Dataset Information

Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study.

ABSTRACT: Cancer treatment with high LET heavy ion beam, especially, carbon ion beam ((12)C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the radiosensitivity and induction of apoptosis by high LET (12)C and low LET gamma radiation in HeLa and PARP-1 knocked down cells. We did comet assay to detect DNA breaks, clonogenic survival assay, and cell cycle analysis to measure recovery after DNA damage. We measured apoptotic parameters like nuclear fragmentation and caspase-3 activation. DNA damage, cell killing, and induction of apoptosis were significantly higher for (12)C than gamma radiation in HeLa. Cell killing and apoptosis were further elevated upon knocking down of PARP-1. Both (12)C and gamma induced G2/M arrest although the (12)C had greater effect. Unlike the gamma, (12)C irradiation affects DNA replication as detected by S-phase delay in cell cycle analysis. So, we conclude that high LET (12)C has greater potential over low LET gamma radiation in killing cells and radiosensitization upon PARP-1 inhibition was several folds greater for (12)C than gamma.

SUBMITTER: Ghorai A

PROVIDER: S-EPMC4083825 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study.

Ghorai Atanu A Bhattacharyya Nitai P NP Sarma Asitikantha A Ghosh Utpal U

Scientifica 20140615

Cancer treatment with high LET heavy ion beam, especially, carbon ion beam ((12)C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the radiosensitivity and induction of apoptosis by high LET (12)C and low LET gamma radiation in HeLa and PARP-1 knocked down cel ...[more]

PMID: 25018892

Similar Datasets

Project description:Background:Patients with recurrent glioma after prior radiotherapy have a poor prognosis. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of this study was to analyze toxicity, local control and overall survival after reirradiation of recurrent high-grade glioma with carbon ion radiotherapy. Methods:Between 10/2015 and 12/2018, 30 patients (median age: 59 years) with recurrent high-grade glioma were reirradiated with carbon ion beams and retrospectively analyzed. Diagnosis of recurrent glioma was based on magnetic resonance imaging. Thirteen patients had repeated resection prior to reirradiation and 24 patients underwent additional chemotherapy. The median initial radiation dose was 60 Gy and the median time interval between the initial and repeated radiotherapy was 10 months. The reirradiation dose was 45 Gy (relative biological effectiveness) applied in 15 fractions. All patients received regular follow-up imaging after reirradiation. Kaplan-Meier estimation, log rank test and Cox regression analysis were used for statistical assessment. Results:Applying common toxicity criteria, there were no grade 5 or 4 adverse events, while 8 patients showed grade 3 adverse events. The median follow-up after reirradiation was 11 months and the median overall survival after diagnosis of recurrent high-grade glioma was 13 months. The 6-, 12- and 24-month overall survival rates after diagnosis of recurrent high-grade glioma were 76%, 50% and 19%, respectively. Upon multivariate Cox regression analysis, a Ki67 score of the initial tumor histology of less than 20% was prognostic. Repeated resection or chemotherapy for the recurrent disease did not result in significantly prolonged survival. Conclusion:Carbon ion reirradiation in recurrent high-grade glioma is safe and feasible. No radiation-associated grade 4 toxicities were documented and treatment was tolerated well.

Project description:Superior sulcus tumors are frequently treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery via a trimodal approach. The INKA study evaluated the replacement of photon irradiation by carbon ion radiation therapy (C12-RT) in this regimen. The prospective INKA study included patients with locally advanced non-small cell superior sulcus tumors (<cN3 cM0). Patients received 2 cycles of cisplatin and vinorelbine as per local standard. During the second cycle, 39 Gy(Relative biological effectiveness (RBE)) of hypofractionated C12-RT in 13 fractions were applied. Surgery following fludeoxyglucose F18 positron emission tomography-computed tomography restaging was performed 2 weeks later. The primary endpoint was feasibility and safety measured by the incidence of Common Terminology Criteria for Adverse Events (version 4.0) grade 3/4 toxicity and/or discontinuation because of any reason. Secondary endpoints included the morphologic (Response Evaluation Criteria in Solid Tumors 1.0), metabolic (Positron Emission Tomography Response Criteria in Solid Tumors 1.0), and histopathologic response after nCRT as well as quality of life measurement (QLQ-C30/LC13). Between 2015 and 2020, 14 patients were included and received nCRT. No grade 3/4 toxicity occurred, with no discontinuation because of toxicity. Before surgery, 8 patients (57%) showed a partial response on computed tomography scan. Thirteen patients showed a metabolic response (metabolic complete remission (mCR), 1; metabolic partial remission (mPR), 12). Three patients (21%) were deemed inoperable after nCRT. In patients with resection, a pathologic Complete remission (CR) was seen in 2 patients (19%) and near-complete remission (<10% vital tumor cells) in 6 patients (55%). Pain score was more than half of that at baseline (mean, 69.2 ± 26.2 vs 30.6 ± 29.1; P = .005) after completion of nCRT and before surgery. The INKA trial is the first study to evaluate nCRT with C12-RT and showed excellent response, low toxicity, and rapid pain relief.

Dataset Information

Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study.

Publications

Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets