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NCT00762801

Studies on the Expression and Functions of RLIP76 in Blood Samples of Healthy Human Subjects

Last Updated: 2016-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2008-09-30

Study Completion Date

2011-09-30

Brief Summary

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RLIP76 (Ral binding protein1) is a 76 kDa splice variant protein encoded by the human gene (RALBP1, 18p11.22). It is a multifunctional modular protein found ubiquitously from Drosophila to humans, in cells ranging from red blood cells to endothelial cells of the brain. Its expression more predominant in breast, heart, liver and less so in colon and brain parenchyma.

Detailed Description

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RLIP76 is shown to be over expressed in a variety of cancer cells. However, no study has yet been done on its expression on normal cells. The studies proposed in this project will study the expression of RLIP76 in blood cells of healthy human subjects in the population of North Texas region.

Conditions

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Healthy

Keywords

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RLIP76 Cancer apoptosis

Study Design

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Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* Healthy as defined by lack of serious health conditions or diseases

Exclusion Criteria

* Children, pregnant women, prisoners, persons with any medical condition that precludes phlebotomy and persons unwilling or unable to provide consent will be excluded.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sanjay Awasthi, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Texas Health Science Center

Locations

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University of North Texas Health Science Center

Fort Worth, Texas, United States

Site Status

University of North Texas Health Science Center

Fort Worth, Texas, United States

Site Status

Countries

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United States

References

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Singhal SS, Yadav S, Singhal J, Zajac E, Awasthi YC, Awasthi S. Depletion of RLIP76 sensitizes lung cancer cells to doxorubicin. Biochem Pharmacol. 2005 Aug 1;70(3):481-8. doi: 10.1016/j.bcp.2005.05.005.

Reference Type BACKGROUND

PMID: 15950949 (View on PubMed)

Cheng JZ, Sharma R, Yang Y, Singhal SS, Sharma A, Saini MK, Singh SV, Zimniak P, Awasthi S, Awasthi YC. Accelerated metabolism and exclusion of 4-hydroxynonenal through induction of RLIP76 and hGST5.8 is an early adaptive response of cells to heat and oxidative stress. J Biol Chem. 2001 Nov 2;276(44):41213-23. doi: 10.1074/jbc.M106838200. Epub 2001 Aug 24.

Reference Type BACKGROUND

PMID: 11522795 (View on PubMed)

Awasthi S, Singhal SS, Srivastava SK, Zimniak P, Bajpai KK, Saxena M, Sharma R, Ziller SA 3rd, Frenkel EP, Singh SV, et al. Adenosine triphosphate-dependent transport of doxorubicin, daunomycin, and vinblastine in human tissues by a mechanism distinct from the P-glycoprotein. J Clin Invest. 1994 Mar;93(3):958-65. doi: 10.1172/JCI117102.

Reference Type BACKGROUND

PMID: 7907606 (View on PubMed)

Awasthi S, Singhal SS, Pikula S, Piper JT, Srivastava SK, Torman RT, Bandorowicz-Pikula J, Lin JT, Singh SV, Zimniak P, Awasthi YC. ATP-Dependent human erythrocyte glutathione-conjugate transporter. II. Functional reconstitution of transport activity. Biochemistry. 1998 Apr 14;37(15):5239-48. doi: 10.1021/bi972131r.

Reference Type BACKGROUND

PMID: 9548755 (View on PubMed)

Zou W, Borvak J, Marches F, Wei S, Galanaud P, Emilie D, Curiel TJ. Macrophage-derived dendritic cells have strong Th1-polarizing potential mediated by beta-chemokines rather than IL-12. J Immunol. 2000 Oct 15;165(8):4388-96. doi: 10.4049/jimmunol.165.8.4388.

Reference Type BACKGROUND

PMID: 11035076 (View on PubMed)

McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene. 2006 Mar 13;25(11):1639-48. doi: 10.1038/sj.onc.1209373.

Reference Type RESULT

PMID: 16550164 (View on PubMed)

Jullien-Flores V, Mahe Y, Mirey G, Leprince C, Meunier-Bisceuil B, Sorkin A, Camonis JH. RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. J Cell Sci. 2000 Aug;113 ( Pt 16):2837-44. doi: 10.1242/jcs.113.16.2837.

Reference Type RESULT

PMID: 10910768 (View on PubMed)

Awasthi S, Cheng J, Singhal SS, Saini MK, Pandya U, Pikula S, Bandorowicz-Pikula J, Singh SV, Zimniak P, Awasthi YC. Novel function of human RLIP76: ATP-dependent transport of glutathione conjugates and doxorubicin. Biochemistry. 2000 Aug 8;39(31):9327-34. doi: 10.1021/bi992964c.

