Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of halogen...halide synthons are investigated on the basis of theoretical and crystallographic studies; the simple halogen...halide synthons and the charge assisted halogen...halide synthons. The former interactions were investigated theoretically (ab initio) by studying the energy of interaction of a halide anion with a halocarbon species as a function of Y...X- separation distance and the C-Y...X- angle in a series of complexes (R-Y...X-, R=methyl, phenyl, acetyl or pyridyl; Y=F, Cl, Br, or I; X-=F-, Cl-, Br-, or I-). The theoretical study of the latter interaction type was investigated in only one system, the [(4BP)Cl]2 dimer, (4BP=4-bromopyrdinium cation). Crystal structure determinations, to complement the latter theoretical calculations, were performed on 13 n-chloropyridinium and n-bromopyridinium halide salts (n=2-4). The theoretical and crystallographic studies indicate that these interactions are controlled by electrostatics and are characterized by linear C-Y...X- angles and separation distances less than the sum of van der Waals radius (rvdW) of the halogen atom and the ionic radii of the halide anion. The strength of these contacts from calculations varies from weak or absent, e.g., H3C-Cl...I-, to very strong, e.g., HCC-I...F- (energy of interaction ca. -153 kJ/mol). The strengths of these contacts are influenced by four factors: (a) the type of the halide anion; (b) the type of the halogen atom; (c) the hybridization of the ipso carbon; (d) the nature of the functional groups. The calculations also show that charge assisted halogen...halide synthons have a comparable strength to simple halogen...halide synthons. The nature of these contacts is explained on the basis of an electrostatic model.
 ...
PMID:The nature of halogen...halide synthons: theoretical and crystallographic studies. 1738 25

In this paper, the suitability of novel cationic solid-lipid nanoparticles (SLN) as a nonviral transfection agent for gene delivery was investigated. SLN were produced by using the microemulsion method and Compritol ATO 888 as matrix lipid, dimethyldioctadecylammonium bromide as charge carrier and Pluronic F68 as surfactant. Obtained nanoparticles were approximately 120 nm in size and positively charged, with a zeta potential value equal to +45 mV in twice-distilled water. Cationic SLN were able to form stable complexes with DNA and to protect DNA against DNase I digestion. The SLN-DNA complexes were characterized by mean diameter and zeta potential measurements. In vitro studies on human liver cancer cells demonstrated a very low degree of toxicity of both SLN and SLN-DNA complexes. Further, SLN-DNA complexes were able to promote transfection of liver cancer cells. These data suggest that our cationic SLN may be potentially useful for gene therapy.
 ...
PMID:Novel cationic solid-lipid nanoparticles as non-viral vectors for gene delivery. 1748 98

Magnetic nanoparticles (MNP) with a diameter of 8 nm were modified with different generations of polyamidoamine (PAMAM) dendrimers and mixed with antisense survivin oligodeoxynucleotide (asODN). The MNP then formed asODN-dendrimer-MNP composites, which we incubated with human tumor cell lines such as human breast cancer MCF-7, MDA-MB-435, and liver cancer HepG2 and then analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, quantitative reverse transcription-PCR, Western blotting, laser confocal microscopy, and high-resolution transmission electron microscopy. Results showed that the asODN-dendrimer-MNP composites were successfully synthesized, can enter into tumor cells within 15 min, caused marked down-regulation of the survivin gene and protein, and inhibited cell growth in dose- and time-dependent means. No.5 generation of asODN-dendrimer-MNP composites exhibits the highest efficiency for cellular transfection and inhibition. These results show that PAMAM dendrimer-modified MNPs may be a good gene delivery system and have potential applications in cancer therapy and molecular imaging diagnosis.
 ...
PMID:Dendrimer-modified magnetic nanoparticles enhance efficiency of gene delivery system. 1780 28

A series of octahedral Ru(II) polypyridyl complexes, [Ru(phen)(2)L](2+) (L=R-PIP and PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elementary analysis, (1)H NMR and ES-MS, as well as UV-visible spectra and emission spectra. The antitumor activities of these complexes and their corresponding ligands were investigated against mouse leukemia L1210 cells, human oral epidermoid carcinoma KB cells, human promyelocytic leukemia cells (HL-60) and Bel-7402 liver cancer cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. It was found that the complexes [Ru(phen)(2)L](2+) (L=R-PIP) exert rather potent activities against all of these cell lines, especially for the KB cells (IC(50)=4.7+/-1.3 microM). The binding affinities of these Ru(II) complexes to CT-DNA (calf thymus DNA), as well as the DNA-unwinding properties on supercoiled pBR322 DNA were also investigated. The results showed that these Ru(II) polypyridyl complexes not only had an excellent DNA-binding property but also possessed a highly effective DNA-photocleavage ability. The structure-activity relationships and antitumor mechanism were also carefully discussed.
 ...
PMID:Synthesis, antitumor activity and structure-activity relationships of a series of Ru(II) complexes. 1782 15

