• BMB Reports
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• v.53 no.11
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• pp.600-604
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• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

• Molecules and Cells
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• v.38 no.3
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• pp.273-278
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• 2015

The induction of angiogenesis is a crucial step in tumor progression, and therefore, efficient inhibition of angiogenesis is considered a powerful strategy for the treatment of cancer. In the present study, we report that the lipophilic antimicrobial peptides from EML-CAP3, a new endophytic bacterial strain isolated from red pepper leaf (Capsicum annuum L.), exhibit potent antiangiogenic activity both in vitro and in vivo. The newly obtained antimicrobial peptides effectively inhibited the proliferation of human umbilical vein endothelial cells at subtoxic doses. Furthermore, the peptides suppressed the in vitro characteristics of angiogenesis such as endothelial cell invasion and tube formation stimulated by vascular endothelial growth factor, as well as neovascularization of the chorioallantoic membrane of growing chick embryos in vivo without showing cytotoxicity. Notably, the angiostatic peptides blocked tumor cell-induced angiogenesis by suppressing the expression levels of hypoxia-inducible $factor-1{\alpha}$ and its target gene, vascular endothelial growth factor (VEGF). To our knowledge, our findings demonstrate for the first time that the antimicrobial peptides from EML-CAP3 possess antiangiogenic potential and may thus be used for the treatment of hypervascularized tumors.

• Journal of Veterinary Clinics
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• v.32 no.1
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• pp.108-111
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• 2015

A 7-month-old intact male Maltese dog was presented with a 1.5-month history of glaucoma in the right eye (OD). Ophthalmic examinations revealed a corneal perforation with iris entrapment, corneal edema and neovascularization, and buphthalmos OD. Intraocular pressures were 33 mmHg OD and 19 mmHg in left eye (OS). The right eye was diagnosed with chronic glaucoma and corneal perforation with iris entrapment. Now that the eye was blind, implantation of intraocular silicone prosthesis (ISP) and conjunctival flap were elected to salvage the globe. The corneal perforation healed with the conjunctival pedicle flap and the cornea accommodated the ISP properly. A satisfactory cosmetic result was achieved without complications in the 15 months following the procedure. Therefore, this case report indicates the combined an ISP and a conjunctival flap would be an alternative for the treatment of glaucoma associated with corneal perforation in dogs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3415-3418
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• 2014

Background: AKAP12 inhibits oncogenic proliferation, invasion, chemotaxis and neovascularization. Bcl-2 and p53 are two important apoptotic markers that play roles in apoptotic processes. It has been found that AKAP12 blocks the cell cycle and induces apoptosis in fibrosarcoma cells. In our study we assessed the relationship of AKAP12 with apoptotic markers, Bcl-2 and p53. Materials and Methods: Our study included 45 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection. AKAP 12, Bcl-2, and p53 expression was examined by immunohistochemistry. Results: A total of 45 colorectal adenocarcinoma patients - 17 (37.8%) females and 28 (62.2%) males - were included in this study. AKAP12 expression was found to be negative in 8 patients (17.8%), and positive in 37 patients (82.2%). Bcl-2 was found positive in 6 patients (13.3%) and p53 in 29 patients (55.6%). AKAP12 expression had no significant relation with Bcl-2 and p53 expression (p:0.939, p:0.079, respectively). Conclusions: Although various studies have pointed to apoptotic activity of AKAP12, the literature is limited regarding relations with p53 or Bcl-2 expression. In the present study, we found no relation in colorectal carcinomas.

• Archives of Reconstructive Microsurgery
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• v.11 no.2
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• pp.125-134
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• 2002

This study was designed to investigate the process of re- or neo-vascularization in the prefabricated cutaneous flap using a skeletonized arteriovenous pedicle implantation. Fourty-eight flaps were divided into six groups of eight flaps, including control group of the conventional epigastric flap. In experimental groups, skin flap was fabricated by subcutaneous implantation of a distally ligated saphenous arteriovenous pedicle in left abdomen. At 2, 4, 6, 8, and 10 weeks after, prefabricated flap was elevated as an island flap based on implanted pedicle and sutured back in place. Three days after flap repositioning, the area of flap viability was quantified, the pattern of flap vascularization was evaluated with microangiography, and the quantification of vessels was assessed histologically. There were statistically significant differences in flap viability between group 2, 3, 4, and the control (p<0.05), with increased survival area in order. But Group 5 and 6 showed higher flap viability as much as the control did. In the microangiographis study, numerous small meander vessels were newly developed in the vicinity of the implanted pedicle just only 2 weeks after pedicle implantation, but neovascularization around the tip of implanted pedicle, and its anastomosis with native vasculatures was more important for overall flap survival, which was usually developed at least 4 weeks after pedicle implantation. Histologically, vessels are evenly spread over all layers of the flap at 6 weeks after pedicle implantation. The quantification of vessels was correlated well with the improvement of flap viability (p<0.05). In conclusion, neo- and re-vascularization around the tip of implanted pedicle was an important factor for overall survival of the prefabricated flap. Therefore, skeletonized pure vascular pedicle transfer, even though it used alone without surrounding was sufficient to get higher flap viability. The optimal duration of pedicle implantation was8 weeks to obtain maximal survival.

• Development and Reproduction
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• v.11 no.3
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• pp.253-261
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• 2007

Lactadherin is a glycoprotein of human milk fat globule membrane that binds to mucin and butyrophilin forming the protein complex. Especially, mucin and lactadherin in human milk efficiently protect infants with poor immune functions right after birth from infections by microorganisms and play important roles for their early survival, growth and development. Lactadherin inhibits the propagation and growth of rotavirus that is a global pathogen causing infants' diarrhea. Recently this protein was known to promote neovascularization and its deficiency related to develop Alzheimer's disease. In this study, the basic biochemical and physiological aspects of lactadherin were investigated. Messenger RNAs were isolated from mammary tissues from Korean women patients to clone a 1.2 kb cDNA and sequenced its DNA to determine its amino acid sequences. The cDNA was cloned to express its 43 kD protein in E. coli, which was confirmed by Western blot. The recombinant protein was purified and injected to 2 rabbits to raise antibodies against it. The semi-purified milk fat globule membrane proteins from Korean women was analyzed by Western blot using the rabbit antibody to give 70, 55, 46, 30 kD bands. Also several polymorphism and SNPs of lactadherin gene from Korean women were observed compared with those of Caucasian women.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.191-198
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• 1998

Objectives: We performed an immunohistochemical study to examine the place of neovascularization in the tumorigenic process of follicular thyroid carcinoma and to determine whether tumor angiogenic activity in follicular carcinoma plays a role in tumor aggression. Materials & Methods: We studied 63 follicular thyroid carcinomas and compared with 22 follicular adenomas. The areas of capsular invasion, vascular invasion and cellular atypism of the tumor were confimed on H & E stains. The paraffin embedded tissues were stained by the use of monoclonal antibodies against Ag CD34. Microvesseles were counted in the area of highest vascular density at 200 times magnification. The microvessel densities(MVD) were analized in relation to histologic type and location of the tumors. Results: There were 59 minimal invasive types and 4 widely invasive types of carcinoma. In the histologic specimens of carcinomas, capsular invasion was identified in all the cases, vascular invasion in 46 and cellular atypism in 24. Mean values of the MVDs of the minimal invasive carcinomas, the widely invasive carcinomas and the adenomas were $263.8{\pm}69.2,\;256.l{\pm}49.3\;and\;241.5{\pm}159.4$, respectively and there was no significant difference between each group. In follicular carcinomas, there was a regional difference of the MVDs. The areas of tumor showing cellular atypism and adjacent to or penetrating the capsule, in which represents the tumorigenic process of carcinoma, had a higher rate of vascularization, than other areas of the tumor(p<0.05). However, these features were not noted in the follicular adenomas. Conclusion: Although there was no significant difference of the MVD between follicular carcinomas and adenomas, there was a regional difference of the MVD within the carcinomas and the values were significantly higher in the more malignant areas, as indicated by cellular atypism and capsular invasion. Therefore, tumor angiogenic activity measured by MVD may play a role in tumor aggression in follicular thyroid carcinoma.

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.645-652
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• 1999

The purpose of the present study was to investigate the effect of bovine amniotic membrane grafts on healing of full-thickness skin wound in dogs. Two $3cm{\times}3cm$ area-matched full-thickness skin wounds were induced bilaterally on the dorsolateral aspect of the trunk of 15 dogs. Chlorhexidine-treated amnion, dried amnion, silver sulfadiazine and 0.9% sterile saline solution were applied on the wound area and examined grossly and histopathologically. Begining 14 days after wounding, amnion applied group had appreciably less amount of inflammatory exudate and hemorrhage than sulfadiazine and saline treated groups. From 14 days after wounding, the degree of wound contraction in amnion groups, especially in the dried amnion group was greater than that of the sulfadiazine and saline treated groups. The percentages of wounds completely healed on 28 days after wounding in saline treated group, chlorhexidine-treated amnion group, dried amnion group and sulfadiazine treated group were 33%, 50%, 83% and 50%, respectively. Microscopically neovascularization and fibrosis were first noticed on 5 days after wounding in the dried amnion group and sulfadiazine treated group, on 7 days in the chlorhexidine-treated amnion group and on 14 days in the saline treated group. Epithelialization in the dried amnion and sulfadiazine treated groups was first noticed on 9 days after wounding, which was faster than that in the other groups. The present study suggests that bovine amniotic membrane, especially dried bovine amnion is effective on healing of full-thickness skin wound in dogs through both wound contraction and epithelialization.

• Advances in pediatric surgery
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• v.8 no.2
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• pp.101-106
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• 2002

The antiangiogenic effects of novel agent KJ3, Betulinic acid, and Fumagillin on the neovascularization were studied by examining ultrastructural alterations in the vasculature of synthetic gelform and mouse neuroblastoma C1300. Small pieces of gelform with 0.4% agar were introduced subcutaneously (s.c.) in 7 week old male CH3/HeJ mice. After the $LD_{50}s$ were determined by FACS analysis, a third of $LD_{50}$ of three drugs were injected either locally or intraperitoneally every other day for 14 days. A/J mice were inoculated s.c. with the C1300 neuroblastoma cell line, then either saline or three drugs were injected in the same manner. The antiangiogenic effects of three drugs were studied by measuring the histologic changes in tumors, and immunostaining for CD34, VIII/vWF, CD105, and thymidine phosphorylase. In the drug treated groups, the number of vessels in gelform experiments and C1300 neuroblastoma experiments were lower than the corresponding values in the control. The histologic findings were significantly different in drug treated groups on day 7, but these were not significant on day 14. These results imply that antiangiogenic agents were effective when the tumor burden is minimal.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.171-180
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• 2005

Background & Objective : Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine whether Puerariae radix could induce angiogenic activity in human umbilical vein endothelial cells (HUVECs). Methods: The angiogenic activity of Puerariae radix were evaluated by using BrdU assay, chemotactic migration assay, tube formation assay, measurement of bFGF in HUVECs, and Matrigel plug assay in mice. Results : Puerariae radix significantly increased HUVECs proliferation in a dose-dependent manner. In addition, Puerariae radix increased migration and tube-like formation in HUVECs. Interestingly,the expression of basic fibroblast growth factor (bFGF), an angiogenesis-stimulating growth factor, was dose-dependently increased by Puerariae radix. The angiogenic activity of Puerariae radix was confirmed using an in vivo Matrigel angiogenesis model, showing promotion of blood vessel formation. Conclusion : Puerariae radix significantly induces angiogenesis in vitro and in vivo. These results suggest that Puerariae radix is a potent angiogenic agent, and a promising drug, for the induction of neovascularization.