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Preoperative treatm...
Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer.
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- Lönnroth, Christina, 1946 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Andersson, Marianne, 1944 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Arvidsson, Annette, 1943 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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visa fler...
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- Nordgren, Svante, 1945 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Brevinge, Hans, 1946 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Lagerstedt, Kristina, 1976 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Lundholm, Kent, 1945 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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visa färre...
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(creator_code:org_t)
- 2008
- 2008
- Engelska.
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Ingår i: Cancer immunity : a journal of the Academy of Cancer Immunology. - 1424-9634. ; 8
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- Adenocarcinoma
- drug therapy
- immunology
- pathology
- surgery
- Aged
- Aged
- 80 and over
- Anti-Inflammatory Agents
- Non-Steroidal
- pharmacology
- therapeutic use
- Cell Movement
- drug effects
- Colorectal Neoplasms
- drug therapy
- immunology
- pathology
- surgery
- Cyclooxygenase 2 Inhibitors
- pharmacology
- therapeutic use
- Cyclooxygenase Inhibitors
- pharmacology
- therapeutic use
- Dendritic Cells
- drug effects
- immunology
- Female
- Gene Expression Profiling
- Gene Expression Regulation
- Neoplastic
- drug effects
- HLA-D Antigens
- biosynthesis
- genetics
- Humans
- Indomethacin
- pharmacology
- therapeutic use
- Lymphocyte Subsets
- drug effects
- immunology
- Lymphocytes
- Tumor-Infiltrating
- drug effects
- Macrophages
- drug effects
- immunology
- Male
- Middle Aged
- Neoplasm Proteins
- biosynthesis
- genetics
- Omeprazole
- therapeutic use
- Premedication
- Preoperative Care
- Pyrazoles
- pharmacology
- therapeutic use
- Sulfonamides
- pharmacology
- therapeutic use
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