ABSTRACT
OBJECTIVE: Transvaginal mesh surgery for pelvic organ prolapse has been widely performed in Japan, but polypropylene mesh has not been used in Japan since the ban on TVM using polypropylene mesh in the United States. Currently, polytetrafluoroethylene mesh ORIHIME® is the only mesh available for TVM in Japan. Although polytetrafluoroethylene is a safe material, its low coefficient of friction and insufficient adhesion to the surrounding tissue make it difficult to maintain the mesh position when it is used in the transvaginal mesh surgery. The aim of this study was to evaluate the feasibility of TVM-A2 using ORIHIME®. METHODS: One hundred cases of TVM-A2 were included in the study. The patients were randomly assigned to two groups: the ORIHIME® group (Group O) and the PolyformTM group (Group P). With 50 patients in each group, the complications and recurrences up to the fourth year were compared. Surgeries were performed using the TVM-A2 method. Statistical analysis was performed using EZR. RESULTS: There were no significant differences in baseline parameters between the two groups. We observed no perioperative complications, and saw one case of postoperative abscess formation in Group O, which resolved successfully after incision and drainage. The 4-year recurrence rate was significantly higher in Group O. CONCLUSION: As the recurrence rate was significantly higher in Group O, we conclude that TVM-A2 using ORIHIME® which is the same procedure as TVM-A2 using polypropylene mesh is not feasible in repairing the pelvic organ prolapse.
ABSTRACT
BACKGROUND: We investigated the unknown mechanisms of osimertinib-resistant EGFR-mutant lung cancer. METHODS: An osimertinib-resistant cell line (PC-9/OsmR2) was established through continuous exposure to osimertinib using an EGFR exon 19 deletion (19Del) lung adenocarcinoma cell line (PC-9). EGFR 19Del (M1), L858R/T790M/C797S (M6), and L858R/C797S (M8) expression vectors were introduced into Ba/F3 cells. A second osimertinib-resistant line (M1/OsmR) was established through continuous exposure to osimertinib using M1 cells. RESULTS: SLC1A3 had the highest mRNA expression level in PC-9/OsmR2 compared to PC-9 cells by microarray analysis and SLC1A3 was increased by flow cytometry. In PC-9/OsmR2 cells, osimertinib sensitivity was significantly increased in combination with siSLC1A3. Because SLC1A3 functions in glutamic acid transport, osimertinib with a glutaminase inhibitor (CB-839) or an SLC1A3 inhibitor (TFB-TBOA) increased the sensitivity. Also, CB-839 plus TFB-TBOA without osimertinib resulted in greater susceptibility than did CB-839 or TFB-TBOA plus osimertinib. Comprehensive metabolome analysis showed that the M1/OsmR cells had significantly more glutamine and glutamic acid than M1 cells. CB-839 plus osimertinib exerted a synergistic effect on M6 cells and an additive effect on M8 cells. CONCLUSION: Targeting glutaminase and glutamic acid may overcome the osimertinib-resistant EGFR-mutant lung cancer.