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)

A semi-purified corn-based diet containing 50 mg/kg of pure (not less than 90%) fumonisin B1 (FB1), isolated from culture material of Fusarium moniliforme strain MRC 826, was fed to a group of 25 rats over a period of 26 months. A control group of 25 rats received the same diet without FB1. Five rats from each group were killed at 6, 12, 20 and 26 months. The liver was the main target organ in the FB1-treated rats and the hepatic pathological changes were identical to those previously reported in rats fed culture material of F.moniliforme MRC 826. All FB1-treated rats that died or were killed from 18 months onwards suffered from a micro- and macronodular cirrhosis and had large expansile nodules of cholangiofibrosis at the hilus of the liver. Ten out of 15 FB1-treated rats (66%) that were killed and/or died between 18 and 26 months developed primary hepatocellular carcinoma. Metastases to the heart, lungs or kidneys were present in four of the rats with hepatocellular carcinoma. No neoplastic changes were observed in any of the control rats. Chronic interstitial nephritis was present in the kidneys of FB1-treated rats killed after 26 months. No lesions were observed in the esophagus, heart or forestomach of FB1-treated rats and this is contrary to previous findings when culture material of the fungus was fed to rats. It is concluded that FB1 is responsible for the hepatocarcinogenic and the hepatotoxic but not all the other toxic effects of culture material of F.moniliforme MRC 826 in rats.
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PMID:Toxicity and carcinogenicity of the Fusarium moniliforme metabolite, fumonisin B1, in rats. 164 15

For the determination of LDL receptor expression on living human cells two monoclonal antibodies specific for the extracellular domain of LDL receptor were established using affinity-purified LDL receptor and carrier-conjugated LDL receptor peptide 163-174 as immunizing antigens. The 125I-labeled antibodies were used to quantify increases in LDL receptor expression on human cells grown in the presence of increasing concentrations of various growth factors. Growth factor-mediated increase of LDL receptor expression was entirely different in various cell lines with respect to a distinct growth factor and for different growth factors when tested with one and the same cell line. An increased LDL receptor expression was observed on A431 epidermoid carcinoma cells of the vulva in the presence of epidermal growth factor (EGF) or insulin but not with platelet-derived growth factor (PDGF), on HUV-EC primary endothelial cells in the presence of insulin or PDGF but not with EGF, and on MRC-5 diploid fetal lung cells only in the presence of PDGF. HEP-3B hepatoma cells did not respond to any of the three growth factors essentially maintaining the original level of LDL receptor expression.
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PMID:Expression of LDL receptor on tumor cells induced by growth factors. 185 Feb 20

Ten strains of hepatitis A virus (HAV) originating from far distant geographical locations were adapted to growth in PLC/PRF/5 (human hepatoma derived and/or MRC-5 (human embryonic lung) cells. In the course of primary adaptation some of these strains exhibited a predilection for distinct cultural conditions such as type of host cell and temperature of incubation. With progressive passage, variant viruses with quite different requirements could be selected; yet, it proved impossible to isolate a virus which replicated equally well in both types of cells and at both 32 and 37 degrees C without at least one preceding passage under the new conditions. Analysis of the virus/cell relationship of well adapted HAV strains revealed that the replication cycle of HAV extends over about 24 h. Moreover, replication evidently passes from a state of active production of infectious virus to a phase during which hepatitis A antigen (HAAg) is synthesized and terminates in the state of persistent infection with markedly reduced synthetic activity. In all three phases replication of HAV is non-cytolytic and the vast majority of both infectious virus and of HAAg remains cell associated. The observations concerning the growth characteristics of HAV were used to develop two rapid in vitro assay systems for HAV infectivity (fluorescent focus assay and in situ RIA). Finally, the conditions for large scale production of infectious HAV and of HAAg in a cell factory system were analysed.
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PMID:Propagation and assay of hepatitis A virus in vitro. 609 9

