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2.
Front Immunol ; 13: 1043512, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304472

RESUMO

CUL7, a gene composed of 26 exons associated with cullin 7 protein, is also an E3 ligase that is closely related to cell senescence, apoptosis, and cell transformation and also plays an important role in human cancer. However, there is no systematic pan-cancer analysis has been performed to explore its role in prognosis and immune prediction. In this study, the expression of CUL7 in colon adenocarcinoma (COAD) was investigated to determine its prognosis value. First, based on the Cancer Genome Atlas (TCGA), Genotypic-Tissue Expression Project(GTEx), Cancer Cell Line Encyclopedias(CCLE), and TISIDB database, the potential role of CUL7 in different tumors was explored. Subsequently, the expression of CUL7 in COAD was explored and verified by Immunohistochemistry (IHC). Furthermore, the mutation frequency of CUL7 in COAD was analyzed, and the prognostic value of CUL7 in COAD was discussed. In addition, the nomogram was constructed, and its prognostic value was verified by follow-up data from Jiangmen Central Hospital. Finally, PPI network analysis explored the potential biological function of CUL7 in COAD. The results show that CUL7 is upregulated in most tumors, which is significantly associated with poor survival. At the same time, CUL7 is correlated with the clinical stage and immune landscape of various tumors. In colorectal cancer, CUL7 was overexpressed in tumor tissues by IHC with a mutation frequency of about 4%. CUL7 is an independent prognostic factor for colorectal cancer. The nomogram constructed has effective predictive performance, and external databases proved the prognostic value of CUL7. In addition, PPI network analysis showed that CUL7 was closely related to FBXW8, and further pathway enrichment analysis showed that CUL7 was mainly involved in ubiquitin-mediated proteolysis. Therefore, our study provides a comprehensive understanding of the potential role of CUL7 in different tumors, and CUL7 might be a prognostic marker for COAD.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Prognóstico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteínas Culina/genética , Proteínas Culina/metabolismo , Nomogramas
3.
BMC Cancer ; 22(1): 922, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028821

RESUMO

BACKGROUND: Lymph node metastasis (LNM) is a critical event during the colorectal cancer (CRC) development and is indicative of poor prognosis. Identification of molecular markers of LNM may facilitate better therapeutic decision-making. METHODS: Six pairs of CRC tissues and corresponding adjacent tissues [3 pairs diagnosed as pT1N0M0 (M_Low group) and 3 pairs diagnosed as pT4N2M0 (M_High group)] collected from CRC patients who underwent surgical resection were used. MicroRNA sequencing was performed to screen differential microRNAs involved in CRC LNM. The selected microRNAs were validated in CRC tissues and cell lines using qRT-PCR. The functions of candidate hsa-miR-1248 were evaluated by CCK-8, colony formation, and Transwell assay. The binding of hsa-miR-1248 with its target PSMD10 was confirmed by luciferase activity assay, and the expression of PSMD10 in tissues was detected by droplet digital polymerase chain reaction. RESULTS: Ninety-five miRNAs were downregulated in carcinoma tissues (M_Low and M_high groups) compared with the normal group. Their expression in M_High group was significantly lower compared with M_Low group. The top 3 were hsa-miR-635, hsa-miR-1248, and hsa-miR-668-3p. After validation in tissues/cell lines, only hsa- hsa-miR-1248 was decreased in high metastatic tissues or SW620 cells compared to low metastatic tissues or SW480 cells. Hsa-miR-1248 was found to inhibit CRC cell viability, proliferation, invasion, and migration. The tumor suppressor effect of has-miR-1248 in CRC cells was attenuated or enhanced by up-regulating or down-regulating PSMD10, respectively. CONCLUSION: Hsa-miR-1248 may act as a tumor suppressor gene in CRC by targeting and inhibiting PSMD10, which provides a clue for CRC treatment.


Assuntos
Neoplasias Colorretais , MicroRNAs , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Metástase Linfática , MicroRNAs/genética , Complexo de Endopeptidases do Proteassoma/genética , Proteínas Proto-Oncogênicas/genética
4.
Curr Drug Metab ; 22(6): 481-490, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34455944

RESUMO

BACKGROUND: Pantoprazole and atorvastatin are often used jointly in the clinic. The drug-drug interaction of pantoprazole and atorvastatin is worthy of being investigated. OBJECTIVE: A highly rapid, sensitive, and selective LC-MS/MS method was developed for simultaneous quantification of pantoprazole and atorvastatin in rat plasma. METHODS: Omeprazole and atorvastatin-d5 were used as the internal standards (ISs) of pantoprazole and atorvastatin, respectively. Simple protein precipitation was used to extract analytes from 50.0 µL plasma samples. RESULTS: The chromatographic separation was achieved on a C18 column and the total chromatographic run time was 3.2 min. Acquisition of mass spectrometric data was performed on a triple-quadrupole mass spectrometer in multiple- reaction-monitoring (MRM) mode with an ESI source using the transition m/z 384→ 200 for pantoprazole and m/z 559.4→ 440.2 for atorvastatin, respectively. The method was validated over the concentration range of 20.0 ∼ 5000 ng/mL for pantoprazole and 1.00 ∼ 250 ng/mL for atorvastatin. All the validation results, including linearity, specificity, precision, accuracy, extraction recovery, matrix effect, and stability, met the acceptance criteria as per FDA guidelines. CONCLUSION: This method was successfully applied to a pharmacokinetic interaction study in Wistar rats. The results revealed significant evidence for the drug-drug interaction between pantoprazole and atorvastatin.


Assuntos
Atorvastatina/sangue , Cromatografia Líquida/métodos , Pantoprazol/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Atorvastatina/farmacologia , Interações Medicamentosas , Ensaios de Triagem em Larga Escala/métodos , Pantoprazol/farmacologia , Ratos , Ratos Wistar
5.
Front Oncol ; 11: 656852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395241

RESUMO

The majority of occult liver metastases cannot be detected by computed tomography (CT), magnetic resonance imaging (MRI) or other traditionally morphological imaging approaches since the lesions are too small or they have not yet formed cancer nodules. Gankyrin is a small molecular protein composed of seven ankyrin domains. In this study, the expression of Gankyrin in colorectal cancer (CRC) patients with liver metastases was investigated to determine its prognosis value. Gankyrin expression in CRC patients was initially analyzed using data from The Cancer Genome Atlas (TCGA) database and bioinformatics tools. RT-qPCR, western blotting, immunohistochemistry (IHC) and transwell migration and invasion assays were then performed to verify the expression and function of Gankyrin in CRC cell line, CRC tissues and matched non-tumor tissues of clinical patients. General clinicopathological information including TNM stage as well as preoperative and postoperative imaging results were collected. The main outcome indicator was overall survival (OS), referring to the length of time from surgery to either death or the last visit. Statistical analyses included chi-squared tests, Cox analyses, progression free survival (PFS) rates and OS rates. Elevated Gankyrin expression was confirmed in CRC patients. The upregulated Gankyrin expression was positively correlated with the progression of disease and liver metastasis in CRC patients. OS analysis revealed that prognosis was worse in CRC patients with high Gankyrin expression compared to those with low expression. CRC patients with higher Gankyrin expression also had a higher risk of occult liver metastases and a lower PFS rate. Therefore, Gankyrin can be used as a potential biomarker for early diagnosis of CRC with occult liver metastasis.

6.
Biochim Biophys Acta Mol Basis Dis ; 1867(1): 165966, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931889

RESUMO

BACKGROUND: Esophageal Squamous Cell Carcinoma (ESCC) is an aggressive malignancy, leading to more than 250,000 deaths in China every year. However, the pathogenesis of ESCC remains unclear, which hinders the diagnosis and treatment of the disease in clinic. METHOD: To elucidate underlying mechanism and identify potential biomarkers, an integrative strategy of combining transcriptome and metabolome has been implemented to find potential causal genes and metabolites for ESCC. RESULTS: At the transcriptional level, dysregulated genes in ESCC patients were identified and pathway enrichment analysis discovered tyrosine metabolic pathway as a promising target. Subsequently, up- and down-stream metabolites of tyrosine pathway were explored through targeted metabolome approach. Five metabolites, i.e. phenylalanine, 4-hydroxyphenyllactic acid, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid and tyrosine were identified as diagnosis biomarkers for ESCC and metastatic ESCC patients. A biological model incorporating both transcriptional and metabolic dysregulation was also established to illustrate the potential mechanism of tumorigenesis and metastasis for ESCC. CONCLUSION: Integrative transcriptomics and metabolomics analysis suggested that tyrosine pathway was essential for the tumorigenesis and metastasis of ESCC primarily through altering immune response and regulating tumor microenvironment. This research sheds light on the pathogenesis of ESCC and discovers potential biomarkers for the diagnosis of the disease.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Metaboloma , Transcriptoma , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral
7.
Transl Cancer Res ; 10(12): 5267-5279, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35116376

RESUMO

BACKGROUND: Cleavage factor Im 25 (CFIm25) affects the prognosis and progression of cancer by regulating alternative polyadenylation; however, its role in colorectal cancer remains unclear. METHODS: A standard EnVision tissue microarray was used to evaluate the expression of CFIm25 by immunohistochemistry in 363 patients with colorectal cancer. The correlation between CFIm25 expression and clinicopathological characteristics was analyzed using the χ2 test. Univariate analysis was used to study the relationship between clinicopathological characteristics and patient prognosis. Multivariate analysis was performed using the Cox regression model to identify independent prognostic factors for patients with colorectal cancer. RESULTS: Statistical analysis revealed that CFIm25 expression was significantly associated with vascular invasion (P=0.000), serous invasion (P=0.007), pT stage (P=0.016), and clinical stage (P=0.007). Age, vascular invasion, nerve invasion, serosal invasion, differentiation, clinical stage, recurrence, and CFIm25 expression were significantly correlated with the survival time of colorectal cancer patients (P<0.05). The mean overall survival rate in colorectal cancer patients with decreased CFIm25 expression was only 88.53 months, compared with 110.69 months in the high expression group (P=0.000). Decreased CFIm25 expression indicated a worse prognosis in patients with colorectal cancer. Further analysis by the Cox multivariate model showed that CFIm25 (HR, 0.543; 95% CI: 0.372-0.792; P=0.002) and serosa invasion (HR, 1.470; 95% CI: 1.032-2.094; P=0.033) are independent prognostic factors for colorectal cancer. CONCLUSIONS: Decreased CFIm25 expression indicates a worse prognosis of colorectal cancer patients and could be a novel target for the treatment of colorectal cancer in the future. KEYWORDS: Polyadenylation; survival analysis; colorectal cancer (CRC); CFIm25.

8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(6): 1032-1037, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31875379

RESUMO

For the researches relating to the biomedical fields such as preparation of drug micro-particulates and biomedical materials coating, according to the modular design concept and combing the piezoelectric micro-jetting technology with electromechanical engineering and automatic control technology, the drug micro-jetting multifunctional system was designed, which included the spraying support subsystem, X - Y motion platform, Z -axis subsystem and rapid installation subsystem. The drug micro-jetting multifunctional system was run and adjusted. The versatility, rationality and feasibility of this system were validated by the experiments of amoxicillin microcapsule preparation, titanium alloy drug-loaded coating preparation and balloon electrode coating preparation. It was shown that the system can be used as basic platform in multi-disciplinary cross technology research such as biomedical engineering, pharmaceutical engineering and so on.


