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1.
J Cell Biochem ; 119(1): 885-895, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28661070

RESUMO

The mammalian target of rapamycin (mTOR) pathway is dysregulated in more than 50% of all human malignancies and is a major target in cancer treatment. In this study, we explored the underlying mechanism involving microRNA-145-3p (miR-145-3p) in the development and progression of non-small cell lung cancer (NSCLC) by targeting PDK1 via the mTOR signaling pathway. NSCLC tissues and adjacent normal tissues were obtained from 83 NSCLC patients. miR-145-3p, PDK1, and mTOR levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Human NSCLC cell lines A549 and H1299 were transfected with miR-145-3p and siPDK1 to confirm the effect of miR-145-3p and PDK1 on NSCLC cells in vitro. Cell growth was evaluated by a CCK8 assay. Cell motility and chemotaxis analysis were determined by the scratch test and chemotaxis assay, respectively. The protein levels of PDK1 and mTOR were measured using the western blotting. Results showed lower level of miR-145-3p and higher levels of PDK1 and mTOR in NSCLC tissues compared to the adjacent normal tissues. In vitro results showed that cell growth, cell motility, and chemotaxis were all inhibited in cells transfected with miR-145-3p and those transfected with siPDK. Additionally, dual luciferase reporter gene assay helped confirmed that PDK1 is a target of miR-145. Finally, levels of PDK1, mTOR, and phosphorylated-mTOR were lower in cells transfected with miR-145-3p as well as those with siPDK1. These findings indicate that miR-145-3p may inhibit cell growth, motility, and chemotaxis in NSCLC by targeting PDK1 through suppressing the mTOR pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Serina-Treonina Quinases TOR/genética , Células A549 , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiotaxia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
2.
Tumour Biol ; 37(11): 15241-15252, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27696291

RESUMO

The present study aims to investigate the effects of microRNA-218 (miR-218) on the proliferation, migration, invasion, and apoptosis of gastric cancer (GC) cells by targeting LIM and SH3 domain protein 1 (LASP1). The GC cells in the logarithmic phase were selected and divided into five groups: the blank group, negative control (NC) group, miR-218 inhibitors group, miR-218 inhibitors + siLASP1 group, and miR-218 mimics + siLASP1 group. The miR-218 expression in each group was also detected by qRT-PCR. The CCK8 assay, Transwell migration, and invasion assays and flow cytometry were performed to determine the effects of miR-218 on cell proliferation, migration, invasion, and apoptosis of GC cells. Western blotting was conducted to measure LASP1 protein expression in GC cells after transfection. The qRT-PCR revealed that the transfection of miR-218 mimics could upregulate the miR-218 expression, and the transfection of miR-218 inhibitors could downregulate the miR-218 expression in the GC cells. Compared with the blank and NC groups, the proliferation, migration, and invasion of GC cells were significantly reduced in the miR-218 mimics, miR-218 inhibitors + siLASP1, and miR-218 mimics + siLASP1 groups but enhanced in the miR-218 inhibitors group. Similarly, compared with the blank and NC groups, the cell apoptosis rates in the miR-218 mimics, miR-218 inhibitors + siLASP1, and the miR-218 mimics + siLASP1 groups were significantly increased, while the miR-218 inhibitors group had a lower apoptosis rate. In conclusion, these results indicate that miR-218 could inhibit the proliferation, migration, and invasion and promote apoptosis of GC cells by downregulating LASP1 expression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/secundário , Apoptose , Movimento Celular , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Proteínas com Domínio LIM/metabolismo , MicroRNAs/genética , Neoplasias Gástricas/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Estudos de Casos e Controles , Ciclo Celular , Proteínas do Citoesqueleto/genética , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Proteínas com Domínio LIM/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas
3.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 11): o2984, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22220004

RESUMO

In the title mol-ecule, C(18)H(11)Cl(3)N(2)O(2), the central benzene ring is oriented at 8.44 (12) and 70.57 (11)° with respect to the terminal chloro-phenol and dichloro-pyridine rings, respectively. The mol-ecular structure is stabilized by an intra-molecular O-H⋯N hydrogen bond, which generates an S(6) ring motif. In the crystal, π-π stacking between parallel pyridine rings is observed [centroid-centroid distance = 3.6561 (14) Å].

