Induction of MxA mRNA in patients with neuroendocrine tumors after interferon treatment. Lack of correlation with antitumor response.
We have investigated the possibility of using induction of MxA mRNA in patients with neuroendocrine tumors undergoing interferon-alpha(IFN-alpha) treatment as a predictive test for antitumor effect. A total of 122 patients with various types of neuroendocrine tumors were included in the study. Blood samples were drawn 12 hours after administration of either recombinant or natural IFN-alpha for analysis of induction of MxA mRNA in peripheral blood leukocyte (PBLs). Total RNA was isolated and slot-blot hybridization was performed using a MxA cDNA fragment as a probe. All patients displayed induction of MxA mRNA. Out of 13 untreated patients, 4 had MxA mRNA as well as 2 out of 11 patients treated with somatostatin analogue. All IFN-alpha treated patients showed induction of MxA mRNA and there was no difference between patients demonstrating partial remission, stable disease or progressive disease. Moreover, there was no difference between recombinant or natural leukocyte IFN-alpha in the ability to induce MxA mRNA. Six patients developed neutralizing IFN-alpha antibodies with 1 patient presenting a tire of 3200 NU/ml. Development of neutralizing antibodies did not abrogate the induction of MxA mRNA, but in 3 patients with high antibody titres the antitumor effect was lost. We therefore conclude that IFN-alpha is able to induce MxA mRNA in PBLs from patients with neuroendocrine tumors but we could not find any correlation with the therapeutic outcome. Furthermore, development of neutralizing IFN-alpha antibodies, although abrogating the antitumor effect, might not block the antiviral activity.
Imam
H
H
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Janson
E T
ET
Gobl
A
A
Alm
G
G
Oberg
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D019204:GTP-Binding Proteins; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000628:therapy*; D009693:Nucleic Acid Hybridization; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*
D000970:Antineoplastic Agents; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D012333:RNA, Messenger; D019204:GTP-Binding Proteins