Fusarium moniliforme Sheldon is one of the most prevalent fungi associated with maize throughout the world. A correlation has been found between the incidence of F. moniliforme in home-grown maize and the human oesophageal cancer rate in Transkei, southern Africa. Culture material on maize of F. moniliforme strain MRC 826, isolated from maize in a high-risk area for oesophageal cancer in Transkei, was either freeze-dried or oven-dried and fed to groups of 20 inbred male BD IX rats on a life-long basis. At a dietary level of 8%, both types of culture material were hepatotoxic and caused 100% mortality. Hepatic lesions in rats that died were characterized by cirrhosis, nodular hyperplasia and bile-duct proliferation. At a dietary level of 4% for 286 days followed by 2% for the remainder of the experiment, both types of culture material were hepatocarcinogenic and caused hepatocellular carcinoma in 80% and ductular carcinoma of the liver in 63% of the rats surviving more than 450 days. Only one of 30 such rats did not have a primary hepatic carcinoma. No hepatocellular or ductular carcinomas occurred in the controls. Hepatocellular carcinomas in the experimental rats invariably developed in severely cirrhotic livers showing nodular hyperplasia. Adenofibrosis also developed concurrently with hepatocellular carcinoma. A higher incidence of basal cell hyperplasia occurred in the oesophageal epithelia of rats fed freeze-dried than in those fed oven-dried material. The chemical nature of the hepatotoxic and hepatocarcinogenic mycotoxin(s) produced by F. moniliforme is unknown.
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PMID:Primary liver cancer and oesophageal basal cell hyperplasia in rats caused by Fusarium moniliforme. 648 Jan 56

The expression of the p53 tumor suppressor gene in ten human cell lines (nine cancers and one normal) was studied using reverse transcription, polymerase chain reaction (PCR) and direct sequencing. Using P53U and P53D primers for amplifying a 371-base pair (bp) target fragment spanning exons 7-10 of p53 cDNA, normal-sized PCR products were amplified from 9 cell lines but not from the Hep3B hepatocellular carcinoma (HCC) cell line. An additional larger band (504 bp) was observed for the Molt-4 T-lymphoblastic leukemia cell line. Employing P531 and P53D primers which flank a 76-bp p53 cDNA fragment, 76 bp as well as 209 bp products were generated by PCR of Molt-4 cDNA. Direct sequencing of the 504 bp and 209 bp bands confirmed the presence of a 133 bp insertion between exons 9 and 10 in the aberrant transcript. This insertion was homologous to a 130-bp sequence within the wild-type p53 intron 9, except for 2 point mutations and 3 base insertions. Sequencing of P53U/P53D PCR products of Molt-4 genomic DNA revealed an 8 bp deletion just downstream to the 133 bp insertion, creating a novel donor splicing site within intron 9. This site, coupled with an inherent acceptor splicing site just upstream to the 133 bp insertion, suggests that the 133 bp stretch represents an alternative exon. The occurrence of a termination signal within this alternative transcript is predicted to culminate in a truncated p53 translational product. The sequences of the 371 bp PCR products of Molt-4, HT-1080, SiHa, CaSki, HeLa and MRC-5 cell lines corresponded with the wild-type p53 cDNA. G-->T transversions at the third base of codon 249 of p53 were detected in Mahlavu and PLC/PRF/5 HCC lines, while a TAC to CAC mutation at codon 234 was observed in an allele of the Raji Burkitt lymphoma line.
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PMID:Alternative splicing of the p53 tumor suppressor gene in the Molt-4 T-lymphoblastic leukemia cell line. 822 26

