Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known about the efficacy of flutamide monotherapy in previously untreated patients with prostatic carcinoma. In this study, 40 patients with advanced disease were treated with 250 mg flutamide, three times daily. The mean follow-up was 7 months. After 3 months, 35 patients were evaluable for efficacy; 17 showed a partial response and 18 showed no change. Tumor response after 6 months was evaluated in 22 patients; 10 had a partial response, nine had stable disease, and three had progression. The level of prostate-specific antigen was reduced markedly following 6 months' treatment with flutamide. Levels of testosterone increased slightly but significantly, and were still elevated not significant after a follow-up period of 1 year. Follicle-stimulating hormone did not change markedly, whereas luteinizing hormone rose significantly. Eighteen patients experienced mild gynecomastia and eight suffered diarrhea. In two patients, flutamide was discontinued for 2 weeks due to serious diarrhea. One patient was withdrawn after 6 weeks because of cholestatic hepatitis. Sexual potency was evaluated in 15 patients, 10 of whom remained sexually active during treatment. Flutamide monotherapy was concluded to be relatively safe and effective in patients with advanced prostatic cancer.
 ...
PMID:Flutamide monotherapy as primary treatment in advanced prostatic carcinoma. 194 17

A case of severe toxic hepatitis in a patient with metastatic prostatic cancer treated for three months with flutamide (Eulexin) combined with an LHRH analogue, goserelin (Zoladex) is described. The patient developed severe liver failure with jaundice, ascites and severe encephalopathy. The condition reversed after discontinuation of flutamide. Less severe, but otherwise similar, adverse reactions have been reported in the literature, and the importance of considering the drug as a potential hepatotoxin is stressed.
 ...
PMID:[Severe toxic hepatitis during flutamide (Eulexin) treatment]. 291 17

Sera from 391 southern African Blacks with hepatocellular carcinoma, matched controls, patients with other malignant tumours, and with various forms of hepatobiliary disease were fractionated by polyacrylamide gradient gel electrophoresis to determine the prevalence of tumour-associated gamma-glutamyl transferase isoenzymes in Black patients with hepatocellular carcinoma. One or more tumour-associated isoenzymes (I', I'' or II') were present in 58.6% of the patients with hepatocellular carcinoma: I' in 54.5%, I'' in 27.1%, and II' in 34%. These isoenzymes were detected in one patient with prostatic cancer, occasionally in patients with acute viral hepatitis, but in no normal individuals. The presence of tumour-associated isoenzymes was not related to patient age, sex or hepatitis-B virus status or to the tumour burden. Isoenzymes were present in 42 percent of hepatocellular carcinoma patients with a normal serum alpha-foetoprotein concentration and in 50% of those with a non-diagnostic value. gamma-glutamyl transferase isoenzymes may be supplementary to alpha-foetoprotein in the diagnosis of hepatocellular carcinoma.
 ...
PMID:Tumour-associated isoenzymes of gamma-glutamyl transferase in the serum of patients with hepatocellular carcinoma. 620 51

Neocarzinostatin (NCZ), a new antitumor antibiotic, was administered to 19 patients with bladder cancer, 16 patients with prostatic cancer, and 3 patients with hepatoma. All patients had objectively measurable metastatic lesions including 21 with palpable nodes or subcutaneous nodules, 10 with pulmonary nodules as demonstrated by chest x-ray, 4 with malignant hepatomegaly, and 3 with bidimensional pelvic masses as demonstrated by CT scanning. Sixty-five courses of NCZ were administered via an intravenous bolus daily for five days with dosages ranging from 1500 to 3000 U/m2. Immediate toxicity was not dose-limiting except for 1 episode of anaphylaxis and 1 of acute renal failure. Myelotoxicity was delayed, dose-dependent, noncumulative, and dose-limiting. Thrombocytopenia was prolonged or irreversible in 5 cases. The maximally tolerated dose was 2750 U/m2. One patient with NCZ-associated pulmonary fibrosis and 1 with biopsy-proven hepatitis are discussed in detail. Neocarzinostatin demonstrated minimal therapeutic activity (1 partial remission) in patients with bladder cancer. There was no response in patients with prostatic cancer or hepatoma.
 ...
PMID:Phase II trial of neocarzinostatin in patients with bladder and prostatic cancer: toxicity of a five-day iv bolus schedule. 644 76

Ketoconazole (KT) and fluconazole (FLU) are azole antifungal agents with a broad spectrum of activity against both superficial and systemic mycoses. KT is also an anticancer agent in the treatment of advanced prostate cancer. In many clinical and retrospective studies, KT has been reported to cause liver damage, i.e. chemical hepatitis. Histologic analysis of KT induced hepatotoxicity shows massive centrilobular necrosis in which the hepatotoxicity was not thought to be mediated through an immunoallergic mechanism. According to the medical literature, the pattern of hepatic injury appears to be primarily of the hepatocellular type. Because of the documented reports of KT and FLU hepatotoxicity, a cytotoxicity comparison of KT and FLU was implemented. The objective of this comparison was to evaluate the cytotoxicity of these azoles such that future mechanistic investigations of hepatotoxicity could be performed. The relative hepatotoxicity of KT and FLU was evaluated using primary cultures of postnatal rat hepatocytes. Cytotoxicity was evaluated by measuring the leakage of the cytosolic enzyme, lactate dehydrogenase (LDH), into the medium; by assessing mitochondrial reduction of 3-(4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT); by assessing lysosomal uptake of neutral red (NR); and by gross morphology (phase contrast microscopy). The cultures were exposed to various concentrations of KT (56-188 microM) for 0.5-4 h and to various concentrations of FLU (50 microM to 1.0 mM) for 0.5-6 h. There was a significant increase (P < 0.05) in LDH leakage and a large decrease in MTT reduction and lysosomal uptake of NR at 4 h for KT. One millimolar FLU had minimal effects on the LDH leakage and MTT reduction. These results demonstrate that KT is a more potent cytotoxicant than FLU; and its toxicity was expressed in a dose- and time-dependent manner.
 ...
PMID:Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. 788 87

