Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.661
Filtrar
3.
Biosci Biotechnol Biochem ; 84(1): 53-62, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31483222

RESUMO

Large numbers of miRNAs are found in biofluid exosomes. We isolated ~50-200 nm diameter exosomes from four types of porcine biofluid (urine, plasma, semen, and bile) using serial centrifugation and ultracentrifugation procedures. A total of 42.15 M raw data were generated from four small RNA libraries. This produced 40.17 M map-able sequences, of which we identified 204 conserved miRNAs, and 190 novel candidate miRNAs. Furthermore, we identified 34 miRNAs specifically expressed in only one library, all with well-characterized immune-related functions. A set of five universally abundant miRNAs (miR-148a-3p, miR-21-5p, let-7f-5p, let-7i-5p, and miR-99a-5p) across all four biofluids was also found. Function enrichment analysis revealed that the target genes of the five ubiquitous miRNAs are primarily involved in immune and RNA metabolic processes. In summary, our findings suggest that porcine biofluid exosomes contain a large number of miRNAs, many of which may be crucial regulators of the immune system.


Assuntos
Secreções Corporais , Líquidos Corporais , Exossomos/genética , Imunidade Inata , MicroRNAs/genética , MicroRNAs/imunologia , Suínos/genética , Animais , Sequência de Bases/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Microscopia de Força Atômica , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA
4.
Cancer Immunol Immunother ; 68(11): 1779-1790, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31620857

RESUMO

Human leukocyte antigen class I (HLA I) molecules composed of alpha (heavy) chain, including HLA-A, -B, or -C encoded by HLA genes, and beta-2-microglobulin (ß2M) are membrane proteins on all nucleated cells that display peptide antigens for recognition by CD8-positive cytotoxic T cells. Here, we examined the clinicopathologic signification of HLA I expression in patients with gastric cancer (GC). Immunohistochemistry was performed to detect HLA A/B/C, ß2M, CD8, p53, and programmed death-ligand 1 (PD-L1) in the center and invasive margin of the tumor in 395 stage II and III GCs using tissue array method. Additionally, Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status were investigated. Negative expression of HLA A/B/C and ß2M was observed in 258 (65.3%) and 235 (59.5%) of 395 stage II and III GCs, respectively. Negative HLA I expression was significantly associated with aggressive clinicopathologic features. Furthermore, negative expression of HLA A/B/C and ß2M was inversely correlated with CD8-positive cytotoxic T cell infiltration, EBV-positivity, and PD-L1 expression (all p < 0.001). Patients with HLA A/B/C-negative GC had worse overall survival (OS) (p = 0.019) and combined analysis with both HLA A/B/C and ß2M expression status significantly predicted OS in univariate (p = 0.004) and multivariate survival analysis (p = 0.016). Negative expression of HLA A/B/C and ß2M was frequently observed in stage II and III GCs, particularly with the aggressive clinicopathologic features, and correlated with an unfavorable prognosis and host immune response status. These findings contribute to further development of immunotherapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Antígenos HLA/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Gástricas/patologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/imunologia , Feminino , Seguimentos , Antígenos HLA/imunologia , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Adulto Jovem , Microglobulina beta-2/imunologia , Microglobulina beta-2/metabolismo
5.
Nat Biotechnol ; 37(11): 1351-1360, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31570899

RESUMO

Genomic analysis of paired tumor-normal samples and clinical data can be used to match patients to cancer therapies or clinical trials. We analyzed 500 patient samples across diverse tumor types using the Tempus xT platform by DNA-seq, RNA-seq and immunological biomarkers. The use of a tumor and germline dataset led to substantial improvements in mutation identification and a reduction in false-positive rates. RNA-seq enhanced gene fusion detection and cancer type classifications. With DNA-seq alone, 29.6% of patients matched to precision therapies supported by high levels of evidence or by well-powered studies. This proportion increased to 43.4% with the addition of RNA-seq and immunotherapy biomarker results. Combining these data with clinical criteria, 76.8% of patients were matched to at least one relevant clinical trial on the basis of biomarkers measured by the xT assay. These results indicate that extensive molecular profiling combined with clinical data identifies personalized therapies and clinical trials for a large proportion of patients with cancer and that paired tumor-normal plus transcriptome sequencing outperforms tumor-only DNA panel testing.


Assuntos
Genômica/métodos , Neoplasias/genética , Análise de Sequência de DNA/métodos , Análise de Sequência de RNA/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Medicina de Precisão
6.
Dis Colon Rectum ; 62(12): 1485-1493, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31567920

RESUMO

BACKGROUND: Systemic inflammation may influence the response to systemic chemotherapy or the prognosis in patients with various cancers. The Naples prognostic score, based on inflammatory and nutritional statuses, is a useful prognostic marker in patients undergoing surgery for colorectal cancer; however, its significance in patients with metastatic colorectal cancer remains unclear. OBJECTIVE: We aimed to evaluate the prognostic significance of the Naples prognostic factor in patients with metastatic colorectal cancer receiving first-line chemotherapy and to compare its prognostic accuracy with the neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and the systemic immune-inflammatory index. DESIGN: This was a retrospective study of prospectively collected data. SETTINGS: This study was conducted at a university hospital. PATIENTS: A total of 259 patients received first-line systemic chemotherapy for metastatic colorectal cancer. MAIN OUTCOME MEASURES: The Naples prognostic score was calculated by a composite score of albumin and cholesterol concentrations, lymphocyte:monocyte ratio, and neutrophil:lymphocyte ratio. The patients were divided into 3 groups based on increasing Naples scores (groups 0-2), and the associations of the Naples prognostic score with clinicopathologic features and overall survival were evaluated. RESULTS: Higher Naples prognostic score was positively associated with right-sided primary tumors and synchronous metastases and negatively with primary tumor resection. Patients in group 2 (high Naples prognostic score) had significantly shorter overall survival than those in groups 0 and 1 (p = 0.012 and 0.022). Multivariate Cox regression analysis identified the Naples prognostic score as an independent prognostic factor for overall survival (HR = 1.574; p = 0.004). Time-dependent receiver operating characteristic curve analysis showed that Naples prognostic score was more sensitive than other prognostic factors for predicting overall survival. LIMITATIONS: The main limitations are the sample size, single institutional feature, and treatment heterogeneity. CONCLUSIONS: The Naples prognostic score may be a useful prognostic marker in patients with metastatic colorectal cancer receiving systemic chemotherapy. See Video Abstract at http://links.lww.com/DCR/B72. LA PUNTUACIÓN PRONÓSTICA DE NÁPOLES ES UN MARCADOR PRONÓSTICO ÚTIL EN PACIENTES CON CÁNCER COLORRECTAL METASTÁSICO: La inflamación sistémica puede influir en la respuesta a la quimioterapia sistémica o el pronóstico en pacientes con varios tipos de cáncer. La puntuación pronóstica de Nápoles, basada en estados inflamatorios y nutricionales, es un marcador pronóstico útil en pacientes sometidos a cirugía por cáncer colorrectal; sin embargo, su importancia en pacientes con cáncer colorrectal metastásico sigue siendo incierta.El objetivo fue evaluar la importancia pronóstica del factor pronóstico de Nápoles en pacientes con cáncer colorrectal metastásico que reciben quimioterapia de primera línea y comparar su precisión pronóstica con la relación neutrófilos: linfocitos, plaquetas: linfocitos y el índice sistémico inmune-inflamatorio.Este estudio se realizó en un hospital universitario.Este fue un estudio retrospectivo de datos recolectados prospectivamente.Un total de 259 pacientes recibieron quimioterapia sistémica de primera línea para el cáncer colorrectal metastásico.La puntuación pronóstica de Nápoles se calculó mediante una puntuación compuesta de concentraciones de albúmina y colesterol, proporción de linfocitos: monocitos y proporción de neutrófilos: linfocitos. Los pacientes se dividieron en tres grupos basados en el aumento de las puntuaciones de Nápoles (grupos 0-2, respectivamente) y se evaluaron las asociaciones de la puntuación pronóstica de Nápoles con las características clínico-patológicas y la supervivencia general.La puntuación pronóstica de Nápoles es más alta se asoció positivamente con los tumores primarios del lado derecho y metástasis sincrónicas, y negativamente con la resección del tumor primario. Los pacientes del grupo 2 (alto puntaje pronóstico de Nápoles) tuvieron una supervivencia general significativamente menor que los de los grupos 0 y 1 (p = 0.012 y 0.022, respectivamente). El análisis de regresión de Cox multivariado identificó la puntuación pronóstica de Nápoles como un factor pronóstico independiente para la supervivencia global (índice de riesgo = 1.574; p = 0.004). El análisis de la curva característica de funcionamiento del receptor dependiente del tiempo mostró que la puntuación pronóstica de Nápoles era más sensible que otros factores pronósticos para predecir la supervivencia global.Las principales limitaciones son el tamaño de la muestra, la característica institucional única y la heterogeneidad del tratamiento.La puntuación pronóstica de Nápoles puede ser un marcador pronóstico útil en pacientes con cáncer colorrectal metastásico que reciben quimioterapia sistémica. Vea el Abstract del video en http://links.lww.com/DCR/B72.


Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias Colorretais/tratamento farmacológico , Estado Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Colesterol/sangue , Neoplasias Colorretais/sangue , Tratamento Farmacológico , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Contagem de Plaquetas , Prognóstico , Curva ROC , Estudos Retrospectivos , Tamanho da Amostra , Albumina Sérica Humana/análise , Resultado do Tratamento
7.
Nat Protoc ; 14(10): 2900-2930, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31534232

RESUMO

Multiplexed tissue imaging enables precise, spatially resolved enumeration and characterization of cell types and states in human resection specimens. A growing number of methods applicable to formalin-fixed, paraffin-embedded (FFPE) tissue sections have been described, the majority of which rely on antibodies for antigen detection and mapping. This protocol provides step-by-step procedures for confirming the selectivity and specificity of antibodies used in fluorescence-based tissue imaging and for the construction and validation of antibody panels. Although the protocol is implemented using tissue-based cyclic immunofluorescence (t-CyCIF) as an imaging platform, these antibody-testing methods are broadly applicable. We demonstrate assembly of a 16-antibody panel for enumerating and localizing T cells and B cells, macrophages, and cells expressing immune checkpoint regulators. The protocol is accessible to individuals with experience in microscopy and immunofluorescence; some experience in computation is required for data analysis. A typical 30-antibody dataset for 20 FFPE slides can be generated within 2 weeks.


Assuntos
Anticorpos , Imunofluorescência/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/patologia , Animais , Biomarcadores Tumorais/imunologia , Imunofluorescência/instrumentação , Formaldeído , Humanos , Imuno-Histoquímica/métodos , Camundongos , Neoplasias/imunologia , Inclusão em Parafina
8.
Int J Cancer ; 145(12): 3436-3444, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31407331

RESUMO

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue-sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV-positive and HPV-negative HNSCC.


Assuntos
Formação de Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/virologia , Papillomaviridae/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Estudos de Coortes , Feminino , Humanos , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Adulto Jovem
9.
DNA Cell Biol ; 38(10): 1088-1099, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31424267

RESUMO

The biological functions of lipocalin-1 (LCN1) are involved in innate immune responses and act as a physiological scavenger of potentially harmful lipophilic molecules. However, the relevance of LCN1 with cancer is rarely concerned currently. The aim of this study is to address the relevance of LCN1 with BRCA by bioinformatics. In this study, we found that the expressions of LCN1 increased significantly in various cancerous tissues, including BRCA, compared with their adjacent normal tissues through the TIMER database. Furthermore, UALCAN database analysis showed that the expression of LCN1 increased gradually from stage 1 to stage 4 and was upregulated in BRCA patients with different races and subtypes compared with that in the normal. In addition, those patients with perimenopause and postmenopause status displayed higher LCN1 expression. Importantly, LCN1 genetic alterations, including copy number amplification, deep deletion, and missense mutation, could be found, and the alteration frequency showed difference in various invasive BRCA through cBioPortal database. Moreover, a positive correlation between LCN1 somatic copy number alterations and immune cell enrichments was revealed in basal like BRCA by GISTIC 2.0. Finally, analysis on prognostic value of LCN1 by Kaplan-Meier plotter showed that low LCN1 expression correlated with poor prognosis for relapse-free survival in all types of BRCA, overall survival in luminal B BRCA, distant metastasis free survival in human epithelial growth factor receptor-2 (HER2) positive BRCA, and postprogression survival (PPS) in luminal A BRCA. But high LCN1 expression also displayed poor prognosis for PPS in HER2 positive BRCA. The results together verified the significance of LCN1 in BRCA, suggesting that it may be a potential biomarker for BRCA diagnosis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Lipocalina 1/genética , Recidiva Local de Neoplasia/genética , Receptor ErbB-2/genética , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Feminino , Humanos , Lipocalina 1/imunologia , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Perimenopausa/genética , Pós-Menopausa/genética , Pós-Menopausa/imunologia , Receptor ErbB-2/imunologia , Análise de Sobrevida
10.
World Neurosurg ; 132: e585-e590, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31442642