Assuntos
Ligas , Sistemas de Liberação de Medicamentos , Eletrodos , Titânio
9.
Mol Ther Oncolytics ; 14: 94-106, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31193124

RESUMO

Leucine-rich-repeat-containing G protein-coupled receptors (LGRs) have been widely found to be implicated with development and progression in multiple cancer types. However, the clinical significance and biological functions of LGR6 in ovarian cancer remains unclear. In this study, LGR6 expression was mainly examined by immunohistochemistry. Functional assays in vitro and animal experiments in vivo were carried out to explore the effect of LGR6 on cancer stem cell (CSC) characteristics and chemotherapeutic responses in ovarian cancer cells. Luciferase assays and GSEA were used to discern the underlying mechanisms contributing to the roles of LGR6 in ovarian cancer. Here, we reported that LGR6 was upregulated in ovarian cancer, which positively correlated with poor chemotherapeutic response and progression survival in ovarian cancer patients. Loss-of-function assays showed that downregulating LGR6 abrogated the CSC-like phenotype and chemoresistance in vitro. More importantly, silencing LGR6 improved the chemoresistance of ovarian cancer cells to cisplatin in vivo. Mechanistic investigation further revealed that silencing LGR6 inhibited stemness and chemoresistance by repressing Wnt/ß-catenin signaling. Collectively, our results uncover a novel mechanism contributing to LGR6-induced chemotherapeutic resistance in ovarian cancer, providing the evidence for LGR6 as a potential therapeutic target in ovarian cancer.

10.
Cell Death Dis ; 9(3): 355, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29500439

RESUMO

Fusobacterium nucleatum (Fn) is a tumor-associated obligate anaerobic bacterium, which has a role in the progression of colorectal cancer (CRC). Fn can invade and promote colon epithelial cells proliferation. However, how Fn survives and proliferates in its host cells remains largely unknown. In this study, we aimed to determine the molecular mechanisms underlying the morphology, survival, and proliferation of Fn in THP-1-derived macrophages (dTHP1). For the first time, we found that Fn is a facultative intracellular bacterium that can survive and limited proliferate in dTHP1 cells up to 72 h, and a live Fn infection can inhibit apoptosis of dTHP1 cells by activating the PI3K and ERK pathways. Both Fn bacteria and dTHP1 cells exhibit obvious morphological changes during infection. In addition, Infection of Fn-induced indoleamine 2,3-dioxygenase (IDO) expression by TNF-α-dependent and LPS-dependent pathway in a time-dependent and dose-dependent manner, and the IDO-induced low tryptophan and high kynurenine environment inhibited the intracellular multiplication of Fn in dTHP1 cells. IDO expression further impaired the function of peripheral blood lymphocytes, permitting the escape of Fn-infected macrophages from cell death. IDO inhibition abrogated this effect caused by Fn and relieved immune suppression. In conclusion, we identified IDO as an important player mediating intracellular Fn proliferation in macrophages, and inhibition of IDO may aggravate infection in Fn-associated tumor immunotherapy.


Assuntos
Infecções por Fusobacterium/enzimologia , Infecções por Fusobacterium/microbiologia , Fusobacterium nucleatum/fisiologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Macrófagos/microbiologia , Apoptose , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Humanos , Interferon gama/metabolismo , Interleucina-6/metabolismo , Cinurenina/metabolismo , Linfócitos/microbiologia , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células THP-1 , Triptofano/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Environ Monit Assess ; 189(12): 602, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29101549

