Expression and prognostic value of M2 macrophages and regulatory T cells in gastric carcinoma tissue / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the prognostic value of M2 macrophages and regulatory T cells(Tregs) in gastric carcinoma.</p><p><b>METHODS</b>Clinicopathological characteristics and follow up data of 135 patients with gastric carcinoma were collected. Patients included were those who underwent D2 radical resection(R0) at Zhongshan Hospital of Fudan University from February 1999 to December 2005. Tissue chips of gastric carcinoma specimen were stained using immunohistochemistry to determine the cells density and number of M2(CD163 positive) and Tregs(Foxp3 positive).</p><p><b>RESULTS</b>The median positive cells density of M2 macrophages and Tregs in tumor tissue were 7.48/HP and 6.33/HP, respectively, higher than that in adjacent tissues(1.37/HP and 2.92/HP, P<0.001). The density of M2 macrophages was positively correlated with that of Treg cells(r=0.415, P<0.001) in tumor tissue. The median survival of patients with low expression of M2 and Tregs(n=43) was significantly longer than those with high expression of the 2 cells(n=45) (99.0 vs. 72.3 months, P<0.05).</p><p><b>CONCLUSION</b>Combined detection of M2 macrophages and Tregs may predict the prognosis of gastric carcinoma.</p>

Inhibition of survivin expression and mechanisms of reversing drug-resistance of human lung adenocarcinoma cells by siRNA / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Survivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effects of survivin-specific siRNA on cell proliferation, apoptosis and chemosensitivity to cisplatin in vitro and in vivo and explore the mechanisms about decreasing expression of survivin in reversing cancer cells resistance to chemotherapeutic drug.</p><p><b>METHODS</b>Survivin-specific siRNA was transfected into A549/DDP cells. The expression of survivin and lung resistance-related protein (LRP) mRNA levels were determined by RT-PCR, chemosensitivity of A549/DDP (cisplatin) cells to cisplatin was determined by MTT assay, and apoptosis and cell cycle were determined by flow cytometry (FCM). The protein expression levels of survivin, LRP, cyclin-D(1), caspase-3 and bcl-2 were determined by Western blotting analyses. The effect of survivin siRNA inhibition on tumor growth was studied in athymic nude mice in vivo.</p><p><b>RESULTS</b>Survivin-specific siRNA efficiently down-regulated survivin expression. The cell cycle was arrested at G2/M phase, and apoptosis was obviously found. Inhibition of survivin expression could make the IC50 and drug-resistant index of cisplatin decrease, and enhance the cancer cells sensitivity to cisplatin. After transfection by survivin-specific siRNA, expression of LRP and cyclin-D1 were downregulated, caspase-3 expression was upregulated, bcl-2 expression had no obvious change. The animal experiment confirmed knockdown of survivin could inhibit the tumor growth.</p><p><b>CONCLUSIONS</b>Survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis, inhibit cells proliferation and enhance the chemosensitivity to cisplatin in vitro and in vivo. Suppression of survivin expression helping to reverse drug-resistance may have relationship with downregulation of LRP and upregulation of caspase-3. Anti-tumor strategies based on the inhibition of survivin may be useful in targeting lung adenocarcinomas.</p>

Expression of MDR1 and KIT in imatinib-resistant gastrointestinal stromal tumor cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between imatinib resistance and genes MDR1 and KIT in gastrointestinal stromal tumor (GIST) cells.</p><p><b>METHODS</b>The MDR1 and KIT mRNA level in GIST882-R and GIST882-S cells were detected by RT-PCR. Immunocytochemistry and Western blot were employed to detect P-gp and CD117 expression in GIST882-R and GIST882-S cells.</p><p><b>RESULTS</b>The relative expression of MDR1 mRNA was 0.321 + or - 0.033 in GIST882-R and 0.157 + or - 0.056 in GIST882-S cells, and the difference was statistically significant (P<0.05). The relative expression of KIT mRNA was 0.389 + or - 0.063 in GIST882-R and 0.339 + or - 0.067 in GIST882-S, and the difference was not statistically significant (P>0.05). The relative density of P-gp was 0.443 + or - 0.058 in GIST882-R and 0.237 + or - 0.094 in GIST882-S, and the difference was statistically significant (P<0.05). The relative density of CD117 was 0.744 + or - 0.123 in GIST882-R and 0.704 + or - 0.094 in GIST882-S, and the difference was not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>Over-expression of gene MDR1 may be associated with imatinib resistance in GIST. KIT may not be involved in imatinib resistance.</p>

Study on the mechanism of imatinib-induced resistance in gastrointestinal stromal tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of imatinib mesylate (IM) induced-resistance in the patients with gastrointestinal stromal tumors (GISTs) and treated with imatinib.</p><p><b>METHODS</b>Eight patients with GIST treated with IM developed secondary IM resistance. A total of 16 tumor samples (pre-IM therapy) and 11 tumor samples (post-IM treatment) were available. Exon 9, 11, 13, and 17 of c-kit gene as well as exon 12 and exon 18 of PDGFRA gene were sequenced.</p><p><b>RESULTS</b>In addition to the changes of baseline genotype, the IM-induced gene changes were concentrated in the kinase domain of c-kit gene in all 8 patients, 2 of them were located in the exon 13 of c-kit gene presenting with V654A, while 6 in exon 17 involving 816 and 820 to 823 codons.</p><p><b>CONCLUSION</b>The mechanism of imatinib mesylate resistance after initial treatment with this agent in gastrointestinal stromal tumors is a novel mutation development in kinase domain of c-kit.</p>

Detection and clinical significance of plasma vascular endothelial growth factor level in gastrointestinal stromal tumor patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of plasma vascular endothelial growth factor (p-VEGF) levels in gastrointestinal stromal tumor (GIST) patients.</p><p><b>METHODS</b>The p-VEGF levels in 61 primary GIST patients, 18 patients with recurrence or metastasis, and 28 healthy blood donators (as control) were measured by enzyme-linked immunosorbent assay. Paired p-VEGF levels of pre- and post-treatment were obtained from 44 patients. One patient received 22 consecutive detections during the follow up.</p><p><b>RESULTS</b>Primary and recurrent GIST patients had higher p-VEGF levels than healthy controls [(145.31+/-45.58) ng/L, (145.72+/-52.73) ng/L vs (89.86+/-18.30) ng/L] (P<0.01). And there were no significant differences between primary patients and patients with recurrence or metastasis (P>0.05). Significant difference were found in the p-VEGF levels between pre- and post-treatment patients (P<0.01). Post-treatment p-VEGF levels decreased markedly both in 26 primary and 11 recurrent patients [(101.81+/-27.63) ng/L and (112.45+/-38.58) ng/L]. As for the patient with 22 consecutive detections during the follow up, p-VEGF levels the period of were higher before surgery and after recurrence, and lower two months after surgery and during Glivec therapy.</p><p><b>CONCLUSIONS</b>The p-VEGF level of GIST patients is significantly higher than that of healthy people, which will decrease markedly after effective management. Monitoring the p-VEGF level in GIST patients will be helpful to evaluate the therapeutic efficacy and predict the recurrence or metastasis.</p>