We previously reported the isolation of the novel human DENN gene, which is differentially expressed in normal and neoplastic cells. DENN is identical to MADD (mitogen-activated protein kinase-activating death domain), which interacts with tumor necrosis factor receptor 1 through their death domains. DENN is also homologous to Rab3 GEP, a rat Rab3 GDP/GTP exchange protein. Real-time reverse transcription-polymerase chain reaction analysis showed that DENN expression in cancer cell lines was 26-50 times that in normal cells. The Jurkat human leukemia, PLC/PRF/5 human hepatoma, and NS-1 mouse myeloma cell lines as well as the MRC-5 human fetal lung and Vero monkey kidney cell lines were treated successfully with four separate DENN-targeted antisense oligodeoxynucleotides (ODNs) to abrogate DENN expression. Quantitative assessment of cell viability and apoptosis by flow cytometry via fluorescein diacetate and propidium iodide membrane-integrity tests, terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick end-labeling, and annexin V assays showed that antisense silencing of DENN resulted in markedly more pronounced cell death in cancer cells compared with nonmalignant cells. Antisense-treated cell lines exhibited extensive loss of DNA content, forming distinct sub-G(1) peaks, while cell proliferation diminished significantly. Ultrastructural features of programmed cell death in cells subjected to antisense ODNs were authenticated by electron microscopy. In contrast, transfection of cell lines with a plasmid construct to achieve DENN overexpression augmented cellular proliferation and could reverse the apoptotic effect of antisense and staurosporine treatment. Our findings suggest that DENN is intimately involved in anti-apoptotic and cell-survival processes.
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PMID:Induction of marked apoptosis in mammalian cancer cell lines by antisense DNA treatment to abolish expression of DENN (differentially expressed in normal and neoplastic cells). 1241 May 63

Benzo[a]pyrene (B[a]P) is present in environmental pollution and cigarette smoke. B[a]P has been shown to induce apoptosis in hepatoma cells, human B cells, human ectocervical cells, macrophages, and rat lungs. Nitrogen oxides (NOx) are the other important indoor and outdoor air pollutants. Many studies have indicated that NO gas causes lung tissue damage both by its oxidative properties and free radicals. In our previous study we demonstrated that NO gas induced proliferation of human lung fibroblast MRC-5 cells. In this study we showed that NO gas inhibits B[a]P-induced MRC-5 cells apoptosis by cell cycle analysis. Western blot data revealed that NO gas increased the expressions of anti-apoptosis proteins (Bcl-2 and Mcl-1) and decreased the expression of apoptosis proteins (Bax, t-Bid, cytochrome c, FasL, and caspases) after B[a]P treatment. We further clarified that B[a]P-induced MRC-5 cell apoptosis via JNK1/FasL and JNK1/p53 signals. In conclusion, NO gas inhibited B[a]P-induced MRC-5 cells apoptosis via inhibition of JNK1 apoptosis pathway and induction of Bcl-2 and Mcl-1 anti-apoptosis pathway.
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PMID:Gaseous nitrogen oxide repressed benzo[a]pyrene-induced human lung fibroblast cell apoptosis via inhibiting JNK1 signals. 1604 17

The selectively oncolytic effects of mtHSV, a HSV icp34.5 mutant with lacz gene insertion, on several tumor cells in vitro and its antitumor effects by the intratumoral (IT) route to nude mice loaded the human hepatoma xenografts were explored. The mtHSV could conditionally replicate in and lyse Hep-3B (human hepatoma cells), Hep-2 (human larynx cancer cells) and SPC-A1 (human lung cancer cells), but not MRC-5 (human fibroblast cells). The 125 nude mice loaded with Hep-3B were randomly divided into five treatment groups and given three IT injections with three different dose of the mtHSV, adriamycin (ADM), or vehicle (supernatant of non-infected Vero cells). Significant tumor growth inhibition (30%-70%) was seen in the nude mice treated IT with mtHSV, whereas tumors treated IT with Vero supernatant displayed rapid tumor growth. The results of regular and biochemical blood examination, systemic necropsy and pathological slices showed that mtHSV almost has no side effect on treated mice. RT-PCR results revealed that the replication of mtHSV was exclusively confined to the treated tumors, but not to other organs. Our results provide further preclinical evidence that mtHSV may be used as an oncolytic agent for cancer therapy.
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PMID:Tumor-targeted therapy with a conditionally replicating mutant of HSV-1 induces regression of xenografted human hepatomas. 1635 8

