Radioresistance in a tumour cell line correlates with radiation inducible Ku 70/80 end-binding activity

Negroni, Anna; Stronati, Laura; Grollino, Maria Giuseppa; Barattini, Paola; Gumiero, Daniela; Danesi, Donatella Tirindelli

doi:10.1080/09553000801953318

Cited by 10 publications

(9 citation statements)

References 46 publications

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“…These methods enhanced the radiation response, as tabulated in Table 4, by a factor of 1.2 to 1.9 (9–11, 31–36) that is much smaller than factors obtained for mutant and knocked-out cells. These gene insertion methods have been established with clinical applications in mind for the safe and successful insertion of anti-Ku70/80 cDNA or fragment.…”

Section: Discussionmentioning

confidence: 78%

Response to Multiple Radiation Doses of Human Colorectal Carcinoma Cells Infected With Recombinant Adenovirus Containing Dominant-Negative Ku70 Fragment

Urano¹,

He²,

Minami³

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To investigate the effect of recombinant replication-defective adenovirus containing DN (dominant-negative)Ku70 fragment on the response of tumor cells to multiple small radiation doses.Ultimate goal is to demonstrate the feasibility of using this virus in gene-radiotherapy to enhance the radiation response of tumor cells.Materials and Methods-Human colorectal HCT8 and HT29 carcinoma cells were plated in glass tubes, infected with virus (25 MOI) and irradiated with single doses or 0-5 doses of 3 Gy with 6 h intervals. Hypoxia was induced by flushing 100% N 2 . Cells were trypsinized 0 or 6 h after (final) irradiation, and cell survival determined by colony formation. Survival data were fitted to L-Q model or exponential line.Results-Virus infection enhanced the radiation response of HCT8 and HT29 cells. Virus enhancement ratio (VER) for single dose irradiation at surviving fraction of 0.1 was ~1.3 for both oxic and hypoxic HCT8, and 1.4 and 1.1 for oxic and hypoxic HT29, respectively. Similar VER of 1.2-1.3 was observed for both oxic and hypoxic cells irradiated with multiple doses but these values were smaller than values found for DNKu70-transfected Rat-1 cells. This difference is discussed. The OERs for HCT8 and HT29 receiving fractionated doses were 1.2 and 2.0, respectively, and virusinfection slightly altered them.Conclusion-Infection of recombinant replication-defective adenovirus containing DNKu70 fragment enhanced the response of human colorectal cancer cells to single and multiple doses.

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Section: Discussionmentioning

confidence: 78%

Response to Multiple Radiation Doses of Human Colorectal Carcinoma Cells Infected With Recombinant Adenovirus Containing Dominant-Negative Ku70 Fragment

Urano¹,

He²,

Minami³

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

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“…Candidate molecules with a potential to fulfil this role include those involved in the cellular DNA damage response (DDR) pathways, such as apoptosis related bcl-225 and survivin,26 as well as DNA double strand break (DSB) recognizing Ku80,27 and those that potentiate the malignant tumour phenotype, such as epidermal growth factor receptor (EGFR)28 and vascular endothelial growth factor 25. However, none of these or others has as yet convincingly shown the clinical applicability as a predictive marker of radiotherapy response.…”

Section: Predictive Markers Of Sensitivity To Radiotherapymentioning

confidence: 99%

Radiotherapy Response in Microsatellite Instability Related Rectal Cancer

et al. 2013

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Preoperative radiotherapy may improve the resectability and subsequent local control of rectal cancers. However, the extent of radiation induced regression in these tumours varies widely between individuals. To date no reliable predictive marker of radiation sensitivity in rectal cancer has been identified. At the cellular level, radiation injury initiates a complex molecular network of DNA damage response (DDR) pathways that leads to cell cycle arrest, attempts at re-constituting the damaged DNA and should this fail, then apoptosis. This review presents the details which suggest the roles of DNA mismatch repair proteins, the lack of which define a distinct subset of colorectal cancers with microsatellite instability (MSI), in the DDR pathways. Hence routine assessment of the MSI status in rectal cancers may potentially serve as a predictor of radiotherapy response, thereby improving patient stratification in the administration of this otherwise toxic treatment.

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“…Some of the candidate molecules which have more recently demonstrated their potential to fulfill this role include those that are directly relevant to DNA damage response following irradiation, such as anti-apoptotic proteins bcl-2 2 and survivin, 3 as well as DNA double strand breaks recognising Ku80, 4 in addition to those that potentiate the malignant behaviour of the tumour cells, such as proliferation promoting epidermal growth factor receptor 5 and angiogenesis sustaining vascular endothelial growth factor. Some of the candidate molecules which have more recently demonstrated their potential to fulfill this role include those that are directly relevant to DNA damage response following irradiation, such as anti-apoptotic proteins bcl-2 2 and survivin, 3 as well as DNA double strand breaks recognising Ku80, 4 in addition to those that potentiate the malignant behaviour of the tumour cells, such as proliferation promoting epidermal growth factor receptor 5 and angiogenesis sustaining vascular endothelial growth factor.…”

Section: Introductionmentioning

confidence: 99%

Telomerase expression as a predictive marker of radiotherapy response in rectal cancer: in vitro and in vivo study

et al. 2012

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Radioresistance in a tumour cell line correlates with radiation inducible Ku 70/80 end-binding activity

Abstract: Our data demonstrate that in a bladder tumour cell line up-regulation of Ku end-binding activity without any marked change in Ku expression underlie radiation resistance.

Cited by 10 publications

References 46 publications

Response to Multiple Radiation Doses of Human Colorectal Carcinoma Cells Infected With Recombinant Adenovirus Containing Dominant-Negative Ku70 Fragment

Response to Multiple Radiation Doses of Human Colorectal Carcinoma Cells Infected With Recombinant Adenovirus Containing Dominant-Negative Ku70 Fragment

Radiotherapy Response in Microsatellite Instability Related Rectal Cancer

Telomerase expression as a predictive marker of radiotherapy response in rectal cancer: in vitro and in vivo study

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