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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(6): 1635-1638, 2023 Dec.
Artículo en Chino | MEDLINE | ID: mdl-38071039

RESUMEN

OBJECTIVE: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). METHODS: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed. RESULTS: Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred. CONCLUSION: Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.


Asunto(s)
Leucemia Mieloide Aguda , Neutropenia , Niño , Femenino , Humanos , Masculino , Azacitidina/uso terapéutico , Cladribina/uso terapéutico , Estudios Retrospectivos , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
2.
Front Pediatr ; 11: 1187607, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37601130

RESUMEN

Objective: To evaluate the clinical efficacy and safety of a short course of blinatumomab in children with refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R-BCP-ALL). Methods: The clinical data of 33 R/R BCP-ALL children aged 0-18 years who underwent a short course of blinatumomab (14 days) between August 2021 and November 2022 were retrospectively collected and analyzed. Results: Among 33 patients with BCP-ALL, 26 achieved complete remission (CR), with a total remission rate of 78.8% (26/33). The duration of remission was approximately 14 days. Of the 7 children without CR, 5 were still in remission at 28 days. In 11 patients with refractory disease and 22 with recurrence, the remission rates were 90.9% (10/11) and 72.7% (16/22), respectively. The overall survival (OS) rates of the 26 patients with CR and seven patients without CR were 96.1% and 57.1% (p = 0.002), respectively, and the disease-free survival (DFS) rates were 96.1% and 42.9% (p < 0.001), respectively. Among the 26 patients with CR, 15 underwent bridging hematopoietic stem cell transplantation (HSCT) and 11 did not receive HSCT; with OS rates of 93.3% and 100% (p = 0.40) and DFS rates of 93.3% and 100% (p = 0.400), respectively. The OS for all patients was 87.9% (29/33) and the DFS was 84.8% (28/33). There were 18 cases (54.5%) of cytokine release syndrome (CRS), 2 cases (6.1%) of severe CRS (all grade 3), 1 case (3.0%) of immune effector cell-associated neurotoxicity syndrome (ICANS), 0 cases (0%) of ICANS ≥ grade 3, and no deaths caused by treatment. Conclusions: Short-term follow-up revealed a high R/R BCP-ALL remission rate in children treated with a short course of blinatumomab. The toxicity was low and controllable. No significant short-term survival benefits were observed after bridging HSCT with blinatumomab. In developing countries, a short course of blinatumomab can achieve satisfactory outcomes, while reducing household costs and saving medical resources.

3.
Heliyon ; 9(4): e14930, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37077678

RESUMEN

This study investigated the hydrochar-based porous carbon prepared by combining the technical route of hydrothermal carbonization (HTC) + chemical activation. The hydrochar morphology was adjusted by changing the activation reaction conditions and adding metal salts. Experiments showed that the activation of KHCO3 significantly increased the specific surface area and pore size of the hydrochar. Besides, oxygen-rich groups on the surface of the activated hydrochar interacted with heavy metal ions to achieve efficient adsorption. The activated hydrothermal carbon adsorption capacity for Pb2+ and Cd2+ ions reached 289 and 186 mg/g, respectively. The adsorption mechanism study indicated that the adsorption of Pb2+ and Cd2+ was related to electrostatic attraction, ion exchange, and complexation reactions. The "HTC + chemical activation" technology was environmentally friendly and effectively implemented antibiotic residues. Carbon materials with high adsorption capacity can be prepared so that biomass resources can be utilized with excessive value, as a consequence presenting technical assistance for the comprehensive disposal of organic waste in the pharmaceutical industry and establishing a green and clean production system.

4.
Water Sci Technol ; 87(1): 228-238, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36640034

RESUMEN

Bioaugmentation is an effective strategy used to speed up the bioremediation of marine oil spills. In the present study, a highly efficient petroleum degrading bacterium (Pseudomonas aeruginosa ZS1) was applied to the bioremediation of simulated crude oil pollution in different sampling sites in the South China Sea. The metabolic pathways of ZS1 to degrade crude oil, the temporal dynamics of the microbial community response to crude oil contamination, and the biofortification process were investigated. The results showed that the abundance and diversity of the microbial community decreased sharply after the occurrence of crude oil contamination. The best degradation rate of crude oil, which was achieved in the samples from the sampling site N3 after the addition of ZS1 bacteria, was 50.94% at 50 days. C13 alkanes were totally oxidized by ZS1 in the 50 days. The degradation rate of solid n-alkanes (C18-C20) was about 70%. Based on the whole genome sequencing and the metabolites analysis of ZS1, we found that ZS1 degraded n-alkanes through the terminal oxidation pathway and aromatic compounds through the catechol pathway. This study provides data support for further research on biodegradation pathways of crude oil and contributes to the subsequent development of more reasonable bioremediation strategies.


Asunto(s)
Microbiota , Contaminación por Petróleo , Petróleo , Biodegradación Ambiental , Contaminación por Petróleo/análisis , Alcanos/metabolismo , Petróleo/análisis , Bacterias/genética , Bacterias/metabolismo , Redes y Vías Metabólicas , Hidrocarburos/metabolismo
5.
Nurs Open ; 10(4): 2376-2391, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36440605

RESUMEN

AIM: To develop a set of evidence-informed strategies to assist older people to improve swallowing functions and prevent further damage from complications. DESIGN: A two-round Delphi survey. METHODS: An initial set of dysphagia care strategies with 74 relevant items for older people was formed based on a literature review by seven researchers. An online survey was conducted by 21 panellists, and data of experts' opinions were collected and analysed by improved Delphi method. RESULTS: The positive coefficients in the two rounds of expert consultation were 85.71% and 83.33%, respectively. Consensus was reached with 53 items included and was allocated into the following five sections: (1) screening, (2) assessment, (3) training, (4) interventions and (5) management. These strategies were named with the acronym of each section-"SATIA". The management strategy can be applied to guide the management of older people with dysphagia.


Asunto(s)
Trastornos de Deglución , Humanos , Anciano , Consenso , Técnica Delphi , Encuestas y Cuestionarios
6.
Ecotoxicol Environ Saf ; 241: 113769, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35738097

RESUMEN

In the process of marine oil spill remediation, adding highly efficient oil degrading microorganisms can effectively promote oil degradation. However, in practice, the effect is far less than expected due to the inadaptability of microorganisms to the environment and their disadvantage in the competition with indigenous bacteria for nutrients. In this article, four strains of oil degrading bacteria were isolated from seawater in Jiaozhou Bay, China, where a crude oil pipeline explosion occurred seven years ago. Results of high-throughput sequencing, diesel degradation tests and surface activity tests indicated that Peseudomonas aeruginosa ZS1 was a highly efficient petroleum degrading bacterium with the ability to produce surface active substances. A diesel oil-degrading bacterial consortium (named SA) was constructed by ZS1 and another oil degrading bacteria by diesel degradation test. Degradation products analysis indicated that SA has a good ability to degrade short chain alkanes, especially n-alkanes (C10-C18). Community structure analysis showed that OTUs of Alcanivorax, Peseudomona, Ruegeria, Pseudophaeobacter, Hyphomonas and Thalassospira on genus level increased after the oil spill and remained stable throughout the recovery period. Most of these enriched microorganisms were related to known alkane and hydrocarbon degraders by the previous study. However, it is the first time to report that Pseudophaeobacter was enriched by using diesel as the sole carbon source. The results also indicated that ZS1 may have a dominant position in competition with indigenous bacteria. Oil pollution has an obvious selective effect on marine microorganisms. Although the oil degradation was promoted after SA injection, the recovery of microbial community structure took a longer time.


Asunto(s)
Contaminación por Petróleo , Petróleo , Alcanos/metabolismo , Bacterias , Biodegradación Ambiental , Hidrocarburos/análisis , Petróleo/análisis , Contaminación por Petróleo/análisis , Agua de Mar/microbiología
7.
J Environ Sci Health B ; 55(6): 525-529, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32077369

RESUMEN

Telomere length was found to be associated with omethoate exposure and polymorphisms in certain genes among occupational workers. However, whether the polymorphisms in telomere-binding protein genes influence telomere length remains unclear. To explore the correlation between telomere length and polymorphisms in telomere-binding protein genes, telomere length in peripheral blood leukocytes was determined by real-time quantitative polymerase chain reaction in 180 omethoate-exposed workers and 115 healthy controls. Polymorphisms in 10 pairs of alleles were detected using flight mass spectrometry or polymerase chain reaction-restriction fragment length polymorphism technique. The results showed that individuals with GG genotype in TRF1 rs3863242 had longer telomere lengths than those with AG + AA genotype in the control group (p = 0.005). The multiple regression analysis suggested that both omethoate exposure (b = 0.526, p < 0.001) and TRF1 rs3863242 GG (b = 0.220, p = 0.002) were related to a longer telomere length. In conclusion, GG genotype in TRF1 rs3863242 is linked to prolongation of telomere length, and individuals with GG genotype are recommended to strengthen health protection in a Chinese occupational omethoate-exposed population.


