Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The H1 histone subtype H1 (0) is a characteristic component of the chromatin of several mammalian tissues. Since H1 (0) is synthesized in nondividing cells upon terminal differentiation, it has been mostly considered either as a prerequisite for or as a consequence of an arrest of DNA replication during the process of differentiation. In several H1 (0)-expressing systems studied until now, inducers of differentiation or inhibitors of DNA synthesis cause an increase of the ratio between H1 (0) and the other H1 proteins. We have studied the steady-state levels of histone H1 (0) mRNA under varied growth conditions in the human hepatoma cell lines HepG2 and Hep3B, and we show in the HepG2 system that H1 (0) is not confined to resting cells, that the H1 (0) gene appears to be expressed throughout the cell cycle and that established inducers of de novo H1 (0) synthesis fail to cause a further increase of the high H1 (0) level. This constitutive expression of H1 (0) appears to reflect the chromatin structure of the liver cells, from which the HepG2 hepatoblastoma cells initially may have evolved. In contrast to the situation in nondividing adult liver cells, the H1 (0) gene is transcribed in HepG2 at a high level, and this expression is compatible with DNA replication.
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PMID:The expression of the histone H1 (0) gene in the human hepatoma cell line HepG2 is independent of the state of cell proliferation. 216 51

Immunotherapy with interleukin (IL)-2 possesses great potential in the treatment of immune-mediated diseases and cancers. However, only a few reports on a small number of children have appeared in the literature. From March 1988 to March 1989, 11 children and adolescents were treated with IL-2. They included 1 patient with hepatocellular carcinoma, 1 with hepatoblastoma, 6 with childhood atopic dermatitis, and 3 with juvenile rheumatoid arthritis. The dosages ranged from 10,000 to 50,000 U/kg every 8 hours by intravenous drip. The following side effects were observed: anorexia, fever, and chillness (100%), general malaise (82%), irritability (64%), diarrhea (100%), nausea and vomiting (73%), weight gain (82%), edema (82%), abdominal distension (73%), oliguria (82%), cough (91%), dyspnea (27%), pleural effusion (40%), hypotension (82%), skin eruption (82%), oral ulcer (18%), enlarged liver (73%) liver function abnormalities (82%), renal function impairment (36%), electrolyte imbalance (73%), anemia (91%), thrombocytopenia (54%), leukopenia (18%), and eosinophilia (73%). Immunologically, numbers of natural killer cells were increased and natural killer and lymphokine-activated killer cell activities were augmented after IL-2 treatment. There was a tendency for serum levels of IL-2 and receptor IL-2 to decrease, especially in patients with atopic eczema. Ten patients (91%) completed one course (9 to 12 days) of therapy, and the remaining patient interrupted the treatment because of intolerable adverse effects. Clinically, complete remission for 3 months was obtained in 1 juvenile rheumatoid arthritis patient, transient improvement (2 to 6 weeks) in all atopic dermatitis patients, minor response in the hepatoblastoma patient, and no response in the patient with hepatocellular carcinoma.
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PMID:Interleukin-2 immunotherapy in children. 217 36

Duck hepatitis B virus (DHBV) is produced in small amounts following transfection of human hepatoma or hepatoblastoma cell lines with cloned viral DNA. In a search for better hosts for DHBV replication, two avian liver cell lines were investigated. One of these cell lines, LMH, produced 5 to 10 times more DNA replicative intermediates and 10 to 20 times more infectious DHBV than did either of the two human cell lines, HuH-7 and Hep G2. Utilization of cell lines in genetic analyses of virus replication is often dependent upon obtaining efficient complementation between cotransfected viral genomes. We assayed transcomplementation of a viral polymerase (pol) gene mutant, which is rather inefficient in transfected human cells, and found that viral DNA synthesis was at least 20 times more efficient following cotransfection of LMH cells than in similarly transfected HuH-7 cells. Recombination, a potential interpretation problem in complementation assays, occurred at low levels in the cotransfected cultures but was substantially reduced or eliminated by creation of an LMH subline stably expressing the viral polymerase. This cell line, pol-7, supported the replication of DHBV pol mutants at ca. 10 to 15% of the level of virus replication obtained following transfection with wild-type viral DNA. By transcomplementation of a pol gene mutant in LMH cells, we were able to produce sufficient virus with the mutant genome to investigate the role of polymerase in covalently closed circular DNA amplification. Our results substantiate the hypothesis that covalently closed circular DNA is synthesized by the viral reverse transcriptase.
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PMID:Efficient duck hepatitis B virus production by an avian liver tumor cell line. 235 24

Congenital defects and other disorders have been reported in association with malignant liver tumours. In order to assess their significance, a population-based survey was undertaken on children aged less than 15 years diagnosed with malignant liver tumours during the 30 years 1957-1986. The cases were identified from information collected by the West Midlands Regional Children's Tumour Registry. Pertinent data were extracted from their clinical records, and the original biopsy and any necropsy material were reviewed by a panel of three paediatric pathologists. Of the 50 eligible cases registered, eight were excluded because histology review showed that they had non-malignant conditions (3) or malignancies of extrahepatic origin (4) or because no pathological material was available (1). The diagnoses in the remaining 42 cases were hepatoblastoma (27), hepatocellular carcinoma (3), rhabdomyosarcoma (6), rhabdoid tumour (3) and yolk sac tumour (3). The incidence of primary malignant liver tumours was 1.20 per 10(6) person years and that of the hepatoblastoma sub-group was 0.77 (average childhood population of the West Midlands for the time period being 1,166,500). The presenting clinical, radiological and biochemical features were similar to those reported in other series and the ethnic and social class distributions were unremarkable compared with the local population. Congenital defects or other possibly related features were present in nine (21%) patients. Our results, taken with other reports, suggest that hepatoblastoma is a malignant tumour related to maldevelopment, possibly associated with 11p or 5q mutations, whereas hepatocellular carcinoma is more usually a complication of metabolic and other disorders which lead to cirrhosis.
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PMID:Malignant hepatic tumours in children: incidence, clinical features and aetiology. 237 47

Eighteen cases of hepatocellular carcinoma in children were examined, and it was found that erythropoiesis exclusively appeared in the well differentiated type of hepatoblastoma. In such foci large immature erythroblasts were found among the tumor cells, whereas mature forms tended to gather in the subendothelial spaces or within sinusoids. Desmosome-like attachments were frequently found between immature erythroblasts and tumor cells. The tumor cells were well differentiated and had a distinct polarity. The erythropoietic foci were never found in lymph nodes, spleens and in the non-neoplastic hepatic tissues obtained by surgery or autopsy. Erythroblastic cells did not show an increase in number in the bone marrows. These findings indicate that hepatoblastoma cells in certain stages of differentiation have the capacity to induce the differentiation of pluripotent hemopoietic stem cells into the cells of erythrocytic series, or that the microenvironment composed of one or more tumor cells offer good soil for the differentiation of erythroblastic cells. There seems to be no intimate relationship between the production of alpha-fetoprotein by tumor cells and the appearance of erythropoiesis.
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PMID:Immunohistochemical and ultrastructural study on erythropoiesis in hepatoblastoma. 240 38

Twenty-four cases of hepatoblastoma, 14 cases of hepatocellular carcinoma and three cases of malignant mesenchymoma out of a total of 54 primary liver tumours were studied by light microscopy and immunohistochemistry. A remarkable finding in one case of hepatoblastoma and one case of hepatocellular carcinoma was a sarcoid-like reaction in the tumour tissue. Three cases of hepatoblastoma presented a macrotrabecular pattern. Among hepatocellular carcinomas, three cases corresponded to the fibrolamellar variant. By immunohistochemistry, the proportion of cases with positive staining for alpha 1-fetoprotein was higher in hepatoblastoma than in hepatocellular carcinoma. HBs-antigen could be demonstrated in non-neoplastic liver cells in two cases of hepatocellular carcinoma, but not in the tumour cells. No strong correlation between histological pattern and prognosis could be established in hepatoblastoma. However, there was a tendency to more aggressive biological behavior in cases with pronounced mitotic activity. The number of mitoses in hepatoblastoma varied widely. As in previous studies, patients with the fibrolamellar variant of hepatocellular carcinoma fared better than those with the classical type of this tumour. Prognosis in malignant mesenchymoma was not as poor as suggested from previous studies.
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PMID:Primary malignant hepatic tumours in childhood. 241 14

The regulation of alpha-fetoprotein (AFP) secretion and growth rate by various hormones in established human hepatoma (HuH-7, PLC/PRF/5, huH-1, huH-4, and KIM-1/c-4) and hepatoblastoma (HUH-6 Clone 5) cell lines was studied. These 6 cell lines replicated continuously in a chemically defined medium and secreted 84 ng (HuH-7) to 23 pg (huH-4) AFP per 24 h per 1 X 10(4) cells into the culture medium. The addition of insulin increased the growth rate of all examined cell lines and partially inhibited the AFP secretion in those cell lines except KIM-1/c-4, while the addition of dexamethasone inhibited the growth and stimulated the AFP secretion in all of the cell lines. The addition of 3,3',5-triiodothyronine inhibited the growth of all cell lines; however, different effects on the AFP secretion were observed depending on the cell lines used. Obviously, the AFP secretion was unrelated to the change in growth rate. When dexamethasone and N6-O2-dibutyryl cyclic AMP were added together, the AFP secretion was further stimulated. On the other hand, when dexamethasone and insulin were added simultaneously, the dexamethasone-mediated stimulation of AFP secretions was diminished. The data indicated that the regulatory mechanisms of AFP secretion by the hormones in the established human hepatoma and hepatoblastoma cell lines cannot be deduced according to the results of one cell line.
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PMID:Hormonal control of alpha-fetoprotein secretion in human hepatoma cell lines proliferating in chemically defined medium. 241 43

The presence of divergent tissue, such as bone or osteoid, is a well recognized occurrence in the hepatoblastoma. However, multiple lines of tissue differentiation in a hepatic tumor that had the overall features of hepatoblastoma have recently been observed. During the brief and eventually fatal clinical course in this case, the tumor initially displayed the features of conventional hepatoblastoma, but evolved into a neoplasm with teratoid features, terminally assuming a hepatoma-like appearance. Immunohistochemistry and ultrastructural studies confirmed the various lines of divergent differentiation in this tumor, which the authors chose to designate as a teratoid hepatoblastoma.
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PMID:Teratoid hepatoblastoma. The nosologic dilemma of solid embryonic neoplasms of childhood. 242 66

Alpha-foetoprotein (AFP) synthesis, although repressed in normal adults, is increased in the majority of patients with hepatocellular carcinoma (HCC). We have investigated whether active transcription of the AFP gene may explain raised serum AFP concentrations in patients with HCC and hepatoblastoma by assaying human tumour and non-neoplastic tissue by molecular hybridization for the presence of mRNA encoding AFP. Ten operative HCC and six autopsy HCC specimens, two HCC cell lines, and one hepatoblastoma specimen were examined. Total cellular RNA and poly-(A)+ RNA were extracted and AFP mRNA sequences sought by dot-blot and Northern blot hybridisation to a human cDNA AFP probe. Cellular AFP was localised by avidin-biotin staining. AFP mRNA was detected in 8/10 operative specimens, as well as PLC/PRF/5 nude mouse tumours. Weaker hybridization was detected in 4/6 autopsy specimens. Signals of comparable intensity to that in operative tumours were detected in non-neoplastic tissue of 6 patients. AFP mRNA from nude mouse tumours migrated as a 20S discrete band on agarose gel electrophoresis, whereas a more complex hybridization pattern was evident in human tumours. Positive cytoplasmic immuno-staining for AFP was observed in 4 tumours and 2 corresponding non-neoplastic specimens and in a HCC cell line. In non-neoplastic liver, AFP was localised in cells that appeared dysplastic. Thus steady-state levels of AFP mRNA are detectable in human HCC tissue and surrounding non-neoplastic liver. These findings may prove pertinent to an understanding of the genetic expression of AFP in malignant hepatocytes, and the sequence of events leading to uncontrolled cellular proliferation.
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PMID:Detection of alpha-foetoprotein messenger RNA in human hepatocellular carcinoma and hepatoblastoma tissue. 243 15

The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease progression remains to be established. In monitoring the response of hepatic metastases, CEA remains the least unsatisfactory marker but should always be used in conjunction with serial ultrasound scans. Tumour markers now play an important role in the diagnosis and monitoring of PLC but a role is also emerging in tumour imaging and drug targeting. The next 20 years should see the introduction of tumour markers of high sensitivity and specificity which make a fundamental contribution not only to detection and monitoring, but also to the effective treatment of liver cancer.
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PMID:Tumour markers in diagnosis and management. 243 83


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