Identifying changes at the molecular level during the development of hepatocellular carcinoma is important for the detection and treatment of the disease. The characteristic structural reorganization of preneoplastic cells may involve changes in the microtubule cytoskeleton. Microtubules are dynamic protein polymers that play an essential role in cell division, maintenance of cell shape, vesicle transport, and motility. They are comprised of multiple isotypes of alpha- and beta-tubulin. Changes in the levels of these isotypes may affect not only microtubule stability and sensitivity to drugs but also interactions with endogenous proteins. We employed a rat liver cancer model that progresses through stages similar to those of human liver cancer, including metastasis to the lung, to identify changes in the tubulin cytoskeleton during carcinogenesis. Tubulin isotypes in both liver and lung tissue were purified and subsequently separated by isoelectric focusing electrophoresis. The C-terminal isotype-defining region from each tubulin was obtained by cyanogen bromide cleavage and identified by mass spectrometry. A novel post-translational modification of betaIVb-tubulin in which two hydrophobic residues are proteolyzed from the C-terminus, thus exposing a charged glutamic acid residue, was identified. The unique form of betaIVb-tubulin was quantified in the liver tissue of all carcinoma stages and found to be approximately 3-fold more abundant in nodular and tumor tissue than in control tissue. The level of this form was also found to be increased in lung tissue with liver metastasis. This modification alters the C-terminal domain of one of the most abundant beta-tubulin isotypes in the liver and therefore may affect the interactions of microtubules with endogenous proteins.
 ...
PMID:Increased levels of a unique post-translationally modified betaIVb-tubulin isotype in liver cancer. 1857 Mar 81

A series of novel unsymmetrically N,N'-substituted ureas were synthesized from dehydroabietic acid and their structures were characterized by IR, 1H-NMR, 13C-NMR spectroscopy and single crystal X-ray diffraction. Three six-membered rings of urea 4c exhibited plane, half-chair and chair configurations, respectively. Their cytotoxicity activities against SMMC7721 liver cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The results showed that the title compounds exhibited highly effective cytotoxicity activities against SMMC7721 cells. Their IC50 values are between 8.8 and 14.2 micromol/l. The change of N' substituted groups resulted little difference to the cytotoxicity activities of ureas, which indicated that the cytotoxicity of this kind of ureas depend strongly on the tricyclic hydrophenanthrene structure.
 ...
PMID:Synthesis, structure analysis and cytotoxicity studies of novel unsymmetrically n,n'-substituted ureas from dehydroabietic Acid. 1898 8

Recently, indole-3-acetic acid (IAA) has been introduced as a new cancer therapeutic agent through oxidative decarboxylation by horseradish peroxidase (HRP). The purpose of this study was to determine the therapeutic feasibility of IAA/light combination against liver cancer. SK-HEP-1 cells were irradiated with UVB or visible light (518 nm) in the presence of IAA. Cell viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then, IAA was injected in SK-HEP-1 liver cancer cell-implanted nude mice, and the tumor area was irradiated with intense pulsed light (IPL). Then, tissue was taken for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay and immunohistochemical staining for 8-hydroxy-deoxyguanosine (8-OHdG), p53, caspase-3, and proliferating cell nuclear antigen (PCNA). In vitro experiments demonstrated that IAA alone was not cytotoxic, but activated IAA by HRP or light caused cell death. In vivo experiments showed that IAA/IPL treatment caused regression of tumor cells in SK-HEP-1-implanted nude mice. The TUNEL assay showed that IAA/IPL induced cancer cell apoptosis, and this was confirmed by increases in 8-OHdG, p53, and caspase-3 in IAA/IPL-treated mice. In contrast, IPL alone did not induce apoptosis, indicating that the apoptotic effect resulted from activated IAA by light. In summary, we showed that IAA/light induced tumor regression in SK-HEP-1-implanted nude mice. These results suggest the potential use of IAA/light combination in liver cancer.
 ...
PMID:Experimental photodynamic therapy for liver cancer cell-implanted nude mice by an indole-3-acetic acid and intense pulsed light combination. 1972 Dec 41

