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)

Human thymidine phosphorylase (dThdPase) is an angiogenic factor identical to platelet-derived endothelial cell growth factor (PD-ECGF). Thymidine phosphorylase is also a converting enzyme of the prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU) in tumors. To assess the role of dThdPase in targeting chemotherapy, we examined the relationship between the expression of dThdPase and the sensitivity of 5'-DFUR in cancer cell lines, and also examined whether transfection of dThdPase cDNA enhanced the drug-sensitivity to 5'-DFUR with or without angiogenesis in breast cancer cells. Thirteen human cancer cell lines consisting of 4 breast cancer, 6 gastric cancer, and 3 colon cancer cell lines were used. Expression of dThdPase was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In vitro drug-sensitivity was assessed by MTT assay, and anti-tumor effect in vivo was assessed using nude mouse xenografts. Intratumoral microvessel density was evaluated by immunohistochemical staining to factor VIII related antigen. Transfection of dThdPase cDNA was performed using pcDNA3 expression vector encoding its cDNA by the lipofection method. An inverse relationship between the expression of dThdPase and the IC50 values of 5'-DFUR was observed (p=0.1278, rho=-0.440) in the 13 cancer cell lines. Transfection of dThdPase cDNA into MCF-7 breast cancer cells resulted in an approximately 2.6- and 10-fold increase of the expression of dThdPase mRNA and its enzyme activity, respectively, compared to the control vector alone. The sensitivity to 5'-DFUR in the transfected cells was increased approximately 20-fold compared to the parent cells and control vector alone, and the sensitivity to 5-FU was also somewhat increased. In contrast, the sensitivity to ADM, CDDP, and VP-16 was not different between the transfected and control cells. In nude mice xenografts of the transfected cells, treatment with 5'-DFUR had a significant anti-tumor effect compared to those of the untreated transfected cells and control vector alone treated with 5'-DFUR (p<0.01). Intratumoral microvessel density in the transfected cells was not significantly increased with or without treatment with 5'-DFUR compared to control vector alone. The high expression of dThdPase was correlated with an increase in the sensitivity to 5'-DFUR in gastrointestinal and breast cancer cell lines. The introduction of dThdPase cDNA in breast cancer cells enhanced the sensitivity to 5'-DFUR without an increase of tumor angiogenesis, and targeting chemotherapy of dThdPase may be a good tumor-specific and personalized therapy for improving the poor prognosis of cancer patients who show high expressions of dThdPase.
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PMID:Effects of introduction of dThdPase cDNA on sensitivity to 5'-deoxy-5-fluorouridine and tumor angiogenesis. 1263 76

A homodimeric trypsin inhibitor with a molecular mass of 54 kDa was isolated from the seeds of Clausena lansium (Lour) Skeels with a very simple procedure comprising extraction with an aqueous buffer and ion exchange chromatography on CM-cellulose. It inhibited trypsin with an IC50 of 2.2 nM but was without any inhibitory effect on chymotrypsin and proteinase K. The uptake of MTT by human leukemia HL60 and hepatoma Hep G2 cells was inhibited with an IC50 of 100 microM. Translation in the cell-free rabbit reticulocyte lysate system was inhibited with an IC50 of 3.6 microM. The activity of HIV-1 reverse transcriptase was reduced in the presence of the trypsin inhibitor. The trypsin inhibitor exerted antifungal activity toward Physalospora piricola but not Mycosphaerella arachidicola, Botrytis cinerea, Fusarium oxysporum or Coprinus comatus.
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PMID:A homodimeric sporamin-type trypsin inhibitor with antiproliferative, HIV reverse transcriptase-inhibitory and antifungal activities from wampee (Clausena lansium) seeds. 1267 22

The purpose of this study was to investigate pulp cell responses during hypoxia and reoxygenation. Pulp tissues obtained from beagle dogs were cultured. In the control group, pulp cells were incubated in normoxic conditions (20% O2) for 1-4 d. In the hypoxia group, pulp cells were incubated under hypoxic conditions (2% O2) for 1-4 d. In the reoxygenation group, pulp cells were first incubated under hypoxic conditions for 24 h, and were then incubated in normoxic conditions (20% O2) for one to three additional days. Cell viability, MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assay, cellular proliferation, and alkaline phosphatase (ALPase) activity were determined. Expression of heat shock protein 70 (HSP70) and vascular endothelial growth factor (VEGF) was analysed by Western blotting. Hypoxia inducible factor-1alpha (HIF-1alpha) in pulp cells was analysed by reverse transcriptase polymerase chain reaction (RT-PCR). The cell growth rate and ALPase activity were significantly higher in the hypoxia group than in the control group. After reoxygenation, cellular proliferation and ALPase activity decreased to the level of the control group while HSP70 expression increased. Hypoxia inducible factor-1alpha expression was detected in pulp cells, and VEGF expression (which is regulated by HIF-1alpha) increased under hypoxic conditions. These results suggest that dynamic responses to hypoxia and reoxygenation occur in pulp cells.
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PMID:Pulp cell responses during hypoxia and reoxygenation in vitro. 1288 99

Several antiretroviral compounds have been shown to be substrates for the efflux protein P-glycoprotein (P-gp) although few studies have investigated the effects of drug on expression of this protein. Here, an in vitro system has been adopted to investigate the effects of protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) on P-gp expression in peripheral blood mononuclear cells (PBMCs). PBMCs isolated from healthy volunteers were incubated with 10 or 100 microM PI (saquinavir, ritonavir, lopinavir, indinavir, nelfinavir, amprenavir) or 10 microM NNRTI (efavirenz, nevirapine) for 72 hours. Surface P-gp expression was measured by flow cytometry and compared with vehicle-incubated controls. Toxicity was assessed by MTT assay and the effects of each compound were compared between individuals with differing genotypes at position 3435 of exon 26 of MDR1, which was assigned by restriction fragment length polymorphism. Significant increases in median P-gp expression were observed following incubation with 10 microM nelfinavir (10.2 versus 6.7% P-gp-positive cells) and efavirenz (10.0 versus 6.7% P-gp-positive cells). No significant differences in induction were observed between genotypes (CC, CT, TT). Following incubation with 100 microM PI, significant upregulation of P-gp occurred except with amprenavir. However, nelfinavir, ritonavir, and lopinavir caused marked toxicity, indicating that at higher concentrations, the increase in P-gp may be at least partially related to a stress response. These results indicate the potential of some PIs and NNRTIs to induce P-gp expression in PBMCs in vitro.
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PMID:The effects of protease inhibitors and nonnucleoside reverse transcriptase inhibitors on p-glycoprotein expression in peripheral blood mononuclear cells in vitro. 1290 97

This preject is to explore the reversal efficacy of calmodulin antagonist berbamine (BBM) on multidrug resistance (MDR) and its mechanism. Human erythroleukemic cell line K562 and its adriamycin-resistant counterpart K562/A02 were used in the study. The cells were co-cultured with ADR and BBM in different concentrations. MTT assay was used to analyze the effect of BBM on cell growth inhibition. According to the MTT assay, the 50% inhibitory concentration (IC(50)), the multiples of drug resistance and increased sensitivity of ADR were calculated. The concentration of intracellular ADR and expression level of P-gp were detected by flow cytometry (FCM). The expression level of mdr1 mRNA and survivin mRNA was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) with beta-actin as internal reference. The results showed that IC(50) of ADR in K562 and K562/A02 cells was 1.16 +/- 0.09 micro mol/L and 37.47 +/- 1.76 micro mol/L, respectively. The resistant multiple of K562/A02 cells to ADR was 32.30 higher than that of K562 cells. BBM increased the chemo-sensitivity of ADR in K562/A02 cells with dose-dependent relationship, i.e. when 5, 10 and 20 micro mol/L BBM was added in the culture the chemo-sensitivity of ADR was increased to 2.01-, 9.68-, and 41.18-fold (P < 0.01), respectively. After treating K562/A02 cells by 5 or 10 micro mol/L BBM for 2 hours the accumulation of intracellular ADR was increased to 1.41- and 1.52-fold (P < 0.01), respectively. Treating by BBM for 72 hours decreased 4.12% (P < 0.05) and 27.09% (P < 0.01) of P-gp expression, respectively, meanwhile down-regulated expression of mdr1 mRNA and survivin mRNA was found. In conclusion, BBM could increase intracellular concentration of ADR in K562/A02 that down-regulated expression level of mdr1 mRNA and P-gp and survivin so that the sensitivity of K562/A02 to ADR was increased significantly.
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PMID:[Reversal effect of berbamine on multidrug resistance of K562/A02 cells and its mechanism]. 1470 44

