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)

Hepatocellular carcinoma (HCC) may uncommonly present with distant metastasis in the absence of a documented neoplasm in the liver. The authors herein describe the case of a 60-year-old man with cirrhosis who developed unilateral enlargement of the breast and a subareolar mass. This problem was clinically thought to represent gynecomastia, but a mammary fine-needle aspiration biopsy demonstrated a malignant epithelial neoplasm composed of large granular amphophilic cells. Bile pigment was visualized in the tumor on aspirate smears and cell block preparations; immunostains showed reactivity for cytokeratin and alpha-fetoprotein, but there was no positivity for epithelial membrane antigen, gross cystic disease fluid protein-15, vimentin, estrogen receptors, progesterone receptors, or S100 protein. These results indicated a diagnosis of metastatic HCC, which was subsequently confirmed by computed tomography of the abdomen.
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PMID:Metastatic hepatocellular carcinoma of the breast, simulating gynecomastia: diagnosis by fine-needle aspiration biopsy. 133 27

alpha 1-Antitrypsin (alpha 1-AT) is considered a typical plasma protein and a prototype of the serine proteinase inhibitor (serpin) family. It is synthesized in hepatocytes and, to a lesser extent, in macrophages. In this study we show that the alpha 1-AT gene is also expressed in human intestine and in a human colonic epithelial tumor cell line, Caco2. A single 1.6-kilobase alpha 1-AT-specific mRNA is present in jejunum and in Caco2 cells. It is identical in apparent size to that present in human hepatoma HepG2 cells but slightly smaller than that present in human macrophages, cells in which an alternative upstream transcriptional start site is used. Synthesis and secretion of alpha 1-AT in Caco2 cells is similar to that in HepG2 cells. It is synthesized as an approximately 52-kDa precursor polypeptide, converted to its mature, fully glycosylated 55-kDa form intracellularly, and the native protein is secreted with a half-time of 37 min. Functionally active alpha 1-AT is secreted into the basolateral and apical (luminal) fluid in pulse-chase labeling experiments of Caco2 cells cultured in polarized orientation on collagen-coated nitrocellulose membranes. Expression of alpha 1-AT in Caco2 enterocytes is not affected by soluble factors that regulate expression of alpha 1-AT in macrophages and hepatocytes. However, expression of alpha 1-AT increases markedly in Caco2 cells as they differentiate into enteric villous-type cells.
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PMID:The alpha 1-antitrypsin gene is expressed in a human intestinal epithelial cell line. 278 94

Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI-3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI-3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK-HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.
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PMID:Constitutive production of leukemia differentiation, colony-stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor. 299 Jun 10

Glucocorticoid hormones induced a stringent dependence on serum for the in vitro proliferation of Fu5 rat hepatoma cells by suppressing the growth rate and final quiescent cell density. Treatment of dexamethasone-suppressed quiescent Fu5 with serum plus insulin caused a rapid reinitiation of cellular proliferation and DNA synthesis that peaked at 16 h. RNA dot blot analysis of this time course showed that the transcript levels for the proto-oncogenes c-fos, c-myc, and c-rasKi peaked at 0.5, 2, and 4 h, respectively, while expression of c-rasHa and ornithine decarboxylase transcripts rose steadily during 16 h. Microspectrofluorimetric measurements of cytosolic calcium (Ca2+i) with fura-2 showed that insulin and serum, alone or in combination, elicited no changes in Ca2+i over a 50-min time course, although ATP, which is not a mitogen, induced large increases in Ca2+i. Cytosolic pH, pHi, was also measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Insulin and serum, alone or in combination, did not cause pHi to increase in either 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (pHi 7.17)- or HCO3/CO2 (pHi 7.19)- buffered media. Acid-loading of cells with NH4Cl indicated that both quiescent and proliferating Fu5 cells have equally active, amiloride-sensitive Na/H exchangers. Therefore, induction of DNA synthesis and proto-oncogene expression occurs in Fu5 epithelial tumor cells in the absence of any short term increases of pHi or Ca2+i.
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PMID:Glucocorticoids confer normal serum/growth factor-dependent growth regulation to Fu5 rat hepatoma cells in vitro. Sequential expression of cell cycle-regulated genes without changes in intracellular calcium or pH. 305 98

We have previously documented that glucocorticoids suppress the proliferation of BDS1 hepatoma cells, a rat epithelial tumor cell line derived from minimal deviation Reuber H35 hepatoma cells. Flow cytometry demonstrated that, after treatment with the synthetic glucocorticoid dexamethasone, the growth of an asynchronous population of BDS1 cells was arrested within one cell cycle which resulted in an accumulation of cells with a G1-G0-like DNA content. Consistent with a glucocorticoid-induced block early in the G1 phase of the cell cycle, propidium iodide flow cytometry revealed that addition of dexamethasone up to 2 h after release from contact inhibition prevented BDS1 hepatoma cells from entering S phase, whereas dexamethasone treatment after 2 h had no effect on the entry of cells into S phase. Moreover, dexamethasone treatment did not prevent BDS1 cells from entering S phase after release from synchronization at the G1-S boundary by a double thymidine block. Analysis of DNA content, [3H]-thymidine incorporation, and autoradiography of [3H]-thymidine-labeled nuclei revealed that, after release from dexamethasone, BDS1 cells synchronously reinitiated cell cycle progression and entered S phase 8 h after hormone withdrawal. Northern blot analysis demonstrated that the level of transcripts encoding the G1 marker genes CYL-1 and CYL-2 G1 cyclins peaked 4 h after dexamethasone withdrawal. Dexamethasone induced a 20-fold increase in the level of c-jun mRNA which was reversed after hormone withdrawal, whereas expression of c-fos transcripts remained at a low level during the time course of hormone treatment and withdrawal. Transient transfections with a collagenase-chloramphenicol acetyltransferase reporter gene showed that dexamethasone inhibited 12-O-tetradecanoylphorbol-13-acetate-inducible, but not basal, AP-1 transcription factor activity. Our results demonstrate that glucocorticoids reversibly induce an early G1 block in cell cycle progression of an epithelial tumor cell line that occurs with a coordinate elevation in the expression of c-jun transcripts.
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PMID:Glucocorticoids reversibly arrest rat hepatoma cell growth by inducing an early G1 block in cell cycle progression. 846 59

By genetic correlation with the growth-suppressible phenotype and direct functional tests, we demonstrate that the glucocorticoid-stimulated expression of the CCAAT/enhancer-binding protein alpha (C/EBP alpha) transcription factor is required for the steroid-mediated G1 cell cycle arrest of minimal-deviation rat hepatoma cells. Comparison of C/EBP alpha transcript and active protein levels induced by the synthetic glucocorticoid dexamethasone in glucocorticoid growth-suppressible (BDS1), nonsuppressible receptor-positive (EDR1) and nonsuppressible receptor-deficient (EDR3) hepatoma cell proliferative variants revealed that the stimulation of C/EBP alpha expression is a rapid, glucocorticoid receptor-mediated response associated with the G1 cell cycle arrest. Consistent with the role of C/EBP alpha as a critical intermediate in the growth suppression response, maximal induction of transcription factor mRNA occurred within 2 h of dexamethasone treatment whereas maximal inhibition of [3H] thymidine incorporation was observed 24 h after steroid treatment. As a direct functional approach, ablation of C/EBP alpha protein expression and DNA-binding activity by transfection of an antisense C/EBP alpha expression vector blocked the dexamethasone-induced G1 cell cycle arrest of hepatoma cells but did not alter general glucocorticoid responsiveness. Transforming growth factor beta induced a G1 cell cycle arrest in C/EBP alpha antisense transfected cells, demonstrating the specific involvement of C/EBP alpha in the glucocorticoid growth suppression response. Constitutive expression of a conditionally activated form of C/EBP alpha caused a G1 cell cycle arrest of BDS1 hepatoma cells in the absence of glucocorticoids. In contrast, overexpression of C/EBP beta or C/EBP delta had no effect on hepatoma cell growth. Taken together, these results demonstrate that the steroid-induced expression of C/EBP alpha is necessary to mediate the glucocorticoid G1 cell cycle arrest of rat hepatoma cells and implicates a role for this transcription factor in the growth control of liver-derived epithelial tumor cells.
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PMID:Glucocorticoid-stimulated CCAAT/enhancer-binding protein alpha expression is required for steroid-induced G1 cell cycle arrest of minimal-deviation rat hepatoma cells. 881 41

Small cell undifferentiated carcinoma (oat cell carcinoma) is a malignant epithelial neoplasm with neuroendocrine features. It can appear as a primary tumor in many organs besides the lung, including the colon. We report a case of primary small cell undifferentiated carcinoma of the left colon with omental metastases in a 23-year-old man with a history of X-linked hyper-IgM syndrome. The patient had a simultaneous primary hepatocellular carcinoma. A literature review of this rare colonic malignancy is presented together with a discussion of the possible relationship of this tumor with hepatic malignancy and immunodeficiency.
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PMID:Small cell undifferentiated carcinoma of the colon associated with hepatocellular carcinoma in an immunodeficient patient. 881

We have developed a new assay, ISET (isolation by size of epithelial tumor cells), which allows the counting and the immunomorphological and molecular characterization of circulating tumor cells in patients with carcinoma, using peripheral blood sample volumes as small as 1 ml. Using this assay, epithelial tumor cells can be isolated individually by filtration because of their larger size when compared to peripheral blood leukocytes. ISET parameters were defined using peripheral blood spiked with tumor cell lines (HepG2, Hep3B, MCF-7, HeLa, and LNCaP). ISET can detect a single, micropipetted tumor cell, added to 1 ml of blood. We also demonstrate that fluorescence in situ hybridization can be used to perform chromosomal analyses on tumor cells collected using ISET. Polymerase chain reaction-based genetic analyses can be applied to ISET-isolated cells, and, as an example, we demonstrate homozygous p53 deletion in single Hep3B cells after filtration and laser microdissection. Finally, we provide evidence for the in vivo feasibility of ISET in patients with hepatocellular carcinoma undergoing tumor resection. ISET, but not reverse transcriptase-polymerase chain reaction, allowed analysis of cell morphology, counting of tumor cells, and demonstration of tumor microemboli spread into peripheral blood during surgery. Overall, ISET constitutes a novel approach that should open new perpectives in molecular medicine.
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PMID:Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells. 1062 54

Hepatocellular carcinoma (HCC) is a malignant epithelial tumor that accounts for over 80% of primary liver tumors. It affects males more than females, and is responsible for over 1 million yearly deaths worldwide. HCC tends to be relentless in nature and of rapid evolution. Most cases of HCC are associated with cirrhosis, usually caused by chronic viral hepatitis or alcohol ingestion. In cases of established cirrhosis, HCC develops with an annual incidence of 3%-10%. Hepatocellular carcinoma may present in a generalized way with overall clinical deterioration and malaise, as a palpable liver mass, or as an asymptomatic lesion that is discovered incidentally. Alpha-fetoprotein (AFP) measurements allow for the differentiation of HCC in cirrhotics, and can act as predictive markers. Patients with cirrhosis and small tumors (up to 3 cm, or 5 cm if solitary), no more than three nodules, and no portal vein involvement were found to benefit more from orthotopic liver transplantation (OLTx) than from resection. Tumors under 3 cm in size were unlikely to recur, while those over 5 cm posed the greatest risk. An incidental HCC in a transplant patient should be treated as seriously and aggressively as if the transplant had been undertaken for HCC.
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PMID:Hepatocellular cancer in liver transplantation. 1170 52

Hepatocellular carcinoma is an epithelial tumor derived from hepatocytes that accounts for more than 80% of all primary hepatic tumors. The severity of the underlying disease is almost always the key factor in deciding whether to consider liver resection or transplantation as its treatment. Data in our registry corresponding to almost 800 patients from transplant centers throughout the world showed that patient survival after liver transplantation was significantly affected by histologic grade, tumor size >5 cm, and the presence of positive nodes. Recurrence-free survival showed a correlation with tumor size >5 cm, positive nodes, bilobar spread, and vascular invasion. At the present time, 59% of patients in our registry are alive, 84% of whom are free of tumor. Of those who died, half did so without evidence of tumor.
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PMID:Liver transplantation in association with hepatocellular carcinoma: an update of the International Tumor Registry. 1220 Jul 72


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