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1.
Medicina (Kaunas) ; 57(7)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34357001

RESUMO

Background and Objectives: Nontuberculous mycobacteria (NTM) infections are increasing worldwide. We evaluated the annual trends of NTM isolation on acid-fast bacillus (AFB) culture, compared to that of Mycobacterium tuberculosis, and the distribution of NTM species nationwide in South Korea. Materials and Methods: The study was conducted in a diagnostic center that is a major referral laboratory for the diagnosis of tuberculosis and NTM in South Korea. All laboratory results of AFB culture from January 2014 to December 2019 were collected. All NTM identified were definitively identified to the species level. Results: A total of 345,871 tests were performed for the diagnosis of mycobacteria. The isolation rate of NTM and M. tuberculosis was 3.7% (12,969 cases) and 4.4% (15,081 cases), respectively. The annual isolation rate of NTM increased gradually from 2.7% in 2014 to 4.8% in 2019, whereas that of M. tuberculosis decreased from 6.2% to 3.3%. There were 4988 cases of NTM identified to the species level. M. avium complex (MAC) was the most common species isolated from pulmonary sites (59.8%), followed by M. gordonae (9.2%), M. abscessus (7.0%), and M. fortuitum (5.5%). Extrapulmonary NTM were identified in 29 cases (0.6%). MAC was also the most common NTM species isolated from extrapulmonary sites (65.5%), followed by M. kansasii (10.3%), M. abscessus (6.9%), and M. fortuitum (6.9%). Conclusions: The annual isolation rate of NTM has increased gradually, whereas that of M. tuberculosis has decreased. Follow-up studies of the increases in NTM identification and NTM infections in South Korea are needed.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Humanos , Laboratórios , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Encaminhamento e Consulta , República da Coreia/epidemiologia
2.
Proteomics Clin Appl ; : e2100044, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370896

RESUMO

PURPOSE: Clinical mass spectrometry requires a simple step process for sample preparation. This study aims to optimize the method for isolating periplasmic protein from Gram-negative bacteria and apply to clinical mass spectrometry. EXPERIMENTAL DESIGN: The Klebsiella pneumoniae carbapenemase (KPC)-producing E. coli standard cells were used for optimizing the osmotic shock (OS) lysis method. The supernatant from OS lysis was analysed by LC-MS/MS and MALDI-TOF MS. The effectiveness of the OS lysis method for KPC-2-producing Enterobacteriaceae clinical isolates were then confirmed by MALDI-TOF MS. RESULTS: The optimized OS lysis using KPC-2 producing E. coli standard cells showed a high yield of KPC-2 protein and enriches periplasmic proteins. Compared with other lysis methods, the detection sensitivity of KPC-2 protein significantly increased in MALDI-TOF MS analysis. Nineteen clinical isolates were validated by MALDI-TOF MS using the OS method, which also showed higher detection sensitivity compared to other lysis method (e.g., 1.5% n-octyl-ß-D-glucopyranoside) (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: This study provides a straightforward, rapid, affordable, and detergent-free method for the analysis of periplasmic proteins from Enterobacteriaceae clinical isolates. This approach may contribute to MS-based clinical diagnostics.

