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Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.
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Progresión de la Enfermedad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteogenómica , Fumar/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinógenos/toxicidad , Estudios de Cohortes , Citosina Desaminasa/metabolismo , Asia Oriental , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Metaloproteinasas de la Matriz/metabolismo , Mutación/genética , Análisis de Componente PrincipalRESUMEN
BACKGROUNDS: Preoperative noninvasive tools to predict pretreatment lymph node metastasis (PLNM) status accurately for esophagogastric junction adenocarcinoma (EJA) are few. Thus, the authors aimed to construct a nomogram for predicting PLNM in curatively resected EJA. METHODS: This study enrolled 638 EJA patients who received curative surgery resection and divided them randomly (7:3) into training and validation groups. For nomogram construction, 26 candidate parameters involving 21 preoperative clinical laboratory blood nutrition-related indicators, computed tomography (CT)-reported tumor size, CT-reported PLNM, gender, age, and body mass index were screened. RESULTS: In the training group, Lasso regression included nine nutrition-related blood indicators in the PLNM-prediction nomogram. The PLNM prediction nomogram yielded an area under the receiver operating characteristic (ROC) curve of 0.741 (95 % confidence interval [CI], 0.697-0.781), which was better than that of the CT-reported PLNM (0.635; 95% CI 0.588-0.680; p < 0.0001). Application of the nomogram in the validation cohort still gave good discrimination (0.725 [95% CI 0.658-0.785] vs 0.634 [95% CI 0.563-0.700]; p = 0.0042). Good calibration and a net benefit were observed in both groups. CONCLUSIONS: This study presented a nomogram incorporating preoperative nutrition-related blood indicators and CT imaging features that might be used as a convenient tool to facilitate the preoperative individualized prediction of PLNM for patients with curatively resected EJA.
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Adenocarcinoma , Nomogramas , Humanos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Unión Esofagogástrica/diagnóstico por imagen , Unión Esofagogástrica/cirugía , Metástasis Linfática , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Intercellular communications are important for maintaining normal physiological processes. An important intercellular communication is mediated by the exchange of membrane-enclosed extracellular vesicles. Among various vesicles, exosomes can be detected in a wide variety of biological systems, but the regulation and biological implication of exosome secretion/uptake remains largely unclear. METHODS: Cellular retinoic acid (RA) binding protein 1 (Crabp1) knockout (CKO) mice were used for in vivo studies. Extracellular exosomes were monitored in CKO mice and relevant cell cultures including embryonic stem cell (CJ7), macrophage (Raw 264.7) and hippocampal cell (HT22) using Western blot and flow cytometry. Receptor Interacting Protein 140 (RIP140) was depleted by Crispr/Cas9-mediated gene editing. Anti-inflammatory maker was analyzed using qRT-PCR. Clinical relevance was accessed by mining multiple clinical datasets. RESULTS: This study uncovers Crabp1 as a negative regulator of exosome secretion from neurons. Specifically, RIP140, a pro-inflammatory regulator, can be transferred from neurons, via Crabp1-regulated exosome secretion, into macrophages to promote their inflammatory polarization. Consistently, CKO mice, defected in the negative control of exosome secretion, have significantly elevated RIP140-containing exosomes in their blood and cerebrospinal fluid, and exhibit an increased vulnerability to systemic inflammation. Clinical relevance of this pathway is supported by patients' data of multiple inflammatory diseases. Further, the action of Crabp1 in regulating exosome secretion involves its ligand and is mediated by its downstream target, the MAPK signaling pathway. CONCLUSIONS: This study presents the first evidence for the regulation of exosome secretion, which mediates intercellular communication, by RA-Crabp1 signaling. This novel mechanism can contribute to the control of systemic inflammation by transferring an inflammatory regulator, RIP140, between cells. This represents a new mechanism of vitamin A action that can modulate the homeostasis of system-wide innate immunity without involving gene regulation. Video Abstract.
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Exosomas/genética , Inflamación/genética , Neuronas/metabolismo , Proteína de Interacción con Receptores Nucleares 1/genética , Receptores de Ácido Retinoico/genética , Animales , Sistemas CRISPR-Cas , Comunicación Celular/genética , Modelos Animales de Enfermedad , Vesículas Extracelulares/genética , Homeostasis/genética , Humanos , Inflamación/patología , Ratones , Ratones Noqueados , Neuronas/patología , Células RAW 264.7 , Transducción de Señal/genética , Tretinoina/metabolismoRESUMEN
BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a prevalent malignant disease that is characterized by high rates of metastasis and postoperative recurrence. The aim of this study was to establish a nomogram to predict the outcome of OTSCC patients after surgery. METHODS: We retrospectively analyzed 169 OTSCC patients who underwent treatments in the Cancer Hospital of Shantou University Medical College from 2008 to 2019. The Cox regression analysis was performed to determine the independent prognostic factors associated with patient's overall survival (OS). A nomogram based on these prognostic factors was established and internally validated using a bootstrap resampling method. RESULTS: Multivariate Cox regression analysis revealed the independent prognostic factors for OS were TNM stage, age, lymphocyte-to-monocyte ratio and immunoglobulin G, all of which were identified to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of TNM stage (292.222 vs. 305.480; 298.444 vs. 307.036, respectively), indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected of concordance index (C-index) of nomogram was 0.784 (95% CI 0.708-0.860), which was higher than that of TNM stage (0.685, 95% CI 0.603-0.767, P = 0.017). The results of time-dependent C-index for OS also showed that the nomogram had a better discriminative ability than that of TNM stage. The calibration curves of the nomogram showed good consistency between the probabilities and observed values. The decision curve analysis also revealed the potential clinical usefulness of the nomogram. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (P < 0.0001). CONCLUSIONS: The nomogram based on clinical characteristics and serological inflammation markers might be useful for outcome prediction of OTSCC patient.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Teorema de Bayes , Carcinoma de Células Escamosas/cirugía , Humanos , Inflamación , Nomogramas , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Lengua/cirugíaRESUMEN
OBJECTIVES: Obesity, an emerging global health issue, involves numerous factors; understanding its underlying mechanisms for prevention and therapeutics is urgently needed. Cellular retinoic acid binding protein 1 (Crabp1) knockout (CKO) mice exhibit an obese phenotype under normal diet (ND) feedings, which prompted us to propose that Crabp1 could play a role in modulating adipose tissue development/homeostasis. Studies were designed to elucidate the underlying mechanism of Crabp1's action in reducing obesity. SUBJECTS/METHODS: In animal studies, 6 weeks old male wild type and CKO mice were fed with ND or high-fat diet (HFD) for 10 weeks. Body weight and food intake were regularly monitored. Glucose tolerance test and biological parameters of plasma (glucose and insulin levels) were measured after 10 weeks of ND vs. HFD feedings. Visceral adipose tissues were collected for histological and molecular analyses to determine affected signaling pathways. In cell culture studies, the 3T3L1 adipocyte differentiation model was used to examine and validate relevant signaling pathways. RESULTS: CKO mice, compared to WT mice, gained more body weight, exhibited more elevated fasting plasma glucose levels, and developed more severe impaired glucose tolerance under both ND and HFD. Histological examination revealed readily increased adipocyte hypertrophy and adipose tissue inflammation under HFD feedings. In 3T3L1 adipocytes, Crabp1 silencing enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, accompanied by elevated markers and signaling pathways of lipid accumulation and adipocyte hypertrophy. CONCLUSIONS: This study identifies Crabp1's physiological role against the development of obesity. The protective function of CRABP1 is likely attributed to its classically proposed (canonical) activity as a trap for RA, which will reduce RA availability, thereby dampening RA-stimulated ERK1/2 activation and adipocyte hypertrophy. The results suggest Crabp1 as a potentially new therapeutic target in managing obesity and metabolic diseases.
