• Archives of Pharmacal Research
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• v.20 no.4
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• pp.297-305
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• 1997

A new serum-free defined medium was developed that supports the growth of normal rat mammary epithelial cells. Mammary organoids from the glands of female F344 rats were cultured in a serum-free medium. Monolayer culture colonies developed within a week and remained viable for months in culture. Upon subculture of one-week-old primary colonies, almost the same morphology of colonies was developed. The scrape loading/dye transfer technique showed that most of colonies that developed in a serum-free medium containing EGF, human transferrin, insulin, and hydrocortisone (basal serum-free medium, BSFM) failed to show cell-cell communication. However, colonies cultured in BSFM supplemented with prolactin, $E_2$, and progesterone (complete hormone serum-free medium, CHSFM) showed cell-cell communication at 14 days of primary culture or of subculture. By flow cytometry with FITCPNA and PE-anti-Thy-1.1 monoclonal antibody, we distinguished four RMEC subpopulations in cultures in both media: Thy-1.1+ cells, PNA+ cells, cells negative to both reagents and cells positive to both reagents. It is likely that combined prolactin, cortisol, and insulin in CHSFM stimulate terminal differentiation of clonogenic cells.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.917-924
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• 2003

This research aims to test a new drug candidate based on a traditional medicinal herb, F1, an herbal extract obtained from Astragalus membranaceus and its main ingredient, 1-monolinolein that may have fewer side effects and less uterine hypertrophy. In vitro experiments, human osteoblast-like cell lines, MG-63 and Saos-2, were analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and an alkaline phosphatase (ALP) assays. Mouse osteoclasts were induced through a calcium-deficient diet and inhibition effects were measured. In vivo experiments were done using ovariectomized (OVX) rats for 9 weeks. At necropsy, uterus weights were measured, trabecular bone area (TBA) of tibia and lumbar vertebra were measured bone histomorphology. In results, cell proliferation and ALP activity in Saos-2 by ether F1 or 1-monolinolein did not increased significantly compared to the control. The F1 inhibited osteoclast development ($IC_{25}=3.37{\times}10^{-5}$mg/mL) less than 17$\beta$-estradiol. The OVX rats administered F1 (2 mg/kg/day and 10 mg/kg/day) showed an increase in TBA of the tibia significantly (136.3${\pm}4.2% and 138.5{\pm}$10.3% of control). In conclusions, the herbal extract, F1 inhibited tibia and lumbar bone loss and did not cause uterine hypertrophy. However, 1-monolinolein, the main ingredient of the herbal extract, did not inhibit bone loss.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.370-375
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• 2005

The objective of this study was to develop a new reverse micelle-based microencapsulation technique to load tetracycline hydrochloride into PLGA microspheres. To do so, a reverse micellar system was formulated to dissolve tetracycline hydrochloride and water in ethyl formate with the aid of cetyltrimethylammonium bromide. The resultant micellar solution was used to dissolve 0.3 to 0.75 g of PLGA, and microspheres were prepared following a modified solvent quenching technique. As a control experiment, the drug was encapsulated into PLGA microspheres via a conventional methylene chloride-based emulsion procedure. The micro­spheres were then characterized with regard to drug loading efficiency, their size distribution and morphology. The reverse micellar procedure led to the formation of free-flowing, spherical microspheres with the size mode of 88 ~m. When PLGA microspheres were prepared follow­ing the conventional methylene chloride-based procedure, most of tetracycline hydrochloride leached to the aqueous external phase: A maximal loading efficiency observed our experimental conditions was below $5\%$. Their surfaces had numerous pores, while their internal architecture was honey-combed. In sharp contrast, the new reverse micellar encapsulation technique permitted the attainment of a maximal loading efficiency of 63.19 $\pm$$0.64\%$. Also, the microspheres had smooth and pore-free surfaces, and hollow cavities were absent from their internal matrices. The results of this study demonstrated that PLGA microspheres could be successfully prepared following the new reverse micellar encapsulation technique.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.343-351
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• 2018

Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

• Toxicological Research
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• v.16 no.3
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• pp.229-238
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• 2000

The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.1-7
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• 2010

