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The widely known vocabulary gap between health consumers and healthcare professionals hinders information seeking and health dialogue of consumers on end-user health applications. The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), which contains health-related terms used by lay consumers, has been created to bridge such a gap. Specifically, the OAC CHV facilitates consumers' health information retrieval by enabling consumer-facing health applications to translate between professional language and consumer friendly language. To keep up with the constantly evolving medical knowledge and language use, new terms need to be identified and added to the OAC CHV. User-generated content on social media, including social question and answer (social Q&A) sites, afford us an enormous opportunity in mining consumer health terms. Existing methods of identifying new consumer terms from text typically use ad-hoc lexical syntactic patterns and human review. Our study extends an existing method by extracting n-grams from a social Q&A textual corpus and representing them with a rich set of contextual and syntactic features. Using K-means clustering, our method, simiTerm, was able to identify terms that are both contextually and syntactically similar to the existing OAC CHV terms. We tested our method on social Q&A corpora on two disease domains: diabetes and cancer. Our method outperformed three baseline ranking methods. A post-hoc qualitative evaluation by human experts further validated that our method can effectively identify meaningful new consumer terms on social Q&A.
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Información de Salud al Consumidor , Minería de Datos , Vocabulario Controlado , Humanos , Internet , Medios de Comunicación Sociales , Traducción , VocabularioRESUMEN
Previous literature has suggested that examining Twitter messages can be productive for studying how the public shares and spreads health information on social media. Preexposure prophylaxis (PrEP) is a promising approach to HIV prevention, yet there are many issues that may influence its effective implementation. This study examined social representations of PrEP on Twitter. One thousand four hundred and thirty-five Tweets were collected and 774 English Tweets were content-analyzed to explore propagation of various issues around daily oral PrEP, as well as characteristics of the sources of those Tweets. We also examined how Twitter message content influenced information propagation. Our findings revealed that PrEP-related information on Twitter covered a wide range of issues, and individual users constituted the majority of the Tweet creators among all the sources, including news media, nonprofit and academic groups, and commercial entities. Using Poisson regression, we also found that a Tweet's affective tone was a significant predictor of message propagation frequency. Implications for health practitioners are discussed.
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Infecciones por VIH/prevención & control , Difusión de la Información/métodos , Profilaxis Pre-Exposición/estadística & datos numéricos , Medios de Comunicación Sociales/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , HumanosRESUMEN
UNLABELLED: Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of <1.0 × 10(-7) , 2.76 × 10(-5) , 5.08 × 10(-5) , 2.78 × 10(-4) and odds ratios (ORs) of 2.45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0 × 10(-16) . As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). CONCLUSION: We identified four missense mutations associated with CHB, our results providing evidence for rare inborn genetic defects that contribute to increased host susceptibility to CHB.
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Predisposición Genética a la Enfermedad/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/genética , Proteínas de la Membrana/metabolismo , Alelos , Estudios de Casos y Controles , Complemento C2/química , Complemento C2/genética , Exoma , Expresión Génica , Genotipo , Células Hep G2 , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/metabolismo , Hepatocitos/metabolismo , Humanos , Interferón-alfa/química , Interferón-alfa/genética , Hígado/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas Mitocondriales/química , Proteínas Mitocondriales/genética , Modelos Estructurales , Mutación Missense , Oportunidad Relativa , Análisis de Secuencia de ADNRESUMEN
BACKGROUND AND OBJECTIVES: CD44 and CD133 have been reported as putative stem cell markers. However, the clinicopathologic significance of CD44 and CD133 expression in patients with gastric carcinoma (GC) has not been clearly elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the CD44 and CD133 expression in gastric carcinomas and normal mucosal tissues. Receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots, and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed CD44 and CD133 were observed in 27/152 (17.7%) and 64/152 (42.1%) of GCs and in 4/60 (6.7%) and 15/60 (25.0%) normal gastric mucosal tissues, respectively (P < 0.05, Fisher's exact test). High expression of CD44 was significantly correlated with tumor poorer differentiation, presence of distant metastasis, advanced TNM stage, and tumor relapse; and high expression of CD133 was positively associated with tumor invasion depth, presence of distant metastasis and advanced TNM stage. More importantly, high-expressed CD44 and CD133 were both associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our study introduces high expression of CD44 and CD133 as adverse independent prognostic factors in GC patients. The combined CD44 and CD133 expression may become a useful tool for identifying patients with different clinical outcomes.
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Antígenos CD/análisis , Biomarcadores de Tumor/análisis , Glicoproteínas/análisis , Receptores de Hialuranos/análisis , Células Madre Neoplásicas , Péptidos/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , Antígeno AC133 , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Fenotipo , Pronóstico , Curva ROCRESUMEN
Particle shape is a significant feature of irregular particles. The interferometric particle imaging (IPI) technique has been introduced to retrieve submillimetric irregular rough particle shapes, while inevitable experimental noises hinder the convergence of two-dimensional (2D) particle shapes from single speckle patterns. In this work, a hybrid input-output algorithm with shrink-wrap support and oversampling smoothness constraints is utilized to suppress the Poisson noise in IPI measurement and recover accurate 2D shapes of particles. Our method is tested in numerical simulations on ice crystal shapes and actual IPI measurements on four different types of irregular, rough particles. The shape similarity of the reconstructed 2D shape has reached an average Jaccard Index score of 0.927, and the relative deviation of the reconstructed size is within 7% for all 60 tested irregular particles at the maximum shot noise level of 7.4%. Furthermore, our method has obviously reduced the uncertainty in the 3D shape reconstruction of irregular, rough particles.
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Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Complejo CD3/análisis , Antígenos CD4/análisis , Antígenos CD8/análisis , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/uso terapéutico , Femenino , Factores de Transcripción Forkhead/análisis , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC. METHODS: NPC tissue microarrays (TMAs) were constructed from Sun Yat-sen University Cancer Center (SYSUCC), another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs) induced by Bmi-1 (NPEC2 Bmi-1). The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. RESULTS: The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001). SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium. In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001) and WHO histological classification (P = 0.023). NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P < 0.001), especially patients with advanced stage disease (log-rank, P < 0.001). Multivariate analysis suggested that the level of SPARC expression was an independent prognostic indicator for the overall survival of patients with NPC (P < 0.001). CONCLUSIONS: SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.
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Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , Osteonectina/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma , Línea Celular Tumoral , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Metástasis de la Neoplasia , Osteonectina/genética , Pronóstico , Modelos de Riesgos Proporcionales , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The clinicopathological significance of Beclin 1 expression in patients with gastric carcinoma (GC) has not been yet elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the Beclin 1 expression in GCs and normal mucosal tissues. Receiver operating characteristic curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed Beclin 1 was observed in 90/155 (58.1%) of GCs, in 24/60 (40.0%) adjacent mucosal tissues and in 13/30 (43.3%) of normal gastric mucosa tissues (P = 0.036). Decreased expression of Beclin 1 in cancer cells was significantly correlated with poor differentiation, nodal and distant metastasis, advanced TNM stage, and tumor relapse. More importantly, Decreased expression of Beclin 1 was associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our findings provide a basis for the concept that decreased expression of Beclin 1 in GC may be important in the acquisition of a metastatic phenotype, suggesting that decreased Beclin 1 expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with GC.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Beclina-1 , Carcinoma/metabolismo , Carcinoma/mortalidad , Carcinoma/patología , Estudios de Casos y Controles , Mucosa Gástrica/metabolismo , Genes Supresores de Tumor , Humanos , Inmunohistoquímica , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Neoplasias Gástricas/patología , Adulto JovenRESUMEN
It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression dynamics of H3K27me3 and its clinicopathological/prognostic significance in hepatocellular carcinoma (HCC) are unclear. In this study, immunohistochemical analysis (IHC) was used to examine protein expression of H3K27me3 in HCC tissues from two independent cohorts and corresponding nontumorous hepatocellular tissues by tissue microarray. The optimal cutpoint of H3K27me3 expression was assessed by the X-tile program. Our results showed that the cutpoint for high expression of H3K27me3 in HCCs was determined when more than 70% of the tumor cells showed positive staining. High expression of H3K27me3 was observed in 134 of 212 (63.2%) and 76 of 126 (60.4%) of HCCs in the testing and validation cohorts, respectively. Correlation analysis demonstrated that high expression of H3K27me3 in HCCs was significantly correlated with large tumor size, multiplicity, poor differentiation, advanced clinical stage and vascular invasion (P < 0.05). In addition, high expression of H3K27me3 in HCC patients was associated closely with shortened survival time, independent of serum α-fetoprotein levels, tumor size and multiplicity, clinical stage, vascular invasion and relapse as evidenced by univariate and multivariate analysis in both cohorts (P < 0.05). In different subsets of HCC patients, H3K27me3 expression was also a prognostic indicator in patients with stage II tumors (P < 0.05). Thus, these findings provide evidence that a high expression of H3K27me3, as detected by IHC, correlates closely with vascular invasion of HCCs and is an independent molecular marker for poor prognosis in patients with HCC.
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Biomarcadores de Tumor , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Histonas/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteína Potenciadora del Homólogo Zeste 2 , Femenino , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Masculino , Análisis Multivariante , Complejo Represivo Polycomb 2 , Pronóstico , Análisis de Supervivencia , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Mast cells promote the progression of experimental tumors and might be a valuable therapeutic target. However, the relevant clinical evidence is still controversial. This study analyzed the relationship between the distribution of mast cells and the survival of patients with colon cancer to study whether mast cells contribute to tumor progression. MATERIALS AND METHODS: Ninety-three cases of pathologically confirmed primary cancer tissues matched with adjacent normal mucosa, metastases of regional-draining lymph nodes and regional-draining lymph nodes without metastases were collected from stage IIIB colon carcinoma patients between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. Tryptase-positive mast cells were counted. The relationships of the distribution of mast cells with clinicopathologic parameters and 5-year survival were analyzed. RESULTS: Although the mast cell count in the mucosa adjacent to the primary colon cancer was significantly higher than that in the stroma of the primary colon cancer, no difference in mast cell counts was observed between the stroma in lymph node metastasis and the lymph tissue adjacent to the metastasis. Additionally, the mast cell count in the regional-draining lymph node without the invasion of cancer cells was significantly higher than that in the stroma of lymph node metastasis and adjacent lymph tissue. However, none of those mast cell counts was related to 5-year survival. CONCLUSION: Although mast cell count varied with location, none of the mast cell counts was related to 5-year survival, suggesting that mast cells do not contribute to the progression of stage IIIB colon cancer.
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Neoplasias del Colon/patología , Mastocitos/patología , Anciano , Recuento de Células , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
OBJECTIVE: Mast cells (MC) reside in the mucosa of the digestive tract as the first line against bacteria and toxins. Clinical evidence has implied that the infiltration of mast cells in colorectal cancers is related to malignant phenotypes and a poor prognosis. This study compared the role of mast cells in adjacent normal colon mucosa and in the invasive margin during the progression of colon cancer. METHODS: Specimens were obtained from 39 patients with colon adenomas and 155 patients with colon cancers treated at the Sun Yat-sen University Cancer Center between January 1999 and July 2004. The density of mast cells was scored by an immunohistochemical assay. The pattern of mast cell distribution and its relationship with clinicopathologic parameters and 5-year survival were analyzed. RESULTS: The majority of mast cells were located in the adjacent normal colon mucosa, followed by the invasive margin and least in the cancer stroma. Mast cell count in adjacent normal colon mucosa (MCC(adjacent)) was associated with pathologic classification, distant metastases and hepatic metastases, although it was not a prognostic factor. In contrast, mast cell count in the invasive margin (MCC(invasive)) was associated with neither the clinicopathlogic parameters nor overall survival. CONCLUSION: Mast cells in the adjacent normal colon mucosa were related to the progression of colon cancer, suggesting that mast cells might modulate tumor progression via a long-distance mechanism.
