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)

Pingyangmycin (PYM), produced by Streptomyces pingyangensis n. sp., was found to be identical to bleomycin A5. In the present study, a comparative observation was carried out in 10 human cancer cell lines. As determined by a colony-forming assay, the dose-response curves obtained from cells exposed to PYM for 1 h were of one type only: biphasic exponential. The sensitivities of these cells derived from different types of tumors, however, varied with a broad range of ID50 values (0.03-0.82 microgram/ml). A hepatoma cell line (BEL-7402) and three lines derived from squamous carcinomas of the esophagus (Eca109 and CaEs17) or the nasopharynx (CNE) were relatively sensitive (ID50 less than 0.20 microgram/ml) to PYM which is known to have clinical activity against these diseases. Two gastric adenocarcinoma cell lines (MGc80-3 and BGC-823) and a pulmonary adenocarcinoma cell line (SPC-A-1) appeared to be less sensitive to the drug, with ID50 values of 0.21-0.47 microgram/ml. PYM was 7-fold more effective against LTEP-78 cells derived from pulmonary squamous carcinoma as opposed to SPC-A-1 cells, resulting in a low ID50 value of 0.04 microgram/ml. However, PYM as a single agent has not yet received full evaluation in relation to this type of lung cancer. In contrast with other cell lines of squamous cancer origin, HeLa and CC-801 cells derived from uterine cervix carcinomas which have been evaluated as highly responsive to PYM had the highest ID50 values (greater than 0.70 microgram/ml).
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PMID:[Anticancer spectrum of pingyangmycin in vitro]. 170 47

The synthesis and structure of the primary translation product of apo AII in a human liver poly(A+) mRNA primed cell-free system and its cotranslational modification was studied parallel to studies in vivo with Hep G2 cells, a human hepatoma cell line. The primary translation product is a preproprotein containing 100 amino acid residues, which is cleaved by the signal peptidase of endoplasmic reticulum to pro-apo AII with the loss of the N-terminal pre-sequence consisting of 18 amino acid residues. Hep G2 cells contain about equal amounts of the proform of apolipoprotein AII and of mature apo AII. Approximately in the same ratio pro- and mature apo AII are secreted into the medium. Determination of the partial amino-acid sequence by automated Edman degradation of the labelled prepro- and proforms of apo AII led to the segmentation of the N-terminus of the primary translation product, consisting of 23 amino acid residues, into the pre-sequence (18 residues) and the pro-sequence (5 residues) with terminal Arg-Arg-residues at the cleavage site to apo AII. We must therefore correct our previously postulated 17 and 6 residues containing segmentation. So far no information has been obtained in which compartment and at what stage of posttranslational events the dimerization occurs by formation of the single disulfide bond at position Cys6 in the mature apo AII structure, leading to the symmetrical molecule.
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PMID:Synthesis and processing of human serum apolipoprotein AII in vitro and in Hep G2 cells. 298 98

A two-step procedure to incorporate 125I-iodotyrosine into protein synthesized in a reticulocyte lysate is described. In the first step, the iodination of tyrosyl tRNA was catalyzed by a solid-state glycouril compound. More than one-third of 200 microCi of radioiodine became bound to 70 micrograms of aminoacyl tRNA after 15 min at 0 degrees C. The isotope was distributed in a three-to-one ratio of monoiodotyrosine to di-iodotyrosine. In the second step, the soluble product of the radioiodination was transferred directly into a nuclease-treated reticulocyte lysate coded with RNA isolated from the human hepatoma cell line Hep G2. Fractional recovery of radioiodine in nascent protein was maximally 7.6%. Reaction of the product of translation with antibody against alpha-antitrypsin separated an 125I-containing protein having a molecular weight estimated as 47,000. The synthesis of unprocessed alpha-antitrypsin was confirmed by cleavage of the labeled protein with leader peptidase and by its displacement from immunocomplex formation with purified alpha-antitrypsin. The amount of 125I incorporated into alpha-antitrypsin was proportionate to iodinated tRNA additions up to a concentration of 70 micrograms/ml. The synthesis of alpha-antitrypsin as detected in radioautograms after gel electrophoresis was more than twice as sensitive using radioiodinated aminoacyl tRNA as compared with [35S]methionine. Iodine labeling of thyroxine-binding globulin was also demonstrated in the translation product of Hep G2 RNA. Since the specific activity of the radioiodine is high and the means for detection of the isotope efficient, the method described can facilitate the demonstration of quantitatively minor translation products.
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PMID:Direct application of radioiodinated aminoacyl tRNA for radiolabeling nascent proteins. 392 14