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Adipocitos , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Receptores de Ácido Retinoico , Células 3T3-L1 , Adipocitos/metabolismo , Adipocitos/patología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Hipertrofia/metabolismo , Hipertrofia/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/etiología , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismoRESUMEN
Cellular retinoic acid-binding protein 1 (CRABP1) is highly expressed in motor neurons. Degenerated motor neuron-like MN1 cells are engineered by introducing SODG93A or AR-65Q to model degenerated amyotrophic lateral sclerosis (ALS) or spinal bulbar muscular atrophy neurons. Retinoic acid (RA)/sonic hedgehog (Shh)-induced embryonic stem cells differentiation into motor neurons are employed to study up-regulation of Crabp1 by Shh. In SODG93A or AR-65Q MN1 neurons, CRABP1 level is reduced, revealing a correlation of motor neuron degeneration with Crabp1 down-regulation. Up-regulation of Crabp1 by Shh is mediated by glioma-associated oncogene homolog 1 (Gli1) that binds the Gli target sequence in Crabp1's neuron-specific regulatory region upstream of minimal promoter. Gli1 binding triggers chromatin juxtaposition with minimal promoter, activating transcription. Motor neuron differentiation and Crabp1 up-regulation are both inhibited by blunting Shh with Gli inhibitor GANT61. Expression data mining of ALS and spinal muscular atrophy (SMA) motor neurons shows reduced CRABP1, coincided with reduction in Shh-Gli1 signaling components. This study reports motor neuron degeneration correlated with down-regulation in Crabp1 and Shh-Gli signaling. Shh-Gli up-regulation of Crabp1 involves specific chromatin remodeling. The physiological and pathological implication of this regulatory pathway in motor neuron degeneration is supported by gene expression data of ALS and SMA patients.
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Proteínas Hedgehog/metabolismo , Neuronas Motoras/citología , Receptores de Ácido Retinoico/genética , Proteína con Dedos de Zinc GLI1/metabolismo , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Minería de Datos , Modelos Animales de Enfermedad , Células Madre Embrionarias/citología , Regulación de la Expresión Génica , Proteínas Hedgehog/genética , Humanos , Ratones Endogámicos C57BL , Neuronas Motoras/patología , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patología , Regiones Promotoras Genéticas , Piridinas/farmacología , Pirimidinas/farmacología , Receptores de Ácido Retinoico/metabolismo , Transducción de Señal , Proteína con Dedos de Zinc GLI1/antagonistas & inhibidores , Proteína con Dedos de Zinc GLI1/genéticaRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
All-trans Retinoic acid (RA) and its derivatives are potent therapeutics for immunological functions including wound repair. However, the molecular mechanism of RA modulation in innate immunity is poorly understood, especially in macrophages. We found that topical application of RA significantly improves wound healing and that RA and IL-4 synergistically activate Arg1, a critical gene for tissue repair, in M2 polarized macrophages. This involves feed forward regulation of Raldh2, a rate-limiting enzyme for RA biosynthesis, and requires Med25 to coordinate RAR, STAT6 and chromatin remodeler, Brg1 to remodel the +1 nucleosome of Arg1 for transcription initiation. By recruiting elongation factor TFIIS, Med25 also facilitates transcriptional initiation-elongation coupling. This study uncovers synergistic activation of Arg1 by RA and IL-4 in M2 macrophages that involves feed forward regulation of RA synthesis and dual functions of Med25 in nucleosome remodeling and transcription initiation-elongation coupling that underlies robust modulatory activity of RA in innate immunity.
