Gamma histone 2AX (<b>γ</b>-H2AX)as a predictive tool in radiation oncology

Pouliliou, Stamatia; Koukourakis, Michael I.

doi:10.3109/1354750x.2014.898099

Cited by 46 publications

(44 citation statements)

References 116 publications

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“…SF2 is an index of cell viability after exposure to 2 Gy, more often applied for the characterization of intrinsic radiation sensitivity in tumor models (8,9). H2AX phosphorylation (gH2AX), on the other hand, being directly involved in DNA damage and repair, represents a strong target for the development of biomarkers related to tissue radiation sensitivity (6). As PBMCs can be easily obtained from the peripheral blood of patients, we postulated that the assessment of SF2 and of H2AX phosphorylation kinetics in these cells could predict early radiation toxicities in patients undergoing radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

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Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

Pouliliou¹,

Lialiaris²,

Dimitriou³

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussionmentioning

confidence: 99%

“…The rate of gH2AX restoration to normal levels is a result of DNA repair activity of cells. Thus, finding tools to quantify these 2 gH2AX-related parameters would prove to be valuable to predict individual radiation sensitivity (6).…”

Section: Introductionmentioning

confidence: 99%

Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

Pouliliou¹,

Lialiaris²,

Dimitriou³

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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“…Thus, γH2AX has been utilized as a pharmacodynamic marker in clinical studies. For example, γH2AX foci were enumerated to determine irradiation toxicity at different dosages and to evaluate chemotherapeutic drug responses [4, 35, 36]. According to our observations, the remaining levels but not initial level of γH2AX positive cells is a better predictor for drug sensitivity.…”

Section: Discussionmentioning

confidence: 99%

XLF-mediated NHEJ activity in hepatocellular carcinoma therapy resistance

Yang

Wang

2017

BMC Cancer

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BackgroundDNA repair pathways are used by cancer cells to overcome many standard anticancer treatments, causing therapy resistance. Here, we investigated the role of XRCC4-like factor (XLF), a core member of the non-homologous end joining (NHEJ) repair pathway, in chemoresistance in hepatocellular carcinoma (HCC).MethodsqRT-PCR analysis and western blotting were performed to detect expression levels of genes and proteins related to NHEJ. NHEJ repair capacity was assessed in vitro (cell-free) and in vivo by monitoring the activity of the NHEJ pathway. Cell viability and IC50 assays were used to measure sensitivity to drug therapy. A xenograft HCC model was used to develop methods of targeting XLF-induced chemosensitization. Clinicopathological analysis was conducted on patients with HCC treated with transarterial chemoembolization (TACE).ResultsMany conventional cancer chemotherapeutics induce DNA double-strand breaks (DSBs). HCC cells respond to these breaks by increasing their NHEJ activity, resulting in resistance. XLF-knockdown cells show an inhibition of NHEJ activity in both cell-free and live-cell assays as well as a high level of unrepaired cellular DSBs. These results indicate that XLF facilitates DNA end-joining and therefore promotes NHEJ activity in cancer cells. Consequently, knockdown of XLF significantly chemosensitized resistant cells both in vitro and in xenograft tumors. A low rate of XLF genomic alteration was found in patients with primary HCC, but XLF expression was induced after drug treatment. Clinically, a high level of XLF expression is significantly associated with advanced HCC and shorter overall survival.ConclusionChemotherapy-induced overexpression of XLF and XLF-mediated enhancements in NHEJ activity contribute to chemoresistance in HCC cells and patients with HCC. Targeting XLF to modulate DSB repair could enhance drug sensitivity and may be a therapeutically useful addition to conventional therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3345-y) contains supplementary material, which is available to authorized users.

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“…[23][24][25][26] Antibodies against phosphorylated serine 139 have been developed which can be useful for the identification of gH2AX foci through immunochemistry. In addition, this method can identify the kinetics of repair over a 24 h period by revealing the cellular differences in DNA DSB repair.…”

Section: Methods Of Gh2ax Detectionmentioning

confidence: 99%

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

Palla¹,

Karaolanis

Katafigiotis

et al. 2017

Tumour Biol.

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Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to doublestrand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.

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Gamma histone 2AX (γ-H2AX)as a predictive tool in radiation oncology

Cited by 46 publications

References 116 publications

Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

XLF-mediated NHEJ activity in hepatocellular carcinoma therapy resistance

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

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