NCT00762801

Brief Summary

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Sep 2008

Typical duration for all trials

Geographic Reach
1 country

2 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2008

Completed
25 days until next milestone

First Submitted

Initial submission to the registry

September 26, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 30, 2008

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2011

Completed
Last Updated

October 26, 2016

Status Verified

October 1, 2016

Enrollment Period

3 years

First QC Date

September 26, 2008

Last Update Submit

October 24, 2016

Conditions

Keywords

RLIP76Cancerapoptosis

Outcome Measures

Primary Outcomes (1)

  • Expression of RLIP76 in red blood cells and white blood cells of 100 healthy human subjects.

    3 years

Secondary Outcomes (1)

  • To investigate the RLIP76 mediated transport of glutathione conjugates and chemotherapeutic drugs.

    3 years

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

100 healthy volunteers

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of North Texas Health Science Center

Fort Worth, Texas, 76107, United States

Location

University of North Texas Health Science Center

Fort Worth, Texas, 76109, United States

Location

Related Publications (21)

  • 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.

    PMID: 15950949BACKGROUND
  • 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.

    PMID: 11522795BACKGROUND
  • 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.

    PMID: 7907606BACKGROUND
  • 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.

    PMID: 9548755BACKGROUND
  • 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.

    PMID: 11035076BACKGROUND
  • 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.

MeSH Terms

Conditions

Neoplasms

Study Officials

  • Sanjay Awasthi, MD

    University of North Texas Health Science Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
observational
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2008

First Posted

September 30, 2008

Study Start

September 1, 2008

Primary Completion

September 1, 2011

Study Completion

September 1, 2011

Last Updated

October 26, 2016

Record last verified: 2016-10

Data Sharing

IPD Sharing
Will not share

Locations