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1.
Clin Neurophysiol ; 151: 50-58, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37156120

RESUMEN

OBJECTIVE: The aim of this feasibility study was to investigate the properties of median nerve somatosensory evoked potential (SEPs) recorded from segmented Deep Brain Stimulation (DBS) leads in the sensory thalamus (VP) and how they relate to clinical and anatomical findings. METHODS: We analyzed four patients with central post-stroke pain and DBS electrodes placed in the VP. Median nerve SEPs were recorded with referential and bipolar montages. Electrode positions were correlated with thalamus anatomy and tractography-based medial lemniscus. Early postoperative clinical paresthesia mapping was performed by an independent pain nurse. Finally, we performed frequency and time-frequency analyses of the signals. RESULTS: We observed differences of SEP amplitudes recorded along different directions in the VP. SEP amplitudes did not clearly correlate to both atlas-based anatomical position and fiber-tracking results of the medial lemniscus. However, the contacts of highest SEP amplitude correlated with the contacts of lowest effect-threshold to induce paraesthesia. CONCLUSIONS: SEP recordings from directional DBS leads offer additional information about the neurophysiological (re)organization of the sensory thalamus. SIGNIFICANCE: Directional recordings of thalamic SEPs bear the potential to assist clinical decision-making in DBS for pain.


Asunto(s)
Dolor , Tálamo , Humanos , Tálamo/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Electrodos , Nervio Mediano
2.
Neuromodulation ; 26(8): 1747-1756, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36266180

RESUMEN

OBJECTIVE: The beneficial effects of thalamic deep brain stimulation (DBS) at various target sites in treating chronic central neuropathic pain (CPSP) remain unclear. This study aimed to evaluate the effectiveness of DBS at a previously untested target site in the central lateral (CL) thalamus, together with classical sensory thalamic stimulation (ventral posterior [VP] complex). MATERIALS AND METHODS: We performed a monocentric retrospective study of a consecutive series of six patients with CPSP who underwent combined DBS lead implantation of the CL and VP. Patient-reported outcome measures were recorded before and after surgery using the numeric rating scale (NRS), short-form McGill pain questionnaire (sf-MPQ), EuroQol 5-D quality-of-life questionnaire, and Beck Depression Inventory. DBS leads were reconstructed and projected onto a three-dimensional stereotactic atlas. RESULTS: NRS-but not sf-MPQ-rated pain intensity-was significantly reduced throughout the follow-up period of 12 months compared with baseline (p = 0.005, and p = 0.06 respectively, Friedman test). At the last available follow-up (12 to 30 months), three patients described a more than 50% reduction. Two of the three long-term responders were stimulated in the CL (1000 Hz, 90 µs, 3.5-5.0 mA), whereas the third preferred VP complex stimulation (50 Hz, 200 µs, 0.7-1.2 mA). No persistent procedure- or stimulation-associated side effects were noted. CONCLUSIONS: These preliminary findings suggest that DBS of the CL might constitute a promising alternative target in cases in which classical VP complex stimulation does not yield satisfactory postoperative pain reduction. The results need to be confirmed in larger, prospective series of patients.


Asunto(s)
Estimulación Encefálica Profunda , Neuralgia , Humanos , Estimulación Encefálica Profunda/métodos , Estudios Retrospectivos , Neuralgia/etiología , Neuralgia/terapia , Tálamo/diagnóstico por imagen , Dimensión del Dolor/métodos
3.
Nanoscale Adv ; 4(21): 4648-4657, 2022 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-36341289

