Experimental study of 99Tcm-3PRGD2 imaging on the angiogenesis of rheumatoid arthritis / 中华核医学与分子影像杂志

Objective@#To observe the uptake of 99Tcm-3 polyethylene glycol Arg-Gly-Asp dimer (3PRGD2) in rat models of rheumatoid arthritis (RA), in order to provide theoretical foundation for early diagnosis of RA.@*Methods@#The healthy female SD rats were divided into collagen induced arthritis (CIA) group (n=100), osteoarthritis (OA) group (n=20) and control group (n=20). Bovine collagen type Ⅱ emulsion was used for arthritis induction to establish CIA models. OA models were established by injection of L-cysteine and papain. Gamma imaging was performed before and 15 d, 30 d after the model establishment. The mediastinum was selected as non-target (NT) area and the target (T)/NT ratios were calculated. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), αVβ3 before and after the model establishment were measured. Pathological and immunohistochemical detection were performed. One-way analysis of variance, Pearson and Spearman correlation analyses were used to analyze the data.@*Results@#There were 58 CIA models successfully established. Before the model establishment, T/NT ratios of CIA group, OA group and control group were 0.215±0.049, 0.210±0.050, 0.209±0.051, respectively (F=0.093, P>0.05). The T/NT ratios of the above three groups were 0.405±0.230, 0.223±0.045, 0.211±0.049 (F=12.601, P<0.05) 15 d post-model establishment, and those were 0.572±0.182, 0.238±0.045, 0.212±0.055 (F=65.147, P<0.05) 30 d post-model establishment. T/NT ratios of CIA group were positively correlated with the levels of serum VEGF, TNF-α, αVβ3, pathological score and the levels of immunohistochemical markers (VEGF, TNF-α, αVβ3, CD31, CD34; r values: 0.391-0.721, rs values: 0.365-0.669, all P<0.05).@*Conclusion@#99Tcm-3PRGD2 can be specifically up-taken by RA lesions in rat models, thus has the potential in early synovial neovascularization imaging of RA.

Arsenic trioxide restores ERα expression in ERα-negative human breast cancer cells and its treatment efficacy in combination with tamoxifen in xenografts in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the demethylation effect of arsenic trioxide (As2O3) on ERα-negative human breast cancer MDA-MB-435s cells and its possible mechanisms, and to observe its treatment efficacy in combination with tamoxifen (TAM) after ERα re-expression.</p><p><b>METHODS</b>MTT assay was used to examine the inhibitory effect of As2O3 treatment alone or in combination with TAM on cell proliferation. A nude mouse xenograft model was used to further examine the treatment efficacy in vivo. MSP was used to detect the methylation status of ERα gene after treated with As2O3 in MDA-MB-435s cells and the transplanted tumor tissues. RT-PCR was used to detect the mRNA expression of DNMT1 and Erα. Western bolt was used to detect the DNMT1 and ERα protein expression. The diameter of xenograft tumors was measured weekly, and the tumor growth curve was drawn.</p><p><b>RESULTS</b>The level of proliferation of the MDA-MB-435s cells was significantly suppressed after treatment with different concentration of As2O3 alone or As2O3 combined with TAM, and the 4 µmol/L As2O3 + TAM treatment for 72 h showed the highest inhibition rate (62.6%). 1, 2, 4 µmol/L As2O3 had demethylation effect on MDA-MB-435s cells, and the DNMT1 mRNA and protein expression was inhibited and accompanied by ERα mRNA and protein re-expression. The unmethylation specific bands of ERα gene were enhanced after treated by As2O3 alone or As2O3 combined with TAM in the xenograft tumors. The expression of DNMT1 mRNA and protein was inhibited, and accompanied by ERα mRNA and protein re-expression. An significant decrease of volume and weight of the xenograft tumors in the As2O3 treated alone or combined with TAM groups was observed compared with those of the normal saline group or TAM alone group (P < 0.05), and the 4 mg/kg As2O3 + TAM group had the highest inhibition rate of tumor weight (79.5%) and volume (76.4%).</p><p><b>CONCLUSIONS</b>ERα can be re-expressed in ERα-negative breast cancer MDA-MB-435s cells after treated with As2O3 by inhibiting the DNMT1 activity. MDA-MB-435s cells are re-sensitized to endocrine therapy after ERα re-expression. As2O3 combined with TAM may provide a new therapeutic approach for patients with ERα-negative breast cancer in the clinic.</p>

