• Journal of Ginseng Research
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• 제45권1호
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• pp.126-133
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• 2021

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권2호
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• pp.55-65
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• 2009

Purpose: We determined the therapeutic effects of blockade of epidermal growth factor(EGF) and vascular endothelial growth factor(VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma(OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor(orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. Results: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators(pMAPK and pAkt), decreased proliferative index, decreased microvessel density(MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.

• KSBB Journal
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• 제19권3호
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• pp.210-214
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• 2004

본 연구에서는 생분해성 고분자 담체인 PGA 담체에 부착된 간세포의 이식을 통해서 이식된 간세포가 괴사하지 않고 남아 있으며 간 조직 구조의 일종인 담세관 유사구조를 확인하였다. 조직공학적인 간세포 이식 방법의 개발은 간 질환에 새로운 치료방법 개발의 가능성을 열어줄 수 있다.

• 대한한방내과학회지
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• 제29권1호
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• pp.25-31
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• 2008

Objectives : The study was intended to investigate whether Iljoong-eum (IJE) significantly affects proliferation and growth of prostate cancer cells. Materials and Methods : In vitro, after the treatment of DU-145 and PC-3 cells with IJE, we performed Sulforhodamine B (SRB) method. In vivo, a total of 8 male nude mice subcutaneously transplanted with the PC-3 cell line were divided in 2 groups. An experimental group was given IJE orally at a dose of 4.29ml/kg per day from the 8th to 31st day following tumor injection. All mice were observed for 31 days, and sacrificed by CO2 gas asphyxiation at the end of the experiment. The mean tumor volume and body weight of both groups were compared using Student's t-tests. Results : In vitro, IJE inhibited significantly proliferation and growth of DU-145 cells and PC-3 cells. In vivo, IJE inhibited significantly proliferation and growth of PC-3 cells xenografted into athymic nude mice. Conclusions : Our data has shown that IJE is effective in suppressing the growth rate of prostate cancer cells.

• Preventive Nutrition and Food Science
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• 제12권1호
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• pp.11-15
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• 2007

This study was conducted to evaluate the influence of diets containing genistein and soy extract on the growth of MDA-MB-231 cells implanted into female Balb/c mice. Four-week-old female athymic nude mice (Balb/c) were acclimated to an AIN-93G control diet for 1 week and then injected MDA-MB-231 cells ($1{\times}10^6$/site) and were continued on the on AIN-93G control diet. Five weeks after injecting the MDA-MB-231 cells ($1{\times}10^6$/site), two experimental groups were assigned to diets containing genistein (750 ${\mu}g/g$ AIN-93G diet) or 0.6% soy extract (containing genistein at 750 ${\mu}g/g$ AIN-93G diet) until they were sacrificed. Tumor growth was significantly reduced in the groups treated with genistein and soy extract compared to the control group. The results of the proliferating cell nuclear antigen (PCNA) assay also revealed that genistein and soy extract treatment reduced the proliferation of MDA-MB-231 cells in vivo. In the present study, dietary isoflavone was provided just before solid tumor formation, and thus the timing of dietary isoflavone administration may be critical to the suppression of tumor growth.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제31권1호
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• pp.8-17
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• 2009

Purpose: We determined the therapeutic effect of an epidermal growth factor receptor (EGFR)-specific monoclonal antibody (mAb), cetuximab (Erbitux) on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We induced subcutaneous tumors by inoculating human tumor cell suspension into the right flank of nude mice. Nude mice with subcutaneous tumors were randomized to receive cetuximab alone, paclitaxel alone, cetuximab plus paclitaxel, or a placebo (control). Antitumor mechanisms of cetuximab were determined by immunohistochemical and apoptosis assays. Results: Cetuximab, paclitaxel, and cetuximab/paclitaxel combined therapy resulted in 50%, 52%, 67% in vivo inhibition of tumor proliferation, respectively. Tumors of mice treated with cetuximab plus paclitaxel demonstrated decreased PCNA-positive tumor cells and increased apoptotic tumor cells, which slowed growth of the murine tumors. Conclusion: These data show that EGFR can be a molecular target for the treatment of OSCC. And combination therapy with cetuximab and paclitaxel warrants further clinical study.

