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1.
Biosens Bioelectron ; 194: 113629, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534949

RESUMO

Accurate and accessible nucleic acid diagnostics is critical to reducing the spread of COVID-19 and resuming socioeconomic activities. Here, we present an integrated platform for the direct detection of SARS-CoV-2 RNA targets near patients. Termed electrochemical system integrating reconfigurable enzyme-DNA nanostructures (eSIREN), the technology leverages responsive molecular nanostructures and automated microfluidics to seamlessly transduce target-induced molecular activation into an enhanced electrochemical signal. Through responsive enzyme-DNA nanostructures, the technology establishes a molecular circuitry that directly recognizes specific RNA targets and catalytically enhances signaling; only upon target hybridization, the molecular nanostructures activate to liberate strong enzymatic activity and initiate cascading reactions. Through automated microfluidics, the system coordinates and interfaces the molecular circuitry with embedded electronics; its pressure actuation and liquid-guiding structures improve not only analytical performance but also automated implementation. The developed platform establishes a detection limit of 7 copies of RNA target per µl, operates against the complex biological background of native patient samples, and is completed in <20 min at room temperature. When clinically evaluated, the technology demonstrates accurate detection in extracted RNA samples and direct swab lysates to diagnose COVID-19 patients.


Assuntos
Técnicas Biossensoriais , COVID-19 , Nanoestruturas , Humanos , Microfluídica , RNA Viral/genética , SARS-CoV-2
3.
Adv Sci (Weinh) ; 8(18): e2101155, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34278742

RESUMO

Accessible and adaptable nucleic acid diagnostics remains a critical challenge in managing the evolving COVID-19 pandemic. Here, an integrated molecular nanotechnology that enables direct and programmable detection of SARS-CoV-2 RNA targets in native patient specimens is reported. Termed synergistic coupling of responsive equilibrium in enzymatic network (SCREEN), the technology leverages tunable, catalytic molecular nanostructures to establish an interconnected, collaborative architecture. SCREEN mimics the extraordinary organization and functionality of cellular signaling cascades. Through programmable enzyme-DNA nanostructures, SCREEN activates upon interaction with different RNA targets to initiate multi-enzyme catalysis; through system-wide favorable equilibrium shifting, SCREEN directly transduces a single target binding into an amplified electrical signal. To establish collaborative equilibrium coupling in the architecture, a computational model that simulates all reactions to predict overall performance and optimize assay configuration is developed. The developed platform achieves direct and sensitive RNA detection (approaching single-copy detection), fast response (assay reaction is completed within 30 min at room temperature), and robust programmability (across different genetic loci of SARS-CoV-2). When clinically evaluated, the technology demonstrates robust and direct detection in clinical swab lysates to accurately diagnose COVID-19 patients.


Assuntos
COVID-19/virologia , DNA Catalítico/genética , Nanoestruturas/química , SARS-CoV-2/genética , Humanos , Limite de Detecção , Técnicas de Diagnóstico Molecular/métodos , Nanotecnologia/métodos , Pandemias/prevenção & controle , RNA Viral/genética , Manejo de Espécimes/métodos
4.
Nat Commun ; 12(1): 4039, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193867

RESUMO

The controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration - spatial organization and distribution - in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais/métodos , Neoplasias Colorretais/diagnóstico , Vesículas Extracelulares/metabolismo , Estruturas Metalorgânicas/química , Nanoestruturas/química , Tensoativos/química , Ascite/metabolismo , Neoplasias Colorretais/metabolismo , Glicosilação , Humanos , Prognóstico
5.
Onco Targets Ther ; 14: 2163-2175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790579

