Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new Ph1-positive acute lymphoblastic leukemia cell line, designated as ALL/MIK, has been developed from a patient with Ph1-positive acute leukemia. The ALL/MIK cells showed an immunophenotype of common ALL with rearranged JH and Jk genes. The ALL/MIK cells showed no M-bcr rearrangement using Southern blot analysis with either 3' or 5' M-bcr probes, but had the bcr gene rearrangement on bcr-2 within the first intron of the bcr gene. Consistent with this result, the reverse transcriptase-dependent polymerase chain reaction (RT-PCR) assay revealed that the ALL/MIK cells contained the transcript derived fusion of the first exon of bcr gene and the second exon of abl gene. Although the ALL/MIK cells were defined as early pre-B cells by immunophenotypical and genotypical analyses, they were capable of differentiating into monocytoid lineage by when cultured with TPA. Furthermore, another Ph1-positive ALL cell line, (TOM-1), was investigated for its ability to differentiate to monocytoid lineage. TOM-1 was also induced to monocytoid lineage by TPA. Thus, the present study suggested that the leukemic transformation in some Ph1-positive ALL may occur at the level of multipotential hematopoietic cells capable of differentiating towards lymphoid and myelo-monocytoid lineage.
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PMID:Establishment and characterization of a new Ph1-positive ALL cell line (ALL/MIK) presenting bcr gene rearrangement on bcr-2 and ALL-type bcr/abl transcript: suggestion of in vitro differentiation to monocytoid lineage. 816 60

Although recent evidence suggests that granulocyte-macrophage colony stimulating factor (GM-CSF) plays a role in cutaneous inflammation induced by topical exposure of phorbol ester tumor promoters to murine epidermis, there is little information available on the temporal sequence of gene expression of this cytokine over the time course of tumor promotion or about its function in this process. The goal of the present studies was to examine the potential role of GM-CSF in tumor promotion in SENCAR mice. Competitive reverse transcriptase polymerase chain reaction (RT-PCR) studies demonstrated that a single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA; 2 micrograms, 10 micrograms) to the dorsal epidermis of SENCAR mouse skin stimulated a dose and time dependent GM-CSF gene expression that was upregulated at 1 h after TPA exposure, peaked at 3 h and declined at 12 h. Although treatment with 7',12'-dimethylbenz[a]anthracene (DMBA) did not stimulate GM-CSF gene expression, GM-CSF gene expression was elevated in epidermal tissue isolated from SENCAR mice treated with a single application of 10 nmol DMBA followed by multiple applications of 2 micrograms TPA over a 1-22 week time course. Immunochemical and autoradiographic studies demonstrated that GM-CSF protein was produced by suprabasal keratinocytes, interfollicular cells, nonproliferating papilloma cells and leukocytes within the dermis. Intraperitoneal injection of recombinant (r) GM-CSF into SENCAR mice at 2 h prior to topical application of 10 micrograms TPA induced a significant increase in epidermal keratinocyte proliferation, leukocyte infiltration into the dermis, hydroperoxide production by circulating neutrophils and chemotactic activity present within the plasma at 24 h compared to treatment with only 10 micrograms TPA. Intravenous injection of anti-GM-CSF antibodies significantly inhibited both local and systemic inflammatory events induced by topical application of TPA. The present studies suggest that GM-CSF has a broad spectrum of activity with at least two target cell populations, epidermal keratinocytes within the proliferative compartment and leukocytes. This cytokine is actively transcribed during the tumor promotion process, acts as a signal peptide that stimulates epidermal proliferation, primes circulating neutrophils to produce hydroperoxide and regulates leukocyte migration.
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PMID:Granulocyte-macrophage colony stimulating factor gene expression and function during tumor promotion. 820 63

This study aimed to elucidate the inhibitory effects of chlorophyllin (CHL) at different promotion stages in a DMBA-TPA-induced mouse skin carcinogenesis model. TPA promotion was undertaken for 6, 18 and 24 weeks, respectively. Proliferating activity was observed immunohistochemically and the ornithine decarboxylase (ODC) mRNA level was analyzed by reverse transcriptase-polymerase chain reaction. Messenger RNAs for c-fos, c-jun and jun-B were also observed. CHL treatment clearly reduced proliferating activity and the level of ODC mRNA at the 18-week-promotion stage. When promoted for 24 weeks, CHL was not effective in reducing proliferating activity and ODC mRNA expression. These results indicate that the promotion stage of each target tissue should be considered in a chemopreventive program.
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PMID:Anti-promotion effect of chlorophyllin in DMBA-TPA-induced mouse skin carcinogenesis. 1092 61

Anaplastic thyroid carcinoma is a rapidly growing, aggressive neoplasm affecting the elderly which does not respond to most of the therapies. We established cultured cell lines from four untreated tumors. The cultures grew in a monolayer of spindle-shaped cells in three cell lines and of small polygonal cells in one line, having relatively long doubling times and chromosomal abnormalities. The xenotransplantation of the lines in athymic nude mice produced tumors with a histology similar to the original tumors. The immunocytochemical staining showed the expression of PCNA, HLA-class 1, cytokeratin, vimentin and FAS (fatty acid synthase) but not CEA, desmin or P-glycoprotein. The lines secreted TPA, IL-6, IL-8 and few or no thyroid-related hormones in the culture supernatant. One cell line produced G-CSF. The chemosensitivity assay revealed intrinsic drug resistance to nine out of 11 antineoplastic agents. The reverse transcriptase-polymerase chain reaction (RT-PCR) detected MRP (multidrug resistance-associated protein) mRNA but not mdr (multidrug resistance protein)-1 and mdr-3 mRNAs. This finding indicates that the multidrug resistance of these lines is mediated by a P-glycoprotein-unrelated mechanism. The RT-PCR also presented FAS mRNA in all the lines, and IL-6 and IL-8 mRNAs in some of the lines.
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PMID:Biological characteristics and chemosensitivity profile of four human anaplastic thyroid carcinoma cell lines. 1168 81

Induction of transforming growth factor beta (TGF-beta) by the immunosuppressive drug cyclosporin A (CsA) in activated lymphocytes has been claimed to add to the renal pro-fibrotic effects of CsA. The aim of this study was to evaluate CsA-mediated TGF-beta induction in a larger number of lymphocyte preparations from different donors. Peripheral blood lymphocytes (PBL) were obtained from healthy blood donors. The cells were stimulated with phytohemagglutinin E (PHA) and phorbol ester (tetradecanoyl phorbol acetate, TPA) in the presence or absence of CsA. TGF-beta, interleukin-2 (IL-2) and cyclooxygenase-2 (Cox-2) mRNA were detected by Northern blot analysis or by real time reverse transcriptase-polymerase chain reaction (RT-PCR). TGF-beta and IL-2 protein were determined in the cellular supernatants by enzyme-linked immunosorbent assay. TGF-beta mRNA and protein were up-regulated when the cells were stimulated with PHA/TPA. Cyclosporin A at high concentrations (500 ng/mL) caused a transient increase in TGF-beta mRNA which was significant after 2 h. CsA did not induce sustained TGF-beta protein expression (24-72 h) in any of the preparations (n = 14), whereas the up-regulation of IL-2 mRNA and protein was prevented by CsA in the same preparations. Furthermore, up-regulation of Cox-2 mRNA was inhibited by CsA. Taken together, there was no evidence for TGF-beta as a clinically relevant mediator being induced by CsA in activated peripheral blood T-lymphocytes.
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PMID:Failure of cyclosporin A to induce transforming growth factor beta (TGF-beta) synthesis in activated peripheral blood lymphocytes. 1258 17

We recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines. In our present study, the anti-tumor initiating and promoting activities of zerumbone in mouse skin were evaluated using a conventional 2-stage carcinogenesis model. A single topical pretreatment to mouse skin (2 micromol) 24 hr before application of dimethylbenz[a]anthracene (0.2 micromol) markedly suppressed tumor incidence by 60% and the number of tumors by 80% per mouse. Repeated pretreatment (16 nmol) twice weekly during the post-initiation phase reduced the number of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1.6 nmol)-induced tumors by 83% as well as their diameter by 57%. Multiple reverse transcriptase (RT) PCR experiments revealed that zerumbone (2 micromol) enhanced the mRNA expression level of manganese superoxide dismutase, glutathione peroxidase-1, glutathione S-transferase-P1 and NAD(P)H quinone oxidoreductase in the epidermis, but not that of cytochrome p450 1A1 or 1B1. Further, it diminished TPA-induced cyclooxygenase-2 protein expression and phosphorylation of extracellular signal-regulated kinase 1/2, while pretreatment(s), in either the priming or activation stage or both, reduced double TPA application-induced hydrogen peroxide formation and edema induction by 29% to 86%, respectively. Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen-labeling indices. Together, our results indicate that zerumbone is a promising agent for the prevention of both tumor initiating and promoting processes, through induction of anti-oxidative and phase II drug metabolizing enzymes as well as attenuation of proinflammatory signaling pathways.
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PMID:Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice. 1512 79

The oncogenic human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), are latent in cultured lymphoma cells. We asked whether reactivation from latency of either virus requires de novo protein synthesis. Using Northern blotting and quantitative reverse transcriptase PCR, we measured the kinetics of expression of the lytic cycle activator genes and determined whether abundance of mRNAs encoding these genes from either virus was reduced by treatment with cycloheximide (CHX), an inhibitor of protein synthesis. CHX blocked expression of mRNAs of EBV BZLF1 and BRLF1, the two EBV lytic cycle activator genes, when HH514-16 Burkitt lymphoma cells were treated with histone deacetylase (HDAC) inhibitors, sodium butyrate or trichostatin A, or a DNA methyltransferase inhibitor, 5-Aza-2'-deoxycytidine. CHX also inhibited EBV lytic cycle activation in B95-8 marmoset lymphoblastoid cells by phorbol ester phorbol-12-myristate-13-acetate (TPA). EBV lytic cycle induction became resistant to CHX between 4 and 6 h after application of the inducing stimulus. KSHV lytic cycle activation, as assessed by ORF50 mRNA expression, was rapidly induced by the HDAC inhibitors, sodium butyrate and trichostatin A, in HH-B2 primary effusion lymphoma cells. In HH-B2 cells, CHX did not inhibit, but enhanced, expression of the KSHV lytic cycle activator gene, ORF50. In BC-1, a primary effusion lymphoma cell line that is dually infected with EBV and KSHV, CHX blocked EBV BRLF1 lytic gene expression induced by TPA and sodium butyrate; KSHV ORF50 mRNA induced simultaneously in the same cells by the same inducing stimuli was resistant to CHX. The experiments show, for the cell lines and inducing agents studied, that the EBV BZLF1 and BRLF1 genes do not behave with "immediate-early" kinetics upon reactivation from latency. KSHV ORF50 is a true "immediate-early" gene. Our results indicate that the mechanism by which HDAC inhibitors and TPA induce lytic cycle gene expression of the two viruses differs and suggest that EBV but not KSHV requires one or more proteins to be newly synthesized between 4 and 6 h after application of an inducing stimulus.
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PMID:De novo protein synthesis is required for lytic cycle reactivation of Epstein-Barr virus, but not Kaposi's sarcoma-associated herpesvirus, in response to histone deacetylase inhibitors and protein kinase C agonists. 1759 2

