Nitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001.

Abstract:

BACKGROUND:RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. OBJECTIVE:In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. METHODS:A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. RESULTS:Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). CONCLUSIONS:Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.

journal_name

Biorheology

journal_title

Biorheology

authors

Cirrik S,Ugurel E,Aksu AC,Oronsky B,Cabrales P,Yalcin O

doi

10.3233/BIR-190213

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

221-235

issue

4

eissn

0006-355X

issn

1878-5034

pii

BIR190213

journal_volume

56

pub_type

杂志文章
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  • Neurobiorheology. A new branch of biorheology. Historical background and current ideas.

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    doi:10.3233/bir-1991-28603

    authors: Sourander P

    更新日期:1991-01-01 00:00:00

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    journal_title:Biorheology

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    doi:

    authors: Weinbaum S,Guo P,You L

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    doi:10.1016/S0006-355X(98)00018-3

    authors: Das B,Johnson PC,Popel AS

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  • Effects of gender and age on thixotropic properties of whole blood from healthy adult subjects.

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    authors: Nicolle S,Lounis M,Willinger R,Palierne JF

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  • Fibrin elasticity and coagulation.

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    pub_type: 杂志文章

    doi:10.3233/bir-1988-251-221

    authors: Hartert H

    更新日期:1988-01-01 00:00:00

  • Rheology of the vitreous body. Part I: Viscoelasticity of human vitreous.

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    pub_type: 杂志文章

    doi:10.3233/bir-1992-295-612

    authors: Lee B,Litt M,Buchsbaum G

    更新日期:1992-09-01 00:00:00

  • Heterogeneous phase fibrinolysis rates by damped oscillation rheometry.

    abstract:BACKGROUND:Devices gauging viscoelastic properties of blood during coagulation like the thromboelastograph support fundamental research as well as point of care needs. Associated fibrinolysis data are based on endogenous species or plasminogen activator added to a homogeneous sample prior to clot formation. Digestion i...

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  • The role of mucus viscoelasticity in cough clearance.

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    journal_title:Biorheology

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    doi:10.3233/bir-1987-24611

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    更新日期:1987-01-01 00:00:00

  • A structural viscoelastic model of soft tissues.

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    doi:10.3233/bir-1988-251-216

    authors: Flaud P,Quemada D

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  • Remodelling of the zero-stress state and residual strains in apoE-deficient mouse aorta.

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    doi:

    authors: Gregersen H,Zhao J,Lu X,Zhou J,Falk E

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    journal_title:Biorheology

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    doi:

    authors: Affeld K,Kertzscher U,Goubergrits L

    更新日期:2002-01-01 00:00:00

  • Effects of diacerein on biosynthesis activities of chondrocytes in culture.

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    journal_title:Biorheology

    pub_type: 杂志文章,评审

    doi:

    authors: Pujol JP,Felisaz N,Boumediene K,Ghayor C,Herrouin JF,Bogdanowicz P,Galera P

    更新日期:2000-01-01 00:00:00

  • Aggregation and disaggregation of red blood cells.

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    doi:10.3233/bir-1987-24302

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    pub_type: 杂志文章

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    更新日期:2009-01-01 00:00:00

  • Mechanical assessment by magnetocytometry of the cytosolic and cortical cytoskeletal compartments in adherent epithelial cells.

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    pub_type: 杂志文章

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    authors: Laurent VM,Planus E,Fodil R,Isabey D

    更新日期:2003-01-01 00:00:00

  • Molecular basis of red cell membrane rheology. Part 1.

    abstract::The biorheological properties and behavior of red blood cells (RBCs), as other types of cells, have a biochemical and molecular basis. The shape maintenance and deformability of RBCs depend on the structural and functional integrity of the membrane proteins. These proteins are composed of transmembrane proteins insert...

    journal_title:Biorheology

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  • Effects of concentration and structure on proteoglycan 4 rheology and interaction with hyaluronan.

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    journal_title:Biorheology

    pub_type: 杂志文章

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    pub_type: 杂志文章

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    authors: Kafka V,Jírová J

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  • Mucous gel transport in a simulated cough machine: effects of longitudinal grooves representing spacings between arrays of cilia.

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    pub_type: 杂志文章

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  • Mechanisms underlying chaotic vasomotion in isolated resistance arteries: roles of calcium and EDRF.

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    pub_type: 杂志文章

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    pub_type: 杂志文章

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    journal_title:Biorheology

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    doi:

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    journal_title:Biorheology

    pub_type: 杂志文章

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    journal_title:Biorheology

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    doi:10.3233/BIR-140652

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