Studies

ENERCEL^® "IN VIVO STUDIES ON EXPERIMENTAL TUMORS "- 1992

Starting from this preliminary study accomplished on rats carrying induced mammary tumors, we emphasize the most important therapeutic effects observed from treatment with ENERCEL^® in various doses.

These effects produced by the treatment with ENERCEL^® are translated into an augmentation of the survival of the animals treated in comparison to the controls. Thus, the statistical studies demonstrate that the survival of the subject animals is significantly greater than that of the controls, with the different doses tested (p <0.01).

These observed responses seem be more obvious at higher doses. Thus, the tumors of the animals treated with a dose of 0.05 ml / day, did not show a marked stabilization of their growth, and in no case regression. Neither was observed at this dose the appearance of the characteristic central lesion. Nor was there meaningful increase in time of survival, as did the majority of the animals.

The effect on the body weight was evidenced with the different doses. The animals that received greater doses showed large fluctuations in the same and this as a rule is interrelated inversely to the evolution of the tumors.

In the animals of the control batch without tumors, which received treatment with 1 ml of ENERCEL^®, important fluctuations in weight were not observed, nor were meaningful increase in the same in relation to the controls without treatment observed.

ENERCEL^® produced fundamentally a recuperation and maintenance of body weight in the animals bearing tumors.

In no dose did the treatment with ENERCEL^® impede development of new tumors. This can be due to the fact that the process of carcinogenesis and subsequent malicious progression of the initial lesions is very slow, and at the moment at which the treatment is started these stages already are advanced. To be able to evaluate a preventive action of ENERCEL^® on the tumors' development, one ought to begin the treatment simultaneously with the administration of the first dose of the carcinogen. This protocol also would permit study of modifications in the latency period for the appearance of tumors.

Even though in almost 90% of the cases the evolution of the tumors was favorable, no complete regression of any tumor was observed. Beginning of the treatment in earlier development stages of the tumors, would permit us to appraise if this therapeutic response can be produced by action of ENERCEL^®.

The characteristic central lesion was observed in the cases of treatment with ENERCEL^® in greater doses. This response was not observed previously in this model in the tumors that regress by action of different treatments such as antiestrogens for action of different treatments as antiestrogens or bilateral ovariectomy.

The scarce quantity of analyzed samples does not permit extracting definitive conclusions in relation to the histopathological studies. Of the effected observations it can be said that:

** No necrotic areas were observed in the biopsies extracted from tumors belonging to rats treated with the drug under study, with any of the administered doses, nor at different treatment times.

** The result is that it is very difficult to obtain a conclusive analysis with respect to the histopathologic variations. As is indicated in the preceeding, in the tumoral model employed it is normal to observe in the histologic views a living together of different variations. This living together is observed as well in the animal tumors under treatment with the drug ENERCEL^®.

** The host reaction observed in the tumoral model is generally moderate, classifiable as 4-4-. The content of mastocites can be evaluated as moderate to high (4-4- to -4-+±), though its significance is not clear.

These parameters do not seem altered in the animal samples under treatment, with the exception of the rat whose photograph is illustrated, and that corresponds to the case 4ax of Table I, that present an exceptional host reaction.

These considerations deserve a more detailed study.

* * The organs of the observed treated animals evidenced conservation of their normal structures, which discards in principle that important toxic effects are produced by the treatment with ENERCEL^®. Finally it is important to clarify that this study 'in vivo' is not yet ended. There remain alive and continue with the treatment animals of the different batches under study. The evolution of these animals and the observations that are accomplished on them may permit us to structure a hypothesis clearer on the biologic mechanisms by which ENERCEL^® produces the therapeutic effects described herein.

Dra. Rose M. Bergoc Dra. Elena S. Rivera