Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/ß-catenin signaling pathways.

ERα and Wnt/ß-catenin pathways are critical for the progression of most endometrial cancers. We aimed to investigate the cytotoxic and apoptotic effects of tamoxifen and quinazoline derivative drugs of doxazosin and erlotinib, and their roles in ERα and Wnt/ß-catenin signaling pathways in human endometrial cancer RL 95-2 cell. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay and xCELLigence systems were performed to evaluate cytotoxicity. Furthermore, apoptotic induction was tested by Annexin V analysis. Caspase-3 and -9 activity and changes in the mitochondrial membrane potential were evaluated. The level of reactive oxygen species was measured by incubating with dichlorofluorescein diacetate. Protein ratios of p-ERα/ERα, GSK3ß/p-GSK3ß, and p-ß-catenin/ß-catenin and expression levels of ESR1, EGFR, c-Myc genes were evaluated to elucidate mechanisms in signaling pathways. We found that the tested drugs showed cytotoxic and apoptotic effects in the cells. Doxazosin significantly reduced ESR1 expression, slightly reduced the p-ß-catenin/ß-catenin ratio and c-Myc expression. Erlotinib significantly increased c-Myc expression while significantly decreasing the p-ß-catenin/ß-catenin and p-ERα/ERα ratio, and ESR1 expression. However, we observed that the cells develop resistance to erlotinib over a certain concentration, suggesting that ERα, ESR1, EGFR, and c-Myc may be a new target for overcoming drug resistance in the treatment of endometrial cancer. We also observed that erlotinib and doxazosin play an important role in the ERα signaling pathway and can act as potent inhibitors of PKA and/or tyrosine kinase in the Wnt/ß-catenin signaling pathway in RL 95-2 cell. In conclusion, doxazosin and erlotinib may have a possible therapeutic potential in human endometrial cancer.

Treatment of Aphthous Ulcers with Photodynamic Therapy: A Randomized Controlled Clinical Study.

BACKGROUND: This study aims to assess whether photodynamic therapy (PDT) offers a clinically effective alternative for treating oral aphthous ulcers, contributing to the ongoing quest for methods to expedite their treatment process amidst the limited understanding of their etiology. MATERIALS AND METHOD: The study involved thirty volunteers with aphthous ulcers, split equally between a control group and a PDT group. Patients in the PDT group received laser treatment using Indocyanine green upon admission, while the control group received no intervention. Lesion diameter was measured at presentation and on the 3rd, 5th, and 7th days for all patients, with wound healing assessed on the 7th day. Additionally, pain levels were evaluated using the Visual Analog Scale (VAS) preoperatively and on the 1st, 3rd, 5th, and 7th days for the PDT group, and on the corresponding days for the control group. RESULTS: Lesion diameters in the PDT group showed a significant reduction over time (p=0.001), particularly from preoperative to final measurements. The control group also exhibited a decrease, albeit slower (p=0.001). The 7th-day healing scores favored the PDT group significantly (p=0.012). VAS scores in the PDT group decreased significantly over time (p=0.001), indicating pain reduction. A similar trend was observed in the control group, albeit slower. Between-group differences in healing data and pain data were statistically significant. CONCLUSION: PDT proves effective in reducing aphthous ulcer diameters and pain intensity, facilitating faster healing than the control group. These results advocate for PDT as a viable treatment option for aphthous lesions.

Higher Complications During the Waiting Period for Interval Cholecystectomy in Patients With Mild Biliary Pancreatitis.

BACKGROUND: Although current guidelines recommend cholecystectomy during the same admission in patients with mild acute biliary pancreatitis (ABP), it involves a waiting list most of the time. We aimed to assess the risk of complications and determine predictors during the waiting period for cholecystectomy after the first episode of ABP. METHODS: A prospective observational study was conducted in patients with mild ABP. Follow-ups were done by phone calls or using electronic health records for a maximum of 6 months after discharge or until cholecystectomy. RESULTS: A total of 194 patients were included in the study. Although all patients were referred to surgeons, only 81 (41.8%) underwent cholecystectomy within 6 months after discharge. During the observation period, gallstone-related biliary events (GRBEs) developed in 68 (35.1%) patients, which included biliary colic, recurrent ABP, acute cholecystitis, choledocholithiasis, gallbladder perforation, cholangitis, and liver abscess. The overall readmission rate was 25.2%, with 44.8% occurred within 4 weeks after discharge. The odds ratio of any complication was 1.58 (95% CI, 1.42 to 1.76, P =0.028) and 1.59 (95% CI, 1.42 to 1.78, P =0.009) in the patients who did not have surgery within 2 to 7 days and 8 to 15 days, respectively. A 4-fold increased risk of readmission was detected (95% CI, 1.16 to 13.70, P =0.019) if cholecystectomy was not performed within 31 to 90 days. The patients who developed complications had significantly higher C-reactive protein at admission, longer waiting time, and had 3 or more gallstones on imaging. CONCLUSIONS: Interval cholecystectomy was associated with a high risk of complications during the waiting period in patients with mild ABP.