Abstract:
:We investigated whether cilengitide could amplify the antitumor effects of radiotherapy in an orthotopic rat glioma xenograft model. Cilengitide is a specific inhibitor of alphav series integrins, and acts as an antiangiogenic. U251 human glioma cells express alphavbeta3 and alphavbeta5 integrins. We used in vitro assays of adhesion and growth of tumor and endothelial cells to evaluate cytotoxicity and the potential for cilengitide to enhance radiation toxicity. Treatment was then evaluated in an orthotopic model to evaluate synergy with therapeutic radiation in vivo. In vitro, cilengitide blocked cell adhesion, but did not influence the effects of radiation on U251 cells; cilengitide strongly amplified radiation effects on endothelial cell survival. In vivo, radiotherapy prolonged the survival of U251 tumor-bearing rats from 50 to over 110 days. Cotreatment with cilengitide and radiation dramatically amplified the effects of radiation, producing survival over 200 days and triggering an enhanced apoptotic response and suppression of tumor growth by histology at necropsy. Signaling pathways activated in the tumor included NFkappab, a documented mediator of cellular response to radiation. Because cilengitide has a short plasma half-life (t((1/2)) approximately 20 min), antiangiogenic scheduling typically uses daily injections. We found that a single dose of cilengitide (4 mg/kg) given between 4 and 12 hr prior to radiation was sufficient to produce the same effect. Our results demonstrate that blockade of alphav integrins mediates an unanticipated rapid potentiation of radiation, and suggests possible clinical translation for glioma therapy.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Mikkelsen T,Brodie C,Finniss S,Berens ME,Rennert JL,Nelson K,Lemke N,Brown SL,Hahn D,Neuteboom B,Goodman SLdoi
10.1002/ijc.24240subject
Has Abstractpub_date
2009-06-01 00:00:00pages
2719-27issue
11eissn
0020-7136issn
1097-0215journal_volume
124pub_type
杂志文章abstract::Although tobacco smoking, pan chewing and alcohol drinking are important risk factors for head and neck cancer (HNC), the HNC risks conferred by products available in Nepal for these habits are unknown. We assessed the associations of tobacco smoking, chewing habits, and alcohol drinking with HNC risk in Nepal. A case...
journal_title:International journal of cancer
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abstract::The following studies were undertaken to determine the levels of serum carotene and vitamin A (retinol) in Egyptian patients with intestinal, urinary, hepatosplenic schistosomiasis, and bladder cancer. These studies have shown that both serum carotene and serum retinol levels are significantly reduced in patients with...
journal_title:International journal of cancer
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abstract::Increases in the incidence of childhood acute lymphoblastic leukemia (ALL) have been reported in some countries, while other reports from similar geographical regions have indicated stable rates. The reasons for the discrepancies have been debated in the literature, with the focus on whether the observed increases are...
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journal_title:International journal of cancer
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