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1.
Genome Med ; 16(1): 20, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297291

RESUMO

BACKGROUND: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. METHODS: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. RESULTS: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. CONCLUSIONS: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Transcriptoma , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Perfilação da Expressão Gênica , Prognóstico , Microambiente Tumoral/genética , Análise de Célula Única , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética
2.
Sci Adv ; 9(50): eadk9752, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38091394

RESUMO

Tailoring transfer dynamics of mobile cations across solid-state electrolyte-electrode interfaces is crucial for high-performance electrochemical soft actuators. In general, actuation performance is directly proportional to the affinity of cations and anions in the electrolyte for the opposite electrode surfaces under an applied field. Herein, to maximize electrochemical actuation, we report an electronically conjugated polysulfonated covalent organic framework (pS-COF) used as a common electrolyte-electrode host for 1-ethyl-3-methylimidazolium cation embedded into a Nafion membrane. The pS-COF-based electrochemical actuator exhibits remarkable bending deflection at near-zero voltage (~0.01 V) and previously unattainable blocking force, which is 34 times higher than its own weight. The ultrafast step response shows a very short rising time of 1.59 seconds without back-relaxation, and substantial ultralow-voltage actuation at higher frequencies up to 5.0 hertz demonstrates good application prospects of common electrolyte-electrode hosts. A soft fluidic switch is constructed using the proposed soft actuator as a potential engineering application.

3.
Small ; 19(30): e2301847, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37170694

RESUMO

An electronically conjugated functional triazine framework is used to synthesize a physicochemically interlocked sulfur cathode that delivers high energy density coupled with exceptional cycle life in lithium-sulfur batteries. Conventional melt-diffusion strategies to impregnate sulfur in the cathode offer poor cycle life due to physical mixing with weak interactions. By contrast, in this approach, sulfur is physicochemically entrapped within a nanoporous and heteroatom doped high surface area covalent triazine framework, resulting in outstanding electrochemical performance (≈89% capacity retention after 1000 cycles, the energy density of ≈2,022 Wh kg-1 sulfur and high-rate capability up to 12 C). The overall structural characteristics and interactions of sulfur with the covalent triazine framework are explored in detail to explain the intriguing properties of the sulfur cathode.

4.
Adv Mater ; 34(35): e2203613, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35772104

RESUMO

There is growing demand for multiresponsive soft actuators for the realization of natural, safe, and complex motions in robotic interactions. In particular, soft actuators simultaneously stimulated by electrical and magnetic fields are always under development owing to their simple controllability and reliability during operation. Herein, magnetically and electrically driven dual-responsive soft actuators (MESAs) derived from novel nickel-based metal-organic frameworks (Ni-MOFs-700C), are reported. Nanoscale Ni-MOFs-700C has excellent electrochemical and magnetic properties that allow it to be used as a multifunctional material under both magnetoactive and electro-ionic actuations. The dual-responsive MESA exhibits a bending displacement of 30 mm and an ultrafast rising time of 1.5 s under a very low input voltage of 1 V and also exerts a bending deflection of 12.5 mm at 50 mT under a high excitation frequency of 5 Hz. By utilizing a dual-responsive MESA, the hovering motion of a hummingbird robot is demonstrated under magnetic and electrical stimuli.

5.
Adv Sci (Weinh) ; 8(23): e2102064, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34693658

RESUMO

Emerging technologies such as soft robotics, active biomedical devices, wearable electronics, haptic feedback systems, and healthcare systems require high-fidelity soft actuators showing reliable responses under multi-stimuli. In this study, the authors report an electro-active and photo-active soft actuator based on a vanadium oxide nanowire (VONW) hybrid film with greatly improved actuation performances. The VONWs directly grown on a cellulose fiber network increase the surface area up to 30-fold and boost the hydrophilicity owing to the presence of oxygen-rich functional groups in the nanowire surfaces. Taking advantage of the high surface area and hydrophilicity of VONWs, a soft thermo-hygroscopic VONW actuator capable of being controlled by both light and electric sources shows greatly enhanced actuation deformation by almost 70% and increased actuation speed over 3 times during natural convection cooling. Most importantly, the proposed VONW actuator exhibits a remarkably improved blocking force of up to 200% compared with a bare paper actuator under light stimulation, allowing them to realize a complex kirigami pop-up and to accomplish repeatable shape transformation from a 2D planar surface to a 3D configuration.

6.
ChemSusChem ; 14(22): 5004-5020, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34463051

RESUMO

In this study, utilizing metallocene and organosulfur chelating agent, an innovative synthetic route was developed towards electrochemically activated transition metal sulfides entrapped in pyridinic nitrogen-incorporated carbon nanostructures for superior oxygen evolution reaction (OER). Most importantly, the preferential electrochemical activation process, which consisted of both anodic and cathodic pre-treatment steps, strikingly enhanced OER and long-lasting cyclic stability. The substantial increase in OER electrocatalytic activity of Ni9 S8 /Ni3 S2 -NC and Co9 S8 -NC during the activation process was mainly attributed to the increase of faradaic active site density on the catalytic layer resulting from the reconstruction of catalytic interfaces. It was also found that Fe-based metallocene [ferrocene (Fc)]-incorporation in the Co9 S8 -NC and Ni9 S8 /Ni3 S2 -NC nanostructures significantly boosted the OER activity. Thus, the combined effects of Fc-incorporation and the electrochemical activation process reduced the overpotential to about 115 and 95 mV on the Ni9 S8 /Ni3 S2 -NC and Co9 S8 -NC nanostructures to derive a current density of 10 mA cm-2 , respectively. Notably, Fc-Ni9 S8 /Ni3 S2 -NC electrocatalysts required very small overpotentials of around 222, 244, and 280 mV to acquire the current densities of 10, 20, and 50 mA cm-2 , respectively. This work opens up a new avenue for superior OER electrocatalysts by the utilization of metallocene and the preferential electrochemical activation process.

7.
Int J Gynecol Pathol ; 40(3): 214-223, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32287115

RESUMO

Transient receptor potential vanilloid type 1 (TRPV1) has been reported to play an important role in human cancers. However, the knowledge about TRPV1 in cervical cancer is sparse. Therefore, we evaluated the expression and clinical significance of TRPV1 in cervical cancer. Immunohistochemical analyses were performed for TRPV1 and phosphatase and tension homolog (PTEN) to delineate clinical significance using 150 cervical cancers, 230 cervical intraepithelial neoplasias, and 312 normal cervical epithelial tissues in a tissue microarray. Furthermore, the role of TRPV1 in cell growth was assessed in a cervical cancer cell line. The TRPV1 expression was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasias, and normal epithelial tissues (P<0.001). In cervical cancer tissues, TRPV1 expression negatively correlated with PTEN expression (Spearman ρ=-0.121, P=0.009). Multivariate survival analysis revealed high TRPV1 expression (hazard ratio=3.41, 95% confidence interval: 1.25-9.27, P=0.016) as an independent prognostic factor for overall survival. Notably. the high TRPV1/low PTEN expression showed the highest hazard ratio (5.87; 95% confidence interval: 2.18-15.82, P<0.001) for overall survival. In vitro results demonstrated that the overexpression of TRPV1 was associated with increased cell viability and colony formation. Overexpression of TRPV1 could be a good biomarker for the prediction of chemoradiation response. Our result suggested promising potential of high TRPV1/low PTEN as prognostic and survival makers. The possible link between the biologic function of TRPV1 and PTEN in cervical cancer warrants further studies.


Assuntos
PTEN Fosfo-Hidrolase/metabolismo , Canais de Cátion TRPV/metabolismo , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Colo do Útero/patologia , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/genética , Prognóstico , Canais de Cátion TRPV/genética , Análise Serial de Tecidos , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia
8.
Nat Commun ; 11(1): 5358, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097728

RESUMO

In the field of bioinspired soft robotics, to accomplish sophisticated tasks in human fingers, electroactive artificial muscles are under development. However, most existing actuators show a lack of high bending displacement and irregular response characteristics under low input voltages. Here, based on metal free covalent triazine frameworks (CTFs), we report an electro-ionic soft actuator that shows high bending deformation under ultralow input voltages that can be implemented as a soft robotic touch finger on fragile displays. The as-synthesized CTFs, derived from a polymer of intrinsic microporosity (PIM-1), were combined with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) to make a flexible electrode for a high-performance electro-ionic soft actuator. The proposed soft touch finger showed high peak-to-peak displacement of 17.0 mm under ultralow square voltage of ±0.5 V, with 0.1 Hz frequency and 4 times reduced phase delay in harmonic response compared with that of a pure PEDOT-PSS-based actuator. The significant actuation performance is mainly due to the unique physical and chemical configurations of CTFs electrode with highly porous and electrically conjugated networks. On a fragile display, the developed soft robotic touch finger array was successfully used to perform soft touching, similar to that of a real human finger; device was used to accomplish a precise task, playing electronic piano.