RESUMO

Background: There is an urgent need for the development of effective noninvasive biomarkers for early pancreatic cancer diagnosis. MicroRNAs (miRNAs) are promising candidates that can be identified in peripheral blood and can act as "liquid biopsy" biomarkers. miR-483-3p is overexpressed in the tumor tissue of pancreatic duct adenocarcinoma, but its potential as noninvasive biomarker remains unknown. Methods: We conducted locked nucleic acid in situ hybridization (LNA-ISH) for miR-483-3p in archival tissues of 107 patients with PDAC. We also used immunohistochemistry to evaluate SMAD4 expression, the putative miR-483-3p target gene. miR-483-3p expression level was also assessed using quantitative real-time PCR (qRT-PCR) in serum and serum exosome samples from 63 patients with PDAC and 22 healthy individuals. Results: LNA-ISH showed that miR-483-3p was overexpressed in PDAC and PanIN tissues compared to normal pancreatic duct cells. miR-483-3p expression levels correlated with increases in PanIN lesion grade. miR-483-3p expression negatively correlated with Smad4 expression (γ=-0.770, p<0.0001) in PDAC and PanIN tissues. Circulating miR-483-3p levels were significantly elevated in the serum and serum exosomes of PDAC patients compared to healthy controls (p<0.0001 and p<0.01, respectively). Specifically, serum miR-483-3p levels were able to distinguish patients with early stage (≤2cm) PDAC from healthy controls with an AUC of 0.83 [95% CI, 0.70-0.96]. Higher serum exosomal miR-483-3p levels predicted worse survival in PDAC patients and serum exosomal miR-483-3p also proved to be an independent prognostic factor for PDAC (hazard ratio = 3.307; 95% CI=1.104 to 9.903; p=0.033). In vitro studies also showed that miR-483-3p promoted pancreatic cancer cell migration and invasion. Conclusion: miR-483-3p overexpression occurs early in PDAC development and is present in premalignant PanIN lesions. Serum miR-483-3p may act as an early PDAC diagnostic biomarker and serum exosomal miR-483-3p may be a PDAC prognostic biomarker.

6.
Nat Nanotechnol ; 16(6): 734-742, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33686255

RESUMO

Current technologies to measure drug-target interactions require complex processing and invasive tissue biopsies, limiting their clinical utility for cancer treatment monitoring. Here we develop an analytical platform that leverages circulating extracellular vesicles (EVs) for activity-based assessment of tumour-specific drug-target interactions in patient blood samples. The technology, termed extracellular vesicle monitoring of small-molecule chemical occupancy and protein expression (ExoSCOPE), utilizes bio-orthogonal probe amplification and spatial patterning of molecular reactions within matched plasmonic nanoring resonators to achieve in situ analysis of EV drug dynamics. It measures changes in drug occupancy and protein composition in molecular subpopulations of EVs. When used to monitor various targeted therapies, the ExoSCOPE revealed EV signatures that closely reflected cellular treatment efficacy. We further applied the technology for clinical cancer diagnostics and treatment monitoring. Using a small volume of blood, the ExoSCOPE accurately classified disease status and rapidly distinguished between targeted treatment outcomes, within 24 h after treatment initiation.


Assuntos
Antineoplásicos/farmacologia , Vesículas Extracelulares/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Antineoplásicos/farmacocinética , Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Estudos de Casos e Controles , Linhagem Celular Tumoral , Receptores ErbB/genética , Cloridrato de Erlotinib/sangue , Cloridrato de Erlotinib/uso terapêutico , Vesículas Extracelulares/química , Estudos de Viabilidade , Humanos , Neoplasias Pulmonares/sangue , Razão Sinal-Ruído
8.
Sci Adv ; 7(12)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33731349

