Antitumor efficacy of an isolated hind legperfusion with a pH-increased solution in thePliss’ lymphosarcoma graft rat model

Abstract

Background: The technique of regional isolated perfusion makes it possible to increase local levels of an anti-tumor agent, to perform the treatment procedure under hypothermia or hyperthermia, to reduce or even eliminate any systemic effect of a cytostatic on the patient. In this context, the use of isolated perfusion to modify the pH milieu of the tumor seems to be a promising strategy that could potentially ensure the anti-tumor effect.
 Aim: To evaluate the efficacy of a rat limb perfusion with 4% NaHCO3 solution in vivo in the Pliss' lymphosarcoma rat graft model.
 Materials and methods: The experiment was carried out in Wistar rats with Pliss' lymphosarcoma graft. The isolated limb was perfused with an isotonic sodium chloride solution (the control group) or a 4% sodium bicarbonate solution (the treatment group). The following parameters were assessed: tumor node growth over time, survival rate, hematology analysis at various time points of the experiment, and histological examination of autopsy samples from the tumor.
 Results: Median survival in the group perfused with 4% NaHCO3 (N = 6) was 17.2 days, whereas in the non-perfused group (the pathogenesis group) (N = 4) and in the group perfused with isotonic saline (N = 5) they were 13.2 and 13.6 days, respectively. The risk of death in the treatment group was lower compared to that in the control group (Cox regression model, hazard ratio 0.129; 95% confidence interval 0.0280.583; p = 0.0079). There were no significant differences in the tumor growth rate over time in the perfused groups.
 Conclusion: A single exposure of the tumor micro-milieu in the model with isolated perfusion of the limb with Pliss' lymphosarcoma graft does not lead to any changes in the tumor growth kinetics, but is associated with a change in the animal survival.

Tumor acidity: From hallmark of cancer to target of treatment

“…In another study, perfusion was performed with a 4% sodium bicarbonate solution of rat limbs with a Pliss lymphosarcoma graft. The median survival in the sodium bicarbonate group was 17 days, while in the nonperfused group and in the isotonic saline group it was 13 days ( 17 ).…”

“…The acidity of the TME could be used for the drug delivery of cytotoxic agents and/or carriers that are more active and/or change physicochemical properties under such conditions ( 11 – 13 ). It is very attractive to increase the pHe by a combination of an alkaline diet and bicarbonate therapy ( 14 – 16 ) or by direct local isolated perfusion of the tumor with bicarbonate solutions ( 17 , 18 ).…”

Tumor alkalization therapy: misconception or good therapeutics perspective? – the case of malignant ascites

“…In our study, we examined the effects of a single perfusion using a 4% sodium bicarbonate solution on rat limbs with a Pliss lymphosarcoma graft. We found that the median survival period for the sodium bicarbonate group was 17 days, which was longer than both the nonperfused group and the isotonic saline group, which had median survival periods of 13 days ( 13 ). The clinical study ChiCTR-IOR-14005319 evaluated and compared the efficacies of conventional transarterial chemoembolization (TACE) and targeting intratumoral lactic acidosis TACE (TILA-TACE) with the local administration of a 5% sodium bicarbonate solution in patients diagnosed with large-focal hepatocellular carcinoma.…”