• Biomolecules & Therapeutics
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• 제22권1호
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• pp.1-9
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• 2014

Vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) system has been shown to play central roles not only in physiological angiogenesis, but also in pathological angiogenesis in diseases such as cancer. Based on these findings, a variety of anti-angiogenic drugs, including anti-VEGF antibodies and VEGFR/multi-receptor kinase inhibitors have been developed and approved for the clinical use. While the clinical efficacy of these drugs has been clearly demonstrated in cancer patients, they have not been shown to be effective in curing cancer, suggesting that further improvement in their design is necessary. Abnormal expression of an endogenous VEGF-inhibitor sFlt-1 has been shown to be involved in a variety of diseases, such as preeclampsia and aged macular degeneration. In addition, various factors modulating angiogenic processes have been recently isolated. Given this complexity then, extensive studies on the interrelationship between VEGF signals and other angiogenesis-regulatory systems will be important for developing future strategies to suppress diseases with an angiogenic component.

• Korean Chemical Engineering Research
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• 제44권1호
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• pp.73-80
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• 2006

본 연구에서는 제대혈 유래의 조혈줄기세포를 효과적으로 배양하기 위한 선행 연구로서 세포 배양 환경에 따른 조혈줄기세포 증식능의 변화를 관찰하였다. 제대혈의 단핵구 세포에서 분리한 $CD34^+$ 세포를 성장인자 조성-I(이하, coc-I) (EPO, GM-CSF, SCF, IL-3) 및 성장인자 조성-II(이하, coc-II) (TPO, G-CSF, SCF, IL-6, Flt3/Flk-2 ligand)가 포함되어 있는 IMDM(Iscove's modified Dulbecco's medium) 및 무혈청 배지(serum free media, SFM)에서 배양하였으며, 우태아혈청(FBS)의 첨가 영향, 2차원 및 3차원 배양 후 각 조건에서의 세포 증식 및 콜로니 형성능을 비교하였다. 일반적으로 coc-I에서의 세포 증식 및 콜로니 증식이 coc-II에서보다 높았다. 3차원 배양(methocult)에서는 가장 높은 세포 증식($2,258{\pm}456$배)을 나타냈으며, 같은 조성의 2차원 배양(IMDM + coc-I + FBS)에서는 가장 높은 콜로니 증식(BFU-E: $652{\pm}19$, CFU-GM: $520{\pm}58$, CFU-GEMM: $339{\pm}100$배)이 나타났다. 배지를 기준으로 보면, coc-II 조성에 우태아혈청이 포함되지 않은 경우를 제외한 모든 경우에서 세포 증식 및 콜로니 증식이 무혈청 배지에서보다 IMDM에서 높았다. 결론적으로, 모든 배양 조건 중에서 'IMDM + coc-I + FBS' 및 'IMDM + coc-I'에서 가장 좋은 콜로니 증식을 보였으며, 우태아혈청의 첨가 및 2차원 배양 조건이 콜로니 증식에 더 효과적인 것으로 확인되었다. 본 연구 결과는 앞으로 조혈줄기세포의 체외 증식에 필요한 공정개발이나 생물반응기 설계에 유용한 정보를 제공할 수 있을 것으로 사료된다.

• Bulletin of the Korean Chemical Society
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• 제31권7호
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• pp.1848-1858
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• 2010

Phenylaminopyrimidines represent a large group of new selective anticancer agents, the majority of which exert their action through the inhibition of specific kinases. In this study, a new series of N-substituted-2-aminopyrimidines has been designed and synthesized. A selected group of the synthesized derivatives was screened at a single dose concentration of 10 ${\mu}M$ over a panel of 60 cancer cell-lines. Compound 12e has showed great inhibitory and strong lethal effect over almost all of the 60 cell-lines and accordingly was further tested in a 5-dose testing mode to determine its $IC_{50}$ values, where it showed great efficacies with intermediate potencies over the tested cell-lines. The compound was also tested over a panel of 52 kinases to explore its kinase inhibitory profile, and was found to be a selective but moderate inhibitor over FLT3 kinase.

• 한국환경보건학회지
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• 제40권1호
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• pp.38-46
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• 2014

Objectives: This study was carried out in order to estimate atmospheric polycyclic aromatic hydrocarbon (PAH) concentrations and sources using pine needles as a passive air sampler (PAS) in urban (Pyeongtaek), semirural (Anseong) and rural (Jincheon) sites. Methods: One-year-old pine needles were collected for analysis of their PAH concentrations ($C_{p,n}g/g$ dry) at the end of December. PAHs concentrations in the ambient air ($C_a$, $ng/m^3$) were calculated with a $Log(C_p/C_a)-LogK_{oa}$ correlational equation. Results: PAHs concentrations in ambient air ($C_a$) were high, in the order of urban ($114.03ng/m^3$), semirural ($105.17ng/m^3$) and rural ($61.91ng/m^3$) sites. However, distributions of PAH isomer concentrations were very similar. PAHs of which molecular weight is smaller than 228.30 (AcPy, Acp, Flu, Phen, Ant, Flt, Pyr, BaA, Chry) made up most of the PAHs in the ambient air (96.6-98.5%). Conclusion: At urban, semirural and rural sites, it was concluded that the main source of PAHs in the ambient air ratio of each PAH isomer concentration was cars, especially diesel vehicles.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.11-14
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• 2010

Human tumors, including those of the hepatobiliary system, express a number of specific antigens that can be recognized by T cells, and may provide potential targets for cancer immunotherapy. Dendritic cells (DCs) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells. The ability to culture sufficient numbers of DCs from human bone marrow or blood progenitors has attracted a great deal of interest in their potential utilization in human tumor vaccination. $CD34^+$ peripheral blood stem cells (PBSCs) were obtained from a patient with a hepatocellular carcinoma. The PBSCs were cultured in the X-VIVO 20 medium supplemented with the Flt-3 Ligand (FL), GM-CSF, IL-4 and TNF-$\alpha$ for 12 days. The morphology and functions of the cells were examined. The generated cells had the typical morphology of DCs. When the DCs were reinjected into the same patient, an augmentation of the cytotoxic T lymphocyte (CTL) activity was observed. Concomitantly, an increase in the natural killer (NK) cell activity was also detected in the patient. These results suggest that DCs-based cancer immunotherapy may become an important treatment option for cancer patients in the future.

• IMMUNE NETWORK
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• 제15권1호
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• pp.9-15
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• 2015

Streptococcus pneumoniae (the pneumococcus) causes a major upper respiratory tract infection often leading to severe illness and death in the elderly. Thus, it is important to induce safe and effective mucosal immunity against this pathogen in order to prevent pnuemocaccal infection. However, this is a very difficult task to elicit protective mucosal IgA antibody responses in older individuals. A combind nasal adjuvant consisting of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligonucleotide (CpG ODN) successfully enhanced S. pneumoniae-specific mucosal immunity in aged mice. In particular, a pneumococcal surface protein A-based nasal vaccine given with pFL and CpG ODN induced complete protection from S. pneumoniae infection. These results show that nasal delivery of a combined DNA adjuvant offers an attractive potential for protection against the pneumococcus in the elderly.

• Korean Chemical Engineering Research
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• 제56권5호
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• pp.663-678
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• 2018

Refractive index and speeds of sound for the binary mixture of isomer of butanol (1) + cyclohexane, benzene and toluene (2) were measured at 308.15 K. The measured data were used to calculate deviation in refractive index ${\Delta}n$, ultrasonic speed ${\Delta}u$, isentropic compressibility $K_s^E$, available volume $V_a$, excess intermolecular free length $L_f$ and molecular association $M_A$. All the derived properties were correlated with polynomial equation. Ultrasonic speed data were predicted using various empirical correlations like Nomoto, van Dael, impedance dependence and theoretically with Schaaff's collision factor theory (CFT). Jacobson free length theory (FLT) was used to calculate $L_f$. The measured refractive index was also correlated with various mixing rules. The deviation in refractive index Δn and ultrasonic speed ${\Delta}u$ was used to determine the intermolecular interactions.

• Environmental Analysis Health and Toxicology
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• 제26권
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• pp.4.1-4.6
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• 2011

Objectives: This study was carried out to determine whether or not pine needles can be used as passive samplers of atmospheric polycyclic aromatic hydrocarbons (PAHs) using the correlation between accumulated PAH concentrations in air (Ca, ng/$m^3$) and those deposited on pine needles (Cp, ng/g dry). Methods: PAHs in ambient air was collected using low volume PUF sampler and pine needles was gathered at same place for 7 months. Results: A good correlation ($R^2$=0.8582, p<0.05) was found between Ca and Cp for PAHs with a higher gaseous state in air (AcPy, Acp, Flu, Phen, Ant, Flt, Pyr, BaA and Chry), but there was a poorer correlation ($R^2$=0.1491, p=0.5123) for the PAHs with a lower gaseous state (BbF, BkF, BaP, DahA, BghiP and Ind123). A positive correlation ($R^2$=0.8542) was revealed between the logarithm of the octanol-air partitioning coefficient ($logK_{oa}$) and Cp/Ca for the PAHs with a higher gaseous state in air, but there was a negative correlation ($R^2$=0.8131) for the PAHs with a lower gaseous state. The Ca-Cp model could not be used to estimate PAHs concentrations in air using deposited PAHs concentrations on pine needles, but the logKoa-Cp/Ca model could be used. Conclusions: It was found that pine needles can be used as passive samplers of atmospheric PAHs.

• BLOOD RESEARCH
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• 제53권4호
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• pp.294-298
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• 2018

Background Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert $CD4^+CD25^-$ conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters. Methods Thirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR. Results Both IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05). Conclusion Higher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.

• Bulletin of the Korean Chemical Society
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• 제32권5호
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• pp.1709-1714
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• 2011

KIST301135 was semi-synthetically prepared by the reaction of Staurosporine with triphosgene in anhydrous dichloromethane. The structure of KIST301135 was confirmed by $^1H$ NMR, $^{13}C$ NMR, and high resolution mass spectrum. KIST301135 was initially tested in a single dose duplicate mode at a concentration of 20 nM over a panel of 53 kinases against Staurosporine as a positive control. KIST301135 has showed inhibitions above 75% in only 2 kinases (FLT3 and JAK3 kinases) of the 53 tested kinases, while Staurosporine has showed inhibitions above 80% in about 62% of the tested kinases. KIST301135 was retested at a 5-dose testing mode over the 9 kinases inhibited by percentages over 20 at the single dose testing in order to determine its $IC_{50}$ values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.