RESUMO

Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native clinical samples. The technology, termed catalytic amplification by transition-state molecular switch (CATCH), leverages DNA-enzyme hybrid complexes to form a molecular switch. By ratiometric tuning of its constituents, the multicomponent molecular switch is prepared in a hyperresponsive state-the transition state-that can be readily activated upon the binding of sparse RNA targets to turn on substantial enzymatic activity. CATCH thus achieves superior performance (~8 RNA copies/µl), direct fluorescence detection that bypasses all steps of PCR (<1 hour at room temperature), and versatile implementation (high-throughput 96-well format and portable microfluidic assay). When applied for clinical COVID-19 diagnostics, CATCH demonstrated direct and accurate detection in minimally processed patient swab samples.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19 , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Testes Imediatos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/genética , Teste de Ácido Nucleico para COVID-19/instrumentação , Teste de Ácido Nucleico para COVID-19/métodos , Humanos , Limite de Detecção
9.
Eur J Neurol ; 28(5): 1479-1489, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33370497

RESUMO

BACKGROUND AND PURPOSE: Various blood biomarkers reflecting brain amyloid-ß (Aß) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. METHODS: Using the same cohort (n = 68), the performances of the single-molecule array (Simoa) Aß40, Aß42, Aß42/Aß40 and the amplified plasmonic exosome (APEX) Aß42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (Aß+) participants. RESULTS: Compared to Simoa biomarkers, APEX-Aß42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 0.995). When utilized for clinical trial recruitment, our simulation showed that pre-screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX-Aß42 and 48.6% for Simoa-Aß42/Aß40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX-Aß42 pre-screening does not increase the required number of initial participants. CONCLUSIONS: With its high diagnostic performance, APEX is an ideal candidate for Aß+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with Aß+ participants whilst halving recruitment costs.


Assuntos
Doença de Alzheimer , Exossomos , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides , Biomarcadores , Humanos , Imunoensaio , Fragmentos de Peptídeos
10.
Sci Adv ; 6(19): eaba2556, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494726

RESUMO

Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis-through simultaneous biophysical and biomolecular evaluation of the same vesicles-directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.

11.
Adv Biosyst ; 4(12): e1900309, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32597034

RESUMO

Neurodegenerative diseases are heterogeneous disorders characterized by a progressive loss of function and/or death of nerve cells, leading to severe cognitive and functional decline. Due to the complex pathology, early detection and intervention are critical to the development of successful treatments; however, current diagnostic approaches are limited to subjective, late-stage clinical findings. Extracellular vesicles (EVs) have recently emerged as a promising circulating biomarker for neurodegenerative diseases. Actively released by diverse cells, EVs are nanoscale membrane vesicles. They abound in blood, readily cross the blood-brain barrier, and carry diverse molecular cargoes in different organizational states: these molecular cargoes are inherited from the parent cells or bound to the EV membrane through surface associations. Specifically, EVs have been found to be associated with several important pathogenic proteins of neurodegenerative diseases, and their involvement could alter disease progression. This article provides an overview of EVs as circulating biomarkers of neurodegenerative diseases and introduces new technological advances to characterize the biophysical properties of EV-associated biomarkers for accurate, blood-based detection of neurodegenerative diseases.

12.
ACS Sens ; 5(1): 4-12, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31888329

RESUMO

Extracellular vesicles (EVs) are diverse, nanoscale membrane vesicles released by cells into the circulation. As an emerging class of circulating biomarkers, EVs contain a trove of molecular information and play important roles in mediating intercellular communication. These EV molecular cargoes are differentially organized in the vesicles; they could be inherited from the parent cells or bound to the EV membrane through surface interactions. While the inherited constituents could serve as cell surrogate biomarkers, extravesicular association could reflect structural states of the bound molecules, revealing distinct subpopulations with different biophysical and/or biochemical properties. Despite the clinical potential of EVs and their diverse contents, conventional sensing technologies have limited compatibility to reveal nanoscale EV features. Complementary analytical platforms are being developed to address these technical challenges and expand the biomedical applications of EVs, to establish novel correlations and empower new diagnostics. This article provides a perspective on recent developments in sensor technologies to profile the diverse contents-different molecular types, quantities, and organizational states-in extracellular vesicles.


