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 standardized extract of Ginkgo biloba leaves (EGb 761) has been shown to inhibit aggressive human breast cancer cell proliferation both in vitro and in vivo. These results were extended to human glioma and hepatoma cells in vitro suggesting that EGb 761 may have a more widespread application for tumor growth control. To understand the mechanism by which EGb 761 acts to inhibit cell proliferation, we investigated the effects of EGb 761 on human breast cancer, glioma and hepatoma cell transcriptomes by means of various large-scale DNA array techniques. The data presented focus on genes regulated by EGb 761 that are common to the three tumor cell types and for which the data were verified by two different types of DNA microarray and/or RNA (Northern) blot analysis and real-time quantitative PCR. These results could therefore help elucidate the mechanism of cytostatic action of EGb 761 and identify genes important for tumor growth.
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PMID:Common gene targets of Ginkgo biloba extract (EGb 761) in human tumor cells: relation to cell growth. 1239 76

The synthesis of a series of anthraquinone moieties bearing symmetrical sulfur-linked substituents in the 1 and 5 positions is described. These compounds were evaluated for their ability to inhibit the growth of suspended rat glioma C6 cells and human hepatoma G2 cells, respectively. In addition, the redox property of the compounds was determined based on the inhibition of lipid peroxidation in model membranes. Compounds 2a and 2h in this series compared favorably and exhibited the most potent cytotoxicity (0.02, 0.05 microM) against C6 cells in the XTT colorimetric assay. As far as redox properties are concerned, all bis-thio-anthraquinones show potential lipid peroxidation in model membranes very close to that of mitoxantrone (MX), and 2a, 2d, 2e, 2i, 2j, and 2k have more potential than that of MX. The lack of cytotoxicity of compound 2i cannot be related to lipid peroxidation, but the steric and electronic properties of the side-chain substituent maybe impair effective recognition of the cleavable complex. In contrast to MX, 2a and 2h are cytotoxic in rat glioma C6 cells and do not enhance lipid peroxidation in model membranes.
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PMID:Synthesis of symmetrical 1,5-bis-thio-substituted anthraquinones for cytotoxicity in cultured tumor cells and lipid peroxidation. 1241 16

The intervention of pyruvate in glucose metabolism was investigated during hypoxic stress in tumour cell cultures having respiratory capacities under normoxic conditions. Results obtained with nuclear magnetic resonance (NMR) spectroscopy showed that, under normoxic conditions, rat glioma C6 and human hepatoma Hep G2 cell cultures metabolised [(13)C(1)]glucose into lactate, alanine, glutamate and other less abundant metabolites, as already known from the literature. In the absence of pyruvate, during hypoxia or cyanide poisoning, both cell types dramatically decreased the label into glutamate and accumulated [(13)C(3)]glycerol-3-phosphate. The compound was further identified by 31P NMR spectroscopy. The accumulation of the label in glycerol-3-phosphate, however, did not occur when the cells were incubated in the presence of pyruvate. The fate of the latter, followed under normoxic conditions by incubating cells with [(13)C(3)]pyruvate and natural glucose, showed that the label was mainly found in alanine, lactate and glutamate. Anoxic conditions increased the label in lactate and reduced that of glutamate. The data show a metabolic effect of pyruvate during mitochondrial blockade due to severe lack of oxygen in tumour cell lines.
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PMID:Pyruvate reverses metabolic effects produced by hypoxia in glioma and hepatoma cell cultures. 1250 80

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

Tumor hypoxia is an important prognostic indicator for cancer therapy outcome. EF5 [2-(2-nitro-1[ H]-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl)-acetamide] has been employed to measure tumor hypoxia in animals and humans using immunohistochemical methods. EF5 is a lipophilic molecule designed to have a very uniform biodistribution, a feature of obvious benefit for use in PET imaging. The present study represents the first demonstration of noninvasive PET imaging of rat tumors using fluorine-18 labeled EF5. Because of the small tumor size, partial volume effects may result in underestimation of concentration of the compound. Therefore, validation of the PET data was performed by gamma counting of the imaged tissue. The tumor models studied were the Morris 7777 (Q7) hepatoma (n=5) and the 9L glioma (n=2) grown subcutaneously in rats. Our previous studies have demonstrated that early passage 9L tumors are not severely hypoxic and that Q7 tumors are characterized by heterogeneous regions of tumor hypoxia (i.e., Q7 tumors are usually more hypoxic than early passage 9L tumors). The seven rats were imaged in the HEAD Penn-PET scanner at various time points after administration of 50-100 micro Ci (18)F-EF5 in 30 mg/kg carrier nonradioactive EF5. The carrier was used to ensure drug biodistribution comparable to prior studies using immunohistochemical methods. (18)F-EF5 was excreted primarily via the urinary system. Images obtained 10 min following drug administration demonstrated that the EF5 distributed evenly to all organ systems, including brain. Later images showed increased uptake in most Q7 tumors compared with muscle. Liver uptake remained relatively constant over the same time periods. Tumor to muscle ratios ranged from 0.82 to 1.73 (based on PET images at 120 min post injection) and 1.47 to 2.95 (based on gamma counts at approximately 180 min post injection). Tumors were easily visible by 60 min post injection when the final tumor to muscle ratios (based on gamma counts) were greater than 2. Neither of the 9L tumors nor the smallest Q7 tumor met this criterion, and these tumors were not seen on the PET images. These preliminary results suggest that (18)F-EF5 is a promising agent for noninvasive assessment of tumor hypoxia. Plans are underway to initiate a research project to determine the safety and preliminary evidence for the efficacy of this preparation in patients with brain tumors.
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PMID:Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5. 1255 44

The Na(+)/I(-) symporter (NIS) is the plasma membrane glycoprotein that mediates the active uptake of I(-) in the thyroid, ie, the crucial first step in thyroid hormone biosynthesis. NIS also mediates I(-) uptake in other tissues, such as salivary glands, gastric mucosa, and lactating (but not nonlactating) mammary gland. The ability of thyroid cancer cells to actively transport I(-) via NIS provides a unique and effective delivery system to detect and target these cells for destruction with therapeutic doses of radioiodide. Breast cancer is the only malignancy other than thyroid cancer to have been shown to functionally express NIS endogenously. The considerable potential diagnostic and therapeutic use of radioiodide in breast cancer is currently being assessed. On the other hand, exogenous NIS gene transfer has successfully been carried out into a variety of other cell lines and tumors, including A375 human melanoma tumors, and SiHa cervix cancer, human glioma, and hepatoma cell lines. Most notably, significant radioiodine therapy results have been obtained in the NIS-transfected human prostatic adenocarcinoma cell line LNCaP and in NIS-transfected myeloma cells, both of which exhibited prolonged retention of radio iodide even in the absence of I(-) organification. The therapeutic potential of alternative NIS-transported radioisotopes with different decay properties and a shorter, physical half-life than 131I(-), such as beta-emitter 188Rhenium (188ReO(4)-) and alpha-emitter 211Astatine (211At(-)), has been evaluated. In conclusion, it is clear that the remarkable progress made in the last few years in the molecular characterization of NIS has created new opportunities for the development of diagnostic and therapeutic applications for NIS in nuclear medicine.
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PMID:The Na/I symporter (NIS): imaging and therapeutic applications. 1473 56

Antineoplastons work as molecular switches, which regulate expression of genes p53 and p21 through demethylation of promoter sequences and acetylation of histones. They also inhibit the uptake of growth-critical amino acids, such as 1-glutamine and 1-leucine in neoplastic cells. Phase II trials indicate efficacy of antineoplastons in low-grade glioma, brain stem glioma, high-grade glioma, adenocarcinoma of the colon, and hepatocellular carcinoma. The best results were observed in children with low-grade glioma, where 74% of patients obtained objective response, and in patients with adenocarcinoma of the colon with liver metastases whose survival rate of more than 5 years is 91% versus 39% in controls on chemotherapy. Gene array studies will explain antineoplaston-induced changes in gene expression.
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PMID:The present state of antineoplaston research (1). 1531 59

Halofuginone, a widely used alkaloid coccidiostat, is a potent inhibitor of collagen alpha 1 (I) and matrix metalloproteinase 2 gene expression. Halofuginone also suppresses extracellular matrix deposition and fibroblast proliferation. It was recently shown to be effective in suppression of bladder carcinoma and glioma. This study sought to evaluate the effect of treatment with halofuginone on growth of hepatocellular carcinoma (HCC) in mice. Athymic Balb/c mice were injected subcutaneously with 10(7) human hepatoma cells (Hep3B), followed by treatment with halofuginone administered in the diet (750 microg/kg) starting on day 3, before tumour innoculation. The control group was received a normal diet. Mice were followed for survival, tumour volume and serum alpha-fetoprotein (alpha FP). The mechanism of the anti-tumour effect of halofuginone was determined in vitro by assessing tumour cell growth, and by measuring the serum concentrations of interferon-gamma (IFN gamma) and interleukin 2 (IL2). Halofuginone treatment induced almost complete tumour suppression in treated mice. Mortality rates were 10% and 50%, in halofuginone-treated and control mice, respectively (P<0.001). No visible tumour was observed in treated mice, as compared with a 364 mm3 tumour in control mice. Serum alpha FP were 0.1 and 212 ng/ml in treated and control mice, respectively (P<0.005). Halofuginone significantly inhibited HCC proliferation in vitro. Maximal inhibition of 64% of tumour cell growth was observed at a concentration of 10(-8) M. The anti-tumour effect was mediated via a significant increase in IFN gamma and IL2 (90 vs. 35, and 210 vs. 34 pg/ml in treated and control groups, respectively, P<0.005). Treatment with halofuginone effectively suppressed the progression of HCC in mice. This effect may be associated with a direct anti-tumour effect, and/or enhancement of a systemic immune response.
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PMID:Suppression of hepatocellular carcinoma growth in mice by the alkaloid coccidiostat halofuginone. 1517 99

The energy and redox states of the HepG2 hepatoma and the C6 glioma cells were studied by quantifying the levels of ATP, ADP, AMP, GSH, and GSSG. These values were used to calculate the energy charge potential (ECP = [ATP + 0.5ADP]/TAN), total adenosine nucleotides (TAN = ATP + ADP + AMP), total glutathione (TG = [GSH + GSSG]/TAN), and the redox state (GSH/GSSG ratio). For comparison between cell types, the level of each energy metabolite (ATP, ADP, and AMP) was normalized against TAN of the respective cell. The results showed that ATP:ADP:AMP ratio was 0.76:0.11:0.13 for the HepG2 cells and 0.80:0.11:0.09 for the C6 glioma cells. ECP was 0.81 +/- 0.01 and 0.85 +/- 0.01 for the HepG2 and the C6 glioma cells, respectively. GSH/GSSG ratio was 2.66 +/- 0.16 and 3.63 +/- 0.48 for HepG2 and C6 glioma cells, respectively. TG was 3.2 +/- 0.54 for the HepG2 cells and 2.43 +/- 0.18 for the C6 glioma cells, indicating that the level of total glutathione is more than two to three times higher than the total energy metabolites in these cell lines. Following a 3-h incubation in medium containing different concentrations of Cd, there was a dose-dependent decrease in cell viability. The 3-h LC50 for the HepG2 cells was 0.5 mM and that for the C6 glioma cells was 0.4 mM. Cellular TAN decreased with a decrease in cell viability. Upon careful analysis of the energy state, there was a significant increase in relative amount of ATP and decrease in ADP and AMP in both cells as Cd concentration increased from 0 to 0.1, 0.2, and 0.6 mM. However, ECP in both cell lines increased, which indicated that the level of high energy phosphate was adequate. There was also a significant increase in TG and a significant decrease in GSH/GSSG in the C6 glioma cells when cells were exposed to as low as 0.1 mM Cd, which suggested that the cellular redox state was compromised. The HepG2 cells, on the other hand, showed no significant change in both TG and GSH/GSSG level until Cd concentration reached 0.6 mM. Results of the present study also showed that there were differences between the two cells in response to the same level of Cd exposure. The C6 glioma cells were more sensitive to Cd-induced injuries. Although there was a decrease in total amount of high energy phosphate as cell viability decreased, the surviving cells were not devoid of high energy phosphates. The relative abundance of ATP amongst the adenosine nucleotide pool and the increase in ECP could be interpreted as a way the cells signal the conservation of energy utilization in response to the damaged mitochondrial function. This move for energy conservation might be the cause of eventual cell death through the process of apoptosis.
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PMID:Analysis of changes in energy and redox states in HepG2 hepatoma and C6 glioma cells upon exposure to cadmium. 1529 25

The broad-complex, tramtrack (ttk) and bric-a-brac/poxvirus and zinc finger proteins (BTB/POZ) domain is highly conserved in a large family of eukaryotic proteins and is crucial for the latter's diverse roles in mediating interactions among proteins that are involved in transcription regulation and chromatin structures. From a fetal brain cDNA library, we isolated a cDNA of 2489 base pairs (bp) encoding a novel human BTB domain-containing protein named BTBD10. The cDNA contained an open-reading frame (ORF) of 1428 bp encoding a putative 475-amino acid (aa) protein. The BTBD10 gene was located on human chromosome 11p15.2 and consisted of nine exons spanning about 75.2 kilobase pairs (kb) of the human genome. The cDNA microarray analysis showed that BTBD10 was down-regulated in all 18 glioma samples. The expression pattern of BTBD10 gene was examined by multiple tissue cDNA (MTC) panels (Clontech), which showed a ubiquitous expression pattern in the 16 tissues examined with high expression in adult brain, testis and small intestine and weak expression in the heart, lung, liver, kidney, pancreas, spleen, thymus, prostate, ovary and colon. The subcellular localization result revealed that BTBD10 was located specifically in the nucleus of HEK293 and COS7 cell lines, suggesting that it may function in transcriptional regulation. The different expression patterns of BTBD10 in different grades of glioma versus normal brain were also examined by RT-PCR and Northern blot. We also investigated the expression of BTBD10 in hepatocellular carcinoma, ovary cancer and lung cancer, and the results revealed no significant difference in these three tumors. All these data suggested that BTBD10 might play a role in glioma.
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PMID:Molecular cloning and characterization of a novel human BTB domain-containing gene, BTBD10, which is down-regulated in glioma. 1555 95


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