• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권3호
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• pp.209-215
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• 2006

Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

• 대한두경부종양학회지
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• 제18권1호
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Parasites, Hosts and Diseases
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• 제57권2호
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• pp.117-125
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• 2019

Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of $HIF1{\alpha}$ through an intracellular oxygen-sensing pathway. Activation of $HIF1{\alpha}$ may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infection actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of $2{\times}10^6$ parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors including VEGF and $HIF1{\alpha}$. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tissues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and $HIF1{\alpha}$ increased with the parasitemia in various tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxiainduced angiogenesis by stimulation of $HIF1{\alpha}$ and VEGF in various tissues.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2277-2281
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• 2015

Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.

• 약학회지
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• 제45권1호
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• pp.71-77
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• 2001

We recently developed a high efficiency expression vectors pCK, which drives a high level of gene expression in the skeletal muscles of mice. In this study, we investigated the pharmacokinetics and biodistribution of pCK-VEGF expressing human VEGF165 after intravenous or intramuscular administration. The quantity of pCK-VEGF in the tissues of mice was measured by the PCR method which has a detection limit of approximately 1 pg of the exogenously added plasmid. In the case of intravenous administration, the half life of the pCK-VEGF plasmid in the bloodstream was 1.68 min. After intra-muscular administration, the half life of pCK-VEGF plasmid in the bloodstream was 6.78 min. At 90 min post-administration, 30% of the injected pCK-VEGF was found at the site of injection, where it persisted for up to 8 hours. Less than 1.6% of the injected pCK-VEGF plasmid DNA was detected in highly vascularized tissues such as the lung, kidney; and liver at 90 min post-administration, but the plasmid was undetectable at later time points. These results suggested that intramuscularly administrated pCK-VEGF persisted for longer periods of time in muscles than in other tissues and that direct intra-muscular injection of pCK-VEGF might be useful for local therapeutic angiogenesis.

• The Journal of Korean Physical Therapy
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• 제15권3호
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• pp.16-44
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• 2003

Skeletal muscle regeneration is a vital process for various muscle myopathies and muscular adaptation to physiological overload. Angiogenesis is the key event in the process of muscle regeneration, and vascular endothelial growth factor(VEGF) plays an important role in it. The purpose of this study was to evaluate the effect of GaAlAs(830nm) laser and immunoreactivity of VEGF on angiogenesis after muscle contusion injury. Muscle contusion injury was induced in the triceps surae muscle by dropping a metal bead(31.4g). GaAlAs laser irradiation(power 20 mW, frequency 2000 Hz, treatment time 15 min) was applied directly to the skin of injured muscle daily for seven days. The experimental group I was irradiated immediately by laser after injury, whereas the experimental group II was irradiated after 1 day of injury. The control group was non-irradiated. The results of this study were as follows. 1. In morphological observation, there were no significant changes in experimental and control groups for 7 days. At 3 days, however, the splited muscle fibers were observed in experimental groups, and the muscle atrophy and granular tissue viewed at 7 days in control group. 2. The VEGF was expressed in muscle fiber that located in the interspace between gastrocnemius and soleus muscles. As the time coursed, the immunoreactivity of VEGF also seemed to be strong in the individual muscle fibers. 3. The experimental group I & II showed higher immunoreactivity of VEGF than control group(p<0.05). Then, the experimental group I showed higher than group II especially(p<0.05). These data suggest GaAlAs semiconduct diode laser irradiation(830nm) enhanced angiogenesis in the skeletal muscle induced contusion injury, and immediate laser irradiation after injury promoted the angiogenesis greatly than after 1 day of injury.

• The Journal of Korean Physical Therapy
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• 제15권4호
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• pp.46-64
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• 2003

Therapeutic angiogenesis is the controlled induction or stimulation of new blood vessel formation to reduce unfavourable tissue effects caused by local hypoxia and to enhance tissue repair. Therapeutic ultrasound can be considered as a physical agent to deliver therapeutic angiogenesis. The purpose of this study was to evaluate the effect of therapeutic ultrasound after muscle contusion injury by observed immunoreactivity of vascular endothelial growth factor(VEGF) that plays an important role in angiogenesis and substance-P in pain transmission. Ultrasound irradiation(1MHz, $1W/cm^2$, continuous mode, treatment time 5 min) was applied through water submersion technique to 1 limb daily by kept off 5cm from muscle belly of gastrocnemius. The result of this study were as follows. 1. In morphological observation, there were no significant changes excepts of 7 days. At 7 days, granular tissue viewed abundantly in control group. In other groups, general feature were increased interspace of muscle fiber; centronucleated muscle fiber; collapsed of muscle and nerve tissue; appeared inflammatory cell. 2. The VEGF was expressed in interspace of muscle fiber. Especially, at 7 days in experimental group, VEGF was showed in connective tissue surrounding gastrocnemius muscle. 3. The VEGF was higher expressed in experimental group at 2 and 3 days, but in control group at 7 days. These data suggest therapeutic ultrasound enhanced production of VEGF in the early day relatively, therefore stimulated angiogenesis in the skeletal muscle induced contusion injury. Also therapeutic ultrasound may stimulate pain relief by diminish of substance-P in dorsal horn of spinal cord.

• Asian-Australasian Journal of Animal Sciences
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• 제22권6호
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• pp.788-795
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• 2009

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis under various physiological and pathological conditions. We found that the VEGF isoforms VEGF120, VEGF164, and VEGF188 were expressed in the bovine mammary gland and bovine mammary epithelial cells (bMECs). Expression of VEGF in the mammary gland was significantly higher during the lactation period than during the dry period. Although dexamethasone or prolactin alone had little effect on the expression of VEGF, that in dexamethasone-treated cells was significantly induced after additional treatment with prolactin. Furthermore, the VEGF expression induced by the combination of dexamethasone and prolactin was reduced by PD98059 in a dose-dependent manner. This combination also stimulated the phosphorylation of p44/p42 MAP kinase in these cells. These results strongly suggest that the combination of dexamethasone and prolactin stimulates VEGF expression in bMECs via p44/p42 MAP kinase.

• 대한한의학회지
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• 제26권4호
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• pp.22-30
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• 2005

Objectives: Recently, angiogenesis has gained an increasing interest as a prognostic factor in breast cancer. In this study we aimed to assess the anti angiogenic effects of HAD, a botanical anticancer remedy which has been prescribed in Daejeon University Oriental Hospital in Korea, on patients with breast carcinoma by measuring the serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF) and platelets levels. Methods: The study included 26 consecutive breast cancer patients (mean age$\pm$standard deviation: 47.5$\pm$8.7 years) with stage II to IV disease who were treated with HAD (mean duration $\pm$ standard deviation: 264.5$\pm$121.6 days). In addition to routine laboratory and staging procedures, serum VEGF, b-FGF levels and platelet counts were determined as antiangiogenic markers. The antiangiogenic effects of HAD were evaluated by analyzing the differences between the values of the antiangiogenic markers before and after the treatment with HAD. Results: Serum b-FGF concentrations were significantly reduced after the treatment with HAD (P=0.042). Serum VEGF concentrations were found to have a somewhat decreasing change, though the change was not statistically significant (P=0.229). Platelet counts had little changes (P=O.80). Conclusions: It is supposed that HAD has effects on decreasing the serum b-FGF levels related with the clinical outcome of breast cancer patients.

• Clinical and Experimental Pediatrics
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• 제51권5호
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• pp.487-491
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• 2008

목 적 : 마이코플라스마 폐렴은 일부 천식의 과거력이 없는 환자에서도 천명, 호흡곤란 등의 증상을 보여 천식의 발생과 관계된다고 한다. VEGF는 천식의 만성 염증 형성에 중요한 역할을 한다. 본 연구는 마이코플라스마 폐렴에서 천명이 동반되는 환아와 천명이 없는 환아에서 혈청 VEGF의 농도가 차이가 있는지 알아보고자 하였다. 방 법 : 2006년 8월부터 2007년 2월까지 고려대학교 안암병원 소아과에 천식의 과거력이 없는 마이코플라스마 폐렴으로 입원한 환아들 중 의사의 청진상 천명음이 처음으로 확인된 환아 9명(천명군)과 천명음이 한번도 없었던 비천명군 63명을 대상으로 혈청 VEGF농도, M. pneumoniae 항체가, 혈액 호산구 염증지표 및 혈청 IgE 농도 등을 측정하였다. 결 과 : 천명군의 혈청 VEGF 농도는 $650.2{\pm}417.9pg/mL$로 비천명군($376.5{\pm}356.2pg/mL$) 보다 높게 나타났고(P=0.049), M. pneumoniae 항체가도 천명군에서 더 높았다(1:1,380 vs. 1:596, P=0.048). 혈청 총IgE 값은 천명군이 591.8 IU/mL, 비천명군이 162.2 IU/mL 이었다(P=0.032). 두 군의 말초혈액 호산구수(천명군 : $263.0/{\mu}L$ vs. 비천명군 : $166.5/{\mu}L$)와 혈청 ECP 농도(천명군 : $22.8{\mu}g/L$ vs. 비천명군 : $17.4{\mu}g/L$)는 유의한 차이가 없었다. 천명군에서 혈청 VEGF 농도는 항체가와 유의한 상관관계를 보였다(r=0.568, P=0.034). 결 론 : 천식의 과거력이 없는 아토피 소아에서 높은 VEGF 농도는 마이코플라스마 폐렴에서 천명 발생과 관계가 있는 것으로 생각할 수 있으며, 이들 환자에서 앞으로 천식 발생 유무에 대한 추적 관찰이 필요하리라 생각한다.