ABSTRACT
Desmoids are rare tumors resulting from the proliferation of fibroblasts. They occur in association with familial adenomatous polyposis (FAP), but they may also occur in the post-traumatic peri-partum or post-abdominal surgery setting, and a few present spontaneously. Presenting features of desmoids are protean and largely relate to the anatomical area of involvement. We describe a 50 year old male not known to have Crohn's disease and without FAP who presented with multiple desmoids. Investigation of post-operative diarrhea confirmed a diagnosis of Crohn's disease. This is the first report of a male patient, who had never undergone prior abdominal surgery, presenting with Crohn's disease and abdominal desmoid tumors. The reasons why Crohn's disease and desmoids may be associated are explored, focusing particularly on alternations in the fibrogenic cytokine TGF-ß now known to be involved in the pathogenesis of both diseases.
Subject(s)
Crohn Disease/complications , Crohn Disease/physiopathology , Fibromatosis, Abdominal/etiology , Fibromatosis, Abdominal/physiopathology , Crohn Disease/diagnosis , Crohn Disease/therapy , Fibromatosis, Abdominal/diagnosis , Fibromatosis, Abdominal/therapy , Humans , Male , Middle Aged , Transforming Growth Factor beta/metabolism , Treatment OutcomeABSTRACT
The aim of the study was to determine if thyroid hormone-induced liver cell proliferation occurs through the Bcl-3 proto-oncogene. Rodents (including Bcl-3 knockout mice and the wild-type strain) were injected with a single dose of tri-iodothyronine (T(3)) and sacrificed at various time points. Hepatic mRNA (real-time polymerase chain reaction ) and protein expression (Western analysis) of Bcl-3 was quantified in rats stimulated with T(3). Cell proliferation was induced in a variety of cell types after T(3) injection at 24 h including hepatocytes (7 +/- 1.1% vs. 0.45 +/- 0.025%; P < 0.01), hepatic nonparenchymal cells (3.8 +/- 1.2% vs. 0.3 +/- 0.01%; P < 0.01), renal tubular cells (8.1 +/- 1.6% vs. 0.2 +/- 0.035%; P < 0.01), and splenic lymphocytes (4.8 +/- 1.2% vs. 0.35 +/- 0.02%; P < 0.01). We showed a twofold increase in hepatic Bcl-3 mRNA (P < 0.01) and protein expression (P < 0.01) at 24 h in rats stimulated with T(3). However, there were no differences in the rate of liver cell proliferation between Bcl-3 knockout mice and the wild-type strain (0.4 +/- 0.15% vs. 0.3 +/- 0.1%), indicating that Bcl-3 was not functionally involved in thyroid hormone-induced liver cell proliferation. A single gene is unlikely to initiate the process of thyroid hormone-induced cell proliferation. A complex interaction between the genomic and nongenomic effects of thyroid hormone is likely to regulate the mitogenic effects.
Subject(s)
Cell Proliferation/drug effects , Liver/cytology , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Triiodothyronine/pharmacology , Animals , B-Cell Lymphoma 3 Protein , Gene Expression Regulation , Liver/metabolism , Mice , Mice, Knockout , RNA, Messenger/genetics , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND AND AIM: A single dose of the thyroid hormone tri-iodothyronine, T3, can enhance both size and function of normal rodent liver, which is potentially of value in the treatment of liver disease. However the mechanism of this has not been fully elucidated, and it cannot be modeled in vitro. We therefore investigated the transcriptome response to T3 in rat liver in vivo. METHODS: After adult rats were administered 5 microg T3 subcutaneously, a whole rat genome microarray comparing global hepatic gene expression against vehicle-only treated liver after 3 h was performed. RESULTS: Informative transcripts which had identifiable gene ontology biological processes were grouped according to function, broadly reflecting general metabolic effects and those linked to cell-proliferation control. We then compared the transcriptome response after 5-microg T3 initiating hepatocyte DNA synthesis (mitogenic) with that after 0.1 microg T3, a supraphysiological amount not initiating hepatocyte DNA synthesis. CONCLUSIONS: We compared the results with published results of the response to other primary mitogens, and identified the Gadd45beta/MyD118 gene as a common early factor upregulated during proliferation.
