The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy

Pożarowska, Dorota; Pożarowski, Piotr

doi:10.5114/ceji.2016.63132

Cited by 75 publications

(49 citation statements)

References 58 publications

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“…No difference between 1 g -controls and RPM-samples could be observed up until 72 h. VEGF plays an important role in neoangiogenesis, proliferation and migration, mainly of endothelial cells but also of various other cells types [72-74]. VEGF seems to be affected considerably in thyroid cancer cells exposed to s-µ g [72, 75].…”

Section: Discussionmentioning

confidence: 99%

Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

Warnke

Pietsch

Kopp

et al. 2017

Cell Physiol Biochem

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Background/Aims: Spaceflight impacts on the function of the thyroid gland in vivo. In vitro normal and malignant thyrocytes assemble in part to multicellular spheroids (MCS) after exposure to the random positioning machine (RPM), while a number of cells remain adherent (AD). We aim to elucidate possible differences between AD and MCS cells compared to 1g-controls of normal human thyroid cells. Methods: Cells of the human follicular epithelial thyroid cell line Nthy-ori 3-1 were incubated for up to 72 h on the RPM. Afterwards, they were investigated by phase-contrast microscopy, quantitative real-time PCR and by determination of cytokines released in their supernatants. Results: A significant up-regulation of IL6, IL8 and CCL2 gene expression was found after a 4h RPM-exposure, when the whole population was still growing adherently. MCS and AD cells were detected after 24 h on the RPM. At this time, a significantly reduced gene expression in MCS compared to 1g-controls was visible for IL6, IL8, FN1, ITGB1, LAMA1, CCL2, and TLN1. After a 72 h RPM-exposure, IL-6, IL-8, and TIMP-1 secretion rates were increased significantly. Conclusion: Normal thyrocytes form MCS within 24 h. Cytokines seem to be involved in the initiation of MCS formation via focal adhesion proteins.

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Section: Discussionmentioning

confidence: 99%

Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

Warnke

Pietsch

Kopp

et al. 2017

Cell Physiol Biochem

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“…Clinical evidence indicates a significant correlation between active STAT3 and VEGF in gastric cancer tissues (Choi et al, 2006). Targeting STAT3/VEGF signaling has been suggested as a promising strategy for anticancer treatment (Kim et al, 2015;Po_ zarowska and Po_ zarowski, 2016).…”

Section: Introductionmentioning

confidence: 99%

C‐X‐C motif chemokine receptor 4 promotes tumor angiogenesis in gastric cancer via activation of JAK2/STAT3

Zhang

Shi

et al. 2017

Cell Biology International

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C-X-C motif chemokine receptor 4 (CXCR4) overexpression promotes gastric cancer growth and metastasis. In this study, we determined its role in regulating tumor angiogenesis. We overexpressed CXCR4 in gastric cancer cells and examined the effects of conditioned medium on endothelial cell proliferation, migration, and tube formation. The effects of CXCR4 overexpression on vascular endothelial growth factor (VEGF) expression and signal transducer and activator of transcription 3 (STAT3) activation were analyzed. In vivo xenograft studies were done to confirm the role of CXCR4 in tumor angiogenesis. Conditioned medium from CXCR4-overexpressing gastric cancer cells stimulated endothelial cell proliferation, migration, and tube formation. Such effects were blocked by addition of a neutralizing anti-VEGF antibody. CXCR4 induced VEGF production and JAK2/STAT3 activation and enhanced STAT3 binding to VEGF promoter in gastric cancer cells. Delivery of a dominant negative variant of STAT3 significantly impaired CXCR4-induced upregulation of VEGF. Overexpression of CXCR4 facilitated tumor growth and angiogenesis in SGC7901 xenograft tumors, which was associated with increased levels of phospho-STAT3. CXCR4 contributes to tumor angiogenesis in gastric cancer by inducing STAT3-dependent VEGF expression and represents a promising therapeutic target for this malignancy.

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“…[47][48][49] The drugs widely used in intravitreal injection include ranibizumab, Conbercept and bevacizumab, and the primary mechanism is anti-VEGF. 50 Clinical studies found that the anti-VEGF drug ranibizumab in two-thirds of PDR or AMD patients has a good curative effect, but one-third of the cases have an uncertain outcome. 51 We investigated the suppression the proliferation, migration, and invasion of HMEC-1 cells, giving us an opportunity to explore other potential effective therapies.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous interference of SP1 and HIF1α retarding the proliferation, migration, and invasion of human microvascular endothelial cells (HMEC‐1) under hypoxia

Lin

Huang

et al. 2019

J of Cellular Biochemistry

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Objective To investigate the regulation of special protein 1 (SP1) and hypoxia‐inducible factor‐1α (HIF1α) on human microvascular endothelial cells (HMEC‐1) under hypoxic conditions. Methods The expression of SP1 and HIF1α under normoxia and hypoxic conditions were assessed by Western blot. SP1 and HIF1α were knocked down by small interfering RNA (siRNA) under hypoxic conditions. The proliferation, migration, and invasion of HMEC‐1 were measured by cell counting kit 8, 5‐ethynyl‐2′‐deoxyuridine and Transwell coculture system. Western blot analysis and Immunofluorescence were carried out to study the mechanisms of simultaneously inhibiting the adenosine triphosphatase (CD39), 5′‐nucleotidase (CD73), adenosine, and vascular endothelial growth factor (VEGF). We compared the inhibitory effects between groups concurrently interfering SP1, HIF‐1α, and ranibizumab under hypoxic conditions. Results Under hypoxic conditions, the protein expression of SP1 and HIF1α was increased in HMEC‐1, contrarily, SP1 siRNA and HIF1α siRNA downregulated the expression. Simultaneous inhibition of SP1 and HIF1α demonstrated a much greater restraint of proliferation, migration, and invasion characteristics on HMEC‐1 than respectively knocking down SP1 or HIF1α and anti‐VEGF drugs (0.5 mg/mL ranibizumab) (siRNA and the VEGF inhibitor were applied separately in different groups). Meanwhile, simultaneous inhibition of SP1 and HIF1α effectively reduced the expression of CD39, CD73, adenosine, and VEGF on HMEC‐1 under hypoxic conditions. Conclusions Our study demonstrated that both SP1 and HIF1α played important roles in HMEC‐1 under hypoxia condition. Simultaneous inhibition of SP1 and HIF1α effectively decreased the activity of HMEC‐1 under hypoxic conditions through the CD39‐CD73‐adenosine and VEGF angiogenesis pathways. Our study may provide a new approach to the treatment of retinal neovascular diseases.

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The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy

Cited by 75 publications

References 58 publications

Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

C‐X‐C motif chemokine receptor 4 promotes tumor angiogenesis in gastric cancer via activation of JAK2/STAT3

Simultaneous interference of SP1 and HIF1α retarding the proliferation, migration, and invasion of human microvascular endothelial cells (HMEC‐1) under hypoxia

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