一种评估抗血管生成药物对人类乳腺癌有效性的新型检测方法。

Lyons John M, Anthony Cathy T, Thomson Jessica L, Woltering Eugene A

Department of Surgery, Sections of Surgical Oncology and Surgical Endocrinology, Louisiana State University Health Sciences Center, Kenner, LA 70065, USA.

Ann Surg Oncol. 2008 Dec;15(12):3407-14. doi: 10.1245/s10434-008-0145-2. Epub 2008 Sep 16.

BACKGROUND

Many cytotoxic drugs maintain antiangiogenic properties, but there are no human, tumor-based assays to evaluate their antiangiogenic potential. We used a fibrin-thrombin clot-based angiogenesis model to evaluate the angiogenic response of human breast cancer to various cytotoxic agents commonly used in its treatment.

METHODS

Fragments of freshly harvested human breast tumors were embedded in fibrin-thrombin clots and treated with five drugs: adriamycin, taxol, 5-fluorouracil (5-FU), methotrexate, and vincristine. Each treatment group included a mean of 28 fragments (range 16-60). A total of four tumors were tested. Tumor fragments were tested with a single dose of each reagent. Angiogenic initiation, angiogenic growth, and overall angiogenic effect were determined for each treatment group using a previously validated scale.

RESULTS

All four breast cancer specimens tested developed an angiogenic response, sprouting neovessels in vitro in a time-dependent fashion (r = 0.84, P = 0.0007). Taxol statistically inhibited angiogenesis in all four specimens with decreases in the mean angiogenic initiation, angiogenic growth, and overall effect that were 69%, 81%, and 94% of control values, respectively. Vincristine and 5-FU inhibited the mean overall angiogenic effect by 89% and 82% compared with control, respectively. Adriamycin inhibited overall effect 49%. Methotrexate was less effective.

CONCLUSION

Freshly harvested breast cancer specimens develop an angiogenic response in a fibrin-thrombin clot-based angiogenesis model and respond to treatment with antineoplastic/antiangiogenic drugs. The antiangiogenic potential of commonly used breast cancer drugs varied among individual tumors. Data obtained from this model is unique and might potentially be used to further enhance the efficacy of cytotoxic regimens and individualize patient therapy.

背景

许多细胞毒性药物具有抗血管生成特性，但尚无基于人体肿瘤的检测方法来评估其抗血管生成潜力。我们使用基于纤维蛋白-凝血酶凝块的血管生成模型，来评估人乳腺癌对其治疗中常用的各种细胞毒性药物的血管生成反应。

方法

将新鲜采集的人乳腺肿瘤碎片包埋于纤维蛋白-凝血酶凝块中，并用五种药物进行处理：阿霉素、紫杉醇、5-氟尿嘧啶（5-FU）、甲氨蝶呤和长春新碱。每个治疗组平均包含28个碎片（范围为16 - 60个）。共检测了四个肿瘤。每个试剂对肿瘤碎片采用单剂量进行检测。使用先前验证的量表确定每个治疗组的血管生成起始、血管生成生长和总体血管生成效应。

结果

所有检测的四个乳腺癌标本均出现血管生成反应，体外新生血管以时间依赖性方式发芽（r = 0.84，P = 0.0007）。紫杉醇在所有四个标本中均能统计学显著抑制血管生成，平均血管生成起始、血管生成生长和总体效应分别降至对照值的69%、81%和94%。与对照相比，长春新碱和5-FU分别将平均总体血管生成效应抑制了89%和82%。阿霉素抑制总体效应49%。甲氨蝶呤效果较差。