EFFECTS OF HIGH-ENERGY SHOCK-WAVES COMBINED WITH BIOLOGICAL RESPONSE MODIFIERS IN DIFFERENT HUMAN KIDNEY CANCER XENOGRAFTS

We have studied the effects of high-energy shock waves (HESW) alone or in combination with biological response modifiers on the growth of five human kidney cancer xenografts in mice. Exposure of the tumors to three sessions of 800 shock waves every 48 hours with 18.4 kV, 37.5 MPa, on the commercially available Lithostar resulted in a temporary growth delay. The sensitivity for HESW was related to the doubling time of the tumor. Several days after stopping the HESW administration the tumors regained their original growth potential with the same doubling time. The systemic application of Tumor Necrosis Factor-alpha (TNF-alpha, 500 ng/g body weight 5 times/week) and/or Interferon-alpha (IFN-alpha 5.0 ng/g body weight, 3 times/week) subcutaneously around the tumor also had a limited effect on the growth of these established tumors (60-80 mm3). The combination of HESW with TNF-alpha and IFN-alpha resulted in an almost complete cessation of tumor growth in the NU-1 human kidney xenograft and had an additive antitumor effect in the NU-3. Synergism was also seen in the NU-1 and NU-3 with the combination of HESW and TNF-alpha, while the combination with IFN-alpha had only a limited effect on tumor growth. So TNF-alpha was the active agent, that enhanced the antiproliferative effects of shock waves. In the NC-65 tumor (same doubling time as the NU-1 and NU-3, but less well vascularized), the antiproliferative effect of HESW was not potentiated by TNF-alpha. In the slowly growing NU-10 and NU-12, the combined treatment was synergistic in the well-vascularized NU-10 but had no potentiating antitumor effect in the poorly vascularized NU-12. We conclude that TNF is able to potentiate the antiproliferative effect of shock waves. The differential sensitivity of the tumors for the combined treatment is likely to be related to the vascularization and doubling time of the tumor.