RESUMO

BACKGROUND: There are no standardized criteria to predict the prognosis of patients with low-grade gliomas. Therefore, novel prognostic biomarkers that can guide follow-up schedules and therapeutic approaches urgently are required in patients with low-grade gliomas. METHODS: One hundred nineteen patients with World Health Organization (WHO) II gliomas were recruited between January 2010 and December 2016 from Xiangya Hospital for this study. We collected neutrophil and lymphocyte values from the full blood counts measured 24 h before surgery. Neutrophil-to-lymphocyte ratios (NLRs) were then calculated. The significance of the NLR was determined based on a nonparametric test. The Kaplan-Meier method was used to estimate survival rates. The influence of the NLR on progression-free survival and overall survival was evaluated using univariate and multivariate Cox proportional hazards models. RESULTS: Preoperative NLRs were upregulated in patients with WHO II gliomas who relapsed or died. Preoperative NLRs were also significantly correlated with age, preoperative neutrophil values, and preoperative lymphocyte values. Compared with the low preoperative NLR group, patients with WHO II gliomas in the high preoperative NLR group had significantly higher relapse and lower survival rates. In addition, the preoperative NLR and tumor type were independent prognostic parameters of progression-free survival for WHO II gliomas, whereas only the preoperative NLR was an independent prognostic parameter of overall survival for WHO II gliomas. CONCLUSIONS: High preoperative NLRs were significantly associated with greater relapse and poor prognosis in patients with WHO II gliomas.


Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/imunologia , Glioma/imunologia , Linfócitos , Neutrófilos , Adulto , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/mortalidade , Estudos de Coortes , Feminino , Glioma/sangue , Glioma/mortalidade , Humanos , Contagem de Linfócitos , Masculino , Prognóstico , Estudos Retrospectivos
11.
World Neurosurg ; 132: e455-e462, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31470166

RESUMO

BACKGROUND: Glioma is the most frequent primary brain tumor. Immunotherapy is one of the most promising therapeutic approaches for gliomas. T cell immunoglobulin domain and mucin domain-3 can induce the malignancy of gliomas. The function of galectin-9 (GAL-9), as one of the ligands of T cell immunoglobulin domain and mucin domain-3, in glioma has remained elusive. The aim of this study was to characterize the expression of GAL-9 in patients with glioma. METHODS: This study enrolled 1292 patients with glioma from the GSE 16011 array set, the Chinese Glioma Genome Atlas, and The Cancer Genome Atlas datasets. Kaplan-Meier analysis was undertaken to explore the prognostic value of GAL-9. Graphpad software and R language were used for statistical analysis. RESULTS: Expression of GAL-9 was highly correlated with major clinical and molecular features. Patients with high expression of GAL-9 were more susceptible to development of malignant tumors. Gene Ontology analysis revealed that expression of GAL-9 was closely associated with function of immune response in glioma. Clinically, the results of Kaplan-Meier analysis showed that expression of GAL-9 was negatively associated with overall survival in all grades of glioma including high-grade gliomas. High expression of GAL-9 was an independent indicator of poor prognosis. CONCLUSIONS: Our results highlight the pivotal role of GAL-9 in regulation of immune suppressive features of gliomas and indicate that GAL-9 is a promising target for cancer immunotherapy and may lead to development of further therapies.


Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/imunologia , Galectinas/imunologia , Glioma/imunologia , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Galectinas/análise , Glioma/mortalidade , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Prognóstico
12.
J Clin Neurosci ; 68: 281-289, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31327593

RESUMO

Interleukin-6 (IL-6) is one of the pleiotropic cytokines and has received attention as a critical factor implicated in the invasion and the angiogenesis of various cancers. In glioma, IL-6 is known to be associated with the prognosis; however, the roles of IL-6 in cerebrospinal fluid (CSF) has not been studied sufficiently. We examined the concentration of CSF IL-6 using 75 CSF samples of glioma (54 glioblastomas (GBMs) and 21 other grades of gliomas) and analyzed the association CSF IL-6 with infiltration levels of tumor-associated macrophages (TAMs) and prognosis. The concentration of CSF IL-6 in GBM patients was significantly higher than that in other grades of gliomas. CSF IL-6 levels were associated with the infiltration rate of TAMs in GBMs, and IL-6 levels were increased in the GBM cells co-cultured with TAM-like macrophages. The CSF of GBM patients, which contained high concentration of IL-6, promoted the migration ability of GBM cells, and neutralization antibodies of IL-6 inhibited its migration ability. Finally, in both univariate and multivariate analysis, higher CSF IL-6 levels were associated with poorer prognosis in GBM patients. These results indicated that the concentration of CSF IL-6 is associated with TAMs' infiltration level and may be a useful prognostic biomarker for the GBM patients.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Interleucina-6/líquido cefalorraquidiano , Macrófagos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/patologia , Movimento Celular/imunologia , Feminino , Glioblastoma/líquido cefalorraquidiano , Glioblastoma/patologia , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
13.
Chem Commun (Camb) ; 55(68): 10060-10063, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31328750
14.
Future Oncol ; 15(22): 2645-2656, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31298573

RESUMO

Hyperprogression and pseudoprogression are two atypical responses to immune checkpoint inhibitor therapy that affect therapeutic decisions and prognosis. Identification of predictive biomarkers for atypical responses either before or during treatment remains a huge unmet need in cancer immunotherapy. Many studies have looked at potential biomarkers, including clinical factors and laboratory findings (e.g., peripheral blood counts, circulating tumor DNA, cytokine levels). The results of these studies have been inconsistent, possibly due to small sample sizes, different tumor types and heterogeneity of the definition of these atypical responses.


Assuntos
Biomarcadores Tumorais/imunologia , Imunoterapia , Neoplasias/terapia , Prognóstico , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
15.
Analyst ; 144(16): 5003-5009, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31332403

RESUMO

By employment of an aptamer-initiated hybridization chain reaction (HCR) to enhance the enzyme biomineralization of cupric subcarbonate, this work develops a novel colorimetric biosensing method for protein analysis. The HCR product was used to specifically attach a large amount of urease-functionalized gold nanoparticles (Au NPs) for the preparation of a gold nanoprobe. After the sandwich biorecognition reactions, this nanoprobe could be quantitatively captured onto the antibody-functionalized magnetic bead (MB) platform. Then, numerous copper ions would be enriched onto the MB surface through the urease-induced biomineralization of cupric subcarbonate. Based on the complete release of Cu2+ ions for the sensitive copper chromogenic reaction, convenient colorimetric signal transduction was thus achieved for the quantitative analysis of the target analyte of the carcinoembryonic antigen. The HCR product provides a large number of biotin sites for the attachment of Au NP nanotags. The biomineralization reaction of high-content urease loaded onto Au NPs leads to highly efficient Cu2+ enrichment for signal amplification. So this method features excellent performance including a very wide linear range and a low detection limit down to 0.071 pg mL-1. In addition, the satisfactory results of real sample experiments reveal that this method possesses huge potential for practical applications.


Assuntos
Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/métodos , Antígeno Carcinoembrionário/sangue , Animais , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/imunologia , Aptâmeros de Nucleotídeos/química , Biomarcadores Tumorais/imunologia , Biomineralização , Carbonatos/química , Antígeno Carcinoembrionário/imunologia , Colorimetria/métodos , Cobre/química , Ouro/química , Humanos , Imunoensaio/métodos , Separação Imunomagnética , Limite de Detecção , Nanopartículas Metálicas/química , Coelhos , Urease/química
16.
Med Sci (Paris) ; 35(6-7): 497-500, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31274074

Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Proteína Acessória do Receptor de Interleucina-1/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Animais , Anticorpos Monoclonais/genética , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Caspase 9/genética , Proteínas de Fusão bcr-abl/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes Transgênicos Suicidas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunoterapia Adotiva/efeitos adversos , Proteína Acessória do Receptor de Interleucina-1/genética , Proteína Acessória do Receptor de Interleucina-1/imunologia , Células Matadoras Naturais/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/transplante , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/imunologia
17.
Medicine (Baltimore) ; 98(27): e16273, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277152

RESUMO

BACKGROUND: Although the outcome of patients with gastric cancer (GC) has improved significantly with the recent implementation of annual screening programs. Reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and GC prognosis. Thus, we aim to build an immune-related signature that can estimate prognosis for GC. METHODS: For identification of a prognostic immune-related gene signature (IRGS), gene expression profiles and clinical information of patients with GC were collected from 3 public cohorts, divided into training cohort (n = 300) and 2 independent validation cohorts (n = 277 and 433 respectively). RESULTS: Within 1811 immune genes, a prognostic IRGS consisting of 16 unique genes was constructed which was significantly associated with survival (hazard ratio [HR], 3.9 [2.78-5.47]; P < 1.0 × 10). In the validation cohorts, the IRGS significantly stratified patients into high- vs low-risk groups in terms of prognosis across (HR, 1.84 [1.47-2.30]; P = 6.59 × 10) and within subpopulations with stage I&II disease (HR, 1.96 [1.34-2.89]; P = 4.73 × 10) and was prognostic in univariate and multivariate analyses. Several biological processes, including TGF-ß and EMT signaling pathways, were enriched in the high-risk group. T cells CD4 memory resting and Macrophage M2 were significantly higher in the high-risk risk group compared with the low-risk group. CONCLUSION: In short, we developed a prognostic IRGS for estimating prognosis in GC, including stage I&II disease, providing new insights into the identification of patients with GC with a high risk of mortality.


Assuntos
Biomarcadores Tumorais/imunologia , DNA de Neoplasias/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Transcriptoma/genética , Biomarcadores Tumorais/genética , DNA de Neoplasias/imunologia , Feminino , Humanos , Masculino , Prognóstico , Fatores de Risco , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo
18.
Analyst ; 144(16): 4813-4819, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31281909

RESUMO

In the clinical diagnosis of tumor, the immunological detection of single tumor markers may lead to errors and missed inspection. Therefore, it is necessary to establish an accurate and effective method for the simultaneous detection of multiple tumor markers. Thus, we developed a time-resolved chemiluminescence immunoassay (TRCLIA) to simultaneously detect carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) in human serum. Horseradish peroxidase (HRP) and alkaline phosphatase (ALP) were used as the detection probes to label the monoclonal antibodies of CEA and NSE by strain-promoted azide-alkyne cycloaddition (SPAAC), respectively. Based on a sandwich immunoassay, the targets in the samples were captured by antibodies immobilized on the surface of carboxylate-modified polystyrene microspheres (CPSMS) and sandwiched by other antibodies labeled with HRP and ALP. Since HRP and ALP had different dynamic characteristics, the CEA and NSE signals were recorded at 0.5 s and 20 min, respectively, and cross-interference could be avoided effectively. The whole signal detection processes could be completed in 20 min. The linear ranges of CEA and NSE were 0.1-64 ng mL-1 and 0.05-64 ng mL-1 and the limits of detection were 0.085 ng mL-1 and 0.044 ng mL-1 (S/N = 2), respectively. Also, 45 human serum samples obtained from patients having lung disease were tested by TRCLIA and commercial chemiluminescence enzyme-linked immunoassay (CLEIA) kits with good correlation. The correlation coefficients of CEA and NSE were 0.985 and 0.970, respectively. The results demonstrated a novel, effective, reliable and convenient TRCLIA method for the clinical diagnosis of CEA and NSE. The TRCLIA method has the potential to be an effective clinical tool for the early screening of lung cancer and can be applied in clinical diagnosis.


