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1.
Zhonghua Gan Zang Bing Za Zhi ; 30(10): 1050-1055, 2022 Oct 20.
Article in Chinese | MEDLINE | ID: mdl-36727228

ABSTRACT

Objective: To compare and analyze the clinicopathological features and significance for indications of different types of antiviral therapy in chronic hepatitis B (CHB). Methods: Clinical data of 861 CHB cases who received liver biopsy, had hepatitis B virus (HBV) DNA-positive (> 30 IU/ml) and met the indications for antiviral therapy from January 2014 to December 2019 were included. Liver pathological changes and their correlation with clinical characteristics were compared and analyzed. According to different data, t-test, analysis of variance, nonparametric test, χ2 test, Ridit and logistic regression analysis were used for statistical analysis. Results: Most of the cases (72.24%) had remarkable pathological damage. The degree of liver fibrosis was higher in the normal than the abnormal group (P<0.001). 17.54% cases had hepatic steatosis. The vast majority of cases (97.33%) had positive hepatitis B surface antigen (HBsAg), while only 50.87% had positive hepatitis B core antigen (HBcAg). The positive correlation factors affecting the severity of liver histopathology were alkaline phosphatase level, while the negative correlation factors were positive HBcAg staining, albumin and platelet level. The degree of liver inflammation and fibrosis had statistically significant differences with different HBcAg staining levels (χ2=44.142 and 102.386, respectively; P<0.001), and the severity was more apparent in the negative group. Conclusion: There exist differences in clinicopathological features for indications of different types of antiviral therapy in patients with CHB. Liver function test range is inconsistent with degrees of hepatic histological severity. The positive and intensity of liver tissue HBcAg staining, and albumin and alanine aminotransferase levels have negative correlation with disease severity.


Subject(s)
Hepatitis B, Chronic , Humans , Hepatitis B Core Antigens , DNA, Viral , Hepatitis B virus/genetics , Liver/pathology , Hepatitis B Surface Antigens/analysis , Antiviral Agents/therapeutic use , Hepatitis B e Antigens
2.
Zhonghua Nei Ke Za Zhi ; 60(10): 891-897, 2021 Oct 01.
Article in Chinese | MEDLINE | ID: mdl-34551478

ABSTRACT

Objective: To analyze the liver pathology, clinical characteristics and influence factors in patients with chronic hepatitis B virus (HBV) infection in immune tolerant phase (IT). Methods: The clinical data of 273 patients in IT phase who underwent liver biopsy from January 2015 to December 2019 were included in this study. The correlation between liver pathological changes and clinical features was analyzed. Results: There were 43 cases (15.75%) with liver histologic activity ≥ G2, 30 cases (10.99%) with liver fibrosis ≥ S2, and 55 cases (20.15%) with liver pathology ≥ G2 and/or ≥ S2. A total of 17.95% patients had liver steatosis. The majority (98.17%) of tissue samples were positive for HBsAg staining, while only 79.49% were positive for HBcAg. The characteristics of liver pathology were comparable in men from women patients. The differences of G and S were not statistically significant according to different HBsAg positivity, while those were statistically significant according to different HBcAg positivity. By univariate and multivariate analysis, the independent risk factors of pathological severity were HBcAg intensity, HBeAg level, and age. However, the differences of liver histologic activity and fibrosis were not statistically significant between those younger than 30 years old group from those older than 30 years old, neither between those younger or older than 40. Although the diagnostic value of liver inflammation and fibrosis 5 (LIF-5) was better than that of aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis 4 score (FIB-4), three diagnostic models for predicting the pathological severity were not strong enough (all area under the curves<0.8). Only the specificity of LIF-5 for predicting≥ G2, ≥ G2 and/or ≥ S2 was over 80%. Conclusions: Approximately 20% patients with chronic HBV infection in IT phase have progressive liver inflammation or fibrosis. The intensity of liver HBcAg and HBeAg level are negatively correlated with the severity of disease. The diagnostic models or most clinical indicators have low predictive effect for chronic HBV infections in IT phase.


