A Phase I Study of In-Situ, Neoadjuvant, Pre-Radical Prostatectomy RTVP-1 Gene Therapy in Patients With Locally Advanced Adenocarcinoma of the Prostate (SPORE)

The purpose of this study is to conduct a Phase I clinical trial involving in situ RTVP-1 gene therapy for prostate cancer. We will conduct necessary safety evaluations on a new adenovirus that contains the human genes for RTVP-1. This virus will then be evaluated for safety in men with prostate cancer prior to radical prostatectomy. Based on the preclinical data, we hope that this treatment will induce not only a local cytotoxic and antiangiogenic effect but also, a systemic antitumor immune response capable of eradicating micrometastatic disease (the reason for recurrence in many of these patients).

开始日期2006-08-01

申办/合作机构

Baylor College of Medicine

100 项与 RTVP-1 Gene Therapy(Baylor College of Medicine) 相关的临床结果

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100 项与 RTVP-1 Gene Therapy(Baylor College of Medicine) 相关的转化医学

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100 项与 RTVP-1 Gene Therapy(Baylor College of Medicine) 相关的专利（医药）

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项与 RTVP-1 Gene Therapy(Baylor College of Medicine) 相关的文献（医药）

2015-09-09·Oncotarget

RTVP-1 promotes mesenchymal transformation of glioma via a STAT-3/IL-6-dependent positive feedback loop

Article

作者: Giladi, Nis David ; Ziv-Av, Amotz ; Brodie, Chaya ; Poisson, Laila ; Lee, Hae Kyung ; Xiang, Cunli ; Finniss, Susan ; Cazacu, Simona ; deCarvalho, Ana ; Mikkelsen, Tom ; Ben-Asher, Hiba Waldman

Glioblastomas (GBMs), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. We explored the role of RTVP-1, a glioma-associated protein that promotes glioma cell migration, in the mesenchymal transformation of GBM. Analysis of The Cancer Genome Atlas (TCGA) demonstrated that RTVP-1 expression was higher in mesenchymal GBM and predicted tumor recurrence and poor clinical outcome. ChiP analysis revealed that the RTVP-1 promoter binds STAT3 and C/EBPβ, two master transcription factors that regulate mesenchymal transformation of GBM. In addition, IL-6 induced RTVP-1 expression in a STAT3-dependent manner. RTVP-1 increased the migration and mesenchymal transformation of glioma cells. Similarly, overexpression of RTVP-1 in human neural stem cells induced mesenchymal differentiation, whereas silencing of RTVP-1 in glioma stem cells (GSCs) decreased the mesenchymal transformation and stemness of these cells. Silencing of RTVP-1 also increased the survival of mice bearing GSC-derived xenografts. Using gene array analysis of RTVP-1 silenced glioma cells we identified IL-6 as a mediator of RTVP-1 effects on the mesenchymal transformation and migration of GSCs, therefore acting in a positive feedback loop by upregulating RTVP-1 expression via the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM.

2015-08-14·Oncotarget

RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP and hnRNPK

Article

作者: Giladi, Nissim David ; Barda-Saad, Mira ; Ziv-Av, Amotz ; Cazacu, Simona ; Brodie, Chaya ; Lee, Hae Kyung ; Poisson, Laila ; Finniss, Susan ; Xiang, Cunli ; Pauker, Maor H.

Glioblastoma (GBM) are characterized by increased invasion into the surrounding normal brain tissue. RTVP-1 is highly expressed in GBM and regulates the migration and invasion of glioma cells. To further study RTVP-1 effects we performed a pull-down assay using His-tagged RTVP-1 followed by mass spectrometry and found that RTVP-1 was associated with the actin polymerization regulator, N-WASP. This association was further validated by co-immunoprecipitation and FRET analysis. We found that RTVP-1 increased cell spreading, migration and invasion and these effects were at least partly mediated by N-WASP. Another protein which was found by the pull-down assay to interact with RTVP-1 is hnRNPK. This protein has been recently reported to associate with and to inhibit the effect of N-WASP on cell spreading. hnRNPK decreased cell migration, spreading and invasion in glioma cells. Using co-immunoprecipitation we validated the interactions of hnRNPK with N-WASP and RTVP-1 in glioma cells. In addition, we found that overexpression of RTVP-1 decreased the association of N-WASP and hnRNPK. In summary, we report that RTVP-1 regulates glioma cell spreading, migration and invasion and that these effects are mediated via interaction with N-WASP and by interfering with the inhibitory effect of hnRNPK on the function of this protein.

2011-12-01·Cellular Signalling3区 · 生物学

RTVP-1 expression is regulated by SRF downstream of protein kinase C and contributes to the effect of SRF on glioma cell migration

3区 · 生物学

Article

作者: Amotz Ziv-Av ; Ronit Sarid ; Cunli Xiang ; Susan Finniss ; Dvir Taller ; Chaya Brodie ; Moshe Attia ; Hae Kyung Lee ; Gila Kazimirsky ; Simona Cazacu

Gliomas are characterized by increased infiltration into the surrounding normal brain tissue. We recently reported that RTVP-1 is highly expressed in gliomas and plays a role in the migration of these cells, however the regulation of RTVP-1 expression in these cells is not yet described. In this study we examined the role of PKC in the regulation of RTVP-1 expression and found that PMA and overexpression of PKCα and PKCε increased the expression of RTVP-1, whereas PKCδ exerted an opposite effect. Using the MatInspector software, we identified a SRF binding site on the RTVP-1 promoter. Chromatin immunoprecipitation (ChIP) assay revealed that SRF binds to the RTVP-1 promoter in U87 cells, and that this binding was significantly increased in response to serum addition. Moreover, silencing of SRF blocked the induction of RTVP-1 expression in response to serum. We found that overexpression of PKCα and PKCε increased the activity of the RTVP-1 promoter and the binding of SRF to the promoter. In contrast, overexpression of PKCδ blocked the increase in RTVP-1 expression in response to serum and the inhibitory effect of PKCδ was abrogated in cells expressing a SRFT160A mutant. SRF regulated the migration of glioma cells and its effect was partially mediated by RTVP-1. We conclude that RTVP-1 is a PKC-regulated gene and that this regulation is at least partly mediated by SRF. Moreover, RTVP-1 plays a role in the effect of SRF on glioma cell migration.

100 项与 RTVP-1 Gene Therapy(Baylor College of Medicine) 相关的药物交易

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