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

Progressive degrees of metabolic alterations are frequent in cirrhosis impairing peripheral tissue and body composition. Hepatocellular carcinoma worsens protein wasting and malnutrition. A normal energy production rate and an abnormal substrate oxidation rate are well-known findings in cirrhosis; however, no data are available on cirrhotic patients with hepatocellular carcinoma. The aim of this study was to measure oxidative metabolism in cirrhotic patients with and without hepatocellular carcinoma and to investigate the correlation between energy production rate, respiratory quotient and nutritional state. Thirteen male cirrhotic patients with hepatocellular carcinoma (8 well-nourished and 5 malnourished) were compared with 17 cirrhotic patients without hepatocellular carcinoma (11 well-nourished and 6 malnourished) and six controls who were age and sex matched. A diagnosis of malnutrition was made if the fat mass percentage was reduced to less than 20% of the patient's body weight. Indirect calorimetry was performed between 8 and 10 AM, after a 12-hr fast, for 30 min (with a 10-min steady-state period), and measured energy production rate was calculated according to Weir's formula. Body composition was assessed by means of the Durnin and Womersley formula. Anthropometry and bioelectric impedance analysis showed no variations in kilograms of fat-free mass in our malnourished patients. Our data show that, when the energy production rate is measured while the patient is at rest and corrected for fat-free mass, the energy requirements of cirrhotic patients and cirrhotic patients with hepatocellular carcinoma matched that of the controls, regardless of nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidative metabolism in cirrhotic patients with and without hepatocellular carcinoma: effects of malnutrition. 133 Aug 66

Severe cachexia of extremely rapid onset typifies the young Black African patient with hepatocellular carcinoma (HCC). In order to assess whether this is a consequence of tumor-associated increases in protein metabolism or simply due to inadequate dietary intake, the following study was undertaken. The technique of constant i.v. infusion of 14C-labeled leucine was used to measure whole body protein flux, breakdown, synthesis, and oxidation rates in 8 adults with HCC, 4 patients with massive hepatomegaly due to metastatic adenocarcinoma from bowel, 6 patients with chronic liver disease, and 10 controls. Endogenous protein breakdown and oxidation were similar between patients with chronic liver disease (breakdown, 4.4 +/- 1.2 g/kg/day; oxidation, 0.8 +/- 0.4 g/kg/day) and controls but were significantly (P less than 0.002) higher in patients with liver tumors, the highest rates being observed in those with HCC (breakdown, 8.5 +/- 4.3 g/kg/day; oxidation, 1.4 +/- 0.5 g/kg/day). Protein turnover was generally higher in the HCC group, with increased rates of reincorporation of amino acids into protein synthesis (P less than 0.05). In one HCC patient a synchronized diagnostic liver biopsy demonstrated high fractional synthesis of rates of HCC proteins of 86%/day. In addition, the incorporation rates of labeled amino acid into fibrinogen, immunoglobulin G, and transferrin were also highest (P less than 0.03) in HCC patients. In order to assess the relative importance of diet in weight loss, dietary intake levels were assessed from hospital records of HCC patients and by dietary recall during the week prior to study. Intakes ranged from 30 to 70% of calculated requirement levels. In conclusion, our results suggest that the rapid wasting seen in patients with HCC is due to an imbalance between the metabolic demands, which can be elevated in some patients, and inadequate dietary replenishment.
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PMID:Contribution of elevated protein turnover and anorexia to cachexia in patients with hepatocellular carcinoma. 215 53

Male and female rats were either trained to swim for a 6-week period or they remained sedentary. Rats were implanted with Morris hepatoma 7777 after 3 weeks of swimming and were sacrificed after a further 3 weeks. Exercised rats of both sexes showed a significant reduction in tumour weight at sacrifice, compared with sedentary controls (p less than 0.01). Similarly, when rats were first implanted with tumours and then placed on an exercise program of 3 weeks duration, tumour growth was also reduced (p less than 0.05). These results suggest that the tumour may be sensitive to exercise at more than one point in its development. Tumour growth was inhibited to a similar extent whether the total swimming time was 10, 20, or 30 h over the 3-week period. Although sedentary, tumour-bearing rats were anorexic; both male and female rats showed significant improvement of appetite during the period of tumour growth, in response to exercise. Tumour implantation was associated with significant losses of whole body and muscle protein. The progression of this wasting was not significantly altered by exercise.
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PMID:Exercise inhibits progressive growth of the Morris hepatoma 7777 in male and female rats. 259 21

