Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 149
Filtrar
1.
Talanta ; 236: 122834, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635224

RESUMO

In this study, we have developed a variable pressure operating hollow cathode discharge (HCD) ion source to investigate the gas phase ion-molecule reactions of nitroaromatic explosive compounds. The developed HCD ion source coupled MS system has also been validated as an analytical method to analyze explosives at trace levels. The ion source was designed in such a way that the plasma can be generated alternatively at high pressure (~30 Torr), medium pressure (~5 Torr) and low pressure (~1 Torr) regions. The plasma contains a sufficient amount of reactant ions, electrons and excited species, thus the gaseous analyte molecules were efficiently ionized when they passed through the plasma. In the ion-molecule reactions of the nitroaromatic explosives, the discharge products of NOx- (x = 2,3), O3 and HNO3 originating from the plasma-excited air were suggested to contribute to the formation of mostly [M - H]-, [M - NO]-, [M+NO3-HNO2]- and [M-NO+HNO3]- adduct ions at the higher ion source pressures (~5 and 28 Torr) while the electron rich plasma leads to the formation of molecular ion, M-•, at the lower ion source pressure (~1 Torr). Formation of the hydride-adduct ions of the nitroaromatic compounds reveals the surface-assisted Birch type reduction in the HCD plasma. The variety of spectral patterns in the air-assisted glow discharge would be useful for high through-put detection of TNT and TNT-related explosives. An ambient helium dielectric barrier discharge (DBD) ion source was also used and gave identical mass spectra of the nitroaromatic explosive compounds to those observed by the HCD ion source, but did not give any hydride-adduct ions of the explosive compounds. Ion formation mechanism of these ions is also discussed.


Assuntos
Substâncias Explosivas , Eletrodos , Gases , Íons , Espectrometria de Massas
2.
Sci Rep ; 11(1): 19068, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561543

RESUMO

Ankle-foot orthoses (AFOs) are devices prescribed to improve mobility in people with neuromuscular disorders. Traditionally, AFOs are manually fabricated by an orthotist based on a plaster impression of the lower leg which is modified to correct for impairments. This study aimed to digitally analyse this manual modification process, an important first step in understanding the craftsmanship of AFO fabrication to inform the digital workflows (i.e. 3D scanning and 3D printing), as viable alternatives for AFO fabrication. Pre- and post-modified lower limb plaster casts of 50 children aged 1-18 years from a single orthotist were 3D scanned and registered. The Euclidean distance between the pre- and post-modified plaster casts was calculated, and relationships with participant characteristics (age, height, AFO type, and diagnosis) were analysed. Modification maps demonstrated that participant-specific modifications were combined with universally applied modifications on the cast's anterior and plantar surfaces. Positive differences (additions) ranged 2.12-3.81 mm, negative differences (subtractions) ranged 0.76-3.60 mm, with mean differences ranging from 1.37 to 3.12 mm. Height had a medium effect on plaster additions (rs = 0.35). We quantified the manual plaster modification process and demonstrated a reliable method to map and compare pre- and post-modified casts used to fabricate children's AFOs.

3.
J Hazard Mater ; 416: 125885, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492823

RESUMO

Iron-based materials have been widely used for treating uranium-containing wastewater. However, the iron-uranium solids originating by treating radioactive water through pollutant transfer methods has become a new uncontrolled source of persistent radioactive pollution. The safe disposal of such hazardous waste is not yet well-resolved. The electrochemical mineralization method was developed to rapidly purify uranium-containing wastewater through lattice doping in magnetite and recover uranium without generating any pollutants. An unexpected isolation of U3O8 from uranium-doped magnetite was discovered through in-situ XRD with a temperature variation from 300 °C to 700 °C. Through HRTEM and DFT calculation, it was confirmed that the destruction of the inverse spinel crystal structure during the gradual transformation of magnetite into γ-Fe2O3 and α-Fe2O3 promoted the migration, aggregation, and isolation of uranium atoms. Uniquely generated U3O8 and Fe2O3 were easily separated and over 80% uranium and 99.5% iron could be recovered. These results demonstrate a new strategy for uranium utilization and the environmentally friendly treatment of uranium-containing wastewater.


