% (35) had toxicity, and of these, 51% (18) had hematological toxicity grade 1-2. The objective response rate was 78% (47), evaluated by pneumotomography, and 10% (6) patients progressed intra-treatment. Surgical compliance was 72% (43), 67% (29) underwent esophagectomy. 14% (6) had a complete pathological response in the post operative part, it was a subrogant of OS with HR 0.4 (CI 0.16 to 0.96) p ¼ 0.041. 22% (13) patients performed adjuvant, the majority of these with capecitabine, there were no significant differences in DFS or OS with the addition of adjuvant treatment. With a mean follow-up of 25 months, 19% (8) of the operated patients relapsed, with 50% systemic relapses. All relapsed patients received FOLFOX. 32% ( 16) died during follow-up with an OS of 18 months and a DFS of 16 months. Neutrophil/lymphocyte ratio greater than 3 at diagnosis was 45% ( 27) and a statistically significant association with mortality was observed (p¼0,034).Conclusion: Good surgical compliance was observed, with acceptable toxicity, and the objective response rate was high. Adjuvant treatment offered no benefit in OS or DFS. The complete pathological response was a surrogate for survival. Neutrophil/ lymphocyte ratio at diagnosis was associated with mortality. The results in our center were similar to those of the CROSS study.Legal entity responsible for the study: The author.
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