Vessel maturation effects on tumour growth: validation of a computer model in implanted human ovarian carcinoma spheroids

被引:34
作者
Arakelyan, L
Merbl, Y
Agur, Z
机构
[1] IMBM, IL-60991 Bene Ataroth, Israel
[2] Optimata Ltd, IL-52522 Ramat Gan, Israel
关键词
angiogenesis; microenvironment; vascular maturation; regression; spheroid; mathematical model;
D O I
10.1016/j.ejca.2004.09.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We analysed measurements of tumour growth, neovascular maturation and function in human epithelial ovarian carcinoma xenografts, studied noninvasively by magnetic resonance imaging. Results suggest that vascular maturation and mature and immature vessel regression occur continuously during tumour neovascularisation. Moreover, in these spheroids, a high tumour growth-rate is associated with monotonic changes in vessel density (VD) and with large proportions of mature blood vessels, whereas a lower tumour growth-rate is associated with fluctuating VD and lower proportions of mature vessels. These results corroborate a mathematical model for tumour dynamics, including vascular maturation and immature and mature vessel regression. The model predicts that rapid tumour growth may result from a high maturation-rate of neo-vasculatures, due to substantial mature VD in the microenvironment, while a slower tumour growth is an outcome of a lower background VD, leading to a lower vessel maturation-rate, larger proportion of immature vessels and, consequently, to regression-driven instabilities. The generality of these results for other tumour types should be validated. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:159 / 167
页数:9
相关论文
共 30 条
[1]   Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance imaging [J].
Abramovitch, R ;
Frenkiel, D ;
Neeman, M .
MAGNETIC RESONANCE IN MEDICINE, 1998, 39 (05) :813-824
[2]  
Abramovitch R, 1999, CANCER RES, V59, P5012
[3]  
Agur Z, 2004, DISCRETE CONT DYN-B, V4, P29
[4]   A computer algorithm describing the process of vessel formation and maturation, and its use for predicting the effects of anti-angiogenic and anti-maturation therapy on vascular tumor growth [J].
Arakelyan L. ;
Vainstein V. ;
Agur Z. .
Angiogenesis, 2002, 5 (3) :203-214
[5]  
ARAKELYAN L, 2002, P AN M AM SOC CLIN, V21, pA440
[6]  
Benjamin LE, 1998, DEVELOPMENT, V125, P1591
[7]  
BREIER G, 1992, DEVELOPMENT, V114, P521
[8]   Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele [J].
Carmeliet, P ;
Ferreira, V ;
Breier, G ;
Pollefeyt, S ;
Kieckens, L ;
Gertsenstein, M ;
Fahrig, M ;
Vandenhoeck, A ;
Harpal, K ;
Eberhardt, C ;
Declercq, C ;
Pawling, J ;
Moons, L ;
Collen, D ;
Risau, W ;
Nagy, A .
NATURE, 1996, 380 (6573) :435-439
[9]   Angiogenesis in cancer and other diseases [J].
Carmeliet, P ;
Jain, RK .
NATURE, 2000, 407 (6801) :249-257
[10]   Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer [J].
Chang, JC ;
Wooten, EC ;
Tsimelzon, A ;
Hilsenbeck, SG ;
Gutierrez, MC ;
Elledge, R ;
Mohsin, S ;
Osborne, CK ;
Chamness, GC ;
Allred, DC ;
O'Connell, P .
LANCET, 2003, 362 (9381) :362-369