• BMB Reports
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• 제41권4호
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• pp.278-286
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• 2008

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been approved for use to treat patients with colorectal, lung, renal and liver cancers. These drugs have opened a novel field of cancer therapy, i.e. anti-angiogenesis therapy. However, as yet they cannot completely cure patients, and cancer cells could become resistant to these drugs. Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy.

• Biomolecules & Therapeutics
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• 제22권1호
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• pp.1-9
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• 2014

Vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) system has been shown to play central roles not only in physiological angiogenesis, but also in pathological angiogenesis in diseases such as cancer. Based on these findings, a variety of anti-angiogenic drugs, including anti-VEGF antibodies and VEGFR/multi-receptor kinase inhibitors have been developed and approved for the clinical use. While the clinical efficacy of these drugs has been clearly demonstrated in cancer patients, they have not been shown to be effective in curing cancer, suggesting that further improvement in their design is necessary. Abnormal expression of an endogenous VEGF-inhibitor sFlt-1 has been shown to be involved in a variety of diseases, such as preeclampsia and aged macular degeneration. In addition, various factors modulating angiogenic processes have been recently isolated. Given this complexity then, extensive studies on the interrelationship between VEGF signals and other angiogenesis-regulatory systems will be important for developing future strategies to suppress diseases with an angiogenic component.

• Journal of Industrial and Engineering Chemistry
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• 제67권
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• pp.284-292
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• 2018

Receptor for advanced glycation end-products (RAGE) is overexpressed in various cancer cells. In this study, a RAGE-binding peptide (RBP) was conjugated to polyethylenimine (25 kDa, PEI). RBP-conjugated PEI (PEI-RBP) was characterized as a dual-functional reagent, a RAGE-mediated gene carrier and an anti-angiogenic reagent. As a gene carrier, PEI-RBP had higher transfection efficiency to the C6 glioblastoma cells than PEI. As an anti-angiogenic reagent, the pEmpty/PEI-RBP complex reduced RAGE expression on the surface of the C6 glioblastoma cells. Also, the complex reduced the VEGF expression and tube formation of endothelial cells. Therefore, PEI-RBP may be useful for development of glioblastoma therapy.

• 대한한방내과학회지
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• 제22권4호
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• pp.639-645
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• 2001

Angiogenesis is a fundamental process in reproduction and wound healing. Under these condition, neovascularization is tightly regulated. Unregulated angiogenesis may lead to several angiogenic diseases, and is thought to be indispensible for solid tumor growth and metastsis. The construction of new vascular network is a multistep cascade involving basement membrane degradation, endothelial cell proliferation, endothelial cell migration, and tube formation. Newly reported anti-angiogenic agents in oriental medical field have targeted both specific and multistep stages in the angiogenic process. From recent approach in oriental medical field with several herb medicines including activating blood flow and removing blood stasis medicine(活血化瘀藥), it may be possible in the future to develope specific anti-angiogenic agents that offer a less toxic potential therapy for cancer and angiogenic disease.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.117-125
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• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2006년도 International Meeting of the Microbiological Society of Korea
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• pp.111-112
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• 2006

• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권1호
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• pp.10-23
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• 2007

Hallmarks of clinical behaviors of adenoid cystic carcinoma(ACC) of salivary glands are the delayed onset of vascular metastasis and poor responses to classical chemotherapeutic agents. Poor prognoses from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, cellular and molecular characteristics that influence the dissemination of metastatic cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of angiogenic proteins in benign (pleomorphic adenoma) and malignant (ACC, mucoepidermoid carcinoma) tumors of salivary glands and compared each other and to those in oral squamous cell carcinoma. Using surgical specimens, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), phosphorylated VEGFR-2 (pVEGFR-2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. Most angiogenic factors were overexpressed in malignant salivary tumors than in pleomorphic adenoma which is benign nature. Moreover, ACC demonstrated more expression of VEGFR-2 than that of squamous cell carcinoma which used as control. Conclusively, these data show those angiogenic factors produced by salivary gland tumors may affect the propagation and metastasis of malignant cells of salivary tumors, and could be used as biomarkers for the malignant transformation of salivary gland tumors. Prospectively, although further studies will be needed, these biomarkers related to angiogenesis can be molecular targets for the therapy of salivary ACC, which has propensity for delayed vascular metastasis.

• 생명과학회지
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• 제26권1호
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• pp.91-100
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• 2016

혈관신생의 억제는 암과 같은 신생혈관형성 질환의 치료를 위해 유용한 접근법이다. 신생혈관형성의 핵심인자인 혈관내피세포성장인자는 신생혈관형성 질환의 치료를 위한 주요한 표적이다. 그러므로, 본 연구에서는 in vitro 분석과 ex vivo 동물 실험을 통해 황금 열수추출물의 신생혈관형성 억제효과를 연구했다. 본 연구결과에서 황금 열수추출물이 혈관내피세포성장인자에 의해 자극된 혈관내피세포에 있어 세포독성 없이 세포의 이동, 침투, 관형성을 농도 의존적으로 억제하였다. 더 나아가 황금 열수추출물은 혈관내피세포성장인자에 의해 유도된 흰쥐 대동맥 주변 미세혈관 발아를 예방하였다. 본 연구결과들은 황금 열수추출물이 신생혈관형성 억제작용이 있고, 이는 혈관내피세포성장인자에 의해 유도된 혈관신생을 억제 하는 잠재적 소재가 될 수 있음을 제안한다.

• Macromolecular Research
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• 제15권2호
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• pp.100-108
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• 2007

Gene therapy has become a promising strategy for the treatment of genetically based diseases, such as cancer, which are currently considered incurable. A major obstacle in the field of cancer gene therapy is the development of a safe and efficient delivery system for therapeutic gene transfer. Non-viral vectors have attracted great interest, as they are simple to prepare, stable, easy to modify and relatively safe compared to viral vectors. In this review, an insight into the strategies developed for polyethylenimine (PEI)-based non-viral vectors has been provide, including improvement of the polyplex properties by incorporating hydrophilic spacer, poly(ethylene glycol) (PEG). Moreover, this review will summarize the strategies for the tumor targeting. Specifically, a targeted polymeric gene delivery system, PEI-g-PEG-RGD, will be introduced as an efficient gene delivery vector for tumor therapy, including its functional analysis both in vitro and in vivo.

• 생약학회지
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• 제53권1호
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• pp.21-28
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• 2022

Sparassis crispa is an edible mushroom that has been widely utilized in Japan and Korea. It has various biological activities, such as anti-hypertensive, anti-allergic, anti-diabetic, anti-inflammatory, anti-angiogenic, and anti-cancer effects. In this study, we investigated the anticancer activity and underlying molecular mechanism of chloroform fraction of methanol extract of S. crispa (CESP) against cervical cancer stem cells (CSCs), which contribute to tumor initiation, recurrence, and resistance to therapy of human cervical cancer. CESP effectively inhibited the proliferation, tumorsphere formation, and migration of HeLa-derived cervical CSCs by promoting apoptosis. In addition, CESP significantly downregulated the expression of key cancer stemness markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct-4, and Sox-2, in HeLa-derived cervical CSCs. Furthermore, CESP remarkably suppressed in vivo tumor growth of HeLa-derived cervical CSCs in a chick embryo chorioallantoic membrane (CAM) model. Therefore, our findings suggest that CESP has potential as a natural medicine for the prevention and treatment of cervical cancer by targeting CSCs.