Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is reported that the number of hepatocellular carcinoma (HCC) in Japan is increasing and this is mainly due to the increase of HBsAg negative HCC patients with history of blood transfusion. However 80% of HCC patients are positive for HBV related serum markers. HBV DNA is detected by PCR method in 15% of HBsAg negative HCC patients with other HBV marker. These findings indicated that at least 40% of HCC patients in Japan are closely related to HBV infection. Several hypotheses on the mechanism of carcinogenesis by HBV have been proposed, however none of these has yet to be established. The type C hepatitis virus (HCV) reported by Chiron Co. is thought to be the majority of viruses which cause chronic non A non B hepatitis in Europe, United States and also Japan. The rate of anti-HCV in HBsAg negative HCC patients is about 70% in Japan. As strategies for HCC, the following 3 steps should be established; 1) prophylaxis against infection, 2) prevention of progression of liver cirrhosis, and 3) early detection of HCC. Though the role of hepatitis virus in hepatocarcinogenesis has not yet been established, it is thought that HBV and HCV are responsible for about 85% of HCC patients in terms of the development of liver cirrhosis which frequently associates with HCC. A marked decrease of HCC in Japan is forthcoming through the establishment of prophylaxis against HBV and HCV infection.
 ...
PMID:[Current status and therapeutic strategy for hepatocellular carcinoma]. 215 67

The existence of facultative stem cells in the liver has been advocated based on observations from models of carcinogenesis in rat liver. Observations of human liver material from cases of fulminant hepatitis have shown the presence of ductular hepatocytes expressing markers of both hepatocytes and bile duct cells. We describe the morphologic features and antigenic expression of a population of ductular hepatocytes identified in a patient with end-stage cirrhosis resulting from hepatitis B infection and secondary biliary cirrhosis. By conventional light microscopy and electron microscopy, ductular hepatocytes were seen to form pseudoductules within periportal areas. Using immunohistochemical methods, these ductular hepatocytes were found to be positive for both the hepatitis B surface antigen and bile duct epithelial cytokeratin, phenotypic markers classically restricted to expression on hepatocytes and bile duct epithelium, respectively. These findings show definitively that ductular hepatocytes are intermediate cells bearing morphologic and phenotypic characteristics of both hepatocytes and bile duct epithelium. The presence of these cells indicates the existence of facultative stem cells in the adult mammalian liver.
 ...
PMID:Characterization of ductular hepatocytes in end-stage cirrhosis. 232

The potential carcinogenic activity of acetaminophen (paracetamol, APAP) was studied in male F344 rats with pre-existing liver damage induced by a choline-devoid (CD) diet. In a short-term experiment, APAP was administered by intragastric intubation as single doses of 0.5-1.5 g/kg body wt after 4 weeks feeding of CD diet had produced fatty livers in rats. Two-thirds partial hepatectomy was performed 4 h subsequent to the initiating treatment step. After a 2 week recovery period, all rats were subjected to the selection procedure of Cayama et al. and killed at week 9 of the experiment. Quantitative analysis of placental form glutathione S-transferase (GST-P)-positive liver lesion development did not reveal any enhancement by APAP, whereas administration of a non-necrogenic dose of diethylnitrosamine (20 mg/kg body wt) in the same protocol demonstrated significant promotion, confirming the utility of the model for detection of weak carcinogenicity of chemicals. In the second long-term experiment, APAP was fed at doses of 0.45 and 0.9% for 25 weeks following 27 weeks administration of CD diet which produced liver cirrhosis in the rats. Despite a slight enhancement of focal liver lesions positive for gamma-glutamyltranspeptidase (GGT), no significant promotion of GST-P-positive altered foci or nodules was observed. In contrast, continuous feeding of CD diet or 0.5% phenobarbital treatment after generation of cirrhosis with CD diet clearly enhanced the induction of both GST-P and GGT-positive liver lesions. Thus, these results indicate that APAP does not possess significant carcinogenic activity in damaged rat liver.
Carcinogenesis 1990 Jun
PMID:Lack of hepatocarcinogenic potential of acetaminophen in rats with liver damage associated with a choline-devoid diet. 234 65

