• Asian Pacific Journal of Cancer Prevention
• /
• 제13권3호
• /
• pp.1059-1063
• /
• 2012

Objective: Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. Methods: Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). Conclusion: Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

• 생명과학회지
• /
• 제19권3호
• /
• pp.327-333
• /
• 2009

건선(psoriasis)은 각화(keratinization)의 장애에 의한 질병으로 잘 알려져 있다. 이 질병에있어서, 몇몇 보고에 따르면 피부 미세혈관이 증가되고, 혈관 신생 유도 인자들인 내피 성장 인자(VEGF) 및 섬유아세포 성장 인자(bFGF)가 과발현된다고 보고 되어져 있다. 신생혈관(angiogenesis)은 건선의 진행성에 있어 중요한 역할을 할지도 모른다. Acitretin은 keratinocyte 성장과 분화에 그것의 잠재적인 활동 때문에 anti-psoriatic 약으로 널리 이용된다. 그러나 신생혈관에 대한 효과는 여전히 불명확하다. 본 면역혈청학적 연구 목표는 건선염 피부에 있는 VEGF의 발현에 acitretin의 효과를 조사하기 위한 것이었다. 우리는 10명의 건선염 피부환자와 대조군으로 3명의 정상인 피부에 acitretin의 치료 전과 후의 VEGF의 발현량을 비교하였다. 치료 전 대조군인 정상인 피부에서보다 건선염 피부환자에서 VEGF의 발현은 명백히 높은 수준이었다. 건선염 피부환자에서 VEGF의 발현량은 acitretin 치료 후 치료 전과 비교시 감소되었다. Acitretin은 건선 피부에서 VEGF와 같은 혈관 신생 유도 인자의 발현을 감소 시켜 신생혈관형성에 있어 억제의 효과가 있음을 나타낸다. 우리는 신생혈관 관점에서 acitretin이 건선에 대한 치료 수단이 될 수 있다는 것을 제안한다.

• 산업융합연구
• /
• 제21권3호
• /
• pp.171-179
• /
• 2023

본 연구는 중년여성 18명을 대상으로 저항성 운동군 A그룹 6명(1RM 40-60%), 유산소 운동군 B그룹 6명(VO2max 60-70%), 유연성 운동군 C그룹(10~60 sec/sets) 6명으로 무선 배정하여 12주간 주 3회(월, 수, 금) 1일 50~60분의 운동 형태에 따른 신체구성과 염증인자, 혈관내피 성장인자에 미치는 영향을 알아보기 위하여 비교·분석한 결과, 첫째, 염증인자의 변화에서는 CRP 및 IL-6의 시기의 주효과에서는 유의한 차이(p<.05)가 나타났다. 둘째, 혈관내피 성장인자의 변화에서는 VEGF의 시기의 주효과 및 시기×그룹의 상호작용에서는 유의한 차이(p<.05)가 나타났다. 본 연구의 결과를 토대로 운동 형태에 따른 염증인자와 혈관내피 성장인자에 관한 다양한 각도의 연구와 개선을 위한 기초 자료로 활용되기를 기대한다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권7호
• /
• pp.3089-3097
• /
• 2012

Background and Aims: Vascular endothelial growth factor (VEGF) is a potential prognostic biomarker for patients with resected gastric cancer. However, its role remains controversial. The objective of this study was to conduct a systematic review and meta-analysis of published literature. Methods: Relevant literature was identified using Medline and survival data from published studies were collected following a methodological assessment. Quality assessment of eligible studies and meta-analysis of hazard ratio (HR) were performed to review the correlation of VEGF overexpression with survival and recurrence in patients with gastric cancer. Results: Our meta-analysis included 44 published studies with 4,794 resected patients. VEGF subtype for the prediction of overall survival (OS) included tissue VEGF (HR=2.13, 95% CI 1.71-2.65), circulating VEGF (HR=4.22, 95% CI 2.47-7.18), tissue VEGF-C (HR=2.21, 95% CI 1.58-3.09), tissue VEGF-D (HR=1.73, 95% CI 1.25-2.40). Subgroup analysis showed that HRs of tissue VEGF for OS were, 1.78 (95% CI 0.90-3.51) and 2.31 (95% CI 1.82-2.93) in non-Asians and Asians, respectively. The meta-analysis was also conducted for disease free survival (DFS) and disease specific survival (DSS). Conclusion: Positive expression of tissue VEGF, circulating VEGF, VEGF-C and VEGF-D were all associated with poor prognosis in resected gastric cancer. However, VEGF demonstrated no significant prognostic value for non-Asian populations. Circulating VEGF may be better than tissue VEGF in predicting prognosis.

