zinostatin and Astrocytoma

Neocarzinostatin (NCS) linked to the thiol group on the hinge region of the Fab' fragment of GA-17, a murine monoclonal antibody reacting with tyrosine-specific phosphorylated antigens, which are exclusively expressed on the cell surface of human astrocytomas, was evaluated for in vivo activity. GA-17-NCS immunoconjugates significantly suppressed the growth of human malignant glioma cell line U87-MG subcutaneous xenografts in nude mice until day 50 when administered intravenously into the tail vein. Disulphide- and thioether-linked GA-17-NCS were nearly equipotent immunoconjugates, but thioether-linked GA-17-NCS was more effective than disulphide-linked conjugates with 250 U/kg NCS content on day 50 (P < 0.05). Thioether-linked GA-17-NCS was significantly more effective on day 50 than free NCS with 500 U/kg or 250 U/kg NCS content (P < 0.05, P < 0.01, respectively). These results suggest that GA-17-NCS may prove useful in the treatment of human malignant gliomas.

Topics: Animals; Antibodies, Monoclonal; Astrocytoma; Cell Survival; Drug Screening Assays, Antitumor; Glioma; Immunotoxins; Mice; Mice, Nude; Zinostatin

Topics: Adult; Aged; Antibiotics, Antineoplastic; Astrocytoma; Brain Neoplasms; Carotid Arteries; Combined Modality Therapy; Female; Glioma; Humans; Injections, Intra-Arterial; Male; Middle Aged; Zinostatin

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Astrocytoma; Brain Neoplasms; Carotid Artery, Internal; Chemotherapy, Cancer, Regional Perfusion; Eye Diseases; Female; Glioma; Humans; Male; Middle Aged; Zinostatin

Topics: Adult; Aged; Antibiotics, Antineoplastic; Astrocytoma; Brain Neoplasms; Child; Female; Glioma; Humans; Male; Zinostatin

Neocarzinostatin as previously reported, appeared to exhibit an intense cytotoxicity to the glioblastoma cells and some other malignant brain tumor cells, such as pineal germinoma or medulloblastoma, which are notoriously known to disseminate into the cerebrospinal fluid space. In vitro study, the minimum susceptibility of glioblastoma cells to neocarzinostatin was found to be below 0.005 microgram/ml, whereas normal glia cells were not affected at 0.3 microgram/ml. This study indicated that neocarzinostatin was extremely effective in the treatment of malignant brain tumor without affecting normal neural tissue. Pharmacokinetic study was performed in order to establish intermittent intrathecal perfusion therapy and to prevent subarachnoid dissemination of the brain tumor cells. Experimental results were applied to the treatment of 12 patients with brain tumor, who had shown positive cytology of the cerebrospinal fluid. Follow-up investigation showed quite a favorable result and it was considered that prophylactic irradiation to the entire spinal column could be replaced with intrathecal administration of neocarzinostatin. During clinical application no noticeable side effect was encountered and active stimulation of macrophages, which were mobilized into the CSF space, was another unexpected advantage of this treatment.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Astrocytoma; Brain Neoplasms; Cerebrospinal Fluid Shunts; Child; Child, Preschool; Female; Glioma; Humans; Injections, Intraventricular; Injections, Spinal; Kinetics; Male; Medulloblastoma; Middle Aged; Pinealoma; Zinostatin