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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00762801
• Other study ID #: 2008-32
• Status: Withdrawn
• Phase: N/A
• First received: September 26, 2008
• Last updated: October 24, 2016
• Start date: September 2008
• Est. completion date: September 2011

Study information

• Verified date: October 2016
• Source: University of North Texas Health Science Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Healthy

Locations

Country	Name	City	State
United States	University of North Texas Health Science Center	Fort Worth	Texas
United States	University of North Texas Health Science Center	Fort Worth	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of North Texas Health Science Center

Country where clinical trial is conducted

United States, 

References & Publications (21)

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 — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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):60 — View Citation

Bøyum A, Løvhaug 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. — View Citation

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. — View Citation

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. Epub 2001 Aug 24. — View Citation

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. — View Citation

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):2 — View Citation

Jullien-Flores V, Mahé 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- — View Citation

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680-5. — View Citation

McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene. 2006 Mar 13;25(11):1639-48. Review. — View Citation

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. — View Citation

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. Epub 2006 Mar 24. — View Citation

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. — View Citation

Steck TL, Kant JA. Preparation of impermeable ghosts and inside-out vesicles from human erythrocyte membranes. Methods Enzymol. 1974;31:172-80. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expression of RLIP76 in red blood cells and white blood cells of 100 healthy human subjects.		3 years	No
Secondary	To investigate the RLIP76 mediated transport of glutathione conjugates and chemotherapeutic drugs.		3 years	No

External Links

•   UNT Health Science Center Clinical Trials Homepage