A modified GnRH antagonist method in combination with letrozole, cabergoline, and GnRH antagonist for PCOS: Safe and effective ovarian stimulation to treat PCOS and prevent OHSS

Abstract Purpose To analyze the therapeutic efficacy of a modified controlled ovarian stimulation (COS) protocol for polycystic ovary syndrome (PCOS) that does not cause ovarian hyperstimulation syndrome (OHSS) while maintaining oocyte quality. Method This study is a retrospective cohort study of reproductive medicine at St. Mother Clinic. We analyzed ART clinical outcomes, embryonic development, and hormone levels in 175 PCOS patients treated with four COS (GnRH agonist based long protocol, Group A; GnRH antagonist protocol with HCG trigger, Group B; GnRH antagonist protocol with GnRH agonist trigger, Group C, and the modified COS group) between 2010 and 2021. Results Of 175 patients with PCOS, 45 and 130 patients underwent 47 and 136 oocyte retrieval cycles, 75 and 250 embryo transfer cycles with the modified COS, and with conventional methods, respectively. The cumulative pregnancy rate at one trial was a significantly higher result than in Group A and higher than in Groups B and C (cumulative pregnancy rate at one trial of Group A, B, C, and modified COS: 40.0%, 54.5%, 56.3%, and 72.3%, respectively). With this method, not clinically problematic OHSS and higher clinical outcomes than in conventional methods were observed. Conclusion This modified COS can significantly improve clinical outcomes and eliminate OHSS

Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8

The use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (PTE) on the human gastric cancer cell lines TMK1 and MKN74 was examined in in vitro and in vivo. Compared with SUN or PTE treatment alone, cotreatment induced pronounced suppression of cell proliferation, with a marked increase in oxidative stress. SUN was associated with a significant retention of mitochondrial Fe2+. SUN-treated cells decreased expression of PDZ domain-containing protein 8 (PDZD8). Knockdown of PDZD8 in both cells induced Fe2+ retention, and siPDZD8+PTE markedly suppressed cell proliferation with suppressed oxidative phosphorylation, as did the combination of SUN+PTE. In a nude mouse tumor model, a pronounced antitumor effect was observed with SUN+PTE treatment compared to SUN alone. PDZD8 may be a newly discovered off-target for SUN, and that the combined use of PTE with SUN significantly promotes antitumor activity in gastric cancer cell lines. The combined use of SUN and PTE might be a new molecular-targeted therapy for gastric cancer

Pterostilbene Induces Apoptosis from Endoplasmic Reticulum Stress Synergistically with Anticancer Drugs That Deposit Iron in Mitochondria

Anticancer agents are playing an increasing role in the treatment of gastric cancer (GC); however, novel anticancer agents have not been fully developed. Therefore, it is important to investigate compounds that improve sensitivity to the existing anticancer drugs. We have reported that pterostilbene (PTE), a plant stilbene, enhances the antitumor effect of low doses of sunitinib in gastric cancer cells accumulating mitochondrial iron (II) (mtFe) at low doses. In this study, we investigated the relationship between the mtFe deposition and the synergistic effect of PTE and different anticancer drugs. For this study, we used 5-fluorouracil (5FU), cisplatin (CPPD), and lapatinib (LAP), which are frequently used in the treatment of GC, and doxorubicin (DOX), which is known to deposit mtFe. A combination of low-dose PTE and these drugs suppressed the expression of PDZ domain-containing 8 (PDZD8) and increased mtFe accumulation and mitochondrial H2O2. Consequently, reactive oxygen species-associated hypoxia inducible factor-1α activation induced endoplasmic reticulum stress and led to apoptosis, but not ferroptosis. In contrast, 5FU and CDDP did not show the same changes as those observed with PTE and DOX or LAP, and there was no synergistic effect with PTE. These results indicate that the combination of PTE with iron-accumulating anticancer drugs exhibits a strong synergistic effect. These findings would help in developing novel therapeutic strategies for GC. However, further clinical investigations are required

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes