1.Preliminary study on quantitative proteomic analysis of differentially expressed proteins in HER-2 posi-tive and negative breast cancer
Jing LI ; Sanqian HUANG ; Quchang OUYANG ; Jingmin ZHONG ; Nina GAO ; Liping LIU ; Zhihong LIU ; Liang ZENG
Journal of International Oncology 2016;43(10):721-727
Objective To seek differentially expressed proteins for human epithelial growth factorreceptor-2 (HER-2)negative and positive breast carcinoma through establishing proteins profiles,and to providenew prognostic markers and therapeutic targets for patients with breast cancer.Methods HER-2 positiveand negative breast cancer protein expression profiles were established using proteomic isobaric tags for relativeand absolute quantitation (iTRAQ)technology.Differences of protein expression were identified and parts ofdifferential expression proteins were analyzed by bio-informatics,including protein function annotation and GOclassification analysis and Kyoto Encyclopedia of Gene and Genome (KEGG)pathway analysis.Results Proteomicanalysis of breast cancer tissue with identified HER-2 positive and negative groups showed 4 999 differentiallyexpressed proteins by iTRAQ.Based on the criteria of the ratio of HER-2(+)/HER-2(-)≥3,119up-regulated proteins were identified in HER-2 positive group.Based on the criteria of the ratio of HER-2(+)/HER-2(-)≤0.5,47 down-regulated proteins were identified in HER-2 positive group.The results ofGO analysis showed that the molecular function,biological process and cellular composition of differentiallyexpressed proteins were complex between HER-2 positive and negative breast cancer.There were differences inthe distribution of up-regulated proteins and down-regulation of proteins.KEGG pathway analysis showed thatdifferentially expressed proteins involved in 168 signal pathways.Conclusion There are differentiallyexpressed proteins between HER-2 positive and negative breast cancer,which involve complex molecular func-tion,biological process and signaling pathway.
2.Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.
Binghe XU ; Qingyuan ZHANG ; Xichun HU ; Qing LI ; Tao SUN ; Wei LI ; Quchang OUYANG ; Jingfen WANG ; Zhongsheng TONG ; Min YAN ; Huiping LI ; Xiaohua ZENG ; Changping SHAN ; Xian WANG ; Xi YAN ; Jian ZHANG ; Yue ZHANG ; Jiani WANG ; Liang ZHANG ; Ying LIN ; Jifeng FENG ; Qianjun CHEN ; Jian HUANG ; Lu ZHANG ; Lisong YANG ; Ying TIAN ; Hongyan SHANG
Acta Pharmaceutica Sinica B 2023;13(5):2250-2258
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).