Clinical trial NCT00762801: Studies on the Expression and Functions of RLIP76 in Blood Samples of Healthy Human Subjects
Official title: Studies on the Expression and Functions of RLIP76 in Blood Samples of Healthy Human Subjects
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Healthy
Keywords: RLIP76
Cancer
apoptosis
Lead sponsor: University of North Texas Health Science Center
Sponsor class: OTHER
First posted: 2008-09-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 100 healthy volunteers

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Expression of RLIP76 in red blood cells and white blood cells of 100 healthy human subjects.
timeFrame: 3 years
Secondary outcomes:
measure: To investigate the RLIP76 mediated transport of glutathione conjugates and chemotherapeutic drugs.
timeFrame: 3 years
Other outcomes:
Locations:
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
Study officials:
affiliation: University of North Texas Health Science Center
name: Sanjay Awasthi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/j.bcp.2005.05.005.
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. doi: 10.1074/jbc.M106838200. Epub 2001 Aug 24.
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. doi: 10.1172/JCI117102.
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. doi: 10.1021/bi972131r.
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. doi: 10.4049/jimmunol.165.8.4388.
citation: 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.
citation: 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.
citation: 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.
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. doi: 10.1124/dmd.30.12.1300.
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):6022-8. doi: 10.1158/0008-5472.CAN-05-0968.
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. doi: 10.1007/s10555-007-9043-5.
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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.
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