Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851341 (infestation)
 10,121 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of repeated Praziquantel administration, subsequent to infection and reinfection with Opisthorchis viverrini (OV), on lesion development in the Syrian hamster liver were investigated. Five applications of the antihelminthic drug were made (300 mg/kg body wt, i.g.), each time approximately 5 weeks after dosing with 60-80 OV metacercariae at weeks 0, 8, 16, 24 and 32. The animals were then maintained until week 40 when they were killed; histopathological investigation revealed no significant development of either hepatocellular of cholangiocellular preneoplastic/neoplastic lesions. The results indicate that repeated exposure to Praziquantel at levels sufficient for successful removal of parasite infestation does not itself carry carcinogenic risk.
Carcinogenesis 1992 Feb
PMID:Repeated exposure to Opisthorchis viverrini and treatment with the antihelminthic Praziquantel lacks carcinogenic potential. 174 24

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

The relationship between different levels of liver fluke, Opisthorchis viverrini infestation and dimethylnitrosamine (DMN) dosage in the induction of cholangiocarcinomas was investigated in Syrian golden hamsters. Two hundred and eighty male, weanling animals were divided into 4 groups: Group 1 served as untreated controls; group 2 received O. viverrini metacercariae only at levels of 100, 50, 25 or 12 per animal; group 3 received DMN only at doses of 12.5, 6.25 or 3.125 ppm; group 4 received various combinations of metacercariae and DMN. Only 2 of 17 animals (12%) in group 3 receiving 12.5 ppm had detectable tumours and no neoplastic lesions were seen in the 6.25 and 3.125 ppm DMN subgroups or in parasite alone or untreated control hamsters. In contrast, high carcinogen and parasite dose-dependent yields of cholangiocarcinomas (incidences up to 93%) and putative preneoplastic cholangiofibrotic lesions were observed in group 4. Thus the results indicate clear dose-dependent synergistic effects for the two agents and reveal the crucial importance of the presence of parasite, even at levels as low as 12 metacercariae, for DMN induction of bile duct carcinogenesis.
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PMID:Level of Opisthorchis infestation and carcinogen dose-dependence of cholangiocarcinoma induction in Syrian golden hamsters. 289 3

The effects of concomitant Opisthorchis infestation and dehydroepiandrosterone (DHEA) or butylated hydroxyanisole (BHA) administration on dihydroxy-di-n-propylnitrosamine (DHPN) induction of preneoplastic lesions were investigated in Syrian golden hamsters. Whereas parasite infection was primarily associated with first-order ductular proliferation in the liver and a secondary appearance of cholangiofibrotic lesions, DHEA treatment brought about increased carcinogen toxicity and enhanced generation of glutathione-S-transferase P (GST-P)-positive hepatocellular foci, liver cysts and focal proliferative changes in the pancreas. BHA also exerted an enhancing influence on pancreatic but not liver carcinogenesis. The results suggest that whereas alteration of DHPN metabolism by DHEA and BHA treatment effected changes at the initiation level, opisthorchiasis principally exerted an enhancing influence subsequent to carcinogen withdrawal.
Carcinogenesis 1988 Jul
PMID:Early lesions induced by DHPN in Syrian golden hamsters: influence of concomitant Opisthorchis infestation, dehydroepiandrosterone or butylated hydroxyanisole administration. 296 88

The influence of Opisthorchis viverrini liver fluke infection on development of diethylnitrosamine (DEN)-induced hepatocellular nodules was investigated in Syrian golden hamsters. Infection with 60 metacercariae, 4 weeks prior to administration of DEN for 12 weeks in the drinking water at dose levels of 10, 20 and 40 p.p.m., resulted in a significantly increased yield of nodular lesions as compared with the group receiving carcinogen treatment alone. The results indicate an importance for parasite-associated liver injury and compensatory regeneration in hepatocarcinogenesis and suggest a possible role for Opisthorchis infestation in the generation of hepatocellular tumours in man.
Carcinogenesis 1987 Sep
PMID:Enhancement of DEN-induced hepatocellular nodule development by Opisthorchis viverrini infection in Syrian golden hamsters. 362 73

