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1.
Geriatr Nurs ; 52: 152-156, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37354754

RESUMEN

OBJECTIVE: The purpose of this study was to analyze the relationship between institutional and individual characteristics that influence changes in the functional outcomes of nursing home residents. METHODS: Long-term Care Insurance claims data with basic information of nursing home(n = 3,263) and long-term care needs assessment data of nursing home residents(n = 34,717) was used. The independent variable was classified into individual (level 1) and nursing home characteristics (level 2). Changes in physical function, cognitive function, and behavioral symptoms were used as dependent variables. RESULTS: The institutional factors of nursing homes contributed relatively little to substantial changes in function of nursing home residents. Ownership, size, and nursing home staff including care worker and physical/occupational therapist were important determinants of functional changes in nursing home residents. CONCLUSION: To improve the quality of nursing homes in Korea, regulations on staffing should be modified, and an disincentive policy should be introduced for low-quality institutions.


Asunto(s)
Seguro de Cuidados a Largo Plazo , Casas de Salud , Humanos , Análisis Multinivel , Cuidados a Largo Plazo , República de Corea
2.
Small ; 18(29): e2202153, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35754305

RESUMEN

Development of a reliable doping method for 2D materials is a key issue to adopt the materials in the future microelectronic circuits and to replace the silicon, keeping the Moore's law toward the sub-10 nm channel length. Especially hole doping is highly required, because most of the transition metal dichalcogenides (TMDC) among the 2D materials are electron-doped by sulfur vacancies in their atomic structures. Here, hole doping of a TMDC, tungsten disulfide (WS2 ) using the silicon substrate as the dopant medium is demonstrated. An ultralow-power current sourcing transistor or a gated WS2 pn diode is fabricated based on a charge plasma pn heterojunction formed between the WS2 thin-film and heavily doped bulk silicon. An ultralow switchable output current down to 0.01 nA µm-1 , an off-state current of ≈1 × 10-14 A µm-1 , a static power consumption range of 1 fW µm-1 -1 pW µm-1 , and an output current ratio of 103 at 0.1 V supply voltage are achieved. The charge plasma heterojunction allows a stable (less than 3% variation) output current regardless of the gate voltage once it is turned on.

3.
Brachytherapy ; 21(3): 362-368, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35249823

RESUMEN

PURPOSE: To evaluate the prevalence of burnout among brachytherapy specialists and to identify factors associated with burnout. METHODS AND MATERIALS: An anonymous, online, cross-sectional survey was administered to non-trainee physician members of the American Brachytherapy Society. Burnout was evaluated using the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Demographic and practice-specific questions were collected from respondents. Univariate and multivariable analysis of outcomes were performed using probabilistic index models. RESULTS: Overall, 51 of 400 physicians responded (13% response rate). Fifty-seven percent of respondents demonstrated at least one symptom of professional burnout. However, only 6% of respondents met strict criteria for high burnout. Analysis of the individual MBI-HSS subdomains demonstrated higher subscale scores for emotional exhaustion and depersonalization, but also higher scores for personal accomplishment. On multivariable analysis after adjusting for increased feelings of burnout due to the COVID-19 pandemic or total hours of work per week, younger age was associated with both increased subscale scores for emotional exhaustion (p = 0.026) and lower personal accomplishment (p = 0.010). Lastly, nearly half of all respondents (47%) reported increased feelings of burnout due to the COVID-19 pandemic. Respondents from academic facilities were significantly more likely to report increased burnout due to COVID-19 compared to those from non-academic facilities (odds ratio, 7.04; 95% CI 1.60-31.0; p = 0.010). CONCLUSIONS: Nearly 60% of brachytherapists demonstrated symptoms of professional burnout, which is higher than other radiation oncology groups (academic chairs, program directors, residents). Managing stressors related to workload, COVID and support for junior physicians are potential areas for improving feelings of burnout.


Asunto(s)
Braquiterapia , Agotamiento Profesional , COVID-19 , Médicos , Braquiterapia/métodos , Agotamiento Profesional/diagnóstico , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Estudios Transversales , Humanos , Satisfacción en el Trabajo , Pandemias , Prevalencia , Encuestas y Cuestionarios , Estados Unidos/epidemiología
4.
Nanotechnology ; 33(20)2022 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-35114648

RESUMEN

Low-temperature process compatibility is a key factor in successfully constructing additional functional circuits on top of pre-existing circuitry without corrupting characteristics thereof, a technique that typically requires die-to-die (wafer-to-wafer) stacking and interconnecting. And against thermal annealing, which is mandatory and is possible only globally for activating amorphous oxide semiconductors, the selective control of electrical characteristics of the oxide thin-films for integrated circuit applications is challenging. Here, a low-temperature process that enables n-type doping of the designed region of insulating In2O3thin-film is demonstrated. A short hydrogen plasma treatment followed by low-temperature annealing is used to increase interstitial and substitutional hydrogen associated bond states creating shallow donor levels in the insulating In2O3surface to transform the thin-film into an n-type semiconductor. As a result, an In2O3thin-film transistor with a high on/off current ratio (>108), a field-effect mobility of 3.8 cm2V-1s-1, and a threshold voltage of ∼3.0 V has been developed. Compared to performing just thermal annealing, the H-plasma assisted annealing process resulted in an n-type In2O3thin-film transistor showing similar characteristics, while the processing time was reduced by ∼1/3 and the plasma-untreated area still remained insulating. With further development, the hydrogen plasma doping process may make possible a monolithic planar process technology for amorphous oxide semiconductors.

5.
Sensors (Basel) ; 21(12)2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34207622

RESUMEN

Self-powered wireless sensor systems have emerged as an important topic for condition monitoring in nuclear power plants. However, commercial wireless sensor systems still cannot be fully self-sustainable due to the high power consumption caused by excessive signal processing in a mini-electronic computing system. In this sense, it is essential not only to integrate the sensor system with energy-harvesting devices but also to develop simple data processing methods for low power schemes. In this paper, we report a patch-type vibration visualization (PVV) sensor system based on the triboelectric effect and a visualization technique for self-sustainable operation. The PVV sensor system composed of a polyethylene terephthalate (PET)/Al/LCD screen directly converts the triboelectric signal into an informative black pattern on the LCD screen without excessive signal processing, enabling extremely low power operation. In addition, a proposed image processing method reconverts the black patterns to frequency and acceleration values through a remote-control camera. With these simple signal-to-pattern conversion and pattern-to-data reconversion techniques, a vibration visualization sensor network has successfully been demonstrated.


Asunto(s)
Suministros de Energía Eléctrica , Nanotecnología , Electrónica , Procesamiento de Señales Asistido por Computador , Vibración
6.
Sensors (Basel) ; 21(13)2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34206489

RESUMEN

In this article we report on a 3 × 3 mm tactile interaction sensor that is able to simultaneously detect pressure level, pressure distribution, and shear force direction. The sensor consists of multiple mechanical switches under a conducting diaphragm. An external stimulus is measured by the deflection of the diaphragm and the arrangement of mechanical switches, resulting in low noise, high reliability, and high uniformity. Our sensor is able to detect tactile forces as small as ~50 mgf along with the direction of the shear force. It also distinguishes whether there is a normal pressure during slip motion. We also succeed in detecting the contact shape and the contact motion, demonstrating potential applications in robotics and remote input interfaces. Since our sensor has a simple structure and its function depends only on sensor dimensions, not on an active sensing material, in comparison with previous tactile sensors, our sensor shows high uniformity and reliability for an array-type integration.


Asunto(s)
Robótica , Tacto , Fenómenos Mecánicos , Reproducibilidad de los Resultados
7.
Nanotechnology ; 32(35)2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34038895

RESUMEN

High energy and high flux protons are used in proton therapy and the impact of proton radiation is a major reliability concern for electronics and solar cells in low earth orbit as well as in the trapped belts. Carbon nanotubes (CNTs), due to their unique characteristics, have been considered for the construction of proton and other radiation sensors. Here, a single wall CNT based proton sensor was fabricated on FR4 substrate and its response to 150 MeV proton irradiation was studied. The change in the resistance of the nanotubes upon irradiation is exploited as the sensing mechanism and the sensor shows good sensitivity to proton radiation. Proton radiation induces dissociation of ambient oxygen, followed by the adsorption of oxygen species on the nanotube surface, which influences its electrical characteristics. Since the nanotube film is thin and the 150 MeV protons are expected to penetrate into and interact with the substrate, control experiments were conducted to study the impact on FR4 substrate without the nanotubes. The dielectric loss tangent or dissipation factor of FR4 increases after irradiation due to an increase in the cross-linking of the resin arising from the degradation of the polymer network.