Glial and glia-derived cells express a variety of receptors for neurotransmitters and hormones, the majority of which evoke both Ca(2+) release from intracellular stores and Ca(2+) entry across the plasma membrane. We investigated the links between histamine H(1) receptor activation, Ca(2+) release from intracellular stores and Ca(2+) influx in human astrocytoma U373 MG cells. Histamine, through a H(1) receptor-mediated effect, evoked an increase in cytoplasmic free calcium concentration ([Ca(2+)](i)) that occurred in two phases: an initial, transient, increase owing to Ca(2+) mobilization from intracellular pools, and a second, sustained increase dependent on both Ca(2+) influx and continuous receptor occupancy. The characteristics of histamine-induced increases in [Ca(2+)](i) were similar to the capacitative entry evoked by emptying of the Ca(2+) stores with thapsigargine, and different from that observed when Ca(2+) influx was activated with OAG (1-oleoyl-2-acetyl-sn-glycerol), a diacylglycerol (DAG) analog. OAG application or increased endogenous DAG, resulting from DAG kinase inhibition, reduced the histamine-induced response. Furthermore, activation of the DAG target, protein kinase C (PKC), by TPA (12-O-tetradecanoyl 4beta-phorbol 13alpha-acetate) resulted in inhibition of the histamine-induced Ca(2+) response, an action prevented by PKC inhibitors. By using reverse transcriptase-polymerase chain reaction analysis, mRNAs for transient receptor potential channels (TRPCs) 1, 4, and 6 as well as for STIM1 (stromal-interacting molecule) and Orai1 were found to be expressed in the U373 MG cells, and confocal microscopy using specific antibodies revealed the presence of the corresponding proteins. Therefore, TRPCs may be candidate proteins forming store-operated channels in the U373 MG cell line. Further, our results confirm the involvement of PKC in the regulation of H(1) receptor-induced responses and point out to the existence of a feedback mechanism acting via PKC to limit the increase in [Ca(2+)](i).
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PMID:Histamine-induced Ca2+ entry in human astrocytoma U373 MG cells: evidence for involvement of store-operated channels. 1862 30

Histone deacetylase inhibitors (HDACi) have been reported to have potent chemopreventive activity because of their effects on the inhibition of cell growth and apoptosis in human cancer cell lines. In the present study, we investigated the apoptotic effect of a novel HDACi, Ky2, and its molecular mechanism in MDA-MB-231 human breast cancer cells in vitro. The chemopreventive effects of Ky2 in MDA-MB-231 cells were evaluated using the MTS assay, anchorage-independent cell transformation assay, DAPI staining, western blot analysis, reverse transcriptase-PCR, and small interfering RNA. Ky2 enhanced histone acetylation and decreased cell viability. Ky2 induced apoptosis evidenced by nuclear condensation and fragmentation, the accumulation of sub-G1 phase, and caspase-dependent PARP cleavage. In addition, Ky2 released cytochrome c from mitochondria to cytosol through the regulation of mitochondria-related proteins (Bid, Bim, and Bcl-xL). Ky2 markedly decreased the level of Sp1 protein expression through both the decrease of Sp1 mRNA level and proteasome-dependent protein degradation. Interestingly, the apoptotic effect of Ky2 is more potent than SAHA, a well-known HDACi. Furthermore, the knockdown of Sp1 protein by Sp1-specific inhibitor, mithramycin A, and siRNA resulted in the alteration of truncated Bid and Bim to induce apoptosis. Furthermore, Ky2 significantly decreased TPA-induced or EGF-induced neoplastic cell transformation in JB6 cells. Our results suggest that Ky2 may be a potential chemopreventive and chemotherapeutic agent by modulating Sp1 in human breast cancer cells.
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PMID:Chemopreventive and chemotherapeutic effect of a novel histone deacetylase inhibitor, by specificity protein 1 in MDA-MB-231 human breast cancer cells. 2487 59

Interleukin-11 (IL-11) has diverse biological effects in hematopoiesis has been shown to share important functions with IL-6. However, unlike IL-6, there has been little information about the expression of IL-11 in lymphoid malignancy. Using reverse transcriptase polymerase chain reaction, IL-11 transcript was found in a number of lymphoid cell lines. A high level of expression was found in follicular lymphoma cell line FL18, and this was also detectable by Northern blotting. When TPA/A23187 were added to the culture of bone marrow stromal cell line KM102, IL-11 transcripts were rapidly upregulated. In contrast, levels of IL-11 transcripts were not increased in FL18 even upon the stimulation. The addition of actinomycin D to the cultures showed that the half life of the transcripts was similar in both FL18 and KM102. This suggests that posttran scriptional processes might not be involved in the constitutive expression of FL18. The results of IL-11 bioassay and enzymed-linked immunosorbent assay showed that FL18 did not secrete biologically active IL-11 into the medium. IL-11 transcript was also found in lymphoma cells in patient with malignant lymphoma, but not in B and T lymphocytes from reactive hyperplasia. Our results indicate that IL-11 transcripts can sometimes be produced in the neoplastic transformation of lymphoid cells.
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PMID:Interleukin-11 Gene Expression in Human Lymphoid Malignancy. 2741 79


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