Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sensors (Basel) ; 24(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38931487

RESUMO

Loop-closure detection plays a pivotal role in simultaneous localization and mapping (SLAM). It serves to minimize cumulative errors and ensure the overall consistency of the generated map. This paper introduces a multi-sensor fusion-based loop-closure detection scheme (TS-LCD) to address the challenges of low robustness and inaccurate loop-closure detection encountered in single-sensor systems under varying lighting conditions and structurally similar environments. Our method comprises two innovative components: a timestamp synchronization method based on data processing and interpolation, and a two-order loop-closure detection scheme based on the fusion validation of visual and laser loops. Experimental results on the publicly available KITTI dataset reveal that the proposed method outperforms baseline algorithms, achieving a significant average reduction of 2.76% in the trajectory error (TE) and a notable decrease of 1.381 m per 100 m in the relative error (RE). Furthermore, it boosts loop-closure detection efficiency by an average of 15.5%, thereby effectively enhancing the positioning accuracy of odometry.

2.
J Opt Soc Am A Opt Image Sci Vis ; 41(4): 739-748, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568675

RESUMO

With the development of autonomous driving, there has been considerable attention on 3D object detection using LiDAR. Pillar-based LiDAR point cloud detection algorithms are extensively employed in the industry due to their simple structure and high real-time performance. Nevertheless, the pillar-based detection network suffers from significant loss of 3D coordinate information during the feature degradation and extraction process. In the paper, we introduce a novel framework with high performance, termed EFNet. The EFNet uses the Enhancing Pillar Feature Module (EPFM) to provide more accurate representations of features from two directions: pillar internal space and pillar external space. Additionally, the Head Up Module (HUM) is utilized in the detection head to integrate multi-scale information and enhance the network's information perception ability. The EFNet achieves impressive results on the nuScenes datasets, namely, 53.3% NDS and 42.4% mAP. Compared to the baseline PointPillars, EFNet improves 8% NDS and 11.9% mAP. The results demonstrate that the proposed framework can effectively improve the network's accuracy while ensuring deployability.

3.
Sensors (Basel) ; 23(14)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37514700

RESUMO

This paper introduces a novel method for computationally efficient Gaussian estimation of high-dimensional problems such as Simultaneous Localization and Mapping (SLAM) processes and for treating certain Stochastic Partial Differential Equations (SPDEs). The authors have presented the Generalized Compressed Kalman Filter (GCKF) framework to reduce the computational complexity of the filters by partitioning the state vector into local and global and compressing the global state updates. The compressed state update, however, still suffers from high computational costs, making it challenging to implement on embedded processors. We propose a low-precision numerical representation for the global filter, such as 16-bit integer or 32-bit single-precision formats for the global covariance matrix, instead of the expensive double-precision, floating-point representation (64 bits). This truncation can inevitably cause filter instability since the truncated covariance matrix becomes overoptimistic or even turns to be an invalid covariance matrix. We introduce a Minimal Covariance Inflation (MCI) method to make the filter consistent while minimizing the truncation errors. Simulation-based experiments results show significant improvement of the proposed method with a reduction in the processing time with minimal loss of accuracy.

4.
Sensors (Basel) ; 22(18)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36146179

RESUMO

This paper proposes a novel method for occupancy map building using a mixture of Gaussian processes. Gaussian processes have proven to be highly flexible and accurate for a robotic occupancy mapping problem, yet the high computational complexity has been a critical barrier for large-scale applications. We consider clustering the data into small, manageable subsets and applying a mixture of Gaussian processes. One of the problems in clustering is that the number of groups is not known a priori, thus requiring inputs from experts. We propose two efficient clustering methods utilizing (1) a Dirichlet process and (2) geometrical information in the context of occupancy mapping. We will show that the Dirichlet process-based clustering can significantly speed up the training step of the Gaussian process and if geometrical features, such as line features, are available, they can further improve the clustering accuracy. We will provide simulation results, analyze the performance and demonstrate the benefits of the proposed methods.

