An isotope agarose assay for rapid testing of the sensitivity of glioma biopsies to chemotherapeutic drugs and biological response modifiers. Effects of BCNU, vincristine, lymphokines and the recombinant agents interferon alpha 2c, interferon gamma and tumour necrosis factor.
A method based on growth of cells from glioma biopsies in a triple layer agarose system has been used to test the sensitivity of the tumour cells to different chemotherapeutic and immunotherapeutic agents. A special agarose that could be melted at 65 degrees C, enabled registration of proliferation by an easy and precise thymidine incorporation technique. The well known concept that agarose permits proliferation of malignant cells and inhibits growth of benign cells was confirmed in this assay by using the malignant glioma cell lines T-MG 1 and U 251 MG, and the benign glia cells T-BG 2 and T-BG 3. All of the 15 glioma biopsies grew exponentially during the first 7 days. The correlation between thymidine incorporation on day 7 and colony number on day 14 was very good for the glioma cell line (r = 0.96) and also for the glioma biopsies (r = 0.89), indicating that the sensitivity evaluation can be done as early as 7 days after the operation. Lymphokines, made by BCG-stimulated lymphocytes, had a strong inhibitory effect on the growth of some glioma biopsies, while others were only slightly inhibited or even stimulated. There was also a huge variation in the sensitivity of the biopsies to BCNU, but the sensitivity pattern was completely different for BCNU and lymphokines. rIF-A had a moderate inhibitory effect on growth of the biopsies, while rTNF had a weak inhibitory effect. The response to rIF-G varied from stimulation of some biopsies to strong inhibition of others. There was no similarity in the sensitivity pattern of the biopsies to rIF-A and rIF-G.(ABSTRACT TRUNCATED AT 250 WORDS)
Unsgaard
G
G
Brain Tumour Research Laboratory, Department of Neurosurgery, University Hospital, Trondheim, Norway.
Helseth
E
E
Vik
R
R
Dalen
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000628:therapy; D001706:Biopsy; D002330:Carmustine / Q000627:therapeutic use; D002478:Cells, Cultured; D002675:Child, Preschool; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008222:Lymphokines / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D014750:Vincristine; D007372:Interferons; D002330:Carmustine