人癌裸小鼠移植瘤的应用研究

人癌裸小鼠移植瘤的应用研究焦伟综述陆胜经审校（广西区人民医院病毒室南宁５３００２１）６０年代由Ｇｒｉｓｔ发现，Ｆｌａｎａｇａｎ等研究证实先天性无毛、无胸腺、Ｔ淋巴细胞缺乏的小鼠（裸小鼠）是进行人癌异种移植的理想动物，并由Ｒｙｇａａｄ和Ｐｏｃｖｌｓｅｎ...

Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts in nude mice

AIM:To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude mice.METHODS: Nude mice bearing HuH7 xenografts were used to assess the anti-HCC effects and mechanisms of silibinin.RESULTS: Silibinin resulted in a potent dosedependent reduction of HuH7 xenografts in association with a significant decrease in Ki-67 and α-fetoprotein production, nuclear NF-κB content, polo-like kinase 1, Rb phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced apoptosis of HuH7 xenografts was associated with inhibited survivin phosphorylation. Silibinin-reduced growth of HuH7 xenografts was associated with decreased p-ERK, increased PTEN expression and the activity of silibinin was correlated with decreased p-Akt production, indicating involvement of PTEN/PI3K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin-reduced growth of HuH7 xenografts was also associated with a significant increase in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-1.CONCLUSION: Silibinin reduces HCC xenograft growth through the inhibition of cell proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing cell apoptosis, and increasing histone acetylation and SOD-1 expression.

Establishment of orthotopic transplantation model of human bladder cancer and detection by MRI

Objective: To establish an orthotopic bladder cancer model bearing human bladder cancer for experimental research, and monitor tumor progression by magnetic resonance imaging (MRI). Methods: The mucosa was mechanically damaged transurethrally under direct vision, and then human bladder cancer cell line T24 was inoculated into the bladders of BALB/c nude mice to establish orthotopic bladder cancer model. To find a suitable concentration of Gd-DTPA for this re- search. MRI was performed weekly to assess tumor growth, using Gd-DTPA as contrast agent. The pathologic morphology of the bladders and other specimens were observed with HE stain. Results: All the 25 mice developed bladder cancer after inoculation. The best concentration of Gd-DTPA was 1.408 mg/mL. On MRI, no change in the bladders was observed on day 7 after inoculation, filling defect in the bladders, accordant to actual tumor size, was detected on days 14, 21 and 28. Pathologic examination showed that tumor grew in the mucosa or superficial muscle of bladder on day 7, confined in muscle layer on days 14–28, and invaded serosa on day 35. Conclusion: Transurethrally damaged bladder mucosa under direct vision and instilled bladder cancer cell T24, we successfully established an orthotopic bladder cancer model. Tumor growth simulated the progression of human bladder cancer approximately. MRI was a reliable way for dynamic detection of murine orthotopic bladder tumor.

重组人VEGF_(121KDR)/rGEL融合毒素抗肿瘤药效学研究

目的：建立荷瘤小鼠模型，观察重组人VEGF121，xoR／rGEL融合毒素的抑瘤作用，为开发更加安全和有效的新型靶向抗癌药奠定基础。方法：选择人肝癌SMM-7721细胞、食管癌KYS-150细胞、胃癌sGC_7901和结肠癌HT-29细胞建立荷瘤小鼠模型；给药后每2-3d测量肿瘤大小，绘制肿瘤生长曲线，计算给药组相对肿瘤增长率。结果：在肝癌、食管癌、胃癌和结肠癌4种裸鼠移植瘤模型中，给药组肿瘤增长明显减慢，给药组肝癌裸鼠肿瘤体积为（89．33士56．36）mm^3，食管癌为（142．47±58．67）mm^3，胃癌为（73．80±31．05）mm^3，结肠癌为（79．64土34．46）mm^3；对照组肝癌为（328．19±200．27）mm^3，食管癌为（474．05±167．42）mm^3，胃癌为（172．34±41．78）mm^3，结肠癌为（480．26±348．34）mm^3。相对肿瘤体积给药组肝癌为5．31±2．13，食管癌为5．72±2．45，胃癌为3．59土1．55，结肠癌为5．82士1．92；对照组肝癌为17．10土6．00，食管癌为23．71士10．36，胃癌为11．65±4．14，结肠癌为23．24±5．74。相对肿瘤增殖率肝癌为31．05％，食管癌为24．12％，胃癌为25．04％，结肠癌为30．82％。给药组肿瘤体积和相对肿瘤体积均显著小于对照组，P值均d0．01。结论：重组人VEGF12KDR/rGEL融合毒素显著抑制多种肿瘤生长，可能是一种具有临床应用前景的候选靶向抗癌药。