Assuntos
Urânio , Poluentes Radioativos da Água , Ferro , Estresse Oxidativo , Águas Residuárias , Poluentes Radioativos da Água/análise
4.
Mol Pharm ; 18(9): 3638-3648, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34424706

RESUMO

Targeting metastatic esophageal squamous cell carcinoma (ESCC) has been a challenge in clinical practice. Emerging evidence demonstrates that C-X-C chemokine receptor 4 (CXCR4) highly expresses in ESCC and plays a pivotal role in the process of tumor metastasis. We developed a copper-64 (t1/2 = 12.7 h, 19% beta+) labeling route of NOTA-CP01 derived from LY2510924, a cyclopeptide-based CXCR4 potent antagonist, in an attempt to noninvasively visualize CXCR4 expression in metastatic ESCC. Precursor NOTA-CP01 was designed by modifying the C-terminus of LY2510925 with bis-t-butyl NOTA via a butane-1,4-diamine linker. The radiolabeling process was finished within 15 min with high radiochemical yield (>95%), radiochemical purity (>99%), and specific activity (10.5-21 GBq/µmol) (non-decay-corrected). The in vitro solubility and stability tests revealed that [64Cu]NOTA-CP01 had a high water solubility (log P = -3.44 ± 0.12, n = 5) and high stability in saline and fetal bovine serum. [64Cu]NOTA-CP01 exhibited CXCR4-specific binding with a nanomolar affinity (IC50 = 1.61 ± 0.96 nM, Kd = 0.272 ± 0.14 nM) similar to that of the parental LY2510924. The in vitro cell uptake assay indicated that the [64Cu]NOTA-CP01-selective accumulation in EC109 cells was CXCR4-specific. Molecular docking of the CXCR4/NOTA-CP01 complex suggested that the Lys, Arg, and NOTA of this ligand have a strong polar interaction with the key residues of CXCR4, which explains the tight affinity of [64Cu]NOTA-CP01 for CXCR4. To test the target engagement in vivo, prolonged-time positron emission computed tomography (PET) imaging was performed at 0.5, 4, 6, 8, 12, 16, and 24 h postinjection of [64Cu]NOTA-CP01 to the EC109 tumor-bearing mice. The EC109 tumors were most visible with high contrast to the contralateral background at 6 h postinjection. The tracer revealed receptor-specific tumor accumulation, which was illustrated by effective blocking via coinjection with a blocking dose of LY2510924. Quantification analysis of the prolonged-time images showed that there was obvious radioactivity accumulation in the tumor (1.27 ± 0.19%ID/g) with the best tumor-to-blood ratio (4.79 ± 0.06) and tumor-to-muscle ratio (15.44 ± 2.94) at 6 h postinjection of the probe. The immunofluorescence and immunohistochemistry confirmed the positive expression of CXCR4 in the EC109 tumor and ESCC and metastatic lymph nodes of patients, respectively. We concluded that [64Cu]NOTA-CP01 possessed a very high target engagement for CXCR4-positive ESCC and could be a potential candidate in the clinical detection of metastatic ESCC.

5.
Talanta ; 233: 122596, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215084

RESUMO

Detection of explosives at trace levels is crucial for security purposes because of increasing worldwide terrorist threats at public places. Previously, a hollow cathode discharge (HCD) ion source has been fabricated for detection of explosives. Recently, the HCD ion source has been modified for a dual pressures operating system and coupled to a linear ion trap MS to analyze explosives simultaneously. Here, trinitrotoluene (TNT), nitroglycerin (NG), pentaerythritol tetranitrate (PETN) and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) were taken as model explosive compounds and the mass spectra were recorded in the negative mode ionization. At the higher ion source pressure (~28.0-30.0 Torr), NG, PETN and RDX gave adduct ions with the NO3- ion while TNT showed the [TNT + NO3-HNO2]- (m/z 242) simultaneously. However, NG and PETN did not give any ion signals at the lower ion source pressure (~0.8-1.0 Torr) while TNT exhibited its molecular ion, [TNT]-• (m/z 227), as a major ion through electron attachment and RDX showed fragment ions that followed electron capture dissociation concurrently. The modified HCD ion source exhibited better sensitivity in simultaneous detection and quantification of the explosives. The NO3- and NO2- as reagent ions in the air HCD plasma form stable adduct ions with the NG, PETN and RDX even with TNT at the higher temperature (140-200 °C). The formation of the NO3-, NO2- in the HCD plasma also causes the formation of [TNT-H]- (m/z 226) at the higher ion source pressure. The inner metallic surface of the hollow tube assists the Birch reduction type reaction that results in the formation of hydride ion of the TNT, [TNT + H]- (m/z 228). No significant difference in the spectral pattern for simultaneous and individual measurements for the explosives was observed at the higher ion source pressure. Therefore, it may conclude that the present modified HCD ion source can be used for simultaneous detection and quantification of the explosive compounds at trace and/or ultra-trace levels using air as a carrier gas.


