medicină veterinară - Ion Ionescu de la Brad

Universitatea de Știinţe Agricole și Medicină Veterinară
and T/C (0.55) values. In this case the T/C x 100 value is 55%. The resulting admissible variability field
has an upper limit of 100.1 % and a lower one of 30.2%. The first retest has confirmed the significant
cytostatic property of EGlClp extract: M.T.R. = 40.9% and T/C ratio = 0.53. The corresponding T/C x
100 value was 53% and the T/C value product of the two tests 0.29.
The second retesting was also correlated with values of the evaluation indices of the
antitumoral effect, induced by EGlClp, that were close to those in the first retesting: 48.9% (M.T.R.)
and 0.51 (T/C ratio). The T/C x 100 value of the final retest was 51%. The product of the ratios
corresponding to all successive tests was 0.15.
DISCUSSIONS
The programs of biphasic and multistage preclinical screening in vitro and in vivo – designed to
identify new oncochemotherapeutic agents – require, among other things: numerous, successive and
interdependent steps of research; evaluation indices of the specific pharmacodynamic effect;
qualitative and quantitative assessment criteria of the induced antitumoral action (3-6, 9-11, 12, 13,
17, 20-22, 24, 27, 30, 34).
The enormous number, the various nature (biosynthesis, semisynthesis and synthesis) and the
structural diversity of the bioactive compounds with putative anticancerous action have made it
necessary to include a preliminary phase of in vitro testing upon tumoral cell cultures (3-5, 18, 21, 22,
24, 27). This ensures – by means of the required assessment criteria – the selection of only the active
cytostatic and/or cytotoxic agents, which will then be included in the successive and interdependent
steps of the in vivo preclinical screening on animals with various experimental tumoral lines (3, 5, 8,
14, 18, 22, 23, 27, 30, 36). The qualitative and quantitative evaluations of their specific inhibitory
effect on the tumor development process may allow the final preclinical pharmacological
characterization of such substances as new oncochemoterapeutic agents.
The preclinical characterization of a substance as an antineoplastic agent requires, on the one
hand, the demonstration of its cytostatic action and of the replicability of its pharmacodynamic effect
in appropiate experimental models. These are the objectives of the qualitative pharmacological
evaluation. On other hand, one needs to assess the antitumoral therapeutic effectiveness by
establishing the existence of a dose – response relationship, comparing the action of the new drug on
the tumor generation process with that of a standard cytostatic used in clinical practice and bringing
proof of a significant anticancerous effect in tumors with different degrees of development. This is
the purpose of the quantitative pharmacological evaluation.
In vitro characterization of the EGlClp glucanic extract as potential cytotoxic and/or cytostatic
agent on some tumoral cell cultures of human origin, was a condition for their passing in the complex
program of the in vivo preclinical screening (19, 25, 26).
Consequently, in a first stage, we have studied, on rats with various experimental solid
tumoral systems, the influence of therapy with EGlClp upon the development of Guerin T8
lymphotropic epithelioma and Walker 256 carcinosarcoma in order to demonstrate their antitumoral
pharmacodynamic effect. The tests, performed on both experimental tumor lines, have revealed the
anticancerous activity of the autochthonous glucanic extract, it being illustrated by the M.T.R. of
48.7%, in the case of lymphotropic epithelioma, and respectively of 44.6%, in the case of the
carcinosarcoma, and by T/C values of 0.51 and respectively 0.55.
In order to appreciate the impact of the studied bioactive agent upon the tumour
development we had to compare our values of the evaluation indices with those stipulated in the
selection criteria for oncochemotherapeutic agents. The reference values are established also by the
multistage preclinical screening program of the Institute of Microbiology and Experimental Therapy in
Germany and of the National Cancer Institute in the U.S.A. In accordance with these reference
programs – for a primary testing – the experimental antitumoral treatment must determine in at
least one solid tumoral system out of three that have been tested a M.T.R. of minimum 35%,
compared to controls (14), or must correlate with a T/C value of 0.54 – 0.64 (5, 18).
The comparative analysis of our evaluation indices values with the standard ones highlights
the antitumoral pharmacodynamic effect of the EGlClp glucanic agent.
This observation has imposed thoroughgoing research in order to demonstrate the
reproducibility and stability of the oncostatic property of this biosynthetic preparation. Thus, we have
290