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)

As the somatostatin analog octreotide suppresses pituitary GH secretion and circulating IGF-1 levels, we examined its effects on human hepatoma (hep G2) cells which selectively express IGFBP-1. Octreotide (60 nM) stimulated IGFBP-1 up to 4.1-fold (p < 0.001 after 24 hrs). Induction of IGFBP-1 was first detectable after 12 hrs of 6 nM octreotide (1.5-fold, p < 0.03), and was confirmed by ligand blotting. Cholera toxin and forskolin induced IGFBP-1 independently and were also additive with octreotide. IGFBP-1 mRNA expression was induced 2.7-fold by octreotide. Thus, octreotide induces basal and stimulated IGFBP-1 in hepatocytes independently of insulin and GH. As IGFBP-1 may regulate peripheral IGF-1 action, induction of IGFBP-1 represents a novel pituitary-independent mechanism for octreotide action.
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PMID:Somatostatin analog induces insulin-like growth factor binding protein-1 (IGFBP-1) expression in human hepatoma cells. 138 3

The gene for human interleukin-1 beta was cloned from SK-hep-1 hepatoma cellular RNA and expressed at high levels in Escherichia coli both as the naturally processed form (rIL-1 beta) and as a variant with an additional sequence of three amino acids on the N-terminus (rIL-1 beta +). Expressed protein was purified to homogeneity by a sequence of steps, which included low pH incubation, adsorption and desorption from Procion Red Sepharose, sizing on a Superose 12 fast-performance liquid chromatography (FPLC) column, and anion exchange chromatography on QAE Sepharose. The final step provided a biologically active protein that migrates on two-dimensional (2-D) gels as a single spot with a pI of 6.7 +/- 0.2 and a molecular mass of 17,500 daltons. Concentrated solutions of rIL-1 beta have produced crystals by ammonium sulfate precipitation. The crystals are tetragonal, show the symmetry of space group P4(1) or its enantiomer, have lattice constants of a = 58.46 (1) and c = 77.02 (3) A, and scatter to at least 2 A resolution. A structure determination based on these crystals is under way.
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PMID:Crystallization of purified recombinant human interleukin-1 beta. 284 Jun 56

9-Alkoxy-1,5-dichloroanthracenes were successfully prepared. Their cytotoxicity was evaluated in vitro on rat glioma C6 cell lines and human hepatoma G2 cell lines, respectively. Alkylation of 1,5-dichloro-9(10H)-anthracenone with either the appropriate alcohols or alkyl chlorides in the presence of sulfuric acid or sodium hydride, respectively, furnished this structural class of anthracenes. Contrary to mitoxantrone, cytotoxic properties were observed as documented by the reactivity of the novel compounds and potent in vitro activity against C6 cells and hep G2 cells over a wide range of structural variants. Among these compounds, 5c, 5h, 5l and 5n are potent cytotoxins. They inhibit C6 cell growth in culture, indicated by using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt (XTT) colorimetric assay. By using this assay it was also shown that 5c, 5d and 5l possess potent cytotoxicity on hep G2 cells. The most active compound displaying in vitro cytotoxicity was the 9-butoxy derivative 5h with IC50 values 0.02 microM against C6 cells, as compared with mitoxantrone with IC50 values 0.07 microM. The most active compound displaying in vitro cytotoxicity against hep G2 cells was 5c with IC50 values 1.7 microM (mitoxantrone: 0.8 microM). Structure-activity relationships (SAR) of these compounds with respect to the nature of the alkoxy substitution in the 9 position are discussed for both cell lines.
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PMID:Synthesis and cytotoxicity of 9-alkoxy-1,5-dichloroanthracene derivatives in murine and human cultured tumor cells. 1193 78

Symmetrical bis-substituted anthraquinones were successfully prepared and demonstrated potent cytotoxicity against the growth of suspended murine and human tumors, i.e. rat glioma C6 cells and human hepatoma G2 cells.We report here a convenient synthetic pathway that leads to symmetrically substituted 1, 5-bisacyloxyanthraquinone derivatives. Acylation of the hydroxyl group of 1, 5-dihydroxyanthraquinone with the appropriate acyl chlorides in the presence of pyridine or sodium hydride, respectively, furnished this structural class of anthraquinones. The bis(butyryloxy) analog 2b, bis(2-chlorobenzoyl) analog 2f, and bisphenylpropionyloxy analog 2n exhibit potent cytotoxicity in inhibition of human hep G2 cell growth in culture, as determined by using XTT colorimetric assay, while their antiproliferative activity is markedly enhanced and is comparable to that of the anticancer agent mitoxantrone. In addition, redox properties of the compounds for the inhibition of lipid peroxidation in model membranes were determined. Compounds 2n also exhibited stronger antioxidant activity than ascorbic acid, (+)-alpha-tocopherol, and anthrarufin. Biological evaluation and SAR studies of these symmetrical anthraquinones have been performed and the results are discussed.
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PMID:Synthesis of symmetrical 1,5-bisacyloxyanthraquinone derivatives and their dual activity of cytotoxicity and lipid peroxidation. 1250 96

The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles.
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PMID:Preparation and Characterization of Paclitaxel-loaded PLGA nanoparticles coated with cationic SM5-1 single-chain antibody. 1792 7

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging (MRI). In this study, a targeted contrast agent (SM-USPIO) was prepared by conjugating coprecipitated USPIO to a humanized SM5-1 antibody which can specifically react with human hepatocellular carcinoma (HCC) cells. The binding and internalization of SM-USPIO to the HCC cell line ch-hep-3 was confirmed by flow cytometry and confocal microscopy. Furthermore, SM-USPIO was demonstrated to be able to selectively accumulate in the tumor cells, resulting in a marked decrease of MRI T2-weighted signal intensity. Biodistribution studies demonstrated the efficient accumulation of SM-USPIO in the ch-hep-3 tumor in nude mice. The in vivo study in the ch-hep-3 tumor-bearing nude mice indicated that MRI using the SM-USPIO as contrast agent possessed good diagnostic ability, suggesting that SM-USPIO had the potential to be a promising targeted contrast agent for diagnosis of HCC.
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PMID:Development of SM5-1-conjugated ultrasmall superparamagnetic iron oxide nanoparticles for hepatoma detection. 1862 Oct 23

Mice lacking hepatocyte IKKbeta (Ikkbeta(Delta hep)) are defective in TNFalpha-activation of hepatocellular transcription factor NF-kappaB, and highly susceptible to hepatotoxicity. Following diethylnitrosamine (DEN) exposure, Ikkbeta(Delta hep) mice develop more hepatocellular carcinoma (HCC) than control mice due partly to enhanced DEN-induced hepatocyte death. Here we show that Ikkbeta(Delta hep) hepatocytes display growth advantages over normal hepatocytes consisting of precocious PCNA and cyclin D1 expression during liver regeneration (shortened hepatocyte G(0)-->G(1) transitions), and enhanced recovery efficiency, cyclin D1 expression and cell proliferation after plating. Ex vivo deletion of Ikkbeta also accelerates hepatocyte growth. Ikkbeta(Delta hep) hepatocyte proliferative responses show heightened sensitivity to TGFalpha and TNFalpha, and heightened expression of fibronectin, collagens I/III, nidogen, beta-actin and integrin beta1 mRNAs. These findings suggest that altered mitogen signaling and expression of extracellular matrix and its associated components underlie growth advantages. Increased HCC development in Ikkbeta(Delta hep) mice may also be caused by growth advantages of surviving Ikkbeta-deleted hepatocytes.
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PMID:Targeted deletion of hepatocyte Ikkbeta confers growth advantages. 1917 Nov 22

