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1.
BMC Genomics ; 25(1): 504, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778260

RESUMEN

BACKGROUND: Skeletal muscle development plays a crucial role in yield and quality of pork; however, this process is influenced by various factors. In this study, we employed whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing to comprehensively investigate the longissimus dorsi muscle (LDM), aiming to identify key genes that impact the growth and development of Duroc pigs with different average daily gains (ADGs). RESULTS: Eight pigs were selected and divided into two groups based on ADGs: H (774.89 g) group and L (658.77 g) group. Each pair of the H and L groups were half-siblings. The results of methylation sequencing revealed 2631 differentially methylated genes (DMGs) involved in metabolic processes, signalling, insulin secretion, and other biological activities. Furthermore, a joint analysis was conducted on these DMGs and the differentially expressed genes (DEGs) obtained from transcriptome sequencing of the same individual. This analysis identified 316 differentially methylated and differentially expressed genes (DMEGs), including 18 DMEGs in promoter regions and 294 DMEGs in gene body regions. Finally, LPAR1 and MEF2C were selected as candidate genes associated with muscle development. Bisulfite sequencing PCR (BSP) and quantitative real-time PCR (qRT-PCR) revealed that the promoter region of LPAR1 exhibited significantly lower methylation levels (P < 0.05) and greater expression levels (P < 0.05) in the H group than in the L group. Additionally, hypermethylation was observed in the gene body region of MEF2C, as was a low expression level, in the H group (P < 0.05). CONCLUSIONS: These results suggest that the differences in the ADGs of Duroc pigs fed the same diet may be influenced by the methylation levels and expression levels of genes related to skeletal muscle development.


Asunto(s)
Metilación de ADN , Músculo Esquelético , Transcriptoma , Animales , Músculo Esquelético/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Porcinos/genética , Epigenoma , Desarrollo de Músculos/genética , Perfilación de la Expresión Génica
2.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6090-6096, 2022 Nov.
Artículo en Zh | MEDLINE | ID: mdl-36471934

RESUMEN

The real-time cell-based assay(RTCA) was used to establish the bioelectrical sensing model of Compound Danshen Dripping Pills with rat cardiomyocytes(H9 c2). The time/dose-dependent cell response profiles(TCRPs) of in vitro dissolution and absorption of the pills were determined to establish the continuous dynamic dissolution and absorption kinetic models. Thereby, the cell index(CI)-based dissolution and absorption kinetic curves and kinetic models of Compound Danshen Dripping Pills were obtained. The optimal dissolution kinetic model was Weibull model. The similarity factors f_2 of dissolution curves were greater than 50 and the correlation coefficients of absorption curves were larger than 0.95. With the experiment about the efficacy on mice, percentages of the bleeding time of mice administrated with Compound Danshen Dripping Pills were calculated, and there was a correlation among dissolution, absorption, and efficacy curves(r > 0.9). RTCA is applicable to the study of the dissolution and absorption kinetics of solid compound Chinese medicine preparations. Thus, it is an innovative and feasible method to evaluate the quality and batch consistency of compound Chinese medicine preparations.


Asunto(s)
Medicamentos Herbarios Chinos , Salvia miltiorrhiza , Ratas , Ratones , Animales , Solubilidad , Miocitos Cardíacos
3.
BMC Med Genet ; 21(1): 163, 2020 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-32811452

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Current studies have shown that PNPLA3 (Patatin-like phospholipase domain containing 3) rs738409 G/C gene polymorphism is associated with adult nonalcoholic fatty liver disease [1, 2].But there is no consensus on the relationship between PNPLA3 rs738409 G/C gene polymorphism and children NAFLD due to differences in population samples. To this end, a meta-analysis of published research is conducted to comprehensively assess the relationship between PNPLA3 gene polymorphism and NAFLD in children. METHODS: We searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children's NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. The Stata 12.0 software was employed for data analysis. RESULTS: A total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children's NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR = 3.343, 95% CI = 1.524-7.334; GG + GC vs CC,OR = 3.157, 95% CI = 1.446-6.892;GG vs GC + CC,OR = 5.692, 95% CI = 1.941-16.689; GG + CC vs GC,OR = 2.756, 95% CI = 1.729-4.392). Four case-control studies compared Children with nonalcoholic fatty liver (NAFL) and children with nonalcoholic steatohepatitis (NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model (GG vs GC + CC,OR = 14.43, 95% CI = 5.985-34.997); The Egger's test revealed no significant publication bias. CONCLUSIONS: Meta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children.


Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Lipasa/genética , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Polimorfismo de Nucleótido Simple/genética , Niño , Femenino , Humanos , Masculino , Oportunidad Relativa , Sesgo de Publicación
4.
BMC Cancer ; 19(1): 1128, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31752753

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth-most common malignancy worldwide. Multiple previous studies have assessed the relationship between TM6SF2 gene polymorphism and the risk of developing HCC, with discrepant conclusions reached. To assess the association of TM6SF2 rs58542926 T/C gene polymorphism with liver cancer, we performed the current meta-analysis. METHODS: This study queried the MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to April 2019. Case-control studies assessing the relationship between TM6SF2 rs5854292 locus polymorphism and liver cancer were selected according to inclusion and exclusion criteria. The Stata 12.0 software was employed for data analysis. RESULTS: A total of 5 articles, encompassing 6873 patients, met inclusion criteria and were included in the meta-analysis. Statistical analysis showed that the TM6SF2 gene polymorphism was significantly associated with liver cancer in the allele contrast, dominant, recessive and over dominant models (T vs C, OR = 1.621, 95%CI 1.379-1.905; CT + TT vs CC. OR = 1.541, 95%CI 1.351-1.758; TT vs CT + CC, OR = 2.897, 95%CI 1.690-4.966; CC + TT vs TC, OR = 0.693, 95%CI 0.576-0.834). The Egger's test revealed no significant publication bias. CONCLUSION: The present findings suggest a significant association of TM6SF2 gene polymorphism with HCC risk in the entire population studied.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos
5.
Future Oncol ; 12(6): 789-99, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26838372

RESUMEN

AIMS: As data on the use of circulating tumor cells (CTCs) to predict patient outcomes in extensive-stage small-cell lung cancer (ES-SCLC) remain inconclusive, we investigated the clinical value of CTC determination in an open-label, multicenter study of 91 patients with newly diagnosed ES-SCLC. MATERIALS & METHODS: Blood CTC counts were determined using the CellSearch® system at baseline, after the second cycle of chemotherapy, and on disease progression. RESULTS & CONCLUSION: Following the second cycle of treatment, CTC numbers and the change in CTCs were strong, significant and independent indicators for both progression-free survival and overall survival in ES-SCLC. The CTC change was associated with both refractory disease (response to initial therapy ≤3 months) and sensitive disease (response to initial therapy >3 months).


Asunto(s)
Recuento de Células , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Células Neoplásicas Circulantes/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Curva ROC , Factores de Riesgo , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico
6.
Electrophoresis ; 36(9-10): 1196-201, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25753218

RESUMEN

Insertion/deletion polymorphisms have become a research hot spot in forensic science due to their tremendous potential in recent years. In the present study, we investigated 30 indel loci in a Chinese Yi ethnic group. The allele frequencies of the short allele of the 30 indel loci were in the range of 0.1025-0.9221. The power of discrimination values were observed ranging from to 0.2630 (HLD111 locus) to 0.6607 (HLD70 locus) and probability of exclusion values ranged from 0.0189 (HLD111 locus) to 0.2343 (HLD56 locus). The combined power of discrimination and power of exclusion for 30 loci in the studied Yi group were 0.99999999995713 and 0.97746, respectively, which showed tremendous potential for forensic personal identification in the Yi group. Moreover, the DA distances, phylogenetic tree, principal component analysis, and cluster analysis showed the Yi group had close genetic relationships with the Tibetan, South Korean, Chinese Han, and She groups.


Asunto(s)
Pueblo Asiatico/genética , Etnicidad/genética , Mutación INDEL/genética , Pueblo Asiatico/clasificación , China , Etnicidad/clasificación , Genética Forense , Genética de Población , Humanos , Desequilibrio de Ligamiento , Filogenia , Polimorfismo Genético
7.
Mol Biol Rep ; 40(2): 1451-61, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23100064

RESUMEN

Walleye dermal sarcoma virus (WDSV) is etiologically associated with a skin tumor, walleye dermal sarcoma (WDS), which develops in the fall and regresses in the spring. WDSV genome contains, in addition to gag, pol and env, three open reading frames (orfs) designated orf a (rv-cyclin), orf b and orf c. Unintegrated linear WDSV provirus DNA isolated from infected tumor cells was used to construct a full-length WDSV provirus clone pWDSV, while orf a was cloned into pSVK3 to construct the expression vector porfA. Stable co-transfection of a walleye cell line (W12) with pWDSV and pcDNA3 generated fewer and smaller G418-resistant colonies compared to the control. By Northern blot analysis, several small transcripts (2.8, 1.8, 1.2, and 0.8 kb) were detected using a WDSV LTR-specific probe. By RT-PCR and Southern blot analysis, three cDNAs (2.4, 1.6 and 0.8 kb) were identified, including both orf a and orf b messenger. Furthermore stable co-transfection of both a human lung adenocarcinoma cell line (SPC-A-1) and a cervical cancer cell line (HeLa) with pcDNA3 and ether porfA or pWDSV also generated fewer and smaller G418-resistant colonies. We conclude that expression of the full-length WDSV clone or the orf a gene inhibits the host fish and human tumor cell growth, and Orf A protein maybe a potential factor which contributes to the seasonal tumor development and regression. This is the first fish provirus clone that has been expressed in cell culture system, which will provide a new in vitro model for tumor research and oncotherapy study.


Asunto(s)
Ciclinas/genética , Epsilonretrovirus/genética , Enfermedades de los Peces/virología , Provirus/genética , Neoplasias Cutáneas/veterinaria , Infecciones Tumorales por Virus/veterinaria , Animales , Línea Celular Tumoral , Proliferación Celular , Ciclinas/metabolismo , Epsilonretrovirus/fisiología , Femenino , Expresión Génica , Genes Virales , Genoma Viral , Interacciones Huésped-Patógeno , Humanos , Masculino , Sistemas de Lectura Abierta , ARN Mensajero/genética , ARN Viral/genética , Neoplasias Cutáneas/virología , Infecciones Tumorales por Virus/virología , Proteínas Virales/genética , Proteínas Virales/metabolismo
8.
Chin J Physiol ; 55(5): 307-13, 2012 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-23282204

RESUMEN

Many studies have shown that the relationship between alcohol consumption and most cardiovascular diseases is U-shaped, with nondrinkers and heavier drinkers having higher risks than moderate drinkers. However, the association between cardiac arrhythmias and acute alcohol consumption is not well understood. We set up several experimental arrhythmia animal models to examine the effects of acute administration of ethanol on arrhythmia. The results showed 0.4, 0.8 and 1.6 g/kg ethanol consumption obviously delayed the onset time of atrial fibrillation (AF) (P < 0.05 or P < 0.01) and increased the survival rates on acetylcholine-CaCl2-induced AF in mice. Ethanol (0.4, 0.8 and 1.6 g/kg) consumption significantly delayed the onset time of ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA) (P < 0.01), and 0.4 and 0.8 g/kg ethanol consumption increased the survival rates on CaCl2-induced arrhythmia in rats. Ethanol (0.4 g/kg) essentially increased the cumulative dosage of aconitine required to CA (P < 0.05), and 0.8 g/kg, 1.6 g/kg ethanol reduced the cumulative aconitine dosage to induce VT, VF and CA (P < 0.05 or P < 0.01) on aconitine-induced arrhythmia in rats. Ethanol (0.4, 0.8 and 1.6 g/kg) consumption remarkably increased the cumulative dosage of deslanoside to induce ventricualr premature contraction (P < 0.01) on deslanoside-induced arrhythmia in guinea pigs. Collectively, our results indicate that low concentrations of ethanol had anti-arrhythmic effect on experimental arrhythmia, and high concentrations of ethanol may aggravated the occurrence of experimental arrhythmia.


Asunto(s)
Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/tratamiento farmacológico , Depresores del Sistema Nervioso Central/farmacología , Etanol/farmacología , Acetilcolina/toxicidad , Aconitina/toxicidad , Animales , Arritmias Cardíacas/mortalidad , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/mortalidad , Cloruro de Calcio/toxicidad , Cardiotónicos/toxicidad , Depresores del Sistema Nervioso Central/sangre , Agonistas Colinérgicos/toxicidad , Deslanosido/toxicidad , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Etanol/sangre , Cobayas , Paro Cardíaco/inducido químicamente , Paro Cardíaco/mortalidad , Paro Cardíaco/fisiopatología , Masculino , Ratones , Ratones Endogámicos ICR , Ratas , Ratas Sprague-Dawley , Factores de Riesgo , Taquicardia Ventricular/inducido químicamente , Taquicardia Ventricular/tratamiento farmacológico , Taquicardia Ventricular/mortalidad , Fibrilación Ventricular/inducido químicamente , Fibrilación Ventricular/tratamiento farmacológico , Fibrilación Ventricular/mortalidad , Agonistas del Canal de Sodio Activado por Voltaje/toxicidad
9.
Eur J Radiol ; 157: 110567, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36283194

RESUMEN

OBJECTIVES: Flow cytometry (FC) is a critical diagnostic approach for guiding targeted chemotherapy and cellular immunotherapy for relapsed and refractory lymphoma patients. The aim of the study was to investigate the value of ultrasound-guided fine needle aspiration (FNA) to improve the quality of FC specimens in relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). METHODS: Twenty patients with R/R DLBCL after standard treatment were included. The primary lesions of all cases were confirmed by pathology. FNA and core needle biopsy (CNB) were both used for ultrasound-guided puncture, the specimens obtained by FNA are directly examined by FC, and the specimens by CNB were subjected to FC after grinding. The accuracy of FC with the two methods were evaluated using histopathology as the gold standard. RESULTS: Of the 20 R/R DLBCL cases, 19 were diagnosed as DLBCL pathologically and one was diagnosed as inflammatory granuloma. Among the specimens obtained by CNB, 14 cases examined by FC after grinding showed abnormal mature B cells, five cases were missed, all cases are not misdiagnosed. Among the specimens obtained by FNA, 18 cases showed FC-confirmed abnormal mature B cells, one case was missed, all cases are not misdiagnosed. The sensitivity, specificity, and accuracy of FC with CNB and FNA were 73.68 % (14/19) vs 94.73 % (18/19), 100 % (1/1) vs 100 % (1/1), and 75 % (15/20) vs 97.14 % (19/20), respectively. The sensitivity of the two puncture methods of FC of DLBCL was statistically different (p < 0.001). CONCLUSION: Sampling with ultrasound-guided FNA is of great value to improve the quality of FC specimens. FNA can significantly improve the sensitivity and accuracy of FC diagnosis in R/R DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Biopsia con Aguja Fina/métodos , Sensibilidad y Especificidad , Biopsia Guiada por Imagen , Biopsia con Aguja Gruesa/métodos , Ultrasonografía Intervencional , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Estudios Retrospectivos
10.
Biosci Rep ; 41(4)2021 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-33870423

RESUMEN

Ovarian cancer (OV) is the main cause of deaths worldwide in female reproductive system malignancies. Enhancer RNAs (eRNAs) are derived from the transcription of enhancers and has attracted increasing attention in cancers recently. However, the biological functions and clinical significance of eRNAs in OV have not been well described presently. We used an integrated data analysis to identify prognostic-related eRNAs in OV. Tissue-specific enhancer-derived RNAs and their regulating genes were considered as putative eRNA-target pairs using the computational pipeline PreSTIGE. Gene expression profiles and clinical data of OV and 32 other cancer types were obtained from the UCSC Xena platform. Altogether, 71 eRNAs candidates showed significant correlation with overall survival (OS) of OV samples (Kaplan-Meier log-rank test, P<0.05). Among which, 23 were determined to be correlated with their potential target genes (Spearman's r > 0.3, P<0.001). It was found that among the 23 prognostic-related eRNAs, the expression of forkhead box P4 antisense RNA 1 (FOXP4-AS1) had the highest positive correlation with its predicted target gene FOXP4 (Spearman's r = 0.61). Moreover, the results were further validated by RT-qPCR analysis in an independent OV cohort. Our results suggested the eRNA FOXP4-AS1 expression index may be a favorable independent prognostic biomarker candidate in OV.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Ováricas/genética , ARN Largo no Codificante/genética , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , ARN Largo no Codificante/metabolismo , Análisis de Supervivencia
11.
Sci Rep ; 11(1): 3382, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33564088

