Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor uptake of 18F-fluorodeoxyglucose (FDG) was studied by dynamic positron emission tomography (PET) in 23 cases of hepatocellular carcinoma. The metabolic rate constants, K1 to K4, were generated by non-linear least square fitting method. We confirmed that K3 from the PET study significantly correlated with directly measured hexokinase activity of the cancer tissue. The region of HCC always had higher K3 values, which represents the hexokinase activity compared with the non-cancerous region. By FDG images, however, in 50% of cases the cancer region could not be clearly defined from the surrounding noncancerous hepatic tissue. These HCC cases without accumulation of FDG had a high ratio of K4/K3 (K4 represents glucose-6-phosphatase activity), which correlated well with the inverse ratio of FDG accumulating images on PET. According to the PET images which is represented by K4/K3 and the hexokinase activity which is represented by K3, we divided these 23 cases into three groups and retrospectively compared their survival rates. The groups with high K4/K3 (greater than or equal to 0.40) had longer survival than other groups. From the view point of glucose metabolism, the value of K4/K3 calculated from dynamic studies of FDG-PET may represent the functional differentiation of HCC.
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PMID:[Can fluorodeoxyglucose-positron emission tomography evaluate the functional differentiation of hepatocellular carcinoma]. 166 76

Paradoxical growth hormone (GH) responses in 50 g or 75 g oral glucose tolerance tests (OGTT) have been demonstrated in 24 patients with hepatocellular carcinoma, whereas no significant changes in serum GH levels after OGTT were shown in 10 normal controls, 6 patients with cirrhosis of liver, and with chronic active hepatitis. There were no significant difference in the GH responses in OGTT as well as in the incidence of paradoxical GH responses between diabetic and non-diabetic patients with HCC. Informatively, the basal somatomedin C level was very low in all cases examined.
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PMID:[Clinical studies on the relation of abnormal growth hormone secretions to hepatic diabetes mellitus in patients with hepatocellular carcinoma]. 254 47

To investigate the predictive value of oral glucose tolerance test (O-GTT) and insulin secretion test (IST) on the risk of hepatectomy in liver cancer patients, we through double-blind method, compared the results of these two tests, clinical course of the patients, and the pathological findings. It was found that: 1) The positive prediction value, negative prediction value, and accuracy of O-GTT were 79.2%, 94.4%, and 85.7%, the corresponding figures of IST were 55.6%, 100%, and 61.9%, respectively. 2) Pattern of the curve of O-GTT believed to depend on roughly normal hepatic energy metabolism and islet secretion capacity suggested better tolerance for hepatectomy. 3) A part of the patients with advanced HCC had a depressed islet secretion capacity. 4) The delta IST/delta O-GTT showed an accurate negative prediction for hepatectomy when the ratio was less than 50 x 10(-9). 5) Apart from O-GTT and delta IST/delta O-GTT, the severity of the hepatitis and cirrhosis should be taken into account in the decision of carrying out hepatectomy.
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PMID:[The glucose tolerance test and insulin secretion test as risk factors in liver cancer surgery]. 256 Oct 96

The value of the superparamagnetic contrast medium AMI-25 and its clinical acceptability was investigated in a phase-III-multicenter study. 18 patients with primary and secondary hepatic tumours were studied using T2- and T1-weighted spin-echo sequences, FATSAT sequences and FLASH-2-D-breathold sequences, both before and after intravenous application of AMI-25 (0.2 mmol GE/ml 15 mmol/kg KG in 100 ml 5% glucose infusion), using a 1.5 Tesla MRT (Magnetom 63 SP, Siemens). In 6 patients the MRT findings could be correlated with in vitro results within 30 minutes following surgical resection. In 8 patients a diagnosis of metastases was made. Amongst patients with primary liver tumours (FNH 6 cases, HCC 3 cases, adenomatosis 1 case) 3 of the 10 patients showed more lesions following the injection of contrast; similarly, in 4 patients of the 8 with secondary tumours contrast increased the number of visible lesions. The absence of contrast enhancement separated primary from secondary lesions. Amongst the patients with secondary liver tumours, in vitro correlation always showed more tumours than had been visualised whereas there was exact in vivo/in vitro correlation amongst patients with primary liver tumours.
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PMID:[The value of the liver-specific superparamagnetic contrast medium AMI-25 for the detection and differential diagnosis of primary liver tumors versus metastases]. 816 44

We studied a selective enhancement of the mitomycin C (MMC)-induced antitumor effect focusing on the intracellular metabolism by NAD(P)H:quinone oxidoreductase (DT-diaphorase, DTD). The level of cellular DTD activity related well to the degree of MMC-induced DNA total cross links and cell growth inhibition in human cancer cell lines, KB, PH101, SH101 and K562. A DTD inhibitor, dicoumarol (DIC) or flavin adenine dinucleotide (FAD), inhibited the MMC-induced DNA damage and cytotoxicity at a non-toxic concentration. The DTD-mediated MMC activation was pH-dependent, and highest at pH 6 and lowest at pH 8. Although an inverse relationship appeared to exist between DTD activity and MMC efficacy in human xenografts implanted into nude mice and 9 fresh human tumor specimens, the investigation in 3 culture cells, HEC-46, HCC-48 and HCC-50, established from those xenografts, showed that DTD activated MMC in a pH-dependent manner as well as the other cell lines. Significant tumor pH reduction from 7.1 to 6.7 by continuous glucose infusion also increased the MMC-induced tumor growth inhibition in the human tumor xenografts. Thus, we conclude that bioreductive activation by DTD in a pH-dependent manner may be of key importance in the MMC-induced antitumor effect and that an increased MMC efficacy at a reduced pH caused by hyperglycemia may be applied to clinical use as a new manipulation for a biochemical modulation of MMC.
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PMID:DT-diaphorase as a target enzyme for biochemical modulation of mitomycin C. 856 14

Twelve patients with liver neoplasms [10 HCC, 1 CCC, 1 multiple breast cancer metastases (BCM)] were treated by transarterial I-131-Lipiodol. Computed tomography (CT) and single photon emission CT (SPECT) showed pronounced I-131-Lipiodol accumulation in the tumor tissue in all cases. In three patients with HCC a reduction of tumor size was achieved after the first treatment. The remaining patients had big tumor masses; 5 of these (4 HCC, 1 CCC) had stable disease after the first treatment, and 2 HCC were progressive. One patient died immediately after therapy due to other reasons. The BCM proved significant reduction in number and size. Eighteen-FDG-PET (positron emission tomography with fluor-18-deoxy-glucose) and CT controls showed in part different results with pretherapeutic PET proving high interindividual variability in tumor activity. Side effects were tolerable. In summary, the therapy procedure with transarterial I-131-Lipiodol is safe and effective in tumors with moderate tumor mass.
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PMID:I-131-Lipiodol therapy in liver neoplasms. 1021 93

The quantities of energy reserves and their utilization were examined in adults of three strains of Tribolium castaneum (Herbst) before and during exposure to two modified atmospheres. It was shown that a strain selected for resistance to high carbon dioxide (CO(2)) content (HCC) contained significantly greater triacylglycerol (TG) reserves than a strain selected for resistance to low oxygen (O(2)) concentration (LOC) and an unselected strain. During exposure to HCC (65% CO(2), 20% O(2), balance nitrogen), the major energy sources were TGs, most of which were consumed during exposure; TG utilization by the unselected strain was more rapid than that by the HCC-selected strain. During exposure to LOC (0.5% O(2), 99.5% nitrogen), TGs were also utilized, but to a lesser extent, revealing an indication of more attenuated mobilization of energy reserves. Here, too, TG utilization by the unselected strain was more rapid than by the LOC-selected strain. The function of TGs in enabling the insects to maintain their water balance during exposure was considered.Concentrations of polysaccharides and glucose were low in all strains and although they decreased during exposure to MAs, their contribution to metabolic energy supply during exposure was small.
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PMID:Comparisons of energy reserves among strains of Tribolium castaneum selected for resistance to hypoxia and hypercarbia, and the unselected strain. 1075 61