3.
J Clin Pediatr Dent ; 45(3): 186-192, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34192754

RESUMO

OBJECTIVE: To compare the shear bond strength (SBS) after thermocycling of four universal adhesives applied in self-etch mode on dentin and etch-and-rinse mode on enamel. STUDY DESIGN: Flat 144 buccal or lingual dentin and enamel surfaces from 72 non-carious primary molars were prepared. Samples were segregated into 12 groups (n=12): Adper Single Bond 2 etch-and-rinse (SB_T) and Clearfil SE Bond self-etch (SE_S) applied to enamel and dentin served as controls. Scotch Bond Universal Adhesive (SBU), Clearfil S3 Bond Universal Adhesive (SEU), Tetric N-Bond Universal Adhesive (TEN), and All Bond Universal (BIS) were applied in etch-and-rinse mode to enamel and in self-etch mode to dentin. They were thermocycled for 5000 cycles. SBS testing and the evaluation of fracture mode were performed. RESULTS: SB_T showed statistically higher SBS than other adhesive groups using etch-and-rinse mode on enamel. SE_S and BIS had statistically higher SBS than other adhesive groups using self-etch mode on dentin. Mixed failure was the most common failure mode in each group. CONCLUSION: The universal adhesives did not show higher SBS than SB_T when using etch-and-rinse on enamel. All universal adhesives showed higher SBS than SB_T and had SBS similar to SE_S, except SBU when using self-etch mode on dentin.


Assuntos
Colagem Dentária , Adesivos Dentinários , Esmalte Dentário , Dentina , Humanos , Teste de Materiais , Cimentos de Resina , Resistência ao Cisalhamento , Dente Decíduo
4.
PLoS One ; 16(6): e0253402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34138947

RESUMO

Classification of clinical symptoms and diagnostic microbiology are essential to effectively employ antimicrobial therapy for lower respiratory tract infections (LRTIs) in a timely manner. Empirical antibiotic treatment without microbial identification hinders the selective use of narrow-spectrum antibiotics and effective patient treatment. Thus, the development of rapid and accurate diagnostic procedures that can be readily adopted by the clinic is necessary to minimize non-essential or excessive use of antibiotics and accelerate patient recovery from LRTI-induced damage. We developed and validated a multiplex real-time polymerase chain reaction (mRT-PCR) assay with good analytical performance and high specificity to simultaneously detect four bacterial pathogens causing pneumonia: Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Moraxella catarrhalis. The analytical performance of mRT-PCR against target pathogens was evaluated by the limit of detection (LOD), specificity, and repeatability. Two hundred and ten clinical specimens from pneumonia patients were processed using an automatic nucleic acid extraction system for the "respiratory bacteria four" (RB4) mRT-PCR assay, and the results were directly compared to references from bacterial culture and/or Sanger sequencing. The RB4 mRT-PCR assay detected all target pathogens from sputum specimens with a coefficient of variation ranging from 0.29 to 1.71 and conservative LOD of DNA corresponding to 5 × 102 copies/reaction. The concordance of the assay with reference-positive specimens was 100%, and additional bacterial infections were detected from reference-negative specimens. Overall, the RB4 mRT-PCR assay showed a more rapid turnaround time and higher performance that those of reference assays. The RB4 mRT-PCR assay is a high-throughput and reliable tool that assists decision-making assessment and outperforms other standard methods. This tool supports patient management by considerably reducing the inappropriate use of antibiotics.

5.
J Korean Med Sci ; 35(39): e350, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045773

RESUMO

BACKGROUND: Except for data in the Korea Hemophilia Foundation Registry, little is known of the epidemiology of congenital bleeding disorders in Korea. METHODS: Data were obtained from the Korean Health Insurance Review and Assessment Service (HIRA) database. RESULTS: From 2010 to 2015, there were 2,029 patients with congenital bleeding disorders in the Korean HIRA database: 38% (n = 775) of these patients had hemophilia A (HA), 25% (n = 517) had von Willebrand disease (vWD), 7% (n = 132) had hemophilia B (HB), and 25% (n = 513) had less common factor deficiencies. The estimated age-standardized incidence rate (ASR) of HA and HB was 1.78-3.15/100,000 and 0.31-0.51/100,000, respectively. That of vWD was 1.38-1.95/100,000. The estimated ASR of HA showed increase over time though the number of new patients did not increase. Most patients with congenital bleeding disorders were younger than 19 years old (47.8%), and most were registered in Gyeonggi (22.1%) and Seoul (19.2%). CONCLUSION: This is the first nationwide population-based study of congenital bleeding disorders in Korea. This study provides data that will enable more accurate estimations of patients with vWD. This information will help advance the comprehensive care of congenital bleeding disorders. We need to continue to obtain more detailed information on patients to improve the management of these diseases.