Subject(s)
Hepatitis B, Chronic , Adult , Female , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus , Humans , Liver , Liver Cirrhosis , Male
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 50(3): 564-571, 2018 Jun 18.
Article in Chinese | MEDLINE | ID: mdl-29930431

ABSTRACT

OBJECTIVE: To analyze and characterize the separation effectiveness of self-constructed asymmetrical flow field-flow fractionation system on proteins and lipoproteins, to achieve the optimization of the experimental conditions when separating lipoproteins by orthogonal design test and to investigate the carrier viscosity's influence on separation effectiveness. METHODS: The evaluation of asymmetrical flow field-flow fractionation separation capacity was conducted by using two standard proteins (carbonic anhydrase and thyroglobulin). Under the optimized separation conditions of carbonic anhydrase and thyroglobulin, the channel actual thickness (after assembling, the actual thickness of separation channel was less than initial thickness) was calculated by the analytes' elution time based on the hydrokinetic theory. With orthogonal design test the optimized experimental conditions were studied and statistical analysis was carried on to find out the factors with statistical significance which needed further exploration. RESULTS: According to the hydrodynamics principle and Stoke's function, the channel actual thickness was measured to be 164 µm by separating the two standard proteins, carbonic anhydrase and thyroglobulin, under proper experimental conditions. By the optimization based on orthogonal design test, base-line separation (the resolution had to be higher than 1.50) was achieved. The resolutions of the two experiments were 1.61 and 1.58. According to previous study/ pre-study and supporting theory, in the orthogonal design test, the total 5 factors were integrated for comprehensive investigation: the total flow rate (3.00, 3.50, 4.00, 4.50 mL/min), focus time (3.00, 3.50, 4.00, 4.50 min), transition time (0.5, 1.0, 1.5, 2.0 min), pH of the carrier fluid(6.8, 7.00, 7.20, 7.40) and viscosity of the carrier fluid hydroxypropylmethylcellulose concentration: 0.00%, 0.03%, 0.06%, 1.00%). Among the 5 factors, viscosity was found to have the statistical significance on separation effectiveness which was further investigated. The resolution of high density lipoprotein and low density lipoprotein was increased by the increasing viscosity which also caused more obvious negative spikes. CONCLUSION: The separating capacities of self-constructed asymmetrical flow field-flow fractionation system on lipoproteins were verified to be effective and an optimized experimental condition was found to achieve the base-line separation of high density lipoprotein and low density lipoprotein. Viscosity of the carrier fluid was proved to have the statistical significance on lipoprotein separation.


Subject(s)
Fractionation, Field Flow , Lipoproteins , Lipoproteins, LDL
4.
Eur Rev Med Pharmacol Sci ; 21(3): 549-553, 2017 02.
Article in English | MEDLINE | ID: mdl-28239813

ABSTRACT

OBJECTIVE: Sepsis, a systemic inflammatory response syndrome caused by infection, is a serious threat to the lives of patients. Sepsis can cause tissue hypoperfusion and septic shock which leads to organ dysfunction and death via a variety of mechanisms. Mitochondrial protein (UCP2) involves in immune response, regulation of oxidative stress, and maintenance of mitochondrial membrane potential as well as energy production. However, the role of UCP2 in sepsis remains to be further explored. PATIENTS AND METHODS: A total of 156 patients with sepsis from our hospital were included in this study (69 patients with sepsis and 87 patients with severe sepsis). A total of 69 healthy volunteers were included as controls. Levels of UCP2 in blood cells before and after treatment were measured using RT-PCR and Western blot. The correlation between levels of UCP2 and sepsis was analyzed. RESULTS: The level of UCPPC2 in blood cells of sepsis patients was significantly higher than that of healthy controls at both mRNA level and protein level. The expression level of UCP2 in blood cells of sepsis patients was significantly reduced after treatment, compared to that before treatment. No significant difference was found in the level of UCP2 in blood cells of healthy controls before and after treatment ((p=0.45). Also, the level of UCP2 in blood cells of patients with severe sepsis was significantly higher than that of patients with sepsis at the protein level (p<0.05). Moreover, a positive correlation was found between the level of UCP2 protein and the severity of sepsis. CONCLUSIONS: UCP2 in blood cells might be a specific biomarker for sepsis and the level of UCP2 is positively correlated with the severity of sepsis.