The enniatins A, A1, B, B1, B2 and B3 were purified from hexane-extracts of Fusarium avenaceum rice cultures, using semi-preparative HPLC, after precipitation of lipids. Their toxicity, as well as the toxicity of the related fungal metabolite beauvericin (Bea) and the trichothecenes deoxynivalenol (DON) and T-2 toxin, was tested in two cell lines of human origin (hepatocellular carcinoma-line Hep G2 and fibroblast-like foetal lung cell line MRC-5) by using the BrdU and Alamar Blue assays. All the compounds evoked toxicity in the in vitro assays at the concentrations tested. The MRC-5 cell line in combination with the BrdU assay resulted in the lowest inhibitory concentrations (IC(50)) for exposure with enniatins in the range 0.8 microM (enniatin A) to 3.6 microM (enniatin B). The cytotoxicity of DON in the BrdU assay was comparable to the cytotoxicity of enniatins A, B and Bea in a multiple regression model, while DON was significantly more cytotoxic than the enniatins in the Alamar assay. This study indicates that enniatins, fungal metabolites that are commonly found in grain in Northern Europe, may have an underestimated toxic potential.
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PMID:Cytotoxicity of enniatins A, A1, B, B1, B2 and B3 from Fusarium avenaceum. 1673 43

The diterpene ferruginol has shown a strong protective effect in animal gastric ulcer models. In the present work, we report the gastroprotective effect and cytotoxicity of 16 new semisynthetic ester derivatives of ferruginol. The gastroprotective effect of these compounds was assessed with the HCl/EtOH-induced gastric lesions model in mice and the cytotoxicity was measured using MRC-5 fibroblasts, gastric adenocarcinoma (AGS) and liver hepatoma Hep G2 cells. The compounds were tested for a gastroprotective effect at a single oral dose of 20 mg/kg. The best gastroprotective effect was elicited by ferruginyl nicotinate ( 13), reducing the lesion index by 71 %, while the derivatives ferruginyl chloroacetate ( 2), ferruginyl palmitate ( 6), ferruginyl oleate ( 7), ferruginyl 3,5-dinitrobenzoate ( 11), ferruginyl 3-methylbenzofuran-2-carbonyl ester ( 12), ferruginyl indoleacetate ( 14), ferruginyl indolebutyrate ( 15) and ferruginyl pthalate ( 16) reduced the lesions by 49 - 66 %. The most promising compounds were 11, 13 and 14, presenting a gastroprotective effect higher or similar to that of ferruginol but with a high selectivity towards the tumor AGS cells. Among the three products, the most selective towards AGS cells was 14, followed by 13, and 11 (IC (50) values of 12, 22 and 29 microM, respectively). The isobutyrate 4, inactive as a gastroprotective agent, showed selective cytotoxicity against AGS and Hep G2 cells (IC (50) values of 60 and 39.2 microM, respectively). The cytotoxicity of the above cited compounds towards fibroblasts was >1000 microM. Considering the aliphatic esters of ferruginol, the best gastroprotective activity was found in the C (16) and C (18) derivatives but tended to decrease with increasing aliphatic chain unsaturation. For short-chain esters, the gastroprotective effect could be observed when the chain contained a chlorine atom. For aromatic esters, the presence of nitro groups or a nitrogen atom in the aromatic ring enhanced the gastroprotective activity. The compounds with the best gastroprotective effect and the highest selectivity against tumor cells bear an amino group (indoleacetate and nicotinate) or nitro group (3,5-dinitrobenzoate).
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PMID:New gastroprotective ferruginol derivatives with selective cytotoxicity against gastric cancer cells. 1849 84


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