• The Journal of Korean Medicine
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• v.29 no.1
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• pp.179-191
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• 2008

Background and Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus,and has increased in Korea. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently skin barrier dysfunction and hyperresponsive Th2 cells in the acute phase have been reported as important mechanisms. Cheonggi-san(CGS) is used in oriental clinics for treatingacute skin lesions of eczema or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic effects of its internaluse on atopic dermatitis-like skin lesions, induced in NC/Nga mice by the mite antigen D. pteronyssinus and disrupting skin barrier. Materials and Methods : The NC/Nga mice were classified into three groups: control group, atopic dermatitis elicitated group(AD), and CGS treated group (CT). Atopic dermatitis-like skin lesions were induced on the back of female NC/Nga mice, 12 weeks of age, by tape stripping, 5% SDS applied to disrupt skin barrier and painting 3 times a week with D. pteronyssinus crude extract solution for 3 weeks. CT was treated with CGS orally after atopic dermatitis was elicitated. We observed changes of skin damage, mast cells, substance P, angiogenesis, skin barrier, Th2 cell differentiation, nuclear factor-${\kappa}B(NF-{\kappa}B)$ p65 activation and COX-2 in NC/Nga mice with atopic dermatitis-like skin lesions. Results : The skin damages as eczema were seenin AD, but mitigated in CT. The degranulated mast cells in dermal papillae increased in AD, but decreased in CT. The substance P positive reacted cells in CT remarkably decreased. The angiogenesis increased in AD, but decreased in CT. The decrease of lipid deposition and ceramide in AD was seen, but anincrease of lipid deposition and ceramide in CT was seen. The distribution of IL-4 positive reacted cells in dermal papillae increased in AD, but decreased in CT. The distribution of NF-${\kappa}B$ p65 positive reacted cells & COX-2 positive reacted cells in CT decreased. Conclusion : The results may suggest that the CGS per os decreases the dysfunction of the skin barrier, inhibits Th2 cell differentiation and inhibits NF-${\kappa}B$ p65 activation in NC/Nga mice with atopic dermatitis-like skin lesions.

• Journal of Life Science
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• v.26 no.12
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• pp.1367-1375
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• 2016

Cilostazol is known to be a selective inhibitor of phosphodiesterase III and is generally used to treat stroke. Our previous findings showed that cilostazol enhanced capillary density through angiogenesis after focal cerebral ischemia. Angiogenesis is an important physiological process for promoting revascularization to overcome tissue ischemia. It is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation. Here, we examined the modulatory effect of cilostazol at each step of the angiogenic mechanism by using human brain microvascular endothelial cells (HBMECs). We found that cilostazol increased the migration of HBMECs in a dose-dependent manner. However, it did not enhance HBMEC proliferation and capillary-like tube formation. We used a cDNA microarray to analyze the mechanisms of cilostazol in cell migration. We picked five candidate genes that were potentially related to cell migration, and we confirmed the gene expression levels by real-time PCR. The genes phosphoserine aminotransferase 1 (PSAT1) and CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$) were up-regulated. The genes tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), and RARRES3 were down-regulated. Our observations suggest that cilostazol can promote angiogenesis by promoting endothelial migration. Understanding the cilostazol-modulated regulatory mechanisms in brain endothelial cells may help stimulate blood vessel formation for the treatment of ischemic diseases.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.12.1-12.17
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• 2024

Exosomes are double phospholipid membrane vesicles that are synthesized and secreted by a variety of cells, including T cells, B cells, dendritic cells, immune cells, are extracellular vesicles. Recent studies have revealed that exosomes can play a significant role in under both physiological and pathological conditions. They have been implicated in regulation of inflammatory responses, immune response, angiogenesis, tissue repair, and antioxidant activities, particularly in modulating immunity in autoimmune diseases (AIDs). Moreover, variations in the expression of exosome-related substances, such as miRNA and proteins, may not only offer valuable perspectives for the early warning, and prognostic assessment of various AIDs, but may also serve as novel markers for disease diagnosis. This article examines the impact of exosomes on the development of AIDs and explores their potential for therapeutic application.

• BMB Reports
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• v.53 no.10
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• pp.533-538
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• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5363-5369
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• 2012

High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-$1{\alpha}$, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8019-8026
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• 2014

The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha ($RAR{\alpha}$). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors.

• BMB Reports
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• v.48 no.4
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• pp.217-222
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• 2015

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Distant metastasis is a major cause of mortality in CRC. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. Many miRNAs are aberrantly expressed in cancer and influence tumor progression. Accumulating studies suggest that multiple miRNAs are actively involved in the CRC metastasis process. Thus, we aim to introduce the role of miRNAs in multi-steps of CRC metastasis, including cancer cell invasion, intravasation, circulation, extravasation, colonization, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, we suggest the potential application of miRNAs as biomarkers for CRC patients with metastasis. [BMB Reports 2015; 48(4): 217-222]

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2437-2444
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• 2012

Tumor metastasis remains the principal cause of treatment failure and poor prognosis in patients with colorectal cancer. It is a multistage process which includes proteolysis, motility and migration of cells, proliferation in a new site, and neoangiogenesis. A crucial step in the process of intra- and extra-vasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM). In this stage, urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs) are necessary. Micrometastases need the presence of growth factor and vascular growth factor so that they can form macrometastasis. In addition, cell adhesion molecules (CAMs) and guanine nucleotide exchange factors (GEFs) play important roles in the progression of colorectal cancer and metastatic migration. Further elucidation of the mechanisms of how these molecules contribute will aid in the identification of diagnostic and prognostic markers as well as therapeutic targets for patients with colorectal metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3043-3051
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• 2016

Controlled remodeling of the extracellular matrix (ECM) is essential for cell growth, invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of secreted, zinc-dependent endopeptidases capable of degradation of ECM components. The expression and activity of MMPs in a variety of human cancers have been intensively studied. They play important roles at different steps of malignant tumor formation and have central significance in embryogenesis, tissue remodeling, inflammation, angiogenesis and metastasis. However, increasing evidence demonstrates that MMPs are involved earlier in tumorigenesis. Recent studies also suggest that MMPs play complex roles in tumor progression. MMPs and membrane type (MT)-MMPs are potentially significant therapeutic targets in many cancers, so that designing of specific MMP inhibitors would be helpful for clinical trials. Here, we review the pleiotropic roles of the MMP system in hematological malignancies in-vitro and in-vivo models.

• Macromolecular Research
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• v.15 no.2
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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.