Two rat tumors, Morris hepatoma 7777 (MH) and Yoshida ascites hepatoma AH130 (YAH) were compared, and the influence of systemic inhibition of prostaglandin (PG) synthesis on muscle protein metabolism was evaluated. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats were also treated with naproxen, an inhibitor of PG synthesis. Tumors caused progressive anorexia and weight loss and resulted in decreased weight and/or protein content of the soleus, extensor digitorum longus, and epitrochlearis muscles. The extent of this wasting varied with muscle and tumor type. Muscle wasting induced by the tumors appeared to result from increased protein degradation and/or decreased protein synthesis, as determined in isolated epitrochlearis muscle. In YAH, reduced feed intake did not appear to be responsible for muscle wasting; however, in MH, it accounted for a significant proportion of the muscle loss. YAH produced large amounts of PGE2. Treatment of rats with naproxen inhibited tumor PGE2 production and muscle protein loss in rats bearing YAH. Naproxen had no effect on muscle weight or protein degradation in rats bearing MH. These results would appear to implicate PGE2 in the development of cachexia in the laboratory rat.
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PMID:Effects of systemic inhibition of prostaglandin production on protein metabolism in tumor-bearing rats. 239 72

Total parenteral nutrition (TPN) is a clinical adjunct to cancer therapy. But it is difficult to do controlled clinical studies on cancer patients undergoing TPN. We therefore turned to a study of TPN on Buffalo strain rats with and without a Morris 7777 transplantable hepatoma. Our results showed that TPN at higher than normal levels (total parenteral hyperalimentation, abbreviated TPH) supported a gain in body weight of nontumorous rats. In tumorous rats, TPH supported body weight gain and stimulated tumor growth. Detailed analysis showed the TPH of the rats with a large rapidly growing hepatoma did gain body weight associated with fluid retention while the carcass weight decreased. Nor did TPH of tumorous rats significantly reverse the low cell proliferative activity to ear epidermis attributed to the tumor though it did stimulate tumor cell proliferation. Thus TPH by itself did not overcome wasting due to presence of the tumor. Using the hypothesis that uncontrolled gluconeogenesis is linked to cancer cachexia, we combined TPH with inhibition of gluconeogenesis (using hydrazine sulfate) and prevented the carcass weight loss (cachexia) in the tumorous rats. Tumor growth was stimulated by this treatment. Stimulation of cell proliferation in the tumor can, however, benefit chemotherapy using an S phase or cell cycle-specific cytotoxic drug.
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PMID:Effect of total parenteral nutrition on tumor-host responses in rats. 680 28

We investigated the use of ornithine alpha-ketoglutarate in treatment of rats bearing Morris hepatoma 7777. Rats received diets containing either ornithine alpha-ketoglutarate, which has been used in other catabolic states (i.e. injury, sepsis), or an isonitrogenous, isocaloric diet containing glycine. Untreated tumors grew to a mass of 11 g/100 g body weight over the 3-wk period after implantation and induced progressive anorexia, negative nitrogen balance, and body and tissue wasting. Compared with glycine, ornithine alpha-ketoglutarate had no effect on tumor growth, but also did not alter the catabolic effects of the tumor on its host. We hypothesized that capture of amino acids by the tumor limited the efficacy of supplemental nutrition here and in published reports in which tumor burden comprised 4-30% of body weight. This is supported by our observation that a 3-wk of implantation the rate of protein deposition plus amino acid oxidation by the tumor was equivalent to approximately 70% of the host's daily protein intake. To parallel the clinical situation in which tumor burden is small at diagnosis and initiation of treatment, the same diets were tested in rats treated by excision of the tumor at a limited stage of the disease. Rats received 3 d preoperative nutrition with ornithine alpha-ketoglutarate or glycine, and continued on the same diets for 3 or 6 d postoperatively. Compared with glycine-fed rats, ornithine alpha-ketoglutarate-fed rats showed a more positive nitrogen balance, higher concentrations of glutamine and branched-chain amino acids in muscle, and accelerated protein deposition in small intestine (P < 0.05). Our results explain the lack of success of nutritional support in untreated cancer and underline the need for clinically relevant animal models for further studies.
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PMID:Supplemental nutrition with ornithine alpha-ketoglutarate in rats with cancer-associated cachexia: surgical treatment of the tumor improves efficacy of nutritional support. 750 Jan 78

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-alpha) are early perturbed after tumor transplantation (Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16-23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH0130 hepatoma probably account for this lack of effect.
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PMID:Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth. 758 74

