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Objective:To synthesize a novel site-specifically labelled probe 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Cys-Asp-Val (CDV)-Nb109 and explore its potential for detection of the programmed cell death ligand 1 (PD-L1) expression level in different tumors. Methods:Firstly, CDV was inserted into the tail of the sequence of Nb109 by genetic engineering. Then the precursor DOTA-CDV-Nb109 was prepared by mixing the maleimide-DOTA and the single-domain antibody CDV-Nb109 (amount of substance ratio 1∶1) via the maleimide-cysteine site-specific coupling strategy. Subsequently, the DOTA-CDV-Nb109 was labeled with 68Ga and purified by PD-10 column. Human melanoma A375, human PD-L1 transfected melanoma A375-hPD-L1 and human glioma U87 tumor-bearing mice models were established, and the diagnostic value of 68Ga-DOTA-CDV-Nb109 was evaluated by stability assay, cellular uptake, and microPET imaging. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:The probe 68Ga-DOTA-CDV-Nb109 was obtained with the radiochemical yield of (69.79±4.69)%, radiochemical purity more than 97%, and molar activity of (12.85±1.51) GBq/μmol. 68Ga-DOTA-CDV-Nb109 had strong binding affinity for A375-hPD-L1 with the dissociation constant ( Kd) of (66.43±17.89) nmol/L. The uptake of 68Ga-DOTA-CDV-Nb109 in A375-hPD-L1 and U87 cells were (3.17±0.15) percentage of the added radioactivity dose (%AD) and (2.08±0.03) %AD respectively, which were significantly higher than that in A375 cells ((1.21±0.14) %AD; F=82.87, t values: 15.23, 9.98, P values: <0.001, 0.003). The tumor uptake of the probe in A375-hPD-L1 ((5.21±0.35) percentage of injected dose per ml (%ID/ml)) and U87 tumor-bearing mice ((3.44±0.69) %ID/ml) were significantly higher than that in A375 tumor-bearing mice ((2.17±0.36) %ID/ml; F=249.72, t values: 35.70, 3.43, both P<0.001). Conclusion:The site-specifically labelled probe 68Ga-DOTA-CDV-Nb109, which can non-invasively and dynamically monitor the change of PD-L1 expression level in different tumors and help screen patients who can benefit from PD-L1 immune checkpoint blocking therapy, is successfully synthesized with high radiochemical purity.
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Objective To investigate the effects of cholesterol-lowering agents on the proliferation, stemness characters, migration, invasion, and neutrophil extracellular traps formation (NETs) formation in liver cancer cells. Methods ASPP2 or HMGCR gene was knocked down in mouse liver cancer cell Hepa1-6 to establish cells with high or low cholesterol, respectively. Simvastatin and berberine were used to reduce cholesterol synthesis. CCK-8 and plate cloning assays were conducted to detect the proliferation ability of liver cancer cells. Sphere formation assay and qRT-PCR were used to analyze the stemness character and expression of related genes. Wound-healing assay and Transwell assay were used to analyze the ability of cell migration and invasion. Immunofluorescence staining was carried out to analyze the effect of lipid-lowering agent on NETs formation. Results Cholesterol-lowering agents significantly inhibited the proliferation and stemness-related gene expression of Hepa1-6 cells (P < 0.001), significantly inhibited the migration and invasion of Hepa1-6 cells (P < 0.001), and significantly inhibited the neutrophil-induced invasion and formation of NETs (P < 0.001). Conclusion Cholesterol-lowering agents suppress the proliferation and invasion via inhibiting the stemness characters and NETs formation in liver cancer cells. It is a potential strategy for the treatment of liver cancer metastasis.
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Objective To study the effect and mechanism of epigallocatechol gallate (EGCG) combined with trastuzu-mab on the proliferation of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. Methods Trastuzumab was expressed and purified. The cell proliferation of HER2 overexpressing breast cancer cells BT474 and SK-BR-3 treated with trastuzumab, EGCG, or trastuzumab plus EGCG was evaluated by CCK8 assay. The effects of EGCG and trastuzumab on the expression of HER2, epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and their phosphorylated proteins in BT474 breast cancer cells were detected by Western blot. Results The results of cell proliferation assay indicated that EGCG and trastuzumab, alone or in combination, effectively inhibited the proliferation of BT-474 and SK-BR-3 cells. And within a certain concentration range, EGCG and trastuzumab showed a synergistic proliferation inhibitory effect on HER2 overexpressing breast cancer cells. Consistent with these results, Western blot results showed that trastuzumab and EGCG, alone or in combination significantly reduced the phosphorylation levels of Akt, MAPK, EGFR, and HER2 in BT474 cells. Moreover, the inhibition effect of EGCG plus trastuzumab was significantly more potent than either EGCG or trastuzumab. Conclusion EGCG and trastuzumab could synergistically inhibit the proliferation of HER2 overexpressing breast cancer cells, which may be related to the regulation of Akt and MAPK signaling pathways.
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Tumors provide materials and energy for themselves through glucose metabolic reprogramming to meet the needs of their rapid growth. Studies have shown that a variety of metabolic enzymes and signal molecules involved in glucose metabolism play an important role in tumorigenesis and development, and are considered to be important targets for the diagnosis and treatment of malignant tumors. The detection technology based on tumor glucose metabolism has been widely used in basic research and clinical diagnosis and treatment of tumor. This paper summarizes the characteristics, driving factors and key regulatory targets of tumor glucose metabolism, and the detection techniques and functions of tumor glucose metabolism from the aspects of basic medical research and clinical diagnosis and treatment.
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OBJECTIVE: To assess the effects of varying the number of diffusion gradient directions (NDGDs) on diffusion tensor fiber tracking (FT) in human brain white matter using tract characteristics. MATERIALS AND METHODS: Twelve normal volunteers underwent diffusion tensor imaging (DTI) scanning with NDGDs of 6, 11, 15, 21, and 31 orientations. Three fiber tract groups, including the splenium of the corpus callosum (CC), the entire CC, and the full brain tract, were reconstructed by deterministic DTI-FT. Tract architecture was first qualitatively evaluated by visual observation. Six quantitative tract characteristics, including the number of fibers (NF), average length (AL), fractional anisotropy (FA), relative anisotropy (RA), mean diffusivity (MD), and volume ratio (VR) were measured for the splenium of the CC at the tract branch level, for the entire CC at tract level, and for the full brain tract at the whole brain level. Visual results and those of NF, AL, FA, RA, MD, and VR were compared among the five different NDGDs. RESULTS: The DTI-FT with NDGD of 11, 15, 21, and 31 orientations gave better tracking results compared with NDGD of 6 after the visual evaluation. NF, FA, RA, MD, and VR values with NDGD of six were significantly greater (smallest p = 0.001 to largest p = 0.042) than those with four other NDGDs (11, 15, 21, or 31 orientations), whereas AL measured with NDGD of six was significantly smaller (smallest p = 0.001 to largest p = 0.041) than with four other NDGDs (11, 15, 21, or 31 orientations). No significant differences were observed in the results among the four NDGD groups of 11, 15, 21, and 31 directions (smallest p = 0.059 to largest p = 1.000). CONCLUSION: The main fiber tracts were detected with NDGD of six orientations; however, the use of larger NDGD (> or = 11 orientations) could provide improved tract characteristics at the expense of longer scanning time.
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Adult , Female , Humans , Male , Young Adult , Anisotropy , Diffusion Tensor Imaging/methods , White Matter/diagnostic imagingABSTRACT
Objective To analyze the worldwide advances on bacterial quantitative proteomics over the past fifteen years with bibliometric approach.Methods Literature retrieval was conducted throughout the databases of Pubmed,Embase and Science citation index (SCI),using bacterium and quantitative proteomics as the key words.The deadline is July 2013.We sorted and analyzed these articles with Endnote X6 from the aspects of published year,the first author,name of journal,published institution,cited frequency and publication type.Results 932 English articles were included in our research after deleting the duplicates.The first article on bacterial quantitative proteomics was reported in 1999.The maximal publications were 163 related articles in 2012.Up till July 2013,authors from more than 23 countries and regions have published articles in this field.China ranks the fourth.The main publication type is original articles.The most frequently cited article is entitled with Absolute quantification of proteins by LCMSE:a virtue of parallel MS acquisition by Silva JC,Gorenstein MV,Li GZ,et al in Mol Cell Proteomics 2006.The most productive author is Smith RD from Biological Sciences Division,Pac.Northwest National Laboratory.The top journal publishing bacterial quantitative proteomics is Proteomics.Conclusion More and more researchers pay attention to quantitative proteomics which will be widely used in bacteriology.
