Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The usefulness of post-operatively serial serum CA15-3 determination with CEA and TPA was evaluated in a group of 285 breast cancer patients. In particular, the CA15-3 sensitivity to 'early' diagnosis and monitoring of the response to treatment of breast cancer relapses, was compared with those of the two other markers in order to define the most suitable association. Moreover, in a group of 169 non relapsed patients with a prolonged follow-up (40 +/- 8 months; mean +/- s.d.) CA15-3 specificity was investigated. During post-operative follow-up in 27 (10%) patients, distant metastases occurred. In most of them, elevated values of one or more tumour markers were the first pathological sign and CA15-3, CEA and TPA sensitivity to 'early' diagnosis of metastases were 46%, 7% and 63% respectively. When each tumour marker was considered in combination, CA15-3-CEA-TPA association showed a higher sensitivity (87%) than both CA15-3-TPA (83%) and the CEA-TPA (70%). Serum CA15-3 increase preceded the certain sign of metastases 2.7 +/- 2.6 months (mean +/- s.d.). Shortly before appearance and during treatment of distant metastases, constant elevation and/or progressive increase in serum CA15-3 values occurred in all evaluated patients except three in whom isolated elevated values were found as well. In 24 (14%) of 169 non relapsed patients with prolonged follow-up (40 +/- 8 months; mean +/- s.d.) high serum CA15-3 values occurred. In 16 of these 24 patients, an isolated elevated value was found, while four (2.3%) or the eight remaining ones with constant elevation and/or progressive increase were falsely suspected of metastases. In this group of non relapsed patients, chronic liver failure, diabetes and/or hepatic steatosis were the reasons more commonly responsible for the CA15-3 increase. In metastatic patients, no organ-specificity was shown either by CA15-3 or by CEA and TPA. In these patients serum TPA values showed the highest sensitivity and paralleled clinical and/or instrumental signs better than the CA15-3 and even more than CEA values. These data indicate that in the post-operative follow-up of breast cancer patients, TPA is the most useful tumour marker and TPA-CA15-3 the most suitable association. Contemporaneous measurement of serum CEA levels only slightly increases sensitivity and positive predictive value of TPA-CA15-3 combination.
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PMID:Evaluation of serum CA15-3 determination with CEA and TPA in the post-operative follow-up of breast cancer patients. 185 15

A 36-year-old woman was treated with tamoxifen for lung metastasis of breast cancer and had marked hyperlipoproteinemia with giant fatty liver, high plasma triglyceride levels (3673 mg/dl), and increased levels of very low density lipoprotein (VLDL) and intermediate density lipoprotein (UDL). A low level of activity of both plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) was also noted. Our observations support the concept that, in some patients, the weak estrogen-like activity of tamoxifen is amplified and, in severe lipemia, reduction of the activities of LPL and HTGL might impede the conversion of VLDL to LDL, thus causing the amplification of the effect.
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PMID:[A case report of hyperlipemia with giant fatty liver during adjuvant endocrine therapy by tamoxifen]. 310 57

Hepatic steatosis is a frequent complication in nonobese patients with breast cancer treated with tamoxifen, a potent antagonist of estrogen. In addition, hepatic steatosis became evident spontaneously in the aromatase-deficient (ArKO) mouse, which lacks intrinsic estrogen production. These clinical and laboratory observations suggest that estrogen helps to maintain constitutive lipid metabolism. To clarify this hypothesis, we characterized the expression and activity in ArKO mouse liver of enzymes involved in peroxisomal and mitochondrial fatty acid beta-oxidation. Northern analysis showed reduced expression of mRNAs for very long fatty acyl-CoA synthetase, peroxisomal fatty acyl-CoA oxidase, and medium-chain acyl-CoA dehydrogenase, enzymes required in fatty acid beta-oxidation. In vitro assays of fatty acid beta-oxidation activity using very long (C24:0), long (C16:0), or medium (C12:0) chain fatty acids as the substrates confirmed that the corresponding activities are also diminished. Impaired gene expression and enzyme activities of fatty acid beta-oxidation were restored to the wild-type levels, and hepatic steatosis was substantially diminished in animals treated with 17beta-estradiol. Wild-type and ArKO mice showed no difference in the binding activities of the hepatic nuclear extracts to a peroxisome proliferator response element. These findings demonstrate the pivotal role of estrogen in supporting constitutive hepatic expression of genes involved in lipid beta-oxidation and in maintaining hepatic lipid homeostasis.
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PMID:Altered expression of fatty acid-metabolizing enzymes in aromatase-deficient mice. 1086 97