8.
Micromachines (Basel) ; 10(10)2019 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-31557853

RESUMEN

In this article, we report on a biomimetic tactile sensor that has a surface kinetic interface (SKIN) that imitates human epidermal fingerprint ridges and the epidermis. The SKIN is composed of a bilayer polymer structure with different elastic moduli. We improved the tactile sensitivity of the SKIN by using a hard epidermal fingerprint ridge and a soft epidermal board. We also evaluated the effectiveness of the SKIN layer in shear transfer characteristics while varying the elasticity and geometrical factors of the epidermal fingerprint ridges and the epidermal board. The biomimetic tactile sensor with the SKIN layer showed a detection capability for surface structures under 100 µm with only 20-µm height differences. Our sensor could distinguish various textures that can be easily accessed in everyday life, demonstrating that the sensor may be used for texture recognition in future artificial and robotic fingers.

9.
Nanotechnology ; 30(40): 405203, 2019 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-31284280

RESUMEN

We investigated the performance improvement of tin disulfide channel transistors by graphene contact configurations. From its two-dimensional nature, graphene can make electric contacts only at the outermost layers of the channel. For intralayer current flow, two graphene flakes are contacted at the channel's top or bottom layer. For interlayer current flow, one flake is contacted at the top and bottom of each layer. We compared the transistor performance in terms of current magnitude, mobility, and subthreshold swing between the configurations. From such observations, we deduced that device characteristics depend on resistivity or doping level of individual graphene flakes. We also found that interlayer flow excels in the on-current magnitude and the mobility, and that top-contact configuration excels in the subthreshold swing.

10.
Nanotechnology ; 30(40): 405707, 2019 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-31247597

RESUMEN

In this work, we report on the layered deposition of few-layer tin disulfide (SnS2) using atomic layer deposition (ALD). By varying the ALD cycles it was possible to deposit poly-crystalline SnS2 with small variation in layer numbers. Based on the ALD technique, we developed the process technology growing few-layer crystalline SnS2 film (3-6 layers) and we investigated their electrical properties by fabricating bottom-gated thin film transistors using the ALD SnS2 as the transport channel. SnS2 devices showed typical n-type characteristic with on/off current ratio of ∼8.32 × 106, threshold voltage of ∼2 V, and a subthreshold swing value of 830 mV decade-1 for the 6 layers SnS2. The developed SnS2 ALD technique may aid the realization of two-dimensional SnS2 based flexible and wearable devices.

11.
Sensors (Basel) ; 19(6)2019 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-30875874

RESUMEN

In this article, we report on a highly sensitive tactile shear sensor that was able to detect minute levels of shear and surface slip. The sensor consists of a suspended elastomer diaphragm with a top ridge structure, a graphene layer underneath, and a bottom substrate with multiple spatially digitized contact electrodes. When shear is applied to the top ridge structure, it creates torque and deflects the elastomer downwards. Then, the graphene electrode makes contact with the bottom spatially digitized electrodes completing a circuit producing output currents depending on the number of electrodes making contact. The tactile shear sensor was able to detect shear forces as small as 6 µN, detect shear direction, and also distinguish surface friction and roughness differences of shearing objects. We also succeeded in detecting the contact slip motion of a single thread demonstrating possible applications in future robotic fingers and remote surgical tools.