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<p><b>BACKGROUND</b>Ertapenem has been demonstrated to be highly effective for the treatment of complicated infections. The aim of this study was to compare the efficacy and safety of ertapenem with ceftriaxone.</p><p><b>METHODS</b>We searched the PubMed, EMBASE, and the Cochrane Library for published randomized controlled trials (RCTs) that compared the efficacy and safety of ertapenem with ceftriaxone for the treatment of complicated infections including community-acquired pneumonia (CAP), complicated urinary tract infections (cUTIs), and complicated intra-abdominal infections (cIAIs). Meta-analysis was performed by RevMan 5.0.</p><p><b>RESULTS</b>Eight RCTs, involving 2 883 patients, were included in our meta-analysis. Ertapenem was associated with similar clinical treatment success with ceftriaxone for complicated infections (1 326 patients, fixed-effect model, OR: 1.13, 95% CI: 0.75-1.71). There was no difference between the compared treatment groups with regard to the microbiological treatment success, and no difference was found with regard to the incidence of clinical and laboratory drug-related adverse events between ertapenem and ceftriaxone groups. As to local tolerability, overall, there was no difference between the compared groups; however, in the subgroup analysis, local reaction was significantly less in the ertapenem subgroup than the ceftriaxone plus ceftriaxone subgroup.</p><p><b>CONCLUSIONS</b>Ertapenem can be used as effectively and safely as ceftriaxone for the treatment of complicated infections. It is an appealing option for the treatment of these complicated infections.</p>
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Humans , Anti-Bacterial Agents , Therapeutic Uses , Ceftriaxone , Therapeutic Uses , Intraabdominal Infections , Drug Therapy , Pneumonia , Drug Therapy , Randomized Controlled Trials as Topic , Urinary Tract Infections , Drug Therapy , beta-Lactams , Therapeutic UsesABSTRACT
OBJECTIVE To study the in virto interaction of allicin combined with cefoperazone against clinical isolates of Pseudomonas aeruginosa.METHODS The protocol was designed by checkerboard method and the MICs of allicin combined with cefoperazone against the 17 strains of sensitive and 14 strains of drug-resistant P.aeruginosa were determined by broth dilution method,the FIC index was calculated according to MIC results.The combined effects were confirmed by FIC index.RESULTS The percentage of the FIC index less than 0.5,from 0.5 to 1,from 1 to 2,and more than 2 was 41.2-64.3% 35.7-41.2% 0-17.6%,and 0%,respectively.CONCLUSIONS Synergism and additivity of allicin combined with cefoperazone against P.aeruginosa are their main action,there are little autonomy and no antagonism.Allicin can significantly improve the antibacterial activity of cefoperazone against drug-resistant P.aeruginosa.
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OBJECTIVE: To investigate the resistance phenotype of acinetobacter baumannii and the expression of ade efflux pump gene. METHODS: Non-repetitive 51 strains of Acinetobacter baumannii were collected in Peking Union Medical Hospital between Feb. 2004 and Feb. 2005. The active efflux system adeB structural gene and sequence were identified by PCR. RESULTS: The tested strains were not susceptible to common broad-spectrum antibiotics. Multidrug resistant Acinetobacter baumannii carried adeB active efflux pump gene. CONCLUSION: The multiple-drug resistance of Acinetobacter baumannii is independent of ?-lactamase. It maybe related to other drug resistance mechanism. The effect of active efflux system is possibly one of the major mechanisms of multidrug resistance of acinetobacter baumannii.
