Exploiting tumour hypoxia in cancer treatment

Targeting HIF-1 for cancer therapy

2003 • 6,321 citations

Hypoxia — a key regulatory factor in tumour growth

2002 • 4,942 citations

Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours

1996 • 2,304 citations

The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy

1955 • 2,174 citations

Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases.

1999 • 2,168 citations

The Concentration of Oxygen Dissolved in Tissues at the Time of Irradiation as a Factor in Radiotherapy

1953 • 2,102 citations

Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix.

1996 • 1,747 citations

The unique physiology of solid tumors: opportunities (and problems) for cancer therapy.

1998 • 1,506 citations

Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene

2003 • 1,276 citations

The Expression and Distribution of the Hypoxia-Inducible Factors HIF-1α and HIF-2α in Normal Human Tissues, Cancers, and Tumor-Associated Macrophages

2000 • 1,272 citations

Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma.

1996 • 1,183 citations

Biochemical detection of left-ventricular systolic dysfunction

1998 • 981 citations

Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements.

1991 • 950 citations

Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck

1996 • 930 citations

Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene.

2002 • 821 citations

The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour

1968 • 764 citations

2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF

2003 • 713 citations

HIF-1 as a target for drug development

2003 • 607 citations

Phase I Study of the Intravenous Administration of Attenuated Salmonella typhimurium to Patients With Metastatic Melanoma

2002 • 606 citations

Oxygenation predicts radiation response and survival in patients with cervix cancer

1998 • 604 citations

Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer.

2001 • 597 citations

Pancreatic tumors show high levels of hypoxia

2000 • 588 citations

Phase I Study of the Intravenous Administration of AttenuatedSalmonella typhimuriumto Patients With Metastatic Melanoma

2002 • 562 citations

Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells.

1981 • 552 citations

Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome

1999 • 543 citations

Combination bacteriolytic therapy for the treatment of experimental tumors

2001 • 532 citations

Tumor-targeted Salmonella as a novel anticancer vector.

1997 • 510 citations

Suppression of tumor growth through disruption of hypoxia-inducible transcription

2000 • 501 citations

YC-1: A Potential Anticancer Drug Targeting Hypoxia-Inducible Factor 1

2003 • 454 citations

Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway.

2002 • 448 citations

SR-4233: A new bioreductive agent with high selective toxicity for hypoxic mammalian cells

1986 • 391 citations

The role of hypoxia in the maintenance of hematopoietic stem cells

1993 • 365 citations

SR 4233 (Tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours

1993 • 354 citations

Cells at Intermediate Oxygen Levels Can Be More Important Than the "Hypoxic Fraction" in Determining Tumor Response to Fractionated Radiotherapy

1997 • 340 citations

Microenvironment-induced cancer metastasis

2000 • 335 citations

The hypoxic tumour microenvironment and metastatic progression.

2003 • 326 citations

Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors

1994 • 301 citations

Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells.

2002 • 296 citations

Tirapazamine Plus Cisplatin Versus Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Report of the International CATAPULT I Study Group

2000 • 283 citations

Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives

2001 • 273 citations

Tumor hypoxia at the micro-regional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers

2003 • 271 citations

Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular tumor spheroids by hypoxia‐inducible factor‐1 and reactive oxygen species

2003 • 267 citations

Localization of the vegetative form of Clostridium tetani in mouse tumors following intravenous spore administration.

1955 • 251 citations

Clinical evaluation of nitroimidazoles as modifiers of hypoxia in solid tumors.

1994 • 218 citations

The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)—I

1992 • 211 citations

Expression of the bacterial nitroreductase enzyme in mammalian cells renders them selectively sensitive to killing by the prodrug CB1954

1995 • 210 citations

The macrophage – a novel system to deliver gene therapy to pathological hypoxia

2000 • 208 citations

Involvement of Hypoxia-Inducible Factor 1 in Human Cancer.

2002 • 206 citations

Hypoxia in Breast Cancer: Pathogenesis, Characterization and Biological/Therapeutic Implications

2002 • 199 citations

Anticancer efficacy of systemically delivered anaerobic bacteria as gene therapy vectors targeting tumor hypoxia/necrosis

2002 • 190 citations

Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas.

1996 • 186 citations

Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors.

1990 • 184 citations

Measurement of Human Tumour Oxygenation Status by a Polarographic Needle Electrode: An analysis of inter- and intratumour heterogeneity

1994 • 180 citations

Anaerobic bacteria as a gene delivery system that is controlled by the tumor microenvironment

1997 • 173 citations

Enzyme/prodrug gene therapy: comparison of cytosine deaminase/5-fluorocytosine versus thymidine kinase/ganciclovir enzyme/prodrug systems in a human colorectal carcinoma cell line.

1995 • 171 citations

Anaerobic bacteria as a delivery system for cancer gene therapy: in vitro activation of 5-fluorocytosine by genetically engineered clostridia.

1996 • 169 citations

Expression of HIF‐1α by human macrophages: implications for the use of macrophages in hypoxia‐regulated cancer gene therapy

2001 • 168 citations

A new cytotoxic, DNA interstrand crosslinking agent, 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide, is formed from 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by a nitroreductase enzyme in walker carcinoma cells

1988 • 167 citations

AQ4N: a new approach to hypoxia-activated cancer chemotherapy

2000 • 162 citations

Polarographic measurements of oxygen tension in human glioma and surrounding peritumoural brain tissue

1999 • 162 citations

Clostridia in cancer therapy

2003 • 161 citations

The nitroreductase enzyme in walker cells that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) to 5-(aziridin-1-YL)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2)

1988 • 147 citations

The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas

1996 • 147 citations

Effects of 5,6-Dimethylxanthenone-4-Acetic Acid on Human Tumor Microcirculation Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

2002 • 146 citations

Gene transfer of antisense hypoxia inducible factor-1 α enhances the therapeutic efficacy of cancer immunotherapy

2001 • 144 citations

Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin.

1993 • 144 citations

Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas

2003 • 143 citations

Conventional cancer therapy: promise broken or promise delayed?

1998 • 142 citations

ONCOLYSIS BY CLOSTRIDIA. I. ACTIVITY OF CLOSTRIDIUM BUTYRICUM (M-55) AND OTHER NONPATHOGENIC CLOSTRIDIA AGAINST THE EHRLICH CARCINOMA.

1964 • 139 citations

Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent

1993 • 138 citations

The experimental development of bioreductive drugs and their role in cancer therapy

1993 • 137 citations

Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954.

2001 • 136 citations

DNA Cleavage by the Antitumor Agent 3-Amino-1,2,4-benzotriazine 1,4-Dioxide (SR4233): Evidence for Involvement of Hydroxyl Radical

1996 • 135 citations

2,4-Dinitro-5-ethyleneiminobenzamide (CB 1954): A potent and selective inhibitor of the growth of the Walker carcinoma 256

1969 • 133 citations

Unusual oxygen concentration dependence of toxicity of SR-4233, a hypoxic cell toxin.

1993 • 131 citations

Anticancer Prodrugs for Application in Monotherapy Targeting Hypoxia, Tumor-Associated Enzymes, and Receptors

2001 • 127 citations

Clinical trials of radiosensitizers: What should we expect?

1984 • 124 citations

Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors, neck node metastases, and normal tissue

1998 • 123 citations

Tumour Cytochrome P450 and Drug Activation

2002 • 123 citations

Tirapazamine: a hypoxia-activated topoisomerase II poison.

2002 • 121 citations

Mutagenesis induced by the tumor microenvironment

1998 • 119 citations

Induction of endothelial cell apoptosis by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid

2002 • 119 citations

The influence of microenvironmental factors during cancer therapy.

1994 • 113 citations

Clostridial oncolysis in man

1967 • 110 citations

Activation of 3-Amino-1,2,4-benzotriazine 1,4-Dioxide Antitumor Agents to Oxidizing Species Following Their One-Electron Reduction

2002 • 109 citations

Hypoxia in Human Prostate Carcinoma

2001 • 106 citations

Multicellular resistance to tirapazamine is due to restricted extravascular transport: a pharmacokinetic/pharmacodynamic study in HT29 multicellular layer cultures.

2003 • 106 citations

Bioreductive therapies: an overview of drugs and their mechanisms of action

1998 • 104 citations

Hypoxia-specific cytotoxins in cancer therapy

1996 • 98 citations

Hypoxia-mediated tumour targeting

2003 • 94 citations

Enhancement of gene expression under hypoxic conditions using fragments of the human vascular endothelial growth factor and the erythropoietin genes

1998 • 93 citations

2-Amino metabolites are key mediators of CB 1954 and SN 23862 bystander effects in nitroreductase GDEPT

2004 • 92 citations

The liquefaction (oncolysis) of malignant gliomas by a non pathogenic Clostridium

1978 • 91 citations

ONCOLYSIS BY CLOSTRIDIA. III. EFFECTS OF CLOSTRIDIA AND CHEMOTHERAPEUTIC AGENTS ON RODENT TUMORS.

1964 • 82 citations

BIOREDUCTIVELY ACTIVATED ANTITUMORN-OXIDES: THE CASE OF AQ4N, A UNIQUE APPROACH TO HYPOXIA-ACTIVATED CANCER CHEMOTHERAPY

2002 • 82 citations

Quantitation of bystander effects in nitroreductase suicide gene therapy using three-dimensional cell cultures.

2002 • 81 citations

Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial

1997 • 80 citations

ONCOLYSIS BY CLOSTRIDIA. V. TRANSPLANTED TUMORS OF THE HAMSTER.

1964 • 78 citations

Stimulation of tumors to synthesize tumor necrosis factor-alpha in situ using 5,6-dimethylxanthenone-4-acetic acid: a novel approach to cancer therapy.

1999 • 78 citations

True

2000 • 78 citations

Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia

1997 • 77 citations

Hypoxia-selective antitumor agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells

1992 • 75 citations

Use of hypoxia-directed drugs in the therapy of solid tumors.