Reference Type RESULT

PMID: 10924126 (View on PubMed)

Awasthi S, Sharma R, Singhal SS, Zimniak P, Awasthi YC. RLIP76, a novel transporter catalyzing ATP-dependent efflux of xenobiotics. Drug Metab Dispos. 2002 Dec;30(12):1300-10. doi: 10.1124/dmd.30.12.1300.

Reference Type RESULT

PMID: 12433796 (View on PubMed)

Awasthi S, Singhal SS, Yadav S, Singhal J, Drake K, Nadkar A, Zajac E, Wickramarachchi D, Rowe N, Yacoub A, Boor P, Dwivedi S, Dent P, Jarman WE, John B, Awasthi YC. RLIP76 is a major determinant of radiation sensitivity. Cancer Res. 2005 Jul 15;65(14):6022-8. doi: 10.1158/0008-5472.CAN-05-0968.

Reference Type RESULT

PMID: 16024601 (View on PubMed)

Yadav S, Zajac E, Singhal SS, Awasthi S. Linking stress-signaling, glutathione metabolism, signaling pathways and xenobiotic transporters. Cancer Metastasis Rev. 2007 Mar;26(1):59-69. doi: 10.1007/s10555-007-9043-5.

Reference Type RESULT

PMID: 17260165 (View on PubMed)

Jullien-Flores V, Dorseuil O, Romero F, Letourneur F, Saragosti S, Berger R, Tavitian A, Gacon G, Camonis JH. Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J Biol Chem. 1995 Sep 22;270(38):22473-7. doi: 10.1074/jbc.270.38.22473.

Reference Type RESULT

PMID: 7673236 (View on PubMed)

Shurin GV, Tourkova IL, Chatta GS, Schmidt G, Wei S, Djeu JY, Shurin MR. Small rho GTPases regulate antigen presentation in dendritic cells. J Immunol. 2005 Mar 15;174(6):3394-400. doi: 10.4049/jimmunol.174.6.3394.

Reference Type RESULT

PMID: 15749872 (View on PubMed)

DODGE JT, MITCHELL C, HANAHAN DJ. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119-30. doi: 10.1016/0003-9861(63)90042-0. No abstract available.

Reference Type RESULT

PMID: 14028302 (View on PubMed)

Stuckler D, Singhal J, Singhal SS, Yadav S, Awasthi YC, Awasthi S. RLIP76 transports vinorelbine and mediates drug resistance in non-small cell lung cancer. Cancer Res. 2005 Feb 1;65(3):991-8.

Reference Type RESULT

PMID: 15705900 (View on PubMed)

Singhal SS, Wickramarachchi D, Singhal J, Yadav S, Awasthi YC, Awasthi S. Determinants of differential doxorubicin sensitivity between SCLC and NSCLC. FEBS Lett. 2006 Apr 17;580(9):2258-64. doi: 10.1016/j.febslet.2006.03.038. Epub 2006 Mar 24.

Reference Type RESULT

PMID: 16579994 (View on PubMed)

Boyum A, Lovhaug D, Tresland L, Nordlie EM. Separation of leucocytes: improved cell purity by fine adjustments of gradient medium density and osmolality. Scand J Immunol. 1991 Dec;34(6):697-712. doi: 10.1111/j.1365-3083.1991.tb01594.x.

Reference Type RESULT

PMID: 1749920 (View on PubMed)

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248-54. doi: 10.1016/0003-2697(76)90527-3. No abstract available.

Reference Type RESULT

PMID: 942051 (View on PubMed)

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680-5. doi: 10.1038/227680a0. No abstract available.

Reference Type RESULT

PMID: 5432063 (View on PubMed)

Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4. doi: 10.1073/pnas.76.9.4350.

Reference Type RESULT

PMID: 388439 (View on PubMed)

Steck TL, Kant JA. Preparation of impermeable ghosts and inside-out vesicles from human erythrocyte membranes. Methods Enzymol. 1974;31:172-80. doi: 10.1016/0076-6879(74)31019-1. No abstract available.

Reference Type RESULT

PMID: 4370662 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2008-32

Identifier Type: -

Identifier Source: org_study_id

Studies on the Expression and Functions of RLIP76 in Blood Samples of Healthy Human Subjects

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

University of North Texas Health Science Center

Responsible Party

Principal Investigators

Sanjay Awasthi, MD

Locations

University of North Texas Health Science Center

University of North Texas Health Science Center

Countries

References

Singhal SS, Yadav S, Singhal J, Zajac E, Awasthi YC, Awasthi S. Depletion of RLIP76 sensitizes lung cancer cells to doxorubicin. Biochem Pharmacol. 2005 Aug 1;70(3):481-8. doi: 10.1016/j.bcp.2005.05.005.

