Regulation of p53 by siRNA in radiation treated cells: Simulation studies

Krzysztof Puszyński; Roman Jaksik; Andrzej Świerniak

International Journal of Applied Mathematics and Computer Science (2012)

  • Volume: 22, Issue: 4, page 1011-1018
  • ISSN: 1641-876X

Abstract

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Ionizing radiation activates a large variety of intracellular mechanisms responsible for maintaining appropriate cell functionality or activation of apoptosis which eliminates damaged cells from the population. The mechanism of such induced cellular death is widely used in radiotherapy in order to eliminate cancer cells, although in some cases it is highly limited by increased cellular radio-resistance due to aberrations in molecular regulation mechanisms of malignant cells. Despite the positive correlation between the radiation dose and the number of apoptotic cancer cells, radiation has to be limited because of extensive side effects. Therefore, additional control signals whose role will be to maximize the cancer cells death-ratio while minimizing the radiation dose and by that the potential side effects are worth considering. In this work we present the results of simulation studies showing possibilities of single gene regulation by small interfering RNA (siRNA) that can increase radio-sensitivity of malignant cells showing aberrations in the p53 signaling pathway, responsible for DNA damage-dependant apoptosis. By blocking the production of the p53 inhibitor Mdm2, radiation treated cancer cells are pushed into the apoptotic state on a level normally achievable only with high radiation doses. The presented approach, based on a simulation study originating from experimentally validated regulatory events, concerns one of the basic problems of radiotherapy dosage limitations, which, as will be shown, can be partially avoided by using the appropriate siRNA based control mechanism.

How to cite

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Krzysztof Puszyński, Roman Jaksik, and Andrzej Świerniak. "Regulation of p53 by siRNA in radiation treated cells: Simulation studies." International Journal of Applied Mathematics and Computer Science 22.4 (2012): 1011-1018. <http://eudml.org/doc/244519>.

@article{KrzysztofPuszyński2012,
abstract = {Ionizing radiation activates a large variety of intracellular mechanisms responsible for maintaining appropriate cell functionality or activation of apoptosis which eliminates damaged cells from the population. The mechanism of such induced cellular death is widely used in radiotherapy in order to eliminate cancer cells, although in some cases it is highly limited by increased cellular radio-resistance due to aberrations in molecular regulation mechanisms of malignant cells. Despite the positive correlation between the radiation dose and the number of apoptotic cancer cells, radiation has to be limited because of extensive side effects. Therefore, additional control signals whose role will be to maximize the cancer cells death-ratio while minimizing the radiation dose and by that the potential side effects are worth considering. In this work we present the results of simulation studies showing possibilities of single gene regulation by small interfering RNA (siRNA) that can increase radio-sensitivity of malignant cells showing aberrations in the p53 signaling pathway, responsible for DNA damage-dependant apoptosis. By blocking the production of the p53 inhibitor Mdm2, radiation treated cancer cells are pushed into the apoptotic state on a level normally achievable only with high radiation doses. The presented approach, based on a simulation study originating from experimentally validated regulatory events, concerns one of the basic problems of radiotherapy dosage limitations, which, as will be shown, can be partially avoided by using the appropriate siRNA based control mechanism.},
author = {Krzysztof Puszyński, Roman Jaksik, Andrzej Świerniak},
journal = {International Journal of Applied Mathematics and Computer Science},
keywords = {siRNA; p53; combined therapy; cancer cells; intracellular mechanisms; small interfering RNA (SIRNA); p53 signaling pathway},
language = {eng},
number = {4},
pages = {1011-1018},
title = {Regulation of p53 by siRNA in radiation treated cells: Simulation studies},
url = {http://eudml.org/doc/244519},
volume = {22},
year = {2012},
}

TY - JOUR
AU - Krzysztof Puszyński
AU - Roman Jaksik
AU - Andrzej Świerniak
TI - Regulation of p53 by siRNA in radiation treated cells: Simulation studies
JO - International Journal of Applied Mathematics and Computer Science
PY - 2012
VL - 22
IS - 4
SP - 1011
EP - 1018
AB - Ionizing radiation activates a large variety of intracellular mechanisms responsible for maintaining appropriate cell functionality or activation of apoptosis which eliminates damaged cells from the population. The mechanism of such induced cellular death is widely used in radiotherapy in order to eliminate cancer cells, although in some cases it is highly limited by increased cellular radio-resistance due to aberrations in molecular regulation mechanisms of malignant cells. Despite the positive correlation between the radiation dose and the number of apoptotic cancer cells, radiation has to be limited because of extensive side effects. Therefore, additional control signals whose role will be to maximize the cancer cells death-ratio while minimizing the radiation dose and by that the potential side effects are worth considering. In this work we present the results of simulation studies showing possibilities of single gene regulation by small interfering RNA (siRNA) that can increase radio-sensitivity of malignant cells showing aberrations in the p53 signaling pathway, responsible for DNA damage-dependant apoptosis. By blocking the production of the p53 inhibitor Mdm2, radiation treated cancer cells are pushed into the apoptotic state on a level normally achievable only with high radiation doses. The presented approach, based on a simulation study originating from experimentally validated regulatory events, concerns one of the basic problems of radiotherapy dosage limitations, which, as will be shown, can be partially avoided by using the appropriate siRNA based control mechanism.
LA - eng
KW - siRNA; p53; combined therapy; cancer cells; intracellular mechanisms; small interfering RNA (SIRNA); p53 signaling pathway
UR - http://eudml.org/doc/244519
ER -

References

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