• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7601-7605
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• 2013

Background: Gambogenic acid is a major active compound of gamboge which exudes from the Garcinia hanburyi tree. Gambogenic acid anti-cancer activity in vitro has been reported in several studies, including an A549 nude mouse model. However, the mechanisms of action remain unclear. Methods: We used nude mouse models to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members. Results: We found that gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner. Conclusion: Our observations suggested that Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.

• Bulletin of the Korean Chemical Society
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• 제29권10호
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• pp.2023-2025
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• 2008

To evaluate the potential of radioiodine labelled hypericin as a malignant glioma imaging agent, U-251 MG, U-373 MG, C6 glioma and fibroblast were treated with a I-123 labelled hypericin derivative and C6 glioma transplanted nude mouse were injected with a I-124 labelled hypericin derivative for a micro PET imaging. 2- Iodohypericin was prepared as a reference compound. In this paper, we describe the syntheses of 2- iodohypericin and 2-[$^{123}I/^{124}I$]iodohypericin and the results of a corresponding biological evaluation. In all glioma cell lines, 2-[$^{123}I$]iodohypericin uptake was increased in a time dependant manner and an accumulation of 2-[$^{124}I$]iodohypericin was observed in C6 glioma bearing nude mouse. These results suggest that radioiodine labelled hypericin can visualize a PKC overexpressed malignant glioma.

• 대한기관식도과학회지
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• 제5권2호
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• pp.119-126
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• 1999

Objectives : To analyze the effect of retinoids on the differentiation in HNSCC xenografts. Materials and Methods : RA (20mg/kg) or 13-cis-RA (60mg/kg) was orally administered once in a day for 30 days in the xenograft model we prepared using athymic nude mice with AMCHN-4 and -6. We carried out H & E staining and immunohistochemical staining with the monoclonal antibody against involucrin and cytokeratin 10. Results : Both RA and 13-cis-RA were found to suppress the differentiation of AMC-HN-4. Interestingly, RA enhanced the differentiation of AMC-HN-6, although 13-cis RA did not exhibit any effect on the differentiation. These results suggest that in vivo effect of retinoids on the HNSCC growth and differentiation might be various. Retinoids-induced P450 in AMC-HN-6 might be one of the mechanisms to explain the reason why the retinoids exhibit various functions in the HNSCC.

• Journal of Periodontal and Implant Science
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• 제53권1호
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• pp.54-68
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• 2023

Purpose: The purpose of this study was to determine whether metformin (MF) could alleviate the expresssion of reactive oxygen species (ROS) and improve the osteogenic ability of bone marrow mesenchymal stem cells derived from diabetic rats (drBMSCs) in vitro, and to evaluate the effect of MF on the ectopic osteogenesis of drBMSCs in a nude mouse model in vivo. Methods: BMSCs were extracted from normal and diabetic rats. In vitro, a cell viability assay (Cell Counting Kit-8), tests of alkaline phosphatase (ALP) activity, and western blot analysis were first used to determine the cell proliferation and osteogenic differentiation of drBMSCs that were subjected to treatment with different concentrations of MF (0, 50, 100, 200, 500 µM). The cells were then divided into 5 groups: (1) normal rat BMSCs (the BMSCs derived from normal rats group), (2) the drBMSCs group, (3) the drBMSCs + Mito-TEMPO (10 µM, ROS scavenger) group, (4) the drBMSCs + MF (200 µM) group, and (5) the drBMSCs + MF (200 µM) + H₂O₂ (50 µM, ROS activator) group. Intracellular ROS detection, a senescence-associated β-galactosidase assay, ALP staining, alizarin red staining, western blotting, and immunofluorescence assays were performed to determine the effects of MF on oxidative stress and osteogenic differentiation in drBMSCs. In vivo, the effect of MF on the ectopic osteogenesis of drBMSCs was evaluated in a nude mouse model. Results: MF effectively reduced ROS levels in drBMSCs. The cell proliferation, ALP activity, mineral deposition, and osteogenic-related protein expression of drBMSCs were demonstrably higher in the MF-treated group than in the non-MF-treated group. H₂O₂ inhibited the effects of MF. In addition, ectopic osteogenesis was significantly increased in drBMSCs treated with MF. Conclusions: MF promoted the proliferation and osteogenic differentiation of drBMSCs by inhibiting the oxidative stress induced by diabetes and enhenced the ectopic bone formation of drBMSCs in nude mice.

• Journal of Periodontal and Implant Science
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• 제35권2호
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• pp.263-269
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• 2005

Bone morphogenetic protein(BMP) and platelet-derived growth factor(PDGF) have been demonstrated tostimulate bone formation when applied locally in vivo. To explore whether or not the combined use of BMP and PDGF could have promotive effect and synergic interaction on bone formation in vivo, bone marrow mesenchymal stem cells were treated with BMP-2, PDGF-BB, or BMP-2 plus PDGF-BB, and then these cells were injected into the subcutaneous space on the dorsum of nude mice. The bone formation was evaluated after 12 weeks. Histomorphometric analysis demonstrated that the subcutaneous nodules formed in nude mice contained 25.3% newly formed bone in the BMP-2 treated cells, 14.4% newly formed bone in the PDGF-BB treated cells, and 8.9% newly formed bone in the RMP-2 plus PDGF-BB treated cells. The results showed that the combination of BMP-2 and PDGF-BB had neither a promotive effect nor synergic interact on bone formation in vivo.

• IMMUNE NETWORK
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• 제12권6호
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• pp.247-252
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• 2012

Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14 days. The resulting populations of CIK cells comprised 94% $CD3^+$, 4% $CD3^-CD56^+$, 41% $CD3^+CD56^+$, 11% $CD4^+$, and 73% $CD8^+$. This heterogeneous cell population was called cytokine-induced killer (CIK) cells. At an effector-target cell ratio of 100 : 1, CIK cells destroyed 51% of AsPC-1 human pancreatic cancer cells, as measured by the $^{51}Cr$-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 42% and 70% of AsPC-1 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for pancreatic cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5371-5374
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• 2013

Objective: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low-dose photodynamic therapy of 5, 10, 15, 20-tetrakis(1-methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. Materials and Methods: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously ($1{\times}10^7cells/200{\mu}L$). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, $108J/cm^2$), and the C group given three-treatments with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. Results: Tumour growth in C group was significantly inhibited compared with A and B groups (P<0.05), without any injury to the skin and internal organs. Conclusion: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects.

• 대한골관절종양학회지
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• 제11권1호
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• pp.46-53
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• 2005

목적: Bisphosphonate(BPs)는 endogenous pyrophosphates의 유사체로 Paget's disease, 골다공증, 종양 유발성 골용해와 같은 골격계 질환의 치료에 쓰이고 있으며, 유방암의 골파괴성 전이에 대한 치료제로 사용되어 지고 있다. 골전이의 양상이 골흡수성 및 골생성이 혼합되어 나타나는 전립선암의 전이에서도 치료제의 하나로 이용되고 있다. BPs는 파골세포성 골흡수가 과하게 일어난 질환에 대해서는 비교적 널리 알려져 있지만, 골종양 세포에 대한 직접적인 효과에 대해서는 아직 밝혀져 있지 않다. 가장 강력한 질소 함유(nitrogen-containing) BPs인 Zoledronic acid(ZOL)로서 골육종이 발현된 nude mouse model을 이용하여 ZOL의 종양 억제능을 생체내 실험으로 확인하고자 하였다. 대상 및 방법: 인간 골육종 세포주로는 MG-63과 HOS 골육종 세포주를 이용하였고, 종양의 크기 변화를 육안으로 확인하기 위하여 GFP 유전자가 형질 전환된 MG-63-GFP, HOSGFP 세포를 6주령된 수컷 마우스 10마리에 각각 피하주사하여 종양의 조각이 $3{\times}3{\times}3$ mm이 될 때까지 사육한 후, ZOL을 120 ug/kg의 농도로 일주일에 2번 피하에 주사하였다. 종양의 크기를 일주일에 두 번씩 측정하고, 형광조명을 이용하여 촬영하였다. 결과: HOS 골육종 세포주를 이용한 생체실험에서 대조군의 종양의 평균 크기는 2,520 $mm^3$이며 ZOL 투여군은 131 $mm^3$로서 94%의 감소를 보이며, MG-63 골육종 세포주를 이용한 생체실험에서는 대조군의 종양의 평균 크기는 2,866 $mm^3$이며 실험군은 209 $mm^3$로서 72%의 감소를 보였다(P<0.05). 결론: Nude mouse를 이용한 생체실험에서 ZOL은 골육종의 세포사멸에 직접적인 영향을 미치며 이것은 앞으로 골육종 치료의 약제중 하나로 선택되어 질수 있다고 판단되며, 종양세포주에 따라 ZOL의 영향이 다를 수 있으므로 ZOL에 감수성 있는 종양세포를 찾아 적용하는 것이 좋을 것으로 사료된다.

• Archives of Plastic Surgery
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• 제44권3호
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• pp.194-201
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• 2017

Background Platelet-rich plasma (PRP) contains high concentrations of growth factors involved in wound healing. Hydrogel is a 3-dimensional, hydrophilic, high-molecular, reticular substance generally used as a dressing formulation to accelerate wound healing, and also used as a bio-applicable scaffold or vehicle. This study aimed to investigate the effects of PRP and hydrogel on wound healing, in combination and separately, in an animal wound model. Methods A total of 64 wounds, with 2 wounds on the back of each nude mouse, were classified into 4 groups: a control group, a hydrogel-only group, a PRP-only group, and a combined-treatment group. All mice were assessed for changes in wound size and photographed on scheduled dates. The number of blood vessels was measured in all specimens. Immunohistochemical staining was used for the analysis of vascular endothelial growth factor (VEGF) expression. Results Differences in the decrease and change in wound size in the combined-treatment group were more significant than those in the single-treatment groups on days 3, 5, 7, and 10. Analysis of the number of blood vessels through histological examination showed a pattern of increase over time that occurred in all groups, but the combined-treatment group exhibited the greatest increase on days 7 and 14. Immunohistochemical staining showed that VEGF expression in the combined-treatment group exhibited its highest value on day 7. Conclusions This experiment demonstrated improved wound healing using a PRP-hydrogel combined treatment compared to either treatment individually, resulting in a decrease in wound size and a shortening of the healing period.

• International Journal of Stem Cells
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• 제9권2호
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• pp.186-191
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• 2016

Background and Objectives: With the global demand for dairy protein for consumption growing annually, there has been increasing activity in the research field of dairy protein synthesis and production. From a manipulation perspective, it is more difficult to use live cattle for laboratory studies on the production of milk as well as of dairy protein such as casein, as compared with using laboratory animals like rodents. Therefore, we aimed to develop a mouse model of bovine mammary alveolar ducts for laboratory-scale studies. We studied the formation of the bovine mammary gland ductal structure by transplanting the MAC-T bovine alveolar cell line into mice. Methods and Results: MAC-T cells ($1{\times}10^7$) were suspended in Matrigel and injected into the dorsal tissue of 8-week-old male BALB/C nude mice. Histological analysis of tissue dissected from the MAC-T cell-transplanted mice after 6 weeks showed the typical morphology of the tubuloalveolar female gland, as well as glands made up of branching ducts that were surrounded by smooth muscle with small alveoli budding off the ducts. In addition, the epithelial markers CK14 and CK18 were expressed within the duct-like structure. Prolactin was detected in the duct interior in these CK14+ and CK18+ cells but not in the non-transplanted MAC-T cells. Conclusions: These results showed that duct-like tissue had been successfully formed after 6 weeks of transplantation of the CK14+ and CK18+ MAC-T cells into mice dorsal tissue. This mouse model will be a useful tool for further research on the bovine mammary gland.