We previously reported that increased endogenous nitrosation in human subjects infected with the liver fluke Opisthorchis viverrini in north-east Thailand could be a risk factor for the development of cholangiocarcinoma. In the present study we examined our hypothesis that this increased endogenous nitrosation is mediated by nitric oxide (NO) synthase induced by O. viverrini infestation. Syrian golden hamsters experimentally infected with O. viverrini liver fluke excreted in the urine significantly greater amounts of nitrate, a stable oxidization product of NO, than untreated hamsters (3.64 +/- 0.86 versus 2.64 +/- 0.60 mumol/hamster/day, P < 0.001). When the rapidly nitrosatable thiazolidine 4-carboxylic acid was administered orally, the infected hamsters also excreted significantly elevated levels of N-nitrosothiazolidine 4-carboxylic acid than untreated hamsters (4.27 +/- 2.20 versus 2.33 +/- 1.13 nmol/hamster/day, P < 0.01), indicating that endogenous nitrosation is elevated in the animals with liver fluke. NO synthase activity measured in liver cytosol was about twice as high in the infected hamsters as in untreated animals. The enzyme, whose biochemical characteristics were similar to that induced in activated murine macrophages, was immunohistochemically localized in the cytoplasm of macrophages and eosinophils in the inflammation zone surrounding the parasite-containing bile ducts. These results support our hypothesis that, in fluke-infected subjects, NO synthase induction leads to excess production of NO and the observed elevated endogenous nitrosation. Since high concentrations of NO exert cytotoxic and mutagenic effects per se, excess NO produced in chronically infected/inflamed tissues may also play a role in initiation and subsequent modulation stages of cholangiocarcinoma development.
Carcinogenesis 1994 Feb
PMID:Increased nitrosamine and nitrate biosynthesis mediated by nitric oxide synthase induced in hamsters infected with liver fluke (Opisthorchis viverrini). 750 24

Synergy between exposure to chemical carcinogens (nitrosamines) and infestation with the liver fluke Opisthorchis viverrini has been demonstrated in a hamster model of hepatocarcinogenesis (Flavell et al., Carcinogenesis 4:927-930, 1983; Thamavit et al., Carcinogenesis 8:1351-1353, 1987). To elucidate the mechanisms of this interaction we tested the hypothesis that liver parasitism might influence the expression and activity of carcinogen metabolizing enzymes. We found that one, and perhaps more, hamster liver cytochrome P450 (CYP) isozymes immunorelated to mouse CYP2A5 contributed up to 50 or 60% of the hepatic aflatoxin B1 (AFB) and N-nitrosodiethylamine (NDEA) metabolism, respectively. As inferred from average enzyme activities and from western blot, immunoinhibition, and substrate (coumarin) inhibition analyses, O. viverrini infestation increased the expression of enzymes detectable by anti-CYP2A5 antibody as well as NDEA metabolism in male but not in female hamsters. Immunohistochemical analysis of CYP2A expression by anti-mouse CYP2A5 antibody demonstrated that the O. viverrini-associated increase was not uniformly distributed throughout the liver but occurred in hepatocytes immediately adjacent to areas of inflammation. Immunohistochemical analysis of AFB-DNA adducts in the livers of O. viverrini-infested hamsters treated with AFB showed that the highest levels of adducts were found in the regions of liver where hepatocellular expression of enzymes detectable by anti-CYP2A5 antibody is induced. These results suggest that a high local expression of CYP isozymes in O. viverrini-infested livers could be a contributing risk factor in the development of liver cancers associated with parasitic hepatitis.
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PMID:Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver. 791 96