5.
Front Aging Neurosci ; 14: 898940, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992586

RESUMO

Purpose: Amnestic mild cognitive impairment (aMCI) is a transitional state between normal aging and Alzheimer's disease (AD). However, not all aMCI patients are observed to convert to AD dementia. Therefore, developing a predictive algorithm for the conversion of aMCI to AD dementia is important. Parametric methods, such as logistic regression, have been developed; however, it is difficult to reflect complex patterns, such as non-linear relationships and interactions between variables. Therefore, this study aimed to improve the predictive power of aMCI patients' conversion to dementia by using an interpretable machine learning (IML) algorithm and to identify the factors that increase the risk of individual conversion to dementia in each patient. Methods: We prospectively recruited 705 patients with aMCI who had been followed-up for at least 3 years after undergoing baseline neuropsychological tests at the Samsung Medical Center between 2007 and 2019. We used neuropsychological tests and apolipoprotein E (APOE) genotype data to develop a predictive algorithm. The model-building and validation datasets were composed of data of 565 and 140 patients, respectively. For global interpretation, four algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) were compared. For local interpretation, individual conditional expectations (ICE) and SHapley Additive exPlanations (SHAP) were used to analyze individual patients. Results: Among the four algorithms, the extreme gradient boost model showed the best performance, with an area under the receiver operating characteristic curve of 0.852 and an accuracy of 0.807. Variables, such as age, education, the scores of visuospatial and memory domains, the sum of boxes of the Clinical Dementia Rating scale, Mini-Mental State Examination, and APOE genotype were important features for creating the algorithm. Through ICE and SHAP analyses, it was also possible to interpret which variables acted as strong factors for each patient. Conclusion: We were able to propose a predictive algorithm for each aMCI individual's conversion to dementia using the IML technique. This algorithm is expected to be useful in clinical practice and the research field, as it can suggest conversion with high accuracy and identify the degree of influence of risk factors for each patient.

6.
Sensors (Basel) ; 21(22)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34833677

RESUMO

This paper presents a novel dense optical-flow algorithm to solve the monocular simultaneous localisation and mapping (SLAM) problem for ground or aerial robots. Dense optical flow can effectively provide the ego-motion of the vehicle while enabling collision avoidance with the potential obstacles. Existing research has not fully utilised the uncertainty of the optical flow-at most, an isotropic Gaussian density model has been used. We estimate the full uncertainty of the optical flow and propose a new eight-point algorithm based on the statistical Mahalanobis distance. Combined with the pose-graph optimisation, the proposed method demonstrates enhanced robustness and accuracy for the public autonomous car dataset (KITTI) and aerial monocular dataset.


Assuntos
Fluxo Óptico , Algoritmos , Movimento (Física) , Incerteza
7.
Sensors (Basel) ; 21(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502806

RESUMO

This paper presents a practical yet effective solution for integrating an RGB-D camera and an inertial sensor to handle the depth dropouts that frequently happen in outdoor environments, due to the short detection range and sunlight interference. In depth drop conditions, only the partial 5-degrees-of-freedom pose information (attitude and position with an unknown scale) is available from the RGB-D sensor. To enable continuous fusion with the inertial solutions, the scale ambiguous position is cast into a directional constraint of the vehicle motion, which is, in essence, an epipolar constraint in multi-view geometry. Unlike other visual navigation approaches, this can effectively reduce the drift in the inertial solutions without delay or under small parallax motion. If a depth image is available, a window-based feature map is maintained to compute the RGB-D odometry, which is then fused with inertial outputs in an extended Kalman filter framework. Flight results from the indoor and outdoor environments, as well as public datasets, demonstrate the improved navigation performance of the proposed approach.


Assuntos
Algoritmos , Movimento (Física)
8.
Adv Exp Med Biol ; 1240: 25-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060885

RESUMO

Interleukin (IL)-8 is a chemokine that is essential for inflammation and angiogenesis. IL-8 expression is elevated in tumor cell lines and tissues, as well as in peripheral blood obtained from cancer patients. Primary works have attempted to determine the biological effect of IL-8 on tumor cells, including cell proliferation, survival, and migration. More recently, IL-8 has acquired considerable attention as an immune modulator in the context of certain tumor microenvironments (TME); specifically, it can support a niche that favors tumor progression and metastasis. Tumor-derived IL-8 stimulates inflammation by interacting with the microenvironmental constituents, including fibroblasts, endothelial cells, and immune cells. However, the tumor immune system is complex, and mechanisms that construct the immune phenotype remain incompletely characterized. Herein, we will (1) address a potential role of IL-8 in regulating gene expression to establish immune landscape in tumor. Then, we will (2) review IL-8 signaling in the maintenance of stem cells and regulation of hematopoietic progenitors. Finally, (3) IL-8 functions will be discussed in naturally occurring animal cancers that offer a clinically realistic model for translational research. This chapter will provide a new insight into the tumor immune niche and help us develop immunotherapies for cancers.


Assuntos
Interleucina-8/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral/imunologia , Animais , Humanos , Imunoterapia , Interleucina-8/metabolismo , Neoplasias/genética , Neoplasias/terapia
9.
Mol Cancer Res ; 17(12): 2410-2421, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31570656

RESUMO

Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with few effective treatment options and high patient mortality. It is both rare and heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from a similar cancer, called hemangiosarcoma, with breeds like the golden retriever carrying heritable genetic factors that put them at high risk. If the clinical similarity of canine hemangiosarcoma and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine hemangiosarcoma via whole-exome sequencing (47 golden retriever hemangiosarcomas) and RNA sequencing (74 hemangiosarcomas from multiple breeds). Somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). The predominant mutational signature was the age-associated deamination of cytosine to thymine. As reported in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. We compared the canine data to human data recently released by The Angiosarcoma Project, and found many of the same genes and pathways significantly enriched for somatic mutations, particularly in breast and visceral angiosarcomas. Canine hemangiosarcoma closely models the genomic landscape of human angiosarcoma of the breast and viscera, and is a powerful tool for investigating the pathogenesis of this devastating disease. IMPLICATIONS: We characterize the genomic landscape of canine hemangiosarcoma and demonstrate its similarity to human angiosarcoma.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Hemangiossarcoma/genética , Proteína Supressora de Tumor p53/genética , Animais , Vasos Sanguíneos/patologia , Mama/metabolismo , Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Cães , Feminino , Genoma/genética , Genômica , Hemangiossarcoma/patologia , Humanos , Mutação/genética , Vísceras/metabolismo , Vísceras/patologia , Sequenciamento do Exoma
10.
Cereb Cortex ; 29(6): 2499-2508, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29850790

RESUMO

d-Aspartate (d-Asp), the stereoisomer of l-aspartate, has a role in memory function in rodents. However, the mechanism of the effect of d-Asp has not been fully understood. In this study, we hypothesized that ingested d-Asp directly reaches the hippocampal tissues via the blood circulation and modifies the functional connectivity between hippocampus and other regions through spinogenesis in hippocampal CA1 neurons. The spinogenesis induced by the application of d-Asp was investigated using rat acute hippocampal slices. The density of CA1 spines was increased following 21 and 100 µM d-Asp application. The nongenomic spine increase pathway involved LIM kinase. In parallel to the acute slice study, brain activation was investigated in awake rats using functional MRI following the intragastric administration of 5 mM d-Asp. Furthermore, the concentration of d-Asp in the blood serum and hippocampus was significantly increased 15 min after intragastric administration of d-Asp. A functional connectivity by awake rat fMRI demonstrated increased slow-frequency synchronization in the hippocampus and other regions, including the somatosensory cortex, striatum, and the nucleus accumbens, 10-20 min after the start of d-Asp administration. These results suggest that ingested d-Asp reaches the brain through the blood circulation and modulates hippocampal neural networks through the modulation of spines.


Assuntos
Ácido D-Aspártico/farmacologia , Espinhas Dendríticas/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Animais , Espinhas Dendríticas/fisiologia , Hipocampo/fisiologia , Masculino , Vias Neurais/fisiologia , Ratos , Ratos Wistar
11.
Genes Chromosomes Cancer ; 58(1): 12-22, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239046

