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1.
Pharm Res ; 40(6): 1569-1576, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37081303

RESUMEN

OBJECTIVE: Bone morphogenetic protein-2 (BMP-2) impacts fertility in women by affecting the menstrual cycle and embryonic development. We aimed to determine the reproductive toxicity of Escherichia coli (E. coli)-derived recombinant human BMP-2 (rhBMP-2) by measuring changes in the reproductive performance and organs in rhBMP-2-treated rats. METHODS: Overall, 88 male and female rats each were categorized into one control and three experimental groups. rhBMP-2 was intravenously administered to the experimental groups at 0.05, 0.15, and 0.50 mg/kg/day, respectively. The male rats were administered rhBMP-2 daily, starting from 28 days before mating until the day of necropsy (48 days), after which they were euthanized and necropsied. The female rats were administered rhBMP-2 daily, starting from 14 days before mating until 7 days after fertilization (22-36 days), after which they were necropsied 13 days after fertilization. RESULTS: No rhBMP-2-related death occurred throughout the study period. All rhBMP-2-treated groups showed swelling in the tail at the site of rhBMP-2 administration. In the high-dose rhBMP-2 group, the male rats showed a slight reduction in body weight and food consumption, whereas the female rats showed a reduction in the weights of the ovary and oviduct. Examining the fertilization status and necropsy showed no effect of rhBMP-2 on fertility and early embryonic development. The no-observed-adverse-effect level of rhBMP-2 was 0.50 mg/kg/day in all rats. CONCLUSION: rhBMP-2 had no reproductive toxicity on the reproductive performance and organs in female and male rats. Therefore, these results provide new toxicology information on E. coli-derived rhBMP-2 as a therapeutic protein.


Asunto(s)
Proteína Morfogenética Ósea 2 , Escherichia coli , Humanos , Embarazo , Ratas , Masculino , Femenino , Animales , Proteínas Recombinantes , Desarrollo Embrionario , Fertilización
2.
Enzyme Microb Technol ; 161: 110117, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36049397

RESUMEN

Cordyceps militaris, an entomopathogenic Cordyceps mushroom, is a crucial ethnopharmacological agricultural product with applications in traditional oriental remedies in East Asia. Since lipases are reported to serve as key enzymatic equipment for entomopathogenic fungi during the host infection, the presence of various lipases with different biochemical features in C. militaris was elucidated. Three lipases from C. militaris (CML) of 60-70 kDa were isolated according to protein hydrophobicity; isoform relationships were identified by peptide mapping using liquid chromatography-electrospray ionization-tandem mass spectrometry. The CML isoforms exhibited distinct substrate specificities, which were related to the hydrophobicity of each isoform. Furthermore, the integral stereoselectivity of each lipase towards trioleoylglycerol diverged into two classes (sn-1,3 and sn-2 regioselectivity) that are rare in canonical fungal lipases. Overall, our results demonstrate that C. militaris secretes lipase isoforms with cocktail-like enzyme functions that may contribute to the entomopathogenic life cycle of C. militaris. Each CML isoform has distinct advantages for biocatalyst applications in the food and oleochemical industries.


Asunto(s)
Agaricales , Cordyceps , Lipasa/metabolismo , Isoformas de Proteínas/metabolismo , Especificidad por Sustrato
3.
AMB Express ; 12(1): 106, 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35947236

RESUMEN

Recombinant human bone morphogenetic protein-2 (rhBMP-2), a key regulator of osteogenesis, induces the differentiation of mesenchymal cells into cartilage or bone tissues. Early orthopedic and dental studies often used mammalian cell-derived rhBMP-2, especially Chinese hamster ovary (CHO) cells. However, CHO cell-derived rhBMP-2 (C-rhBMP-2) presents disadvantages such as high cost and low production yield. To overcome these problems, Escherichia coli-derived BMP-2 (E-rhBMP-2) was developed; however, the E-rhBMP-2-induced signaling pathways and gene expression profiles during osteogenesis remain unclear. Here, we investigated the E-rhBMP-2-induced osteogenic differentiation pattern in C2C12 cells and elucidated the difference in biological characteristics between E-rhBMP-2 and C-rhBMP-2 via surface plasmon resonance, western blotting, qRT-PCR, RNA-seq, and alkaline phosphatase assays. The binding affinities of E-rhBMP-2 and C-rhBMP-2 towards BMP receptors were similar, both being confirmed at the nanomolecular level. However, the phosphorylation of Smad1/5/9 at 3 h after treatment with E-rhBMP-2 was significantly lower than that on treatment with C-rhBMP-2. The expression profiles of osteogenic marker genes were similar in both the E-rhBMP-2 and C-rhBMP-2 groups, but the gene expression level in the E-rhBMP-2 group was lower than that in the C-rhBMP-2 group at each time point. Taken together, our results suggest that the osteogenic signaling pathways induced by E-rhBMP-2 and C-rhBMP-2 both follow the general Smad-signaling pathway, but the difference in intracellular phosphorylation intensity results in distinguishable transcription profiles on osteogenic marker genes and biological activities of each rhBMP-2. These findings provide an extensive understanding of the biological properties of E-rhBMP-2 and the signaling pathways during osteogenic differentiation.

4.
Nat Commun ; 11(1): 612, 2020 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-32001712

RESUMEN

The kinase Aurora B forms the chromosomal passenger complex (CPC) together with Borealin, INCENP, and Survivin to mediate chromosome condensation, the correction of erroneous spindle-kinetochore attachments, and cytokinesis. Phosphorylation of histone H3 Thr3 by Haspin kinase and of histone H2A Thr120 by Bub1 concentrates the CPC at the centromere. However, how the CPC is recruited to chromosome arms upon mitotic entry is unknown. Here, we show that asymmetric dimethylation at Arg2 on histone H3 (H3R2me2a) by protein arginine methyltransferase 6 (PRMT6) recruits the CPC to chromosome arms and facilitates histone H3S10 phosphorylation by Aurora B for chromosome condensation. Furthermore, in vitro assays show that Aurora B preferentially binds to the H3 peptide containing H3R2me2a and phosphorylates H3S10. Our findings indicate that the long-awaited key histone mark for CPC recruitment onto mitotic chromosomes is H3R2me2a, which is indispensable for maintaining appropriate CPC levels in dynamic translocation throughout mitosis.


Asunto(s)
Arginina/metabolismo , Aurora Quinasa B/metabolismo , Segregación Cromosómica , Cromosomas Humanos/metabolismo , Histonas/metabolismo , Proteínas Nucleares/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Secuencia de Aminoácidos , Neoplasias de la Mama/patología , Centrómero/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Citocinesis , Desmetilación , Progresión de la Enfermedad , Femenino , Células HeLa , Histonas/química , Humanos , Células MCF-7 , Metilación , Mitosis , Fosforilación , ARN Interferente Pequeño/metabolismo
5.
Environ Pollut ; 241: 194-199, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29807279

RESUMEN

Recently, a novel method for carbon capture and storage has been proposed, which converts gaseous CO2 into aqueous bicarbonate ions (HCO3-), allowing it to be deposited into the ocean. This alkalinization method could be used to dispose large amounts of CO2 without acidifying seawater pH, but there is no information on the potential adverse effects of consequently elevated HCO3- concentrations on marine organisms. In this study, we evaluated the ecotoxicological effects of elevated concentrations of dissolved inorganic carbon (DIC) (max 193 mM) on 10 marine organisms. We found species-specific ecotoxicological effects of elevated DIC on marine organisms, with EC50-DIC (causing 50% inhibition) of 11-85 mM. The tentative criteria for protecting 80% of individuals of marine organisms are suggested to be pH 7.8 and 11 mM DIC, based on acidification data previously documented and alkalinization data newly obtained from this study. Overall, the results of this study are useful for providing baseline information on ecotoxicological effects of elevated DIC on marine organisms. More complementary studies are needed on the alkalinization method to determine DIC effects on seawater chemistry and marine organisms.


Asunto(s)
Organismos Acuáticos/fisiología , Bicarbonatos/toxicidad , Agua de Mar/química , Contaminantes Químicos del Agua/toxicidad , Ácidos , Carbono/análisis , Dióxido de Carbono/química , Ecotoxicología , Concentración de Iones de Hidrógeno
6.
Healthc Inform Res ; 23(2): 94-100, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28523207

RESUMEN

OBJECTIVES: This paper describes an evaluation study on the effectiveness of developing an in-hospital medical device safety information reporting system for managing safety information, including adverse incident data related to medical devices, following the enactment of the Medical Device Act in Korea. METHODS: Medical device safety information reports were analyzed for 190 cases that took place prior to the application of a medical device safety information reporting system and during a period when the reporting system was used. Also, questionnaires were used to measure the effectiveness of the medical device safety information reporting system. The analysis was based on the questionnaire responses of 15 reporters who submitted reports in both the pre- and post-reporting system periods. RESULTS: Sixty-two reports were submitted in paper form, but after the system was set up, this number more than doubled to 128 reports in electronic form. In terms of itemized reporting, a total of 45 items were reported. Before the system was used, 23 items had been reported, but this increased to 32 items after the system was put to use. All survey variables of satisfaction received a mean of over 3 points, while positive attitude, potential benefits, and positive benefits all exceeded 4 points, each receiving 4.20, 4.20, and 4.13, respectively. Among the variables, time-consuming and decision-making had the lowest mean values, each receiving 3.53. Satisfaction was found to be high for system quality and user satisfaction, but relatively low for time-consuming and decision-making. CONCLUSIONS: We were able to verify that effective reporting and monitoring of adverse incidents and the safety of medical devices can be implemented through the establishment of an in-hospital medical device safety information reporting system that can enhance patient safety and medical device risk management.

7.
Cell Signal ; 31: 124-134, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28077325

RESUMEN

In this study, we presented the role of 14-3-3σ to activate CK2-Hsp90ß-PXR-MDR1 pathway on rifampin and paclitaxel treated LS174T cells and in vivo LS174T cell-xenografted nude mouse model. Following several in vitro and in vivo experiments, rifampin and paclitaxel were found to be stimulated the CK2-Hsp90ß-PXR-MDR1 pathway. Of the proteins in this pathway, Pregnane X receptor (PXR) is a representative transcription factor of multidrug resistance protein 1 (MDR1). We constructed FLAG-PXR-LS174T stable cell lines and discovered 22 proteins that interacted with PXR on rifampin treatment. Among them, Hsp90ß and 14-3-3σ were isolated for further study. Both the proteins were found to be localized in cytoplasm on rifampin treatment by using confocal microscopy. On the other hand, PXR was found to be localized in nucleus after rifampin and paclitaxel treatment by using cell fractionation assay. In Western blot analysis, rifampin did not influence the expression of 14-3-3σ protein. Transient transfection of 14-3-3σ into LS174T cells induced overexpression of PXR; however, P-glycoprotein (P-gp) was not changed significantly. P-gp overexpression was induced only when 14-3-3σ transfected LS174T cells were treated with rifampin and paclitaxel, whereas 14-3-3σ inhibition by nonpeptidic inhibitor, BV02 and 14-3-3σ siRNA reduced rifampin induced PXR and P-gp expression. Cell survival rates were much higher at 14-3-3σ-LS174T stable cell lines than LS174T cells following paclitaxel and vincristine treatment. This data indicates that 14-3-3σ contributes to P-gp overexpression through interaction with PXR with rifampin and paclitaxel treatment.


