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Displaying Results 76 - 100 of 614 on page 4 of 25

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Regulated Expression of Adenoviral Vectors-Based Gene Therapies: Therapeutic Expression of Toxins and Immune-Modulators (2008)

Curtin, James; Candolfi, Marianela; Puntel, Mariana; Xiong, Weidong; Muhammad, AKM Ghul...

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Live and let die: regulatory mechanisms in Fas-mediated apoptosis (2003)

Curtin, James; Cotter, Thomas

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Transcriptional regulation of cholesterol 24-hydroxylase by histone deacetylase inhibitors. (2009)

Shafaati, Marjan; O'Driscoll, Riona; Bjorkhem, Ingemar; Meaney, Steve

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JNK Regulates HIPK3 Expression and Promotes Resistance to Fas-mediated Apoptosis in DU 145 Prostate Carcinoma Cells (2004)

Curtin, James; Cotter, Thomas

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Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells (2003)

Curtin, James; Cotter, Thomas

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Study of the Efficacy, Biodistribution, and Safety Profile of Therapeutic Gutless Adenovirus Vectors as a Prelude to a Phase I Clinical Trial for Glioblastoma (2010)

Muhammad, AKM Ghulam; Puntel, Mariana; Candolfi, Marianela; Salem, A; Yagiz, Kader; Far...

Study of the Efficacy, Biodistribution, and Safety Profile of Therapeutic Gutless Adenovirus Vectors as a Prelude to a Phase I Clinical Trial for Glioblastoma (2010)

Muhammad, AKM Ghulam; Puntel, Mariana; Candolfi, Marianela; Salem, A; Yagiz, Kader; Farrokhi, C; Kroeger, Kurt M; Xiong, Weidong; Curtin, James; Liu, Chunyan; Lawrence, K; Bondale, Niyati; Lerner, Jonathan; Baker, G; Foulad, David; Pechnick, Robert; Palmer, Donna; Ng, Philip; Lowenstein, Pedro; Castro, Maria

Abstract:

Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in humans. Systemic immunity against gene therapy vectors has been shown to hamper therapeutic efficacy; however, helper-dependent high-capacity adenovirus (HC-Ad) vectors elicit sustained transgene expression, even in the presence of systemic anti-adenoviral immunity. We engineered HC-Ads encoding the conditional cytotoxic herpes simplex type 1 thymidine kinase (TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Flt3L). Flt3L expression is under the control of the regulatable Tet-ON system. In anticipation of a phase I clinical trial for GBM, we assessed the therapeutic efficacy, biodistribution, and clinical and neurotoxicity with escalating doses of HC-Ad-TetOn-Flt3L + HC-Ad-TK in rats. Intratumoral administration of these therapeutic HC-Ads in rats bearing large intracranial GBMs led to long-term survival in ~70% of the animals and development of antiglioma immunologic...