Subject(s)
Sepsis/diagnosis , Shock, Septic , Uncoupling Protein 2/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Case-Control Studies , Early Diagnosis , Humans , Middle Aged , Prognosis , Young Adult
5.
Sci Rep ; 6: 31092, 2016 08 19.
Article in English | MEDLINE | ID: mdl-27538812

ABSTRACT

Ammonia intercalated flower-like MoS2 electrocatalyst film assembled by vertical orientated ultrathin nanosheet on graphite sheethas been successfully synthesized using one-step hydrothermal method. In this strategy, ammonia can effectively insert into the parallel plane of the MoS2 nanosheets, leading to the expansion of lattice and phase transfer from 2H to 1T, generating more active unsaturated sulfur atoms. The flower-like ammoniated MoS2 electrocatalysts with more active sites and large surface area exhibited excellent HER activity with a small Tafel slope and low onset overpotential, resulting a great enhancement in hydrogen evolution. The high efficient activity and recyclable utilization, as well as large-scale, indicate that it is a very promising electrocatalyst to replace Pt in industry application.

6.
Oncogene ; 35(15): 1899-908, 2016 Apr 14.
Article in English | MEDLINE | ID: mdl-26148229

ABSTRACT

Integrin α11ß1 is a stromal cell-specific receptor for fibrillar collagens and is overexpressed in carcinoma-associated fibroblasts (CAFs). We have investigated its direct role in cancer progression by generating severe combined immune deficient (SCID) mice deficient in integrin α11 (α11) expression. The growth of A549 lung adenocarcinoma cells and two patient-derived non-small cell lung carcinoma (NSCLC) xenografts in these α11 knockout (α11(-/-)) mice was significantly impeded, as compared with wild-type (α11(+/+)) SCID mice. Orthotopic implantation of a spontaneously metastatic NCI-H460SM cell line into the lungs of α11(-/-) and α11(+/+) mice showed significant reduction in the metastatic potential of these cells in the α11(-/-) mice. We identified that collagen cross-linking is associated with stromal α11 expression, and the loss of tumor stromal α11 expression was correlated with decreased collagen reorganization and stiffness. This study shows the role of integrin α11ß1, a receptor for fibrillar collagen in differentiation of fibroblasts into CAFs. Furthermore, our data support an important role for α11 signaling pathway in CAFs, promoting tumor growth and metastatic potential of NSCLC cells and being closely associated with collagen cross-linking and the organization and stiffness of fibrillar collagen matrices.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Fibroblasts/physiology , Integrin beta1/physiology , Integrins/physiology , Lung Neoplasms/pathology , Receptors, Collagen/physiology , Stromal Cells/physiology , Animals , Cell Line, Tumor , Collagen/metabolism , Crosses, Genetic , Elasticity , Extracellular Matrix Proteins/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Integrin alpha Chains , Mice , Mice, Inbred Strains , Mice, Knockout , Mice, SCID , Neoplasm Invasiveness , Neoplasm Proteins/metabolism , Protein Kinases/metabolism , Signal Transduction
7.
Genet Mol Res ; 14(2): 6037-41, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-26125803

ABSTRACT

Most plant expressed sequence tag-simple sequence repeats (EST-SSRs) are not polymorphic, and it is important to learn the characteristics of highly polymorphic EST-SSRs. In this study, 357 compound and 5557 non-compound EST-SSRs, identified from the transcriptome of the Chinese bayberry (Myrica rubra 'Biqi'), were divided into 11 types based on their characteristics. Polymorphisms in all 11 EST-SSR types were investigated in 10 cultivars. The percentages of polymorphic loci ranged from 12.9 to 87.5%, with 2-ntL having the highest, followed by 3-ntL, Compound B, and Compound A. The number of alleles and the polymorphic information content of 2-ntL and Compound B were the highest, followed by 2-ntM and Compound A. Therefore, we recommend that 2-ntL, Compound B, and Compound A EST-SSRs should be preferentially selected for the screening of polymorphic EST-SSRs in the Chinese bayberry. Our results should facilitate genetic and breeding studies of this species, and provide a reference for similar study in other plant species.


