Pediatric Growth and Development: Impact on Vulnerability to Normal Tissue Damage from Cancer Therapy

A spatially-distributed continuous mathematical model of solid tumor growth and treatment by fractionated radiotherapy is presented. The model explicitly accounts for three time and space-dependent factors that influence the efficiency of radiotherapy fractionation schemes—tumor cell repopulation, reoxygenation and redistribution of proliferative states. A special algorithm is developed, aimed at finding the fractionation schemes that provide increased tumor cure probability under the constraints of maximum normal tissue damage and maximum fractional dose. The optimization procedure is performed for varied radiosensitivity of tumor cells under the values of model parameters, corresponding to different degrees of tumor malignancy. The resulting optimized schemes consist of two stages. The first stages are aimed to increase the radiosensitivity of the tumor cells, remaining after their end, sparing the caused normal tissue damage. This allows to increase the doses during the second stages and thus take advantage of the obtained increased radiosensitivity. Such method leads to significant expansions in the curative ranges of the values of tumor radiosensitivity parameters. Overall, the results of this study represent the theoretical proof of concept that non-uniform radiotherapy fractionation schemes may be considerably more effective that uniform ones, due to the time and space-dependent effects.

Download Full-text

Radiation-Induced Normal Tissue Damage: Oxidative Stress and Epigenetic Mechanisms

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/3010342 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 14

Author(s):

Jinlong Wei ◽

Bin Wang ◽

Huanhuan Wang ◽

Lingbin Meng ◽

Qin Zhao ◽

...

Keyword(s):

Oxidative Stress ◽

Tissue Damage ◽

Normal Tissue ◽

Noncoding Rna ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Redox System ◽

Epigenetic Mechanisms ◽

Rna Regulation ◽

Normal Tissue Damage ◽

Radiation Induced

Radiotherapy (RT) is currently one of the leading treatments for various cancers; however, it may cause damage to healthy tissue, with both short-term and long-term side effects. Severe radiation-induced normal tissue damage (RINTD) frequently has a significant influence on the progress of RT and the survival and prognosis of patients. The redox system has been shown to play an important role in the early and late effects of RINTD. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the main sources of RINTD. The free radicals produced by irradiation can upregulate several enzymes including nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), lipoxygenases (LOXs), nitric oxide synthase (NOS), and cyclooxygenases (COXs). These enzymes are expressed in distinct ways in various cells, tissues, and organs and participate in the RINTD process through different regulatory mechanisms. In recent years, several studies have demonstrated that epigenetic modulators play an important role in the RINTD process. Epigenetic modifications primarily contain noncoding RNA regulation, histone modifications, and DNA methylation. In this article, we will review the role of oxidative stress and epigenetic mechanisms in radiation damage, and explore possible prophylactic and therapeutic strategies for RINTD.

Download Full-text