Olmutinib (HM61713) reversed multidrug resistance by inhibiting the activity of ATP-binding cassette subfamily G member 2 and

Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [I]-iodoarylazidoprazosin (IAAP). However, olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

Effects of autophagy on the proliferation and migration of cervical cancer cells / 实用肿瘤学杂志

Objective To investigate the effect of autophagy on the proliferation and migration of cervi-cal cancer cells ,as well as the underlining mechanisms .Methods Rapamycin was used to induce the autophagy in HeLa cells,formation of autophagosomes was observed by staining with acridine orange under fluorescence mi -croscope.Western blot was used to detect the expression of LC 3 and PI3K/Akt/mTOR in HeLa cells.The LC3 plasmid was transfected into HeLa cells .The distribution of LC3 in cells and the expression of LC3 was identified by fluorescence microscope and Western blot ,respectively.The autophagy was inhibited with 3-methyladenine(3-MA )in HeLa cells.The cell proliferation was monitored by RTCA real -time instrument.Transwell chamber was carried out to assess cell migration .Results After 6h of rapamycin treatment ,the expression of LC3B was in-creased in HeLa cells ( P<0 .05 ) .The proliferative and migration ability were weakened compared to wild type HeLa cells(P<0.05).The same results in the presence of 3-MA.The expression of PI3K/AKT/mTOR path-way proteins were activated by rapamycin treatment and LC 3 overexpression(P<0.05).Conclusion Autophagy can suppress the proliferation and migration in cervical cancer cells ,which may relate to PI3K/Akt/mTOR path-way.

Meta-analysis on value of miRNA-21 in diagnosing esophageal cancer / 国际检验医学杂志

Objective To evaluate the performance of microRNA‐21(miRNA‐21) for the diagnosis of esophageal cancer .Meth‐ods Published literatures ,investigating the diagnostic performance of miRNA‐21 in esophageal cancer ,were screened .QUADAS‐2 software was used to evaluate the quality of related literatures .All analysis about relevant data was accomplished by using Meta‐DiSc statistical software .The sensitivity ,specificity ,positive likelihood rate ,negative likelihood rate and diagnostic odds ratio were pooled ,using corresponding effects models .Results Four studies met the inclusion criteria ,accumulating 202 esophageal cancer pa‐tients and 124 healthy controls .The summary estimates for miRNA‐21 in the diagnosis of esophageal cancer were with diagnostic sensitivity of 0 .85 and specificity of 0 .65 .The area under summary receiver operating characteristic curve was 0 .817 4 .Conclusion miRNA‐21 might be a novel biomarker for the diagnosis of esophageal cancer ,and could be used for screening and auxiliary diag‐nosis of esophageal cancer .

Association between the GGN tri-nucleotide repeat polymorphism in androgen receptor gene and prostate cancer risk:a systematic review and meta-analysis / 国际检验医学杂志

Objective To provide a powerful and conclusive result for the association between the GGN polymorphic repeats in androgen receptor (AR)gene and prostate cancer (PCa)risk.Methods CNKI,VIP,Wanfang,PubMed/Medline,Embase and The Cochrance Library electronic database were used to retrieve the eligible publications addressing the association between the AR gene GGN polymorphic repeats and prostate cancer risk.16 GGN polymorphism repeats were used as cut off value,meta-analysis was ap-plied to the study on the association between the length of polymorphism repeats and prostate cancer risk.Results 9 cases of con-trol studies were included in this meta-analysis and a total of 2 438 cases and 1 968 controls were included.People with ≤16 GGN polymorphism repeats displayed a higher risk of prostate cancer(OR =1.15,95%CI :1.00 -1.31,P =0.04).Conclusion ≤16 GGN polymorphism repeats polymorphism associated with increased risk of prostate cancer.

Research and practice on the mode of training talents majoring in clinical medicine / 中华医学教育探索杂志

On the basis of innovating the talents training idea, integrating the instruction content, conducting medical simulation education, perfecting the Three-Early-Education mode, improving the research abilities of students, exploring the experimental class manage system and various approaches, the Department of Clinical Medicine of Hubei Medical University has established a mode of talent training for clinical medicine majors, which can guarantee the quality of the talent training, suit the actual conditions of our school and meet the needs of the development health undertakings.

Study on the penetrability of PEP-1-P27mt for cell membranes in vitro / 华中科技大学学报（医学）（英德文版）

Double-stranded oligomeric nucleotide encoding PEP-1 peptides was synthesized, prokaryotic expression pET15b-pep-1-p27mt recombinant constructed, E. coli BL21 (DE3)pLysS transformed and induced with IPTG to highly express fusion protein PEP-1-P27mt. Fusion protein with an N-terminal His-tag could be purified by Ni2+-resin affinity chromatography and identified by SDS-PAGE and Western blotting. Cultured EC9706 cells treated with PEP-1-P27mt revealed that PEP-1-P27mt was transduced into cells after 15 min and reached maximal intracellular concentrations in 2 h. PEP-1-P27mt of 1 micromol/L final concentration could most strongly suppress the growth. It was suggested that PEP-1 can carry P27mt across membrane, which provides a new biological protocol for using cyclin dependent kinase inhibitors p27mt in suppressing the growth of tumor cells.

Study on the Penetrability of PEP-1-P27mt for Cell Membranes in Vitro / 华中科技大学学报（医学）（英德文版）

Double-stranded oligomeric nucleotide encoding PEP-1 peptides was synthesized, prokaryotic expression pET15b-pep-1-p27mt recombinant constructed, E. coli BL21 (DE3)pLysS transformed and induced with IPTG to highly express fusion protein PEP-1-P27mt. Fusion protein with an N-terminal His-tag could be purified by Ni2+-resin affinity chromatography and identified by SDS-PAGE and Western blotting. Cultured EC9706 cells treated with PEP-1-P27mt revealed that PEP-1-P27mt was transduced into cells after 15 min and reached maximal intracellular concentrations in 2 h. PEP-1-P27mt of 1 μmol/L final concentration could most strongly suppress the growth. It was suggested that PEP-1 can carry P27mt across membrane, which provides a new biological protocol for using cyclin dependent kinase inhibitors p27mt in suppressing the growth of tumor cells.

On the course construction of medical communication in Yunyang Medical University / 中华医学教育探索杂志

The principal goal of opening the course of Medical Communication is to develop medical students'basic communication skills which involve three aspects:the proper use of language tools,communication and problem-solving skills in the course of general interper-sonal relationships,information communication skills between doctors and patients in the process of making a diagnosis or treatment,public communication skills on medical education and communication skills in dealing with a medical dispute or crisis between doctors and patients. This paper presents clearly the connotation of medical communication and puts forward specific programs on the organization and implementation of the course.