In vivo radiosensitizing effect of the adenovirus E1A gene in murine and human malignant tumors.

Martín-Duque, Pilar; Sánchez‐Prieto, Ricardo; Romero, Jesús; Martinez-Lamparero, A; Cebrian-Sagarriga, S; Guinea-Viniegra, Juan; Domínguez, Carolina; Lleonart, Matilde E.; Cano, Amparo; Quintanilla, Miguel; Cajal, S. Ramón y

doi:10.3892/ijo.15.6.1163

Cited by 17 publications

(17 citation statements)

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“…ONYX-015 expresses functional E1A proteins. Malignant tumours, when expressing adenovirus E1A, are very sensitive to in vivo treatment with DNA-damaging agents, including irradiation (Sanchez-Prieto et al, 1995Martin-Duque et al, 1999). In addition, sensitisation of p53-functional tumour cells may involve induction of high levels of p53 protein by E1A expression (Lowe and Ruley, 1993).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts

et al. 2003

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In spite of aggressive surgery, irradiation and/or chemotherapy, treatment of malignant gliomas remains a major challenge in adults and children due to high treatment failure. We have demonstrated significant cell lysis and antitumour activity of the E1B-55 kDa-gene-deleted adenovirus ONYX-015 (dl1520, CI-1042; ONYX Pharmaceuticals) in subcutaneous human malignant glioma xenografts deriving from primary tumours. Here, we show the combined efficacy of this oncolytic therapy with radiation therapy. Total body irradiation (5 Gy) of athymic nude mice prior to intratumoral injections of ONYX-015 1 Â 10 8 PFU daily for 5 consecutive days yielded additive tumour growth delays in the p53 mutant xenograft IGRG88. Radiation therapy was potentiated in the p53 functional tumour IGRG121 with a 'subtherapeutic' dose of 1 Â 10 7 PFU daily for 5 consecutive days, inducing significant tumour growth delay, 90% tumour regression and 50% tumour-free survivors 4 months after treatment. These potentiating effects were not due to increased adenoviral infectivity or replication. Furthermore, cell lysis and induction of apoptosis, the major mechanisms for adenoviral antitumour activity, did not play a major role in the combined treatment strategy. Interestingly, the oncolytic adenovirus seemed to accelerate radiation-induced tumour fibrosis. Potentiating antitumour activity suggests the development of this combined treatment for these highly malignant tumours.

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Section: Discussionmentioning

confidence: 99%

Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts

et al. 2003

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“…On the other hand, there was some evidence also supporting the potent radiosensitivity inducer of E1A in a p53-dependent and p53-independent manner (42). Some murine and human malignant tumors, when expressing adenovirus E1A, were very sensitive to irradiation treatment in vivo, regardless of the p53 status of the tumors (43). The most obvious hypothesis for the discrepancy in E1A function is that the specific cellular factors involved in the induction of apoptosis by E1A may be cell type dependent.…”

Section: Discussionmentioning

confidence: 99%

The Superparamagnetic Nanoparticles Carrying the E1A Gene Enhance the Radiosensitivity of Human Cervical Carcinoma in Nude Mice

Shen

Chen

Zeng

et al. 2010

Molecular Cancer Therapeutics

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To explore the effects of early region 1A (E1A) carried by superparamagnetic dextran iron oxide nanoparticles (SDION) on the radiosensitivity of human cervical cancer. The xenograft mice with cervical cancer received weekly intratumoral SDION-E1A injection and a subsequent 50-Gy irradiation. The weekly relative tumor volume and the final tumor volume were compared among different experimental groups. p53 and human epidermal growth factor receptor-2 (HER-2)/Neu expression in final tumor tissue was detected by reverse transcription-PCR and Western blot. The relative tumor volume and the final tissue volume in the SDION-E1A group was significantly smaller than that in Sham and SDION-Vector groups at each time points after irradiation (P < 0.05). Exogenous E1A expression by SDION delivery significantly increased p53 expression, but inhibited HER-2/Neu expression in tumor tissue (P < 0.05). The intratumoral delivery of exogenous E1A carried by SDION increases p53 expression but inhibits HER-2/neu expression, and enhances the radiosensitivity of human cervical cancer in xenograft mice. Mol Cancer Ther; 9(7); 2123-30.

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“…Así, el reemplazamiento usando p53, en combinación con agentes que dañan el DNA es una estrategia usada en numerosos tumores 27 . La proteína E1A de adenovirus tipo 5 y alguno de los mutantes derivados de ella demostraron ser capaces de sensibilizar las células de carcinoma a la radio y quimioterapia de manera independiente de p53 in vitro 29 e in vivo en modelos murinos 30 y humanos 31 . Estudios previos en algunas de las líneas celulares que estudiamos en el presente trabajo, han sido empleadas para correlacionar la sensibilidad o resistencia de las diversas líneas a los tratamientos antitumorales con factores genéticos descritos en la literatura 32,33 .…”

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La actividad de la Caspasa-1 como gen sensibilizador a radio y quimioterapia es independiente de las vías de JNK y p38

Vassaux¹,

Mancheño‐Corvo

López-Barahona

et al. 2005

Oncología (Barc.)

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ResumenEl efecto citotóxico de las drogas antitumorales es producido mediante la inducción de apoptosis. Esta observación implica la posibilidad de que los factores que afecten la activación de caspasas pueden ser determinantes importantes como sensibilizantes a los tratamientos antitumorales. Aquí, examinamos el efecto de la sobreexpresión de caspasa-1 en la respuesta a la quimio y radioterapia. La expresión de la caspasa-1 mediada por un vector adenoviral fue capaz de matar directamente a las células y de sensibilizar las restantes a cisplatino o radiación gamma in vitro. En células HeLa transfectadas establemente con caspasa-1, la sensibilización a cisplatino fue debida a una amplificación en la vía mitocondrial de apoptosis inducida por cisplatino pero este efecto es independiente del estado de p53, JNK o p38 en la célula. Palabras clave:Caspasa-1. Radio y quimiosensibilización. Quinasas y p53. Oncología, 2005; 28 (8):394-406

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In vivo radiosensitizing effect of the adenovirus E1A gene in murine and human malignant tumors.

Cited by 17 publications

References 0 publications

Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts

Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts

The Superparamagnetic Nanoparticles Carrying the E1A Gene Enhance the Radiosensitivity of Human Cervical Carcinoma in Nude Mice

La actividad de la Caspasa-1 como gen sensibilizador a radio y quimioterapia es independiente de las vías de JNK y p38

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