RESUMO

We aimed to determine somatic mutational profiles of stage II/III gastric cancers (GCs) according to their tumor microenvironment immune types (TMITs), which classify cancer based on co-assessment of PD-L1 expression and CD8+ tumor infiltrating lymphocytes. Eighty patients with stage II/III GC were classified as follows: TMIT I (PD-L1+ /CD8High ), TMIT II (PD-L1- /CD8Low ), TMIT III (PD-L1+ /CD8Low ), and TMIT IV (PD-L1- /CD8High ). Deep targeted sequencing using a panel of 170 cancer-related genes was performed on an Illumina HiSeq-2500 system. Most frequently mutated genes included GNAQ (41.3%), TP53 (38.8%), CREBBP (35.0%), and MAP3K1 (35.0%). PIK3CA mutations were observed more frequently in TMIT I (45.8%) and III (66.7%), than in II (12.0%) and IV (8.0%). Other genes with enriched mutations within TMIT I included ATM (33.3%), BRCA2 (33.3%), MAP3K4 (29.2%), and FLT4 (25.0%). FGFR3, MAP3K1, and RUNX1 mutations were more frequently found in TMIT II. TMIT III had a unique somatic mutation profile harboring enriched mutations of histone modifiers including CREBBP and KMT2A, and we found FGFR2 amplification exclusively within TMIT IV. Fuzzy clustering analysis based on somatic mutation frequencies identified a hypermutated group (cluster 1) and a hypomutated group (cluster 2). Cluster 1 had significant associations with TMIT I, EBV+ GCs, and MSI-H GCs (P = .023, .014, and .004), and had better overall survival (P = .057) than Cluster 2. TMIT I, EBV+ , and MSI-H GCs were estimated to have greater tumor mutational burden (P = .023, .003, and .015). By analyzing somatic mutation profiles according to TMIT classification, we identified TMIT-specific genetic alterations that provide clues for biological linkage between GC genetics and microenvironment.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Microambiente Tumoral/imunologia , Idoso , Antígeno B7-H1/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Neoplasias Gástricas/classificação , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Microambiente Tumoral/genética
12.
Sensors (Basel) ; 18(9)2018 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-30223609

RESUMO

Recent paradigm shifts in manufacturing have resulted from the need for a smart manufacturing environment. In this study, we developed a model to detect anomalous signs in advance and embedded it in an existing programmable logic controller system. For this, we investigated the innovation process for smart manufacturing in the domain of synthetic rubber and its vulcanization process, as well as a real-time sensing technology. The results indicate that only analysis of the pattern of input variables can lead to significant results without the generation of target variables through manual testing of chemical properties. We have also made a practical contribution to the realization of a smart manufacturing environment by building cloud-based infrastructure and models for the pre-detection of defects.

13.
Front Neurosci ; 12: 282, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29765299

RESUMO

Dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from an axon terminal at the synapse. Memories are stored in synapses which consist of spines and presynapses. Rapid modulations of dendritic spines induced by hippocampal sex steroids, including dihydrotestosterone (DHT), testosterone (T), and estradiol (E2), are essential for synaptic plasticity. Molecular mechanisms underlying the rapid non-genomic modulation through synaptic receptors of androgen (AR) and estrogen (ER) as well as its downstream kinase signaling, however, have not been well understood. We investigated the possible involvement of Src tyrosine kinase in rapid changes of dendritic spines in response to androgen and estrogen, including DHT, T, and E2, using hippocampal slices from adult male rats. We found that the treatments with DHT (10 nM), T (10 nM), and E2 (1 nM) increased the total density of spines by ~1.22 to 1.26-fold within 2 h using super resolution confocal imaging of Lucifer Yellow-injected CA1 pyramidal neurons. We examined also morphological changes of spines in order to clarify differences between three sex steroids. From spine head diameter analysis, DHT increased middle- and large-head spines, whereas T increased small- and middle-head spines, and E2 increased small-head spines. Upon application of Src tyrosine kinase inhibitor, the spine increases induced through DHT, T, and E2 treatments were completely blocked. These results imply that Src kinase is essentially involved in sex steroid-induced non-genomic modulation of the spine density and morphology. These results also suggest that rapid effects of exogenously applied androgen and estrogen can occur in steroid-depleted conditions, including "acute" hippocampal slices and the hippocampus of gonadectomized animals.