RESUMEN

Thanks to their excellent compatibility with the complementary metal-oxide-semiconductor (CMOS) process, antiferroelectric (AFE) HfO2/ZrO2-based thin films have emerged as potential candidates for high-performance on-chip energy storage capacitors of miniaturized energy-autonomous systems. However, increasing the energy storage density (ESD) of capacitors has been a great challenge. In this work, we propose the fabrication of ferroelectric (FE) Hf0.5Zr0.5O2/AFE Hf0.25Zr0.75O2 bilayer nanofilms by plasma-enhanced atomic layer deposition for high ESD capacitors with TiN electrodes. The effects of the FE/AFE thickness composition and annealing conditions are investigated, revealing that the Hf0.5Zr0.5O2 (1 nm)/Hf0.25Zr0.75O2 (9 nm) bilayer can generate the optimal ESD after optimized annealing at 450 °C for 30 min. This is mainly ascribed to the factor that the introduction of a 1 nm Hf0.5Zr0.5O2 layer enhances the formation of the tetragonal (T) phase with antiferroelectricity in the AFE Hf0.25Zr0.75O2 layer as well as the breakdown electric field of the bilayer while fixing the FE/AFE bilayer thickness at 10 nm. As a result, a ESD as high as 71.95 J cm-3 can be obtained together with an energy storage efficiency (ESE) of 57.8%. Meanwhile, with increasing the measurement temperature from 300 and 425 K, the capacitor also demonstrates excellent stabilities of ESD and ESE. In addition, superior electrical cycling endurance is also demonstrated. Further, by integrating the capacitor into deep silicon trenches, a superhigh ESD of 364.1 J cm-3 is achieved together with an ESE of 56.5%. This work provides an effective way for developing CMOS process-compatible, eco-friendly and superhigh ESD three-dimensional capacitors for on-chip energy storage applications.

4.
Comput Methods Programs Biomed ; 219: 106766, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35395592

RESUMEN

BACKGROUND AND OBJECTIVE: In traditional Chinese medicine and Ayurvedic medicine, wrist pulse wave fluctuations are an important indicator for distinguishing different health states. Owing to the development of modern sensing technology, computational methods have been used in the analysis of pulse wave signals. The description and quantification of the peaks in the pulse wave is significant for the identification of health status. METHODS: In this study, we decomposed the pressure pulse waveform of the radial artery into several components by sparse decomposition with an improved Gabor function. To better represent the position, shape, and relationship of the peaks, we designed an improved Gabor function structure based on the characteristics of the pulse waveform to generate a time-frequency dictionary. Compared with conventional representation methods, the shape of the Gabor function is more variable. In addition, owing to the limitation of windowing, the Gabor function can reduce the influence on other positions when it represents a specific position. Feature vectors consisting of decomposed components can be used for computerized pulse signal analysis and disease diagnosis. RESULTS: In the binary classification of healthy and diseased pulse signals, the proposed method achieved the best results for health/diabetes, health/cardiac disease, health/hypertension, and health/nephropathy with accuracies of 93.54%, 73.42%, 88.42%, and 82.28%, respectively. The multi-classification performance of the different types of features was evaluated by six classifiers, and the proposed method obtained the highest classification performance with support vector machine-radial basis function for both balanced and imbalanced data. CONCLUSIONS: The results indicated that the proposed method enabled to obtain a smaller representation error and exhibited superior performance in distinguishing between the signals collected from patients and healthy individuals. Moreover, for the multi-classification of the pulse signals, the proposed method performed better than the state-of-the-art methods.


Asunto(s)
Arteria Radial , Muñeca , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Medicina Tradicional China/métodos
5.
Phytomedicine ; 87: 153591, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34029937

RESUMEN

BACKGROUND: The outbreak of coronavirus (SARS-CoV-2) disease caused more than 100,000,000 people get infected and over 2,200,000 people being killed worldwide. However, the current developed vaccines or drugs may be not effective in preventing the pandemic of COVID-19 due to the mutations of coronavirus and the severe side effects of the newly developed vaccines. Chinese herbal medicines and their active components play important antiviral activities. Corilagin exhibited antiviral effect on human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Epstein-Barr virus (EBV). However, whether it blocks the interaction between SARS-CoV-2 RBD and hACE2 has not been elucidated. PURPOSE: To characterize an active compound, corilagin derived from Phyllanthus urinaria as potential SARS-CoV-2 entry inhibitors for its possible preventive application in daily anti-virus hygienic products. METHODS: Computational docking coupled with bio-layer interferometry, BLI were adopted to screen more than 1800 natural compounds for the identification of SARS-CoV-2 spike-RBD inhibitors. Corilagin was confirmed to have a strong binding affinity with SARS-CoV-2-RBD or human ACE2 (hACE2) protein by the BLI, ELISA and immunocytochemistry (ICC) assay. Furthermore, the inhibitory effect of viral infection of corilagin was assessed by in vitro pseudovirus system. Finally, the toxicity of corilagin was examined by using MTT assay and maximal tolerated dose (MTD) studies in C57BL/6 mice. RESULTS: Corilagin preferentially binds to a pocket that contains residues Cys 336 to Phe 374 of spike-RBD with a relatively low binding energy of -9.4 kcal/mol. BLI assay further confirmed that corilagin exhibits a relatively strong binding affinity to SARS-CoV-2-RBD and hACE2 protein. In addition, corilagin dose-dependently blocks SARS-CoV-2-RBD binding and abolishes the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of SARS-CoV-2 virus in human host cells. Finally, in vivo studies revealed that up to 300 mg/kg/day of corilagin was safe in C57BL/6 mice. Our findings suggest that corilagin could be a safe and potential antiviral agent against the COVID-19 acting through the blockade of the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. CONCLUSION: Corilagin could be considered as a safe and environmental friendly anti-SARS-CoV-2 agent for its potential preventive application in daily anti-virus hygienic products.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales/farmacología , Glucósidos/farmacología , Interacciones Huésped-Patógeno/efectos de los fármacos , Taninos Hidrolizables/farmacología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Enzima Convertidora de Angiotensina 2/química , Animales , Antivirales/química , Antivirales/toxicidad , COVID-19 , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Glucósidos/química , Glucósidos/toxicidad , Células HEK293 , Humanos , Taninos Hidrolizables/química , Taninos Hidrolizables/toxicidad , Infecciones por Lentivirus/tratamiento farmacológico , Masculino , Dosis Máxima Tolerada , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Glicoproteína de la Espiga del Coronavirus/química
7.
Comput Methods Programs Biomed ; 174: 25-31, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29709314