Subject(s)
Myrica/genetics , Polymorphism, Genetic , Sequence Analysis, RNA/methods , China , Expressed Sequence Tags , Genome, Plant , Microsatellite Repeats , Transcriptome
8.
Oncogene ; 34(32): 4238-47, 2015 Aug 06.
Article in English | MEDLINE | ID: mdl-25381825

ABSTRACT

Using integrative genomics and functional screening, we identified coiled-coil domain containing 68 (CCDC68) as a novel putative tumor suppressor gene (TSG) in pancreatic ductal adenocarcinoma (PDAC). CCDC68 allelic losses were documented in 48% of primary PDAC patient tumors, 50% of PDAC cell lines and 30% of primary patient derived xenografts. We also discovered a single nucleotide polymorphism (SNP) variant (SNP rs1344011) that leads to exon skipping and generation of an unstable protein isoform CCDC68Δ(69-114) in 31% of PDAC patients. Overexpression of full length CCDC68 (CCDC68(wt)) in PANC-1 and Hs.766T PDAC cell lines lacking CDCC68 expression decreased proliferation and tumorigenicity in scid mice. In contrast, the downregulation of endogenous CCDC68 in MIAPaca-2 cells increased tumor growth rate. These effects were not observed with the deletion-containing isoform, CCDC68Δ(69-114).


Subject(s)
Carcinoma, Pancreatic Ductal/genetics , Gene Expression Regulation, Neoplastic , Pancreatic Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Animals , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Mice, SCID , Mutation , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Polymorphism, Single Nucleotide , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, Heterologous , Tumor Burden/genetics , Tumor Suppressor Proteins/metabolism , Pancreatic Neoplasms
9.
Genet Mol Res ; 13(2): 4361-71, 2014 Jun 10.
Article in English | MEDLINE | ID: mdl-25036180

ABSTRACT

Genetic manipulation using linear DNA was applied to the common wheat variety Xindong No. 26 via particle bombardment with the aim to improve bread-making quality of flour. Initially, 2 biolistic parameters, helium pressure and target distance, were optimized using plasmid pAHC25. We transformed wheat immature embryo scutella with the linear 1Dx5 gene without selectable markers. The highest transient ß-glucuronidase expression was obtained when scuttles were bombarded at 1100 psi with a 9-cm target distance. Using the optimized parameters, the transformation of the common wheat variety Xindong No. 26 was carried out using the linear 1Dx5. Three transgenic plants were identified from 1003 transgenic plants, yielding a transformation frequency of 0.4%. A sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis confirmed that the 1Dx5 gene was expressed in 4 T1 seeds of the transgenic plants. These experiments indicate the possibility of obtaining marker-free transgenic wheat plants via particle bombardment using the minimal gene cassettes with the particle bombardment parameters.


Subject(s)
Biolistics/methods , Triticum/growth & development , Triticum/genetics , Genes, Plant , Genetic Markers , Plants, Genetically Modified , Transformation, Genetic
10.
J Appl Microbiol ; 117(3): 690-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24961176

ABSTRACT

AIMS: To utilize excess NADH for 1,3-propanediol production by 2,3-butanediol-deficient mutants, the effect of dhaT overexpression in two distinct 2,3-butanediol-deficient mutants was investigated. METHODS AND RESULTS: Two 2,3-butanediol-deficient mutants, KG1-3 (blocking of the 2,3-butanediol pathway only) and KG1-5 (blocking of both of 2,3-butanediol and lactate pathways) were constructed. Our results showed that although the intracellular redox balance (NADH/NAD(+)) was extremely high at the end of fermentation for both mutants, the status of intracellular redox in KG1-5 was maintained at a normal level following the first stage of fermentation. Analysis of cell growth and metabolite formation confirmed the inhibition of excess lactate in 2,3-butanediol pathway-deficient mutants. Furthermore, dhaT was overexpressed in two 2,3-butanediol-deficient mutants (KG1-3T and KG1-5T). In KG1-5T, the intracellular redox balance was restored to normal and 1,3-propanediol production increased. The yield of 1,3-propanediol from glycerol in KG1-5T was also restored to a normal level of 0·6. CONCLUSIONS: The excess NADH in both the 2,3-butanediol- and lactate-deficient mutants can be used by overexpresstion of dhaT. SIGNIFICANCE AND IMPACT OF STUDY: The metabolic flux tended to increase lactate production by the abolishment of the 2,3-butanediol pathway in Klebsiella pneumoniae, and the high accumulation of lactate prevented the cell from using excess NADH, thereby inhibiting cell growth and 1,3-propanediol production.


Subject(s)
Butylene Glycols/metabolism , Klebsiella pneumoniae/metabolism , NAD/metabolism , Propylene Glycols/metabolism , Alcohol Dehydrogenase/genetics , Alcohol Dehydrogenase/metabolism , Fermentation , Glycerol/metabolism , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/genetics , Lactic Acid/metabolism , Mutation
11.
Pulm Pharmacol Ther ; 27(1): 62-9, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24333186

ABSTRACT

Patients with refractory asthma frequently have neutrophilic airway inflammation and respond poorly to inhaled corticosteroids. This study evaluated the effects of an oral 5-lipoxygenase-activating protein (FLAP) inhibitor, GSK2190915, in patients with asthma and elevated sputum neutrophils. Patients received 14 (range 13-16) days treatment with GSK2190915 100 mg and placebo with a minimum 14 day washout in a double-blind, cross-over, randomised design (N = 14). Sputum induction was performed twice pre-dose in each treatment period to confirm sputum neutrophilia, and twice at the end of each treatment period. The primary endpoint was the percentage and absolute sputum neutrophil count, averaged for end-of-treatment visits. GSK2190915 did not significantly reduce mean percentage sputum neutrophils (GSK2190915-placebo difference [95% CI]: -0.9 [-12.0, 10.3]), or mean sputum neutrophil counts (GSK2190915/placebo ratio [95% CI]: 1.06 [0.43, 2.61]). GSK2190915 resulted in a marked suppression (>90%) of sputum LTB4 and urine LTE4, but did not alter clinical endpoints. There were no safety issues. Despite suppressing the target mediator LTB4, FLAP inhibitor GSK2190915 had no short-term effect on sputum cell counts or clinical endpoints in patients with asthma and sputum neutrophilia.


Subject(s)
5-Lipoxygenase-Activating Protein Inhibitors/therapeutic use , Asthma/drug therapy , Indoles/therapeutic use , Neutrophils/metabolism , Pentanoic Acids/therapeutic use , 5-Lipoxygenase-Activating Protein Inhibitors/pharmacology , Adult , Aged , Asthma/physiopathology , Cross-Over Studies , Double-Blind Method , Female , Humans , Indoles/pharmacology , Leukocyte Count , Male , Middle Aged , Pentanoic Acids/pharmacology , Sputum/metabolism , Time Factors , Treatment Outcome , Young Adult
12.
Nanotechnology ; 22(22): 225702, 2011 Jun 03.
Article in English | MEDLINE | ID: mdl-21454938

ABSTRACT

We present the synthesis and visible-light-induced catalytic activity of one-dimensional (1D) TiO(2)/V(2)O(5) branched heterostructures. The 1D TiO(2)/V(2)O(5) heterostructures were prepared by RF reactive magnetron sputtering of V(2)O(5) onto electrospun TiO(2) nanofibers. Then, the samples were annealed at 300 °C for 2 h in air ambient to form the 1D TiO(2)/V(2)O(5) branched heterostructures. The photodecomposition rate of Rhodamine B (RhB) by the 1D TiO(2)/V(2)O(5) branched heterostructures under visible light was much faster than that of pure TiO(2) nanofibers, revealing that the visible-light-induced catalytic activity of the 1D TiO(2)/V(2)O(5) branched heterostructures was greatly improved. The enhancement of the photocatalytic activity of the 1D TiO(2)/V(2)O(5) branched heterostructures can be ascribed to the coupling with a small bandgap semiconductor material V(2)O(5), where the absorption range is extended, the photogenerated electrons and holes are highly separated and the surface charge carrier transfer rate is promoted.

13.
Lupus ; 19(6): 689-95, 2010 May.
Article in English | MEDLINE | ID: mdl-20179168

ABSTRACT

The aims of this study are to investigate the cytokine, chemokine and adhesion molecule profiles in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus with central nervous system infection. Experimental sets were established which included 108 patients and 132 cerebrospinal fluid samples. The patients were grouped as neuropsychiatric systemic lupus erythematosus (n = 54), systemic lupus erythematosus with central nervous system infection (n = 16), systemic lupus erythematosus controls (n=20), and non-inflammatory neurological disease (n=18). The dynamic changes of 21 patients in the neuropsychiatric systemic lupus erythematosus group before and after induction therapy were further analyzed. IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNFalpha, IFN gamma, IP-10, MCP-1, RANTES, VCAM-1, and P-selectin were measured in cerebrospinal fluid samples by using a fluorescent bead-based assay. Cerebrospinal fluid levels of IL-8, MCP-1, P-selectin and VCAM-1 were significantly increased in neuropsychiatric systemic lupus erythematosus compared with systemic lupus erythematosus controls. IL-6, IL-17, IL-8 and VCAM-1 were higher in systemic lupus erythematosus with central nervous system infection than in systemic lupus erythematosus controls. Among systemic lupus erythematosus with central nervous system infection, the IL-6, IL-17, IL-8 and IP-10 levels were higher than those in neuropsychiatric systemic lupus erythematosus. After sufficient induction therapy, IL-8, MCP-1, P-selectin, VCAM-1 and IL-6 in patients with neuropsychiatric systemic lupus erythematosus decreased significantly. Levels of all molecules tested in non-inflammatory central nervous system disease were not different from those of systemic lupus erythematosus controls. From our data, the intrathecal cytokine/chemokine profile is different among patients with neuropsychiatric systemic lupus erythematosus, systemic lupus erythematosus complicated with central nervous system infection and systemic lupus erythematosus controls. IL-8, MCP-1, VCAM-1, P-selectin and IL-6 in cerebrospinal fluid are effective parameters to monitor neuropsychiatric systemic lupus erythematosus disease activity and response to treatment. Significantly elevated IL-17, IL-6, and to a lesser extent, IL-8, favors central nervous system infection in systemic lupus erythematosus.


Subject(s)
Central Nervous System Infections , Chemokines/cerebrospinal fluid , Cytokines/cerebrospinal fluid , Lupus Erythematosus, Systemic , Lupus Vasculitis, Central Nervous System/cerebrospinal fluid , Lupus Vasculitis, Central Nervous System/immunology , Central Nervous System Infections/cerebrospinal fluid , Central Nervous System Infections/etiology , Central Nervous System Infections/immunology , Chemokines/immunology , Cytokines/immunology , Humans , Lupus Erythematosus, Systemic/cerebrospinal fluid , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology
14.
Br J Cancer ; 96(5): 808-14, 2007 Mar 12.
Article in English | MEDLINE | ID: mdl-17299390

ABSTRACT

The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tumour samples from 146 non-small cell lung carcinoma (NSCLC) patients were analysed for relative expression of DDR1 and DDR2 using quantitative real-time PCR (qRT-PCR). An additional 23 matched tumour and normal tissues were tested for differential expression of DDR1 and DDR2, and previously reported somatic mutations. Discoidin domain receptor 1 was found to be significantly upregulated by 2.15-fold (P=0.0005) and DDR2 significantly downregulated to an equivalent extent (P=0.0001) in tumour vs normal lung tissue. Discoidin domain receptor 2 expression was not predictive for patient survival; however, DDR1 expression was significantly associated with overall (hazard ratio (HR) 0.43, 95% CI=0.22-0.83, P=0.014) and disease-free survival (HR=0.56, 95% CI=0.33-0.94, P=0.029). Multivariate analysis revealed DDR1 is an independent favourable predictor for prognosis independent of tumour differentiation, stage, histology, and patient age. However, contrary to previous work, we did not observe DDR mutations. We conclude that whereas altered expression of DDRs may contribute to malignant progression of NSCLC, it is unlikely that this results from mutations in the DDR1 and DDR2 genes that we investigated.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptors, Mitogen/biosynthesis , Animals , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , DNA Mutational Analysis , Discoidin Domain Receptors , Humans , Lung Neoplasms/genetics , Male , Mice , Mutation , Polymorphism, Genetic , Prognosis , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Mitogen/genetics , Reverse Transcriptase Polymerase Chain Reaction
15.
J Clin Pathol ; 59(8): 790-800, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16873561

ABSTRACT

Characteristics of the tumour that affect and predict the survival outcome of patients with cancer are prognostic markers for cancer. In non-small cell lung carcinoma (NSCLC), stage is the main determinant of prognosis and the basis for deciding options for treatment. Patients with early-stage tumour are treated by complete surgical resection, which is curative in 40-70% of patients. That there are other factors important in determining the biology of these tumours, especially genes that have a role in metastasis, is indicated. Such factors could potentially be used to further classify patients into groups according to substages that may be treated differently. During the past decade, a large number of proteins that are putatively important in carcinogenesis and cancer biology have been studied for their prognostic value in NSCLC, but none of them have been proved to be sufficiently useful in clinical diagnosis. Several markers (epidermal growth factor receptor, human epidermal growth factor receptor 2, Ki-67, p53 and Bcl-2) have been studied exhaustively. Ki-67, p53 and Bcl-2 are suggested to be important but weak prognostic markers, by meta-analyses of the results. Cyclin E, vascular endothelial growth factor A, p16(INK4A), p27(kip1) and beta-catenin are promising candidates, but require further study in large randomised clinical trial samples by using standardised assays and scoring systems. Some issues and inconsistencies in the reported studies to date are highlighted and discussed. A guideline for a multi-phase approach for conducting future studies on prognostic immunohistochemistry markers is proposed here.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Apoptosis , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Cycle Proteins/metabolism , ErbB Receptors/metabolism , Growth Substances/metabolism , Humans , Lung Neoplasms/metabolism , Neoplasm Proteins/metabolism , Prognosis
16.
Br J Cancer ; 94(10): 1452-9, 2006 May 22.
Article in English | MEDLINE | ID: mdl-16641908

ABSTRACT

Telomerase reactivation is a hallmark of human carcinogenesis. Increased telomerase activity may result from gene amplification and/or overexpression. This study evaluates the prognostic value of hTERT gene amplification and mRNA overexpression in 144 resectable non-small-cell lung cancer (NSCLC) specimens. The hTERT gene copy number was assessed by quantitative polymerase chain reaction (qPCR) on laser-capture microdissected tumour cells of 81 tumours, and by fluorescence in situ hybridisation (FISH) on a subset of 59 tumours. hTERT mRNA level was determined by reverse transcription (RT)-qPCR in 130 tumours. In total, 57% of (46 out of 81) primary NSCLC specimens demonstrated hTERT amplification, which was significantly more common (P<0.001) in adenocarcinoma (30 out of 40) than in squamous cell carcinoma (13 out of 37). The hTERT mRNA overexpression was noted in 74% (94 out of 130) of tumours; it was more frequent in squamous cell than in adenocarcinoma (87 vs 68%, P=0.03). Overexpression was significantly associated with amplification (P=0.03), especially in adenocarcinoma. The hTERT gene amplification was prognostic for shorter recurrence-free survival (hazard ratio=2.16, P=0.03). These data indicate that gene amplification is an important mechanism for hTERT overexpression in lung adenocarcinoma and is an independent poor prognostic marker for disease-free survival in NSCLC.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , DNA-Binding Proteins/genetics , Gene Amplification , Lung Neoplasms/diagnosis , Telomerase/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , DNA, Neoplasm/genetics , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization, Fluorescence , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction
17.
Am J Ind Med ; 40(1): 87-91, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11439400

ABSTRACT

BACKGROUND: An investigation of a small private agate mill was prompted by an agate worker who presented with silicosis in Guangzhou, China, in December 1998. METHODS: The work processes and records of dust measurements of the mill were examined. The mean total dust concentrations ranged from 3.0 to 9.9 mg/m3; 86-88% of the particles' diameter was smaller than 5.0 microm. Free SiO2 content from agate samples was measured. Occupational history was obtained and X-ray chest and lung function was carried out. RESULTS: Free SiO2 content of the agate was 90.5%. Thirty-two men involved in processing agate stone were examined. The mean ( +/- SD) age was 29.8 ( +/- 4.9) years and the mean (+/- SD) duration of exposure was 3.5 (+/- 1.7) years. Fifteen cases (47%) were diagnosed as accelerated silicosis. Up to September 1999, three had died from respiratory failure and five were in critical condition. CONCLUSIONS: Silicosis is an important problem in primitive work environments.


