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)

Human neutrophil-mediated oxidative processes against a human hepatoma cell line, HCC-M, was visualized at the cellular level by using a silicon-intensified target camera and subsequently processing with a computer-assisted digital-imaging processor. Neutrophils were activated by a streptococcal preparation, OK-432. A hydroperoxide-sensitive tracer, dichlorofluorescein diacetate, was loaded in HCC-M and temporal and spatial changes of lipid peroxides in this cell after addition of stimulated neutrophils were analyzed. The luminol-dependent chemiluminescence activity of neutrophils was significantly enhanced and continued for at least 2 hr by stimulation with OK-432, and its activity was shown to be accumulated at the site where a neutrophil attached with HCC-M. The intensity of dichlorofluorescein fluorescence in HCC-M rapidly increased after adding stimulated neutrophils, and their reaction was significantly attenuated by superoxide dismutase. The number of non-viable cells was increased as the dichlorofluorescein fluorescence increase. It is suggested that oxidative stress may play an important role in neutrophil-mediated tumor-cell damage.
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PMID:Visualization of oxidative processes at the cellular level during neutrophil-mediated cytotoxicity against a human hepatoma cell line, HCC-M. 131 29

Various contrast agents are applied in both CT and MR imaging to improve the detection as well as the differentiation of focal liver lesions. In detecting hepatocellular carcinoma, the accuracy of Lipiodol-enhanced CT is comparable to that of CT during arterial portography. Tissue-specific contrast agents for the liver are superparamagnetic iron oxide particles, which are characterized by uptake in the reticuloendothelial system, and the paramagnetic hepatobiliary contrast agent manganese (II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate). Both substances have the potential for markedly improving the detection of malignant liver tumors. The already good differentiation of focal hepatic lesions on plain MR images can be further improved by dynamic gadolinium diethylenetriamine penta-acetic acid-enhanced MR imaging. In the diagnosis of bile duct disorders, contrast-enhanced CT continues to be the method of choice. Water applied as a gastrointestinal contrast agent improves the staging of rectal carcinoma by CT. The development of suitable orally applied gastrointestinal contrast agents has now also improved the differentiation of the intestine from other abdominal structures on MR images, and this will lead to a general improvement of abdominal MR imaging.
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PMID:Contrast material for computed tomography and magnetic resonance imaging of the gastrointestinal tract. 185 83

Changes in arterial and hepatic venous blood ketone bodies were investigated following transcatheter hepatic artery embolization (THAE) in patients with hepatocellular carcinoma. Acetoacetate/ beta-hydroxybutyrate ratio (ketone body ratio) in arterial blood was positively correlated with those of hepatic venous blood (r = 0.960, p less than 0.001), which reflects the mitochondrial redox potential in the embolized lobe. Nine cirrhotic patients were classified into three groups according to the changes in arterial blood ketone body ratio following THAE: Type A without decrease to below 0.7; Type B with a transient decrease to below 0.7, followed by its restoration within 5 hours; and Type C with decrease to below 0.7 without recovery within 5 hours. There were no serious complications in Type A and B patients. By contrast, severe sepsis and hepatic failure developed in Type C patients, possibly due to the extended embolization of both lobes. It is suggested that THAE can be successfully performed even in severely cirrhotic patients, as long as the embolized area is restricted to one lobe. In addition, changes in arterial blood ketone body ratios can give early information about the likely consequences of the THAE procedure just performed.
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PMID:Short-term changes in blood ketone body ratios in the phase immediately after hepatic artery embolization: their clinical significance. 300 12

FK973, a new, substituted dihydrobenzoxazine (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11- diazatetracyclo[7.4.1.0.0]tetra-deca-2,4,6-trien-6,9-diyl diacetate), was obtained by chemical modification of a novel antibiotic which was isolated from the fermentation products of Streptomyces sandaensis No. 6897. FK973 had cytotoxic effects against in vitro cultured human and murine tumor cells. FK973 in doses of 0.032-5.6 mg/kg (i.p.) had stronger antitumor activities and higher chemotherapeutic ratio than mitomycin C against such murine ascitic tumors as P388 and L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma of ovarian origin, Colon 26 carcinoma, Ehrlich carcinoma, and MH134 hepatoma. In tests against murine and human solid tumors implanted s.c. in normal mice and nude mice, respectively, FK973 (i.v.) inhibited growth of murine tumors (M5076 sarcoma, Colon 38 carcinoma, B16 melanoma, and Lewis lung carcinoma) by 66-100% and human tumors (LX-1 lung, MX-1 mammary, and SC-6 stomach carcinoma) by 84-99%. In studies with drug-resistant P388 leukemia, FK973 was also effective against vincristine-resistant P388, moderately effective against mitomycin C (MMC)- and adriamycin-resistant P388, and partially effective against cyclophosphamide-resistant P388 cells in mice. Leukopenic effects of FK973 and MMC in mice were comparable at doses which gave antitumor activity almost equally. FK973 had no effect on the numbers of platelets and red blood cells, whereas MMC markedly decreased both. FK973 decreased the numbers of colony forming units in spleen and in culture and the effect was less than that of MMC. Therefore, FK973 may give weaker myelosuppression than MMC. The results suggest that FK973 will be a beneficial drug for the treatment of cancer.
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PMID:Antitumor activity and hematotoxicity of a new, substituted dihydrobenzoxazine, FK973, in mice. 334 97

Metabolic characteristics of experimental hepatoma cells include elevated rates of glycolysis and lipid synthesis. However, pyruvate derived from glucose is not redily oxidized, and the source of acetyl CoA for lipid synthesis in As-39D cells has not been characterized. In this study ketone bodies were examined as a possible source of acetyl CoA in AS-30D hepatoma cells. The major findings were: 1. Acetoacetate was utilized by AS-30D cells, with 14C-lipid and 14CO2 as major products of [3-14C] acetoacetate. 2. Lipid synthesis from acetoacetate was dependent on the presence of glucose in the medium. 3. Acetoacetate supported rapid respiration by AS-30D mitochondria in the presence of 0.1 mM malate. 4. Succinyl CoA acetoacetyl CoA transferase activity in AS-30D mitochondria was approximately 40 fold greater than that found in rat liver mitochondria. 5. Addition of acetoacetate, but not beta-hydroxybutyrate decreased conversion of [1-14C] acetate to 14CO2, presumably by diluting the specific radioactivity of the acetyl CoA derived from the acetate tracer. 6. In the presence of glucose, approximately one fourth of acetoacetate utilized was converted to lipid. This result is consistent with elevated lipogenesis postulated by the truncated TCA cycle hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetoacetate metabolism in AS-30D hepatoma cells. 784 66

Photodynamic therapy has been applied quite extensively over the last few years, whereby the activation of photosensitizers by light causes the production of reactive oxygen species such as singlet oxygen, which is cytotoxic. The goal of this study was the enhancement of the photodynamic activity of photosensitizers through their delivery to specific, sensitive intracellular compartments of target cells. We synthesized a BSA-insulin-chlorin e6 conjugate that bound specifically to the insulin receptors (EC50, 1 nM) of the human hepatoma cell line PLC/PRF/5 and could be internalized by receptor-mediated endocytosis. Photodynamic activity, as assessed by various tests, indicated EC50s at about 100 times lower concentrations of conjugate compared to free chlorin e6 itself; and lower doses of irradiation were necessary to activate the conjugate compared to free chlorin e6. Inhibition of endocytosis of the conjugate abrogated the enhanced photodynamic activity of the conjugate above that of free chlorin e6. Endocytosis and subsequent localization around and in the cell nucleus of the BSA-insulin-chlorin e6 conjugate could be visualized using both FITC-labeled conjugate and 2',7'-dichlorofluorescin diacetate, a fluorescent indicator of the production of active oxygen species due to chlorin e6 activation. It was concluded that photodynamic activity of the conjugate is higher than that of free chlorin e6 through its receptor-mediated delivery into sensitive intracellular compartments.
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PMID:Insulin-mediated intracellular targeting enhances the photodynamic activity of chlorin e6. 786 84

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N' diacetate 5,5'-bis(phosphate) (MnDPDP) is a hepatobiliary agent that is incorporated into the hepatocyte. We retrospectively reviewed our experience with 39 focal liver lesions in 20 patients studies with MnDPDP-enhanced hepatic magnetic resonance (MR) imaging to determine whether hepatocellular carcinoma (HCC) could be differentiated from tumors of nonhepatocyte origin (metastases, cavernous hemangiomas, etc.) For all cases, liver parenchyma enhanced significantly following MnDPDP administration. All HCCs (6) showed significant tumor enhancement resulting in decreased tumor conspicuity compared to precontrast images [average 37% decrease in tumor-liver contrast to noise ratio (C/N)]. In contradistinction, other focal liver lesions showed little or no tumor enhancement resulting in increased lesion conspicuity (average 100% increase in tumor-liver C/N ratio). Our preliminary data suggest that MnDPDP-enhanced MR images may enable differentiation of HCC from other focal liver masses of nonhepatocyte origin.
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PMID:Differentiation of hepatomas from nonhepatomatous masses: use of MnDPDP-enhanced MR images. 829 10