• 생명과학회지
• /
• 제26권10호
• /
• pp.1189-1195
• /
• 2016

Vascular endothelial growth factor (VEGF)와 hepatocyte growth factor (HGF)는 강력한 혈관신생 유도인자로 알려져 있다. 세포가 이동하고 침윤하기 위해서는 세포의 증식과 더불어 주변의 세포외기질을 분해하는 단백질분해효소의 분비가 선행되어야 한다. 본 연구에서는 인간의 악성신경교종 유래 세포주인 U-373-MG 세포에 VEGF와 HGF를 처리하여 세포의 증식, matrix metalloproteinase-2 (MMP-2)와 MMP-9 및 플라스민의 분비, 세포의 이동 및 침윤에 미치는 효과를 조사하였다. 또한 단백질분해효소 억제제 처리를 통하여 세포의 증식, 이동 및 침윤에 미치는 단백질분해효소의 역할을 조사하였다. 연구 결과, VEGF와 HGF의 병용처리 시 VEGF와 HGF의 단독 처리 시보다 세포의 증식, MMP-2, MMP-9 및 플라스민의 분비, 세포의 이동 및 침윤이 유의할만하게 증가되었다. 한편 VEGF와 HGF 처리에 의한 U-373-MG 세포의 증식, 이동 및 침윤 증가에 미치는 단백질분해효소의 효과를 MMPs 억제제인 BB-94를 처리하여 조사한 결과 최대 이동 효과를 나타낸 HGF와 VEGF의 병용처리군 보다 세포의 이동이 32% 억제되었고 플라스민 억제제인 α2AP에 의해서도 29% 억제되었다. 또한 U-373-MG 세포의 침윤 역시 BB-94와 α2AP 처리에 의해 유의할 만하게 억제되었다. 이러한 결과는 VEGF와 HGF에 의한 MMP-2, MMP-9 및 플라스민의 분비증가에 의해 직접 또는 간접적인 경로를 통하여 U-373-MG 세포의 증식, 이동 및 침윤을 증가시킨다고 여겨진다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권5호
• /
• pp.1677-1682
• /
• 2015

Cancer progression is attained by uncontrolled cell division and metastasis. Increase in tumor size triggers different vascular channel formation to address cell nutritional demands. These channels are responsible for transferring of nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by numerous factors including vascular endothelial growth factors (VEGFs). These factors play an important role during embryonic development. Members included in this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence cellular growth and apoptosis. Being freely diffusible these proteins act in both autocrine and paracrine fashions. In this review, genetic characterization these molecules and their putative role in cancer staging has been elaborated. Prognostic significance of these molecules along with different stages of cancer has also been summarized. Brief outline of ongoing efforts to target hot spot target sites against these VEGFs and their cognate limitations for therapeutic implications are also highlighted.

• Journal of Korean Neurosurgical Society
• /
• 제29권12호
• /
• pp.1584-1591
• /
• 2000

Objective : Until now, it has been little known about the biological mechanisms associated with the genesis, growth, and rupture of intracranial aneurysm. This study was performed to investigate and understand a part of these mechanisms. Materials and Methods : Immunohistochemical stains for angiogenesis growth factors(basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF)) and selected vascular wall matrix proteins(alpha smooth muscle actin(${\alpha}SMA$) and collagen Type IV) were performed in fixed sections from a normal circle of Willis artery which was taken from the autopsy specimen as a control vessel and 17 aneurysmal wall specimens which was taken during surgical clipping of aneurysms. The staining intensity and distribution of immunoreactivity to angiogenesis growth factors and selected wall matrix proteins in control vessel and aneurysmal wall were examined and compared with each other. The difference of staining intensity according to the size of aneurysm was also investigated. Results : There was no immunoreactivity to bFGF and VEGF in the control vessel. bFGF immunoreactivity was exhibited in 15 of 17 aneurysm specimens around smooth muscle cells within the media of aneurysm. VEGF immunoreactivity was also exhibited in all aneurysm specimens in patches or diffusely affecting all layers of the aneurysmal wall. The degrees of intensity of bFGF and VEGF immunoexpression were proportionate roughly to the size of aneurysm. Strong immunoexpression of both factors were noticed in large aneurysm. A regularly arranged and defined band of immunoreactivity of ${\alpha}SMA$ was noticed in the media of the control vessel, whereas diffuse, faint, irregularly arranged ${\alpha}SMA$ was noticed in the aneurysmal wall. A regularly defined band of collagen Type IV immunoreactivity was also noticed in the subendothelium of the control vessel, whereas diffuse disorganized immunoreactivity of collagen Type IV was noticed in the entire wall of the aneurysm. Conclusion : These results indicate substantial evidences of abnormal expression of angiogenesis factors and changes of selected vascular wall matrix proteins in the wall of intracranial aneurysm. The unbalanced changes of angiogenesis factors and vascular wall matrix proteins in the wall of aneurysm may be one of the biological mechanisms for the growth and rupture of aneurysm.

• Clinical and Experimental Pediatrics
• /
• 제48권8호
• /
• pp.886-893
• /
• 2005

목 적 : 가와사키병은 어린 소아에서 전신성 혈관염을 일으키는 가장 흔한 원인이다. 가와사키병이 발병한 경우 여러 혈관 성장인자들의 분비가 촉진되어 내막층의 증식과 신생 혈관 생성작용이 진행되면서 관상동맥이 재구성된다. 수년간 가와사키병의 치료제로 IVIG와 코르티코스테로이드가 사용되었으나 그 치료기전이 명확히 밝혀진 바는 없다. 이런 IVIG와 코르티코스테로이드가 가와사키병의 관상동맥합병증을 감소시키는데 어떠한 기전으로 작용하는지 알아보고자 본 연구에서는 Matrigel을 이용하여 in vitro에서 VEGF에 의해 유도된 내막세포 분화에 대한 IVIG와 methylprednisolone의 효과를 보고자 하였다. 방 법 : Matrigel을 이용하여 in vitro에서 VEGF에 의해 유도된 내막세포 분화에 대한 IVIG와 methylprednisolone의 효과를 보고자 VEGF, VEGF와 IVIG, VEGF와 VEGF antibody, VEGF와 methylprednisolone, VEGF, IVIG와 methylprednisolone을 각각 넣어주고, HUVECs를 18시간 동안 배양 후 튜브의 총 길이를 측정하였다. 결 과 : 1) IVIG의 농도를 25 mg/mL, 그리고 40 mg/mL로 증량하였을 경우 IVIG를 투여하지 않은 대조군에 비하여 통계학적으로 각각 유의한 세포수(HUVECs) 감소 효과를 관찰할 수 있었으며(P<0.001), 40 mg/mL를 처리한 경우가 25 mg/mL를 처리한 경우보다 세포수 감소 효과가 더 뚜렷하였다(P<0.05). 세포배양 시간에 따른 억제 효과는 25 mg/mL과 40 mg/mL에서 배양 후 24시간과 48시간 모두에서 대조군과 비교하여 통계학적으로 유의한 효과를 보였다(P<0.001). 2) VEGF 20 ng/mL를 처리한 군에 IVIG 40 mg/mL 또는 여러 농도의 methylprednisolone($10^{-12}M$, $10^{-9}M$ or $10^{-6}M$)을 처치해 주었을 때 튜브 형성이 유의하게 억제되었으며(P<0.05), methylprednisolone의 경우 그 억제 정도가 농도에 비례하여 일어났으나 IVIG 투여시 보다는 억제 효과가 약하였다. 한편, IVIG와 methylprednisolone와 병합투여한 경우는 methylprednisolone 농도에 상관없이 모두 튜브 형성을 잘 억제하였으며(P<0.001), IVIG만 단독 투여한 것과 통계적 차이는 없었다. 결 론 : 본 연구에서는 in vitro에서 VEGF가 HUVECs의 분화를 유도하고 분화된 내막세포의 맥관 형성이 IVIG와 methylprednisolone에 의해 저해된다는 것을 보여주었다. 이는 가와사키병의 관상동맥합병증이 생기는 기전 중 VEGF와 내막세포의 분화로 인해 일어나는 관상동맥의 재구성을 IVIG와 methylprednisolone이 억제한다는 것을 시사하며 치료 기전 중 하나로 제시될 수 있다.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제32권1호
• /
• pp.1-8
• /
• 2010

Background and Purpose: Vascular endothelial growth factor (VEGF)-C and VEGF receptor (VEGFR)-3 are involved in tumor lymphangiogenesis. Oral mucosal squamous cell carcinoma (OMSCC) preferentially metastasizes to cervical lymph nodes, so we investigated the expression and distribution of VEGFR-3 signaling proteins in OMSCC. Materials and Methods: Tissue samples of 18 OMSCC, 10 oral mucosal leukoplakia, and 3 normal oral mucosa were evaluated for expression of VEGF-C, VEGF-D, and VEGFR-3 by immunohistochemical staining. The presence of lymphatic vessels was determined using D2-40 staining, by which we also measured lymphatic vessel density (LVD). Results: 72% (13/18) and 56% (10/18) of tissue samples showed VEGF-C and VEGF-D immunopositivity in tumor cells and tumor-associated endothelial cells. VEGFR-3 was also expressed in most of OMSCC, which was up-regulated when compared with normal mucosa or with leukoplakia. Furthermore, LVD was higher in OMSCC than in leukoplakia. Conclusion: Taken together, our results suggest that autocrine activation of lymphatic endothelial cell via VEGFR-3 by VEGF-C and/or VEGF-D could be involved in progression of OMSCC. Therefore, VEGF-C/VEGFR-3 signaling pathway can be a molecular target for anti-metastatic therapy in OMSCC.

• 한국전문물리치료학회지
• /
• 제13권2호
• /
• pp.9-15
• /
• 2006

Skeletal muscle injury occurs frequently in sports medicine and is the most general form of injury followed by physical impact. There are growth factors which conduct proliferation, differentiation, and synthesis of myogenic prodromal cells and regulate vascular generation for the continued survival of myocytes. The purpose of the present study was to confirm the effects of electroacupuncture (EA) and electrical stimulation (ES) on muscle recovery processes according to vascular endothelial growth factor (VEGF) expression. Eighteen Sprague-Dawley rats were separated into 2 experimental groups and a controlled group. All animals had suffered from crush damage in the extensor digitorum longus for 30 seconds and were killed 1, 3, and 7 days after injury. 30 Hz and 1 mA impulsion for 15 minutes was applied to the EA experimental groups Zusanli (ST36) and Taichong (LR3) using electroacupuncture and the same stimulation was applied to the ES group using an electrical node. Hematoxyline-Eosin staining and VEGF immunohistochemistry were used to ascertain the resulting muscle recovery. There were few morphological differences between the EA and ES groups, and both groups were observed to have tendencies to decrease atrophy as time passed. In the controlled group, gradually diminishing atrophy could be observed, but their forms were mostly disheveled. There were few differences in VEGF expression between the EA and ES groups, and tendencies to have an increased quantity of VEGF with the lapse of time were observed in both groups. In the controlled group, a little VEGF expression could be observed merely 7 days after injury. In conclusion, EA and ES contributed to muscle recovery processes and could be used for the treatment of muscle injury.