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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma cells obtained from ascitic fluid after diethylnitrosamine treatment of Sewall Wright strain-2 guinea pigs produce solid (primary) tumors, lymph-node metastases and malignant ascites when reinjected into animals of the same strain. When brought into culture the cells settle, form multilayer cultures and can be maintained in passage. In addition to epithelium-specific cytokeratin intermediate filaments (IF), these latter cells, like most cultured cells, also contain vimentin. Hepatocellular carcinoma cells in solid tumors and in metastatic tumors retain their original keratin IF and in general do not have an additional vimentin-IF system. When the tumor cells are present in ascites they develop vimentin-IF in addition to cytokeratin filaments. Vimentin is gradually lost when these cells sediment onto the peritoneal surface and proliferate continuously to form papillary projections, or when they are detected as circumscribed metastases. It seems likely, therefore, that in this system the synthesis of an additional vimentin cytoskeleton is related to reduced cell-to-cell contact and to the ability of the cells to survive individually or as cell clusters in body fluids, without being part of a cohesive tissue.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Changing intermediate-sized filament patterns in metastatic hepatocellular carcinoma cells of the guinea pig. 242 67

Hepatocellular carcinoma cells (Line-10), obtained from ascitic fluid after diethylnitrosamine treatment of Sewall Wright strain-2 guinea pigs, produce solid (primary) tumours, lymph-node and lung metastases and malignant ascites when reinjected into animals of the same strain. Monoclonal antibodies were raised against the tumour cells by immunizing BALB/c mice with viable ascitic hepatocellular Line-10 tumour cells. Three hybridomas producing anti-Line-10 monoclonal antibodies were selected for further studies (10TL1, 10TL40 and 10TL43) and compared with monoclonal antibodies against intermediate filament keratins. The anti-Line-10 monoclonal antibodies did not cross react with Line-1 hepatocellular carcinoma cells, nor with normal guinea pig hepatocytes. When ascitic Line-10 cells form high papillary projections on the peritoneal surface, they significantly reduced their antigen expression of 10TL40 and of 10TL43 defined antigens, while the expression of 10TL1 defined antigens remained unaltered. Invading Line-10 cells in the deep submesothelial stromal tissue, however, lost reactivity with MoAb 10TL43 but not with the MoAb's 10TL40 and 10TL1. The antigens on lung- and lymphnode metastases remained largely unaffected. The reactivity with MoAb's 10TL40 and with 10TL43 was also lost upon prolonged culturing of Line-10 cells. The reactivity of Line-10 and Line-1 cells with all monoclonal antibodies against keratin filaments remained unaltered. Line-1 cells could be distinguished from Line-10 cells by the absence of any reactivity with the MoAb's 10TL1, -40, -43, but also by the fact that 100% of the Line-1 cells were positive with antibodies against keratins 5/8, 18, and 7.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Changing tumour antigen expression in metastatic hepatocellular carcinoma cells of the guinea pig. 246 49

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in humans and in most cases a consequence of chronic infection of the liver by hepatotropic viruses (Hepatitis B Virus (HBV) and possibly Hepatitis C Virus (HCV)). Formation of HCC results from a stepwise process involving different preneoplastic lesions that reflect multiple genetic events, like protooncogene activation, tumor suppressor gene inactivation, and growth factor over- or reexpression. Recent investigations have gained new insights into how these factors are activated and may interact. In addition, improved knowledge of the molecular biology of HBV has led to better understanding of its pleiotropic effects on induction and progression in hepatocarcinogenesis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Current pathogenetic and molecular concepts in viral liver carcinogenesis. 809 24

Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis and is highly amenable to the development of novel therapeutic strategy. The human alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but overexpressed in HCC. In order to destroy AFP-producing HCC specifically, replication defective adenoviral vectors containing the transcriptional control elements of the AFP gene were designed. Expression of suicide genes by the AFP promoter/enhancer induced prodrug sensitivity in AFP (+) cells but not AFP (-) cells. The expression of suicide genes by ubiquitous promoter, however, showed no selectivity after prodrug treatment. Adenoviral vector transduced genes efficiently not only in vitro but also in vivo, and AFP-producing HCC xenografts regressed by transduction with transcriptionally targeted vectors and subsequent systemic administration of prodrug in animal model. Utilization of the transcriptional regulatory element to drive drug sensitive genes can be a promising strategy for cancer specific therapy.
Mol Biotechnol 2001 Jul
PMID:Transcriptional targeted gene therapy for hepatocellular carcinoma by adenovirus vector. 1150 18

Hepatocellular carcinoma is a lethal disease and methods that develop effective cellular-based immunotherapy are needed. We retrovirally transduced non-immunogenic mouse Hepa1-6 hepatoma cells with the gene encoding the membrane form of macrophage colony stimulating factor (mM-CSF). Excess recombinant M-CSF and phagocytosis-inhibiting chemicals blocked macrophage-mediated killing of cloned mM-CSF transfected Hepa1-6 hepatoma cells. Macrophages derived from Hck(-/-)Fgr(-/-) and Lyn(-/-) triple knockout mice, which are incapable of performing phagocytosis, failed to kill the mM-CSF transduced cells. The mM-CSF transfected tumor clones failed to grow when injected into C57BL/6 or C57L/J mice. Splenocytes from these vaccinated mice displayed cytotoxicity against parental Hepa1-6 cells, but not against B16 and CT-26 tumor cells in vitro. Mice that rejected the mM-CSF transfected Hepa1-6 tumor subsequently rejected parental Hepa1-6 cells but not the B16 melanoma cells when rechallenged. Elimination of the CD8+ effector cells by an anti-CD8 antibody and complement treatment prevented the adoptive transfer of anti-Hepa1-6-specific immunity into naive animals. Thus, mM-CSF provides a method of generating effective anti-tumor immune responses by macrophages and cytotoxic T cells against the parental Hepa1-6 cells. Our work suggests that mM-CSF transduced hepatoma cells could be used as a tumor vaccine to stimulate immune responses against hepatocellular carcinoma.
Mol Ther 2001 Nov
PMID:Non-immunogenic murine hepatocellular carcinoma Hepa1-6 cells expressing the membrane form of macrophage colony stimulating factor are rejected in vivo and lead to CD8+ T-cell immunity against the parental tumor. 1170 79

Hepatocellular carcinoma (HCC) is characterized by multiple somatic mutations, including DNA rearrangements, that affect many cell-growth regulatory pathways. Many genes differentially expressed in HCC have been reported previously, but the patterns of expression varied significantly between patients who bore different risk factors for HCC. To identify genes whose differential expression could serve as a "signature" for diagnosis and prognosis of HCC, we performed analyses of differentially expressed genes in three cases of HCC with different risk factors using the Atlas Human Cancer cDNA Expression Arrays. Among all 597 genes present on the array, only three were found to be coordinately differentially expressed in all three HCC cases, in agreement with published data. These three genes, Cu/Zn superoxide dismutase, osteonectin/secreted protein acidic and rich in cysteine, and matrix metalloproteinase 14, could serve as candidates for the HCC "signature." Ten genes were found to be coordinately differentially expressed in only two of three tested HCC cases. On the other hand, many genes that had been reported previously as differentially expressed in HCC failed to show the described pattern of expression in this group. The results of this study confirm the great variability in gene-expression patterns in HCC and establish the utility of the array technology for identifying both the HCC signature genes and individual gene-expression patterns for purposes of patient-oriented therapy.
Mol Carcinog 2002 Feb
PMID:Analysis of differentially expressed genes in hepatocellular carcinoma using cDNA arrays. 1181 4

Hepatocellular carcinoma is the most common malignant tumor of the liver. The discrimination between well-differentiated hepatocellular carcinoma and reactive lesions and benign tumors may be difficult, especially when performed on the basis of needle biopsies. A promising means of solving this problem is provided by chromosomal analysis of imbalances in hepatocellular carcinoma. This article describes the different approaches to ascertain differential diagnosis by chromosomal studies in a reliable and cost-effective manner. It is shown that in situ hybridization techniques provide a reliable means of defining chromosome alterations. These techniques allow the detection of genetic gains and losses of defined chromosomes in a histopathological context and can serve as a helpful tool in establishing diagnosis of liver cell proliferation.
Expert Rev Mol Diagn 2002 Mar
PMID:Detection of chromosomal imbalances in hepatocellular carcinoma. 1196 32

Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA microarrays to characterize patterns of gene expression in HCC, we found consistent differences between the expression patterns in HCC compared with those seen in nontumor liver tissues. The expression patterns in HCC were also readily distinguished from those associated with tumors metastatic to liver. The global gene expression patterns intrinsic to each tumor were sufficiently distinctive that multiple tumor nodules from the same patient could usually be recognized and distinguished from all the others in the large sample set on the basis of their gene expression patterns alone. The distinctive gene expression patterns are characteristic of the tumors and not the patient; the expression programs seen in clonally independent tumor nodules in the same patient were no more similar than those in tumors from different patients. Moreover, clonally related tumor masses that showed distinct expression profiles were also distinguished by genotypic differences. Some features of the gene expression patterns were associated with specific phenotypic and genotypic characteristics of the tumors, including growth rate, vascular invasion, and p53 overexpression.
Mol Biol Cell 2002 Jun
PMID:Gene expression patterns in human liver cancers. 1205 60

Hepatocellular carcinoma (HCC) is one of the most common malignancy in the world and it usually occurs in individuals with chronic liver disease. The neoplasm is predominant in the male gender, where it is characterized also by a worst prognosis than in females. The pathogenesis of HCC is obscure. Because of its striking male predominance, androgens have been investigated as potential factors able to induce or at least promote hepatic carcinogenesis; this hypothesis has been also supported by the ability of androgens of inducing liver neoplasms in experimental models. On the other hand, due to the fact that HCC occurs predominantly in male cirrhotics who present a characteristic hormone imbalance with a relative hyperestrogenic state, the potential role of estrogen in liver cancer has been studied as well. In this paper, the potential role of sex hormones in liver carcinogenesis has been reviewed.
Mol Cell Endocrinol 2002 Jul 31
PMID:Sex hormones and liver cancer. 1216 Oct 2

Hepatocellular carcinoma is a typical hypervascular tumor. Generally, hepatocellular carcinoma is developed through liver cirrhosis induced by chronic liver injury. This chronic injury leads to changes in the cellular property of the liver and subsequently causes fibrogenesis to demolish normal liver blood system. The catastrophe of the normal liver blood system leads to the shortage of blood circulation in the liver and causes hypoxia. Moreover, the increased cellularity due to highly proliferative tumor cells also induces local hypoxia inside hepatocellular carcinoma. Hypoxia can stimulate angiogenesis to support tumor growth by induction of angiogenic factors. Thus hypoxia may be a major cause of hypervasculature of hepatocellular carcinoma. Recently it has been reported that several hypoxia-regulatory factors are closely involved in angiogenesis of hepatocellular carcinoma. The stability and function of these factors can be regulated by interaction with other protein factors and consequently modulate the expression of angiogenic factors depending on oxygen tension. Therefore induction mechanism of hypoxia and the role of hypoxia-regulatory factors could provide new insights into hepatocarcinogenesis and the treatment of hepatocellular carcinoma.
J Mol Med (Berl) 2002 Nov
PMID:Hypoxia-induced angiogenesis in human hepatocellular carcinoma. 1243 47


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