RNA interference and potential therapeutic applications of short interfering RNAs

Karagiannis, Tom C.; El‐Osta, Assam

doi:10.1038/sj.cgt.7700857

Cited by 111 publications

(78 citation statements)

References 108 publications

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“…These findings indicate that HDAC inhibitor-mediated radiosensitization is associated with a decrease in the repair of DSBs. Furthermore, a recent study using TSA demonstrated an increase in the number of radiationinduced g-H2AX foci, suggesting that the change in chromatin structure caused by histone hyperacetylation results in an increase in the number of DSBs (Karagiannis et al, 2005).…”

Section: Mechanisms Of Hdac Inhibitor-mediated Enhanced Radiation Senmentioning

confidence: 97%

“…The common theme is a synergistic effect following treatment of cells with HDAC inhibitors and subsequent irradiation. Mechanisms including modulation of cellcycle regulation, particularly G1-phase arrest, inhibition of DNA synthesis and apoptosis, have been identified to explain this phenomenon (Zhang et al, 2004b;Karagiannis et al, 2005;Nome et al, 2005). Clearly these are important mechanisms underlying radiation sensitization by HDAC inhibitors at relatively high doses.…”

Section: Mechanisms Of Hdac Inhibitor-mediated Enhanced Radiation Senmentioning

confidence: 99%

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Modulation of cellular radiation responses by histone deacetylase inhibitors

Karagiannis

El‐Osta

2006

Oncogene

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Histone deacetylase (HDAC) inhibitors are emerging as a new class of targeted cancer chemotherapeutics. Several HDAC inhibitors are currently in clinical trials and promising anticancer effects at well-tolerated doses have been observed for both hematologic and solid cancers. HDAC inhibitors have been shown to induce cell-cycle and growth arrest, differentiation and in certain cases apoptosis in cell cultures and in vivo. However, it is known that these compounds induce varying responses in different cells and biological settings, and identifying their precise mechanisms of action is an area of great interest. Important findings are continually expanding our understanding of the cellular effects of HDAC inhibitors and recent studies will be briefly outlined in this review. In addition to their intrinsic anticancer properties, numerous studies have demonstrated that HDAC inhibitors can modulate cellular responses to other cytotoxic modalities including ionizing radiation, ultraviolet radiation and chemotherapeutic drugs. Hence, there is a growing interest in potential clinical use of HDAC inhibitors in combination with conventional cancer therapies. In this review, the interaction of HDAC inhibitors with other anticancer agents is discussed. The focus of the article is on the different mechanisms by which HDAC inhibitors enhance the sensitivity of cells to the effects of ionizing radiation.

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Section: Mechanisms Of Hdac Inhibitor-mediated Enhanced Radiation Senmentioning

confidence: 97%

Section: Mechanisms Of Hdac Inhibitor-mediated Enhanced Radiation Senmentioning

confidence: 99%

Modulation of cellular radiation responses by histone deacetylase inhibitors

Karagiannis

El‐Osta

2006

Oncogene

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“…The first demonstration in 2001 that siRNA duplexes could be used in mammalian cells to suppress gene expression [6] , provided a new tool for studying gene function in mammalian cells and that may eventually be developed into gene-specific therapeutics. Since these initial reports of RNAi have emerged, it is hoped that this system can be exploited to develop a new class of drugs and numerous review articles have been published focusing on the evolution of RNAi as a therapeutic strategy [7][8][9] .…”

Section: The Rnai Pathway and Sirnamentioning

confidence: 99%

Therapeutic targeting in the silent era: advances in non-viral siRNA delivery

et al. 2010

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Access to the full text of the published version may require a subscription. Rights AbstractGene silencing using RNA-interference, first described in mammalian systems almost a decade ago, is revolutionizing therapeutic target validation efforts both in vitro and in vivo. Moreover, the potential for using short interfering RNA (siRNA) as a therapy in its own right is also progressing at a significant pace. However, the widespread use of such approaches is contingent on having appropriate delivery systems to achieve clinically appropriate, safe, and efficient delivery of siRNA. There are many physicochemical and biological barriers to such delivery, and a growing emphasis on the design and characterisation of non-viral technologies that will overcome these barriers and expedite targeted delivery. This review discusses the considerations and challenges associated with use of siRNA-based therapeutics, including stability and off-target effects. Speculation is made on the properties of an ideal delivery system and the non-viral delivery approaches used to date, both in vitro and in vivo, are classified and discussed. Moreover, the ability of cyclodextrin-based delivery vectors to fulfil many of the criteria of an ideal delivery construct is also elaborated.3 Introduction:

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“…85 Therefore, RNAi-mediated knockdown of cancerassociated genes to inhibit tumor growth, lymphangiogenesis, metastasis, induce apoptosis and subsequently decrease the chemoradiotherapy resistance could be developed either as a stand-alone therapeutic modality or as an adjunct to conventional anticancer therapies. 13 In addition to determining the possible roles of RNAi in cancer treatment, RNAi-based therapies have been conducted to provide new alternatives for the treatment of infectious and neurologic diseases, including viral hepatitis, HIV infection and spinocerebellar ataxia. Most importantly, RNAi-based therapy has been performed in preclinical and phase I clinical trials to develop potential clinical applications of siRNA in various human diseases.…”

Section: 73mentioning

confidence: 99%

RNAi-mediated knockdown of target genes: a promising strategy for pancreatic cancer research

Chang

2007

Cancer Gene Ther

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Pancreatic cancer is one of the most aggressive malignancies with a very poor prognosis, partially due to its very low accessibility to resection and resistance to chemoradiotherapy. As such, it is reasonable to find more effective, specific therapies and the related therapeutic targets. The identification of certain genes contributing to the tumorigenesis and poor prognosis provides the specific targets for efficient silencing by RNA interference (RNAi). As a powerful tool to suppress gene expression in mammalian cells, RNAi can be directed against pancreatic cancer through various pathways, including the inhibition of overexpressed oncogenes, suppression of tumor growth, metastasis and enhancement of apoptosis. In combination with chemoradiotherapy agents, RNAi can also attenuate the chemoradiation resistance of pancreatic cancer. In addition, RNAi has been used to define the 'loss of function' of endogenous genes in pancreatic cancer. This review provides a brief introduction to recent developments of RNAi applications in pancreatic cancer studies and suggestions for further exploration. It substantially demonstrates that RNAi holds a promising therapeutic potential as a future treatment for pancreatic cancer.

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RNA interference and potential therapeutic applications of short interfering RNAs

Cited by 111 publications

References 108 publications

Modulation of cellular radiation responses by histone deacetylase inhibitors

Modulation of cellular radiation responses by histone deacetylase inhibitors

Therapeutic targeting in the silent era: advances in non-viral siRNA delivery

RNAi-mediated knockdown of target genes: a promising strategy for pancreatic cancer research

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