Suppression of Ehrlich ascites tumor growth by immunization with ganglioside GT1b of its origin, its IgM antibody or anti-idiotype of the anti-GT1b IgM.

Ehrlich tumor expresses the ganglioside GT1b. The plasma of mice with Ehrlich ascites tumor burden also contains GT1b. The structural identity of plasma GT1b was ascertained by a series of enzymatic degradation and mass spectral analysis. Mice were vaccinated with purified plasma GT1b admixed with Freund's adjuvant (FA). Sixty nine percent suppression of Ehrlich ascites tumor growth was observed in vaccinated mice. The suppression was dose-dependent. It is hypothesized that the tumor growth-suppression is a result of immune response to GT1b Humoral immune response to GT1b was demonstrated by passive hemagglutination assay of the sera of vaccinated mice. To test the hypothesis, the mice were administered with rabbit polyclonal anti-GT1b IgM antibody in varying doses and challenged with Ehrlich tumor. A significant reduction in tumor growth (65%) was observed in mice administered with anti-GT1b IgM antibody. Again, the suppression was dose-dependent. To verify further, another batch of mice was immunized with anti-idiotypic antibodies to rabbit anti-GT1b IgM raised in rat. The polyclonal anti-idiotype antibody is expected to carry the structural image of GT1b. In a dose-dependent manner, a maximum of 82% suppression of tumor growth was observed in mice immunized with the anti-idiotype antibody. This observation further strengthened the hypothesis that ganglioside mediated suppression of tumor growth may be a result of immunogenicity of the target ganglioside. This was also supported by positive reaction of the sera of anti-idiotype vaccinated mice with both anti-idiotype antibody and ganglioside GT1b in passive hemagglutination assay. The results favour the therapeutic potential of immunogenic tumor-associated gangliosides.

Correlation and modulation of Ehrlich ascites tumor growth with tumor-plasma IgA.

Plasma IgA level of Ehrlich ascites tumor bearing mice showed correlation with progress of tumor growth. In PAGE analysis total plasma IgA separated into 3 major bands corresponding to mol. wt. > or = 669,000 daltons, identical to 443,000 daltons and between 443,000 and 150,000 daltons. All the three bands increased gradually with progress of tumor growth upto day 14 and then declined on day 16. Total plasma IgA isolated by anti-IgA affinity chromatography when adoptively transferred to mice inhibited tumor growth. Affinity-purified plasma IgA separated into three major peak fractions after Sephadex G-200 column chromatography which corresponded with the bands of IgA on PAGE analysis. Three Sephadex G-200 IgA fractions when adoptively transferred to tumor-bearing mice showed effect different from total IgA. High mol. wt. IgA fraction (> or = 669,000 daltons) inhibited tumor growth whereas medium mol. wt. fraction (identical to 443,000 daltons) enhanced tumor growth. The low mol. wt. IgA fraction (< 443,000 and > 150,000 daltons) had no significant effect on tumor growth. The high mol. wt. IgA fraction enhanced tumor killing ability of peripheral blood lymphocytes (PBL) and peritoneal macrophages of tumor bearer in vitro. Medium mol. wt. IgA fraction inhibited tumor-killing ability of PBL in vitro but had no significant effect on peritoneal macrophages. The low mol. wt. IgA fraction showed a mild enhancing effect on tumor-killing ability of PBL but had no significant effect on peritoneal macrophages. The results established importance of IgA in tumor growth regulation and its therapeutic potentiality. The results indicated that tumor growth modulation by tumor plasma IgA is also mediated by its effect on cellular anti-tumor immune factors of the host.

Study of interactions between Listeria monocytogenes and experimental tumors

OBJECTIVE--to verify the effects of Listeria monocytogenes (LM) inoculation in the survival of animals bearing Ehrlich's tumor. KIND OF STUDY--experimental. Animals-isogenic mice, Balb/c, female, 19-21 g. Tumor-Ascitic Ehrlich's tumor, dilution of 5 x 10(5) cells/0.1 ml. Bacteria-LM serotype 4a, solution with 7 x 10(3) bacteria (standard sub-lethal dose). Intervention-a) inoculation of LM in mice bearing Ehrlich tumor at the same time as ascitic cells transplantation. b) inoculation of LM seven days before and, again, seven and fourteen days after ascitic cells transplantation. c) to study the effect of using ampicillin 100 mg/kg, im, simultaneously with the inoculation of Ehrlich tumor and LM organisms and, again, 3, 5, 7, 14, 21 and 30 days after the ascitic cells transplantation. ANALYSIS--Chi-square test; p < 0.05 RESULTS AND CONCLUSION--LM increases significantly the survival of mice bearing Ehrlich tumor even when only one inoculum of viable LM was used, seven days before or seven days after the ascitic cells transplantation. The use of ampicillin after the inoculation of LM and tumor transplantation does not alter the survival of mice

Alteraçäo da resposta inflamatória e imunológica em animais portadores de tumor experimental / Alteration on inflammatory and immunological response in animal carriers of experimental tumor

Os autores estudaram em camundongos portadores de tumor de Walker as alteraçöes de resposta a agente inflamatório e as modificaçöes de reaçöes imunológicas, assim como o período no qual se tornam evidentes. Usaram como agente inflamatório a carragenina e como parâmetro imunológico o teste de hipersensibilidade ao BCG. As conclusöes foram que os animais portadores de tumor apresentam diminuiçäo na capacidade de resposta inflamatória inespecífica à carragenina e ao CBG, assim como no teste de hipersensibilidade tardia ao BCG

Characterization of the antitumor activity of a polyantigenic immunomodulator (PAI): I. Utilization of cimetidine and cyclosporine A

