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)

Cancer is a genomic functional disease with features of oncogene activation and tumor suppressor inactivation. These genomic features have resulted in the limited effectiveness of conventional therapies and therefore forced considerable efforts to explore new types of anticancer agents. It has been clear that chemically synthesized or in vivo-expressed short interfering RNA (siRNA) can specifically and effectively direct homology-dependent post-transcriptional gene silencing. In the present study, we intended to investigate whether siRNA could suppress the proliferation of human cancer cells through interfering oncogene activities and recovering the functions of tumor-suppressor gene. Single siRNA or combinatorial siRNAs were successfully transfected into HeLa cells, lung adenocarcinoma cells, hepatoma cells, ovarian carcinoma cells, and melanoma cells with cationic lipid complexes. These siRNA molecules not only specifically knocked down their cognate targets such as bcl-2, cdk-2, mdm-2, pkc-alpha, tgf-beta1, H-ras, vegf, and GFP mRNAs, but also effectively suppressed the proliferation of cancer cells to different extents. These data suggest that (1) all these human cancer cells preserve RNAi machinery; (2) chemically synthesized and vector-driven siRNAs can be incorporated into intrinsic RNAi system for silencing target mRNA molecules; and (3) the combination of different siRNAs inhibits the growth and proliferation of cancer cells.
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PMID:siRNA agents inhibit oncogene expression and attenuate human tumor cell growth. 1456 90

Cationic lipids have been often used as one of the major components in making most promising non-viral gene delivery systems, whereas sodium cholate, a surfactant so-called edge activator has been used in preparing ultradeformable and ultraflexible liposomes called Transfersomes. Using both a cationic lipid, DOTAP and sodium cholate, a novel formulation of ultradeformable cationic liposome (UCL) has been prepared. The average particle size of this formulation was approximately 80 nm. The physical and chemical stabilities at two different temperatures (4 degrees C and 20 degrees C) were also evaluated for 60 days. The ultradeformability of new formulation was also assessed, and it has been proved that the formulation is deformable. In vitro transfection efficiency of plasmid DNA/UCL was assessed by the expression of green fluorescent protein (GFP) in four cell lines, OVCAR-3 (human ovarian carcinoma cells), HepG2 (human hepatoma cells), H-1299 (human lung carcinoma cells) and T98G (human brain carcinoma cells). The optimal ratio of DNA to liposome for maximal transfection efficiency was 1:14 (w/w) in all the cell lines except for the human brain carcinoma cells. The same formulation was tested for in vivo transfection efficiency and its retention time within the organs by applying the DNA/UCL complexes on hair-removed dorsal skin of mice non-invasively. It was found that genes were transported into several organs for 6 days once applied on intact skin.
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PMID:In vitro and in vivo transfection efficiency of a novel ultradeformable cationic liposome. 1458 18

Three new xanthanolides, 1-3, along with nine known compounds, were isolated from the aerial parts of Carpesium longifolium. The structures of the new compounds were elucidated as 1beta,4beta-epoxy-5beta-hydroxy-10alphaH-xantha-11(13)-en-12,8beta-olide (1), 1beta,4beta,4alpha,5beta-diepoxy-10alphaH,11alphaH-xantha-12,8beta-olide (2), and 4-acetoxy-1beta,5beta-epoxy-10alphaH-xantha-11(13)-en-12,8beta-olide (3) by spectroscopic methods including IR, EIMS, HRESIMS, and 1D and 2D NMR experiments. Parthenolide and michelenolide exhibited significant cytotoxic activity against cultured SMMC-7721 (human hepatoma) and HO-8910 (human ovarian carcinoma) cells.
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PMID:Xanthanolides, germacranolides, and other constituents from Carpesium longifolium. 1469 95

From the roots of Asparagus gobicus, four new nor-lignans, 3'-methoxynyasin, iso-agatharesinol, gobicusins A, B and one new steroidal saponin, 3-O-[beta-D-xylopyranosyl(1-4)-beta-D-glucopyranosyl(1-2)-beta-D-glucopyranosyl]-(25S)-5beta-spirostan-3beta-ol (11) were isolated, together with twelve known compounds. The structures of the new compounds were established by spectroscopic methods including 2D-NMR techniques (1H-1H COSY, HMBC, HMQC) and chemical transformations. Nyasol (5) and 11 exhibited remarkable in vitro cytotoxic activity against cultured HO-8910 (human ovarian carcinoma) and Bel-7402 (human hepatoma) cells with IC50 vales of 30.6 and 29.4 microM, 5.2 and 5.2 microM, respectively.
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PMID:Nor-lignans and steroidal saponins from Asparagus gobicus. 1512 91

Lysophosphatidic acid (LPA; 1-acyl-2-hydroxy-sn-glycero-3-phosphate) is a lipid growth factor that stimulates the proliferation of ovarian cancer cells. Recent studies indicate that elevation of cellular cAMP levels inhibits ovarian epithelial cancer cell growth. In this study, we investigated the effects of elevating cellular cAMP levels on LPA stimulation of OVCAR-3 ovarian cancer cell growth and on LPA stimulation of the serum response factor (SRF) transcription factor. Treatment of OVCAR-3 cells with forskolin and isobutylmethylxanthine (IBMX; 3-Isobutyl-1-methylxanthine) inhibited LPA stimulation of growth. LPA stimulation of SRF-mediated transcription was also inhibited in OVCAR-3 cells that were incubated with forskolin, dibutyryl cyclic AMP (db-cAMP), or paired cAMP analogues (N(6)-mono-tert-butylcarbamoyladenosine-3', 5'-cyclic monophosphate [6-MBC-cAMP] and Sp-5,6-DCl-BIMPS), which selectively activate type II protein kinase A. In contrast, incubation with a cAMP analogue (8-(4-chloro-phenylthio)-2'-O-methyadenosine-3',5'-cyclic monophosphate [8CPT-2Me-cAMP]) that specifically activates the cAMP inducible Rap1 exchange factor, Epac, did not inhibit SRF. Similar results were obtained when HepG2 hepatoma cells, which do not express endogenous LPA receptors, were transfected with a single LPA receptor (LPA(1)). We observed that treatment of OVCAR-3 cells with forskolin greatly reduced both F-actin staining and focal adhesion labeling with anti-paxillin antibodies. Treatment of OVCAR-3 cells with the F-actin stabilizing compound, jasplakinolide, prevented the protein kinase A (PKA)-mediated inhibition of SRF. These results suggest that PKA inhibits LPA stimulation of SRF by promoting the dissolution of F-actin and that this is likely to contribute to the cAMP-mediated inhibition of ovarian cancer cell growth.
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PMID:Protein kinase A inhibits lysophosphatidic acid induction of serum response factor via alterations in the actin cytoskeleton. 1524 9

1. The prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) is activated by Escherichia coli nitroreductase (NTR) to a potent DNA-crosslinking agent. 2. Virus-mediated expression of NTR in tumour cells sensitizes them to CB1954 in vitro and in vivo, providing the basis for a strategy of cancer gene therapy. 3. A phase I trial of CB1954 in cancer patients has been completed, documenting the pharmacokinetics and establishing an acceptable dose. Subsequent trials of the replication-defective adenovirus CTL102 in patients with resectable tumours have documented expression of NTR in injected colorectal liver metastases, hepatocellular carcinoma, head and neck cancer and prostate cancer. Trials combining CTL102 and CB1954 are underway. 4. An oncolytic (replication-competent) adenovirus vector allowed increased expression of NTR in vitro and in a mouse tumour model, resulting in a greater reduction in tumour growth when combined with CB1954 treatment. 5. Alternative prodrugs may eventually prove superior to CB1954; a nitroaryl phosphoramide mustard prodrug activated by NTR shows a greater therapeutic index than CB1954 in a human ovarian carcinoma. 6. The crystal structure of NTR provided the basis for site-directed mutagenesis, which has identified a number of mutants with improved kinetics of CB1954 activation. These can provide improved cell sensitization to CB1954. Combinations of these are being tested. 7. The basis for a positive selection for improved NTR variants has been demonstrated.
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PMID:Nitroreductase: a prodrug-activating enzyme for cancer gene therapy. 1556 99