Assuntos
Biomarcadores/metabolismo , Técnicas Biossensoriais/métodos , Vesículas Extracelulares/química , Humanos
13.
J Extracell Vesicles ; 9(1): 1689784, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31839905

RESUMO

Tumour cells release diverse populations of extracellular vesicles (EVs) ranging in size, molecular cargo, and function. We sought to characterize mRNA and protein content of EV subpopulations released by human glioblastoma (GBM) cells expressing a mutant form of epidermal growth factor receptor (U87EGFRvIII) in vitro and in vivo with respect to size, morphology and the presence of tumour cargo. The two EV subpopulations purified from GBM U87EGFRvIII cancer cells, non-cancer human umbilical vein endothelial cells (HUVEC; control) and serum of U87EGFRvIII glioma-bearing mice using differential centrifugation (EVs that sediment at 10,000 × g or 100,000 × g are termed large EVs and small EVs, respectively) were characterized using transmission electron microscopy (TEM), confocal microscopy, nanoparticle tracking analysis (NTA), flow cytometry, immunofluorescence (IF), quantitative-polymerase chain reaction (qPCR), droplet digital polymerase chain reaction (ddPCR) and micro-nuclear magnetic resonance (µNMR). We report that both U87EGFRvIII and HUVEC release a similar number of small EVs, but U87EGFRvIII glioma cells alone release a higher number of large EVs compared to non-cancer HUVEC. The EGFRvIII mRNA from the two EV subpopulations from U87EGFRvIII glioma cells was comparable, while the EGFR protein (wild type + vIII) levels are significantly higher in large EVs. Similarly, EGFRvIII mRNA in large and small EVs isolated from the serum of U87EGFRvIII glioma-bearing mice is comparable, while the EGFR protein (wild type + vIII) levels are significantly higher in large EVs. Here we report for the first time a direct comparison of large and small EVs released by glioma U87EGFRvIII cells and from serum of U87EGFRvIII glioma-bearing mice. Both large and small EVs contain tumour-specific EGFRvIII mRNA and proteins and combining these platforms may be beneficial in detecting rare mutant events in circulating biofluids.

14.
Front Oncol ; 9: 831, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552169

RESUMO

Objective: The identification of DNA polymerase epsilon (POLE) mutation subtypes in endometrial cancer is critical for molecular classification. The mutation of the POLE gene could only be detected by sequencing until now. We propose to validate and develop the feasibility of using BaseScope, an in situ hybridization (ISH) assay, for the detection of POLE mutations in high-grade endometrioid carcinomas (EC). Methods: Among 51 paraffin-embedded samples of high-grade EC, BaseScope-ISH assays were used to detect the RNA mutation status of the POLE gene, mainly focusing on two hotspot mutations of P286R and V411L. The number of positive signals in the cytoplasm was counted, setting the positive threshold and determining the in situ hybridization results. The sensitivity and specificity of BaseScope-ISH assay were compared with that of the Sanger sequencing results. Results: Based on the BaseScope assay, there were 19 positive samples and 32 negative samples in a total of 51 samples. Of the 19 positive samples, 10 samples showed P286R site mutations in the POLE gene, while the other nine samples were V411L site mutations. Only one sample with the V411L site mutation identified by Sanger sequencing showed negative signal value. The remaining 31 cases without the P286R site mutation or V411L site mutations all showed negative signal. This analysis result showed the sensitivity was 95% and the specificity was 100% for the BaseScope assay detecting POLE mutants in high-grade EC. Conclusion: In the case of high-grade EC, combined with morphological characteristics, the BaseScope assay can effectively and specifically identify POLE mutation cases, providing a reliable foundation for the application of clinical diagnosis and molecular classification.

