Specific Enhancement of Vascular Endothelial Growth Factor (VEGF) Production in Ischemic Region by Alprostadil — Potential Therapeutic Application in Pharmaceutical Regenerative Medicine

Inoue, Hajime; Aihara, Masaki; Tomioka, Miyuki; Watabe, Yuichi

doi:10.1254/jphs.13033sc

Cited by 7 publications

(8 citation statements)

References 11 publications

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“…When an endothelial cell is damaged following hypoxic conditions, an MR contrast agent can extravagate, leading to the accumulation of contrast agent in the tumor tissue that causes abnormal enhancement. Thus, neovascular permeability is associated with the enhancement degree of gliomas [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Vascular endothelial growth factor (VEGF) is a well-known tumor-related biomarker that regulates pathological angiogenesis [ 9 ]. In vivo, VEGF expression promotes angiogenesis and the permeabilization of blood vessels, which is associated with the degree of enhancement in gliomas [ 10 ]. VEGF can also serve as an independent indicator for the prognosis of patients with liver cancer [ 11 ], breast cancer [ 12 , 13 ] and gastric cancer [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Wang

et al. 2015

PLoS ONE

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Contrast enhancement is a crucial radiologic feature of malignant brain tumors, which are associated with genetic changes of the tumor. The purpose of the current study was to investigate the potential relationship among tumor contrast enhancement with MR imaging, vascular endothelial growth factor (VEGF) expression, and survival outcome in anaplastic gliomas. MR images from 240 patients with histologically confirmed anaplastic gliomas were retrospectively analyzed. The volumes of T2 hyperintense, contrast enhanced regions and necrotic regions on postcontrast T1-weighted images were measured. The ratio of the enhanced volume to necrotic volume was compared between patients with high versus low levels of VEGF expression and was further used in the survival analysis. The volumetric ratio of enhancement to necrosis was significantly higher in patients with low VEGF expression than in those with high VEGF expression (Mann-Whitney, p = 0.009). In addition, the enhancement/necrosis ratio was identified as a significant predictor of progression-free survival (Cox regression model, p = 0.004) and overall survival (Cox regression model, p = 0.006) in the multivariate analysis. These results suggest that the volumetric ratio of enhancement to necrosis could serve as a noninvasive radiographic marker associated with VEGF expression and that this ratio is an independent predictor for progression-free survival and overall survival in patients with anaplastic gliomas.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Wang

et al. 2015

PLoS ONE

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“…For example, PGE 1 is reported to be effective for treating patients with severe hepatitis and primary graft non-function after liver transplantation (Andrade Jr, Andrade & Santos, 2009). Moreover, it is reported that PGE 1 is a potent stimulator of angiogenesis via upregulation of VEGF expression (Haider et al, 2005; Inoue et al, 2013; Mehrabi et al, 2003). However, the molecular mechanisms behind the phenomena are as yet largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E₁in vascular-derived cells under non-hypoxic conditions

Suzuki

Nishi

Takabuchi

et al. 2013

PeerJ

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Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil, has vasodilatory properties and is used widely in various clinical settings. In addition to acute vasodilatory properties, PGE1 may exert beneficial effects by altering protein expression of vascular cells. PGE1 is reported to be a potent stimulator of angiogenesis via upregulation of VEGF expression, which is under the control of the transcription factor hypoxia-inducible factor 1 (HIF-1). However, the molecular mechanisms behind the phenomenon are largely unknown. In the present study, we investigated the mechanism by which PGE1 induces HIF-1 activation and VEGF gene expression in human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs), both vascular-derived cells. HUVECs and HASMCs were treated with PGE1 at clinically relevant concentrations under 20% O2 conditions and HIF-1 protein expression was investigated. Expression of HIF- 1α protein and the HIF-1-downstream genes were low under 20% O2 conditions and increased in response to PGE1 treatment in both HUVECs and HASMCs in a dose- and time-dependent manner under 20% O2 conditions as comparable to exposure to 1% O2 conditions. Studies using EP-receptor-specific agonists and antagonists revealed that EP1 and EP3 are critical to PGE1-induced HIF-1 activation. In vitro vascular permeability assays using HUVECs indicated that PGE1 increased vascular permeability in HUVECs. Thus, we demonstrate that PGE1 induces HIF- 1α protein expression and HIF-1 activation under non-hypoxic conditions and also provide evidence that the activity of multiple signal transduction pathways downstream of EP1 and EP3 receptors is required for HIF-1 activation.

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“…Prostaglandin E1 is known to mediate vasodilation and improve microcirculation perfusion. 11,12 Recently, PGE1 has been reported to stimulate fibroblast proliferation. 13 Vitamin C is also well-known for promoting fibroblast production.…”

mentioning

confidence: 99%

Tracking and Increasing Viability of Topically Injected Fibroblasts Suspended in Hyaluronic Acid Filler

You

Namgoong²,

Rhee³

et al. 2016

Journal of Craniofacial Surgery

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A new injectable tissue-engineered soft tissue consisting of a mixture of hyaluronic acid (HA) filler and cultured human fibroblasts have been developed by the authors. To establish this method as a standard treatment, a further study was required to determine whether the injected fibroblasts could stay at the injected place or move to other sites. In addition, effective strategies were needed to increase viability of the injected fibroblasts. The purpose of this study was to track the injected fibroblasts and to determine the effect of adding prostaglandin E1 (PGE1) or vitamin C on the viability of fibroblasts.Human fibroblasts labeled with fluorescence dye were suspended in HA filler and injected into 4 sites on the back of nude mice. The injected bioimplants consisted of one of the 4 followings: HA filler without cells (HA group), fibroblasts suspended in HA filler (HA þ FB group), PGE1-supplemented fibroblasts in HA filler (HA þ FB þ PGE1 group), and vitamin C-supplemented fibroblasts in HA filler (HA þ FB þ VC group). At 4 weeks after injection, locations and intensities of the fluorescence signals were evaluated using a live imaging system.The fluorescence signals of the fibroblast-containing groups were visible only at the injected sites without dispersing to other sites. The HA þFB þ PGE1 group showed a significantly higher fluorescence signal than the HA þ FB and the HA þ FB þVC groups (P < 0.05, each). There was no statistical difference between the HA þ FB and HA þ FB þVC groups (P ¼ 0.69).The results of the current study collectively suggest that injected fibroblasts suspended in HA filler stay at the injected place without moving to other sites. In addition, PGE1 treatment may increase the remaining rhodamine B isothiocynanate dye at the injected site of the human dermal fibroblasts.F or correction of facial wrinkles or soft-tissue augmentation, a number of commercially prepared injectable fillers have been developed. 1-4 Currently, soft-tissue filler products based on hyaluronic acid (HA) are widely used, because they have a low potential for allergic reactions, require no skin testing, can be stored at room temperature, and have no risk of bovine spongiform encephalopathy unlike collagen. Although HA fillers have shown to be relatively safe and convenient to administrate, their variable degrees of resorption require repeated injections. To overcome these drawbacks, the authors created a new injectable filler consisting of a mixture of HA filler and living cultured human fibroblasts. 5,6 The results of our previous experimental and clinical studies showed that cultured human dermal fibroblasts mixed into HA filler can produce human dermal matrices with extended in vivo stability and may have a potential to be used as a long-lasting injectable soft-tissue filler. To establish this method as a standard treatment, a further study, however, is required to determine whether the fibroblasts could stay at the injected place or move to other sites through examination of the location, distribution, and long-...

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Specific Enhancement of Vascular Endothelial Growth Factor (VEGF) Production in Ischemic Region by Alprostadil — Potential Therapeutic Application in Pharmaceutical Regenerative Medicine

Cited by 7 publications

References 11 publications

Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E₁in vascular-derived cells under non-hypoxic conditions

Tracking and Increasing Viability of Topically Injected Fibroblasts Suspended in Hyaluronic Acid Filler

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Specific Enhancement of Vascular Endothelial Growth Factor (VEGF) Production in Ischemic Region by Alprostadil — Potential Therapeutic Application in Pharmaceutical Regenerative Medicine

Cited by 7 publications

References 11 publications

Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E1in vascular-derived cells under non-hypoxic conditions

Tracking and Increasing Viability of Topically Injected Fibroblasts Suspended in Hyaluronic Acid Filler

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Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E₁in vascular-derived cells under non-hypoxic conditions