Assuntos
Substâncias Explosivas , Tetranitrato de Pentaeritritol , Trinitrotolueno , Eletrodos , Humanos , Alta do Paciente
6.
Medicine (Baltimore) ; 100(27): e26528, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232188

RESUMO

ABSTRACT: It remains unknown whether dissecting the intrapulmonary lymph nodes (stations 13 and 14) when resecting peripheral non-small cell lung cancer (NSCLC) is necessary for accurate tumor node metastasis (TNM) staging. This study investigated intrapulmonary lymph node dissection (stations 13 and 14) on the pathological staging of peripheral NSCLC and the metastatic pattern of the lymph nodes.This retrospective study included patients with primary peripheral NSCLC who underwent radical dissection between January 2013 and December 2015. The clinical data of patients and examination results of intrapulmonary stations 12, 13, and 14 lymph nodes were analyzed.Of 3019 resected lymph nodes in a total of 234 patients (12.9/patient), 263 (8.7%) had metastasis. Ninety-nine patients had lymph node metastasis (42.3%): 40 (17.1%) were N1, 11 (4.7%) were N2, 48 (20.5%) were both N1 and N2, and 135 (57.7%) had no N1 or N2 metastasis. Sixteen (6.8%) patients had metastasis of stations 13 and/or 14. Metastasis in N1 positive patients of stations 10, 11, 12, 13, and 14 were 2.7%, 10.5%, 9.8%, 10.4%, and 8.5%, respectively. Missed detection without station 13 and 14 dissection was up to 6.8% (16/234).Dissection of stations 13 and 14 could be helpful for the identification of lymph node metastasis and for the accurate TNM staging of primary NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Estadiamento de Neoplasias , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
7.
Nucl Med Biol ; 100-101: 52-60, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214768

RESUMO

OBJECTIVE: Lysosomal protein transmembrane 4 beta (LAPTM4B) is selectively expressed in hepatocellular carcinoma (HCC) cells and thus a potential biomarker for diagnosing HCC. In this study, we designed a novel 18F-labeled PET probe to non-invasively visualize LAPTM4B expression in mouse model of HCC tumor. METHODS: A PET targeting tracer named [18F]FP-LAP2H was radio-synthesized using a LAPTM4B targeting peptide, LAP2H, coupled with 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). Radio-stability, cell uptake, micro PET/CT imaging and ex vivo biodistribution were performed for determining its stability, cell binding specificity, and tumor targeting in vivo. RESULTS: [18F]FP-LAP2H was successfully synthesized with radiochemical yields of 6-14% (decay-corrected yield) and molar activity of 10-44 GBq/µmol. The tracer showed stable (~90%) in phosphate-buffered saline, pH 7.4, and in human serum (~80%) for 2 h. In vitro cell uptake studies indicated the radioactivity accumulation in HCC cells was LAPTM4B protein-specific. Micro PET/CT demonstrated that implanted LAPTM4B positive HepG2 and BEL7402 tumors could be clearly visualized. The ex vivo biodistribution studies demonstrated that the tumor/liver ratio were 1.80 ± 0.65 and 2.09 ± 0.68 in implanted HepG2 and BEL7402 tumors respectively. Negative control and blocking experiments revealed that the radioactivity uptake in the HCC tumor was LAPTM4B protein-specific. CONCLUSIONS: [18F]FP-LAP2H appears to be a potential PET tracer for imaging LAPTM4B-positive HCC tumor. Further endeavors need to do to improve tumor/liver ratio.

