This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This is a phase I study of suberoylanilide hydroxamic acid (SAHA) plus temozolomide for children and adolescents with recurrent or refractory central nervous system tumors. SAHA is an inhibitor of histone deacetylase (HDAC) that causes the arrest of cell cycle transition at G1 and G2M phases. SAHA binds to HDAC by inserting a hydroxamic group, most of the aliphatic chain and part of the phenyl amino group in the active site of the enzyme. The insertion of SAHA into the active site prevents the binding of the natural substrate and blocks enzymatic deacetylation. Temozolomide is an oral imidazotetrazine prodrug that undergoes spontaneous hydrolysis to the active metabolite MTIC, which methylates DNA at O6-guanine and other sites. Since we theorize that pretreatment with SAHA may potentiate the activity of temozolomide by relaxing DNA and increasing susceptibility to methylating agents, we will first escalate the dose of SAHA while holding the temozolomide dose constant at 150 mg/m2/day x 5. Previous studies suggest this temozolomide dose is well tolerated and has potential for antitumor activity. If the highest dose of SAHA appears tolerable, then temozolomide dosing will be increased to the standard single-agent dose of 200 mg/m2/day.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000188-47
Application #
8356753
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2010-12-01
Project End
2011-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
47
Fiscal Year
2011
Total Cost
$3,562
Indirect Cost
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Utzinger, Linsey M; Gowey, Marissa A; Zeller, Meg et al. (2016) Loss of control eating and eating disorders in adolescents before bariatric surgery. Int J Eat Disord 49:947-952
Lee, B; Diaz, G A; Rhead, W et al. (2016) Glutamine and hyperammonemic crises in patients with urea cycle disorders. Mol Genet Metab 117:27-32
El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W et al. (2016) Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation. Mol Genet Metab 117:407-12
Bansal, N; Hampe, C S; Rodriguez, L et al. (2016) DPD epitope-specific glutamic acid decarboxylase (GAD)65 autoantibodies in children with Type 1 diabetes. Diabet Med :
Nishimura, Katherine K; Iwanaga, Kensho; Oh, Sam S et al. (2016) Early-life ozone exposure associated with asthma without sensitization in Latino children. J Allergy Clin Immunol 138:1703-1706.e1
Inge, Thomas H; Courcoulas, Anita P; Jenkins, Todd M et al. (2016) Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents. N Engl J Med 374:113-23
Spurney, Christopher F; McCaffrey, Francis M; Cnaan, Avital et al. (2015) Feasibility and Reproducibility of Echocardiographic Measures in Children with Muscular Dystrophies. J Am Soc Echocardiogr 28:999-1008
Pino-Yanes, Maria; Thakur, Neeta; Gignoux, Christopher R et al. (2015) Genetic ancestry influences asthma susceptibility and lung function among Latinos. J Allergy Clin Immunol 135:228-35
Zeller, Meg H; Inge, Thomas H; Modi, Avani C et al. (2015) Severe obesity and comorbid condition impact on the weight-related quality of life of the adolescent patient. J Pediatr 166:651-9.e4
Nagamani, Sandesh C S; Diaz, George A; Rhead, William et al. (2015) Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials. Mol Genet Metab 116:29-34

Showing the most recent 10 out of 422 publications