Incorporation of doxorubicin into polyethylene glycol-coated (pegylated) liposomes increases the therapeutic index, prolongs circulation time and enhances tumor localization. Pegylated liposomal doxorubicin (PLD) is an established therapeutic agent in epithelial ovarian carcinoma (EOC), breast carcinoma or Kaposi's sarcoma, and PLD administration results in reduction of toxicity. Addition of regional hyperthermia increases liposome extravasation, induces the doxorubicin release from the liposomes, and the combination of hyperthermia and doxorubicin itself may be supra-additive, resulting in enhanced antitumor efficacy in the heated region. Encouraging results have been reported for the combination of PLD and hyperthermia in EOC, breast carcinoma and hepatocellular carcinoma.
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PMID:Liposomal doxorubicin combined with regional hyperthermia: reducing systemic toxicity and improving locoregional efficacy in the treatment of solid tumors. 1567 74

A urine tumor marker, diacetylspermine, was examined in patients with recurrent pancreato-biliary carcinoma, liver tumor, lung carcinoma and gynecologic malignancies. The urine marker increased together with recurrence, suggesting a recurrence monitoring marker at the outpatient ward. Regarding hepatocellular carcinoma, the sensitivity of the urine marker was as high as conventional markers such as AFP and PIVKA II. Synchronous examination of serum and urine markers showed a higher sensitivity than the single serum or urine marker for hepatocellular carcinoma. The sensitivity for non-advanced hepatocellular carcinoma was 50%, while that for advanced hepatocellular carcinoma was 83%. The urine marker may be useful to detect non-advanced hepatocellular carcinoma. The sensitivity for lung cancer was 83% and that for Stage I or II was 82%. Concerning uterine cervical tumor, the value of the urine marker increased with the grade of dysplasia. The sensitivity for ovarian carcinoma was 100%, while that for benign ovarian tumor was 0%. These findings suggest that urine diacetylspermine is a useful tumor marker in hepatocellular carcinoma, lung cancer and gynecologic malignancy as well as pancreatobiliary carcinoma.
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PMID:[Urine diacetylspermine as a novel tumor marker]. 1579 46

Eight new camphorato platinum complexes have been synthesized and evaluated for their in vitro cytotoxicity against HL-60 human leukemia, 3AO human ovarian carcinoma, BEL-7402 human hepatocarcinoma, and A549 human lung carcinoma cell lines. Most complexes showed good cytotoxic activity against the above-selected cell lines. Among the complexes, two compounds were assayed for their in vivo antitumor activity against LS-174T human colon carcinoma cells implanted in mice. One complex exhibited not only higher in vivo antitumor activity, but also less toxicity than oxaliplatin when it was administered intravenously at a dose of 6 mg/kg three times.
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PMID:Potential new antitumor agents from an innovative combination of camphorato, a ramification of traditional Chinese medicine, with a platinum moiety. 1595 27

A series of novel cisplatin-type platinum complexes, formulated as [PtA2(OCOCH2OR)2] (A2 = two monoamines or one diamine, R is an alkyl group), were designed, characteristic of alkoxyacetate as carboxylato ligands. The pertinent compounds were prepared and characterized by elementary analyses, IR, 1H NMR, and ESI-MS spectra. The cytotoxic activities of compound 1a in vitro toward HL-60 human leukemia and BEL-7402 human hepatocellular carcinoma cell lines were pioneeringly studied. Then, compounds 1b-3d were evaluated for their in vitro cytotoxicity against Ramos human lymphoma, 3AO human ovarian carcinoma, and A549 human non-small cell lung cancer cell lines. Most of them showed better cytotoxic activity than carboplatin against above selected cell lines.
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PMID:Novel cisplatin-type platinum complexes and their cytotoxic activity. 1655 55


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