NF-κB as a key player in regulation of cellular radiation responses and identification of radiation countermeasures

Singh, Vijay K.; Gupta, Damodar; Arora, Rajesh

doi:10.15190/d.2015.27

Cited by 49 publications

(55 citation statements)

References 260 publications

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“…Therefore, it is important that the FDA provides more guidance to such companies throughout the development process. This approach is not uncommon to the FDA as there are a large number of countermeasures for various threats at different stages of development and several recent review articles cover this area of development [95][96][97].…”

Section: Resultsmentioning

confidence: 99%

Medical countermeasures for unwanted CBRN exposures: Part I chemical and biological threats with review of recent countermeasure patents

Singh

Garcia

Wise

et al. 2016

Expert Opinion on Therapeutic Patents

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The threat of chemical, biological, radiological, and nuclear (CBRN) warfare has been addressed as the uppermost risk to national security since the terrorist attacks on 11 September 2001. Despite significant scientific advances over the past several decades toward the development of safe, non-toxic and effective countermeasures to combat CBRN threats, relatively few countermeasures have been approved by the US Food and Drug Administration (US FDA). Therefore, countermeasures capable of protecting the population from the effects of CBRN attack remain a significant unmet medical need. Chemical and biological (CB) threat agents can be particularly hazardous due to their effectiveness in small quantities and ease of distribution. Area covered: This article reviews the development of countermeasures for CB threats and highlights specific threats for which at least one countermeasure has been approved following the FDA Animal Rule. Patents of CB countermeasures since 2010 have been included. Expert opinion: Nine CB countermeasures have received FDA approval for use in humans following the Animal Rule, and a number of promising CB countermeasures are currently under development. In the next few years, we should expect to have multiple countermeasures approved by the FDA for each indication allowing for more flexible and effective treatment options.

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Section: Resultsmentioning

confidence: 99%

Medical countermeasures for unwanted CBRN exposures: Part I chemical and biological threats with review of recent countermeasure patents

Singh

Garcia

Wise

et al. 2016

Expert Opinion on Therapeutic Patents

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show abstract

“…Amifostine undergoes de-phosphorylation by alkaline phosphatase and becomes an active sulfhydryl compound (WR 1065); with easy cell permeability for free radical scavenging. Since alkaline phosphatase is less expressed in tumor cells, risk of tumor protection was not there [12,13]. Even though it went to phase III trials in reversing mucositis, xerostomia, dysphagia, pneumonitis and dermatitis, its side effects such as nausea, vomiting, hypotension and neurotoxicity outweighed the benefits and therefore is now not being used as a radioprotector [14].…”

Section: Radiation Countermeasures: Current Status Of Radioprotectorsmentioning

confidence: 99%

“…Even though it went to phase III trials in reversing mucositis, xerostomia, dysphagia, pneumonitis and dermatitis, its side effects such as nausea, vomiting, hypotension and neurotoxicity outweighed the benefits and therefore is now not being used as a radioprotector [14]. Similar to sulfhydryls, nitroxide free radicals and their reduction productshydroxylamines are another group currently being investigated, where Tempol (4-hydroxy-2, 2, 6, 6-tetra methyl piperidine-1-oxyl) is a representative [12]. Nonetheless; therapeutic efficacy of all these, are yet to be ascertained.…”

Section: Radiation Countermeasures: Current Status Of Radioprotectorsmentioning

confidence: 99%

“…Vis-a-vis nuclear accidents, radiotherapy for cancer treatment represents controlled exposure of radiation for killing malignant cells. Acute and chronic toxicities of normal tissues during radiotherapy are still an unresolved clinical issue [12]. Implicitly, efforts to repeal the side effects of cancer radiotherapy on normal cells would be a primary target for all the currently researched radioprotectors and mitigators.…”

Section: Spin-offs In Health Care From Radiation Researchmentioning

confidence: 99%

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Emerging Strategies in Radiation Countermeasure Research

Krishnan¹,

Singh²

2017

IJRRT

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“…Transcription factor like p53 can regulate various signal transduction pathways, including apoptosis. Mitogen activated protein kinase (MAPK) pathway consists of three tiered kinase (ERK, SAPK, and p38), involved in cell proliferation, differentiation and apoptosis [12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells

Lal

Gupta

2016

Discoveries (Craiova)

Self Cite

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Recent reports demonstrated the role of silymarin as a cytoprotective agent for normal cells against ionizing or non-ionizing (UV) radiation, and in inhibiting the chemically initiated or promoted carcinogenesis in several malignancies, such as skin or prostate cancers. Silymarin is a plant flavonoid obtained from milk thistle; the main active principles in milk thistle are silybin (silibinin), sylichrisitin and silydianin, commonly referred as silymarin. In the present study, we aimed to investigate the radiation modulatory effects of silymarin on cancer cells. For this, we used the HCT-15 and RKO colon cancer cell lines as a model. Pre-irradiation treatment of cells with silymarin (20 µg/ml) followed by radiation exposure inhibits colon cancer cell proliferation and enhances cell death in a time-dependent manner. We have also examined the changes in p53 phosphorylation at Ser15, phosphorylation of p38 and their association with DNA damage. Silymarin was found to reduce proliferation of the human colon carcinoma cells in a concentration and timedependent manner. Moreover, percentage of cell death was also increased in combined treatment (20µg/ml of silymarin + radiation). Our studies indicate that the combination increases the arrest of cells in G 2 /M phase of cell cycle, DNA damageinduced decrease in mitochondrial membrane potential (MMP) and a decrease of the reactive oxygen species (ROS) levels, which are associated with an increase in cell death. Altogether, these results suggest that silymarin sensitizes colon cancer cells to radiation, strategy with potential for colon cancer treatment. Noteworthy, since silymarin was previously shown to confer protection against radiation in at least some types of normal tissues, additional studies are needed to further investigate the potential of silymarin in colon cancer therapy when combined with radiation, its potential protective effects on normal tissues and its mechanisms of action.

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NF-κB as a key player in regulation of cellular radiation responses and identification of radiation countermeasures

Cited by 49 publications

References 260 publications

Medical countermeasures for unwanted CBRN exposures: Part I chemical and biological threats with review of recent countermeasure patents

Medical countermeasures for unwanted CBRN exposures: Part I chemical and biological threats with review of recent countermeasure patents

Emerging Strategies in Radiation Countermeasure Research

Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells

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