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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2008-2-29
pubmed:abstractText
This study evaluates HLA gene expression and tumor infiltration by B-cells, macrophages, dendritic cells, T-helper and cytotoxic T-lymphocytes in response to short-term preoperative treatment with cyclooxygenase inhibitors. Patients with colorectal carcinoma were randomized to receive oral NSAID (indomethacin or celebrex) for three days preoperatively; controls received esomeprazol. Peroperative tumor biopsies and normal colon tissue were analyzed by microarray, quantitative PCR and immunohistochemistry. Efficacy of short-term systemic NSAID treatment was confirmed by measurement of PGE2 production in blood monocytes from healthy volunteers. NSAID treatment upregulated genes at the MHC locus on chromosome 6p21 in tumor tissue, but not in normal colon tissue, from the same patient. 23 of the 100 most upregulated genes belonged to MHC class II. HLA-DM, -DO (peptide loading), HLA-DP, -DQ, -DR (antigen presentation), granzyme B, H, perforin and FCGR3A (CD16) (cytotoxicity) displayed increased expression, as did CD8, a marker of cytotoxic T-lymphocytes, while HLA-A and -C expression were not increased by NSAID treatment. MHC II protein (HLA-DP, -DQ, -DR) levels and infiltration by CD4+ T-helper cells of tumor stroma increased upon NSAID treatment, while CD8+ cytotoxic T-lymphocytes increased in both tumor stroma and epithelium. Molecules associated with immunosuppressive T regulatory cells (FOXP3, IL-10) were significantly decreased in indomethacin-exposed tumors. Standard oral administration of NSAID three days preoperatively was enough to increase tumor infiltration by seemingly activated immune cells. These findings agree with previous information that high prostanoid activities in colorectal cancer increase the risk for reduced disease-specific survival following tumor resection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1424-9634
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5
pubmed:dateRevised
2010-12-15
pubmed:meshHeading
pubmed-meshheading:18307280-Adenocarcinoma, pubmed-meshheading:18307280-Aged, pubmed-meshheading:18307280-Aged, 80 and over, pubmed-meshheading:18307280-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:18307280-Cell Movement, pubmed-meshheading:18307280-Colorectal Neoplasms, pubmed-meshheading:18307280-Cyclooxygenase 2 Inhibitors, pubmed-meshheading:18307280-Cyclooxygenase Inhibitors, pubmed-meshheading:18307280-Dendritic Cells, pubmed-meshheading:18307280-Female, pubmed-meshheading:18307280-Gene Expression Profiling, pubmed-meshheading:18307280-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18307280-HLA-D Antigens, pubmed-meshheading:18307280-Humans, pubmed-meshheading:18307280-Indomethacin, pubmed-meshheading:18307280-Lymphocyte Subsets, pubmed-meshheading:18307280-Lymphocytes, Tumor-Infiltrating, pubmed-meshheading:18307280-Macrophages, pubmed-meshheading:18307280-Male, pubmed-meshheading:18307280-Middle Aged, pubmed-meshheading:18307280-Neoplasm Proteins, pubmed-meshheading:18307280-Omeprazole, pubmed-meshheading:18307280-Premedication, pubmed-meshheading:18307280-Preoperative Care, pubmed-meshheading:18307280-Pyrazoles, pubmed-meshheading:18307280-Sulfonamides
pubmed:year
2008
pubmed:articleTitle
Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer.
pubmed:affiliation
Department of Surgery, Surgical Metabolic Research Laboratory at Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, University of Gothenburg, Sweden. Christina.lonnroth@surgery.gu.se
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't