Tumour pH drop after cryotreatment and enhancement of hyperthermia antitumour effect.

Our previous study demonstrated a selective drop of pH, PO2 and blood flow in tumours under induced hyperglycaemia that enhanced the antitumour effect of hyperthermia. However, there are contraindications restricting the use of hyperglycaemia. Cryotreatment, as a method of altering tumour microphysiology similar to hyperglycaemia, was investigated. Guerin carcinoma pH was measured after cryotreatment (-15 to -20 degrees C at the tumour and normal tissue boundary; -110 to -120 degrees C at the cryoinstrument tip). It was determined that tumour pH immediately after complete tumour thawing (10 degrees C) was 6.08 (range 5.5-6.3), by 2 h it was 6.34 (range 6.2-6.4), by 4 h it was 6.42 (range 6.1-6.8) and by 24 h it was 6.54 (range 6.3-6.6). Complete tumour regression (%) and survival of rats with both the tumour regrowth and the partial tumour regression (days) after a single treatment were as follows: control -zero, 28 +/- 4; hyperthermia (2450 MHz, 43 degrees C, 60 min) -zero, 30 +/- 3; cryotreatment -14, 35 +/- 5; cryotreatment+hyperthermia -41, 46 +/- 5. It is planned to use combined cryotreatment+hyperthermia in a clinical trial for certain accessible tumours.

Induced hyperglycemia and tumor chemotherapy: experimental and clinical studies.

In order to clarify the influence of induced hyperglycemia upon antitumor effects of chemotherapy we studied some animal and human tumors. We observed that hyperglycemia enhances the antitumor effects of some cytostatic drugs several fold, due in part to the changes in the microphysiology induced by the hyperglycemia. Time doubling of some transplanted rat tumors and survival time of rats, rabbits and dogs bearing the transplanted and spontaneous tumors increased two to ten fold when the chemotherapy was used under hyperglycemia. Remission duration in patients with malignant brain glioma was enhanced by an average of six months; two years survival increased two-fold and the three years survival in patients with ovarian carcinoma in Stage III-IV increased two-fold; five years survival, 1.5-fold. The number of complications due to the combination of hyperglycemia and chemotherapy were not increased significantly. The problems of combination chemotherapy and hyperglycemia for oncologic patients' treatment are under discussion.

Tumour pH under induced hyperglycemia and efficacy of chemotherapy.

Blood glucose and insulin content, as well as tumour pH, were evaluated under induced hyperglycemia in Wistar or strain IOP rats bearing Guerin carcinoma. The average tumour pH decreased to 5.2-5.4, and could be maintained at this level for at least 24 hr. It was demonstrated that the antitumour effect of thiophosphamide was greatly enhanced under conditions of low tumour pH. The length of survival of rats bearing a Guerin carcinoma increased 6-fold when thiophosphamide was injected during the induced hyperglycemia.

[Intensification of tumor acidification in artificial hyperglycemia using inorganic phosphate]. / Verstärkung der Tumorübersäuerung unter Bedingungen von künstlicher Hyperglykämie mit Hilfe anorganischen Phosphats.

Using pH glass microelectrodes with maximum diameters of 100-200 micron (sensitivity 55-60 mV/pH unit at 37 degrees C; drift 0,001-0,002 pH unit/hr) pH has been measured in transplanted tumors (Guerin carcinoma, Pliss lymphosarcoma, Krocker sarcoma) and in muscle under artificial hyperglycaemia. We showed the ability of inorganic phosphate to amplify the process of acidification of the tumor tissue under these conditions. Using inorganic phosphate it was possible to reach pH values of 4,6-5,0 in different experimental tumors.