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Featured researches published by Don Haeng Lee.


Biomaterials | 2010

Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer

Jin Hee Maeng; Don Haeng Lee; Kyung Hee Jung; You Han Bae; In Suh Park; Seok Jeong; Yong Sun Jeon; Chang Koo Shim; Wooyoung Kim; Jungahn Kim; Jeongmi Lee; Yoon Mi Lee; Ji Hee Kim; Won Hong Kim; Soon Sun Hong

To develop a drug delivery system with enhanced efficacy and minimized adverse effects, we synthesized a novel polymeric nanoparticles, (YCC-DOX) composed of poly (ethylene oxide)-trimellitic anhydride chloride-folate (PEO-TMA-FA), doxorubicin (DOX) and superparamagnetic iron oxide (Fe(3)O(4)) and folate. The efficacy of the nanoparticles was evaluated in rats and rabbits with liver cancer, in comparison with free-DOX (FD) and a commercial liposome drug, DOXIL. YCC-DOX showed the anticancer efficacy and specifically targeted folate receptor (FR)-expressing tumors, thereby increasing the bioavailability and efficacy of DOX. The relative tumor volume of the YCC-DOX group was decreased two- and four-fold compared with the FD and DOXIL groups in the rat and rabbit models, respectively. Furthermore, YCC-DOX showed higher MRI sensitivity comparable to a conventional MRI contrast agent (Resovist), even in its lower iron content. In the immunohistochemical analysis, YCC-DOX group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC-DOX group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. These results indicate that YCC-DOX is a promising candidate for treating liver cancer and monitoring the progress of the cancer using MRI.


Helicobacter | 1999

Randomized Placebo‐Controlled Trial of Helicobacter pylori Eradication for Iron‐Deficiency Anemia in Preadolescent Children and Adolescents

Yon Ho Choe; Soon Ki Kim; Byong Kwan Son; Don Haeng Lee; Yun Chul Hong; Soo Hwan Pai

Background. A few cases relating H. pylori infection to iron‐deficiency anemia have been described recently. We investigated the role of H. pylori infection in iron‐deficiency anemia in preadolescent children and adolescents.


Journal of Drug Targeting | 2005

Doxorubicin loaded pH-sensitive micelle targeting acidic extracellular pH of human ovarian A2780 tumor in mice.

Zhonggao Gao; Don Haeng Lee; Dongin Kim; You Han Bae

The purpose of this study was to examine the efficacy of a chemotherapeutic drug, doxorubicin (DOX), loaded in pH-sensitive micelles poly(l-histidine) (Mn:5K)-b-PEG (Mn:5K) micelles. The micelles were designed to target the acidic extracellular pH of solid tumors. Studies of pH-dependent cytotoxicity, growth rate of the tumor, pharmacokinetics and biodistribution were conducted. In vitro DOX uptake upon A2780 cells by incubating the cells in a pH 6.8 complete medium at a concentration of 20 μg DOX/ml in the micelle formulation was more than five times that of pH 7.4 condition for initial 20 min. In vivo pharmacokinetic data showed that AUC (area under concentration curve) and half life time (t1/2) (plasma half life) of DOX in the pH sensitive micelles increased about 5.8- and 5.2-fold of free DOX in phosphate buffered saline (PBS), respectively. It appeared that DOX in the pH-sensitive micelles preferentially accumulated in the tumor site. The distributions at 12 h post injection in other organs including liver, kidney, spleen, lung and heart were not significantly different from those of DOX in PBS at a 6 mg DOX/kg dose. The in vivo test of anti-tumor activity was performed with human ovarian carcinoma A2780 which was subcutaneously xenografted in female nu/nu athymic mice. The pH-sensitive micelle formulation significantly retarded tumor growth rate without serious body weight loss. The triggered drug release by the reduced tumor pH is believed to be a major mechanism of the observed efficacy after passive accumulation of the micelles by EPR effect. This may have resulted in a local high dose of drug in the tested solid tumor.


