Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54–56 Gy given in 9–7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size

AbstractThe lung is one of the most sensitive tissues to ionizing radiation, thus, radiation-induced lung injury (RILI) stays a key dose-limiting factor of thoracic radiotherapy. However, there is still little progress in the effective treatment of RILI. Ras-related C3 botulinum toxin substrate1, Rac1, is a small guanosine triphosphatases involved in oxidative stress and apoptosis. Thus, Rac1 may be an important molecule that mediates radiation damage, inhibition of which may produce a protective effect on RILI. By establishing a mouse model of radiation-induced lung injury and orthotopic lung tumor-bearing mouse model, we detected the role of Rac1 inhibition in the protection of RILI and suppression of lung tumor. The results showed that ionizing radiation induces the nuclear translocation of Rac1, the latter then promotes nuclear translocation of P53 and prolongs the residence time of p53 in the nucleus, thereby promoting the transcription of Trp53inp1 which mediates p53-dependent apoptosis. Inhibition of Rac1 significantly reduce the apoptosis of normal lung epithelial cells, thereby effectively alleviating RILI. On the other hand, inhibition of Rac1 could also significantly inhibit the growth of lung tumor, increase the radiation sensitivity of tumor cells. These differential effects of Rac1 inhibition were related to the mutation and overexpression of Rac1 in tumor cells.

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The influence of the drug LHS-1208 on cardiovascular system

Russian Journal of Biotherapy ◽

10.17650/1726-9784-2018-17-3-70-80 ◽

2018 ◽

Vol 17 (3) ◽

pp. 70-80

Author(s):

N. P. Ermakova ◽

I. V. Merkulova ◽

O. I. Konyaeva ◽

N. Yu. Kulbachevskaya ◽

T. V. Abramova ◽

...

Keyword(s):

Lactate Dehydrogenase ◽

Total Dose ◽

Cardiovascular System ◽

Anticancer Drug ◽

Aspartate Aminotransferase ◽

Heart Muscle ◽

Maximum Dose ◽

Morphological Changes ◽

Toxicological Study ◽

Functional Changes

Introduction.This article presents a fragment of a preclinical toxicological study of a new Russian anticancer drug derived from n-glycoside indolokarbazole LCS-1208 – study of cardiotoxicity, which is one of the specific complications of anticancer chemotherapy.Objective.Preclinical toxicological study of the effect of the drug LCS-1208 on the cardiovascular system of animals to assess its cardiotoxic effects.Materials and methods.Studies were conducted on 40 healthy non-harmless mongrel male rats and 4 dogs Beagle, male and female. The drug was administered daily 15 times to rats-intraperitoneal in total doses of 50, 100 and 200 mg/kg; to dogs – intravenously in total doses of 20 and 30 mg/kg. The period of observation of rats was 30 days, for dogs was 60 days. Changes in electrocardiogram indices, macroscopic and histological picture of heart changes and changes in biochemical parameters of enzymes activity – lactate dehydrogenase and aspartate aminotransferase were evaluated.Results.In rats LCS-1208 throughout the period of observation caused functional changes in electrocardiogram: increase in PQ and QT intervals and cardiac rhythm disturbance (loss of R wave), which indicates a violation of electrical conductivity. Morphological changes in the heart muscle were detected on the 3rd day of observation in total doses of 100 and 200 mg/kg, which remained until 30 days of observation only in animals receiving the drug in the total dose of 200 mg/kg. In some dogs for different periods of observation the drug caused functional changes in the electrical activity of the heart: an increase in the QRS interval, the inversion of the T wave, the appearance of a deep Q wave and an increase in the activity of lactate dehydrogenase and aspartate aminotransferase compared to back ground indicators. Morphological changes in the heart muscle were detected on the 3rd day of observation only in the total dose of 30 mg/kg, which persisted up to 60 days of observation.Conclusion.It was found that the new Russian anticancer drug LHC-1208, a derivative of indocarbazole N-glycoside, has a cardiotoxic effect, causing functional changes in the cardiovascular system of rats in all doses studied, and in dogs only in the maximum dose. Morphologically, cardiotoxicity is not confirmed in animals receiving a minimal dose of the drug, but only in animals receiving the maximum dose of the drug.

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Genome-wide identification and analysis of A-to-I RNA editing events in the malignantly transformed cell lines from BEP2D induced by α-particles radiation

10.1101/551499 ◽

2019 ◽

Author(s):

Qiaowei Liu ◽

Hao Li ◽

Lukuan You ◽

Tao Li ◽

Lingling Li ◽

...

Keyword(s):

Cancer Cells ◽

Rna Editing ◽

Cancer Progression ◽

Lung Tumor ◽

Transformed Cells ◽

Integrated Analysis ◽

Nucleotide Polymorphisms ◽

Systematic Analysis ◽

Radiation Induced ◽

Transformed Cell Lines

AbstractAdenosine (A) to inosine (I) RNA editing is the most prevalent RNA editing mechanism in humans and play critical roles in tumorigenesis. However, the effects of radiation on RNA editing and the mechanisms of radiation-induced cancer were poorly understood. Here, we analyzed human bronchial epithelial BEP2D cells and radiation-induced malignantly transformed cells with next generation sequencing. By performing an integrated analysis of A-to-I RNA editing, we found that genome-encoded single-nucleotide polymorphisms (SNPs) might induce the downregulation of ADAR2 enzymes, and further caused the abnormal occurrence of RNA editing in malignantly transformed cells. These editing events were significantly enriched in differentially expressed genes between normal cells and cancer cells. In addition, oncogenes CTNNB1 and FN1 were highly edited and significantly overexpressed in cancer cells, thus may be responsible for the lung cancer progression. Our work provides a systematic analysis of RNA editing from lung tumor specimens with high-throughput RNA sequencing and DNA sequencing. Moreover, these results demonstrate further evidence for RNA editing as an important tumorigenesis mechanism.

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