The action of interferon alpha on human carcinoid tumours.
The action of IFN-alpha has been studied in patients with carcinoid tumours. More than 300 patients have been treated with IFN-alpha for long periods of time (median 2.5 years). IFN-alpha exerts many pleiotrophic effects in carcinoid tumours. Antiproliferative effects are manifest mainly by a cell cycle block in GO-G1 phase and prolongation of the S-phase. Hormone synthesis is impaired with reduced circulating hormone levels after IFN-alpha therapy and the mechanism includes reduction of mRNA expression for various hormones. Induction in vitro of the nuclear enzyme 2'-5-A synthetase in tumour cells correlates with biochemical response and might account for reduced mRNA expression. IFN-alpha induces significantly increased intratumoral fibrosis in carcinoid metastases without significant changes in tumour size. Finally IFN-alpha causes alteration of the major histocompatibility complex (MHC) with increased expression of class I antigens on the tumour cells. The net result of all these effects of IFN-alpha is an antitumour effect in 70-80% of carcinoid tumour patients with biochemical control and abrogated tumour growth for extended periods of time. However, when IFN-alpha therapy is withdrawn tumour progression occurs within 3-9 months, indicating a controlling but not curing effect.
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
K
K
Oberg
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis; D005355:Fibrosis / Q000139:chemically induced; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008285:Major Histocompatibility Complex / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015320:Tachykinins
D015088:2',5'-Oligoadenylate Synthetase; D053379:Chromogranin A; D002864:Chromogranins; D006133:Growth Substances; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D009479:Neuropeptides; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D015320:Tachykinins; C045206:neuropeptide K