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

Int J Cancer. 1995 Nov 27;63(5):665-72. doi: 10.1002/ijc.2910630511.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Blood Platelets / drug effects
  • C-Reactive Protein / metabolism
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / drug therapy
  • Chemical and Drug Induced Liver Injury
  • Chemotherapy, Cancer, Regional Perfusion
  • Dose-Response Relationship, Drug
  • Extremities*
  • Female
  • Humans
  • Interferon-gamma / administration & dosage
  • Interleukin-6 / blood
  • Male
  • Melanoma / blood
  • Melanoma / drug therapy
  • Melanoma / secondary
  • Melphalan / administration & dosage
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / drug therapy*
  • Recombinant Proteins
  • Sarcoma / blood
  • Sarcoma / drug therapy
  • Soft Tissue Neoplasms / blood
  • Soft Tissue Neoplasms / drug therapy
  • Tenascin / blood*
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Recombinant Proteins
  • Tenascin
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • C-Reactive Protein
  • Melphalan