Ionizing Radiation-Induced Adenovirus Infection Is Mediated by Dynamin 2

Qian, Jun; Yang, Jiong; Dragovic, Aleksandar F.; Abu-Isa, Eyad; Lawrence, Theodore S.; Zhang, Ming

doi:10.1158/0008-5472.can-04-4526

Cited by 37 publications

(37 citation statements)

References 20 publications

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“…We and others have previously shown that IR increased oncolytic HSV-1 replication. [11][12][13][14][15][16][17][18][19][20][21][22][23] The hypothesis tested in this series of experiments was that if varying the timing of IR in relation to the timing of viral injection would result in a further enhancement of viral replication.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16][17][18][19][20][21][22][23] Specifically, g 1 34.5 deleted HSV-1 combined with IR resulted in increased viral replication and glioma-xenograft regression in hindlimb and orthotopic preclinical murine glioma models. 11,17 Mechanistic studies have elucidated multiple pathways through which IR enhances viral replication.…”

Section: Introductionmentioning

confidence: 99%

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Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

et al. 2011

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Oncolytic viruses have been combined with standard cancer therapies to increase therapeutic efficacy. Given the sequential activation of herpes viral genes (herpes simplex virus-1, HSV-1) and the temporal cellular changes induced by ionizing radiation, we hypothesized an optimal temporal sequence existed in combining oncolytic HSV-1 with ionizing radiation. Murine U-87 glioma xenografts were injected with luciferase encoding HSV-1, and ionizing radiation (IR) was given at times before or after viral injection. HSV-1 replication and tumor-volume response were followed. Radiation given 6-9 h after HSV-1 injection resulted in maximal viral luciferase expression and infectious viral production in tumor xenografts. The greatest xenograft regression was also seen with radiation given 6 h after viral injection. We then tested if HSV-1 replication had a dose response to ionizing radiation. HSV-1 luciferase expression exhibited a dose response as xenografts were irradiated from 0 to 5 Gy. There was no difference in viral luciferase expression as IR dose increased from 5 Gy up to 20 Gy. These results suggest that the interaction of IR with the HSV-1 lytic cycle can be manipulated for therapeutic gain by delivering IR at a specific time within viral replicative cycle.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

et al. 2011

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“…This is similar to our previous finding that radiation induces adenovirus uptake in tumors by increasing the expression of dynamin 2, a membrane-bound GTPase that is important in a receptormediated internalization process, whereas coxsackie and adenovirus receptor is not changed by radiation. 17 In addition, it has been demonstrated that dynamin is crucial for liposome endocytosis and intracellular trafficking in neurons. 22 The role of dynamin 2 in radiation-induced liposome uptake is certainly worth further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Our own study has demonstrated that radiation induces adenovirus uptake in tumors, contributing to enhanced transgene expression. 16,17 For liposome-mediated delivery, radiation has been shown to increase drug delivery to tumor blood vessels 18 and to sustain an enhanced transgene expression in human breast cancer cells. 19 In addition, liposome-mediated delivery of the cytosine deaminase gene has resulted in radiosensitization of rectal cancer.…”

Section: Introductionmentioning

confidence: 99%

“…First, radiation induces adenovirus gene transfer in tumor cells and xenografts by increasing viral uptake through dynamin 2-mediated membrane action. 17 Second, Tf-lipoplex, a highly compact nanoparticle with a relatively uniform size of 50-90 nm, structurally resembles that of a virus with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. 21 Furthermore, this strategy is becoming increasingly attractive with the development of body stereotactic radiation, which permits high doses of radiation to be selectively administered to tumors compared to normal tissues.…”

Section: Introductionmentioning

confidence: 99%

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Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells

Abela

Qian

et al. 2008

Cancer Gene Ther

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Selective gene transfer to tumor is critical in cancer gene therapy. We previously used ionizing radiation to improve adenovirus uptake in intrahepatic tumors but liver cytotoxicity associated with the viral administration still occurred. Here, we explore the potential of radiation for improving gene delivery by a virus-mimicking nanoparticle, transferrin (Tf)-cationic liposome-DNA complex (Tf-lipoplex). Transduction by Tf-lipoplex was highly efficient in various cell lines and further increased by radiation in a dose-and time-dependent manner. This radiation induction, which was associated with an increase in Tf-lipoplex uptake (3-to 4-folds in hepatocytes WB and lung cancer cells, LLC1), was absent when a Tf-deficient complex was used or abolished by the presence of free Tf, suggesting that Tf receptor (TfR) interaction is required for radiation induction. Radiation (10-20 Gy) markedly induced transgene (LacZ) expression in LLC1 xenografts (3.5-to 7.4-folds), correlating with increased plasmid content and TfR expression in irradiated tumors. Moreover, Tf-lipoplex-mediated gene expression was not observed in the liver or other normal tissues regardless of radiation treatment. We conclude that radiation improves Tf-lipoplex gene delivery selectively to tumor cells both in vitro and in vivo. Our findings may provide insight in developing ligand-specific lipoplex for molecularly targeted cancer gene therapy.

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Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation

Rajecki

Hällström

Hakkarainen

et al. 2009

Intl Journal of Cancer

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New treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti-cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment. Prostate cancer cells were infected with oncolytic adenoviruses, irradiated and synergy mechanisms were assessed. In vivo models of combination treatment were tested. Radiation and oncolytic viruses were synergistic when viral infection was scheduled 24 hr after irradiation. Combination of oncolytic adenovirus with radiotherapy significantly increased antitumor efficacy in vivo compared to either agent alone. Microarray analysis showed dysregulated pathways including cell cycle, mTOR and antigen processing pathways. Functional analysis showed that adenoviral infection was accompanied with degradation of proteins involved in DNA break repair. Mre11 was degraded for subsequent inactivation of Chk2-Thr68 in combination treated cells, while cH2AX-Ser139 was elevated implicating the persistence of DNA double strand breaks. Increased autophagocytosis was seen in combination treated cells. Combination treatment did not increase apoptosis or virus replication. The results provide evidence of the antitumor efficacy of combining oncolytic adenoviruses with irradiation as a therapeutic strategy for the treatment of prostate cancer. Further, these findings propose a molecular mechanism that may be important in radiation induced cell death, autophagy and viral cytopathic effect. ' 2009 UICC

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Ionizing Radiation-Induced Adenovirus Infection Is Mediated by Dynamin 2

Cited by 37 publications

References 20 publications

Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells

Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation

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