Literature DB >> 22021675

Amelioration of radiation esophagitis by orally administered p53/Mdm2/Mdm4 inhibitor (BEB55) or GS-nitroxide.

Hyun Kim1, Mark E Bernard, Michael W Epperly, Hongmei Shen, Andrew Amoscato, Tracy M Dixon, Alexander S Doemling, Song Li, Xiang Gao, Peter Wipf, Hong Wang, Xichen Zhang, Valerian E Kagan, Joel S Greenberger.   

Abstract

BACKGROUND/AIM: Esophagitis is a significant toxicity of radiation therapy for lung cancer. In this study, reduction of irradiation esophagitis in mice, by orally administered p53/Mdm2/Mdm4 inhibitor, BEB55, or the GS-nitroxide, JP4-039, was evaluated.
MATERIALS AND METHODS: BEB55 or JP4-039 in F15 (liposomal) formulation was administered intraesophageally to C57BL/6 mice prior to thoracic irradiation of 29 Gy × 1 or 11.5 Gy × 4 thoracic irradiation. Progenitor cells were sorted from excised esophagus, and nitroxide was quantified, by electron paramagnetic resonance (EPR). Mice with Lewis lung carcinoma (3LL) orthotopic lung tumors were treated with BEB55 or JP4-039 prior to 20 Gy to determine if the drugs would protect the tumor cells from radiation.
RESULTS: Intraesophageal BEB55 and JP4-039 compared to formulation alone increased survival after single fraction (p=0.0209 and 0.0384, respectively) and four fraction thoracic irradiation (p=0.0241 and 0.0388, respectively). JP4-039 was detected in esophagus, liver, bone marrow, and orthotopic Lewis lung carcinoma (3LL) tumor. There was no significant radiation protection of lung tumors by BEB55 or JP4-039 compared to formulation only as assessed by survival (p=0.3021 and 0.3693, respectively). Thus, BEB55 and JP4-039 safely ameliorate radiation esophagitis in mice.

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Year:  2011        PMID: 22021675      PMCID: PMC3521513     

Source DB:  PubMed          Journal:  In Vivo        ISSN: 0258-851X            Impact factor:   2.155


  20 in total

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Authors:  Yunyun Niu; Hongmei Shen; Michael Epperly; Xichen Zhang; Suhua Nie; Shaonan Cao; Joel S Greenberger
Journal:  In Vivo       Date:  2005 Nov-Dec       Impact factor: 2.155

2.  A phase I study of concurrent chemotherapy (paclitaxel and carboplatin) and thoracic radiotherapy with swallowed manganese superoxide dismutase plasmid liposome protection in patients with locally advanced stage III non-small-cell lung cancer.

Authors:  Ahmad A Tarhini; Chandra P Belani; James D Luketich; Athanassios Argiris; Suresh S Ramalingam; William Gooding; Arjun Pennathur; Daniel Petro; Kevin Kane; Denny Liggitt; Tony Championsmith; Xichen Zhang; Michael W Epperly; Joel S Greenberger
Journal:  Hum Gene Ther       Date:  2011-02-02       Impact factor: 5.695

3.  Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators.

Authors:  Jean-Claude M Rwigema; Barbara Beck; Wei Wang; Alexander Doemling; Michael W Epperly; Donna Shields; Julie P Goff; Darcy Franicola; Tracy Dixon; Marie-Céline Frantz; Peter Wipf; Yulia Tyurina; Valerian E Kagan; Hong Wang; Joel S Greenberger
Journal:  Int J Radiat Oncol Biol Phys       Date:  2011-04-13       Impact factor: 7.038

4.  Biology of marrow stromal cell lines derived from long-term bone marrow cultures of Trp53-deficient mice.

Authors:  M W Epperly; J A Bray; T M Carlos; E Prochownik; J S Greenberger
Journal:  Radiat Res       Date:  1999-07       Impact factor: 2.841

5.  Intraesophageal administration of GS-nitroxide (JP4-039) protects against ionizing irradiation-induced esophagitis.

Authors:  Michael W Epperly; Julie P Goff; Song Li; Xiang Gao; Peter Wipf; Tracy Dixon; Hong Wang; Darcy Franicola; Hongmei Shen; Jean-Claude M Rwigema; Valerian Kagan; Mark Bernard; Joel S Greenberger
Journal:  In Vivo       Date:  2010 Nov-Dec       Impact factor: 2.155

6.  Degradation of MDM2 by the interaction between berberine and DAXX leads to potent apoptosis in MDM2-overexpressing cancer cells.