To study the anticancer activities of curcumin on human hepatocarcinoma cell line Sk-hep-1 and its related molecular mechanism which has not been elucidated. In the present study,we showed that curcumin inhibited proliferation of Sk-hep-1 cells in a dose-dependent manner through MTF assay. The effect of curcumin on apoptosis in Sk-hep-1 cells was investigated by DAPI staining and the various apoptosis was observed in hepatocarcinoma cell lines Sk-hep-1, HepG2 and Hep3B, but not in normal liver cell line Chang's liver with curcumin treatment. Cell cycle analysis results showed that curcumin treatment resulted in dramatic accumulation of Sk-hep-1 cells at the G0/G1 or G2/M phase. The effect of curcumin on the expression of anti-apoptosis genes (Survivin and BCl-xL) and drug resistance genes (DRG2 and MDR1) was studied by reverse transcription-polymerase chain reaction (RT-PCR). The expression of MDR1 mRNA was significantly decreased in Sk-hep-1 cells treated with curcumin, while no alterations in the amount of DRG2 and anti-apoptosis genes' mRNA levels were found. These results indicate that curcumin is able to inhibit proliferation and induce apoptosis in Sk-hep-1 cells and it may cause by down-regulating the expression of MDR1 mRNA.
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PMID:[Anticancer activities of curcumin on human hepatocarcinoma cell line Sk-hep-1]. 2045 49

The expression profiles of the erythropoietin producing hepatocellular carcinoma (Eph) receptor family of tyrosine kinases have been previously shown to provide molecular signatures of normal breast cells, breast tumor cells and invasive breast carcinoma cells. In particular, the expression of EphB6 receptor is lost in invasive breast carcinoma cell line MDA-MB-231. The comparative proteomic profiles of native and EphB6-expressing MDA-MB-231 cells using difference gel electrophoresis (DIGE) and liquid chromatography-mass spectrometry of selected proteins are presented in this study. The expression of more than 70 proteins was significantly altered in EphB6-transfected MDA-MB-231 cells. These altered proteins are involved in glycolysis, cell cycle regulation, tumor suppression, cell proliferation, mitochondrial metabolism, mRNA splicing, DNA replication and repair. Although the majority of these proteins have been implicated in tumorigenesis, the impairment of energy homeostasis and altered regulation of signaling pathways appear to be noteworthy targets of EphB6. Based on the identities of altered proteins and the pathways regulated by these proteins, this study suggests that the interactions of EphB6 with a wide variety of proteins lead to altered proteomic profile of EphB6-transfected MDA-MB-231 cells.
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PMID:Tyrosine kinase-deficient EphB6 receptor-dependent alterations in proteomic profiles of invasive breast carcinoma cells as determined by difference gel electrophoresis. 2095 60

Mallory-Denk Bodies (MDB) are important as investigators, suggesting MDB as an indicator of the histologic severity of chronic hepatitis, causes of which include hepatitis C, primary biliary cirrhosis (PBC), and nonalcoholic fatty liver disease (NAFLD). Matteoni et al scored MDB in patients with NAFLD as none, rare and many, and reported that MDB plays a prominent role in this classification scheme in an earlier classification system. In this study, we evaluated 258 patients with chronic hepatitis due to metabolic, autoimmune and viral etiologies. Liver biopsy samples were evaluated with hematoxylin and eosin, periodic acid-Schiff-diastase, Gordon and Sweet's reticulin, Masson's trichrome, and iron stains. Both staging and grading were performed. Additionally, MDB were evaluated and discussed for each disease. We examined patients with nonalcoholic steatohepatitis (NASH; 50 patients), alcoholic hepatitis (10 patients), PBC (50 patients), Wilson disease (WD; 20 patients), hepatitis B (50 patients), hepatitis C (50 patients) and hepatocellular carcinoma (HCC; 30 patients). Frequency of MDB was as follows; NASH: 10 patients with mild in 60% and moderate in 40% and observed in every stage of the disease and frequently seen in zone 3. PBC: 11 patients with mild in 10%, moderate in 70%, and cirrhosis in 20%, and frequently seen in zone 1. WD: 16 patients with moderate and severe in 60% and cirrhosis in 40% and frequently seen in zone 1. Hep B: 3 patients with mild in 66% and severe in 34%. Hep C: 7 patients with mild in 40% and moderate in 60% and observed in every stage. HCC: 3 patients with hep B in 2 patients. We found that there is no relationship between MDB and any form of chronic hepatitis regarding histologic severity such as alcoholic steatohepatitis and NAFLD and variable zone distribution by etiology.
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PMID:Mallory-Denk Bodies in chronic hepatitis. 2163 25


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