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1.
J Cell Mol Med ; 27(3): 392-402, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36647700

RESUMEN

Flotillin-1(FLOT1) has long been recognized as a tumour-promoting gene in several types of cancer. However, the expression and function of FLOT1 in glioblastomas (GBM) has not been elucidated. Here, in this study, we find that the expression level of FLOT1 in GBM tissue was much higher than that in normal brain, and the expression was even higher in the more aggressive subtypes and IDH status of glioma. Kaplan-Meier survival revealed that high FLOT1 expression is closely associated with poor outcome in GBM patients. FLOT1 knockdown markedly reduced the proliferation, migration and invasiveness of GBM cells, while FLOT1 overexpression significantly increases GBM cell proliferation, migration and invasiveness. Mechanistically, FLOT1 expression may play a potential role in the microenvironment of GBM. Therefore, FLOT1 promotes GBM proliferation and invasion in vitro and in vivo and may serve as a biomarker of prognosis and therapeutic potential in the fight against GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patología , Pronóstico , Microambiente Tumoral/genética , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica/genética , Movimiento Celular/genética
2.
World J Surg Oncol ; 21(1): 299, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735407

RESUMEN

BACKGROUND: To explore the diagnostic value of Caprini risk assessment model (2005) combined with D-dimer for deep vein thrombosis, and to exclude patients with low incidence of thrombosis who might not need anticoagulation after surgery. METHODS: A total of 171 colorectal cancer patients who underwent surgery from January 2022 to August 2022 were enrolled in this study. Caprini risk assessment model was used to evaluate patients the day before surgery, and full-length venous ultrasonography of lower extremity was used to assess whether patients had thrombosis one day before surgery and the sixth day after surgery. The value of D-dimer was measured by enzyme-linked immunosorbent assays on the first day after surgery, and clinical data of patients were collected during hospitalization. RESULTS: A total of 171 patients were divided into IPC Group and IPC + LMWH Group according to whether low molecular weight heparin (LMWH) were used to prevent thrombus after surgery. Eventually, 17.6% (15/85) patients in IPC Group and 7% (6/86) patients in IPC + LMWH Group developed DVT. Through separate analysis of IPC Group, it is found that Caprini score and D-dimer were independent risk factors for DVT (Caprini OR 3.39 [95% CI 1.38-8.32]; P = 0.008, D-Dimer OR 6.142 [95% CI 1.209-31.187]; P = 0.029). The area under ROC curve of Caprini risk assessment model is 0.792 (95% CI 0.69-0.945, P < 0.01), the cut-off value is 9.5, and the area under ROC curve of D-dimer is 0.738 (95%CI 0.555-0.921, P < 0.01), the cut-off value is 0.835 µg/mL, and the area under the ROC curve was 0.865 (95% CI 0.754-0.976, P < 0.01) when both of them were combined. Based on decision curve analysis, it is found that Caprini risk assessment model combined with D-dimer can benefit patients more. All patients are divided into four groups. When Caprini score < 10 and D-dimer < 0.835 µg/mL, only 1.23% (1/81) of patients have thrombosis and LMWH has little significance. When Caprini score > 10 and D-dimer > 0.835 µg/mL, the incidence of DVT is 38.7% (12/31) and LMWH should be considered. CONCLUSIONS: The Caprini risk assessment model and D-dimer can provide more accurate risk stratification for patients after laparoscopic radical resection of colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Laparoscopía , Trombosis de la Vena , Humanos , Heparina de Bajo-Peso-Molecular , Medición de Riesgo , Laparoscopía/efectos adversos , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Neoplasias Colorrectales/cirugía
3.
Chemistry ; 28(5): e202103715, 2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-34837718

RESUMEN

Electron-transferable oxidants such as B(C6 F5 )3 /nBuLi, B(C6 F5 )3 /LiB(C6 F5 )4 , B(C6 F5 )3 /LiHBEt3 , Al(C6 F5 )3 /(o-RC6 H4 )AlH2 (R=N(CMe2 CH2 )2 CH2 ), B(C6 F5 )3 /AlEt3 , Al(C6 F5 )3 , Al(C6 F5 )3 /nBuLi, Al(C6 F5 )3 /AlMe3 , (CuC6 F5 )4 , and Ag2 SO4 , respectively were employed for reactions with (L)2 Si2 C4 (SiMe3 )2 (C2 SiMe3 )2 (L=PhC(NtBu)2 , 1). The stable radical cation [1]+. was formed and paired with the anions [nBuB(C6 F5 )3 ]- (in 2), [B(C6 F5 )4 ]- (in 3), [HB(C6 F5 )3 ]- (in 4), [EtB(C6 F5 )3 ]- (in 5), {[(C6 F5 )3 Al]2 (µ-F)]- (in 6), [nBuAl(C6 F5 )3 ]- (in 7), and [Cu(C6 F5 )2 ]- (in 8), respectively. The stable dication [1]2+ was also generated with the anions [EtB(C6 F5 )3 ]- (9) and [MeAl(C6 F5 )3 ]- (10), respectively. In addition, the neutral compound [(L)2 Si2 C4 (SiMe3 )2 (C2 SiMe3 )2 ][µ-O2 S(O)2 ] (11) was obtained. Compounds 2-11 are characterized by UV-vis absorption spectroscopy, X-ray crystallography, and elemental analysis. Compounds 2-8 are analyzed by EPR spectroscopy and compounds 9-11 by NMR spectroscopy. The structure features are discussed on the central Si2 C4 -rings of 1, [1]+. , [1]2+ , and 11, respectively.

4.
Inorg Chem ; 61(44): 17855-17863, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36282015

RESUMEN

Deep-ultraviolet (DUV; <200 nm) nonlinear optical crystals arouse a great research interest in modern optical material science as they are key parts of solid-state lasers. Since KBe2BO3F2 (KBBF) still is the only crystal which can generate DUV coherent light practically, exploring other available structures in the DUV region by revising KBBF-family structure templates is necessary. In this paper, two KBBF-family structures are designed by adjusting the directions of BO3 groups or docking B and F atoms in known ß-Be2BO3F (BBF). The first BBF structure with a P6322 space group is designed by strictly aligning the BO3 groups of even layers and odd layers in ß-BBF. It is very interesting that docking B and F atoms forms novel B-F bonds, which destroy the inversion symmetry of the structure, making the centrosymmetric ß-BBF structure with the R3̅c space group convert to a noncentrosymmetric BBF structure having the R3c space group. This noncentrosymmetric BBF structure exhibits a DUV cutoff edge shorter than 150 nm and a second harmonic generation effect comparable to that of KH2PO4 (KDP; d36 = 0.39 pm/V), indicating its feasibility as a frequency-doubling crystal in the DUV region. Our conversion design provides an effective way for uncovering noncentrosymmetric structures in KBBF-family structures.

5.
Inorg Chem ; 61(6): 2713-2718, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35107974

RESUMEN

Three mixed-alkali-metal fluorooxoborates, KNaB3O4F3 (I), K2B3O4F3 (II), and KCsB3O4F3 (III), were acquired in a closed system. I-III are isomorphic and adopt orthorhombic structures [Pbcn (No. 60)] with wavy parallelly arranged pseudolayers composed of ∞1[B3O4F3] chains, which exhibit slight differences in the arrangement modes of the fundamental building blocks. First-principles calculations illustrate that they all have moderate birefringence and large band gaps on the order of 7.0 eV, suggesting deep-ultraviolet (DUV) cutoff edges. In order to investigate the main source of the optical properties, the electronic structure and anisotropy of the response electron distribution were analyzed. Experimental characterizations for I confirm the structure and DUV transparence ability.

6.
Inorg Chem ; 61(13): 5215-5223, 2022 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-35312318

RESUMEN

Two borylaminoamidinatosilylenes (L)[(1,5-C8H14)B(Ar)N]Si (L = PhC(NtBu)2, Ar = 2,6-iPr2C6H3 (1)) and (L)[(1,5-C8H14)B(Ar')N]Si (Ar' = 2,4,6-Me3C6H2 (2)) have been prepared and utilized to investigate the reaction toward isocyanide. Reactions of 1 with the respective CN-2,6-Me2C6H3 and CNCy (Cy = cyclo-C6H11) produced compounds (L)Si(NAr)C(N-2,6-Me2C6H3)B(1,5-C8H14)(CN-2,6-Me2C6H3) (3) and (L)Si(NAr)C(NCy)C(NCy)B(1,5-C8H14)(CNCy) (4). Reactions of 2 with the respective CNCy and CN-2,6-Me2C6H3 yielded compounds cyclo-(L)SiN(Ar')C(NCy)B(1,5-C8H14)C(NCy) (5) and cyclo-(L)[(1,5-C8H14)B(Ar')N]SiC(CN-2,6-Me2C6H3)N(2,6-Me2C6H3)C(N-2,6-Me2C6H3) (6). Compounds 3-6 have different compositions and structures from each other. Density functional theory (DFT) calculations suggest initial formation of (L)[(1,5-C8H14)B(←:CN-2,6-Me2C6H3)(Ar)N]Si (A), (L)[(1,5-C8H14)B(←:CNCy)(Ar)N]Si (A'), (L)[(1,5-C8H14)B(←:CNCy)-(Ar')N]Si (A″), and (L)[(1,5-C8H14)B(←:CN-2,6-Me2C6H3)(Ar')N]Si (A‴) as the respective intermediates. The as-followed transition states TS, TS1', TS1″, and TS‴ all feature probable Si:→C(═N):→B bonding with different Gibbs energies of 7.24, 2.46, 3.86, and 6.59 kcal/mol, respectively, due to variation among the Ar, Ar', 2,6-Me2C6H3, and Cy groups in these species, and reacted in different ways.

7.
Int J Cancer ; 146(7): 1937-1949, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31376289

RESUMEN

Yes-associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, stem cell maintenance and tissue homeostasis. The YAP activity is primarily regulated through an inhibitory phosphorylation by the serine/threonine kinases of Hippo pathway. Here, we show that receptor tyrosine kinase (RTK) erythropoietin-producing hepatocellular receptor A2 (EphA2) interacts with and phosphorylates YAP protein, leading to stabilization, nuclear translocation and activation of YAP in gastric cancer (GC) cells. EphA2 induces chemotherapy-resistance by increasing YAP stability and nuclear YAP protein. Knockdown of YAP blocks EphA2-induced tumor growth in GC xenograft mouse models. Importantly, the coactivation of EphA2 and YAP is manifested in clinical human GC, and is related to GC recurrence. Thus, our results establish a novel EphA2-to-YAP pathway that drives GC growth, progression and therapy-resistance, targeting this pathway would be an efficient way for the treatment of GC, particularly chemotherapy-resistant GC.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Efrina-A2/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Factores de Transcripción/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Humanos , Ratones , Modelos Biológicos , Fosforilación , Unión Proteica , Transporte de Proteínas , Receptor EphA2 , Recurrencia , Neoplasias Gástricas/etiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Scand J Gastroenterol ; 55(2): 202-208, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32008420

RESUMEN

Aim: This study aims to establish and validate an effective nomogram to predict cancer-specific survival (CSS) in elderly patients with stages I-III colon cancer.Methods: The data of elderly colon cancer patients with stages I-III were enrolled from the Surveillance, Epidemiology, and End Results database (SEER) between 2010 and 2015. The eligible patients were randomly divided into a training cohort and a validation cohort (ratio 1:1). All predictors of cancer-specific survival were determined by Cox regression. The concordance index (C-index) and calibration curves were used for validation of nomograms. Decision curve analysis (DCA) was performed to evaluate the clinical net benefit of the nomogram.Results: Cox hazard analysis in the training cohort indicated that grade, tumor stage, node stage, colectomy, and CEA were independent predictors of CSS. Nomogram was constructed based on these predictors. The C-index of nomograms for CSS was 0.728 (95%CI: 0.7133-0.7427), and were superior to that of AJCC TNM Stage (C-index: 0.625, 95%CI: 0.6093-0.6406). The calibration curves showed satisfactory consistency between actual observation and nomogram-predicted CSS probabilities. The validation cohort demonstrated similar results. The DCA showed high net benefit of nomogram in a clinical context. The population was divided into three groups based on the scores of the nomogram, and the survival analysis showed that this prognostic stratification was statistically significant (p < 0.01).Conclusion: The nomograms showed significant accuracy in predicting 1-, 3-, and 5-year CSS in elderly patients with stages I-III colon cancer and may be helpful inpatient counseling clinical decision guidance.


Asunto(s)
Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Nomogramas , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Metástasis Linfática , Masculino , Estadificación de Neoplasias , Pronóstico , Curva ROC , Medición de Riesgo , Factores de Riesgo , Programa de VERF , Análisis de Supervivencia , Estados Unidos/epidemiología
9.
Int J Colorectal Dis ; 35(12): 2185-2195, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32720185

RESUMEN

PURPOSE: Neuroendocrine differentiation (NED) may serve as a prognostic factor in colorectal cancer; however, the prognostic relevance of NED remains controversial. The aim of the present study was to determine whether NED influenced the survival of patients in colorectal cancer while exploring its potential interactions with other clinicopathological features. METHODS: Patients with primary stage I to IV colorectal adenocarcinoma ranging between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier technique, Cox proportional hazards model, propensity score matching, and stratification analyses were employed in this study. RESULTS: A total of 94,291 patients (including 101 patients with NED and 94,190 patients without NED) were included. In the univariable analyses, NED was found to be correlated with a significantly poorer overall survival (hazard ratio (HR) of death = 3.09, 95% CI 2.42-3.95, P < 0.001) and cancer-specific survival (HR of death = 3.77, 95% CI 2.94-4.83, P < 0.001). Moreover, NED remained independently correlated with overall survival (HR of death = 1.84, 95% CI 1.34-2.51, P < 0.001) and cancer-specific survival (HR of death = 2.01, 95% CI 1.45-2.79, P < 0.001) after adjusting in multivariable and propensity score analyses. Furthermore, further stratification analyses indicated that the influence of NED on survival was not affected by tumor location, differentiation, T stage, and distant metastasis status; however, it was found to be associated with lymph node metastasis. CONCLUSIONS: NED is associated with poor survival outcomes among colorectal cancer patients, especially in those with positive lymph nodes.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Humanos , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales
10.
Cell Physiol Biochem ; 46(3): 1275-1285, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29680837

RESUMEN

BACKGROUND/AIMS: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). METHODS: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. RESULTS: The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/ß-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/ß-catenin signaling inhibition induced by HOTAIR knockdown. CONCLUSIONS: Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/ß-catenin signaling pathway.


Asunto(s)
Neoplasias Colorrectales/patología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Secuencia de Bases , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Resistencia a Antineoplásicos , Femenino , Células HT29 , Humanos , Masculino , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/metabolismo , Alineación de Secuencia , Regulación hacia Arriba , Vía de Señalización Wnt , beta Catenina/antagonistas & inhibidores , beta Catenina/metabolismo
11.
Med Sci Monit ; 24: 2360-2367, 2018 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-29670073

RESUMEN

BACKGROUND The aim of this study was to determine whether polymorphisms of the Ras-association domain family 1 isoform A (RASSF1A) gene were associated with ovarian cancer and with tumor grade and stage, which affect the prognosis of ovarian cancer, in women in Southern China. MATERIAL AND METHODS Women from Southern China with histologically confirmed, graded and staged ovarian cancer (n=1,375), and cancer-free controls (n=1,227), provided samples of peripheral blood. DNA was extracted from the blood samples, and five tagging single nucleotide polymorphisms (SNPs) (rs4688728G>T, rs72932987C>T, rs1989839C>T, rs2073497A>C, and rs2236947A>C) were evaluated using an online assay-by-design platform. Polymerase chain reaction (PCR) DNA amplification was performed and computational haplotyping analysis of genetic associations between the five tagging SNPs was performed to identify frequent haplotypes in women with ovarian cancer, and the associations with tumor grade and stage. RESULTS In women in Southern China, the CT genotype of rs1989839 was associated with the patients with ovarian cancer (P=0.001), and was significantly correlated with tumor grade and stage (P=0.008). One of the remaining four SNPs studied, rs2073497A>C showed an association with the prognostic factors of grade and stage, but this association did not reach statistical significance. CONCLUSIONS Polymorphisms of the RASSF1A gene, most significantly the CT genotype of rs1989839, might play a role in the development and prognosis of ovarian cancer in women in Southern China. To our knowledge, this is the first study to demonstrate an association between polymorphisms in the RASSF1A gene in ovarian cancer.


Asunto(s)
Estadificación de Neoplasias/métodos , Neoplasias Ováricas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , China/epidemiología , Metilación de ADN , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Isoformas de Proteínas/genética , Proteínas Supresoras de Tumor/metabolismo
12.
Cell Physiol Biochem ; 43(5): 2022-2036, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29059680

RESUMEN

BACKGROUND/AIMS: In order to further characterize the biological traits of Dp71, HBE over expressing two most abundantly expressed Dp71 spliced isoforms, Dp71d and Dp71f, were established and their biological traits were explored. METHODS: The proliferation, migration and invasion capabilities of HBE-Dp71d and HBE-Dp71f cells were evaluated by MTT, colony formation, transwell and scratch assay. Cell cycle and apoptosis induced by H2O2 were measured by flow cytometer. Co-IP was performed to prove the interaction between lamin B1, FAK and Dp71. Western blot was performed to detect lamin B1, FAK, ERK and Cyclin D expression in HBE-Dp71d and HBE-Dp71f cells. RESULTS: HBE-Dp71d and HBE-Dp71f cells proliferated faster than their mock and blank controls; shortened their G0/G1 phase; enhanced their invasion and migration capabilities; reduced their apoptosis induced by H2O2. Co-IP proved Dp71 directly interacting with focal adhesion kinase (FAK) and lamin B1 in HBE cells. Increased lamin B1, FAK mRNA and protein expression, over activation of integrin/focal adhesion kinase/extracellular signal-regulated kinase (ERK)/cyclin D pathway were observed in HBE-Dp71d and HBE-Dp71f cells. CONCLUSIONS: Via increasing FAK in the cytoplasmic FAK-Dp71 , lamin B1 of nucleus laminB1-Dp71 complex, HBE-Dp71d and HBE-Dp71f cells alter their proliferation, migration, invasion, cell cycle and apoptosis rate induced by H2O2.


Asunto(s)
Distrofina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Ciclina D/metabolismo , Distrofina/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Quinasa 1 de Adhesión Focal/metabolismo , Fase G1/genética , Fase G1/fisiología , Células HeLa , Humanos , Peróxido de Hidrógeno/farmacología , Células PC12 , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratas , Fase de Descanso del Ciclo Celular/genética , Fase de Descanso del Ciclo Celular/fisiología
13.
Med Sci Monit ; 23: 5892-5898, 2017 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-29232358

RESUMEN

BACKGROUND Insulin-like growth factor 1 (IGF-1) gene plays an important role in bone and soft tumors. IGF-1 gene polymorphisms have been revealed to be correlated with the carcinogenesis and progression of solid malignancies. We therefore hypothesized that IGF-1 genetic polymorphisms might be associated with the risks and outcomes of osteosarcomas in Chinese individuals. MATERIAL AND METHODS This study included 173 conventional osteosarcoma individuals and 175 tumor-free controls. Five single nucleotide polymorphisms (SNPs) of IGF-1 (rs6214, rs6218, rs35767, rs5742612, and rs5742714) were genotyped. DNA was extracted from peripheral blood and analyzed for SNP genotyping using PCR. RESULTS We found that rs6218 had a predictive role for the susceptibility and progression of osteosarcoma. The presence of TC and CC genotypes of rs6218 indicated higher risk of osteosarcoma. In addition, rs6218 TC and CC genotypes were discovered to be associated with later stage and elevated risk of osteosarcoma metastasis. CONCLUSIONS IGF-1 polymorphisms are potential prognostic predictors of osteosarcoma susceptibility and outcomes.


Asunto(s)
Factor I del Crecimiento Similar a la Insulina/genética , Osteosarcoma/genética , Adolescente , Alelos , Estudios de Casos y Controles , China/epidemiología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Osteosarcoma/sangre , Osteosarcoma/metabolismo , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Factores de Riesgo , Adulto Joven
14.
Med Sci Monit ; 23: 3185-3191, 2017 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-28663539

RESUMEN

BACKGROUND The transcription factor 21 (TCF21) gene is believed to be a tumor suppressor gene. TCF21 gene polymorphisms were found to play a role in the tumorigenesis of some solid malignancies. We raised a hypothesis that genetic polymorphisms of TCF21 were correlated with risk and prognosis of osteosarcoma. MATERIAL AND METHODS We recruited 225 young osteosarcoma individuals and 250 cancer-free controls. Five tagging SNPs (TCF21 rs2327429 T>C, rs2327433 A>G, rs2327433 A>G, rs12190287 C>G, and rs4896011 T>A) were genotyped. Preserved DNA samples from blood underwent PCR analysis for genotyping. RESULTS rs12190287 C>G is a good predictor of osteosarcoma risk and outcomes. The CG and GG genotypes of rs12190287 predict elevated risk of osteosarcoma. Besides, rs12190287 CG and GG genotypes are associated with Enneking stage and potential in forming metastasis of osteosarcoma. CONCLUSIONS Genetic polymorphisms of TCF21 are potentially predictive for osteosarcoma risk and outcomes.


Asunto(s)
Pueblo Asiatico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Osteosarcoma/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Factores de Confusión Epidemiológicos , Femenino , Genoma Humano , Haplotipos/genética , Humanos , Modelos Logísticos , Masculino , Metástasis de la Neoplasia , Factores de Riesgo , Resultado del Tratamiento
15.
Cancer Invest ; 34(1): 16-25, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26691328

RESUMEN

Dp71 is one of the most ubiquitously expressed isoforms of dystrophin, the pathological genes of DMD. In order to find whether the alteration of Dp71 can affect the phenotypes of cell other than PC12, an A549 cell line with stably transfected Dp71 siRNA plasmids was set up and named A549-Dp71AS cell. It is demonstrated for the first time that the A549-Dp71AS cell line displayed decreased invasion capabilities, reduced migration ability, decreased proliferation rate, and lessened clonogenic formation. Cisplatin-induced apoptosis was also increased in A549-Dp71AS cell line via enhancing the Caspase 3, Caspase 8, and Caspase 9 activities. Knocking down Dp71 expression can significantly inhibit the A549 xenograft tumor growth in nude mice. The A549-Dp71AS cells and xenograft tumor tissues displayed reduced lamin B1, Bcl-2, and MMP2 protein expression, which accounts for the reduced malignancy of A549-Dp71AS cells in vivo and in vitro.


