Therapeutic effect of in vitro 5-aza-2'-deoxycytidine combined with imatinib on gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of 5-aza-2'-deoxycytidine(5-aza-CdR) combined with imatinib on the proliferation, motility, invasion, and apoptosis of gastrointestinal stromal tumors(GIST) cells in vitro.</p><p><b>METHODS</b>MTT assay was used to investigate the effect of the two agents on proliferation of GIST882. Plate colony forming assay was used to determine the number of colony-forming. Motility and invasion abilities were tested to evaluate the inhibitory effect of each agent. Flow cytometry was used to observe apoptosis and cell cycle.</p><p><b>RESULTS</b>5-aza-CdR or imatinib effectively inhibited the growth of GIST882 cells in concentration- and time-dependent manner. The inhibitory rate of combined treatment using 5-aza-CdR and imatinib was significantly higher than that of 5-aza-CdR or imatinib alone(P<0.05). After treatment for 48 h, the apoptosis rates of 5-aza-CdR group (1000 μg/L) and imatinib group (100 μmol/L) were (11.7±1.2)% and (14.6±0.8)%, respectively. Compared with the control group (2.8±0.3)%, the difference was statistically significant(P=0.000). Furthermore, the difference in apoptosis rate was significant between combined treatment group (19.4±1.1)% and single drug treatment group(vs. 5-aza-CdR group, P=0.000, vs. imatinib group, P=0.013). 5-aza-CdR raised G0/G1 ratio and reduced S ratio of GIST882. Imatinib and combined group had no apparent influence on the cell cycle of GIST882 cells.</p><p><b>CONCLUSION</b>5-aza-CdR may be a potential agent of GIST treatment in the near future.</p>

Prognostic value of P16 gene methylation and P16 protein expression in gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the methylation status of P16 gene promoter and the expression of P16 protein in gastrointestinal stromal tumors(GIST) and to explore the prognostic value.</p><p><b>METHODS</b>Methylation status of the P16 promoter was detected by methylation- specific polymerase chain reaction (MSP) and the expression of P16 protein by immunohistochemistry in 62 patients with GIST.</p><p><b>RESULTS</b>The status of P16 gene methylation and the expression of P16 protein were significantly different among the patients with different subclassification of GIST using Fletcher's scheme (P < 0.05, P < 0.01). And there were significant differences in progressive disease (PD) among various levels of P16 expression (P < 0.01). P16 gene methylation was closely related to P16 protein. P16 gene methylation accounted for 75% in the tumor tissue with less than 50% P16 positive cells, and accounted for only 10% in the tumor tissue with more than 50% P16 positive cells (P< 0.01).</p><p><b>CONCLUSION</b>P16 immunohistochemical assessment can be used as a prognostic index for GIST. The patients with more than 50% fraction of cells with low P16 immunostaining have poor prognosis.</p>