12.
Korean J Fam Med ; 40(1): 31-38, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30400700

RESUMEN

BACKGROUND: This study analyzed the relationship between health behaviors and marital adjustment in multicultural couples to evaluate their health status. METHODS: Married couples (70 Korean men and their immigrant wives) completed a structured interview on health behaviors and sociodemographic factors, the Revised Dyadic Adjustment Scale (RDAS), and the Marital Intimacy Scale. Based on the cutoff value of the RDAS, respondents were classified into two groups: high or low dyadic adaptation groups. The collected data were compared with health behavior regarding smoking, alcohol consumption, exercise, and weight. RESULTS: The odds ratio (OR) (95% confidence interval [CI]) by logistic regression with adjustment for age, educational level, career, occupation, length of residence in Korea, nationality, religion, age difference between couple, number of children, monthly income, and proficiency in Korean was 1.279 (1.113-1.492) for unhealthy exercise and 1.732 (1.604-1.887) for unhealthy body weight in female immigrants with low marital adjustment. In Korean husbands with low marital adjustment, the OR (95% CI) was 1.625 (1.232-2.142) for smoking and 1.327 (1.174- 1.585) for unhealthy exercise. No significant relationship was found between marital intimacy and health behaviors in female immigrants or Korean husbands. CONCLUSION: More desirable health behaviors were observed in highly adapted couples. Therefore, family physicians should be concerned with marital adjustment and other associative factors to evaluate and improve multicultural couples' health status.

13.
Cancer Med ; 8(1): 147-154, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30575303

RESUMEN

BACKGROUND: There is conflicting evidence regarding the role of peritumoral lymphatic vessel density (LVD) and blood microvessel density (MVD) in the metastasis and prognosis of head and neck squamous cell carcinoma (HNSCC). Existing studies are limited to one or two head and neck subsites and/or small sample sizes. A larger study incorporating multiple sub-sites is needed to address the role of peritumoral LVD and MVD in HNSCC metastasis and prognosis. METHODS: Tissue samples from 200 HNSCC cases were stained simultaneously using immunohistochemistry (IHC) for markers of peritumoral LVD (lymphatic vessel marker D240) and MVD (blood vessel marker CD31). Of the stained slides, 166 and 167 were evaluable for LVD and MVD, respectively. The results were then correlated with clinicopathologic features and patient outcomes. RESULTS: Patients with metastatic disease were more likely to have high peritumoral MVD. Through multivariable analyses, MVD was not significantly related to DFS and OS, while low LVD was related to higher risk of disease progression and poor survival. CONCLUSIONS: Peritumoral MVD was found to be positively associated with metastasis, while LVD was found to be inversely related to both metastasis and progression of HNSCC. These findings may suggest a prognostic role of both peritumoral LVD and MVD in patients with HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello/patología , Linfangiogénesis , Neovascularización Patológica , Microambiente Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Adulto Joven
14.
Korean J Fam Med ; 39(6): 333-339, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30369217

RESUMEN

BACKGROUND: There is a distinction in alcohol consumption behavior between adults and college students. This study aims to verify the usability and the optimal cutoff point of Alcohol Use Disorders Identification Test-Korean revised version (AUDIT-KR) for screening alcohol use disorder in college students when the diagnostic and statistical manual of mental disorders (DSM), 5th edition diagnostic criteria is applied. METHODS: A total of 922 college students living in Daejeon were enrolled and divided into two groups based on how many items they corresponded to among DSM-5 alcohol use disorder diagnostic criteria: those who corresponded to ≥2 of the 11 items were classified into the patient group (107 males, 89 females) while the others into the control group (311 males, 415 females). The participants were evaluated using AUDIT-KR to find the optimal cutoff point for screening alcohol use disorder, sensitivity, and specificity. RESULTS: The mean±standard deviation scores in the AUDIT-KR were 12.76±7.27, 10.72±4.62 for males and females, respectively, in the patient group. In contrast, in the control group the scores were 6.26±5.23 and 3.95±3.59 in males and females, respectively. The area under the receiver operating characteristic curve (95% confidence interval) regarding alcohol use disorder screening by AUDIT-KR was 0.768 (0.715-0.821) and 0.883 (0.848-0.919) for males and females, respectively. The optimal cutoff point of alcohol use disorder for males was >9, sensitivity 64.49%, and specificity 76.85%. The optimal cutoff point for females was >6, sensitivity 82.02%, and specificity 80.48%. CONCLUSION: This study suggested that AUDIT-KR can be used as a screening tool for alcohol use disorder in groups of college students when DSM-5 diagnosis criteria are applied.

