비글개에서 l-muscone의 급성독성 및 아급성독성시험 연구

유아선,권오경,성하정,곽형일,방명주,박대규,정규혁,윤효인,조명행 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

Single and 4 weeks oral administration of l-muscone, a major active ingredient of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dosage of 2,000 ㎎/㎏ and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of l-muscone, 0.2㎎/㎏/day(low dosage group), 2 ㎎/㎏/day(middle dosage group), or 20 ㎎/㎏day(high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korean Food and Drug Administration(1996.4.16). LD_50 value for beagle dogs was more than 2,000 ㎎/㎏ on oral route for both male and females. In animals administered with l-muscone, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, eye examination, hematology, serum chemistry, organ weight and other findings. No histolopathological lesions were observed in both control and treatment groups. Above data strongly suggest that l-muscone in beagle dogs is considered to be safe.

W/O/W Emulsion의 안정성 증대에 관한 연구

조애리 德成女子大學校 藥學硏究所 1998 藥學論文誌 Vol.9 No.1

W/O/W multiple emulsion has been prepared by a two-step procedure using Sorbitan Emulsifiers. W/O/W Emulsion was evaluated by microscopy, viscosity and conduction resistivity test. The yield of W/O/W emulsion was measured by the dialysis method and the stability was estimated by measuring the viscosity and the extent of phase seperation as a function of time. Aracel-83 produced more stable emulsion as compared with Aracel-80 or Aracel-85. The ratio of Emulsifier Ⅰ to Emulsifier Ⅱ was the significant factor affecting the stability and the production yield of W/O/W Emulsion. The stability of W/O/W emulsion has been improved by adding Aluminum-stearate and Bees-wax as an oil phase thickner. Conduction Resistivity Test can be a useful method to optimize the second emulsification time.

Antibody–drug conjugates and bispecific antibodies targeting cancers: applications of click chemistry

Yeji Hong,Su‑Min Nam,Aree Moon 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.3

Engineering approaches using antibody drug conjugates (ADCs) and bispecific antibodies (bsAbs) are designed to overcome the limitations of conventional chemotherapies and therapeutic antibodies such as drug resistance and non-specific toxicity. Cancer immunotherapies have been shown to be clinically successful with checkpoint blockade and chimeric antigen receptor T cell therapy; however, overactive immune systems still represent a major problem. Given the complexity of a tumor environment, it would be advantageous to have a strategy targeting two or more molecules. We highlight the necessity and importance of a multi-target platform strategy against cancer. Approximately 400 ADCs and over 200 bsAbs are currently being clinically developed for several indications, with promising signs of therapeutic activity. ADCs include antibodies that recognize tumor antigens, linkers that stably connect drugs, and powerful cytotoxic drugs, also known as payloads. ADCs have direct therapeutic effects by targeting cancers with a strong payload. Another type of drug that uses antibodies are bsAbs, targeting two antigens by linking to antigen recognition sites or bridging cytotoxic immune cells to tumor cells, resulting in cancer immunotherapy. Three bsAbs and one ADC have been approved for use by the FDA and the EMA in 2022. Among these, two of the bsAbs and the one ADC are used for cancers. We introduced that bsADC, a combination of ADC and bsAbs, has yet to be approved and several candidates are in the early stages of clinical development in this review. bsADCs technology helps increase the specificity of ADCs or the internalization and killing ability of bsAbs. We also briefly discuss the application of click chemistry in the efficient development of ADCs and bsAbs as a conjugation strategy. The present review summarizes the ADCs, bsAbs, and bsADCs that have been approved for anti-cancer or currently in development. These strategies selectively deliver drugs to malignant tumor cells and can be used as therapeutic approaches for various types of cancer.

Model for Membrane Organization and Protein Sorting in the Cyanobacterium <i>Synechocystis</i> sp. PCC 6803 Inferred from Proteomics and Multivariate Sequence Analyses

Pisareva, Tatiana,Kwon, Joseph,Oh, Jihyun,Kim, Soohyun,Ge, Changrong,Wieslander, Å,ke,Choi, Jong-Soon,Norling, Birgitta American Chemical Society 2011 Journal of proteome research Vol.10 No.8

<P>Cyanobacteria are unique eubacteria with an organized subcellular compartmentalization of highly differentiated internal thylakoid membranes (TM), in addition to the outer and plasma membranes (PM). This leads to a complicated system for transport and sorting of proteins into the different membranes and compartments. By shotgun and gel-based proteomics of plasma and thylakoid membranes from the cyanobacterium <I>Synechocystis</I> sp. PCC 6803, a large number of membrane proteins were identified. Proteins localized uniquely in each membrane were used as a platform describing a model for cellular membrane organization and protein intermembrane sorting and were analyzed by multivariate sequence analyses to trace potential differences in sequence properties important for insertion and sorting to the correct membrane. Sequence traits in the C-terminal region, but not in the N-terminal nor in any individual transmembrane segments, were discriminatory between the TM and PM classes. The results are consistent with a contact zone between plasma and thylakoid membranes, which may contain short-lived “hemifusion” protein traffic connection assemblies. Insertion of both integral and peripheral membrane proteins is suggested to occur through common translocons in these subdomains, followed by a potential translation arrest and structure-based sorting into the correct membrane compartment.</P><P>Are thylakoid and plasma membranes in <I>Synechocystis</I> (A) connected, or (B) physically separated? Integral membrane proteins with unique localization from proteomics were used for multivariate sequence property analyses. Different properties were found in the protein C-terminal tails. Since integral membrane proteins are cotranslationally inserted, this supports a common insertion site of these proteins for both membranes and a connection between them, allowing a restricted lateral diffusion to the final destination.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2011/jprobs.2011.10.issue-8/pr200268r/production/images/medium/pr-2011-00268r_0002.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr200268r'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr200268r'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr200268r'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr200268r'>ACS Electronic Supporting Info</A></P>

