Therapeutic activity of the topoisomerase I inhibitor J-107088 [6-N-(1-hydroxymethyla-2-hydroxyl) ethylamino-12,13-dihydro-13-(beta-D-glucopyranosyl) -5H-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7(6H)-dione]] against pediatric and adult central nervous system tumor xenografts.

The in vivo antitumor activity of a novel topoisomerase I inhibitor, J-107088, was tested in athymic nude mice bearing subcutaneous or intracranial pediatric and adult malignant CNS tumor-derived xenografts.
J-107088 was administered to animals on days 1-5 and 8-12 via intraperitoneal injection at a dose of 54 mg/kg (162 mg/m2) per day in 10% dimethyl sulfoxide in 0.9% saline. The xenografts evaluated were derived from a childhood glioblastoma multiforme (D-456 MG), a childhood medulloblastoma (D-341 MED), an adult anaplastic astrocytoma (D-54 MG), an adult glioblastoma multiforme (D-245 MG), and a procarbazine-resistant subline of D-245 MG [D-245 MG (PR)].
J-107088 produced regressions and significant growth inhibition in all five of the xenograft lines growing subcutaneously. Growth delays ranged from 7.6 days with D-245 MG to 62.1 days with D-456 MG (P < 0.001). J-107088 also produced an 83% increase in survival in mice bearing intracranial D-456 MG (P < 0.001).
These results indicate that J-107088 may be active in the treatment of childhood and adult malignant brain tumors and provide the rationale for initiation of clinical trials with this agent.
AuthorsC M Cavazos, S T Keir, T Yoshinari, D D Bigner, H S Friedman
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 48 Issue 3 Pg. 250-4 (Sep 2001) ISSN: 0344-5704 [Print] Germany
PMID11592348 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Carbazoles
  • Enzyme Inhibitors
  • Glucosides
  • Indoles
  • Topoisomerase I Inhibitors
  • edotecarin
  • Adult
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Brain Neoplasms (drug therapy)
  • Carbazoles (therapeutic use)
  • Child
  • Enzyme Inhibitors (therapeutic use)
  • Female
  • Glioma (drug therapy)
  • Glucosides (therapeutic use)
  • Humans
  • Indoles
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Survival Rate
  • Topoisomerase I Inhibitors
  • Transplantation, Heterologous
  • Treatment Outcome
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: