Chen Jianghao, Yao Qing, Li Dong, Zhang Bin, Li Liwen, Wang Ling
Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Cancer Biol Ther. 2008 May;7(5):721-5. doi: 10.4161/cbt.7.5.5721. Epub 2008 May 12.
Lymph node status is one of the decisive prognostic factors in breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising approach for the treatment of malignancies with high tendency to disseminate lymphatically. In this study, rabbits bearing well-developed VX2 tumors in the mammary gland received carboplatin-activated carbon suspension (CP-CH) administered subcutaneously (s.c.), carboplatin solution (CP-Sol) s.c., CP-Sol intravenously (i.v.), or a sham therapy, respectively, 6 weeks after tumor implantation. The platinum concentrations in breast tumors, axillary lymph nodes and distant metastases were determined by Zeeman atomic absorption spectrometry (AAS). Therapeutic effects were assessed in terms of tumor and node volume ratio, cell proliferation and necrosis. Compared to CP-CH or CP-Sol s.c., CP-Sol i.v. exhibited more marked cytotoxic efficacy on breast tumor and distant metastases. In contrast, CP-CH s.c. produced much higher drug concentrations and more evident antitumor activities in axillary nodes, as demonstrated by the inhibited node growth, declined mRNA level of proliferating cell nuclear antigen (PCNA), and more extensive tumor necrosis. Based on these data, we recommend lymphatic chemotherapy to be used as an effective component of the approach to the systemic treatment on breast cancer patients with positive lymph nodes.
淋巴结状态是乳腺癌决定性的预后因素之一。针对区域淋巴组织的化疗已成为治疗具有高淋巴转移倾向恶性肿瘤的一种有前景的方法。在本研究中,乳腺有发育良好VX2肿瘤的兔子在肿瘤植入6周后分别接受皮下注射卡铂-活性炭混悬液(CP-CH)、皮下注射卡铂溶液(CP-Sol)、静脉注射CP-Sol或假治疗。通过塞曼原子吸收光谱法(AAS)测定乳腺肿瘤、腋窝淋巴结和远处转移灶中的铂浓度。根据肿瘤与淋巴结体积比、细胞增殖和坏死情况评估治疗效果。与CP-CH或皮下注射CP-Sol相比,静脉注射CP-Sol对乳腺肿瘤和远处转移灶表现出更显著的细胞毒性作用。相反,皮下注射CP-CH在腋窝淋巴结中产生更高的药物浓度和更明显的抗肿瘤活性,表现为淋巴结生长受抑制、增殖细胞核抗原(PCNA)mRNA水平下降以及更广泛的肿瘤坏死。基于这些数据,我们推荐淋巴化疗作为对淋巴结阳性乳腺癌患者进行全身治疗方法的有效组成部分。