Adjuvant tamoxifen has become the treatment of choice against estrogen receptor-positive breast cancer. Adverse effects are rarely observed and since symptoms of hepatic steatosis, non-alcoholic steatohepatitis and cirrhosis are usually negligible, such effects are not well characterized despite large cohort studies of adjuvant tamoxifen. This issue remains to be systematically studied. The present study consisted of 136 breast cancer patients treated with or without tamoxifen. Patients had laboratory tests once each month and underwent abdominal computed tomography (CT) annually for 5 years. The extent of hepatic steatosis was assessed by CT as the liver/spleen ratio. While receiving adjuvant tamoxifen, 40 of 105 patients developed hepatic steatosis (liver/spleen ratio <0.9) without obvious changes in body mass index. Twenty-one had a liver spleen ratio of <0.5, whereas none of the 31 patients treated without tamoxifen had a ratio <0.9 or <0.5 (p<0.0001 and p<0.0001, respectively). Hepatic steatosis was recognized in 35 of the 40 patients within the first 2 years of receiving adjuvant tamoxifen and 21 of the 40 had increased transaminase levels. Liver biopsy revealed NASH in 6 of 7 patients among the 21 with a liver/spleen ratio of <0.5. A subset of individuals given adjuvant tamoxifen developed progressive hepatic steatosis without significant changes in the body mass index. We suggest a liver/spleen ratio of <0.5 as a criterion upon which liver biopsy should be recommended since NASH frequently occurred in such patients.
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PMID:Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients. 1103 33

We have described fatty liver, diagnosed by computed tomography scanning (CT) in more than 30% of patients with breast cancer who received tamoxifen. Therefore, it is urgent to elucidate the frequency and the degree of fatty liver induced by toremifene, an analogue of tamoxifen, which is also used in breast cancer. We enrolled 52 breast cancer patients who were treated with breast-conservation treatment and administered oral toremifene for 3-5 years as adjuvant endocrine therapy. We evaluated the degree of fatty liver by abdominal CT performed annually. CT demonstrated toremifene-induced fatty liver in four (7.7%) of 52 breast cancer patients. Toremifene-induced fatty liver did not correlate with abnormal levels of AST, ALT, GGT or total cholesterol. One patient who demonstrated moderate fatty liver by CT was histologically diagnosed as non-alcoholic steatohepatitis (NASH) by liver biopsy. The incidence of toremifene-induced fatty liver was significantly lower than that induced by tamoxifen. Accordingly, in terms of fatty liver and NASH, toremifene is considered to be more appropriate agent than tamoxifen. Though toremifene is less likely to induce fatty liver, the possibility remains that toremifene-induced steatohepatitis occurs. Because the diagnosis of fatty liver or NASH can be easily missed if only a blood test is performed, it is necessary to screen fatty liver by annual CT examination for patients who receive an antiestrogen agent.
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PMID:Toremifene-induced fatty liver and NASH in breast cancer patients with breast-conservation treatment. 1107 96

Tamoxifen is a nonsteroidal anti-estrogenic drug used for adjuvant treatment of breast cancer and recently as a chemopreventative agent for breast cancer and, on an investigational basis, for other cancers. To date there are case reports of hypertriglyceridemia and fatty liver disease in tamoxifen users. Fatty liver is associated with visceral obesity and other components of the metabolic syndrome. Here we evaluated steatosis and adipose tissue distribution by CT scan in a cross-sectional study of 32 women on tamoxifen and 39 control women. Tamoxifen users had more visceral adipose tissue (VAT) and more liver fat than controls. This is the first study to demonstrate that fatty liver and intra-abdominal fat accumulation are common in breast cancer patients receiving tamoxifen. Prospective studies of tamoxifen should monitor metabolic changes in obese women with or without breast cancer.
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PMID:Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer. 1141 Aug 35

In general, the selective estrogen receptor modulators (SERMs) currently indicated for the treatment and prevention of breast cancer, i.e. tamoxifen and toremifene, are fairly well tolerated. However, tamoxifen has been shown to induce hepatocellular carcinomas in rats, but not in humans, and can increase the risk of endometrial cancer in humans by two to three times. Other potentially serious adverse effects which have been associated with tamoxifen and toremifene therapy include vasomotor symptoms, an increased risk of venous thromboembolic events, and an increased incidence of cataracts and ocular toxicity, fatty liver, and nonmalignant hepatic and uterine changes. In addition, long term tamoxifen use almost always results in resistance to the drug and, indeed, has actually been shown to promote tumour proliferation in human breast cancer cells. Both tamoxifen and toremifene display drug interactions with a variety of drug classes. The adverse events associated with these compounds have raised significant concerns regarding their widespread use for the treatment and prevention of breast cancer. In addition, because of the weakness and scarcity of the data on toremifene, any conclusions about its tolerability remain tentative until outcomes of ongoing clinical trials in the adjuvant setting are known. A third SERM, raloxifene, is the focus of several large randomised trials examining its efficacy in the prevention of breast cancer. At present, each potential adverse event needs to be weighed against potential benefits in the decision to undergo SERM treatment. An array of therapies is currently available for patients with breast cancer and women at increased risk of disease; the risk-to-benefit ratio for each agent should be carefully examined in determining the most advantageous regimen.
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PMID:Comparative tolerability of first-generation selective estrogen receptor modulators in breast cancer treatment and prevention. 1173 60

Tamoxifen is a potent antagonist of estrogen, and hepatic steatosis is a frequent complication in adjuvant tamoxifen for breast cancer. Recently, aromatase-deficient (ArKO, Ar-/-) mice lacking intrinsic estrogen was developed and the molecular mechanism involved in progression of massive hepatic steatosis in estrogen-deficiency was elucidated; impairment in hepatic fatty acid beta-oxidation of peroxisomes, microsomes and mitochondria. This impairment is latent, but is potentially serious, because hepatic energy supply depends greatly on fatty acid beta-oxidation. Therefore in the present study, we tried to conquer impaired hepatic fatty acid beta-oxidation by administrating bezafibrate, a potent peroxisome proliferator, to Ar-/- mice through activating fatty acid beta-oxidation via the peroxisome proliferator activated receptor-alpha mediated signaling pathway. Northern blot analysis of Ar-/- mice liver revealed a significant restoration of mRNA expression of very long fatty acyl-CoA synthetase in peroxisome, peroxisomal fatty acyl-CoA oxidase, and medium-chain acyl-CoA dehydrogenase in mitochondria, essential enzymes in fatty acid beta-oxidation by administration of bezafibrate. Severe hepatic steatosis observed in Ar-/- mice regressed dramatically. Consistent findings were obtained in the in vitro assays of fatty acid beta-oxidation activity. These findings demonstrate that bezafibrate is capable of restoring impaired fatty acid beta-oxidation in vivo via the peroxisome proliferator-activated receptor-alpha mediated signaling pathway and is potent enough to regress severe hepatic steatosis in mice deficient in intrinsic estrogen.
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PMID:Aromatase-deficient (ArKO) mice are retrieved from severe hepatic steatosis by peroxisome proliferator administration. 1192 13

Tamoxifen has been used for a long time as a hormonal treatment in breast cancer. Recent studies in pre and postmenopausal women have shown that tamoxifen exhibits favorable effects on the lipid profile. In this study we investigated the effects of tamoxifen on lipid profile and hepatic steatosis. Fifty two (31 postmenopausal and 21 premenopausal) women with breast cancer treated with tamoxifen at a dose of 20 mg daily were included in the study. Serum lipid parameters (total cholesterol, high and low density lipoprotein cholesterol and triglyceride) were measured baseline and at the 6th month of tamoxifen treatment. Upper abdominal ultrasonography was performed before and at the 6th month of therapy for assessment of liver steatosis. We obtained decreased levels of serum total cholesterol after 6 months of tamoxifen treatment (p < 0.05). However, we did not detect any changes in triglyceride and high-density lipoprotein cholesterol levels (p > 0.05). Increased liver steatosis was observed in 22 patients (42.3%) after tamoxifen treatment. We could not detect increase in lipid levels in these patients. There was no significant difference between the lipid levels in the patients with increased liver steatosis and stable or no liver steatosis. Whether hepatic steatosis is dependent on lipid changes in tamoxifen use should be further investigated.
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PMID:Tamoxifen therapy and hepatic steatosis. 1204 63

C75, a known inhibitor of fatty acid synthase is postulated to cause significant weight loss through decreased hypothalamic neuropeptide Y (NPY) production. Peripherally, C75, an alpha-methylene-gamma-butyrolactone, reduces adipose tissue and fatty liver, despite high levels of malonyl-CoA. To investigate this paradox, we studied the effect of C75 on fatty acid oxidation and energy production in diet-induced obese (DIO) mice and cellular models. Whole-animal calorimetry showed that C75-treated DIO mice had a 50% greater weight loss, and a 32.9% increased production of energy because of fatty acid oxidation, compared with paired-fed controls. Etomoxir, an inhibitor of carnitine O-palmitoyltransferase-1 (CPT-1), reversed the increased energy expenditure in DIO mice by inhibiting fatty acid oxidation. C75 treatment of rodent adipocytes and hepatocytes and human breast cancer cells increased fatty acid oxidation and ATP levels by increasing CPT-1 activity, even in the presence of elevated concentrations of malonyl-CoA. Studies in human cancer cells showed that C75 competed with malonyl-CoA, as measured by CPT-1 activity assays. Thus, C75 acts both centrally to reduce food intake and peripherally to increase fatty acid oxidation, leading to rapid and profound weight loss, loss of adipose mass, and resolution of fatty liver. The pharmacological stimulation of CPT-1 activity is a novel finding. The dual action of the C75 class of compounds as fatty acid synthase inhibitors and CPT-1 agonists has therapeutic implications in the treatment of obesity and type II diabetes.
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PMID:C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. 1209 27


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