Abstract

The Synthesis and Nanoformulation Core (SNC) will supply ceramide analogs, acid ceramidase (AC) inhibitors, sphingosine kinase inhibitors, and tamoxifen metabolites essential to the members of this Program Project. In addition, the Core will also provide liposomal formulations of C6-ceramide derivatives, acid ceramidase inhibitors, sphingosine kinase inhibitor SKI-178, and tamoxifen metabolites to the Projects 1, 2, 3, and 4, respectively. Furthermore, the Core will also synthesize [^H] AC inhibitors and [^

Public Health Relevance

A successful completion of this Program Project, that is focused on defining the biological basis of dysfunctional sphingoiipid metabolism in AML and new therapeutic targets for molecular and lipidomimetic treatment approaches, requires novel chemical agents. Since the syntheses techniques are beyond the scope and experience of individual Project leaders, the inclusion of SNC in this proposal is highly relevant.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA171983-01A1
Application #
8554598
Study Section
Project Start
2013-09-10
Project End
2018-08-31
Budget Start
2013-09-10
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$150,605
Indirect Cost
$47,317

  Institution

Name
Pennsylvania State University
Department
Type
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033

  Publications

Shaw, Jeremy; Costa-Pinheiro, Pedro; Patterson, Logan et al. (2018) Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era. Adv Cancer Res 140:327-366
Zhang, Xuewei; Kitatani, Kazuyuki; Toyoshima, Masafumi et al. (2018) Ceramide Nanoliposomes as a MLKL-Dependent, Necroptosis-Inducing, Chemotherapeutic Reagent in Ovarian Cancer. Mol Cancer Ther 17:50-59
Verma, Mohit K; Clemens, Julia; Burzenski, Lisa et al. (2017) A novel hemolytic complement-sufficient NSG mouse model supports studies of complement-mediated antitumor activity in vivo. J Immunol Methods 446:47-53
Olson, Kristine C; Kulling, Paige M; Olson, Thomas L et al. (2017) Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL leukemia. Cancer Biol Ther 18:290-303
Hengst, Jeremy A; Dick, Taryn E; Sharma, Arati et al. (2017) SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med 3:109-121
Morad, Samy A F; Davis, Traci S; MacDougall, Matthew R et al. (2017) Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer. Biochem Pharmacol 130:21-33
Doshi, Ushma A; Shaw, Jeremy; Fox, Todd E et al. (2017) STAT3 mediates C6-ceramide-induced cell death in chronic lymphocytic leukemia. Signal Transduct Target Ther 2:17051
Tan, Su-Fern; Pearson, Jennifer M; Feith, David J et al. (2017) The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia. Expert Opin Ther Targets 21:583-590
Linton, Samuel S; Sherwood, Samantha G; Drews, Kelly C et al. (2016) Targeting cancer cells in the tumor microenvironment: opportunities and challenges in combinatorial nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol 8:208-22
Tan, Su-Fern; Liu, Xin; Fox, Todd E et al. (2016) Acid ceramidase is upregulated in AML and represents a novel therapeutic target. Oncotarget 7:83208-83222

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