Supplementary Data from Targeted Radionuclide Therapy Using a Wnt-Targeted Replicating Adenovirus... more Supplementary Data from Targeted Radionuclide Therapy Using a Wnt-Targeted Replicating Adenovirus Encoding the Na/I Symporter
Supplementary Figures S1-S4 from Radiation-Mediated Up-Regulation of Gene Expression from Replica... more Supplementary Figures S1-S4 from Radiation-Mediated Up-Regulation of Gene Expression from Replication-Defective Adenoviral Vectors: Implications for Sodium Iodide Symporter Gene Therapy
Supplementary Figure Legends 1-2 from Cancer-Specific Transgene Expression Mediated by Systemic I... more Supplementary Figure Legends 1-2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles
Purpose: The Na/I symporter (hNIS) promotes concentration of iodine in cells. In cancer gene ther... more Purpose: The Na/I symporter (hNIS) promotes concentration of iodine in cells. In cancer gene therapy, this transgene has potential as a reporter gene for molecular imaging of viral biodistribution and as a therapeutic protein promoting 131I-mediated radiotherapy. Here, we combined the imaging and therapeutic potential of hNIS in an oncolytic adenoviruses targeting colorectal cancer cells.Experimental Design: We generated an adenovirus (AdIP2) encoding hNIS and capable of selective replication in colorectal carcinoma cells. The selectivity of this virus was verified in vitro and in vivo. Its spread in tumors was monitored in vivo using single-photon emission computed tomography/CT imaging upon 99mTcO4ā injection and confirmed by immunohistochemistry. Metabolic radiotherapy was done through injection of therapeutic doses of 131Iā.Results: We showed in vitro and in vivo the selectivity of AdIP2 and that hNIS expression is restricted to the target cells. Imaging and immunohistochemical data showed that viral spread is limited and that the point of maximal hNIS expression is reached 48 hours after a single intratumoral injection. Administration of a single therapeutic dose of 131I at this time point led to a dramatic reduction in tumor size not observed in hNIS-negative viruses.Conclusions: This report showed for the first time that the combination of the imaging and therapeutic potentials of hNIS can be applied to oncolytic adenoviruses in experimental models of cancer. (Clin Cancer Res 2009;15(21):6595ā601)
Purpose: To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transg... more Purpose: To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transgene expression in vitro and in vivo and to define an optimal strategy for combining sodium iodide symporter (NIS)āmediated 131I therapy with EBRT.Experimental Design: Expression of reporter genes [NIS, green fluorescent protein (GFP), Ī²-galactosidase (lacZ), and luciferase (Luc)] from replication-deficient adenoviruses was assessed in tumor cell lines under basal conditions and following irradiation. The effects of viral multiplicity of infection (MOI) and EBRT dose on the magnitude and duration of gene expression were determined. In vivo studies were done with Ad-CMV-GFP and Ad-RSV-Luc.Results: EBRT increased NIS, GFP, and Ī²-galactosidase expression in colorectal, head and neck, and lung cancer cells. Radiation dose and MOI were important determinants of response to EBRT, with greatest effects at higher EBRT doses and lower MOIs. Radiation exerted both transductional (through increased coxsackie-adenoviral receptor and integrin Ī±v) and nontransductional effects, irrespective of promoter sequence (CMV, RSV, hTR, or hTERT). Analysis of the schedule of EBRT followed by viral infection revealed maximal transduction at 24 hours. Radiation maintained increasing radioiodide uptake from Ad-hTR-NIS over 6 days, in direct contrast to reducing levels in unirradiated cells. The effects of EBRT in increasing and maintaining adenovirus-mediated transgene expression were also seen in vivo using GFP- and luciferase-expressing adenoviral vectors.Conclusions: Radiation increased the magnitude and duration of NIS gene expression from replication-deficient adenoviruses. The transductional effect is maximal at 24 hours, but radioiodide uptake is maintained at an elevated level over 6 days after infection.
Supplementary Figure 2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection o... more Supplementary Figure 2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles
Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 3 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 3 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 1 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 1 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Due to their ease of isolation and their properties, mesenchymal stem cells (MSCs) have been wide... more Due to their ease of isolation and their properties, mesenchymal stem cells (MSCs) have been widely investigated. MSCs have been proved capable of migration towards areas of inflammation, including tumors. Therefore, they have been suggested as vectors to carry therapies, specifically to neoplasias. As most of the individuals joining clinical trials that use MSCs for cancer and other pathologies are carefully recruited and do not suffer from other diseases, here we decided to study the safety and application of iv-injected MSCs in animals simultaneously induced with different inflammatory pathologies (diabetes, wound healing and tumors). We studied this by in vitro and in vivo approaches using different gene reporters (GFP, hNIS, and f-Luc) and non-invasive techniques (PET, BLI, or fluorescence). Our results found that MSCs reached different organs depending on the previously induced pathology. Moreover, we evaluated the property of MSCs to target tumors as vectors to deliver adenov...
