scholarly journals A Mathematical Radiobiological Model (MRM) to Predict Complex DNA Damage and Cell Survival for Ionizing Particle Radiations of Varying Quality

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 840
Author(s):  
Spyridon A. Kalospyros ◽  
Zacharenia Nikitaki ◽  
Ioanna Kyriakou ◽  
Michael Kokkoris ◽  
Dimitris Emfietzoglou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Therapy ◽  
Cell Survival ◽  
Radiation Protection ◽  
Multiscale Approach ◽  
Cross Sectional ◽  
Beam Radiation ◽  
Biological Damage ◽  
Radiobiological Model ◽  
Radiobiological Effects

Predicting radiobiological effects is important in different areas of basic or clinical applications using ionizing radiation (IR); for example, towards optimizing radiation protection or radiation therapy protocols. In this case, we utilized as a basis the ‘MultiScale Approach (MSA)’ model and developed an integrated mathematical radiobiological model (MRM) with several modifications and improvements. Based on this new adaptation of the MSA model, we have predicted cell-specific levels of initial complex DNA damage and cell survival for irradiation with 11Β, 12C, 14Ν, 16Ο, 20Νe, 40Αr, 28Si and 56Fe ions by using only three input parameters (particle’s LET and two cell-specific parameters: the cross sectional area of each cell nucleus and its genome size). The model-predicted survival curves are in good agreement with the experimental ones. The particle Relative Biological Effectiveness (RBE) and Oxygen Enhancement Ratio (OER) are also calculated in a very satisfactory way. The proposed integrated MRM model (within current limitations) can be a useful tool for the assessment of radiation biological damage for ions used in hadron-beam radiation therapy or radiation protection purposes.

scholarly journals A theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy

2020 ◽  
Vol 65 (9) ◽  
pp. 095006
Author(s):  
Yusuke Matsuya ◽  
Tatsuhiko Sato ◽  
Rui Nakamura ◽  
Shingo Naijo ◽  
Hiroyuki Date
Keyword(s):  
Dna Damage ◽  
Radiation Therapy ◽  
Cell Survival ◽  
Cell Killing ◽  
Survival Endpoints ◽  
Oxygen Enhancement

scholarly journals EXTH-29. INHIBITION OF LYSINE-SPECIFIC HISTONE DEMETHYLASE 1A (KDM1A/LSD1) SENSITIZES GLIOBLASTOMA CELLS TO CHEMO AND RADIATION THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii93-ii93
Author(s):  
Salvador Alejo ◽  
Bridgitte Palacios ◽  
Prabhakar Pitta Venkata ◽  
Yihong Chen ◽  
Yi He ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Therapy ◽  
Cell Viability ◽  
Clonogenic Survival ◽  
Histone Demethylase ◽  
External Beam Radiation ◽  
Rna Seq ◽  
Current Standard ◽  
Beam Radiation

Abstract BACKGROUND Despite treatment advances, glioblastoma (GBM) is the deadliest tumor of the central nervous system. Patients face a dismal 15-month median survival and average 5-year survival rate of 13%. Current standard of care includes surgical resection, external beam radiation therapy, and adjuvant chemotherapy with temozolomide (TMZ). Unfortunately, GBM patients often relapse and succumb to their disease. Recently, we have shown that lysine-specific histone demethylase 1A (KDM1A/LSD1) is overexpressed in GBM. In this study, we tested the hypothesis that KDM1A is essential for DNA damage response (DDR), inhibiting KDM1A thereby sensitizes GBM to either TMZ or radiation therapy. METHODS KDM1A knockout (KDM1A-KO) and knockdown (KDM1A-KD) cells were generated using CRISPR/Cas9 and KDM1A specific shRNA, respectively. Cell viability, clonogenic survival, and apoptotic assays were used to study the effect of KDM1A-KO, -KD, or pharmacological KDM1A inhibitors (NCD-38 and NCL-1) on radiation and TMZ sensitization. Mechanistic studies were conducted using RNA-seq, RT-qPCR, and western blot analysis. Furthermore, in vivo efficacy of KDM1A inhibitor and TMZ was established using orthotopic models of GBM. RESULTS Cell viability, survival, and apoptotic assays demonstrated that knockout/knockdown or inhibition of KDM1A sensitized GBM cells to both TMZ or radiation therapy. KDM1A inhibitors used in combination with radiation or TMZ significantly increased apoptosis in GBM cells. RNA-seq analysis and signaling studies showed attenuation of DDR pathways in KDM1A-KD cells. Radiation or TMZ treatment enhanced DNA damage in KDM1A-KD cells compared to controls. Importantly, combination of KDM1A inhibitor and TMZ significantly reduced in vivo tumor progression and improved overall survival in orthotopic GBM murine models. CONCLUSIONS Our results provide strong evidence that KDM1A inhibition sensitizes GBM to TMZ or radiation therapy via modulation of DDR. This suggests combination of KDM1A inhibitors with TMZ or radiation therapy could serve as a novel treatment for GBM patients.

