RESUMEN
PURPOSE: We aimed to evaluate the prognostic value of 18F-FDG PET/CT in patients with relapsed or refractory T-Lymphoblastic lymphoma (T-LBL) undergoing hematopoietic stem cell transplantation (HSCT). METHODS: PET/CT was performed in 21 consecutive relapsed or refractory T-LBL patients scheduled for HSCT. All PET/CT images were assessed using the Deauville criteria, and patients were divided into negative (Deauville ≤ 3) and positive (Deauville > 3) groups for comparison. The predictive value of sex, age, Ann Arbor stage, presence of B symptoms, lactate dehydrogenase level, presence of extranodal disease, and PET/CT results before and after HSCT were evaluated. RESULTS: Kaplan-Meier analysis showed that only PET/CT after HSCT (post-PET) was correlated with progression-free survival (PFS) (P = 0.030). The Cox regression model also showed that the post-PET-positive group had a higher hazard ratio (HR) than the negative group (HR = 3.884 and P = 0.049). However, none of the evaluated factors were predictive of overall survival (OS). CONCLUSIONS: Pre-PET cannot predict the PFS and OS of patients with T-LBL undergoing HSCT, which means that 18F-FDG PET/CT cannot be used for identifying patients who can benefit from HSCT. Post-PET is not predictive for OS in patients with T-LBL undergoing HSCT. However, post-PET showed strong correlations with PFS, which means that it may be useful for guiding subsequent clinical treatment decisions.
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Trasplante de Células Madre Hematopoyéticas , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico por imagen , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Adulto , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/sangre , Masculino , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Valor Predictivo de las Pruebas , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Radiofármacos , Recurrencia , Estudios Retrospectivos , Factores Sexuales , Vincristina/uso terapéutico , Adulto JovenRESUMEN
Tocochromanols constitute the different forms of vitamin E (VTE), essential components of the human diet, and display a high membrane protectant activity. By combining interval mapping and genome-wide association studies (GWAS), we unveiled the genetic determinants of tocochromanol accumulation in tomato (Solanum lycopersicum) fruits. To enhance the nutritional value of this highly consumed vegetable, we dissected the natural intraspecific variability of tocochromanols in tomato fruits and genetically engineered their biosynthetic pathway. These analyses allowed the identification of a total of 25 quantitative trait loci interspersed across the genome pinpointing the chorismate-tyrosine pathway as a regulatory hub controlling the supply of the aromatic head group for tocochromanol biosynthesis. To validate the link between the chorismate-tyrosine pathway and VTE, we engineered tomato plants to bypass the pathway at the arogenate branch point. Transgenic tomatoes showed moderate increments in tocopherols (up to approximately 20%) and a massive accumulation of tocotrienols (up to approximately 3400%). Gene expression analyses of these plants reveal a trade-off between VTE and natural variation in chorismate metabolism explained by transcriptional reprogramming of specific structural genes of the pathway. By restoring the accumulation of alpha-tocotrienols (α-t3) in fruits, the plants produced here are of high pharmacological and nutritional interest.
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Ácido Corísmico/metabolismo , Solanum lycopersicum/metabolismo , Vitamina E/análisis , Mapeo Cromosómico , Frutas/química , Frutas/metabolismo , Genes de Plantas/genética , Ingeniería Genética , Sitios Genéticos , Variación Genética , Estudio de Asociación del Genoma Completo , Solanum lycopersicum/química , Solanum lycopersicum/genética , Redes y Vías Metabólicas/genética , Plantas Modificadas Genéticamente , Polimorfismo de Nucleótido Simple , Carácter Cuantitativo Heredable , Tirosina/metabolismo , Vitamina E/metabolismoRESUMEN
Pollinators foraging for food resources can be waylaid by mass-flowering plants located in their foraging pathway in landscapes. The waylaying effect of pollinators is often studied at a single spatial scale; to date, little is known about the best spatial extent at which waylaying effect of pollinators can be measured. In this study, we selected a landscape with mass-flowering tufted vetches to determine the spatial scale of waylaying effect of honey bees as well as the consequence of waylaying effect on vetch pollination service. The spatial scale of waylaying effect was determined by the strongest association between honey bee density and distance, selected from a gradient of nested circular buffers centering on apiaries in three different locations. Linear models were used to predict the influence of flower visitor densities on pollination service. For our landscape, honey bee densities were best associated with distances at spatial scales of 500 m, 1150 m, and 1400 m respectively for the three locations of apiaries. Honey bee was the only pollinator whose density displayed a positive relationship with pollination service. At the scales of effect, honey bee density and pollination service declined along the distance. Our findings suggest that the waylaying effect of pollinators needs to be examined at a specific spatial scale and farmers who use honey bees to pollinate their mass-flowering crops need to consider the spatial scale of waylaying effect of pollinators in order to maximize pollination service within agricultural ecosystems.