RESUMEN

BACKGROUND AND OBJECTIVES: Radial artery pulse diagnosis has been playing an important role in traditional Chinese medicine (TCM). For its non-invasion and convenience, the pulse diagnosis has great significance in diseases analysis of modern medicine. The practitioners sense the pulse waveforms in patients' wrist to make diagnoses based on their non-objective personal experience. With the researches of pulse acquisition platforms and computerized analysis methods, the objective study on pulse diagnosis can help the TCM to keep up with the development of modern medicine. METHODS: In this paper, we propose a new method to extract feature from pulse waveform based on discrete Fourier series (DFS). It regards the waveform as one kind of signal that consists of a series of sub-components represented by sine and cosine (SC) signals with different frequencies and amplitudes. After the pulse signals are collected and preprocessed, we fit the average waveform for each sample using discrete Fourier series by least squares. The feature vector is comprised by the coefficients of discrete Fourier series function. RESULTS: Compared with the fitting method using Gaussian mixture function, the fitting errors of proposed method are smaller, which indicate that our method can represent the original signal better. The classification performance of proposed feature is superior to the other features extracted from waveform, liking auto-regression model and Gaussian mixture model. CONCLUSIONS: The coefficients of optimized DFS function, who is used to fit the arterial pressure waveforms, can obtain better performance in modeling the waveforms and holds more potential information for distinguishing different psychological states.


Asunto(s)
Medicina Tradicional China/métodos , Análisis de la Onda del Pulso , Arteria Radial/fisiología , Adolescente , Adulto , Anciano , Algoritmos , Niño , Preescolar , Femenino , Análisis de Fourier , Frecuencia Cardíaca , Humanos , Lactante , Recién Nacido , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Distribución Normal , Procesamiento de Señales Asistido por Computador , Signos Vitales , Muñeca , Adulto Joven
8.
Nanotechnology ; 29(24): 244004, 2018 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-29583135

RESUMEN

In the past fifty years, complementary metal-oxide-semiconductor integrated circuits have undergone significant development, but Moore's law will soon come to an end. In order to break through the physical limit of Moore's law, 2D materials have been widely used in many electronic devices because of their high mobility and excellent mechanical flexibility. And the emergence of a negative capacitance field-effect transistor (NCFET) could not only break the thermal limit of conventional devices, but reduce the operating voltage and power consumption. This paper demonstrates a 2D NCFET that treats molybdenum disulfide as a channel material and organic P(VDF-TrFE) as a gate dielectric directly. This represents a new attempt to prepare NCFETs and produce flexible electronic devices. It exhibits a 10^6 on-/off-current ratio. And the minimum subthreshold swing (SS) of the 21 mV/decade and average SS of the 44 mV/decade in four orders of magnitude of drain current can also be observed at room temperature of 300 K.