In this review, some common food plants and their toxic or otherwise bioactive components and mycotoxin contaminants have been considered. Crucifers contain naturally occurring components that are goitrogenic, resulting from the combined action of allyl isothiocyanate, goitrin, and thiocyanate. Although crucifers may provide some protection from cancer when taken prior to a carcinogen, when taken after a carcinogen they act as promoters of carcinogenesis. The acid-condensed mixture of indole-3-carbinol (a component of crucifers) binds to the TCDD receptor and causes responses similar to those of TCDD. Herbs contain many biologically active components, with more than 20% of the commercially prepared human drugs coming from these plants. Onion and garlic juices can help to prevent the rise of serum cholesterol. Most herbs used in treatments may have many natural constituents that act oppositely from their intended use. Some herbs like Bishop's week seed contain carcinogens, and many contain pyrrolizidine alkaloids that can cause cirrhosis of the liver. The general phytoalexin response in plants (including potatoes, tomatoes, peppers, eggplant, celery, and sweet potatoes) induced by external stimuli can increase the concentrations of toxic chemical constituents in those plants. In potatoes, two major indigenous compounds are alpha-solanine and alpha-chaconine, which are human plasma cholinesterase inhibitors and teratogens in animals. Because of its toxicity, the potato variety Lenape was withdrawn from the market. Celery, parsley, and parsnips contain the linear furanocoumarin phytoalexins psoralen, bergapten, and xanthotoxin that can cause photosensitization and also are photomutagenic and photocarcinogenic. Celery field workers and handlers continually have photosensitization problems as a result of these indigenous celery furanocoumarins. A new celery cultivar (a result of plant breeding to produce a more pest-resistant variety) was responsible for significant incidences of phytophotodermatitis of grocery employees. Since there is no regulatory agency or body designated to oversee potential toxicological issues associated with naturally occurring toxicants, photodermatitis continues to occur from celery exposure. Sweet potatoes contain phytoalexins that can cause lung edema and are hepatotoxic to mice. At least one of these, 4-ipomeanol, can cause extensive lung clara cell necrosis and can increase the severity of pneumonia in mice. Some phytoalexins in sweet potatoes are hepatotoxic and nephrotoxic to mice. The common mushroom Agaricus bisporus contains benzyl alcohol as its most abundant volatile, and A. bisporus and Gyromitra esculenta both contain hydrazine analogues. Mycotoxins are found in corn, cottonseed, fruits, grains, grain sorghums, and nuts (especially peanuts); therefore, they also occur in apple juice, bread, peanut butter, and other products made from contaminated starting materials.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Natural pesticides and bioactive components in foods. 240 25

The effects of carbon tetrachloride-induced liver cirrhosis and xerostomia on oral carcinogenesis were studied in rats given the lipid-soluble carcinogen 7,12-dimethylbenz-[a]anthracene (DMBA). The first carcinoma was detected after only 1 month of DMBA applications. After a further 8 months 85% of the animals had developed one or more squamous cell carcinomas. The latency period for DMBA-induced oral cancer in cirrhotic rats with xerostomia was markedly reduced in comparison with previous findings from xerostomic rats without liver cirrhosis. The results support earlier epidemiologic studies indicating a relationship between liver cirrhosis and oral cancer.
 ...
PMID:Induction of oral cancer by 7,12-dimethylbenz[a]anthracene in rats with liver cirrhosis. 251 33

Serum thyroxine was significantly higher in 59 patients with hepatocellular carcinoma than in normal subjects, patients with uncomplicated cirrhosis (48), or other primary tumours with or without hepatic metastases (50). Elevated thyroxine levels appeared attributable to high levels of thyroxine binding globulin which showed a positive linear correlation with serum thyroxine in all groups studied. Despite this hyperthyroxinaemia all patients appeared clinically euthyroid and, consistent with this, T3 was elevated in only one patient and the free thyroxine index was normal in all. Amongst a group of 25 cirrhotic patients who were followed-up for between 12 and 72 months, there was a striking dissociation between the TBG values of those destined to develop HCC and those who did not. In the former group TBG rose steadily with time whereas in the latter group levels remained stable, or, more often, fell. The rises in TBG occurred prior to any clinical signs of tumour development and may be one of the earliest serological changes to occur during carcinogenesis in the cirrhotic liver.
 ...
PMID:Hyperthyroxinaemia in hepatocellular carcinoma: relation to thyroid binding globulin in the clinical and preclinical stages of the disease. 283 1

Infection with 100 Opisthorchis viverrini (OP) metacercariae prior to two injections of dihydroxy-di-n-propyl nitrosamine (DHPN) (1000 mg/kg body weight) brought about significant enhancement of resultant preneoplastic lesion development in Syrian hamster liver and pancreas tissue. Thus combined treatment with carcinogen and parasite was associated with pancreatic atypical (dysplastic) foci, hepatocellular nodules, cholangiofibrosis and cholangiocarcinomas. No such lesions were observed in carcinogen alone, parasite alone or untreated control groups. In addition, parasite induced hyperplastic gall bladder epithelium was found to include areas of putative preneoplastic cells only in the DHPN-OP combined group. The results strongly suggest that pancreatitis and biliary cirrhosis associated with liver fluke infestation are responsible for the observed enhancement of carcinogenesis, and that the resultant increased proliferation plays a major role in tumorigenesis.
Carcinogenesis 1988 Jun
PMID:Enhancement of DHPN induced hepatocellular, cholangiocellular and pancreatic carcinogenesis by Opisthorchis viverrini infestation in Syrian golden hamsters. 283 5

To investigate the possible role of sex-hormone imbalance in hepatocellular carcinogenesis in male alcoholic cirrhotic patients, we determined plasma levels of testosterone (T), dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHA), estrone (E1), estradiol (E2), and sex-hormone-binding globulin (SHBG) in 15 men with alcoholic cirrhosis alone and in 15 similar men with alcoholic cirrhosis and hepatocellular carcinoma (HCC). The groups were matched for age and severity of liver disease using Child-Pugh scoring. Patients of both groups had evidence of hypogonadism with a decrease in plasma T levels (P less than 0.02) and of hyperestrogenemia with an increase in E1 (P less than 0.001), E2 (P less than 0.01), and SHBG (P less than 0.01) plasma levels compared with ten healthy age-matched controls. Cirrhotic patients with HCC had significantly lower plasma concentrations of T (P less than 0.02), DHT (P less than 0.01), and DHA (P less than 0.001) than patients with cirrhosis alone. However, the plasma concentrations of A, E1, E2, and SHBG did not significantly differ between these two groups. These results suggest a possible alteration of the estrogen-to-androgen ratio during carcinogenesis of the cirrhotic liver. This is shown by a greater reduction of circulating androgens and a similar elevation of estrogens in the group of cirrhotics with HCC.
 ...
PMID:Sex hormone imbalance in male alcoholic cirrhotic patients with and without hepatocellular carcinoma. 284 Jan 90

The liver is, under normal conditions, mitotically inactive and relatively resistant to chemical carcinogenesis. When rat or mouse hepatocytes are stimulated to divide, however, the liver becomes exquisitely sensitive to carcinogenesis. The heightened sensitivity of dividing liver cells to carcinogens is one of the most dramatic phenomena in the field of experimental chemical carcinogenesis and is reproducible with a wide variety of chemical agents and experimental conditions. This same phenomenon seems to apply to humans, as circumstances that produce a sustained hepatocellular proliferation in man are associated with an increased risk of hepatocellular carcinoma (HCC). These include inborn errors of metabolism (e.g., haemochromatosis, Wilson's disease, hereditary tyrosinaemia) as well as alcoholism. A recent editorial in this Journal suggested that any condition resulting in cirrhosis is also associated with an increased risk of HCC, and this may in turn be due to regenerative hyperplasia always present in cirrhotic liver (Johnson PJ, Williams R. J Hepatol 1987; 4: 140-147). In the case of HCC associated with hepatitis B virus (HBV) infection, the possibility must be entertained that chronic HBV infection serves to produce a sustained hepatonecrosis with concurrent (regenerative) hyperplasia. This proliferative state would in theory serve to increase the liver's susceptibility to environmental dietary carcinogens and may tend to increase the risk of HCC by this indirect mechanism. Until a molecular mechanisms is demonstrated whereby HBV produces a defined cellular lesion that endows hepatocytes with a malignant phenotype, it should not be assumed that HBV is a direct cause of HCC.
 ...
PMID:Cell proliferation and the aetiology of hepatocellular carcinoma. 285 89

The potentiating effect of pre-existing cirrhosis on the formation of hyperplastic liver nodules and/or foci was investigated by feeding a low dose (0.008%) of 2-N-fluorenylacetamide (FAA) in a choline-deficient (CD) diet for 32 weeks to cirrhotic and non-cirrhotic rats. Liver cirrhosis was induced by feeding the rats a CD diet for the preceding 36 weeks. The number and area of gamma-glutamyltranspeptidase-positive hyperplastic liver nodules and/or foci were significantly larger in cirrhotic rats exposed to low-dose FAA than in non-cirrhotic rats similarly treated. Hyperplastic liver nodules and/or foci were not observed in rats continuously fed a CD diet alone for 68 weeks (control cirrhotic rats). The results suggest that cirrhotic liver might alter the metabolic response to FAA, even at low doses, and lead to enhanced induction of hyperplastic liver nodules and/or foci.
Carcinogenesis 1987 Oct
PMID:Enhancement of low-dose N-2-fluorenylacetamide-induced hyperplastic liver nodules by pre-existing cirrhosis. 288 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>