Supplementary Data from Targeted Radionuclide Therapy Using a Wnt-Targeted Replicating Adenovirus... more Supplementary Data from Targeted Radionuclide Therapy Using a Wnt-Targeted Replicating Adenovirus Encoding the Na/I Symporter
Supplementary Figures S1-S4 from Radiation-Mediated Up-Regulation of Gene Expression from Replica... more Supplementary Figures S1-S4 from Radiation-Mediated Up-Regulation of Gene Expression from Replication-Defective Adenoviral Vectors: Implications for Sodium Iodide Symporter Gene Therapy
Supplementary Figure Legends 1-2 from Cancer-Specific Transgene Expression Mediated by Systemic I... more Supplementary Figure Legends 1-2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles
Purpose: The Na/I symporter (hNIS) promotes concentration of iodine in cells. In cancer gene ther... more Purpose: The Na/I symporter (hNIS) promotes concentration of iodine in cells. In cancer gene therapy, this transgene has potential as a reporter gene for molecular imaging of viral biodistribution and as a therapeutic protein promoting 131I-mediated radiotherapy. Here, we combined the imaging and therapeutic potential of hNIS in an oncolytic adenoviruses targeting colorectal cancer cells.Experimental Design: We generated an adenovirus (AdIP2) encoding hNIS and capable of selective replication in colorectal carcinoma cells. The selectivity of this virus was verified in vitro and in vivo. Its spread in tumors was monitored in vivo using single-photon emission computed tomography/CT imaging upon 99mTcO4ā injection and confirmed by immunohistochemistry. Metabolic radiotherapy was done through injection of therapeutic doses of 131Iā.Results: We showed in vitro and in vivo the selectivity of AdIP2 and that hNIS expression is restricted to the target cells. Imaging and immunohistochemical data showed that viral spread is limited and that the point of maximal hNIS expression is reached 48 hours after a single intratumoral injection. Administration of a single therapeutic dose of 131I at this time point led to a dramatic reduction in tumor size not observed in hNIS-negative viruses.Conclusions: This report showed for the first time that the combination of the imaging and therapeutic potentials of hNIS can be applied to oncolytic adenoviruses in experimental models of cancer. (Clin Cancer Res 2009;15(21):6595ā601)
Purpose: To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transg... more Purpose: To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transgene expression in vitro and in vivo and to define an optimal strategy for combining sodium iodide symporter (NIS)āmediated 131I therapy with EBRT.Experimental Design: Expression of reporter genes [NIS, green fluorescent protein (GFP), Ī²-galactosidase (lacZ), and luciferase (Luc)] from replication-deficient adenoviruses was assessed in tumor cell lines under basal conditions and following irradiation. The effects of viral multiplicity of infection (MOI) and EBRT dose on the magnitude and duration of gene expression were determined. In vivo studies were done with Ad-CMV-GFP and Ad-RSV-Luc.Results: EBRT increased NIS, GFP, and Ī²-galactosidase expression in colorectal, head and neck, and lung cancer cells. Radiation dose and MOI were important determinants of response to EBRT, with greatest effects at higher EBRT doses and lower MOIs. Radiation exerted both transductional (through increased coxsackie-adenoviral receptor and integrin Ī±v) and nontransductional effects, irrespective of promoter sequence (CMV, RSV, hTR, or hTERT). Analysis of the schedule of EBRT followed by viral infection revealed maximal transduction at 24 hours. Radiation maintained increasing radioiodide uptake from Ad-hTR-NIS over 6 days, in direct contrast to reducing levels in unirradiated cells. The effects of EBRT in increasing and maintaining adenovirus-mediated transgene expression were also seen in vivo using GFP- and luciferase-expressing adenoviral vectors.Conclusions: Radiation increased the magnitude and duration of NIS gene expression from replication-deficient adenoviruses. The transductional effect is maximal at 24 hours, but radioiodide uptake is maintained at an elevated level over 6 days after infection.
Supplementary Figure 2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection o... more Supplementary Figure 2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles
Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 3 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 3 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 1 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 1 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Ex... more Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors
Due to their ease of isolation and their properties, mesenchymal stem cells (MSCs) have been wide... more Due to their ease of isolation and their properties, mesenchymal stem cells (MSCs) have been widely investigated. MSCs have been proved capable of migration towards areas of inflammation, including tumors. Therefore, they have been suggested as vectors to carry therapies, specifically to neoplasias. As most of the individuals joining clinical trials that use MSCs for cancer and other pathologies are carefully recruited and do not suffer from other diseases, here we decided to study the safety and application of iv-injected MSCs in animals simultaneously induced with different inflammatory pathologies (diabetes, wound healing and tumors). We studied this by in vitro and in vivo approaches using different gene reporters (GFP, hNIS, and f-Luc) and non-invasive techniques (PET, BLI, or fluorescence). Our results found that MSCs reached different organs depending on the previously induced pathology. Moreover, we evaluated the property of MSCs to target tumors as vectors to deliver adenov...
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Papers by Georges Vassaux