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ABSTRACT: Poly (L-lactic acid) (PLLA), a biodegradable and biocompatible polyester, has been used as material of for tissue engineered scaffold and regenerative medicine. In this study, hydroxyapatite (HAp) and PLLA composite was electrospun. PLLA fibers were treated with an amino groups containing base in order to fabricate amino groups modified polymeric microcylinders. Simvastatin was loaded into the PLLA/HAp microcylinders. Our study focuses on the incorporation HAp and Simvastatin into the fibrous and cylindrical structure, its effects on the loading and release of simvastatin, and biological responses to osteoblast cells. The aspect ratio of microcylinders was tunable by varying the aminolysis treatment time and density of the base. The effects of the PLLA/HAp composites on osteoblast cell proliferation were evaluated. The PLLA/HAp may interact with osteoblast and obtain desired effects that were stimulating osteoblast function and restraining the osteoclast function for bone tissue regeneration. The potential of the developed composite microcylinders could be a promising way to fabricate the microfibrous structural scaffold that accelerates cell proliferation and functions for bone tissue engineering.
Journal of Biomedical Nanotechnology 03/2013; 9(3):424-9. · 4.22 Impact Factor
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ABSTRACT: Despite the fact that advances of burn treatment have led to reduction in the morbidity caused by burns, burn infection is still a serious problem. In this study, we designed blended synthetic and natural polymers nanofiber scaffolds using polyurethane (PU) and gelatin, which were prepared by an electrospinning method. Silver-sulfadiazine (SSD) was co-mixed to the blended polymer solution for being incorporated into the nanofibers after the electrospinning, followed by examination of burn-wound healing effect. The nanofiber scaffolds containing SSD should not only serve as a substrate for skin regeneration, but may also deliver suitable drugs, within a controlled manner during healing. The SSD release was able to prevent the growth of a wide array of bacteria and accelerate the wound healing by preventing infection. Therefore it could accelerate the burn-wound closure rate. We confirmed that PU/gelatin nanofiber scaffolds containing SSD lead to enhanced regeneration of burn-wounds.
Journal of Biomedical Nanotechnology 03/2013; 9(3):511-5. · 4.22 Impact Factor
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ABSTRACT: The objective of this study was to modify zirconium dioxide (ZrO(2)) with photo-cured hyaluronic acid hydrogel (pcHAgel), and to subsequently evaluate the bone regeneration potential of the modified ZrO(2). In the present study, HA grafted onto a ZrO(2) substrate was investigated for its biocompatibility and other properties. We describe the positive influences of ZrO(2) surface-modified with pcHAgel (Zr-3) containing two different loads of growth and differentiation factor-5 (GDF-5) to aid new bone formation as compared to the same amount of BMP-2 (Zr-4-7). We characterized the Zr-3 for their surface morphology and chemical properties. Atomic force microscopy (AFM), scanning electron microscope (SEM), and X-ray photoelectron spectroscopy (XPS) showed that the pcHAgel was successfully grafted onto the ZrO(2) surface. The sustained release of GDF-5 and BMP-2 were observed to occur in the Zr-4-7. In vitro cell tests showed a higher level of MG63 cell proliferation and differentiation on Zr-4-7 than on Zr-3. The Zr-3 is a good biomaterial to deliver osteogenic differentiation factors such as BMP-2 and GDF-5, and GDF-5 can be useful as an effective alternative to aid new bone formation as compared to BMP-2.
Carbohydrate polymers. 01/2013; 92(1):167-75.
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ABSTRACT: Hematopoietic cells derived from human embryonic stem cells (hESCs) have a number of potential utilities, including the modeling of hematological disorders in vitro, whereas the use for cell replacement therapies has proved to be a loftier goal. This is due to the failure of differentiated hematopoietic cells, derived from human pluripotent stem cells (hPSCs), to functionally recapitulate the in vivo properties of bona fide adult hematopoietic stem/progenitor cells (HSPCs). To better understand the limitations of differentiation programming at the molecular level, we have utilized differential gene expression analysis of highly purified cells that are enriched for hematopoietic repopulating activity across embryonic, fetal, and adult human samples, including in vivo explants of human HSPCs 8-weeks post-transplantation. We reveal that hESC-derived hematopoietic progenitor cells (eHPCs) fail to express critical transcription factors which are known to govern self-renewal and myeloid/lymphoid development and instead retain the expression of Polycomb Group (PcG) and Trithorax Group (TrxG) factors which are more prevalent in embryonic cell types that include EZH1 and ASH1L, respectively. These molecular profiles indicate that the differential expression of the core epigenetic machinery comprising PcGs/TrxGs in eHPCs may serve as previously unexplored molecular targets that direct hematopoietic differentiation of PSCs toward functional HSPCs in humans.
Stem cells and development 07/2012; · 4.15 Impact Factor
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Eleftherios Sachlos,
Ruth M Risueño,
Sarah Laronde,
Zoya Shapovalova,
Jong-Hee Lee,
Jennifer Russell,
Monika Malig,
Jamie D McNicol,
Aline Fiebig-Comyn,
Monica Graham, [......],
Andrew O Giacomelli,
John A Hassell,
Daniela Fischer-Russell,
Michael R Trus,
Ronan Foley,
Brian Leber,
Anargyros Xenocostas,
Eric D Brown,
Tony J Collins,
Mickie Bhatia
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ABSTRACT: Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy.
Cell 05/2012; 149(6):1284-97. · 32.40 Impact Factor
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ABSTRACT: Nanofibrous poly(D,L-lactide-co-glycolide) (PLGA)/gelatin/hydroxyapatite (HAp) composites (blending ratio; 0, 30, 70, and 100 wt% gelatin to PLGA combined
with 20 wt% HAp) were electrospun for bone tissue engineering. The morphological, mechanical, surface, thermal and cellular
growth properties of the nanofibrous composites were investigated. The amount of HAp was greater on the surface of the nanofibrous
composites of PLGA and gelatin than that of the plain PLGA nanofibers. Scanning electron microscopy (SEM) showed that the
nanofibrous composites were uniformly electrospun. The mean diameter of the electrospun nanofibrous composite increased with
increasing gelatin content or the incorporation of HAp. HAp particles were distributed over the surface of nanofibrous composite
in direct proportion to the amount of gelatin incorporated. In mechanical testing, gelatin incorporated HAp nanofibrous composites
showed the highest elongation ratio compared to the other HAp incorporated composites under wet conditions. These nanofibrous
composites were further investigated as a promising scaffold for bone tissue engineering. Cell proliferation assays and confocal
laser microscopy showed that the cells could favorably attach and grow well on the surface of these scaffolds. These results
highlight the potential of using nanofibrous PLGA/gelatin/HAp composites for bone tissue engineering.
Keywordsnanofibrous composite–gelatin–hydroxyapatite–PLGA–bone tissue engineering
Macromolecular Research 04/2012; 18(12):1195-1202. · 1.15 Impact Factor
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ABSTRACT: This study was performed to determine if a combination of previously undifferentiated bone marrow-derived mesenchymal stem
cells (BMMSCs) and exogenous bone morphogenetic protein-2 (BMP-2) delivered via heparin-conjugated PLGA nanoparticles (HCPNs)
would extensively regenerate bone in vivo. In vitro testing found that the HCPNs were able to release BMP-2 over a 2-week
period. Human BMMSCs cultured in medium containing BMP-2-loaded HCPNs for 2weeks differentiated toward osteogenic cells expressing
alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN) mRNA, while cells without BMP-2 expressed only ALP. In
vivo testing found that undifferentiated BMMSCs with BMP-2-loaded HCPNs induce far more extensive bone formation than either
implantation of BMP-2-loaded HCPNs or osteogenically differentiated BMMSCs. This study demonstrates the feasibility of extensive
in vivo bone regeneration by transplantation of undifferentiated BMMSCs and BMP-2 delivery via HCPNs.
Journal of Biomedical Science 04/2012; 15(6):771-777. · 2.01 Impact Factor
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ABSTRACT: We describe in this study whether the gold nanoparticle (AuNP) surface-functionalized with PEG, biotin, paclitaxel (PTX) and rhodamine B linked beta-cyclodextrin (β-CD) (AuNP-5') can be useful as a theranostic agent for cancer therapy without the cytotoxic effect on normal cells. Prior to surface-functionalizing AuNPs, the cytotoxicity of the nanoparticles was evaluated, followed by their cytocompatibility. PTX, an anti-cancer agent, formed inclusion complexations with β-CD conjugated AuNPs, and effectively released from the AuNP-2' surface-functionalized with PEG, beta-cyclodextrin (β-CD) and paclitaxel (PTX) using the intracellular glutathione (GSH) level (10 mm). Two types of AuNP-4 surface-functionalized with PEG and rhodamine B linked β-CD and AuNP-5 surface-functionalized PEG, biotin and rhodamine B linked β-CD were used for evaluating their specific interaction on cancer cells such as HeLa, A549 and MG63. These were also tested against normal NIH3T3 cell, determining that the AuNP-5 was more effectively involved with the cancer cells. Confocal laser scanning microscopy (CLSM), fluorescence-activated cell-sorting (FACS) and cell viability analyses showed that the AuNP-5' plays a significant role in the diagnosis and therapy of the cancer cells, and may be used in theranostic agents.
Biomaterials 01/2012; 33(3):856-66. · 7.40 Impact Factor
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11/2011; , ISBN: 978-953-307-420-7
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Min Soo Bae,
Dae Hyeok Yang, Jung Bok Lee,
Dong Nyoung Heo,
Yong-Dae Kwon,
In Chan Youn,
Kuiwon Choi,
Jong Hyun Hong,
Gye Tae Kim,
Yong Suk Choi,
Eui Hwan Hwang,
Il Keun Kwon
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ABSTRACT: We describe in this study the positive influences on in vitro and in vivo osteogenesis of photo-cured hyaluronic acid (HA) hydrogels loaded with simvastatin (SIM). Prior to loading SIM, we first characterized the HA hydrogels for their mechanical properties and swelling ratios. The results from this testing indicated that these two factors improved as the substitution degree of 2-aminoethyl methacrylate (AEMA) increased. MTT and live/dead assays showed that the HA hydrogels have good biocompatibility for use as scaffolds for bone tissue regeneration. Moreover, another MTT assay showed that the photo-cured HA hydrogels III fabricated with 30% AEMA (300 mg) conjugated HA (HA-AEMA iii) loaded with between 0.1 and 1 mg of SIM had a similar cytotoxicity as compared to the HA hydrogel III itself. The sustained release of SIM was observed to occur in the HA hydrogel III loaded with 1 mg of SIM. In vitro and in vivo experiments showed that the HA hydrogel III loaded with 1 mg of SIM had a significant influence on osteogenesis.
Biomaterials 08/2011; 32(32):8161-71. · 7.40 Impact Factor
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ABSTRACT: In the case of tracheal rupture or stenosis, most effective way is to insert a commercially available metal stent. However, the implantation often causes a fever or a pain on the contact surface between trachea and the stent. And also the metal stent should be removed after a certain time implantation. Thus, we developed a functional tracheal drug eluting stent consisting of indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), loaded nanofibers on a bare metal stent. To control the drug release kinetics and enhancement of mucosal regeneration, gelatin and PLCL were coated layer by layer on a metal stent by an electrospinning method. Indomethacin was loaded in the gelatin layer by soaking and drying method (0.1, 0.5, and 1 wt% in ethanol for 10 min). The morphology of functional drug eluting tracheal stent was characterized by scanning electron microscope (SEM). And mechanical properties of the constructs such as air leak pressure, ultimate tensile stress, and modulus were calculated and evaluated. Drug release was performed by a high performance liquid chromatography (HPLC). Stably coated gelatin and poly(L-lactide- co-epsilon-caprolactone) (PLCL) nanofibers were observed by SEM. Bi-layered nanofibers-coated stent showed enough mechanical properties as a tracheal stent, which confirmed by a custom-designed air leak mechanical test. For indomethacin loading on a stent, stent was immersed in a series of drug solutions (different concentrations) for 10 min. At the result of HPLC, total amounts of indomethacin on a stent were approximately 77, 323, and 670 ug/stent, respectively. Time dependent drug release kinetics of the tracheal stent showed a sustained release profile regardless of indomethacin content. Thus, functionally designed nanofiber coated tracheal stent with anti-inflammatory drug may be useful for tracheal regeneration.
Journal of Nanoscience and Nanotechnology 07/2011; 11(7):5711-6. · 1.56 Impact Factor
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ABSTRACT: Electrospun Nanofiber sheets have been shown to mimic the structure of extracellular matrix (ECM). Although these nanofibers have shown great potential for use as tissue engineering scaffolds, it is difficult for the electrospun nanofiber based sheets to be shaped into the desired three-dimensional structure. In this study, poly(L-lactic acid) (PLLA), a biodegradable and biocompatible polyester, was electrospun to produce nanofibers that were treated with an amino group containing base in order to fabricate polymeric nanocylinders. The aspect ratio of the PLLA nanocylinders was tunable by varying the aminolysis time and density of the amino group containing base. The effects of changes in nanofibrous morphology of the PLLA nanocylinders/macro-porous gelatin scaffolds on cell adhesion and proliferation were evaluated. The results revealed different cell morphology, adhesion, and proliferation in the nanocylinders composite gelatin scaffold versus gelatin scaffold alone. Confocal laser scanning microscopy observation showed more spreading and a more flattened cell morphology after NIH3T3 cells were cultured on PLLA nanocylinders/gelatin scaffolds for 10 hours and 4 days. These results indicate that the gelatin/PLLA nanocylinder composite is a promising way to fabricate 3D nanofibrous scaffolds that accelerates cell adhesion and proliferation for tissue engineering.
Journal of Nanoscience and Nanotechnology 07/2011; 11(7):6371-6. · 1.56 Impact Factor
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ABSTRACT: A significant problem that affects tissue-engineered electrospun nanofibrous scaffolds is poor infiltration of cells into the three-dimensional (3D) structure. Physical manipulation can enhance cellular infiltration into electrospun scaffolds. The porosity of electrospun nanofibers was highly enlarged by ultrasonication in an aqueous solution. The porosity and related property changes on a series of nanofibers were observed to be dependent on ultrasonication time and energy. To evaluate cell infiltration into the scaffold, fibroblasts were seeded onto these nanofibers and cultured for different lengths of time. The penetration levels of these cells into the scaffold were monitored using confocal lazer scanning microscopy. The cell infiltration potential was greatly increased with regard to an increase in pore size and porosity. These 3D nanofibrous scaffolds fabricated by an ultrasonication process allowed cells to infiltrate easily into the scaffold. This approach shows great promise for design of cell permeable nanofibrous scaffolds for tissue-engineering applications.
Tissue Engineering Part A 06/2011; 17(21-22):2695-702. · 4.64 Impact Factor
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ABSTRACT: The purpose of this study was to assess the prevalence and extent of clinical attachment loss of periodontal tissue and to find out variables related to clinical attachment loss (CAL) in Korean adults older than 40 years of age.
Data were collected from 2,519 subjects who were part of a cohort study conducted in Ansan city by Korea University Medical School for Korean Genome project. Age, sex, smoking, drinking, fast glucose, blood pressure, obesity and total cholesterol levels were examined. The oral examination included probing pocket depth, gingival recession and CAL of Ramford's teeth. The severity of periodontitis was classified based on the mean value of CAL. The relationship between each risk factor and the severity of CAL was independently estimated using the chi-square test, the test or one-way ANOVA. Multiple regression analysis was used to determine the significance of each factor in the periodontal disease.
The prevalences of clinical attachment between 1 and 3 mm, between 3 and < 5 mm, and ≥ 5 mm were 80.27%, 16.75% and < 1%, respectively. Although the univariate analysis showed age, gender, smoking, fasting glucose, blood pressure and total cholesterol levels were significantly related to the severity of CAL, multiple regression analysis indicated that age (P < .0001), gender (P < .0001) and smoking (P < .05) were only significantly related.
Older age, male gender and smoking were significant risk factor for the increase of CAL, and these may be useful indicators of periodontitis high-risk groups.
The journal of advanced prosthodontics 03/2011; 3(1):25-32.
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ABSTRACT: Anthropometric abnormalities of the mandible and neck may contribute to snoring in non-obese Asians. The study evaluated the clinical implications of mandible and neck measurements in non-obese Asian snorers.
The external mandible and neck measurements (neck circumference, two lengths of neck, mandibular body angle, and lengths of mandibular ramus and body) were compared between snorers and non-snorers in a sample of 2,778 non-obese Koreans (1,389 males, 1,389 females) aged 40 to 69 years (mean, 48.47±7.72 years).
The overall prevalence of snoring was 64.7% (899/1,389) and 48.3% (671/1,389) in non-obese male and female subjects, respectively. In non-obese males, snorers had significantly a greater neck circumference (P<0.0001) and shorter mandibular body length (P=0.0126) than non-snorers. In non-obese females, snorers had significantly greater neck circumferences (P=0.0165), compared with non-snorers. However, there were no statistically significant differences in other variables between non-snorers and snorers.
Anthropometric abnormalities of the mandible and neck, including thick neck circumference in both genders and small mandible size in males, may be relevant contributing factors to snoring in non-obese Asian snorers.
Clinical and Experimental Otorhinolaryngology 03/2011; 4(1):40-3. · 0.92 Impact Factor
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ABSTRACT: The aim of this study was to examine the relationship between tooth loss and sub-clinical atherosclerosis in Korean adults.
The subjects were part of a cohort study conducted in Ansan city by the Korea University medical school as part of the Korean Genome project. 749 subjects over than 40 years old were evaluated. After taking panoramic radiography, the amount of tooth loss was calculated. The intima-media thickness (IMT) was assessed by using ultrasonography at the common carotid artery. Traditional cardiovascular risk factors for atherosclerosis were also evaluated. The relationship between tooth loss and the IMT was evaluated using ANOVA with Scheffe's multiple comparison method in univariate analysis. Multiple regression analysis was also performed to determine the significance between the IMT and tooth loss.
With age, tooth loss increased, but there was no significant increase in other traditional cardiovascular risk factors. Univariate analysis revealed the IMT to be positively related with the amount of tooth loss. Regression analysis of the IMT in the anterior and posterior tooth loss revealed that only the posterior tooth loss was significantly related with the IMT at all sites of the common carotid artery (right far wall, P = .015; left far wall, P = .008; right near wall, P < .001; left near wall, P = .001).
This study verified the positive relationship between the increased tooth loss at the posterior area and the accumulation of atheroma in arteries.
The journal of advanced prosthodontics 12/2010; 2(4):122-7.
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ABSTRACT: The hepatitis E virus (HEV) is an emerging zoonotic agent, for which pigs are the most important reservoir. Complete genome sequences of two swine HEV strains, designated swKOR-1 and swKOR-2, were determined via RT-PCR and RACE-PCR. The strains contained genomes composed of 7,222- and 7,221-bp excluding the poly(A) tails, respectively. The swKOR-1 and swKOR-2 strains were classified into subtype 3a of genotype 3 via phylogenetic analysis. These strains formed a distinctive cluster in the phylogenetic tree with human and swine HEVs isolated in the USA and human HEVs isolated in Japan. Anti-HEV antibodies were identified via ELISA in 8 of 99 (8.1%) cats, whereas, among 115 cattle and 213 dogs, no HEV-specific antibodies were detected. The conserved RNA-dependent RNA polymerase (RdRp) gene of HEV could be detected via RT-PCR in 8.7% of raw oysters collected from coastal regions in Korea. The HEV RNAs detected in oysters were identified as belonging to subtype 3a. The HEV RNAs in oysters most closely resembled that of the swKOR-2 strain. They also showed a close genetic relationship with the swKOR-1 strain and the swine and human HEVs isolated in the USA. This is the first report describing the detection in oysters of HEV that may have originated from genotype 3 swine HEV in Korea. Pigs and cats infected with HEV, as well as oysters contaminated with HEV, are potential risk factors for HEV transmission to humans.
Journal of Medical Virology 02/2010; 82(4):583-91. · 2.82 Impact Factor
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ABSTRACT: A lateral position (LP) during sleep is effective in reducing sleep disorder symptoms in mild or moderate sleep apnea patients. However, the effect of head and shoulder posture in LP on reducing sleep disorders has not been reported. In this study, effective sleeping positions and a combination of sleep position determinants were evaluated with respect to their ability to reduce snoring and apnea. The positions evaluated included the following: cervical vertebrae support with head tilting (CVS-HT), scapula support (SS), and LP. A central composite design was applied for response surface analysis (RSA). Sixteen patients with mild or moderate positional sleep apnea and snoring who underwent polysomnography for two nights were evaluated. Based on an estimated RSA equation, LP (with a rotation of at least 30 degrees) had the most dominant effect [P = 0.0057 for snoring rate, P = 0.0319 for apnea-hypopnea index (AHI)]. In addition, the LP was found to interact with CVS-HT (P = 0.0423) for snoring rate and CVS-HT (P = 0.0310) and SS (P = 0.0265) for AHI. The optimal sleep position reduced mild snoring by more than 80% (i.e. snoring rate in the supine position was <20%) and the snoring rate was approximately zero with a 40 degrees rotation. To achieve at least 80% reduction of AHI, LP and SS should be >30 degrees and/or 20 mm respectively. To determine an effective sleep position, CVS-HT and SS, as well as the degree of the LP, should be concurrently considered in patients with positional sleep apnea or snoring.
Journal of Sleep Research 03/2009; 18(1):26-35. · 3.16 Impact Factor
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ABSTRACT: This study examined the efficacy and safety of nifedipine sustained release (nifedipine SR) compared with Ginkgo biloba extract as treatment for primary Raynaud's phenomenon (RP) in Korea. Primary RP were screened and assigned to either the nifedipine SR group (Group N) or the Ginkgo biloba extract group (Group G) in the ratio of 2:1. After a run-in period of 2 weeks, patients received treatment for 8 weeks. We observed the percent improvement of the RP attack rate between before and after the 8-week treatment. Ninety-three subjects were randomly assigned. The percent improvement in Group N was 50.1% at 8 weeks after treatment, while it was 31.0% in Group G (p = 0.03). No serious adverse events occurred, and almost adverse events were mild and improved without specific treatment. nifedipine SR was more effective than Ginkgo biloba extract for treatment of primary RP in Korean patients. Both drugs were tolerable with primary RP patients.
Clinical Rheumatology 02/2009; 28(5):553-9. · 2.00 Impact Factor
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ABSTRACT: To evaluate the clinical significance of gene expression-based classification and define the characteristic features of the new basal-like subtype, invasive breast carcinomas were divided into ER, HER2, basal-like and null subtypes by immunohistochemical analysis. A total of 401 invasive breast carcinomas were submitted to tissue microarray and stained with ER, HER2, EGFR, c-KIT and cytokeratin (CK) 5/6. The basal-like tumors, defined as positive for one or more basal markers but negative for both ER and HER2, comprised 18.5%. They were larger (p=0.041), showed higher grade (p<0.001), and more frequently expressed p53 (p=0.003). Expression of the basal marker itself showed negative prognostic effect, particularly in node-positive group. Even ER-positive patients had far shorter disease-free survival (DFS) when the tumor coexpressed one or more basal marker (p<0.001). Discrimination of basal-like subtype or tumors positive for basal markers may be clinically significant also in the treatment and prognosis of breast carcinomas.
Oncology Reports 03/2008; 19(3):617-25. · 1.84 Impact Factor
