Growth of astrocytomas in the human tumor clonogenic assay and sensitivity to mismatched dsRNA and interferons.
Nine astrocytoma specimens were received from seven patients and processed for testing in the human tumor clonogenic assay (HTCA). Cells derived from these specimens were challenged with human natural alpha-interferon (alpha-IFN) and beta interferon (beta-IFN), recombinant beta interferon (beta ser-IFN), and mismatched double-stranded (ds) RNA (Ampligen). Six of the astrocytoma specimens formed adequate colonies for drug sensitivity testing (greater than or equal to 30 colonies/plate), and all were high-grade (III-IV) tumors. Sensitivity was defined as a greater than or equal to 50% decrease in tumor colony formation following drug exposure and was observed with alpha-IFN (2/4), beta-IFN (3/4), and mismatched dsRNA (4/5) exposure. No decrease in colony growth was observed after recombinant beta ser-IFN exposure, and in 2 of 3 cases, colony formation was stimulated. The sensitivity of 75 non-CNS solid tumors to mismatched dsRNA was compared to the high-grade astrocytomas in the HTCA. Of the 10 additional histologic tumor types studied, carcinoid and renal cell carcinomas exhibited the greatest sensitivity to mismatched dsRNA: 63% and 52%, respectively. However, in comparison, 80% of the high-grade astrocytomas were sensitive, demonstrating that these gliomas are among the most sensitive of human tumors to mismatched dsRNA in vitro. Clinical trials of interferons and mismatched dsRNA, coupled with in vitro sensitivity studies, should further define their therapeutic potential.
D001254:Astrocytoma / Q000188:drug therapy / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D002330:Carmustine / Q000627:therapeutic use; D002460:Cell Line; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D011070:Poly I-C; D011072:Poly U; D011131:Polyribonucleotides / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D014410:Tumor Stem Cell Assay
D007370:Interferon Type I; D011131:Polyribonucleotides; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D011072:Poly U; D016899:Interferon-beta; C047490:poly(I).poly(c12,U); D011070:Poly I-C; D002330:Carmustine; D000068556:Interferon beta-1a