Flutamide is a nonsteroidal antiandrogen commonly used in the treatment of prostate cancer. Hepatic toxicity associated with flutamide has been reported with an incidence from less than 1% to about 5%. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been widely used in the treatment of cholesterol gallstones and of several liver diseases, but few data are now available concerning its use in the management of drug-induced hepatitis. The case of a patient who presented severe hepatitis with jaundice following use of flutamide is reported. UDCA treatment was started on admission and, contemporaneously, flutamide was withdrawn. Clinical and biochemical improvement was progressively observed, and the patient was discharged six weeks after the admission. Since fatal flutamide-related hepatitis has been reported, monitoring of serum liver tests is advocated during flutamide administration, and the effectiveness of UDCA in the treatment of drug-induced hepatotoxicity requires further study.
 ...
PMID:Flutamide-induced toxic hepatitis. Potential utility of ursodeoxycholic acid administration in toxic hepatitis. 894 75

Flutamide is a nonsteroidal antiandrogen drug used in the treatment of prostatic cancer. Hepatotoxic reactions due to flutamide have been reported with an incidence ranging from 1% to 5%. These reactions are usually reversible upon withdrawal of the drug but can occasionally be life-threatening. The mechanism of flutamide-associated hepatotoxicity is not well established. We report a case of a 69-year-old man with prostatic carcinoma in whom flutamide induced an acute hepatitis which resolved completely soon after drug withdrawal. In this patient, we have studied the possible involvement of an immunological mechanism in causing flutamide hepatitis by investigating the presence of circulating antibodies directed against reactive metabolites of flutamide bound to liver proteins with enzyme-linked immunosorbent assay technique. Although, in the present case, we have failed to detect IgG reacting with rat liver microsomes incubated in vitro with flutamide, this does not completely rule out the possibility of an immunological involvement in flutamide hepatotoxicity. The possibility of severe flutamide-related injury, independently of the underlying pathogenic mechanism, strongly suggests the need for careful monitoring of liver enzymes in patients taking this drug.
 ...
PMID:Flutamide-induced acute hepatitis: investigation on the role of immunoallergic mechanisms. 975 5

A case-control study of prostate cancer (PC) was undertaken in Athens, Greece. Cases were 320 patients with histologically confirmed incident disease, whereas controls were 246 patients without history or symptomatology of benign prostatic hyperplasia, treated in the same hospitals as the cases for minor diseases or conditions. Cases and controls had similar distributions with respect to height, body mass index, sibship size and birth order in the parental family, marital status and number of offspring in the subject's own family and a long series of previous surgical operations and medical diagnoses, including diabetes mellitus, hepatitis and sexually transmitted diseases. There was also no evidence for a positive association between vertex baldness, tobacco smoking and drinking of coffee or alcoholic beverages, on the one hand, and PC, on the other. There was evidence, however, that some aspect of urban life may increase the risk for PC and a suggestion that sexual activity in early adulthood may be inversely associated with this risk.
 ...
PMID:Risk factors for prostate cancer: a case-control study in Greece. 1004 70

This study profiles aggregate-specific cancer risk factors of Southeast Asian Americans residing along the Central Gulf Coast in the United States. An investigator-designed cross-sectional survey was conducted with 332 volunteer Southeast Asian community residents aged 18 years and above. Aggregate-specific cancer risk factors include high prevalence of hepatitis, high smoking and drinking rates in men, extended ultraviolet light exposure without protection, low colorectal and prostate cancer screening rates, and knowledge deficits of cancer and cancer screenings. Based on the study findings, progress toward the targets of the Alabama Comprehensive Cancer Control Plan: 2001-2005 is evaluated and compared to available national data. Implications for public health nursing practice and future research are also addressed. In particular, the study findings underscore the importance of developing culturally tailored interventions to reduce cancer risk factors in this underserved Asian American population.
 ...
PMID:Cancer risk factors among Southeast Asian American residents of the U.S. Central Gulf Coast. 1586 67

The non-steroidal antiandrogen flutamide is widely used for treatment of prostatic cancer, but causes side effects, including cholestatic hepatitis and fulminant hepatitis. We investigated the pathogenesis of flutamide-induced cholestatic hepatitis, focusing on the bile salt export pump (BSEP; ABCB11), which exports bile salts to the bile. We examined the inhibitory effects of flutamide and its active metabolite, hydroxyflutamide, on the transport of taurocholic acid (TCA) by membrane vesicles derived from hBSEP-expressing Sf9 cells. Flutamide inhibited the transport of TCA by hBSEP (IC50 value, about 50 microM), while hydroxyflutamide had no effect at up to 100 microM. When flutamide was administered to rats as a single oral dose of 100 mg/kg, the biliary excretion rate of bolus-injected [3H]TCA was decreased and the liver tissue concentration of flutamide exceeded 50 microM. Repeated doses of flutamide for 5 d (10 mg/kg/d) also decreased the biliary excretion rate of bolus-injected [3H]TCA. In this case, the liver tissue concentration of flutamide was below 0.1 microM. In both cases, no change in the mRNA level of rat Bsep was detected by RT-PCR. These results suggest that flutamide itself, but not its major metabolite, may cause cholestasis by inhibiting BSEP-mediated bile salt excretion.
 ...
PMID:Involvement of bile salt export pump in flutamide-induced cholestatic hepatitis. 1740 13


1 2 3 Next >>