8.
Biomed Res Int ; 2021: 6616547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34212035

RESUMO

Objective: To observe the therapeutic effect of Carvacrol on oral squamous cell carcinoma (OSCC) and dissect underlying molecular mechanisms. Methods: Keap1/Nrf2, NALP3, Vimentin, and E-cadherin expression was detected in OSCC and normal oral mucosa (NOM) tissues using immunofluorescence or western blot. When treated with Carvacrol or tert-butylhydroquinone (TBHQ) that activates Nrf2, the expression of Keap1/Nrf2/HO-1, epithelial-mesenchymal transition- (EMT-) related proteins, and NALP3 was examined in OSCC cells. Nrf2 was silenced by treatment with sh-Nrf2 or ML385. After silencing Nrf2 or Carvacrol treatment, cell proliferation and migration were assessed by clone formation and scratch and transwell tests in OSCC cells. Moreover, the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 was detected. Results: Keap1/Nrf2, NALP3, Vimentin, and E-cadherin proteins were all significantly upregulated in OSCC than NOM tissues. Carvacrol significantly suppressed Keap1/Nrf2/HO-1 activation. Carvacrol or silencing Nrf2 markedly inhibited the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 inflammasome in OSCC cells. Furthermore, clone formation and migration capacities were suppressed following treatment with Carvacrol or Nrf2 depletion. The opposite results were found when there is overexpression of Nrf2. However, Carvacrol distinctly improved the cancer-promoting effect induced by Nrf2 overexpression. Conclusion: Our findings suggested that Carvacrol ameliorated inflammation, proliferation, and migration for OSCC, which was related to inhibition of the Nrf2/Keap1 pathway.

9.
Comput Med Imaging Graph ; 91: 101952, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34144318

RESUMO

Automated segmentation of left ventricular cavity (LVC) in temporal cardiac image sequences (consisting of multiple time-points) is a fundamental requirement for quantitative analysis of cardiac structural and functional changes. Deep learning methods for segmentation are the state-of-the-art in performance; however, these methods are generally formulated to work on a single time-point, and thus disregard the complementary information available from the temporal image sequences that can aid in segmentation accuracy and consistency across the time-points. In particular, single time-point segmentation methods perform poorly in segmenting the end-systole (ES) phase image in the cardiac sequence, where the left ventricle deforms to the smallest irregular shape, and the boundary between the blood chamber and the myocardium becomes inconspicuous and ambiguous. To overcome these limitations in automatically segmenting temporal LVCs, we present a spatial sequential network (SS-Net) to learn the deformation and motion characteristics of the LVCs in an unsupervised manner; these characteristics are then integrated with sequential context information derived from bi-directional learning (BL) where both chronological and reverse-chronological directions of the image sequence are used. Our experimental results on a cardiac computed tomography (CT) dataset demonstrate that our spatial-sequential network with bi-directional learning (SS-BL-Net) outperforms existing methods for spatiotemporal LVC segmentation.

10.
IEEE Trans Biomed Eng ; PP2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34185636

RESUMO

ObjectiveThe increasing demand for unraveling cellular heterogeneity has boosted single cell metabolomics studies. However, current analytical methods are usually labor-intensive and hampered by lack of accuracy and efficiency. METHODS: we developed a first-ever automated single cell mass spectrometry system (named SCMS) that facilitated the metabolic profiling of single cells. In particular, extremely small droplets of sub nano-liter were generated to extract the single cells, and the underlying mechanism was verified theoretically and experimentally. This was crucial to minimize the dilution of the trace cellular contents and enhance the analytical sensitivity. Based on the precise 3D positioning of the pipette tip, we established a visual servoing robotic micromanipulation platform on which single cells were sequentially extracted, aspirated, and ionized, followed by the mass spectrometry analyses. RESULTS: With the SCMS system, inter-operator variability was eliminated and working efficiency was improved. The performance of the SCMS system was validated by the experiments on bladder cancer cells. MS and MS2 analyses of single cells enable us to identify several cellular metabolites and the underlying inter-cell heterogeneity. CONCLUSION: In contrast to traditional methods, the SCMS system functions without human intervention and realizes a robust single cell metabolic analysis. SIGNIFICANCE: the SCMS system upgrades the way how single cell metabolites were analyzed, and has the potential to be a powerful tool for single cell metabolomics studies.

11.
Biomed Res Int ; 2021: 6650791, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34189138

RESUMO

Objective: To clarify the role and molecular mechanism of mitochondrial calcium uniporter (MCU) in the malignant biological behaviors of oral squamous cell carcinoma (OSCC) cells through clinical and cellular experiments. Methods: Immunohistochemistry and qRT-PCR techniques were used to observe the expression of MCU, nuclear factor erythroid 2-related factor 2 (Nrf2), mitochondrial calcium uptake 1 (MICU1), and MICU2 in OSCC and normal tissues. After treatment with si-MCU, spermine, and/or sh-Nrf2, malignant biological behaviors of OSCC cells including proliferation, migration, and apoptosis were detected by clone formation, migration, and mitochondrial membrane potential (MMP) assays. Furthermore, MCU, MICU1, MICU2, Nrf2, and other proteins related to malignant biological behaviors were examined using western blot, immunohistochemistry, and immunofluorescence assays. Results: MCU, Nrf2, and MICU1 were strongly expressed in OSCC as compared to normal tissues, while MICU2 was relatively weakly expressed in OSCC tissues. Knockdown of MCU distinctly weakened proliferation and migration and lowered MMP level in CAL 27 cells. Conversely, its activation reinforced migrated capacity and increased MMP level in CAL 27 cells, which was reversed after cotransfection with sh-Nrf2. After treatment with si-MCU or spermine, Nrf2 expression was not affected in CAL 27 cells. However, MCU expression was distinctly suppressed in CAL 27 cells transfected with sh-Nrf2. Furthermore, knockdown of Nrf2 significantly reversed the increase in expression of MICU1 and MICU2 induced by MCU activation in CAL 27 cells. Conclusion: MCU, as a novel oncogene of OSCC, augments malignant biological behaviors of OSCC cells, which could be transcriptionally regulated by Nrf2.

12.
BMC Cancer ; 21(1): 644, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34053447

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify potential biomarkers for facilitating TNBC diagnosis and management. METHODS: We identified potential biomarkers and analyzed their diagnostic and prognostic values using bioinformatics approaches. Including differential expression gene (DEG) analysis, Receiver Operating Characteristic (ROC) curve analysis, functional enrichment analysis, Protein-Protein Interaction (PPI) network construction, survival analysis, multivariate Cox regression analysis, and Non-negative Matrix Factorization (NMF). RESULTS: A total of 105 DEGs were identified between TNBC and other breast cancer subtypes, which were regarded as heterogeneous-related genes. Subsequently, the KEGG enrichment analysis showed that these genes were significantly enriched in 'cell cycle' and 'oocyte meiosis' related pathways. Four (FAM83B, KITLG, CFD and RBM24) of 105 genes were identified as prognostic signatures in the disease-free interval (DFI) of TNBC patients, as for progression-free interval (PFI), five genes (FAM83B, EXO1, S100B, TYMS and CFD) were obtained. Time-dependent ROC analysis indicated that the multivariate Cox regression models, which were constructed based on these genes, had great predictive performances. Finally, the survival analysis of TNBC subtypes (mesenchymal stem-like [MSL] and mesenchymal [MES]) suggested that FAM83B significantly affected the prognosis of patients. CONCLUSIONS: The multivariate Cox regression models constructed from four heterogeneous-related genes (FAM83B, KITLG, RBM24 and S100B) showed great prediction performance for TNBC patients' prognostic. Moreover, FAM83B was an important prognostic feature in several TNBC subtypes (MSL and MES). Our findings provided new biomarkers to facilitate the targeted therapies of TNBC and TNBC subtypes.

13.
J Neural Eng ; 18(4)2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33836509

RESUMO

Objective. In this study, a hybrid method combining hardware and software architecture is proposed to remove stimulation artefacts (SAs) and extract the volitional surface electromyography (sEMG) in real time during functional electrical stimulations (FES) with time-variant parameters.Approach. First, an sEMG detection front-end (DFE) combining fast recovery, detector and stimulator isolation and blanking is developed and is capable of preventing DFE saturation with a blanking time of 7.6 ms. The fragment between the present stimulus and previous stimulus is set as an SA fragment. Second, an SA database is established to provide six high-similarity templates with the current SA fragment. The SA fragment will be de-artefacted by a 6th-order Gram-Schmidt (GS) algorithm, a template-subtracting method, using the provided templates, and this database-based GS algorithm is called DBGS. The provided templates are previously collected SA fragments with the same or a similar evoking FES intensity to that of the current SA fragment, and the lengths of the templates are longer than that of the current SA fragment. After denoising, the sEMG will be extracted, and the current SA fragment will be added to the SA database. The prototype system based on DBGS was tested on eight able-bodied volunteers and three individuals with stroke to verify its capacity for stimulation removal and sEMG extraction.Results.The average stimulus artefact attenuation factor, SA index and correlation coefficient between clean sEMG and extracted sEMG for 6th-order DBGS were 12.77 ± 0.85 dB, 1.82 ± 0.37 dB and 0.84 ± 0.33 dB, respectively, which were significantly higher than those for empirical mode decomposition combined with notch filters, pulse-triggered GS algorithm, 1st-order and 3rd-order DBGS. The sEMG-torque correlation coefficients were 0.78 ± 0.05 and 0.48 ± 0.11 for able-bodied volunteers and individuals with stroke, respectively.Significance.The proposed hybrid method can extract sEMG during dynamic FES in real time.


Assuntos
Algoritmos , Artefatos , Estimulação Elétrica , Eletromiografia , Humanos , Volição
14.
Comput Methods Programs Biomed ; 203: 106043, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33744750

RESUMO

BACKGROUND AND OBJECTIVE: [18f]-fluorodeoxyglucose (fdg) positron emission tomography - computed tomography (pet-ct) is now the preferred imaging modality for staging many cancers. Pet images characterize tumoral glucose metabolism while ct depicts the complementary anatomical localization of the tumor. Automatic tumor segmentation is an important step in image analysis in computer aided diagnosis systems. Recently, fully convolutional networks (fcns), with their ability to leverage annotated datasets and extract image feature representations, have become the state-of-the-art in tumor segmentation. There are limited fcn based methods that support multi-modality images and current methods have primarily focused on the fusion of multi-modality image features at various stages, i.e., early-fusion where the multi-modality image features are fused prior to fcn, late-fusion with the resultant features fused and hyper-fusion where multi-modality image features are fused across multiple image feature scales. Early- and late-fusion methods, however, have inherent, limited freedom to fuse complementary multi-modality image features. The hyper-fusion methods learn different image features across different image feature scales that can result in inaccurate segmentations, in particular, in situations where the tumors have heterogeneous textures. METHODS: we propose a recurrent fusion network (rfn), which consists of multiple recurrent fusion phases to progressively fuse the complementary multi-modality image features with intermediary segmentation results derived at individual recurrent fusion phases: (1) the recurrent fusion phases iteratively learn the image features and then refine the subsequent segmentation results; and, (2) the intermediary segmentation results allows our method to focus on learning the multi-modality image features around these intermediary segmentation results, which minimize the risk of inconsistent feature learning. RESULTS: we evaluated our method on two pathologically proven non-small cell lung cancer pet-ct datasets. We compared our method to the commonly used fusion methods (early-fusion, late-fusion and hyper-fusion) and the state-of-the-art pet-ct tumor segmentation methods on various network backbones (resnet, densenet and 3d-unet). Our results show that the rfn provides more accurate segmentation compared to the existing methods and is generalizable to different datasets. CONCLUSIONS: we show that learning through multiple recurrent fusion phases allows the iterative re-use of multi-modality image features that refines tumor segmentation results. We also identify that our rfn produces consistent segmentation results across different network architectures.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
15.
J Biosci ; 462021.
Artigo em Inglês | MEDLINE | ID: mdl-33737493

RESUMO

Circular RNAs (circRNAs) have been reported to play important roles in human cancers. Circular RNA homeodomain interacting protein kinase 3 (Circ-HIPK3) was investigated to be involved in tumorigenesis. However, the functions of circ-HIPK3 in oral squamous cell carcinoma (OSCC) remain vague. The expression of circ-HIPK3, microRNA (miR)-381-3p and Yes-associated protein1 (YAP1) was detected by qRT-PCR or western blot. Cell proliferation, apoptosis, invasion and migration were measured by MTT assay, flow cytometry, or transwell assay. The dual-luciferase reporter assay was employed to test the target correlations miR-381-3p and circ-HIPK3 or YAP1. Murine xenograft model was established to conduct in vivo assay. CircHIPK3 was elevated in OSCC tissues and cell lines, and decrease of circ-HIPK3 suppressed OSCC cell proliferation, invasion, migration and induced apoptosis in vitro as well as inhibited tumor growth in vivo. Rescue assay indicated circ-HIPK3 silence mediated OSCC progression inhibition by sponging miR-381-3p, which was a target of circ-HIPK3. Furthermore, miR-381-3p directly interacted with YAP1 and miR-381-3p inhibition could attenuate YAP1 deletion-induced suppression on cell malignant biological behavior in OSCC. Meanwhile, co-expression analysis showed circ-HIPK3 could regulate YAP1 expression by competing for miR-381-3p. Circ-HIPK3 contributed to OSCC growth and development through regulating YAP1 expression by sponging miR-381-3p, indicating a promising therapeutic strategy for OSCC.

16.
Braz J Med Biol Res ; 54(5): e10093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33729388

RESUMO

The aim of this study was to explore the effect of hsa_circ_0002162 on regulating cell proliferation, apoptosis, and invasion, and investigate its potential target microRNA (miRNA) in tongue squamous cell carcinoma (TSCC). Hsa_circ_0002162 expression was detected in human TSCC cell lines and human oral keratinocytes (HOK) cell line. Cell proliferation, apoptosis, invasion, and candidate target miRNA expressions were detected in hsa_circ_0002162 knockdown-treated CAL-27 cells and hsa_circ_0002162 overexpression-treated SCC-9 cells. In the rescue experiment, miR-33a-5p knockdown plasmid was transfected into hsa_circ_0002162 knockdown-treated CAL-27 cells, while miR-33a-5p overexpression plasmid was transfected into hsa_circ_0002162 overexpression-treated SCC-9 cells. Subsequently, cell proliferation, apoptosis, and invasion were detected, and then luciferase reporter assay was performed. Hsa_circ_0002162 expression was increased in human TSCC cell lines SCC-9, CAL-27, HSC-4, and SCC-25 compared with HOK. In CAL-27 cells, hsa_circ_0002162 knockdown inhibited cell proliferation and invasion and promoted apoptosis. In SCC-9 cells, hsa_circ_0002162 overexpression enhanced cell proliferation and invasion and suppressed apoptosis. Furthermore, a negative regulation of hsa_circ_0002162 on miR-33a-5p (but not miR-302b-5p and miR-545-5p) was observed. In the rescue experiment, miR-33a-5p knockdown increased cell proliferation and invasion, and decreased apoptosis in hsa_circ_0002162 knockdown-treated CAL-27 cells, whereas miR-33a-5p overexpression decreased cell proliferation and invasion, but increased apoptosis in hsa_circ_0002162 overexpression-treated SCC-9 cells. The luciferase reporter assay showed the direct binding of hsa_circ_0002162 to miR-33a-5p. In conclusion, hsa_circ_0002162 had an important role in malignant progression of TSCC through targeting miR-33a-5p.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , Neoplasias da Língua , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , RNA Circular , Língua , Neoplasias da Língua/genética
17.
Oxid Med Cell Longev ; 2021: 6685282, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777320

RESUMO

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3ß/ß-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Lewis , Medicamentos de Ervas Chinesas/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Metástase Neoplásica
18.
IEEE J Biomed Health Inform ; 25(9): 3507-3516, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33591922

RESUMO

Multimodal positron emission tomography-computed tomography (PET-CT) is used routinely in the assessment of cancer. PET-CT combines the high sensitivity for tumor detection of PET and anatomical information from CT. Tumor segmentation is a critical element of PET-CT but at present, the performance of existing automated methods for this challenging task is low. Segmentation tends to be done manually by different imaging experts, which is labor-intensive and prone to errors and inconsistency. Previous automated segmentation methods largely focused on fusing information that is extracted separately from the PET and CT modalities, with the underlying assumption that each modality contains complementary information. However, these methods do not fully exploit the high PET tumor sensitivity that can guide the segmentation. We introduce a deep learning-based framework in multimodal PET-CT segmentation with a multimodal spatial attention module (MSAM). The MSAM automatically learns to emphasize regions (spatial areas) related to tumors and suppress normal regions with physiologic high-uptake from the PET input. The resulting spatial attention maps are subsequently employed to target a convolutional neural network (CNN) backbone for segmentation of areas with higher tumor likelihood from the CT image. Our experimental results on two clinical PET-CT datasets of non-small cell lung cancer (NSCLC) and soft tissue sarcoma (STS) validate the effectiveness of our framework in these different cancer types. We show that our MSAM, with a conventional U-Net backbone, surpasses the state-of-the-art lung tumor segmentation approach by a margin of 7.6% in Dice similarity coefficient (DSC).

19.
Cancer Res ; 81(8): 2015-2028, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33602787

RESUMO

Hepatocellular carcinoma (HCC) contains a subset of cancer stem cells (CSC) that cause tumor recurrence, metastasis, and chemical resistance. Histone deacetylase 11 (HDAC11) mediates diverse immune functions and metabolism, yet little is known about its role in HCC CSCs. In this study, we report that HDAC11 is highly expressed in HCC and is closely related to disease prognosis. Depletion of HDAC11 in a conditional knockout mouse model reduced hepatocellular tumorigenesis and prolonged survival. Loss of HDAC11 increased transcription of LKB1 by promoting histone acetylation in its promoter region, thereby activating the AMPK signaling pathway and inhibiting the glycolysis pathway, which in turn leads to the suppression of cancer stemness and HCC progression. Furthermore, HDAC11 overexpression reduced HCC sensitivity to sorafenib. Collectively, these data propose HDAC11 as a new target for combination therapy in patients with kinase-resistant HCC. SIGNIFICANCE: This study finds that HDAC11 suppresses LKB1 expression in HCC to promote cancer stemness, progression, and sorafenib resistance, suggesting the potential of targeting HDAC11 to treat HCC and overcome kinase inhibitor resistance.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Hepatocelular/metabolismo , Histona Desacetilases/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Acetilação , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Metabolismo Energético , Perfilação da Expressão Gênica , Inativação Gênica , Glicólise/fisiologia , Células Hep G2 , Histona Desacetilases/deficiência , Histona Desacetilases/genética , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , Regiões Promotoras Genéticas , Transdução de Sinais , Sorafenibe/uso terapêutico , Esferoides Celulares/metabolismo , Ensaio Tumoral de Célula-Tronco
20.
Future Oncol ; 17(7): 837-851, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33522289

RESUMO

Older acute myeloid leukemia patients usually experience a bleak outcome, especially those in the unfit group. For this unfit category, intensive chemotherapy and allogeneic stem cell transplantation are usually accompanied by higher early mortality, which results from higher risk genetic profiles and worse psychological and physiological conditions. The significant improvement in genetic technology recently has driven the appearance of several mutation-targeted therapies, such as FLT3, Bcl-2, IDH and Hedgehog pathway inhibitors and an anti-CD33 antibody-drug conjugate, which have changed enormously the therapeutic landscape of acute myeloid leukemia. This review describes the treatment dilemma of the unfit group and discusses the objective clinical data of each targeted drug and mechanisms of resistance, with a focus on combination strategies with fewer toxicities and abrogation of drug resistance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Atividades Cotidianas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Avaliação Geriátrica , Humanos , Avaliação de Estado de Karnofsky , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Terapia de Alvo Molecular/métodos , Mutação , Intervalo Livre de Progressão
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...