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The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.
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Background:Bioinformatics is an effective technology for microarray data mining and gene function prediction. Aims:To analyze the gene CRELD2 that associated with pathogenesis,disease activity and efficacy of biological agents in ulcerative colitis( UC)by bioinformatics to provide a theoretical basis for subsequent studies on its biological function and molecular mechanism in the development and progress of UC. Methods:The microarray data associated with pathogenesis, disease activity and efficacy of biological agents in UC were downloaded from the Gene Expression Omnibus( GEO database);the data mining and analyses were conducted by using bioinformatics tools such as BRB-ArrayTools, ProtParam,ELM,SignalP 4. 1,PBIL-IBCP Lyon Gerland,GO and STRING. Results:Cross-over analyses revealed that expressions of four genes(CDC25B,CRELD2,IL1RN,PITPNC1)were up-regulated in the order from colonic mucosa of healthy subjects,un-inflamed mucosa of active UC patients to inflamed mucosa of active UC patients,meanwhile these four genes were significantly down-regulated in infliximab responders after treatment when compared with that before treatment and infliximab non-responders. The function of CRELD2 gene was unknown. Bioinformatics analyses showed that CRELD2 gene was located on the long arm of chromosome 22(22q13. 33),and encoded a secreted protein composed of 402 amino acids. This protein contained several epidermal growth factor( EGF)-like domains,mainly distributed in Golgi apparatus, endoplasmic reticulum and extracellular site and had calcium- and protein-binding effect. Interactions existed between CRELD2 and CHRNA4,CHRNB2 and RHBDD3 proteins. Conclusions:Gene CRELD2 may have EGF-like biological function and via participating directly or indirectly the regulation of immunocytes to affect the pathogenesis and disease activity of UC. It might be used as a biomarker for diagnosis and assessment of disease activity and therapeutic efficacy of UC. Furthermore,it might be a potential target for treatment of UC.
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Objective To investigate genes and involved biological processes closely associated with stem cell markers of colorectal cancer-epithelial cell adhesion molecule (EpCAM) + and CD44+.Methods By the bioinformatics method,with microarray data of colorectal cancer from gene expression omnibus (GEO) database and R2 platform,the genes significantly related with CD44 and EpCAM expression were screened out.The differences in expression of related genes were analyzed on the basis of gender,family history of cancer,alcohol and Dukes stage.The expression of related genes in colorectal cancer was compared with that of other tumors and healthy subjects.At same time,the pathways of the genes and Kyoto encyclopedia of genes and genomes (KEGG) of CD44 and EpCAM significantly related genes were analyzed with gene ontology (GO) and KEGG method.Single factor analysis of variance and Chi-square test of four-fold table with correction for continuity were used for statistical analysis by R2 platform embedded statistical tools.Results The expressions of CD44 and EpCAM were detected in all 315 colorectal cancer samples.A total of 888 and 6 316 genes were screened out which were significantly associated with CD44 and EpCAM expression.CD44 was positively correlated with EpCAM.There was no obvious correlation between the expression of five genes which expressed in all 315 tissues and gender family history of cancer,alcohol and Dukes stage (all P>0.05).By further compared with the expression in other tumors and tissues,the expressions of two genes solute carrier family 12,member 2 (SLC12A2) and proteome of centriole 1 centriolar protein B (POC1B) in colorectal tumor were significantly higher than that in other tumors (F=289.422、128.456,all P<0.01),and its expression in colorectal cancer was obviously higher than that in tissues of health subjects (F=349.519、128.456,all P<0.01).GO analysis indicated there were 15 GO semantics related with both CD44 and EpCAM.The genes related with CD44 and EpCAM were analyzed by KEGG access pathway method,while seven and 10 pathways were found to be statistically significant (all P<0.01).Conclusions CD44 and FpCAM commonly expressed in colorectal cancer.The genes related with CD44 and EpCAM expression are involved in multiple tumor biological processes.
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It is necessary for the improvement of the medical education and medical system to reform the model of clinical teaching.This article analyzes some problems of today's clinical teaching and clarifies specific demands and aims of teaching,learning and managing in the process of clinical teaching.In order to improve the quality of clinical teaching,the author puts forward some conceives about constructing the "three-in-one" system including teaching,learning and managing in clinical education.
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Objective To investigate the expression of inducible nitric oxide synthase (iNOS) in human gastric carcinoma and its relationship with angiogenesis, lymph nodes metastasi s and clinical staging of gastric carcinoma. Methods The expression of iNOS in 50 patients with gastric carcinoma was studied with im munohistochemical method. Microvessel density (MVD) of human gastric carcinoma was also determined with anti-CD34 as the labelled vascular endothelial cells. Results The rate of expression of iNOS in 50 cases of gastric carcinoma was 70.0% , and MVD averaged 22.0?9.8, higher than those in the tissues around cancer (16 .2%,6.1?3.4) and normal gastric tissues (15.0%,5.5?2.6; P