Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts, effects of carbogen and nicotinamide

Background and purpose: A better understanding of the vascular architecture and the microenvironmental parameters (VAMP) will allow the identification of tumours that can be more effectively treated by intensified fractionate d radiotherapy or modifiers of bloodflow and oxygenation or combinations of these approaches. Materials and methods: Proliferation (BrdUrd), vascular architecture (endot helial marker), perfusion (Hoechst 33342) and oxygenation (NITP) were studi ed in two human laryngeal squamous cell carcinoma tumour lines grown as xen ografts in nude mice. The effects of carbogen and nicotinamide on these par ameters were evaluated. Results: Carbogen treatment resulted in a decrease of the number of perfuse d blood vessels from 66% to 55% in one of the two tumour lines. In this tum our line nicotinamide prevented this reduction of tumour blood flow by carb ogen. In both tumour lines the labelling index (LI) decreased after treatme nt with carbogen for 1 h, from 11-13% to 5-7%. Both tumour Lines showed a d rastic reduction of hypoxia by carbogen alone or by carbogen plus nicotinam ide. Conclusions: In both laryngeal squamous cell carcinoma xenograft tumour lin es carbogen was very effective in reducing diffusion limited hypoxia. Only in one of the two tested tumour lines carbogen also caused a reduction of t umour blood perfusion, which could be compensated for by nicotinamide. In a ddition, carbogen reduced tumour cell proliferation. The fact that differen ces in response to nicotinamide and carbogen were observed and that they ca n be studied in vivo provides a basis for further development of a 'predict ive profile' which will guide the clinician to select the optimal treatment for individual patients or groups of patients. (C) 1999 Elsevier Science I reland Ltd. All rights reserved.