Abstract

The long-term goal of this proposal is to test the efficacy of SapC-DOPS: a unique targeting nanotherapeutic for brain tumors, in combination with chemotherapy. Saposin C (SapC) is a sphingolipid activating protein found ubiquitously throughout the body that functions to catabolize glycosphingolipids. SapC preferentially associates with negatively charged phospholipids at an acidic pH. When SapC is coupled with dioleoylphosphatidylserine (DOPS), stable nanovesicles are formed which can selectively fuse with cancer cells, leading to activation of acid sphingomyelinase and subsequent ceramide accumulation, caspase activation, and eventual apoptosis. In this proposal we seek to investigate any synergistic interactions between SapC-DOPS and chemotherapy, which has broad implications on the future treatment paradigms for glioma and other cancers as well.

Public Health Relevance

The American Cancer Society predicts that there will be 12,740 deaths due to cancers of the brain/nervous system this year. Despite decades of research, survival for patients suffering from glioblastoma remains less than 15 months. Thus, there is an unmet and urgent need to develop new treatment modalities.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA171733-02
Application #
8648398
Study Section
Special Emphasis Panel (ZRG1-F09-P (21))
Program Officer
Schmidt, Michael K
Project Start
2013-04-03
Project End
2015-04-02
Budget Start
2014-04-03
Budget End
2015-04-02
Support Year
2
Fiscal Year
2014
Total Cost
$30,780
Indirect Cost

  Institution

Name
Ohio State University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Wojton, Jeffrey; Meisen, Walter Hans; Kaur, Balveen (2016) How to train glioma cells to die: molecular challenges in cell death. J Neurooncol 126:377-84
Lasso-Pirot, Anayansi; Delgado-Villalta, Silvia; Spanier, Adam J (2015) Early childhood wheezers: identifying asthma in later life. J Asthma Allergy 8:63-73
Basu, Rajit K; Kaddourah, Ahmad; Terrell, Tara et al. (2015) Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in critically ill children (AWARE): study protocol for a prospective observational study. BMC Nephrol 16:24
Yaraghi, Ahmad; Eizadi-Mood, Nastaran; Salehi, Marzieh et al. (2015) Risk factors and the outcome of therapy in patients with seizure after Carbamazepine poisoning: A two-year cross-sectional study. J Res Pharm Pract 4:18-23
Schwandt, Peter; Scholze, Juergen E; Bertsch, Thomas et al. (2015) Response to ""Right Analysis-Wrong Conclusion: Obese Youth With Higher BP Are at Risk for Target Organ Damage"". Am J Hypertens 28:1072-3
Mullins, Tanya L Kowalczyk; Widdice, Lea E; Rosenthal, Susan L et al. (2015) Risk perceptions, sexual attitudes, and sexual behavior after HPV vaccination in 11-12 year-old girls. Vaccine 33:3907-12
Wojton, Jeffrey; Meisen, Walter Hans; Jacob, Naduparambil K et al. (2014) SapC-DOPS-induced lysosomal cell death synergizes with TMZ in glioblastoma. Oncotarget 5:9703-9
Wojton, Jeffrey; Elder, James; Kaur, Balveen (2014) How efficient are autophagy inhibitors as treatment for glioblastoma? CNS Oncol 3:5-7
Van Brocklyn, James R; Wojton, Jeffrey; Meisen, Walter H et al. (2014) Aurora-A inhibition offers a novel therapy effective against intracranial glioblastoma. Cancer Res 74:5364-70
Froehlich, Tanya E; Delgado, Sergio V; Anixt, Julia S (2013) Expanding medication options for pediatric ADHD. Curr Psychiatr 12:20-29

Showing the most recent 10 out of 11 publications