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)

While magnetic resonance imaging (MRI) is not a screening examination in the search for metastatic disease, it has already demonstrated its value when performed as a carefully directed study to detect focal hepatic lesions. In the past 18 months we have encountered nine patients (six men, three women--ages 14-66) with a variety of primary tumors (renal cell carcinoma, two; colon carcinoma, two; hepatocellular carcinoma, two; pancreatic carcinoma, one; pheochromocytoma, one; rhabdomyosarcoma, one) whose MR scans revealed hepatic metastases after normal or nondiagnostic computed tomographic (CT) scans. The lesions were most clearly demonstrated using spin echo (SE) technique with recovery times (TR) of 2.0 seconds and delay times (TE) of 56 msec; metastases usually imaged with greater signal intensity than surrounding liver parenchyma. Lesions were solitary in three patients, multiple in six, and were found in all hepatic lobes without any specific location predominating. Pathologic confirmations of MR diagnoses were available in six of nine patients. In two patients, CT scans were of poor technical quality because streak artifacts from surgical clips obscured portions of the liver. In one patient iodinated contrast medium could not be given. In the remaining six patients CT scan quality was acceptable. This report is not a comparison study of the two modalities. We simply present nine patients in whom metastases were not detected by CT for various reasons but were found by MRI using SE technique.
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PMID:Magnetic resonance imaging diagnosis of hepatic metastases in the presence of negative CT studies. 408 52

A proliferating cell nuclear antigen (PCNA) was identified with autoantibodies from a patient with systemic lupus erythematosus. Specific antibodies were purified by affinity chromatography in which Novikoff hepatoma nucleolar proteins were conjugated to Sepharose-4B. The purified anti-PCNA antibodies produced bright nucleolar fluorescence in tumor cells as shown by indirect immunofluorescence. PCNA was found in nucleoli of human cell lines, HeLa, Hep-2, and Namalwa, and a solid human renal and a prostate carcinoma. Both strong and weak nucleolar fluorescence areas were found in the renal and prostate carcinoma indicating that there are varying degrees of proliferation among tumor cells. Two human colon carcinoma cell lines, omega (an aggressive, fast-growing clone of human colon carcinoma cell line HCT 116) and CBS [a slow-growing human colon carcinoma cell line (group 3)], with different growth rates were compared. The fast-growing colon carcinoma cells, omega, exhibited a higher percentage of nucleolar fluorescence (28.5%) than that of the slow growing colon cells (13.6%). By enzyme-linked immunosorbent assays, the omega cell extract had a higher PCNA antigen content (2.8-fold) than that of the CBS cell extract which, in turn, was higher than that of human liver extract. PCNA was also found in a human fetal lung fibroblast cell line (IMR-90). Very weak or negative nucleolar fluorescence was observed in several normal human tissues including liver, kidney, prostate, and cheek cells. Nucleolar fluorescence was also observed in rat Novikoff hepatoma cells. Although normal rat livers do not have PCNA nucleolar fluorescence, nuclear and nucleolar fluorescence were observed at 18 hr after partial hepatectomy.
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PMID:Indirect immunofluorescence studies of proliferating cell nuclear antigen in nucleoli of human tumor and normal tissues. 613 81

In vitro and in vivo animal studies and some clinical trials have shown apparent benefit from thermochemotherapy; however, this treatment modality has not been adequately tested in humans. This investigation evaluated response to and toxicity of secondary thermochemotherapy, using each patient as his own control. Patients with advanced cancer who had documented disease progression while receiving chemotherapy alone were subsequently treated with the same drug, by the same dose and route, combined with localized hyperthermia. Thirty-four patients whose diseases included metastatic colon carcinoma, melanoma, sarcoma and hepatoma in viscera (29) or surface tissues (5) were treated with combination thermochemotherapy for 1 hour daily for 5 days/month. Effective heating from 41 to 45 degrees C minimum tumor temperature was possible in 17/19 (89%) tumors in which temperatures could be measured safely. The authors observed 5 (15%) tumor regressions for 1 to 5 months (median, 2 months), and 19 (56%) tumor stabilizations (growth arrest of previously progressive disease) for 1 to 9 months (median, 4 months). Subjective improvement in activity and/or pain control occurred in 6 (18%) patients and 20 (59%) had no progression of symptoms during treatment. Moreover, there was no detectable morbidity from localized hyperthermia, and no evidence of increased chemotherapy toxicity. While the mechanism(s) of response is poorly understood, the documented disease regressions and stabilizations of previously progressive disease in 24 (71%) patients during secondary combination thermochemotherapy indicates that the addition of hyperthermia may have useful anticancer activity. Expanded trials are warranted.
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PMID:Clinical thermochemotherapy. A controlled trial in advanced cancer patients. 636 31

