Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic gastrointestinal and liver infections account for a significant percentage of human cancer deaths. Rodent models help elucidate how infection can lead to malignancy. Helicobacter pylori, the leading cause of human gastric tumors, produces similar disease in Mongolian gerbils. H. pylori, H. felis, and H. hepaticus induce stomach, lower bowel, or liver tumors in susceptible wild-type and genetically engineered mice. Immune dysregulated mice recapitulate features of inflammatory bowel disease including colon carcinoma. Hepatitis B and C virus transgenic mice provide insights into viral hepatitis and hepatocellular carcinoma. Rodent models enhance our understanding of infectious cancer pathogenesis and suggest novel targets for intervention.
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PMID:Inflammation and Cancer. I. Rodent models of infectious gastrointestinal and liver cancer. 1476 34

The major acute-phase protein serum amyloid A, A-SAA, is upregulated by a variety of inflammatory stimuli, including cytokines and glucocorticoids (GCs). Elevated systemic concentrations of both A-SAA and tumour necrosis factor (TNF)-alpha are a feature of inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Here, we examine the roles of TNF-alpha, interleukin-6 (IL-6) and GCs on the transcriptional regulation of the two human A-SAA genes (SAA1 and SAA2) and show that these stimuli have different effects on the SAA1 and SAA2 promoters in HepG2 hepatoma and KB epithelial cell lines. Both genes are induced modestly by TNF-alpha and IL-6 alone and synergistically by TNF-alpha plus IL-6. The TNF-driven induction of SAA1, but not that of SAA2, can be enhanced by GCs in both cell lines, whereas GCs alone can upregulate SAA1 only in epithelial cells. The upregulation of both genes by cytokines, and of SAA1 by GCs, is more rapid in epithelial cells than hepatoma cells. We established that the order in which either cell line was treated with TNF-alpha and IL-6 influenced A-SAA promoter transcriptional activation. Treatment with TNF-alpha followed by IL-6 resulted in a much greater induction of both A-SAA genes than treatment with IL-6 followed by TNF-alpha.
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PMID:Regulation of the human acute phase serum amyloid A genes by tumour necrosis factor-alpha, interleukin-6 and glucocorticoids in hepatic and epithelial cell lines. 1487 Dec 91

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. There is growing evidence to suggest that this association is not coincidental but may indeed be causal. In this review, we discuss the role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy and outline some of the possible mechanisms involved.
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PMID:Inflammation and Cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. 1501 Mar 60

Macrophage migration inhibitory factor (MIF) is a unique protein, participating in inflammation, immune response, and cell growth. MIF was first discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including phagocytosis, spreading, and tumoricidal activity. It has been reported that MIF is associated with the pathogenesis of a variety of diseases. MIF expression was increased at inflammatory sites in diseases such as rheumatoid arthritis and glomerulonephritis. In experimental inflammatory disease, blockade of MIF bioactivity inhibited the severity of disease activity. On the other hand, MIF expression is also increased in tumor lesions, and MIF plays a role as a cell growth factor. MIF has been reported to be constitutively expressed in gut, liver, and pancreas. In patients with gastritis, inflammatory bowel disease, hepatitis, and pancreatitis, MIF expression was remarkably increased in both the serum and the local lesions. Blockade of MIF bioactivity inhibited and prevented inflammation in experimental gastritis, colitis, hepatitis, and pancreatitis. On the other hand, MIF expression was higher than that in normal tissues in colonic carcinomas and hepatocellular carcinoma both in vivo and in vitro. Blockade of MIF bioactivity successfully inhibited tumor cell growth in vivo and in vitro. MIF plays important roles in the pathogenesis of gastrointestinal, hepatic, and pancreatic disorders.
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PMID:Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders. 1577 Mar 93

Cancer commonly arises at the sites of chronic inflammation and infection. Although this association has long been recognized, the reason has remained unclear. Within the gastrointestinal tract, there are many examples of inflammatory conditions associated with cancer, and these include reflux disease and Barrettos adenocarcinoma of the esophagus, Helicobacter infection and gastric cancer, inflammatory bowel disease and colorectal cancer and viral hepatitis leading to hepatocellular carcinoma. There are several mechanisms by which chronic inflammation has been postulated to lead to cancer which includes enhanced proliferation in an endless attempt to heal damage, the presence of a persistent inflammatory environment creating a pro-carcinogenic environment and more recently a role for engraftment of circulating marrow-derived stem cells which may contribute to the stromal components of the tumor as well as the tumor mass itself. Here we review the recent advances in our understanding of the contributions of circulating bone marrow-derived stem cells to the formation of tumors in animal models as well as in human beings.
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PMID:Stem cells and cancer: evidence for bone marrow stem cells in epithelial cancers. 1648 34

Infection and chronic inflammation are proposed to contribute to carcinogenesis through inflammation-related mechanisms. Infection with hepatitis C virus, Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are important risk factors for hepatocellular carcinoma (HCC), gastric cancer and cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with colon carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We performed a double immunofluorescence labeling study and found that nitrative and oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS) was expressed in epithelial cells and inflammatory cells at the site of carcinogenesis in humans and animal models. Antibacterial, antiviral and antiparasitic drugs dramatically diminished the formation of these DNA lesion markers and iNOS expression. These results suggest that oxidative and nitrative DNA damage occurs at the sites of carcinogenesis, regardless of etiology. Therefore, it is considered that excessive amounts of reactive nitrogen species produced via iNOS during chronic inflammation may play a key role in carcinogenesis by causing DNA damage. On the basis of our results, we propose that 8-nitroguanine is a promising biomarker to evaluate the potential risk of inflammation-mediated carcinogenesis.
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PMID:Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis. 1660 33