Subject(s)
Dust/adverse effects , Mining , Quartz/adverse effects , Silicosis/etiology , Adult , China/epidemiology , Humans , Male , Respiratory Mechanics , Risk , Silicosis/epidemiology , Silicosis/pathology , Time Factors
18.
Mutat Res ; 491(1-2): 173-81, 2001 Apr 05.
Article in English | MEDLINE | ID: mdl-11287310

ABSTRACT

To study the effect of occupational exposure, smoking, and drinking on lymphocyte DNA damage in bus manufacturing workers, 346 employees (106 women and 240 men) from six job categories (welders, mechanics, painters, and assembling, auxiliary and managerial workers) in a bus manufacturing factory in Guangzhou were included. Significant differences of tail moment among the six job categories were found (P=0.003) with adjustment for age and gender. Smoking increased tail moment significantly (3.14 (2.89-3.40) versus 2.79 microm (2.63-2.97), P=0.023). Analysis of covariance showed that occupational exposure (P=0.001) and smoking (P=0.019) had significant effect on tail moment after adjusting for all factors, whereas age and gender had no effect on DNA damage. Stratified analysis showed that painters (P=0.002), auxiliary workers (P=0.011), and mechanics (P=0.044) had larger tail moments than managerial workers after adjusting for age, gender, smoking, and drinking.


Subject(s)
DNA Damage , Lymphocytes/ultrastructure , Occupational Exposure , Comet Assay , Female , Humans , Male
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 21(11): 822-4, 2001 Nov.
Article in Chinese | MEDLINE | ID: mdl-12575374

ABSTRACT

OBJECTIVE: To investigate the effect of New Zhengtian Pill (NZTP) on expression of whole blood platelet membrane adhesion molecules (PMAM) in patients of migraine. METHODS: Sixty-eight patients were divided into two groups, the 35 patients in the treated group treated by NZTP orally and the 33 patients in the control group treated by Fuguiqin Capsule with a therapeutic course of 30 days for both groups. Changes of PMAM GP II b/III a(CD41) and P-selectin (CD62P) were observed by flow-cytometry and compared with those in healthy persons. RESULTS: The markedly effective rate and total effective rate in the treated group was higher than those in the control group respectively (P < 0.05 and P < 0.01). The PMAM expression was also higher in patients, both at onset stage and intermittent stage, than in healthy persons (P < 0.01), NZTP treatment could reduce their increased expression significantly (P < 0.01). CONCLUSION: NZTP could reduce the PMAM expression and inhibit the activation of platelet.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Migraine Disorders/drug therapy , Migraine Disorders/metabolism , Phytotherapy , Platelet Glycoprotein GPIIb-IIIa Complex/biosynthesis , Adolescent , Adult , Female , Humans , Male , Middle Aged , P-Selectin/blood , Platelet Activation
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 21(11): 834-6, 2001 Nov.
Article in Chinese | MEDLINE | ID: mdl-12575378

ABSTRACT

OBJECTIVE: To study the regulatory effect and possible mechanism of Tiaoxin Recipe (TXR) on animal's Alzheimer disease related tau protein phosphorylation. METHODS: NG108 cell model was treated with Okadaic acid and related parameters were determined using MTT staining, immunoblot, coimmunoprecipitation assay, etc. RESULTS: Shown by MTT staining, NG108 cell activity decreased significantly after treated with Okadaic acid for 12 hrs, which could be ameliorated by TXR rat serum. Revealed by immunoblot method, the Okadaic acid induced elevation of phosphorylated tau protein could partly be reversed after co-treated with TXR rat serum. TXR extract could inhibit the binding of tau protein with presenilin-1, which may regulate the tau protein phosphorylation, and could be observed by coimmunoprocipitation. CONCLUSION: TXR could inhibit tau protein hyperphosphorylation, which might partially be due to the TXR caused binding of presenilin-1 with tau protein.


Subject(s)
Alzheimer Disease/metabolism , Drugs, Chinese Herbal/pharmacology , Phytotherapy , tau Proteins/metabolism , Animals , Glioma/pathology , Male , Membrane Proteins/metabolism , Mice , Neuroblastoma/pathology , Okadaic Acid , Phosphorylation/drug effects , Plasma , Presenilin-1 , Rats , Tumor Cells, Cultured
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