Zou W, Borvak J, Marches F, Wei S, Galanaud P, Emilie D, Curiel TJ. Macrophage-derived dendritic cells have strong Th1-polarizing potential mediated by beta-chemokines rather than IL-12. J Immunol. 2000 Oct 15;165(8):4388-96. doi: 10.4049/jimmunol.165.8.4388.

McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene. 2006 Mar 13;25(11):1639-48. doi: 10.1038/sj.onc.1209373.

Jullien-Flores V, Mahe Y, Mirey G, Leprince C, Meunier-Bisceuil B, Sorkin A, Camonis JH. RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. J Cell Sci. 2000 Aug;113 ( Pt 16):2837-44. doi: 10.1242/jcs.113.16.2837.

Awasthi S, Cheng J, Singhal SS, Saini MK, Pandya U, Pikula S, Bandorowicz-Pikula J, Singh SV, Zimniak P, Awasthi YC. Novel function of human RLIP76: ATP-dependent transport of glutathione conjugates and doxorubicin. Biochemistry. 2000 Aug 8;39(31):9327-34. doi: 10.1021/bi992964c.

Awasthi S, Sharma R, Singhal SS, Zimniak P, Awasthi YC. RLIP76, a novel transporter catalyzing ATP-dependent efflux of xenobiotics. Drug Metab Dispos. 2002 Dec;30(12):1300-10. doi: 10.1124/dmd.30.12.1300.

Awasthi S, Singhal SS, Yadav S, Singhal J, Drake K, Nadkar A, Zajac E, Wickramarachchi D, Rowe N, Yacoub A, Boor P, Dwivedi S, Dent P, Jarman WE, John B, Awasthi YC. RLIP76 is a major determinant of radiation sensitivity. Cancer Res. 2005 Jul 15;65(14):6022-8. doi: 10.1158/0008-5472.CAN-05-0968.

Yadav S, Zajac E, Singhal SS, Awasthi S. Linking stress-signaling, glutathione metabolism, signaling pathways and xenobiotic transporters. Cancer Metastasis Rev. 2007 Mar;26(1):59-69. doi: 10.1007/s10555-007-9043-5.

Jullien-Flores V, Dorseuil O, Romero F, Letourneur F, Saragosti S, Berger R, Tavitian A, Gacon G, Camonis JH. Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J Biol Chem. 1995 Sep 22;270(38):22473-7. doi: 10.1074/jbc.270.38.22473.

Shurin GV, Tourkova IL, Chatta GS, Schmidt G, Wei S, Djeu JY, Shurin MR. Small rho GTPases regulate antigen presentation in dendritic cells. J Immunol. 2005 Mar 15;174(6):3394-400. doi: 10.4049/jimmunol.174.6.3394.

DODGE JT, MITCHELL C, HANAHAN DJ. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119-30. doi: 10.1016/0003-9861(63)90042-0. No abstract available.

Stuckler D, Singhal J, Singhal SS, Yadav S, Awasthi YC, Awasthi S. RLIP76 transports vinorelbine and mediates drug resistance in non-small cell lung cancer. Cancer Res. 2005 Feb 1;65(3):991-8.

Singhal SS, Wickramarachchi D, Singhal J, Yadav S, Awasthi YC, Awasthi S. Determinants of differential doxorubicin sensitivity between SCLC and NSCLC. FEBS Lett. 2006 Apr 17;580(9):2258-64. doi: 10.1016/j.febslet.2006.03.038. Epub 2006 Mar 24.

Boyum A, Lovhaug D, Tresland L, Nordlie EM. Separation of leucocytes: improved cell purity by fine adjustments of gradient medium density and osmolality. Scand J Immunol. 1991 Dec;34(6):697-712. doi: 10.1111/j.1365-3083.1991.tb01594.x.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248-54. doi: 10.1016/0003-2697(76)90527-3. No abstract available.

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680-5. doi: 10.1038/227680a0. No abstract available.

Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4. doi: 10.1073/pnas.76.9.4350.

Steck TL, Kant JA. Preparation of impermeable ghosts and inside-out vesicles from human erythrocyte membranes. Methods Enzymol. 1974;31:172-80. doi: 10.1016/0076-6879(74)31019-1. No abstract available.

Other Identifiers

2008-32