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Arginasa/genética , Ensamble y Desensamble de Cromatina/genética , Interleucina-4/farmacología , Elongación de la Transcripción Genética/efectos de los fármacos , Iniciación de la Transcripción Genética/efectos de los fármacos , Activación Transcripcional/genética , Tretinoina/farmacología , Animales , Arginasa/metabolismo , Inflamación/patología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Complejo Mediador/metabolismo , Ratones , Ratones Endogámicos C57BL , Nucleosomas/efectos de los fármacos , Nucleosomas/metabolismo , Células RAW 264.7 , Receptores de Ácido Retinoico/metabolismo , Factor de Transcripción STAT6/metabolismo , Activación Transcripcional/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Atherosclerosis, a syndrome with abnormal arterial walls, is one of the major causes that lead to the development of various cardiovascular diseases. The key initiator of atherosclerosis is cholesterol accumulation. The uncontrolled cholesterol deposition, mainly involving low-density lipoprotein (LDL), causes atheroma plaque formation, which initiates chronic inflammation due to the recruitment of inflammatory cells such as macrophages. Macrophages scavenge excess peripheral cholesterol and transport intracellular cholesterol to high-density lipoprotein (HDL) for excretion or storage. Cholesterol-laden macrophage-derived foam cell formation is the main cause of atherogenesis. It is critical to understand the regulatory mechanism of cholesterol homeostasis in the macrophage in order to prevent foam cells formation and further develop novel therapeutic strategies against atherosclerosis. Here we identified a protein, RIP140 (receptor interacting protein 140), which enhances macrophage-derived foam cell formation by reducing expression of reverse cholesterol transport genes, A TP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1). In animal models, we found that reducing RIP140 levels by crossing macrophage-specific RIP140 knockdown (MÏRIP140KD) mice with ApoE null mice effectively ameliorates high-cholesterol diet-induced atherosclerosis. Our data suggest that reducing RIP140 levels in macrophages significantly inhibits atherosclerosis, along with markers of inflammation and the number of macrophages in a western diet fed ApoE null mouse. This study provides a proof-of-concept for RIP140 as a risk biomarker of, and a therapeutic target for, atherosclerosis.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/patología , Colesterol/metabolismo , Células Espumosas/metabolismo , Homeostasis , Proteínas Nucleares/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Acetilación/efectos de los fármacos , Animales , Apolipoproteínas E/deficiencia , Apolipoproteínas E/metabolismo , Transporte Biológico/efectos de los fármacos , Dieta Occidental , Células Espumosas/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Homeostasis/efectos de los fármacos , Lipoproteínas LDL/farmacología , Receptores X del Hígado , Lisina/metabolismo , Ratones Transgénicos , Proteína de Interacción con Receptores Nucleares 1 , Receptores Nucleares Huérfanos/metabolismoRESUMEN
A module is a fundamental unit forming with highly connected proteins and performs a certain kind of biological functions. Modules and module-module interaction (MMI) network are essential for understanding cellular processes and functions. The MoNetFamily web server can identify the modules, homologous modules (called module family) and MMI networks across multiple species for the query protein(s). This server first finds module candidates of the query by using BLASTP to search the module template database (1785 experimental and 1252 structural templates). MoNetFamily then infers the homologous modules of the selected module candidate using protein-protein interaction (PPI) families. According to homologous modules and PPIs, we statistically calculated MMIs and MMI networks across multiple species. For each module candidate, MoNetFamily identifies its neighboring modules and their MMIs in module networks of Homo sapiens, Mus musculus and Danio rerio. Finally, MoNetFamily shows the conserved proteins, PPI profiles and functional annotations of the module family. Our results indicate that the server can be useful for MMI network (e.g. 1818 modules and 9678 MMIs in H. sapiens) visualizations and query annotations using module families and neighboring modules. We believe that the server is able to provide valuable insights to determine homologous modules and MMI networks across multiple species for studying module evolution and cellular processes. The MoNetFamily sever is available at http://monetfamily.life.nctu.edu.tw.
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Mapeo de Interacción de Proteínas/métodos , Programas Informáticos , Animales , Humanos , Internet , Janus Quinasa 2/metabolismo , Complejo Mediador/metabolismo , Ratones , Glicoproteínas de Membrana Plaquetaria/metabolismo , Psoriasis/enzimología , Psoriasis/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , TYK2 Quinasa/metabolismo , Pez Cebra/metabolismoRESUMEN
OBJECTIVES: Tea is supposed to have chemopreventive effect against various cancers. However, the protective role of tea in prostate cancer is still controversial. The aim of this study is to elucidate the association between tea consumption and prostate cancer risk by meta-analysis. METHODS: A total of 21 published articles were retrieved via both computerized searches and review of references. Estimates of OR/RR for highest versus non/lowest tea consumption levels were pooled on the basis of random effect model or fixed effect model as appropriate. Stratified analyses on tea type, population and study design were also conducted. RESULTS: No statistical significance was detected between tea consumption and prostate cancer risk in meta-analysis of all included studies (odds ratio (OR) = 0.86, 95% CI (0.69-1.04)). Furthermore, stratified analyses on population (Asian, OR = 0.81, 95% CI (0.55-1.08); non-Asian, OR = 0.89, 95% CI (0.72-1.07)) and tea type (green tea, OR = 0.79, 95% CI (0.43-1.14); black tea, OR = 0.88, 95% CI (0.73-1.02)) also yielded non-significant association. Only the case-control study subgroup demonstrated a borderline protective effect for tea consumption against prostate cancer (OR = 0.77, 95% CI (0.55-0.98)). CONCLUSION: Our analyses did not support the conclusion that tea consumption could reduce prostate cancer risk. Further epidemiology studies are needed.
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Neoplasias de la Próstata/prevención & control , Té , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/etiología , Factores de RiesgoRESUMEN
BACKGROUND: Epidemiological studies of the association between nonsteroidal anti-inflammatory drug (NSAID) intake and the risk of prostate cancer still remain controversial. Therefore, we conducted a meta-analysis to evaluate the potential association between NSAID intake and prostate cancer risk. METHODS: Eligible studies were retrieved by both computerized searches and reviews of references. Subgroup analyses on country and design of study were also performed. Random or fixed-effect models were used to pool estimates of odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We observed that the intake of aspirin was associated with a marginally decreased risk of prostate cancer (OR = 0.95, 95% CI = 0.93 to 0.98). A similar result was found between nonaspirin NSAIDs and prostate cancer risk (OR = 0.94, 95% CI =0.90 to 0.98). However, a positive relation between all-NSAID intake and prostate cancer risk was observed (OR = 1.18, 95% CI = 1.15 to 1.22). CONCLUSIONS: We observed a marginally inverse correlation between the intake of aspirin and prostate cancer risk. On the contrary, a positive relationship between all-NSAID intake and prostate cancer was detected. Further research needs to be conducted to better clarify potential biological mechanisms.
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Antiinflamatorios no Esteroideos/uso terapéutico , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/prevención & control , Humanos , Incidencia , Masculino , Pronóstico , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Relatively cheaper high-acid oil was used to make biodiesel through supercritical methanol transesterification, where high FFA contents in feedstock might conversely enhance the reaction extent. A direct-injection diesel engine and a dynamometer were used to analyze the engine characteristics of the high-acid oil-biodiesel. The experimental results show that the biodiesel made in this study had adequate fuel properties. This present biodiesel from high-acid oil was found to bear a lower heating value and equivalence ratio, with higher exhaust gas temperature, brake-specific fuel consumption (bsfc), and excess air ratio, than super-low sulfur diesel (SLSD). The biodiesel appeared to have larger-sized carbon residue left after the burning process in comparison with that of SLSD. The higher engine speed resulted in higher exhaust gas temperature and equivalence ratio, while lower bsfc, excess air ratio, was observed for the biodiesel. Supercritical methanol transesterification has been successfully proven to convert those low-cost feedstocks to renewable biodiesel products which own competitive engine performance in this study.
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Transient elastography (TE), recommended by the WHO, is an established method for characterizing liver fibrosis via liver stiffness measurement (LSM). However, technical barriers remain towards point-of-care application, as conventional TE requires wired connections, possesses a bulky size, and lacks adequate imaging guidance for precise liver localization. In this work, we report the design, phantom validation, and clinical evaluation of a palm-sized TE system that enables simultaneous B-mode imaging and LSM. The performance of this system was validated experimentally using tissue-equivalent reference phantoms (1.45-75 kPa). Comparative studies against other liver elastography techniques, including conventional TE and two-dimensional shear wave elastography (2D-SWE), were performed to evaluate its reliability and validity in adults with various chronic liver diseases. Intra- and inter-operator reliability of LSM were established by an elastography expert and a novice. A good agreement was observed between the Young's modulus reported by the phantom manufacturer and this system (bias: 1.1-8.6%). Among 121 patients, liver stiffness measured by this system and conventional TE were highly correlated (r = 0.975) and strongly agreed with each other (mean difference: -0.77 kPa). Inter-correlation of this system with conventional TE and 2D-SWE was observed. Excellent-to-good operator reliability was demonstrated in 60 patients (ICCs: 0.824-0.913). We demonstrated the feasibility of employing a fully integrated phased array probe for reliable and valid LSM, guided by real-time B-mode imaging of liver anatomy. This system represents the first technical advancement toward point-of-care liver fibrosis assessment. Its small footprint, along with B-mode guidance capability, improves examination efficiency and scales up screening for liver fibrosis.
