Studies on tumor induced angiogenesis.
Methods were developed to test angiogenic response to human tumor implants and various biologic agents in the cornea of rabbits and non-human primates (Macaca arctoides). Crude PDGF preparations were found to have significant angiogenic effect. Purified, recombinant PDGF preparations were also effective inhibitors (e.g. pentoxifylline (Px) (which also were found to release PgI2 and t-PA) inhibited human tumor implant induced angiogenesis and reduced spontaneous metastases in 3 transplantable murine tumors (Furth-Columbia Wilms' tumor in Furth-Wistar rats, C-1300 neuroblastoma in A/J mice and HM-Kim mammary carcinoma in Wistar rats) but not in the NIH adenocarcinoma in Balb/c mice. Sodium diethyldithiocarbamate (DDTC), a metal complexing agent with special affinity to copper and anti-thyroid as well as, immune stimulating activity was shown to be anti-angiogenic and to potentiate the effect of Px. The anti-fibrinolytic agents epsilon amino caproic acid (EACA) and tranaxamic acid (t-AMCHA) were anti-angiogenic. DDTC and Px were synergistic from this point of view.
Ambrus
J L
JL
Roswell Park Cancer Institute, State University of New York, Buffalo.
Ambrus
C M
CM
Forgach
P
P
Stadler
S
S
Halpern
J
J
Sayyid
S
S
Niswander
P
P
Toumbis
C
C
D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology; D015119:Aminocaproic Acid / Q000627:therapeutic use*; D000818:Animals; D003315:Cornea / Q000098:blood supply*; D004050:Ditiocarb / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000473:pathology; D008251:Macaca; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology; D008545:Melanoma / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control; D009447:Neuroblastoma / Q000098:blood supply / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014148:Tranexamic Acid / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D009396:Wilms Tumor / Q000098:blood supply / Q000473:pathology
D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D014148:Tranexamic Acid; D004050:Ditiocarb; D010431:Pentoxifylline; D015119:Aminocaproic Acid