9.
Nanoscale ; 12(40): 20868-20874, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33043946

RESUMO

Herein, we report vanadium carbide (V8C7) nanowires (NWs) axially grown on carbon cloths (CCs) as a dual-ion accepting cathode for both lithium (LIBs) and sodium-ion batteries (SIBs). Using a facile hydrothermal method, we grew V2O3 NWs on CCs and subsequently reduced them to V8C7 by annealing with carbon sources under a H2/Ar atmosphere. In striking contrast to V2O5 NW cathodes obtained by annealing under air, the V8C7 NWs exhibit outstanding cycling stability during 500 cycles, and good rate capability for both LIBs and SIBs. V8C7 NWs as cathode active materials for LIBs exhibited 203.9 mA h g-1 specific capacity at 0.1 C after 500 cycles, 91.12% cycling retention and a coulombic efficiency of 99.84%. As cathodes in SIBs, the V8C7 NWs delivered 176.34 mA h g-1 specific capacity at 0.1 C during 300 cycles. Their defect sites by removal of the oxygen framework in V2O3 NWs have a high surface area (183.27 m2 g-1) and the unique 1D NW structure highly mitigates the volume changes during charge and discharge showing a superior electrochemical performance. Compared to commercially available cathodes, V8C7 nanowires have very good cycling stability and enhanced electrical conductivity. Moreover, the synergistic effect with 3D CCs utilized here as a current collector provides a large number of cation-accessible active sites in conjunction with high electrical conductivity and chemical stability.

10.
Small ; 16(31): e2001665, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32597017

RESUMO

Here, ferrocene(Fc)-incorporated cobalt sulfide (Cox Sy ) nanostructures directly grown on carbon nanotube (CNT) or carbon fiber (CF) networks for electrochemical oxygen evolution reaction (OER) using a facile one-step solvothermal method are reported. The strong synergistic interaction between Fc-Cox Sy nanostructures and electrically conductive CNTs results in the superior electrocatalytic activity with a very small overpotential of ≈304 mV at 10 mA cm-2 and a low Tafel slope of 54.2 mV dec-1 in 1 m KOH electrolyte. Furthermore, the Fc-incorporated Cox Sy (FCoS) nanostructures are directly grown on the acid pretreated carbon fiber (ACF), and the resulting fabricated electrode delivers excellent OER performance with a low overpotential of ≈315 mV at 10 mA cm-2 . Such superior OER catalytic activity can be attributed to 3D Fc-Cox Sy nanoarchitectures that consist of a high concentration of vertical nanosheets with uniform distribution of nanoparticles that afford a large number of active surface areas and edge sites. Besides, the tight contact interface between ACF substrate and Fc-Cox Sy nanostructures could effectively facilitate the electron transfer rate in the OER. This study provides valuable insights for the rational design of energy storage and conversion materials by the incorporation of other transition metal into metal sulfide/oxide nanostructures utilizing metallocene.

11.
Cancer Genomics Proteomics ; 17(3): 309-319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32345672

RESUMO

BACKGROUND: Transient receptor potential vanilloid type 1 (TRPV1) has been studied in human malignancies, but has not been studied in epithelial ovarian cancer (EOC). We, therefore, investigated the significance of TRPV1 and correlation with phosphatase and tension homolog (PTEN) in EOC. MATERIALS AND METHODS: Immunohistochemical analyses for TRPV1 and PTEN were performed using a tissue microarray. Moreover, the role of TRPV1 in cell growth was assessed in a EOC cell line. RESULTS: High TRPV1 expression and the combination of high TRPV1 and low PTEN expression were an independent prognostic factor for overall survival and disease-free survival. In vitro results demonstrated that knockdown of TRPV1 was associated with decreased cell viability and colony formation. CONCLUSION: There is a strong association between TRPV1 and PTEN and the combination of TRPV1 and PTEN is a strong indicator of prognostic predictor in EOC.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Neoplasias Ovarianas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Canais de Cátion TRPV/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Estudos de Casos e Controles , Proliferação de Células/fisiologia , Feminino , Seguimentos , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , PTEN Fosfo-Hidrolase/biossíntese , PTEN Fosfo-Hidrolase/genética , Prognóstico , Canais de Cátion TRPV/biossíntese , Canais de Cátion TRPV/genética , Células Tumorais Cultivadas
12.
ACS Appl Mater Interfaces ; 12(10): 11657-11668, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32109039

