The evaluation of low dose hyper-radiosensitivity in normal human skin

Harney, J.; Shah, Nihal; Short, Susan; Groom, N.; Wilson, George D.; Joiner, Michael C.; Saunders, Michele I.

doi:10.1016/j.radonc.2004.01.015

Cited by 35 publications

(15 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clearly, more molecular-based experiments are needed using whole-animal models to characterize the mechanisms of HRS in normal tissue radiation injury. Clinical data obtained so far are also consistent with the concept of transitional low-dose radiation responses in tumor nodules derived from solid tumors [30]. …”

Section: Experimental Studiessupporting

confidence: 77%

Three-Times Daily Ultrafractionated Radiation Therapy, A Novel and Promising Regimen for Glioblastoma Patients

Beauchesne

2013

Cancers

View full text Add to dashboard Cite

Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cell lines are sensitive to low radiation doses of <1 Gy. This phenomenon has been termed low-dose hyper-radio-sensitivity (HRS), and is more apparent in radio resistant cell lines, such as glioblastoma cells. Sensitivity may result from the inability of low dose radiation to efficiently induce repair mechanisms, whereas higher doses cause enough damage to trigger repair responses for radio resistance. In vitro studies have demonstrated this phenomenon using various human malignant glioma cell lines: (1) daily repeated irradiation of cells with low doses compared to irradiation using a single biologically equivalent dose resulted in significantly higher cell killing; (2) experiments conducted on glioma xenografts demonstrated that repeated irradiation with low doses was more effective for inhibiting tumor growth than a single dose. In order to confirm and validate these promising studies on HRS, a few phase II trials were developed. For translating the experimental observations into the clinic, ultra fractionation protocols (with three daily doses) were tested in glioblastoma patients. Tolerance and toxicity were the primary endpoints, with overall survival as a secondary endpoint. These protocols were initiated before concomitant radio chemotherapy became the standard of care. For these trials, patients with an unfavorable clinical prognostic factor of newly unresectable GBM were included. When comparing the results of these trials with international literature using multivariate analysis for both progression free survival and overall survival, ultra fractionated irradiation showed superiority over radiotherapy alone. In addition, it was found to be equivalent to treatment using radiotherapy and temozolomide. Therefore, ultra fractionated protocols may prolong survival of glioblastoma patients. In this review, we describe the main experimental data regarding low-dose hypersensitivity as well as the findings of clinical trials that have investigated this new radiotherapy regimen.

show abstract

Section: Experimental Studiessupporting

confidence: 77%

Three-Times Daily Ultrafractionated Radiation Therapy, A Novel and Promising Regimen for Glioblastoma Patients

Beauchesne

2013

Cancers

View full text Add to dashboard Cite

show abstract

“…Cells were irradiated with either a 2 Gy single dose or 10  0.2 Gy pulse dose and fixed at 24 hour post irradiation. slowly-proliferating metastatic skin nodules (Harney et al 2004a(Harney et al , 2004b. In addition, human and rodent cells in tissue culture (Lin and Wu 2005) and U87MG intracranial tumors in vivo (Park et al 2011) were shown to be more sensitive to ultra-fractionation with 10  0.2 Gy when compared with the same total dose given continuously.…”

Section: Discussionmentioning

confidence: 99%

Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: A cell line study in four glioblastoma multiforme (GBM) cell lines

Schoenherr

Krueger

Martin

et al. 2013

International Journal of Radiation Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…This is termed low dose HRS (LDHRS). Evidence for the existence of LDHRS has been confirmed, excluded or disputed in cell line experiments, animal models and human normal tissue studies [8] . According to our experimental results, A549 cells showed HRS/IRR responses to γ-rays at the threshold dose (Dc) of 0.3 Gy.…”

Section: Discussionmentioning

confidence: 99%

Low dose hyper-radiosensitivity in human lung cancer cell line A549 and its possible mechanisms

Dai

Tao

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

View full text Add to dashboard Cite

The low dose hyper-radiosensitivity (HRS) in human lung cancer cell line A549 was investigated, the changes of ATM kinase, cell cycle and apoptosis of cells at different doses of radiation were observed, and the possible mechanisms were discussed. A549 cells in logarithmic growth phase were irradiated with (60)Co gamma-rays at doses of 0-2 Gy. Together with flow cytometry for precise cell sorting, cell survival fraction was measured by means of conventional colony-formation assay. The expression of ATM1981Ser-P protein was examined by Western blot 1 h after radiation. Apoptosis was detected by Hoechst 33258 fluorescent staining, and Annexin V-FITC/PI staining flow cytometry 24 h after radiation. Cell cycle distribution was observed by flow cytometry 6, 12 and 24 h after radiation. The results showed that the expression of ATM1981Ser-P protein was observed at 0.2 Gy, followed by an increase at >0.2 Gy, and reached the peak at 0.5 Gy, with little further increase as the dose exceeded 0.5 Gy. Twenty-four h after radiation, partial cells presented the characteristic morphological changes of apoptosis, and the cell apoptosis curve was coincident with the survival curve. As compared with control group, the cell cycle almost had no changes after exposure to 0.1 and 0.2 Gy radiation (P>0.05). After exposure to 0.3, 0.4 and 0.5 Gy radiation, G(2)/M phase arrest occurred 6 and 12 h after radiation (P<0.05), and the ratio of G(2)/M phase cells was decreased 24 h after radiation (P<0.05). It was concluded that A549 cells displayed the phenomenon of HRS/IRR. The mode of cell death was mainly apoptosis. The activity of ATM and cell cycle change may take an important role in HRS/IRR.

show abstract

The evaluation of low dose hyper-radiosensitivity in normal human skin

Cited by 35 publications

References 30 publications

Three-Times Daily Ultrafractionated Radiation Therapy, A Novel and Promising Regimen for Glioblastoma Patients

Three-Times Daily Ultrafractionated Radiation Therapy, A Novel and Promising Regimen for Glioblastoma Patients

Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: A cell line study in four glioblastoma multiforme (GBM) cell lines

Low dose hyper-radiosensitivity in human lung cancer cell line A549 and its possible mechanisms

Contact Info

Product

Resources

About