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

In 37 patients with Crohn's disease the 25-hydroxycholecalciferol (25-HCC) serum level, serum concentration of calcium and inorganic phosphate, and the enzyme activity of alkaline phosphatase were measured. Furthermore the activity index of Crohn's disease was determined in every patient. There was no statistically significant difference of 25-HCC serum levels in these patients compared to a healthy control group. Correspondingly most patients showed normal alkaline phosphatase enzyme activity and normal serum concentration of calcium and inorganic phosphate. No correlation between 25-HCC concentration and site of inflammation or activity index was found.
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PMID:25-hydroxycholecalciferol serum levels in patients with Crohn's disease. 90 78

Nine hundred and ninety nine patients were admitted in our Department (the Third Department of Internal Medicine, School of Medicine, UOEH) during the five years more since the opening date of the University Hospital (July, 9, 1979), and 864 cases in them (86.2%) suffered from the various digestive diseases. Most of the in-patients with digestive diseases in our Department are resident in Kitakyushu city and its suburbs, especially in Yahatanishi-ku, Wakamatsu-ku and Onga county, therefore, it may be possible to investigate the ecological characteristics of the in-patients of our Department in the relation to the outbreak, clinical course and outcome of the digestive diseases. Namely, it may be assumed that the incidence and prevalence of the idiopathic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease are relatively high in this area (Kitakyushu city and its suburbs) as compared with the average of all Japan. Although the true causes of these illness are still unknown, the inclination of haptoglobin phenotypes (HP) which include 2-2, 2-1 & 1-1 type 1-1 strongly suggests to the association with some genetical factors on the high incidence of these diseases (IBD). In this connection, Hp type 1-1 were recognized 4 in 11 cases (36.4%) with ulcerative colitis, and 3 in 7 cases (42.9%) with Crohn's disease in our Department whereas only 3-5% in normal controls. Secondly, the patients with carcinoma of the biliary tree (bile duct and gall bladder) are relatively more, namely, 17 cases of bile duct cancer and 3 cases of gall bladder cancer were admitted in our Department during this term. It is interesting to note that hepatohilar type of the bile duct cancer was observed comparatively high (4 in 17 cases, 52.9%) in the past five years-more although the etiology is unknown. Finally, several characteristics in liver diseases particularly in viral hepatitis were illustrated in this study, namely, the ratio of transient HBV infection to whole (transient and persistent) HBV infection in the patients with acute viral hepatitis (due to HBV) is high (80.9%), HBeAg positivity is high in chronic B-hepatitis (44.9%), the ratio of alcoholic cirrhosis to whole liver cirrhosis is relatively high (34.9%) and HBsAg positivity is lower in liver cirrhosis due to non-alcoholic origin (mainly due to hepatitis virus) than the average of this country, and also, hepatocellular carcinoma (HCC) without liver cirrhosis is higher (23.0%) than the average of whole Japan (less than 15%) statistically.
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PMID:[Ecological approach to the patients with digestive diseases in Kitakyushu City and its suburbs]. 372 13

Recent studies have demonstrated that angiogenesis and suppressed cell-mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein-Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-alpha, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-alpha have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease.
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PMID:The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease. 1074 Dec 73

A 22-year-old woman without predisposing liver disease developed focal hepatic glycogenosis and hepatocellular carcinoma after 6 years of azathioprine therapy for Crohn's disease. Hepatocellular carcinoma without cirrhosis has previously been described during immunosuppression, but this is the first report of disseminated focal hepatic glycogenosis after long-term azathioprine therapy.
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PMID:Hepatocellular carcinoma and focal hepatic glycogenosis after prolonged azathioprine therapy. 1092 28

Complications of oral contraceptives (OCs) affecting the gastrointestinal tract, liver and pancreas are rare but potentially serious. Hepatobiliary complications are by far the most frequent and varied. Hepatic lesions will probably decline in frequency as low-dose OCs replace higher dosed pills. Intrahepatic cholestasis induced by OCs resembles that of pregnancy. There may be a genetic predisposition to both conditions involving a dose-dependent estrogen effect of decreasing bile secretion. Intrahepatic cholestasis appears within 6 cycles of OC use. Symptoms include pruritus with anorexia, asthenia, vomiting, and weight loss without fever, rash or abdominal pain. Termination of OCs clears the condition without sequelae within 1-3 months, sometimes after a temporary aggravation. A moderate and asymptomatic cytolysis may appear when OC treatment is begun. Sinusoidal dilatation has been conclusively linked to OCs although few cases have been published. Clinical manifestations other than hepatomegaly are variable. Abdominal pain and fever are the most common. The condition is not related to duration of use and disappears 5-15 days after OC use is terminated. The relative risk of Budd-Chiari syndrome in OC users is estimated at 2.37. OCs increase the prevalence of hepatic adenomas as a function of duration of treatment. They are usually discovered fortuitously but may be revealed by vague abdominal pains. Hemorrhagic complications are more likely in OC users. It may be difficult to distinguish between adenomas, hepatocellular carcinoma, and focal nodular hyperplasia. A puncture biopsy guided by sonography may aid diagnosis. The natural history of adenomas is poorly understood and treatment remains controversial. OCs do not appear to increase the risk of focal nodular hyperplasia but they increase the size of the tumor and the risk of hemorrhage. OCs should be terminated because of risk of hemorrhage. Surgical resection is not indicated unless there are complication or diagnostic doubts. While hepatocellular carcinoma is very rare, its risk is increased by a factor of 7-20 in women using OCs for 8 years or more. Use of combined OCs appears to speed development of lithiasis in predisposed women. Risk of lithiasis is linked to estrogen content in women under 30. Several cases of acute pancreatitis in the 1st 3 months of treatment have been reported in women with preexisting lipid metabolic anomalies. Cases of ischemic lesions of the small intestine or colon have been reported in OC users with A positive blood type. Such lesions can be fatal without early diagnosis and termination of OCs. Gastric esophageal reflux is increased by progestins. Preexisting constipation may be aggravated and the incidence of Crohn's disease increased by OCs. It is advisable to rule out preexisting hepatic pathology before prescribing OCs. OCs should be stopped in case of viral hepatitis.
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PMID:[Contraception and hepatogastroenterology]. 1231 76

Ileovesical fistula is a very rare clinical entity, the most frequent cause of which is Crohn's disease. Furthermore, it is an exceptionally rare complication of malignancies. We experienced one case of ileovesical fistula which had been caused by hepatocellular carcinoma (HCC) arising from the noncirrhotic liver. A 27-year-old man was diagnosed with HCC in a noncirrhotic liver. Despite treatment with transarterial chemoembolization (TACE), the disease status became more aggravated. The patient complained of dysuria, fecaluria, and intermittent lower abdominal pain. Pelvic CT scan showed a soft tissue mass of 6 cm abutting on the distal ileum which was downwardly displaced. Barium study of the small bowel showed a fistula between the small bowel loop and the urinary bladder. Upon operation, adhesion and fistula were found between the ileum and the urinary bladder. The microscopic findings of the surgical specimen were compatible with metastatic HCC. We confirmed that ileovesical fistula had been caused by metastatic HCC.
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PMID:Ileovesical fistula caused by hepatocellular carcinoma. 1590 58

Chronic inflammatory processes produce an excess of ROS and DNA-reactive aldehydes from lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA), which can modify cellular macromolecules and drive to malignancy. Etheno-modified DNA bases are generated inter alia by reaction of DNA with the major LPO product, HNE. We are investigating steady-state levels of etheno-DNA adducts in organs with diseases related to persistent inflammatory processes that can lead to malignancies. We have developed ultrasensitive and specific methods for the detection of etheno-DNA base adducts in human tissues and in urine. Etheno-DNA adduct levels were found to be significantly elevated in the affected organs of subjects with chronic pancreatitis, ulcerative colitis and Crohn's disease. When patients with alcohol abuse-related hepatitis, fatty liver, fibrosis and cirrhosis were compared with asymptomatic livers, excess hepatic DNA damage was seen in the three latter patient groups. Etheno-deoxyadenosine excreted in urine was measured in HBV-infected patients diagnosed with chronic hepatitis, cirrhosis and hepatocellular carcinoma. As compared to controls, these patients had up to 90-fold increased urinary levels. Impaired or imbalanced DNA-repair pathways may influence the steady-state levels of etheno-DNA adducts in inflamed tissues. In conclusion, etheno-DNA adducts may serve as potential lead markers for assessing progression of inflammatory cancer-prone diseases. If so, the efficacy of human chemopreventive interventions for malignant disease prevention could be verified.
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PMID:Accumulation of lipid peroxidation-derived DNA lesions: potential lead markers for chemoprevention of inflammation-driven malignancies. 1609 77

Hepatocellular carcinoma is known to be associated with underlying liver diseases, such as cirrhosis, hemochromatosis, and chronic viral hepatitis. All reported cases of hepatocellular carcinoma in association with Crohn's disease involve patients treated previously with azathioprine or both azathioprine and steroids. However, hepatocellular carcinoma associated with the use of azathioprine and infliximab has not been reported. In this report, we describe an unusual case of hepatocellular carcinoma and focal hepatic glycogenosis (FHG) occurring in a non-cirrhotic Crohn's disease patient who has been treated with both azathioprine and infliximab.
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PMID:Hepatocellular carcinoma occurring in a patient with Crohn's disease treated with both azathioprine and infliximab. 1667 Sep 38

In murine models of Crohn's disease, rheumatoid arthritis and colon cancer, IL-6 (interleukin-6) signalling via the sIL-6R (soluble IL-6 receptor; termed IL-6 trans-signalling) has been shown to promote the pathology associated with these conditions. These detrimental activities can, however, be selectively blocked by soluble forms of the gp130 (glycoprotein 130) receptor. Although sgp130 (soluble gp130) therefore represents a viable therapeutic modality for the treatment of these conditions, the mass manufacture of such biologics is often expensive. The advent of molecular farming has, however, provided an extremely cost-effective strategy for the engineering of recombinant proteins. Here, we describe the expression and production of a biologically active sgp130 variant that is expressed in transgenic tobacco plants as an ELP (elastin-like peptide)-fusion protein (mini-gp130-ELP). Mini-gp130-ELP consists of the first three domains of gp130 (Ig-like domain and cytokine binding module) fused to 100 repeats of ELP. Expression of mini-gp130-ELP did not affect the growth rate or morphology of the transgenic plants, and purification was achieved using inverse transition cycling. This approach led to an overall yield of 141 microg of purified protein per g of fresh leaf weight. The purified mini-gp130-ELP specifically inhibited sIL-6R-mediated trans-signalling as measured by binding to the IL-6-sIL-6R complex and through its ability to block sIL-6R-mediated activation of STAT3 (signal transducer and activator of transcription 3) phosphorylation and proliferation in human hepatoma cells and murine pre-B-cells. Consequently, the present study validates the potential application of molecular farming in transgenic tobacco plants as a strategy for the expression and purification of therapeutically advantageous biologics such as sgp130.
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PMID:Functional expression of a biologically active fragment of soluble gp130 as an ELP-fusion protein in transgenic plants: purification via inverse transition cycling. 1671 47

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


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