RESUMO

Considerable growth in the economy and population of the Dongting Lake watershed in Southern China has increased phosphorus loading to the lake and resulted in a growing risk of lake eutrophication. This study aimed to reveal the spatial pattern and sources of phosphorus export and loading from the watershed. We applied an export coefficient model and the Dillon-Rigler model to quantify contributions of different sub-watersheds and sources to the total phosphorus (TP) export and loading in 2010. Together, the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area contributed 60.9% of the TP exported from the entire watershed. Livestock husbandry appeared to be the largest anthropogenic source of TP, contributing more than 50% of the TP exported from each secondary sub-watersheds. The actual TP loading to the lake in 2010 was 62.9% more than the permissible annual TP loading for compliance with the Class III water quality standard for lakes. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-contributed 91.2% of the total TP loading. As the largest contributor among all sources, livestock husbandry contributed nearly 50% of the TP loading from the Dongting Lake Area and more than 60% from each of the other primary sub-watersheds. This study provides a methodology to identify the key sources and locations of TP export and loading in large lake watersheds. The study can provide a reference for the decision-making for controlling P pollution in the Dongting Lake watershed.


Assuntos
Monitoramento Ambiental , Fósforo/análise , Poluentes Químicos da Água/análise , Qualidade da Água , China , Eutrofização , Lagos/química , Modelos Teóricos , Rios/química
12.
Environ Sci Pollut Res Int ; 24(34): 26706-26723, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28956238

RESUMO

Socioeconomic development in lake watersheds is closely related with lake nutrient pollution. As the second largest freshwater lake in China, the Dongting Lake has been experiencing an increase in nutrient loading and a growing risk of eutrophication. This study aimed to reveal the likely impacts of the socioeconomic development of the Dongting Lake watershed on the phosphorous pollution in the lake. We estimated the contributions from different sources and sub-watersheds to the total phosphorous (TP) export and loading from the Dongting Lake watershed under two most likely socioeconomic development scenarios. Moreover, we predicted the likely permissible and actual TP loadings to the Dongting Lake. Under both two scenarios, three secondary sub-watersheds-the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area-are expected to dominate the contribution to the TP export from the Dongting Lake watershed in 2020. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-are predicted to be the major contributors to the TP loading from the entire watershed. The two scenarios are expected to have a slight difference in TP export and lake TP loading. Livestock husbandry is expected to be the predominant anthropogenic TP source in each of the sub-watersheds under both scenarios. Compared to 2010, permissible TP loading is not expected to increase but actual TP loading is predicted to grow significantly in 2020. Our study provides methodologies to identify the key sources and regions of lake nutrient loading from watersheds with complex socioeconomic context, and to reveal the potential influences of socioeconomic development on nutrient pollution in lake watersheds.


Assuntos
Desenvolvimento Econômico , Monitoramento Ambiental/métodos , Lagos/química , Fósforo/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental/economia , Eutrofização , Rios/química , Fatores Socioeconômicos
13.
Int J Nanomedicine ; 12: 5359-5372, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28794628

RESUMO

We developed fibroblast activation protein α (FAPα)-sensitive magnetic iron oxide nanoparticles (MNPs) by conjugating a substrate-reporter tandem peptide as a synthetic biomarker to the surface of MNPs (marker-MNPs). In vitro, the marker-MNPs showed stability when treated with serum or urine and exhibited high susceptibility and specificity for FAPα enzyme and 3T3/FAPα cell line. Furthermore, the marker-MNPs were administered to esophageal squamous cell carcinoma xenograft tumor mice; they reached the tumor tissues in the mice, where they were cleaved effectively by the local overexpressed FAPα to release the reporter peptide and filter it into the urine. The tumor targeting and biodistribution of marker-MNPs were verified by in vivo imaging. The cleaved reporter peptides in urine detected by enzyme-linked immunosorbent assay have high diagnostic accuracy for esophageal squamous cell carcinoma (area under the receiver-operating characteristic curve =1.0). Our study implies a promising strategy of utilizing the low-cost and noninvasive synthetic urinary probe-coated nanoparticles for the diagnosis of FAPα-positive solid tumors, except for in renal cancer.


Assuntos
Biomarcadores Tumorais/urina , Gelatinases/metabolismo , Proteínas de Membrana/metabolismo , Nanopartículas/química , Neoplasias Experimentais/diagnóstico , Peptídeos/química , Serina Endopeptidases/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Endopeptidases , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago , Humanos , Magnetismo , Camundongos , Camundongos Endogâmicos BALB C , Imagem Molecular/métodos , Nanopartículas/uso terapêutico , Peptídeos/metabolismo , Peptídeos/farmacocinética , Distribuição Tecidual
14.
Mol Cancer ; 16(1): 147, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28851360

RESUMO

BACKGROUND: Phospholipid phosphatase 4 (PPAPDC1A or PLPP4) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to investigate the clinical significance and biological roles of PLPP4 in lung carcinoma. METHODS: PLPP4 expression was examined in 8 paired lung carcinoma tissues by real-time PCR and in 265 lung carcinoma tissues by immunohistochemistry (IHC). Statistical analysis was performed to evaluate the clinical correlation between PLPP4 expression and clinicopathological features and survival in lung carcinoma patients. In vitro and in vivo assays were performed to assess the biological roles of PLPP4 in lung carcinoma. Fluorescence-activated cell sorting, Western blotting and luciferase assays were used to identify the underlying pathway through which PLPP4 silencing mediates biological roles in lung carcinoma. RESULTS: PLPP4 is differentially elevated in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SQC) tissues. Statistical analysis demonstrated that high expression of PLPP4 significantly and positively correlated with clinicopathological features, including pathological grade, T category and stage, and poor overall and progression-free survival in lung carcinoma patients. Silencing PLPP4 inhibits proliferation and cell cycle progression in vitro and tumorigenesis in vivo in lung carcinoma cells. Our results further reveal that PLPP4 silencing inhibits Ca2+-permeable cationic channel, suggesting that downregulation of PLPP4 inhibits proliferation and tumorigenesis in lung carcinoma cells via reducing the influx of intracellular Ca2+. CONCLUSION: Our results indicate that PLPP4 may hold promise as a novel marker for the diagnosis of lung carcinoma and as a potential therapeutic target to facilitate the development of novel treatment for lung carcinoma.


Assuntos
Canais de Cálcio/metabolismo , Carcinogênese/metabolismo , Neoplasias Pulmonares/química , Neoplasias Pulmonares/metabolismo , Fosfatidato Fosfatase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Estimativa de Kaplan-Meier , Pulmão/química , Neoplasias Pulmonares/mortalidade , Fosfatidato Fosfatase/genética , Prognóstico
15.
Oncotarget ; 8(18): 30050-30062, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28415791

RESUMO

To evaluate whether circulating fibroblast activation protein α (FAPα) could serve as a biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), enzyme-linked immunosorbent assay (ELISA) was used to detect plasma FAPα in 556 participants including ESCC group, benign esophageal disease group, healthy controls and other cancer controls group. The levels of plasma FAPα were significantly decreased in ESCC patients (P < 0.001) and showed a positive correlation with HDL-C levels (R = 0.372, P < 0.001). The sensitivity and specificity of plasma FAPα were 56.1% and 85.6% based on the optimal cut-off (49.04 ng/ml, AUC = 0.714). The combination of FAPα and the traditional biomarkers (CEA, CYFR211 and SCCA) improved the sensitivity (41.5%) without compromising the specificity (95.0%). Contradictorily, the immunohistochemical staining revealed the overexpression of FAPα in stroma of ESCC tissues. So the source of soluble FAPα was further explored by qRT-PCR, Western blotting, ELISA and immunoprecipitation in fibroblast cell lines and mouse xenograft models. We found that the plasma FAPα was not correlated with the FAPα expressed in tumor, and the multi-organ might contribute to the circulating levels of FAPα including skeletal muscle, liver and bone marrow. These results indicated that the low plasma FAPα level might due to the systemic reaction to the presence of tumor and circulating FAPα level might be a potential indicator for diagnosing ESCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/diagnóstico , Gelatinases/sangue , Proteínas de Membrana/sangue , Serina Endopeptidases/sangue , Adulto , Idoso , Animais , Linhagem Celular , Modelos Animais de Doenças , Endopeptidases , Ensaio de Imunoadsorção Enzimática , Carcinoma de Células Escamosas do Esôfago , Feminino , Fibroblastos/metabolismo , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC
16.
J Transl Med ; 13: 338, 2015 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-26511079

RESUMO

BACKGROUND: Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in esophageal squamous cell carcinoma (ESCC) remain unknown. METHODS: HSF1 was detected in ESCC cell lines, fibroblast cell lines and ESCC xenograft tumors and human ESCC tissues by real-time RT-PCR and western blotting. HSF1 protein expression was analyzed by immunochemistry in 134 ESCC patients followed by correlation with clinicopathological parameters. RESULTS: HSF1 expression is weak in fibroblast cell 3T3 and moderate in ESCC cell Eca109, but increasing expression of HSF1 was observed in both of 3T3 and Eca109 cells when they interplayed with each other. In Eca109 xenograft tumors, both tumor cells and stromal fibroblasts showed stronger expression of HSF1. In ESCC patients, the HSF1 expression in tumor or in stromal cells was significantly associated with tumor stage, lymph node metastasis and clinical stage. Multivariate analysis demonstrated a significant negative correlation between disease-free survival (DFS), overall survival (OS) and the HSF1 expression in stromal cells (P < 0.05) but not in tumor cells. Additionally, the expression of HSF1 in tumor cells or stromal cells was an independent factor for DFS (P = 0.032 or P = 0.012) and OS (P = 0.017 or P = 0.013) in metastatic ESCC patients but not for locoregional ESCC. ESCC patients with low HSF1 in both tumor cells and stromal cells had the longest survivals (P < 0.001). CONCLUSIONS: The interaction of tumor cells and stromal fibroblasts increases the expression of HSF1 reciprocally in tumor microenvironment. The HSF1 expression in stromal cells was significantly associated with poor prognosis of ESCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Esofágicas/metabolismo , Células Estromais/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Feminino , Fatores de Transcrição de Choque Térmico , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Células NIH 3T3 , Prognóstico , Microambiente Tumoral
17.
Open Biomed Eng J ; 9: 115-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25937851

RESUMO

With polylactic-co-glycolic acid(PLGA) as shell material of microcapsule, amoxicillin as the model, poly(vinyl alcohol) and twain as surfactant, amoxicillin-PLGA microcapsules were manufactured using digital micro-jetting technology and a glass nozzle of 40µm diameter. The influences of the parameters of micro-jetting system on the mean grain size and size distribution of amoxicillin-PLGA microcapsules were studied with single factor analysis and orthogonal experiment method, namely, PLGA solution concentration, driving voltage, jetting frequency, stirrer speed, etc. The optimal result was obtained; the form representation of microcapsule was analyzed as well. The results show that, under certain conditions of experimental drug prescription, driving voltage was proportional to the particle size; jetting frequency and stirrer speed were inversely proportional. When the PLGA concentration for 3%, driving voltage for 80V, the jetting frequency for 10000Hz and the stirrer speed for 750rpm, the particles were in an ideal state with the mean grain size of 60.246µm, the encapsulation efficiency reached 62.39% and 2.1% for drug loading.

18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 32(1): 187-91, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25997290

RESUMO

In an anti-thrombotic pressure circulatory device, relays and solenoid valves serve as core execution units. Thus the therapeutic efficacy and patient safety of the device will directly depend on their performance. A new type of testing system for relays and solenoid valves used in the anti-thrombotic device has been developed, which can test action response time and fatigue performance of relay and solenoid valve. PC, data acquisition card and test platform are used in this testing system based on human-computer interaction testing modules. The testing objectives are realized by using the virtual instrument technology, the high-speed data acquisition technology and reasonable software design. The two sets of the system made by relay and solenoid valve are tested. The results proved the universality and reliability of the testing system so that these relays and solenoid valves could be accurately used in the antithrombotic pressure circulatory equipment. The newly-developed testing system has a bright future in the aspects of promotion and application prospect.


Assuntos
Monitorização Ambulatorial/instrumentação , Trombose/diagnóstico , Desenho de Equipamento , Humanos , Pressão , Reprodutibilidade dos Testes , Software
19.
Chemosphere ; 83(3): 295-301, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21239041

RESUMO

This study investigates synthesis of biogenic schwertmannite by Acidithiobacillus ferrooxidans and its role and mechanism in adsorption of As(III) from water. Results indicate that schwertmannite particles formed through oxidation of ferrous sulfate by A. ferrooxidans cells for different times vary greatly in size and in morphology. The hedge-hog like schwertmannite formed after reaction for 72h are aggregative spheroid particles with a diameter of approximately 2.5µm and its chemical formula can be expressed as Fe(8)O(8)(OH)(4.42)(SO(4))(1.79). Batche studies show that both Freundlich and Langmuir model are suitable for describing the adsorption behavior of As(III) on schwertmannite at pH 7.5 and As(III) in simulated groundwater can be effectively removed by biogenic schwertmannite with a maximum adsorption capacity of 113.9mg As(III) g(-1) and the optimal pH is in the range of 7-10. The arsenic removal is hardly affected by the competing anions often observed in groundwater unless the mole concentration of PO(4)(3-) and SO(4)(2-) in groundwater are 75 or 750 times higher than As(III), respectively. The mechanism of As(III) adsorption on biogenic schwertmannite involves ligand exchanges between arsenic species and surface hydroxyl group and sulfate. In addition, experiments show that As(III)-sorbed biogenic schwertmannite aged in deionized water at 25°C exhibits no mineralogy phase changes even after ageing at pH 6.0 and 8.5 for 90d.


Assuntos
Arsênio/química , Recuperação e Remediação Ambiental/métodos , Água Doce/química , Compostos de Ferro/química , Poluentes Químicos da Água/química , Acidithiobacillus/metabolismo , Adsorção , Arsênio/análise , Compostos Ferrosos/química , Compostos Ferrosos/metabolismo , Concentração de Íons de Hidrogênio , Compostos de Ferro/metabolismo , Cinética , Oxirredução , Poluentes Químicos da Água/análise
20.
Environ Sci Technol ; 42(11): 4165-9, 2008 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18589982

RESUMO

Akaganéite (beta-FeOOH) is a major iron oxyhydroxide component in some soils, marine concretions, and acid mine drainage environments. Recently, synthetic beta-FeOOH has been found to be a promising absorbent in the treatment of metal-contaminated water. It has been recognized in previous study that akaganéite could be formed via FeCl2 chemical oxidation under specific conditions. Here we report a novel and simple method for akaganéite bioformation from FeCl2 solution oxidized by Acidithiobacillus ferrooxidans LX5 cells at 28 degrees C. After acclimation in modified 9K medium containing 0.2 M chloride, Acidithiobacillus ferrooxidans cells had great potential for oxidization of Fe2+ as FeCl2 solution, and then resulted in the formation of precipitates. The resulting precipitates were identified by powder X-ray diffraction and transmission FT-IR analyses to be akaganéite. Scanning electron microscopy images showed the akaganéite was spindle-shaped, approximately 200 nm long with an axial ratio of about 5, and the spindles had a rough surface. X-ray energy-dispersive spectral analyses indicated the chemical formula of the crystalloid akaganéite could be expressed as Fe8O8(OH)7.1(Cl)0.9 with Fe/Cl molar ratio of 8.93. The biogenetic akaganéite had a specific surface area of about 100 m2 g(-1) determined by BET method.


Assuntos
Acidithiobacillus/metabolismo , Compostos Férricos/metabolismo , Compostos Ferrosos/metabolismo , Nanopartículas , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Oxirredução , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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