Assuntos
Antígeno Carcinoembrionário/sangue , Técnicas Imunoenzimáticas/métodos , Fosfopiruvato Hidratase/sangue , Fosfatase Alcalina/química , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/imunologia , Armoracia/enzimologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Antígeno Carcinoembrionário/imunologia , Peroxidase do Rábano Silvestre/química , Humanos , Limite de Detecção , Luminescência , Substâncias Luminescentes/química , Medições Luminescentes/métodos , Luminol/química , Pneumopatias/sangue , Fosfopiruvato Hidratase/imunologia
19.
Talanta ; 204: 248-254, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357289

RESUMO

An ultrasensitive strategy based on sandwich immunoassay coupled with isothermal exponential amplification reaction (IMEXPAR) is proposed for the determination of tumor protein Mucin 1 (MUC1). An immuno-PCR plate was prepared from modification of the primary MUC1-antibody (Ab1) onto the inner-well of the PCR plate. A biotinylated secondary MUC1-antibody tagged with the biotinylated EXPAR primer (P-Ab2) was prepared through biotin-streptavidin reaction. In the presence of target MUC1, sandwich-type combinations were specifically formed in the immuno-PCR plate. With further addition of amplification template, polymerase and nicking enzyme, EXPAR was specifically triggered, producing numerous primer replica in minutes, and greatly enhanced fluorescence of SYBR Green I. The proposed strategy has a good linear relationship with the logarithm of the MUC1 concentration ranging from 3 pM to 3 nM with a limit of detection of 1.63 pM (S/N = 3), which is two orders of magnitude lower than those of other methods. Owing to the specificity of immuno-reaction and EXPAR, the selectivity of the strategy is favorable, even if for the homologous protein. The proposed strategy was further applied for the MUC1 determination in human serum, and a satisfactory recovery range of 98.7%-105.3% was obtained. The strategy can be facilely extended to the ultrasensitive determination of various proteins.


Assuntos
Biomarcadores Tumorais/sangue , Imunoensaio/métodos , Mucina-1/sangue , Técnicas de Amplificação de Ácido Nucleico/métodos , Anticorpos Monoclonais Murinos/imunologia , Sequência de Bases , Biomarcadores Tumorais/imunologia , DNA/química , DNA Polimerase Dirigida por DNA/química , Desoxirribonucleases de Sítio Específico do Tipo II/química , Corantes Fluorescentes/química , Geobacillus stearothermophilus/enzimologia , Humanos , Limite de Detecção , Mucina-1/imunologia , Compostos Orgânicos/química , Espectrometria de Fluorescência/métodos , Thermococcus/enzimologia
20.
Analyst ; 144(13): 4051-4059, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31157328

RESUMO

Rapid, simultaneous, and sensitive quantification of multiplex prostate biomarkers plays an important role in early diagnosis, especially for obese men and patients. Herein, a surface-enhanced Raman scattering (SERS)-based vertical flow assay (VFA) is presented for simultaneous detection of multiplex prostate cancer biomarkers, such as prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) on a single test spot. In practice, Raman dyes (RDs) encoded core-shell SERS nanotags instead of conventional gold colloids used in the colorimetric assay are employed in the sensing membrane of SERS based VFAs for multiplex protein detection. Because of the enhanced Raman signal of the core-shell nanostructure and the high surface area to volume ratio (SVR) of the porous sensing membrane, this proposed biosensor shows a wide linear dynamic range (LDR) with detection limits of 0.37, 0.43, and 0.26 pg mL-1 for PSA, CEA, and AFP, respectively, suggesting that this approach can be a good candidate in point of care testing (POCT) for rapid and sensitive biomarker detection and has a huge potential in multiplex analysis and cancer diagnosis.


Assuntos
Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/métodos , Antígeno Carcinoembrionário/sangue , Calicreínas/sangue , Nanopartículas Metálicas/química , Antígeno Prostático Específico/sangue , alfa-Fetoproteínas/análise , Animais , Anticorpos/imunologia , Biomarcadores Tumorais/imunologia , Antígeno Carcinoembrionário/imunologia , Colódio/química , Corantes/química , Cabras , Ouro/química , Humanos , Imunoensaio/métodos , Calicreínas/imunologia , Limite de Detecção , Masculino , Oxazinas/química , Porosidade , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/sangue , Prata/química , Análise Espectral Raman/métodos , Compostos de Sulfidrila/química , alfa-Fetoproteínas/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA