• 한국환경성돌연변이발암원학회지
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• 제24권3호
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• pp.128-136
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• 2004

CYP1A1 is known to be inducible by xenobiotic compouds such as polyciclic aromatic hydrocarbons(PAHs) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). These chemicals have been identified worldwide and can have a significant impact on the human health and well being of human and wildlife. Given these issues, the detection and quantification of these chemicals in biological, environmental and food samples is important. First, we investigated the effect of on CYP1A1 promoter activity, 7-ethoxyresorufin-O-deethylase(EROD) activity and CYP1A1 mRNA expression induced by benzo(k)fluoranthene(B(k)F) in MCF-7 cells. We found that B(k)F significantly up-regulates the level of CYP1A1 prompter activity, EROD and CYP1A1 mRNA. When cells were treated with genistein, it was not changed that EROD and CYP1A1 mRNA, compared to that of control. However, genistein inhibited the B(k)F-induced CYP1A1 promoter activity and mRNA level at high concentration. Furthermore, in this study, effects of HDAC(histone deacetvlase) inhibitors on human prostate cancer cells proliferation were examined. HC-toxin, SAHA and TSA inhibited cell proliferation in PC3 cells. A novel HDAC inhibitor, IN2001 also suppressed the growth of PC3 cells. And IN2001 and SAHA increased S phase and G2/M phase at 12 hrs treatment but cells were arrested G0/G1 phase at 45 hrs treatment. The HC-toxin treatment for 24 hrs and 48 hrs increased G0/G1 at low concentration ($0.1\mu\textrm{m}$) but increased G2/M at more than concentration of $1\mu\textrm{m}$. TSA increased G2/M phase. These findings height the possbility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of prostate cancer.

• 한국발생생물학회지:발생과생식
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• 제20권1호
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• pp.1-10
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• 2016

Molecular targeting for the altered signaling pathways has been proven to be effective for the treatment of many types of human cancer, including colorectal cancer (CRC). The dual phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 has shown to exhibit potent antitumor activity against solid tumors. Autophagy is a cellular lysosomal catabolic process to maintain metabolic homeostasis, which has been known to be induced in response to many therapeutic agents in cancer cells. This process is negatively regulated by mTOR and often acts as prosurvival or prodeath mechanism following cancer therapeutics. The current study was designed to investigate the antiproliferation activity of BEZ235 and to evaluate the role of autophagy induced by BEZ235 using HCT15 CRC cells bearing ras oncogene mutation. We found that BEZ235 decreases cell viability, which was mostly dependent on $G_1$ arrest of cell cycle via suppression of cyclin A expression. BEZ235 affects PI3K/Akt/mTOR signaling pathway by increasing the phosphorylation of AKT at $Ser^{473}$ and RAS/RAF/MEK/ERK pathway by decreasing the phosphorylation of ERK at $Tyr^{204}$. BEZ235 also stimulated autophagy induction as evidenced by the increased expression of LC3-II and abundant acidic vesicular organelles (AVOs) in the cytoplasm. In addition, the combination of BEZ235 with autophagy inhibitor chloroquine, a known antagonist of autophagy, counteracted the antiproliferation effect of BEZ235. Thus, our study indicates that autophagy induced in response to BEZ235 treatment appears to act as cell death mechanism in HCT15 CRC cells.

• 공업화학
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• 제28권4호
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• pp.383-396
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• 2017

광열치료는 빛을 받아 열로 변환하는 광열특성을 가진 광열변환기를 통해 세포의 병변, 특히 암세포를 선택적으로 사멸시키는 치료법이다. 광열특성을 가지는 다양한 물질들이 광열치료에 적용되어왔지만, 그중에서도 금 나노입자는 그 고유한 물리화학적 특성으로 지난 20년 가까이 과학자와 의료인들에게 큰 관심을 받아왔다. 본 총설에서는 금 나노입자를 사용하여 광열치료효과를 향상시키기 위한 전략들을 최근의 광열치료 연구를 중심으로 정리하여 서술하였다. 특히, 광열변환기로서 사용되는 다양한 금 나노입자 구조체의 합성 및 광학 성질 제어를 통해 광열변환 효율 향상을 시도한 연구들과 금 나노입자를 병소에 효과적으로 축적시키기 위한 선별적 전달 방법들을 논의하였으며, 마지막에는 근래에 적극적으로 시도되고 있는 다른 치료법 및 진단기술과의 융합 연구들을 소개했다.

