Significance of HIF-1-active cells in angiogenesis and radioresistance.
Hiroshi Harada,Shinae Kizaka-Kondoh,G Li,Satoshi Itasaka,Keiko Shibuya,Masahiro Inoue,Masahiro Hiraoka +6 more
TLDR
The results further strengthen the argument that HIF-1-active/hypoxic cells play crucial roles in angiogenesis and radioresistance.Abstract:
Human solid tumors contain hypoxic regions that have considerably lower oxygen tension than the normal tissues. Hypoxia offers resistance to radiotherapy and anticancer chemotherapy, as well as predispose to increased tumor metastases. Furthermore, hypoxia induces hypoxia-inducible factor-1 (HIF-1), which in turn increases tumor angiogenesis. Thus, eradication of HIF-1-active/hypoxic tumor cells is very important for cancer therapy. We have previously reported that procaspase-3 fused with a von Hippel–Lindau (VHL)-mediated protein destruction motif of alpha subunit of HIF-1 (HIF-1α) containing Pro564, named TAT-ODD-procaspase-3 (TOP3), specifically induced cell death to hypoxic cells in vivo as well as in vitro. We now report that TOP3 also eradicates the radiation-induced HIF-1-active tumor cells. HIF-1 activity in the xenografts of human tumor cells, which express luciferase under the transcriptional control of HIF-1, were monitored and quantified daily with an in vivo bioluminescence photon-counting device. HIF-1 activity in tumors was more rapidly increased by ionizing radiation (IR) compared to untreated tumors. TOP3 efficiently decreased the HIF-1-activity in irradiated tumors as well as unirradiated ones, indicating TOP3 eradicated tumor cells with HIF-1-activity induced by IR as well as hypoxia. Eradication of HIF-1-active/hypoxic cells in the xenografts during irradiation exhibited significant suppression in angiogenesis and strong enhancement in a long-term growth suppression of tumor xenografts. These results further strengthen the argument that HIF-1-active/hypoxic cells play crucial roles in angiogenesis and radioresistance.read more
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Cancer stem cells and drug resistance: the potential of nanomedicine.
Serguei V. Vinogradov,Xin Wei +1 more
TL;DR: This review is focused on tumor drug resistance-related properties of CSCs and describes current nanomedicine approaches, which could form the basis of novel combination therapies for eliminating metastatic and C SCs.
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TWIST activation by hypoxia inducible factor-1 (HIF-1) : Implications in metastasis and development
Muh Hwa Yang,Kou Juey Wu +1 more
TL;DR: The findings suggest that hypoxia and/or HIF-1 orchestrates EMT and metastasis through the coordinated regulation of different EMT regulators.
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HIF-1-Dependent Reprogramming of Glucose Metabolic Pathway of Cancer Cells and Its Therapeutic Significance
TL;DR: Findings revealing that a novel HIF-1-activating factor enhances the antioxidant capacity and resultant radioresistance of cancer cells though reprogramming of the glucose metabolic pathway are summarized.
Journal ArticleDOI
Role of metabolism in cancer cell radioresistance and radiosensitization methods.
Le Tang,Le Tang,Fang Wei,Fang Wei,Yingfen Wu,Yi He,Yi He,Lei Shi,Fang Xiong,Zhaojian Gong,Can Guo,Xiayu Li,Xiayu Li,Hao Deng,Ke Cao,Ming Zhou,Ming Zhou,Bo Xiang,Bo Xiang,Xiaoling Li,Xiaoling Li,Yong Li,Yong Li,Guiyuan Li,Guiyuan Li,Wei Xiong,Wei Xiong,Zhaoyang Zeng,Zhaoyang Zeng +28 more
TL;DR: The aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients.
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Significance of nitroimidazole compounds and hypoxia-inducible factor-1 for imaging tumor hypoxia
TL;DR: The significance of pimonidazole and HIF‐1 as exogenous and endogenous hypoxia markers, respectively, as well as their evaluation and imaging of tumorHypoxia are discussed, particularly in the therapy against refractory cancers.
References
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Targeting HIF-1 for cancer therapy
TL;DR: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion.
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Hypoxia — a key regulatory factor in tumour growth
TL;DR: Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death, and many elements of the hypoxia-response pathway are good candidates for therapeutic targeting.
Journal Article
Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review
TL;DR: Current knowledge of blood flow and perfusion-related parameters, which usually go hand in hand and in turn define the cellular metabolic microenvironment of human malignancies, are summarized for predicting the acute and/or long-term response of tumors to therapy.
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C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
Andrew C. R Epstein,Jonathan M. Gleadle,Luke A. McNeill,Kirsty S. Hewitson,J F O'Rourke,David R. Mole,Mridul Mukherji,Eric Metzen,Michael A Wilson,Anu Dhanda,Ya-Min Tian,Norma Masson,Donald L. Hamilton,Panu Jaakkola,Robert Barstead,Jonathan Hodgkin,Patrick H. Maxwell,Christopher W. Pugh,Christopher J. Schofield,Peter J. Ratcliffe +19 more
TL;DR: Direct modulation of recombinant enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrors the characteristics of HIF induction in vivo, fulfilling requirements for these enzymes being oxygen sensors that regulate HIF.
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In Vivo Protein Transduction: Delivery of a Biologically Active Protein into the Mouse
TL;DR: It is shown that intraperitoneal injection of the 120-kilodalton beta-galactosidase protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain.