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doi:10.1054/bjoc.2000.1150

Cited by 75 publications

(14 citation statements)

References 23 publications

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“…Hypoxia subsequently induces the expression of vascular endothelial growth factor (VEGF) and promotes further CNV formation 16. In cancer and inflammation, a positive feedback loop exists between VEGF and TF; TF can induce angiogenesis by upregulating VEGF,17–19 and enhanced VEGF can in turn increase TF expression 20…”

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confidence: 99%

Evidence for enhanced tissue factor expression in age-related macular degeneration

Cho

Cao

Shen

et al. 2011

Laboratory Investigation

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Tissue factor (TF) is the primary initiator of blood coagulation. In addition to hemostasis, TF can initiate intracellular signaling and promote inflammation and angiogenesis, the key processes underlying the pathogenesis of age-related macular degeneration (AMD). AMD, the leading cause of irreversible blindness among the elderly, involves many genetic and environmental risk factors, including oxidative stress and inflammation. In this study, TF expression was examined in human AMD tissue and in the eyes of a model of AMD, the Ccl2−/−/Cx3cr1−/− (DKO) mouse, as well as in the ARPE-19 cell line after lipopolysaccharide (LPS) and H2O2 stimulation. Total RNA was extracted from tissue samples and further analyzed by real-time RT-PCR. Immunohistochemistry was performed to evaluate TF protein expression. In the human retina, a 32-fold increase of TF mRNA expression was detected in AMD macular lesions compared to normal maculae. TF protein expression was also enhanced in human AMD maculae. Similarly, TF transcript and protein expression were moderately increased in retinal lesions, neuroretinal tissue, and cultured RPE cells of DKO mice compared to age-matched wild-type mice. TF expression level correlated with age in both wild-type and DKO mice. In order to better understand how AMD might lead to enhanced TF expression, 1, 5, and 10 μg/mL LPS as well as 100 and 200 μM H2O2 were used to stimulate ARPE-19 cells for 24 and 2 hours, respectively. LPS treatment consistently increased TF transcript and protein expression. H2O2 alone or in combination with LPS also moderately enhanced TF expression. These results indicate that upregulated TF expression may be associated with AMD, and inflammatory and oxidative stress may contribute to TF expression in AMD eyes.

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confidence: 99%

Evidence for enhanced tissue factor expression in age-related macular degeneration

Cho

Cao

Shen

et al. 2011

Laboratory Investigation

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“…In addition, a number of studies have utilized co-culture systems to mimic the tumor microenvironment in vitro and investigate its influence on ECs [ 29 , 34 ]. Pro-angiogenic genes such as VEGFR2 , MMPs and integrins are reported upregulated in ECs by tumor-conditioned medium [ 35 – 37 ]. Vascular expression of vWF can also be reprogrammed by the tissue microenvironment [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

GATA3-induced vWF upregulation in the lung adenocarcinoma vasculature

Pan

Liu

et al. 2017

Oncotarget

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Lung adenocarcinoma (LAC) is the leading cause of cancer-related death worldwide. Aberrant expression of genes expressed preferentially in the lung tumor vasculature may yield clues for prognosis and treatment. Von Willebrand factor (vWF) is a large multifunctional glycoprotein with a well-known function in hemostasis. However, vWF has been reported to exert an anti-tumor effect, independent of its role in hemostasis. We investigated the expression of vWF in LAC through immunohistochemical staining of tumor tissue microarrays (TMAs). We found that vWF was overexpressed preferentially in the tumor vasculature of LAC compared with the adjacent tissue vasculature. Consistently, elevated vWF expression was found in endothelial cells (ECs) of fresh human LAC tissues and transplanted mouse LAC tissues. To understand the mechanism underlying vWF up-regulation in LAC vessels, we established a co-culture system. In this system, conditioned media (CM) collected from A549 cells increased vWF expression in human umbilical vein endothelial cells (HUVECs), suggesting enhanced expression is regulated by the LAC secretome. Subsequent studies revealed that the transcription factor GATA3, but not ERG, a known regulator of vWF transcription in vascular cells, mediated the vWF elevation. Chromatin immunoprecipitation (ChIP) assays validated that GATA3 binds directly to the +220 GATA binding motif on the human vWF promoter and A549 conditioned media significantly increases the binding of GATA3. Taken together, we demonstrate that vWF expression in ECs of LAC is elevated by the cancer cell-derived secretome through enhanced GATA3-mediated transcription.

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“…In one of these studies Hussain et al designed a cytotoxic AsiC that used a previously described aptamer [65] targeting the αVβ3 integrin [60]. Elevated surface expression of this integrin has been reported in several cancers including cancers of the cervix [66], brain [67] and prostate [68]. The authors covalently linked the αVβ3 integrin aptamer to a siRNA directed against the EEF2 gene transcript.…”

Section: Aptamer-sirna Cancer Therapiesmentioning

confidence: 99%

Current Progress on aptamer-targeted Oligonucleotide Therapeutics

Dassie

Giangrande

2013

Ther. Deliv.

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Exploiting the power of the RNAi pathway through the use of therapeutic siRNA drugs has remarkable potential for treating a vast array of human disease conditions. However, difficulties in delivery of these and similar nucleic acid-based pharmacological agents to appropriate organs or tissues, remains a major impediment to their broad clinical application. Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery vehicles for therapeutic oligonucleotides, including siRNAs. In this review, we summarize recent attractive developments in creatively employing cell-internalizing aptamers to deliver therapeutic oligonucleotides (e.g., siRNAs, miRNAs, anti-miRs and antisense oligos) to target cells. We also discuss advancements in aptamer-siRNA chimera technology, as well as, aptamer-functionalized nanoparticles for siRNA delivery. In addition, the challenges and future prospects of aptamer-targeted oligonucleotide drugs for clinical translation are further highlighted.

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Cited by 75 publications

References 23 publications

Evidence for enhanced tissue factor expression in age-related macular degeneration

Evidence for enhanced tissue factor expression in age-related macular degeneration

GATA3-induced vWF upregulation in the lung adenocarcinoma vasculature

Current Progress on aptamer-targeted Oligonucleotide Therapeutics

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