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1.
Biomed Eng Online ; 22(1): 88, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670316

RESUMO

BACKGROUND: Robot-assisted gait training is incorporated into guidelines for stroke rehabilitation. It is a promising tool combined with conventional therapy for low ambulatory patients. The heavy weight and bulky appearance of a robotic exoskeleton limits its practicality. On the other hand, soft robotic exosuit (SRE) based on its light weight and inconspicuous property, is better tolerated by patients in daily life. The aim of this study is to review the efficacy of the SRE with regard to walking ability and biomechanical properties in stroke patients. METHODS: Electronic searches were carried out in PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database. Clinical trials that investigated the effectiveness of SREs on ambulation ability in patients with post-stroke hemiparesis were eligible. Qualitative data synthesis was subsequently performed. RESULTS: Nine studies were identified as relevant, involving a total of 83 patients. For the assessment of SRE efficacy, outcome measures were walking ability and biomechanical properties. In terms of both immediate effect and training effect, SREs improved the walking speed, walking distance, peak ankle dorsiflexion angle during swing phase, peak paretic propulsion, stride length and compensated gait in stroke patients. CONCLUSIONS: SRE improved the ambulation ability of stroke patients in terms of walking ability and biomechanical properties. The small number of studies limits the generalizability of interpretation. More controlled studies with better quality are required to reach a more solid conclusion on this issue.


Assuntos
Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Marcha , Bases de Dados Factuais
2.
Acta Cardiol Sin ; 39(6): 783-806, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38022422

RESUMO

Cardiac rehabilitation is a comprehensive intervention recommended in international and Taiwanese guidelines for patients with acute myocardial infarction. Evidence supports that cardiac rehabilitation improves the health-related quality of life, enhances exercise capacity, reduces readmission rates, and promotes survival in patients with cardiovascular disease. The cardiac rehabilitation team is comprehensive and multidisciplinary. The inpatient, outpatient, and maintenance phases are included in cardiac rehabilitation. All patients admitted with acute myocardial infarction should be referred to the rehabilitation department as soon as clinically feasible. Pre-exercise evaluation, including exercise testing, helps physicians identify the risks of cardiac rehabilitation and organize appropriate exercise prescriptions. Therefore, the Taiwan Myocardial Infarction Society (TAMIS), Taiwan Society of Cardiology (TSOC), and Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation (TACVPR) address this consensus statement to assist healthcare practitioners in performing cardiac rehabilitation in patients with acute myocardial infarction.

3.
Angew Chem Int Ed Engl ; 55(28): 7924-9, 2016 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-27239980

RESUMO

All-inorganic CsPbX3 (X=I, Br, Cl) perovskite quantum dots (PQDs) have been investigated because of their optical properties, such as tunable wavelength, narrow band, and high quantum efficiency. These features have been used in light emitting diode (LED) devices. LED on-chip fabrication uses mixed green and red quantum dots with silicone gel. However, the ion-exchange effect widens the narrow emission spectrum. Quantum dots cannot be mixed because of anion exchange. We address this issue with a mesoporous PQD nanocomposite that can prevent ion exchange and increase stability. We mixed green quantum-dot-containing mesoporous silica nanocomposites with red PQDs, which can prevent the anion-exchange effect and increase thermal and photo stability. We applied the new PQD-based LEDs for backlight displays. We also used PQDs in an on-chip LED device. Our white LED device for backlight display passed through a color filter with an NTSC value of 113 % and Rec. 2020 of 85 %.

4.
Nanomaterials (Basel) ; 14(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38869608

RESUMO

Recently, UVC LEDs, which emit deep ultraviolet light, have found extensive applications across various fields. This study demonstrates the design and implementation of thin films of three-dimensional photonic crystals (3D PhCs) as reflectors to enhance the light output power (LOP) of UVC LEDs. The 3D PhC reflectors were prepared using the self-assembly of silica nanospheres on a UVC LED lead frame substrate via the evaporation-induced method (side) and the gravitational sedimentation method (bottom), respectively. These PhCs with the (111) crystallographic plane were deposited on the side wall and bottom of the UVC LED lead frame, acting as functional materials to reflect UVC light. The LOP of UVC LEDs with 3D PhC reflectors at a driving current of 100 mA reached 19.6 mW. This represented a 30% enhancement compared to commercial UVC LEDs with Au-plated reflectors, due to the UVC light reflection by the photonic band gaps of 3D PhCs in the (111) crystallographic plane. Furthermore, after aging tests at 60 °C and 60% relative humidity for 1000 h, the relative LOP of UVC LEDs with 3D PhC reflectors decreased by 7%, which is better than that of commercial UVC LEDs. Thus, this study offers potential methods for enhancing the light output efficiency of commercial UVC light-emitting devices.

