MiR-665 Promotes the Biological Behavior of Small Cell Lung Cancer by Targeting LLGL1 / 中国肺癌杂志

BACKGROUND@#MicroRNAs (miRNAs) are non-coding small molecule RNAs that are widely found in eukaryotic organisms, although some miRNAs have been found in tumors, the expression and effects of miR-665 on small cell lung cancer (SCLC) are unclear. The aim of this study was to analyze the effects of miR-665 on proliferation, cycle, invasion and migration of SCLC cells, and to explore the role of miR-665 in SCLC and its working mechanism.@*METHODS@#The expression of miR-665 in SCLC tissues and adjacent normal tissues was detected by qRT-PCR. TargetScan predicted potential target genes for miR-665 and validated with dual luciferase reporter assays, qRT-PCR and Western blot. CCK8 assay, flow cytometry, Transwell and wound healing assay to detect the effects of miR-665 and LLGL1 on proliferation, invasion, migration and S-phase fraction of SCLC cell line NCI-H446, NCI-H1688. A nude mouse xenograft model of SCLC was constructed and the effect of miR-665 on tumor growth in mice was observed.@*RESULTS@#The expression of miR-665 in SCLC tissues was significantly higher than that in non-tumor normal tissues. MiR-665 could target 3'-UTR of LLGL1 and inhibit its expression. Compared with non-tumor normal tissues, the expression of LLGL1 was significantly lower in SCLC tissues. Inhibition of miR-665 expression could inhibit proliferation, S-phase fraction, invasion and migration ability of SCLC NCL-H446 cells, and interference LLGL1 expression could reverse this inhibition effect. Up-regulation of miR-665 expression could promoted proliferation, S-phase fraction, invasion and migration ability of SCLC NCI-H1688 cells, but this promotion effect was also reversed by overexpression of LLGL1. In a nude mouse xenograft model of SCLC, inhibition of miR-665 expression could up-regulate LLGL1 protein expression and inhibit tumor growth, while up-regulation of miR-665 expression could produce opposite results.@*CONCLUSIONS@#The expression of miR-665 is closely related to SCLC. miR-665 can promote the biological behavior of SCLC cells by inhibiting the expression of target gene LLGL1, and miR-665 play a role in tumor-promoting genes in SCLC.

A multicenter clinical study for the comparison of S-1 versus capecitabine in the treatment of advanced breast cancer / 中华肿瘤杂志

Objective@#To investigate the safety, efficacy and prognostic factors of S-1 versus capecitabine in patients with advanced breast cancer (ABC).@*Methods@#From January 1, 2012 to December 31, 2014, 154 ABC patients with pathological diagnosis were separated into two groups: S-1 with or without the 3rd generation chemotherapy drug (group S-1) and capecitabine with or without the 3rd generation chemotherapy drug (Group capecitabine). The efficacy, side effects and prognostic factors were compared between the two groups.@*Results@#There were 70 patients in group S-1 and 84 patients in group capecitabine. The objective response rates (ORR) were 31.4% (22/70) in group S-1 and 28.6% (24/84) in group capecitabine. The disease control rates (DCR) were 74.3% (52/70) and 83.3% (70/84), respectively. There were no significant differences in DCR and ORR between two groups (P>0.05). The DCR of patients treated with capecitabine monotherapy was significantly higher than that of S-1 monotherapy [94.4%(17/18) and 64.0%(16/25), P=0.028]. The median PFS was 7.5 and 8.9 months for the patients in the group S-1 and group capecitabine, with no statistically significant difference (P=0.423). The 1-year survival rates of group S-1 and group capecitabine were 81.4% and 66.7%, respectively, with no significant differences(P=0.020). Univariate analysis showed that ER and/or PR status (P=0.004), T stage (P=0.041), and molecular typing (P=0.046) were associated with PFS. Multivariate analysis showed ER and/or PR status (P=0.034) was an independent prognostic factor related with PFS. The incidence of hemoglobin reduction was 14.3% (10/70) and 36.9% (31/84) in the group S-1 and group capecitabine, and the differences were statistically significant (P=0.002). There was no significant difference in the incidence of leukopenia, neutropenia, thrombocytopenia and hand-foot syndrome between the two groups(P>0.05).@*Conclusions@#S-1 and capecitabine are both effective for advanced breast cancer. Neither ORR nor DCR were significantly different between these two groups. The incidence of gastrointestinal reactions and thrombocytopenia of S-1 was slightly lower than that of capecitabine.

Research progress on androgen receptor in triple-negative breast carcinoma / 中国癌症杂志

Triple-negative breast cancers (TNBC) comprise a heterogeneous group of tumors characterized by poor survival and lack of targeted therapeutics. In recent years, androgen receptor (AR) has been demonstrated to play an important role in the genesis and development of TNBC. There has been increased interest in the role of AR in TNBC and AR-targeting has been introduced as a novel therapeutic option for TNBC. This review offers an overview of the relationship between AR expression and TNBC, and provides insights into the novel drugs in the development for targeting this signaling pathway.

Effects of Sorafenib on the cytotoxic sensitivity of nasopharyngeal carcinoma cells with high expression of ATP-binding cassette superfamily G member 2(ABCG_2) / 解放军医学杂志

Objective To investigate the mechanisms and effects of Sorafenib on cytotoxic sensitivity of allo-reactive natural killer(Allo-NK) cells against human multi-drug resistant nasopharyngeal carcinoma CNE2/DDP cells which expressing highly ATP-binding cassette superfamily G member 2(ABCG2)(abbr.as ABCG2HighCNE2/DDP cells).Methods ABCG2HighCNE2/DDP and Allo-NK cells were isolated by magnetic bead technique.The target cells were divided into 3 groups: a) treated group(ABCG2HighCNE2/DDP cells incubated with 10 ng/ml sorafenib for 4h);b) untreated group(conventionally cultured ABCG2HighCNE2/DDP cells);and c) control group(conventionally cultured K562 cells).Expression rates of ABCG2 in treated and untreated groups,and of five NKG2D-ligands(MICA,MICB,ULBP1,ULBP2,ULBP3) were evaluated by flow cytometry.The cytotoxic effects of NK cells against different groups of target cells were detected with LDH releasing assay.Results Expression rate of ABCG2 in isolated CNE2/DDP cells was 91.40%?2.32%.The purity of sorted CD3-CD16+CD56+ Allo-NK cells was 90% and higher.The expression rates of NKG2D-ligands(MICA,MICB,ULBP1,ULBP2 and ULBP3) in untreated group were 2.92%?0.33%,4.27%?0.33%,5.80%?0.62%,11.10%?3.15% and 7.75%?1.14%,respectively,which were remarkablely higher than that in treated group(10.38%?1.23%,10.68%?1.26%,11.62%?1.22%,43.24%?4.42% and 11.91%?0.88%,respectively,P

Inhibitory effects of sorafenib combined with cisplatin on hepatocellular carcinoma cells HepG2 in vitro / 解放军医学杂志

Objective To explore the inhibitory effects of sorafenib combined with cisplatin (DDP) on human hepatocellular carcinoma cells HepG2 in vitro, and the possible underlying mechanisms. Methods The HepG2 cells were divided to 4 groups as control group, sorafenib group, cisplatin group and sorafenib-cisplatin group. Sorafenib and cisplatin were used in single agent or in combination against HepG2 in vitro. The inhibitory effects of sorafenib and/or cisplatin on proliferation of HepG2 were determined by MTT assay at 24h, 48h, 72h and 96h after the addition of the drugs to HepG2 culture. Cell cycle at 24h time point and apoptosis at 48h time point were examined by flow cytometry (FCM). At 24h time point, cells were labeled by Rhodamine123 and mitochondrial transmembrane potential (??m) was determined by FCM, while caspase-3 activity was assessed by caspase-3 colorimetric assay. Results MTT assay showed that sorafenib and cisplatin, when used as a single agent or in combination, could inhibit the growth of HepG2 cells and induce apoptosis in vitro, while synergistic effect was noted when lower doses of sorafenib and DDP were used in combination. It was also found that combined use of sorafenib and cisplatin arrested HepG2 cells at G0/G1 and G2 phase as shown by cell cycle analysis, and the highest apoptosis rate appeared in sorafenib-cisplatin combination group (P