• Journal of Life Science
• /
• v.22 no.9
• /
• pp.1224-1230
• /
• 2012

Cancer chemotherapy drugs command a large share of the market, and the development of new therapeutics with high efficacy and specificity is an active area of study. Recently, the development of cancer therapeutics from natural products targeting angiogenesis has drawn attention due to conventional chemotherapeutics showing serious side effects and resistance in cancer cells. In this study, we investigated the pharmacological efficacy of Gomisin A, an active ingredient of Schizandra chinensis baillon, on tumor growth and metastasis. Administration of Gomisin A at 10 and 100 ${\mu}g/ml$ reduced tumor growth in vivo by $80.5{\pm}8.1%$ and $96.2{\pm}2%$, respectively, compared with positive tumor controls. Treatment of Gomisin A in normal and various tumor cell lines did not exert significant toxicity. Mice treated with Gomisin A at a concentration of 10 and 100 ${\mu}g$/head showed a significant reduction in tumor-induced angiogenesis of $151{\pm}16.9%$ and $98.5{\pm}29.5%$, respectively. Furthermore, tumor metastasis analysis revealed that the administration of Gomisin A at a concentration of 10 and 100 ${\mu}g$/head inhibited tumor metastasis by $13.5{\pm}8.56%$ and $58.3{\pm}9.12%$, respectively. In addition, Gomisin A significantly decreased cell adhesion of the B16BL6 cells to the extracellular matrix. These results demonstrate that Gomisin A inhibits tumor growth via suppression of angiogenesis and tumor metastasis inhibition, without cellular toxicity. The pharmacological efficacy of Gomisin A suggests that it may be a potential candidate for the development of cancer drugs.

• Biomedical Science Letters
• /
• v.24 no.4
• /
• pp.285-291
• /
• 2018

Gremlin-1 (GREM1) has been defined as an antagonist of bone morphogenetic proteins (BMPs), particularly during embryonic development and tissue differentiation. However, recent studies have shown that GREM1 has BMPs-dependent or -independent functions in diverse human diseases. GREM1 plays a key role in the process of organ fibrosis, including lungs, kidneys, and so on. The GREM1-induced fibrosis typically promotes the development of other diseases, such as pulmonary hypertension, renal inflammation, and diabetic nephropathy. More recently, considerable evidence has been reported showing that GREM1 is involved in the promotion and/or progression of tumors in vitro and in vivo. It also performs an oncogenic role in the maintenance of cancer stem cells. Although GREM1 is known to function in a variety of diseases, here we focus on the role of GREM1 in cancer, and suggest GREM1 as a potential therapeutic target in certain types of cancer.

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

• International Journal of Stem Cells
• /
• v.17 no.1
• /
• pp.15-29
• /
• 2024

The development and differentiation of endothelial cells (ECs) are fundamental processes with significant implications for both health and disease. ECs, which are found in all organs and blood vessels, play a crucial role in facilitating nutrient and waste exchange and maintaining proper vessel function. Understanding the intricate signaling pathways involved in EC development holds great promise for enhancing vascularization, tissue engineering, and vascular regeneration. Hematopoietic stem cells originating from hemogenic ECs, give rise to diverse immune cell populations, and the interaction between ECs and immune cells is vital for maintaining vascular integrity and regulating immune responses. Dysregulation of vascular development pathways can lead to various diseases, including cancer, where tumor-specific ECs promote tumor growth through angiogenesis. Recent advancements in single-cell genomics and in vivo genetic labeling have shed light on EC development, plasticity, and heterogeneity, uncovering tissue-specific gene expression and crucial signaling pathways. This review explores the potential of ECs in various applications, presenting novel opportunities for advancing vascular medicine and treatment strategies.

• Macromolecular Research
• /
• v.15 no.2
• /
• pp.100-108
• /
• 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.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.164.1-164.1
• /
• 2003

Wm was isolated from Cynanchum wilfordii (Asclepiadaceae) as a mixture form of polypregnane glycosides that included wilfoside K1N and wilfoside C1N. In the present study, we investigated the anti-angiogenic effect of wilfoside glycosides using in vivo and in vitro assay systems. We first demonstrated that concentrated conditioned media obtained from Wm-treated HepG2 human hepatoblastoma cells blocked the angiogenic activation of Wm-untreated concentrated conditioned media, suggesting that Wm may have an inhibitory effect on tumor-induced angiogenesis. (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1998.11a
• /
• pp.95-98
• /
• 1998

Ginseng (the root of Panax ginseng C. A. MEYER, Araliaceae) has been used for traditional medicine in China, Korea, Japan and other Asian countries for the treatment of various diseases including psychiatric and neurologic diseases as well as diabetes mellitus. So far, ginseng saponins (ginsenosides) have been regarded as the principal components responsible for the pharmacological activities of ginseng. Ginsenosides are glycosides containing an aglycone (protopanaxadiol or protopanaxatriol) with a dammarane skeleton and have been shown to possess various biological activities including the enhancement of cholesterol biosynthesis, stimulation of serum protein synthesis, immuno- modulatory effects and anti-inflammatory activity. Several studies using ginsenosides have also reported anti-tumor effects, particularly the inhibition of tumor-induced angiogenesis, tumor invasion and metastasis, and the control of phenotypic expression and differentiation of tumor cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.28 no.3
• /
• pp.205-215
• /
• 2002

The purpose of this study was to evaluate the tissue response in various bone grafting materials, especially xenogenous bone materials in vivo, compare of bone formation capacity of various bone grafting materials on rat skull defects and evaluate the effect of Hyaluronic acid on healing of human Demineralized Freezed Dried Bone allogenous graft (DFDBA) materials in rat calvarial defects. 30 Sprague-Dawly rats were divided into 4 groups. $7{\times}7mm$ size bony defect were artificially prepared in the calvaria (both parietal bone) of all 30 rats and follwed group grafting of autogenous bone graft on right side and allogenic DFDBA on left side bone graft (rat DFDB) in 15 control group, but in 15 experimental group, xenograft (human DFDB) on left side, hyaluronic acid treated with xenograft on right side. Sequential sacrifices was performed at 1, 2, 4, 6, 8 weeks of experiment. These specimens were stained with H&E and MT stain, and then histologic analysis under light microscope was carried out. There were inflammatory reaction in all graft material during early stage. Autogenous and Allogenous DFDBA graft group observed inflammatory reaction at 1 week. Xenograft group persistant inflammatory reaction until 4 weeks, but in HA treated xenograft group inflammatory reaction was decreased at 2 weeks. Osteoblastic activity in control group was begun at 2 week, xenograft group was delayed at 6 weeks, however HA treated xenograft group was begun at 4 weeks. At 2 week, mild osteoclastic activity were observed in all xenograft group not in concerned to HA, but there was no difference each group after 4 weeks. There are most activated angiogenesis around graft mateirals in xenograft group at 2 weeks, but in HA treated xenograft group, decreased angiogenesis was observed at same time. Bone formation and bone maturation of xenograft group, there was no difference in HA treatment, was less than control group. Fibrosis around xenograft materials were observed until 6 weeks, there was no difference between xenograft and HA treated groups.

• Molecules and Cells
• /
• v.45 no.10
• /
• pp.729-737
• /
• 2022

Carboplatin-based chemotherapy is the primary treatment option for the management of retinoblastoma, an intraocular malignant tumor observed in children. The aim of the present study was to establish carboplatin-resistant retinoblastoma cell lines to facilitate future research into the treatment of chemoresistant retinoblastoma. In total, two retinoblastoma cell lines, Y79 and SNUOT-Rb1, were treated with increasing concentrations of carboplatin to develop the carboplatin-resistant retinoblastoma cell lines (termed Y79/CBP and SNUOT-Rb1/CBP, respectively). To verify resistance to carboplatin, the degree of DNA fragmentation and the expression level of cleaved caspase-3 were evaluated in the cells, following carboplatin treatment. In addition, the newly developed carboplatin-resistant retinoblastoma cells formed in vivo intraocular tumors more effectively than their parental cells, even after the intravitreal injection of carboplatin. Interestingly, the proportion of cells in the G₀/G₁ phase was higher in Y79/CBP and SNUOT-Rb1/CBP cells than in their respective parental cells. In line with these data, the expression levels of cyclin D1 and cyclin D3 were decreased, whereas p18 and p27 expression was increased in the carboplatin-resistant cells. In addition, the expression levels of genes associated with multidrug resistance were increased. Thus, these carboplatin-resistant cell lines may serve as a useful tool in the study of chemoresistance in retinoblastoma and for the development potential therapeutics.

• The Journal of Korean Medicine
• /
• v.32 no.2
• /
• pp.1-13
• /
• 2011

Background and Objective: Coptidis Rhizoma is a medicinal herb known for its antioxidant and anti-inflammatory effect. The purpose of this study was to examine the effects of CR on the experimental burn elicitation in vitro and in vivo. Material and Methods: In order to know the antioxidant effect on skin cell of mice after burn elicitation, superoxide dismutase (SOD) activity was measured. In vitro, the RAW 264.7 macrophage cells were treated with lipopolysaccharides for experimental inflammation. iNOS mRNA expression was observed after CR-treatment. In order to know effects on the skin regeneration in the burned mice, we counted the nitric oxide (NO) in blood. We also observed the histological structure in the epidermal basal layer and the dermal section, and we studied changes of angiogenesis in the capillaries surrounding the basal layer and dermal papilla. The changes of transcription of iNOS mRNA (inducible nitric oxide synthase mRNA) and changes of NF-${\kappa}$B (nuclear factor ${\kappa}$B) p65 positive reaction were also observed to investigate the changes of the stress in the skin. Results: The results indicated that CR has significant effects on the antioxidant effect on skin cells of mice after burn elicitation by increasing SOD activity in the in vitro test. It seemed that CR decreased the amount of NF-${\kappa}$B which induced the iNOS mRNA dose-dependently and suppress activating NO and angiogenesis. Furthermore, CR facilitated the process of skin recovery after experimental burn. Conclusion: CR can be applied for burned skin via antioxidant effect and skin regeneration.