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  • 四種P-糖蛋白在胃癌組織中表達的研究
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  • 四種P-糖蛋白在胃癌組織中表達的研究


    丁呋洛爾
         俗稱:乙苯呋心安    藥物簡介  【藥理】 對β1受體阻斷作用無選擇性,具有內在擬交感活性   【應用及用法】 用於輕、中度高血壓   【注意】   (1)除對心髒的β受體(β1受體)有阻斷作用外,對支氣…    摘要:目的了解術後胃癌的多藥耐藥性與胃癌組織中P-gp過量表達的關系。方法利用免疫組化方法,以4種抗不同亞型P-gp(C494,MRK16,JSB1和C219)的單克隆抗體(mAb),以及4種不同抗P-gpmAb的混合抗體和抗p53蛋白mAb,分別檢測66例胃癌術後石蠟包埋組織中P-gp和p53的表達(其中16例為冰凍切片)。結果P-gp呈中等或高度表達(占40%~70%)。依次為:C494(75.75%,50/66),JSB1(62.12%,41/66),MRK16(48.49%,32/66)和C219(36.36%,24/66)。4種抗P-gpmAb的混合物的陽性檢出率為78.79%(52/66),抗p53蛋白mAb的陽性檢出率為60.61%(40/66)。4種抗P-gpmAb的混合物與抗P-gpmAbC494(G=0.90,P∨0.00001);抗P-gpmAbC494與抗JSB1mAb(G=0.60,P∨0.00005);抗MRK16mAb與抗C219mAb(G=0.64,P∨0.0001)均高度相關。石蠟和冰凍切片中P-gpC494和JSB1呈中度表達以上者陽性率基本一致;而C219和MRK16的陽性率相差則明顯(P∨0.05)。p53蛋白的表達與C494和JSB1的表達相關性顯著(P∨0.002和P∨0.002),與MRK16和C219的表達也有相關性(P∨0.01和P∨0.05)。結論C494陽性表達率最高,可作為胃癌組織中耐藥基因檢測的標志物。P-gp的過量表達與p53蛋白的表達關系密切。

      中圖號:R735.2 文獻標識碼:A 文章編號:1007-8738(2000)03-0264-04

    Expression of P- glycoprotein in the gastric carcinoma tissues

      using a panel of four mAbs

    FAN Miao CAO Jin-long CAI Qing-quan

      (Department of Pathology, The 455th Hospital of PLA, Shanghai 200052)

      NI Can-rong

      (Department of Pathology, The Second Medical University, Shanghai, 2000433, China)

      Abstract: Aim To understand relationship between multidrug resistance of post operative gastric cancer and P- gp overexpression in the gastric cancer tissues. Methods Paraffin sections from 66 cases of gastric carcinoma(16 cases of them were frozen sections) were immunohistochemically(IHC) analyzed using a panel of 4 different anti P- glycoprotein monoclonal antibodies (mAbs) composed of C494, MRK16, JSB 1 and C219. Cocktail of the 4 mAbs and mAb against p53 protein were also used. Results Moderate to high levels of P- glycoprotein were detected in 40% to 70% of gastric cancer. The positive rate of C494 (75.75% , 50/66)was higher than those of JSB 1(62.12% ; 41/66), MRK16(48.49% , 32/66)and C219(36.36% , 24/66). The positive rate of cocktail of the 4 anti P- glycoprotein antibodies was 78.79% (52/66). The positive rate of p53 protein was 60.61% (40/66). The positive expression of cocktail of the 4 anti P- glycoproteins was closely related to 4 anti P- gly coprotein C494(G=0.90, P∨ 0.00001); The positive expression of C494 was closely related to JSB 1(G=0.60,P∨ 0.00005). The positive expression of MRK16 was closely related to C219(G=0.64, P∨ 0.0001). There were similar positive expressions of C494 and JSB 1 between corresponding paraffin and frozen sections, but different ones between C219 and MRK16. Expression of p53 protein was closely related to C494(P∨ 0.002), JSB 1 (P∨ 0.002), MRK16 (P∨ 0.01) and C219 mAbs(P∨ 0.05). Conclusion The positive expression of C494 was the highest and could be as a marker for multidrug resistance gene assay. Overexpression of P- glycoprotein was closely related to p53 protein.

      Keywords: P- glycoprotein; gastric cancer; IHC; CSA; p53 protein ▲

      胃癌的發病率很高,大多數患者被確診後已是中晚期,並可遠距離轉移,複發率高,預後較差;另一方面,因該腫瘤對化療藥物不敏感,療效僅15%~20%,較其它腫瘤的療效(40%~70%)低。多柔比星(epidoxorubicin)或鬼臼乙叉甙(etoposide/VP16)是胃癌患者術後常用的化療藥,療效最高,但最終的治療效果較差,這可能與天然或繼發多藥耐藥(multidrugresistance,MDR)的產生,P-糖蛋白(P-gp)的過量表達及其它耐藥機制的啟動有關。

      許多研究者〔1,2〕已經在該腫瘤中檢測到MDR1mRNA的表達,應用斑點雜交檢測的陽性率為41%~80%;而用免疫組化法(immunohistochemicalstaining,IHC)檢測P-gp的不同亞型(C219,C494,MRK16和JSB1)的陽性率僅為26%~42%。然而,幾種抗P-gpmAb的混合使用,可使P-gp的檢出陽性率更准確,其多肽更全面,更能反映出腫瘤組織中P-gp的含量。我們應用4種抗P-gpmAb的  混合物,做催化信號放大系統免疫組化(catalyzedsignalamplificationimmunohistochemicalstaining,CSAIHC)染色,檢測了P-gp4個亞型(C494,C219,MRK16和JSB1)在66例胃癌術後石蠟包埋組織切片(其中16例同時采用冰凍切片)中的表達,並與抗P-gp各個亞型的mAb檢測的敏感性相比較,觀察了P-gp及各個亞型的表達與p53蛋白表達的相關性。

      1 材料和方法

      1.1材料66例胃癌組織標本為我院1994年~1998年外科手術切除標本。患者術前均未經過化療。標本經100mL/L中性福爾馬林固定,常規石蠟包埋,4μm厚連續切片分別做HE和IHC染色。其中16例為液氮速凍保存的胃癌標本,臨用前解凍後用40mL/L多聚甲醛固定,250g/L蔗糖浸泡24h,8μm厚恒冷箱冰凍切片後,於80℃保存備用。66例胃癌中,男52例,女14例,年齡34~75歲(平均58.75歲)。其中高分化腺癌10例,中等分化腺癌30例,低分化腺癌22例(有2例為印戒細胞癌),未分化腺癌4例。有淋巴細胞轉移者38例,無淋巴細胞轉移者28例;有隨訪結果者36例,其中術後生存時間≥ 做愛後不要有這四種行為
    性生活是一項比較劇烈的運動,肌肉、骨骼,尤其是神經系統極度興奮,全身血管擴張,血流速度增快,能量消耗大。因此,性生活之後,應該:    一不要吸煙。此時吸煙,會促使煙中有害物質的吸收,影響健康。   …

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