• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권2호
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• pp.110-122
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• 2005

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

• 한국동물학회지
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• 제14권2호
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• pp.57-74
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• 1971

들쥐의 被害를 막기위한 基礎로 들쥐의 生態學的 硏究를 서울大 農大農場에서 한바 들쥐의 大部分이 등줄쥐 이어서 結果的으로 등줄쥐의 硏究가 되고 말았으나 要約하면 다음과 같다. (1) 들쥐무리 4屬(Apodemus, Cricetulus, Rattus, Micromys) 155마리를 採集했으며 그중 등줄쥐(A. agrarius coreae)가 95%(148마리)를 차지했다. (2) 등줄쥐의 옥수수밭에 있어서의 棲息密度는 활동 범위를 감안하여 1970年8月6日 $\\sim$ 8日까지 55/ha는 日本 菅平地方의 900/ha에 비교하면 대단히 낮았다. (3) 體重에 의한 年齡構造는 成體에 대한 幼鼠 및 亞鼠의 합계가 13%에 이르렀고 性比는 ♂ : ♀ = 1.8 : 1 이었다. (4) 쥐굴(쥐집)이 構造는 한 개의 쥐굴에 구멍(出入口)이 3個以上, 貯藏庫 1個以上, 둥지(寢所) 1個에 한 마리가 살고 있으며 저장식량은 가을의 農作物인데 特히 벼가 主가 되고 벼보다는 玄米로 저장해 둔다. (5) 活動時刻은 日沒後 1 $\\sim$ 2時間, 子正前後, 및 日出前 1時間 內外가 왕성하나 낮에라도 주위가 조용하여 安全하고 먹이가 필요하거나 求愛行動이 필요하면 활동 한다. (6) 옥수수의 被害相은 高株에서 30 $\\sim$ 40%, 低株 에서 80 $\\sim$ 90%의 被害率이었다. 벼에 있어서는 논(1,200坪)에서 벼로 11,400g가 被害되었으니 全國的으로 349.695kg, 그리고 이것을 白米로 推算하면 8,268입 가 등줄쥐에 提供되었다. (7) 등줄쥐의 分娩仔數는 平均體重 30g 의 암컷이 5마리를 낳고 3週후에 離乳했으며 멧밭쥐(16g)도 5마리를 낳았다. (8) 天敵은 食肉目(족제비, 고양이, 살쾡이, 여우, 너구리, 수달, 개) 猛禽目(독수리, 부엉이, 말똥가리, 소리개, 매) 및 뱀이며 시궁쥐와 비단털쥐도 등줄쥐의 天敵이다. (9) 등줄쥐의 食性(嗜好性)은 옥수수, 콩, 밀, 고구마, 밤, 들깨등을 좋아하며 보리, 조, 수수, 팥, 녹두등은 그렇게 좋아하지 아니한다. 그리고 하루에 한 마리의 成鼠의 攝食量은 벼라면 5.5g, 밀 인 경우 4.9g, 여기에 물 5ml 가량을 먹는 경우이다. (10) 물만 提供하고 다른 먹이를 주지 아니한 饑餓實驗에 의하면 營養좋게 飼育된 등줄쥐는 71 $\\sim$ 79時間後에, 그렇지 못한 쥐는 32 $\\sim$ 39時間後에 죽었다.

• 약학회지
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• 제42권3호
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• pp.302-306
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• 1998

In the previous study we described the antitumor activity of GLB, a protein-polysaccharide fraction of the growing tips of Ganoderma lucidum, against sarcoma 180 solid tu mor in ICR mice. In this study we investigated the stimulatory activity of GLB on macrophages. When analyzed using a flow cytometer, GLB ($100{\mu}g/ml$) was found to increase the phagocytic activity of the BALB/c mouse peritoneal macrophages as well as chicken macrophage BM2CL cells against FITC-labeled C.albicans by 55.2% and 21.2%, respectively. GLB also increased the spreading and the expression of MHC class II molecules of BM2CL cells as well as the mouse peritoneal macrophages. From these results, it is clear that GLB is a strong stimulator to the macrophages.

• IMMUNE NETWORK
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• 제1권1호
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• pp.7-13
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• 2001

Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.

• Journal of Microbiology and Biotechnology
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• 제26권9호
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• pp.1613-1619
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• 2016

Francisella tularensis is a highly virulent pathogen of humans and other mammals. Moreover, F. tularensis has been designated a category A biothreat agent, and there is growing interest in the development of a protective vaccine. In the present study, we determine the in vitro and in vivo immune responses of a subunit vaccine composed of recombinant peptides Tul4 and FopA from epitopes of the F. tularensis outer membrane proteins. The recombinant peptides with adjuvant CpG induced robust immunophenotypic change of dendritic cell (DC) maturation and secretion of inflammatory cytokines (IL-6, IL-12). In addition, the matured DCs enabled ex vivo proliferation of naive splenocytes in a mixed lymphocyte reaction. Lastly, we determined the in vivo immune response by assessment of antibody production in C57BL/6 mice. Total IgG levels were produced after immunization and peaked in 6 weeks, and moreover, Tul4-specific IgG was confirmed in the mice receiving peptides with or without CpG. Based on these results, we concluded that the recombinant peptides Tul4 and FopA have immunogenicity and could be a safe subunit vaccine candidate approach against F. tularensis.