Asunto(s)
Dimetoato/análogos & derivados , Exposición Profesional , Polimorfismo de Nucleótido Simple , Telómero/efectos de los fármacos , Proteína 1 de Unión a Repeticiones Teloméricas/genética , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , Dimetoato/toxicidad , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Complejo Shelterina , Proteínas de Unión a Telómeros/genética , Proteína 2 de Unión a Repeticiones Teloméricas/genética
8.
Front Pharmacol ; 11: 588549, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33510637

RESUMEN

Guizhi Fuling prescription (GFP), a prestigious prescription of traditional Chinese medicine (TCM) recorded in "Jingui Yaolue," was composed of five Chinese medicines, including Moutan Cortex, Paeoniae Radix Alba, Persicae Semen, Poria Cocos, and Cinnamomi Ramulus. It was used for the treatment of endometriosis, primary dysmenorrhea, and blood stasis for centuries. However, its Quality Markers of treating endometriosis have not been clearly elucidated. In this study, a rapid ultraperformance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS/MS) method was established for Quality Markers investigation on GFP, and a total of 50 potentially bioactive constituents including triterpenoids, paeoniflorin and its derivatives, phenolic acids, and other species were identified based on their retention time, fragmentation pattern, and accurately measured mass value. Furthermore, regularity of recipe composition and gray correlation analysis revealed that all of the characteristic peaks contributed to the treatment of endometriosis. The relative correlation degrees were greater than 0.6. Among them, peaks 1 and 10, which were most closely correlated to the endometriosis, were identified as amygdalin and cinnamic acid. Finally, all of the active ingredients were molecularly docked with proteins associated with endometriosis by Schrodinger method. Among them, amygdalin, cinnamic acid, paeonol, gallic acid, and paeoniflorin had the lower binding energies. It was proposed that these constituents could be directed at Quality Markers for GFP. Thus, the integrated approach describing for revealing Quality Markers of GFP could be expected to provide a method for quality evaluation.

9.
Chemosphere ; 238: 124863, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31551201

RESUMEN

Peripheral blood leukocyte telomere length in omethoate-exposed workers is related to environmental exposure and single nucleotide polymorphisms (SNPs) in genes including p21, GSTM1, miR-145, etc. However, the roles of SNPs in tankyrase (TNKS) gene in telomere length are still unknown. The aim of this study was to explore the association between SNPs in TNKS gene and telomere length in omethoate-exposed workers. Telomere length in peripheral blood leukocyte DNA from 180 omethoate-exposed workers and 115 healthy controls was measured using Real-time quantitative polymerase chain reaction (PCR). Genotyping of the selected functional and susceptible SNPs was performed by the flight mass spectrometry based on PCR and single-base extension. The analysis of covariance was performed to find effects of SNPs on telomere length. Generalized linear models were used to analyze the environment, gene, and interaction on telomere length. The results showed that telomere length in the CG + CC genotypes in rs1055328 in TNKS gene was significantly longer than that in the wild homozygous GG genotype both in exposure group (P = 0.017) and in control group (P = 0.038) after adjusting the covariates. The variables kept in the generalized linear models included omethoate-exposure (ß = 0.580, P = 0.001) and rs1055328 (CG + CC) in TNKS gene (ß = 0.339, P = 0.002). The study suggests that the prolongation of telomere length is associated with omethoate-exposure and the CG + CC genotypes in rs1055328 in TNKS gene.


Asunto(s)
Dimetoato/análogos & derivados , Exposición Profesional/efectos adversos , Tanquirasas/genética , Homeostasis del Telómero/efectos de los fármacos , Telómero/fisiología , Adulto , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , ADN/genética , Daño del ADN/efectos de los fármacos , Dimetoato/toxicidad , Femenino , Genotipo , Glutatión Transferasa/genética , Humanos , Leucocitos/citología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Telómero/genética
10.
J Environ Sci Health B ; 54(12): 948-953, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31405322

RESUMEN

Omethoate is an organophosphorus pesticide that poses a major health hazard, especially DNA damage. The purpose of this study was to investigate the factors affecting telomere length in workers exposed to omethoate by analyzing the interaction between cell cycle gene polymorphism and environmental factors. The exposure group consisted of 118 workers exposed to omethoate for 8-10 years, the control group comprised 115 healthy people without occupational toxicant exposure history. The telomere length of genomic DNA from peripheral blood leucocyte was determined with real-time PCR. Polymerase chain reaction and restriction fragment length polymorphism was used to detect the polymorphisms in p53, p21 and MDM2 gene. The telomere length in the (CA + AA) genotypes for p21 rs1801270 polymorphism was longer than that in the CC genotype in control group (P = 0.015). The generalized linear model analysis indicated the interaction of the p21 rs1801270 polymorphic (CA + AA) genotypes and smoking has a significant effect on telomere length (ß = -0.258, P = 0.085). The prolongation of telomere length in omethoate-exposed workers was associated with genotypes (CA + AA) of p21 rs1801270, and interactions of (CA + AA) genotypes and smoking factor.


Asunto(s)
Dimetoato/análogos & derivados , Exposición Profesional/efectos adversos , Plaguicidas/toxicidad , Fumar/efectos adversos , Telómero/metabolismo , Adulto , Daño del ADN/efectos de los fármacos , Dimetoato/toxicidad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/efectos de los fármacos , Proteínas Proto-Oncogénicas c-mdm2/genética , Telómero/genética , Proteína p53 Supresora de Tumor/genética
11.
Ecotoxicol Environ Saf ; 172: 82-88, 2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-30684755

RESUMEN

Omethoate, an organophosphorous pesticide, causes a variety of health effects, especially the damage of chromosome DNA. The aim of the study was to assess the correlation between polymorphisms of encoding miRNA genes and telomere length in omethoate-exposure workers. 180 workers with more than 8 years omethoate-exposure and 115 healthy controls were recruited in the study. Genotyping for the selected single nucleotide polymorphisms loci were performed using the flight mass spectrometry. Real-time fluorescent quantitative polymerase chain reaction(PCR) method was applied to determine the relative telomere length(RTL) in human peripheral blood leukocytes DNA. After adjusting the covariate of affecting RTL, covariance analysis showed that the female was significantly longer than that of the male in control group(P < 0.046). For the miR-145 rs353291 locus, this study showed that RTL of mutation homozygous AG+GG individuals was longer than that of wild homozygous AA in the exposure group (P = 0.039). In the control group, RTL with wild homozygous TT genotype in miR-30a rs2222722 polymorphism locus was longer than that of the mutation homozygous CC genotype (P = 0.038). After multiple linear regression analysis, the independent variables of entering into the model were omethoate-exposure (b = 0.562, P < 0.001), miR-145 rs353291 (AG+GG) (b = 0.205, P = 0.010). The prolongation of relative telomere length in omethoate exposed workers was associated with AG+GG genotypes in rs353291 polymorphism of encoding miR-145 gene.


Asunto(s)
Dimetoato/análogos & derivados , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Homeostasis del Telómero/efectos de los fármacos , Telómero/efectos de los fármacos , Adulto , Estudios de Casos y Controles , ADN/genética , Daño del ADN/efectos de los fármacos , Dimetoato/toxicidad , Femenino , Sitios Genéticos , Genotipo , Humanos , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad
12.
J Occup Environ Med ; 61(1): e19-e23, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30475314

RESUMEN

OBJECTIVE: The aim of this study was to explore the association between telomere length and metabolizing enzyme gene polymorphisms and environmental factors in omethoate-exposed workers. METHODS: The gene-environment interactions were analyzed with generalized linear model method. RESULTS: The relative telomere lengths in the individuals with GSTM1-deletion were longer than that in non-deletion genotype in the control group (P = 0.011); the relative telomere lengths with GG+AG genotypes in GSTP1 rs1695 were longer than that of AA genotype in the exposure group (P = 0.039). The interaction between the GG+AG genotypes in GSTP1 rs1695 and smoking exposure had significant effect on telomere length (P < 0.05). CONCLUSIONS: The prolongation of relative telomere length in omethoate-exposed workers was associated with GSTM1-deletion, GG+AG genotypes, and interactions of GG+AG genotypes and smoking factor.


