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Liposome‐Encapsulated Hemoglobin Ameliorates Tumor Hypoxia and Enhances Radiation Therapy to Suppress Tumor Growth in Mice

We hypothesize that liposome‐encapsulated hemoglobin with high O affinity (P0 = 12 mm Hg, h‐LEH) may increase O delivery to hypoxic tumors and enhance radiation therapy synergistically to suppress tumor growth. First, h‐LEH (5, 10, and 20 mL/kg) was intravenously infused 30 min before radiation (20 ... Full description

Journal Title: Artificial Organs February 2012, Vol.36(2), pp.170-177
Main Author: Murayama, Chieko
Other Authors: Kawaguchi, Akira T. , Ishikawa, Kenji , Kamijo, Akemi , Kato, Nobusuke , Ohizumi, Yukio , Sadahiro, Sotaro , Haida, Munetaka
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ID: ISSN: 0160-564X ; E-ISSN: 1525-1594 ; DOI: 10.1111/j.1525-1594.2011.01418.x
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recordid: wj10.1111/j.1525-1594.2011.01418.x
title: Liposome‐Encapsulated Hemoglobin Ameliorates Tumor Hypoxia and Enhances Radiation Therapy to Suppress Tumor Growth in Mice
format: Article
creator:
  • Murayama, Chieko
  • Kawaguchi, Akira T.
  • Ishikawa, Kenji
  • Kamijo, Akemi
  • Kato, Nobusuke
  • Ohizumi, Yukio
  • Sadahiro, Sotaro
  • Haida, Munetaka
subjects:
  • Tumor Hypoxia
  • Hypoxia‐Inducible Factor‐1α
  • Radiotherapy
  • Tumor Growth Delay
  • Oxygen
  • Liposome‐Encapsulated Hemoglobin
ispartof: Artificial Organs, February 2012, Vol.36(2), pp.170-177
description: We hypothesize that liposome‐encapsulated hemoglobin with high O affinity (P0 = 12 mm Hg, h‐LEH) may increase O delivery to hypoxic tumors and enhance radiation therapy synergistically to suppress tumor growth. First, h‐LEH (5, 10, and 20 mL/kg) was intravenously infused 30 min before radiation (20 Gy) of SCCVII tumor grown in C3H/HeN mice. Second, 10 mL/kg of h‐LEH was administered 30, 60, 90, and 120 min prior to radiation to determine optimal timing. Tumor size was monitored thereafter to titrate tumor growth suppression. Third, additional mice with SCCVII tumor were infused with h‐LEH or empty liposome (EL), and tumors were excised at various time points for immunohistochemical examination of h‐LEH and hypoxia‐inducible factor‐1α (HIF‐1α). h‐LEH was most effective at 10 mL/kg in comparison to 5 or 20 mL/kg of h‐LEH or EL. Tumor growth was most suppressed when the interval between h‐LEH infusion and radiation was shortest, 30 min. As a result, 10 mL/kg of h‐LEH infusion 30 min prior to radiation prolonged 5‐fold tumor‐growth time from 20.0 days (radiation and EL) to 26.5 days,  
language:
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identifier: ISSN: 0160-564X ; E-ISSN: 1525-1594 ; DOI: 10.1111/j.1525-1594.2011.01418.x
fulltext: fulltext
issn:
  • 0160-564X
  • 0160564X
  • 1525-1594
  • 15251594
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titleLiposome‐Encapsulated Hemoglobin Ameliorates Tumor Hypoxia and Enhances Radiation Therapy to Suppress Tumor Growth in Mice
creatorMurayama, Chieko ; Kawaguchi, Akira T. ; Ishikawa, Kenji ; Kamijo, Akemi ; Kato, Nobusuke ; Ohizumi, Yukio ; Sadahiro, Sotaro ; Haida, Munetaka
ispartofArtificial Organs, February 2012, Vol.36(2), pp.170-177
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subjectTumor Hypoxia ; Hypoxia‐Inducible Factor‐1α ; Radiotherapy ; Tumor Growth Delay ; Oxygen ; Liposome‐Encapsulated Hemoglobin
descriptionWe hypothesize that liposome‐encapsulated hemoglobin with high O affinity (P0 = 12 mm Hg, h‐LEH) may increase O delivery to hypoxic tumors and enhance radiation therapy synergistically to suppress tumor growth. First, h‐LEH (5, 10, and 20 mL/kg) was intravenously infused 30 min before radiation (20 Gy) of SCCVII tumor grown in C3H/HeN mice. Second, 10 mL/kg of h‐LEH was administered 30, 60, 90, and 120 min prior to radiation to determine optimal timing. Tumor size was monitored thereafter to titrate tumor growth suppression. Third, additional mice with SCCVII tumor were infused with h‐LEH or empty liposome (EL), and tumors were excised at various time points for immunohistochemical examination of h‐LEH and hypoxia‐inducible factor‐1α (HIF‐1α). h‐LEH was most effective at 10 mL/kg in comparison to 5 or 20 mL/kg of h‐LEH or EL. Tumor growth was most suppressed when the interval between h‐LEH infusion and radiation was shortest, 30 min. As a result, 10 mL/kg of h‐LEH infusion 30 min prior to radiation prolonged 5‐fold tumor‐growth time from 20.0 days (radiation and EL) to 26.5 days,  < 0.01, synergy ratio 1.42. While human hemoglobin (h‐LEH) was detected in tumors 0.5 to 24 h after administration, HIF‐1α accumulation was sparse and became significantly reduced compared to controls 48 and 72 h after h‐LEH infusion. h‐LEH (10 mL/kg) was highly effective in enhancing radiation therapy synergistically under ambient respiration against tumor growth in mice. Decreased accumulation of HIF‐1α in h‐LEH‐treated tumor may suggest targeted tumor oxygenation as a potential mechanism.
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titleLiposome‐Encapsulated Hemoglobin Ameliorates Tumor Hypoxia and Enhances Radiation Therapy to Suppress Tumor Growth in Mice
descriptionWe hypothesize that liposome‐encapsulated hemoglobin with high O affinity (P0 = 12 mm Hg, h‐LEH) may increase O delivery to hypoxic tumors and enhance radiation therapy synergistically to suppress tumor growth. First, h‐LEH (5, 10, and 20 mL/kg) was intravenously infused 30 min before radiation (20 Gy) of SCCVII tumor grown in C3H/HeN mice. Second, 10 mL/kg of h‐LEH was administered 30, 60, 90, and 120 min prior to radiation to determine optimal timing. Tumor size was monitored thereafter to titrate tumor growth suppression. Third, additional mice with SCCVII tumor were infused with h‐LEH or empty liposome (EL), and tumors were excised at various time points for immunohistochemical examination of h‐LEH and hypoxia‐inducible factor‐1α (HIF‐1α). h‐LEH was most effective at 10 mL/kg in comparison to 5 or 20 mL/kg of h‐LEH or EL. Tumor growth was most suppressed when the interval between h‐LEH infusion and radiation was shortest, 30 min. As a result, 10 mL/kg of h‐LEH infusion 30 min prior to radiation prolonged 5‐fold tumor‐growth time from 20.0 days (radiation and EL) to 26.5 days,  < 0.01, synergy ratio 1.42. While human hemoglobin (h‐LEH) was detected in tumors 0.5 to 24 h after administration, HIF‐1α accumulation was sparse and became significantly reduced compared to controls 48 and 72 h after h‐LEH infusion. h‐LEH (10 mL/kg) was highly effective in enhancing radiation therapy synergistically under ambient respiration against tumor growth in mice. Decreased accumulation of HIF‐1α in h‐LEH‐treated tumor may suggest targeted tumor oxygenation as a potential mechanism.
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abstractWe hypothesize that liposome‐encapsulated hemoglobin with high O affinity (P0 = 12 mm Hg, h‐LEH) may increase O delivery to hypoxic tumors and enhance radiation therapy synergistically to suppress tumor growth. First, h‐LEH (5, 10, and 20 mL/kg) was intravenously infused 30 min before radiation (20 Gy) of SCCVII tumor grown in C3H/HeN mice. Second, 10 mL/kg of h‐LEH was administered 30, 60, 90, and 120 min prior to radiation to determine optimal timing. Tumor size was monitored thereafter to titrate tumor growth suppression. Third, additional mice with SCCVII tumor were infused with h‐LEH or empty liposome (EL), and tumors were excised at various time points for immunohistochemical examination of h‐LEH and hypoxia‐inducible factor‐1α (HIF‐1α). h‐LEH was most effective at 10 mL/kg in comparison to 5 or 20 mL/kg of h‐LEH or EL. Tumor growth was most suppressed when the interval between h‐LEH infusion and radiation was shortest, 30 min. As a result, 10 mL/kg of h‐LEH infusion 30 min prior to radiation prolonged 5‐fold tumor‐growth time from 20.0 days (radiation and EL) to 26.5 days,  < 0.01, synergy ratio 1.42. While human hemoglobin (h‐LEH) was detected in tumors 0.5 to 24 h after administration, HIF‐1α accumulation was sparse and became significantly reduced compared to controls 48 and 72 h after h‐LEH infusion. h‐LEH (10 mL/kg) was highly effective in enhancing radiation therapy synergistically under ambient respiration against tumor growth in mice. Decreased accumulation of HIF‐1α in h‐LEH‐treated tumor may suggest targeted tumor oxygenation as a potential mechanism.
copMalden, USA
pubBlackwell Publishing Inc
doi10.1111/j.1525-1594.2011.01418.x
pages170-7
date2012-02