BACKGROUND: Distraction osteogenesis (DO) is a useful method for treating cases demanding the generation of new bone. During DO, the angiogenic activity is crucial factor in the new bone formation. The aim of this study was to detect the autocrine growth activity in the cellular components of the distracted bone with observation of the co-expression of vascular endothelial growth factor (VEGF) and its receptors following the mandibular DO. MATERIALS AND METHODS: Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in six mongrel dogs. Two animals were killed at 7, 14, and 28 days after completion of distraction, respectively. Immediately after the animals were killed, the right mandibles were harvested en block. Immunohistochemical staining was processed for observation of the VEGF expression, and double immunofluorescent staining was also processed for detection of the co-expression of osteocalcin and VEGF's two distinct receptors (VEGFR-1 and VEGFR-2). RESULTS: At 7 and 14 days after distraction, the expressions of VEGF were significantly increased in the osteogenic cells of the distracted bone. Up to 28 days after distraction, VEGF was still expressed moderate in the osteoblastic cells of distracted bone. The co-expressions of osteocalcin / VEGFR-1 and osteocalcin / VEGFR-2 were observed in the distracted bone at 7 and 14 days after distraction. In the double immunofluorescent staining, the co-expression's level of osteocalcin / VEGFR-1 was more than that of osteocalcin / VEGFR-2. Conclusion: Taken together, this study suggested that VEGF plays an important role in the osteogenesis, and these osteoblastic cell-derived VEGF might act as autocrine growth factor during distraction osteogenesis. In the other word, the cellular components, such as osteoblasts and immature fibroblast-like cellsor mesenchymal cells in the distracted bone, might have autocrine growth activity during distraction osteogenesis.
Animals ; Dogs ; Mandible ; Osteoblasts ; Osteocalcin ; Osteogenesis ; Osteogenesis, Distraction* ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2

OBJECTIVES: Vascular endothelial growth factor(VEGF), one of potent cytokines, and its receptors were related with various biological functions and pathological conditions. The purpose of this study was to investigate the changes of serum level of free VEGF, soluble VEGFR-1, and soluble VEGFR-2 after treatment with atypical antipsychotic drug in schizophrenia. METHOD: The schizophrenic patients were diagnosed with DSM-IV and were prospectively followed up for 4 and 8 weeks. Thirteen schizophrenic patients were evaluated their clinical assessment with serum levels of free VEGF, sVEGFR-1, sVEGFR-2, and positive and negative symptom scale(PANSS) at baseline, 4 weeks, and 8 weeks after treatment with atypical antipsychotic drug. Thirteen normal control subjects were recruited and matched with the patient group by age and sex. RESULT: The serum level of free VEGF(295.2+/-43.7pg/ml)and sVEGFR-2(8259+/-336.7) at baseline(before treatment) in schizophrenic patients were not significantly different, compared with the control group(199.0+/-28.8 and 8481+/-371.9) respectively. However, the serum level of sVEGFR-1(86.2+/-10.3, p<0.05) was significantly increased in the schizophrenic patients compared with the control group(59.0+/-6.4). After treatment with antipsychotic drug, the serum levels of free VEGF at 4 weeks(338.9+/-56.5) and 8 weeks(309.5+/-58.7) were not significantly, different compared with baseline. But the serum levels of sVEGFR-1 was significantly decreased at 8 weeks(57.3+/-6.3, p<0.05) after antipsychotic drug treatment. The serum levels of sVEGFR-2 were decreased at 4 weeks(7761+/-403.0, p<0.05) and 8 weeks(7435+/-333.5, p<0.05) compared with baseline. CONCLUSION: The decreased serum level of sVEGFR-1 and sVEGFR-2 might be affected by dopaminergic system which was influenced by antipsychotic drug.
Cytokines ; Diagnostic and Statistical Manual of Mental Disorders ; Dopamine ; Humans ; Prospective Studies ; Schizophrenia* ; Vascular Endothelial Growth Factor A* ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2

Vascular endothelial growth factor (VEGF) exerts its biological functions by its specific VEGF receptors (VEGFRs), which includes VEGFR-1, VEGFR-2, VEGFR-3, neuropilin-1 and neuropilin-2. These VEGF receptors not only distribute in endothelial cells, but also in epidermal keratinocytes. VEGFRs may play a significant role in pathogenesis of the epidermal neoplasm and the VEGF-VEGFR signaling pathway may be a novel therapy target for neoplasm derived from epidermis.
Animals ; Epidermis ; metabolism ; Humans ; Neoplasms ; metabolism ; Neuropilins ; genetics ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; genetics ; metabolism

The study was to investigate the expression of VEGFA, VEGFC, angiopoietin-1, angiopoietin-2 and their receptors on yolk sac blood island, AGM region during gestation of 3th-12th weeks of human embryo. Human embryo contingently aborted at 3 - 12 weeks of gestation were collected with signed agreements of the pregnant women suffered from accidental abortions. The specimens were fixed by 4% paraformaldehyde and embedded by paraffin. 5 micro m serial sections were made. HE and immunohistochemistry method (SABC) and light-microscope were employed. The results showed that VEGFA and its receptors flt1/flk-1, VEGFC and its receptor flt-4, angiopoietin-2 and its receptor tie-2 proteins were expressed strongly and angiopoietin-1 was weakly expressed by hematopoietic cells and vascular endothelial cells of blood island at 21 and 25 days of gestation. In the 4th week of gestation, immuno-positive reaction of these factors and their receptors appeared in the aorta and mesonephros deposited in larger, rounded and nucleated cells which represented hematopoietic cells. Up to 7th week, positive hematopoietic cells in the regions were much abundant. The number of positive cells decreased at 8th week. Up to 12th week, almost all blood cells were immuno-negative. VEGFA, flt-1, flt-4, angiopoietin-1, angiopoietin-2 and Tie-2 protein were expressed mainly by gonad at 6 - 8 weeks, but it did not express VEGFC and flk-1. The immuno-reaction of the factors and their receptors could not detected in vascular endothelial cells during 3-12th weeks of gestation. It is concluded that hematopoietic cells and endothelial cells in blood island of yolk sac, mesonephros and dorsal aorta co-expressed some factors and their receptors in relation to vasculogenesis and hematopoiesis. Intraembryonic hematopoiesis began in the 4th week of gestation.
Angiopoietin-1 ; analysis ; Angiopoietin-2 ; analysis ; Embryo, Mammalian ; chemistry ; Extracellular Matrix Proteins ; analysis ; Humans ; Immunohistochemistry ; Receptor, TIE-2 ; analysis ; Receptors, Vascular Endothelial Growth Factor ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor C ; analysis ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; Vascular Endothelial Growth Factor Receptor-3 ; analysis ; Yolk Sac ; chemistry

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant neoplasms and is a leading cause of mortality worldwide. Metastasis to the liver is a frequent event in patients with CRC. An essential step in the metastatic cascade is angiogenesis. METHODS: This study included 45 patients who underwent a partial colectomy with hepatic resection for CRC with hepatic metastases. Immunohistochemistry was performed using vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)-1, VEGFR-2, and CD34 antibodies to examine the relationship between CRC with liver metastases and angiogenesis. RESULTS: CRC showed significantly stronger expression of VEGF-A, VEGFR-1, and VEGFR-2 than liver metastases (p < 0.05). Microvessel density was also higher in CRC than in liver metastases (p < 0.05). CONCLUSIONS: Compared with previous studies, we found a higher expression of VEGF-A, VEGFR-1, VEGFR-2, and microvessel density in CRC than in liver metastases, which could be ascribed to a difference in vessel distribution and blood supply in each organ. Given its profuse blood supply and distinct cell populations, the liver might provide a rich milieu for tumor cell growth with less expression of angiogenesis-inducing agents.
Antibodies ; Colectomy ; Colorectal Neoplasms ; Glycosaminoglycans ; Humans ; Immunohistochemistry ; Liver ; Microvessels ; Neoplasm Metastasis ; Receptors, Vascular Endothelial Growth Factor ; Thymus Gland ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2 ; World Health Organization

OBJECTIVE: To Investigate the expression of vascular endothelial growth factor receptor-1, -2, and -3 (VEGFR-1, -2, and -3) mRNA in the eutopic and ectopic tissues in women with endometriosis. METHODS: At the time of laparoscopy or laparotomy for endometriosis, infertility or other benign gynecologic conditions, a biopsy specimen was taken from the endometrial cavity and a peritoneal endometriotic implant simultaneously whenever appropriate. For control samples, endometrial tissues were obtained from women without visual evidence of endomtriosis. We employed real time quantitative RT-PCR to quantify VEGFR gene expression of these tissues. Comparisions between each group were made using ANOVA (analysis of variance) and Kruskal-Wallis test and statistical significance was defined as p<0.05. RESULTS: The expression of VEGFR-1, -2, and, -3 mRNA was significantly higher in both eutopic and ectopic endometrial tissues of women with endometriosis than in control endometrial tissues during both proliferative and mid-secretory phase. In ectopic endometrial tissue, VEGFR-1 mRNA expression was significantly increased during the mid-secretory phase compared to the proliferative phase. There was a marked increase especially in VEGFR-3 mRNA expression in ectopic endometriotic lesions during the proliferative phase but its expression decreased during the mid-secretory phase. CONCLUSION: mRNA for VEGFR-1, -2, and -3 in an endometriotic lesions might be differentially expressed and their expression appears to be associated with the development of endometriosis.
Biopsy ; Choristoma ; Endometriosis* ; Female ; Gene Expression ; Humans ; Infertility ; Laparoscopy ; Laparotomy ; Receptors, Vascular Endothelial Growth Factor* ; RNA, Messenger ; Vascular Endothelial Growth Factor A* ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-3

This study was to evaluate the expression of vascular endothelial growth factor receptors (VEGFRs) in tumor and stromal cells of tougue squamous cell carcinoma (SCC). We also wanted to characterize the differences, from the angiogenic aspect, between cancer-associated stromal cells and non-malignant stromal cells. Paraffin-embedded tumor specimens from eleven patients with tongue SCCs were studied. Immunohistochemical staining for VEGFR-1,-2, and -3 was performed on the tumor cells, stromal fibroblasts and tumor-associated macrophages of the specimens. The expression of all 3 receptors was detected in the tumor cells themselves of the biopsy specimens. All 3 receptors were also expressed on stromal cells, except that VEGFR-2 was not expressed in stromal fibroblasts. In radical excision specimens, the staining intensity for VEGFR-1, -2 in the tumor cells and VEGFR-1,-3 in the tumor-associated macrophages was significantly lower than that in the biopsy specimens (P < 0.05). By using the general marker of fibroblast and macrophage, 5B5 and CD68, respectively, we performed double immunofluorescence staining for 5B5 and each VEGFR in the stromal fibroblasts and for CD68 and each VEGFR in the tumor-associated macrophages of the radical excision specimens. We used 4 cases of fibroma and 4 cases of chronic inflammation tissue as the controls. It was found that only each marker was expressed in the control group, however, 5B5/VEGFR-1 and 5B5/VEGFR-3 in the stromal fibroblasts, and CD68/VEGFR-1 and CD68/VEGFR-3 in the tumor-associated macrophages were double stained in the radical excision specimens. Although our study used small number of specimens, the results of our study showed that in tongue SCC, in association with the angiogenesis, the stromal cells showed the activated phenotype and this was different from the nonmalignant stromal cells.
Biopsy ; Carcinoma, Squamous Cell* ; Fibroblasts ; Fibroma ; Fluorescent Antibody Technique ; Humans ; Inflammation ; Macrophages ; Phenotype ; Receptors, Vascular Endothelial Growth Factor* ; Stromal Cells* ; Tongue* ; Vascular Endothelial Growth Factor A* ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2

Humans ; Psoriasis ; etiology ; therapy ; Signal Transduction ; Vascular Endothelial Growth Factor Receptor-1 ; antagonists & inhibitors ; physiology ; Vascular Endothelial Growth Factor Receptor-2 ; antagonists & inhibitors ; physiology

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCs' migration under high glucose conditions. MATERIAL AND METHOD: The balloon-injury method was employed to induce neointima formation by VEGF. For 14 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5 mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). RESULT: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, (0.15+/-0.04 mm2 and 36.03+/-3.78% compared to 0.24+/-0.03 mm2 and 61.85+/-5.11%, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from 52.82+/-4.20% to 38.11+/-6.89% by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCs. CONCLUSION: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition.
Animals ; Arteries ; Carotid Arteries ; Cell Proliferation ; Constriction, Pathologic ; Endothelial Growth Factors* ; Glucose ; Hyperplasia ; Muscle, Smooth, Vascular* ; Neointima* ; Phenobarbital ; Rats* ; Rats, Inbred OLETF ; Receptors, Vascular Endothelial Growth Factor ; RNA, Messenger ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1

Angiokeratoma is a benign cutaneous lesion of the capillaries, presenting as dilated vessels in the upper part of the dermis. Although this disorder is classified into various types and has been occasionally reported in the skin of the scrotum or extremities, the involvement of the oral cavity mucosa has been rarely reported. The present study reports a case of angiokeratoma circumscriptum in the buccal mucosa. The expression of vascular endothelial growth factor (VEGF) and both of its receptors (VEGFR-1 and VEGFR-2) was demonstrated by immunohistochemistry in the endothelial cells lining the dilated vessels. The expression of VEGFR-2 was higher than that of VEGFR-1 in the endothelial cells in the lesion, indicating an increased rate of endothelial cell proliferation within the lesion. Interestingly, some of the endothelial cells co-expressed VEGF and its two receptors. These results suggest that endothelial cells in the pathologically dilated vessels possess VEGF autocrine growth activity involved in vasculogenesis and maintenance in angiokeratoma lesions. To our knowledge, this is the second report published on isolated oral angiokeratoma confined to the buccal mucosa and the first case report on angiokeratoma circumscriptum involving the buccal mucosa.
Angiokeratoma* ; Capillaries ; Dermis ; Endothelial Cells ; Extremities ; Immunohistochemistry ; Mouth ; Mouth Mucosa* ; Mucous Membrane ; Scrotum ; Skin ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2