We studied the effect of photodynamic therapy with phycobiliproteins on human liver cancer cells in vitro. With 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay), we used two phycobiliproteins, R-phycoerythrin (R-PE) and C-phycocyanin (C-PC) prepared from Porphyra yezoensis, to determine the killing rates and apoptosis rates of human liver cancer cells (SMMC-7721) mediated by laser. When the concentration of R-PE was 120 mg/L, the survival rate of human liver cancer cells was 27% after treated by Argon laser with 100 J/cm2 doses, while the survival rate in the control group (without adding R-PE) was 65%. When the C-PC concentration was 120 mg/L, the survival cell rate was 47% after treated by He-Ne laser with 35 J/cm2 dose, while the survival rate in the control group (without adding C-PC) was 70%. After handled only with these two kinds of phycobiliproteins for 72 h, the growth of cancer cells presented significant inhibition. The maximal inhibition rates reached up to 31% with R-PE (120 mg/L concentration) and 27% with C-PC (250 mg/L concentration) respectively. After irradiated by laser for 8 h, the maximal cell apoptosis rates were 31.54% with R-PE and 32.54% with C-PC, respectively. It indicated that R-PE and C-PC extracted from Porphyra yezoensis could develop to new photosensitizers for cancer photodynamic therapy.
 ...
PMID:[Photodynamic effect of two kinds of phycobiliproteins on human liver cancer cell line SMMC-7721 in vitro]. 1993 87

The interactions of a ruthenium porphyrin complex [(Py-3')TPP-Ru(phen)(2)Cl]Cl (phen=1,10-phenanthroline, (Py-3')TPP=5-(3'-pyridyl-10,15,20-triphenylporphyrin) (1) and its heterometallic derivatives, [Ni(Py-3')TPP-Ru(phen)(2)Cl][PF(6)] (2) and [Cu(Py-3')TPP-Ru(phen)(2)Cl][PF(6)] (3), with calf thymus DNA have been investigated by spectroscopic and viscosity measurements in this study. The results showed that these synthetic complexes can bind to double strand helix DNA in groove binding mode, and the intrinsic binding constants of complexes 1, 2 and 3, as calculated according to the decay of the Soret absorption, are (1.35+/-0.5) x10(5)M(-1) (s=4.2), (1.29+/-0.5)x10(5)M(-1) (s=5.6) and (1.22+/-0.5)x10(5)M(-1) (s=6.2) (s is the binding-site size), respectively, which are consistent with those obtained from ethidium bromide-quenching experiments. Further investigations on the photocleavage properties of these complexes on plasmid pBR 322 DNA showed that complexes 1, 2 and 3 could cleave single chain DNA and convert DNA molecules from supercoiled form to the nicked form. As determined by MTT assay, the complexes were also identified as potent antiproliferative agents against A375 human melanoma cells, MCF-7 human breast adrenocarcinoma cells, Colo201 human colon adenocarcinoma cells and HepG2 human liver cancer cells. Complex 1 inhibits the growth of A375 cells through induction of apoptotic cell death and G0/G1 cell cycle arrest. Further investigation on intracellular mechanisms indicated that Complex 1 induced depletion of mitochondrial membrane potential (DeltaPsi(m)) in A375 cells through regulating the expression of pro-survival and pro-apoptotic Bcl-2 family members. Our results suggest that ruthenium porphyrin complexes could be candidates for further evaluation as chemopreventive and chemotherapeutic agents for human cancers.
 ...
PMID:DNA binding and photocleavage properties and apoptosis-inducing activities of a ruthenium porphyrin complex [(Py-3')TPP-Ru(phen)2Cl]Cl and its heterometallic derivatives. 1995 51

Recently, dendrimers have been widely used in medical applications such as drug delivery and gene transfection. In this study, a pH-sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and polyethylene glycol (PEG) modified by lactose (LA-PEG-b-PSD) was synthesized. The pK(a) value of the LA-PEG-b-PSD was also measured. Then, polyamidoamine (PAMAM) complexes were prepared with PAMAM (G4.0) and LA-PEG-b-PSD by electrostatic interaction. To investigate drug pH-sensitive release in vitro, doxorubicin (DOX) was loaded in PAMAM. A higher drug cumulative release from LA-PEG-b-PSD/PAMAM complexes in phosphate buffered saline (PBS) was found at pH 6.5 than at pH 7.4. The cytotoxicity and cellular uptake of PAMAM complexes were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and confocal microscopy. LA-PEG-b-PSD/PAMAM/DOX complexes were able to enhance the cytotoxicity of DOX against HepG2 cells at pH 7.4. Confocal microscopy showed a higher cellular uptake of PEG-b-PSD/PAMAM complexes at pH 6.5. PAMAM complexes modified by lactose showed a higher affinity for hepatic cancer cells than those without lactose at pH 7.4. These results suggest that LA-PEG-b-PSD/PAMAM complexes exhibit selective targeting and cytotoxicity against HepG2 cells. In vivo antitumor studies showed that the LA-PEG-b-PSD/PAMAM/DOX complexes displayed higher antitumor efficacy compared with non-targeted PAMAM/DOX and DOX solution. These results indicate that this strategy should be applicable to the treatment of liver cancers.
 ...
PMID:Drug pH-sensitive release in vitro and targeting ability of polyamidoamine dendrimer complexes for tumor cells. 2121 49


<< Previous 1 2 3 4 5 6 7 8 Next >>