9.
Genome Med ; 9(1): 89, 2017 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-29082853

RESUMEN

BACKGROUND: Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. METHODS: We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs) using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. RESULTS: Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN) guideline genes. Most notably, we discovered JAK2 p.V617F somatic mutation, a hallmark of myeloproliferative neoplasms, in 1% (9/932) of the NSCLCs. Analysis of cancer cell line pharmacogenomic data showed that a high level of JAK2 expression in a panel of NSCLC cell lines is correlated with increased sensitivity to a selective JAK2 inhibitor. Further analysis of TCGA genomic data revealed JAK2 gain or loss due to genetic alterations in NSCLC clinical samples are associated with significantly elevated or reduced PD-L1 expression, suggesting that the activating JAK2 p.V617F mutation could confer sensitivity to both JAK inhibitors and anti-PD1 immunotherapy. We also detected JAK3 germline activating mutations in 6.7% (62/932) of the patients who may benefit from anti-PD1 treatment, in light of recent findings that JAK3 mutations upregulate PD-L1 expression. CONCLUSION: Taken together, this study demonstrated the clinical utility of targeted NGS with a focused hotspot cancer gene panel in NSCLCs and identified activating mutations in JAK2 and JAK3 with clinical implications inferred through integrative analysis of cancer genetic, genomic, and pharmacogenomic data. The potential of JAK2 and JAK3 mutations as response markers for the targeted therapy against JAK kinases or anti-PD1 immunotherapy warrants further investigation.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Janus Quinasa 2/genética , Janus Quinasa 3/genética , Neoplasias Pulmonares/genética , Mutación , Transcriptoma , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inhibidores Enzimáticos/uso terapéutico , Mutación de Línea Germinal , Humanos , Inmunoterapia , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 3/antagonistas & inhibidores , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/terapia , Receptor de Muerte Celular Programada 1/inmunología
10.
IEEE J Biomed Health Inform ; 21(4): 978-985, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28113961

RESUMEN

Traditional Chinese pulse diagnosis, known as an empirical science, depends on the subjective experience. Inconsistent diagnostic results may be obtained among different practitioners. A scientific way of studying the pulse should be to analyze the objectified wrist pulse waveforms. In recent years, many pulse acquisition platforms have been developed with the advances in sensor and computer technology. And the pulse diagnosis using pattern recognition theories is also increasingly attracting attentions. Though many literatures on pulse feature extraction have been published, they just handle the pulse signals as simple 1-D time series and ignore the information within the class. This paper presents a generalized method of pulse feature extraction, extending the feature dimension from 1-D time series to 2-D matrix. The conventional wrist pulse features correspond to a particular case of the generalized models. The proposed method is validated through pattern classification on actual pulse records. Both quantitative and qualitative results relative to the 1-D pulse features are given through diabetes diagnosis. The experimental results show that the generalized 2-D matrix feature is effective in extracting both the periodic and nonperiodic information. And it is practical for wrist pulse analysis.


Asunto(s)
Frecuencia Cardíaca/fisiología , Medicina Tradicional China , Pulso Arterial/métodos , Procesamiento de Señales Asistido por Computador , Muñeca/irrigación sanguínea , Algoritmos , Diabetes Mellitus/diagnóstico , Femenino , Humanos , Embarazo
11.
IEEE J Biomed Health Inform ; 20(2): 450-9, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25608317

RESUMEN

Pulse diagnosis, recognized as an important branch of traditional Chinese medicine (TCM), has a long history for health diagnosis. Certain features in the pulse are known to be related with the physiological status, which have been identified as biomarkers. In recent years, an electronic equipment is designed to obtain the valuable information inside pulse. Single-point pulse acquisition platform has the benefit of low cost and flexibility, but is time consuming in operation and not standardized in pulse location. The pulse system with a single-type sensor is easy to implement, but is limited in extracting sufficient pulse information. This paper proposes a novel system with optimal design that is special for pulse diagnosis. We combine a pressure sensor with a photoelectric sensor array to make a multichannel sensor fusion structure. Then, the optimal pulse signal processing methods and sensor fusion strategy are introduced for the feature extraction. Finally, the developed optimal pulse system and methods are tested on pulse database acquired from the healthy subjects and the patients known to be afflicted with diabetes. The experimental results indicate that the classification accuracy is increased significantly under the optimal design and also demonstrate that the developed pulse system with multichannel sensors fusion is more effective than the previous pulse acquisition platforms.