RESUMO

Herein, we report a straigthforward procedure to prepare an excellent intertwined nanosponge solid-state polymer electrolyte (INSPE) for highly bendable, rollable, and foldable lithium-ion batteries (LIBs). The mechanically reliable and electrochemically superior INSPE is conjugated with intertwined nanosponge (IN) poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-co-HFP) and ion-conducting polymer electrolyte (PE) containing poly(ethylene glycol) diacrylate (PEGDA), succinonitrile (SCN) plasticizer, and lithium bis(trifluoromethanesilfonyl)imide (LiTFSI). The conjugated INSPE has both high strength with great flexibility (tensile strength of 2.1 MPa, elongation of 36.7%), and excellent ionic conductivity (1.04 × 10-3 S·cm-1, similar to the values of liquid electrolytes). As a result of such special combination, the as-prepared INSPE retains almost 100% of its ionic conductivity when subjected to many types of severe mechanical deformations. Therefore, the INSPE is successfully applied to bendable, rollable, and foldable LIBs that show excellent energy storage performance despite the intense mechanical deformations.

13.
BMC Cancer ; 19(1): 1202, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823759

RESUMO

BACKGROUND: Transcription factors forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) have been reported to play important roles in various cancers. However, their role in epithelial ovarian cancer (EOC) has not been elucidated yet. Therefore, we evaluated the expression and clinical significance of FOXO1 and PAX3 in EOC. METHODS: Immunohistochemical analyses of FOXO1 and PAX3 in 212 EOCs, 57 borderline ovarian tumors, 153 benign epithelial ovarian tumors, and 79 nonadjacent normal epithelial tissues were performed using tissue microarray. Various clinicopathological variables, including the survival of EOC patients, were compared. In addition, the effect of FOXO1 on cell growth was assessed in EOC cell lines. RESULTS: FOXO1 and PAX3 protein expression levels were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues, and borderline tumors (all p < 0.001). In EOC tissues, FOXO1 expression was positively correlated with PAX3 expression (Spearman's rho = 0.118, p = 0.149). Multivariate survival analysis revealed that high FOXO1 expression (hazard ratio = 2.77 [95% CI, 1.48-5.18], p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed a high hazard ratio (4.60 [95% CI, 2.00-10.55], p < 0.001) for overall survival. Also in vitro results demonstrated that knockdown of FOXO1 was associated with decreased cell viability, migration, and colony formation. CONCLUSIONS: This study revealed that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results suggest the promising potential of FOXO1 and PAX3 as prognostic and therapeutic markers. The possible link between biological functions of FOXO1 and PAX3 in EOC warrants further studies.


Assuntos
Carcinoma Epitelial do Ovário/patologia , Proteína Forkhead Box O1/metabolismo , Neoplasias Ovarianas/patologia , Fator de Transcrição PAX3/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Prognóstico , Análise de Sobrevida
14.
Int J Clin Oncol ; 24(11): 1429-1439, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31302815

RESUMO

PURPOSE: Forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) have been reported to play an imported role in human cancers, but their role in cervical cancer has not yet been clarified. In this study, we evaluated the functional role of FOXO1 in cervical cancer cells and investigated the expression and clinical significance of FOXO1 and PAX3 in cervical lesions. METHODS: In vitro assessment of cell function by cell viability, migration, and invasion assays were performed on FOXO1-knockdown cervical cancer cells. Immunohistochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with a tissue microarray (TMA). The clinical significance was evaluated by comparing the data with various clinicopathologic characteristics, including survival of patients with cervical cancer. RESULTS: In vitro results revealed that knockdown of FOXO1 is associated with decreased cell viability (p < 0.001), migration (p < 0.001), and invasion (p < 0.05), supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p < 0.001) and cancer tissue (both p < 0.001) than in normal tissue. Multivariate analysis indicated that FOXO1 expression (hazard ratio 4.01 [95% CI 1.22-13.10], p = 0.021) and an advanced FIGO stage (hazard ratio 3.89 [95% CI 1.35-11.19], p = 0.012) were independent prognostic factors for overall survival. CONCLUSIONS: This study reveals increased FOXO1 and PAX3 expression in cervical cancers and indicates an oncogenic role of FOXO1 in cervical cancer cells that correlates with poor patient survival.


Assuntos
Proteína Forkhead Box O1/genética , Fator de Transcrição PAX3/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/mortalidade , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/genética , Feminino , Proteína Forkhead Box O1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Fator de Transcrição PAX3/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Ensaio Tumoral de Célula-Tronco , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/patologia
15.
Sci Robot ; 4(33)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-33137782

RESUMO

Existing ionic artificial muscles still require a technology breakthrough for much faster response speed, higher bending strain, and longer durability. Here, we report an MXene artificial muscle based on ionically cross-linked Ti3C2T x with poly(3,4 ethylenedioxythiophene)-poly(styrenesulfonate), showing ultrafast rise time of within 1 s in DC responses, extremely large bending strain up to 1.37% in very low input voltage regime (0.1 to 1 V), long-term cyclic stability of 97% up to 18,000 cycles, markedly reduced phase delay, and very broad frequency bandwidth up to 20 Hz with good structural reliability without delamination under continuous electrical stimuli. These artificial muscles were successfully applied to make an origami-inspired narcissus flower robot as a wearable brooch and dancing butterflies and leaves on a tree as a kinetic art piece. These successful demonstrations elucidate the wide potential of MXene-based soft actuators for the next-generation soft robotic devices including wearable electronics and kinetic art pieces.

16.
Radiat Prot Dosimetry ; 175(3): 297-303, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27885084

RESUMO

A new treatment facility for heavy ion therapy since 2010 was constructed. In the broad beam, a range shifter, ridge filter and multi leaf collimator (MLC) for the generation of the spread-out Bragg peak is used. In this case, secondary neutrons produced by the interactions of the ion field with beam-modifying devices (e.g. double-scattering system, beam shaping collimators and range compensators) are very important for patient safety. Therefore, these components must be carefully examined in the context of secondary neutron yield and associated secondary cancer risk. In this article, Monte Carlo simulation has been carried out with the FLUktuierende KAskade particle transport code, the fluence and distribution of neutron generation and the neutron dose equivalent from the broad beam components are compared using carbon and proton beams. As a result, it is confirmed that the yield of neutron production using a carbon beam from all components of the broad beam was higher than using a proton beam. The ambient dose by neutrons per heavy ion and proton ion from the MLC surface was 0.12-0.18 and 0.0067-0.0087 pSv, respectively, which shows that heavy ions generate more neutrons than protons. However, ambient dose per treatment 2 Gy, which means physical dose during treatment by ion beam, is higher than carbon beam because proton therapy needs more beam flux to make 2-Gy prescription dose. Therefore, the neutron production from the MLC, which is closed to the patient, is a very important parameter for patient safety.


Assuntos
Método de Monte Carlo , Nêutrons , Dosagem Radioterapêutica , Humanos , Prótons , Radioterapia Conformacional
17.
Anticancer Res ; 34(7): 3557-62, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24982369

RESUMO

BACKGROUND: Despite the selectivity of Tumor necrosis factor Related Apoptosis-Inducing Ligand (TRAIL) for cancer cell killing activity, breast cancer cells are resistant to TRAIL-induced apoptosis for various reasons. MATERIALS AND METHODS: From a functionally-characterized small-molecule dataset, CGP74514A was identified as a TRAIL sensitizer in MCF-7 breast cancer cells. Combination of sub-toxic dose of TRAIL with CGP74514A was evaluated in three TRAIL-resistant breast cancer cells, MCF-7, T47D and SK-BR-3. RESULTS: In all tested cells, CGP74514A enhanced TRAIL sensitivity. Combination treatment triggered apoptotic events faster than single treatment. Regarding its mechanism of action, CGP74514A reduced cytosolic X-linked inhibitor of apoptosis protein (XIAP). Small interfering RNA-mediated knockdown experiments showed that reduction of XIAP is the reason of sensitization. CONCLUSION: CGP74514A sensitized breast cancer cells to TRAIL via reduction of XIAP expression level.


Assuntos
2-Aminopurina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , 2-Aminopurina/administração & dosagem , 2-Aminopurina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem
18.
Apoptosis ; 19(4): 615-28, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24173372

RESUMO

AMP-activated protein kinase (AMPK) performs a pivotal function in energy homeostasis via the monitoring of intracellular energy status. Once activated under the various metabolic stress conditions, AMPK regulates a multitude of metabolic pathways to balance cellular energy. In addition, AMPK also induces cell cycle arrest or apoptosis through several tumor suppressors including LKB1, TSC2, and p53. LKB1 is a direct upstream kinase of AMPK, while TSC2 and p53 are direct substrates of AMPK. Therefore, it is expected that activators of AMPK signal pathway might be useful for treatment or prevention of cancer. In the present study, we report that cryptotanshinone, a natural compound isolated from Salvia miltiorrhiza, robustly activated AMPK signaling pathway, including LKB1, p53, TSC2, thereby leading to suppression of mTORC1 in a number of LKB1-expressing cancer cells including HepG2 human hepatoma, but not in LKB1-deficient cancer cells. Cryptotanshinone induced HepG2 cell cycle arrest at the G1 phase in an AMPK-dependent manner, and a portion of cells underwent apoptosis as a result of long-term treatment. It also induced autophagic HepG2 cell death in an AMPK-dependent manner. Cryptotanshinone significantly attenuated tumor growth in an HCT116 cancer xenograft in vivo model, with a substantial activation of AMPK signal pathways. Collectively, we demonstrate for the first time that cryptotanshinone harbors the therapeutic potential for the treatment of cancer through AMPK activation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Fenantrenos/farmacologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ativação Enzimática , Células Hep G2 , Xenoenxertos , Humanos , Masculino , Metformina/farmacologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fenantrenos/uso terapêutico , Transdução de Sinais
19.
J Nanosci Nanotechnol ; 13(5): 3455-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23858878

RESUMO

Medical radiation imaging systems employ phosphors such as CaWO4 as X-ray receptor materials. Unfortunately, the conversion efficiencies of these materials are rather low (approx. 5%). Alternatives that comprise a bulk structure have been fabricated from rare earth metals, but they are not efficient enough to produce high quality images. Nano-phosphors do not suffer from the limitations inherent to the bulk structures of conventional phosphors. We examined the effects of sensitizer doping conditions on the optical characteristics and morphology of the rare earth phosphor Gd2O3:Eu to fabricate a novel type of nano-phosphor. We optimized a temperature solution-combustion procedure for producing phosphors doped with 5 wt% Eu. Scanning electron microscopy images showed that the phosphors were 20-30 nm in diameter and X-ray diffraction analysis revealed that they underwent polycrystalline growth upon the addition of a sensitizer, similar to the polycrystalline growth of bulk phosphors. In addition, the phosphors exhibited a strong peak at 613 nm and luminescence similar to conventional phosphors. Phosphors that were produced using citric acid as a sensitizer showed more than double the level of luminescence and could be used to produce higher quality images compared to non-sensitized phosphors. The phosphors also exhibited a high degree of luminescence stability.


Assuntos
Gadolínio/química , Gadolínio/efeitos da radiação , Medições Luminescentes/métodos , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Radiografia/métodos , Teste de Materiais , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Raios X
20.
Cell Oncol ; 27(4): 237-44, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16308473

RESUMO

Multi-resolution images of histological sections of breast cancer tissue were analyzed using texture features of Haar- and Daubechies transform wavelets. Tissue samples analyzed were from ductal regions of the breast and included benign ductal hyperplasia, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (CA). To assess the correlation between computerized image analysis and visual analysis by a pathologist, we created a two-step classification system based on feature extraction and classification. In the feature extraction step, we extracted texture features from wavelet-transformed images at 10x magnification. In the classification step, we applied two types of classifiers to the extracted features, namely a statistics-based multivariate (discriminant) analysis and a neural network. Using features from second-level Haar transform wavelet images in combination with discriminant analysis, we obtained classification accuracies of 96.67 and 87.78% for the training and testing set (90 images each), respectively. We conclude that the best classifier of carcinomas in histological sections of breast tissue are the texture features from the second-level Haar transform wavelet images used in a discriminant function.


Assuntos
Neoplasias da Mama/patologia , Processamento de Imagem Assistida por Computador , Carcinoma Intraductal não Infiltrante , Análise Discriminante , Feminino , Humanos , Redes Neurais de Computação
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