Varlamov A V, Pal'tseva E M, Sekacheva M I, Skipenko O G, Fedorov D N
B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia; Research Institute of Human Morphologyr, Moscow, Russia.
B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
Arkh Patol. 2017;79(1):36-42. doi: 10.17116/patol201779136-42.
to study changes in the expression of angio- and vasculogenesis markers in colorectal adenocarcinoma metastases to the liver during combined cytotoxic and targeted anti-VEGF therapy versus cytotoxic monotherapy.
Intraoperative samples from 96 patients with colorectal adenocarcinomas metastases to the liver were immunohistochemically examined. The investigation enrolled patients who had preoperatively received either combined FOLFOX6 cytotoxic therapy and targeted anti-VEGF therapy with bevacizumab or only FOLFOX6 therapy, as well as patients who had not received preoperative anti-tumor drug treatment. The expression of SDF1α, CXCR4, CXCR7, and VEGF-A was compared in these groups. Statistical significance was accepted at p<0.05.
The expression of CXCR4 in the vessel endothelial cells was significantly less frequently detected in the patients who had received combined cytotoxic therapy and targeted anti-VEGF therapy as compared to those had not drug therapy. Comparing the patients treated with cytotoxic drugs with those who had not received anti-tumor therapy revealed similar results in the women. CXCR7 expression in the tumor cells and stromal cells from the metastatic foci was significantly more common in the group of male patients treated with cytotoxic drugs according to the FOLFOX6 regimen. The expression of SDF1α in the tumor cells was significantly more often observed in the male patients who had received combined cytotoxic therapy and targeted anti-VEGF therapy than in those who had not drug therapy. VEGF expression in the stromal cells was significantly less frequently seen in the patients who had received the combined therapy.
Combined cytotoxic therapy and targeted anti-VEGF therapy for colorectal adenocarcinoma metastases to the liver leads to some suppression of the alternative pathway in the formation of new vessels, by reducing the expression of CXCR4 in the vessel endothelial cells and that of VEGF in the stromal cells from the metastatic foci. In men, this therapy simultaneously causes an increase in the expression of SDF1α in the tumor cells and in that of CXCR4 in the stroma. Preoperative FOLFOX6 therapy significantly increases the expression of CXCR7 in the tumor cells and stromal cells in the male patients, which may suggest that this pathway in vessel formation can be activated.
研究细胞毒性联合靶向抗血管内皮生长因子（VEGF）治疗与单纯细胞毒性治疗相比，结直肠癌肝转移灶中血管生成和血管发生标志物表达的变化。
对96例结直肠癌肝转移患者的术中样本进行免疫组织化学检查。研究纳入术前接受FOLFOX6细胞毒性联合贝伐单抗靶向抗VEGF治疗或仅接受FOLFOX6治疗的患者，以及未接受术前抗肿瘤药物治疗的患者。比较这些组中基质细胞衍生因子1α（SDF1α）、CXC趋化因子受体4（CXCR4）、CXC趋化因子受体7（CXCR7）和VEGF-A的表达。p<0.05具有统计学意义。
与未接受药物治疗的患者相比，接受细胞毒性联合靶向抗VEGF治疗的患者血管内皮细胞中CXCR4的表达明显较少被检测到。比较接受细胞毒性药物治疗的患者与未接受抗肿瘤治疗的患者，女性患者结果相似。根据FOLFOX6方案接受细胞毒性药物治疗的男性患者转移灶肿瘤细胞和基质细胞中CXCR7的表达明显更常见。接受细胞毒性联合靶向抗VEGF治疗的男性患者肿瘤细胞中SDF1α的表达明显比未接受药物治疗的患者更常见。联合治疗患者基质细胞中VEGF的表达明显较少被观察到。
结直肠癌肝转移的细胞毒性联合靶向抗VEGF治疗通过降低转移灶血管内皮细胞中CXCR4的表达和基质细胞中VEGF的表达，导致新血管形成的替代途径受到一定抑制。在男性中，这种治疗同时导致肿瘤细胞中SDF1α的表达和基质中CXCR4的表达增加。术前FOLFOX6治疗显著增加男性患者肿瘤细胞和基质细胞中CXCR7的表达，这可能表明该血管形成途径可被激活。