Asunto(s)
Proteínas 14-3-3/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Biomarcadores de Tumor/metabolismo , Exorribonucleasas/metabolismo , Paclitaxel/farmacología , Receptores de Esteroides/metabolismo , Rifampin/farmacología , Secuencia de Aminoácidos , Animales , Antineoplásicos/farmacología , Sitios de Unión , Supervivencia Celular/efectos de los fármacos , Cromatografía Liquida , Femenino , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Ratones Desnudos , Modelos Biológicos , Receptor X de Pregnano , Unión Proteica/efectos de los fármacos , Receptores de Esteroides/química , Espectrometría de Masas en Tándem
8.
Osong Public Health Res Perspect ; 5(3): 131-7, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25180145

RESUMEN

OBJECTIVES: Japanese encephalitis is considered as a secondary legal infectious disease in Korea and is transmitted by mosquitoes in the summer season. The purpose of this study was to predict the ratio of Culex tritaeniorhynchus to all the species of mosquitoes present in the study regions. METHODS: From 1999 to 2012, black light traps were installed in 10 regions in Korea (Busan, Gyeonggi, Gangwon, Chungbuk, Chungnam, Jeonbuk, Jeonnam, Gyeongbuk, Gyeongnam, and Jeju) to capture mosquitoes for identification and classification under a dissecting microscope. The number of mosquitoes captured/week was used to calculate its daily occurrence (mosquitoes/trap/night). To predict the characteristics of the mosquito population, an autoregressive model of order p (AR(p)) was used to execute the out-of-sample prediction and the in-sample estimation after presumption. RESULTS: Compared with the out-of-sample method, the sample-weighted regression method's case was relatively superior for prediction, and this method predicted a decrease in the frequency of Cx. tritaeniorhynchus for 2013. However, the actual frequency of this species showed an increase in frequency. By contrast, the frequency rate of all the mosquitoes including Cx. tritaeniorhynchus gradually decreased. CONCLUSION: The number of patients with Japanese encephalitis has been strongly associated with the occurrence and density of vector mosquitoes, and the importance of this infectious disease has been highlighted since 2010. The 2013 prediction indicated an increase after an initial decrease, although the ratio of the two mosquito species decreased. The increase in vector density may be due to changes in temperature and the environment. Thus, continuous prevalence prediction is warranted.

9.
Biodegradation ; 25(3): 383-94, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24197220

RESUMEN

Forty-five fenobucarb-degrading bacteria were isolated from rice paddy soils, and their genetic and phenotypic characteristics were investigated. The isolates were able to utilize fenobucarb as a sole source of carbon and energy. Analysis of the 16S rRNA gene sequence indicated that all the isolates were related to members of the genera Sphingobium and Novosphingobium. Among 45 isolates, 21 different chromosomal DNA fingerprinting patterns were obtained. All these strains exhibited similar growth and degradation patterns on fenobucarb. 2-sec-butylphenol was identified as an intermediate during fenobucarb degradation by HPLC analysis. All of the isolates were able to degrade another carbamate insecticide, carbaryl, and 2-sec-butylphenol, but not other fenobucarb related compounds such as aldicarb and fenoxycarb. Representative strains of the different repetitive extragenic palindromic sequence PCR fingerprint types had one to six plasmids. The plasmid-cured strains lost their degradation abilities, suggesting that fenobucarb degradative genes were on their plasmid DNAs in these strains. When analyzed with PCR amplification using the primers targeting for the previously reported carbamate hydrolase genes, most of the isolates did not exhibit any positive signals for different genes involved in carbamate degradation such as mcd, cahA and cehA genes. This is the first report that microorganisms involved in the degradation of fenobucarb have been isolated and the intermediate of fenobucarb biodegradation was identified.