It is clinically evident that administration of estriol (E3) increases the bone mass density of the lumbar vertebrae in postmenopausal women, and that combined treatment with estrogen and 1,25-dihydroxyvitamin D3 (VD3) increases femoral neck bone mass density compared with treatment with estrogen alone in postmenopausal osteoporotic women. However, the molecular mechanism whereby treatment with E3 affects osteoblast cell function is still unknown. This study was conducted first to examine the comparative effects of E3 and VD3 on the cell viability of cultured human osteoblast-like cells (HOS) and second to determine whether E3 affects VD3 receptor mRNA expression in HOS. The cell viability and VD3 receptor mRNA expression of cultured HOS were assessed by MTT assay and semi-quantitative reverse transcriptase-polymerase chain reaction with Southern blot analysis, respectively. The treatment with E3 increased the cell viability of cultured HOS compared with untreated control cultures. The increase in cell viability caused by the treatment with E3 was further augmented by the combined treatment with VD3. The addition of either E3 (3.52 x 10(-8) mol/l) or E3 (3.52 x 10(-7) mol/l) to cultured HOS for 24 h resulted in a fourfold and eightfold increase, respectively, in VD3 receptor mRNA expression in HOS, compared with that in untreated control cultures. These results suggest that E3 may up-regulate the cell viability of osteoblast cells, and that the concomitant treatment with E3 and VD3 further augments the cell viability being associated with an E3-induced increase in VD3 receptor mRNA expression in those cells.
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PMID:Effects of estriol on cell viability and 1,25-dihydroxyvitamin D3 receptor mRNA expression in cultured human osteoblast-like cells. 1499 64

Limited information is available on the activity of antiretroviral drugs against human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) strains to guide their use in treatment or prophylaxis. We evaluated the antiviral activity of 16 approved drugs and one experimental drug, AMD3100, against two wild-type HIV-2 (ROD and EHO) isolates, two strains of SIV (mac251 and B670), and two strains of simian-human immunodeficiency virus (SHIV) that contain the reverse transcriptase (RTSHIV) or envelope glycoprotein (SHIV89.6) of human immunodeficiency virus type 1 (HIV-1) in a SIV(mac239) background. Drug susceptibility was measured conventionally by the MT-4/MTT assay, and results were analysed as fold changes in 50% effective concentration (EC50) relative to the EC50 for HIV-1 (IIIB). The nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine, lamivudine, stavudine, didanosine, zalcitabine and abacavir as well as the nucleotide reverse transcriptase inhibitor tenofovir retained full activity against all six viruses except for SIV and SHIV89.6 that showed low-level resistance to didanosine. The protease inhibitors (PIs) ritonavir, indinavir, saquinavir and nelfinavir were found to be active against some HIV-2 or SIV strains. However, a significant reduction in susceptibility was seen with indinavir against SHIV89.6 (3.3-fold), and with amprenavir against HIV-2(ROD) (8.8-fold). All viruses except for RTSHIV showed a >200-fold decrease in susceptibility for the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine, delavirdine and efavirenz, indicating high-level resistance. AMD3100, a CXCR4 antagonist, was active against HIV-2 and SHIV89.6, a finding consistent with the use of the CXCR4 co-receptor by these isolates, but was inactive against SIV strains. In contrast, enfuvirtide (T-20) was active against SHIV89.6 but had reduced inhibitory activity against both HIV-2 and SIV strains predicting little therapeutic value against these viruses. These findings support the use of NRTIs, tenofovir, but not NNRTIs, for treating HIV-2-infected persons or for prophylaxis against HIV-2 and SIV. The clinical significance of the low-level resistance of HIV-2 and SIV to some PIs is unclear. Co-receptor antagonists such as AMD3100 show promising anti-HIV-2 therapeutic modalities. Both AMD3100 and enfuvirtide could be used for prophylaxis against SHIV89.6.
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PMID:Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. 1504 May 30

