RESUMO
Study of tumorigenic activity of cultured human chondroblasts intended for autologous transplantations showed that subcutaneous injection of human chondroblast suspension in a dose of 10(7)cells/0.2 ml did not cause the development of tumors in C.B-17 SCID immunodeficient mice over 12 weeks. Subcutaneous formations of compact cartilaginous consistency persisted at the site of chondroblast transplantation in all animals; these formations gradually shrank. Subcutaneous injection of tumor cell suspension (A204 human embryonic sarcoma) to C.B-17 SCID mice under the same conditions caused 100% development of tumors (poorly differentiated sarcomas) by day 14.
Assuntos
Transplante de Células , Condrócitos/citologia , Animais , Células Cultivadas , Humanos , Camundongos , Camundongos SCIDRESUMO
Pre-clinical toxicologic studies were conducted of a new drug teraphtal-Lio (TPh) and a teraphtal-Lio + ascorbic acid (TPh + AA) catalytic system recommended for binary catalytic therapy of malignant tumors. Quantitative criteria for "acute" and "chronic" toxicity of TPh and TPh + AA were established, which describe their toxic effects in single or multiple application. The coefficient of specific sensitivity and cumulation index for TPh and TPh + AA were determined. The toxicodynamic characteristics of TPh and TPh + AA were investigated. The results were used to prognose pulmonary, cardio-vascular, hemato- and hepatotoxic as well as hemodynamic and ophthalmologic disorders and functional changes in the central nervous system involved in clinical use of TPh and TPh + AA.
Assuntos
Antineoplásicos/toxicidade , Indóis/toxicidade , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Camundongos , Prognóstico , Ratos , Fatores de TempoRESUMO
A binary teraphtal-Lio + ascorbic acid (Tph + AA) catalytic system has been tested for untoward side-effects using three procedures of regional intraarterial infusion on dogs. On the basis of the data on local-tissue and overall toxicity, an optimal one was selected and recommended for clinical use.
Assuntos
Antineoplásicos/toxicidade , Indóis/toxicidade , Animais , Antineoplásicos/administração & dosagem , Cães , Feminino , Humanos , Indóis/administração & dosagem , Infusões Intra-Arteriais , Masculino , Prognóstico , Fatores de TempoRESUMO
Teraphtal-Lio (Tph) exerted a toxic dose-dependent effect on the hemostatic system. Treatment of experimental animals with maximum tolerated and highly toxic doses was followed by acute DVS syndrome formation involving a hemophilic condition, soaring activated partial prothrombin time, absence of fibrinogen, sharp rise in fibrinogen degradation product and D-dimer matched by fall in thrombocyte count. No toxic influence on the hemostatic system was registered when Tph doses recommended for humans in the course of phase II clinical trials were administered to animals.