RESUMO
OBJECTIVE: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms. METHODS: HSP90B1 expression was analyzed in NPC tissues and its relationship with patient's prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway. RESULTS: HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway. CONCLUSION: Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis.
RESUMO
OBJECTIVE: To compare the clinical effects of repairing tympanic membrane perforation (TMP) with the tragus perichondrium-cartilage island and temporalis muscle fascia (TMF) under the otoendoscope. METHODS: The clinical data of 84 patients (total 84 ears) with TMP repaired by otoendoscopy from March 2019 to April 2021 were analyzed. The patients were randomly divided into the control group (n = 42, TMF repair) and the experimental group (n = 42, perichondrium-cartilage island repair). The intraoperative blood loss, operation time, length of hospital stay, success rate of the TMP repair, mean air-conducted sound, and air-bone gap before and after surgery were compared between the two groups. RESULTS: The mean air-bone gap and mean air-conducted hearing threshold in the experimental group were significantly lower after surgery at all frequencies than those of the control group (all P < .05). The reduction of the mean air-conducted hearing threshold in the experimental group was significantly higher than that of the control group (P < .001). The surgery time of the experimental group was significantly shorter than the control group (78.04 ± 2.23 vs. 84.27 ± 1.67 minutes, P < .001). The success rate of the TMP repair was 95.24% (40/42) in the experimental group and 92.86% (39/42) in the control group, indicating that there was no significant difference in the success rate of TMP repair between the two materials (risk ratio = 1.75; 95% confidence interval: .31-12.04; P = .71). CONCLUSION: Repairs with the tragus perichondrium-cartilage island have a short operation time, high healing rate, and more significant postoperative hearing improvement, which makes it a more effective method of TMP repair.