Search

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX&ndash, TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 &mu, M of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.

Background: Patients undergoing kidney transplantation (KT) often receive red blood cell (RBC) transfusion during admission for KT which may increase the risk of allosensitization. The association between peri-transplant RBC transfusion and graft survival was evaluated using a nationwide cohort. Methods: This retrospective study analyzed 13,871 patients who underwent KT in Korea between 2007 and 2015. The outcomes were graft failure rate and overall patient survival depending on the amount of RBC transfusion. Results: The overall graft failure rate was 15.5%. Compared to the graft failure rate of 13.5% in the no transfusion group, the graft failure rate was 15.4% in the 1–2 units group (sHR 1.06 (95% CI 0.97–1.17), p = 0.216), 21.4% in the 3–5 units group (sHR 1.39 (1.21–1.61), p &lt, 0.001), and 35.3% in the 6 or more units group (sHR 2.20 (1.70–2.85), p &lt, 0.001). The overall survival rate was 97.5% in the no transfusion group, compared to 95.9% in the 1–2 units group (HR 1.50 (1.22–1.83), p &lt, 0.001), 92.0% in the 3–5 units group (HR 2.43 (1.87–3.15), p &lt, 0.001), and 67.5% in the 6 or more units group (HR 6.81 (5.03–9.22), p &lt, 0.001). Conclusions: Peri-transplant RBC transfusion was independently associated with the increased risk of renal allograft failure and death in KT patients.

In this study, we synthesized a Zr-89-labeled anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) for applications in immuno-positron emission tomography (PET) and evaluated its feasibility for angiogenesis imaging. The cellular uptake of Zr-89 ATPS mAb was measured after treatment of cancer cell lines in vitro, and its biodistribution was evaluated at 4, 24 and 48 h in vivo in mice bearing xenografts. PET images were acquired at 4, 24, 48, and 96 h after Zr-89 ATPS mAb administration. Tumor angiogenesis was analyzed using anti-CD31 immunofluorescence staining. The cellular uptake of Zr-89 ATPS mAb increased over time in MDA-MB-231 breast cancer cells but did not increase in PC3 prostate cancer cells. The tumor uptake of Zr-89 ATPS mAb at 24 h was 9.4 &plusmn, 0.9% ID/g for MDA-Mb-231 cells and was 3.8 &plusmn, 0.6% ID/g for PC3 cells (p = 0.004). Zr-89 ATPS mAb uptake in MDA-MB-231 xenografts was inhibited by the administration of cold ATPS mAb (4.4 &plusmn, 0.5% ID/g, p = 0.011). Zr-89 ATPS mAb uptake could be visualized by PET for up to 96 h in MDA-MB-231 tumors. In contrast, there was no distinct tumor uptake detected by PET in the PC3 xenograft model. CD31-positive tumor vessels were abundant in MDA-MB-231 tumors, whereas they were scarcely detected in PC3 tumors. In conclusion, ATPS mAb was successfully labeled with Zr-89, which could be used for immuno-PET imaging targeting tumor angiogenesis.