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2.
Bioelectrochemistry ; 131: 107352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31494386

RESUMO

The designed synthesis of efficient materials can significantly enhance the performance of electrochemical immunoassay in the detection of diseases, pesticide residues and environmental pollutants. The hollow AgPt@Pt core-shell nanoparticles (AgPt@Pt HNs) have exhibited high catalytic efficiency to the hydrogen peroxide (H2O2) reduction for its high mass activity from their hollow structure. Their limitation of instability can be overcome by loading on polypyrrole nanosheet (PPy NS). Besides, PPy NS exhibits good conductivity, and there exists environmentally-friendly method for its synthetic. Thus, AgPt@Pt HNs loaded on PPy NS (AgPt@Pt HNs/PPy NS) exhibits high catalytic efficiency to the reduction of H2O2 and good stability. Furthermore, the quick electron transfer of AgPt@Pt HNs/PPy NS modified glassy carbon electrode has been evidenced by the finding that the large constant of apparent electron transfer rate has also enlarged the current signal when the amount of electron is invariant. The modified electrode has fabricated a label-free amperometric immunosensor to detect sensitively prostate-specific antigen (PSA) with H2O2 as the electroactive material. The immunosensor in hollow core-shell nanosheet structure exhibiting good detection performance of PSA shows its promising applications in the clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Eletrodos , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Platina/química , Polímeros/química , Pirróis/química , Biomarcadores Tumorais/análise , Catálise , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredução , Antígeno Prostático Específico/análise
3.
Talanta ; 207: 120280, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594565

RESUMO

Thrombin and its aptamers have been well studied and widely used as models in aptamer based assays and sensors. Here we reported a thrombin-linked sandwich immunoassay for proteins to demonstrate new applications of thrombin and the aptamers, converting protein detection to analysis of thrombin label. In this assay, target protein was sandwiched by the capture antibody on a microplate and the biotinylated detection antibody. Thrombin bound to one biotinylated aptamer, and then the thrombin-labeled aptamer was attached on the sandwich complex through streptavidin-biotin interaction by using streptavidin as a linker. Thrombin catalyzed cleavage of fluorogenic peptide substrates, generating fluorescence signals for target detection. Among a few different anti-thrombin aptamers, the use of one nuclease resistant RNA aptamer having phosphorodithioate (PS2) modification on a specific backbone position enabled higher assay sensitivity due to its much higher affinity. This thrombin-linked sandwich immunoassay allowed detection of prostate-specific antigen (PSA) at 2 pM, an important protein related cancer disease, with high sensitivity and specificity. The strategy was general, and also enabled sensitive detection of botulinum neurotoxin type A (BoNTA) light chain, one toxin protein causing risk to human health. This assay combines advantages of antibody recognition, aptamer affinity labeling, high affinity of aptamers, and enzyme activity of thrombin. Labeling thrombin on the immunosandwich complex through simple affinity binding overcomes limitations of covalent conjugating enzyme on antibody in conventional immunoassay. This assay is promising in applications for protein detection.


Assuntos
Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Limite de Detecção , Fosfatos/química , Proteínas/análise , Estudos de Viabilidade , Humanos , Antígeno Prostático Específico/análise , Antígeno Prostático Específico/metabolismo , Proteínas/metabolismo
4.
PLoS Med ; 16(12): e1002998, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31860675

RESUMO

BACKGROUND: The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit-harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening. METHODS AND FINDINGS: A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model's cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval [UI]: 16,792-59,685) at the expense of 94,831 (95% UI: 84,827-105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382-72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853-15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose. CONCLUSIONS: Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit-harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms and cost-effectiveness.


Assuntos
Detecção Precoce de Câncer , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Idoso , Análise Custo-Benefício , Detecção Precoce de Câncer/métodos , Inglaterra , Humanos , Incidência , Tábuas de Vida , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco
5.
Actas urol. esp ; 43(10): 562-567, dic. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-185263

RESUMO

Introducción: El objetivo del estudio fue establecer los factores que se relacionan de forma independiente con el desarrollo de resistencia a la castración (RC) a medio plazo en el cáncer de próstata (CP). Material y métodos: Ciento cincuenta y cinco pacientes con CP metastásicos al diagnóstico del registro nacional de CP con un seguimiento de hasta 39 meses. Las variables estudiadas fueron: edad, PSA, nadir de PSA, Gleason, invasión perineural, estadios T, N y M y tipo de bloqueo (intermitente/continuo). Resultados: Media de seguimiento 26,2 ± 13,4 meses. El 47,1% desarrolló RC precoz, con una media hasta el desarrollo de RC 12,2 ± 8,7 meses. Análisis univariante: se relacionaron con la RC la media de PSA (290 ± 905,1ng/ml en no RC, 519,1 ± 1437,2 ng/ml en RC, p < 0,001), media de edad (73,3 ± 8,3 años en no RC, 69,1 ± 9,3 en RC, p = 0,01), media de nadir de PSA (15,5 ± 57,3 ng/ml en no RC, 15,9 ± 23,7 ng/ml en RC, p < 0,001), Gleason (en ≥ 8, HR: 2,11; IC 95%: 1,22-3,65, p = 0,006) y estadio T (en T3-T4, HR: 2,85; IC 95%: 1,57-5,19, p < 0,001). Análisis multivariante: las variables independientes relacionadas con la RC son edad (HR: 0,96; IC 95%: 0,94-0,99, p = 0,01), nadir de PSA (HR: 1,65; IC 95%: 1,43-1,91, p < 0,001) y estadio T3-T4 (HR: 2,11; IC 95%: 1,10-4,04, p = 0,02). Conclusiones: El nadir de PSA y un estadio tumoral T3-T4 al diagnóstico se relacionan con un riesgo aumentado de desarrollar RC. Además, la edad al diagnóstico se muestra como una variable que disminuye el riesgo, de forma que, a más edad, menos riesgo de desarrollar RC a medio plazo


Introduction: The objective of the study was to determine the factors independently related with the development of castration resistance (CR) in prostate cancer (PC) in the medium term. Material and methods: 155 patients diagnosed with metastatic PC with a follow-up of up to 39 months. Data taken from the National PC Registry. The evaluated variables were age, PSA, nadir PSA, Gleason, perineural invasion, TNM stages, and ADT type (intermittent/continuous). Results: Mean follow-up 26,2 ± 13,4 months. 47.1% developed early CR, with mean time until onset of 12,2 ± 8,7 months. Univariate analysis the mean PSA was correlated with CR (290 ± 905,1 ng/mL in non CR, 519,1 ± 1437,2 ng/mL in CR, P < .001), mean age (73,3 ± 8,3 years in non CR, 69,1 ± 9,3 in CR P = .01), mean PSA nadir (15,5 ± 57,3 ng/mL in non CR, 15,9 ± 23,7 ng/mL in CR, p < 0,001), Gleason (in ≥ 8, HR: 2,11. 95% CI: 1.22-3.65, p = 0.006), and T stage (in T3-T4, HR: 2.85. 95% CI: 1.57-5.19, P < .001). Multivariate analysis the independent variables associated to CR are age (HR: 0.96. 95% CI: 0.94-0.99, P = .01), PSA nadir (HR: 1.65. 95% CI: 1,43-1,91, P < .001), and T3-T4 stage (HR: 2.11. 95% CI: 1.10-4.04, P = .02). Conclusions: PSA nadir and T3-T4 tumor stage at diagnosis are associated to an increased risk of developing CR. In addition, age at diagnosis is shown as a variable that decreases risk. Therefore, an older age would be associated with lower risk probability of CR in the medium term


Assuntos
Humanos , Masculino , Idoso , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Sistema de Registros , Metástase Neoplásica , Antígeno Prostático Específico/análise , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Espanha/epidemiologia , Análise Multivariada
7.
Forensic Sci Int ; 304: 109899, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31383478

RESUMO

Immunochromatographic assays are used by crime laboratories to conduct simple and quick analyses of bodily fluids. These streamlined tests are ideal for decreasing the sexual assault kit backlog in the United States. A large-scale analysis of the frequency of positive results of amylase and prostate specific antigen (PSA) endogenously found in the vaginal cavity was conducted using the SERATEC PSA Semiquant and Amylase tests. Vaginal swabs were self-collected by participants after 7-10 days of no oral contact or male ejaculation. In this study of 50 participants, 98% were negative for PSA and 92% were negative for amylase. Positive results were confirmed to contain no exogenous DNA by male-specific quantitation, short tandem repeat (STR) typing, and Y-STR typing. These results can be used by crime laboratories to help guide interpretation of immunochromatographic test results from vaginal swabs and aid in decision-making in downstream DNA testing.


Assuntos
Amilases/análise , Imunoensaio , Antígeno Prostático Específico/análise , Saliva/enzimologia , Vagina/química , Cromossomos Humanos Y , Impressões Digitais de DNA , Feminino , Ciências Forenses , Humanos , Masculino , Repetições de Microssatélites
8.
Nanoscale ; 11(33): 15659-15667, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31411624

RESUMO

Methods based on the photothermal effect (a common phenomenon in nature) have been widely applied in different fields; however, their application in bioanalysis has lagged behind. Herein, we designed a near-infrared (NIR) photothermal immunoassay for the qualitative or quantitative detection of prostate-specific antigen (PSA) using titanium carbide (Ti3C2) MXene quantum dot (QD)-encapsulated liposomes with high photothermal efficiency. This system involves a sandwich-type immunoreaction and photothermal measurements. Ti3C2 MXene QDs were utilized as innovative photothermal signal beacons and were encapsulated in liposomes for the labeling of the secondary antibody. The assay was carried out by coupling a low-cost microplate with a homemade 3D printed device. Under NIR-laser irradiation, the Ti3C2 MXene QDs converted the light energy into heat, and a shift in temperature corresponding with the analyte concentration was obtained on a handheld thermometer. Under optimal conditions, the Ti3C2 MXene QD-based photothermal immunoassay exhibited a dynamic linear range from 1.0 ng mL-1 to 50 ng mL-1 with a limit of detection of 0.4 ng mL-1 for PSA detection. Also, we constructed portable equipment using a portable near-infrared imaging camera to collect visual thermal data for the semi-quantitative analysis of the target PSA within 3 min. The specificity, reproducibility and accuracy of the photothermal immunoassay were acceptable. Importantly, our strategy opens new opportunities for protein point-of-care (POC) testing and biosecurity diagnostics.


Assuntos
Imunoensaio/métodos , Lipossomos/química , Antígeno Prostático Específico/análise , Pontos Quânticos/química , Titânio/química , Humanos , Imunoensaio/instrumentação , Lasers , Limite de Detecção , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos Testes , Smartphone
9.
Biosens Bioelectron ; 142: 111484, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284103

RESUMO

Early stage detection of prostate cancer, one of the main causes of mortality among men, is of great importance for better treatment of the patients. Prostate specific antigen (PSA) is a glycoprotein which has been considered as the most potential serological biomarker for the detection of prostate cancer. Among the various techniques employed for PSA detection, aptamer-based biosensors (aptasensors) have achieved notable attention because of their unique features and great potentials as diagnostic tools. A variety of strategies such as integration of nanomaterials (NMs) into the structure of aptasensors have also been applied for enhancing the sensitivity of PSA detection. This article reviews recent advances in various optical and electrochemical aptasensors used for PSA detection.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Calicreínas/sangue , Antígeno Prostático Específico/sangue , Animais , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Desenho de Equipamento , Humanos , Calicreínas/análise , Medições Luminescentes/instrumentação , Medições Luminescentes/métodos , Masculino , Nanoestruturas/química , Antígeno Prostático Específico/análise , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico
10.
Curr Urol Rep ; 20(7): 40, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31168725

RESUMO

PURPOSE OF REVIEW: In this article, we review why patients may fail medical therapy for benign prostatic hyperplasia (BPH) and by doing so, gain a better understanding of the disease process and how to optimize the care of these patients. RECENT FINDINGS: A growing body of literature has attempted to better characterize the various mechanisms by which patients develop BPH as well as identify predictors of disease progression and treatment failure. BPH is a heterogenous disease process. A more personalized approach to treatment, including patient selection for medical or surgical management, would allow us to optimize patient care.


Assuntos
Resistência a Medicamentos , Hiperplasia Prostática/tratamento farmacológico , Falha de Tratamento , Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas Adrenérgicos alfa/uso terapêutico , Fatores Etários , Ensaios Clínicos como Assunto , Progressão da Doença , Quimioterapia Combinada , Humanos , Masculino , Obesidade/complicações , Inibidores da Fosfodiesterase 5/uso terapêutico , Antígeno Prostático Específico/análise , Prostatite/complicações
11.
Talanta ; 202: 111-122, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171159

RESUMO

A new dual-modality immunosensor based on molecularly imprinted polymer (MIP) and a nanostructured biosensing layer has fabricated for the simultaneous detection of two important markers including prostate-specific antigen (PSA) and myoglobin (Myo) in human serum and urine samples. In the first step, 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester) (DSP) was self-assembled on a gold screen printed electrode (SPE). Then, the target proteins were attached covalently to the DSP-SPE. The imprinted cocktail polymer ((MIP(PSA, Myo)-SPE)) was synthesized at the SPE surface using acrylamide as monomer, N,N'-methylenebisacrylamide as a crosslinker, and PSA and Myo as the templates, respectively. The MIP-SPE was specific for the impedimetric sensing of PSA and Myo. After that, a nanocomposite (NCP) was synthesized based on the decorated magnetite nanoparticles with multi-walled carbon nanotube, graphene oxide and specific antibody for PSA (Ab). Then, NCP incubated with (MIP(PSA, Myo)-SPE. The modified electrodes and synthesized nanoparticles were characterized using electrochemical impedance spectroscopy, dynamic light scattering, surface plasmon resonance and scanning electron microscopy. The limits of detections were found to be 5.4 pg mL-1 and 0.83 ng mL-1 with the linear dynamic ranges of 0.01-100 and 1-20000 ng mL-1 for PSA and Myo, respectively. The ability of proposed biosensor to detect PSA and Myo simultaneously with high sensitivity and specificity offers a powerful opportunity for the new generation of biosensors. This dual-analyte specific receptors-based device is highly desired for the integration with lab-on-chip kits to measure a wide panel of biomarkers present at ultralow levels during early stages of diseases progress.


Assuntos
Biomarcadores Tumorais/análise , Técnicas Biossensoriais , Técnicas Eletroquímicas , Mioglobina/análise , Polímeros/química , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Anticorpos/imunologia , Reações Antígeno-Anticorpo , Biomarcadores Tumorais/imunologia , Eletrodos , Humanos , Masculino , Impressão Molecular , Mioglobina/imunologia , Nanopartículas/química , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/imunologia
12.
Analyst ; 144(12): 3716-3720, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31134993

RESUMO

A photothermal immune-imaging assay was innovatively designed for the visual quantitative detection of cancer biomarkers by coupling CuxS nanocrystals with a portable infrared thermal imager on a smartphone. The rolling circle amplification (RCA) technique was used for the formation of a CuxS nanocrystal concatemer, thus opening up new territories in immunoassay development.


Assuntos
Biomarcadores Tumorais/análise , Imunoensaio/métodos , Nanocompostos/química , Antígeno Prostático Específico/análise , Smartphone , Anticorpos/imunologia , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Biomarcadores Tumorais/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Cobre/química , DNA/química , DNA/genética , Humanos , Imunoensaio/instrumentação , Raios Infravermelhos , Masculino , Nanocompostos/efeitos da radiação , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico , Antígeno Prostático Específico/imunologia , Sulfetos/química , Temperatura Ambiente
13.
Nat Commun ; 10(1): 2109, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068594

RESUMO

Nanopore sensors detect individual species passing through a nanoscale pore. This experimental paradigm suffers from long analysis times at low analyte concentration and non-specific signals in complex media. These limit effectiveness of nanopore sensors for quantitative analysis. Here, we address these challenges using antibody-modified magnetic nanoparticles ((anti-PSA)-MNPs) that diffuse at zero magnetic field to capture the analyte, prostate-specific antigen (PSA). The (anti-PSA)-MNPs are magnetically driven to block an array of nanopores rather than translocate through the nanopore. Specificity is obtained by modifying nanopores with anti-PSA antibodies such that PSA molecules captured by (anti-PSA)-MNPs form an immunosandwich in the nanopore. Reversing the magnetic field removes (anti-PSA)-MNPs that have not captured PSA, limiting non-specific effects. The combined features allow detecting PSA in whole blood with a 0.8 fM detection limit. Our 'magnetic nanoparticle, nanopore blockade' concept points towards a strategy to improving nanopore biosensors for quantitative analysis of various protein and nucleic acid species.


Assuntos
Anticorpos/química , Técnicas Biossensoriais/instrumentação , Nanopartículas de Magnetita/química , Nanoporos , Anticorpos/imunologia , Técnicas Biossensoriais/métodos , Calicreínas/análise , Calicreínas/imunologia , Limite de Detecção , Membranas Artificiais , Antígeno Prostático Específico/análise , Antígeno Prostático Específico/imunologia , Compostos de Silício/química , Fatores de Tempo
14.
Anal Bioanal Chem ; 411(17): 3979-3988, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31089787

RESUMO

Herein, a universal and multifunctional fluorescence sensor platform is designed by the interaction of aggregation/dispersion gold nanoparticles (AuNPs) with Tb-metal-organic frameworks (Tb-MOFs). It is found that the dispersed AuNPs rather than the aggregated ones can quench effectively the fluorescence of Tb-MOFs, and the quenching process presumably involves the mechanism of inner filter effect (IFE), dynamic quenching effect (DQE), and fluorescence resonance energy transfer (FRET). The different affinities of aptamer and aptamer-target complex toward AuNPs are employed to modulate the fluorescence signal change of Tb-MOFs. As the proof of concept, prostate-specific antigen (PSA), an efficient tumor indicator for prostate cancer, is selected as the target. At first, the PSA aptamer can protect AuNPs against salt-induced aggregation, leading to the fluorescence of Tb-MOFs quenching. Subsequently, upon PSA introduction, the rigid aptamer-PSA complex is formed and cannot stabilize AuNPs in high salt conditions, so the AuNPs aggregate significantly and the fluorescence of Tb-MOFs is restored. The linear range of PSA is achieved from 1 to 100 ng/mL with a detection limit of 0.36 ng/mL. Finally, this method has been validated to be sensitive and specific for PSA in human urine samples. Graphical abstract.


Assuntos
Técnicas Biossensoriais , Ouro/química , Imunoensaio/métodos , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Antígeno Prostático Específico/análise , Térbio/química , Fluorescência , Humanos , Limite de Detecção , Masculino , Microscopia Eletrônica de Transmissão , Antígeno Prostático Específico/urina , Espectroscopia de Infravermelho com Transformada de Fourier , Ressonância de Plasmônio de Superfície
15.
PLoS One ; 14(4): e0215582, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002732

