Emerging evidence has shown that the therapy-induced senescent growth arrest in cancer cells is of durable nature whereby a subset of cells can reinstate proliferative capacity. Promising new drugs named senolytics selectively target senescent cells and commit them into apoptosis. Accordingly, senolytics have been proposed as adjuvant cancer treatment to cull senescent tumor cells, and thus, screening for agents that exhibit senolytic properties is highly warranted. Our study aimed to investigate three agents, sorafenib, rapamycin, and venetoclax for their senolytic potential in doxorubicin-induced senescence in HCT116 cells. HCT116 cells were treated with one of the three agents, sorafenib (5 µM), rapamycin (100 nM), or venetoclax (10 µM), in the absence or presence of doxorubicin (1 µM). Senescence was evaluated using microscopy-based and flow cytometry-based Senescence-associated-β-galactosidase staining (SA-β-gal), while apoptosis was assessed using annexin V-FITC/PI, and Muse caspase-3/-7 activity assays. We screened for potential genes through which the three drugs exerted senolytic-like action using the Human Cancer Pathway Finder PCR array. The three agents reduced doxorubicin-induced senescent cell subpopulations and significantly enhanced the apoptotic effect of doxorubicin compared with those treated only with doxorubicin. The senescence genes IGFBP5 and BMI1 and the apoptosis genes CASP7 and CASP9 emerged as candidate genes through which the three drugs exhibited senolytic-like properties. These results suggest that the attenuation of doxorubicin-induced senescence might have shifted HCT116 cells to apoptosis by exposure to the tested pharmacological agents. Our work argues for the use of senolytics to reduce senescence-mediated resistance in tumor cells and to enhance chemotherapy efficacy. 相似文献
Central illustration: cumulative major adverse cardiac events (MACE) and bioresorbable vascular scaffold (BVS) thrombosis rates after 1, 2, 3, 4 and 5 years.相似文献
PurposeTo retrospectively evaluate the safety and effectiveness of the Covera stent graft (SG) for the treatment of dysfunctional or thrombosed arteriovenous grafts (AVGs).Materials and MethodsWithin 29 months (February 2016–August 2018), 79 patients underwent Covera SG placement in the authors’ department for the treatment of dysfunctional AVGs. Data were available for 64 patients who underwent 64 procedures, using 64 devices. Minimum follow-up was 6 months, unless reintervention occurred. Mean follow-up was 277 days (6–923 days). Treatment characteristics were 51 cases with venous-graft anastomosis (VGA) stenosis (79.7%), 13 cases of puncture zone stenosis (20.3%), 14 cases of in SG stenosis (21.9%), 8 cases of pseudoaneurysm treatment (12.5%) (1 treatment area might have had more than 1 characteristic). Thirty-six patients presented with thrombosis (56.2%), and 31 of 64 case were de novo treatment areas (48.4%). Primary outcome measurements were technical success and post-intervention primary patency (PIPP) at 6 months, whereas secondary outcome measurements included factors influencing primary outcome.ResultsTechnical success was 100%. Median PIPP was 336 days, and 73.6% of treatment areas were patent at 6 months. There were no significant differences in terms of PIPP when de novo treatment areas were compared with restenotic areas (519 vs. 320 days, respectively; P = .1); patients who presented with versus those who presented without thrombosis (320 vs. 583 days, respectively; P = .07); puncture zone stenosis or elsewhere (329 vs. 686 days, respectively; P = .52); and VGA stenosis or elsewhere (336 vs. 335 days, respectively; P = .9).ConclusionsUse of the Covera SG for AVG treatment was safe and effective in every type of treatment area presented in this retrospective analysis. 相似文献
Summary A new modification of microvenous anastomosis, which has increased patency rates while simultaneously decreasing the difficulty of the procedure, is presented in this paper. The primary purpose of this study was to compare the classical and the temporary stent techniques of microvenous anastomosis. Because of problems such as mixing and tangling of strings during insertion and tying of the last four sutures while applying the temporary stent technique, we decided to modify the procedure. The silastic tube was removed through an incision (venotomy), distant from the actual suture line. This modified technique and the other above mentioned techniques were carried out on rat femoral veins. The results indicate that this modification has increased patency rates, shortened the time of anastomosis and facilitated the procedure. 相似文献