Mechanism of apoptosis of esophageal cancer EC9706 in nude mice induced by all-trans retinoic acid / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of apoptosis of EC9706 tumor-bearing nude mice induced by all-trans retinoic acid (ATRA).</p><p><b>METHODS</b>Human esophageal carcinoma cell line EC9706 cells were inoculated into nude mice to establish the solid tumor model. The tumor models were divided into the following groups: ATRA group, fluorouracil group, the two-drugs combination group, and with an equal volume fraction of solvent as the control group. The nude mice were sacrificed after 10 days of medication. TUNEL staining was used to detect cell apoptosis. RT-PCR was used to detect the expression level of mRNA and immunohistochemistry was used to detect the expression level of protein of caspase-3 and survivin, the apoptosis-related genes in the tumor tissue.</p><p><b>RESULTS</b>The apoptosis rates of the ATRA group, 5-Fu group and ATRA + 5-Fu group were 44.3%, 39.7% and 91.0%, respectively. There was a significant difference in comparison with the control group (0.7%), and the ATRA group had no significant difference compared with that of the fluorouracil group (P > 0.05), but the apoptosis rate of the two-drugs combination group was significantly higher than that in the two single-drug groups (P < 0.05). The average gray value of caspase-3 protein expressed in the control group was 46.12 ± 0.33 and the relative expression of caspase-3 mRNA was 0.14 ± 0.03, both were significantly lower than that in the ATRA group, 5-Fu group and the two-drugs combination group (P < 0.05). The average gray value of survivin protein expressed in the control group was 96.07 ± 0.13 and the relative expression of survivin mRNA was 0.84 ± 0.04, both were significantly higher than those of other groups (P < 0.05). The ATRA group had no significant difference compared with the fluorouracil group (P > 0.05), but the two-drugs combination group was significantly different compared with the single-drug groups (P < 0.05).</p><p><b>CONCLUSION</b>Apoptosis in the EC9706 tumor cells in nude mice can be induced by ATRA. The mechanism may be related with down-regulation of the level of survivin gene expression and up-regulation of the level of caspase-3 gene expression.</p>

Nedaplatin combined with tegafur in the treatment for advanced esophageal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and toxicity of nedaplatin combined with tegafur in the treatment for patients with advanced esophageal cancer.</p><p><b>METHODS</b>Among the 65 patients with advanced esophageal cancer, 27 had no history of prior chemotherapy and the other 38 had ever received postoperative adjuvant chemotherapy before. The median age of those cases was 58.0 years. Nedaplatin was given daily by intravenous infusion at a dose of 20 mg/m(2) for 2 hours and tegafur at a dose of 500 mg/m(2) for 8 hours on D1 approximately D5, every 21 days as a cycle.</p><p><b>RESULTS</b>193 cycles of chemotherapy were accomplished in the 65 patients, and 63 patients were evaluable for response evaluation. Of 27 patients with no prior history of chemotherapy, 6 achieved complete response and 16 partial response, with a response rate (CR + PR) of 81.5%. Among the 36 patients who had ever received postoperative adjuvant chemotherapy, 6 obtained complete response and 10 partial response with a response rate (CR + PR) of 44.4%. The overall median time to tumor progression in this series was 5.6 months. The overall median actuarial survival was 9.3 months, and the one-year survival rate was 24.9%. Nausea and vomiting were the major toxicities, but were mild and well tolerable. Grade 3 to 4 neutropenia was only observed in two patients (3.2%).</p><p><b>CONCLUSION</b>The regimen of nedaplatin combined with tegafur is effective and tolerable for the treatment of advanced esophageal cancer.</p>

Effects of silencing HIF-1 α gene by RNA interference on taxol-induced apoptosis of human esophageal squamous cell line EC9706 / 肿瘤

Objective: To study the mechanism of hypoxia-induced drug-resistance in esophageal squamous cell carcinoma and observe the effect of hypoxia inducible factor 1 alpha (HIF-1α) on the Taxol-induced apoptosis of EC9706 cells. Methods: Small interference RNA (siRNA) targeting HIF-1α was constructed and transfected into human EC9706 cells. Then EC9706 cells were cultured under chemical hypoxia conditions induced by CoCl2, a chemical hypoxia inducer. The expression of HIF-1α in EC9706 cells were detected by Western blot before and after RNA interference. The effect of Taxol on apoptosis of EC9706 cells were determined by TUNEL assay and Annexin V/PI double staining. Results: The expression of HIF-1α protein was induced by CoCl2 75 μmol/L after 4 h, and was significantly inhibited by siRNA-HIF-1α. The apoptosis rate of EC9706 cells induced by hypoxia were significantly higher in siRNA-HIF-1α transfection group than those without transfection or transfected with control siRNA (P < 0.05). Conclusion: Over-expression of HIF-1α inhibited the apoptosis of EC9706 cells induced by Taxol under hypoxia. siRNA targeting HIF-1α increases the therapeutic efficacy of esophageal squamous cell carcinoma.