Hemos utilizado cimetidina (CMT), ciclosporina a (CsA) e interleuquina 2 (IL-2) para caracterizar el efecto anticanceroso de un inmunomodular poliantigéncio (polyantigenic immunomodulator, PAI). PAI consiste de una mezcla inactivada de bacterias y virus de influenza, emulsificada en una preparación de aceite de maní-arlacel A-monoesterato de alumini. La actividad antitumoral fue evaluada utilizando el tumor ascítico de Ehrlich implantado en ratones Swiss-Webster (alogenéicos) o C57BL/6J (singenéicos). La actividad antitumoral de PAI aumentó con la CMT actuando sinergisticamente al reducir sustancialmente el crecimiento tumoral e incrementar el porciento de sobrevivencia de los ratones, mientras que la CsA suprimió esta actividad. PAI o sus componentes individuales indujeron blastogénesis en linfocitos de bazo de ratón C57BL/6J e interleuquina 2 aumentó considerablemente esa respuesta. Los resultados sugieren que PAI actúa a nivel de la inmunidad celular

Characterization of the antitumor activity of a polyantigenic immunomodulator (PAI): II. Involvement of NK cells and adoptive immunotherapy

La actividad de células naturales (natural Killer cells, NK) y la inmunoterapia adoptiva fueron utilizados para caracterizar el efecto antitumoral del inmunomodulador poliantigénic immunomodulator, PAI). PAI consiste de una mezcla inactivada de bacterias y virus de influenza, emulsificada de bacterias y virus de influenza, emulsificada en una preparación de aceite de maní - arlacel A-monoesterato de aluminio, la cual se ha demostrado previamente que posée actividad antitumoral enratones implantados con el tumor de ascites de Ehrlich. La administración de PAI, su componente de Ehrlich. La administración de PAI, su componente bacteriano o el viral injectados en ratones Swiss-Webster (alogenéicos) y C57BL/6J (singenéicos) aumentaron maracadamente la actividad in vitro de células NK del bazo, especialmente durante el período temprano post-inducción. Además, linfocitos alogenéicos o singenéicos sensitizados por PAI fueron efectivos en ser transferidos a ratones con tumor ascítico de Ehrlich reduciendo el crecimiento tumoral e incrementando la sobrevivencia. Estos resultados confirman nuestra previa sugerencia de que PAI actua a nivel de inmunidad celular. Por lo tanto substancias poliantigénicas complejas, tal como PAI, podrían utilizarse directamente solas, en combinación con otros inmunoadyuvantes o para sensitizar en una forma global células immunocompetentes para ser utilizadas en inmunoterapia adoptivas

Açäo da cimetidina na sobrevida de camundongos inoculados com tumor de Ehrlich / Action of cimetidine on the survival of mice inoculated with Ehrlich's tumor

Os autores estudaram o efeito da cimetidina na sobrevida de camundongos inoculados com o tumor de Ehrlich e concluíram que a droga aumenta a sobrevida desses animais, sugerindo ainda uma açäo imunomoduladora dessa substância

Efeitos anti-tumorais de drogas anti-H2 / Antitumor effects of histamine H2 receptor blockaders

Os autores estudaram a sobrevida de camundongos inoculados com o tumor de Ehrlich e concluíram que a famotidina e a ranitidina aumentaram a sobrevida destes aimais. Os autores também descreveram que a cimetidina, famotidina e a ranitidina näo alteram a hipersensibilidade tardia do BCG

Evoluçäo do carcinoma mamário: novos parâmetros imunopatológicos de avaliaçäo; estudo experimental em camundongos (MuMT), I - Hematopoiese esplênica / Course of mammary carcinoma: new immunopathological parameters of evaluation; experimental study in mice (MuMT), T-Splenic hematopoiesis

Foram identificadas e contadas especificamente colônias das diferentes linhagens hematopoiéticas no baço. Grupo controle - Trinta camundongos normais constituiram os parâmetros normais. Grupo experimental - Duzentos camundongos foram inoculados intraperitonealmente com MuMT e sacrificados diariamente em sub-grupos de dez, abrangendo toda a evoluçäo da neoplasia. Os resultados mostraram uma primária excitaçäo dos monócitos e linfócitos B, seguida de progressiva regressäo porcentual. Há depressäo abrupta inicial dos linfócitos T, os quais após dois dias passam a apresentar lenta recuperaçäo, sem contudo atingir os níveis normais. Os granulócitos apresentam aumento progressivo em seu porcentual do 1§ ao 20§ dia. Os eritrócitos apresentam ligeiro aumento porcentual nos primeiro dois dias e depois progressivamente decaem até o final da experimentaçäo. Os megacariócitos apresentam aumento de porcentagem média inicial (0-2 dias) e no 5§ dia sofrem uma queda abrupta seguida da recuperaçäo gradual até o 20§ dia. As porcentagens nunca ficaram abaixo da normal

Estrógeno em tumor de Ehrlich: estudo da sobrevida e avaliaçäo da resposta imunológica / Estrogen in Ehrlich's tumor survival study and immune response evaluation

Estudou-se a sobrevida de camundongos inoculados com tumor de Ehrlich na vigência de tratamento estrogênico, e concomitantemente fêz-se uma avaliaçäo da atividade imunológica em um grupo paralelo. Concluiu-se que os estrógenos aceleram a mortalidade de camundongos machos portadores de tumor de Ehrlich e näo provocavam alteraçöes no número de macrófagos e atividade fagocitária em resposta à inflamaçäo. Os camundongos que receberam tumor de Ehrlich também näo apresentaram diferenças em relaçäo ao grupo de camundongos normais