Authors:  Xiaoling Zhang; Lubing Gu; Jiansha Li; Noopur Shah; Jing He; Lin Yang; Qun Hu; Muxiang Zhou
Journal:  Cancer Res       Date:  2010-10-08       Impact factor: 12.701

7.  In vitro differentiation capacity of esophageal progenitor cells with capacity for homing and repopulation of the ionizing irradiation-damaged esophagus.

Authors:  Michael W Epperly; Hongmei Shen; Mia Jefferson; Joel S Greenberger
Journal:  In Vivo       Date:  2004 Nov-Dec       Impact factor: 2.155

8.  Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence.

Authors:  Kensuke Kumamoto; Elisa A Spillare; Kaori Fujita; Izumi Horikawa; Taro Yamashita; Ettore Appella; Makoto Nagashima; Seiichi Takenoshita; Jun Yokota; Curtis C Harris
Journal:  Cancer Res       Date:  2008-05-01       Impact factor: 12.701

9.  A mitochondria-targeted triphenylphosphonium-conjugated nitroxide functions as a radioprotector/mitigator.

Authors:  Jianfei Jiang; Detcho A Stoyanovsky; Natalia A Belikova; Yulia Y Tyurina; Qing Zhao; Muhammad A Tungekar; Valentyna Kapralova; Zhentai Huang; Arlan H Mintz; Joel S Greenberger; Valerian E Kagan
Journal:  Radiat Res       Date:  2009-12       Impact factor: 2.841

10.  A mitochondria-targeted nitroxide/hemigramicidin S conjugate protects mouse embryonic cells against gamma irradiation.

Authors:  Jianfei Jiang; Natalia A Belikova; Adam T Hoye; Qing Zhao; Michael W Epperly; Joel S Greenberger; Peter Wipf; Valerian E Kagan
Journal:  Int J Radiat Oncol Biol Phys       Date:  2008-03-01       Impact factor: 7.038

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  6 in total

1.  The impact of ionizing radiation on placental trophoblasts.

Authors:  D J Kanter; M B O'Brien; X-H Shi; T Chu; T Mishima; S Beriwal; M W Epperly; P Wipf; J S Greenberger; Y Sadovsky
Journal:  Placenta       Date:  2014-01-02       Impact factor: 3.481

2.  Synthesis of analogs of the radiation mitigator JP4-039 and visualization of BODIPY derivatives in mitochondria.

Authors:  Marie-Céline Frantz; Erin M Skoda; Joshua R Sacher; Michael W Epperly; Julie P Goff; Joel S Greenberger; Peter Wipf
Journal:  Org Biomol Chem       Date:  2013-07-07       Impact factor: 3.876

3.  Fanconi Anemia Mouse Genotype-specific Mitigation of Total Body Irradiation by GS-Nitroxide JP4-039.

Authors:  Michael W Epperly; Renee Fisher; Xichen Zhang; Wen Hou; Donna Shields; Peter Wipf; Hong Wang; Stephanie Thermozier; Joel S Greenberger
Journal:  In Vivo       Date:  2020 Jan-Feb       Impact factor: 2.155

4.  Strategies for discovery of small molecule radiation protectors and radiation mitigators.

Authors:  Joel S Greenberger; David Clump; Valerian Kagan; Hülya Bayir; John S Lazo; Peter Wipf; Song Li; Xiang Gao; Michael W Epperly
Journal:  Front Oncol       Date:  2012-01-13       Impact factor: 6.244

5.  Antioxidant Approaches to Management of Ionizing Irradiation Injury.

Authors:  Joel Greenberger; Valerian Kagan; Hulya Bayir; Peter Wipf; Michael Epperly
Journal:  Antioxidants (Basel)       Date:  2015-01-23

Review 6.  New approaches to radiation protection.

Authors:  Eliot M Rosen; Regina Day; Vijay K Singh
Journal:  Front Oncol       Date:  2015-01-20       Impact factor: 6.244

  6 in total

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