Abstract

Preclinical and clinical experience suggests that both retinoids and interferon inhibit HIV replication and have anti-tumor activity against KaposiUs sarcoma (KS). In this study, the combination of interferon- alpha-2b (IFN-a) and 9-cis retinoic acid (9-cRA) will be tested to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy in patients with AIDS-associated KS. A minimum of 6 and a maximum of 24 patients will be studied. Patients will be given 9-cRA (ALRT1057, NSC #659772) at a starting dose of 25 mg/m2/day. No dose escalation of 9-cRA will occur within a designated dose level. The 9-cRA will be given alone for the first 7 days of therapy. Beginning on day 8, patients will be given IFN-a. Patients will be observed at a given dose level for a minimum of four weeks before proceeding to the next dose level. In addition, the study will assess the following in these patients: 1) the levels of the various subtypes of retinoic acid receptor (RAR), retinoid X receptor (RXR), and retinoid orphan receptor (ROR/RZR) mRNA and protein in KS tissue obtained by 2-mm punch biopsy prior to and during therapy with the 9-cRA/IFN-a combination; 2) the pharmacokinetics of 9-cRA and IFN-a; 3) the effects of 9-cRA and IFN-a on HIV activity; and 4) the antitumor effects of 9-cRA and IFN-a.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
2M01RR000096-38
Application #
6115771
Study Section
Project Start
Project End
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
New York University
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016

  Publications

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Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M et al. (2016) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21:108-17
Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-129
Hohman, Timothy J; Cooke-Bailey, Jessica N; Reitz, Christiane et al. (2016) Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk. Alzheimers Dement 12:233-43
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Ghani, Mahdi; Reitz, Christiane; Cheng, Rong et al. (2015) Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals. JAMA Neurol 72:1313-23
Beecham, Gary W; Dickson, Dennis W; Scott, William K et al. (2015) PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease. Neurology 84:972-80

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