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V Castro-Leyva A Espejel-Nuñez G Barroso V Zaga-Clavellina A Flores-Pliego I Morales-Mendez S Giono-Cerezo SW Walsh G Estrada-Gutierrez 《PloS one》2012,7(8):e43605
Objective
To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection.Methods
Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E2 (PGE2) was measured by enzyme immunoassay.Results
Subclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE2 was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages.Conclusions
Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure. 相似文献3.
Background
Heat shock protein 60 (HSP60) is a chaperonin with essential functions for cell physiology and survival, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of HSP60 status with clinicopathological parameters and prognosis in gastric cancer.Methods
The levels of HSP60 and matrix metallopeptidase 9 (MMP-9) antigen was evaluated by immunohistochemistry in 223 gastric carcinoma samples. The association between HSP60 and MMP-9, clinicopathological parameters, and prognosis of gastric cancer was examined.Results
The level of HSP60 protein was significantly associated with depth invasion, lymph node metastasis and stage of disease (all P<0.05). Both univariate and multivariate analyses revealed that HSP60 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) (both P<0.05). Furthermore, HSP60 overexpression was associated with a poor prognosis in patients with advanced gastric cancer in different risk groups. Moreover, HSP60 was significantly correlated with MMP-9 among 223 gastric cancer tissues (P<0.001). Patients who had HSP60 overexpression, in which tumor cells displayed high invasiveness, had poor OS and shorter RFS.Conclusion
HSP60 plays an important role on tumor aggressiveness and prognosis, and may act as a promising target for prognostic prediction. 相似文献4.
Martha Monta?o Raul H Sansores Carina Becerril Jose Cisneros Georgina González-Avila Bettina Sommer Leticia Ochoa Iliana Herrera Alejandra Ramírez-Venegas Carlos Ramos 《Respiratory research》2014,15(1):74
Background
Matrix metalloproteinases (MMPs) and C-reactive protein (CRP) are involved in chronic obstructive pulmonary disease (COPD) pathogenesis. The aim of the present work was to determine plasma concentrations of MMPs and CRP in COPD associated to biomass combustion exposure (BE) and tobacco smoking (TS).Methods
Pulmonary function tests, plasma levels of MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP were measured in COPD associated to BE (n = 40) and TS (n =40) patients, and healthy non-smoking (NS) healthy women (controls, n = 40).Results
Plasma levels of MMP-1, MMP-7, MMP-9, and MMP-9/TIMP-1 and CRP were higher in BE and TS than in the NS healthy women (p <0.01). An inverse correlation between MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP plasma concentrations and FEV1 was observed.Conclusions
Increase of MMPs and CRP plasma concentrations in BE suggests a systemic inflammatory phenomenon similar to that observed in COPD associated to tobacco smoking, which may also play a role in COPD pathogenesis. 相似文献5.
Laura Amado-Rodríguez Adrián González-López Inés López-Alonso Alina Aguirre Aurora Astudillo Estefanía Batalla-Solís Jorge Blazquez-Prieto Emilio García-Prieto Guillermo M Albaiceta 《Respiratory research》2013,14(1):52
Background
Mechanical ventilation can promote lung injury by triggering a pro-inflammatory response. Macrolides may exert some immunomodulatory effects and have shown significant benefits over other antibiotics in ventilated patients. We hypothesized that macrolides could decrease ventilator-induced lung injury.Methods
Adult mice were treated with vehicle, clarithromycin or levofloxacin, and randomized to receive mechanical ventilation with low (12 cmH2O, PEEP 2 cmH2O) or high (20 cmH2O, ZEEP) inspiratory pressures for 150 minutes. Histological lung injury, neutrophil infiltration, inflammatory mediators (NFκB activation, Cxcl2, IL-10) and levels of adhesion molecules (E-selectin, ICAM) and proteases (MMP-9 and MMP-2) were analyzed.Results
There were no differences among groups after low-pressure ventilation. Clarithromycin significantly decreased lung injury score and neutrophil count, compared to vehicle or levofloxacin, after high-pressure ventilation. Cxcl2 expression and MMP-2 and MMP-9 levels increased and IL-10 decreased after injurious ventilation, with no significant differences among treatment groups. Both clarithromycin and levofloxacin dampened the increase in NFκB activation observed in non-treated animals submitted to injurious ventilation. E-selectin levels increased after high pressure ventilation in vehicle- and levofloxacin-treated mice, but not in those receiving clarithromycin.Conclusions
Clarithromycin ameliorates ventilator-induced lung injury and decreases neutrophil recruitment into the alveolar spaces. This could explain the advantages of macrolides in patients with acute lung injury and mechanical ventilation. 相似文献6.
Background
Breast to bone metastases frequently induce a “vicious cycle” in which osteoclast mediated bone resorption and proteolysis results in the release of bone matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis of human breast to bone metastases unexpectedly revealed that bone forming osteoblasts were consistently positive for the proteinase, MMP-2. Given the role of MMP-2 in extracellular matrix degradation and growth factor/cytokine processing, we tested whether osteoblast derived MMP-2 contributed to the vicious cycle of tumor progression in the bone microenvironment.Methodology/Principal Findings
To test our hypothesis, we utilized murine models of the osteolytic tumor-bone microenvironment in immunocompetent wild type and MMP-2 null mice. In longitudinal studies, we found that host MMP-2 significantly contributed to tumor progression in bone by protecting against apoptosis and promoting cancer cell survival (caspase-3; immunohistochemistry). Our data also indicate that host MMP-2 contributes to tumor induced osteolysis (μCT, histomorphometry). Further ex vivo/in vitro experiments with wild type and MMP-2 null osteoclast and osteoblast cultures identified that 1) the absence of MMP-2 did not have a deleterious effect on osteoclast function (cd11B isolation, osteoclast differentiation, transwell migration and dentin resorption assay); and 2) that osteoblast derived MMP-2 promoted tumor survival by regulating the bioavailability of TGFβ, a factor critical for cell-cell communication in the bone (ELISA, immunoblot assay, clonal and soft agar assays).Conclusion/Significance
Collectively, these studies identify a novel “mini-vicious cycle” between the osteoblast and metastatic cancer cells that is key for initial tumor survival in the bone microenvironment. In conclusion, the findings of our study suggest that the targeted inhibition of MMP-2 and/or TGFβ would be beneficial for the treatment of bone metastases. 相似文献7.
Background and Aims
Osteopontin, SDF-1α, and MMP-2 are important secreted molecules involved in the pathophysiology of human hepatocellular carcinoma (HCC). This study investigates the effect of the SDF-1α/CXCR4 axis on expression and activity of MMP-2 induced by osteopontin.Methods
The expression of CXCR4, SDF-1α, MMP-2 and their associated cellular signaling cascades, involving Akt and MAP Kinases, were determined by Western blotting. The activities of MMP-2 and MMP-9 were assayed by gel zymography. The role of the osteopontin receptors integrin αvβ3 and CD44v6 was evaluated using neutralizing antibodies. We also established CXCR4-deficient SMMC7721 cell lines by transfection with miRNA-CXCR4 plasmids and determined cell invasion activity in a transwell assay.Results
In comparison with untreated cells, recombinant human osteopontin (rhOPN) up-regulated CXCR4, SDF-1α, and MMP-2 expression about 5-, 4-, and 6-fold on the protein levels through binding to integrin αvβ3 and CD44v6 in hepatocellular carcinoma cells (SMMC7721 and HepG2). Inhibition of the SDF-1α/CXCR4 axis down-regulated the rhOPN-induced MMP-2 expression and activity. rhOPN also activated Akt, p38 and JNK. Down-regulation of CXCR4 decreased the rhOPN-induced invasion in SMMC7721 cells.Conclusion
These results indicate that rhOPN up-regulates MMP-2 through the SDF-1α/CXCR4 axis, mediated by binding to integrin αvβ3 and CD44v6 and activating the PI-3K/Akt and JNK pathways in HepG2 and SMMC7721 cells. Therefore, the osteopontin-SDF-1α/CXCR4-MMP-2 system may be a new therapeutic target for treating HCC progression. 相似文献8.