• 한국식품위생안전성학회지
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• 제28권3호
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• pp.202-206
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• 2013

악성도가 높은 점액표피양 암종은 치료가 어렵고 5년 생존률이 매우 낮다. 따라서, 새로운 치료 물질과 분자표적을 찾는 것이 필요하다. Betulinic acid (BA)는 세계적으로 쉽게 얻을 수 있는 물질인 동시에 여러 종류의 종양에서 항암효과를 보인다. 또한 여러 정상 조직은 BA에 저항성을 보인다. 이 연구에서는 BA의 증식억제 효능과 MC-3 세포주에서의 분자 표적을 확인하고자 하였다. BA는 MC-3 세포주에서 세포 생존을 저해하였고 세포사멸을 유도하였다. BA는 Sp 1과 그의 하향 분자 표적인 survivin에 영향을 주었으나, 다른 하향 분자 표적인 Mcl-1에서는 유의한 변화를 일으키지 못하였다. 따라서, BA는 Sp1과 survivin을 조절하여 세포사멸을 일으키는 잠재적인 항암제 후보가 될 수 있을 것이라 사료된다.

• BMB Reports
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• 제36권1호
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• pp.95-109
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• 2003

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.

• 대한한방내과학회지
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• 제39권4호
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• pp.520-549
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• 2018

Objectives: We performed a systematic review and meta-analysis to explore the recent clinical research trends regarding the effects of traditional herbal medicine (THM) on chemotherapy-induced leukopenia. Methods: Randomized controlled trials that verified effects of herbal medicine treating chemotherapy induced leukopenia were included in the study. A literature search was performed in the English, Chinese, and Korean databases for papers published from January 1, 2007, to September 1, 2017. The selected literature was assessed by Cochrane's Risk of Bias (RoB). Results: Forty-two of 232 randomized controlled trials met the inclusion criteria. The most commonly used herbal prescriptions called '升白湯 (shengbai decoction)' which means elevating the numbers of White blood cells (WBCs). And the mostly included herbs such as Astragali Radix, Angelicae Gigantis Radix, Atractylodis Rhizoma Alba, Codonopsis Pilosulae, Glycyrrhizae Radix, Ligustri Lucidi Fructus are commonly used to elevate qi, blood and yin. The count of WBC in peripheral blood, the level of leukopenia presented in WHO (World Health Organization), and clinical symptoms were used to evaluate the treatments. The effective rate was 68.6-98.18% and the effectiveness was significantly higher in the intervention group than in the control group in 38 articles (p<0.05). No serious adverse events were reported. Only five articles (5/42, 11.9%) were rated as having adequate methodological quality with a low level of bias. Conclusion: Some traditional herbal medicines may be effective as therapeutic treatments for chemotherapy-induced leukopenia, but the majority of reviewed studies were of poor quality. The present findings need to be confirmed by rigorously conducted high-quality trials, including pharmacokinetic studies, to confirm the absence of interactions between traditional herbal medicine agents and chemotherapy.

• 한국임상약학회지
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• 제1권1호
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• pp.31-36
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• 1991

Tobramycin is one of the most frequently selected agents for pharmacokinetic drug monitoring because of its narrow therapeutic index and essential role for the management of serious infections, especially gram-negative infections. Its pharmacokinetic parameters are dependent on race, sex, age, ideal body weight. disease states, and etc. Therefore, to schedule the dosing of tobramycin, the individual pharmacokinetic parameters such as half-life and volume of distribution are needed. However, these pharmacokinetic parameters have never been reported in Koreans. The purposes of this study were to evaluate the volume of distribution of tobramycin in cancer patients who had normal renal function, to compare the mean values of Vd reported in the literature, and to compare the measured half-life with the expected half-life based on ABW, LBW, and IBW, respectively. Venous blood samples were collected just before and thirty minutes after dosing during steady state. Serum tobramycin concentrations were determined by $TD_x$ (fluorescence immunoassay). IBW were measured by the method of Devine: and LBW were measured by the method of Hallynck. Creatinine clearances (CLcr) of the patients were estimated using the Cockcroft and Gault equation. Elimination rate constants (kel) were determined using the Welling and Craig equation. Infusion rate (ko), volume of distribution (Vd), and half-life $(t_{1/2})$ were determined using the Saw chuk and Zaske equation. The volume of distribution Was $27\%$ greater than the Schentag's study (0.26 vs 0.33 l/kg), but the half-life was similar to the Levy's study. The predicted half-lives based on IBW were the closest to actual half-lives (1.85 vs 2.01 hr).

• 대한본초학회지
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• 제25권3호
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• pp.35-41
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• 2010

Objectives : Allergy is an immune dysfunction caused by degranulation from mast cells in the early phase of allergic disease including allergic rhinitis (AR). The purpose of this study was to investigate the effects of Osterici Radix, roots of Ostericum koreanum Maximowicz in human mast cells and experimental allergic animal models. Methods : The anti-allergic effect of Osterici Radix water extract (NK-W) was investigated in human mast cell line, HMC-1 cells, and compound 48/80-induced systemic anaphylactic response in rats and ovalbumin (OVA)-induced AR in mice. Animals were orally administrated with NK-W (10 and 50 mg/kg) or anti-histamine drug, dosodium cromoglycate (50 mg/kg), and then intraperitoneally injected with compound 48/80 (8 mg/kg) or sensitized with 0.1% OVA into nasal. Animals were observed plasma histamine and histological changes of nasal mucosa. Also, mast cell degranulation and histamine production were determined in compound 48/80-stimulated HMC-1 cells. Results : NK-W inhibited compound 48/80-induced degranulation of mast cells and histamine releasing in HMC-1 cells. NK-W decreased mortality and serum histamine releasing in compound 48/80-induced anaphylatic rats in a dose-dependently manner. NK-W also inhibited serum histamine levels in OVA-induced AR mice and improved abnormal histological changes such as expansion of grandular cells and hypertrophy of epithelium in the nasal mucosa. These results indicate that Osterici Radix water extract suppress allergic response through downregulation of mast cell activation. Conclusions : This study suggests that a therapeutic potential of Osterici Radix as a source of anti-allergic agents for use in a number of allergic diseases.

• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.75-82
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• 2010

Specific diseases like cancer and acquired immune deficiency syndrome (AIDS) occur at various organs including lymphatics and spread through lymphatic system. Thus, if therapeutic agents for such diseases are more distributed or targeted to lymphatic system, we can obtain several advantages like reduction of systemic side effect and increase of efficacy. For these reasons, much interest has been focused on the nature of lymphatics and a lot of studies for lymphatic delivery of drugs have been carried out. Because lymphatics consist of single layer endothelium and have high permeability compared with blood capillaries, especially, the studies using nano-sized carriers have been performed. Polymeric nano-particle, liposome, and lipid-based vehicle have been adopted for lymphatic delivery as carriers. According to the administration route and the kind of carrier, the extent of lymphatic delivery efficiency of nano-sized carriers has been changed and influenced by several factors such as size, charge, hydrophobicity and surface feature of carrier. In this review, we summarized the key factors which affect lymphatic uptake and the major features of carriers for achieving the lymphatic delivery. Lymphatic delivery of drug using nano-sized carriers has many fold improved ability of lymphatic delivery compared with that of conventional dosage forms, but it has not shown whole lymph selectivity yet. Even though nano-sized carriers still have the potential and worth to study as lymphatic drug delivery technology as before, full understanding of delivery mechanism and influencing factors, and setting of pharmacokinetic model are required for more ideal lymphatic delivery of drug.

• 대한한방내과학회지
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• 제32권1호
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• pp.10-25
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• 2011

Objectives : Asthma is considered an inflammation disease characterized by airway hyperresponsiveness and pulmonary eosinophilia. Chungsang boha-tang is a herbal medication which has been frequently used in traditional therapeutic agents for asthma. We aimed to observe the clinical effects of Chungsangboha-tang on blood eosinophil, serum IgE, AST, ALT and pulmonary function in asthmatic outpatients. Methods : The subjects consisted of 66 asthmatic patients who had been treated with Chungsangboha-tang among all the asthmatic patients who visited the 5th Internal Medicine of the Oriental Medicine Hospital of Kyung Hee University from November,2004 to November,2009. We observed blood eosinophil, serum IgE, AST, ALT levels and pulmonary function test results as well as medical records of patients to evaluate the effects. Results : Pulmonary function significantly improved after 8 weeks of treatment, and blood eosinophil and serum IgE level significantly decreased after 8 weeks of treatment. AST, ALT levels changed in normal ranges. Chungsangboha-tang was significantly effective on the male patients who had a smoking history and worse initial lab findings. We also observed a significant improvement of pulmonary function and decrease of eosinophil and serum IgE levels in the patient group who had a single treatment of Chungsangboha-tang without steroid therapy. Conclusions : This study shows that Chungsangboha-tang has effects on the improvement of pulmonary function and decrease of eosinophil and serum IgE levels as well as improvement of symptoms. And, 8 weeks of long-term treatment showed no negative effects such as significant increase of AST, ALT levels.