Rapid increase in plasma tenascin-C concentration after isolated limb perfusion with high-dose tumor necrosis factor (TNF), interferon gamma (IFN gamma) and melphalan for regionally advanced tumors.
The matrix protein tenascin-C (TN-C) is present in the blood of healthy individuals at concentrations around 1 mg/l. Elevated serum levels have been reported in cancer patients. In this study we have measured the concentration of circulating TN-C in 40 patients with melanoma, soft-tissue sarcoma (STS) or squamous-cell carcinoma (SCC) of the limbs, and have found a minor increase in the mean concentration compared with healthy subjects. Only 10 patients had TN-C levels above the normal range. No correlation was observed between TN-C levels and tumor burden. Nineteen patients were treated by isolation limb perfusion (ILP) with TNF, IFN gamma, melphalan (11 melanoma, 2 SCC and I STS), melphalan alone (3 melanoma) or hyperthermia at 41.5 degrees C (2 melanoma). ILP with TNF, IFN gamma and melphalan induced a rapid increase in plasma TN-C levels, peaking in most patients between 24 or 48 hr after ILP. Two patients treated with hyperthermia only had a slow increase in TN-C concentration peaking at day 4, while the patients treated with melphalan alone had no significant change. In some cases elevated TN-C levels persisted for over 8 weeks after ILP. The early rise in TN-C concentration correlates with the increase in circulating C-reactive protein. Our findings suggest that circulating TN-C behaves, at least in part, as an acute-phase protein and that it may play a role in the inflammatory response.
Schienk
S
S
Friedrich Miescher-Institut, Basel, Switzerland.
Liénard
D
D
Gerain
J
J
Baumgartner
M
M
Lejeune
F J
FJ
Chiquet-Ehrismann
R
R
Rüegg
C
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001792:Blood Platelets / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy; D056486:Chemical and Drug Induced Liver Injury; D010478:Chemotherapy, Cancer, Regional Perfusion; D004305:Dose-Response Relationship, Drug; D005121:Extremities; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy*; D011994:Recombinant Proteins; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000188:drug therapy; D019063:Tenascin / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism
D015850:Interleukin-6; D011994:Recombinant Proteins; D019063:Tenascin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002097:C-Reactive Protein; D008558:Melphalan