This review highlights areas of clinical research in gastroenterology and hepatology that were published predominantly in the journal Clinical Gastroenterology and Hepatology during the last year and were summarized during the American Gastroenterological Association Presidential Plenary Session in May 2006. The topics included eosinophilic esophagitis in children, detecting high-grade dysplasia or carcinoma in Barrett's esophagus, advances in management of celiac disease with elemental diet or gluten predigestion, the safety of NSAIDs in inflammatory bowel disease, the role of steroids in development of abscesses, prognosis of colorectal cancer associated with inflammatory bowel disease, screening for familial colorectal cancer in apparently sporadic disease, a new syndrome of familial colorectal cancer, new drugs in the treatment of chronic constipation and obesity, hepatoma risk factors and underserved racial/ethnic groups, and the application of new imaging and biology in diagnosis of gastroenterological disorders.
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PMID:Gastroenterology and hepatology clinical research update: 2005-2006. 1694 47

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, developing colorectal cancer similar to human inflammatory bowel disease-associated neoplasia. TGF-beta1 is a multifunctional signaling molecule with a wide array of roles. Animal experiments suggest that TGF-beta1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting a significant stimulation of tumor growth invasion and metastasis during tumor progression. We assessed association of functional polymorphisms (-1082G/A; -592C/A) and TGF-beta1 (-509C/T; +869C/T) influencing the IL-10 production to colorectal cancer risk in a case-control study of 62 patients and 124 matched controls. No significant differences were observed among cancer patients and controls for IL-10 -1082G/A; -592C/A genotype frequencies. Evaluation of odds ratios (OR) for the TGF-beta1 +869C/T genotypes showed a significant increased risk for individuals bearing +869CC genotype compared to +869CT- and +869TT-positive individuals. These results suggest that the +869C allele, responsible for a Leu-->Pro substitution in the signal peptide sequence of the TGF-beta1 protein, may have a predisposing role in the development of colorectal cancer.
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PMID:Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma. 1726 58

Crohn's disease (CD) is a common, chronic, inflammatory bowel disease characterized by intestinal infiltration of activated immune cells and distortion of the intestinal architecture. In this study, we demonstrate that IL-22, a cytokine that is mainly produced by activated Th1 and Th17 cells, was present in high quantities in the blood of CD patients in contrast to IFN-gamma and IL-17. In a mouse colitis model, IL-22 mRNA expression was elevated predominantly in the inflamed intestine but also in the mesenteric lymph nodes. IL-22BP, the soluble receptor for IL-22, demonstrated an affinity to IL-22 that was at least 4-fold higher than its membrane-bound receptor, and its strong constitutive expression in the intestine and lymph nodes was decreased in the inflamed intestine. To investigate the possible role of systemic IL-22 in CD, we then administered IL-22 to healthy mice and found an up-regulation of LPS-binding protein (LBP) blood levels reaching concentrations known to neutralize LPS. This systemic up-regulation was associated with increased hepatic but not renal or pulmonary LBP mRNA levels. IL-22 also enhanced the secretion of LBP in human primary hepatocytes and HepG2 hepatoma cells in vitro. This increase was mainly transcriptionally regulated and synergistic with that of other LBP inducers. Finally, elevated LBP levels were detected in CD patients and the mouse colitis model. These data suggest that systemic IL-22 may contribute to the prevention of systemic inflammation provoked by LPS present in the blood of CD patients through its induction of hepatic LBP.
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PMID:IL-22 induces lipopolysaccharide-binding protein in hepatocytes: a potential systemic role of IL-22 in Crohn's disease. 1744 82

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease that causes fibrosis of the biliary tree. Life expectancy of patients is reduced by liver failure and a high incidence of malignancy. It is closely associated with inflammatory bowel disease, particularly ulcerative colitis, which coexists in approximately three-quarters of northern European patients. Cancers include cholangiocarcinoma, gallbladder cancer, hepatocellular carcinoma, pancreatic cancer and colorectal cancer. Ursodeoxycholic acid appears to reduce the incidence of colorectal neoplasia in patients with PSC, and there is some suggestion that it may also reduce the incidence of cholangiocarcinoma. A chemoprotective benefit of 5-aminosalicylates has not been confirmed in patients with PSC with associated inflammatory bowel disease. There is no accepted screening programme for cholangiocarcinoma, but methods for detecting early disease using biochemical markers, scanning using positron emission tomography or MRI, and endoscopic procedures such as endosonography and endoscopic retrograde cholangiopancreatography are discussed. A combination of techniques is often used in an attempt to diagnose early cholangiocarcinoma. Cholecystectomy should be performed for gallbladder polyps, as many are malignant, and ultrasonography and alpha-fetoprotein testing are suggested for screening for hepatocellular carcinoma. Colorectal carcinoma screening should be performed after the diagnosis of PSC, and surveillance colonoscopy should be performed annually if there is concomitant colitis.
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PMID:Chemoprevention and screening in primary sclerosing cholangitis. 1850 79


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