Azhar Abbas P?l Aukrust David Russell Kirsten Krohg-S?rensen Trine Alm?s Dorte Bundgaard Vigdis Bjerkeli Ellen Lund Sagen Annika E. Michelsen Tuva B. Dahl Sverre Holm Thor Ueland Mona Skjelland Bente Halvorsen 《PloS one》2014,9(1)
Background
Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process.Methods
Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined.Results
Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality.Conclusion
Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms. 相似文献9.
Background/Purpose
Local and systemic control of soft tissue sarcoma (STS) remains a clinical challenge, particularly for retroperitoneal, deep truncal, or advanced extremity disease. 2′,2′-Difluoro-2′-deoxycytidine (gemcitabine) is a potent radiosensitizer in many tumor types, but it has not been studied in human STS. The purpose of this study was to determine the radiosensitizing potential of gemcitabine in preclinical models of human STS.Materials and Methods
The in vitro radiosensitizing activity of gemcitabine was assessed with clonogenic survival assay on three human STS cell lines: SK-LMS-1 (leiomyosarcoma), SW-872 (liposarcoma), and HT-1080 (fibrosarcoma). Cell cycle distribution was determined using dual-channel flow cytometry. The in vivo radiosensitizing activity of gemcitabine was assessed with subcutaneous SK-LMS-1 nude mice xenografts. Tumor-bearing mice were treated with concurrent weekly gemcitabine and fractionated daily radiotherapy (RT) (2 Gy daily) for 3 weeks (a total dose of 30 Gy).Results
The 50% inhibitory concentration (IC50) of gemcitabine for the human STS cell lines ranged from 10 to 1000 nM. Significant in vitro radiosensitization was demonstrated in all three human STS cell lines using gemcitabine concentrations at and below the IC50. Maximal radiosensitization was associated with accumulation of cells in early S-phase. SK-LMS-1 xenografts displayed significant tumor growth delay with combined gemcitabine and RT compared to either treatment alone. Treatment related toxicity was greatest in the gemcitabine plus RT arm, but remained at an acceptable level.Conclusions
Gemcitabine is a potent radiosensitizer in preclinical models of human STS. Clinical trials combining gemcitabine and RT in human STS are warranted. 相似文献10.
Anna Nolan Sophia Kwon Soo Jung Cho Bushra Naveed Ashley L Comfort David J Prezant William N Rom Michael D Weiden 《Respiratory research》2014,15(1):5
Rationale
After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery.Methods
We performed a nested case–control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75th percentile defined elevated biomarker expression. An FEV1 one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV1.Results
FEV1 in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV1 while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.Conclusions
Resistant cases displayed healing, returning to 99% of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure. 相似文献11.
Taís M. Campos Sara T. Passos Fernanda O. Novais Daniel P. Beiting Rúbia S. Costa Adriano Queiroz David Mosser Phillip Scott Edgar M. Carvalho Lucas P. Carvalho 《PLoS neglected tropical diseases》2014,8(11)
Introduction
Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase.Methods
Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA.Results
We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production.Conclusions
These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection. 相似文献12.
Aina Noguera Cristina Gomez Rosa Faner Borja Cosio Ana González-Périz Joan Clària Angel Carvajal Alvar Agustí 《Respiratory research》2012,13(1):101
Background
Chronic Obstructive Pulmonary Disease (COPD) is characterized by an enhanced inflammatory response to smoking that persists despite quitting. The resolution of inflammation (catabasis) is a complex and highly regulated process where tissue resident macrophages play a key role since they phagocytose apoptotic cells (efferocytosis), preventing their secondary necrosis and the spill-over of their pro-inflammatory cytoplasmic content, and release pro-resolution and tissue repair molecules, such as TGFβ, VEGF and HGF. Because inflammation does not resolve in COPD, we hypothesized that catabasis may be abnormal in these patients.Methods
To explore this hypothesis, we studied lung tissue samples obtained at surgery from 21 COPD patients, 22 smokers with normal spirometry and 13 non-smokers controls. In these samples we used: (1) immunohistochemistry to assess the expression of CD44, CD36, VEGF and TGFβ in lung macrophages; (2) real time PCR to determine HGF, PPARγ, TGFβ, VEGF and MMP-9 gene expression; and, (3) ELISA to quantify lipoxin A4, a lipid mediator of catabasis.Results
We found that current and former smokers with COPD showed: (1) more inflammation (higher MMP-9 expression); (2) reduced macrophage surface expression of CD44, a key efferocytosis receptor; and, (3) similar levels of TGFβ, VEGF, HGF, PPARγ, and lipoxin A4 than smokers with normal spirometry, despite the presence of inflammation and disease.Conclusions
These results identify several potential abnormalities of catabasis in patients with COPD. 相似文献13.
Background
Emodin has been showed to induce apoptosis of pancreatic cancer cells and inhibit tumor growth in our previous studies. This study was designed to investigate whether emodin could inhibit the angiogenesis of pancreatic cancer tissues and its mechanism.Methodology/Principal Finding
In accordance with our previous study, emodin inhibited pancreatic cancer cell growth, induced apoptosis, and enhanced the anti-tumor effect of gemcitabine on pancreatic caner cells in vitro and in vivo by inhibiting the activity of NF-κB. Here, for the first time, we demonstrated that emodin inhibited tumor angiogenesis in vitro and in implanted pancreatic cancer tissues, decreased the expression of angiogenesis-associated factors (NF-κB and its regulated factors VEGF, MMP-2, MMP-9, and eNOS), and reduced eNOS phosphorylation, as evidenced by both immunohistochemistry and western blot analysis of implanted tumors. In addition, we found that emodin had no effect on VEGFR expression in vivo.Conclusions/Significance
Our results suggested that emodin has potential anti-tumor effect on pancreatic cancer via its dual role in the promotion of apoptosis and suppression of angiogenesis, probably through regulating the expression of NF-κB and NF-κB-regulated angiogenesis-associated factors. 相似文献14.
Background
Next-generation sequencing techniques, such as genotyping-by-sequencing (GBS), provide alternatives to single nucleotide polymorphism (SNP) arrays. The aim of this work was to evaluate the potential of GBS compared to SNP array genotyping for genomic selection in livestock populations.Methods
The value of GBS was quantified by simulation analyses in which three parameters were varied: (i) genome-wide sequence read depth (x) per individual from 0.01x to 20x or using SNP array genotyping; (ii) number of genotyped markers from 3000 to 300 000; and (iii) size of training and prediction sets from 500 to 50 000 individuals. The latter was achieved by distributing the total available x of 1000x, 5000x, or 10 000x per genotyped locus among the varying number of individuals. With SNP arrays, genotypes were called from sequence data directly. With GBS, genotypes were called from sequence reads that varied between loci and individuals according to a Poisson distribution with mean equal to x. Simulated data were analyzed with ridge regression and the accuracy and bias of genomic predictions and response to selection were quantified under the different scenarios.Results
Accuracies of genomic predictions using GBS data or SNP array data were comparable when large numbers of markers were used and x per individual was ~1x or higher. The bias of genomic predictions was very high at a very low x. When the total available x was distributed among the training individuals, the accuracy of prediction was maximized when a large number of individuals was used that had GBS data with low x for a large number of markers. Similarly, response to selection was maximized under the same conditions due to increasing both accuracy and selection intensity.Conclusions
GBS offers great potential for developing genomic selection in livestock populations because it makes it possible to cover large fractions of the genome and to vary the sequence read depth per individual. Thus, the accuracy of predictions is improved by increasing the size of training populations and the intensity of selection is increased by genotyping a larger number of selection candidates.Electronic supplementary material
The online version of this article (doi:10.1186/s12711-015-0102-z) contains supplementary material, which is available to authorized users. 相似文献15.
