ABSTRACT
Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.
ABSTRACT
Unified examination refers to the examination given by the university for medical students to graduate after they pass six curriculum examinations,including diagnostics,introduce of surgery,internal medicine,surgery,obstetrics and gynecology and pedology during the clinical study phases.It is a necessary process for cultivation of the professionals of the clinic medicine and has practice significance.Through the organization and management of the unified examination process,as well as analysis of examination result and feedback,education quality has been enhanced and educational reform promoted.
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In the program entitled "Studies and Practice on the Community-Oriented Teaching Model of Preventive Medicine for Non-Preventive Medicine Specialty", we have renovated the curricular arrangements, textbooks, teaching contents and methods of traditional preventive medicine for non-preventive medicine specialty so as to explore a new pattern of teaching preventive medicine for non-preventive medicine specialty in West China.
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This paper reports the postoperative managenment of 58 cases who had various types of congenital heart disease and received artificial valves due to rheumatic heart disease in our institute from 1982 to 1984. Vaso-active agents were administered with the monitoring of the cardiac function. According to the hemodynamic parameters and the criterion for clinical typing, the vaso-active agents therapy can provide a precise prognosis and the therapy is of certain value in cardiac surgery.