14.
Forensic Sci Int ; 287: 195-206, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29702416

RESUMO

In various types of traffic accidents, including car-to-car crash, vehicle-pedestrian collision, and hit-and-run accident, driver overspeed is one of the critical issues of traffic accident analysis. Hence, analysis of vehicle speed at the moment of accident is necessary. The present article proposes a vehicle speed estimate method (VSEM) applying a virtual plane and a virtual reference line to a forensic video. The reliability of the VSEM was verified by comparing the results obtained by applying the VSEM to videos from a test vehicle driving with a global positioning system (GPS)-based Vbox speed. The VSEM verified by these procedures was applied to real traffic accident examples to evaluate the usability of the VSEM.

15.
Sci Rep ; 8(1): 6017, 2018 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-29662219

RESUMO

We investigate spin orbit torque (SOT) efficiencies and magnetic properties of Pt/GdFeCo/MgO multilayers by varying the thicknesses of GdFeCo and MgO layers. Our studies indicate that the ferrimagnetism in the GdFeCo alloy is considerably influenced by both thicknesses due to the diffusion of Gd atoms toward the MgO layer. Comparing to conventional Pt/ferromagnet/MgO structures, the Pt/GdFeCo/MgO exhibits a lower efficiency of SOTs associated with ferrimagnetic order and a similar magnitude of magnetic damping. The previous models that have been developed for rigid ferromagnets are inappropriate to analyze our experimental data, leading to an unphysical consequence of spin transmission larger than unity. Our results imply that the heavy-metal/ferrimagnet system is quite different from heavy-metal/ferromagnet systems in terms of magnetic dynamical modes, spin angular momentum transfer, and relaxation processes.

16.
Sensors (Basel) ; 18(4)2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29570684

RESUMO

We introduce current home Internet of Things (IoT) technology and present research on its various forms and applications in real life. In addition, we describe IoT marketing strategies as well as specific modeling techniques for improving air quality, a key home IoT service. To this end, we summarize the latest research on sensor-based home IoT, studies on indoor air quality, and technical studies on random data generation. In addition, we develop an air quality improvement model that can be readily applied to the market by acquiring initial analytical data and building infrastructures using spectrum/density analysis and the natural cubic spline method. Accordingly, we generate related data based on user behavioral values. We integrate the logic into the existing home IoT system to enable users to easily access the system through the Web or mobile applications. We expect that the present introduction of a practical marketing application method will contribute to enhancing the expansion of the home IoT market.

17.
Mol Cancer Ther ; 16(5): 956-965, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28193671

RESUMO

Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly, so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature. eBAT is a bispecific angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to EGF and the amino terminal fragment of urokinase. Here, we study the drug in an in vivo "ontarget" companion dog trial as eBAT effectively kills canine hemangiosarcoma and human sarcoma cells in vitro We reasoned the model has value due to the common occurrence of spontaneous sarcomas in dogs and a limited lifespan allowing for rapid accrual and data collection. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I-II study of 23 dogs with spontaneous, stage I-II, splenic hemangiosarcoma. eBAT improved 6-month survival from <40% in a comparison population to approximately 70% in dogs treated at a biologically active dose (50 µg/kg). Six dogs were long-term survivors, living >450 days. eBAT abated expected toxicity associated with EGFR targeting, a finding supported by mouse studies. Urokinase plasminogen activator receptor and EGFR are targets for human sarcomas, so thorough evaluation is crucial for validation of the dog model. Thus, we validated these markers for human sarcoma targeting in the study of 212 human and 97 canine sarcoma samples. Our results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies. Mol Cancer Ther; 16(5); 956-65. ©2017 AACR.


Assuntos
Receptores ErbB/genética , Hemangiossarcoma/tratamento farmacológico , Terapia de Alvo Molecular , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , ADP Ribose Transferases/administração & dosagem , ADP Ribose Transferases/química , ADP Ribose Transferases/genética , Animais , Toxinas Bacterianas/administração & dosagem , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Cães , Doxorrubicina/administração & dosagem , Fator de Crescimento Epidérmico/química , Fator de Crescimento Epidérmico/genética , Receptores ErbB/antagonistas & inibidores , Exotoxinas/administração & dosagem , Exotoxinas/química , Exotoxinas/genética , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Humanos , Camundongos , Estadiamento de Neoplasias , Receptores de Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Ativador de Plasminogênio Tipo Uroquinase/química , Ativador de Plasminogênio Tipo Uroquinase/genética , Fatores de Virulência/administração & dosagem , Fatores de Virulência/química , Fatores de Virulência/genética , Exotoxina A de Pseudomonas aeruginosa
18.
Oncotarget ; 7(36): 57752-57769, 2016 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-27458163

RESUMO

Since epidermal growth factor receptor (EGFR) is commonly deregulated in pre-malignant lung epithelium, targeting EGFR may arrest the development of lung cancer. Here, we showed that honokiol (2.5-7.5 µM), a bioactive compound of Magnolia officinalis, differentially suppressed proliferation (up to 93%) and induced apoptosis (up to 61%) of EGFR overexpressing tumorigenic bronchial cells and these effects were paralleled by downregulation of phospho-EGFR, phospho-Akt, phospho-STAT3 and cell cycle-related proteins as early as 6-12 h post-treatment. Autocrine secretion of EGF sensitized 1170 cells to the effects of honokiol. Molecular docking studies indicated that honokiol binds to the tyrosine kinase domain of EGFR although it was less efficient than erlotinib. However, the anti-proliferative and pro-apoptotic activities of honokiol were stronger than those of erlotinib. Upon combinatory treatment, honokiol sensitized bronchial cells and erlotinib resistant H1650 and H1975 cells to erlotinib. Furthermore, in a mouse lung tumor bioassay, intranasal instillation of liposomal honokiol (5 mg/kg) for 14 weeks reduced the size and multiplicity (49%) of lung tumors and the level of total- and phospho-EGFR, phospho-Akt and phospho-STAT3. Overall, our results indicate that honokiol is a promising candidate to suppress the development and even progression of lung tumors driven by EGFR deregulation.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Compostos de Bifenilo/farmacologia , Receptores ErbB/metabolismo , Lignanas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Animais , Apoptose , Bioensaio , Brônquios/metabolismo , Carcinogênese , Ciclo Celular , Proliferação de Células , Sobrevivência Celular , Progressão da Doença , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Feminino , Neoplasias Pulmonares/patologia , Magnolia/química , Camundongos , Simulação de Acoplamento Molecular , Nitrosaminas/química , Extratos Vegetais/farmacologia , RNA Interferente Pequeno/metabolismo
19.
PLoS One ; 11(3): e0152397, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27031512

RESUMO

Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares many features with human type-1 diabetes, there are differences that have cast doubt on the immunologic origin of the canine disease. In this study, we examined whether peripheral immune responses directed against islet antigens were present in dogs with diabetes. Routine diagnostics were used to confirm diabetic status, and serum samples from dogs with (N = 15) and without (N = 15) diabetes were analyzed for the presence of antibodies against islet antigens (insulin, glutamic acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet beta-cell zinc cation efflux transporter) using standard radioassays. Interferon-γ production from peripheral blood T cells stimulated by porcine insulin and by human insulin was tested using Elispot assays. Anti-insulin antibodies were detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated T cells and incipient insulin-reactive T cells in response to porcine or human insulin were identified in non-diabetic dogs and in dogs with diabetes. The data show that humoral and cellular anti-insulin immune responses are detectable in dogs with diabetes. This in turn provides support for the potential to ethically use dogs with diabetes to study the therapeutic potential of antigen-specific tolerance.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Insulina/imunologia , Animais , Autoanticorpos/sangue , Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/veterinária , Cães , ELISPOT , Insulina/uso terapêutico , Anticorpos Anti-Insulina/sangue , Interferon gama/análise , Ilhotas Pancreáticas/imunologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
20.
PLoS Genet ; 11(2): e1004922, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25642983

RESUMO

Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.


Assuntos
Carcinogênese/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hemangiossarcoma/genética , Linfoma de Células B/genética , Animais , Linfócitos B/patologia , Cruzamento , Carcinogênese/imunologia , Cães , Genótipo , Mutação em Linhagem Germinativa , Haplótipos/genética , Hemangiossarcoma/imunologia , Hemangiossarcoma/patologia , Hemangiossarcoma/veterinária , Humanos , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Células B/veterinária , Polimorfismo de Nucleotídeo Único , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...