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Nitric Oxide, Coagulation and Cancer

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Nitric Oxide and Cancer: Pathogenesis and Therapy

Abstract

Nitric Oxide (NO) is a well-known potent and rapid vasodilator and inhibitor of coagulation. Synthesized from an L-arginine precursor, NO is produced via the Nitric Oxide Synthase enzyme which is expressed constitutively in endothelial cells. Nitric oxide has a wide range of biological properties that maintain vascular homeostasis and protection of the vessel from injurious consequences. The decreased production of NO in pathological states causes deleterious effects, creating an endothelial dysfunction state with a wide variety of subsequent diverse biological effects. There is now evidence of the link between hypoxia and/or reduction of NO availability and coagulopathies. NO is also a modulator of various cancer-related events and has anti-tumor properties. Cancer is a known hypercoagulable state and hypoxia is a typical feature of the tumor micro-environment. Cancer patients—particularly those with advanced or metastatic states—are at higher risk of developing venous and arterial thromboembolic events. The dichotomous nature of nitric oxide with regard to its tumorigenic and tumoricidal properties are at present under intense investigation. The transcendent field of nanotechnology has moved into the realm of NO donor therapy, though currently there are no commercially available carriers of NO. While nanotechnology is not quite at the translational research stage, it poses the greatest potential for storage and site-specific delivery of high concentrations of NO to tumors. In this chapter, we review the effects of NO on various hemostatic elements, the pro-tumoral and anti-tumoral effects of NO and finally shed some light on the link between NO, cancer and coagulopathies.

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Abbreviations

NO:

nitric oxide

NOS:

nitric oxide synthase

aPTT:

activated partial thromboplastin time

vWF:

von Willebrand factor

LPS:

lipoproteinpolysaccharides

TEG:

thromboelastography

TF:

tissue factor

MPs:

microparticles

PCa:

prostate cancer

GTN:

glyceryl trinitrate

tPA:

tissue plasminogen activator

uPA:

urokinase type plasminogen activator

PAI:

plasminogen activator inhibitors

L-NMMA:

L-NG-monomethylarginine

nNOS:

neuro-isoform of NOS

eNOS:

endothelial isoform of NOS

iNOS:

inducible NOS

PGE2:

prostaglandin E2

VEGF:

vascular endothelial growth factor

COX-2:

cyclooxygenase-2

EMT:

epithelial-mesenchymal transition

MMP:

matrix metalloproteinases

NODD:

NO-donating drugs

NSAID:

non-steroidal anti-inflammatory drug

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Authors and Affiliations

  1. Northwestern University Feinberg School of Medicine, Chicago, USA

    Benjamin A. Derman & Hau C. Kwaan

  2. Department of Biomedical and Molecular Sciences, Queen’s University, Boterell Hall Room 513, K7L 3N6, Kingston, ON, Canada

    Malak Elbatarny & Dr. Maha Othman MD, MSc, PhD

  3. School of Baccalaureate Nursing, St Lawrence College, Kingston, ON, Canada

    Malak Elbatarny & Dr. Maha Othman MD, MSc, PhD

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  1. Benjamin A. Derman
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  2. Hau C. Kwaan
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  3. Malak Elbatarny
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  4. Dr. Maha Othman MD, MSc, PhD
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Correspondence to Maha Othman MD, MSc, PhD .

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Editors and Affiliations

  1. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California of Los Angeles, Los Angeles, California, USA

    Benjamin Bonavida

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Derman, B., Kwaan, H., Elbatarny, M., Othman, M. (2015). Nitric Oxide, Coagulation and Cancer. In: Bonavida, B. (eds) Nitric Oxide and Cancer: Pathogenesis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-13611-0_17

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