Guest guest Posted December 22, 2003 Report Share Posted December 22, 2003 (OK, this IS novel. Not applicable to CLL, but interesting nevertheless.) Experimental Therapeutic British Journal of Cancer (2003) 89, 2333-2339. doi:10.1038/sj.bjc.6601457 Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth and metabolic microenvironment D K Kelleher1, O Thews1, A Scherz2, Y Salomon3 and P Vaupel1 1Institute of Physiology and Pathophysiology, Johannes Gutenberg- University Mainz, Duesbergweg 6 D-55099 Mainz, Germany 2Department of Plant Science, The Weizmann Institute of Science, 76100 Rehovot, Israel 3Department of Biological Regulation, The Weizmann Institute of Science, 76100 Rehovot, Israel Received 30 July 2003; revised 7 October 2003; accepted 8 October 2003 The effects of combined and simultaneously applied localised 43°C hyperthermia (HT) and an antivascular bacteriochlorophyll-serine- based photodynamic therapy (Bchl-ser-PDT) on tumour growth and several microenvironmental parameters were examined. Rats bearing DS- sarcomas were allocated to treatment groups: (i) sham-treatment (control), (ii) Bchl-ser-PDT (20 mg kg-1 i.v.), (iii) localised HT, (iv) Bchl-ser-PDT+HT. The light source used was an infrared-A irradiator, which, by use of appropriate filters, delivered the different ranges of wavelengths required. Following treatment, tumour volume was monitored. The greatest tumour growth inhibition was seen with Bchl-ser-PDT+HT, and subsequent experiments identified the pathophysiological basis for this effect. Red blood cell flux in tumour microvessels declined rapidly upon Bchl- ser-PDT+HT, reaching approximately 10% of initial values by the end of treatment. Similarly, tumour oxygenation worsened, reaching almost anoxic levels by the end of the treatment period. Assessment of metabolic parameters showed a pronounced increase in lactate levels and a decrease in ATP concentrations after combined treatment. The results presented suggest that vascular collapse and flow stasis resulting in a deterioration of tumour oxygenation and a switch from oxidative to glycolytic glucose turnover are key elements in the tumour eradication seen with this novel approach in which an antivascular PDT and HT are combined and simultaneously applied. Quote Link to comment Share on other sites More sharing options...
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