During both animal and clinical studies with manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (DPDP), enhanced rims around liver tumors on magnetic resonance (MR) images have been observed. To elucidate the origins of these rims and to assess their potential value in the differential diagnosis of liver masses, the authors studied 15 rats with induced hepatocellular carcinoma (HCC), 10 rats with implanted Novikoff hepatomas, and 11 rabbits with implanted VX2 carcinomas. A total of 69 primary and secondary liver cancers from these three animal models were studied. Mn-DPDP- and gadolinium tetraazacyclododecantetra acetic acid (DOTA)-enhanced MR images were compared. On the Mn-DPDP-enhanced images, 34 peritumoral rims of various patterns were displayed, all of which were exclusively related to the presence of highly malignant primary and secondary liver tumors. Peritumoral zones of malignant infiltration, surrounding parenchymal compression, and bile duct proliferation were seen to be the origin of these rims after comparison of MR images with the corresponding microangiograms and histologic specimens.
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PMID:Experimental liver cancers: Mn-DPDP-enhanced rims in MR-microangiographic-histologic correlation study. 851

Chromium is an important industrial metal, an environmental pollutant, and a human carcinogen. To investigate the mechanisms of chromium-induced carcinogenesis, activation of mitogen-activated protein (MAP) kinases ERK1 and ERK2 was examined in rat hepatoma cells following exposure to hexavalent chromium (Cr(VI)). Cr(VI) was found to activate both forms of MAP kinase in a dose- and time-dependent manner. In contrast to the protein kinase C (PKC) agonist, phorbol 12-myristate 13-acetate, which induced a transient activation of MAP kinases, Cr(VI) caused persistent activation of these enzymes. Furthermore, unlike phorbol 12-myristate 13-acetate, the ability of chromium to activate MAP kinases was found to be independent of PKC since chromium-induced MAP kinase activation occurred in PKC-depleted cells. Stimulation of ERK1 and ERK2 was associated with the ability of Cr(VI) to increase cellular peroxide levels as determined using the H2O2-sensitive fluorescent probe 2',7'-dichlorofluorescein diacetate and flow cytometry. Furthermore, the activation of these kinases by chromium was enhanced in cells treated with the glutathione-depleting agent, L-buthionine-[S,R]-sulfoximine, and attenuated in cells pretreated with an agent that elevates cellular levels of glutathione (i.e., N-acetyl-L-cysteine). The ability of chromium to modulate MAP kinase activity in this manner suggests a mechanism of chromium-induced carcinogenesis that involves the persistent stimulation of cellular regulatory pathways.
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PMID:Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. 861 49

Fumonisin B1 is associated with various animal and human carcinomas and toxicoses, including leukoencephalomalacia, hepatocarcinoma, pulmonary edema and esophageal carcinoma. We have examined the cellular effects of fumonisin B1 in vitro using cellular model systems relevant to potential human target tissues. Although fumonisin B1 has been described as a mitogen in Swiss 3T3 cells based on stimulation of [3H]thymidine incorporation, in the current work it was found that fumonisin B1 inhibited incorporation of [3H]thymidine by cultured neonatal human keratinocytes and HepG2 human hepatocarcinoma cells at 10(-7) and 10(-4) M respectively. Fumonisin B1 also inhibited clonal expansion of normal human keratinocytes and HET-1A human esophageal epithelial cells at 10(-5) M and growth in mass culture of normal human fibroblasts at 10(-7) M. The clonogenicity of normal human keratinocytes decreased to 45.5% of controls after exposure to 10(-4) M fumonisin B1 for 2 days. However, no differences in the cell cycle distribution of cultured keratinocytes was noted after exposure to 10(-5) M fumonisin B1 for 40 h. The viability of normal human keratinocytes and HET-1A cells decreased as a result of fumonisin B1 treatment, as determined by a fluorescein diacetate/propidium iodide flow cytometric cell viability assay. Fumonisin B1-treated keratinocytes released nucleosomal DNA fragments into the medium 2-3 days after exposure to 10(-4) M fumonisin B1 and increased DNA strand breaks were detected in attached keratinocytes exposed to 0-10(-4) M fumonisin B1 using a terminal deoxynucleotidyl transferase-based immunochemical assay system. Furthermore, fumonisin B1-treated keratinocytes and HET-1A cells developed morphological features consistent with apoptosis, as determined by phase contrast microscopy, fluorescent microscopy of acridine orange stained cells and electron microscopy. These results are consistent with the occurrence of fumonisin B1-mediated apoptosis in vitro.
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PMID:Apoptotic and anti-proliferative effects of fumonisin B1 in human keratinocytes, fibroblasts, esophageal epithelial cells and hepatoma cells. 862 45


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