• Journal of Yeungnam Medical Science
• /
• v.23 no.1
• /
• pp.10-18
• /
• 2006

Epithelial to mesenchymal transition (EMT) is an important etiologic factor for the development of peritoneal fibrosis in CAPD patients. Mesothelial cells are main source of trans-differentiated fibroblasts under stress from the bioincompatible peritoneal dialysate. In our study there was no difference in dialysate TGF-${\beta}$ and VEGF between the low and high GDP groups during an initial 12 months. However, after adjusting with D-CA125, the low GDPs group showed a significantly lower D-TGF-${\beta}$/D-CA125 and D-VEGF/CA125 during the initial 12 months. Among the adjusted peritoneal growth factors for CA125, VEGF/CA125 and TGF-b/CA125 were factors significantly associated with greater EMT in this study. Adjustment of the peritoneal growth factor for effluent CA125 (surrogate for mass of HPMCs) revealed significant association with EMT suggesting that the fibroblastoid transition from HPMCs could be affected by the amount of intraperitoneal growth factors (TGF-b, VEGF) per unit mass of HPMCs. There was significant improvement in both cell score and D-CA125 at the sixth and 12th months after switching from a high GDPs solution to a low GDPs solution. Use of icodextrin solution in patients who had average peritoneal transport showed not only better systemic effects such as decreased glucose absorption via dialysate but also preservation of the peritoneum, including less EMT and high mesothelial bulk mass. In conclusion, Therapy with low GDP solution including icodextrin may positively impact preservation of the peritoneal membrane integrity and prevention of peritoneal fibrosis with time on PD.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.3
• /
• pp.2053-2058
• /
• 2013

Background: Formation of new blood vessels is necessary for the development and spread of neoplasms more than 1 mm3 in volume, angiogenesis being responsible for formation of new from pre-existing blood vessels. Vascular endothelial growth factor (VEGF) is pivotal and the best studied angiogenic factor in all human cancers. Therefore we designed this study to investigate the role of VEGF-A and VEGF-C in prostate cancer in comparison with BPH controls in a north Indian population. Methods: In this case-control study a total of 100 subjects were included on the basis of confirmed histopathological reports, out of which 50 were prostate cancer patients and the other 50 were BPH patients with PSA levels >2 ng/ml and abnormal digital rectal examination (DRE) findings during September 2009 to August 2011 from the Department of Urology, KGMU, Lucknow, India. Plasma levels of VEGF were determined using quantitative immunoassay (ELISA-enzyme linked immunosorbent assay). Statistical analysis was carried out using SPSS 15.0 version. Results: The mean age of prostate cancer ($67.6{\pm}5.72$) patients was significantly higher (p=0.005) than BPH ($63.6{\pm}7.92$) patients. Expression of VEGF-A was not significantly higher in disease stage C1 than D1 or D2 and A or B (p=0.13) while the level of VEGF-A was significantly higher (p=0.04) in prostate cancer as compared to BPH subjects (PCa=13.0 pg/ml, BPH=6.8 pg/ml). Levels of VEGF-C were similar in both groups (PCa=832.6 pg/ml, BPH=823.7 pg/ml). In ROC curve, the area under curve (AUC) was 0.70 (95%CI: 0.60-0.80) and the cut-off value for which a higher proportion of patients was correctly classified (20%) was 26.0 pg/mL. Conclusion: Although VEGF-A is increased in cancer prostate patients a statistically significant correlation could not be established in this study. VEGF-C was not found to be a useful biomarker.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.42 no.4
• /
• pp.329-336
• /
• 2016

Cutaneous microvasculature plays a critical role in age-associated skin changes. A considerable reduction of number and size of vessels has been observed in the upper dermis of elderly skin. Forsythiae fructus (FF), the dried fruit of plant Forsythia suspensa (F. suspensa), has been traditionally used as an herbal medicine to treat inflammatory diseases and bacterial diseases. However, its regulatory effect on angiogenic responses has not been elucidated in skin. Therefore, we analyzed secretory profiles upon treatment of FF extract using array designed to detect angiogenesis-associated mediators in human keratinocytes. Because keratinocyte-derived VEGF (vascular endothelial growth factor) has been regarded as a potent factor for new microvasculature under the epidermis, we further investigated the effect of FF extract on VEGF production. We observed that the VEGF expression of mRNA and protein level was increased by about 2 folds in a dose-dependent manner after FF extract treatment. In signaling experiments, FF extract induced rapid p38 MAPK activation within 5 min, and the activation was totally abrogated by pretreatment with a p38 MAPK specific inhibitor. The FF-induced VEGF upregulation was also significantly attenuated by a p38 MAPK inhibition. Taken together, FF extract induces VEGF production via p38 MAPK activation in human epidermal keratinocytes. These novel findings suggest that FF is useful as a potential agent with pro-angiogenic activity and may help to improve age-dependent reduction of the microvasculature in aged skin or to heal skin wound.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.31 no.5
• /
• pp.363-369
• /
• 2005

Purpose: To determine the role of Insulin-like Growth Factor-I (IGF-I) in the regulation of Vascular Endothelial Growth Factor (VEGF) expression in MG-63 cells and then to find the mechanism b which this regulation occurs. Materials and methods: MG-63 cells were grown to confluence in 60-mm dishes. To determine the effects of IGF-I on expression of VEGF mRNA according to time and concentration, the cells were treated with 10 nM IGF-I, following isolation of total RNA and Northern blot analysis after 1, 2, 4, 8, 12, 24 hours and after 2 hours of treatment with 0.5, 2, 10, 25, 50 nM IGF-I respectively, isolation of total RNA and Northern blot analysis were followed. To determine the mechanism of action of IGF-I, inhibitors such as hydroxyurea $(76.1\;{\mu}g/ml)$, actinomycin D $(2.5\;{\mu}g/ml)$, cycloheximide $(10\;{\mu}g/ml)$ were added 1 hour after treatment of 10 nM IGF-I. Results: 1. the expression of VEGF mRNA was increased with treatment of IGF-I. 2. The expression of VEGF mRNA was increased according to time-and concentration dependent manner of IGF-I. 3. The effect of IGF-I was decreased by hydroxyuera, actinomycin D, but not by cycloheximide. Conclusion: IGF-I regulate the expression of VEGF mRNA in the level of DNA synthesis and transcription. These results could suggest that IGF-I plays an important role in angiogenesis in the process of new bone formation and remodeling.

• Clinical and Experimental Reproductive Medicine
• /
• v.34 no.1
• /
• pp.33-39
• /
• 2007

Objective: The objective of this study was to investigate whether serum levels of vascular endothelial growth factor (VEGF) measured at ovulation triggering day reflect ovarian response in intrauterine insemination (IUI) cycles. Methods: Forty-nine fertile women who undergoing superovulation and IUI were included. Superovulation was performed using clomiphene citrate (100 mg/d on day 3$\sim$7) in combination with human menopausal gonadotropin (150 IU every other day starting on day 5). Serum samples were obtained on the day of hCG administration and the levels of VEGF-A and estradiol were measured. The numbers of mature follicle $\geq$17 mm in diameter were also counted. Results: Serum VEGF-A levels did not correlate with the numbers of mature follicle count nor serum estradiol levels. Serum estradiol level was positively associated with mature follicle count. Serum VEGF-A levels tended to be lower in women with mature follicle count less than three or women with more than five. Conclusion: Our results indicate that serum VEGF-A levels do not have an association with superovulation outcome in IUI cycles. However, a tendency of lower VEGF-A level in poor and high responder suggests that those with extreme response to superovulation may be related with abnormal angiogenesis. Further studies should be warranted in larger populations.

• Clinical and Experimental Reproductive Medicine
• /
• v.31 no.4
• /
• pp.235-244
• /
• 2004

Objective: The effects on spermatogenesis by expression of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were investigated. Materials and Methods: Testicular specimens were obtained from 40 infertile males due to primary testicular failure and from 10 fertile males with other urologic problems. The specimens of infertile males were devided into 4 groups according to histologic findings; Sertoli cell only syndrome (A), maturation arrest (B), hypospermatogenesis (C) and sloughing and disorganization (D). VEGF and ET-1 expression were detected with immunohistochemical stain. Results: VEGF expression on Leydig cell was detected in all cases. But, VEGF expression rates on germ cell were significantly higher in infertile group B, C, D compared to that of the control group (p<0.05). ET-1 expression rates on Leydig cell was significantly lower in all infertile group compared to that of the control group (p<0.05). But, ET-1 expression rates on Sertoli cell was significantly higher in all infertile group compared to that of the control group (p>0.05). In germ cell of infertile group, LH, FSH and prolactin were significantly decreased, and estradiol is increased in positive stain group on ET-1 immunohistochemical stain (p<0.05). VEGF and ET-1 expression were not correlated mean seminiferous tubule diameter (p>0.05). Conclusions: Abnormal spermatogenesis would be reflected in VEGF expression in germ cell.

• Childhood Kidney Diseases
• /
• v.14 no.2
• /
• pp.166-173
• /
• 2010

Purpose : Genetic and clinical factors can influence the permeability of the peritoneal membrane. The peritoneal equilibration test (PET) is helpful in measuring peritoneal permeability in peritoneal dialysis (PD). We investigated the influence of genetic polymorphism of vascular endothelial growth factor (VEGF) on the PET parameters. Methods : Pediatric patients who underwent PET within 12 months of initiating PD at Seoul National University Children's Hospital and Samsung Medical Center were selected. The patients with positive history of peritonitis before PET were excluded. The VEGF -2578C/A, -14978T/C, -1154G/A, -634G/C, and +936C/T single-nucleotide polymorphisms were genotyped. Results : The mean 4-hour dialysate-to-plasma ratio for creatinine (D/P creatinine) and the mean 4-hour dialysate glucose to baseline dialysate glucose ratio (D/$D_0$ glucose) were $0.56{\pm}0.13$ and $0.43{\pm}0.11$, respectively. The patients with haplotype CTGGC showed higher 4-hour D/P creatinine ($0.67{\pm}0.12$ vs $0.50{\pm}0.09$, P=0.007) and lower 4-hour D/$D_0$ glucose ($0.35{\pm}0.12$ vs $0.47{\pm}0.08$, P=0.037) than those without haplotype CTGGC. Conclusion : The VEGF genetic polymorphism may influence the peritoneal solute transport.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.35 no.1
• /
• pp.1-12
• /
• 2013

Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

• Journal of Embryo Transfer
• /
• v.22 no.4
• /
• pp.213-218
• /
• 2007

This study was performed to investigate the effect of VEGF on in vitro maturation of porcine oocytes. The base medium for IVM, TCM-199 was supplemented with 0.6 mM cysteine, 0.91 mM pyruvate, 10 ng/ml epidermal growth factor, $75{\mu}g/ml$ kenamycin, $1{\mu}g/ml$ insulin and 10% (V/V) porcine follicular fluid (pFF) as a Group A; Group B was consists of Group A plus 5 ng/ml VEGF; Group C was consists of replacement of pFF by 10% PVA and Group D: was consists of Group C plus 5 ng/ml VEGF. 1. The maturation rate was significantly higher (p<0.05) in control and VEGF+pFF group than other two groups ($76.1{\pm}9.6,\;78.9{\pm}6.0\;vs\;60.4{\pm}14.2\;and\;58.3{\pm}14.3$, respectively). 2. Addition of VEGF without pFF showed a negative effect on oocytes maturation and about 58.26% oocytes were reached to M-II stage. 3. In the parthenogenetic development, the cleavage rate was significantly higher (p<0.05) in control and VEGF+pFF group ($73.2{\pm}1.8\;and\;64.6{\pm}1.1$, respectively) than other groups ($47.9{\pm}1.8\;and\;48.3{\pm}1.7$, respectively). 4. The blastocyst formation rate was significantly higher (p<0.05) in VEGF+pFF group ($32.6{\pm}2.4$) compared to control and other groups. 5. There was no significant difference in cell numbers (inner cell mass or trophectoderm) among these groups.

• BMB Reports
• /
• v.53 no.10
• /
• pp.533-538
• /
• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.