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AIMS: Metaplastic breast cancer (MBC) comprises a heterogeneous group of tumors, of which MBC with osseous differentiation (MBC-OD) is extremely rare that only few cases have been reported. This study aimed to present the clinicopathologic and molecular features of MBC-OD. METHODS: We collected 6 cases of MBC-OD from five different centers and described its clinicopathologic and molecular characteristics based on the next-generation sequencing. Another 11 cases from the literature were also reviewed to better characterize the tumor. RESULTS: The tumor primarily showed an osteosarcoma-like appearance, which composed of high cellularity with spindle cells and osteoblast-like cells producing coarse lace-like neoplastic bone (4/6) or osteoid matrix (6/6). 55 somatic mutations including 39 missenses (70.9%), 9 frameshifts (16.4%), 3 splice sites (5.5%), 3 in-frame InDels (5.5%) and 1 nonsense (1.8%) were identified. TP53 was the most frequently mutated genes (5/6, 83.3%), followed by RB1 (3/6, 50.0%), BCOR (2/6, 33.3%), MED12 (2/6, 33.3%), PIK3CA (2/6, 33.3%), and TET2 (2/6, 33.3%). Genetic alterations suggesting therapies with clinical benefit, including mTOR inhibitors, tyrosine kinase inhibitors (TKI), and poly-ADP ribose polymerase inhibitor (PARPi), were observed in five cases. The median follow-up was 21 months (range, 3-80 months). Local recurrence was observed in two cases and three patients displayed distant metastasis. Two patients died of the disease at 3 months and 7 months, respectively. CONCLUSIONS: Based on this series, MBC-OD is a highly aggressive breast tumor with osteosarcoma-like morphology and a high incidence of recurrent disease showing specific genetic profiles.
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Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias de la Mama/genética , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , MutaciónRESUMEN
BACKGROUND: Although an abundance of evidence has indicated that tumor-associated macrophages (TAMs) are associated with a favorable prognosis in patients with colon cancer, it is still unknown how TAMs exert a protective effect. This study examined whether TAMs are involved in hepatic metastasis of colon cancer. MATERIALS AND METHODS: One hundred and sixty cases of pathologically-confirmed specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. The density of macrophages in the invasive front (CD68TFHotspot) was scored with an immunohistochemical assay. The relationship between the CD68TFHotspot and the clinicopathologic parameters, the potential of hepatic metastasis, and the 5-year survival rate were analyzed. RESULTS: TAMs were associated with the incidence of hepatic metastasis and the 5-year survival rate in patients with colon cancers. Both univariate and multivariate analyses revealed that the CD68TFHotspot was independently prognostic of survival. A higher 5-year survival rate among patients with stage IIIB after radical resection occurred in patients with a higher macrophage infiltration in the invasive front (81.0%) than in those with a lower macrophage infiltration (48.6%). Most importantly, the CD68TFHotspot was associated with both the potential of hepatic metastasis and the interval between colon resection and the occurrence of hepatic metastasis. CONCLUSION: This study showed evidence that TAMs infiltrated in the invasive front are associated with improvement in both hepatic metastasis and overall survival in colon cancer, implying that TAMs have protective potential in colon cancers and might serve as a novel therapeutic target.
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Neoplasias del Colon , Neoplasias Hepáticas , Macrófagos/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Macrófagos/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de SupervivenciaRESUMEN
BACKGROUND: The oncoprotein Epstain-Barr Virus (EBV)-encoded latent membrane protein1 (LMP1) modulates the pathological effects of the NF-kappaB, AP-1 and JAK/STAT pathways in nasopharyngeal carcinoma (NPC). METHODS: Microarray analysis was performed on the NPC cell line HONE1 stably transfected with a LMP1-expression plasmid or an empty vector. Based on assigned pathways analyzed using the KEGG database, the mTOR signaling pathway was selected for verification by quantitative RT-PCR. Western blot, RNA interference and immunofluorescence were used to determine the relationship between LMP1 and mTOR signing pathway genes, and their clinical significance to NPC. RESULTS: Our studies revealed that overexpression of LMP1 upregulated the mTOR signaling pathway, possibly through phosphorylation of AKT/mTOR/P70S6K/4EBP1 in the NPC cell lines HONE1 and 6-10B. Knockdown of LMP1 reduced expression of p-mTOR and p-4EBP1 in EBV-positive NPC cell line C666-1. In addition, LMP1 expression closely correlated with expression of p-mTOR, p-P70S6K and p-4EBP1 in NPC tumors. Expression of p-P70S6K, p-4EBP1 and LMP1, but not p-mTOR, significantly correlated with overall survival of NPC patients. However, only LMP1 was an independent prognostic factor. CONCLUSIONS: These results suggest that the mTOR signaling pathway is regulated by LMP1 expression in NPC. LMP1 and the genes in the mTOR pathway such as p-P70S6K and p-4EBP1 may be potential prognostic biomarkers.
