Document Detail


Poly(β-amino ester) nanoparticle delivery of TP53 has activity against small cell lung cancer in vitro and in vivo.
MedLine Citation:
PMID:  23364678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Small cell lung cancer (SCLC) is an aggressive disease with one of the highest case-fatality rates among cancer. The recommended therapy for SCLCs has not changed significantly over the past 30 years; new therapeutic approaches are a critical need. TP53 is mutated in the majority of SCLC cases and its loss is required in transgenic mouse models of the disease. We synthesized an array of biodegradable poly(β-amino ester) (PBAE) polymers that self-assemble with DNA and assayed for transfection efficiency in the p53-mutant H446 SCLC cell line using high-throughput methodologies. Two of the top candidates were selected for further characterization and TP53 delivery in vitro and in vivo. Nanoparticle delivery of TP53 resulted in expression of exogenous p53, induction of p21, induction of apoptosis, and accumulation of cells in sub-G1 consistent with functional p53 activity. Intratumoral injection of subcutaneous H446 xenografts with polymers carrying TP53 caused marked tumor growth inhibition. This is the first demonstration of TP53 gene therapy in SCLC using nonviral polymeric nanoparticles. This technology may have general applicability as a novel anticancer strategy based on restoration of tumor suppressor gene function.
Authors:
Chandrashekhar D Kamat; Ron B Shmueli; Nick Connis; Charles M Rudin; Jordan J Green; Christine L Hann
Related Documents :
24344728 - The role of acupoint stimulation as an adjunct therapy for lung cancer: a systematic re...
24816738 - P16 methylation is associated with chemosensitivity to fluorouracil in patients with ad...
23024188 - Cancer-associated fibroblasts drive the progression of metastasis through both paracrin...
23283368 - Pazopanib enhances paclitaxel-induced mitotic catastrophe in anaplastic thyroid cancer.
10466438 - Primary cancer of the fallopian tube with transitional differentiation. clinical and pa...
20650508 - Vulvar field resection: novel approach to the surgical treatment of vulvar cancer based...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-30
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  12     ISSN:  1538-8514     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-10     Completed Date:  2013-10-22     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-15     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / genetics
Cell Line, Tumor
Disease Models, Animal
Female
Gene Expression
Gene Transfer Techniques*
Genes, p53*
Humans
Lung Neoplasms / genetics*,  pathology
Mice
Nanoparticles / chemistry*
Polymers / chemistry*
Small Cell Lung Carcinoma / genetics*,  pathology
Tumor Burden / genetics
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
R21 CA152473/CA/NCI NIH HHS; R21CA152473/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Polymers; 0/poly(beta-amino ester)
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Analysis of DNA Repair-Related Genes in Breast Cancer Reveals CUL4A Ubiquitin Ligase as a Novel Biom...
Next Document:  Potential of pretreatment neural activity in the visual cortex during emotional processing to predic...