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Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.
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Objective:To analyze the efficacy and safety of curcumin in the treatment of knee osteoarthritis.Methods:The randomized controlled trials of curcumin in the treatment of knee osteoarthritis published from January 2011 to August 2021 were retrieved. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the efficacy related indexes and the incidence of adverse events were analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference of efficacy indexes, the odds ratio ( OR) was calculated for the difference of safety indexes, the difference was compared by t test. Results:① A total of 9 relevant literatures were included, all of which were in English. ② A total of 724 patients were included in the study, of which 383 were treated with curcumin capsules and 341 were treated with placebo. ③ The visual analogue scale/score (VAS) of patients treated with oral curcumin at 3-4, 6 and 8 weeks were significantly lower than those of patients treated with oral placebo, the differences were statistically significant [weighted mean difference ( WMD)=-1.09, 95% CI (-1.44, -0.73), P<0.001; WMD=-1.52, 95% CI (-2.35, -0.69), P<0.001; WMD=-1.20, 95% CI(-1.71, -0.69), P<0.001]. ④ The western Ontario and McMaster universities osteoarthritis index (WOMAC) scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-7.96, 95% CI(-14.89, -1.04), P=0.020; WMD=-15.34, 95% CI(-20.51, -10.18), P<0.001]. Specifically, the WOMAC pain and stiffness scores of patients treated with oral curcumin for 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-2.16, 95% CI(-3.69, -0.63), P=0.010; WMD=-1.00, 95% CI (-1.54, -0.46), P<0.001]. The WOMAC joint function scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, the difference was statistically significant [ WMD=-3.21, 95% CI(-4.51, -1.92), P<0.001; WMD=-7.07, 95% CI(-11.19, -2.94), P<0.001]. ⑤ There was no significant difference in the incidence of adverse events between oral curcumin and placebo [ OR=1.19, 95% P(0.74, 1.90), P=0.478]. Conclusion:Compared with placebo, oral curcumin can significantly alleviate the pain, stiffness and joint function of patients with knee osteoarthritis, and its safety is similar to placebo.
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Objective:To compare the clinical efficacy and safety of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis.Methods:The relevant literatures including the randomized control study of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis published from January 2010 to December 2021 were searched. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the data were processed and analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference ofefficacy indexes, and the difference was compared by t-test. The odds ratio ( OR) was calculated for the difference of safety index, and the difference was compared by t-test. Results:① A total of 10 literatures were included, all of which were in English. ② A total of 921 patients were included in the study, of which 479 patients were treated with intra-articular injection of platelet rich plasma and 442 patients were treated with intra-articular injection of hyaluronic acid. ③ Comparing the VAS scores of platelet rich plasma injection and hyaluronic acid injection, the visual analogue scale (VAS) scores of platelet rich plasma injection patients were significantly lower than those of hyaluronic acid injection patients after 6 and 12 months of injection treatment, and the difference was statistically significant [ WMD(95% CI)=-0.66(-1.25, -0.77), P=0.029; WMD(95% CI)= -0.90(-1.51, -0.29), P=0.004]. ④ The specific performance was that the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of patients injected with platelet rich plasma after 6 and 12 months of injection treatment was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-0.76(-1.06, 0.45), P<0.001; WMD(95% CI)=-1.35(-2.05, -0.65), P<0.01]; After 3, 6 and 12 months of injection treatment, the WOMAC stiffness score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [( WMD(95% CI)=-0.37(-0.66, -0.08), P=0.011; WMD(95% CI)=-0.30(-0.57, -0.04), P=0.023; WMD(95% CI)=-0.62(-0.92, -0.33), P<0.001]; After 3, 6 and 12 months of injection treatment, the WOMAC function score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-1.90 (-2.53, -1.27), P<0.001; WMD(95% CI)=-5.77(-9.20, -2.34), P=0.001; WMD(95% CI)=-5.72(-8.62, -2.82), P<0.001]. ⑤There was no significant difference in the incidence of adverse events between the two intra-articular injection methods [ OR(95% CI)=1.28(0.68, 2.42), P=0.440]. Conclusion:Compared with intra-articular injection of hyaluronic acid, the short-term clinical efficacy of injection of platelet rich plasma is equivalent to that of injection of hyaluronic acid, but the long-term clinical efficacy is better, and the safety of the two methods is similiar.
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Objective To explore the mechanism resistance of medroxyprogesterone 17-acetate (MPA) on the endometrial cancer side-population (SP) cells.Methods (1) Ishikawa-SP cells from endometrial cancer cell lines Ishikawa were be separated by Hoechst 33342 dyeing method and flow cytometry analysis.The clone formation efficiency between Ishikawa-SP cells and Ishikawa-non-SP cells were performed by clone formation assay.Breast cancer resistance protein (BCRP) was examined by immunocytochemistry method.(2)Ishikawa,Ishikawa-SP,Ishikawa-non-SP cells were treated with various concentrations of MPA at 5,10,15,20 μmoL/L.After cultured for 24,48,and 72 hours,cells growth were measured by methanethiosulfomate(MTS) assay.(3) The groups of Ishikawa,Ishikawa-SP,Ishikawa-non-SP cells incubated with MPA at the half maximal inhibitory concentration(IC50) were selected for cell apoptosis assay by using flow cytometry.After MPA treatment,the expression of caspase-3 was examined by immunocytochemistry method.Results (1)There were few proportion of Ishikawa-SP cells in Ishikawa endometrial carcinoma,which were 2.7％.There were stronger clone formation efficiency for Ishikawa-SP cells than that for Ishikawa-non-SP cells in Ishikawa [(6.02 ± 1.17)％ vs.(0.53 ±0.20)％,P =0.001].And there were higher level expression of BCRP (P =0.001)and also more resistant Taxol and radiation between Ishikawa-SP cells and Ishikawa-non-SP cells.(2)The inhibitory effect of MPA was concentrationdependent and time-dependent.(3)After MPA treatment,the apoptosis rates of Ishikawa-SP,Ishikawa-nonSP,Ishikawa were (4.01 ± 0.43) ％,(9.30 ± 0.67) ％,and (4.64 ± 0.18) ％,respectively (P ＜ 0.05).The level expression of caspase-3 in Ishikawa group after MPA treated were higher than that in Ishikawa-SP group.Conclusion MPA may be inhibit the growth of endometrial cancer,Ishikawa-SP and Ishikawa-nonSP cells,while Ishikawa-SP may be more resistant to MPA than Ishikawa-non-SP,which mechanism of resistance on MPA may be related to the properties of cancer stem-like cells and cell apoptosis.
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Objective To investigate the occurrence of cardiotoxicity of chemotherapeutic drugs in gynecological cancer patients without heart disease,and patients with coronary heart disease or congenital heart disease for providing a basis for the clinical prevention of heart side effects during chemotherapy.Methods Thirty cases with gynecological cancer complication with or without coronary heart disease or congenital heart disease before or during chemotherapy admitted from Jan.2004 to Dec.2010 were retrospectively analyzed.Results For all 30 patients,there were heart failures in 3 cases ( 10％,3/30),myocardial infarction in 3 cases (10％,3/30),angina pectoris in 1 cases (3％,1/30),ST-T or T-wave changes in 9 cases (30％,9/30),and arrhythmia in 8 cases (27％,8/30).Conclusions Cancer chemotherapy drugs to the heart may produce an immediate or long-term toxicity,in which could significantly effects on the survival and prognosis of patients.It is very important to prevent the occurrence of cardiotoxicity of chemotherapeutic drugs in gynecological cancer patients with heart diseases during chemotherapy.