The authors report a 36-year old man, who had hepatocellular carcinoma with lung metastasis and presented with coma from hypoglycemia. Serum insulin and c-peptide level were suppressed. Serum cortisol level was appropriately increased during the event. He needed glucose at least 3.65 mg/kg/min intravenously to maintain euglycemia. Cytoreduction of the tumor was not possible due to advanced stage disease. The patient had several episodes of morning hypoglycemia, despite having oral prednisolone 40 mg/day. However, glucose requirement was decreased after steroid usage. Normoglycemia was accomplished by adjunctive frequent high carbohydrate meal. Prednisolone was replaced to a lower dosage dexamethasone (2 mg/day). He did not have recurrent hypoglycemia as long as he had a midnight snack. Articles regarding hypoglycemia in HCC were extensively reviewed.
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PMID:Hepatocellular carcinoma with persistent hypoglycemia: successful treatment with corticosteroid and frequent high carbohydrate intake. 1651 97

Akt kinases 1, 2, and 3 are important regulators of cell survival and have been shown to be constitutively active in a variety of human tumors. GSK690693 is a novel ATP-competitive, low-nanomolar pan-Akt kinase inhibitor. It is selective for the Akt isoforms versus the majority of kinases in other families; however, it does inhibit additional members of the AGC kinase family. It causes dose-dependent reductions in the phosphorylation state of multiple proteins downstream of Akt, including GSK3 beta, PRAS40, and Forkhead. GSK690693 inhibited proliferation and induced apoptosis in a subset of tumor cells with potency consistent with intracellular inhibition of Akt kinase activity. In immune-compromised mice implanted with human BT474 breast carcinoma xenografts, a single i.p. administration of GSK690693 inhibited GSK3 beta phosphorylation in a dose- and time-dependent manner. After a single dose of GSK690693, >3 micromol/L drug concentration in BT474 tumor xenografts correlated with a sustained decrease in GSK3 beta phosphorylation. Consistent with the role of Akt in insulin signaling, treatment with GSK690693 resulted in acute and transient increases in blood glucose level. Daily administration of GSK690693 produced significant antitumor activity in mice bearing established human SKOV-3 ovarian, LNCaP prostate, and BT474 and HCC-1954 breast carcinoma xenografts. Immunohistochemical analysis of tumor xenografts after repeat dosing with GSK690693 showed reductions in phosphorylated Akt substrates in vivo. These results support further evaluation of GSK690693 as an anticancer agent.
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PMID:Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. 1838 44

The Wnt/beta-catenin signaling pathway has been increasingly implicated in liver development and physiology. Aberrant activation of this pathway is one of the major genetic events observed during the process of human HCC development. To gain insight into the mechanism underlying beta-catenin action in the liver, we conducted a quantitative differential proteomic analysis using 2-D DIGE combined with MS, in mice with liver-specific deletion of Apc resulting in acute activation of beta-catenin signaling (Apc(KOliv) mice). We identified 94 protein spots showing differential expression between mutant Apc(KOliv) and control mice, corresponding to 56 individual proteins. Most of the proteins identified were associated with metabolic pathways, such as ammonia and glucose metabolism. Our analysis showed an increase in lactate dehydrogenase activity together with a downregulation of two mitochondrial ATPase subunits (ATP5a1 and ATP5b). These observations indicate that beta-catenin signaling may induce a shift in the glucose metabolism from oxidative phosphorylation to glycolysis, known as the "Warburg effect". Imaging with (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography suggests that the specific metabolic reprogramming induced by beta-catenin in the liver does not imply the first step of glycolysis. This observation may explain why some HCCs are difficult to assess by fluoro-2-deoxy-D-glucose-positron emission tomography imaging.
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PMID:Proteomic analysis of beta-catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway. 1963 98


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