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Abejas/fisiología , Flores/fisiología , Polinización , Animales , China , Productos Agrícolas/fisiología , Modelos Lineales , Magnoliopsida/fisiologíaRESUMEN
BACKGROUND: Advanced non-small cell lung cancer (NSCLC) has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with chemotherapy (CT) in this malignancy. METHODS: We have developed a new clinical trial design termed as the prospective patient's preference-based study (PPPS). Consecutive patients (n = 135) with advanced NSCLC were treated with DC-CIK administered with CT or mono-therapy (CT or DC-CIK alone). RESULTS: For all the patients, the median PFS was 5.7 months and the median OS was 17.5 months. The 1-year PFS and OS rates were 29.4% and 58.2%, respectively. The 1-year PFS and OS rates for DC-CIK plus CT were significantly higher than that in the group of patients who received DC-CIK alone and CT alone (P < 0.05). The number of adoptively infused DC-CIK cells was associated with clinical efficacy. After adjusting for competing risk factors, DC-CIK combined with CT and infused number of CIKs remained independent predictors of PFS and OS. Phenotypic analysis of peripheral blood mononuclear cells showed that CD8+CD28+, and CD8+CD28- T cells, changed significantly in all groups (P < 0.01). The CD3+ T cells increased in the chemotherapy plus immunotherapy and the immunotherapy alone group (P < 0.01), while CD3-CD16+CD56 T cells decreased in the chemotherapy plus immunotherapy and the immunotherapy alone group (P < 0.01). CONCLUSIONS: DC-CIK combined with chemotherapy administration resulted in numerically superior PFS and OS compared with monotherapy in advanced NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Células Asesinas Inducidas por Citocinas/trasplante , Células Dendríticas/trasplante , Inmunoterapia Adoptiva , Neoplasias Pulmonares/terapia , Prioridad del Paciente , Linfocitos T/trasplante , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Adenocarcinoma/terapia , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Células Asesinas Inducidas por Citocinas/inmunología , Células Dendríticas/inmunología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Linfocitos T/inmunologíaRESUMEN
Circular RNAs (CircRNAs) are a type of non-coding RNAs (NcRNAs) with a closed annular structure. Until next-generation sequencing (NGS) is developed, the misunderstanding of circRNAs 'splicing error' has changed, and the mysterious veil of circRNAs has been revealed. NGS provides an approach to investigate circRNAs. Many scholars point out that circRNAs may play an important role in many diseases, especially cancer. At the same time, exosomes, as a kind of extracellular vesicles loaded with many contents, are a hotspot in recent years. They can act as 'messengers' between cells, especially in cancer. Lately, it is interesting circRNAs are enriched and stable in exosomes, also called exo-circRNAs, and there have been several articles on circRNAs associated with exosomes. In this review, we summarize the characteristics of circRNAs, especially its main functions. Then, we briefly introduce exosomes and their function in cancer. Finally, the known relation between circRNAs and exosomes is discussed. With further researches, exo-circRNAs may be a novel pathway for cancer diagnosis and targeted therapy.
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Exosomas/fisiología , Neoplasias/genética , ARN/fisiología , Humanos , Sistema Inmunológico/fisiología , MicroARNs/fisiología , Metástasis de la Neoplasia , ARN CircularRESUMEN
PURPOSE: To compare the clinical remission and survival between CLAG and FLAG induction chemotherapy in treating patients with refractory or relapsed acute myeloid leukemia (R/R AML). METHODS: 103 R/R AML patients were consecutively enrolled in this prospective cohort study. 55 patients were treated by CLAG induction chemotherapy as follows: 5 mg/m2/day cladribine (days 1-5); 2 g/m2/day cytarabine (days 1-5) and 300 µg/day filgrastim (days 0-5). While 48 patients were treated by FLAG: 30 mg/m2/day fludarabine (days 1-5), 2 g/m2/day cytarabine (days 1-5), and 300 µg/day filgrastim (days 0-5). RESULTS: CLAG induction chemotherapy achieved 61.7% complete remission rate (CR) and 78.7% overall remission rate (ORR), which was similar with FLAG chemotherapy which realized 48.7% CR and 69.2% ORR. No difference of overall survival (OS) was discovered between two groups either. Age cytarabine 60 years, secondary disease, poor risk stratification and BM blast ≥ 42.7% and second or higher salvage therapy were independent factors for worse prognosis. Subgroups analysis revealed that in patients with second or higher salvage therapy, CLAG seemed to achieve a higher CR than FLAG. And in patients with relapsed disease, poor risk stratification or CR at first induction, CLAG seemed to realize a prolonged OS compared to FLAG. CONCLUSION: CLAG was equally effective to FLAG induction chemotherapy in total R/R AML patients, while CLAG seemed to be a better option than FLAG in patients with relapsed disease, poor risk stratification, CR at first induction or second or higher salvage therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Terapia Recuperativa , Cladribina/administración & dosificación , Citarabina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Tasa de Supervivencia , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
Ischemic stroke can lead to loss of neurologic functions. It occurs due to obstruction in blood supply to the brain. It has been proposed that C807T(C/T) polymorphism within the platelet glycoprotein gene may be associated with density and function of glycoprotein Ia/IIa receptors and contributes to the pathogenesis of thrombotic disease. We assessed the association between C807T(C/T) and risk of ischemic stroke. Databases such as PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library, Google scholar, Wanfang Data (Chinese), and Chinese National Knowledge Infrastructure (CNKI, Chinese) were used to search for relevant studies. We found 16 eligible studies, which totaled to 4897 (case group 2340; control group 2557) participants. Overall, our results showed significant associations between C807T(C/T) polymorphism and risk of ischemic stroke based on T-allele comparisons (T vs C, pooled OR = 0.78, 95%CI = 0.68-0.90, P < 0.01), TT vs CC comparisons (pooled OR = 0.58, 95%CI = 0.42-0.81, P < 0.01), recessive models (TT vs TC + CC, pooled OR = 0.72, 95%CI = 0.59-0.87, P < 0.01) and dominant models (TT + TC vs CC, pooled OR = 0.70, 95%CI = 0.54-0.92, P < 0.05). There was no association in TC vs CC comparisons (pooled OR = 0.81, 95%CI = 0.63-1.04, P > 0.05). Subgroup analyses stratified according to Hardy-Weinberg equilibrium, sample size, and ethnicity also demonstrated significant associations between the two variables. Therefore, C807T(C/T) polymorphism in the platelet glycoprotein gene may be associated with susceptibility to ischemic stroke, and the T allele at this locus may decrease risk to ischemic stroke.
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Glicoproteínas de Membrana Plaquetaria/genética , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Oportunidad RelativaRESUMEN
PURPOSE: Changes in EGFR profiles of non small cell lung cancer (NSCLC) patients correlates to clinical outcome. Extracting quality tumor tissue remains a challenge for molecular profiling. Our study aims to ascertain the clinical relevance of urinary cell free DNA as an alternative tumor material source. METHODS: 150 patients with activating EGFR mutation and received EGFR-TKIs were recruited to participate in the serial monitoring study. Matched primary tumor samples were taken together with blood and urine specimens before the initiation of TKIs. The EGFR mutation testing was performed and quantified using ddPCR. For serial time point measurements, urine and blood samples were extracted at 1-month intervals for duration of 9 months. RESULTS: Urinary ctDNA yielded a close agreement of 88 % on EGFR mutation status when compared to primary tissue at baseline. Almost all samples detected via urine specimens were uncovered in plasma samples. Analysis of urinary cell free DNA at different time points showed a strong correlation to treatment efficacy. Interestingly, a secondary EGFR mutation T790M was detected for 53 % of the patients during monitoring. The results were corroborated with the plasma ctDNA analysis. The T790M+ group had a reduced median survival when compared to the wildtype group. CONCLUSION: Urinary cell free DNA may be a potential alternative to conventional primary tissue based EGFR mutation testing. Our findings showed that the assay sensitivity was comparable to results from blood plasma. Urinary samples being noninvasive and readily available have clinical utility for monitoring of EGFR TKI treatment.
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Biomarcadores de Tumor/orina , Carcinoma de Pulmón de Células no Pequeñas/orina , ADN de Neoplasias/orina , Receptores ErbB/genética , Mutación/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/orina , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Casos y Controles , ADN de Neoplasias/genética , Receptores ErbB/orina , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/orina , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Células Neoplásicas Circulantes/efectos de los fármacos , Células Neoplásicas Circulantes/metabolismo , Reacción en Cadena de la Polimerasa , Pronóstico , Tasa de SupervivenciaRESUMEN
Heroin dependence is a chronic relapsing brain disease. Researchers have reported that the dopamine D2 receptor (DRD2) is involved in the development of opiate dependence. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin dependence and six polymorphisms of the DRD2 gene using the MassARRAY system. Three hundred and thirty-four patients with heroin dependence and 299 healthy controls participated in the research. Compared with the healthy controls, heroin-dependent patients had a significantly lower frequency of the AA genotype of rs6275 (P = 0.038), and a significantly higher frequency of the C allele of rs1125394 (P = 0.030). Statistically significant differences were observed in the genotypic and allelic frequencies of rs17115583 (P = 0.005 and P = 0.001, respectively) and rs1079597 (P = 0.03 and P = 0.02, respectively). Haplotype analysis revealed that the T-G-A (block 1) haplotype of the DRD2 gene conferred a protective effect (P = 0.020). These findings point to a role for DRD2 polymorphism in heroin dependence in the Chinese Han population, and may be informative for future genetic or neurobiological studies on heroin dependence.
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Dependencia de Heroína/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Dopamina D2/genética , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The shipment and storage conditions of clinical samples pose a major challenge to the detection accuracy of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Ureaplasma urealyticum (UU) when using quantitative real-time polymerase chain reaction (qRT-PCR). The aim of the present study was to explore the influence of storage time at 4°C on the DNA of these pathogens and its effect on their detection by qRT-PCR. CT, NG, and UU positive genital swabs from 70 patients were collected, and DNA of all samples were extracted and divided into eight aliquots. One aliquot was immediately analyzed with qRT-PCR to assess the initial pathogen load, whereas the remaining samples were stored at 4°C and analyzed after 1, 2, 3, 7, 14, 21, and 28 days. No significant differences in CT, NG, and UU DNA loads were observed between baseline (day 0) and the subsequent time points (days 1, 2, 3, 7, 14, 21, and 28) in any of the 70 samples. Although a slight increase in DNA levels was observed at day 28 compared to day 0, paired sample t-test results revealed no significant differences between the mean DNA levels at different time points following storage at 4°C (all P>0.05). Overall, the CT, UU, and NG DNA loads from all genital swab samples were stable at 4°C over a 28-day period.