15.
Nat Biomed Eng ; 3(9): 684-694, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31285580

RESUMO

Massively parallel DNA sequencing is established, yet high-throughput protein profiling remains challenging. Here, we report a barcoding approach that leverages the combinatorial sequence content and the configurational programmability of DNA nanostructures for high-throughput multiplexed profiling of the subcellular expression and distribution of proteins in whole cells. The barcodes are formed by in situ hybridization of tetrahedral DNA nanostructures and short DNA sequences conjugated with protein-targeting antibodies, and by nanostructure-assisted ligation (either enzymatic or chemical) of the nanostructures and exogenous DNA sequences bound to nanoparticles of different sizes (which cause these localization sequences to differentially distribute across subcellular compartments). Compared with linear DNA barcoding, the nanostructured barcodes enhance the signal by more than 100-fold. By implementing the barcoding approach on a microfluidic device for the analysis of rare patient samples, we show that molecular subtypes of breast cancer can be accurately classified and that subcellular spatial markers of disease aggressiveness can be identified.


Assuntos
Código de Barras de DNA Taxonômico/métodos , DNA/química , DNA/classificação , Perfilação da Expressão Gênica/métodos , Nanoestruturas , Anticorpos/imunologia , Anticorpos/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Código de Barras de DNA Taxonômico/instrumentação , Humanos , Cinética , Dispositivos Lab-On-A-Chip , Proteínas , Coloração e Rotulagem
16.
Nat Commun ; 10(1): 1144, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30850633

RESUMO

Despite intense interests in developing blood measurements of Alzheimer's disease (AD), the progress has been confounded by limited sensitivity and poor correlation to brain pathology. Here, we present a dedicated analytical platform for measuring different populations of circulating amyloid ß (Aß) proteins - exosome-bound vs. unbound - directly from blood. The technology, termed amplified plasmonic exosome (APEX), leverages in situ enzymatic conversion of localized optical deposits and double-layered plasmonic nanostructures to enable sensitive, multiplexed population analysis. It demonstrates superior sensitivity (~200 exosomes), and enables diverse target co-localization in exosomes. Employing the platform, we find that prefibrillar Aß aggregates preferentially bind with exosomes. We thus define a population of Aß as exosome-bound (Aß42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aß, the exosome-bound Aß measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Encéfalo/patologia , Exossomos/química , Neurônios/patologia , Fragmentos de Peptídeos/química , Placa Amiloide/patologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/sangue , Técnicas Biossensoriais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Exossomos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas Analíticas Microfluídicas , Neurônios/metabolismo , Neurônios/ultraestrutura , Fragmentos de Peptídeos/sangue , Placa Amiloide/diagnóstico por imagem , Placa Amiloide/metabolismo , Tomografia por Emissão de Pósitrons , Agregados Proteicos , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Ressonância de Plasmônio de Superfície , Células THP-1 , Tetraspanina 30/química , Tetraspanina 30/metabolismo
17.
Theranostics ; 9(2): 311-323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809276

RESUMO

Motor neuron diversification and regionalization are important hallmarks of spinal cord development and rely on fine spatiotemporal release of molecular cues. Here, we present a dedicated platform to engineer complex molecular profiles for directed neuronal differentiation. Methods: The technology, termed microhexagon interlace for generation of versatile and fine gradients (microHIVE), leverages on an interlocking honeycomb lattice of microstructures to dynamically pattern molecular profiles at a high spatial resolution. By packing the microhexagons as a divergent, mirrored array, the platform not only enables maximal mixing efficiency but also maintains a small device footprint. Results: Employing the microHIVE platform, we developed optimized profiles of growth factors to induce rostral-caudal patterning of spinal motor neurons, and directed stem cell differentiation in situ into a spatial continuum of different motor neuron subtypes. Conclusions: The differentiated cells showed progressive RNA and protein signatures, consistent with that of representative brachial, thoracic and lumbar regions of the human spinal cord. The microHIVE platform can thus be utilized to develop advanced biomimetic systems for the study of diseases in vitro.


Assuntos
Técnicas de Cultura de Células/métodos , Diferenciação Celular , Microfluídica/métodos , Neurônios Motores/fisiologia , Células-Tronco/fisiologia , Técnicas de Cultura de Células/instrumentação , Humanos , Microfluídica/instrumentação
18.
Hum Pathol ; 85: 101-111, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30447299

RESUMO

Pancreatic neuroendocrine neoplasms (PanNENs) have an unpredictable clinical course that varies from indolent to highly malignant. No immunohistochemical markers are available for reliable prediction of the biological behavior of early stage PanNENs. Minichromosome maintenance protein 7 (MCM7) is a putative powerful marker of cell proliferation. Whether the expression of MCM7 is related to the risk of PanNENs progression remains unclear. We assessed the clinical behavior of 156 PanNENs with respect to stage, grade, Ki-67 index, MCM7 index, and other pathologic features. A high MCM7 index was significantly associated with larger tumor size (P < .001), nonfunctioning tumor (P < .001), increased grade (P < .0001), and later TNM stage (P < .001). In multivariate analysis, G2/G3 (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.35-3.62; P < .001), stage III/IV (HR, 2.11; 95% CI, 1.31-3.41; P < .001), and MCM7 labeling index >5% (HR, 3.81; 95% CI, 1.30-11.17; P = .02) were independent negative prognostic factors related to the risk of tumor progression in stage I-IV disease. MCM7 labeling index >5% was associated with an increased risk of progression in stages I-V, I-III, and I-II. Our study confirms that MCM7 is a valuable marker for assessing the progression of PanNENs, especially in patients with early stage disease and without distant metastasis.


Assuntos
Proliferação de Células , Componente 7 do Complexo de Manutenção de Minicromossomo/metabolismo , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/metabolismo , Adolescente , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67 , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Intervalo Livre de Progressão , Adulto Jovem
19.
Quant Imaging Med Surg ; 8(9): 957-970, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30505724

RESUMO

Sensitive and quantitative characterization of clinically relevant biomarkers can facilitate disease diagnosis and treatment evaluation. Magnetic nanomaterials and their biosensing strategies have recently received considerable attention. Magnetic signals experience little interference from native biological background as most biological molecules have negligible magnetic susceptibilities and thus appear transparent to external magnetic fields. Because of this unique property, magnetic sensing can be applied to both in vivo deep tissue imaging as well as ex vivo point-of-care diagnostics. To exploit this mode of magnetic detection, new advancements in both magnetic material syntheses and sensing technologies have been made. This review focuses on recent developments of magnetic nanomaterials as image contrast agents and diagnostic sensors. These developments have not only enabled precise control of magnetic nanomaterial properties but also expanded the reach of magnetic detection for biomedical diagnostics.

20.
Nat Commun ; 9(1): 3238, 2018 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-30104566

RESUMO

Rapid, visual detection of pathogen nucleic acids has broad applications in infection management. Here we present a modular detection platform, termed enzyme-assisted nanocomplexes for visual identification of nucleic acids (enVision). The system consists of an integrated circuit of enzyme-DNA nanostructures, which function as independent recognition and signaling elements, for direct and versatile detection of pathogen nucleic acids from infected cells. The built-in enzymatic cascades produce a rapid color readout for the naked eye; the assay is thus fast (<2 h), sensitive (<10 amol), and readily quantified with smartphones. When implemented on a configurable microfluidic platform, the technology demonstrates superior programmability to perform versatile computations, for detecting diverse pathogen targets and their virus-host genome integration loci. We further design the enVision platform for molecular-typing of infections in patient endocervical samples. The technology not only improves the clinical inter-subtype differentiation, but also expands the intra-subtype coverage to identify previously undetectable infections.


Assuntos
DNA/química , Peroxidase do Rábano Silvestre/metabolismo , Ácidos Nucleicos/análise , Papillomaviridae/genética , Bioensaio , Humanos , Nanoestruturas/química , Papillomaviridae/isolamento & purificação
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