In vitro and in vivo anti-tumor activity of recombinant mouse tumor necrosis factor (TNF) in a mouse bladder tumor (MBT-2). 1990

R R Bahnson, and T L Ratliff
Division of Urologic Surgery, University of Pittsburgh School of Medicine, PA.

Tumor necrosis factor (TNF) has confirmed anti-tumor activity. When used in combination with interferon gamma (IFNG) or chemotherapeutic drugs targeted at DNA topoisomerase II, synergistic cytotoxicity has been observed. Investigations of the anti-tumor activity of recombinant mouse TNF in a mouse bladder tumor model (MBT-2) were performed. The cytotoxicity of TNF and low dose actinomycin-D (AMD) against MBT-2 in vitro was examined alone and following preincubation with IFNG. The activity of TNF/AMD in vivo utilizing an intravesical implantation mode (MBT-2) was also evaluated. TNF alone had no cytotoxic effect in vitro. TNF/AMD was cytotoxic for MBT-2 growth in vitro. Maximum cytotoxicity (86%) occurred at one microgram./ml. TNF/one microgram./ml. AMD with 50% cytotoxicity at .64 micrograms./ml. TNF/one/microgram./ml. AMD. A two hour preincubation with IFNG markedly increased the cytotoxicity of TNF/AMD whereas longer incubations did not enhance cytotoxic activity. TNF alone and in combination with AMD did not significantly reduce the percentage of intravesical tumor outgrowth in vivo compared to controls. This study demonstrated that TNF/AMD exhibits cytotoxicity for MBT-2 cells in vitro but is ineffective in reducing implantation of intravesical tumors in vivo. The in vitro data suggest brief exposure of MBT-2 cells to IFNG augments the subsequent anti-tumor activity of TNF/AMD.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008809 Mice, Inbred C3H An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research. Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D001749 Urinary Bladder Neoplasms Tumors or cancer of the URINARY BLADDER. Bladder Cancer,Bladder Neoplasms,Cancer of Bladder,Bladder Tumors,Cancer of the Bladder,Malignant Tumor of Urinary Bladder,Neoplasms, Bladder,Urinary Bladder Cancer,Bladder Cancers,Bladder Neoplasm,Bladder Tumor,Cancer, Bladder,Cancer, Urinary Bladder,Neoplasm, Bladder,Neoplasm, Urinary Bladder,Tumor, Bladder,Tumors, Bladder,Urinary Bladder Neoplasm
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003609 Dactinomycin A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015) Actinomycin,Actinomycin D,Meractinomycin,Cosmegen,Cosmegen Lyovac,Lyovac-Cosmegen,Lyovac Cosmegen,Lyovac, Cosmegen,LyovacCosmegen
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260 Female Females
D000283 Administration, Intravesical The instillation or other administration of drugs into the bladder, usually to treat local disease, including neoplasms. Bladder Drug Administration,Drug Administration, Bladder,Instillation, Bladder,Intravesical Drug Administration,Administration, Intravesical Drug,Injections, Intravesical,Intravesical Administration,Intravesical Injection,Intravesical Instillation,Administration, Bladder Drug,Administrations, Bladder Drug,Administrations, Intravesical,Administrations, Intravesical Drug,Bladder Drug Administrations,Bladder Instillation,Bladder Instillations,Drug Administration, Intravesical,Drug Administrations, Bladder,Drug Administrations, Intravesical,Injection, Intravesical,Instillation, Intravesical,Instillations, Bladder,Instillations, Intravesical,Intravesical Administrations,Intravesical Drug Administrations,Intravesical Injections,Intravesical Instillations

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