5.
Respir Care ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889928

RESUMO

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a unique diagnostic tool that assesses the functional capacity of the heart, lungs, and peripheral oxidative system in an integrated manner. However, the clinical utility of CPET for evaluating interstitial lung disease (ILD) remains uncertain. The objective of this study was to determine the predictive value of CPET for mortality in subjects with ILD. METHODS: We prospectively enrolled subjects with ILD who underwent CPET at a tertiary medical center in Taiwan and followed up their survival status for 12 months. Mortality prediction was based on comparing CPET parameters between subjects who survived and those who died. We further analyzed CPET parameters that showed significant differences using receiver operating characteristic curves to identify their optimal cutoff values. RESULTS: A total of 106 newly diagnosed subjects with ILD underwent CPET, and the 1-y mortality rate was 7.5%. Six CPET variables were found to be significant predictors of mortality: peak oxygen consumption, oxygen pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1 min after CPET, minute ventilation to carbon dioxide output slope, and functional aerobic impairment. We calculated a summed score by adding the number of CPET variables that exceeded their cutoff values. Subjects with a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects with scores of 0-5 had a survival rate of 98%. CONCLUSIONS: In conclusion, the summed score represents a useful tool for screening patients with ILD who can undergo a CPET to determine their prognosis.

6.
Brain Sci ; 13(6)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37371378

RESUMO

Wearable robotic devices have been strongly put into use in both the clinical and research fields of stroke rehabilitation over the past decades. This study aimed to explore the effectiveness of soft robotic gloves (SRGs) towards improving the motor recovery and functional abilities in patients with post-stroke hemiparesis. Five major bibliographic databases, PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database, were all reviewed for enrollment regarding comparative trials prior to 7 March 2023. We included adults with stroke and compared their rehabilitation using SRGs to conventional rehabilitation (CR) on hand function in terms of the Fugl-Meyer Upper Extremity Motor Assessment (FMA-UE), Fugl-Meyer Distal Upper Extremity Motor Assessment (FMA-distal UE), box and blocks test score, grip strength test, and the Jebsen-Taylor hand function test (JTT). A total of 8 studies, comprising 309 participants, were included in the analysis. Compared to CR, rehabilitation involving SRGs achieved better FMA-UE (MD 6.52, 95% CI: 3.65~9.39), FMA-distal UE (MD 3.27, 95% CI: 1.50~5.04), and JJT (MD 13.34, CI: 5.16~21.53) results. Subgroup analysis showed that stroke latency of more than 6 months and training for more than 30 min offered a better effect as well. In conclusion, for patients with stroke, rehabilitation using SRGs is recommended to promote the functional abilities of the upper extremities.

7.
Clin Breast Cancer ; 23(6): 576-590, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37286435

RESUMO

BACKGROUND: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO2peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive. RESULTS: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO2peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO2peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO2peak. CONCLUSION: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Estudos de Viabilidade , Volume Sistólico , Função Ventricular Esquerda , Exercício Físico
8.
J Mater Chem B ; 8(24): 5204-5214, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32490480

RESUMO

Human adipose-derived stem cells (hASCs) cultured for 5 passages were filtered through nylon (NY) mesh filter membranes coated with and without extracellular matrix proteins to obtain the permeation solution. Subsequently, the culture media were filtered via the membranes to obtain the recovery solution. Then, the membranes were cultured in cell culture medium to obtain the migrated cells from the membranes. The hASCs in the permeation solution, through any type of NY mesh filter membrane having 11 and 20 µm pore sizes, had lower osteogenic differentiation ability than conventional hASCs cultured on tissue culture polystyrene (TCP) dishes for passage 5, whereas the hASCs purified by the membrane migration method through NY mesh filter membranes coated with recombinant vitronectin, which have 11 and 20 µm pore sizes, showed a higher proliferation speed as well as higher osteogenic differentiation potential than the conventional hASCs cultured on TCP dishes for passage 5. The membrane filtration and migration methods would be useful for cell sorting for specific cells, such as hASCs with high proliferation and high osteogenic differentiation ability, which do not need antibody binding or genetic modification of the cells for the specific isolation of the cells.