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Chlamydia trachomatis/genética , ADN Bacteriano/aislamiento & purificación , Neisseria gonorrhoeae/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Manejo de Especímenes , Ureaplasma urealyticum/genética , Adulto , Carga Bacteriana , Chlamydia trachomatis/aislamiento & purificación , Femenino , Genitales/microbiología , Humanos , Masculino , Persona de Mediana Edad , Neisseria gonorrhoeae/aislamiento & purificación , Valores de Referencia , Factores de Tiempo , Ureaplasma urealyticum/aislamiento & purificación , Adulto JovenRESUMEN
This study was designed to evaluate bone matrix gelatin (BMG)/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering. Chondrocytes were isolated from costal cartilage of Sprague-Dawley rats and seeded on BMG/fibrin glue or chitosan/gelatin composite scaffolds. After different in vitro culture durations, the scaffolds were subjected to hematoxylin and eosin, Masson's trichrome, and toluidine blue staining, anti-collagen II and anti-aggrecan immunohistochemistry, and scanning electronic microscopy (SEM) analysis. After 2 weeks of culture, chondrocytes were distributed evenly on the surfaces of both scaffolds. Cell numbers and the presence of extracellular matrix components were markedly increased after 8 weeks of culture, and to a greater extent on the chitosan/gelatin scaffold. The BMG/fibrin glue scaffold showed signs of degradation after 8 weeks. Immunofluorescence analysis confirmed higher levels of collagen II and aggrecan using the chitosan/gelatin scaffold. SEM revealed that the majority of cells on the surface of the BMG/fibrin glue scaffold demonstrated a round morphology, while those in the chitosan/gelatin group had a spindle-like shape, with pseudopodia. Chitosan/gelatin scaffolds appear to be superior to BMG/ fibrin glue constructs in supporting chondrocyte attachment, proliferation, and biosynthesis of cartilaginous matrix components.
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Condrocitos/efectos de los fármacos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Adhesivos/efectos adversos , Agrecanos/genética , Agrecanos/metabolismo , Animales , Matriz Ósea/química , Adhesión Celular , Células Cultivadas , Quitosano/efectos adversos , Condrocitos/citología , Condrocitos/metabolismo , Condrogénesis/efectos de los fármacos , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Fibrina/efectos adversos , Gelatina/efectos adversos , Ratas , Ratas Sprague-Dawley , Andamios del Tejido/efectos adversosRESUMEN
Pelodiscus sinensis is a common freshwater soft-shell turtle found in China, and is an important aquaculture species. In this study, 20 polymorphic microsatellite primers were developed from the transcriptome. The genetic diversity of three populations of P. sinensis was evaluated, using 72 individuals. The number of alleles per locus ranged from 3 to 26. The observed and expected heterozygosities varied from 0.208 to 0.958, and from 0.302 to 0.963, respectively. The polymorphic information content varied from 0.283 to 0.953. No significant linkage disequilibrium was detected. These markers will be useful for future population genetic studies and molecular breeding of P. sinensis.
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Tortugas/genética , Animales , Acuicultura , Cruzamiento , Heterocigoto , Desequilibrio de Ligamiento , Repeticiones de Microsatélite , Filogenia , Polimorfismo Genético , TranscriptomaRESUMEN
Previous case-control studies having investigated the relationship between the X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp polymorphism and thyroid cancer (TC) have drawn inconsistent conclusions. The current study aimed to clarify the role of this polymorphism in susceptibility to TC. An up-to-date search of PubMed and Web of Science databases was conducted, including articles published up to August 2015. Crude odds ratios (ORs) with 95%CIs were calculated to establish the association between the XRCC1 Arg194Trp polymorphism and TC risk. Five studies were used, comprising 911 patients and 1476 controls. Our meta-analysis indicated that this polymorphism is associated with TC risk in Caucasians (TrpTrp vs ArgArg: OR = 5.72, 95%CI = 1.39-23.54; ArgTrp vs ArgArg: OR = 1.20, 95%CI = 0.87-1.66; dominant model: OR = 1.31, 95%CI = 0.96-1.79; recessive model: OR = 0.18, 95%CI = 0.04-0.73). This investigation demonstrates that the XRCC1 Arg194Trp polymorphism constitutes a risk factor for TC in Caucasian individuals.
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Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Neoplasias de la Tiroides/genética , Estudios de Asociación Genética , Humanos , Oportunidad Relativa , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
The aim of this study was to evaluate the performance of three new high-risk human papillomavirus (HPV) assays for primary cervical cancer screening, by using self-collected samples, and to identify an HPV assay that could overcome the major obstacles faced during large-scale population-based screening. Two hundred and ten women showing abnormal cervical cytology (and referred for a colposcopy) were recruited in this study. Self-collected samples obtained from all women were tested with the Cobas, Seq, and BioPerfectus Multiplex Real Time HPV assays; simultaneously, clinician-collected samples (from the same women) were tested with the gold-standard Cobas HPV assay. The results of all the assays were consistent. The sensitivity, positive predictive value, and negative predictive value for cervical intraepithelial neoplasia 2+ (CIN2+) and CIN3+ were comparable between the self-collected samples tested with the three new assays and the clinician-collected samples tested with the Cobas HPV assay (P > 0.05). The single-genotype HPV load per sample did not differ significantly between the self- and clinician-collected samples (P = 0.195). In conclusion, the results of this study demonstrated the applicability of the three new HPV assays for primary cervical cancer screening based on self-collection.
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Pruebas de ADN del Papillomavirus Humano/métodos , Autoexamen/métodos , Manejo de Especímenes/métodos , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Femenino , Pruebas de ADN del Papillomavirus Humano/normas , Humanos , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Autoexamen/normas , Sensibilidad y Especificidad , Manejo de Especímenes/normasRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate of 5%. Biomarkers for the early detection of pancreatic cancer are urgently needed. Transforming growth factor-beta1 (TGF-ß1) is elevated in the tissues and plasma of patients with PDAC. However, no studies systemically report prognostic significance of plasma TGF-ß1 levels in PDAC. In the present study, we assessed the prognostic significance of serum TGF-ß levels in patients with PDAC. TGF-ß levels were determined in serum from 146 PDAC patients, and 58 patients with benign pancreatic conditions. Regression models were used to correlate TGF-ß levels to gender, age, stage, class, and metastasis. Survival analyses were performed using multivariate Cox models. Serum levels of TGF-ß1 distinguished PDAC from benign pancreatic conditions (P<0.001) and healthy control subjects (P<0.001). Serum levels of TGF-ß also distinguished tumor stage (P=0.002) and lymph node metastasis (P=0.001). High serum levels of TGF-ß1 were significantly correlated with reduced patient survival. Multivariate analysis revealed that TGF-ß1, lymph node metastasis and tumor stage were independent factors for PDAC survival. Our results indicate that serum TGF-ß1 may be used as a potential prognostic marker for PDAC.
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Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/sangre , Neoplasias Pancreáticas/sangre , Factor de Crecimiento Transformador beta1/sangre , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/secundario , Humanos , Estimación de Kaplan-Meier , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/secundario , Pronóstico , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
ErbB4 is an oncogene belonging to the epidermal growth factor receptor family and contributes to the occurrence and development of multiple cancers, such as gastric, breast, and colorectal cancers. Therefore, studies of the regulation of ErbB4 in cancerigenic pathway will advance molecular targeted therapy. Advanced bioinformatic analysis softwares, such as ExPASy, Predictprotei, QUARK, and I-TASSER, were used to analyze the regulatory mechanism after ErbB4 gene mutation in terms of amino acid sequence, primary, secondary, and tertiary structure of the protein and upstream-downstream receptor/ligands. Mutation of the 19th and 113th amino acids at the carboxyl terminus of ErbB4 protein did not affect its biological nature, but its secondary structure changed and protein binding sites were near 2 mutational sites; moreover, after mutation introduction, additional binding sites were observed. Tertiary structure modeling indicated that local structure of ErbB4 was changed from an α helical conformation into a ß chain folding structure; the α helical conformation is the functional site of protein, while active sites are typically near junctions between helical regions, thus the helical structures are easily destroyed and change into folding structures or other structures after stretching. Mutable sites of ErbB4 is exact binding sites where dimer formed with other epidermal growth factor family proteins; mutation enabled the ErbB4 receptor to bind to neuregulin 1 ligand without dimer formation, disrupting the signal transduction pathway and affecting ErbB4 function.
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Modelos Genéticos , Mutación , Receptor ErbB-4/genética , Secuencia de Aminoácidos , Biología Computacional/métodos , Humanos , Modelos Moleculares , Neoplasias/genética , Neoplasias/metabolismo , Fosforilación , Unión Proteica , Estructura Secundaria de Proteína , Receptor ErbB-4/química , Receptor ErbB-4/metabolismo , Transducción de Señal , Relación Estructura-ActividadRESUMEN
Eucommia ulmoides Oliver, a single extant species of Eucommiaceae, is an endemic dioecious tree in China. The natural resources of E. ulmoides have rapidly declined in recent years because of the over-collection of its cortex. To design a suitable protection strategy, it is necessary to develop a set of molecular markers to investigate genetic diversity and population structure of E. ulmoides. Pyrosequencing of an enriched microsatellite library by Roche 454 FLX+ platform was used to isolate simple sequence repeats (SSRs) for E. ulmoides. A total of 1568 SSRs that contained enough flanking sequences for primer pair design were identified from 45,236 raw sequence reads. One hundred SSRs were randomly selected to design primer pairs and polymerase chain reaction was performed. Among these 100 tested primer pairs, 16 were polymorphic across 18 individuals from three E. ulmoides populations. The number of alleles ranged from 3 to 8, with an average of 5.1. The expected heterozygosity ranged from 0.110 to 0.830, with an average of 0.648, and the observed heterozygosity ranged from 0.111 to 0.833, with an average of 0.524. The inbreeding coefficient ranged from -0.349 to 0.547. This set of microsatellite markers could be valuable for landscape genetic structure assessment and molecular marker-assisted breeding in E. ulmoides.
Asunto(s)
Eucommiaceae/genética , Repeticiones de Microsatélite , Alelos , Especies en Peligro de Extinción , Heterocigoto , EndogamiaRESUMEN
Despite more than a century of intensive study, the mechanisms of successful pregnancy remain unclear. Recent research suggests that NF-κB (nuclear factor kappa B) plays an important role in embryo implantation. In the current study, we aimed to identify SNPs that contribute to genetic susceptibility for recurrent implantation failure (RIF). Thus, we examined the potential associations between RIF and ten SNPs (rs28362491, rs3774932, rs1598856, rs230528, rs230521, rs3774956, rs4648055, rs3774964, rs4648068, and rs3774968) of the NF-κB gene. Participants included 209 patients with RIF and 395 controls. Our results revealed that there were statistically significant differences observed in the allelic and genotypic frequencies of the rs28362491 promoter in the NF-κB gene. The frequency of the del/ del genotype was significantly higher in RIF patients than in healthy controls (P = 0.004). Compared with healthy controls, the RIF patients carried a higher frequency of the rs28362491 del allele (P = 0.010). Furthermore, strong linkage disequilibrium was observed in the three identified haplotype blocks (D' > 0.9). Particularly, in block 1 (rs230528-rs230521), the A-C haplotype occurred significantly more frequently (P = 0.029) in subjects with RIF (P = 0.0003). In contrast, the A-G haplotype occurred significantly less frequently (P = 0.008) in RIF subjects. These findings support an important role for G-712A polymorphisms of NF-κB in RIF, and may guide future studies that aim to characterize genetic risk factors for RIF.
Asunto(s)
Implantación del Embrión/genética , FN-kappa B/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Transferencia de Embrión/efectos adversos , Femenino , Haplotipos , Humanos , Desequilibrio de Ligamiento , EmbarazoRESUMEN
Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD.
Asunto(s)
Colitis/fisiopatología , Linfangiogénesis/fisiología , Neovascularización Patológica/fisiopatología , Factor C de Crecimiento Endotelial Vascular/metabolismo , Enfermedad Aguda , Adenoviridae/genética , Animales , Colitis/etiología , Colitis/metabolismo , Colitis/patología , Modelos Animales de Enfermedad , Femenino , Inmunohistoquímica , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Recombinación Genética/fisiología , Factor C de Crecimiento Endotelial Vascular/fisiologíaRESUMEN
The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this gene polymorphism interacts with BMI in the risk of ischemic stroke.