Variability and Discontinuity of the Pathognomonic Systemic Effects Caused by Walker 256 Tumor Progression in Rats

Abstract

Cancer pathognomonic systemic effects (PSE) have high individual variability. For this reason present data were collected daily and synchronized considering four main points: inoculation day, onset of PSE, aggravation and death. The subclinical period free of PSE ranged between 15.7 +/- 2.2 days, the clinical period was less variable, 8.9 +/- 0.5 days, divided in a moderate and a grave phase of nearly the same length. PSE involved disturbances of fundamental homeostatic regulations: appetite, sodium, water, immune, etc. PSE triggering correlated highly with survival (r2 = 0.95, P < 0.01), but poorly with primary tumor growth, and it was anticipated by metastases from 20.5 +/- 2.6 to 10.6 +/- 1.1 days (P < 0.01). After multifocal simultaneous inoculations, PSE triggering was anticipated to 4.2 +/- 0.2 days (marked reduction of individual variability), in the presence of small total-tumor masses, absence of macroscopic metastases, and without changes in the following clinical period features. PSE triggering seems to be a major prognostic indicator probably related to multifocal tumor growth.

The hemolytic component of cancer anemia: effects of osmotic and metabolic stress on the erythrocytes of rats bearing multifocal inoculations of the Walker 256 tumor

“…The effects began 3-4 days after inoculation and progressed rapidly thereafter, and would have resulted in death 8-9 days later (7,8) if the rats had not been sacrificed at fixed times according to the experimental protocol. The effects developed in the absence of complications such as bleeding, invasions or visible metastases, as confirmed at autopsy.…”

“…However, if instead of the usual unifocal tumor growth model, the studies are initiated using multifocal simultaneous tumor inoculations (simulating the metastatic dissemination of the final stage), the systemic effects of cancer, including anemia, appear rapidly and synchronously in all animals (7,8). The development of anemia under these conditions is similar to that found in terminal cancer patients, in which the rate of RBC destruction is very high (4,9).…”

Tumor growth characteristics of the Walker 256 AR tumor, a regressive variant of the rat Walker 256 A tumor

“…At autopsy, tumors were dissected and weighed, allowing the confirmation of the estimated tumor weight. When necessary, correction of tumor weights recorded along the sc development of the tumors was carried out by introducing a correction factor, as previously described (Rettori et al, 1995).…”

“…The Walker 256 (W256) tumor has been extensively used in the studies of cancer pathophysiology, tumor cell metabolism and immune response (Toal et al, 1960;Morrison, 1971;Rettori et al, 1995;Guimarães et al, 1999;Buffon et al, Degasperi et al, 2006;Perroud et al, 2006). Two variants of this tumor have been previously reported as W256 A and B (Guaitani et al, 1982), which are currently known by their growth capacity and lethality after subcutaneous (sc) injection in Wistar rats.…”

“…Two variants of this tumor have been previously reported as W256 A and B (Guaitani et al, 1982), which are currently known by their growth capacity and lethality after subcutaneous (sc) injection in Wistar rats. This lethality is associated to the severe homeostatic disturbances induced by the W256 tumor, which includes anorexia (Rettori et al, 1995;Guaitani et al, 1982), anemia (Zucker et al, 1977;Vido et al, 2000), thymus atrophy (Rettori et al, 1995) and hydro electrolyte disturbances with glomerular filtration and tubular function alterations (Toal et al, 1960;Morrison, 1971;Rettori et al, 1995;Guimarães et al, 1999;Rettori et al, 2000). Nevertheless, spontaneous W256 tumor regression can occur.…”