Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector

I., H.; Lin, Shinn‐Zong; Chiang, Yawen; Li, J.; Chen, S. L.; Tsao, Yeou‐Ping; Xiao, Xianmin

doi:10.1038/sj.gt.3301616

Cited by 103 publications

(67 citation statements)

References 45 publications

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“…To our knowledge, studies of angiostatins in the brain tissue have described only effects of angiostatin-encoding genetic con- structions in animal models of pathologies. Besides, recent studies have suggested that adeno-associated virus angiostatin vector causes markedly smaller tumors with reduced neovascularization and higher apopto tic indices in C6 glioma cells, when they are propa gated intracerebrally and are injected to animals [33]. One of the most significant and novel results of our study is detection of angiostatins in brain tissue, determination of their polypeptide composition and regional distribution.…”

Section: Fig 2 Representative Fluorescence Micrographs Of Plasminogmentioning

confidence: 74%

Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Tykhomyrov¹,

Nedzvetsky²,

Ağca³

et al. 2017

Ukr.Biochem.J.

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Section: Fig 2 Representative Fluorescence Micrographs Of Plasminogmentioning

confidence: 74%

Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Tykhomyrov¹,

Nedzvetsky²,

Ağca³

et al. 2017

Ukr.Biochem.J.

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“…The use of T cells and macrophages has been extensively studied due to the homing properties of these immune cells. Recently, problems with sustained production of antiangiogenic proteins were overcome by adeno-associated virus-mediated intratumoural delivery (Ma et al, 2002b) or systemic delivery through intramuscular injection of angiostatin for treatment of intracranial tumours (Ma et al, 2002a) or endostatin for treatment of ovarian carcinoma (Subramanian et al, 2006). Long-term survival of mice with intracranial human glioblastoma was also seen when the Sleeping Beauty transposon system was used for the transfer of a gene encoding soluble vascular endothelial growth factor receptor or a fusion gene for angiostatin -endostatin (Ohlfest et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

et al. 2007

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Angiogenesis and post-natal vasculogenesis are two processes involved in the formation of new vessels, and both are essential for tumour growth and metastases. We isolated endothelial cells from human blood mononuclear cells by selective culture. These blood outgrowth cells expressed endothelial cell markers and responded correctly to functional assays. To evaluate the potential of blood outgrowth endothelial cells (BOECs) to construct functional vessels in vivo, NOD-SCID mice were implanted with Lewis lung carcinoma cells subcutaneously (s.c.). Blood outgrowth endothelial cells were then injected through the tail vein. Initial distribution of these cells occurred throughout the lung, liver, spleen, and tumour vessels, but they were only found in the spleen, liver, and tumour tissue 48 h after injection. By day 24, they were mainly found in the tumour vasculature. Tumour vessel counts were also increased in mice receiving BOEC injections as compared to saline injections. We engineered BOECs to deliver an angiogenic inhibitor directly to tumour endothelium by transducing them with the gene for human endostatin. These cells maintained an endothelial phenotype and decreased tumour vascularisation and tumour volume in mice. We conclude that BOECs have the potential for tumour-specific delivery of cancer gene therapy.

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“…Fourth, when coupled to a strong promoter like the hybrid CMV enhancer/chicken b-actin (CAG) promoter used in this study, it is capable of delivering high levels of transgene expression in a wide variety of cell types. For these reasons, AAV carrying therapeutic genes like angiostatin, 31,32 herpes simplex virus thymidine kinase (HSV-tK), 33,34 and interleukin-2 (IL-2) 35 have been employed in the treatment of malignant gliomas with varying degree of success. In the present study, we demonstrated that intratumoral delivery of rAAVhTERTC27, but not rAAV-EGFP, potently inhibits the growth of the glioblastoma cells by more than 80% at 5 weeks post-treatment and significantly prolongs the median survival time of the treated mice by approximately twofold.…”

Section: Raav-htertc27 Treatment Induces Differential Expression Of Gmentioning

confidence: 99%

A novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide

Gao

Chau

et al. 2007

Cancer Gene Ther

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Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27-mediated antitumor effects, we analyzed the global gene expression profiles of the rAAV-hTERTC27-treated tumor tissues and cell line as compared with that of the control rAAV-green fluorescent protein-treated samples by DNA microarray. Our results suggest that hTERTC27 exerts its effect through complex mechanisms, which involve genes regulating apoptosis, cell adhesion, cell cycle, immune responses, metabolism, signal transduction, transport, transcription and telomere maintenance.

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Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector

Abstract: We have utilized a recombinant adeno-associated viral (AAV)

Cited by 103 publications

References 45 publications

Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

A novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide

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