Jeffrey D. Karron Karsten G. Holmquist Rebecca J. Flanagan Randall J. Mitchell 《Annals of botany》2009,103(9):1379-1383
Background and Aims
Adjacent flowers on Mimulus ringens floral displays often vary markedly in selfing rate. We hypothesized that this fine-scale variation in mating system reflects the tendency of bumble-bee pollinators to probe several flowers consecutively on multiflower displays. When a pollinator approaches a display, the first flower probed is likely to receive substantial outcross pollen. However, since pollen carryover in this species is limited, receipt of self pollen should increase rapidly for later flowers. Here the first direct experimental test of this hypothesis is described.Methods
In order to link floral visitation sequences with selfing rates of individual flowers, replicate linear arrays were established, each composed of plants with unique genetic markers. This facilitated unambiguous assignment of paternity to all sampled progeny. A single wild bumble-bee was permitted to forage on each linear array, recording the order of floral visits on each display. Once fruits had matured, 120 fruits were harvested (four flowers from each of five floral displays in each of six arrays). Twenty-five seedlings from each fruit were genotyped and paternity was unambiguously assigned to all 3000 genotyped progeny.Key Results
The order of pollinator probes on Mimulus floral displays strongly and significantly influenced selfing rates of individual fruits. Mean selfing rates increased from 21 % for initial probes to 78 % for the fourth flower probed on each display.Conclusions
Striking among-flower differences in selfing rate result from increased deposition of geitonogamous (among-flower, within-display) self pollen as bumble-bees probe consecutive flowers on each floral display. The resulting heterogeneity in the genetic composition of sibships may influence seedling competition and the expression of inbreeding depression.Key words: Autogamy, bee, Bombus fervidus, floral display, geitonogamy, mating system, monkeyflower, Mimulus ringens, paternity analysis, pollen carryover, pollinator visitation sequence, self-fertilization 相似文献16.
Alejandro Carmona Eva Friero Alfredo de Bustos Nicolás Jouve Angeles Cuadrado 《Annals of botany》2013,112(9):1845-1855
Background and Aims Hordeum marinum
is a species complex that includes the diploid subspecies marinum and both diploid and tetraploid forms of gussoneanum. Their relationships, the rank of the taxa and the origin of the polyploid forms remain points of debate. The present work reports a comparative karyotype analysis of six H. marinum accessions representing all taxa and cytotypes.Methods
Karyotypes were determined by analysing the chromosomal distribution of several tandemly repeated sequences, including the Triticeae cloned probes pTa71, pTa794, pAs1 and pSc119·2 and the simple sequence repeats (SSRs) (AG)10, (AAC)5, (AAG)5, (ACT)5 and (ATC)5.Key Results
The identification of each chromosome pair in all subspecies and cytotypes is reported for the first time. Homologous relationships are also established. Wide karyotypic differences were detected within marinum accessions. Specific chromosomal markers characterized and differentiated the genomes of marinum and diploid gussoneanum. Two subgenomes were detected in the tetraploids. One of these had the same chromosome complement as diploid gussoneanum; the second subgenome, although similar to the chromosome complement of diploid H. marinum sensu lato, appeared to have no counterpart in the marinum accessions analysed here.Conclusions
The tetraploid forms of gussoneanum appear to have come about through a cross between a diploid gussoneanum progenitor and a second, related—but unidentified—diploid ancestor. The results reveal the genome structure of the different H. marinum taxa and demonstrate the allopolyploid origin of the tetraploid forms of gussoneanum. 相似文献17.
Hongguang Liu Gang Ren Zheng Miao Xiaofen Zhang Xiaodong Tang Peizhen Han Sanjiv S. Gambhir Zhen Cheng 《PloS one》2010,5(3)
Background
Optical imaging (OI) techniques such as bioluminescence and fluorescence imaging have been widely used to track diseases in a non-invasive manner within living subjects. These techniques generally require bioluminescent and fluorescent probes. Here we demonstrate the feasibility of using radioactive probes for in vivo molecular OI.Methodology/Principal Findings
By taking the advantages of low energy window of light (1.2–3.1 eV, 400–1000 nm) resulting from radiation, radionuclides that emit charged particles such as β+ and β− can be successfully imaged with an OI instrument. In vivo optical images can be obtained for several radioactive probes including 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), Na18F, Na131I, 90YCl3 and a 90Y labeled peptide that specifically target tumors.Conclusions/Significance
These studies demonstrate generalizability of radioactive OI technique. It provides a new molecular imaging strategy and will likely have significant impact on both small animal and clinical imaging. 相似文献18.
F Finetti E Terzuoli E Bocci I Coletta L Polenzani G Mangano MA Alisi N Cazzolla A Giachetti M Ziche S Donnini 《PloS one》2012,7(7):e40576
Background
Blockade of Prostaglandin (PG) E2 production via deletion of microsomal Prostaglandin E synthase-1 (mPGES-1) gene reduces tumor cell proliferation in vitro and in vivo on xenograft tumors. So far the therapeutic potential of the pharmacological inhibition of mPGES-1 has not been elucidated. PGE2 promotes epithelial tumor progression via multiple signaling pathways including the epidermal growth factor receptor (EGFR) signaling pathway.Methodology/Principal Findings
Here we evaluated the antitumor activity of AF3485, a compound of a novel family of human mPGES-1 inhibitors, in vitro and in vivo, in mice bearing human A431 xenografts overexpressing EGFR. Treatment of the human cell line A431 with interleukin-1beta (IL-1β) increased mPGES-1 expression, PGE2 production and induced EGFR phosphorylation, and vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) expression. AF3485 reduced PGE2 production, both in quiescent and in cells stimulated by IL-1β. AF3485 abolished IL-1β-induced activation of the EGFR, decreasing VEGF and FGF-2 expression, and tumor-mediated endothelial tube formation. In vivo, in A431 xenograft, AF3485, administered sub-chronically, decreased tumor growth, an effect related to inhibition of EGFR signalling, and to tumor microvessel rarefaction. In fact, we observed a decrease of EGFR phosphorylation, and VEGF and FGF-2 expression in tumours explanted from treated mice.Conclusion
Our work demonstrates that the pharmacological inhibition of mPGES-1 reduces squamous carcinoma growth by suppressing PGE2 mediated-EGFR signalling and by impairing tumor associated angiogenesis. These results underscore the potential of mPGES-1 inhibitors as agents capable of controlling tumor growth. 相似文献19.
Nina S McCarthy Phillip E Melton Gemma Cadby Seyhan Yazar Maria Franchina Eric K Moses David A Mackey Alex W Hewitt 《BMC genomics》2014,15(1)
Background
Several individual studies have suggested that autosomal CpG methylation differs by sex both in terms of individual CpG sites and global autosomal CpG methylation. However, these findings have been inconsistent and plagued by spurious associations due to the cross reactivity of CpG probes on commercial microarrays. We collectively analysed 76 published studies (n = 6,795) for sex-associated differences in both autosomal and sex chromosome CpG sites.Results
Overall autosomal methylation profiles varied substantially by study, and we encountered substantial batch effects. We accounted for these by conducting random effects meta-analysis for individual autosomal CpG methylation associations. After excluding non-specific probes, we found 184 autosomal CpG sites differentially methylated by sex after correction for multiple testing. In line with previous studies, average beta differences were small. Many of the most significantly associated CpG probes were new. Of note was differential CpG methylation in the promoters of genes thought to be involved in spermatogenesis and male fertility, such as SLC9A2, SPESP1, CRISP2, and NUPL1. Pathway analysis revealed overrepresentation of genes differentially methylated by sex in several broad Gene Ontology biological processes, including RNA splicing and DNA repair.Conclusions
This study represents a comprehensive analysis of sex-specific methylation patterns. We demonstrate the existence of sex-specific methylation profiles and report a large number of novel DNA methylation differences in autosomal CpG sites between sexes.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-981) contains supplementary material, which is available to authorized users. 相似文献20.