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Role of TNF in colon carcinogenesis
Author(s) -
Gyulai Zsofia,
Salcedo Rosalba,
Dai RenMing,
Anderson Kimberley,
Lyakh Lyudmila,
Mazzoni Alessandra,
Young Matthew,
Colburn Nancy,
Oshima Akira,
Grivennikov Sergei,
Nedospasov Sergei
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1079.7
Subject(s) - azoxymethane , tumor necrosis factor alpha , carcinogenesis , immune system , inflammation , medicine , cancer , colorectal cancer , tumor promotion , colitis , cancer research , immunology
The degree of inflammation and the type of inflammatory/immune response are responsible for tilting the balance between tumor progression and regression. TNF‐α has conflicting roles in cancer, as being both a necrotic and promoting/growth factor. There is much clinical interest in blocking TNF in anti‐cancer therapy but relatively little is known about the exact role of TNF in the development of cancer. We focused on defining the contribution of tissue specific TNF towards chronic colitis promotion and cancer using a chemical carcinogenesis model. TNF and conditional TNF deficient mice were treated with a single dose of the mutagenic agent azoxymethane followed by 3 or 4 cycles of 2% dextran sodium sulfate (AOM/DSS) administered in the drinking water. Mice were monitored for weight loss and intestinal bleeding. At the end of the treatment, mice were sacrificed for macroscopic and histological analysis of the intestine. TNF −/− mice developed significantly less pathology when compared with floxed TNF control mice. Most lesions were localized to the distal portion of the colon. To elucidate the contribution of TNF produced by different cell types, experiments with conditional TNF deficient mice are in progress. Our data indicate that the lack of TNF plays a protective role in the AOM/DSS carcinogenesis model.