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Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/virología , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/genética , Proteínas de la Matriz Viral/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Modelos de Riesgos Proporcionales , Serina-Treonina Quinasas TOR , Adulto JovenRESUMEN
Fundamental studies have suggested that matrix metalloproteinases-7 (MMP-7) expression is associated with chemoresistance and constitutes a prognostic factor in several solid tumors. The present study assessed the prognostic and predictive value of MMP-7 in tumors of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. Immunohistochemistry was performed to evaluate the expression of MMP-7, apoptosis-related proteins Bcl-2, Bax, Fas and FasL and the Ki-67 proliferation marker. The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) method was performed to investigate tumor apoptosis. Ninety carcinomas (56.6%) were identified as high expression of MMP-7. Overexpression of MMP-7 was more frequent in adenocarcinomas than in squamous cell carcinomas (P = 0.032). The expression of MMP-7 was positively related with Ki-67 index and Bcl-2, but not apoptosis index. MMP-7 status was correlated inversely with response to chemotherapy in overall patients (response rates, 20.0% and 35.8%, for patients with high-MMP-7 and low-MMP-7 tumors, respectively, P = 0.036), especially in adenocarcinoma (P = 0.021), but not in patients with squamous cell carcinomas (P = 0.373). The overall survival was significantly lower in NSCLC patients with high MMP-7 than in those with low MMP-7 (P < 0.001). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 5.49 P = 0.001). These findings suggest that the expression level of MMP-7 in tumor cells is predictive of response to chemotherapy and outcome in patients with advanced NSCLC receiving platinum-based chemotherapy.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Metaloproteinasa 7 de la Matriz/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Masculino , Metaloproteinasa 7 de la Matriz/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China. The China 1992 TNM staging system has been widely used for prognosis prediction of NPC patients in China. Although NPC patients can be classified according to their clinical stage in this system, their prognosis may vary significantly. METHOD: 280 cases of NPC with clinical follow-up data were collected and expressions of survivin and VEGF in tumor tissues were investigated by immunohistochemistry (IHC). Apoptosis index (AI) in 100 cases of NPC was detected by the TUNEL method. RESULTS: Expression of survivin and VEGF were significantly associated with TNM stage, T-stage and metastasis of NPC. The patients with survivin and VEGF over-expression presented lower 5-year survival rate, as compared to those of low-expression (42.32% vs. 70.54%, 40.1% vs. 67.8%, respectively, P < 0.05), especially in advanced stage patients (36.51% vs. 73.41%, 35.03% vs. 65.22%, respectively, P < 0.05). The 5-year survival rate in NPC patients with survivin and VEGF dual over-expression was significantly lower than that of patients with dual low-expression (18.22% vs. 73.54%, respectively; P = 0.0003). Multivariate analysis indicated that both survivin and VEGF over-expression in NPC tumor tissues were strong independent factors of poor prognosis in NPC patients. The mean AI in the 39 survivin low-expression cases was 144.7 +/- 39.9, which was significantly higher than that in 61 survivin over-expression cases (111.6 +/- 39.8) (T test, P < 0.05). CONCLUSION: Survivin and VEGF over-expression are independent prognostic factors for the patients with NPC. These results also suggest that tumor survivin and VEGF expressions are valuable prognostic markers for prognosis prediction in NPC patients.
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Carcinoma/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/fisiología , Carcinoma/diagnóstico , Carcinoma/mortalidad , Carcinoma/patología , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis , Masculino , Proteínas Asociadas a Microtúbulos/biosíntesis , Persona de Mediana Edad , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Proteínas de Neoplasias/biosíntesis , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Survivin , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
While the senior population has been increasingly engaged with reading on mobile technologies, research that specifically documents the impact of technologies on reading for this age group has still been lacking. The present study investigated how different reading media (screen versus paper) might result in different reading outcomes among older adults due to both cognitive and psychological factors. Using a laboratory experiment with 81participants aged 57 to 85, our results supported past research and showed the influence of cognitive map formation on readers' feelings of fatigue. We contributed empirical evidence to the contention that reading on a screen could match that of reading from paper if the presentation of the text on screen resemble that of the print. Our findings also suggested that individual levels of technophobia was an important barrier to older adults' effective use of mobile technologies for reading. In the post hoc analyses, we further showed that technophobia was correlated with technology experience, certain personality traits, and age. The present study highlights the importance of providing tailored support that helps older adults overcome psychological obstacles in using technologies.
