Hypoxia and radiation response in human tumors

Höckel, Michael; Schlenger, Karlheinz; Mitze, M.; Schäffer, U.; Vaupel, Peter

doi:10.1016/s1053-4296(96)80031-2

Cited by 255 publications

(139 citation statements)

References 26 publications

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“…Some tissues, for example, solid tumours, contain regions of low oxygen tension (hypoxia) generally thought to arise as a consequence of a poor and disorganized blood supply. The O 2 tension influences deeply the outcome of biological electrochemical reactions, 6 as shown in the next sections. All those facts must be considered in the attempt to mimic biological environments.…”

Section: General Commentsmentioning

confidence: 93%

Some Applications of Electrochemistry in Biomedical Chemistry. Emphasis on the Correlation of Electrochemical and Bioactive Properties

Abreu¹,

Ferraz²,

Goulart³

2002

J. Braz. Chem. Soc.

153

124

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Essa revisão resume alguns dos aspectos mais relevantes na correlação entre processos e parâmetros eletroquímicos e atividades biológicas, relacionadas, principalmente, a doenças tropicais e câncer. Apesar da gama de possibilidades e da complexidade da química celular/tecidual/extracelular, é possível racionalizar o papel da eletroquímica em poucas bases teóricas, principalmente: transferência eletrônica -estresse oxidativo, geração eletroquímica in situ de agentes tóxicos diferentes das espécies oxigenadas reativas, interação com endobióticos, com ênfase particular em alquilação biorredutiva e substituição de endobióticos com função em reações de oxi-redução biológicas. O uso de métodos eletroquímicos para a obtenção de mecanismos de ação de drogas e na análise de eventos celulares é também apresentado. Nessas correlações, métodos e/ou parâmetros eletroquímicos exercem papel relevante, porém, não absoluto.This review summarises some of the more relevant achievements in the correlation between electrochemical processes and parameters and bioactive properties, mainly related to cancer and tropical diseases. Despite the broad range of possibilities and the complexity of cell/tissue/extracell chemistry, it is possible to rationalise the role of electrochemistry in few basic theoretical frameworks, mainly, the one based on electron transfer-oxidative stress and in situ generation of toxic species, other than the reactive oxygen species; interaction with endobiotics, with emphasis on bioreductive alkylation and replacement of endobiotics with function in biological redox reactions. The use of electrochemical methods to obtain relevant informations about drugs' mechanism of action and analysis of cellular events is also presented. Electrochemical methods and/or parameters play essential but not absolute roles.

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Section: General Commentsmentioning

confidence: 93%

Some Applications of Electrochemistry in Biomedical Chemistry. Emphasis on the Correlation of Electrochemical and Bioactive Properties

Abreu¹,

Ferraz²,

Goulart³

2002

J. Braz. Chem. Soc.

153

124

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“…In a series of experimental and clinical studies, Vaupel and others showed definitively that measurements of pO 2 by polarographic microelectrodes provided useful criteria for predicting the response of tumors to radiation therapy. [36][37][38][39][40][41][42] According to Swartz, 43 these results are remarkable in two ways:…”

Section: Tumor Hypoxia Increases the Resistance To Radiotherapymentioning

confidence: 99%

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

2004

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This review paper attempts to provide an overview of the principles and techniques that are often termed electron paramagnetic resonance (EPR) oximetry. The paper discusses the potential of such methods and illustrates they have been successfully applied to measure oxygen tension, an essential parameter of the tumor microenvironment. To help the reader understand the motivation for carrying out these measurements, the importance of tumor hypoxia is first discussed: the basic issues of why a tumor is hypoxic, why these hypoxic microenvironments promote processes driving malignant progression and why hypoxia dramatically influences the response of tumors to cytotoxic treatments will be explained. The different methods that have been used to estimate the oxygenation in tumors will be reviewed. To introduce the basics of EPR oximetry, the specificity of in vivo EPR will be discussed by comparing this technique with NMR and MRI. The different types of paramagnetic oxygen sensors will be presented, as well as the methods for recording the information (EPR spectroscopy, EPR imaging, dynamic nuclear polarization). Several applications of EPR for characterizing tumor oxygenation will be illustrated, with a special emphasis on pharmacological interventions that modulate the tumor microenvironment. Finally, the challenges for transposing the method into the clinic will also be discussed.

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“…[1][2][3] This has been attributed to the finding that hypoxic cells are both more resistant to current therapies (chemo and radio) and are more aggressive i.e., more likely to be resistant to apoptosis and/or metastasise. [4][5][6] Regions of hypoxia occur in tumours due to the demand for oxygen outstripping the supply. [7][8][9] This is due, in part, to the poor Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1…”

Section: Introductionmentioning

confidence: 99%

Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1

Pires¹,

Bencokova²,

McGurk³

et al. 2010

Cell Cycle

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Severe hypoxia has been demonstrated to induce a replication arrest which is associated with decreased levels of nucleotides. Chk1 is rapidly phosphorylated in response to severe hypoxia and in turn deactivates TLK1 through phosphorylation. Loss of Chk1 has been shown to sensitize cells to hypoxia/reoxygenation. After short (acute) exposure to hypoxia this is due to an increased rate of reoxygenation-induced replication restart and subsequent p53-dependent apoptosis. After longer (chronic) exposure to hypoxia S phase cells do not undergo reoxygenation-induced replication restart. Cells exposed to these levels of hypoxia are however sensitive to loss of Chk1. This suggests a new role for Chk1 in the cell cycle response to reoxygenation.

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Hypoxia and radiation response in human tumors

Cited by 255 publications

References 26 publications

Some Applications of Electrochemistry in Biomedical Chemistry. Emphasis on the Correlation of Electrochemical and Bioactive Properties

Some Applications of Electrochemistry in Biomedical Chemistry. Emphasis on the Correlation of Electrochemical and Bioactive Properties

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1

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