Abstract

) Objectives: 1) The measurement of prodrugs and activated drugs from in-vitro assays and in samples of brain tumor, plasma and other tissues. This CORE has been strongly affiliated with Projects 1 and 4 over the prior three years. During the five years of funding requested, this CORE will provide measurements of metabolites of CPA, CPT-11 from tissue culture systems and rodent models whether the prodrugs are activated by herpes vectors or herpes-based amplicons. 2) Evaluation of the interaction of the effects of CPA and CPT-11. This CORE will provide the pharmacologic basis for the scheduling and mode of administration of drug combinations for the MGH-2 vector system. 3) To provide biodegradable polymers containing prodrugs for implantation in animals for local prodrug delivery. As in prior years, Dr. Ludeman will construct CPA and CPT-11 polymer systems for implantation into rodent brains. Contractual arrangements will be made for GMP polymers in human studies. 4) Studies of drug resistance in transfected tumor cells. Tumor cells from rodents will be examined for scavenger enzyme, mismatched repair enzymes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA069246-07
Application #
6618157
Study Section
Project Start
2002-08-01
Project End
2003-07-31
Budget Start
Budget End
Support Year
7
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Ricklefs, Franz L; Alayo, Quazim; Krenzlin, Harald et al. (2018) Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv 4:eaar2766
Park, Jongmin; Im, Hyungsoon; Hong, Seonki et al. (2018) Analyses of Intravesicular Exosomal Proteins Using a Nano-Plasmonic System. ACS Photonics 5:487-494
Antoury, Layal; Hu, Ningyan; Balaj, Leonora et al. (2018) Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies. Nat Commun 9:3906
Zhou, Shuang; Appleman, Vicky A; Rose, Christopher M et al. (2018) Chronic platelet-derived growth factor receptor signaling exerts control over initiation of protein translation in glioma. Life Sci Alliance 1:e201800029
Min, Jouha; Nothing, Maria; Coble, Ben et al. (2018) Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis. ACS Nano 12:3378-3384
Lee, Kyungheon; Fraser, Kyle; Ghaddar, Bassel et al. (2018) Multiplexed Profiling of Single Extracellular Vesicles. ACS Nano 12:494-503
Reátegui, Eduardo; van der Vos, Kristan E; Lai, Charles P et al. (2018) Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles. Nat Commun 9:175
Speranza, Maria-Carmela; Passaro, Carmela; Ricklefs, Franz et al. (2018) Preclinical investigation of combined gene-mediated cytotoxic immunotherapy and immune checkpoint blockade in glioblastoma. Neuro Oncol 20:225-235
Boussiotis, Vassiliki A; Charest, Alain (2018) Immunotherapies for malignant glioma. Oncogene 37:1121-1141
Sahin, Ayguen; Sanchez, Carlos; Bullain, Szofia et al. (2018) Development of third generation anti-EGFRvIII chimeric T cells and EGFRvIII-expressing artificial antigen presenting cells for adoptive cell therapy for glioma. PLoS One 13:e0199414

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