RESUMEN

To construct and validate a nomogram to predict the overall survival (OS) of colorectal signet ring cell carcinoma (SRCC). The potentially eligible cases were obtained against the SEER database from 2004 to 2015. Log-rank test and Cox analysis were conducted to identify the independent prognostic factors for predicting OS. The identified prognostic factors were later integrated for the construction of an OS prediction nomogram. Altogether 2904 eligible cases were identified, and the median survival time was 18 (range: 0-155) months. As suggested by multivariate analysis, age, primary site, grade, tumor size, T stage, N stage, M stage, surgery, lymph node dissection and chemotherapy were identified as the independent factors for predicting OS. Afterwards, the above variables were incorporated into the nomogram. The C-index indicated better discriminatory ability of the nomogram than AJCC 8th TNM staging and SEER summary stage systems (both P < 0.001). Calibration plots further showed good consistency between the nomogram prediction and actual observation. The time independent area under the curves (tAUCs) for 3-year and 5-year OS in nomogram were larger than AJCC and SEER summary stage system. The constructed nomogram could potentially predict the survival of colorectal SRCC individuals.


Asunto(s)
Carcinoma de Células en Anillo de Sello/mortalidad , Neoplasias Colorrectales/mortalidad , Nomogramas , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Programa de VERF , Estados Unidos/epidemiología
12.
Cancer Med ; 8(12): 5600-5608, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31407527

RESUMEN

In the present study, we examined the factors affecting survival of women with inflammatory breast cancer (IBC) and constructed and validated a nomogram to predict overall survival (OS) in these patients. The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) program between 1 January 2004 and 31 December 2013. Univariate and multivariate Cox proportional hazards regression models were constructed. A nomogram was developed based on significant prognostic indicators of OS. The discriminatory and predictive capacities of the nomogram were assessed using Harrell's concordance index (C-index) and calibration plots. A total of 1651 eligible patients were identified, with a median survival time of 31 months (range 0-131 months), and the 3- and 5-year OS rates were 52.8% and 39.5%, respectively. Multivariate analysis revealed that race (P < .001), marital status (P = .011), N stage (P = .002), M stage (P < .001), hormone receptor (P < .001), human epidermal growth factor receptor-2 (HER2) (P = .001), surgery (P < .001), chemotherapy (P < .001), and radiotherapy (P = .010) were independent prognostic indicators of IBC. These nine variables were incorporated to construct a nomogram. The C-indexes of the nomogram were 0.738 (95% confidence interval [CI]: 0.717, 0.759) and 0.741 (95% CI: 0.717, 0.765) for the internal and external validations, respectively. The nomogram had a better discriminatory capacity for predicting OS than did the SEER summary stage (P < .001) or the American Joint Committee on Cancer tumor-node metastasis staging systems (8th edition; P < .001). The calibration plot revealed satisfactory agreement between the findings and predicted outcomes in both the internal and external validations. The nomogram-based 3- and 5-year OS predictions for patients with IBC exhibited superior accuracy over the existing models.


Asunto(s)
Neoplasias Inflamatorias de la Mama/mortalidad , Neoplasias Inflamatorias de la Mama/patología , Nomogramas , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Programa de VERF , Tasa de Supervivencia , Adulto Joven
13.
Chin Med J (Engl) ; 120(13): 1192-7, 2007 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-17637252

RESUMEN

BACKGROUND: Macrophage stimulating protein (MSP) is produced by human bone marrow endothelial cells. In this study, we sought to observe its effects on inducing the expansion of early hematopoietic progenitor cells which were cultured in a liquid culture system in the presence of the combination of stem cell factor (SCF), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO) (Cys) and MSP or of Cys and bone marrow endothelial cell conditioned medium (EC-CM). METHODS: Human bone marrow CD34(+) cells were separated and cultured in a liquid culture system for 6 days. Granulocyte-macrophage colony forming unit (CFU-GM) and colony forming unit-granulocyte, erythrocyte, macrophage, megakaryocyte (CFU-GEMM) were employed to assay the effects of different treatment on the proliferation of hematopoeitic stem/progenitor cells. The nitroblue tetrazolium (NBT) reductive test and hoechest 33258 staining were employed to reflect the differentiation and apoptosis of the cells respectively. RESULTS: MSP inhibited the proliferation of CFU-GM and CFU-GEMM in semi-solid culture and the inhibitory effect on CFU-GEMM was stronger than on CFU-GM. MSP inhibited the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators. Bone marrow (BM) CFU-GEMM was 2.3-fold or 1.7-fold increase or significantly decreased in either Cys + EC-CM, Cys + MSP or Cys compared with 0 hour control in liquid culture system after 6 days. CONCLUSION: MSP, a hematopoietic inhibitor, inhibits the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators and makes the early hematopoietic progenitor cells expand in a liquid culture system.


Asunto(s)
Células Madre Hematopoyéticas/efectos de los fármacos , Factor de Crecimiento de Hepatocito/farmacología , Proteínas Proto-Oncogénicas/farmacología , Antígenos CD34/análisis , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Quimiocina CCL3 , Quimiocinas CC/farmacología , Humanos
14.
Medicine (Baltimore) ; 94(2): e249, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25590835

RESUMEN

Preclinical studies have shown synergism between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is to investigate the efficacy and tolerability of erlotinib plus capecitabine as first-line treatment in older Chinese patients (≥ 65 years) with lung adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma and age 65 years or above were enrolled at four tertiary teaching hospitals and 2 provincial hospitals in China; 58 patients fulfilled the study requirements. Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14) were administered during every 21-day cycle. The primary endpoint was the non-progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using PCR. Tumor expression of different biomarkers was assessed using immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease progression at 12 weeks following treatment. The objective response rate was 29.3%, and the disease control rate was 75.9%. The objective response rate was significantly higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with thymidine phosphorylase-negative tumors had significantly longer overall survival after one year than patients with thymidine phosphorylase-positive tumors. Forty-four patients had at least one primary adverse events (AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n = 7). This is the first phase II clinical trial to assess erlotinib plus capecitabine combination therapy as first-line treatment in older patients with lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better in patients with EGFR mutations and in those with thymidine phosphorylase-negative tumors. The use of fluorouracil derivatives for the treatment of lung adenocarcinoma warrants further study.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Genes erbB-1/genética , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Biomarcadores , Capecitabina , China , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Supervivencia sin Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Clorhidrato de Erlotinib , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Genes ras/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Mutación , Estadificación de Neoplasias , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Timidina Fosforilasa/metabolismo , Resultado del Tratamiento
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 29(2): 135-8, 2004 Apr.
Artículo en Zh | MEDLINE | ID: mdl-16145894

RESUMEN

OBJECTIVE: To observe the effects of bone marrow endothelial cells on the expansion of human umbilical cord blood (UCB) hematopoietic progenitors in vitro. METHODS: Bone marrow endothelial cells were cultured and the serum free conditioned media (ECM) were collected. CD34+ cells derived from human umbilical cord blood (UCB) were isolated by MiniMACS. Hematopoietic progenitor cells were assayed after culturing with ECM or co-culturing with endothelial cell layer (ECL) for 24 hours. The effects of conditioned medium of endothelial cells which were cultured with bFGF (bFGF-ECM) on the expansion of cord blood hematopoietic progenitors also were investigated. RESULTS: UCB hematopoietic progenitors were significantly expanded by adding ECM or co-cultured with ECL, and ECM cultures and ECL cultures showed similar expansion effect on early progenitor cells. The effect of bFGF-ECM on the expansion of UCB hematopoietic progenitors was significantly better than that of ECM. CONCLUSION: Murine bone marrow endothelial cells support the quantitative expansion of UCB hematopoietic progenitor cells in vitro.


