Aqueous vascular endothelial growth factor and clinical outcomes correlation after single intravitreal injection of bevacizumab in patients with neovascular age-related macular degeneration

Cabral, Thiago; Lima, Luiz H.; Polido, Júlia; Duong, Jimmy; Okuda, Erika Araki; Oshima, Akiyoshi; Serracarbassa, Pedro Durães; Regatieri, Caio V.; Belfort, Rubens

doi:10.1186/s40942-017-0066-y

Cited by 17 publications

(14 citation statements)

References 34 publications

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“…The vascular endothelial growth factor sub-family, which includes five members (VEGF-A, -B, -C and -D, and PlGF), is the main target investigated in ocular angiogenesis, and part of platelet-derived growth factor family. VEGF-A is well established as an important factor contributing to neovascularization, and current anti-VEGF therapies focus on this form [ 7 , 22 ]. However, other members of VEGF family also influence angiogenesis and have been recently investigated [ 5 ].…”

Section: Resultsmentioning

confidence: 99%

Retinal and choroidal angiogenesis: a review of new targets

et al. 2017

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Retinal and choroidal neovascularization are a major cause of significant visual impairment, worldwide. Understanding the various factors involved in the accompanying physiopathology is vital for development of novel treatments, and most important, for preserving patient vision. The intraocular use of anti-vascular endothelial growth factor therapeutics has improved management of the retinal and choroidal neovascularization but some patients do not respond, suggesting other vascular mediators may also contribute to ocular angiogenesis. Several recent studies examined possible new targets for future anti-angiogenic therapies. Potential targets of retinal and choroidal neovascularization therapy include members of the platelet-derived growth factor family, vascular endothelial growth factor sub-family, epidermal growth factor family, fibroblast growth factor family, transforming growth factor-β superfamily (TGF-β1, activins, follistatin and bone morphogenetic proteins), angiopoietin-like family, galectins family, integrin superfamily, as well as pigment epithelium derived factor, hepatocyte growth factor, angiopoietins, endothelins, hypoxia-inducible factors, insulin-like growth factors, cytokines, matrix metalloproteinases and their inhibitors and glycosylation proteins. This review highlights current antiangiogenic therapies under development, and discusses future retinal and choroidal pro- and anti-angiogenic targets as wells as the importance of developing of new drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40942-017-0084-9) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Retinal and choroidal angiogenesis: a review of new targets

et al. 2017

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“…However, repeated intravitreal injections of anti-VEGF drugs (e.g., ranibizumab, bevacizumab) increase the risk of side effects, which have a high clinical cost [10, 11]. With an efficiency of 60%-70% and disease progression still occurring in some patients receiving anti-VEGF treatment, the retinal VEGF levels are still not altered [12]. Thus, there may be other causative agents affecting VEGF expression in CNV…”

Section: Introductionmentioning

confidence: 99%

Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells

Sun¹,

Cai²,

Liu³

2017

Cell Physiol Biochem

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Background/Aims: The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells. Methods: D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002). The anti-proliferative effect of celecoxib was assessed using the MTT assay. RT-PCR, Western blotting and ELISA were performed to detect the levels of PI3K, phosphorylated AKT (p-AKT), HIF-1α, VEGF and COX-2. Results: Celecoxib inhibited the proliferation of RPE cells in a dose-dependent manner. Celecoxib suppressed the expression of VEGF at both the mRNA and protein levels and decreased HIF-1α protein expression. HIF-1α activation was regulated by the PI3K/AKT pathway. The celecoxib-induced down-regulation of HIF-1α and VEGF required the suppression of the hypoxia-induced PI3K/AKT pathway. However, the down-regulation of COX-2 did not occur in cells treated with celecoxib. Conclusions: The antiangiogenic effects of celecoxib in RPE cells under hypoxic conditions resulted from the inhibition of HIF-1α and VEGF expression, which may be partly mediated by a COX-2-independent, PI3K/AKT-dependent pathway.

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“…Uveal melanoma (UM) accounts for only <5% of all melanomas 1 and first-line UM treatment options currently include surgical enucleation and plaque brachytherapy, which show effective local tumor control. 2 3 Therefore, there is renewed interest in treating UM with a focus on functional outcomes, such as retaining visual function and preserving the eye without causing adverse side effects. Moreover, although UM is a rare disease and treatment options are successful in removing early-stage UM, the prognosis of patients with UM is poor, with nearly 50% of patients with UM developing metastatic disease.…”

Section: Introductionmentioning

confidence: 99%

In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis

Kim

Nam

et al. 2021

J Immunother Cancer

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BackgroundUveal melanoma (UM) is the most frequent intraocular malignancy and is resistant to immunotherapy. Nearly 50% of patients with UM develop metastatic disease, and the overall survival outcome remains very poor. Therefore, a treatment regimen that simultaneously targets primary UM and prevents metastasis is needed. Here, we suggest an immunotherapeutic strategy for UM involving a combination of local photodynamic therapy (PDT), rho-kinase (ROCK) inhibitor, and PD-1/PD-L1 immune checkpoint blockade.MethodsThe antitumor efficacy and immune response of monotreatment or combinational treatment were evaluated in B16F10-bearing syngeneic mouse models. Abscopal antitumor immune responses induced by triple-combinational treatment were validated in syngeneic bilateral B16F10 models. After each treatment, the immune profiles and functional examinations were assessed in tumors and tumor draining lymph nodes by flow cytometry, ELISA, and immunofluorescence assays. In orthotopic intraocular melanoma models, the location of the immune infiltrate in the tumor microenvironment (TME) was evaluated after each treatment by multiplex immunohistochemistry and metastatic nodules were monitored.ResultsPDT with Ce6-embedded nanophotosensitizer (FIC-PDT) elicited immunogenic cell death and stimulated antigen-presenting cells. In situ immunogenic clearance induced by a combination of FIC-PDT with ripasudil, a clinically approved ROCK inhibitor, stimulated antigen-presenting cells, which in turn primed tumor-specific cytotoxic T cells. Moreover, local immunogenic clearance sensitized PD-1/PD-L1 immune checkpoint blockade responses to reconstruct the TME immune phenotypes of cold tumors into hot tumors, resulting in recruitment of robust cytotoxic CD8+ T cells in the TME, propagation of systemic antitumor immunity to mediate abscopal effects, and prolonged survival. In an immune-privileged orthotopic intraocular melanoma model, even low-dose FIC-PDT and ripasudil combined with anti-PD-L1 antibody reduced the primary tumor burden and prevented metastasis.ConclusionsA combination of localized FIC-PDT and a ROCK inhibitor exerted a cancer vaccine-like function. Immunogenic clearance led to the trafficking of CD8+ T cells into the primary tumor site and sensitized the immune checkpoint blockade response to evoke systemic antitumor immunity to inhibit metastasis, one of the major challenges in UM therapy. Thus, immunogenic clearance induced by FIC-PDT and ROCK inhibitor combined with anti-PD-L1 antibody could be a potent immunotherapeutic strategy for UM.

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Aqueous vascular endothelial growth factor and clinical outcomes correlation after single intravitreal injection of bevacizumab in patients with neovascular age-related macular degeneration

Cited by 17 publications

References 34 publications

Retinal and choroidal angiogenesis: a review of new targets

Retinal and choroidal angiogenesis: a review of new targets

Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells

In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis

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