Pharmacologically increased tumor hypoxia can be measured by 18F-Fluoroazomycin arabinoside positron emission tomography and enhances tumor response to hypoxic cytotoxin PR-104.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Rob A CairnsNicholas C Denko

Abstract

Solid tumors contain microenvironmental regions of hypoxia that present a barrier to traditional radiotherapy and chemotherapy, and this work describes a novel approach to circumvent hypoxia. We propose to overcome hypoxia by augmenting the effectiveness of drugs that are designed to specifically kill hypoxic tumor cells. We have constructed RKO colorectal tumor cells that express a small RNA hairpin that specifically knocks down the hypoxia-inducible factor 1a (HIF1a) transcription factor. We have used these cells in vitro to determine the effect of HIF1 on cellular sensitivity to the hypoxic cytotoxin PR-104, and its role in cellular oxygen consumption in response to the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA). We have further used these cells in vivo in xenografted tumors to determine the role of HIF1 in regulating tumor hypoxia in response to DCA using (18)F-fluoroazomycin arabinoside positron emission tomography, and its role in regulating tumor sensitivity to the combination of DCA and PR-104. HIF1 does not affect cellular sensitivity to PR-104 in vitro. DCA transiently increases cellular oxygen consumption in vitro and increases the extent of tumor hypoxia in vivo as measured with (18)F-fluoroazomyc...Continue Reading

References

Jul 1, 1986·International Journal of Radiation Oncology, Biology, Physics·E M ZemanW W Lee
Apr 5, 2000·The Journal of Biological Chemistry·J C BakerT E Roche
Jul 16, 2004·Seminars in Radiation Oncology·Peter Vaupel
Mar 4, 2006·Molecular Cancer Research : MCR·Rob CairnsNicholas Denko
May 8, 2007·Clinical Oncology : a Journal of the Royal College of Radiologists·S R McKeownK J Williams
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rob A CairnsNicholas C Denko
May 31, 2007·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Roswitha BeckMorand Piert
Jul 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adam V PattersonWilliam R Wilson
Jul 24, 2008·Advanced Drug Delivery Reviews·Peter W StacpooleTaimour Langaee
Jan 15, 2009·Nature Reviews. Cancer·Nicholas C Denko

❮ Previous
Next ❯

Citations

Jan 25, 2011·Nature Reviews. Cancer·Rob A CairnsTak W Mak
Feb 22, 2012·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·A YarominaM Baumann
Jun 25, 2013·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·F ZwickerK J Weber
Jan 27, 2016·Cancer Chemotherapy and Pharmacology·Roger M Phillips
Jun 12, 2010·Cancer Letters·Siranoush ShahrzadBrenda L Coomber
Oct 20, 2010·International Journal of Cancer. Journal International Du Cancer·Ioanna PapandreouNicholas C Denko
May 16, 2015·Expert Opinion on Therapeutic Targets·Helena PópuloPaula Soares
Aug 27, 2014·Biochimica Et Biophysica Acta·Shyam Kankotia, Peter W Stacpoole
Aug 21, 2013·Biochemical and Biophysical Research Communications·Zhan ChengyeLi Shusheng
Jun 26, 2007·FEBS Letters·M Christiane Brahimi-Horn, Jacques Pouysségur
Aug 30, 2017·World Journal of Clinical Oncology·Akbar KhanAnneke C Blackburn
Jun 7, 2014·Brain Tumor Research and Treatment·Mithilesh Kumar Jha, Kyoungho Suk
Jul 6, 2014·The Journal of Biological Chemistry·Keith R LaderouteLaszlo G Boros
Mar 18, 2015·Hormone Molecular Biology and Clinical Investigation·Jonathan DiedrichIzabela Podgorski
Aug 17, 2021·Frontiers in Oncology·Yue LiXiao-Feng Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.