Combination effect of poly (ADP-ribose) polymerase inhibitor and DNA demethylating agents for treatment of epithelial ovarian cancer.

OBJECTIVE: Poly (ADP)-ribose polymerase inhibitors (PARPi) are effective clinical agents for treatment of epithelial ovarian cancer (EOC) harboring BRCA mutations as well as those without BRCA mutations. In this study, we evaluate the efficacy of combined PARPi and DNA methyltransferase inhibitor (DNMTi) in EOCs. METHODS: Expression levels of DNMT1 and PARP1 proteins in EOC cells were assessed using western blot analysis and immunohistochemistry. To evaluate the effects of co-treatment of PARPi (olaparib) and DNMTi (5-azacitidine, 5-AZA), we performed cell proliferation, apoptosis, and wound-healing assays in EOC cells. In addition, we performed in vivo experiments using both cell-line and patient-derived xenograft (PDX) models of EOC. RESULTS: The combination of olaparib and 5-AZA significantly inhibited cell proliferation and migration and induced apoptosis compared with olaparib or 5-AZA alone in EOC cell lines including A2780, HeyA8, A2780-CP20, and HeyA8-MDR. Moreover, in vivo experiments with this combination showed significantly decreased weight and nodule numbers of tumors in cell-line xenograft models with A2780 cells and a PDX model compared with control, olaparib, and 5-AZA groups. As a potential mechanism, the expression of intracellular reactive oxygen species (ROS) and its related proteins, including p-ERK, NRF2, p-p38, HO-1, and γH2AX, was affected in EOC cells. CONCLUSIONS: Co-treatment with PARPi and DNMTi had a significant anti-tumor effect in EOC cells. This combination might be a potential therapeutic strategy for EOCs.

Changes in Ulnar Variance after a Triangular Fibrocartilage Complex Tear.

Purpose The relationship between triangular fibrocartilage complex (TFCC) tear and ulnar impaction syndrome has not been fully understood. We hypothesized that a TFCC tear could change the ulnar variance, which may be the cause of ulnar impaction syndrome. Patients and Methods A total of 72 patients who underwent TFCC foveal repair between January 2011 and June 2016 were included in this retrospective study. Among them, 44 patients diagnosed with TFCC foveal tear with distal radioulnar joint instability and no ulnar impaction syndrome underwent TFCC foveal repair only (group A) and 28 patients diagnosed with TFCC foveal tear with ulnar impaction syndrome underwent TFCC foveal repair and ulnar shortening osteotomy simultaneously (group B). We measured their ulnar variances in preoperative, postoperative, and last follow-up plain radiography. We also compared them with the ulnar variance of the contralateral (uninjured) wrist. Postoperative clinical outcomes, such as range of motions of the wrist, the visual analog scale (VAS) for pain, grip strength, and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, were assessed. Results Ulnar variance increased after TFCC tears compared with that on the uninjured side in both groups (group A: 0.98 vs. 0.52 mm, p = 0.013; group B: 2.71 vs. 2.13 mm, p = 0.001). Once the TFCC was repaired, ulnar variance decreased (group A: 0.98 to 0.01 mm, p < 0.01; group B: 2.71 to 0.64 mm, p < 0.01). However, it was increased on the last follow-up radiograph (group A: 0.01 to 0.81 mm, p < 0.01; group B: 0.64 to 1.05 mm, p = 0.004). There were no significant improvement of range of motion, except for pronation-supination motion ( p = 0.04). Mean grip strength increased from 56.8 to 70.8% of the contralateral unaffected hand at the last assessment ( p = 0.01). Mean VAS for pain decreased from 7.4 ± 2.5 preoperatively to 2.7 ± 2 postoperatively ( p = 0.001). The QuickDASH score significantly improved from 45 to 9 ( p = 0.001). Conclusion Ulnar variance may be changed after a TFCC tear. In our study, it decreased after TFCC foveal repair. However, as time went on, the ulnar variance increased again, which could be one of the causes of ulnar impaction syndrome and ulnar-sided wrist pain. Level of Evidence This is a therapeutic Level IV study.

Repair of a radial tear in the posterior horn of the lateral meniscus.

BACKGROUND: There have been no studies evaluating the clinical results after repair of a radial tear in the posterior horn of the lateral meniscus (PHLM) using the FasT-Fix system. This study was undertaken to evaluate the clinical outcomes after repair of a radial tear in the PHLM using the FasT-Fix system in conjunction with anterior cruciate ligament (ACL) reconstruction. METHODS: Between September 2008 and August 2011, 15 radial tears in the PHLM identified during 132 consecutive ACL reconstructions were repaired using the FasT-Fix meniscal repair system. We classified the radial tears into three types according to the tear patterns: simple radial tear, complex radial tear, and radial tear involving the popliteal hiatus. Postoperative evaluation was performed using the Lysholm knee score and Tegner activity level. Second-look arthroscopy was performed in all cases. RESULTS: The mean follow-up period was 24 months. None of the patients had a history of recurrent effusion, joint line tenderness or a positive McMurray test. The meniscal repair was considered to have a 100% clinical success rate. At the final follow-up, the Lysholm knee score and Tegner activity level were significantly improved compared to the preoperative values. On the second-look arthroscopy, repair of radial tears in the PHLM in conjunction with ACL reconstruction using the FasT-Fix device resulted in complete or partial healing in 86.6% of cases. CONCLUSION: Clinical results after meniscal repair of a radial tear in the PHLM by using the FasT-Fix system were satisfactory. LEVEL OF EVIDENCE: Case series, Level IV.