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Our previous study showed that levels of circulating insulin-like growth factor binding protein-1 (IGFBP-1) has potential diagnostic value for early-stage upper gastrointestinal cancers. This study aimed to assess whether serum IGFBP-1 is a potential diagnostic and prognostic biomarker for CRC patients. IGFBP-1 mRNA expression profile data of peripheral blood in colorectal cancer (CRC) patients were downloaded and analyzed from Gene Expression Omnibus database. We detected serum IGFBP-1 in 138 CRC patients and 190 normal controls using enzyme-linked immunosorbent assay. Blood IGFBP-1 mRNA levels were higher in CRC patients than those in normal controls (P = 0.027). In addition, serum IGFBP-1 protein levels in the CRC group were significantly higher than those in normal control group (P < 0.0001). Serum IGFBP-1 demonstrated better diagnostic accuracy for all CRC and early-stage CRC, respectively, when compared with carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA 19-9) or the combination of CEA and CA19-9. Furthermore, Cox multivariate analysis revealed that serum IGFBP-1 was an independent prognostic factor for OS (HR = 2.043, P = 0.045). Our study demonstrated that serum IGFBP-1 might be a potential biomarker for the diagnosis and prognosis of CRC. In addition, the nomogram might be helpful to predict the prognosis of CRC.
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Neoplasias Colorrectales , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina , Humanos , Antígeno Carcinoembrionario , Pronóstico , ARN Mensajero , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genéticaRESUMEN
Mixed epithelial and stromal tumor of the kidney (MESTK) is the term given to a class of uncommon biphasic tumors of the kidney, with few reported cases. We describe eight cases of MESTK with detailed clinicopathological data and follow-up information. With this report, we hope to increase clinical awareness that MESTK should be considered as one of the possible diagnoses for cystic renal mass, especially in peri-menopausal women or those who receive hormone therapy. In addition, regular follow-up is necessary for the any cases with malignant potential.
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Neoplasias Renales/patología , Neoplasias Complejas y Mixtas/patología , Neoplasias Glandulares y Epiteliales/patología , Células del Estroma/patología , Adulto , Biomarcadores de Tumor/análisis , Femenino , Humanos , Neoplasias Renales/complicaciones , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Neoplasias Complejas y Mixtas/complicaciones , Neoplasias Complejas y Mixtas/cirugía , Neoplasias Glandulares y Epiteliales/complicaciones , Neoplasias Glandulares y Epiteliales/cirugía , Pronóstico , Literatura de Revisión como Asunto , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: p53 is the most frequently mutated tumor-suppressor gene in human cancers. It has been reported that mutations in p53 result not only in the loss of its ability as a tumor suppressor, but also in the gain of novel cancer-related functions that contribute to oncogenesis. The present study evaluated the potential of silencing of mutant p53 by small interfering RNA in the treatment of bladder cancer cells in vitro. METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability and flow cytometry to detect cell cycle alterations and apoptosis. The related molecular mechanisms were assessed by western blotting. We also used the MTT assay and flow cytometry to investigate if silencing of mutant p53 by knockdown with small interfering (si)RNA would change the sensitivity to cisplatin treatment. RESULTS: Using 5637 and T24 human bladder cancer cell lines characterized by mutations in p53, we found that silencing of the mutant p53 by RNA interference induced evident inhibition of cell proliferation and viability, which was related to the induction of G2 phase cell cycle arrest and apoptosis. Moreover, our study also showed that the p53-targeting siRNA cooperated with cisplatin in the inhibition of bladder cancer cells. CONCLUSIONS: These findings suggest that RNA interference targeting mutant p53 may be a promising therapeutic strategy for the treatment of bladder cancer.