Asunto(s)
Dimetoato/análogos & derivados , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/genética , Exposición Profesional/efectos adversos , Fumar/efectos adversos , Telómero/efectos de los fármacos , Adulto , Estudios de Casos y Controles , Dimetoato/efectos adversos , Femenino , Eliminación de Gen , Interacción Gen-Ambiente , Humanos , Masculino , Exposición Profesional/estadística & datos numéricos , Polimorfismo de Nucleótido Simple/genética , Telómero/genética
13.
Ecotoxicol Environ Saf ; 161: 563-568, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29929132

RESUMEN

Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P < 0.001). Multivariate analysis indicates that exposure group (b = - 1.016, P < 0.001), agender (b = 0.365, P < 0.001), drinking (b = 0.271, P = 0.004) and TERF1rs3863242 (b = - 0.368, P = 0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate.


Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Colinesterasas/sangre , Dimetoato/análogos & derivados , Exposición Profesional/análisis , Polimorfismo Genético , Proteínas de Unión a Telómeros/genética , Adulto , China , Dimetoato/toxicidad , Eritrocitos/enzimología , Genotipo , Humanos , Exposición Profesional/efectos adversos , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Adulto Joven
14.
Int J Gynecol Cancer ; 28(4): 704-712, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29498984

RESUMEN

OBJECTIVES: The purpose of this study was to distinguish synchronous primary endometrial and ovarian carcinomas from single primary tumor with metastasis by clinical pathologic criteria and whole exome sequencing (WES). MATERIAL AND METHODS: Fifty-two patients with synchronous endometrial and ovarian carcinomas (SEOCs) between 2010 and 2017 were reviewed and subjected to WES. RESULTS: On the basis of the Scully criteria, 11 cases were supposed as synchronous primary endometrial and ovarian carcinomas, 38 cases as single primary tumor with metastasis, and the remaining 3 cases (S50-S52) cannot be defined. Through a quantization scoring analysis, 9 cases that were scored 0-1 point were defined as synchronous primary endometrial and ovarian carcinomas, and 42 cases that were scored 3-8 points were defined as single primary tumor with metastasis. Two of the undefined cases were classified into metastatic disease, and another one that scored 2 points (S52) was subjected to WES. S52 was deemed synchronous primary endometrial and ovarian carcinomas, with few shared somatic mutations and overlapping copy number varieties. The finding of a serous component examined from the uterine endometrium samples further illustrated that the case was synchronous primary endometrial and ovarian carcinomas. CONCLUSION: By scoring criterion, SEOCs were divided into 2 groups: synchronous primary endometrial and ovarian carcinoma group and single primary tumor with metastasis group. The analysis of clonality indicated that the case that scored 2 (S52) can be considered as synchronous primary endometrial and ovarian carcinomas. Scoring criteria of clinical pathology, along with the study of the WES, may further identify the classification of SEOCs.


Asunto(s)
Carcinoma/diagnóstico , Neoplasias Endometriales/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Ováricas/diagnóstico , Adulto , Anciano , Carcinoma/genética , Carcinoma/patología , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Secuenciación del Exoma
15.
Oncotarget ; 8(46): 80638-80644, 2017 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-29113331

RESUMEN

PURPOSE: This study aimed to explore the effects of genetic polymorphisms in metabolic enzymes on relative telomere length changes and explore the mechanism of canceration induced by omethoate. MATERIALS AND METHODS: 180 long-term omethoate-exposed workers and 115 healthy controls were recruited. Real-time PCR method was applied to determine the relative telomere length in peripheral blood leukocytes DNA, and Six polymorphic loci of GSTT1(+/-), GSTM1(+/-), GSTP1 rs1695, CYP2E1 rs6413432, CYP2E1 rs3813867 and PON2 rs12026 were detected by polymerase chain reaction and restriction fragment length polymorphism method; Multiple linear regression was conducted to explore the effects of omethoate exposure and genetic polymorphisms on the telomere length. RESULTS: The relative telomere lengths in the control group (0.94 [0.76, 1.32]) were significantly shorter than that in the exposure group (1.50 [1.11, 2.57]) (Z = 7.910, P < 0.001). Univariate analysis showed that the relative telomere lengths of the GSTM1-deletion individuals were significantly longer than that of the non - deletion genotype in the control group (Z = 2.911, P = 0.004), and the relative telomere lengths of GSTP1 rs1695 polymorphism locus (GG+AG) genotype individuals were longer than that of AA genotype in the exposure group. The difference was statistically significant (Z = 2.262, P = 0.024). Multivariate analysis found that pesticide-exposure (b = 0.524, P < 0.001) and GSTM1 polymorphism (b = -0.136, P = 0.029) had an impact on telomere length. CONCLUSIONS: The relative telomere lengths of omethoate-exposure workers were longer than that in the control population. Also GSTM1 genetic polymorphism may influence the changes of the telomere length induced by omethoate.