• Journal of Microbiology and Biotechnology
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• 제18권5호
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• pp.975-982
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• 2008

We investigated whether transplantation of osteogenically differentiated bone marrow-derived mesenchymal stem cells (BMMSCs) and the use of an hydroxyapatite (HAp) scaffold can enhance the in vivo bone formation efficacy of human BMMSCs. Three months after implantation to the subcutaneous dorsum of athymic mice, transplantation of osteogenically differentiated human BMMSCs increased the bone formation area and calcium deposition to 7.1- and 6.2-folds, respectively, of those of transplantation of undifferentiated BMMSCs. The use of the HAp scaffold increased the bone formation area and calcium deposition to 3.7- and 3.5-folds, respectively, of those of a polymer scaffold. Moreover, a combination of transplantation of osteogenically differentiated BMMSCs and HAp scaffold further increased the bone formation area and calcium deposition to 10.6- and 9.3-folds, respectively, of those of transplantation of undifferentiated BMMSCs seeded onto polymer scaffolds. The factorial experimental analysis showed that osteogenic differentiation of BMMSCs prior to transplantation has a stronger positive effect than the HAp scaffold on in vivo bone formation.

• 대한의생명과학회지
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• 제27권1호
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• pp.1-11
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• 2021

Cancer stem cells, which are known to drive tumor formation and maintenance, are a major obstacle in the effective treatment of various types of cancer. Trans-membrane glycoprotein mucin 1 antigen and cell surface glycogen CD44 antigen are well-known surface markers of breast cancer cells and breast cancer stem cells, respectively. To effectively treat cancer cells and cancer stem cells, we developed a new drug-encapsulating liposome conjugated with dual-DNA aptamers specific to the surface markers of breast cancer cells and their cancer stem cells. These two aptamer (Apt)-targeted liposomes, which were prepared to encapsulate doxorubicin (Dox), were named "Dual-Apt-Dox". Dual-Apt-Dox is significantly more cytotoxic to both cancer stem cells and cancer cells compared to liposomes lacking the aptamers. Furthermore, we demonstrated the inhibitory efficacy of Dual-Apt-Dox against the experimental lung metastasis of breast cancer stem cells and cancer cells in athymic nude mice. We also showed the potent antitumor effects of dual-aptamer-conjugated liposome systems by targeting cancer cells as well as cancer stem cells. Thus, our data indicate that dual-aptamer-conjugated liposome systems can prove to be effective drug delivery vehicles for breast cancer therapy.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제35권6호
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• pp.353-359
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• 2013

Purpose: Extensive research is actively ongoing for development of an ideal bone substitute that meets the gold standard. Tooth was selected as a donor site for evaluation of potentials in bone substitutes based on its similar chemical compositions to alveolar bone. Previous studies have evaluated inorganic components of autogenous tooth bone graft material (AutoBT) and osteoconductivity. In continuation from the previous studies, the current study was conducted for analysis of organic components and evaluation of osteoinductivity of AutoBT. Methods: Forty-six extracted teeth were collected from actual patients (Korea Tooth Bank, R&D Institute). Extracted teeth were processed into AutoBT and implanted in dorsal subcutaneous muscular tissues of 15 athymic mice. Biopsy samples were harvested at two, five, and eight weeks. The Bradford assay, sodium dodecyl sulphate polyacrylamide gradient gel, and western blotting were performed for investigation of organic contents of AutoBT. Results: Histology analyses showed signs of new bone formation as early as two weeks. Results of the Bradford assay indicated the existence of noncollagenous proteins (NCP). 0.29% (2.89 mg/g) of proteins were extracted by weight in the root portion of AutoBT; 0.02% (0.029 mg/g) and 1.79% (17.93 mg/g) of proteins were measured by weight in crown and block-form of AutoBT, respectively. However, recombinant human bone morphogenetic protein-2 was not observed in AutoBT. Conclusion: Within the limitation of the current study, AutoBT induced new bone formation by NCP embedded in dentin.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2003년도 생물공학의 동향(XIII)
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• pp.356-358
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• 2003

각질형성세포의 배양법이 개발 후 피부 결손 부위의 치료에 인체 각질형성세포를 배양하여 얻어진 표피를 이식하거나 세포부유물을 도포하는 기존의 방법들은 trypsin 처리 과정을 거치면서 배양된 세포의 부착능력을 가진 단백질이 손상되어 성공적인 피부 재생이 불가능하다. 이 연구에서는 면역결핍 생쥐 모델에서 인간 피부 각질형성에포와 EGF-피브린 고분자 혼합물을 분사하여 피부의 전층 상처를 재생하였다. 조직학 검사와 면역화학검사를 통하여 각질형성세포와 EGF-피브린 고분자를 함께 분사한 경우 이식된 인간 표피세포에 의한 빠른 표피재생을 확인할 수 있었다. 이 피부 재생술은 기존의 배양된 인공피부 sheet의 이식을 이용한 피부재생법에 비해 여러 가지 장점을 가지고 있으므로, 앞으로 화상이나 피부궤양과 같은 피부결손의 효율적인 새로운 치료법으로 사용되어질 수 있을 것이다.