The mechanisms leading to the development of cancer cachexia are still poorly understood. Recently, cytokines such as interleukin 1 and tumour necrosis factor-alpha have been involved as mediators of the tissue wasting consequent to tumour growth. The rat ascites hepatoma Yoshida AH-130 is a highly anaplastic tumour that causes in the host an early and marked depletion of both the skeletal muscle and the adipose tissue, mainly accounted for by a hypercatabolic state. Profound hormonal alterations and the release of tumour necrosis factor-alpha and interleukin 1 by the tumour cells likely concur in forcing the metabolic balance towards the catabolic side [1]. In order to possibly achieve the correction of this wasting condition, the AH-130 bearing rats were administered a daily s.c. dose of interleukin 1 receptor antagonist (IL-1ra; 2 mg/kg). This factor, however, was completely ineffective in either inhibiting tumour proliferation or in preventing the consequent tissue depletion and protein hypercatabolism. These observations suggest that interleukin 1 is not important, at least in this model system, for either the development of cachexia or tumour growth.
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PMID:Interleukin-1 receptor antagonist (IL-1ra) is unable to reverse cachexia in rats bearing an ascites hepatoma (Yoshida AH-130). 765 41

Rats bearing the Yoshida AH-130 ascites hepatoma, a cachectic rat tumour, showed signs of important muscle wasting with reduced muscle weights. This phenomenon was associated with a decreased rate of in vivo alanine oxidation as measured by the production of 14CO2 from [U-14C]alanine intragastrically administered. It was later found that the decreased amino acid oxidation was associated with a reduced uptake in skeletal muscle as measured in incubated soleus muscles, thus suggesting that the decreased in vivo oxidation is basically due to a reduced oxidation of the amino acid in skeletal muscle. The decrease in alanine oxidation in the tumour-bearing animals was also associated with higher circulating alanine concentrations in their blood. In addition, tumour-bearing rats presented a lower (26%) protein synthetic rate in skeletal muscle, as measured by the incorporation of [14C]phenylalanine into muscle protein. The addition of insulin to the incubation medium abolished the lower rate of protein synthesis, thus suggesting a greater response to this hormone by the muscle of tumour-bearing rats. In conjunction with a reduced protein synthesis, tumour-bearing rats showed a clearly enhanced rate of protein degradation in isolated skeletal muscles. The results presented confirm previous observations suggesting that the skeletal muscle of tumour bearing animals is in a profound negative nitrogen balance which partially accounts for the wasting observed in the tissue. In addition, the present study allows us to conclude that, in spite of the increased alanine utilization for both gluconeogenesis and tumour growth, the oxidation of alanine by the whole animal is decreased in the tumour-bearing rats. This seems to be associated with a decreased ability of skeletal muscle to handle this amino acid.
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PMID:Alanine metabolism in rats bearing the Yoshida AH-130 ascites hepatoma. 781 30

The growth of the Yoshida ascites hepatoma AH130 (YAH) is associated with early wasting, depletion of intracellular amino acid pools, and a pronounced activation of protein degradation in skeletal muscle of the host animal. Ornithine alpha-ketoglutarate (OKG) is used in the treatment of hypercatabolic states, and it has been suggested that it may improve nitrogen balance through repletion of free amino acid pools and suppression of protein catabolism. In cancer, OKG might similarly improve host nutritional status or stimulate tumor growth if its metabolites are limiting for tumor growth. Enteral supplementation with OKG was investigated in Sprague-Dawley rats bearing YAH. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats received OKG (3.4 to 4.0 g/kg body weight/d) or an equal amount of nitrogen as glycine (n = 8 in each group) for 5 days. Tumor implantation decreased cumulative food intake (-40%), host weight (-6%), skeletal muscle weight, and free amino acid levels in muscle and plasma. Muscle protein balance was estimated in vitro; decreased protein synthesis (-30%) and increased proteolysis (+113%) were observed in epitrochlearis muscles (EPI) of YAH-bearing rats compared with control groups. OKG had no effect on the wet weight (10 +/- 1 g) and nitrogen content of the tumor, or on free amino acid levels in the tumor. In tumor-bearing rats, OKG improved muscle protein balance by reducing breakdown by 33% and overall amino acid release of incubated EPI by 46%.
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PMID:Ornithine alpha-ketoglutarate limits muscle protein breakdown without stimulating tumor growth in rats bearing Yoshida ascites hepatoma. 802 16


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