• IMMUNE NETWORK
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• 제14권6호
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• pp.307-320
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• 2014

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-${\kappa}B$ together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-${\kappa}B$ activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.

• 운동영양학회지
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• 제23권3호
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• pp.1-12
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• 2019

[Purpose] The purpose of this study was to determine whether different types of carbohydrate diets with or without exercise changes energy metabolism at rest and during exercise. [Methods] To minimize differences in food and energy intake between experimental groups, mice were pairfed. After 1 week of adaptation, 40 male ICR mice (6 weeks old) were randomly divided into four groups: Sta. (high fat + high starch), Scu. (high fat + high sucrose), StaEX. (high fat + high starch + exercise), and SucEX. (high fat + high sucrose + exercise). StaEX. and ScuEX. groups underwent training by running on a treadmill five times a week. After 10 weeks of training, energy metabolism was measured for 24 h and during a 1 h exercise period. [Results] The final body weight showed no significant difference between the groups. However, the weight of abdominal tissues (epididymal, perirenal, and mesenteric adipose tissue) in training groups was markedly decreased following 10 weeks of training. Results of all energy metabolism (24 h at rest and during 1 h of exercise) showed no significant interactions between diet and exercise. A brief summary of the results of the energy metabolism is that the metabolism related indicators over 24 h were more affected by the dietary pattern than the exercise but during the 1 h of exercise, training had more effect on energy metabolism than diet. [Conclusion] Our findings confirm that: (a) the type of carbohydrates included in the diet influence the metabolic responses over 24 h, (b) training had more effect on energy metabolism than diet during 1 h of exercise, (c) both results; abdominal adipose tissue weight and fat oxidation during exercise are suggestive for a beneficial effect of moderate physical activity on weight maintenance.

• Nutrition Research and Practice
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• 제17권5호
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• pp.855-869
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• 2023

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity. MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 ㎍/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS: These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권6호
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• pp.460-465
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• 2010

Introduction: A cleft palate is a common birth defect in humans with an incidence of 1/500 to 1/1,000 births. It appears to be caused by multiple genetic and environmental factors during palatogenesis. Many molecules are involved in palate formation but the biological mechanisms underlying the normal palate formation and cleft palate are unclear. Accumulating evidence suggests that transforming growth factor $\beta$/bone morphogenetic proteins (TGF-$\beta$/BMP) family members mediate the epithelial-mesenchymal interactions during palate formation. However, their roles in palatal morphogenesis are not completely understood. Materials and Methods: To understand the roles of TGF-$\beta$/BMP signaling in vivo during palatogenesis, mice with a palatal mesenchyme- specific deletion of Smad4, a key intracellular mediator of TGF-$\beta$/BMP signaling, were generated and analyzed using the Osr2Ires-Cre mice. Results: The mutant mice were alive at the time of birth with open eyelids and complete cleft palate but died within 24 hours after birth. In skeletal preparation, the horizontal processes of the palatine bones in mutants were not formed and resulted in a complete cleft palate. At E13.5, the palatal shelves of the mutants were growing as normally as those of theirwild type littermates. However, the palatal shelves of the mutants were not elevated at E14.5 in contrast to the elevated palatal shelves of the wild type mice. At E15.5, the palatal shelves of the mutants were elevated over the tongue but did not come in contact with each other, resulting in a cleft palate. Conclusion: These results suggest that mesenchymal Smad4 mediated signaling is essential for the growth of palatal processes and suggests that TGF-$\beta$/BMP family members are essential regulators during palate development.

• Journal of Radiation Protection and Research
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• 제39권3호
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• pp.134-141
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• 2014

방사선요법은 항암 치료에서 널리 이용되는 요법으로, 항암치료에 저선량 방사선을 이용하는 것에 대한 관심이 증가되고 있고, 저선량 방사선의 다양한 생물학적 효과가 있음이 보고되고 있다. 그러므로 본 연구에서는 마우스 모델에서 저선량 방사선이 면역반응에 어떠한 영향을 미치는지, 또한 이를 감지할 수 있는지를 조사하였다. C57BL/6 마우스에 $^{137}Cs$ 선원을 이용하여 연속 3일간 총 90 mGy의 저선량 방사선을 전신 조사한 후 마지막 방사선 조사 2, 14, 28일 후에 마우스를 희생시켜 말초 혈액 세포수, 비장 세포수, 비장 내 면역세포의 비율과 활성화 정도를 분석하였다. 말초 혈액 검사를 통해, 저선량 방사선 조사군에서 적혈구와 혈소판 수의 유의적 변화는 관찰할 수 없었으며, 백혈구 수는 마지막 방사선 조사 후 2일째에 선량-의존적인 감소를 보였으나, 점차 회복되는 경향을 나타냈다. 비장세포 수도 2일째 감소를 보였지만 서서히 그 수가 증가됨을 확인하였다. 2일과 14일째에 비장세포의 Foxp3 mRNA가 감소된 반면, CD4 T 세포와 CD69 양성세포가 증가되었다. 마우스에서 분할 저선량 방사선을 전신조사한 결과, 방사선조사군에서 특이적인 임상 증상이나 유의적인 체중감소를 보이지 않았다. 본 연구에서는 마우스를 대상으로 저선량을 분할 조사하였을 경우에도 면역학적 변화를 확인할 수 있으며 이를 통해 향후 저선량 방사선의 생물학적 효과를 뒷받침하는 자료로 활용할 수 있으리라 기대한다.