Evaluation and treatment of children with radiation-induced cerebral vasculopathy

2019 ◽  
Vol 24 (6) ◽  
pp. 680-688
Author(s):  
David S. Hersh ◽  
Kenneth Moore ◽  
Vincent Nguyen ◽  
Lucas Elijovich ◽  
Asim F. Choudhri ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Proton Beam ◽  
Tumor Imaging ◽  
Clinic Visit ◽  
Surgical Patient ◽  
Beam Radiation ◽  
Proton Beam Radiotherapy ◽  
Cranial Radiation ◽  
Delayed Complication ◽  
Radiation Induced

OBJECTIVEStenoocclusive cerebral vasculopathy is an infrequent delayed complication of ionizing radiation. It has been well described with photon-based radiation therapy but less so following proton-beam radiotherapy. The authors report their recent institutional experience in evaluating and treating children with radiation-induced cerebral vasculopathy.METHODSEligible patients were age 21 years or younger who had a history of cranial radiation and subsequently developed vascular narrowing detected by MR arteriography that was significant enough to warrant cerebral angiography, with or without ischemic symptoms. The study period was January 2011 to March 2019.RESULTSThirty-one patients met the study inclusion criteria. Their median age was 12 years, and 18 (58%) were male. Proton-beam radiation therapy was used in 20 patients (64.5%) and photon-based radiation therapy was used in 11 patients (35.5%). Patients were most commonly referred for workup as a result of incidental findings on surveillance tumor imaging (n = 23; 74.2%). Proton-beam patients had a shorter median time from radiotherapy to catheter angiography (24.1 months [IQR 16.8–35.4 months]) than patients who underwent photon-based radiation therapy (48.2 months [IQR 26.6–61.1 months]; p = 0.04). Eighteen hemispheres were revascularized in 15 patients. One surgical patient suffered a contralateral hemispheric infarct 2 weeks after revascularization; no child treated medically (aspirin) has had a stroke to date. The median follow-up duration was 29.2 months (IQR 21.8–54.0 months) from the date of the first catheter angiogram to last clinic visit.CONCLUSIONSAll children who receive cranial radiation therapy from any source, particularly if the parasellar region was involved and the child was young at the time of treatment, require close surveillance for the development of vasculopathy. A structured and detailed evaluation is necessary to determine optimal treatment.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 37-41 ◽  
Author(s):  
William F. Regine ◽  
Roy A. Patchell ◽  
James M. Strottmann ◽  
Ali Meigooni ◽  
Michael Sanders ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Content Type ◽  
Group B ◽  
Fine Print

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.

Diode in Vivo Dosimetry for Patients Receiving External Beam Radiation Therapy

10.37206/88 ◽  
2005 ◽  
Author(s):  
Ellen Yorke ◽  
Rodica Alecu ◽  
Li Ding ◽  
Doracy Fontenla ◽  
Andre Kalend ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
External Beam Radiation Therapy ◽  
External Beam Radiation ◽  
In Vivo Dosimetry ◽  
External Beam ◽  
Beam Radiation
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