Asunto(s)
Frecuencia Cardíaca/fisiología , Pulso Arterial/instrumentación , Procesamiento de Señales Asistido por Computador/instrumentación , Diagnóstico Tradicional por el Pulso/instrumentación , Adulto , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Femenino , Humanos , Masculino , Medicina Tradicional China , Persona de Mediana Edad
12.
IEEE J Biomed Health Inform ; 20(1): 119-27, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25532142

RESUMEN

Increasing interest has been focused on computational pulse diagnosis where sensors are developed to acquire pulse signals, and machine learning techniques are exploited to analyze health conditions based on the acquired pulse signals. By far, a number of sensors have been employed for pulse signal acquisition, which can be grouped into three major categories, i.e., pressure, photoelectric, and ultrasonic sensors. To guide the sensor selection for computational pulse diagnosis, in this paper, we analyze the physical meanings and sensitivities of signals acquired by these three types of sensors. The dependence and complementarity of the different sensors are discussed from both the perspective of cardiovascular fluid dynamics and comparative experiments by evaluating disease classification performance. Experimental results indicate that each sensor is more appropriate for the diagnosis of some specific disease that the changes of physiological factors can be effectively reflected by the sensor, e.g., ultrasonic sensor for diabetes and pressure sensor for arteriosclerosis, and improved diagnosis performance can be obtained by combining three types of signals.


Asunto(s)
Frecuencia Cardíaca/fisiología , Pulso Arterial/métodos , Procesamiento de Señales Asistido por Computador , Muñeca/irrigación sanguínea , Adolescente , Adulto , Aterosclerosis , Niño , Preescolar , Diabetes Mellitus , Femenino , Humanos , Lactante , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Muñeca/fisiología , Adulto Joven
13.
Expert Opin Biol Ther ; 14(2): 157-64, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24295560

RESUMEN

INTRODUCTION: Rheumatoid arthritis (RA) demonstrates a high heterogeneity in clinical responses to treatment. Although the efficacy of biological therapy has undoubtedly been established, the response differs considerably between individuals. This variability between individuals has aroused the research for biomarkers predictive of treatment response. Pharmacogenomics underlying individual responses to drugs is rapidly developed and has the potential of realizing the personalized therapy in RA. This review will summarize the pharmacogenomics of biological therapies approved for clinical RA treatment. AREAS COVERED: The pharmacogenomics underlies individual responses to biological drugs in RA. Current studies on pharmacogenomics of biological therapy in RA are presented. EXPERT OPINION: The personalized treatment in RA according to pharmacogenomics is promising, but the available pharmacogenomic data on biological treatment in RA are not adequate and consistent and still require further larger sample studies to corroborate.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Productos Biológicos/uso terapéutico , Farmacogenética/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/química , Terapia Biológica/métodos , Etanercept , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Medicina de Precisión/métodos , Receptores de Interleucina-6/antagonistas & inhibidores , Receptores del Factor de Necrosis Tumoral/química , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Reproducibilidad de los Resultados , Rituximab
14.
Artículo en Inglés | MEDLINE | ID: mdl-23737824

RESUMEN

An in-depth systematic tongue color analysis system for medical applications is proposed. Using the tongue color gamut, tongue foreground pixels are first extracted and assigned to one of 12 colors representing this gamut. The ratio of each color for the entire image is calculated and forms a tongue color feature vector. Experimenting on a large dataset consisting of 143 Healthy and 902 Disease (13 groups of more than 10 samples and one miscellaneous group), a given tongue sample can be classified into one of these two classes with an average accuracy of 91.99%. Further testing showed that Disease samples can be split into three clusters, and within each cluster most if not all the illnesses are distinguished from one another. In total 11 illnesses have a classification rate greater than 70%. This demonstrates a relationship between the state of the human body and its tongue color.

