Intracarotid recombinant human tumor necrosis factor-alpha reduces cerebral blood flow and methionine uptake in rat brain tumors.
The aim of the present study is to understand the therapeutic effects of recombinant human tumor necrosis factor-alpha (rH-TNF) on hemocirculation and metabolism of brain tumors. Using double-label autoradiographic technique, we have monitored changes in regional cerebral blood flow (rCBF) and protein-bound fraction of (3H-methyl)-L-methionine, expressed as acid-insoluble fraction (AIF), in rat brain tumors following treatment with intracarotid rH-TNF. The central portion of tumors showed a significant decrease in rCBF and AIF at 4 hours after the injection (p < 0.01, p < 0.05, respectively, as compared with non-treated control rats), turned microscopically necrotic at 24 hours, and became more extensively necrotic at 72 hours. Tumor cells remained viable only in the peripheral portion of the tumors after the treatment. The peripheral portion also showed a moderate decrease in rCBF, but less change in AIF to 4 to 72 hours after the treatment. Neither ipsilateral nor contralateral non-involved cortex demonstrated appreciable changes in rCBF and AIF during the observed period. Intracarotid rH-TNF selectively reduces tumor rCBF and AIF, resulting in histological modification.
Sasajima
T
T
Neurosurgical Service, Akita University Hospital, Japan.
Mineura
K
K
Kowada
M
M
Hatazawa
J
J
Miura
S
S
D000818:Animals; D001345:Autoradiography; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002343:Carotid Artery, Internal; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008715:Methionine / Q000378:metabolism*; D009336:Necrosis; D011865:Radioisotope Dilution Technique; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D008715:Methionine