Journal of Pineal Research | 2010

Melatonin ameliorates cerulein‐induced pancreatitis by the modulation of nuclear erythroid 2‐related factor 2 and nuclear factor‐kappaB in rats

Kyung Hee Jung; Sang-Won Hong; Hong-Mei Zheng; Hee-Seung Lee; H. Lee; Don Haeng Lee; Sang Yoon Lee; Soon-Sun Hong

Abstract:  Melatonin exhibits a wide variety of biological effects, including antioxidant and anti‐inflammatory functions. Its antioxidant role impedes the etiopathogenesis of pancreatitis, but little is known about the signaling pathway of melatonin in the induction of antioxidant enzymes in acute pancreatitis (AP). The aim of this study was to determine whether melatonin could prevent cerulein‐induced AP through nuclear factor erythroid 2‐related factor 2 (Nrf2) and curtail inflammation by inhibition of NF‐κB. AP was induced by two intraperitoneal (i.p.) injections of cerulein at 2 h intervals (50 μg/kg) in Sprague‐Dawley rats. Melatonin (10 or 50 mg/kg/daily, i.p.) was administered 24 h before each injection of cerulein. The rats were killed 12 h after the last injection. Acinar cell degeneration, pancreatic edema, and inflammatory infiltration were significantly different in cerulein‐ and melatonin‐treated rats. Melatonin significantly reduced amylase, lipase, MPO, and MDA levels, and increased antioxidant enzyme activities including SOD and GPx, which were decreased in AP (P < 0.05). Melatonin increased the expression of NQO1, HO‐1, and SOD2 when compared with the cerulein‐induced AP group (P < 0.05). In addition, melatonin increased Nrf2 expression, and reduced expressions of tumor necrosis factor‐alpha, IL‐1β, IL‐6, IL‐8, and iNOS. The elevated nuclear binding of NF‐κB in the cerulein‐induced pancreatitis group was inhibited by melatonin. These results show that melatonin increases antioxidant enzymes and Nrf2 expression, and limits inflammatory mediators in cerulein‐induced AP. It is proposed that melatonin may play an important role in oxidative stress via the Nrf2 pathway in parallel with reduction of inflammation by NF‐κB inhibition.


Journal of Hepatology | 2010

A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer.

He Wen; Sung Soo Yoo; Jinho Kang; Hee Goo Kim; Jin-Seok Park; Seok Jeong; Jung Il Lee; Hyuk Nam Kwon; S. Kang; Don Haeng Lee; Sunghyouk Park

BACKGROUND & AIMS Biliary tract cancer is highly lethal at presentation, with increasing mortality worldwide. Current diagnostic measures employing multiple criteria such as imaging, cytology, and serum tumor markers are not satisfactory, and a new diagnostic tool is needed. Because bile is a cognate metabolite-rich bio-fluid in the biliary ductal system, we tested a new metabolomic approach to develop an effective diagnostic tool. METHODS Biles were collected prospectively from patients with cancer (n=17) or benign biliary tract diseases (n=21) with percutaneous or endoscopic methods. Nuclear magnetic resonance spectra (NMR) of these biles were analyzed using orthogonal partial least square discriminant analysis (OPLS-DA). RESULTS The metabolomic 2-D score plot showed good separation between cancer and benign groups. The contributing NMR signals were analyzed using a statistical TOCSY approach. The diagnostic performance assessed by leave-one-out analysis exhibited 88% sensitivity and 81% specificity, better than the conventional markers (CEA, CA19-9, and bile cytology). CONCLUSION The NMR-based metabolomics approach provides good performance in discriminating cancer and benign biliary duct diseases. The excellent predictability of the method suggests that it can, at least, augment the currently available diagnostic approaches.


Journal of Pineal Research | 2009

Melatonin downregulates nuclear erythroid 2-related factor 2 and nuclear factor-kappaB during prevention of oxidative liver injury in a dimethylnitrosamine model

Kyung Hee Jung; Sang-Won Hong; Hong-Mei Zheng; Don Haeng Lee; Soon-Sun Hong

Abstract:  Melatonin has potent hepatoprotective effects as an antioxidant. However, the signaling pathway of melatonin in the induction of antioxidant enzymes against acute liver injury is not fully understood. The study aimed to determine whether melatonin could prevent dimethylnitrosamine (DMN)‐induced liver injury through nuclear erythroid 2‐related factor 2 (Nrf2) and inflammation. Liver injury was induced in rats by a single injection of DMN (30 mg/kg, i.p.). Melatonin treatment (50 mg/kg/daily, i.p.) was initiated 24 hr after DMN injection for 14 days, after which the rats were killed and samples were collected. Serum and antioxidant enzyme activities improved in melatonin‐treated rats, compared with DMN‐induced liver injury group (P < 0.01). Melatonin reduced the infiltration of inflammatory cells and necrosis in the liver, and increased the expression of NADPH: quinone oxidoreductase‐1, heme oxygenase‐1, and superoxide dismutase‐2, which were decreased by DMN. Melatonin increased expression of novel transcription factor, Nrf2, and decreased expression of inflammatory mediators including tumor necrosis factor‐alpha, interleukin (IL)‐1β, IL‐6, and inducible nitric oxide synthase. The increased nuclear binding of nuclear factor‐kappa B (NF‐κB) in the DMN‐induced liver injury group was inhibited by melatonin. Our results show that melatonin increases antioxidant enzymes and Nrf2 expression in parallel with the decrease of inflammatory mediators in DMN‐induced liver injury, suggesting that melatonin may play a role of antioxidant defense via the Nrf2 pathway, by reducing inflammation by NF‐κB inhibition.


