Table 2.

Translational Studies Supporting BEV-Induced GBM Hypoxia and Enhanced Invasive Phenotype

Study	Animal model	Tumor material	Time between implanting tumor and starting BEV	BEV regimen	Controls	Time between initiating BEV and sacrificing mice
Keunen et al, 201120	Athymic nude rats	Standardized pool of GBM-derived spheroids obtained from one patient and expanded through serial transplantation in nude rats	3 weeks	10 mg/kg i.v. weekly	Yes	3 weeks
Hamans et al, 201321	Athymic BALB/c nu/nu mice	E98 or E473 GBM cells	When signs of tumor growth became apparent: presence of edema on T2-weighted MRI	5 mg/kg i.p. twice weekly	Yes	Signs of clinical deterioration: >15% weight loss in 2 days; severe neurologic abnormalities
de Groot et al, 201023	Nude mice	U87 GBM cell line	5 days after tumor implantation	10 mg/kg i.p. twice weekly	Yes	Signs of clinical deterioration (4–6 weeks)
Kumar et al, 201324	BALB/c SCID or athymic nude mice	U87-MG or U118-MG cells	Tumor volume reached 150 mm3	10 mg/kg i.p. every 3 days	Yes	Until tumors reached 600–800 mm3
Rapisarda et al, 200925	Athymic nude mice	U251-HRE cells	Tumors reached ∼175 mg	5 mg/kg, every 3 days × 4 times	Yes	Day 29 of treatment

BALB, Bagg albino; BEV, bevacizumab; GBM, glioblastoma; MRI, magnetic resonance imaging; SCID, severe combined immunodeficiency.