Since the introduction of the biopharmaceutics classification system (BCS) in 1995, it has viewed as an effective tool to categorize drugs in terms of prediction for bioavailability (BA) and bioequivalence (BE). The BCS consist of four drug categories: class I (highly soluble and highly permeable), class II (low soluble and highly permeable), class III (highly soluble and low permeable) and class IV (low soluble and low permeable), and almost all drugs belong to one of these categories. Likewise, classifying drugs into four categories according to their solubility and permeability is simple and relatively not controversial, and thus the FDA adopted the BCS as a science-based approach in establishing a series of regulatory guidance for the industry. Actually, many pharmaceutical companies have gained a lot of benefits, which directly connect to cost loss and failure decrease in the early stage of drug development. Recently, instead of solubility, using dissolution characteristics (e.g. intrinsic dissolution rate) have provided an improvement in the classification in correlating more closely with in vivo drug dissolution rather than solubility by itself. Furthermore, a newly modified-version of BCS, biopharmaceutics drug disposition classification system (BDDCS), which classify drugs into four categories according to solubility and metabolism, has been introduced and gained much attention as a new insight in respect with the drug classification. This report gives a brief overview of the BCS and its implication, and also introduces the recent new trend of drug classification.

• The Journal of Korean Medicine
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• v.42 no.3
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• pp.44-55
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• 2021

Objectives: As the use of herbal medicinal products (HMPs) increases worldwide, systematic verification of the safety of HMPs is required. The induction of cardiotoxicity is one of the major factors in post-approval withdrawal of medicinal products, and drug-induced cardiotoxicity assessment is emerging as an important step in drug development. In the present study, we evaluated human ether-à-go-go-related gene (hERG) potassium channel-related cardiotoxicity to predict the risk of cardiac arrhythmia in thirteen herbal medicines known to have cardiac toxicity. Methods: We measured the inhibition rate of hERG potassium channel activity of 13 medicinal herbal extracts in hERG-expressing HEK 293 cells using an automated patch-clamping system. Quinidine was used as a positive control for inhibition of hERG activity. Results: Extracts of Evodiae Fructus, Strychni Semen, and Corydalis Tuber potently inhibited the activity of hERG, and IC₅₀ values were 3.158, 19.87, and 41.26 ㎍/mL, respectively. Cnidi Fructus, Ephedra Herba, Lithospermi Radix, Polygoni Multiflori Radix, Visci Ramulus et Folium, Asiasari Radix et Rhizoma, and Scolopendra weakly inhibited hERG activity, and the IC₅₀ value for each herbal medicine was more than 400 ㎍/mL. Aconiti Kusnezoffii Tuber and two types of Aconiti Lateralis Radix Preparata (Po and Yeom) had weak inhibitory activity against hERG, and the IC₅₀ values were more than 700 ㎍/mL. The IC₅₀ value of quinidine against hERG was 1.021 𝜇M. Conclusion: Evodiae Fructus, Strychni Semen, and Corydalis Tuber acted as potent inhibitors against hERG. These herbal medicines may cause cardiac arrhythmia through QT prolongation, so care should be taken when taking them.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.190.1-190.1
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• 2002

• Applied Microscopy
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• v.51
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• pp.13.1-13.7
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• 2021

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has arisen as a global pandemic affecting the respiratory system showing acute respiratory distress syndrome (ARDS). However, there is no targeted therapeutic agent yet and due to the growing cases of infections and the rising death tolls, discovery of the possible drug is the need of the hour. In general, the study for discovering therapeutic agent for SARS-CoV-2 is largely focused on large-scale screening with fragment-based drug discovery (FBDD). With the recent advancement in cryo-electron microscopy (Cryo-EM), it has become one of the widely used tools in structural biology. It is effective in investigating the structure of numerous proteins in high-resolution and also had an intense influence on drug discovery, determining the binding reaction and regulation of known drugs as well as leading the design and development of new drug candidates. Here, we review the application of cryo-EM in a structure-based drug design (SBDD) and in silico screening of the recently acquired FBDD in SARS-CoV-2. Such insights will help deliver better understanding in the procurement of the effective remedial solution for this pandemic.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.171-174
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• 2004

Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenesis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available proges include RGD sequence containing peptides that target ${\alpha}_v\;{\beta}_3$ integrin, endothelial growth factors such as VEGF or FGF, metalloptoteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases.