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)

The murine monoclonal antibody (Mab) against human common epithelial ovarian carcinoma, CF511, was generated by immunising mice with human fetal tissue extract from early first trimester, followed by booster injection of an ovarian cancer cell line. Mab CF511 recognised the 600 kDa sialylated glycoprotein as different from previously known tumour associated-marker antigens. Distribution of the Mab CF511-recognised antigen (CF511 antigen) in various tissues and sera was investigated. In immunohistochemical analysis, Mab CF511 reacted strongly with tumour cells of ovarian serous, clear cell, endometrioid and undifferentiated carcinoma and partially with those of mucinous carcinoma. Mab CF511 also reacted with breast carcinoma as well as lung carcinoma. In normal tissues, Mab CF511 cross-reacted with only five tissues, namely lung, breast, thyroid gland, fallopian tube and uterus. Serum levels of CF511 antigen were tested by ELISA inhibition using Mab CF511. This assay showed the circulating CF511 antigen levels to be elevated in 25 of 36 sera from patients with various clinical stages of common epithelial ovarian carcinoma compared to three of 47 and three of 111 sera from patients with other benign gynaecological diseases, including ovarian cysts, uterine fibroids with or without endometriosis and normal healthy subjects, respectively. For the relation between antigen levels and clinical stages of common epithelial ovarian carcinoma, greater than 34.0% ELISA inhibition was detected in 100% of patients with advanced stages (FIGO III and IV) compared with in 35.3% with early stages (FIGO I and II) patients. While patients with breast carcinoma (100%) and lung carcinoma (100%) also had elevated circulating CF511 antigen levels, patients with hepatoma, colorectal carcinoma and gastric carcinoma had no detectable elevation of antigen. Although the test showed a high degree of specificity, the detection of an elevated CF511 antigen level would not be so helpful in distinguishing patients with ovarian carcinoma from those with either breast carcinoma or lung carcinoma. These data suggest that CF511 antigen is a useful new ovarian tumour marker for diagnosis and management of the disease.
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PMID:Serum levels and biochemical characteristics of human ovarian carcinoma-associated antigen defined by murine monoclonal antibody, CF511. 260 5

CGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i.m. or s.c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.
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PMID:CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties. 271 56

Mortality, major causes of moribundity, and spontaneous tumors in CD-1 mice were studied in 891 males and 890 females, which were used as controls in 11 different 2-year chronic and oncogenicity studies during the past 5 years. Average mortality of males and females at 83 weeks of age was 32.6% and 28.6%, respectively, and at 109 weeks of age was 66.4% and 63.3%, respectively. Mortality was significantly lowered in males and females born after 1980 in accordance with an abruptly decreased occurrence of systemic amyloidosis in these animals. The major cause of death or moribundity included systemic arteritis, systemic amyloidosis, auricular thrombosis, glomerulosclerosis, lymphoma, and pulmonary adenocarcinoma in both sexes. Dysuria and hepatocellular carcinoma in males and mammary adenocarcinoma in females were also critical lesions. The major tumors occurring at more than 3% incidence were systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver and adenoma/adenocarcinoma of the Harderian gland for males, and systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver, leiomyoma/leiomyosarcoma of the uterus, adenoma/adenocarcinoma of the pituitary (anterior), adenoma/adenocarcinoma of the mammary gland and adenoma/adenocarcinoma of the Harderian gland for females. Intralaboratory heterogeneities in the incidence were recorded as follows: systemic lymphoma in 1 of 11 control groups (1/11) and adenoma/adenocarcinoma in 1/11 for males, and systemic lymphoma in 3/11, adenoma/adenocarcinoma of the lung in 2/11, adenoma/adenocarcinoma of the liver in 1/11, and adenoma/adenocarcinoma in 1/11 for females.
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PMID:Mortality, major cause of moribundity, and spontaneous tumors in CD-1 mice. 319 56