Asunto(s)
Distrofina/deficiencia , Distrofina/genética , Técnicas de Silenciamiento del Gen , Neoplasias/genética , Neoplasias/patología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Modelos Animales de Enfermedad , Expresión Génica , Xenoinjertos , Humanos , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Clasificación del Tumor , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Ensayo de Tumor de Célula Madre
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(2): 127-33, 2016 Feb.
Artículo en Zh | MEDLINE | ID: mdl-26932209

RESUMEN

OBJECTIVE: To examine the expression of liver X receptor-ß (LXR-ß) in human gastric cancer tissue, and to explore the effect of GW3965, an agonist of LXRs, on proliferation of gastric cancer cell line SGC-7901.
 METHODS: The immunohistochemical assay was used to detect the expression of LXR-ß, activating transcription factor 4 (ATF4) in gastric cancer tissues and the corresponding pericarcinoma tissues in 114 patients. Real-time quantitative PCR and Western blot were used to determine mRNA and protein levels of ATF4 and ATP-binding cassette 1 (ABCA1), one of the downstream target genes of LXRs, in SGC-7901 cells with or without GW3965 treatment. Cell counting kit-8 (CCK-8) assay was performed to detect cell proliferation. The expression of ATF4 was silenced by short hairpin RNA (shRNA).
 RESULTS: The expressions of LXR-ß and ATF-4 were obviously down-regulated in the gastric cancer tissues than that in the corresponding pericarcinoma tissues (both P<0.05). Compared with the control cells, GW3965 treatment inhibited proliferation of SGC-7901 cells and up-regulated ATF4 and ABCA1 expressions (both P<0.05). Knockdown of ATF4 can reverse the antiproliferative effect of GW3965 on SGC-7901 cells.
 CONCLUSION: The expression of LXR-ß is decreased in human gastric cancer tissues, and activation of LXRs by GW3965 could inhibit the proliferation of SGC-7901 cells via ATF4.


Asunto(s)
Benzoatos/farmacología , Bencilaminas/farmacología , Proliferación Celular , Receptores Nucleares Huérfanos/metabolismo , Neoplasias Gástricas/patología , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Línea Celular Tumoral/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Receptores X del Hígado , Receptores Nucleares Huérfanos/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Regulación hacia Arriba
17.
Am J Med Genet B Neuropsychiatr Genet ; 168(8): 712-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26345603

RESUMEN

Relapse is a typical feature of heroin addiction and rooted in genetic and psychological determinants. The aim of this study was to evaluate the effect of personality traits, impulsivity, and COMT gene polymorphism (rs4680) on relapse to heroin use during 5-year follow up. 564 heroin dependent patients were enrolled in compulsory drug rehabilitation center. 12 months prior to their release, personality traits were measured by BIS-11 (Barratt Impulsiveness Scale-11) and Temperament and Character Inventory (TCI). The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. The heroin use status was evaluated for 5 years after discharged. Among the 564 heroin-dependent patients, 500 were followed for 5 years after discharge and 53.0% (n = 265) were considered as relapsed to heroin use according to a strict monitor system. Univariate analysis showed that age, having ever been in methadone maintenance treatment (MMT), the total scores and non-planning scores of BIS-11, and the COMT rs4680 gene variants were different between relapse and abstinent groups. Logistic regression analysis showed higher BIS total score, having ever been in MMT and younger first heroin use age are the predictors of relapse to heroin use during 5 years follow-up, and the COMT rs4680 gene had an interaction with BIS scores. Our findings indicated that the impulsive personality traits, methadone use history, and onset age could predict relapse in heroin-dependent patients during 5 year's follow up. The COMT gene showed a moderational effect in part the relationship of impulsivity with heroin relapse.


Asunto(s)
Catecol O-Metiltransferasa/genética , Dependencia de Heroína/genética , Adulto , Edad de Inicio , China , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Dependencia de Heroína/rehabilitación , Humanos , Conducta Impulsiva , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Personalidad/genética , Polimorfismo de Nucleótido Simple , Recurrencia
18.
World J Surg Oncol ; 12: 166, 2014 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-24885006

RESUMEN

The small bowel rarely suffers from metastatic tumors from outside the abdomen. Small bowel obstructions caused by the metastatic spread of squamous cell carcinoma (SCC) of the hand to the intestines are even rarer. A 71-year-old man with intermittent abdominal distension and pain for 4 months was diagnosed with partial bowel obstruction. The patient underwent a video capsule endoscopic examination; however, the patient was unable to pass the capsule, which worsened the abdominal distension. He was transferred to our department for acute intestinal obstruction, and an emergency exploratory laparotomy was performed. Intraoperatively, a tumoral stricture of the intestine at a distance of 150 cm from the ileo-cecum and dilation of the proximal bowel was found. The involved segment was resected, and ileo-ileal anastomosis was performed. The pathological sections confirmed the lesion to be a moderately differentiated SCC with whole bowel layer infiltration. Immunohistochemical staining showed positive expression of cytokeratin 5/6 and p63. The patient had an uneventful recovery. However, 6 months later, he was hospitalized again with intestinal obstruction. Reoperation was performed and revealed multiple metastases in the small bowel. He died 4 months later. In this unusual case, metastasizing SCC of the hand skin led to intestinal obstruction and poor prognosis. Therefore, follow-up procedures regarding intestinal spread should be performed in patients with SCC who present with abdominal symptoms.


Asunto(s)
Carcinoma de Células Escamosas/complicaciones , Obstrucción Intestinal/etiología , Intestino Delgado/patología , Neoplasias Cutáneas/complicaciones , Anciano , Carcinoma de Células Escamosas/secundario , Humanos , Obstrucción Intestinal/patología , Masculino , Pronóstico , Neoplasias Cutáneas/patología
19.
Chin J Cancer ; 33(5): 231-40, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24103789

RESUMEN

Erythropoietin-producing hepatoma (EPH) receptors are considered the largest family of receptor tyrosine kinases and play key roles in physiological and pathologic processes in development and disease. EPH receptors are often overexpressed in human malignancies and are associated with poor prognosis. However, the functions of EPH receptors in epithelial-mesenchymal transition (EMT) remain largely unknown. This review depicts the relationship between EPH receptors and the EMT marker E-cadherin as well as the crosstalk between EPH receptors and the signaling pathways involved EMT. Further discussion is focused on the clinical significance of EPH receptors as candidates for targeting in cancer therapeutics. Finally, we summarize how targeted inhibition of both EPH receptors and EMT-related signaling pathways represents a novel strategy for cancer treatment.


Asunto(s)
Antineoplásicos , Transición Epitelial-Mesenquimal , Neoplasias , Receptores de la Familia Eph/fisiología , Transducción de Señal , Cadherinas , Humanos , Proteínas Tirosina Quinasas Receptoras
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 39(4): 338-43, 2014 Apr.
Artículo en Zh | MEDLINE | ID: mdl-24820271

RESUMEN

OBJECTIVE: To construct effective short hairpin RNA (shRNA) recombinant plasmids targeting human Dystrophin Dp71 gene, and evaluate their interference efficiency. METHODS: Three pairs of siRNA sequences targeting human Dp71 gene and one pair of control siRNA sequence were designed, synthesized, and then inserted into the pRNAT-U6.1/Neo vector. The shRNA recombinant vectors were evaluated by enzyme digestion and sequencing. Dp71-shRNA and control shRNA plasmids were transfected into human normal gastric epithelial cells (GES-1) and human bronchial epithelium (HBE). Western blot was used to evaluate its interfering efficiency. RESULTS: Restriction enzyme digestion and sequencing showed that the Dp71-shRNA vectors were successfully constructed. Western blot displayed that Dp71 protein expression was reduced to a significant degree after transfection with the 3 Dp71-shRNA plasmids, and Dp71-shRNA2 plasmid inhibit the Dp71 expression most efficiently. CONCLUSION: Dp71-shRNA vectors have been successfully constructed. The 3 Dp71-shRNA plasmids can inhibit Dp71 expression in GES-1 and HBEC, with Dp71-shRNA2 plasmid displaying the highest inhibition efficiency.


Asunto(s)
Distrofina/genética , Vectores Genéticos , Interferencia de ARN , ARN Interferente Pequeño/genética , Células Epiteliales/metabolismo , Epitelio/metabolismo , Humanos , Plásmidos , Transfección
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