6.
Patient Educ Couns ; 103(4): 717-723, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32044192

RESUMO

OBJECTIVES: This study compared the effects of a tailored inhaler use education program with routine clinical practice in asthma and chronic obstructive pulmonary disease patients treated with inhalers. METHODS: The participants included 59 patients from a ≥900-bed university hospital in J city. Participants were divided into two groups and received either the tailored inhaler use education program (n = 29) or routine clinical care (n = 30). Disease knowledge and correct inhaler use were assessed using a questionnaire and observational checklists at admission and discharge. Chi-square and Mann-Whitney U tests were used for data analysis. RESULTS: Disease knowledge (asthmaz = -2.69, p = .007; chronic obstructive pulmonary disease z = -6.08, p < .001) and correct inhaler use (z = -5.51, p < .001) were significantly higher in the tailored inhaler use education program group compared to the control group. CONCLUSIONS: Nurses play a pivotal role in educating patients. Our results indicate that nurses are needed to identify diseases and inhaler types and to provide patients with individually tailored education that includes demonstration and feedback. PRACTICE IMPLICATIONS: One-on-one health literacy education tailored to inhaler type and patient age shows promise for chronic disease interventions provided by nurses, physicians, and pharmacists--all the parties involved in patient care.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Asma/tratamento farmacológico , Lista de Checagem , Hospitalização , Humanos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
7.
J Clin Pediatr Dent ; 44(1): 55-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995414

RESUMO

Molar root-incisor malformation (MRIM) or molar-incisor malformation (MIM) is a new type of dental anomaly characterized by dysplastic roots of permanent first molars, occasionally second primary molars, and the crowns of maxillary central incisors. MRIM involving permanent first molars and second primary molars is characterized by normal crowns with short, thin, and narrow roots, whereas MRIM involving permanent maxillary central incisors exhibits constrictions of the crown in the cervical area. In the first case, we extracted the affected first permanent molars at the optimal timing to minimize space deficiencies and induce space closure. In addition, composite resin restorations were performed on the anterior central incisors. In the second case, a mandibular lingual arch was used to stabilize the affected teeth in order to mitigate discomfort by reducing rotational biting forces.


Assuntos
Incisivo , Raiz Dentária , Criança , Coroas , Humanos , Dente Molar , Dente Decíduo
8.
Endocrinol Metab (Seoul) ; 33(3): 364-371, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30229575

RESUMO

BACKGROUND: Genetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been reported to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific calpain-10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients. METHODS: Overall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical characteristics and measure of glucose metabolism were compared within these genotypes. RESULTS: Among calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not significantly associated with diabetes, insulin resistance, nor insulin secretion. CONCLUSION: Variations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.

9.
Cardiovasc Diabetol ; 17(1): 41, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29562908

RESUMO

BACKGROUND: The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. METHODS: A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. RESULTS: The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively. CONCLUSION: The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.


Assuntos
Glicemia/análise , Doenças Cardiovasculares/fisiopatologia , Transtornos do Metabolismo de Glucose/sangue , Resistência à Insulina , Triglicerídeos/sangue , Rigidez Vascular , Adulto , Índice Tornozelo-Braço , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Transtornos do Metabolismo de Glucose/diagnóstico , Transtornos do Metabolismo de Glucose/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Medição de Risco , Fatores de Risco , Seul/epidemiologia
10.
Int J Biol Macromol ; 105(Pt 1): 541-548, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28711618

RESUMO

Bi-layer scaffold composed of human hair keratin/chitosan nanofiber mat and gelatin methacrylate (GelMA) hydrogel was fabricated by using electrospinning and photopolymerization techniques. To prepare the nanofiber layer, the blend solution of human hair keratin and chitosan (mixture ratio: 5/5) was electrospun using formic acid as a solvent in the presence of poly(ethylene glycol), followed by cross-linking with glutaraldehyde. The tensile strength of the human hair keratin/chitosan nanofiber mat was much higher than that of pure human hair keratin nanofiber mat. Meanwhile, the blend nanofiber mat was relatively more compatible with HaCaT cell proliferation and keratinocyte differentiation than the pure chitosan nanofiber mat. The bi-layer scaffold was prepared by photopolymerization of GelMA under the cross-linked nanofiber mat. To evaluate the feasibility as a skin graft, human fibroblast was encapsulated in the hydrogel layer and HaCaT cells were cultured on the nanofiber layer and they were co-cultured for 10days. As a result, the encapsulated fibroblasts proliferated in the hydrogel matrix and HaCaT cells formed a cell layer on the top of scaffold, mimicking dermis and epidermis of skin tissue.


Assuntos
Materiais Biocompatíveis/química , Gelatina/química , Hidrogéis/química , Queratinas/química , Metacrilatos/química , Nanofibras/química , Transplante de Pele , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Eletricidade , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Processos Fotoquímicos , Polimerização , Engenharia Tecidual
11.
Gut Liver ; 11(3): 434-439, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28104896

RESUMO

Background/Aims: Treatment for cholangitis without common bile duct (CBD) stones has not been established in patients with gallstones. We investigated the usefulness of endoscopic biliary drainage (EBD) without endoscopic sphincterotomy (EST) in patients diagnosed with gallstones and cholangitis without CBD stones by endoscopic retrograde cholangiopancreatography (ERCP) and intraductal ultrasonography (IDUS). Methods: EBD using 5F plastic stents without EST was performed prospectively in patients with gallstones and cholangitis if CBD stones were not diagnosed by ERCP and IDUS. After ERCP, all patients underwent laparoscopic cholecystectomy. The primary outcomes were clinical and technical success. The secondary outcomes were recurrence rate of biliary events and procedure-related adverse events. Results: Among 187 patients with gallstones and cholangitis, 27 patients without CBD stones according to ERCP and IDUS received EBD using 5F plastic stents without EST. The stents were maintained in all patients until laparoscopic cholecystectomy, and recurrence of cholangitis was not observed. After cholecystectomy, the stents were removed spontaneously in 12 patients and endoscopically in 15 patients. Recurrence of CBD stones was not detected during the follow-up period (median, 421 days). Conclusions: EBD using 5F plastic stents without EST may be safe and effective for the management of cholangitis accompanied by gallstones in patients without CBD stones according to ERCP and IDUS.


Assuntos
Colangite/complicações , Drenagem/métodos , Endoscopia do Sistema Digestório/métodos , Cálculos Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Ducto Colédoco/cirurgia , Drenagem/instrumentação , Feminino , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/etiologia , Humanos , Masculino , Estudos Prospectivos , Stents , Resultado do Tratamento , Ultrassonografia/métodos
12.
Ann Lab Med ; 37(1): 1-8, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27834059

RESUMO

BACKGROUND: For correct interpretation of the high-density lipoprotein cholesterol (HDL-C) data from the Korea National Health and Nutrition Examination Survey (KNHANES), the values should be comparable to reference values. We aimed to suggest a way to calibrate KNHANES HDL-C data from 2008 to 2015 to the Centers for Disease Control and Prevention (CDC) reference method values. METHODS: We derived three calibration equations based on comparisons between the HDL-C values of the KNHANES laboratory and the CDC reference method values in 2009, 2012, and 2015 using commutable frozen serum samples. The selection of calibration equation for correcting KNHANES HDL-C in each year was determined by the accuracy-based external quality assurance results of the KNHANES laboratory. RESULTS: Significant positive biases of HDL-C values were observed in all years (2.85-9.40%). We created the following calibration equations: standard HDL-C=0.872×[original KNHANES HDL-C]+2.460 for 2008, 2009, and 2010; standard HDL-C=0.952×[original KNHANES HDL-C]+1.096 for 2012, 2013, and 2014; and standard HDL-C=1.01×[original KNHANES HDL-C]-3.172 for 2011 and 2015. We calibrated the biases of KNHANES HDL-C data using the calibration equations. CONCLUSIONS: Since the KNHANES HDL-C values (2008-2015) showed substantial positive biases compared with the CDC reference method values, we suggested using calibration equations to correct KNHANES data from these years. Since the necessity for correcting the biases depends on the characteristics of research topics, each researcher should determine whether to calibrate KNHANES HDL-C data or not for each study.


Assuntos
HDL-Colesterol/sangue , Inquéritos Nutricionais , Algoritmos , Calibragem , HDL-Colesterol/normas , Humanos , Valores de Referência , República da Coreia
14.
Cell Physiol Biochem ; 38(2): 571-88, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26845171

RESUMO

BACKGROUND/AIMS: Hypoxia is an environmental factor that aggravates liver fibrosis. HIF1α activates hepatic stellate cells (HSCs) and increases transforming growth factor-ß (TGF-ß) signaling and the epithelial mesenchymal transition (EMT), accelerating the progression of fibrosis. We evaluated the anti-fibrotic therapeutic potential of a small-molecule inhibitor of TGF-ß type I receptor kinase, EW-7197, on HIF1α-derived TGF-ß signaling in cholestatic liver fibrosis. METHODS: We used a bile duct ligation (BDL)-operated rat model to characterize the role of HIF1α-derived TGF-ß signaling in liver fibrosis. Cellular assays were performed in LX-2 cells (human immortalized HSCs). The anti-fibrotic effects of EW-7197 in liver tissues and HSCs were investigated via biochemical assays, immunohistochemistry (IHC), immunofluorescence (IF), chromatin immunoprecipitation (ChIP) assays, real-time PCR, and western blotting. RESULTS: In our BDL rat model, orally administered EW-7197 inhibited fibrosis and attenuated HIF1α-induced activation of HSCs and EMT in vivo. In addition, EW-7197 inhibited HIF1α-derived HSC activation and expression of EMT markers in LX-2 cells in vitro. CONCLUSION: This study suggests that EW-7197 exhibits potential as a treatment for liver fibrosis because it inhibits HIF1α-induced TGF-ß signaling.


Assuntos
Compostos de Anilina/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Triazóis/uso terapêutico , Animais , Linhagem Celular , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
15.
Clin Chem Lab Med ; 54(7): 1157-60, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26587743

RESUMO

BACKGROUND: Quantifying the BCR-ABL1 rearrangement is important for monitoring chronic myelogenous leukemia (CML). To standardize BCR-ABL1 quantification, the World Health Organization (WHO) established the first international genetic reference panel. Here, we compared the BCR-ABL1 levels determined using international scale (IS)-based commercially available assays. METHODS: BCR-ABL1 transcripts were quantified using two IS-based assays. 10-1, 10-2, 10-3, 10-4, 10-5 and 10-6 dilutions of the b3a2 positive RNA were used for evaluating linearity, precision, and limit of detection. Correlation of the assay was evaluated by using DNA obtained from CML patients carrying the BCR-ABL1 b3a2 and b2a2 types. RESULTS: Both Ipsogen and Asuragen assays showed fine linearity with reasonable %CV. LOD of each assay was calculated as 0.003% for Ipsogen, and 0.005% for Asuragen. By comparing the results that were lower than 10% by either one of the assay, Ipsogen and Asuragen results showed an overall good linear correlation with a tendency for the Ipsogen assay to show slightly higher levels than the Asuragen assay for b3a2 transcript. For b2a2, the tendency was opposite, with Asuragen showing higher values than the Ipsogen. CONCLUSIONS: Two commercially available IS-based BCR-ABL1 assays showed an overall good quantitative correlation. It should be taken into consideration that each assay tended to produce higher values than the other, depending on the BCR-ABL1 subtypes, suggesting that a separate conversion factor for each subtype can be more helpful when BCR-ABL1 transcript levels are converted into IS.


Assuntos
Bioensaio/normas , Proteínas de Fusão bcr-abl/genética , Testes Genéticos/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Padrões de Referência , Bioensaio/métodos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença
16.
Sci Rep ; 5: 16492, 2015 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-26549110

RESUMO

Transforming growth factor-ß (TGF-ß) signaling plays a key role in progression and metastasis of HCC. This study was undertaken to gain the proof of concept of a small-molecule inhibitor of TGF-ß type I receptor kinase, EW-7197 as a potent anti-cancer therapy for HCC. We identified tissue inhibitors of metalloproteinases-1 (TIMP-1) as one of the secreted proteins of hepatic stellate cells (HSCs) and a key mediator of TGF-ß-mediated crosstalk between HSCs and HCC cells. TGF-ß signaling led to increased expression of TIMP-1, which activates focal adhesion kinase (FAK) signaling via its interaction with CD63. Inhibition of TGF-ß signaling using EW-7197 significantly attenuated the progression and intrahepatic metastasis of HCC in an SK-HEP1-Luc orthotopic-xenograft mouse model. In addition, EW-7197 inhibited TGF-ß-stimulated TIMP-1 secretion by HSCs as well as the TIMP-1-induced proliferation, motility, and survival of HCC cells. Further, EW-7197 interrupted TGF-ß-mediated epithelial-to-mesenchymal transition and Akt signaling, leading to significant reductions in the motility and anchorage-independent growth of HCC cells. In conclusion, we found that TIMP-1 mediates TGF-ß-regulated crosstalk between HSCs and HCC cells via FAK signaling. In addition, EW-7197 demonstrates potent in vivo anti-cancer therapeutic activity and may be a potential new anti-cancer drug of choice to treat patients with liver cancer.


Assuntos
Carcinoma Hepatocelular/metabolismo , Comunicação Celular , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Células Estreladas do Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Compostos de Anilina/farmacologia , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Transformada , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Triazóis/farmacologia
17.
Oncotarget ; 6(35): 37526-43, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26462028

RESUMO

Distant relapse after chemotherapy is an important clinical issue for treating breast cancer patients and results from the development of cancer stem-like cells (CSCs) during chemotherapy. Here we report that blocking epithelial-to-mesenchymal transition (EMT) suppresses paclitaxel-induced CSCs properties by using a MDA-MB-231-xenografted mice model (in vivo), and breast cancer cell lines (in vitro). Paclitaxel, one of the cytotoxic taxane-drugs such as docetaxel, increases mesenchymal markers (Vimentin and Fibronectin) and decreases an epithelial marker (Zo-1). Blocking TGF-ß signaling with the TGF-ß type I receptor kinase (ALK5) inhibitor, EW-7197, suppresses paclitaxel-induced EMT and CSC properties such as mammosphere-forming efficiency (MSFE), aldehyde dehydrogenase (ALDH) activity, CD44+/CD24- ratio, and pluripotency regulators (Oct4, Nanog, Klf4, Myc, and Sox2). The combinatorial treatment of EW-7197 improves the therapeutic effect of paclitaxel by decreasing the lung metastasis and increasing the survival time in vivo. We confirmed that Snail is increased by paclitaxel-induced intracellular reactive oxygen species (ROS) and EW-7197 suppresses the paclitaxel-induced Snail and EMT by attenuating paclitaxel-induced intracellular ROS. Knock-down of SNAI1 suppresses paclitaxel-induced EMT and CSC properties. These data together suggest that blocking the Snail-induced EMT with the ALK5 inhibitor attenuates metastasis after paclitaxel-therapy and that this combinatorial approach could prove useful in treating breast cancer.


Assuntos
Neoplasias da Mama/prevenção & controle , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/prevenção & controle , Células-Tronco Neoplásicas/efeitos dos fármacos , Paclitaxel/farmacologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Animais , Antineoplásicos Fitogênicos/farmacologia , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/genética , Células Tumorais Cultivadas , Cicatrização , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Ann Clin Lab Sci ; 45(3): 327-32, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26116598

RESUMO

INTRODUCTION: We compared the Xpert MTB/RIF assay with a real-time PCR assay using samples from culture-positive patients with TB. In addition, drug susceptibility test results were compared to evaluate the usefulness of these methods. MATERIALS AND METHODS: Fifty-two clinical specimens were analyzed by standard smear-microscopy, mycobacterial growth indicator tube (MGIT) culture, solid culture, MGIT drug-susceptibility testing, TB real-time PCR, and the Xpert MTB/RIF assay. RESULTS: Diagnostic sensitivity of AdvanSure TB/NTM real-time PCR was 80.0%. As shown from smear positive and negative specimens, sensitivities were 87.5% and 75.9%, respectively. The diagnostic sensitivity of Xpert MTB/RIF assay was 75.5%, and from smear positive and negative specimens, sensitivities were 93.8% and 65.5%, respectively. There were 10 cases with discrepant results between two methods. 2 cases were found resistant to rifampin, although Xpert MTB/RIF assay was able to detect rifampin resistance in only one specimen. DISCUSSION: Xpert MTB/RIF assay is an easier method to conduct and while its ability to detect rifampin resistance simultaneously is a benefit, its sensitivity from smear negative-culture positive specimens was lower than Advansure TB/NTM real-time PCR. Further investigation to increase the sensitivity and detect other drug resistances by kit-based assays is required for the rapid and accurate diagnosis of tuberculosis.


Assuntos
Bioensaio/métodos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Rifampina/farmacologia , Antituberculosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Sensibilidade e Especificidade
20.
Korean J Intern Med ; 30(3): 308-15, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25995661

RESUMO

BACKGROUND/AIMS: (18)F-Fluorodeoxyglucose positron-emission tomography ((18)F-FDG PET) has been used to assess the biological behavior of hepatocellular carcinoma (HCC). In this study, we investigated the usefulness of (18)F-FDG PET for predicting tumor progression and survival in patients with intermediate Barcelona Clinic Liver Cancer (BCLC) intermediate-stage HCC treated by transarterial chemoembolization (TACE). METHODS: From February 2006 to March 2013, 210 patients treated with TACE, including 77 patients with BCLC intermediate-stage HCC, underwent examination by (18)F-FDG PET. (18)F-FDG uptake was calculated based on the tumor maximum (Tmax) standardized uptake value (SUV), the liver mean (Lmean) SUV, and the ratio of the Tmax SUV to the Lmean SUV (Tmax/Lmean). RESULTS: The mean follow-up period for the 77 patients (52 males, 25 females; average age, 63.3 years) was 22.2 months. The median time to progression of HCC in patients with a low Tmax/Lmean (< 1.83) and high Tmax/Lmean (≥ 1.83) was 17 and 6 months, respectively (p < 0.001). The median overall survival time of patients with a low and high Tmax/Lmean was 44 and 14 months, respectively (p = 0.003). Multivariate analysis revealed that the Tmax/Lmean was an independent predictor of overall survival (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.210 to 3.156; p = 0.006) and tumor progression (HR, 2.05; 95% CI, 1.264 to 3.308; p = 0.004). CONCLUSIONS: (18)F-FDG uptake calculated by the Tmax/Lmean using PET predicted tumor progression and survival in patients with BCLC intermediate-stage HCC treated by TACE.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica , Fluordesoxiglucose F18 , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Idoso , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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