Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules
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TLDR
Novel pathways contributing significantly to the understanding of HIF-1 regulation which may be major determinants of tumor radiosensitivity, potentially having high clinical relevance are described.About:
This article is published in Cancer Cell.The article was published on 2004-05-01 and is currently open access. It has received 928 citations till now. The article focuses on the topics: Radiosensitivity & Angiogenesis.read more
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Why do cancers have high aerobic glycolysis
TL;DR: In this article, the authors propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions, which leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.
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Targeting hypoxia in cancer therapy
William R. Wilson,Michael P. Hay +1 more
TL;DR: The two main approaches, namely bioreductive prodrugs and inhibitors of molecular targets upon which hypoxic cell survival depends are reviewed, and the particular challenges and opportunities these overlapping strategies present are addressed.
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HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
TL;DR: It is shown by genetic means that HIF-1-dependent block to oxygen utilization results in increased oxygen availability, decreased cell death when total oxygen is limiting, and reduced cell death in response to the hypoxic cytotoxin tirapazamine.
Journal ArticleDOI
Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics
TL;DR: This review summarizes the current state of knowledge regarding the molecular mechanisms by which Hif-1 contributes to cancer progression, focusing on clinical data associating increased HIF-1 levels with patient mortality and pharmacological data showing anticancer effects of H IF-1 inhibitors in mouse models of human cancer.
Journal ArticleDOI
STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors
Liufu Deng,Hua Liang,Meng Xu,Xuanming Yang,Byron Burnette,Ainhoa Arina,Xiao Dong Li,Helena J. Mauceri,Michael A. Beckett,Thomas E. Darga,Xiaona Huang,Thomas F. Gajewski,Zhijian J. Chen,Yang Xin Fu,Ralph R. Weichselbaum +14 more
TL;DR: Radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy.
References
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Endothelial Apoptosis as the Primary Lesion Initiating Intestinal Radiation Damage in Mice
François Paris,Zvi Fuks,Anthony Kang,Paola Capodieci,Gloria Juan,Desiree Ehleiter,Adriana Haimovitz-Friedman,Carlos Cordon-Cardo,Richard Kolesnick +8 more
TL;DR: It is shown in mouse models that microvascular endothelial apoptosis is the primary lesion leading to stem cell dysfunction, and this study provides a basis for new approaches to prevent radiation damage to the bowel.
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RNA-Binding Proteins Tia-1 and Tiar Link the Phosphorylation of Eif-2α to the Assembly of Mammalian Stress Granules
TL;DR: The ability of a TIA-1 mutant lacking its RNA-binding domains to function as a transdominant inhibitor of SG formation suggests that this RNA- binding protein acts downstream of the phosphorylation of eIF-2α to promote the sequestration of untranslated mRNAs at SGs.
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Tumor Regression by Targeted Gene Delivery to the Neovasculature
John Hood,Mark D. Bednarski,Ricardo F. Frausto,Samira Guccione,Ralph A. Reisfeld,Rong Xiang,David A. Cheresh +6 more
TL;DR: It is shown that a cationic nanoparticle coupled to an integrin αvβ3–targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice.
Journal ArticleDOI
Signal transduction to hypoxia-inducible factor 1.
TL;DR: In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.
Journal Article
Blockade of the Vascular Endothelial Growth Factor Stress Response Increases the Antitumor Effects of Ionizing Radiation
David H. Gorski,Michael A. Beckett,Nora Jaskowiak,Douglas P. Calvin,Helena J. Mauceri,Rabih M. Salloum,Saraswathy Seetharam,Ann Koons,Danielle M. Hari,Donald Kufe,Ralph R. Weichselbaum +10 more
TL;DR: It is reported that VEGF expression is induced in Lewis lung carcinomas (LLCs) both in vitro and in vivo after exposure to ionizing radiation (IR) and in human tumor cell lines (Seg-1 esophageal adenocarcinoma, SQ20B squamous cell carcinoma, T98 and U87 glioblastomas, and U1 melanoma) in vitro.