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Bladder carcinoma ( BC) is the ninth most common cause of cancer worldwide. Surgical resection and conventional chemotherapy and radiotherapy will ultimately fail due to tumor recurrence and resistance. Thus, the development of novel treatment is urgently needed. Fibroblast growth factor receptor 3 ( FGFR3) is an important and well-established target for BC treatment. In this study, we utilized the free and open-source protein-ligand docking software idock to prospectively identify potential inhibitors of FGFR3 from 3,167 worldwide approved small-molecule drugs using a repositioning strategy. Six high-scoring compounds were purchased and tested in vitro. Among them, the acaricide drug fluazuron exhibited the highest antiproliferative effect in human BC cell lines RT112 and RT4. We further demonstrated that fluazuron treatment significantly increased the percentage of apoptosis cells, and decreased the phosphorylation level of FGFR3 and its downstream proteins FRS2-α, AKT, and ERK. We also investigated the anticancer effect of fluazuron in vivo in BALB/C nude mice subcutaneously xenografted with RT112 cells. Our results showed that oral treatment with fluazuron (80 mg/kg) significantly inhibited tumor growth. These results suggested for the first time that fluazuron is a potential inhibitor of FGFR3 and a candidate anticancer drug for the treatment of BC. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to provide a potential surgical efficacy assessment in the treatment of pelvic organ prolapse (POP)., Methods: A retrospective cohort study was performed on magnetic resonance imaging (MRI) imaging data of 16 non-prolapsed (control group) and 30 preoperative and postoperative POP (case group) women from 2019 to 2021 at the First Affiliated Hospital of Kunming Medical University. MRI diagnoses and measures of the relevant anatomical points at rest were used to analyze the healthy control data and the data from POP women before and after surgery., Results: The middle vaginal-PICS line angle (78.12°±15.03° vs. 69.35°±11.51°, 78.12°±15.03° vs. 61.56°±9.58°, P<0.05) and the middle-lower vaginal angle (179.30°±12.96° vs. 161.73°±10.42°, 179.30°±12.96° vs. 147.01°±12.20°, P<0.05) in the preoperative group were significantly larger than those in the control and postoperative groups. Y-axis coordinates of the endocervical orifice (-52.39±15.63 vs. -59.04±11.49 mm, -52.39±15.63 vs. -65.27±7.25 mm, P<0.05), posterior vaginal fornix (-34.25±13.30 vs. -46.69±11.09 mm, -34.25±13.30 vs. -49.93±8.02 mm, P<0.05), the junction of the middle and lower vagina (-0.48±8.65 vs. -11.34±7.33 mm, -0.48±8.65 vs. -10.11±9.77 mm, P<0.05), and anterior vaginal fornix (-23.14±13.71 vs. -34.68±9.07 mm, -23.14±13.71 vs. -38.64±6.48 mm, P<0.05), as well as the x-axes of the junction of the middle and lower parts of the vagina (26.79±6.71 vs. 19.56±5.24, 26.79±6.71 vs. 17.67±5.81, P<0.05), and vaginal introitus (23.39±7.12 vs. 18.55±4.22, 23.39±7.12 vs. 19.00±4.55, P<0.05) in the preoperative group were smaller than those of the control and postoperative groups. Differences between the control and postoperative groups were not statistically significant (P>0.05)., Conclusions: The current study established that the uterine-vaginal axis of POP women moved backward and downward in the coordinate system, as shown on MRI sagittal images. Further, it moved forward and upwards after surgical repair and more closely resembled that of the control group. The uterine-vaginal axis may provide an evaluation of surgical efficacy in women with POP., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1173/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Activation of the phosphoinositide 3 kinase (PI3K)/AKT pathway is frequently implicated in resistance to anticancer therapies. PI3K inhibitors can restore sensitivity to standard breast cancer therapies, including endocrine therapy, HER2-targeted agents, and chemotherapy. Our previous research showed that econazole, a novel PI3Ka inhibitor, inhibits the PI3K/AKT pathway and induces apoptosis in lung cancer cells. In this study, econazole showed significant cytotoxic activity against Adriamycin-resistant breast cancer cells in vitro and in vivo . Additionally, econazole significantly sensitized MDA-MB-231 and MCF-7 cells to Adriamycin via inhibiting the PI3K/AKT pathway. Overexpression of constitutively active AKT1 abolished the function of econazole. The combination of econazole and Adriamycin exerted synergistic inhibitory effects in breast cancer cells in vitro and in vivo . Taken together, the PI3K inhibitor econazole could effectively overcome Adriamycin resistance and showed synergistic effects with chemotherapy on breast cancer., Competing Interests: None., (AJCR Copyright © 2020.)