Asunto(s)
Alphaproteobacteria/metabolismo , Genes Bacterianos , Insecticidas/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Alphaproteobacteria/clasificación , Alphaproteobacteria/genética , Alphaproteobacteria/aislamiento & purificación , Biodegradación Ambiental , Biotransformación , Carbamatos/metabolismo , Carbaril/metabolismo , Dermatoglifia del ADN , Fenoles/metabolismo , Filogenia , Plásmidos , ARN Ribosómico 16S/genética
10.
FEMS Microbiol Lett ; 344(2): 114-20, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23617893

RESUMEN

Two bacterial strains involved in syntrophic degradation of chloroacetamide herbicide butachlor were isolated from a rice paddy soil. Analysis of 16S rRNA gene sequences indicated that the two isolates were related to members of the genera Mycobacterium and Sphingobium, respectively. Thus, a pair consisted of Mycobacterium sp. J7A and Sphingobium sp. J7B could rapidly degrade butachlor (100 mg L(-1)) at 28 °C within 24 h, while each isolate alone was not able to completely degrade butachlor. The isolate Mycobacterium sp. J7A was observed to grow slightly on butachlor, possibly utilizing the alkyl side chain of butachlor as its carbon and energy source, but the isolate Sphingobium sp. J7B alone could not grow on butachlor at all. Gas chromatography-mass spectrometry on catabolic intermediates revealed that the strain J7A produced and accumulated 2-chloro-N-(2,6-diethylphenyl) acetamide (CDEPA) during growth on butachlor. This intermediate was not further degraded by strain J7A, but strain J7B was observed to be able to completely degrade and grow on it through 2,6-diethylaniline (DEA). The results showed that butachlor was completely degraded by the two isolates by syntrophic metabolism, in which strain Mycobacterium sp. J7A degraded butachlor to CDEPA, which was subsequently degraded by strain Sphingobium sp. J7B through DEA.


Asunto(s)
Acetanilidas/metabolismo , Herbicidas/metabolismo , Mycobacterium/aislamiento & purificación , Mycobacterium/metabolismo , Microbiología del Suelo , Acetanilidas/química , Biodegradación Ambiental , ADN Bacteriano/genética , Herbicidas/química , Datos de Secuencia Molecular , Estructura Molecular , Mycobacterium/clasificación , Mycobacterium/genética , Oryza/crecimiento & desarrollo , Filogenia , ARN Ribosómico 16S/genética
11.
Biochem Biophys Res Commun ; 432(1): 60-5, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23380452

RESUMEN

In this study, we investigate the molecular mechanism by which protein arginine methyltransferase 6 (PRMT6) exerts anti-invasiveness effect against breast cancer cells and prostate cancer cells. PRMT6 has been known to be responsible for asymmetric dimethylation of histone H3 at R2 (H3R2me2a). To investigate the biological role of PRMT6, we first established stable cell lines expressing GFP-PRMT6 with MCF7 and PC3 cells. Growth rates and colony forming abilities of PRMT6-overexpressing cells were significantly retarded compared to control GFP expressing cells. This growth retardation seems to be associated with p21(WAF1) induction. In addition, our data show that migration and invasion of prostate cancer cells was strongly suppressed by PRMT6 overexpression. In parallel, the levels of thrombospondin-1 (TSP-1), a potent natural inhibitor of angiogenesis, were highly up-regulated in both PRMT6-overexpressing cells. Furthermore, this suppression of migration and invasion by PRMT6 overexpression was significantly rescued by specific knock-down of TSP-1. Concomitantly, down-regulations of MMP-2 and -9 were observed in PRMT6-overexpressing cells. Taken together, our data demonstrate that PRMT6 overexpression is associated with regulation of motility and invasion through up-regulation of TSP-1 and down-regulation of MMPs in human cancer cells.


Asunto(s)
Neoplasias de la Mama/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Nucleares/biosíntesis , Neoplasias de la Próstata/patología , Proteína-Arginina N-Metiltransferasas/biosíntesis , Trombospondina 1/biosíntesis , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Células MCF-7 , Masculino , Invasividad Neoplásica , Proteínas Nucleares/genética , Neoplasias de la Próstata/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Trombospondina 1/genética
12.
Biochem Biophys Res Commun ; 418(4): 616-21, 2012 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-22301191

RESUMEN

In this study, we investigate an anti-mitotic potential of the novel synthetic coumarin-based compound, 7-diethylamino-3(2'-benzoxazolyl)-coumarin, in 5-fluorouracil-resistant human gastric cancer cell line SNU-620-5FU and its parental cell SNU-620. It exerts the anti-proliferative effects with similar potencies against both cancer cells, which is mediated by destabilization of microtubules and subsequent mitotic arrest. Furthermore, this compound enhances caspase-dependent apoptotic cell death via decreased expression of anti-apoptotic genes. Taken together, our data strongly support anti-mitotic potential of 7-diethylamino-3(2'-benzoxazolyl)-coumarin against drug-resistant cancer cells which will prompt us to further develop as a novel microtubule inhibitor for drug-resistant cancer chemotherapy.


Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Antimitóticos/farmacología , Benzoxazoles/farmacología , Cumarinas/farmacología , Resistencia a Antineoplásicos , Fluorouracilo/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Moduladores de Tubulina/farmacología
13.
ACS Appl Mater Interfaces ; 3(7): 2179-83, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21728363

RESUMEN

Herein, we present a one-step facile spray-deposition process for fabricating a new superhydrophobic surface with a novel statistical copolymer. The polymeric material is relatively inexpensive, easily prepared, transparent, solvent-processable, very simple, and applicable to rugged substrates. The materials presented herein also feature a near-perfect superhydrophobic surface with a static water contact angle of 178° and a transmittance of higher than 75% at 550 nm wavelength.

14.
Biochem Biophys Res Commun ; 404(4): 915-21, 2011 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-21184735

RESUMEN

In this study, we investigate the molecular mechanism by which histone deacetylase (HDAC) inhibitors exert anti-invasiveness effect against prostate cancer cells. We first evaluate the growth inhibition effect of HDAC inhibitors in prostate cancer cells, which is accompanied by induction of p21(WAF1) expression and accumulation of acetylated histones. And we found that the migration and invasion of prostate cancer cells is strongly inhibited by treatment with HDAC inhibitors. In parallel, E-cadherin level is highly up-regulated in HDAC inhibitor-treated prostate cancer cells. And siRNA knockdown of E-cadherin significantly diminishes the anti-invasion effect of HDAC inhibitors, indicating that E-cadherin overexpression is one of possible mechanism for anti-invasion effect of HDAC inhibitors. Furthermore, specific downregulation of HDAC1, but not HDAC2, causes E-cadherin expression and subsequent inhibition of cell motility and invasion. Collectively, our data demonstrate that HDAC1 is a major repressive enzyme for E-cadherin expression as well as HDAC inhibitor-mediated anti-invasiveness.


Asunto(s)
Antineoplásicos/farmacología , Cadherinas/biosíntesis , Histona Desacetilasa 1/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Neoplasias de la Próstata/patología , Antígenos CD , Cadherinas/antagonistas & inhibidores , Cadherinas/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación de la Expresión Génica , Histona Desacetilasa 1/antagonistas & inhibidores , Histona Desacetilasa 1/genética , Humanos , Masculino , Invasividad Neoplásica , Neoplasias de la Próstata/enzimología , ARN Interferente Pequeño/genética
15.
Int J Oncol ; 38(3): 807-12, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21170509

RESUMEN

Although histone deacetylase (HDAC) inhibitors are emerging as a promising class of cancer chemotherapeutic agents, their effects on multidrug resistance (MDR) are poorly understood. In this study, we investigated whether HDAC inhibitors overcome MDR phenotype. HDAC inhibitors suppress the growth of both MDR positive cancer cells KBV20C and its parental cells KB with similar potencies. In parallel, histone acetylation and p21WAF1 expression by the HDAC inhibitors were similarly increased in both cell types, indicating that these HDAC inhibitors are poor substrates of ABC drug transporters and effective in MDR cancer cells. In addition, multidrug resistance protein 2 (MRP2) expression is selectively attenuated by HDAC inhibitors, especially SAHA and TSA, in KBV20C cells, whereas MDR1 and BCRP expressions are not affected. This downregulation of MRP2 contributes to increase in paclitaxel-induced G2/M arrest and apoptosis, which might be due to intracellular accumulation of paclitaxel. Collectively, our data provide a molecular rationale for the application of HDAC inhibitors to overcome MDR in cancer cells.