Inflammatory and microenvironmental factors involved in breast cancer progression

Mina Ham,Aree Moon 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.12

The primary reason for the high mortality rate ofbreast cancer is metastasis, which can result in a poor survivalrate. The tumor environment is important for promotionand invasion of cancer cells. Recent studies have shownthat inflammation is associated with breast cancer. Therefore,it is important to investigate the role of the inflammatoryand microenvironment in breast cancer progression andmetastasis. The present review summarizes some of themarkers for inflammation and breast cancer invasion, whichmay aid in the design of an appropriate therapy for metastaticbreast cancer. The following four inflammatorymarkers are discussed in this review: (1) Tumor associatedmacrophages (TAMs); (2) Matrix metalloproteinases(MMPs); (3) Sphingosine 1-phosphate (S1P); (4) C-reactiveprotein (CRP). TAMs are commonly found in breast cancerpatients, and high infiltration is positively correlated withpoor prognosis and low survival rate. MMPs are well-knownfor their roles in the degradation of ECM components whencancer cells invade and migrate. MMPs are also associatedwith inflammation through recruitment of a variety of stromalcells such as fibroblasts and leukocytes. S1P is aninflammatory lipid and is involved in various cellular processessuch as proliferation, survival, and migration. Recentstudies indicate that S1P participates in breast cancer invasionin various ways. CRP is used clinically to indicate theoutcome of cancer patients as well as acute inflammatorystatus. This review summarizes the current understanding onthe role of S1P in CRP expression which promotes the breastepithelial cell invasion, suggesting a specific mechanismlinking inflammation and breast cancer. The present review might be useful for understanding the relationship betweeninflammation and breast cancer for the development ofpharmacological interventions that may control the primarymolecules involved in the breast cancer microenvironment.

Optoelectronic properties of Cu1−xPtxFeO2 (0 ≤ x ≤ 0.05) delafossite for p-type transparent conducting oxide

Chesta Ruttanapun,Wutthisak Prachamon,Aree Wichainchai 한국물리학회 2012 Current Applied Physics Vol.12 No.1

The samples of Cu1-xPtxFeO2 (0 ≤ x ≤ 0.05) delafossite have been synthesized by solid-state reaction method to investigate their optical and electrical properties. The properties of electrical resistivity and Seebeck coefficient were measured in the high temperature ranging from 300 to 960 K, and the Hall effect and the optical properties were measured at room temperature. The obtained results of Seebeck showed the samples are p-type conductor. The optical properties at room temperature exhibited the samples are transparent visible light material with optical direct gap 3.45 eV. The low electrical resistivity,hole mobility and carrier density at room temperature displayed value ranging from 0.29 to 0.08Ω cm, 1.8 to 8.6 cm2/V s and 1.56 × 1018 to 4.04 × 1019 cm-3, respectively. The temperature range for transparent visible light is below 820 K because the direct energy gap contains value above 3.1 eV. Consequently, the Cu1-xPtxFeO2 delafossite enhance performance for materials of p-type transparent conducting oxide (TCO) with low electrical resistivity. The samples of Cu1-xPtxFeO2 (0 ≤ x ≤ 0.05) delafossite have been synthesized by solid-state reaction method to investigate their optical and electrical properties. The properties of electrical resistivity and Seebeck coefficient were measured in the high temperature ranging from 300 to 960 K, and the Hall effect and the optical properties were measured at room temperature. The obtained results of Seebeck showed the samples are p-type conductor. The optical properties at room temperature exhibited the samples are transparent visible light material with optical direct gap 3.45 eV. The low electrical resistivity,hole mobility and carrier density at room temperature displayed value ranging from 0.29 to 0.08Ω cm, 1.8 to 8.6 cm2/V s and 1.56 × 1018 to 4.04 × 1019 cm-3, respectively. The temperature range for transparent visible light is below 820 K because the direct energy gap contains value above 3.1 eV. Consequently, the Cu1-xPtxFeO2 delafossite enhance performance for materials of p-type transparent conducting oxide (TCO) with low electrical resistivity.

Differential Functions of Ras for Malignant Phenotypic Conversion

Aree Moon 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.2

Among the effector molecules connected with the group of cell surface receptors, Ras proteins have essential roles in transducing extracellular signals to diverse intracellular events, by controlling the activities of multiple signaling pathways. For over 20 years since the discovery of Ras proteins, an enormous amount of knowledge has been accumulated as to how the proteins function in overlapping or distinct fashions. The signaling networks they regulate are very complex due to their multiple functions and cross-talks. Much attention has been paid to the pathological role of Ras in tumorigenesis. In particular, human tumors very frequently express Ras proteins constitutively activated by point mutations. Up to date, three members of the Ras family have been identified, namely H-Ras, K-Ras (A and B), and N-Ras. Although these Ras isoforms function in similar ways, many evidences also support the distinct molecular function of each Ras protein. This review summarizes differential functions of Ras and highlights the current view of the distinct signaling network regulated by each Ras for its contribution to the malignant phenotypic conversion of breast epithelial cells. Four issues are addressed in this review: (1) Ras proteins, (2) membrane localization of Ras, (3) effector molecules downstream of Ras, (4) Ras signaling in invasion. In spite of the accumulation of information on the differential functions of Ras, much more remains to be elucidated to understand the Ras-mediated molecular events of malignant phenotypic conversion of cells in a greater detail.

Differential Functions of Ras for Malignant Phenotypic Conversion

Moon Aree The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.2

Among the effector molecules connected with the group of cell surface receptors, Ras proteins have essential roles in transducing extracellular signals to diverse intracellular events, by controlling the activities of multiple signaling pathways. For over 20 years since the discovery of Ras proteins, an enormous amount of knowledge has been accumulated as to how the proteins function in overlapping or distinct fashions. The signaling networks they regulate are very complex due to their multiple functions and cross-talks. Much attention has been paid to the pathological role of Ras in tumorigenesis. In particular, human tumors very frequently express Ras proteins constitutively activated by point mutations. Up to date, three members of the Ras family have been identified, namely H-Ras, K-Ras (A and B), and N-Ras. Although these Ras isoforms function in similar ways, many evidences also support the distinct molecular function of each Ras protein. This review summarizes differential functions of Ras and highlights the current view of the distinct signaling network regulated by each Ras for its contribution to the malignant phenotypic conversion of breast epithelial cells. Four issues are addressed in this review: (1) Ras proteins, (2) membrane localization of Ras, (3) effector molecules downstream of Ras, (4) Ras signaling in invasion. In spite of the accumulation of information on the differential functions of Ras, much more remains to be elucidated to understand the Ras-mediated molecular events of malignant phenotypic conversion of cells in a greater detail.

Subinertial Oscillations on the Amundsen Sea Shelf, Antarctica

Wå,hlin, A. K.,Kalé,n, O.,Assmann, K. M.,Darelius, E.,Ha, H. K.,Kim, T. W.,Lee, S. H. AMERICAN METEOROLOGICAL SOCIETY 2016 Journal of physical oceanography Vol.46 No.9

<P>Mooring data from the western flank of Dotson trough, Amundsen Sea shelf region, show the presence of barotropic oscillations with a period of 40-80 h. The oscillations are visible in velocity, temperature, salinity, and pressure and are comparable to tides in magnitude. The period of the oscillations corresponds to topographic Rossby waves of low group velocity and a wavelength of about 40 km, that is, the half-width of the channel. It is suggested that these resonant topographic Rossby waves cause the observed peak in the wave spectra. The observations show that sparseCTDdata from this region should be treated with caution and need to be complemented with moorings or yo-yo stations in order to give a representative picture for the hydrography.</P>

Roles of calcium-binding proteins, S100A8 and S100A9, in invasive phenotype of human gastric cancer cells

Yong, Hae-Young,Moon, Aree 덕성여자대학교 대학원 2007 덕성여자대학교 대학원 논문집 Vol.9 No.-

Gastric cancer is one of the most common malignancies and is a frequent cause of cancer-related death in Korea. Cure rate of gastric cancer is quite low because of local invasion and metastasis. S100 proteins are calcium-binding proteins which exert various calcium-mediated cellular functions including cell growth, differentiation, migration and signal transduction. S100A8 and S100A9 are overexpressed in many human tumors and have been shown to be implicated in tumor development or progression. In the present study, we investigated the role of S100A8 and S100A9 in invasive phenotype of a human gastric cancer cell line, SNU484. Expression of S100A8 and S100A9 were detected in SNU484 cells. When the expression of these proteins was suppressed by small-interfering RNA (siRNA) targeting S100A8 or S100A9, the invasive and migratory phenotypes of SNU484 cells were significantly inhibited. The siRNAs for S100A8 and S100A9 inhibited matrix metalloproteinase (MMP)-2 expression in SNU484 cells as evidenced by gelatin zymogram assay, immunoblot analysis and reverse transcription (RT)-PCR. These results demonstrate that S100A8 and S100A9 are required for transcriptional activation of MMP-2 gene in SNU484 cells. Taken together, this study revealed a functional contribution of S100A8 and S100A9 proteins to processes required for malignant progression including invasion, migration and proteinase expression in SNU484 human gastric cancer cells.