Effects of Ultrasonic Disintegrates from Epimastigote Biomass of Trypanosoma cruzi Albarrada Strain (Mexico) on the Development of L5178Y Solid Malignant Transplanted Tumors in Male BALB/c Mice.

We studied in vivo antitumor effect of epimastigote form detritus of Trypanosoma cruzi, Mexican Albarrada strain, on L5178Y malignant tumor in BALB/c mice. The antitumor effect of ultrasonic detritus of the parasite was confirmed by shrinkage of the tumor and changed size of its symplastic necroses.

Effects of specific antibodies and immunocompetent cells on tumor growth in passive transfer experiment.

Experiments with passive transfer of immunocompetent cell and serum demonstrated suppression of tumor growth after transfer of splenocytes from animals immunized with Trypanosoma cruzi. The nonspecific constituent of antitumor effect of immunocompetent cells was detected. The previously reported oncoprotective effect of mucins 2 and 3 was not confirmed.

Integral approach to evaluation of the pathogenic activity of Trypanosoma cruzi clones as exemplified by the Mexican strain.

Comparative histopathological study and analysis of parasite load in different muscle groups were carried out in BALB/c mice during the acute phase of Chagas disease. Activities of C104 clone of T. cruzi strain TPAP/MX/2002/Albarrada and the parental strain were compared. Panoramic 2D-microscopy imaging of sample surface was used and quantitative analysis of parasitism and pathologic damage was performed. The infection rates in various muscle groups were as follows: myocardium=abdominal muscles=lumbar muscles=femoral muscles<--diaphragm for the clone and myocardium¬abdominal muscles=lumbar muscles=femoral muscles-->diaphragm for the parental strain.

Effects of human defensin-α(1)on Trypanosoma cruzi trypomastigotes in vitro.

Human defensin-α(1)is a biologically active peptide exhibiting a dose-dependent trypanocidal effect in vitro against trypomastigotes and amastigotes of Trypanosoma cruzi line Tulahuen. This effect is determined by fragmentation of parasite DNA reducing the capacity of passaged T. cruzi to invade HeLa cells.

[Antibodies against Trypanosoma cruzi in intact mice and their oncoprotective effect].

Trypanosoma cruzi antibodies that are important in the anticancer effect of this species of Trypanosoma were first detected in 14% of the 374 examined intact mice. These background antibodies were polyclonal, i.e. they reacted with one or other of 9 genetically different T. cruzi clones and detected antigenic determinants in different structures of a Trypanosoma cell. Their spread in the population varied with animal batches; the titers were not greater than 1:40 and the level remained steady during a one-month observation. The growth of Ehrlich's adenomacarcinoma inoculated to these mice was inhibited by 1.5-2.5 times and, in some cases, terminated in total regression. The paper discusses the capacities of such antibodies in man and their inductor-commonness of the antigens of the normal intestinal microflora and the cells of the vertebrate with T. cruzi.

[Immunization against Trypanosoma cruzi and tumor growth in mice].

The evidence has been produced that immunological mechanisms are involved in the known anticancer phenomenon of T. cruzi. Non-inbred albino mice were immunized with avirulent cultures of three strains and seven clones and then transplanted a tumor--sarcoma-180 or Ehrlich's adenocarcinoma. The used cultures induced the generation of T. cruzi antibodies whose level peaked by postimmunization days 50-60: the titers being 1:40-1:80 and the spread among the mice being 60%. Concurrently, immunization against T. cruzi provided a certain oncoprotective effect. In the immunized mice, the sizes of sarcoma-180 and adenocarcinoma were 1.5-2.0 and 2.0-2.5 times, respectively, less than those in the non-immunized ones. The antitumor protection was directly related to the murine blood T. cruzi antibody level during which implantation of a tumor occurred. At the peak of an immune response, the effect was 2 times higher than that in the early postimmunization periods. T. cruzi strains that were more immunogenic than clones ensured a more significant oncoprotection. The latter was more considerable in mice having antibody titers of 1:40-1:80 than in those with antibody titers of 1:10-1:20 and particularly in the animals showing no humoral response to the administration of the parasites at all.

The study of immunological component in antitumor effect of Trypanosoma cruzi.

The experiments with passive transfer of splenocytes obtained from animals immunized with Trypanosoma cruzi lysate revealed the role of cell-mediated component of the immunity in the antitumor effect of T. cruzi. The common features of T. cruzi antigens and tumor-specific antigens of Ehrlich's adenocarcinoma were demonstrated. These antigens were shown to have common epitopes with mammalian mucins. The oncoprotective effect was achieved by immunization with type II and III mucins and was reproduced after passive transfer of splenocytes from immunized animals.

In vivo anticancer activity of lysates from trypanosoma cruzi of different genetic groups.

Lyzed epimastigotes of Trypanosoma cruzi clones P209-1, Gamba1, Sp104-1, MASu, Y7/1, MN12, Cl-Brener, 86/2036, Y7/2-1 inhibit the growth of Ehrlich adenocarcinoma in mice. the tumor decreased 1.5-3 times after 12 daily injections of lysates from 15 million epimastigotes. The protective effect progressed after the injections were discontinued and depended on the dose and lysate producer clone. Trypanosoma lysates in the studied doses were nontoxic.

Genetic heterogeneity of Trypanosoma cruzi and its direct anticancer effect in cultured human tumor cells.

The direct inhibitory effect of Trypanosoma cruzi epimastigote lysates on in vitro cultured human breast cancer MCF-7 cells differs in various genetic groups and cloned subgroups of Trypanosoma.