Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-18
pubmed:abstractText
Given the high fatality rate of pancreatic cancer, an effective treatment for this devastating disease is urgently needed. We have shown that mesothelin expression was higher in human pancreatic cancer cells than in human pancreatic duct epithelial cells, and mesothelin mRNA was substantially overexpressed in 18 of 21 (86%) clinical pancreatic adenocarcinoma specimens when compared with the surrounding normal tissues. However, the biological functions of mesothelin in tumor progression are not clearly understood. Here we studied the effects of mesothelin overexpression in pancreatic cancer cell proliferation and migration in vitro and pancreatic cancer progression in vivo. We found that forced expression of mesothelin significantly increased tumor cell proliferation and migration by 90% and 300%, respectively, and increased tumor volume by 4-fold in the nude mice xenograft model when compared with the vector control cell line. Silencing of mesothelin inhibited cell proliferation and migration in pancreatic cancer cells and ablated tumor progression in vivo. Vaccination with chimeric virus-like particles that contain human mesothelin substantially inhibited tumor progression in C57BL/6J mice. The increases in mesothelin-specific antibodies and CTL activity and the decrease in regulatory T cells correlated with reduced tumor progression and prolonged survival. This study revealed novel functions of mesothelin and suggested a new therapeutic vaccine strategy whereby mesothelin is targeted to control pancreatic cancer progression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
286-96
pubmed:dateRevised
2011-10-26
pubmed:meshHeading
pubmed-meshheading:18281514-Adenocarcinoma, pubmed-meshheading:18281514-Animals, pubmed-meshheading:18281514-Cell Line, Tumor, pubmed-meshheading:18281514-Cell Movement, pubmed-meshheading:18281514-Cell Proliferation, pubmed-meshheading:18281514-Cell Transformation, Neoplastic, pubmed-meshheading:18281514-Cells, Cultured, pubmed-meshheading:18281514-Disease Progression, pubmed-meshheading:18281514-GPI-Linked Proteins, pubmed-meshheading:18281514-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18281514-Gene Silencing, pubmed-meshheading:18281514-Humans, pubmed-meshheading:18281514-Immunotherapy, Active, pubmed-meshheading:18281514-Male, pubmed-meshheading:18281514-Membrane Glycoproteins, pubmed-meshheading:18281514-Mice, pubmed-meshheading:18281514-Mice, Inbred C57BL, pubmed-meshheading:18281514-Mice, Nude, pubmed-meshheading:18281514-Pancreatic Neoplasms, pubmed-meshheading:18281514-Recombinant Fusion Proteins, pubmed-meshheading:18281514-Transfection, pubmed-meshheading:18281514-Virion, pubmed-meshheading:18281514-Xenograft Model Antitumor Assays
pubmed:year
2008
pubmed:articleTitle
Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer.
pubmed:affiliation
Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural