[Correlation of tumor vessel function to synergistic antitumor effect of Avastin combined cyclophosphamide].
OBJECTIVE
Dysfunction of tumor vessels renders high interstitial pressure, hypoxia and acidosis, causing the barrier of cytotoxic efficacy of chemotherapeutic agents. This study was to observe the dynamic alteration of vessel function in neuroblastoma (NB) after treatment of Avastin, and explore the correlation of tumor vessel function to synergistic antitumor effect of Avastin plus cyclophosphamide (CPM).


METHODS
Human NB cells were incubated and transplanted into nude mice to form NB xenografts. Avastin at a dose of 5 mg/kg was administered to the mice through the tail veins. The mice were killed on the 6th hour, 3rd day, 6th day and 9th day after Avastin treatment, separately. Tumor vessel function was tested with fluorescein Hoechst33342 staining. NB-bearing mice were treated with Avastin plus CPM. The synergistic antitumor effects were compared when CPM was administered simultaneously with Avastin (combined regimen I) or at the time the tumor vessel function was mostly improved after Avastin administration (combined regimen II).


RESULTS
The tumor vessel function was mostly improved on the 6th day after Avastin treatment. Tumor inhibition rates were 36.4% in Avastin monotherapy group, 38.2% in CPM monotherapy group, 55.9% in combined regimen I group, and 66.8% in combined regimen II group at 3 weeks after treatment. The synergistic antitumor effect was better when CPM was administered on the 6th day after Avastin treatment as compared with it used simultaneously with Avastin (P<0.05).


CONCLUSIONS
The synergistic antitumor effect can be augmented when CPM is administered at the time the tumor vessel function is mostly improved after Avastin treatment.
Zhen
Zi-Jun
ZJ
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, PR China.
He
You-Jian
YJ
Sun
Xiao-Fei
XF
Ling
Jia-Yu
JY
Zheng
Lei
L
Luo
Wen-Biao
WB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000008:administration & dosage; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003520:Cyclophosphamide