1992 • 74 citations

The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice

2002 • 73 citations

Effect of Nitroreduction on the Alkylating Reactivity and Cytotoxicity of the 2,4-Dinitrobenzamide-5-aziridine CB 1954 and the Corresponding Nitrogen Mustard SN 23862: Distinct Mechanisms of Bioreductive Activation

2003 • 73 citations

Cisplatin anti-tumour potentiation by tirapazamine results from a hypoxia-dependent cellular sensitization to cisplatin

1999 • 72 citations

Bioreducible mustards: a paradigm for hypoxia-selective prodrugs of diffusible cytotoxins (HPDCs)

1993 • 72 citations

Bioreductive drugs for cancer therapy: The search for tumor specificity

1994 • 72 citations

Hypoxia-Inducible Regulation of a Prodrug-Activating Enzyme for Tumor-Specific Gene Therapy

2002 • 71 citations

DNA-Targeted 1,2,4-Benzotriazine 1,4-Dioxides: Potent Analogues of the Hypoxia-Selective Cytotoxin Tirapazamine

2003 • 66 citations

Bioreductive GDEPT using cytochrome P450 3A4 in combination with AQ4N

2002 • 62 citations

Hypoxia-Dependent Retinal Toxicity of Bioreductive Anticancer Prodrugs in Mice

2000 • 61 citations

Hypoxia-Selective Antitumor Agents. 16. Nitroarylmethyl Quaternary Salts as Bioreductive Prodrugs of the Alkylating Agent Mechlorethamine

2001 • 59 citations

Synthesis and Evaluation of Nitroheterocyclic Phosphoramidates as Hypoxia-Selective Alkylating Agents

2000 • 58 citations

Oxygen-sensitive enzyme-prodrug gene therapy for the eradication of radiation-resistant solid tumours

2002 • 58 citations

Recent developments in the design of bioreductive drugs.

1996 • 56 citations

Nitro reduction as an electronic switch for bioreductive drug activation.

1997 • 54 citations

Onkolyseversuche mit apathogenen, anaeroben Sporenbildnern am Ehrlich-Tumor der Maus

1959 • 50 citations

Exploiting tumor hypoxia through bioreductive release of diffusible cytotoxins: The cobalt(III)-nitrogen mustard complex SN 24771

1994 • 50 citations

Oxygen Dependence of the Metabolic Activation and Cytotoxicity of Tirapazamine: Implications for Extravascular Transport andActivity in Tumors

2004 • 45 citations

Comparison of the comet assay and the oxygen microelectrode for measuring tumor oxygenation in head-and-neck cancer patients

2003 • 44 citations

Improvement ofClostridiumtumour targeting vectors evaluated in rat rhabdomyosarcomas

2001 • 44 citations

NLCQ-1 (NSC 709257): exploiting hypoxia with a weak DNA-intercalating bioreductive drug.

2003 • 44 citations

Extravascular transport of the DNA intercalator and topoisomerase poison N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide (DACA): diffusion and metabolism in multicellular layers of tumor cells.

2001 • 41 citations

Oxygen and exposure kinetics as factors influencing the cytotoxicity of porfiromycin, a mitomycin C analogue, in Chinese hamster ovary cells.

1988 • 39 citations

Optimization of the Auxiliary Ligand Shell of Cobalt(III)(8-hydroxyquinoline) Complexes as Model Hypoxia-Selective Radiation-Activated Prodrugs

2004 • 39 citations

A mass spectrometry study of tirapazamine and its metabolites: Insights into the mechanism of metabolic transformations and the characterization of reaction intermediates

2003 • 37 citations

Oxygen dependence of the cytotoxicity and metabolic activation of 4-alkylamino-5-nitroquinoline bioreductive drugs

1994 • 37 citations

Recent Advances in Bioreductive Drug Targeting

2001 • 37 citations

Radiosensitizing and Cytotoxicity Studies with CB 1954 (2,4-Dinitro-5-Aziridinylbenzamide)

1981 • 31 citations

Mitochondrial dysfunction after aerobic exposure to the hypoxic cytotoxin tirapazamine.

2001 • 29 citations

Improved potency of the hypoxic cytotoxin tirapazamine by DNA-targeting

2003 • 29 citations

Radiation-activated prodrugs as hypoxia-selective cytotoxins: model studies with nitroarylmethyl quaternary salts.

1998 • 28 citations

Modifying rates of reductive elimination of leaving groups from indolequinone prodrugs: a key factor in controlling hypoxia-selective drug release

2002 • 27 citations

A Novel Class of Antitumor Prodrug, 1‐(2′‐Oxopropyl)‐5‐fluorouracil (OFU001), That Releases 5‐Fluorouracil upon Hypoxic Irradiation

2000 • 27 citations

Identification of a hypoxic population of bone marrow cells

1983 • 26 citations

Oxygen dependence of the cytotoxicity of the enediyne anti-tumour antibiotic esperamicin A1.

1996 • 17 citations

Pathways of Reductive Fragmentation of Heterocyclic Nitroarylmethyl Quaternary Ammonium Prodrugs of Mechlorethamine

2002 • 13 citations