Interferon-induced enhancement of 2',5'-oligoadenylate synthetase in mid-gut carcinoid tumours.
Freshly explanted tumour cells from 22 patients with mid-gut carcinoid were used for in-vitro analysis of the capacity of recombinant interferon (rIFN) to induce the enzyme 2',5'-oligoadenylate synthetase (2',5'-A synthetase). 21 samples (95%) could be evaluated. IFN achieved a clinical response, by predetermined criteria, in 9 of the 21 patients (43%). There was a significant association between induction of 2',5'-A synthetase and clinical response: if the in-vitro intracellular concentrations of the enzyme increased by less than a factor of 3, remission did not occur (9 of 9; 100%), whereas remission was observed in 9 of 12 patients (75%) in whom in-vitro intracellular 2',5'-A synthetase concentrations at least trebled. Anti-IFN antibodies developed in 6 of 12 patients treated with rIFN-alpha 2a but in 0 of 10 who received rIFN-alpha 2b. This in-vitro test may help to identify patients with carcinoid tumours who are unlikely to benefit from IFN therapy, so that other forms of treatment can be started early and the side-effects of IFN are not suffered unnecessarily. Adaptations of this test may be possible for other tumours that may respond to treatment by IFN or similar compounds.
Grandér
D
D
Division of Experimental Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Oberg
K
K
Lundqvist
M L
ML
Janson
E T
ET
Eriksson
B
B
Einhorn
S
S
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D002276:Carcinoid Tumor / Q000201:enzymology* / Q000628:therapy; D004790:Enzyme Induction; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000201:enzymology* / Q000628:therapy; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012044:Regression Analysis; D012074:Remission Induction; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase