Journal ArticleDOI
Role of cell cycle in mediating sensitivity to radiotherapy.
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TLDR
This work describes how cell cycle and DNA damage checkpoint control relates to exposure to ionizing radiation and suggests that one way in which chemotherapy and fractionated radiotherapy may work better is by partial synchronization of cells in the most radiosensitive phase of the cell cycle.Abstract:
Multiple pathways are involved in maintaining the genetic integrity of a cell after its exposure to ionizing radiation. Although repair mechanisms such as homologous recombination and nonhomologous end-joining are important mammalian responses to double-strand DNA damage, cell cycle regulation is perhaps the most important determinant of ionizing radiation sensitivity. A common cellular response to DNA-damaging agents is the activation of cell cycle checkpoints. The DNA damage induced by ionizing radiation initiates signals that can ultimately activate either temporary checkpoints that permit time for genetic repair or irreversible growth arrest that results in cell death (necrosis or apoptosis). Such checkpoint activation constitutes an integrated response that involves sensor (RAD, BRCA, NBS1), transducer (ATM, CHK), and effector (p53, p21, CDK) genes. One of the key proteins in the checkpoint pathways is the tumor suppressor gene p53, which coordinates DNA repair with cell cycle progression and apoptosis. Specifically, in addition to other mediators of the checkpoint response (CHK kinases, p21), p53 mediates the two major DNA damage-dependent cellular checkpoints, one at the G(1)-S transition and the other at the G(2)-M transition, although the influence on the former process is more direct and significant. The cell cycle phase also determines a cell's relative radiosensitivity, with cells being most radiosensitive in the G(2)-M phase, less sensitive in the G(1) phase, and least sensitive during the latter part of the S phase. This understanding has, therefore, led to the realization that one way in which chemotherapy and fractionated radiotherapy may work better is by partial synchronization of cells in the most radiosensitive phase of the cell cycle. We describe how cell cycle and DNA damage checkpoint control relates to exposure to ionizing radiation.read more
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The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy.
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A Consensus Molecular Classification of Muscle-invasive Bladder Cancer.
Aurélie Kamoun,Aurélien de Reyniès,Yves Allory,Yves Allory,Gottfrid Sjödahl,A. Gordon Robertson,Roland Seiler,Katherine A. Hoadley,Clarice S. Groeneveld,Clarice S. Groeneveld,Hikmat Al-Ahmadie,Woonyoung Choi,Mauro A. A. Castro,Jacqueline Fontugne,Jacqueline Fontugne,Pontus Eriksson,Qianxing Mo,Jordan Kardos,Alexandre R. Zlotta,Arndt Hartmann,Colin Dinney,Joaquim Bellmunt,Thomas Powles,Núria Malats,Keith S. Chan,William Y. Kim,David J. McConkey,Peter C. Black,Lars Dyrskjøt,Mattias Höglund,Seth P. Lerner,Francisco X. Real,François Radvanyi,Mattias Aine,Isabelle Bernard-Pierrot,Bogdan Czerniak,Ewan A. Gibb,Jaegil Kim,David J. Kwiatkowski,Thierry Lebret,Fredrik Liedberg,Arlene O. Siefker-Radtke,Nanor Sirab,Ann Taber,John N. Weinstein +44 more
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Journal ArticleDOI
Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements.
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Journal ArticleDOI
Autophagy and cancer therapy.
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Physical basis and biological mechanisms of gold nanoparticle radiosensitization
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References
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Journal ArticleDOI
p53, the Cellular Gatekeeper for Growth and Division
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
Journal ArticleDOI
CDK inhibitors: positive and negative regulators of G1-phase progression
TL;DR: This work challenges previous assumptions about how the G1/S transition of the mammalian cell cycle is governed, helps explain some enigmatic features of cell cycle control that also involve the functions of the retinoblastoma protein (Rb) and the INK4 proteins, and changes the thinking about how either p16 loss or overexpression of cyclin D-dependent kinases contribute to cancer.
Journal ArticleDOI
Apoptosis by death factor.
TL;DR: This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan and by a Research Grant from the Princess Takamatsu Cancer Research Fund, and performed in part through Special Coordination Funds of the Science and Technology Agency of the Japanese Government.
Journal ArticleDOI
Mdm2 promotes the rapid degradation of p53
TL;DR: It is proposed that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.
Journal Article
Participation of p53 Protein in the Cellular Response to DNA Damage
TL;DR: A role for the wild-type p53 protein in the inhibition of DNA synthesis that follows DNA damage is suggested and a new mechanism for how the loss of wild- type p53 might contribute to tumorigenesis is suggested.
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