RESUMO
The treatment of exponentially-growing B16 melanoma cells with teniposide causes a dose- and time-dependent decrease of cell survival. By means of the nucleoid technique, the formation of double strand breaks was demonstrated in the nuclei of the treated cells, indicating a possible involvement of topoisomerase II. DNA double strand breaks were rapidly but ineffectively repaired. Morphometric and densitometric analyses showed that teniposide treatment causes a considerable increase of nuclear area, nuclear DNA and cell size, associated with a lowering of the mitotic index to less than one hundredth of that of the controls. The cytocidal effect of VM-26 can be potentiated by the addition of a non-lethal dose of lonidamine, whose synergism is particularly evident at low teniposide concentrations.
Assuntos
Antineoplásicos/farmacologia , Indazóis/farmacologia , Podofilotoxina/análogos & derivados , Pirazóis/farmacologia , Teniposídeo/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Interações Medicamentosas , Ensaios de Seleção de Medicamentos Antitumorais , Melanoma Experimental , Camundongos , Índice Mitótico/efeitos dos fármacos , Células Tumorais Cultivadas/citologiaRESUMO
Papain-immunized mice possess serum antibodies which cross-react with cathepsin-B- and cathepsin-H-like endopeptidases isolated from B16 melanoma cells. The growth rate, invasion and metastasis of both the B16 melanoma and the Lewis lung carcinoma were inhibited in mice immunized with papain. These animals presented an increased mean survival time as compared to the tumor-bearing nonimmunized controls. Quantitative microscopy suggested that vasodilation and edema, associated with tumor invasion, are, at least partially, sustained by proteolytic enzymes, being strongly reduced when tumor cells were inoculated in papain-immunized mice.
Assuntos
Cisteína Endopeptidases , Neoplasias Pulmonares/imunologia , Melanoma Experimental/imunologia , Papaína/imunologia , Músculos Abdominais/anatomia & histologia , Músculos Abdominais/patologia , Animais , Anticorpos/imunologia , Formação de Anticorpos/efeitos dos fármacos , Caseínas/metabolismo , Catepsina D/sangue , Catepsina D/imunologia , Catepsina D/metabolismo , Catepsina H , Catepsinas/imunologia , Catepsinas/metabolismo , Divisão Celular/efeitos dos fármacos , Reações Cruzadas/imunologia , Eletroforese em Gel de Poliacrilamida , Imunização , Injeções Intraperitoneais , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Melanoma Experimental/enzimologia , Melanoma Experimental/patologia , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Papaína/metabolismo , Transplante HeterólogoRESUMO
A doxorubicin-lecithin preparation was tested in vitro on B16 melanoma and Lewis lung carcinoma cells, and in vivo on C57BL/6 mice inoculated with 3LL cells. Results obtained demonstrated that the preparation possesses the same antitumor activity as doxorubicin. The cardiotoxicity of doxorubicin and of the doxorubicin-lecithin association were studied for 120 days after the end of the treatments in Wistar rats inoculated once a week for 5 weeks with equivalent doses of the drugs. Myocardial lesions were observed in both the groups of animals, but their severity and extent were reduced in rats treated with the doxorubicin-lecithin association, and their onset was also delayed.
