• 대한방사성의약품학회지
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• 제4권2호
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• pp.106-114
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• 2018

Angiogenesis is the new blood vessel formation process and has known to a fundamental event of tumor growth and metastasis. Especially, vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the crucial regulators of angiogenesis in tumor. VEGF-A is one of the VEGF family and binds to endothelial cell specific VEGFR1 and VEGFR2, which are associated with tumor growth and tumor angiogenesis. $VEGF_{121}$ is more tumorigenic isomer of VEGF-A. Targeted VEGF or VEGFR molecular imaging has been widely used to enable diagnosis and monitoring of proliferation and development of angiogenic tumors. Therefore, in this review, we have focused on the radioligands with $VEGF_{121}$ for angiogenesis of tumor.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.499-503
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• 2012

The present study was based on the unexpected discovery that norcantharidin exerted anti-angiogenesis activity when effects on growth of human colon cancer were studied. The aim was to further verify this finding and explore possible mechanisms using a tumor xenograft model in nude mice. We confirmed that norcantharidin (5 or 15 mg/kg) could inhibit angiogenesis of human colon cancer in vivo. In vitro, crossing river assay, cell adhesion assay and tube formation assay indicated that NCTD could reduce the migration, adhesion and vascular network tube formation ability of HUVECs. At the same time, the expression levels of VEGF and VEGFR-2 proteins which play important roles in angiogenesis were reduced as examined by western blotting analysis. Taken together, the results firstly showed NCTD could inhibit angiogenesis of human colon cancer in vivo, probably associated with effects on migration, adhesion and vascular network tube formation of HUVECs and expression levels of VEGF and VEGFR-2 proteins.

• Genomics & Informatics
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• 제2권3호
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• pp.134-141
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• 2004

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and a typical hypervascular tumor. Therefore, it is important to find factors related to angiogenesis in the process of HCC malignancy. In order to find angiogenesis-related factors in HCC, we used combined methods of in silico prediction and an experimental assay. We analyzed 1457 genes extracted from cDNA microarray of HCC patients by text-mining, sequence similarity search and domain analysis. As a result, we predicted that 16 genes were likely to be involved in angiogenesis and then the effects of these genes were confirmed by hypoxia response element(HRE)-luciferase assay. For instant, we classified osteopontin into a potent angiogenic factor and coagulation factor XII into a significant anti­angiogenic factor. Collectively, we suggest that using a combination of in silico prediction and experimental approaches, we can identify HCC-specific angiogenesis­related factors effectively and rapidly.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제44권3호
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• pp.93-102
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• 2018

Angiogenesis is one of the essential processes that occur during wound healing. It is responsible for providing immunity as well as the regenerative cells, nutrition, and oxygen needed for the healing of the alveolar socket following tooth extraction. The inappropriate removal of formed blood clots causes the undesirable phenomenon of alveolar osteitis (AO) or dry socket. In this review, we aimed to investigate whether enhanced angiogenesis contributes to a more effective prevention of AO. The potential pro- or anti-angiogenic activity of different materials used for the treatment of AO were evaluated. An electronic search was performed in the PubMed, MEDLINE, and EMBASE databases via OVID from January 2000 to September 2016 using the keywords mentioned in the PubMed and MeSH (Medical Subject Headings) terms regarding the role of angiogenesis in the prevention of AO. Our initial search identified 408 articles using the keywords indicated above, with 38 of them meeting the inclusion criteria set for this review. Due to the undeniable role of angiogenesis in the socket healing process, it is beneficial if strategies for preventing AO are directed toward more proangiogenic materials and modalities.

• 생명과학회지
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• 제6권4호
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• pp.286-292
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• 1996

Angiogenesis is a fundamental process by which new blood vessels are formed. It is essential in embryo development, and wound healing. Furthermore, malignant tumor growth and metastasis are also angiogenesis-dependent. In the catilage tissue, normal angiogenesis process is suppressed. In fact, it was reported that angiogenesis-inhibitory substances were isolated from the extracts of cow and shark catilage tissue. In order to isolate genes involved in the regulation of angiogenesis from a catilage fish, we constructed a shark cDNA library from Scylliohinus torazame. We then screened the library using hyman tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene as a probe. Among the 4 X 10$^{4}$ plaques screened, we isolated 2 positive clones (T-1, T-2). Restriction enzyme analysis revealed that the T-1 clone contains 0.8 kb cDNA insert, and the T-2 clone contains 1.2 kb and 2.2 kb inserts, respectively. Further DNA sequence analysis shows that the DNA sequence of the T-1 clone is 53% homologous to that of the human TIMP-1 gene.

• Genomics & Informatics
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• 제9권4호
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• pp.161-172
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• 2011

Angiogenesis is regulated by a large number of molecules and complex signaling mechanisms. The G protein $G{\alpha}_{13}$ is a part of this signaling mechanism as an endothelial cell movement regulator. Gene expression analysis of $G{\alpha}_{13}$ knockout mouse embryos was carried out to identify the role of $G{\alpha}_{13}$ in angiogenesis signaling during embryonic development. Hypoxia-inducible response factors including those acting as regulators of angiogenesis were over expressed, while genes related to the cell cycle, DNA replication, protein modification and cell-cell dissociation were under expressed. Functional annotation and network analysis indicate that $G{\alpha}_{13}{^{-/-}}$ embryonic mice were exposed to hypoxic conditions. The present analysis of the time course highlighted the significantly high levels of disorder in the development of the cardiovascular system. The data suggested that hypoxia-inducible factors including those associated with angiogenesis and abnormalities related to endothelial cell division contributed to the developmental failure of $G{\alpha}_{13}$ knockout mouse embryos.

• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.327-334
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• 2015

The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin- A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.

• Bulletin of the Korean Chemical Society
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• 제22권9호
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• pp.984-988
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• 2001

Since anti-angiogenesis could lead to the suppression of tumor growth, angiogenesis inhibitors have received particular attention for their therapeutic potential. In this study, two angiogenic inhibitors using the bioactive sequence from the kring le 5, AK1(KLYDY), AK2(KLWDF) were designed and synthesized. We have investigated their solution structures using NMR spectroscopy and their activities as angiogenesis inhibitors. AK2 has an intramolecular hydrogen bon d between the side chain amino proton of Lys1 and the carboxyl oxygen of Asp4 with a N ${\cdot}{\cdot}{\cdot}$O distance of $3.27\AA$, while AK1 shows more flexible structures than AK2. Indole ring in Trp is much bigger than the phenyl ring in Tyr and may have good face-to-edge interaction enforcing more rigid and constrained conformational features of AK2. Because of this relatively stable structure, Trp3 in AK2 may have better hydrophobic interaction with Phe5 than Tyr3 in AK1 if two adjacent aromatic groups are located in hydrophobic pocket of receptor. Since AK2 shows the similar anti-angiogenic activities to AK1, we are also able to confirm that the activity of AK1 is irrelevant to the Tyr phosphorylation. More rigid drug with higher activities can be provided by the mimetic approaches. For the further development of the angiogenesis inhibitors, these conformational studies on our lead peptides will be helpful in design of peptidomimetics.

• 생명과학회지
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• 제24권5호
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• pp.588-593
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• 2014

본 논문은 RLIP76 단백질이 암, 종양 혈관 신생 및 그 치료에 미치는 중요성을 보고함에 있다. 암의 연구에 있어서, 종양의 혈관 신생을 억제시키는 인자와 영향을 끼치는 인자를 밝혀내는 것은 암의 억제와 치료를 위한 분자 생물학적 기전에 중대한 영향을 미친다. 최근 연구에서, RLIP76 단백질이 혈관 신생에 영향을 끼치는 역할을 발견하였다. RLIP76 제거 마우스의 종양은 일반 종양과 비교하여 혈관의 크기가 작으며, 가늘고, 그 혈관의 수가 적고 길이가 짧은 것으로 보고되고 있다. 게다가, Matrigel plugs을 이용한 혈관 신생 실험에서, RLIP76이 제거된 마우스에서는 혈관 생성이 억제 되었으나, 일반 마우스에서는 혈관이 생성되었다. 또한, 혈관세포를 이용한 in vitro 실험에 있어서, proliferation, migration 및 cord formation 모두가 RLIP76에 의해서 조절되었다. 일반적으로 RLIP76은 대부분의 인간 조직과 종양에서 발현되며, 약의 저항 기전 연구에 이용되고 있기도 한다. 또한, 이RLIP76은 small GTPase R-Ras와 상호작용을 통하여 세포 spreading 및 migration에 관여하고 있다. 이러한 결과는 RLIP76와 암 연구의 중요성을 보고하고 있으며, 혈관 세포의 기능의 기전 및 종양의 혈관 신생을 위한 RLIP76 단백질의 중요성을 알리고 있고, RLIP76의 추가적인 연구를 통하여 종양의 혈관 신생의 기전을 밝히는 것이 필요함을 제안하는 바이다.

• BMB Reports
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• 제50권11호
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• pp.590-595
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• 2017

High-mobility group box-1 (HMGB-1) is expressed in almost all cells, and its dysregulated expression correlates with inflammatory diseases, ischemia, and cancer. Some of these conditions accompany HMGB-1-mediated abnormal angiogenesis. Thus far, the mechanism of HMGB-1-induced angiogenesis remains largely unknown. In this study, we performed time-dependent DNA microarray analysis of endothelial cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways were also activated by VEGF, although the activation time and gene sets belonging to the pathways differed. In addition, HMGB-1 upregulated some VEGFR signaling-related angiogenic factors including EGR1 and, importantly, novel angiogenic factors, such as ABL2, CEACAM1, KIT, and VIPR1, which are reported to independently promote angiogenesis under physiological and pathological conditions. Our findings suggest that HMGB-1 independently induces angiogenesis by activating HMGB-1-specific angiogenic factors and also functions as an accelerator for VEGF-mediated conventional angiogenesis.