發(fā)布時(shí)間：2018-01-02 06:13

  本文關(guān)鍵詞：阿霉素前體藥物PADM靶向治療高轉(zhuǎn)移性人肝癌裸鼠原位移植模型的動(dòng)物實(shí)驗(yàn)研究　出處：《武漢大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)》2015年06期 　論文類型：期刊論文

  更多相關(guān)文章： PADM 阿霉素 癌 肝細(xì)胞 靶向治療

【摘要】：目的:比較阿霉素(ADM)與阿霉素前體藥物(PADM)治療高轉(zhuǎn)移性人肝癌裸鼠原位移植模型的療效和毒副作用,初步探索PADM的作用機(jī)制。方法:建立HCCLM9人肝癌裸鼠原位移植模型成功后,隨機(jī)分為PADM組、ADM組和對(duì)照組,每8d給藥一次,每4d記錄一次一般狀況。當(dāng)腫瘤進(jìn)展導(dǎo)致裸鼠死亡時(shí),即終止實(shí)驗(yàn),余裸鼠行安樂(lè)死,取血行常規(guī)、生化及腫瘤標(biāo)志物檢查;解剖裸鼠,詳細(xì)記錄解剖所見(jiàn);進(jìn)行組織病理學(xué)檢查,觀察肺及其他轉(zhuǎn)移情況;行免疫組化檢測(cè)Cat B、Ki-67和VEGF表達(dá),行統(tǒng)計(jì)學(xué)分析。結(jié)果:在腫瘤局部控制指標(biāo)中,PADM組和ADM組的肝腫瘤質(zhì)量、體積均顯著低于對(duì)照組(P0.05)。在區(qū)域控制指標(biāo)中,PADM組和ADM組ePCI值和腹膜后淋巴結(jié)轉(zhuǎn)移率均顯著低于對(duì)照組(P0.05)。在控制遠(yuǎn)處轉(zhuǎn)移指標(biāo)中,PADM組肺轉(zhuǎn)移率顯著低于對(duì)照組和ADM組(P0.05)。PADM組和ADM組的血清AFP水平顯著低于對(duì)照組(P0.05)。在血常規(guī)指標(biāo)中,PADM組白細(xì)胞計(jì)數(shù)顯著高于ADM組(P0.05);PADM組血小板計(jì)數(shù)顯著高于對(duì)照組(P0.05)。在肝功能指標(biāo)中,PADM組和ADM組GGT、AST水平均顯著低于對(duì)照組(P0.05)。在腎功能指標(biāo)中,PADM組BUN和Cr顯著低于ADM組和對(duì)照組(P0.05)。免疫組化指標(biāo)中,Cat B和VEGF的表達(dá)在3組中差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);但Ki-67陽(yáng)性率在3組中具有顯著差異(P0.05),PADM組最低,其次為ADM組,對(duì)照組陽(yáng)性率最高。結(jié)論:與ADM比較,PADM有更好的抗癌轉(zhuǎn)移和抑制腫瘤細(xì)胞增殖的作用,同時(shí)可降低血液和腎臟毒性。
[Abstract]:Objective: to compare the efficacy and side effects of adriamycin adriamycin (ADM) and adriamycin precursor drug (PADM) in the treatment of nude mice with high metastatic human hepatocellular carcinoma (HCC). Methods: after successful orthotopic transplantation of human hepatocellular carcinoma (HCCLM9) in nude mice, HCCLM9 group was randomly divided into PADM group and control group, once every 8 days. The general condition was recorded every 4 days. When tumor progression resulted in the death of nude mice, the experiment was terminated, and euthanasia was performed in the remaining nude mice. Blood samples were taken for routine, biochemical and tumor markers examination. Anatomize nude mice and record anatomical findings in detail; Histopathological examination was performed to observe lung and other metastasis. Immunohistochemistry was used to detect the expression of Ki-67 and VEGF in Cat, and statistical analysis was made. Results: in the local control index of the tumor, the quality of liver tumor was detected in the ADM group and the PADM group. The volume was significantly lower than that of the control group (P 0.05). The ePCI value and retroperitoneal lymph node metastasis rate in PADM group and ADM group were significantly lower than those in control group (P 0.05). The pulmonary metastasis rate in PADM group was significantly lower than that in control group and ADM group. The serum AFP level in P0.05 group and ADM group was significantly lower than that in control group. The white blood cell count in PADM group was significantly higher than that in ADM group (P 0.05). The platelet count in PADM group was significantly higher than that in control group (P 0.05). Among the liver function indexes, GGT was found in PADM group and ADM group. The levels of AST were significantly lower than those of control group (P 0.05). The levels of BUN and Cr were significantly lower in AST group than those in ADM group and control group. There was no significant difference in the expression of Cat B and VEGF among the three groups. But the positive rate of Ki-67 was the lowest in the three groups, followed by the ADM group and the control group. Conclusion: compared with ADM, the positive rate of Ki-67 was the highest. PADM has better effects on tumor metastasis and tumor cell proliferation, and can reduce blood and renal toxicity.
【作者單位】： 武漢市第五醫(yī)院腫瘤綜合科;武漢大學(xué)中南醫(yī)院腫瘤科/腫瘤生物學(xué)行為湖北省重點(diǎn)實(shí)驗(yàn)室;武漢市第五醫(yī)院血液內(nèi)分泌科;
【基金】：國(guó)家衛(wèi)生計(jì)生委醫(yī)藥衛(wèi)生科技發(fā)展研究中心資助項(xiàng)目(編號(hào):W2013GJ47)
【分類號(hào)】：R735.7;R-332
【正文快照】： 我國(guó)原發(fā)性肝癌死亡人數(shù)占全球肝癌死亡人數(shù)的53%[1],能接受外科手術(shù)切除或肝移植的病人有限,術(shù)后5年復(fù)發(fā)率高達(dá)60%以上[2]。阿霉素(adri-amycin,ADM)是臨床治療肝癌較為常用的化療藥物,因毒副反應(yīng)限制其臨床應(yīng)用,為此尋找低毒高效的藥物是近年來(lái)研究肝癌治療的熱點(diǎn),目前針對(duì)

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