Asunto(s)
Células de la Médula Ósea/citología , Proliferación Celular , Células Endoteliales/citología , Sangre Fetal/citología , Células Madre Hematopoyéticas/citología , Animales , Células Cultivadas , Técnicas de Cocultivo , Medios de Cultivo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Humanos , Ratones
16.
Zhonghua Er Ke Za Zhi ; 48(11): 834-8, 2010 Nov.
Artículo en Zh | MEDLINE | ID: mdl-21215027

RESUMEN

OBJECTIVE: Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor-encoding gene, core binding factor α1 (CBFA1). Over 90 mutations in CBFA1 gene have been published to date in 500 independent cases of CCD, including missense mutations, deletions, insertions, frameshift, and splice mutations. However, mutational screening of the CBFA1 gene is still far from saturation, and more novel mutations will be identified to enrich the insights into the molecular basis for the pathogenesis of CCD. The aim of this study was to explore the clinical and image features and detect the mutations of CBFA1 gene in two CCD families. METHOD: In this study, the clinical features were investigated in two CCD families, radiological and CT examinations regarding osseous malformation were carried out over the entire body of these patients with CCD. Blood (2 ml) was drawn from all affected individuals, unaffected family members and one hundred unrelated normal controls, Genomic DNA was extracted from whole blood with PureGene DNA extraction kit and PCR was performed with eight pairs of PCR primers for exons 0 to 7 of the CBFA1 gene. The mutations of CBFA1 gene were screened in these two CCD families. RESULT: (1) The clinical features of patients with CCD include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. X-ray and CT examination showed the bulging calvarium, patent fontanelles, wide cranial sutures, multiple Wormian bones, dental dysplasia or aplasia of clavicles. (2) Two mutations were identified, one is novel missense mutation (c.1259C > T[p.T420I]) in CBFA1 gene exon 7, other (c.577C > T[p.R193X]) was reported in Chinese cases with CCD for the first time. CONCLUSION: (1) The clinical and image features of patients in two CCD families include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. (2) The T420I and R193X mutations of CBFA1 were reported, expanding the spectrum of CBFA1 mutations causing CCD.


Asunto(s)
Displasia Cleidocraneal/genética , Displasia Cleidocraneal/patología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Mutación , Niño , Preescolar , Análisis Mutacional de ADN , Exones , Femenino , Humanos , Masculino , Linaje , Fenotipo
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 22(3): 368-70, 2006 May.
Artículo en Zh | MEDLINE | ID: mdl-16643802

RESUMEN

AIM: To prepare anti-morphine vaccine antibody with high titer and good specificity and to identify its properties. METHODS: Chemically synthesized 6-succinylmorphine (M-6-S) was cross-linked to BSA in pH 9.0 carbonate buffer. After being purified by gel filtration and (NH4)2SO4 salting out, the immunogen was used to immunize BALB/c mice and SD rats. The titer and specificity of antisera were identified by ELISA and neutralization inhibition test, respectively. The effect of the immunization was examined by the radiant heat tail-flick (TF) reflex test. RESULTS: The titers of antiserum from immunized BALB/c mice and SD rats were up to 1:200,000 and over 1:20,000, respectively. Neutralization inhibition test proved that the anti-morphine vaccine antibody had the cross-reactions to following drugs with analogous structure as morphine: 6-monoacetylmorphine, heroin and codeine. The TF reflex test showed: (1) TF reflexes were notable inhibited after intraperitoneal injection of 2 mg/kg morphine, and (2) percentage of the maximum possible effect (% MPE) reduced 74.7%, (3) the TF latency recovered to the baseline level much more rapidly compared with the control rats. CONCLUSION: The M-6-S-BSA vaccine has been prepared successfully. The BALB/c mice and SD rats immunized with the vaccine can produce anti-morphine antibody with high titer and satisfactory specificity, which may significantly reduce rats' antinociception against morphine.


Asunto(s)
Dependencia de Morfina/etiología , Morfina/toxicidad , Albúmina Sérica Bovina/efectos adversos , Animales , Especificidad de Anticuerpos , Relación Dosis-Respuesta Inmunológica , Inmunización , Masculino , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Morfina/administración & dosificación , Morfina/efectos adversos , Derivados de la Morfina/administración & dosificación , Derivados de la Morfina/efectos adversos , Ratas , Ratas Sprague-Dawley , Albúmina Sérica Bovina/administración & dosificación , Vacunas/administración & dosificación , Vacunas/efectos adversos
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