Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts: effects of carbogen and nicotinamide.
OBJECTIVE
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 fractionated radiotherapy or modifiers of blood flow and oxygenation or combinations of these approaches.


METHODS
Proliferation (BrdUrd), vascular architecture (endothelial marker), perfusion (Hoechst 33342) and oxygenation (NITP) were studied in two human laryngeal squamous cell carcinoma tumour lines grown as xenografts in nude mice. The effects of carbogen and nicotinamide on these parameters were evaluated.


RESULTS
Carbogen treatment resulted in a decrease of the number of perfused blood vessels from 66% to 55% in one of the two tumour lines. In this tumour line nicotinamide prevented this reduction of tumour blood flow by carbogen. In both tumour lines the labelling index (LI) decreased after treatment with carbogen for 1 h, from 11-13% to 5-7%. Both tumour lines showed a drastic reduction of hypoxia by carbogen alone or by carbogen plus nicotinamide.


CONCLUSIONS
In both laryngeal squamous cell carcinoma xenograft tumour lines carbogen was very effective in reducing diffusion limited hypoxia. Only in one of the two tested tumour lines carbogen also caused a reduction of tumour blood perfusion, which could be compensated for by nicotinamide. In addition, carbogen reduced tumour cell proliferation. The fact that differences in response to nicotinamide and carbogen were observed and that they can be studied in vivo provides a basis for further development of a 'predictive profile' which will guide the clinician to select the optimal treatment for individual patients or groups of patients.
Bussink
J
J
Institute of Radiotherapy, University of Nijmegen, The Netherlands.
Kaanders
J H
JH
Rijken
P F
PF
Peters
J P
JP
Hodgkiss
R J
RJ
Marres
H A
HA
van der Kogel
A J
AJ
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D002245:Carbon Dioxide / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000648:ultrastructure; D006801:Humans; D000860:Hypoxia / Q000517:prevention & control; D007822:Laryngeal Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
D001562:Benzimidazoles; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C075173:7-(4'-(2-nitroimidazole-1-yl)butyl)theophylline; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D013806:Theophylline; C017807:bisbenzimide ethoxide trihydrochloride; D010100:Oxygen