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AIM: To investigate the antimicrobial activity of linezolid,vancomycin and other antibacterials against 111 methicillin resistant staphylococcus aureus.METHODS: Broth dilution method was used to determine the minimum inhibitory concentrations(MICs) of linezolid,vancomycin and other antibacterials against 111 methicillin resistant staphylococcus aureus identified by cefoxitin.RESULTS: The resistant rates of 111 MRSA to ?-lactam,erythromycin,aminoglycosides(netilmicin and gentamycin),fluoroquinolones(gatifloxacin,moxifloxacin and levofloxacin) and chloromycin were 100%,92.8%,99.1%,91.9%-99.1%,3.6%.All 111 MRSA were sensitive to linezolid and vancomycin,and MIC50 and MIC90 of vancomycin were 0.5 and 1 ?g/mL,MIC50 and MIC90 of linezolid were 2 ?g/mL.CONCLUSION: 111 MRSA were resistant to most antibacterials including ?-lactam,erythromycin,aminoglycosides and fluoroquinolones.Linezolid and vancomycin have strong antimicrobial activity against MRSA.
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The infection caused by pseudomonas aeruginosa biofilm has becoming one of the most urgent problems in hospital.Recent reports of possible mechanism of iron in biofilm formation were reviewed in this paper.The possible effects of iron on adsorption,microcolony formation,mature of colony and desorb were explained,and the prospect of clinical use of local iron or chelator spray was also reviewed here.
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AIM: To study the changes of bacterial ultrastructure, membrance potential and membrance patency of Escherichia coli during the postantibiotic effect after exposure to gatifloxacin and ciprofloxacin in order to investigate the mechanisms of PAE. METHODS: During the Postantibiotic effect after exposure to gatifloxacin and ciprofloxacin, the aliquots were taken from the bacterial culture at regular intervals. Then the fluorescence microscope was used to observe changes in bacterial ultrastructure and at the same time we studied the changes of membrance potential and membrance patency in Escherichia coli during the postantibiotic effect by flow cytometry in conjunction with fluorescent probes. RESULTS: The PAE phase characterized by filament formation after exposure to gatifloxacin by fluorescence microscopy,yet no significant changes in membrance potential and membrance patency of Escherichia coli were observed. CONCLUSION: Gatifloxacin and ciprofloxacin can induce filamentation, and this change is indifferent with membrance potential and membrance patency of Escherichia coli.
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AIM: To study effects and adverse drug reactions of mtrisone in the treatment of patients with severe acute respiratory syndrome. METHODS: The information of the medications in 680 patients with severe acute respiratory syndrome (SARS) in Xiaotangshan Hospital was collected by HIS system and the effects and ADRs of metrisone were staiated. RESULTS: The kinds of drugs of SARS patients who had been cured by metrisone were more than those which were not cured by metrisone. Condition of SARS patients who had been cured by metrisone was more serious than those which were not cured by metrisone. The ADRs rate, blood glucose and leukocyte of SARS patients who had been cured by metrisone are higher than those which were not cured by metrisone while blood K+ is lower. CONCLUSION: The utilization of metrison to SRAS patient should be more cautious to balance the effects and ADRs of metrisone.
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AIM:To compare the mutant prevention concentration(MPC)of linezolid and vancomycin against methicillin resistant staphylococcus aureus(MRSA)and study the correlation between minimal inhibitory concentration(MIC)and MPC.METHODS:MICs and MPCs of two drugs against 35 MRSA clinical stains were determined by agar plates dilution method.The correlations between MIC and MPC were determined by linear regression.The ability to restrict the resistance was evaluated according the pharmacokinetics of two drugs.RESULTS:The MPCs of two drugs against MRSA were 16 and 8 ?g/mL and the MPC/MIC was 8.MPCs and MICs correlated poorly(R2 were 0.32 and 0.008,respectively).According to pharmacokinetics of two drugs,the concentration of linezolid was inside the MSW(mutant selective window)for the entire dosage interval,while the concentration of vancomycin exceeded the MPC for the most dosage interval.CONCLUSION:The capacity of vancomycin for restricting the selection of MRSA resistant mutants is stronger than that of linezolid.There is low correlation between MPC and MIC.