Asunto(s)
Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Inhibidores de Histona Desacetilasas/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Neoplasias/genética , Antineoplásicos/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Evaluación Preclínica de Medicamentos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ácidos Hidroxámicos/farmacología , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/fisiología , Neoplasias/metabolismo , Neoplasias/patología , Paclitaxel/farmacocinética , Paclitaxel/farmacología , Vorinostat
16.
Healthc Inform Res ; 16(1): 60-4, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21818425

RESUMEN

OBJECTIVES: The purpose of this study was to review an implementation of u-Severance information system with focus on electronic hospital records (EHR) and to suggest future improvements. METHODS: Clinical Data Repository (CDR) of u-Severance involved implementing electronic medical records (EMR) as the basis of EHR and the management of individual health records. EHR were implemented with service enhancements extending to the clinical decision support system (CDSS) and expanding the knowledge base for research with a repository for clinical data and medical care information. RESULTS: The EMR system of Yonsei University Health Systems (YUHS) consists of HP integrity superdome servers using MS SQL as a database management system and MS Windows as its operating system. CONCLUSIONS: YUHS is a high-performing medical institution with regards to efficient management and customer satisfaction; however, after 5 years of implementation of u-Severance system, several limitations with regards to expandability and security have been identified.

17.
Bioelectromagnetics ; 30(8): 641-50, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19551766

RESUMEN

With the number of cellular phone users rapidly increasing, there is a considerable amount of public concern regarding the effects that electromagnetic fields (EMFs) from cellular phones have on health. People with self-attributed electromagnetic hypersensitivity (EHS) complain of subjective symptoms such as headaches, insomnia, and memory loss, and attribute these symptoms to radio frequency (RF) radiation from cellular phones and/or base stations. However, EHS is difficult to diagnose because it relies on a person's subjective judgment. Various provocation studies have been conducted on EHS caused by Global System for Mobile Communications (GSM) phones in which heart rate and blood pressure or subjective symptoms were investigated. However, there have been few sham-controlled provocation studies on EHS with Code Division Multiple Access (CDMA) phones where physiological parameters, subjective symptoms, and perception of RF radiation for EHS and non-EHS groups were simultaneously investigated. In this study, two volunteer groups of 18 self-reported EHS and 19 non-EHS persons were tested for both sham and real RF exposure from CDMA cellular phones with a 300 mW maximum exposure that lasted half an hour. We investigated not only the physiological parameters such as heart rate, respiration rate, and heart rate variability (HRV), but also various subjective symptoms and the perception of EMF. In conclusion, RF exposure did not have any effects on physiological parameters or subjective symptoms in either group. As for EMF perception, there was no evidence that the EHS group better perceived EMF than the non-EHS group.


Asunto(s)
Teléfono Celular , Ondas de Radio , Adulto , Temperatura Corporal , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Ondas de Radio/efectos adversos , Respiración
18.
Biochem Pharmacol ; 77(12): 1773-9, 2009 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-19428332

RESUMEN

Microtubules are a proven target for anticancer drug development because they are critical for mitotic spindle formation and the separation of chromosomes at mitosis. We here report a novel synthetic microtubule inhibitor 7-diethylamino-3(2'-benzoxazolyl)-coumarin (DBC). DBC causes destabilization of microtubules, leading to a cell cycle arrest at G(2)/M stage. In addition, human cancer cells are more sensitive to DBC (IC(50) 44.8-475.2nM) than human normal fibroblast (IC(50) 7.9microM), and DBC induces apoptotic cell death of cancer cells. Furthermore, our data show that DBC is a poor substrate of drug efflux pumps and effective against multidrug resistant (MDR) cancer cells. Taken together, these results describe a novel pharmacological property of DBC as a microtubule inhibitor, which may make it an attractive new agent for treatment of MDR cancer.


Asunto(s)
Aminocumarinas/farmacología , Benzoxazoles/farmacología , Cumarinas/farmacología , Resistencia a Antineoplásicos , Moduladores de Tubulina/farmacología , Aminocumarinas/uso terapéutico , Antimitóticos/farmacología , Antimitóticos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Benzoxazoles/uso terapéutico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Cumarinas/uso terapéutico , Fase G2/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Microtúbulos/efectos de los fármacos , Moduladores de Tubulina/uso terapéutico
19.
Mol Cancer Res ; 7(5): 735-44, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19435809

RESUMEN

Although histone deacetylase (HDAC) inhibitors are appreciated as a promising class of anticancer drugs, recent reports show that P-glycoprotein (P-gp) is induced by HDAC inhibitor treatment in cancer cells, resulting in multidrug resistance of cancer cells to other chemotherapeutic agents. In this study, we investigated the molecular mechanism of HDAC inhibitor induction of P-gp expression. HDAC inhibitor treatment causes cell type-specific induction of P-gp expression without changes in the CpG methylation status of the promoter region. In addition, our data show that HDAC inhibitor does not alter the DNA binding activity of Sp1 but facilitates both the recruitment of a coactivator complex that includes CAAT/enhancer binding protein beta and pCAF and the dissociation of the repressive complex, HDAC1, to the Sp1 binding region. Subsequently, the hyperacetylated histone H3 becomes enriched in the promoter region, leading to RNA polymerase II recruitment to activate P-gp gene transcription. Furthermore, specific down-regulation of HDAC1, but not HDAC2, by RNA silencing was enough to induce P-gp expression in HeLa cells, strongly supporting the essential role of HDAC1 in HDAC inhibitor induction of P-gp. Concomitantly, cell type-specific induction of P-gp expression seems to be dependent on phosphatidylinositol 3-kinase activity. Taken together, our findings show that HDAC inhibitor treatment leads to an increase in P-gp expression through dynamic changes in chromatin structure and transcription factor association within the promoter region.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores de Histona Desacetilasas , Regiones Promotoras Genéticas/genética , Factores de Transcripción p300-CBP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Secuencia de Bases , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Cromonas/farmacología , Células HeLa , Histona Desacetilasa 1 , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Immunoblotting , Morfolinas/farmacología , Péptidos Cíclicos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Unión Proteica/efectos de los fármacos , ARN Interferente Pequeño/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Factor de Transcripción Sp1/metabolismo , Transcripción Genética/efectos de los fármacos , Transfección
20.
Asian Spine J ; 3(1): 27-31, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20404943

RESUMEN

A 23-year-old male whose medical history included tuberculous spondylitis presented with a kyphotic deformity and incomplete paraplegia of twenty days duration. Preoperative radiographs demonstrated a T12-L4 kyphotic Cobb's angle of 100 degrees with a complete block showing on the lumbar myelogram at L4-5. The patient underwent anterior osteotomy and release. After the operation, a halo-pelvic apparatus was fit onto the patient, and distraction was begun. After distraction for 2 months, posterior osteotomy and release was performed for final correction, and distraction was maintained for another three weeks. Finally, the kyphotic deformity was corrected to a Cobb's angle of 62 degrees from T12 to L4. Supplementary anterior fusion was done, and the apparatus was removed after consolidation of the fusion mass.Even twenty years after correction of a tuberculous kyphosis, he had no neurological deterioration, and could work as a farmer using agricultural machines. Correction angle and sagittal balance were well maintained.

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