15.
Clin Cancer Res ; 17(13): 4414-24, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21606178

RESUMEN

PURPOSE: The development of new effective therapeutic agents with minimal side effects for prostate cancer (PC) treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine-Qing Dai (Indigo naturalis), has been used to treat leukemia for decades. However, the anticancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in PC. EXPERIMENTAL DESIGN: The growth kinetics and invasion ability of on human PC cell lines with or without Natura-alpha treatment were measured by cell proliferation and invasion assays. The antitumor effects of Natura-alpha were examined in nude mice tumor xenograft models, and in a patient with advanced hormone-refractory metastatic PC. Signal network proteins targeted by Natura-alpha were analyzed by using proteomic pathway array analysis (PPAA) on xenografts. RESULTS: Natura-alpha inhibited the growth of both androgen-dependent (LNCaP) and androgen-independent (LNCaP-AI, PC-3, and DU145) PC cells with IC(50) between 4 to 10 mmol/L, and also inhibited invasion of androgen-independent PC cells. Its antitumor effects were further evident in in vivo tumor reduction in androgen-dependent and androgen-independent nude mice tumor xenograft models and reduced tumor volume in the patient with hormone refractory metastatic PC. PPAA revealed that antiproliferative and antiinvasive activities of Natura-alpha on PC might primarily be through its downregulation of Forkhead box M1 (FOXM1) protein. Forced overexpression of FOXM1 largely reversed the inhibition of growth and invasion by Natura-alpha. CONCLUSION: Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone-sensitive and hormone-refractory PC with minimal side effects.


Asunto(s)
Andrógenos/metabolismo , Factores de Transcripción Forkhead/antagonistas & inhibidores , Indoles/farmacología , Neoplasias de la Próstata/patología , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resultado Fatal , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Indoles/uso terapéutico , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Transducción de Señal/efectos de los fármacos , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Nutr Cancer ; 63(3): 466-75, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21391127

RESUMEN

Green tea and its major active component, epigallocatechin-3-gallate (EGCG), have been reported to have anticancer activity on various cancers. However, the exact molecular mechanism of its anticancer activity is still not well understood. We investigated the anticancer activity of green tea extract (GTE) and EGCG on 3 human squamous carcinoma cell lines (CAL-27, SCC-25, and KB) in vitro. We also examined the effects of GTE and EGCG on cell signaling networks using our newly developed Pathway Array technology, which is an innovative proteomic assay to globally screen changes in protein expression and phosphorylation. Our results demonstrated that GTE and EGCG inhibited all 3 squamous carcinoma cells' growth via S and G(2)/M phase arrest, but different sensitivities to GTE and EGCG in different cell lines were observed: CAL-27 cells were more sensitive to the both agents than SCC-25 and KB cells, and GTE at an EGCG equivalent concentration displayed a stronger inhibition than EGCG alone. The Pathway Array assessment of 107 proteins indicated that different signaling pathways were activated in different cell lines, suggesting heterogeneity at the signaling network level. After treatment with GTE or EGCG, a total of 21 proteins and phosphorylations altered significantly in all 3 cell lines based on analysis of variance (ANOVA) (P < 0.05). The major signaling pathways affected by GTE and EGCG were EGFR and Notch pathways, which, in turn, affected cell cycle-related networks. These results suggested that GTE and EGCG target multiple pathways or global networks in cancer cells, which resulted in collective inhibition of cancer cell growth. The finding pointed out the future direction to study the underlying mechanism of the chemotherapeutic and chemopreventive activities of EGCG and GTE.


Asunto(s)
Anticarcinógenos/farmacología , Carcinoma de Células Escamosas/metabolismo , Catequina/análogos & derivados , Extractos Vegetales/farmacología , Transducción de Señal , Té/química , Antioxidantes , Catequina/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Fosforilación
17.
Front Biosci (Elite Ed) ; 3(1): 326-40, 2011 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-21196313

RESUMEN

The effects of Coptis chinensis on the behavior of squamous cell carcinoma have not yet been established. We examined the anticancer activity of Coptis chinensis on human squamous carcinoma cells, both in vitro and in xenografted nude mice, and applied Pathway Array Technology to understand possible involvement of signaling pathways in Coptis Chinensis induced tumor cells inhibition as well. Following Coptis chinensis treatment, a time-dependent reduction in proliferation was observed in both cell lines and NCR/NU mice. Coptis chinensis has a wide effect on cell signaling, including cell cycle regulation (Cdk6, Cdk4, cyclin B1, cyclin E, cyclin D1, p27), cell adhesion (E-cadherin, osteopontin), differentiation, apoptosis(p-Stat3, p53, BRCA1), cytoskeleton (p-PKC α/ß II, Vimentin, p-PKCα), MAPK signaling (raf-1, ERK1/2, p-p38, p-ERK), and the phosphatidylinositol 3-kinase signaling pathway (p-Akt, Akt, p-PTEN). In our conclusions, Coptis chinensis may be a novel therapeutic drug for squamous cell carcinoma.


Asunto(s)
Antineoplásicos/farmacología , Berberina/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Coptis/química , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Adhesión Celular/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Biología Computacional , Proteínas del Citoesqueleto/metabolismo , Humanos , Ratones , Ratones Desnudos , Extractos Vegetales/aislamiento & purificación , Transducción de Señal/fisiología , Sales de Tetrazolio , Tiazoles
18.
Nutr Cancer ; 62(5): 692-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20574930

RESUMEN

The protective effect of natural products such as fruits and vegetables against cancer has attracted great attention because of their fewer side effects and therefore, potentially greater safety. We have previously reported that cactus pear mixture aqueous extract (CME) reduces gynecologic cancer cells growth by inducting apoptosis. This study aimed to elucidate the cellular pathway(s) triggered by CME in cancer cells. Normal, immortalized ovarian and ovarian cancer cells (OVCA420, SKOV3) were treated with 5 and 10% CME. After 2 days of treatment, immortalized cells treated with 10% CME accumulated more ROS than untreated cells, whereas cancer cells cultured with 5% and 10% CME exhibited a dramatic increase of reactive oxygen species (ROS). Greater levels of DNA fragmentation, together with a perturbed expression of apoptotic-related (Bax, Bad, caspase 3, Bcl2, p53, and p21) and ROS-sensitive (NF-kappaB, c-jun/c-fos) genes were observed in the treated cancer cells. After three days of treatment, the NF-kappaB and p-/SAPK/JNK expressions were decreased, whereas p-AKT was upregulated. The CME significantly induced apoptosis in cancer cells. The results suggest an inhibitory effect of Arizona CME on cancer cell growth through the accumulation of intracellular ROS, which may activate a cascade of reactions leading to the apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Cactaceae , Neoplasias Ováricas/tratamiento farmacológico , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Femenino , Frutas , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , FN-kappa B/antagonistas & inhibidores , Proteínas de Neoplasias/análisis , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología
19.
Nutr Cancer ; 61(4): 530-7, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19838925

RESUMEN

Scutellaria baicalensis is an anti-inflammatory and antineoplastic Chinese herbal therapy. We have previously shown that S. baicalensis can inhibit hepatocellular carcinoma (HCC) cell growth in vitro. In this study, we sought to determine the effect of S. baicalensis on the cell signaling network using our newly developed Pathway Array technology, which screens cell signaling pathways involved in cell cycle regulation. The HCC cell line (HepG2) was treated with S. baicalensis extract in vitro. The effect on the cell cycle was analyzed by flow cytometry, and the expression of various signaling proteins was assayed with Pathway Array. Our results indicate that S. baicalensis exerts a strong growth inhibition of the HepG2 cells via G(2)/M phase arrest. The Pathway Array analysis of 56 proteins revealed a total of 14 differentially expressed proteins or phosphorylations after treatment. Of these, 9 showed a dose-dependent decrease (p53, ETS1, Cdc25B, p63, EGFR, ERK1/2, XIAP, HIF-2alpha, and Cdc25C) whereas one demonstrated a dose-dependent increase (Cyclin E) after treatment with 200 microg/ml of S. baicalensis. Using computer simulation software, we identified additional hubs in the signaling network activated by S. baicalensis. These results indicate that S. baicalensis exerts a broad effect on cell signaling networks leading to a collective inhibition of cell proliferation.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/metabolismo , Medicamentos Herbarios Chinos/farmacología , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Simulación por Computador , Fase G2/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Crecimiento/farmacología , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Modelos Biológicos , Fosforilación/efectos de los fármacos , Fitoterapia , Raíces de Plantas , Polvos , Análisis por Matrices de Proteínas/métodos , Scutellaria baicalensis
20.
Comput Med Imaging Graph ; 31(8): 672-8, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17920813

RESUMEN

Human tongue is one of the important organs of the body, which carries abound of information of the health status. The images of the human tongue that are used in computerized tongue diagnosis of traditional Chinese medicine (TCM) are all RGB color images captured with color CCD cameras currently. However, this conversional method impedes the accurate analysis on the subjects of tongue surface because of the influence of illumination and tongue pose. To address this problem, this paper presents a novel approach to analyze the tongue surface information based on hyperspectral medical tongue images with support vector machines. The experimental results based on chronic Cholecystitis patients and healthy volunteers illustrate its effectiveness.


Asunto(s)
Lengua/anatomía & histología , Humanos , Medicina Tradicional China , Enfermedades de la Lengua/diagnóstico
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