15.
Adv Mater ; 30(26): e1707594, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29761603

RESUMEN

New binder concepts have lately demonstrated improvements in the cycle life of high-capacity silicon anodes. Those binder designs adopt adhesive functional groups to enhance affinity with silicon particles and 3D network conformation to secure electrode integrity. However, homogeneous distribution of silicon particles in the presence of a substantial volumetric content of carbonaceous components (i.e., conductive agent, graphite, etc.) is still difficult to achieve while the binder maintains its desired 3D network. Inspired by mucin, the amphiphilic macromolecular lubricant, secreted on the hydrophobic surface of gastrointestine to interface aqueous serous fluid, here, a renatured DNA-alginate amphiphilic binder for silicon and silicon-graphite blended electrodes is reported. Mimicking mucin's structure comprised of a hydrophobic protein backbone and hydrophilic oligosaccharide branches, the renatured DNA-alginate binder offers amphiphilicity from both components, along with a 3D fractal network structure. The DNA-alginate binder facilitates homogeneous distribution of electrode components in the electrode as well as its enhanced adhesion onto a current collector, leading to improved cyclability in both silicon and silicon-graphite blended electrodes.


Asunto(s)
Grafito/química , ADN , Electrodos , Litio , Mucinas , Polisacáridos , Silicio
16.
Biomacromolecules ; 19(6): 2053-2061, 2018 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-29601721

RESUMEN

For the increasing demand of soft materials with wide ranges of applications, hydrogels have been developed exhibiting variety of functions (e.g., stretchable, self-healing, stimuli-responsive, and etc.). So far, add-in components such as inorganic nanoparticles, carbon materials, clays, and many others to main polymers have been used to achieve various unique functions of hydrogels. The multicomponent hydrogel systems often exhibit batch-dependent inconsistent results and problems in multicomponent mixings, require labors during preparations, and accompany unpredictable cross-talk between the added components. Here, we developed 'single polymeric component', alginate-boronic acid (alginate-BA) hydrogel to overcome the aforementioned problems. It exhibits unprecedented multifunctionalities simultaneously, such as high stretchability, self-healing, shear-thinning, pH- and glucose-sensitivities, adhesive properties, and reshaping properties. Multifunctionalities of alginate-BA hydrogel is resulted from the reversible inter- and intramolecular interactions by dynamic equilibrium of boronic acid-diol complexation and dissociation, which was proved by single molecule level Atomic Force Microscopy (AFM) pulling experiments. We also found that the alginate-BA gel showed enhanced in vivo retentions along gastrointestinal (GI) tract. Our findings suggest that rational polymer designs can result in minimizing the number of a participating component for multifunctional hydrogels, instead of increasing complexity by adding various additional components.


Asunto(s)
Adhesivos/química , Alginatos/química , Ácidos Borónicos/química , Hidrogeles/química , Hidrogeles/farmacocinética , Adhesivos/farmacología , Administración Oral , Animales , Glucosa/química , Hidrogeles/administración & dosificación , Concentración de Iones de Hidrógeno , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Microscopía de Fuerza Atómica , Reología , Termodinámica
17.
Oncotarget ; 8(70): 114845-114855, 2017 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-29383125

RESUMEN

Although various mechanisms of castration-resistant prostate cancer (CRPC) have been discovered, reliable biomarkers for monitoring CRPC progression are lacking. We sought to identify molecules that predict the progression of advanced prostate cancer (AdvPC) into CRPC. The study used primary-site samples (N=45 for next-generation sequencing (NGS); N=243 for real-time polymerase chain reaction) from patients with prostate cancer (PC). Five public databases containing microarray data of AdvPC and CRPC samples were analyzed. The NGS data showed that each progression step in PC associated with distinct gene expression profiles. Androgen receptor (AR) associated with tumorigenesis, advanced progression, and progression into CRPC. Analysis of the paired and unpaired AdvPC and CRPC samples in the NGS cohort showed that 15 genes associated with progression into CRPC. This was validated by cohort-1 and public database analyses. Analysis of the third cohort with AdvPC showed that higher serine peptidase inhibitor, Kazal type 1 (SPINK1) and lower Sp8 transcription factor (SP8) expression associated with progression into CRPC (log-rank test, both P<0.05). Multivariate regression analysis showed that higher SPINK1 (Hazard Ratio (HR)=4.506, 95% confidence intervals (CI)=1.175-17.29, P=0.028) and lower SP8 (HR=0.199, 95% CI=0.063-0.632, P=0.006) expression independently predicted progression into CRPC. Gene network analysis showed that CRPC progression may be mediated through the AR-SPINK1 pathway by a HNF1A-based gene network. Taken together, our results suggest thatSPINK1 and SP8 may be useful for classifying patients with AdvPC who have a higher risk of progressing to CRPC.

18.
Mol Pharm ; 13(11): 3700-3711, 2016 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-27654060

RESUMEN

Herein, we elucidated the mechanisms and key factors for the tumor-targeting ability of nanoparticles that presented high targeting efficiency for liver tumor. We used several different nanoparticles with sizes of 200-300 nm, including liposome nanoparticles (LNPs), polystyrene nanoparticles (PNPs) and glycol chitosan-5ß-cholanic acid nanoparticles (CNPs). Their sizes are suitable for the enhanced permeation and retention (EPR) effect in literature. Different in vitro characteristics, such as the particle structure, stability, and bioinertness, were carefully analyzed with and without serum proteins. Also, pH-dependent tumor cell uptakes of nanoparticles were studied using fluorescence microscopy. Importantly, CNPs had sufficient stability and bioinertness to maintain their nanoparticle structure in the bloodstream, and they also presented prolonged circulation time in the body (blood circulation half-life T1/2 = about 12.2 h), compared to the control nanoparticles. Finally, employing liver tumor bearing mice, we also observed that CNPs had excellent liver tumor targeting ability in vivo, while LNPs and PNPs demonstrated lower tumor-targeting efficiency due to the nonspecific accumulation in normal liver tissue. Liver tumor models were produced by laparotomy and direct injection of HT29 tumor cells into the left lobe of the liver of athymic nude mice. This study provides valuable information concerning the key factors for the tumor-targeting ability of nanoparticles such as stability, bioinertness, and rapid cellular uptake at targeted tumor tissues.


Asunto(s)
Quitosano/administración & dosificación , Quitosano/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Neoplasias Hepáticas/metabolismo , Nanopartículas/química , Animales , Microscopía por Crioelectrón , Electroforesis en Gel de Poliacrilamida , Células HT29 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Electrónica , Células RAW 264.7 , Ratas
19.
Neuro Oncol ; 18(4): 486-96, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26995790

RESUMEN

BACKGROUND: We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. METHODS: The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. RESULTS: Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. CONCLUSIONS: Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/farmacología , Pirimidinas/farmacología , Receptores de Endotelina/química , Sulfonamidas/farmacología , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Quimioterapia Combinada , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Desnudos , Células 3T3 NIH , Receptores de Endotelina/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Angew Chem Int Ed Engl ; 55(10): 3342-6, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26833974

RESUMEN

Mussel-inspired self-polymerized catecholamine coatings have been widely utilized as a versatile coating strategy that can be applied to a variety of substrates. For the first time, nanomechanical measurements and an evaluation of the contribution of primary amine groups to poly(catecholamine) coatings have been conducted using a surface-forces apparatus. The adhesive strength between the poly(catecholamine) layers is 30-times higher than that of a poly(catechol) coating. The origin of the strong attraction between the poly(catecholamine) layers is probably due to surface salt displacement by the primary amine, π-π stacking (the quadrupole-quadrupole interaction of indolic crosslinks), and cation-π interactions (the monopole-quadrupole interaction between positively charged amine groups and the indolic crosslinks). The contribution of the primary amine group to the catecholamine coating is vital for the design and development of mussel-inspired catechol-based coating materials.


Asunto(s)
Materiales Biocompatibles Revestidos , Espectroscopía de Fotoelectrones , Soluciones , Propiedades de Superficie , Agua
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