16.
Tumour Biol ; 39(7): 1010428317719782, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28718371

RESUMEN

Organophosphorous pesticides (OPs), with high efficiency, broad-spectrum and low residue, are widely used in China. Omethoate is a broad category of organophosphorous pesticides and is more domestically utilized which has chronic toxic effect on human health caused by long-term, low-dose exposure to Ops, recently its potential genotoxicity has attracted wide attention which can cause chromosomal DNA damage. Thus, the aim of this study is screen susceptible biomarkers and explore the mechanism of canceration induced by omethoate. 180 long-term organophosphorus pesticide-exposed workers and 115 healthy controls were recruited. Quantitative polymerase chain reaction method was applied to determine the relative telomere length in peripheral lymphocyte DNA as well as p53 and p21 gene expression levels. Genetic polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Multiple linear regression was conducted to explore the effects of exposure, expression levels, and polymorphisms in genes on the telomere length. The results showed the relative telomere lengths in the exposure group were significantly longer than that in the control group. The messenger RNA expression levels of p53 and p21 in exposure group were significantly lower than that in the control group; telomere lengths of the CA genotype individuals of p21 rs1801270 polymorphism locus were significantly longer than that of the CC genotype in the control group that were estimated using the Bonferroni method; and bivariate correlation analysis showed that the messenger RNA expression level of gene p53 was negatively correlated with telomere length, and the messenger RNA expression level of gene p21 was positively correlated with telomere length. Multivariate analysis found that p53 messenger RNA and p21 messenger RNA had an impact on telomere length. These results demonstrated that the messenger RNA expression levels of p53 and p21 may have a relationship with the changes in telomere length induced by omethoate and provided strong evidence for the mechanism of canceration induced by poison.


Asunto(s)
Carcinogénesis/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Neoplasias/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Ciclo Celular/efectos de los fármacos , China , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Daño del ADN/efectos de los fármacos , Dimetoato/análogos & derivados , Dimetoato/toxicidad , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genotipo , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/patología , Masculino , Persona de Mediana Edad , Neoplasias/inducido químicamente , Neoplasias/patología , Exposición Profesional , Polimorfismo de Nucleótido Simple , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Homeostasis del Telómero/efectos de los fármacos , Proteína p53 Supresora de Tumor/biosíntesis
17.
Urol Oncol ; 32(2): 162-70, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23570708

RESUMEN

OBJECTIVES: The identification of critical proteins regulating cancer cell metastasis, in clear cell renal cell carcinoma (CCRCC), is important for prediction of prognosis, prevention of metastasis, and treatment of this lethal malignancy. In the present study, we evaluated the role of CX3CR1 in cellular adhesion, migration, and metastasis in CCRCC. We further investigated the downstream molecular signaling mechanism of fractalkine (FKN)-CX3CR1-induced migration and metastasis. MATERIALS AND METHODS: The expression and localization of CX3CR1 in RCC cell lines were assessed by immunofluorescence analysis. The migration of cancer cells was examined by wound healing and transwell migration assay. The expression level of CX3CR1 and FKN in 78 CCRCC individual samples, 16 normal kidney cortex tissue samples, and 16 cases of metastatic lesions of CCRCC were evaluated using immunohistochemical analysis on tissue microarray. The signal pathway of functional FKN was analyzed by the use of the western-blotting method and inhibitory migration assay. RESULTS: CX3CR1 was expressed in human RCC cell lines, and only membrane positive cells were responsible for FKN-induced cell migration. Extracellular signal-related kinases (ERK1/2) and phosphatidyl-inositide 3 kinase/Akt (PI3K/Akt) were each activated upon soluble FKN stimulation in a time-dependent manner, whereas blockades of MEK, PI3K, and G proteins prevented FKN-mediated cellular migration. Furthermore, CCRCC tissue microarray immunohistochemistry data revealed a clear association of strong CX3CR1 expression with tumor metastasis and poor prognosis. CONCLUSIONS: CX3CR1 expression is associated with the process of cellular migration in vitro and tumor metastasis of CCRCC in vivo. Both clinical and molecular cellular evidence suggest that CX3CR1 is a potential marker and therapeutic target for CCRCC prognostic prediction and treatment.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Movimiento Celular , Neoplasias Renales/metabolismo , Receptores de Quimiocina/biosíntesis , Western Blotting , Receptor 1 de Quimiocinas CX3C , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/farmacología , Quimiotaxis/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Células HEK293 , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Microscopía Confocal , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Análisis de Matrices Tisulares
19.
Zhonghua Zhong Liu Za Zhi ; 32(10): 752-6, 2010 Oct.
Artículo en Chino | MEDLINE | ID: mdl-21163065

RESUMEN

OBJECTIVE: To detect the expression of VEGF receptors in papillary renal cell carcinoma and to explore the correlation between their expression and clinical prognosis. METHODS: Expression of VEGF receptors and PCNA (proliferating cell nuclear antigen) were evaluated in 82 patients with papillary renal cell carcinoma using tissue microarray and SP immunohistochemical staining. RESULTS: The expression of VEGFR-1 in papillary renal cell carcinoma was 82.93%, VEGFR-2 63.41%, VEGFR-3 34.15% and PCNA 67.07%, respectively. Increased VEGFR-2 expression was significantly correlated with tumor size (P = 0.016), histological grade (P = 0.034) and distant metastasis (P = 0.002). VEGFR-3 expression was correlated with histological grade (P = 0.028), lymph node status (P = 0.010) and distant metastasis (P = 0.018), but not correlated with gender, age, location, tumor size and TNM staging. VEGFR-1 expression had no correlation with any clinic and pathologic factors. PCNA expression was correlated with histological grade (P = 0.011), but not correlated with other factors. The expression of VEGFR-2 and VEGFR-3 in death cases were higher than that in surviving patients. CONCLUSION: Both VEGFR-2 and VEGFR-3 can serve as markers for prognosis of papillary renal cell carcinoma. Differently, VEGFR-3 is a predictor of lymph node metastasis, increased VEGFR-2 expression could be used to predict a potential blood dissemination.


Asunto(s)
Carcinoma Papilar , Carcinoma de Células Renales , Neoplasias Renales , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Antígeno Nuclear de Célula en Proliferación/metabolismo , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Carga Tumoral , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo
20.
Zhonghua Zhong Liu Za Zhi ; 32(10): 772-6, 2010 Oct.
Artículo en Chino | MEDLINE | ID: mdl-21163070

RESUMEN

OBJECTIVE: To compare the old classification and 2004 WHO histological classification of renal cell carcinoma, summarize the differences and possible reasons, and correct the traditional pathological concepts of kidney cancer. METHODS: Specimens of 79 cases histopathologically diagnosed as non-clear cell renal cell carcinomas after radical nephrectomy during 1998 to 2005 in Tianjin Medical University Cancer Hospital were reclassified according to the 2004 WHO renal cell carcinoma histological classification system. RESULTS: After reclassification, there were 14 cases of clear cell renal cell carcinoma (CCRCC), 23 cases of papillary renal cell carcinoma (PRCC), 34 cases of chromophobe renal cell carcinoma (ChRCC), one collecting duct renal cell carcinoma, one unclassified renal cell carcinoma, 5 cases of mixed cell renal cell carcinoma (CCRCC + PRCC 2 cases, CCRCC + ChRCC 2 cases, PRCC + ChRCC 1 case), and one oncocytoma diagnosed. CONCLUSIONS: Some chromophobe renal cell carcinomas and papillary renal cell carcinomas were easier to be diagnosed as granular cell renal cell carcinoma in the past. The eosinophilic cytoplasm similar to that in the granular cells, and some confusion between PRCC and ChRCC are the main reasons. The cellular characteristic features of granular renal cell carcinoma can be found in many types of renal tumors. Granular cell renal cell carcinoma is not an independent entity, therefore, it should be removed from the histological classification of renal cell carcinoma. The diagnosis standard of mixed renal cell carcinoma (MRCC) need to be determined and consummated.


Asunto(s)
Carcinoma de Células Renales/clasificación , Neoplasias Renales/clasificación , Organización Mundial de la Salud , Adenocarcinoma/patología , Carcinoma de Células Renales/patología , Diagnóstico Diferencial , Humanos , Neoplasias Renales/patología
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