4.
J Chem Phys ; 131(16): 164305, 2009 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-19894945

RESUMO

Pyridine generally acts as the proton acceptors in the hydrogen bonding interaction by using its lone pair n(N) or pi-electrons. Some previous research indicated that for the N-type H-bond, the ring breathing mode v(1), the N-para-C stretching mode v(6a) and the meta-CC stretching mode v(8a) of pyridine showed a frequency blueshift but the triangle mode v(12) had no change in frequency. Both electrostatic interaction and charge transfer caused by intermolecular hyperconjugation n(N)-->sigma( *)(HX) have contributions to the frequency blue shifts, while charge transfer is predominant at equilibrium intermolecular distance. An intramolecular hyperconjugation between the lone pair n(N) and the two sigma( *)(meta-CC) orbitals in the pyridine ring provides a reasonable interpretation for the effect of charge transfer on the ring stretching modes upon formation of the N-type H-bonding.

5.
Kaohsiung J Med Sci ; 35(1): 39-48, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30844146

RESUMO

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.


Assuntos
Povo Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Xeroderma Pigmentoso/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Haplótipos/genética , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Modelos Genéticos , Fatores de Risco , Fumar , Fuligem
6.
Genet Test Mol Biomarkers ; 21(5): 305-311, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28287835

RESUMO

OBJECTIVE: This case-control study investigated the association of single nucleotide polymorphisms in the PTPN1 gene with susceptibility to esophageal squamous cell carcinoma (ESCC) in Inner Mongolia, China. METHODS: A total of 302 patients living in Inner Mongolia China who were pathologically diagnosed with ESCC between April 2012 and 2016 were selected for the ESCC group; 373 healthy individuals were selected for the control group. The rs2904268 C>G, rs2230605 A>G, and rs16995309 C>T polymorphisms in the PTPN1 gene were detected by bidirectional polymerase chain reaction amplification of specific alleles. The haplotype frequencies were analyzed by SHEsis software. Binary logistic regression analysis was conducted to analyze risk factors associated with ESCC. RESULTS: Statistical differences between the ESCC and control groups were observed for history of smoking, drinking, and poor eating habits (all p < 0.05). Both the rs2904268 C>G CG and GG genotype frequencies were markedly higher in the ESCC group relative to the control group (both p < 0.05). However, the genotype frequencies of rs2230605 A>G and rs16995309 C>T were similar between the ESCC and control groups (all p > 0.05). Compared with the control group, the ESCC group had notably elevated frequencies of the GGC and GAT haplotypes and significantly reduced frequencies of CGC and GGT haplotypes (all p < 0.05). A history of smoking, drinking, poor eating habits, the rs2904268 C>G CG+GG genotypes, and the GAT haplotype were all identified as risk factors for ESCC (all p < 0.05). CONCLUSION: These results indicated that the PTPN1 gene polymorphism rs2904268 is associated with susceptibility to ESCC in Inner Mongolia.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Adenocarcinoma/genética , Adulto , Alelos , Sequência de Bases/genética , Estudos de Casos e Controles , China , Carcinoma de Células Escamosas do Esôfago , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Fatores de Risco , Neoplasias Gástricas/genética
7.
J Cancer Res Clin Oncol ; 138(1): 125-32, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22057732

RESUMO

BACKGROUND: In international prognostic index (IPI) risk-tailored adult patients with diffuse large B-cell lymphoma (DLBCL), it is still unclear whether the addition of maintenance rituximab (MR) improves progression-free (PFS) and overall survival (OS), after RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. METHODS: In our study, 207 patients (age: 21-59 years) received six 14-day cycles of RCHOP and gained overall response. After RCHOP, 98 patients were enrolled in the observation (OBS) arm. 109 patients continued to receive MR therapy. RESULTS: In IPI risk <2 profile, PFS at 5 years reached 72.9% (MR arm) versus 56% (OBS arm) (P = 0.033). In IPI risk ≥2 profile, PFS estimation at 5 years was 44.9% (MR arm) versus 33.5% (OBS arm) (P = 0.006). It is noteworthy that patients with IPI ≥2 who received MR achieved PFS similar to that for patients in the OBS arm with the IPI <2, 44.9% versus 56% (P = 0.97). In patients with an IPI <2, OS at 5 years was 83.2% (MR arm) versus 81.2% (OBS arm) (P = 0.708). In patients with an IPI ≥2, 5-year OS estimation was 44.6% (MR arm) versus 40.5% (OBS arm) (P = 0.067). Subgroup analysis of patients with an IPI ≥3 risk profile shows a survival benefit for patients receiving MR. OS at 5 years was 62% (MR arm) versus 49% (OBS arm), (P = 0.033). CONCLUSIONS: In conclusion, maintenance rituximab after RCHOP improves progression-free survival. In addition, overall survival is improved for patients with an IPI ≥3 risk profile receiving MR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Esquema de Medicação , Humanos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Rituximab , Vincristina/administração & dosagem , Adulto Jovem
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