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OBJECTIVE: To evaluate the predictive value of echo features of radial probe endobronchial ultrasound (RP-EBUS) in the differential diagnosis of malignant and benign 1esions. METHODS: The clinical data of 336 patients with peripheral pulmonary lesions (PPLs) undergoing RP-EBUS were analyzed in order to evaluate the predictive value of the three EBUS echo features including continuous margin, absence of a linear-discrete air bronchogram, and heterogeneous in pulmonary lesions. The sensitivity and specificity for each echoic feature or in combination in diagnosing malignancy or benignity were determined. RESULTS: 336 cases of PPLs including 216 cases of malignant lesions and 120 cases of benign lesions. The sensitivity and specificity of the continuous margin to the diagnosis of malignant lesions were 86.11% and 17.50%. The sensitivity and specificity of the absence of a linear-discrete air bronchogram to the diagnosis of malignant lesions were 66.67% and 57.50%, and the positive predictive value was 73.85%. The sensitivity and specificity of heterogeneity to the diagnosis of malignant lesions were 65.28% and 72.50%, and the positive predictive value was 81.03%. The combination of heterogeneous and absence of a linear-discrete air bronchogram could improve the diagnostic specificity to 87.50%, and the positive predictive value to 80.77%. CONCLUSION: The two EBUS echo features of heterogeneous and absence of a linear-discrete air bronchogram have predictive value for PPLs, especially in the presence of two features the pulmonary lesions should be highly suspected malignant tumors.
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Broncoscopia , Endossonografia , Neoplasias Pulmonares , Sensibilidade e Especificidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Idoso , Endossonografia/métodos , Diagnóstico Diferencial , Broncoscopia/métodos , Adulto , Estudos Retrospectivos , Valor Preditivo dos Testes , Pulmão/diagnóstico por imagem , Pulmão/patologia , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: We aim to explore the expression of Cripto-1 (CR-1) protein in patients with early stage non-small cell lung cancer (NSCLC). METHODS: We investigated CR-1 expression status in specimens obtained from 240 patients with resected NSCLC and 30 cases of para-carcinous normal lung tissues. RESULTS: Compared with normal lung tissue, the positive expression of CR-1 protein in NSCLC was significantly increased (p < 0.005). Cox multivariate regression analysis showed that the expression of CR-1 protein was an independent prognostic factor for early stage NSCLC (p = 0.002). CONCLUSION: Detecting CR-1 protein can predict the prognosis and recurrence in patients with NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Prognóstico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Peptídeos e Proteínas de Sinalização Intercelular/genéticaRESUMO
Extracellular vesicle (EV)-encapsulated circRNAs have the potential role in affecting brain disorders. However, the role of circ_0000075 in cerebral ischemic injury remains unclear. Here, we tried to investigate the mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs carrying circ_0000075 in the control of cerebral ischemic injury. Initially, a mouse model with cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO), followed by the determination of circ_0000075 expression. Then, neurons were isolated and subjected to oxygen-glucose deprivation/reperfusion. BMSCs were isolated for extraction of EVs. The correlation among circ_0000075, microRNA (miR)-218-5p, and Smad ubiquitination regulatory factor 2 (SMURF2) was detected with their roles in cerebral ischemic injury analyzed in vivo and in vitro. circ_0000075 was down-regulated in MCAO mice and engineered RVG-EVs were internalized by neurons to up-regulate circ_0000075 expression. Treatment of RVG-circ_0000075-EVs reduced brain tissue damage, increased neuronal count, and significantly curtailed apoptosis rate, suppressing cerebral ischemic injury in vitro and in vivo. miR-218-5p was targeted by circ_0000075 in neurons, which promoted SMURF2 expression. A negative correlation between SMURF2 and transcriptional regulator Yin Yang 1 (YY1) was identified. In vitro experiments further proved that circ_ 00,000 75 could down-regulate the expression of YY1 through SMURF2, and finally relieving cerebral ischemic injury. Collectively, engineered EVs delivered circ_0000075 into brain tissues and increased circ_0000075 expression, which down-regulated miR-218-5p and up-regulated SMURF2, thus alleviating cerebral ischemic injury.
