scholarly journals A Novel Mechanism of High Dose Radiation Sensitization by Metformin

2019 ◽  
Vol 9 ◽  
Author(s):  
Stephen L. Brown ◽  
Andrew Kolozsvary ◽  
Derek M. Isrow ◽  
Karine Al Feghali ◽  
Karen Lapanowski ◽  
...  
2021 ◽  
Vol 3 (3) ◽  
pp. 100-112
Author(s):  
Sarah Martinez Roth ◽  
Eveline E. Vietsch ◽  
Megan E. Barefoot ◽  
Marcel O. Schmidt ◽  
Matthew D. Park ◽  
...  

Thoracic high-dose radiation therapy (RT) for cancer has been associated with early and late cardiac toxicity. To assess altered rates of cardiomyocyte cell death due to RT we monitored changes in cardiomyocyte-specific, cell-free methylated DNA (cfDNA) shed into the circulation. Eleven patients with distal esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy (RT) and concurrent carboplatin and paclitaxel were enrolled. Subjects underwent fasting blood draws prior to the initiation and after completion of RT as well as 4–6 months following RT. An island of six unmethylated CpGs in the FAM101A locus was used to identify cardiomyocyte-specific cfDNA in serum. After bisulfite treatment this specific cfDNA was quantified by amplicon sequencing at a depth of >35,000 reads/molecule. Cardiomyocyte-specific cfDNA was detectable before RT in the majority of patient samples and showed some distinct changes during the course of treatment and recovery. We propose that patient-specific cardiac damages in response to the treatment are indicated by these changes although co-morbidities may obscure treatment-specific events.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shuai Liu ◽  
Yanwei Liu ◽  
Guanzhang Li ◽  
Jin Feng ◽  
Li Chen ◽  
...  

Abstract Background As molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG. Methods In the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy. Results In total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival. Conclusions In conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.


2002 ◽  
Vol 63 (3-6) ◽  
pp. 719-722 ◽  
Author(s):  
Ana M.Sisti Galante ◽  
Barbara M. Rzyski ◽  
Letı́cia L. Campos ◽  
Anna L. Villavicencio

2010 ◽  
Vol 89 (1) ◽  
pp. 200-206 ◽  
Author(s):  
Mark J. Krasna ◽  
Ziv Gamliel ◽  
Whitney M. Burrows ◽  
Joshua R. Sonett ◽  
King F. Kwong ◽  
...  

2017 ◽  
Vol 58 (3) ◽  
pp. 329-340 ◽  
Author(s):  
Ji-Hye Yim ◽  
Jung Mi Yun ◽  
Ji Young Kim ◽  
In Kyung Lee ◽  
Seon Young Nam ◽  
...  

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation.


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