Abstract

This application has as its fundamental premise the concept the concept that the therapy of the acute nonlymphocytic leukemias can be approached, the initiation of terminal differentiation and that this phenomenon can be induced by granulocyte-colony stimulating factor (G-CSF) to produce therapeutic benefit to patients with these diseases. This study will involve the role of the G-CSFR in the regulation of hematopoietic cell differentiation; evaluation of the synergistic interaction between RA and G-CSF on leukemia cell differentiation; extension of in vitro findings in the WEHI-3B leukemia in vitro to therapeutic evaluation in mice; and extension of findings in the WEHI- 3B leukemia to the clinical level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA002817-39
Application #
2376726
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1978-01-01
Project End
1999-02-28
Budget Start
1997-03-01
Budget End
1998-02-28
Support Year
39
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Ishiguro, Kimiko; Rice, Anna M; Rice, Kevin P et al. (2009) Inhibition of all-trans retinoic acid-induced granulocytic differentiation of WEHI-3B D+ cells by forced expression of SCL (TAL1) and GATA-1. Leuk Res 33:1249-54
Lin, Z Ping; Zhu, Yong-Lian; Johnson, Dennis R et al. (2008) Disruption of cAMP and prostaglandin E2 transport by multidrug resistance protein 4 deficiency alters cAMP-mediated signaling and nociceptive response. Mol Pharmacol 73:243-51
Ishiguro, Kimiko; Sartorelli, Alan C (2008) Relationship between the induction of leukemia cell differentiation and the enhancement of reporter gene expression in 3T3 Swiss cells. Leuk Res 32:89-96
Cai, Jiyang; Kirlin, Ward G; Chen, Yan et al. (2006) Overexpression of heat shock factor 1 inhibits butyrate-induced differentiation in colon cancer cells. Cell Stress Chaperones 11:199-207
Cai, Jiyang; Chen, Yan; Murphy, T J et al. (2004) Role of caspase activation in butyrate-induced terminal differentiation of HT29 colon carcinoma cells. Arch Biochem Biophys 424:119-27
Holtz, Kathleen M; Rice, Anna M; Sartorelli, Alan C (2003) Lithium chloride inactivates the 20S proteasome from WEHI-3B D+ leukemia cells. Biochem Biophys Res Commun 303:1058-64
Bordonaro, Michael; Lazarova, Darina L; Augenlicht, Leonard H et al. (2002) Cell type- and promoter-dependent modulation of the Wnt signaling pathway by sodium butyrate. Int J Cancer 97:42-51
Koay, Debbie C; Nguyen, Tr- Hung; Sartorelli, Alan C (2002) Distinct region of the granulocyte colony-stimulating factor receptor mediates proliferative signaling through activation of Janus kinase 2 and p44/42 mitogen-activated protein kinase. Cell Signal 14:239-47
Lazarova, D L; Bordonaro, M; Sartorelli, A C (2001) Transcriptional regulation of the vitamin D(3) receptor gene by ZEB. Cell Growth Differ 12:319-26
Rice, A M; Sartorelli, A C (2001) Inhibition of 20 S and 26 S proteasome activity by lithium chloride: impact on the differentiation of leukemia cells by all-trans retinoic acid. J Biol Chem 276:42722-7

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