• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.2
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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.

• The Korean Journal of Zoology
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• v.14 no.2
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• pp.57-74
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• 1971

The present investigation has been done to observe the ecological habits of field mice to protect the rice from damages during the growing season in paddy-field and during the storge period. The results obtained are summarized as follows: 1. Of 155 mice captured in the period of April-November 1970, which belong to four genera (Apodemus, Cricetulus, Rattus, and Micromys), 148 mice(95%) were found as striped field mice (Apodemus agrarius coreae). The population density of striped field mouse was revealed by the present study as 55/ha, which is quite a low level compared with that in Japan of 900/ha. 2. The age distribution of the mice as judged by their body weight was found mainly composed of adult and the sex ratio was found to be 1.8 as determined with 147 individuals. The nest was found to be occupied by an adult and was composed of at least three openings and more than one food storage tunnels. The mice usually keep hulled rice rather than unhulled one in storage tunnel. The weight of food found in a nest was about 50 grams on an average. 3. The mice show a most active behaviour 1-2 hours after the sunset, around midnight, and an hour before the sunrise, but they are active even in daytime in order for searching for food and for breeding. 4. The ratio (%) of damage appeared in high stem of sweet corn in August was 30 ~ 40 percent, whereas that in low stem was 80 ~ 90 percent. The weight of spoiled grains in paddy-field was 11, 400gm/0.4ha and this gives an estimate of 349, 695 for whole country. 5. The female striped field mouse weighs average of about 30 grams and gives birth to average of 4.8 younglings which wean away from female mouse three weeks after delivery. 6. The natural enemies to the mice are found to be carnivores (weasel, cat, mountain cat, fox, raccoon, and otter), raptatores(eagle, owl, kete, buzzard), and snakes. Two kinds of field rats(Rattus norvegicus, Cricetulus tritor) are also the predator to the mice. 7. The feeding preference of striped field mice follows in decreasing order of sweet corn, soybean, sweet potatoes, chestnut, and wheat. The mice do not have a preference for barley, millet, rough millet, red bean, and green bean. 8. The starvation experiment, in which water alone was supplied, revealed that the mice in good physical and nutritional conditions survived for 71 ~ 79 hours, whereas those in worse conditions survived for only 32 ~ 39 hours.

• YAKHAK HOEJI
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• v.42 no.3
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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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• v.1 no.1
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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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• v.26 no.9
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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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• v.14 no.6
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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.

• Korean Journal of Exercise Nutrition
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• v.23 no.3
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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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• v.17 no.5
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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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• v.36 no.6
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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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• v.39 no.3
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• pp.134-141
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• 2014

Along with the wide use of radiotherapy in cancer treatment, there is growing interest in beneficial effect of low-dose irradiation (LDI) in cancer therapy. Therefore, we investigate how LDI affects immune responses in mice model. Total body irradiation (TBI) on C57BL/6 mice was given at low-dose rate of $1mGy{\cdot}min^{-1}$ using $^{137}Cs$ source at three times for consecutive three days. Hematological examination, total cell numbers of spleen, populations and characteristics of splenocytes were determined. Total numbers of RBC or platelet in irradiated mice showed no significant changes. WBC counts were decreased in a dose-dependent manner 2 days after TBI, however, these differences are gradually waned until 28 days. Dose-dependent decrease in the number of splenocytes of TBI mice at day 2 was also improved as time progressed. While the level of Foxp3 mRNA was decreased, the frequency of $CD4^+$ T cells and $CD69^+$ cells in spleen was increased at day 2 and 14. Fractionated low-dose TBI on mice exhibited normal body weight with no distinguishable behavior during whole experimental periods. These results suggest that some parameters of immune system could be altered and evaluated by fractionated low-dose TBI and be used to broaden boundary of low dose radiation research.