Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Más filtros

Banco de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
J Med Virol ; 95(1): e28327, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36415105

RESUMEN

Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein, we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure-activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC50 values of 2.14 and 4.88 µM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, rendering this scaffold attractive for pursuing novel anti-influenza agents.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Animales , Perros , Humanos , Antivirales/uso terapéutico , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana/tratamiento farmacológico , Células de Riñón Canino Madin Darby
2.
Planta Med ; 81(2): 160-6, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25626143

RESUMEN

Four new cytochalasins, arthriniumnins A-D (1-4), a new natural product, ketocytochalasin (5), as well as five known cytochalasin analogues (6-10) were isolated and identified from the fungus Arthrinium arundinis ZSDS1-F3 from the sponge Phakellia fusca. Their structures were elucidated by NMR spectroscopic and mass spectrometric analyses, as well as single crystal X-ray diffraction. Compounds 6 and 9 showed cytotoxicity against K562, A549, Huh-7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4 cell lines, with IC50 values ranging from 1.13 to 47.4 µM.


Asunto(s)
Antineoplásicos/farmacología , Ascomicetos/química , Citocalasinas/farmacología , Poríferos/microbiología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocalasinas/química , Citocalasinas/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Difracción de Rayos X
3.
Bioorg Med Chem Lett ; 21(7): 1965-8, 2011 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-21376587

RESUMEN

A series of 2,4-disubstituted thiazole derivatives were designed and synthesized as new Bcr/Abl inhibitors by hybriding the structural moieties from FDA approved imatinib, nilotinib and dasatinib. The new inhibitors strongly suppressed the activity of Bcr/Abl kinase and potently inhibited the proliferation of K562 and KU812 leukemia cancer cells. Compound 4i displayed comparable potency with that of nilotinib in both biochemical kinase assay and cancer cell growth inhibition assay. These inhibitors might serve as lead compounds for further developing new anticancer drugs.


Asunto(s)
Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Tiazoles/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Leucemia/patología , Modelos Moleculares , Relación Estructura-Actividad , Tiazoles/química
4.
Acta Biochim Biophys Sin (Shanghai) ; 42(12): 873-82, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21106769

RESUMEN

Small RNAs, generally expressed at low levels, are difficult to reach usable levels from limited material. In this study, we have developed a novel method to amplify target RNA. The amplification procedure was carried out by sequential RT-PCR, effective separation, restriction enzymatic cleavage of cDNA strand, and run-off transcription in vitro of target RNA from its cDNA. Introduction of a unique stem-loop linker into cDNA strand is the key step to form a unique restriction enzyme recognition sequence that is not in cDNA sequence of target RNA. This method can be used to amplify RNA samples from various origins and has many advantages in amplifying unknown small RNAs and small RNA mixtures. The amplified RNA has the full sequence of original RNA except for an extra 5' G and an additional 3' A or C. The method worked well for amplifications of a microRNA, a piwi interacting RNA and two small RNA mixtures.


Asunto(s)
Enzimas de Restricción del ADN/metabolismo , Técnicas de Amplificación de Ácido Nucleico , ARN Ligasa (ATP)/metabolismo , ARN/metabolismo , Proteínas Virales/metabolismo , Secuencia de Bases , ADN Ligasas/genética , ADN Ligasas/metabolismo , Enzimas de Restricción del ADN/genética , ADN Complementario/genética , ADN Complementario/metabolismo , Datos de Secuencia Molecular , ARN/genética , ARN Ligasa (ATP)/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Virales/genética
5.
Zhongguo Fei Ai Za Zhi ; 9(5): 409-12, 2006 Oct 20.
Artículo en Zh | MEDLINE | ID: mdl-21176460

RESUMEN

BACKGROUND: FUS2 gene locating at 3p21.3 is considered a promising candidate tumor suppressor gene. The aim of this study is to examine the difference in FUS2-767A/T polymorphism site between lung cancer patients and normal controls in Chinese population. METHODS: The genotype FUS2-767A/T was detected in 146 lung cancer patients and 113 normal controls by PCR-SSCP method. The relationship between lung cancer risk and difference in genotypes of FUS2 gene was analysed. RESULTS: FUS2-767A/T was significantly related to histological type (P=0.044), age of the patients with lung cancer (P=0.011) and vessel cancer embolus (P=0.031) in lung cancer group. There was no significant difference in distribution of FUS2 genotypes between lung cancer patients and normal controls (P=0.945). CONCLUSIONS: The results suggest that the FUS2-767A/T polymorphism may be a susceptibility factor for lung cancer among Chinese population.