Iosulamide, an experimental cholangiographic agent recently being evaluated for hepatic contrast enhancement in computed tomography, has been investigated in the rat for the differential enhancement between the liver and three histologically different experimental tumors (a well differentiated mammary adenocarcinoma, a poorly differentiated colon carcinoma, and a hepatoma). After intravenous injection of iosulamide in dosages of 140 and 280 mg iodine per kg, iodine concentrations were determined in blood, liver and tumors at 1, 5, 10, and 30 minutes, using x-ray energy spectrometry. Compared with the surrounding liver parenchyma, the iodine concentrations were generally higher in the breast carcinoma. With respect to the liver, iodine concentrations varied greatly in the colon carcinoma and hepatoma. The iodine washout from all three tumors was relatively slow. Since the distribution volume of cholangiographic contrast agents includes both vascular and interstitial space, the relatively high and prolonged iosulamide accumulation in tumors can be explained by a relatively large interstitial compartment, which is apparently characteristic of neoplastic lesions. This, together with the modest iodine concentrations found in the liver, suggests that iosulamide is of little use in computed tomography for the differential enhancement of liver and hepatic tumors.
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PMID:Failure of iosulamide to enhance hepatic tumors in rats. 707 33

In order to evaluate a monoclonal antibody KM01 which was developed in mice immunized against a human colon carcinoma cell line, serum levels of KM01 and other tumor markers were studied in patients with both hepatocellular carcinoma and liver cirrhosis and in patients with liver cirrhosis alone. The KM01 levels in the sera of 50 patients with hepatocellular carcinoma plus liver cirrhosis and 50 patients with liver cirrhosis were measured using an enzyme immunoassay method and compared with various tumor markers including alpha-fetoprotein (AFP), DUPAN-2, and protein induced vitamin K absence or antagonist-II (PIVKA-II). The mean serum level (+/- S.D.) and sensitivity of KM01 in patients with hepatocellular carcinoma plus liver cirrhosis were 734 (+/- 716) units/ml and 64%, respectively, and they were significantly higher than those of liver cirrhosis patients (P < 0.001). Three out of 9 cases showing negative serum AFP levels had positive serum KM01 levels. Although the sensitivity of serum KM01 level for hepatocellular carcinoma was inferior to serum AFP and plasma PIVKA-II values, the sensitivity of a combination assay of serum KM01 or AFP was increased to 88%. Clinical data of the patients with markedly elevated serum KM01 levels (more than 1000 units/ml) were compared with patients with moderately elevated levels (530-1000 units/ml); serum bilirubin and alkaline-phosphatase were statistically higher in the former group (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical evaluation of a monoclonal antibody to serum KM01 for the diagnosis of hepatocellular carcinoma. 754 92

Our in vivo studies in mice have shown that LDL-receptor gene expression is regulated differently in both liver and intestine by dietary cholesterol and dietary saturated fat. While dietary cholesterol serves to regulate at transcriptional levels, dietary fatty acids do not. To study the mechanism of regulation of LDL-receptor by saturated fat and cholesterol at the cellular level, where any secondary effects of long-term feeding in vivo are minimized we used the cultured hepatoma and colon carcinoma cells, HepG2 and Caco2. LDL-receptor activity was determined by 125I-labeled LDL binding and uptake, LDL-receptor protein by Western blotting, LDL-receptor mRNA by RNase protection assay, and relative rates of LDL-receptor mRNA transcription by nuclear 'run-off' assay. Incubation of cells in lipoprotein-deficient serum (LPDS) for 48 h progressively induced LDL-receptor activity and LDL-receptor protein by 5- to 6-fold in HepG2 cells and 2- to 3-fold in Caco2 cells. Absolute levels of LDL-receptor mRNA and relative rates of LDL-receptor mRNA transcription also increased in parallel to the LDL-receptor activity and protein levels in both cell lines. These data suggest that LPDS induced the LDL-receptor gene by transcriptional mechanism. The suppressive effect of 25-hydroxycholesterol on LDL-receptor regulation was studied by incubating HepG2 and Caco2 cells grown either in 10% FCS or 10% LPDS for 24 h and then for 0-24 h with various doses of 25-hydroxycholesterol. In HepG2 cells, LDL-receptor activity and protein mass progressively decreased to 50% of zero time controls over 24 h. LDL-receptor mRNA levels and relative rates of transcription decreased in parallel. In Caco2 cells, 25-hydrocholesterol lowered LDL-receptor activity, mRNA, and transcription by approximately 35%. To examine the effects of palmitate on LDL-receptor regulation, palmitate was complexed with albumin. Palmitate decreased LDL-receptor activity by 25% in HepG2 cells without altering LDL-receptor mass, mRNA levels, or rates of mRNA transcription. Similarly, in Caco2 cells, palmitate decreased LDL-receptor activity and protein mass 30% of controls, but did not change LDL-receptor mRNA levels and/or rates of transcription. The combination of palmitate (0.8 mM) and 25-hydroxycholesterol (2.5-5 micrograms/ml) suppressed LDL-receptor activity by 65% in HepG2 cells and by 52% in Caco2 cells. However, LDL-receptor mRNA decreased by approximately 50% in HepG2 cells and 30-40% in Caco2 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of low density lipoprotein receptor gene expression in HepG2 and Caco2 cells by palmitate, oleate, and 25-hydroxycholesterol. 759 67

We have used apolipoprotein genes to investigate the signal transduction mechanisms involved in the control of intestinal specific gene expression. The human apoAI, apoCIII, and apoAIV genes are tandemly organized within a 15-kb DNA segment and are expressed predominantly in the liver and intestine. Transient transfection of various human apoAI gene plasmid constructs into human hepatoma (HepG2) and colon carcinoma (Caco-2) cells showed that apoAI gene transcription is under the control of two separate and distinct cell-specific promoters. The region between nucleotides -192 and -41 is essential for expression in HepG2 cells, whereas the region from -595 to -192 is essential for expression in Caco-2 cells. A third 0.6 kb DNA fragment in the apoCIII gene promoter region, approximately 5 kb down-stream from the human apoAI gene, enhances transcription mediated by either of these two tissue-specific apoAI promoters. In Caco-2 cells, expression of the apoAI gene and activation by the distal enhancer required the presence of a nuclear hormone receptor response element (NHRRE) located in the -214 to -192 apoAI promoter region. Overexpression of the orphan receptor hepatocyte nuclear factor 4 (HNF-4), which binds to the NHRRE, dramatically stimulates apoAI gene expression in Caco-2 cells but not in HepG2 cells. Maximal stimulation of transcription by HNF-4 in Caco-2 cells required the presence of both the intestinal specific promoter, the NHRRE, and distal enhancer elements. Transactivation by HNF-4 thus appears to result from functional synergy between the NHRRE binding HNF-4 and distal DNA elements containing intestinal-specific DNA binding activities. The apoAI gene provides a model system to define the mechanism(s) governing intestinal cell specific gene regulation and the role of nuclear hormone receptors in the establishment and regulation of enterocytic gene transcription.
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PMID:Intestinal apolipoprotein AI gene transcription is regulated by multiple distinct DNA elements and is synergistically activated by the orphan nuclear receptor, hepatocyte nuclear factor 4. 761 25

We compared the influence of exogenous N-ras oncogene and treatment with PKC agonist 12-O-tetradecanoylphorbol-13-acetate (TPA) on P-glycoprotein (Pgp) function in various human, rat and dog cell lines. Two approaches were used: (a) flow cytometry analysis of Rhodamine 123 (Rh123) exclusion; and (b) sensitivity to cytotoxic action of colchicine. We have found that in Rat1 fibroblasts, rat IAR2 epithelial cells and rat McA RH 7777 (hepatoma), ras activates Pgp function, while in MDCK (dog kidney), K562 (human chronic myelogenous leukaemia) and LIM1215 (human colon carcinoma) cells it either has no effect or even acts in opposite direction. TPA-induced Pgp function shows dissimilar pattern of cell specificity. It is assumed that PKC and ras oncogene regulate mdr1 gene expression through at least partially distinct signalling pathways.
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PMID:Cell-specific effects of RAS oncogene and protein kinase C agonist TPA on P-glycoprotein function. 762 41

To determine whether c-kit and kit ligand (KL) mRNAs could be expressed in human epithelial tumors, reverse transcriptase-polymerase chain reaction and Northern blot analysis were performed. KL mRNA was shown to be expressed in a variety of epithelial tissues and cell lines. The expression of c-kit mRNA was then examined in hepatocellular and colon carcinoma cell lines. While hepatocellular carcinoma cell lines did not express c-kit mRNA as far as we could ascertain, 2 of 5 colon carcinoma cell lines showed the expression of both c-kit and KL mRNAs. Furthermore, the expression of c-kit in these cells was demonstrated at the protein level by flow cytometry. These data suggest that c-kit and KL may play an important role as an autocrine loop in the proliferation of some colon carcinoma cells.
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PMID:Expression of c-kit and kit ligand in human colon carcinoma cells. 769 50

The phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), known to induce murine glutathione S-transferase (GST) Ya, was examined for its effect on the expression of human GST alpha. Unexpectedly, 24-h treatment of the human hepatoma cell line HepG2 with 100 nmol/l TPA caused a decrease of the GST alpha mRNA level to below 5% of controls, i.e. opposite to the known response in the mouse. The level of mRNA for GST Mu was also decreased, but the mRNAs of c-jun and jun-B were elevated after 2 h. The decrease of GST alpha mRNAs was inhibited by staurosporine, suggesting an involvement of protein kinase C. Inhibition of transcription and translation by actinomycin D and cycloheximide also partially inhibited the effect of TPA on the expression of GST alpha. In the presence of actinomycin D, GST alpha mRNA halflife was 14.5 h, compared to 3.5 h in the presence of TPA. The calcium ionophore A23187 caused a loss of GST alpha mRNAs to levels almost as low as those obtained with TPA. The effects of TPA and the calcium ionophore were also observed in CaCo2 colon carcinoma cells. As a consequence of the decrease of mRNA levels, GST alpha protein levels and total GST enzyme activity were also diminished. Also, the morphology of the cells was changed after 3 h exposure to TPA. These data suggest that human GST alpha expression can be regulated at the level of mRNA stability by a pathway involving protein kinase C.
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PMID:Turnover of glutathione S-transferase alpha mRNAs is accelerated by 12-O-tetradecanoyl phorbol-13-acetate in human hepatoma and colon carcinoma cell lines. 774 32


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