An Adenovirus Vector Containing the Suicide Gene Thymidine Kinase for a Broad Application in Cancer Gene Therapy

Magalhães, Geraldo Santana; Muotri, Alysson R.; Marchetto, Maria C.; Menck, C. F. M.; Ventura, Armando Morais

doi:10.1590/s0074-02762002000400018

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…To determine the biological function of EPCs in tumor angiogenesis and to accomplish selective EPC ablation, the Id1pr/p-LV was used to express the suicide gene, HSV- tk (33) (Fig. 3A Upper, Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Using the Transcription Factor Inhibitor of DNA Binding 1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumor Angiogenesis and Growth

et al. 2010

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Tumor angiogenesis is essential for malignant growth and metastasis. Bone marrow (BM)-derived endothelial progenitor cells (EPC) contribute to angiogenesis-mediated tumor growth. EPC ablation can reduce tumor growth; however, the lack of a marker that can track EPCs from the BM to tumor neovasculature has impeded progress in understanding the molecular mechanisms underlying EPC biology. Here, we report the use of transgenic mouse and lentiviral models to monitor the BM-derived compartment of the tumor stroma; this approach exploits the selectivity of the transcription factor inhibitor of DNA binding 1 (Id1) for EPCs to track EPCs in the BM, blood, and tumor stroma, as well as mature EPCs. Acute ablation of BM-derived EPCs using Id1-directed delivery of a suicide gene reduced circulating EPCs and yielded significant defects in angiogenesis-mediated tumor growth. Additionally, use of the Id1 proximal promoter to express microRNA-30-based short hairpin RNA inhibited the expression of critical EPCintrinsic factors, confirming that signaling through vascular endothelial growth factor receptor 2 is required for EPC-mediated tumor biology. By exploiting the selectivity of Id1 gene expression in EPCs, our results establish a strategy to track and target EPCs in vivo, clarifying the significant role that EPCs play in BM-mediated tumor angiogenesis. Cancer Res; 70(18); 7273-82. ©2010 AACR.

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Section: Resultsmentioning

confidence: 99%

Using the Transcription Factor Inhibitor of DNA Binding 1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumor Angiogenesis and Growth

et al. 2010

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“…More than 50% of miRNA-encoding loci reside in chromosomal regions altered during tumorigenesis (Calin et al, 2004), and expression profiling reveals characteristic miRNA signatures for many tumor types, including breast neoplasia, that predict disease status and clinical outcome (Calin and Croce, 2006). In addition, miRNAs have been identified that function as oncogenes or tumor suppressor genes (Magalhaes et al, 2002;Ventura et al, 2008),…”

Section: Introductionmentioning

confidence: 99%

Suppression of miRNA-708 by Polycomb Group Promotes Metastases by Calcium-Induced Cell Migration

et al. 2013

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The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.

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“…Future studies will evaluate the immunogenicities of the adenoviral vectors and the pShuttle vectors (as DNA vaccine) obtained during the constructions described here. In our laboratory, we have been using adenovirus vectors for the expression of several genes (11,13), and we are developing adenoviral vectors expressing the other structural proteins of HRSV (SH, P, N, L and M). Currently, we are doing experiments associating these vectors with the aim of developing an ideal immunization protocol.…”

Section: Discussionmentioning

confidence: 99%

Construction of adenoviral vectors expressing F and G glycoproteins of human respiratory syncytial virus (HRSV)

Kosaka

Carromeu

Durigon

et al. 2004

Braz. J. Microbiol.

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Human Respiratory Syncytial Virus (HRSV) was first characterized in 1957 and has since been recognized as the most common viral cause of severe respiratory tract infection in young infants worldwide. Despite many years of research there is still no effective treatment or any immediate prospect of a vaccine. The HRSV genome is composed of single stranded negative sense RNA and the virion consists of a nucleocapsid packaged within a lipid envelope. The envelope contains spike-like projections, each being a homooligomer of one of three transmembrane viral envelope proteins: the attachment protein G, the fusion protein F involved in viral penetration and the small hydrofobic protein SH. The aim of this work was to construct two recombinant replication-defective adenoviruses carrying separately F and G genes from HRSV. This system was chosen because adenovirus delivers genes into target cells with high efficiency in a variety of cell lines and can be used in vitro and in vivo. In order to obtain the recombinant viruses, we did RT-PCR of RNA extracted from the HRSV A2 strain, the genes F and G were cloned in to pAdeno-X vectors. pAdeno-F and pAdeno-G were transfected in HEK-293 cells for the production of recombinant viruses, that expressed efficiently these two proteins and provide us the means for doing functional assays and immunization tests.

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An Adenovirus Vector Containing the Suicide Gene Thymidine Kinase for a Broad Application in Cancer Gene Therapy

Cited by 4 publications

References 27 publications

Using the Transcription Factor Inhibitor of DNA Binding 1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumor Angiogenesis and Growth

Using the Transcription Factor Inhibitor of DNA Binding 1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumor Angiogenesis and Growth

Suppression of miRNA-708 by Polycomb Group Promotes Metastases by Calcium-Induced Cell Migration

Construction of adenoviral vectors expressing F and G glycoproteins of human respiratory syncytial virus (HRSV)

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