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Lesões Encefálicas , Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Animais , Camundongos , Ubiquitina-Proteína Ligases/genética , MicroRNAs/genéticaRESUMO
Gliomas are the most common primary intracranial tumor, accounting for more than 70% of brain malignancies. Studies indicate that highly upregulated in liver cancer (HULC), a long noncoding RNA (lncRNA), functions as an oncogene in gliomas. However, the underlying mechanism of HULC in gliomas remains under-studied and was subsequently investigated in the current study. Brain tissues were clinically collected from 50 patients with glioblastoma (GBM) and 35 patients with acute craniocerebral injury, followed by immunohistochemical detection of the expression patterns of Forkhead box M1 (FOXM1), anterior gradient 2 (AGR2), and hypoxia-inducible factor-1α (HIF-1α). After flow cytometry-based sorting of the CD133+ glioma stem cells (GSCs) from the U251 cell line, the obtained cells were subjected to lentivirus infection. Afterwards, the proliferation, stemness, and apoptosis of GSCs were evaluated using sphere formation, immunofluorescence, and flow cytometry assays, respectively. In addition, the interactions among HULC, FOXM1, AGR2, and HIF-1α were identified using RNA immunoprecipitation (RIP), RNA pull-down, Chromatin immunoprecipitation (ChIP), IP, and dual luciferase reporter assays. Last, the specific effects were validated in vivo. HULC was upregulated in GBM tissues and GSCs, which may promote the progression of glioma. On the other hand, silencing of HULC reduced the stemness, inhibited the proliferation, and promoted the apoptosis and differentiation of GSCs. In addition, HULC further stabilized FOXM1 expression in GSCs through ubiquitination, while FOXM1 activated AGR2 transcription to promote HIF-1α expression. Moreover, HULC promoted the glycolysis and stemness of GSCs through its regulation of the FOXM1/AGR2/HIF-1α axis, consequently exacerbating the occurrence and development of glioma. The findings obtained in our study indicate that HULC stabilizes the FOXM1 protein by ubiquitination to upregulate the expression of AGR2 and HIF-1α, which further promote the glycolysis of and maintain the stemness of GSCs, to enhance the tumorigenicity of GSCs, highlighting a novel therapeutic target for glioma.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Células-Tronco Neoplásicas , RNA Longo não Codificante , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioma/genética , Glicólise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mucoproteínas/genética , Mucoproteínas/metabolismo , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , RNA Longo não Codificante/genéticaRESUMO
OBJECTIVE: Anti-programmed cell death-1 and programmed cell death ligand-1 (PD-1/PD-L1) inhibitors have been proved to have a significant clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Many studies have demonstrated that immune-related adverse events (irAEs) are significantly correlated with clinical efficacy, but the results are not consistent. This meta-analysis aimed to evaluate the associations between irAEs and efficacy. METHODS: Comprehensive searches were conducted on PubMed and EMBASE database. The HR and 95% CI were used to assess the associations between immune-related adverse events and efficacy of overall survival and progression-free survival. Subgroup analyses were performed based on irAEs type and grade of irAEs. Heterogeneity and publication bias were also assessed by Q test, I2, and funnel plot. RESULTS: Compared with non-irAEs, the development of irAEs was significantly improved PFS and OS (PFS: HR = 0.55, 95% CI = 0.51-0.60, p < 0.001; OS: HR = 0.74, 95% CI = 0.68-0.81, p < 0.001). In the subgroup analyses, the occurrence of endocrine irAEs, gastrointestinal irAEs, skin lesions and low-grade irAEs was also significantly correlated with the efficacy. Additionally, the association between severe-grade irAEs and survival benefits on PFS was significant, but not on OS. CONCLUSIONS: The results indicated that the occurrence of irAEs was significantly associated with a better efficacy in the treatment of NSCLC, especially endocrine, gastrointestinal, skin and low-grade irAEs.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Neoplasias Pulmonares/imunologia , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
[This corrects the article on p. 6632 in vol. 11, PMID: 31737213.].
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INTRODUCTION: Rapid on-site evaluation (ROSE) has the potential to increase endobronchial ultrasound transbronchial lung biopsy with guide sheath (EBUS-GS-TBLB) accuracy in the diagnosis of peripheral lung cancer. However, studies have reported controversial results. OBJECTIVES: The aim of the study was to evaluate the diagnosis value of EBUS-GS-TBLB combination with ROSE in peripheral lung cancer. METHODS: A total of 138 patients undergoing EBUS-GS-TBLB and ultimately diagnosed with lung cancer were allocated into the ROSE group and non-ROSE group. The result of the diagnostic yields, number of biopsy sites, the complication, cytopathological diagnostic cost and procedure times of EBUS-GS-TBLB with ROSE and without ROSE were compared. RESULTS: The diagnostic yields of TBLB were 87.8% and 78.1% in ROSE group and non-ROSE group, respectively (P < .05). The number of biopsy, procedure times and the percentage of the complication in ROSE group was significantly lower than in non-ROSE group (P < .05, respectively). The cytopathological diagnostic cost of ROSE group was lower compared with non-ROSE group (P < .05). CONCLUSIONS: EBUS-GS-TBLB combined with ROSE could be helpful to diagnose peripheral lung cancer, and could reduce the number of biopsy, procedure times, cytopathological diagnostic cost and complication.
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Endossonografia/métodos , Biópsia Guiada por Imagem/instrumentação , Biópsia Guiada por Imagem/estatística & dados numéricos , Neoplasias Pulmonares/patologia , Adulto , Idoso , Broncoscopia/métodos , China/epidemiologia , Feminino , Humanos , Biópsia Guiada por Imagem/economia , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodosRESUMO
It is well established that human marrow stromal cells (hMSCs) can directly migrate towards tumor microenvironments associated with tumor formation and intracellular communication. Gene regulatory networks in tumors may be targeted by microRNAs (miRNAs), especially those derived in exosomes from hMSCs. However, the potential functional roles of hMSCs in glioma cell growth still remain controversial. Therefore, this study aimed at exploring the regulatory mechanisms of hMSC exosomal microRNA-375 (miR-375) in glioma. Microarray analysis was used to initially screen out glioma-related genes. The interaction between miR-375 and solute carrier family 31 member 1 (SLC31A1) was confirmed by dual-luciferase reporter gene assay. miR-375 and SLC31A1 expression in glioma cells were determined. Glioma cells were initially exposed to exosomes derived from hMSCs treated with miR-375. Subsequently, the rates of proliferation, migration, invasion and apoptosis were determined in glioma cells using in vitro assays. The effects of exosomal miR-375 from hMSCs on tumor growth in vivo were also measured using xenograft tumor in nude mice. We found that miR-375 and SLC31A1 showed significantly lower and higher expression of glioma cells respectively. Additionally, restored miR-375 expression resulted in suppressed cell proliferation, migration and invasion, and increased apoptosis by targeting SLC31A1. Next, in vitro experiments demonstrated that hMSC-derived exosomes overexpressing miR-375 promoted apoptosis while suppressing proliferation, migration and invasion. Furthermore, in vivo experiments confirmed the negative regulatory effects of hMSC-derived exosomes with overexpressed miR-375. We conclude that exosomal miR-375 from hMSCs inhibits glioma cell progression through SLC31A1 suppression, and ultimately serves as a potential target in the treatment of gliomas.
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Neoplasias Encefálicas/genética , Transportador de Cobre 1/genética , Glioma/genética , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Progressão da Doença , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , MicroRNAs/agonistas , Invasividade Neoplásica/genética , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genéticaRESUMO
Gliomas are aggressive type of brain tumors and cause significant human mortality world over. The frequent relapses, development of drug resistance, the adverse effects of the chemotherapy and dearth of the therapeutic targets form the major hurdles in glioma treatment. Several studies suggest that microRNAs (miRs) are involved in the development and progression of different cancers. Herein, the therapeutic potential of miR-181 was explored in human glioma cells. The results showed that miR-181 is significantly downregulated in human glioma cells. Overexpression of miR-181 caused significant inhibition in the proliferation of U87 and U118 glioma cells. The miR-181 triggered growth inhibition was found to be mainly due to the induction of apoptosis which was concomitant with increase in the Bax/Bcl-2 ratio. Additionally, miR-181 enhanced the chemosensitivity of the glioma cells to temozolomide and suppressed their invasion. Bioinformatic analysis showed that miR-181 exerts its effects by inhibiting the expression of Selenoprotein K (SELK). The expression of SELK was found to be significantly upregulated in glioma cells and silencing of SELK suppressed the proliferation of glioma cells. Nonetheless, overexpression of SELK could nullify the effects of miR-181 on the proliferation of the glioma cells. Taken together, miR-181 may exhibit therapeutic implications in the treatment of glioma.
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microRNAs (miRNAs) have been found to affect various cancers, and expression of numerous miRNAs is revealed in glioma. However, the role of microRNA-30b-3p (miR-30b-3p) in glioma remains elusive. Therefore, the present study aims to explore the specific mechanism by which miR-30b-3p influence the development of glioma in relation to the AKT signaling pathway. First, glioma cell lines were collected with miR-30b-3p and reversion-inducing cysteine-rich protein with kazal motifs (RECK) expression measured. The functional role of miR-30b-3p and RECK in glioma was determined via gain- and loss-of-function approaches. Subsequently, the expression of invasion- and migration-related factors (MMP-2 and MMP-9) and the AKT signaling pathway-related factors (AKT, p-AKT and PI3K-p85) was detected. Moreover, in vivo experiments were also conducted to investigate how miR-30b-3p influences in vivo tumorigenesis. The results showed that miR-30b-3p was up-regulated and RECK was down-regulated in glioma. RECK was a target gene of miR-30b-3p. Decreased miR-30b-3p and overexpressed RECK led to decreased expression of MMP-2, MMP-9 and p-AKT. Overexpressed RECK and LY294002 could decrease p-AKT and PI3K-p85 expression accompanied with unchanged expression of total protein of AKT. Additionally, proliferation, migration and invasion of glioma cells and tumor formation in nude mice were repressed owing to reduced expression of miR-30b-3p or elevated expression of RECK. In summary, miR-30b-3p inhibition suppresses metastasis of glioma cells by inactivating the AKT signaling pathway via RECK up-regulation, providing a new target for glioma treatment.
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Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Proteínas Ligadas por GPI/genética , Glioma/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , Regulação para Cima/genética , Animais , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular , Linhagem Celular Tumoral , Glioma/patologia , Células HEK293 , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Angiogenesis is a major pathologic characteristic of glioblastoma, which is one aggressive primary brain tumor. MicroRNA-221/222 (miR-221/222) cluster has been previously reported to function importantly in malignant glioma biological process. The current study aims at evaluating the effects of miR-221/222 cluster on angiogenesis of glioblastoma cells. Microarray data were analyzed to select glioblastoma-associated differentially expressed genes, and dual-luciferase reporter assay was performed to assess targeting correlation between miR-221/222 cluster and suppressor of cytokine signaling-3 (SOCS3). Subsequently, the expression patterns of miR-221 and miR-222 in glioblastoma cells were identified. miR-221 and miR-222 were overexpressed or silenced in glioblastoma cells to identify the effect of miR-221/222 cluster in cell invasion, migration, proliferation, and angiogenesis. To define downstream pathway of miR-221/222 cluster or SOCS3 in glioblastoma, levels of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway-related proteins were assessed. Additionally, the functions of miR-221/222 on glioblastoma cell angiogenesis were measured in vivo with microvessel density assayed. miR-221 and miR-222 were expressed at a high level and SOCS3 was at a low level in glioblastoma. Downregulation of the miR-221/222 cluster diminished the invasion, migration, proliferation, and angiogenesis with reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor in glioblastoma cells. Also, silencing miR-221/222 cluster reduced p-JAK2/JAK2 and p-STAT3/STAT3. Consistently, the inhibitory role of silencing miR-221/222 cluster on tumorigenesis of glioblastoma cells was confirmed in vivo. Collectively, the inhibition of miR-221/222 cluster could attenuate the glioblastoma angiogenesis through inactivation of the JAK/STAT pathway by upregulating SOCS3.
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Inativação Gênica , Glioblastoma/irrigação sanguínea , Janus Quinases/metabolismo , MicroRNAs/metabolismo , Neovascularização Patológica/genética , Fatores de Transcrição STAT/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Animais , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Nus , MicroRNAs/genética , Modelos Biológicos , Família Multigênica , Invasividade Neoplásica , Neovascularização Patológica/patologia , Transdução de Sinais , Regulação para Cima/genéticaRESUMO
OBJECTIVES: Dihydrodiol dehydrogenase 2 (DDH2) plays an important role in pathogenesis of non-small-cell lung cancer (NSCLC). This study aimed to evaluate the value of serum DDH2 levels in NSCLC patients. METHODS: Serum samples were obtained from 863 NSCLC patients and 439 healthy controls. The samples were randomly divided into a training set and a test set. Serum DDH2 levels were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of DDH2 in NSCLC patients were significantly higher than those in healthy controls ( P < 0.001). The diagnostic use of DDH2 in lung adenocarcinoma was significantly greater than that of carcinoembryonic antigen, cytokeratin 19 fragment (CYFRA21-1), and carbohydrate antigen 125 ( P < 0.001). Combining DDH2 with carcinoembryonic antigen, CYFRA21-1, and carbohydrate antigen 125 was more effective for lung adenocarcinoma diagnosis than DDH2 alone. In addition, the levels of DDH2 could contribute to the diagnosis of lung squamous cell carcinoma. CONCLUSIONS: The measurement of serum DDH2 is a valuable diagnostic marker for NSCLC patients.
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Helicases harness the energy of nucleotide triphosphate hydrolysis to unwind double-stranded DNA (dsDNA) in discrete steps. In spite of intensive studies, the mechanism of stepping is still poorly understood. Here, we applied single-molecule fluorescent resonant energy transfer to characterize the stepping of two nonring helicases, Escherichia coli RecQ ( E. coli RecQ) and Saccharomyces cerevisiae Pif1 (ScPif1). Our data showed that when forked dsDNA with free overhangs are used as substrates, both E. coli RecQ and ScPif1 unwind the dsDNA in nonuniform steps that distribute over broad ranges. When tension is exerted on the overhangs, the overall profile of the step-size distribution of ScPif1 is narrowed, whereas that of E. coli RecQ remains unchanged. Moreover, the measured step sizes of the both helicases concentrate on integral multiples of a half base pair. We propose a universal stepping mechanism, in which a helicase breaks one base pair at a time and sequesters the nascent nucleotides and then releases them after a random number of base-pair breaking events. The mechanism can interpret the observed unwinding patterns quantitatively and provides a general view of the helicase activity.
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DNA Helicases/metabolismo , DNA/metabolismo , RecQ Helicases/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Trifosfato de Adenosina/metabolismo , Pareamento de Bases , DNA/química , DNA Helicases/química , DNA Helicases/genética , Escherichia coli/enzimologia , Transferência Ressonante de Energia de Fluorescência , Cinética , Método de Monte Carlo , Conformação de Ácido Nucleico , RecQ Helicases/química , RecQ Helicases/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
INTRODUCTION: Cripto-1 (CR-1) is a member of the epidermal growth factor (EGF)-CFC protein family, which is involved in tumor pathogenesis. OBJECTIVES: This study aimed to explore the diagnostic and prognostic value of serum CR-1 level in patients with non-small cell lung cancer (NSCLC). METHODS: Serum specimens from 312 NSCLC patients and 120 healthy controls were collected. Serum CR-1 level was measured using enzyme-linked immunosorbent assay. RESULTS: The serum CR-1 level was significantly elevated in NSCLC patients compared with healthy controls (P < .001). Higher serum CR-1 level was associated with advanced TNM stage, lymph node metastasis and distant metastasis. With a cutoff value of 1.67 ng/mL, CR-1 showed a good diagnostic performance for NSCLC. Kaplan-Meier log rank analysis revealed that the low serum CR-1 patients had a better overall survival (OS) and progression-free survival (PFS) compared with high CR-1 patients (P = .004 and .001, respectively). Further univariate and multivariate Cox regression analyses showed that serum CR-1 level was an independent risk factor of prognosis of NSCLC patients. CONCLUSIONS: Our study suggests that serum CR-1 level is a useful diagnostic and prognostic marker for NSCLC patients.
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Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas Ligadas por GPI/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/sangue , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Casos e Controles , China , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
Reporter genes are widely applied in biotechnology and biomedical research owning to their easy observation and lack of toxicity. Taking advantage of the reporter genes in conjunction with imaging technologies, a large number of reporter mouse models have been generated. Reporter mouse models provide systems that enable the studies of live cell imaging, cell lineage tracing, immunological research and cancers etc. in vivo. In this review, we describe the types of different reporter genes and reporter mouse models including, random reporter strains, Cre reporter strains and ROSA26 reporter strains. Collectively, these reporter mouse models have broadened scientific inquires and provided potential strategies for generation of novel reporter animal models with enhanced capabilities.
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INTRODUCTION: Macrophage inhibitory cytokine-1 (MIC-1), a transforming growth factor-ß superfamily cytokine, is involved in tumor pathogenesis, and its measurement can be used as a clinical tool for the diagnosis of a wide range of cancers. OBJECTIVES: The aim of this study was to explore the diagnostic value of serum MIC-1 in patients with solitary pulmonary nodules (SPNs). METHODS: Serum specimens from 158 malignant SPN patients, 110 benign SPN patients, along with 120 healthy volunteers. The levels of serum MIC-1 were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: Serum levels of MIC-1 in malignant SPN patients were significantly higher than those in benign SPN patients (P < .01), or those in healthy volunteers (P < .01). With a cutoff of 685.8 pg/ml, the sensitivity and specificity of MIC-1 in differentiating between malignant SPN patients and benign SPN patients, and between malignant SPN patients and healthy volunteers was, 56.3% and 92.7%, and 65.8% and 96.7%, respectively. An area under the curve (AUC) for malignant SPN resulting from MIC-1, which was significantly better than any other tumor markers tested including carbohydrate antigens 12-5 (CA125), and carcinoembryonic antigen (CEA). CONCLUSIONS: In conclusion, measurement of serum MIC-1 levels could be considered as a diagnostic biomarker for malignant SPN patients.
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Fator 15 de Diferenciação de Crescimento/administração & dosagem , Pneumopatias/diagnóstico , Neoplasias Pulmonares/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico , Biomarcadores/sangue , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Biópsia Guiada por Imagem , Pneumopatias/sangue , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Nódulo Pulmonar Solitário/sangue , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: B7-H4, a member of the inhibitory B7 family, can restrain T cell proliferation, activation, cytokine secretion, and may be involved in immune evasion in cancer patients. OBJECTIVES: This aim of the study was to determine the expression level of soluble B7-H4 (sB7-H4) in circulation and to subsequently evaluate the clinical significance of circulating sB7-H4 in patients with non-small cell lung cancer (NSCLC). METHODS: Serum specimens from 128 patients with NSCLC, 100 healthy volunteers (HV), and 80 patients with benign lung diseases (BLD) were collected. The concentrations of sB7-H4 were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sB7-H4 levels in patients with NSCLC were significantly higher than those in patients with BLD (P < 0.05), or those in HV (P < 0.05). Using a cutoff of 27.8 ng/mL, the sensitivity and specificity of sB7-H4 in differentiating between patients with NSCLC and patients with BLD, and between patients with NSCLC and HV was, 46.9% and 92.5%, and 54.7% and 95.0%, respectively. An area under the curve (AUC) for NSCLC resulting from sB7-H4 (0.863), which was significantly better than any other tumour markers tested including CA125 (0.763), and CEA (0.775). CONCLUSION: In conclusion, assessment of serum sB7-H4 levels could be considered as a diagnostic biomarker for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Inibidor 1 da Ativação de Células T com Domínio V-Set/biossíntese , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Curva ROC , Estudos Retrospectivos , Inibidor 1 da Ativação de Células T com Domínio V-Set/sangueRESUMO
The present study aimed to investigate the effect of dihydroartemisinin on the proliferation of chemotherapyresistant C6 rat glioma cells. The results revealed that incubation of C6 glioma cells with a range of dihydroartemisinin concentrations for 48 h led to a significant (P<0.02) reduction in the cell number. There was a 0.8-fold reduction in the cell count following treatment with 20 µM dihydroartemisinin when compared with the control cultures. Analysis of DNA synthesis using bromodeoxyuridine (BrdU) staining demonstrated a reduction in the BrdUlabeling index (LI) following treatment with 20 µM dihydroartemisinin. There was a 6fold reduction in the BrdULI compared with the control cultures. Incubation of the C6 glioma cells with dihydroartemisinin led to a concentration dependent reduction in the level of cyclic adenosine 3',5'monophosphate following 48 h. The percentage of apoptotic cells in the cultures incubated with 20 µM dihydroartemisinin was 54.78% compared with 2.57% in the control cultures. Incubation of the C6 glioma cells with dihydroartemisinin for 48 h led to a reduction in the percentage of cells in G2/M phase with an increase in G0/G1 phase. The control cells exhibited spindleshaped morphology and were actively undergoing mitosis following 48 h of culture. The morphological characteristics of the cells treated with dihydroartemisinin were demonstrated to be round with small surface projections. Therefore, treatment of glioma cells with dihydroartemisinin exhibited an antitumor effect by the induction of apoptosis. Therefore, dihydroartemisinin should be evaluated further in the animal models for the treatment of glioma.
Assuntos
Apoptose/efeitos dos fármacos , Artemisininas/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Glioma/tratamento farmacológico , Animais , Bromodesoxiuridina/administração & dosagem , Linhagem Celular Tumoral , Fase G1/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Glioma/genética , Glioma/patologia , Humanos , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The aim of this study was to assess the usefulness of endobronchial ultrasound transbronchial biopsy with guide-sheath (EBUS-GS-TBB) for the diagnosis of solitary pulmonary nodules (SPNs). One hundred and eighty patients, who were diagnosed with SPNs and underwent an endobronchial ultrasound procedure. The diagnostic yield, safety and the associated factors were analyzed. Mean EBUS-GS procedure time was 14±8 min. The average number of biopsy specimens obtained in each SPNs was 5±1.2. One hundred and thirty-four SPNs were diagnosed by EBUS-GS-TBB and the diagnostic rate was 74.4 %. The diagnosis rate of malignancy was 83.3 %, while that of benign disease was 56.7 %. The most important factors that helped enhance EBUS-GS diagnostic accuracy included lesion diameter greater than 20mm, EBUS probe within the lesions and central lesions. No pneumothorax, hemoptysis or other serious complications occurred with the diagnostic procedures. EBUS-GS-TBB is a safe and effective method for diagnosing SPNs.
RESUMO
Chemerin plays an important role in adipogenesis and chemotaxis of the innate immune system. The aim of this study was to explore the significance and prognostic value of serum chemerin levels in patients with non-small cell lung cancer (NSCLC). Serum specimens from 189 NSCLC patients and 120 healthy controls were collected. The levels of serum chemerin were measured by sandwich enzyme-linked immunosorbent assay (ELISA). The serum chemerin levels were significantly elevated in NSCLC patients compared with healthy controls (P < 0.001). Higher serum chemerin levels were associated with advanced TNM stage, lymph node metastasis, and distant metastasis. Area under receiver operating characteristic curve (ROC) for serum chemerin was 0.809 (95% CI: 0.722-0.896) at a sensitivity of 0.624 and of specificity 0.675. The cut-off value of chemerin was 1500 pg/ml for discriminating NSCLC from healthy controls. Kaplan-Meier log rank analysis revealed that the higher serum chemerin patients had a shorter overall survival (OS) and progression-free survival (PFS) compared with lower chemerin patients (P = 0.004, P = 0.001, respectively). Further univariate and multivariate Cox regression analysis showed that serum chemerin was an independent risk factor of prognosis of NSCLC patients. In conclusion, measurement of chemerin might be a useful diagnostic and prognostic biomarker for NSCLC patients.