Three alkaloids, lycorine, homolycorine and 2- O-acetyllycorine, were isolated from the bulbs of Leucojum vernum (Amaryllidaceae) and identified by means of NMR analysis. The alkaloids obtained from L. vernum and from other Amaryllidaceae species were studied in vitro for HIV-1 replication inhibitory activity on MT4 cells. The cytotoxicity of the compounds in uninfected cells was evaluated by using the MTT assay and the [ (3)H]thymidine incorporation test. The antiviral activities were determined by means of the p24 antigen assay and solid-phase reverse transcriptase testing. The results demonstrate that trisphaeridine, lycorine, homolycorine, and haemanthamine possess high antiretroviral activities (IC (50) = 0.4 - 7.3 microg/mL), accompanied by low therapeutic indices (TI (50) = 1.3 - 1.9).
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PMID:Alkaloids from Leucojum vernum and antiretroviral activity of Amaryllidaceae alkaloids. 1538 96

This study was aimed to investigate the effects and the mechanism of mangiferin on chronic myeloid leukemia cell lines K562 cells in vitro. The antiproliferation effects of mangiferin on K562 leukemia cells were tested by tetrazolium salt (MTT) method; the apoptosis induced by mangiferin on K562 cell line was explored by means of cell morphology, DNA gel electrophoresis and flow cytometry. The changes in bcr/abl gene expression was detected by using reverse transcriptase (RT)-PCR. The results showed that five different concentrations of mangiferin (25 - 200 micromol/L) dose-dependently and time-dependently inhibited the proliferation of K562 cells, and induced apoptosis in K562 cell line. RT-PCR revealed that bcr/abl gene expression was down-regulated when K562 cells had been treated with different concentrations of mangiferin. In conclusion, mangiferin remarkably inhibits the proliferation of K562 leukemia cells in vitro, and induces apoptosis in K562 cell line probably through down-regulation of bcr/abl gene expression.
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PMID:[CML cell line K562 cell apoptosis induced by mangiferin]. 1549 16

It is important to elucidate whether the leptin receptor, especially the long signal-transducing form of the leptin receptor (OB-Rb) is expressed in human osteoblasts. We detected the expression of human OB-Rb in cultured commercially available human osteoblasts (NHOst cells) using real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). After confirming the expression of OB-Rb, we investigated the effect of leptin on NHOst cells. Leptin enhanced cell proliferation of the cells shown by the MTT assay. Furthermore, leptin changed the copy numbers of Bax and Bcl-2 mRNAs in the cultured cells as shown by real-time quantitative RT-PCR, although the effect was not consistent. Leptin did not change the production of osteocalcin and osteopontin by the cells. Leptin did not change the expression of OB-Rb mRNA in the cells. In conclusion, OB-Rb mRNA is expressed in cultured commercially available human osteoblasts. Leptin may have some effects on bone metabolism by directly modulating cell proliferation and apoptosis of osteoblasts in humans.
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PMID:The leptin receptor in human osteoblasts and the direct effect of leptin on bone metabolism. 1562 71


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