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Apoptosis/genética , Puntos de Control del Ciclo Celular/genética , Mutación/genética , ARN Interferente Pequeño/genética , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vejiga Urinaria/patología , Western Blotting , Proliferación Celular , Citometría de Flujo , Silenciador del Gen , Humanos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
OBJECTIVE: Previous studies on the association between tea consumption and bladder cancer risk have only illustrated contradictory results. The role of tea in bladder carcinogenesis still remains conflicting. In order to illustrate the potential relationship between tea consumption and bladder cancer, a meta-analysis of case-control and cohort studies was conducted. METHODS: Eligible studies were retrieved via both computerized searches and review of references. Stratified analyses on types of tea, gender, study design, ethnicity and smoking status were performed. Fixed- or random-effect models were used to summarize the estimates of OR with 95% CIs. RESULTS: Seventeen studies were eligible for our analysis. No statistical significance was detected between tea consumption and bladder cancer risk when comparing the highest with the lowest intake of tea (OR = 0.825, 95% CI 0.652-1.043). In the subgroup of green tea, we observed it illustrated a protective effect on bladder cancer (OR = 0.814, 95% CI 0.678-0.976). CONCLUSION: Our analysis indicated that green tea may have a protective effect on bladder cancer in Asian people. Further studies need to be conducted to better clarify the biological mechanisms.
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Antineoplásicos/administración & dosificación , Bebidas , Té , Neoplasias de la Vejiga Urinaria/prevención & control , Administración Oral , Pueblo Asiatico , Humanos , Oportunidad Relativa , Plantas Medicinales , Medición de Riesgo , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/etnología , Población BlancaRESUMEN
In this study, UV-curable resin was formed into different patterns through the programmable control of dielectric force. The dielectric force is mainly generated by the dielectric chip formed by the interdigitated electrodes. This study observed that of the control factors affecting the size of the UV resin driving area, current played an important role. We maintained the same voltage-controlled condition, changing the current from 0.1 A to 0.5 A as 0.1 A intervals. The area of droplets was significantly different at each current condition. On the other hand, we maintained the same current condition, and changed the voltage from 100 V to 300 V at 50 V intervals. The area of droplets for each voltage condition was not obviously different. The applied frequency of the AC (Alternating Current) electric field increased from 10 kHz to 50 kHz. After driving the UV resin, the pattern line width of the UV resin could be finely controlled from 224 um to 137 um. In order to form a specific pattern, controlling the current and frequency could achieved a more accurate shape. In this article, UV resin with different patterns was formed through the action of this dielectric force, and after UV curing, tiny structural parts could be successfully demonstrated.
RESUMEN
Background: The results regarding the association between insulin-like growth factor binding protein 1 (IGFBP1) expression and cancer risk were controversial. We performed a meta-analysis to provide novel evidence on relationship between IGFBP1 expression and cancer risk. Methods: PubMed, Embase, Cochrane library and Web of science were searched for relevant cohort and case-control studies exploring the relationship between IGFBP1 expression and cancer risk. Odds ratios (ORs) were pooled in this meta-analysis using random model. Subgroup analyses were performed based on ethnicity, tumor types, publication year, study type, Newcastle-Ottawa Scale (NOS) score and sex. Results: A total of 27 studies including 16 cohort and 11 case-control studies were identified by literature search. No significant association was found between IGFBP1 expression and risk of various cancers [0.90, 95% confidence interval (CI): 0.79, 1.03]. The overall results showed that the pooled ORs were 0.71 (95% CI: 0.57, 0.88] for prostate cancer risk and 0.66 (95%CI: 0.44, 0.99) for colorectal cancer (CRC) risk. However, there is no significant association between IGFBP1 expression and risk for ovarian cancer (1.70, 95%CI: 0.41, 6.99), breast cancer (1.02, 95%CI: 0.85, 1.23), endometrial cancer (1.19, 95%CI: 0.64, 2.21), colorectal adenoma (0.93; 95%CI: 0.81, 1.07), lung cancer (0.81, 95%CI: 0.39, 1.68) or multiple myeloma (1.20, 95%CI: 0.98, 1.47). Conclusion: In this study, compared with individuals at low IGFBP1 expression adjusted for age, smoking status, alcohol intake and so on, risk of the prostate cancer and CRC were decreased among individuals of high IGFBP1 expression. There needs further study to confirm this issue.