Effect of trastuzumab combined with paclitaxel neoadjuvant chemotherapy on the cell proliferation and invasion in HER-2-positive breast cancer lesions

Objective: To study the effect of trastuzumab combined with paclitaxel neoadjuvant chemotherapy on the cell proliferation and invasion in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer lesions. Methods: Patients who were diagnosed with HER-2-positive breast cancer in the Central Hospital of Enshi Autonomous Prefecture Hubei Province between April 2015 and January 2017 were selected and randomly divided into two groups, the combined group received trastuzumab combined with paclitaxel chemotherapy, and the control group accepted paclitaxel chemotherapy. The surgically removed breast cancer lesions were collected to determine the expression of cell proliferation genes, cell invasion genes and angiogenesis molecules. Results: USP39, EphA2, NUAK1, Gab2, Raptor, ICAM-1, HIF-1α, VEGF, ANGPLT-2 and ANGPLT-4 mRNA expression in tumor lesion of combined group were significantly lower than those of control group while CCN5, ALEX1, ATG2B, ATG4D, E-cadherin and EBP50 mRNA expression were significantly higher than those of control group. Conclusion: Trastuzumab combined with paclitaxel neoadjuvant chemotherapy can inhibit the cell proliferation and invasion and decrease the angiogenesis in HER-2-positive breast cancer lesions.

基于GC-MS代谢组学技术的甲氨蝶呤毒性机制探究

目的:采用基于气相色谱-质谱联用(GC-MS)的代谢组学技术探究甲氨蝶呤(MTX)的毒性机制。方法:喂养第7天时小鼠腹腔注射MTX(20 mg·kg^(-1)),对照组小鼠腹腔注射等量的生理盐水。摘除眼球后采集血样,并收集心脏、肝脏、肾脏、肺、肠、胃和海马进行代谢组学分析。通过正交偏最小二乘判别分析(OPLS-DA)进行差异代谢物筛选,随后采用MetaboAnalyst 5.0(http://www.metaboanalyst.ca)及京都基因和基因组百科全书数据库(KEGG;http://www.kegg.jp)进行通路分析。最后以肠组织为例,进行病理学分析及代谢物验证。结果:非靶向代谢组学分析显示,MTX暴露后,小鼠整体代谢轮廓发生改变,其中肝脏与肠道中代谢轮廓改变最为显著;通路分析结果表明MTX主要影响小鼠体内多种氨基酸代谢/合成、能量代谢、泛酸盐和辅酶A生物合成、嘧啶代谢以及谷胱甘肽代谢等代谢通路。MTX处理能够明显破坏肠道上皮结构,同时炎性细胞增加。通过全自动氨基酸分析仪分析发现,L-谷氨酸,L-天冬氨酸和甘氨酸的含量在MTX处理后明显上升,这与代谢组学分析的结果一致。结论:本研究阐明了甲氨蝶呤暴露后对小鼠各组织代谢轮廓的影响,识别MTX毒性相关的代谢生物标记物和代谢通路,为MTX毒理机制的研究提供新见解。