Gastrointestinal Endoscopy | 2009

Endoscopic large-balloon sphincteroplasty without preceding sphincterotomy for the removal of large bile duct stones: a preliminary study.

Seok Jeong; Sung-Ho Ki; Don Haeng Lee; Jung Il Lee; Jin-Woo Lee; Kye Sook Kwon; Hyung Gil Kim; Yong Woon Shin; Young Soo Kim

BACKGROUND Endoscopic sphincterotomy (EST) has usually been performed before large-balloon sphincteroplasty (LBS) to retrieve large bile duct stones because of the high risk of pancreatitis and some advantages of EST. However, there are no available data on the preceding EST to confirm these assertions. OBJECTIVE We investigated the safety and efficacy of LBS without a preceding EST for the management of large bile duct stones. DESIGN Single-institution retrospective study. SETTING Tertiary referral center. PATIENTS Thirty-eight patients with large bile duct stones. INTERVENTIONS Endoscopic LBS without preceding EST. MAIN OUTCOME MEASUREMENTS Efficacy of stone removal and complications related to the procedure. RESULTS The overall success rate irrespective of whether mechanical lithotripsy (ML) was used was 97.4% (37/38). Complete duct clearance by LBS alone without ML was achieved in 29 (76.3%) patients. Complete stone retrieval was achieved by LBS alone in the first session in 25 (65.8%) patients. ML was required in 8 (21.1%) patients. Failure to extract a stone occurred in 1 (2.6%) patient. There was a mild degree of postprocedure pancreatitis in only 1 (2.6%) patient and asymptomatic hyperamylasemia in 3 (7.9%) patients. The maximum diameters of the stones and the balloon/stone diameter ratio had a tendency to affect complete stone retrieval in the success and failure groups: 16.7 +/- 3.9 mm vs 20.8 +/- 6.5 mm and 0.96 +/- 0.19 mm vs 0.80 +/- 0.23 mm, respectively (results are presented as mean +/- standard deviation). LIMITATIONS Small-scale, single-arm study. CONCLUSIONS Our data suggest that LBS without EST is safe and effective in patients with large bile duct stones.


International Journal of Pharmaceutics | 2009

A smart flower-like polymeric micelle for pH-triggered anticancer drug release

Kyung Taek Oh; Young Taik Oh; Nam-Muk Oh; Kwangmyung Kim; Don Haeng Lee; Eun Seong Lee

Novel pH-responsive flower-like micelles were developed to provide the mechanism for pH-triggered drug release from drug carriers. The micelles (particle size: approximately 165 nm; critical micelle concentration (CMC): approximately 4 microg/ml), constructed from poly(N(epsilon)-(3-diethylamino)propyl isothiocyanato-L-lysine)-b-poly(ethylene glycol)-b-poly(L-lactide) [poly(DEAP-Lys)-b-PEG-b-PLLA], were designed to have a self-assembled flower-like arrangement consisting of two hydrophobic blocks [deprotonated poly(DEAP-Lys) block and PLLA block] and a petal-like hydrophilic PEG block at physiological pH. As the pH decreases to slightly acidic pH (<pH 7.0), as in tumor extracellular pH (pH(e)), the flower-like micelles undergo a change in the hydrophobicity of the micellar core. The protonation of poly(DEAP-Lys) changed the physical property of the polymer from hydrophobic to hydrophilic, resulting in disintegration of the micellar core. The co-presence of a pH-insensitive PLLA block in the micellar core affected the protonation of poly(DEAP-Lys), allowing the micelle to be stable at pH 7.0-7.4. In this study using doxorubicin (DOX) as the model drug, DOX release from the micelles accelerated in response to tumor pH(e).


The American Journal of Gastroenterology | 2009

Effect of Biliary Stenting Combined With Ursodeoxycholic Acid and Terpene Treatment on Retained Common Bile Duct Stones in Elderly Patients: A Multicenter Study

Jimin Han; Jong Ho Moon; Hyun Cheol Koo; Jee Heon Kang; Joon Hyuck Choi; Seok Jeong; Don Haeng Lee; Moon Sung Lee; Ho Gak Kim

OBJECTIVES:For frail, elderly patients with large impacted common bile duct (CBD) stones, long-term treatment with biliary stenting provides palliation. Biliary stenting with choleretic agents such as ursodeoxycholic acid (UDCA) and terpene preparations may promote CBD stone size reduction. We studied the effectiveness of biliary stenting combined with UDCA and a terpene preparation as a medical treatment for difficult-to-remove CBD stones in patients older than 65 years in this multicenter, prospective study.METHODS:A total of 28 elderly patients with CBD stones refractory to conventional endoscopic removal, including mechanical lithotripsy, underwent endoscopic placement of a straight 10-F plastic biliary stent. Each patient was administered 600 mg of UDCA and 300 mg of a terpene preparation daily for a mean of 6 months. After 6 months of medication following the initial endoscopic retrograde cholangiopancreatography (ERCP), a second ERCP was performed and endoscopic stone removal was again attempted. Differences in stone size and CBD diameter before and after biliary stenting and medication were compared. The complete stone removal rate after treatment was obtained.RESULTS:The mean size (transverse × longitudinal diameter) of the CBD stones was initially 21.6 × 29.5 mm, and it decreased significantly to 12.2 × 20.1 mm at the second ERCP (P<0.01). The mean CBD diameter measured initially at the cystic duct insertion level was 23.2 mm, and it decreased significantly to 19.5 mm at the second ERCP (P<0.01). After biliary stenting with medication, endoscopic stone removal was successful in 26 of 28 patients (92.8%), with a mean of 1.7 subsequent ERCP sessions.CONCLUSIONS:Endoscopic biliary stenting with a period of combined UDCA and terpene preparation administration seems to be a safe and effective method for retained CBD stones in elderly patients. A prospective study with randomization and a control group is required to confirm these results.


Journal of Computer Assisted Tomography | 2005

Differentiation of chronic focal pancreatitis from pancreatic carcinoma by in vivo proton magnetic resonance spectroscopy

Soon Gu Cho; Don Haeng Lee; Keon Young Lee; Hoon Ji; Kyung Hee Lee; Pablo R. Ros; Chang Hae Suh

Objective: To determine the differences between the in vivo proton magnetic resonance spectroscopy (1H-MRS) features of chronic focal pancreatitis and pancreatic carcinoma and to evaluate the possibility of discriminating chronic focal pancreatitis from pancreatic carcinoma by analysis of in vivo 1H-MR spectra. Methods: The 1H-MR spectra from 36 human pancreases were evaluated in vivo. This series included 15 cases of chronic focal pancreatitis and 21 cases of pancreatic carcinoma. All cases were confirmed histopathologically after surgical resection. The ratios of the peak area (P) of all peaks at 1.6-4.1 ppm to lipid (0.9-1.6 ppm) (P [1.6-4.1 ppm]/P [0.9-1.6 ppm]) in the chronic focal pancreatitis and pancreatic carcinoma groups were evaluated, and the results were compared. The sensitivity and specificity of the analysis were also evaluated by in vivo 1H-MR spectra for discriminating between chronic focal pancreatitis and pancreatic carcinoma. Results: In vivo 1H-MR spectra showed significantly less lipid in chronic focal pancreatitis than in pancreatic carcinoma. The ratio of P (1.6-4.1 ppm)/P (0.9-1.6 ppm) in chronic focal pancreatitis was significantly higher than that in pancreatic carcinoma (P < 0.05) because of a decreased peak area of lipids. The means ± SDs of P (1.6-4.1 ppm)/P (0.9-1.6 ppm) in the chronic focal pancreatitis and pancreatic carcinoma groups were 2.78 ± 1.67 and 0.51 ± 0.49, respectively. Using a value of <2.5 as positive for pancreatic cancer, the sensitivity and the specificity for pancreatic cancer were 100% and 53.3%, respectively. Conclusion: Chronic focal pancreatitis and pancreatic carcinoma can be distinguished from each other by analysis of in vivo 1H-MR spectra, and in vivo 1H-MRS can be a useful method for making a differential diagnosis between chronic focal pancreatitis and pancreatic carcinoma.

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Young Soo Kim

Korea Institute of Science and Technology

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