• 한국산학기술학회논문지
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• 제18권4호
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• pp.366-379
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• 2017

본 연구는 운동중재가 심장질환자의 혈관내피전구세포에 미치는 효과에 대한 선행연구들을 체계적으로 고찰하고, 그 효과에 대한 메타분석을 위해 실시되었다. 국내외 데이터베이스인 Cochrane Library, PubMed, EMBASE, ScienceDirect, CINAHL, Scopus, KoreaMed, KISS, RISS, KMBASE 온라인 검색을 실시하였고, 검색어는 심질환, 관상동맥질환, 심부전, 심혈관질환, 운동, 신체활동, 재활, 혈관내피전구세포를 조합하여 사용하였다. 그 결과, 539편의 논문이 검색되었고, 논문 선정기준에 부합하는 9편의 논문을 최종 분석에 이용하였다. Comprehensive Meta-Analysis version 2.0을 활용하여 효과크기, 출판편중을 분석하였다. 운동군의 혈관내피성장인자(VEGF), 혈관내피세포의 수(CD34+KDR+), 혈관내피세포의 기능(FMD)은 대조군에 비해 각각 2.008 (95% CI 0.204-3.812), 1.399 (95% CI 0.310-2.489), 1.881 (95% CI 0.848-2.914) 효과크기가 나타났다. 따라서 운동 중재가 혈관내피성장인자와 혈과내피전구세포의 수를 증가시키고, 혈관내피세포의 기능을 향상시키는데 효과가 있음을 알 수 있다. 국내 심혈관질환자의 유병률과 사망률이 증가하고 있음을 고려할 때, 심혈관질환자를 대상으로 한 운동중재의 효과를 분석한 본 연구결과는 심혈관질환자의 운동중재를 계획하는데 있어 실질적인 가이드라인을 제시할 수 있을 것이다.

• 대한두경부종양학회지
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• 제21권1호
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• pp.3-9
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• 2005

Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

• Korean Journal of Ophthalmology
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• 제32권6호
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• pp.451-458
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• 2018

Purpose: To investigate the efficacy, safety, and anatomical outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) treatment of retinopathy of prematurity (ROP). Methods: We performed a retrospective review of intravitreal anti-VEGF (bevacizumab or ranibizumab) treatment of 153 eyes (83 infants) diagnosed with ROP at two tertiary hospitals from June 2011 to January 2017. The primary outcome was the rate of recurrence requiring additional treatment; secondary outcomes included incidence of major complications and final refractive error. Results: A total of 101 eyes were treated with bevacizumab, and 52 with ranibizumab. The bevacizumab and ranibizumab groups were characterized by mean birthweights of $941.8{\pm}296.1$ and $1,257.7{\pm}514.5g$, gestational ages at birth of $26.9{\pm}1.9$ and $28.1{\pm}3.2$ weeks, and postmenstrual ages at treatment of $40.4{\pm}2.4$ and $39.2{\pm}2.3$ weeks, respectively. The two groups differed significantly in birthweights and gestational ages at birth, but not in postmenstrual ages at treatment. The mean follow-up duration was $30.9{\pm}18.4$ months for the bevacizumab group, and $13.9{\pm}12.5$ months for ranibizumab. More cases were classified as zone 1 ROP in the ranibizumab group (44.2% vs. 11.9%, p < 0.001). Major surgical interventions included scleral encircling and vitrectomy (one and two eyes, respectively, both in the bevacizumab group). Retinal detachment was noted in one eye treated with bevacizumab. There was no significant difference in the most recent spherical equivalence for the two groups ($+0.10{\pm}3.66$ and $+0.22{\pm}3.00$ diopters for bevacizumab and ranibizumab, respectively). Univariable analysis revealed that only ROP stage influenced the occurrence of major complications (odds ratio, 9.046; p = 0.012). Conclusions: Intravitreal anti-VEGF treatment of ROP with both bevacizumab and ranibizumab achieved stable retinal vascularization with a low rate of complications and recurrence. Ranibizumab achieved similar anatomical outcomes as bevacizumab, without additional risk for major complications.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.737-741
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• 2014

Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.2031-2035
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• 2015

Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

• 대한안과학회지
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• 제59권11호
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• pp.1030-1038
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• 2018

목적: 신생혈관 연령관련황반변성 환자에서 유리체강 내 항혈관내피세포성장인자 주입술 1회 시행 후 1개월째 시력 반응의 정도 및 3회 시행 후 1개월째 시력 반응의 정도와 치료 시작 12개월 후의 시력과의 상관관계를 알아보고자 하였다. 대상과 방법: 신생혈관 연령관련황반변성으로 진단받은 환자들 중 유리체강 내 항혈관내피세포성장인자 주입술로 치료하면서 12개월 이상 경과관찰이 가능했던 환자 30명의 의무기록을 분석하였다. 유리체강 내 주입술 1회 시행 후 1개월째 최대교정시력을 측정하였고 3회 주입술 후 1개월째 최대교정시력을 측정하여 상승 정도(<1, 1-<3, ${\geq}3$줄; logMAR)에 따른 치료 시작 후 12개월째 최대교정시력과 비교하였다. 결과: 첫 주사 후 1개월째 1줄 미만의 시력 향상을 보인 군은 6안(20%), 1줄 이상 3줄 미만의 시력 향상을 보인 군은 7안(23.3%), 3줄 이상 시력 향상을 보인 군은 17안(56.6%)이었다. 세 번째 주사 후 1개월째 1줄 미만의 시력 향상을 보인 군은 9안(30%), 1줄 이상 3줄 미만의 시력 향상을 보인 군은 9안(30%), 3줄 이상의 시력 향상을 보인 군은 12안(40%)이었다. 로지스틱 회귀 분석 및 선형회귀분석에서 3회 주입술 후 1개월째의 3줄 이상의 시력 향상은 치료 시작 12개월 후의 3줄 이상의 시력상승과 유의한 상관관계를 보였다(p=0.04). 결론: 신생혈관 연령관련황반변성 환자에서 유리체강 내 주입술 3회 시행 후 1개월째 3줄 이상의 시력 향상 여부는 치료 시작 12개월 후의 3줄 이상의 시력예후와 통계적으로 유의한 상관관계를 보였다.

• Genomics & Informatics
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• 제21권4호
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• pp.44.1-44.10
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• 2023

Tumor hypoxia, oxygen deprivation state, occurs in most cancers and promotes angiogenesis, enhancing the potential for metastasis. The vascular endothelial growth factor (VEGF) family genes play crucial roles in tumorigenesis by promoting angiogenesis. To investigate the malignant processes triggered by hypoxia-induced angiogenesis across pan-cancers, we comprehensively analyzed the relationships between the expression of VEGF family genes and hypoxic microenvironment based on integrated bioinformatics methods. Our results suggest that the expression of VEGF family genes differs significantly among various cancers, highlighting their heterogeneity effect on human cancers. Across the 33 cancers, VEGFB and VEGFD showed the highest and lowest expression levels, respectively. The survival analysis showed that VEGFA and placental growth factor (PGF) were correlated with poor prognosis in many cancers, including kidney renal cell and liver hepatocellular carcinoma. VEGFC expression was positively correlated with glioma and stomach cancer. VEGFA and PGF showed distinct positive correlations with hypoxia scores in most cancers, indicating a potential correlation with tumor aggressiveness. The expression of miRNAs targeting VEGF family genes, including hsa-miR-130b-5p and hsa-miR-940, was positively correlated with hypoxia. In immune subtypes analysis, VEGFC was highly expressed in C3 (inflammatory) and C6 (transforming growth factor β dominant) across various cancers, indicating its potential role as a tumor promotor. VEGFC expression exhibited positive correlations with immune infiltration scores, suggesting low tumor purity. High expression of VEGFA and VEGFC showed favorable responses to various drugs, including BLU-667, which abrogates RET signaling, an oncogenic driver in liver and thyroid cancers. Our findings suggest potential roles of VEGF family genes in malignant processes related with hypoxia-induced angiogenesis.

• 생명과학회지
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• 제26권4호
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• pp.439-445
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• 2016

콩잎은 골다공증 및 유방암 발생을 예방한다고 널리 보고되고 있다. 이를 바탕으로 콩잎낙엽 에탄올 추출물(SBFL)을 제조하여 암 전이와 관련 있는 세포침윤에 대한 효과를 조사하기 위하여 섬유아육종세포(HT1080)에서 SBFL이 항산화와 matrix metalloproteinases (MMPs)에 미치는 영향을 분석하였다. 본 연구에서 활성산소의 소거 효과에 대한 SBFL효과는 DPPH radical, 환원력 및 지질과산화실험으로 평가되었다, 본 연구에서 SBFL은 양성 대조군으로 사용된 vitamin C 및 vitamin E와 비교 시 우수한 항산화 효과를 보여주었다. 다음으로 SBFL의 세포 독성을 측정하기 위하여 MTT assay를 수행한 결과 16 µg/ml 이상의 농도에서 세포독성을 보여주었다. SBFL은 gelatin zymography 실험에서 phorbol 12-myristate 13-acetae (PMA) 혹은 phenazine methosulfate (PMS)로 자극된 암 전이에서 중요한 MMP-9의 활성을 감소시켰다. 특히 SBFL은 단백질 발현 실험에서 SOD-1, p-FoxO-1의 발현을 증가시켰다. 더욱이 vascular endothelial growth Factor (VEGF)로 자극된 세포 침윤이 SBFL처리에 의하여 억제되는 것으로 나타났다. 이러한 연구결과를 바탕으로 SBFL은 뛰어난 항산화 효과는 산화적 스트레스를 감소시키고 MMP-9의 활성과 세포침윤을 억제시켜 암 전이의 예방을 위한 유효성분으로 이용될 수 있다는 것을 암시하고 있다.

• Journal of Korean Neurosurgical Society
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• 제62권2호
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• pp.153-165
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• 2019

Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.53-62
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• 2016

Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride ($CoCl_2$) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of $CoCl_2$ preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. $CoCl_2$ treatment of MSCs markedly increased HIF-$1{\alpha}$ and VEGF mRNA, and protein expression of HIF-$1{\alpha}$. Temporary preconditioning of MSCs with $CoCl_2$ induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. $CoCl_2$ also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. $CoCl_2$ suppressed the expression of adipogenic markers including $PPAR{\gamma}$, aP2, and $C/EBP{\alpha}$, and inhibited adipogenesis. Temporary preconditioning with $CoCl_2$ could affect the multi-lineage differentiation of MSCs.