Alterations in tumor necrosis factor–induced endothelial cell procoagulant activity by hyperthermia

TNF is a cytokine with potent antitumor activity in murine models and when administered clinically via regional perfusion. There is substantial evidence that this antitumor activity depends in large part on TNF's procoagulant effect on tumor neovasculature, which is mediated by induction of end...

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Veröffentlicht in:International journal of cancer 2004-09, Vol.111 (3), p.457-462
Hauptverfasser: Carroll, Nancy M., Elaraj, Dina M., Puhlmann, Markus, Weinreich, David M., Turner, Ewa M., Xu, Hui, Alexander, H. Richard
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container_end_page 462
container_issue 3
container_start_page 457
container_title International journal of cancer
container_volume 111
creator Carroll, Nancy M.
Elaraj, Dina M.
Puhlmann, Markus
Weinreich, David M.
Turner, Ewa M.
Xu, Hui
Alexander, H. Richard
description TNF is a cytokine with potent antitumor activity in murine models and when administered clinically via regional perfusion. There is substantial evidence that this antitumor activity depends in large part on TNF's procoagulant effect on tumor neovasculature, which is mediated by induction of endothelial cell tissue factor (TF), a component of the extrinsic clotting cascade. In regional perfusion of a cancer‐bearing limb or organ, TNF is always administered under hyperthermic temperatures; however, little is known about the effect of hyperthermia on TNF‐mediated procoagulant activity in endothelium. We examined the effects of hyperthermia on TNF‐mediated procoagulant activity in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TNF at normothermic (37°C) and hyperthermic (41°C) temperatures for 90 min, then assayed for clotting activity, TF protein production and mRNA production of TF and tissue factor pathway inhibitor‐2 (TFPI‐2), an endogenous inducible inhibitor of TF activity in HUVECs. TNF treatment at 41°C significantly reduced clotting activity, TF protein and mRNA as well as TFPI‐2 mRNA compared to treatment at 37°C. These data show that hyperthermia significantly reduces the procoagulant effects of TNF on endothelial tissue compared to normothermia, which may have important clinical implications for the use of TNF in regional perfusion. © 2004 Wiley‐Liss, Inc.
doi_str_mv 10.1002/ijc.20272
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Richard</creator><creatorcontrib>Carroll, Nancy M. ; Elaraj, Dina M. ; Puhlmann, Markus ; Weinreich, David M. ; Turner, Ewa M. ; Xu, Hui ; Alexander, H. Richard</creatorcontrib><description>TNF is a cytokine with potent antitumor activity in murine models and when administered clinically via regional perfusion. There is substantial evidence that this antitumor activity depends in large part on TNF's procoagulant effect on tumor neovasculature, which is mediated by induction of endothelial cell tissue factor (TF), a component of the extrinsic clotting cascade. In regional perfusion of a cancer‐bearing limb or organ, TNF is always administered under hyperthermic temperatures; however, little is known about the effect of hyperthermia on TNF‐mediated procoagulant activity in endothelium. We examined the effects of hyperthermia on TNF‐mediated procoagulant activity in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TNF at normothermic (37°C) and hyperthermic (41°C) temperatures for 90 min, then assayed for clotting activity, TF protein production and mRNA production of TF and tissue factor pathway inhibitor‐2 (TFPI‐2), an endogenous inducible inhibitor of TF activity in HUVECs. TNF treatment at 41°C significantly reduced clotting activity, TF protein and mRNA as well as TFPI‐2 mRNA compared to treatment at 37°C. 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Richard</creatorcontrib><title>Alterations in tumor necrosis factor–induced endothelial cell procoagulant activity by hyperthermia</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>TNF is a cytokine with potent antitumor activity in murine models and when administered clinically via regional perfusion. There is substantial evidence that this antitumor activity depends in large part on TNF's procoagulant effect on tumor neovasculature, which is mediated by induction of endothelial cell tissue factor (TF), a component of the extrinsic clotting cascade. In regional perfusion of a cancer‐bearing limb or organ, TNF is always administered under hyperthermic temperatures; however, little is known about the effect of hyperthermia on TNF‐mediated procoagulant activity in endothelium. We examined the effects of hyperthermia on TNF‐mediated procoagulant activity in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TNF at normothermic (37°C) and hyperthermic (41°C) temperatures for 90 min, then assayed for clotting activity, TF protein production and mRNA production of TF and tissue factor pathway inhibitor‐2 (TFPI‐2), an endogenous inducible inhibitor of TF activity in HUVECs. TNF treatment at 41°C significantly reduced clotting activity, TF protein and mRNA as well as TFPI‐2 mRNA compared to treatment at 37°C. These data show that hyperthermia significantly reduces the procoagulant effects of TNF on endothelial tissue compared to normothermia, which may have important clinical implications for the use of TNF in regional perfusion. © 2004 Wiley‐Liss, Inc.</description><subject>Biological and medical sciences</subject><subject>Blood Coagulation Factors - genetics</subject><subject>Cell Line</subject><subject>coagulation</subject><subject>endothelium</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glycoproteins - genetics</subject><subject>Hot Temperature</subject><subject>Humans</subject><subject>hyperthermia</subject><subject>Hyperthermia, Induced</subject><subject>Induced hyperthermia. Cryotherapy</subject><subject>isolated limb perfusion</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Thromboplastin - genetics</subject><subject>tissue factor</subject><subject>tissue factor pathway inhibitor‐2</subject><subject>Transcription, Genetic - drug effects</subject><subject>Treatment with physical agents</subject><subject>Treatment. 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Cryotherapy</topic><topic>isolated limb perfusion</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Thromboplastin - genetics</topic><topic>tissue factor</topic><topic>tissue factor pathway inhibitor‐2</topic><topic>Transcription, Genetic - drug effects</topic><topic>Treatment with physical agents</topic><topic>Treatment. General aspects</topic><topic>tumor necrosis factor</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Tumors</topic><topic>Umbilical Veins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carroll, Nancy M.</creatorcontrib><creatorcontrib>Elaraj, Dina M.</creatorcontrib><creatorcontrib>Puhlmann, Markus</creatorcontrib><creatorcontrib>Weinreich, David M.</creatorcontrib><creatorcontrib>Turner, Ewa M.</creatorcontrib><creatorcontrib>Xu, Hui</creatorcontrib><creatorcontrib>Alexander, H. 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source MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals
subjects Biological and medical sciences
Blood Coagulation Factors - genetics
Cell Line
coagulation
endothelium
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Gene Expression Regulation - drug effects
Glycoproteins - genetics
Hot Temperature
Humans
hyperthermia
Hyperthermia, Induced
Induced hyperthermia. Cryotherapy
isolated limb perfusion
Kinetics
Medical sciences
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Thromboplastin - genetics
tissue factor
tissue factor pathway inhibitor‐2
Transcription, Genetic - drug effects
Treatment with physical agents
Treatment. General aspects
tumor necrosis factor
Tumor Necrosis Factor-alpha - pharmacology
Tumors
Umbilical Veins
title Alterations in tumor necrosis factor–induced endothelial cell procoagulant activity by hyperthermia
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