Assuntos
Tecido Adiposo/citologia , Nylons/química , Células-Tronco/citologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Filtração , Humanos , Tamanho da Partícula , Propriedades de Superfície
9.
Biomater Sci ; 7(12): 5467-5481, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31656967

RESUMO

Current xeno-free and chemically defined methods for the differentiation of hPSCs (human pluripotent stem cells) into cardiomyocytes are not efficient and are sometimes not reproducible. Therefore, it is necessary to develop reliable and efficient methods for the differentiation of hPSCs into cardiomyocytes for future use in cardiovascular research related to drug discovery, cardiotoxicity screening, and disease modeling. We evaluated two representative differentiation methods that were reported previously, and we further developed original, more efficient methods for the differentiation of hPSCs into cardiomyocytes under xeno-free, chemically defined conditions. The developed protocol successively differentiated hPSCs into cardiomyocytes, approximately 90-97% of which expressed the cardiac marker cTnT, with beating speeds and sarcomere lengths that were similar to those of a healthy adult human heart. The optimal cell culture biomaterials for the cardiac differentiation of hPSCs were also evaluated using extracellular matrix-mimetic material-coated dishes. Synthemax II-coated and Laminin-521-coated dishes were found to be the most effective and efficient biomaterials for the cardiac differentiation of hPSCs according to the observation of hPSC-derived cardiomyocytes with high survival ratios, high beating colony numbers, a similar beating frequency to that of a healthy adult human heart, high purity levels (high cTnT expression) and longer sarcomere lengths similar to those of a healthy adult human heart.


Assuntos
Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Miócitos Cardíacos/citologia , Animais , Linhagem Celular , Humanos , Miócitos Cardíacos/efeitos dos fármacos
10.
Bioorg Med Chem ; 16(3): 1262-78, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-17988878

RESUMO

Previously, ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3) was identified by us as the first non-peptide protease-activated receptor 4 (PAR4) antagonist. To continue on our development of novel anti-PAR4 agents, YD-3 was used as a lead compound and a series of its derivatives were synthesized and evaluated for their selective anti-PAR4 activity. Through structure-activity relationship (SAR) study, we identified the important functional groups contributing to anti-PAR4 activity, and these functional groups were kept intact during subsequent structural modification. Several new compounds with anti-PAR4 activity comparable to YD-3 were identified. Among them, ethyl 4-[1-(3-chlorobenzyl)-1H-indazol-3-yl]benzoate (33) showed the most potent inhibitory effect on PAR4-mediated platelet aggregation, ATP release, and P-selectin expression. On the other hand, ethyl 4-(1-phenyl-1H-indazol-3-yl)benzoate (83) exhibited dual inhibitory effects on PAR4 and thromboxane formation from arachidonic acid. The above findings can be used as guidelines for development of novel antiplatelet drug candidates.


Assuntos
Benzoatos/síntese química , Benzoatos/farmacologia , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/farmacologia , Trifosfato de Adenosina/metabolismo , Benzoatos/química , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Humanos , Estrutura Molecular , Selectina-P/metabolismo , Inibidores da Agregação Plaquetária/química , Relação Estrutura-Atividade
11.
RSC Adv ; 8(63): 35966-35972, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-35558485

RESUMO

High reliability and wide color gamut light-emitting diodes (LEDs) that use composite quantum dot films (CQDFs) protected by chip-scale package (CSP) structures are presented. CQDFs containing CdZnSeS/ZnS core-shell QDs and the K2SiF6:Mn4+ phosphors were mixed with silicone gel and used as color converters in the CSP QD-LEDs. The CSP QD-LEDs, used for backlight displays, transmitted through a color filter and exhibited ITU-R Recommendation BT.2020 of approximately 86% (a National Television System Committee value of 115%). Furthermore, we performed a long-term reliability analysis test on the CSP QD-LEDs for 2352 h to verify whether the optical performance of CSP QD-LEDs does not significantly degrade relative to that of a conventional plastic leaded chip carrier QD-LEDs. We implemented a highly reliable package technology that can protect the QDs, solve the moisture/oxygen problems in defective QD-LEDs, and produce a backlight source for display with a wide color gamut.

12.
Medicine (Baltimore) ; 96(46): e8633, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29145285

RESUMO

RATIONALE: Holmes' tremor is an uncommon neurologic disorder following brain insults, and its pathogenesis is undefined. The interruption of the dento-rubro-thalamic tract and secondary deterioration of the nigrostriatal pathway are both required to initiate Holmes' tremor. We used nuclear medicine imaging tools to analyze a patient with concurrent infarction in different zones of each side of the thalamus. Finding whether the paramedian nuclear groups of the thalamus were injured was a decisive element for developing Holmes' tremor. PATIENT CONCERNS: A 36-year-old woman was admitted to our department due to a bilateral paramedian thalamic infarction. Seven months after the stroke, a unilaterally involuntary trembling with irregularly wavering motions occurring in both her left hand and forearm. DIAGNOSIS: Based on the distinct features of the unilateral coarse tremor and the locations of the lesions on the magnetic resonance imaging (MRI), the patient was diagnosed with bilateral paramedian thalamic infarction complicated with a unilateral Holmes' tremor. INTERVENTIONS: The patient refused our recommendation of pharmacological treatment with levodopa and other dopamine agonists based on personal reasons and was only willing to accept physical and occupational training programs at our outpatient clinic. OUTCOMES: We utilized serial anatomic and functional neuroimaging of the brain to survey the neurologic deficit. A brain magnetic resonance imaging showed unequal recovery on each side of the thalamus. The residual lesion appeared larger in the right-side thalamus and had gathered in the paramedian area. A brain perfusion single-photon emission computed tomography (SPECT) revealed that the post-stroke hypometabolic changes were not only in the right-side thalamus but also in the right basal ganglion, which was anatomically intact. Furthermore, the brain Technetium-99m-labeled tropanes as a dopamine transporter imaging agents scan ( Tc-TRODAT-1) displayed a secondary reduction of dopamine transporters in the right nigrostriatal pathway which had resulted from the damage on the paramedian nuclear groups of the right-side thalamus. LESSONS: Based on the functional images, we illustrated that a retrograde degeneration originating from the thalamic paramedian nuclear groups, and extending forward along the direct innervating fibers of the mesothalamic pathway, played an essential role towards initiating Holmes' tremor.


Assuntos
Infarto Encefálico/complicações , Doenças Talâmicas/complicações , Tremor/etiologia , Adulto , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/patologia , Artérias Cerebrais/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Doenças Talâmicas/diagnóstico por imagem , Doenças Talâmicas/patologia , Tálamo/irrigação sanguínea , Tálamo/diagnóstico por imagem , Tálamo/patologia , Tomografia Computadorizada de Emissão de Fóton Único , Tremor/reabilitação , Tropanos
13.
J Hazard Mater ; 138(2): 350-6, 2006 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-16814464

RESUMO

The decomposition of 2-chlorophenol by UV/TiO2 process with the application of external bias voltage was examined in this study. Experiments were conducted in a batch reactor using TiO2-coated titanium sheet as anode and platinum sheet as cathode. The anode photocatalysis of 2-chlorophenol was totally inhibited for experiments conducted with the application of external anodic bias voltage lower than the flat band potential of TiO2. The decomposition rate of 2-chlorophenol was then increased with increasing external anodic bias voltage applied up to 0.0 V (versus SCE). The application of external bias voltage higher than 1.0 V did not markedly promote the photocatalysis of 2-chlorophenol possibly because the photocurrent induced was constant. Experimental results indicated that the decomposition of 2-chlorophenol was more effective for experiments conducted in acidic solutions due to the lower flat band potential of TiO2 and the higher photocurrent induced. The presence of electron scavengers in aqueous solution, such as oxygen molecules, may increase the decomposition rate of 2-chlorophenol. However, the effect of dissolved oxygen was diminished for experiments conducted with applied external bias voltage. The photocatalytic decomposition rate of 2-chlorophenol was enhanced linearly with the increasing UV light intensity when the external bias voltage was applied.


Assuntos
Clorofenóis/metabolismo , Raios Ultravioleta , Purificação da Água/métodos , Catálise , Eletroquímica , Humanos , Cinética , Oxirredução , Fotoquímica , Dióxido de Silício , Titânio
14.
Neural Comput ; 3(3): 440-449, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-31167319

RESUMO

Results of recent research suggest that carefully designed multilayer neural networks with local "receptive fields" and shared weights may be unique in providing low error rates on handwritten digit recognition tasks. This study, however, demonstrates that these networks, radial basis function (RBF) networks, and k nearest-neighbor (kNN) classifiers, all provide similar low error rates on a large handwritten digit database. The backpropagation network is overall superior in memory usage and classification time but can provide "false positive" classifications when the input is not a digit. The backpropagation network also has the longest training time. The RBF classifier requires more memory and more classification time, but less training time. When high accuracy is warranted, the RBF classifier can generate a more effective confidence judgment for rejecting ambiguous inputs. The simple kNN classifier can also perform handwritten digit recognition, but requires a prohibitively large amount of memory and is much slower at classification. Nevertheless, the simplicity of the algorithm and fast training characteristics makes the kNN classifier an attractive candidate in hardware-assisted classification tasks. These results on a large, high input dimensional problem demonstrate that practical constraints including training time, memory usage, and classification time often constrain classifier selection more strongly than small differences in overall error rate.

15.
Diabetes Res Clin Pract ; 63(2): 119-25, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14739052

RESUMO

This study examined healthcare costs for medication-using diabetic patients in Taiwan and predicted which factors were associated with costs. We analyzed claims data from the National Health Insurance (NHI) program in Taiwan from 1998 to 1999. The approach included estimates of costs attributable to diabetes, diabetes-related complications, comorbidity incurred by diabetic patients. A multiple regression model was used to assess the contribution of patients' characteristics in 1998 on outpatient, inpatient, and total costs in 1998 and 1999. The prevalence of medication-using patients with diabetes was 2.6% in 1998 and 2.8% in 1999. Costs of healthcare were 13.3% of total costs of NHI in 1998 versus 13.0% in 1999. Health services delivered near the end of life consumed large portions of medical dollars. The three most prevalent clinical associations of diabetes were congestive heart failure, neuropathy, and ischemic heart disease. Adjusted for demographic and clinical characteristics in 1998, this model could explain 8.0, 9.3, and 12.5%, respectively, of the cost variation in outpatient, inpatient, and total costs in 1999.


Assuntos
Diabetes Mellitus/economia , Custos de Cuidados de Saúde , Fatores Etários , Complicações do Diabetes , Diabetes Mellitus/terapia , Neuropatias Diabéticas/economia , Neuropatias Diabéticas/etiologia , Custos de Medicamentos , Feminino , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Isquemia Miocárdica/economia , Isquemia Miocárdica/etiologia , Programas Nacionais de Saúde , Análise de Regressão , Fatores Sexuais , Taiwan
16.
Neuro Oncol ; 14(10): 1227-38, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22946104

RESUMO

Tumor cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. However, how tumor cycling hypoxia impacts chemotherapy is unclear. In the present study, we explored the impact and the mechanism of cycling hypoxia on tumor microenvironment-mediated chemoresistance. Hoechst 33342 staining and hypoxia-inducible factor-1 (HIF-1) activation labeling together with immunofluorescence imaging and fluorescence-activated cell sorting were used to isolate hypoxic tumor subpopulations from human glioblastoma xenografts. ABCB1 expression, P-glycoprotein function, and chemosensitivity in tumor cells derived from human glioblastoma xenografts or in vitro cycling hypoxic stress-treated glioblastoma cells were determined using Western blot analysis, drug accumulation and efflux assays, and MTT assay, respectively. ABCB1 expression and P-glycoprotein function were upregulated under cycling hypoxia in glioblastoma cells concomitant with decreased responses to doxorubicin and BCNU. However, ABCB1 knockdown inhibited these effects. Moreover, immunofluorescence imaging and flow cytometric analysis for ABCB1, HIF-1 activation, and Hoechst 3342 in glioblastoma revealed highly localized ABCB1 expression predominantly in potentially cycling hypoxic areas with HIF-1 activation and blood perfusion in the solid tumor microenvironment. The cycling hypoxic tumor cells derived from glioblastoma xenografts exhibited higher ABCB1 expression, P-glycoprotein function, and chemoresistance, compared with chronic hypoxic and normoxic cells. Tumor-bearing mice that received YC-1, an HIF-1α inhibitor, exhibited suppressed tumor microenvironment-induced ABCB1 induction and enhanced survival rate in BCNU chemotherapy. Cycling hypoxia plays a vital role in tumor microenvironment-mediated chemoresistance through the HIF-1-dependent induction of ABCB1. HIF-1 blockade before and concurrent with chemotherapy could suppress cycling hypoxia-induced chemoresistance.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/fisiopatologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Animais , Biomarcadores Tumorais/metabolismo , Western Blotting , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Proliferação de Células , Citometria de Fluxo , Imunofluorescência , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células Tumorais Cultivadas , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
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