6.
Antiviral Res ; 129: 13-20, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26802557

RESUMEN

Among many subtypes of influenza A viruses, influenza A(H1N1) and A(H3N2) subtypes are currently circulating among humans (WHO report 2014-15). Therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. To this regard, the design and synthesis of nucleoside analog inhibitors as potential anti-influenza A agents is a very active field of research nowadays. In this study, we designed and synthesized a series of hitherto unknown 6-methyl-7-substituted-7-deaza purine nucleoside analogs, and evaluated for their biological activities against influenza A virus strains, H1N1 and H3N2. From the viral inhibition assay, we identified some effective compounds, among which, compounds 5x (IC50 = 5.88 µM and 6.95 µM for H1N1 and H3N2, respectively) and 5z (IC50 = 3.95 µM and 3.61 µM for H1N1 and H3N2, respectively) demonstrated potent anti-influenza A activity. On the basis of selectivity index, we conceive that compound 5x may serve as a chemical probe of interest for further lead optimization studies with a general aim of developing novel and effective anti-influenza A virus agents.


Asunto(s)
Antivirales/síntesis química , Antivirales/farmacología , Descubrimiento de Drogas , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Nucleósidos de Purina/síntesis química , Nucleósidos de Purina/farmacología , Antivirales/química , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Subtipo H3N2 del Virus de la Influenza A/fisiología , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Oseltamivir/farmacología , Nucleósidos de Purina/química , Ribavirina/farmacología , Zanamivir/farmacología
7.
J Antibiot (Tokyo) ; 68(2): 121-5, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25118104

RESUMEN

A new (2) and four known (1, 8-10) sesquiterpenoids, two new (3 and 4) and eight known (5-7, 11-15) xanthone derivatives were isolated from the cultures of sponge-derived fungus Stachybotry sp. HH1 ZDDS1F1-2. The structure of the compounds 1-15 was determined mainly by analysis of the one-dimensional and two-dimensional NMR spectroscopic data and by analogy with the data of those reported. Compound 1 was confirmed by X-ray crystallography. All the compounds were tested for their cytotoxic, antiinflammatory and antiviral (EV71) effects. Compounds 5, 7 and 11 showed significant cytotoxicity against selected human tumor cell lines. Compounds 3, 4 and 11 also displayed significant inhibitory activity against cycloooxygenase (COX-2). Compounds 4, 5 and 11 showed activities against intestinal virus EV71.


Asunto(s)
Poríferos/microbiología , Sesquiterpenos/farmacología , Stachybotrys/metabolismo , Xantonas/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Antivirales/farmacología , Línea Celular Tumoral , Cristalografía por Rayos X , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Stachybotrys/aislamiento & purificación , Xantonas/química , Xantonas/aislamiento & purificación
8.
ACS Med Chem Lett ; 6(7): 814-8, 2015 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-26191372

RESUMEN

A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One of the representative compounds (5k) significantly reduces the bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.

9.
PLoS One ; 10(3): e0119341, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25760622

RESUMEN

In our previous study, we demonstrated that the use of the autoluminescent Mycobacterium tuberculosis as a reporter strain had the potential to drastically reduce the time, effort, animals and costs consumed in evaluation of the activities of drugs and vaccines in live mice. However, the strains were relatively unstable and lost reporter with time without selection. The kanamycin selection marker used wasn't the best choice as it provides resistance to amino glycosides which are an important class of second line drugs used in tuberculosis treatment. In addition, the marker could limit utility of the strains for screening of new potential drugs or evaluating drug combinations for tuberculosis treatment. Limited selection marker genes for mycobacterial genetic manipulation is a major drawback for such a marker-containing strain in many research fields. Therefore, selectable marker-free, more stable autoluminescent mycobacteria are highly needed. After trying several strategies, we created such mycobacterial strains successfully by using an integrative vector and removing both the resistance maker and integrase genes by Xer site-specific recombination in one step. The corresponding plasmid vectors developed in this study could be very convenient in constructing other selectable marker-free, more stable reporter mycobacteria with diverse applications.


Asunto(s)
Ingeniería Genética/métodos , Proteínas Luminiscentes/metabolismo , Mycobacterium tuberculosis/genética , Animales , Proteínas Bacterianas/genética , Descubrimiento de Drogas/economía , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Integrasas/genética , Resistencia a la Kanamicina , Proteínas Luminiscentes/genética , Ratones , Mycobacterium tuberculosis/enzimología , Mycobacterium tuberculosis/metabolismo , Plásmidos/genética , Plásmidos/metabolismo , Transformación Bacteriana
10.
J Antibiot (Tokyo) ; 67(6): 451-7, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24690916

RESUMEN

Five alkenyl phenol and benzaldehyde derivatives, pestalols A-E (1-5), as well as seven known compounds (6-12), were isolated from endophytic fungus Pestalotiopsis sp. AcBC2 derived from the Chinese mangrove plant Aegiceras corniculatum. Their structures were determined by spectroscopic analyses. Compounds 2 and 3 showed cytotoxicity against a panel of 10 tumor cell lines. Compounds 1-5, 8, 9, 11, and 12 showed inhibitory activities against Influenza A virus subtype (H3N2) and Swine Flu (H1N1) viruses. Compound 2 also showed inhibitory activity against tuberculosis.


Asunto(s)
Benzaldehídos/química , Benzaldehídos/farmacología , Hongos/química , Fenol/química , Fenol/farmacología , Primulaceae/microbiología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Células K562 , Células MCF-7 , Tuberculosis/tratamiento farmacológico , Células U937
11.
Nat Prod Res ; 28(14): 1070-4, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24735402

RESUMEN

One new naphthalene derivative, 1,8-dihydroxynaphthol-1-O-α-l-rhamnopyranoside (1), together with one known α-dibenzopyrone, alternariol (2), and five xanthones (3-7) were isolated from the sponge-derived fungus Arthrinium sp. ZSDS1-F3. All the isolated compounds (1-7) were established by comprehensive analysis of the spectral data, especially 1D and 2D NMR (HMQC and HMBC) spectra. In the primary bioassays, compound 3 exhibited moderate COX-2 inhibition, with IC50 values of 12.2 µM.


Asunto(s)
Ascomicetos/química , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Glicósidos/aislamiento & purificación , Naftoles/aislamiento & purificación , Poríferos/microbiología , Xantonas/aislamiento & purificación , Animales , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/farmacología , Glicósidos/química , Glicósidos/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Naftoles/química , Naftoles/farmacología , Resonancia Magnética Nuclear Biomolecular , Xantonas/química , Xantonas/farmacología
12.
Eur J Med Chem ; 70: 631-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24211639

RESUMEN

Fumagillin (1), a natural product of fungal origin, and its analogs were discovered to be extremely potent and highly selective inhibitors restraining endothelial cell proliferation in vitro by covalently binding to MetAP2. In order to further understand the unclear biological mechanisms and pharmacological processes of fumagillin and its derivatives, fumagillin-biotin conjugate 8 was designed and synthesized, which is linked with a 27-atom connection chain and by urethane (carbamate) bonds between fumagillol and D-norbiotinamine. The conjugate 8 shows comparable activity and selectivity against HUVEC proliferation as fumagillin. It was demonstrated that the conjugate 8 is stable inside the cell and its linker is of a suitable length for the detection of biotin in native and denatured conditions. Using the conjugate 8, it was determined that the cell permeability of fumagillin (1) and its analogs are not responsible for their inhibitory activity difference against the proliferation of endothelial and cancer cells. Furthermore, we confidently believe that our present strategy is a versatile and convenient method for investigating drug's cell permeability along with other studies regardless of reversible or irreversible interaction between the drug and binding target/s.


Asunto(s)
Permeabilidad de la Membrana Celular/efectos de los fármacos , Ciclohexanos/farmacología , Diseño de Fármacos , Ácidos Grasos Insaturados/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Biotinilación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclohexanos/síntesis química , Ciclohexanos/química , Relación Dosis-Respuesta a Droga , Ácidos Grasos Insaturados/síntesis química , Ácidos Grasos Insaturados/química , Células Hep G2 , Humanos , Células MCF-7 , Estructura Molecular , Sesquiterpenos/síntesis química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Relación Estructura-Actividad
13.
J Med Chem ; 55(5): 2144-53, 2012 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-22332894

RESUMEN

The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC(50) values ranging from 0.5 to 4.6 µM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC(50) values in sub-µM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.


Asunto(s)
Amidas/síntesis química , Antivirales/síntesis química , Virus de la Influenza A/efectos de los fármacos , Nucleoproteínas/metabolismo , Piperazinas/síntesis química , Triazoles/síntesis química , Proteínas del Núcleo Viral/metabolismo , Amantadina/farmacología , Amidas/química , Amidas/farmacología , Animales , Antivirales/química , Antivirales/farmacología , Línea Celular , Perros , Diseño de Fármacos , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/metabolismo , Modelos Moleculares , Oseltamivir/farmacología , Piperazinas/química , Piperazinas/farmacología , Relación Estructura-Actividad , Triazoles/química , Triazoles/farmacología , Ensayo de Placa Viral , Replicación Viral/efectos de los fármacos
14.
Antiviral Res ; 96(2): 91-9, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22982118

RESUMEN

The adamantanes are a class of anti-influenza drugs that inhibit the M2 ion channel of the influenza A virus. However recently, the clinical effectiveness of these drugs has been called into question due to the emergence of adamantane-insensitive A/M2 mutants. Although we previously reported (1R,2R,3R,5S)-3-pinanamine 3 as a novel inhibitor of the wild type influenza A virus M2 protein (WT A/M2), limited inhibition was found for adamantane-resistant M2 mutants. In this study, we explored whether newly synthesized pinanamine derivatives were capable of inhibiting WT A/M2 and selected adamantane-resistant M2 mutants. Several imidazole and guanazole derivatives of pinanamine were found to inhibit WT A/M2 to a comparable degree as amantadine and one of these compounds 12 exhibits weak inhibition of A/M2-S31N mutant and it is marginally more effective in inhibiting S31NM2 than amantadine. This study provides a new insight into the structural nature of drugs required to inhibit WT A/M2 and its mutants.


Asunto(s)
Antivirales/aislamiento & purificación , Antivirales/farmacología , Virus de la Influenza A/efectos de los fármacos , Canales Iónicos/antagonistas & inhibidores , Proteínas de la Matriz Viral/antagonistas & inhibidores , Animales , Antivirales/síntesis química , Antivirales/química , Línea Celular , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Ensayo de Placa Viral
15.
Eur J Med Chem ; 46(4): 1117-21, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21296467

RESUMEN

Miltipolone (1) was discovered as a good and broad-spectrum inhibitor against the growth of cancer cells from "Danshen" based on the activity-driven screening of TCMs. The structural features make 1 easily tautomerize between different forms and 1 is linked and stabilized by intermolecular O-H⋯O hydrogen bonds in the crystal structure. The interaction of 1 in ddH(2)O solution with Co(2+), Mn(2+), Zn(2+), Fe(2+) or Fe(3+) changed UV absorption values; the chelation of 1 with Fe(2+) or Fe(3+) also altered the characteristic UV absorption peaks. However, only did Fe(2+) reverse 1's inhibition against the growth of cancer cells; therefore, we concluded that 1 possibly acts as a Fe(2+) chelator to conduct its inhibitory activity.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Quelantes del Hierro/química , Quelantes del Hierro/farmacología , Tropolona/análogos & derivados , Antineoplásicos/análisis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Diterpenos/análisis , Humanos , Hierro/química , Quelantes del Hierro/análisis , Isomerismo , Modelos Moleculares , Conformación Molecular , Tropolona/análisis , Tropolona/química , Tropolona/farmacología , Agua/química
16.
Clin Cancer Res ; 17(21): 6802-11, 2011 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-21890451

RESUMEN

PURPOSE: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients. EXPERIMENTAL DESIGN: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I-III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined. RESULTS: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan-Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan-Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2. CONCLUSIONS: Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , ARN Helicasas DEAD-box/biosíntesis , ARN Helicasas DEAD-box/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Pronóstico , Proteína Fosfatasa 2/genética , Proteínas Serina-Treonina Quinasas/genética , Ribonucleasa III/biosíntesis , Ribonucleasa III/genética , Tasa de Supervivencia , Transfección , Proteínas Supresoras de Tumor/genética , Adulto Joven
17.
Cancer Biol Ther ; 9(2): 111-9, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20009523

RESUMEN

Lung cancer remains the most common cause of death for malignancy in both men and women. Current therapies for NSCLC patients are inefficient due to the lack of diagnostic and therapeutic markers. The phospho-Ser/Thr-Pro specific prolyl-isomerase Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a target for cancer therapy. We identified 79 cases with the follow-up survival and investigated the clinical relevance of Pin1 expression in NSCLC patients. To validate the oncogenic potential of Pin1 in lung cells, we overexpressed Pin1 in Glc82 cells, and downregulated Pin1 by RNA interference in H1299 cells. The 5-year survival rate of the 79 patients was 54.6%. High expression of Pin1 correlated with poor survival by univariate analysis as well as by multivariate analysis, demonstrating that high expression of Pin1 was an independent prognostic factor. Consistent with the clinical findings, overexpression of Pin1 in Glc82 cells increased cell growth and colony formation and tumorigenicity in nude mice including cell migration, invasion. To further validate the role of Pin1 in lung cancer carcinogenesis, lentivirus-mediated siRNA targeting of Pin1 resulted in the stable suppression of both cell growth, anchorage-independent growth in soft agar and tumorigenic including cell migration, invasion in H1299 cells. Pin1 expression may be an unfavorable prognostic factor in patients of NSCLC patients, and these results indicate that Pin1 may have a role in tumor development and metastasis and thus could serve as a novel target for treatment of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/fisiología , Isomerasa de Peptidilprolil/fisiología , Adulto , Anciano , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral/metabolismo , Línea Celular Tumoral/trasplante , Movimiento Celular , Transformación Celular Neoplásica , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Peptidilprolil Isomerasa de Interacción con NIMA , Invasividad Neoplásica , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Trasplante de Neoplasias , Isomerasa de Peptidilprolil/biosíntesis , Isomerasa de Peptidilprolil/genética , Pronóstico , Interferencia de ARN , ARN Interferente Pequeño/farmacología , Análisis de Supervivencia , Ensayo de Tumor de Célula Madre
19.
Ann Surg Oncol ; 14(9): 2628-35, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17525835

RESUMEN

BACKGROUND: Increasing evidence has suggested that RhoE plays an important role in carcinogenesis and progression. However, the correlation between RhoE expression and clinical outcome in lung cancer has not been investigated. METHODS: RhoE expression was detected by immunohistochemistry on tissue microarray containing samples from 115 patients with non-small cell lung cancer with a median follow-up of 54 months. RESULTS: RhoE was overexpressed in the cytoplasm of lung cancer cells compared with undetectable expression of RhoE in the adjacent nontumoral cells. Patients with RhoE-negative tumors had substantially longer cancer-related survival than did patients with RhoE-positive tumors. Multivariate analysis showed that RhoE overexpression was an independent marker for cancer-related survival in the entire population after adjusting for other prognostic factors. CONCLUSIONS: RhoE expression may serve as an unfavorable prognostic factor in patients with non-small cell lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Western Blotting , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Regulación hacia Arriba
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA