A novel assay to assess the effectiveness of antiangiogenic drugs in human breast cancer.
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.


CONCLUSIONS
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.
Lyons
John M
JM
Department of Surgery, Sections of Surgical Oncology and Surgical Endocrinology, Louisiana State University Health Sciences Center, Kenner, LA 70065, USA.
Anthony
Cathy T
CT
Thomson
Jessica L
JL
Woltering
Eugene A
EA
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001681:Biological Assay; D001777:Blood Coagulation / Q000187:drug effects; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D004317:Doxorubicin; D005337:Fibrin; D013917:Thrombin; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate