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Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).
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Objective:To explore the effects of knocking down glycine cleavage system H protein (GCSH) on proliferation, apoptosis, oxidative stress and migration of gastric cancer SNU-1 cells in vitro. Methods:SNU-1 cells were cultured in vitro and divided into control group (no transfection) , negative control group (transfection of negative control siRNA) and GCSH knockdown group (transfection of GCSH siRNA) . Quantitative PCR was used to detect the knockdown effect. Immunofluorescence was used to observe the morphology of cells in each group. CCK-8 was used to test the proliferation of SNU-1 cells. Flow cytometry was used to detect the apoptosis and oxidative stress level, and scratch test was used to detect the cell migration. Results:Quantitative PCR experiment showed that the relative expression levels of GCSH in the control group, negative control group and GCSH knockdown group were 1.29±0.16, 1.36±0.17 and 0.32±0.04, respectively ( F=90.32, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.497) . Compared to the negative control group, the GCSH knockdown group was significantly decreased ( P<0.001) . Immunofluorescence experiment showed no significant difference in the morphology of cells among the groups. The CCK-8 experiment results showed that the cell proliferation activities of the control group, negative control group and GCSH knockdown group were 2.63±0.12, 2.61±0.14, 2.45±0.14, respectively ( F=6.35, P=0.005) . There was no significant difference between the control group and negative control group ( P=0.751) , and the GCSH knockdown group significantly decreased compared to the negative control group ( P=0.011) . The results of flow cytometry showed that the early stage apoptosis rates of SNU-1 cells in the control group, negative control group and GCSH knockdown group were (13.38±0.45) %, (12.86±0.65) %, (20.04±3.61) %, respectively ( F=15.37, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.559) . Compared to the negative control group, the GCSH knockdown group significantly increased ( P=0.002) . The late stage apoptosis rates of the three groups were (2.21±0.25) %, (2.68±0.45) %, (5.67±1.67) %, respectively ( F=18.24, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.356) . Compared to the negative control group, the GCSH knockdown group showed a significant increase ( P=0.024) . The reactive oxygen species positive rates in the control group, negative control group and GCSH knockdown group were (26.98±8.79) %, (28.27±5.63) %, (48.41±0.94) %, respectively ( F=22.56, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.950) . Compared to the negative control group, the GCSH knockdown group significantly increased ( P<0.001) . The cell migration rates of the control group, negative control group and GCSH knockdown group were (48.29±5.79) %, (51.66±2.29) %, (14.01±1.56) %, respectively ( F=148.80, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.328) . Compared with the negative control group, the GCSH knockdown group significantly decreased ( P<0.001) . Conclusion:Knock down of GCSH gene can inhibit the proliferation and migration, increase cell apoptosis rate and oxidative stress of SNU-1 cells in vitro. GCSH gene may be a potential target for the treatment of gastric cancer.
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Objective:To investigate the effect and molecular mechanism of procyanidin on the proliferation, apoptosis and reactive oxygen species (ROS) level of gastric cancer cell line SNU-1 in vitro. Methods:SNU-1 cells were divided into control group and 12.5, 50.0, 200.0 μg/ml procyanidin groups. The effect of procyanidin on the proliferation of SNU-1 cells was detected by CCK-8 assay. The apoptosis level and ROS positive rate of cells were detected by flow cytometry, and 2 mmol/L glutathione was added to SNU-1 cells added with 200.0 μg/ml procyanidin to detect the apoptosis level and ROS positive rate of cells. The expression of apoptosis-related protein in cells was detected by Western blotting.Results:The results of CCK-8 experiment showed that the proliferation activities of SNU-1 cells in the control group and the 12.5, 50.0, 200.0 μg/ml procyanidin groups were 3.69±0.30, 3.29±0.41, 0.91±0.39, 0.45±0.22 respectively, with a statistically significant difference ( F=279.84, P<0.001) . Compared with the control group, the proliferation activities of SNU-1 cells in the three procyanidin groups were significantly inhibited ( P=0.006, P<0.001, P<0.001) . The results of flow cytometry showed that the early apoptosis rates of SNU-1 cells in the control group and the 12.5, 50.0, 200.0 μg/ml procyanidin groups were (0.00±0.00) %, (0.00±0.00) %, (0.09±0.07) % and (0.45±0.22) % respectively, with a statistically significant difference ( F=7.14, P=0.003) . The 50.0 and 200.0 μg/ml procyanidin groups increased significantly compared with the control group ( P=0.003, P=0.007) . The late apoptosis rates of SNU-1 cells in the four groups were (0.00±0.00) %, (0.01±0.00) %, (6.98±0.77) % and (33.32±2.78) % respectively, with a statistically significant difference ( F=654.28, P=0.003) . The 50.0 and 200.0 μg/ml procyanidin groups increased significantly compared with the control group ( P<0.001, P<0.001) . The positive rates of ROS in SNU-1 cells in the four groups were (0.02±0.01) %, (0.10±0.05) %, (1.15±0.26) % and (1.58±0.22) % respectively, with a statistically significant difference ( F=162.24, P<0.001) . The 50.0 and 200.0 μg/ml procyanidin groups increased significantly compared with the control group ( P<0.001, P<0.001) . The positive rates of ROS in SNU-1 cells in the 200.0 μg/ml procyanidin group and the glutathione intervention group were (1.25±0.63) % and (0.13±0.02) % respectively, with a statistically significant difference ( t=5.39, P=0.001) . The early apoptosis rates of the two groups were (10.56±3.24) % and (2.09±0.24) % respectively, and the late apoptosis rates were (29.65±6.01) % and (23.63±1.52) % respectively, with statistically significant differences ( t=2.61, P=0.048; t=3.97, P=0.012) . The expressions of Bcl-2 protein in SNU-1 cells in the control group and the 12.5, 50.0, 200.0 μg/ml procyanidin groups were 1.00±0.00, 0.83±0.05, 0.60±0.14 and 0.41±0.23 respectively, with a statistically significant difference ( F=10.63, P=0.004) . The 50.0 and 200.0 μg/ml procyanidin groups decreased significantly compared with the control group ( P<0.001, P<0.001) . Conclusion:Procyanidin can inhibit proliferation and promote apoptosis of gastric cancer SNU-1 cells in vitro, which may be achieved by increasing intracellular ROS levels and reducing Bcl-2 protein expression.