RESUMEN
The present study was aimed to determine twist expression in nasopharyngeal carcinoma (NPC) and to investigate the clinicopathological significance in the progress of NPC. Semiquantitative RT-PCR and Western blotting were carried out to investigate the expression of Twist in NPC cell lines and normal nasopharyngeal epithelial cell line, which showed that both Twist mRNA and protein were up-regulated in the tumor cells in comparison with the normal cells. We then examined Twist mRNA expression in non-cancerous nasopharyngeal mucosa (10 cases) and NPC (95 cases) using in situ hybridization. The results showed that Twist was overexpressed in 59 of 95 (62.1%) NPC samples. In contrast, there was no obvious expression of Twist mRNA in non-cancerous tissues. In addition, another 75 NPC samples were analyzed by immunohistochemistry, and 33 of the 75 samples were shown to be positive for Twist protein. Both Twist mRNA expression and Twist protein expression were positively associated with lymph-node metastasis and distant metastasis. Furthermore, expression of Twist protein was correlated with the NPC prognosis. Patients with NPC who were Twist protein-positive had a worse 5-year survival rate. These findings demonstrate that the Twist may play an important role in the invasion and metastasis of NPC. Twist protein is valuable marker for assessing the prognosis of NPC.
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Carcinoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Nasofaríngeas/metabolismo , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/fisiología , Proteína 1 Relacionada con Twist/biosíntesis , Proteína 1 Relacionada con Twist/fisiología , Biomarcadores de Tumor , Línea Celular Tumoral , Proliferación Celular , Células Epiteliales/metabolismo , Humanos , Inmunohistoquímica , Metástasis Linfática , Metástasis de la Neoplasia , Pronóstico , ARN Mensajero/metabolismo , Factores de TiempoRESUMEN
OBJECTIVE: To detect the expression of EGFR and p-ERK in nasopharyngeal carcinoma (NPC) and investigate their clinical significance. METHODS: Immunohistochemistry LSAB method was adopted to detect the expression of EGFR and p-ERK. Statistical analysis was performed using SPSS statistical software package (10.0) to correlate their expression with clinical characteristics and prognosis. RESULTS: Positive staining for EGFR was observed in 39 of 55 cases (70.9%). The EGFR expression was correlated with clinical stage and gender. EGFR expression was correlated with poorer overall survival (OS) and shorter time to progression (TTP). Positive staining for p-ERK was observed in 29 of 55 cases (52.7%). There was a statistically significant association between positive p-ERK expression and advanced clinical stage. Positive p-ERK expression was correlated with poorer OS, disease-free survival (DFS) and TTP. EGFR expression was correlated with the expression of p-ERK. On multivariate analysis, age over 50 years was an independent poor prognostic factor for NPC. Both EGFR and p-ERK were not independent prognostic factors for NPC. CONCLUSION: Expressions of EGFR and p-ERK are detected in NPC. Their abnormally high expression signifies poor prognosis in NPC patients.
Asunto(s)
Receptores ErbB/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Factores de Edad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Factores Sexuales , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Through comparison of HER2/neu oncogene detected by chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) in breast cancer, to explore the effect of CISH on detecting gene amplification of HER2. METHODS: Selected formalin-fixed paraffin-embedded breast samples whose pathological types were infiltrating ductal carcinomas (255 retrospective samples, 271 prospective samples), and these samples were detected by IHC and CISH. RESULTS: (1) In the retrospective study, CISH identified gene amplification in 91.6% of IHC score 3+ tumors (120/131) and in 56.5% of IHC score 2+ tumors (39/69), thus the concordant ratio between IHC and CISH was 81.2% (207/255). The two results showed significant correlation (P<0.01). (2) In the prospective study, the ratio of HER2 protein over expression detected by IHC was 31.7%, the ratio of HER2 gene amplification detected by CISH was 27.3%. CISH identified gene amplification in 91.4% of IHC score 3+ tumors (53/58) and in 46.4% of IHC score 2+ tumors (13/28), Concordant ratio between IHC and CISH was 89.7% (243/271). Two results showed significant correlation (P<0.01). (3) Paired CISH/FISH results were concordant in 14 of 15 cases. The remaining case was detected by FISH, but showed no HER2 gene amplification by CISH. (4) The gene amplification by CISH had a significantly reverse correlation with ER and PR expression (P<0.01). CONCLUSIONS: The results of HER2 gene amplification detected by CISH have high concordance with the results detectd by IHC and FISH. CISH is a novel technique for detecting HER2 gene amplification.