Hepatitis C virus (HCV) is the major causative pathogen associated with liver cirrhosis and hepatocellular carcinoma. The virus has a positive-sense RNA genome encoding a single polyprotein with the virion components located in the N-terminal portion. During biosynthesis of the polyprotein, an internal signal sequence between the core protein and the envelope protein E1 targets the nascent polypeptide to the endoplasmic reticulum (ER) membrane for translocation of E1 into the ER. Following membrane insertion, the signal sequence is cleaved from E1 by signal peptidase. Here we provide evidence that after cleavage by signal peptidase, the signal peptide is further processed by the intramembrane-cleaving protease SPP that promotes the release of core protein from the ER membrane. Core protein is then free for subsequent trafficking to lipid droplets. This study represents an example of a potential role for intramembrane proteolysis in the maturation of a viral protein.
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PMID:Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. 1214 99

Within the minimum LOH region on chromosome 17p13.3 deleted in hepatocellular carcinoma, a novel human plasma membrane-associated gene, named CT120, was isolated from a human kidney cDNA library using electronical cloning and RACE. The novel gene CT120 consists of 2145bp and encodes a protein with 257 amino acids. Database search revealed that homologs of CT120 exist in different organisms from plant to animal kingdoms, which suggests that CT120 is a highly conserved gene during biological evolution. Different expression patterns of CT120 were observed in many different human normal tissues and in various human tumor cell lines. Transcript of CT120 was not detectable in normal lung tissue, but was abundant in SPC-A-1 (human epithelial-like lung adenocarcinoma) cell line, suggesting that CT120 may be involved in lung cancer development. Subcellular localization analysis showed that CT120 is a novel membrane-associated protein. CT120 can interact with SLC3A2 (member 2 of solute carrier family 3) and GGTL3B (isoform of gamma-glutamyltranspeptidase-like 3) in eukaryotic cells by yeast two-hybrid screen and co-immunoprecipitation assay, which suggested that CT120 may assume very essential physiological functions involved in amino acid transport and glutathione metabolism.
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PMID:Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism. 1227 Jan 27

We have cloned a new member of human ankyrin repeat and SOCS box containing protein family (ASB), designed as hASB-8, from a human placental cDNA library and further extended by 5(') and 3(')-RACE. The full-length cDNA was 2545bp in length, with a predicted open reading frame encoding a protein of 288 amino acids, which was 96% identical to mouse ASB-8 protein. Computer analysis revealed that the deduced amino acid sequence of the human ASB-8 contained four Ankyrin repeats and one SOCS box. The gene had four exons separated by three introns and was mapped to human chromosome 12q13. Human ASB-8 mRNA was expressed at the highest level of expression in skeletal muscle and at a varied level of expression in heart, brain, placenta, liver, kidney, and pancreas. The transcript of hASB-8 was not detected in adult normal lung tissue, but found in lung carcinoma cell lines SPC-A1, A549, and NCI-H446. Subcellular localization analysis showed that the EGFP-tagged hASB-8 protein was localized at cytoplasm in human hepatocellular carcinoma cell line BEL-7402. We also provided evidence that hASB-8 could interact with Elongin B-C complex in vitro. Furthermore, transfection with the truncated mutant of hASB-8 cDNA lacking SOCS box could suppress cell growth of lung adenocarcinoma SPC-A1 cells in vitro, which suggests that this gene might be related to the development of lung cancer.
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PMID:Molecular cloning and characterization of the human ASB-8 gene encoding a novel member of ankyrin repeat and SOCS box containing protein family. 1255 69

With the aim of enhancing the efficacy of chemotherapeutic agents, we investigated the antitumor actions and reversal effect on drug resistance of proanthocyanidin plus doxorubicin. The results showed that proanthocyanidin 12.5-200 mg/L significantly inhibited proliferation of K562, K562/DOX, SPC-A-1, and Lewis cells in vitro in a time- and concentration-dependent manner, as determined by microculture tetrazolium assay. A combination of proanthocyani din 12.5, or 25 mg/L and doxorubicin treatment synergistically inhibited cell proliferation with decreased IC50 values. Proanthocyanidin reverses drug resistance in doxorubicin-resistant K562/DOX cells, and IC50 values were decreased by 9.19 (3.64-23.19), 2.56 (1.48-.44), and 0.94 (0.81-1.09) mg/L, respectively, after 24 h treatment with doxorubicin 0.1-9.0 mg/L alone or in combination with proanthocyanidin 12.5 or 25 mg/L; the proanthocyanidin reversal fold was 3.6 and 9.8, respectively. Under confocal laser scanning microscope, the combination of proanthocyanidin 25 or 50 mg/L with doxorubicin 3 mg/L significantly increased the accumulation of intracellular doxorubicin, Ca2+, and Mg2+, and reduced the pH value and mitochondrial membrane potential in K562/DOX cells as compared with doxorubicin alone (p < 0.01). Additionally, the apoptosis rate was increased by 11.3% +/- 3.3%, 14.2% +/- 5.4%, and 23.8% +/- 2.8%, respectively, for doxorubicin 3 mg/L alone or with proanthocyanidin 12.5 or 25 mg/L, as compared with controls (3.0% +/- 1.4%), as demonstrated by flow cytometry. In vivo experiments demonstrated that i.p. administration of proanthocyanidin 10 mg/kg with doxorubicin 2 mg/kg had an inhibitory effect on the growth of transplantation tumor sarcoma 180 and hepatoma 22 in mice as compared with doxorubicin alone (p < 0.05). These results suggest that proanthocyanidin enhances doxorubicin-induced antitumor effect and reverses drug resistance, and its mechanism is attributed partially to the promotion of doxorubicin-induced apoptosis through an elevation of intracellular doxorubicin, and Ca2+, Mg2+ concentration, and a reduction of pH value and mitochondrial membrane potential.
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PMID:Proanthocyanidin from grape seeds enhances doxorubicin-induced antitumor effect and reverses drug resistance in doxorubicin-resistant K562/DOX cells. 1587 Aug 45

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

Hepatitis C virus (HCV) core protein is believed to play critical roles in the virus morphogenesis and pathogenesis. In HCV polyprotein, core protein terminates with a signal peptide followed by E1 envelope protein. It has remained unclear whether cleavage by host cell signal peptidase (SP) at the core-E1 junction to generate the complete form of core protein, which is anchored in the endoplasmic reticulum membrane, is absolutely required for cleavage within the signal peptide by host cell signal peptide peptidase (SPP) to liberate the mature form of core protein, which is then free for trafficking to lipid droplets. In this study, the possible sources of disagreement in published reports have been examined, and we conclude that a product generated upon inhibition of SP-catalysed cleavage at the core-E1 junction in heterologous expression systems was incorrectly identified as mature core protein. Moreover, inhibition of this cleavage in the most relevant model of human hepatoma cells replicating a full-length HCV genome was shown to abolish interaction of core protein with lipid droplets and production of infectious progeny virus. These results firmly establish that SPP-catalysed liberation of mature core protein is absolutely dependent on prior cleavage by SP at the correct core-E1 site to generate the complete form of core protein, consistent with this obligatory order of processing playing a role in HCV infectious cycle.
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PMID:Sequential processing of hepatitis C virus core protein by host cell signal peptidase and signal peptide peptidase: a reassessment. 1928 87

The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC(50) of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans.
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PMID:A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity. 1933 74


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