Using a monospecific, monoclonal antibody against the glucocorticoid receptor (GR), an immunocytochemical study was performed to investigate the intracellular localization of GR both in the presence or absence of ligand. With all fixation methods tested (paraformaldehyde, acetic acid in ethanol, Bouin's fixative, and bensochinone in PBS), it was possible to obtain specific GR staining. Fixation with paraformaldehyde was chosen for further studies on the effect of permeabilization, using several concentrations of Triton X-100 or saponin. A rat Rueber hepatoma (H-4-II-E) and a human uterus carcinoma (NHIK 3025) cell line were used as well as cultured hepatocytes from normal rat. The accessibility of the different cell compartments after fixation and permeabilization was tested for by using antibodies against cellular constituents with known locations (i.e. core-nucleosome proteins and tubulin), in combination with the anti-GR antibody in double immunofluorescence staining experiments. The specific GR stain obtained with the indirect peroxidase antiperoxidase technique or with fluorescein isothiocyanate-labeled second antibodies was shown to be present both in the cytoplasm and in the nucleus. Staining of all cellular compartments was abolished (peroxidase antiperoxidase) or diminished (fluorescein isothiocyanate) if the monoclonal antibody was preincubated with a 90% pure GR preparation. These findings are in contrast to recently reported immunocytochemical studies, where a strict nuclear existence of the estrogen and progestin receptors has been reported. Consequently, generalizations with regard to steroid receptor localization cannot be made. Furthermore, an in vitro model is described, where the effect of dexamethasone administration upon the localization of receptor staining in H-4-II-E cells can be studied.
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PMID:Intracellular localization of the glucocorticoid receptor: evidence for cytoplasmic and nuclear localization. 354 55

Gentian violet is a dye belonging to a chemical class known as the di- and triaminophenylmethanes. Although it has been used for many years for the control of fungal and intestinal parasites, for various uses in veterinary medicine, and as an additive to the feed of chickens to inhibit propagation of mold and fungus, very few long-term toxicity data are available. A life span dosing study of gentian violet in the diet of 720 males and 720 females of B6C3F1 mice (C57BL/6 X C3H) at dose levels of 0, 100, 300, and 600 ppm was done to determine its toxicity and carcinogenicity. Sacrifices were conducted after 12, 18, and 24 months of continuous dosing. There was no effect on food consumption or body weight gain; however, a dose effect was noted for mortality rates. Mortality (adjusted for sacrifices) in the controls of both sexes was less than 15% at 24 months, but was approximately 64% in the females and 23% in the males given the high dose. Females appeared to be more susceptible than males. A positive dose response for hepatocellular carcinoma was noted in males at 24 months and in females at 18 and 24 months. Statistical tests for dose-related trends with respect to mortality due to liver neoplasms, prevalence of liver neoplasms, and time to onset of liver neoplasms showed positive trends in both males and females. Other dose-related toxicological responses, particularly in the female mice, included erythropoiesis in the spleen, atrophy of the ovaries, adenoma of the Harderian gland, and the presence of type A reticulum cell sarcomas in the urinary bladder, uterus, ovaries, and vagina. The estimation of risk of 10(-6) over background for malignant liver neoplasms using linear extrapolations showed a lower bound on the virtually safe dose (VSD) to be 2 ppb for the female mice and 1 ppb for the male mice. For benign and malignant liver tumors together, the lower bound on the VSD was essentially the same as for malignant liver neoplasm alone. Under the conditions of the experiment described above, gentian violet appears to be a carcinogen in mice at several different organ sites.
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PMID:Chronic toxicity and carcinogenicity studies of gentian violet in mice. 406 63

In regulating gene expression in mammalian tissues, steroid hormones bind to cytoplasmic receptors and the resulting complex associates with the nucleus. In an attempt to study this nuclear association under more precisely controlled conditions, we examined the binding of receptor-[(3)H]steroid complexes to isolated nuclei. Two systems were used: the glucocorticoid-responsive hepatoma cell and the estrogen-sensitive immature rat uterus. Cell-free nuclear binding resembles that observed in the intact cell; it requires the receptor-steroid complex in the appropriate form ("active" complex); it is of high affinity; and it appears to involve about 4000 nuclear acceptor sites per haploid genome. Furthermore, whether binding occurs in intact cells or in cell-free extracts, complexes dissociate from nuclei at similar rates, and the ability of NaCl to extract either type of nuclear-bound complex and the sedimentation velocities of the extracted complexes are identical. Despite these similarities, acceptor sites detected in isolated nuclei differ from those of intact cells, since in neither hepatoma cells nor in the uterus do complexes bound to the nuclei of intact cells prevent further cell-free binding. We conclude that receptor-steroid complexes bind to acceptor sites in isolated nuclei that are chemically similar to, but topographically different from, those of the intact cell.
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PMID:Nuclear binding of steroid receptors: comparison in intact cells and cell-free systems. 435 70

Three stable monoclonal antibody-producing mouse hybridoma lines have been developed which produce high-titer, immunoglobulin M antibodies specific for the Novikoff ascites hepatoma (NAH) Mr 39,000 cytokeratin antigen (p39). Immunotransfer assays of cytoskeletal protein-enriched fractions indicated p39 to be present in a range of rat tissues, including colon, breast, lung, and uterus. Two-dimensional gel immunoblots confirmed that immunoreactivity in the latter tissues was for polypeptides with similar isoelectric points to those of NAH p39; however, reactivity in the colon contained a wide range of additional isomeric forms. Immunohistochemical localization studies with these antibodies revealed enrichment of p39 in the simple epithelia or ductular structures of organs containing this antigen. In all sections examined, glandular epithelia were observed to be only weakly immunoreactive. Additional immunoblot and immunocytochemical analyses with the monoclonal antibodies and polyspecific antisera to NAH cytokeratin suggest the human Mr 40,000 cytokeratin to be similar to but not identical to NAH p39.
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PMID:Characterization of monoclonal antibodies to novikoff hepatoma cytokeratin antigen p39. 620 5

MCF-7 cells contain progesterone, estradiol and glucocorticoid receptors. Following addition of these hormones to the growth medium of the cells, hormone-receptor complexes were found to sediment with chromatin fragments produced by trace digestion with micrococcal nuclease. The binding in all cases could be competed by excess unlabeled hormone. In each case the fragments with which the hormone-receptor complexes were associated tended to be smaller than the bulk chromatin fragments, indicating a greater sensitivity of those chromatin regions to the nuclease. The mononucleosomes released by more extensive digestion with micrococcal nuclease contained different amounts of each of the three hormone-receptor complexes. Progesterone could usually be detected on mononucleosomes only after very brief sedimentation analyses, whereas glucocorticoid- and estradiol-labeled mononucleosomes were stable during long centrifugations. Comparison of glucocorticoid- and estradiol-labeled mononucleosomes indicated that their sedimentation rates differed from one another and from bulk nucleosomes. Estradiol nucleosomes from MCF-7 cells and rat uterus (Senior and Frankel, 1978) sediment significantly faster than bulk nucleosomes, while glucocorticoid nucleosomes from MCF-7 cells and rat hepatoma cells sediment with, or even fractionally slower than, bulk nucleosomes.
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PMID:Progesterone, glucocorticoid and estradiol receptors in MCF-7 cells bind to chromatin. 686 95

All mammalian gap junction channels are sensitive to the voltage difference imposed across the junctional membrane, and parameters of voltage sensitivity have been shown to vary according to the gap junction protein that is expressed. For connexin43, the major gap junction protein in the cardiovascular system, in the uterus, and between glial cells in brain, voltage clamp studies have shown that transjunctional voltages (Vj) exceeding +/- 50 mV reduce junctional conductance (gj). However, substantial gj remains at even very large Vj values; this residual voltage-insensitive conductance has been termed gmin. We have explored the mechanism underlying gmin using several cell types in which connexin43 is endogenously expressed as well as in communication-deficient hepatoma cells transfected with cDNA encoding human connexin43. For pairs of transfectants exhibiting series resistance-corrected maximal gj (gmax) values ranging from < 2 to > 90 nS, the ratio gmin/gmax was found to be relatively constant (about 0.4-0.5), indicating that the channels responsible for the voltage-sensitive and -insensitive components of gj are not independent. Single channel studies further revealed that different channel sizes comprise the voltage-sensitive and -insensitive components, and that the open times of the larger, more voltage-sensitive conductance events declined to values near zero at large voltages, despite the high gmin. We conclude that the voltage-insensitive component of gj is ascribable to a voltage-insensitive substate of connexin43 channels rather than to the presence of multiple types of channels in the junctional membrane. These studies thus demonstrate that for certain gap junction channels, closure in response to specific stimuli may be graded, rather than all-or-none.
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PMID:Gap junction channels: distinct voltage-sensitive and -insensitive conductance states. 752 96

Hepatocellular carcinoma is characterized by changes in gene expression associated with cell growth and differentiation. Cell surface antigenic changes have also been described based on differential antibody reactivity between normal and neoplastic liver. We obtained a novel tumor-associated cDNA designated TA1 on the basis of its differential expression between hepatoma cells and normal liver. Sequence analysis predicted a 723-base pair open reading frame with the deduced amino acid sequence encoding an integral membrane protein containing multiple hydrophobic transmembrane domains. Database searches revealed TA1 as the likely rat homologue of E16, a recently cloned human cDNA associated with lymphocyte activation. Although noncoding sequences diverged significantly, the 95% conservation of the predicted proteins between species strongly suggests an important, although as yet undefined, function in normal cells. TA1 transcripts were detected in normal adult rat tissues including testes, brain, ovary, spleen, mammary gland, and uterus with the highest steady-state expression in placenta. Although no expression was detected in normal liver, all rat hepatomas examined expressed an abundant 3.2-kilobase transcript. TA1 expression was closely associated with progression in this tumor model and suggests this molecule, originally linked to cell activation, also plays a role in the malignant phenotype.
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PMID:TA1, a highly conserved oncofetal complementary DNA from rat hepatoma, encodes an integral membrane protein associated with liver development, carcinogenesis, and cell activation. 753 44


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