• Parasites, Hosts and Diseases
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• 제52권6호
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• pp.605-612
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• 2014

Toxoplasma gondii is an intracellular protozoan parasite that causes a Th1 cellular immunity. Our previous study showed that T. gondii lysate antigen (TLA) treatment in S180 tumor-bearing mice resulted in tumor reduction by suppressing CD31 expression, a marker of angiogenesis. In the present study, to investigate tumor suppressive effect of TLA under the absence of T lymphocytes, athymic nude mice were compared with euthymic mice in the anti-tumorigenic effect triggered by TLA in CT26 tumors. According to the results, intratumorally injected TLA reduced tumor growth and TIMP-1 level, a metastatic marker, in both euthymic and athymic mice. TLA treatment led to a sharp increase in IL-12 expression in serum cytokine profiling of athymic mice, and increased MyD88 signals in macrophages derived from the bone marrow, implying the activation of innate immunity. The selective induction of IL-12 by TLA treatment had an anti-tumorigenic effect.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권2호
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• pp.81-93
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• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• International journal of advanced smart convergence
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• 제8권1호
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• pp.184-195
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• 2019

This study investigates the hair restoration efficacy of selected radish saponin extracts on nude mice. Nude mice genetically predisposed to pattern balding were used in this study. Our study revealed the underlying mechanism of stimulating hair growth in athymic nude mice by repair the nu/nu follicular keratin differentiation defect. Thus, the topical application of radish saponin may represent a novel strategy for the management and therapy of certain forms of alopecia. The term of hair density of PEE treated nude mice were significantly increase as compared with of control nude mice. Histological observation of skin sample showed no hair follicle or only distorted hair follicles were observed in the control samples, in contrast, by the PEE treatment groups showed a fully formed and increased the number of hair follicles up to three times higher than that of control group in terms of the number of hair follicles in nude mouse skin.PEE treated mice the number of BrdU-labeled keratinocytes per anagen follicle increased significantly, especially in the follicular bulbs and outer root sheath compared with the control mice. Moreover, PEE-treated nude mice also exhibited a significant increase in the number of BrdU-labeled epidermal keratinocyte proliferation.

• 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.

• 약학회지
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• 제59권4호
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• pp.164-169
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• 2015

In the present study, we determined the effect of $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that $18{\beta}$-GA induced cell death in HT-29. The cytotoxicity was enhanced as the $18{\beta}$-GA treatment was prolonged. In case of 72 hrs treatment, $LD_{50}$ of $18{\beta}$-GA was approximately $90{\mu}M$, and the efficacy at $100{\mu}M$ of $18{\beta}$-GA appeared to be equivalent to that of doxorubicin at $1{\mu}M$. Based on the in vitro data, we tested the anti-tumor effect of $18{\beta}$-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 ($3{\times}10^6cells/mouse$) to mice and the mice were treated intraperitoneally with $18{\beta}$-GA ($50{\mu}g/time/mouse$) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the $18{\beta}$-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that $18{\beta}$-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권6호
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• pp.499-508
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• 2007

Background and Purpose: Some subtypes of malignant salivary gland tumors such as adenoid cystic carcinoma (ACC) frequently result in distant metastasis of vascular origin, which are main causes of treatment failure. The reasons for the affinity for vascular metastatic potential are unclear. Therefore, molecular characteristics that influence the dissemination of metastatic tumor 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 vascular metastasis related factors in orthotopic (parotid) murine models of parotid ACC and compared with those in ectopic (subcutis) tumors of athymic mice. Experimental Design: Using specimens from murine parotid (orthotopic, experimental group) and subcutaneous (ectopic, control group) tumors, which have developed via transplantation of tumor cells, originated from human parotid ACC, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. We also performed immunohistochemical assays with VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and phosphorylated VEGFR-2. Results: Transplantation of human ACC tumor cell $(5{\times}10^5)$ into the parotid and subcutis successfully resulted in orthotopic (parotid) and ectopic (subcutaneous) tumors in athymic mice. Immunohistochemical staining demonstrated higher expression of major angiogenic factors (VEGF, bFGF, MMP-9) in the orthotopic tumors than in ectopic tumors (P<0.05). But the expression level of angiogenic receptors were same in orthotopic and ectopic tumors of parotid ACC. Conclusion: VEGF, bFGF, and MMP-9 could be a good candidates for antiangiogenic therapy for the contol of vascular metastatic lesions of salivary ACC.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권6호
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• pp.529-539
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• 2008

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

• The Journal of Advanced Prosthodontics
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• 제2권1호
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• pp.7-13
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• 2010

Although most researchers agree that platelet-rich plasma (PRP) is a good source of autogenous growth factors, its effect on bone regeneration is still controversial. The purpose of this study was to evaluate whether increasing angiogenic factors in the human PRP to enhance new bone formation through rapid angiogenesis. MATERIAL AND METHODS. In vitro, the human platelets were activated with application of shear stress, $20\;{\mu}g/ml$ collagen, 2 mM $CaCl_2$ and 10U thrombin/$1\;{\times}\;10^9$ platelets. Level of vascular endothelial growth factor (VEGF) and platelet microparticle (PMP) in the activated platelets were checked. In the animal study, human angiogenic factors-enriched PRP was tested in 28 athymic rat's cranial critical bone defects with $\beta$-TCP. Angiogenesis and osteogenesis were evaluated by laser Doppler perfusion imaging, histology, dual energy X-ray densinometry, and micro-computed tomography. RESULTS. In vitro, this human angiogenic factors-enriched PRP resulted in better cellular proliferation and osteogenic differentiation. In vivo, increasing angiogenic potential of the PRP showed significantly higher blood perfusion around the defect and enhanced new bone formation around acellular bone graft material. CONCLUSION. Angiogenic factor-enriched PRP leads to faster and more extensive new bone formation in the critical size bone defect. The results implicate that rapid angiogenesis in the initial healing period by PRP could be supposed as a way to overcome short term effect of the rapid angiogenesis.

• Journal of Veterinary Science
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• 제23권6호
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• pp.89.1-89.7
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• 2022

It is challenging to diagnose metastatic tumors whose cellular morphology is different from the primary. We characterized canine primary pulmonary adenocarcinoma (PAC) and its xenografted tumors by histological and immunohistochemical analyses for critical diagnostic and cancer stem cell (CSC) markers. To generate a tumor xenograft model, we subsequently transplanted the tissue pieces from the PAC into athymic nude mice. Immunohistochemical examination was performed for diagnostic (TTF-1, Napsin A, and SP-A) and CSC markers (CD44 and CD133). The use of CSC markers together with diagnostic markers can improve the detection and diagnosis of canine primary and metastatic adenocarcinomas.

• 폴리머
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• 제27권3호
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• pp.226-234
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• 2003

이프리플라본은 이소플라본의 파생물로서 골의 재흡수를 방지하여 골의 재형성을 방해함으로써 골 형성에 도움을 준다. 이프리플라본은 칼슘의 양을 안정적으로 증가시킴과 함께 골수 줄기 세포의 작용으로 세포층에 칼슘을 침착시킨다. 조직공학적 골을 형성시키기 위해 락타이드-글리를라이드 공중합체 (PLGA)에 이프리플라본을 함유시킨 지치체를 용매 캐스팅/염 추출법으로 제조하였다. 수은 다공도계, 주사 전자 현미경, 시차 주사 열량계, X선 회절기를 이용하여 특성결정을 수행하였고, 이프리플라본이 함유된 지지체와 이프리플라본이 함유되지 않은 지지체를 면역이 결핍된 쥐의 피하에 삽입하여 이들의 골 형성을 비교하였다. 조직을 hematoxylin & eosin, 본쿠사 염색과 면역화학적 염색법인 콜라겐 I 형과 오스테오칼신 염색을 하였다. 이프리플라본이 함유된 담체의 다공도는 91.7% 이상이었고, 평균 다공 크기도 101 $\mu\textrm{m}$였다. PLGA로만 제조된 지지체와 이프리플라본을 50% 함유시킨 지지체를 동물 실험을 수행한 결과 이프리플라본은 피하 층과 다른 연조직에서 미분화 줄기 세포가 칼슘 침착, 골아 세포, 골상으로의 유도에 더 많은 영향을 주는 것을 관찰하였다. 결론적으로 이프리플라본을 함유한 지지체에서 이프리플라본이 골형성에 중요한 요인으로 작용한다고 사료된다.