In the North-east of Thailand, repeated antihelminthic therapy has been introduced for control of the opisthorchiasis known to be a major risk factor for cholangiocellular carcinomas. What influence this may have on tumorigenesis, however, remains unclear. The effects of administration of praziquantel, an antihelminthic drug, at different time points subsequent to infection with Opisthorchis viverrini (OV) on 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN)-initiated lesion development in the liver of female Syrian hamsters were therefore investigated. Praziquantel (250 mg/kg body weight, i.p.) was given 4, 12 or 20 weeks after infection of DHPN-treated animals (two 1000 mg/kg i.p. injections at weeks 0 and 2) with 60 OV metacercariae (at week 4). Survivors at week 38 were killed and examined. It was found that whereas praziquantel administration at the earlier two time points was effective at reducing hepatocellular nodule development, the results for cholangiocellular lesions were less pronounced, significant reduction only being evident in hamsters treated 4 weeks after parasite infestation. The findings thus indicate that enhancement of DHPN-initiated bile duct carcinogenesis by opisthorchiasis is both rapid and to a large degree irreversible. Hepatocellular lesion development in this model, on the other hand, appears to correlate more closely with the duration of parasite-associated proliferative stimulus.
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PMID:Time-dependent modulation of liver lesion development in Opisthorchis-infected Syrian hamster by an antihelminthic drug, praziquantel. 846 30

In Thailand, smoking of commercial cigarettes and of handmade cigarettes has drastically increased in recent decades. Cancer of the lung and of the upper aero-digestive tract have also increased in Thailand as they have in many other countries. It is our working hypothesis that the increase of primary cancer of the liver, especially of cholangiocarcinoma in the north-eastern provinces of Thailand is associated with the use of tobacco in men infested with the liver fluke Opisthorchis viverrini (OV). Bioassays have shown that volatile nitrosamines and tobacco-specific nitrosamines induce cholangiocarcinoma in laboratory animals and that the hepatocarcinogenic action of nitrosodimethylamine in hamsters is significantly increased by infestation with the liver fluke OV. The endogenous formation of nitrosamines is significantly increased by OV infestation. This report presents analytical data on the concentration of volatile nitrosamines and tobacco-specific nitrosamines in mainstream smoke of nine leading brands of commercially produced Thai cigarettes which represent approximately 85% of the market share in Thailand. Observed ranges (ng/cigarette) were 8.5-31.9 for nitrosodimethylamine, 8.8-49.6 for nitrosopyrrolidine and 4.2-18.9 for nitrosodi-n-butylamine. These values are exceptionally high compared with the smoke of light and blended cigarettes from North America and Western Europe. Among the tobacco-specific nitrosamines, the range was 28-730 for nitrosonornicotine and 16-370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. There was a correlation between volatile and tobacco-specific nitrosamines, and tar and nicotine deliveries in the mainstream smoke. The analytical data are in line with the rate for lung cancer and support our working hypothesis that nitrosamines, and especially the tobacco-specific nitrosamines, are associated with the increased risk for primary liver cancer among those Thai people who smoke cigarettes and also carry OV infestation.
Carcinogenesis 1999 Jan
PMID:Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai cigarettes: a risk factor for lung cancer and a suspected risk factor for liver cancer in Thailand. 993 60

Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National Cancer Institute (NCI), Cairo, it constitutes 30.3% of all cancers. The median age at diagnosis is 46 years, with a male preponderance of 5:1. Whether in Egypt or other African countries such as Sudan, Kenya, Uganda, Gold Coast, and Senegal, it is mostly of the squamous cell type, and arises in a background of schistosomiasis or bilharziasis. Tumors are usually advanced at the time of presentation. Bladder carcinogenesis is probably related to bacterial and human papilloma virus (HPV) infections, usually associated with bilharzial infestation. Management is mainly surgery, with 5-year survival rates after radical cystectomy increasing from 35% in the 1970s to 48% in the 1990s. The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to surgery since 1976 significantly improved both disease-free and overall survival rates. Molecular genetic studies concerning potential prognostic markers, tumorigenesis, and tumor progression in bilharzial bladder cancer are limited. However, a comprehensive detailed analysis of these factors is underway. Bilharzial bladder cancer is a preventable malignant disease. Primary prevention could be possible if the parasite is eliminated nationwide. Chemoprevention using retinoids or cyclooxygenase 2 (COX-2) inhibitors is a possible alternative. Semin Oncol 28:174-178.
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PMID:Bladder cancer in Africa: update. 1130 80


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