RESUMO

INTRODUCTION: Brachytherapy is a well-established treatment of localized prostate cancer. Few studies have documented long-term results, specifically biochemical progression-free survival (bPFS) in men with brachytherapy alone, with or without short-term androgen deprivation therapy (ADT), or in combination with external beam radiotherapy (EBRT). Our aim was to analyze long-term bPFS of brachytherapy treated patients. MATERIALS AND METHODS: Retrospective analysis of 1457 patients with low and intermediate risk prostate cancer treated with brachytherapy alone (1255) or combined with EBRT (202). Six-months ADT was administrated for all EBRT combined patients and for prostate volume downsizing when >55 cc (328). Failure was by the Phoenix definition. Kaplan-Meier analysis and multivariate Cox regression estimated and compared 10-yr and 15-yr rates of bPFS. RESULTS: Median follow-up was 6.1 yr. Ten and 15-yr bPFS rates of the entire cohort were 93.2% and 89.2%, respectively. On multivariate analysis, PSA density (PSAD), ADT and clinical stage were significantly associated with failure. The most powerful independent factor was PSAD with a HR of 3.5 (95% CI, 1.7-7.4) for PSAD above 0.15. No significant difference was found between low and intermediate risks patients regardless of treatment regimen. However, comparison of two intermediate risk groups, Gleason score (GS) 7, PSA<20 ng/ml versus GS≤6 and PSA = 10-20 ng/ml, revealed 10- and 15-yr bPFS rates of 94.2% and 94.2% compared to 88.2% and 79.9%, (P = 0.022), respectively. ADT improved bPFS rates in low risk patients. The ten and 15-yr bPFS rates were 97.6% and 94.6% compared to 92.3% and 88.2%, (P = 0.020), respectively. CONCLUSIONS: Our retrospective large scale study suggests that brachytherapy provides excellent long-term bPFS rates in low and intermediate risk disease. Combination of brachytherapy with EBRT yields favorable outcomes in GS 7 intermediate risk patients and short-term ADT has a positive effect on outcomes in low risk patients. Further prospective studies are warranted to discriminate the role of adding either EBRT and/or ADT to brachytherapy protocols.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Braquiterapia/métodos , Neoplasias da Próstata/terapia , Radioterapia de Intensidade Modulada/métodos , Idoso , Terapia Combinada , Intervalo Livre de Doença , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , /estatística & dados numéricos , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/análise , Estudos Retrospectivos
16.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 38(2): 100-105, mar.-abr. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-182392

RESUMO

Objetivo: El 68Ga-PSMA muestra captación en las lesiones malignas de los pacientes de cáncer de próstata a los 5 min postinyección. Los estudios realizados para comprender el valor de añadir una imagen pélvica precoz al protocolo de imagen de 68Ga-PSMA-11 PET/TC muestran resultados contradictorios. En este estudio, planificamos la evaluación de la relevancia de añadir una imagen precoz a 68Ga-PSMA-I&T PET/TC en los pacientes con cáncer de próstata. Materiales y métodos: Reunimos a un total de 35 pacientes con cáncer de próstata, a quienes se les prescribió 68Ga-PSMA-I&T PET/TC para reestadificar la enfermedad, debido a sospecha de recidiva tras la terapia definitiva. En primer lugar, se obtuvo una imagen pélvica estática precoz, a un máximo de 300 s tras la inyección del radiotrazador. A los 60 min de la inyección se realizó una PET/TC de cuerpo entero, con un tiempo de emisión de 3min por posición del lecho. Se compararon las lesiones categorizadas en las imágenes precoces como recidiva local, lesión ósea y metástasis ganglionar con las imágenes tardías en términos de lesiones detectadas y valores SUVmax. Resultados: La68Ga-PSMA-I&T PET/TC fue positiva en 23 de los 35 pacientes (65,7%). Se observó una captación patológica en el lecho prostático, en los ganglios pélvicos y en los huesos en 17 pacientes (48,5%), 12 pacientes (34,2%) y 13 pacientes (37,1%), respectivamente. En un paciente, se detectó una captación incrementada patológica focal en el lecho prostático con un valor SUVmax de 5,8, aunque esta lesión desapareció en las imágenes tardías. Los valores SUVmax medios de las lesiones en el lecho prostático fueron 13,7±12,1 frente a 26,3±23,8 en los estudios a los 5min y 60min, respectivamente (p<0,001). En un paciente, la captación patológica ganglionar en el estudio temprano desapareció en el estudio tardío, mientras que en otro paciente la acumulación de actividad se detectó en un ganglio pélvico en el estudio tardío, pero no se detectó ningún ganglio en el estudio temprano. Los valores SUVmax ganglionares medios fueron 12,1±8,8 frente a 26,3±22,6 en los estudios a los 5min y 60min, respectivamente (p<0,001). Los valores SUVmax medios de las lesiones óseas fueron 11,4±6,9 frente a 15±10,7 en los estudios a los 5min y 60min, respectivamente. Conclusión: Nuestro estudio es el primero en la literatura que evalúa el impacto de añadir una imagen pélvica estática temprana a 68Ga-PSMA-I&T, para valorar la tasa de detección de las lesiones. Aunque no se produjo una discordancia marcada entre los 2conjuntos de imágenes, la adición de una imagen temprana al protocolo de imagen de 68Ga-PSMA-I&T podría incrementar la eficacia en la detección de las lesiones pélvicas malignas, lo cual podría reflejar un rápido aclaramiento, con el riesgo de que fuera enmascarado por la actividad del sistema urinario


Objective: 68Ga-PSMA-uptake shows accumulation in the malignant lesions of prostate cancer patients as early as 5min p.i. Studies indicate the value of adding an early image of the pelvis to the imaging protocol of 68Ga-PSMA-11 PET/CT scan showed contradictory results. In this study we planned to assess the significance of an additional early imaging in 68Ga-PSMA-I&T PET/CT imaging in prostate cancer patients. Materials and methods: A total of 35 prostate cancer patients referred to 68Ga-PSMA-I&T PET/CT imaging for restaging of the disease due to suspicion of relapse after definitive therapy were enrolled. First an early static pelvic image was obtained at a maximum of 300s following injection of the radiotracer. Sixty minutes postinjection a whole-body PET/CT scan was conducted with an emission time of 3min per bed position. The lesions which were categorized as local recurrence, bone lesion and lymph node metástasis in the early images, were compared with the late images in terms of number of lesions detected and SUVmax values. Results: 68Ga-PSMA-I&T PET/CT was positive in 23 of 35 patients (65.7%). A pathological uptake was observed in the prostatic bed site, in the pelvic lymph nodes, and in the bones in 17 patients (48.5%), 12 patients (34.2%), and 13 patients (37.1%), respectively. In one patient, focal pathological increased uptake in the prostatic bed with a SUVmax value of 5.8 was detected but this lesion disappeared in the late images. The average SUVmax values of the lesions in the prostatic bed were 13.7±12.1 versus 26.3±23.8 in the 5min and 60min studies respectively (p<0.001). In one patient, the pathological uptake in the lymph node in the early study cleared in the late study, whereas in another accumulation of activity was detected in a pelvic lymph node in the late study, while there was no lymph node detected in the early study. The average SUVmax values of the lymph nodes were 12.1±8.8 versus 26.3±22.6 in the 5min and 60min studies respectively (p<0.001). The average SUVmax values of the bone lesions were 11.4±6.9 versus 15±10.7 in the 5min and 60min studies respectively. Conclusion: Our study is the first in the literature to evaluate the impact of adding an early static pelvic image to the 68Ga-PSMA-I&T scan, in the detection rate of the lesions. Although there was no marked discordance between the 2sets of images, the addition of an early image to the imaging protocol of 68Ga-PSMA-I&T scan would increase the efficacy of detection of malignant lesions in the pelvis, which might show rapid clearance and has the risk of being masked by the urinary system activity


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias da Próstata/diagnóstico por imagem , Antígeno Prostático Específico/análise , Gadolínio , Mucina-1 , Metástase Linfática/diagnóstico por imagem , Prostatectomia/estatística & dados numéricos , Estadiamento de Neoplasias/métodos , Estudos Retrospectivos , Neoplasias Ósseas/diagnóstico por imagem
18.
Methods Mol Biol ; 1972: 221-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30847795

RESUMO

The Capillary Electrophoresis (CE) profile of isoforms (peaks) of a glycoprotein can be useful to show alterations in its posttranslational modifications (PTMs) linked to diseases. These changes can modify the electrophoretic mobility of these isoforms in a minor extent and, therefore, very reproducible CE methods are needed to detect them. In this chapter, a method for the analysis of prostate-specific antigen (PSA) by Capillary Zone Electrophoresis (CZE) with UV detection is detailed. High reproducibility in the separation of a large number of PSA isoforms is achieved by performing capillary conditioning in acid media and by using a background electrolyte (BGE) at pH 8.0 formulated with decamethonium bromide and urea.


Assuntos
Eletroforese Capilar/métodos , Antígeno Prostático Específico/análise , Humanos , Masculino , Isoformas de Proteínas/análise , Fatores de Tempo
19.
Mikrochim Acta ; 186(4): 252, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30903388

RESUMO

The authors describe an integrated microfluidic chip for immunodetection of the prostate specific antigen (PSA) by using giant magnetoimpedance (GMI) sensor. This chip contains an immunoreaction platform and a biomarker detection system. The immunoreaction platform contains an incubation chamber and a reactive chamber to implement immunological reaction in microfluidics. The system can detect PSA rapidly with ultra-high sensitivity. Both are fabricated by MEMS technology. Immunomagnetic beads (If PSA binds to its antibody (that is labeled with immunomagnetic beads; IMBs) it will be trapped on the surface of self-assembled film. Trapped IMBs generate a stray magnetic field under the magnetization of the external applied magnetic field and can be detected by the GMI sensor. The chip can detect PSA with a detection limit as low as 0.1 ng ∙ mL-1 and works in the 0.1 ng ∙ mL-1 to 20 ng ∙ mL-1 concentration range. Compared to established GMI biosensors, the magnetic microfluidic chip reduces assay time, and lends itself to fast detection. It also avoids complex handling steps, enhances reaction efficiency and decreases experimental errors. Graphical abstract An integrated magnetic microfluidic chip which contains immunoreaction platform and biomarker detection system was designed and microfabricated by micro-electromechanical systems (MEMS) technology to detect prostate specific antigen (PSA) rapidly, and has promise in Point-of-care (PoC) diagnostic applications.


Assuntos
Imunoensaio/instrumentação , Separação Imunomagnética/instrumentação , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Antígeno Prostático Específico/análise , Animais , Anticorpos/imunologia , Biomarcadores/análise , Desenho de Equipamento , Humanos , Imunoensaio/métodos , Separação Imunomagnética/métodos , Limite de Detecção , Camundongos , Técnicas Analíticas Microfluídicas/métodos , Antígeno Prostático Específico/imunologia
20.
Anticancer Res ; 39(3): 1391-1396, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842173

RESUMO

BACKGROUND/AIM: It is important to delay the emergence of castration-resistant phenotype to improve the prognosis in patients with metastatic castration-sensitive prostate cancer (mCSPC). The objective of this study was to investigate the prognostic impact of time to castration resistance (TTCR) in mCSPC patients. PATIENTS AND METHODS: This study included 437 consecutive mCSPC patients whose primary androgen deprivation therapy was judged to have failed. Prognostic outcomes in these patients were investigated by dividing them into the following 4 groups of 82, 104, 133 and 118 patients with TTCR 0-6, 6.1-12, 12.1-18 and ≥18.1 months, respectively. RESULTS: The mean value of TTCR in the 437 patients was 18.7 months. Of several baseline parameters, significant differences among the 4 groups were noted in the performance status, prostate-specific antigen (PSA) level, lactate dehydrogenase (LDH) level, alkaline phosphatase (ALP) level and Gleason score, all of which favored longer TTCR groups. Furthermore, despite the lack of a significant difference in time from the development of castration-resistant disease to death among the 4 groups, there was a significant difference in overall survival (OS) from diagnosis among these groups, showing prolonged OS proportional to TTCR. Univariate analysis identified the age, PSA level, LDH level, ALP level, Gleason score, visceral metastasis and TTCR as significant predictors of OS, of which only age, ALP level and TTCR were shown to be independently associated with OS on multivariate analysis. CONCLUSION: mCSPC patients with a longer TTCR are likely to achieve a more favorable OS.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Fosfatase Alcalina/sangue , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Gradação de Tumores , Prognóstico , Antígeno Prostático Específico/análise , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Fatores de Tempo
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