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Objective:To investigate the correlation between preoperative blood platelet-to-lymphocyte ratio (PLR) and clinico-pathological features, as well as the effect of PLR on the prognosis of non-small cell lung cancer (NSCLC) patients after surgical resec-tion. Methods:Retrospective analysis was performed for 255 cases with histologically confirmed NSCLC that underwent curative re-section from January 2004 to December 2007. All patients were classified into two groups based on the median value of PLR. The rela-tionship between PLR and clinicopathological features was studied. Univariate and multivariate analyses were performed to assess the prognostic effect of preoperative PLR. Results:The median value of preoperative PLR was 130 (range:45.45 to 272.66). Based on the cut-off value of 130, all patients were divided into two groups:low PLR (≤130, n=127) and high PLR (>130, n=128). PLR was corre-lated with tumor site, T stage, and clinical stage. Five-year survival rates of low and high PLR patients were 49.6%and 33.6%, respec-tively, which indicated a statistically significant difference (χ2=12.577, P<0.001) between the two groups. Univariate analysis showed that smoking status, histological differentiation, clinical stage, T stage, N stage, postoperative adjuvant therapy and PLR were associat-ed with survival (P<0.05 for all). Multivariate analysis identified N stage, postoperative adjuvant therapy, and PLR as independent prog-nostic factors of all the patients. In addition, stratified analysis showed that the five-year survival rate of the low PLR group was higher than that of the high PLR group with or without lymph node metastasis, and the differences were statistically significant (P=0.020 and 0.037). Conclusion:An elevated blood preoperative PLR indicates poor prognosis in NSCLC patients. Preoperative PLR is an indepen-dent prognostic factor of NSCLC after curative resection.
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Objective: This study aims to observe the efficacy and toxicity of three-dimensional conformal radiotherapy (3DCRT) combined with weekly topotecan hydrochloride (Top-Hyd) chemotherapy on patients with platinum-resistant recurrent ovarian cancer. Methods: Medical data of 42 patients with platinum-resistant recurrent ovarian cancer between June 2008 and June 2011 were retrospectively reviewed. OAOf these 42 patients, 22 underwent 3DCRT combined with weekly Top–Hyd chemotherapy, whereas the remaining 20 underwent simple chemotherapy (SCT). Doses from 45 Gy to 65 Gy were planned to deliver fractions ranging from 1.8 Gy to 2 Gy to patient abdomen and pelvis. Top–Hyd (4 mg/m2) was aintravenously administered 1, 8, and 15 days from radiotherapy, with a cycle of 28 days. Results: By December 31, 2011, the median follow-up time for the 3DRT group was 18.5 months, whereas that for the SCT group was 10.8 months . The total response rate and the clinical beneficial rate were significantly higher in the 3DCRT group than in the SCT group (total response rate, 42.1% vs. 11.1%; clinical beneficial rate, 68.4% vs 22.2% at P0.05). Conclusion: The combined 3DCRT treatment and Top-Hyd chemotherapy results in enhanced response and tolerable toxicity compared with SCT in patients with recurrent ovarian cancer infiltrating the pelvic and retroperitoneal lymph node metastasis. So, it may be the salvage regimen for recurrent ovarian cancer and provide a new therapeutic option for the consolidation treatment of advanced ovarian carcinoma.
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Objective To analyze the result of late course accelerated hyperfractionation (LCAFR) and three dimensional conformal radiotherapy plus concurrent chemotherapy (LCAFR+C)on stage Ⅲ esophageal carcinoma. Methods Ninety-eight patients with stage Ⅲ esophageal carcinoma were divided randomly into two groups:1. LCAFR group: patients were treated with conventional fractionated radiotherapy during the first two-thirds of the treatment to a dose of 40?Gy in 20 fractions over 4 weeks, then followed by LCAFR with reduced fields using three dimensional conformal radiotherapy to a dose of 15-24?Gy over 7-12 days, 1.5Gy per fraction, to the total dose of 55-64?Gy in 30～36 fractions over 35-40 days. 2. LCAFR+C group:The radiotherapy schedule was the same as the LCAFR group,but with concurrent chemotherapy of DDP 20?mg d1-5, LF 200?mg and 5-Fu 500?mg d 6-10 , 28 days in one cycle to totally 5 cycles. Results The 1-, 2-, and 3-year actuarial survival rates were 73%, 53%, 35% and 76%, 73%, 55% respectively (? 2=4.12,P