DNA Double-Strand Break Induction and Repair in Irradiated Lymphoblastoid, Fibroblast Cell Lines and White Blood Cells from ATM, NBS and Radiosensitive Patients

Abstract

Despite showing a clinically elevated radiosensitivity after irradiation, the DNA repair of the patients with clinical hypersensitivity grade 3 (RTOG) appeared to be normal. Other mechanisms such as mutations, altered cell cycle or defective apoptosis could play a critical role toward determining radiosensitivity.

High-Grade Acute Organ Toxicity as Positive Prognostic Factor in Primary Radio(chemo)therapy for Locally Advanced, Inoperable Head and Neck Cancer

“…This hypothesis was tested by Strasser et al [17] analyzing in vitro radiosensitivity of lymphoblastoid cell lines, fibroblasts and white blood cells from healthy donors and cancer patients with or without late effects (grade 3-4 according to the RTOG (Radiation Therapy Oncology Group) Score as well as donors with known radiosensitivity syndromes like heterozygous or homozygous genotype for ataxia-telangiectasia and Nijmegen breakage syndrome. Interestingly, cells of cancer patients with radiation-induced high-grade toxicity showed a normal repair capacity in comparison to cells of patients with known deficiency syndromes.…”

“…It is still unclear, whether a relationship exists between patients' tumor-and normal-tissue radiosensitivity. Until now, only few reports analyzed treatment-related toxicity with respect to treatment outcome [3,4,7,8,12,17,18,22,23]. Therefore, the aim of the present study was to test for a possible correlation between high-grade acute organ toxicity (CTC ≥ grade 3) during radio(chemo)therapy for inoperable HNSCC and prognosis (overall survival and locoregional control).…”

High-Grade Acute Organ Toxicity During Preoperative Radiochemotherapy as Positive Predictor for Complete Histopathologic Tumor Regression in Multimodal Treatment of Locally Advanced Rectal Cancer*

“…It is still unclear whether a relationship exists between patients' tumor and normal-tissue radiosensitivity. Until now, only few reports analyzed treatment-related toxicity with respect to treatment outcome [2,3,7,28].…”

Nuclear EGFR as Novel Therapeutic Target

“…This activation is not associated with a proliferative cell response, but seems to be more related to regulation of cell survival and DNA damage repair [14] as indicated by means of clonogenic survival assays in vitro. Both, regulation of cell survival [10] and DNA repair [55] during treatment regimens with chemo-/radiotherapy were identified as attractive molecular targets during the last years. In such a scenario it is noteworthy, that treatment with tyrosine kinase inhibitors or antibodies in combination with radiation results in inhibition of EGFR-dependent Akt phosphorylation, which is linked with regulation of cell survival [40].…”