目的 采用Meta分析的方法評價TNF-α基因中–308G/A位點多態性和前列腺癌易感性之間的關系，為進一步闡明前列腺癌發病的分子機制及篩查前列腺癌高風險人群提供參考。方法 計算機檢索PubMed（1950～2011）、EMbase（1990～2011）、CNKI、CBM、VIP和WanFang Data，按照納入與排除標準篩出關于TNF-α-308位點多態性與前列腺癌相關性的病例-對照研究或隊列研究，檢索時限均為從建庫至2012年1月。在提取數據和評價納入研究的方法學質量后，采用RevMan 5.1.4 和Stata 11.0 軟件進行統計分析。結果 共納入11個研究，4 919例前列腺癌患者，5 210例健康對照。Meta分析結果顯示：① 前列腺癌組與對照組中基因型AA vs. GG［OR=0.92，95%CI（0.71，1.20），P=0.55］、GA vs. GG［OR=1.11，95%CI（0.90，1.37），P=0.33）、AA vs. GG + GA［OR=0.91，95%CI（0.70，1.18），P=0.47）、GA + AA vs. GG［OR=1.11，95%CI（0.90，1.36），P=0.33）、等位基因A vs. G［OR=1.07，95%CI（0.91，1.26），P=0.39］與前列腺癌易感性之間均無相關性；② 以人種為亞組進行分層分析，發現TNF-α–308位點的多樣性在不同人種中也無明顯相關性（Pgt;0.05）。結論 現有證據顯示，TNF-α–308位點等位基因和基因型可能與前列腺癌易感性無關。由于納入研究數量有限，上述結論尚需開展更多高質量、大樣本的隨機對照試驗加以驗證。
【摘要】 目的 觀察低頻超聲（20 kHz）輻照聯合靜脈注射微泡造影劑SonoVue對裸鼠前列腺癌（Du145）移植瘤的抑瘤效應，并探討其可能的抑瘤機制。 方法 通過細胞移植和瘤塊移植方法建立24只裸鼠前列腺癌Du145移植瘤模型，隨機分為超聲微泡組、單純超聲組、單純微泡組和對照組，每組各6只。超聲微泡組：尾靜脈注射0.2 mL SonoVue的同時對瘤體行20 kHz超聲輻照，輻照強度200 mW/cm2；單純超聲組：尾靜脈注射生理鹽水0.2 mL，同時超聲輻照2 min；單純微泡組：尾靜脈注射SonoVue 0.2 mL同時行假照，各組均隔天1次，共3次，對照組不做任何處理。治療后測量瘤體大小，繪制瘤體生長曲線，計算抑瘤率。首次治療后14 d剝離瘤體，通過光學顯微鏡、電子顯微鏡觀察腫瘤組織病理改變。免疫組織化學方法觀察CD34陽性染色血管，計算腫瘤微血管密度（micro vessel density，MVD），比較各組間MVD的差異。 結果 24只裸鼠均成功植瘤。治療后超聲微泡組瘤體體積均數明顯小于其他3組（Plt;0.05），抑瘤率為62.7%。光學顯微鏡下超聲微泡組瘤體組織大部分損傷壞死，電子顯微鏡下超聲微泡組腫瘤內微血管的內皮細胞損傷，線粒體腫大，基底膜斷裂。超聲微泡組瘤體內CD34陽性染色微血管數減少，其MVD值顯著低于其他各組。 結論 20 kHz低頻超聲輻照聯合微泡造影劑SonoVue可有效抑制裸鼠人前列腺癌移植瘤的生長，其抑瘤機制可能是通過超聲空化效應破壞腫瘤的微血管實現的。【Abstract】 Objective To investigate the anti-tumor effect induced by low-frequency ultrasound (20 kHz) radiation combined with intravenous injection of microbubbles on human prostate carcinoma xenograft in nude mice, and to discuss its probable mechanism. Methods Human prostate carcinoma xenograft model in 24 nude mice were established with human prostate carcinoma Du145 cells inoculation and sub-graft through mice, which were randomly divided into ultrasound+microbubble, ultrasound, microbubble, and control group, with 6 mice in each group. In the ultrasound+microbubble group, 0.2 mL SonoVue was injected intravenously, followed by 20 kHz ultrasound exposure of 200 mW/cm2 at every other day for 3 times totally. Mice in the ultrasound group and the microbubbles group were only treated with ultrasound radiation and microbubbles injection, respectively. The volume of gross tumors was measured, and tumor growth curve was drawn. The ratio of anti-tumor growth was calculated. The mice were sacrificed 14 days after the last ultrasound exposure. Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope. CD34 positive vessels were counted in all the tumor slices by immunohistochemistry, and the micro-vessels density（MVD）of the tumor was also calculated. Results Du145 prostate tumor model was successfully established in all the mice. The average gross tumor volume of the ultrasound+microbubble group was significant lower compared with the other two groups after treatment (Plt;0.05), and the ratio of anti-tumor growth was 62.7%. Histological examination showed signs cell injury in the ultrasound+microbubble group. Electron microscopic examination revealed that the endothelium of vessels in the tumor was injured. The amount of CD34 positive vessels and MVD of the ultrasound+microbubble group was less than that of the other two groups. Conclusion The low-frequency ultrasound of 20 kHz exposure combined with microbubbles can be used to ablate human prostate carcinoma xenograft in nude mice, which is probably realized through micro-vessels destroyed by cavitation effect of ultrasound.
