Abstract
TNP-740, minocycline, suramin and genistein have demonstrated antiangiogenic activity in various experimental systems. The effect of these agents alone and in two agent combinations on the number of intratumoral vessels and response to cytotoxic anticancer therapies was assessed in animals bearing the Lewis lung carcinoma. Treatment with each of the antiangiogenic agents alone and in two agent combinations decreased the number of intratumoral vessels visualized by CD31 or Factor VIII staining to 30% to 50% of the number in the untreated control tumors. In general, the antiangiogenic agents are more effective adjuvants to cytotoxic therapies when used as two agent combinations than as single agents. The most effective antiangiogenic combinations were: TNP-470/minocycline > TNP-470/genistein > TNP-470/suramin. The increases in the response of the primary tumor to cyclophosphamide, adriamycin, CDDP, BCNU, x-rays or 5-fluorouracil and the lung metastases occur to about the same level with the addition of antiangiogenic agents to the therapies. With the treatment combination TNP-470/minocycline/cyclophosphamide 40% of the animals were cured. The results of these studies indicate that antiangiogenic agents can be very useful additions to treatment regimens for solid tumors.
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology
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Anti-Bacterial Agents / therapeutic use
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Antibiotics, Antineoplastic / pharmacology
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Antibiotics, Antineoplastic / therapeutic use
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Antineoplastic Agents, Alkylating / pharmacology
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Antineoplastic Agents, Alkylating / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Carcinoma, Lewis Lung / blood supply
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Carcinoma, Lewis Lung / drug therapy*
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Carcinoma, Lewis Lung / pathology
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Carmustine / pharmacology
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Carmustine / therapeutic use
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Cell Division / drug effects
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Cisplatin / pharmacology
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Cisplatin / therapeutic use
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Cyclohexanes
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Cyclophosphamide / pharmacology
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Cyclophosphamide / therapeutic use
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Doxorubicin / pharmacology
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Doxorubicin / therapeutic use
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Drug Synergism
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Genistein
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Isoflavones / pharmacology
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Isoflavones / therapeutic use
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Lung Neoplasms / drug therapy
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Lung Neoplasms / radiotherapy
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Lung Neoplasms / secondary
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Male
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Mice
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Mice, Inbred C57BL
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Minocycline / pharmacology
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Minocycline / therapeutic use
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Neoplasm Invasiveness
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / radiotherapy
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O-(Chloroacetylcarbamoyl)fumagillol
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Random Allocation
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Sesquiterpenes / pharmacology
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Sesquiterpenes / therapeutic use
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Suramin / pharmacology
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Suramin / therapeutic use
Substances
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Anti-Bacterial Agents
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Antibiotics, Antineoplastic
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Antineoplastic Agents, Alkylating
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Cyclohexanes
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Isoflavones
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Sesquiterpenes
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Suramin
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Doxorubicin
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Cyclophosphamide
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Genistein
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Minocycline
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Cisplatin
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Carmustine
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O-(Chloroacetylcarbamoyl)fumagillol