Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment

Tian, Dan; Sun, Yan; Yang, Yang; Lei, Mingde; Ding, Na; Han, Renzhi

doi:10.2147/ott.s41978

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Telomerase is activated in >85% of all malignant tumor cells, including colorectal cancer cells, but is repressed in normal somatic cells ( 32 – 34 ), the transcriptional activity that is regulated by hTERTp. hTERTp was confirmed to drive specific target gene expression in various tumor cells ( 9 , 35 – 37 ). Therefore, hTERTp was used in the current study to cause tumor-specific gene expression of yCDglyTK.…”

Section: Discussionmentioning

confidence: 98%

Construction of a novel vector expressing Survivin‑shRNA and fusion suicide gene yCDglyTK and its application in inhibiting proliferation and migration of colon cancer cells

Yang

et al. 2017

Exp Ther Med

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Despite progress achieved in cancer chemotherapy in recent decades, adverse effects remain a limiting factor for a number of patients with colorectal cancer, suggesting the requirement for novel therapeutic strategies. Gene therapy appears to be a promising strategy for treating cancer. The present study aimed to investigate the anti-tumor effect of a combined gene therapy, using Survivin downregulation by RNAi and a fusion suicide gene yCDglyTK therapy system. A triple-gene vector expressing Survivin-targeted small hairpin RNA (Survivin-shRNA) and fusion suicide gene yCDglyTK was constructed, and administered to HCT116 cells. Survivin expression decreased significantly and yCDglyTK fusion gene expression was confirmed by both reverse transcription-quantitative polymerase chain reaction and western blot analysis. Introduction of Survivin-shRNA into yCDglyTK/prodrug system eradicated colon cancer cells and induced apoptosis more effectively. Furthermore, this therapeutic system is able to inhibit the migration of HCT116 cells. These results indicate that the recombinant plasmid may serve as a novel gene therapy approach to treat colorectal carcinoma.

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Section: Discussionmentioning

confidence: 98%

Construction of a novel vector expressing Survivin‑shRNA and fusion suicide gene yCDglyTK and its application in inhibiting proliferation and migration of colon cancer cells

Yang

et al. 2017

Exp Ther Med

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“…However, in such a setting, the pro-drug would kill the whole graft, including the cells for which there was a need in the first place. The use of the hTERT promoter driving HSV-TK has been recently described to address this problem ( Tian et al., 2013 ), but such approach by itself does not offer differentiation selectivity. Our method is innovative because it allows for the selective preservation and enrichment of the desired cells while destroying those with tumorigenic potential.…”

Section: Discussionmentioning

confidence: 99%

A Double Fail-Safe Approach to Prevent Tumorigenesis and Select Pancreatic β Cells from Human Embryonic Stem Cells

et al. 2019

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SummaryThe transplantation of human embryonic stem cell (hESC)-derived insulin-producing β cells for the treatment of diabetes is finally approaching the clinical stage. However, even with state-of-the-art differentiation protocols, a significant percentage of undefined non-endocrine cell types are still generated. Most importantly, there is the potential for carry-over of non-differentiated cell types that may produce teratomas. We sought to modify hESCs so that their differentiated progeny could be selectively devoid of tumorigenic cells and enriched for cells of the desired phenotype (in this case, β cells). Here we report the generation of a modified hESC line harboring two suicide gene cassettes, whose expression results in cell death in the presence of specific pro-drugs. We show the efficacy of this system at enriching for β cells and eliminating tumorigenic ones both in vitro and in vivo. Our approach is innovative inasmuch as it allows for the preservation of the desired cells while eliminating those with the potential to develop teratomas.

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“…In a recent study, Xu et al demonstrated that combination therapy with Ad‐CMV‐mIL‐12 and Ad‐hTERT‐HRP/IAA could markedly suppress tumor cell growth and enhance host cell survival in a Lewis lung carcinoma model, without any major systemic side effects. Another study showed that Ad‐hTERT‐herpes simplex virus thymidine kinase (HSV‐TK)/ganciclovir (Ad‐hTERT‐HSV‐TK/GCV) is an effective inhibitor not only in human renal cell carcinoma cells in vitro, but also in mouse cancer models in vivo . In addition, Yu et al found that the expression of HSV‐TK and Escherichia coli nitroreductase genes by Ad‐hTERT‐TK/NTR‐enh in combination with GCV and CB1954 (5‐(azaridin‐1‐yl)‐2,4‐dinitrobenzamide) led to specific and significant cytotoxic effects in breast cancer cell lines.…”

Section: Gene Therapymentioning

confidence: 99%

Therapeutic strategies for targeting telomerase in cancer

Chen

Tang

Shi

et al. 2019

Medicinal Research Reviews

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Telomere and telomerase play important roles in abnormal cell proliferation, metastasis, stem cell maintenance, and immortalization in various cancers. Therefore, designing of drugs targeting telomerase and telomere is of great significance. Over the past two decades, considerable knowledge regarding telomere and telomerase has been accumulated, which provides theoretical support for the design of therapeutic strategies such as telomere elongation. Therefore, the development of telomere‐based therapies such as nucleoside analogs, non‐nucleoside small molecules, antisense technology, ribozymes, and dominant negative human telomerase reverse transcriptase are being prioritized for eradicating a majority of tumors. While the benefits of telomere‐based therapies are obvious, there is a need to address the limitations of various therapeutic strategies to improve the possibility of clinical applications. In this study, current knowledge of telomere and telomerase is discussed, and therapeutic strategies based on recent research are reviewed.

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Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment

Cited by 5 publications

References 29 publications

Construction of a novel vector expressing Survivin‑shRNA and fusion suicide gene yCDglyTK and its application in inhibiting proliferation and migration of colon cancer cells

Construction of a novel vector expressing Survivin‑shRNA and fusion suicide gene yCDglyTK and its application in inhibiting proliferation and migration of colon cancer cells

A Double Fail-Safe Approach to Prevent Tumorigenesis and Select Pancreatic β Cells from Human Embryonic Stem Cells

Therapeutic strategies for targeting telomerase in cancer

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