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1.
Radiology ; 311(3): e231680, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888480

RESUMO

BACKGROUND: Women with dense breasts benefit from supplemental cancer screening with US, but US has low specificity. PURPOSE: To evaluate the performance of breast US tomography (UST) combined with full-field digital mammography (FFDM) compared with FFDM alone for breast cancer screening in women with dense breasts. MATERIALS AND METHODS: This retrospective multireader multicase study included women with dense breasts who underwent FFDM and UST at 10 centers between August 2017 and October 2019 as part of a prospective case collection registry. All patients in the registry with cancer were included; patients with benign biopsy or negative follow-up imaging findings were randomly selected for inclusion. Thirty-two Mammography Quality Standards Act-qualified radiologists independently evaluated FFDM followed immediately by FFDM plus UST for suspicious findings and assigned a Breast Imaging Reporting and Data System (BI-RADS) category. The superiority of FFDM plus UST versus FFDM alone for cancer detection (assessed with area under the receiver operating characteristic curve [AUC]), BI-RADS 4 sensitivity, and BI-RADS 3 sensitivity and specificity were evaluated using the two-sided significance level of α = .05. Noninferiority of BI-RADS 4 specificity was evaluated at the one-sided significance level of α = .025 with a -10% margin. RESULTS: Among 140 women (mean age, 56 years ±10 [SD]; 36 with cancer, 104 without), FFDM plus UST achieved superior performance compared with FFDM alone (AUC, 0.60 [95% CI: 0.51, 0.69] vs 0.54 [95% CI: 0.45, 0.64]; P = .03). For FFDM plus UST versus FFDM alone, BI-RADS 4 mean sensitivity was superior (37% [428 of 1152] vs 30% [343 of 1152]; P = .03) and BI-RADS 4 mean specificity was noninferior (82% [2741 of 3328] vs 88% [2916 of 3328]; P = .004). For FFDM plus UST versus FFDM, no difference in BI-RADS 3 mean sensitivity was observed (40% [461 of 1152] vs 33% [385 of 1152]; P = .08), but BI-RADS 3 mean specificity was superior (75% [2491 of 3328] vs 69% [2299 of 3328]; P = .04). CONCLUSION: In women with dense breasts, FFDM plus UST improved cancer detection by radiologists versus FFDM alone. Clinical trial registration nos. NCT03257839 and NCT04260620 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Mann in this issue.


Assuntos
Densidade da Mama , Neoplasias da Mama , Mamografia , Sensibilidade e Especificidade , Ultrassonografia Mamária , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Ultrassonografia Mamária/métodos , Adulto , Mama/diagnóstico por imagem , Detecção Precoce de Câncer/métodos
2.
Acad Radiol ; 31(6): 2248-2258, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38290888

RESUMO

RATIONALE AND OBJECTIVES: Quantitative transmission (QT) imaging is an emerging volumetric ultrasound modality for women too young for mammography. QT images tissue without overlap seen in mammography, thereby can potentially improve breast mass detection and characterization and noncancer recall. We compared radiologists' interpretation of QT vs digital breast tomosynthesis (DBT) with a multireader multicase observer performance study. MATERIALS AND METHODS: Study subjects received screening DBT and QT scans in HIPAA-compliant, institutional review board-approved prospective case-collection studies at four clinical sites. Twenty-four Mammography Quality Standards Act-qualified radiologists interpreted 177 cases (66 with cancer, atypia, or solid mass and 111 normal or with nonsolid benign abnormality), first QT, then 2 weeks later DBT synthesized 2D-views. Readers reported up to three findings per case and for each finding a recall or no recall decision and confidence of that decision. The study hypothesis was area under receiver operating characteristic curve (AUC) of QT was noninferior to DBT. Sensitivity and specificity were also compared. RESULTS: AUC of QT (0.746 ± 0.028, mean ± SD) was noninferior to DBT (0.700 ± 0.028) for AUC difference margin of -0.05 (P < .05). AUC difference was 0.046 ± 0.028 (95% CI: [-0.008, 0.101]). Sensitivity was 70.6 ± 7.2% for QT and 85.2 ± 6.4% for DBT, specificity was 60.1 ± 12.3% vs 37.2 ± 11.0%, and both differences were statistically significant. Of a total of 21 cases of cysts, readers recommended recall, on average, in 1.1 ± 1.4 cases with QT, but not with DBT, and 10.6 ± 2.2 cases with DBT, but not with QT. CONCLUSION: QT can be a potential alternative to mammography for breast cancer screening of women too young to undergo mammography.


Assuntos
Neoplasias da Mama , Mamografia , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia Mamária , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Pessoa de Meia-Idade , Ultrassonografia Mamária/métodos , Estudos Prospectivos , Mamografia/métodos , Idoso , Adulto , Variações Dependentes do Observador
3.
J Biomol Struct Dyn ; : 1-17, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37827992

RESUMO

The identification of potential epigenetic targets for a known bioactive compound is essential and promising as more and more epigenetic drugs are used in cancer clinical treatment and the availability of chemogenomic data related to epigenetics increases. In this study, we introduce a novel epigenetic target identification strategy (ETI-Strategy) that integrates a multi-task graph convolutional neural network prior model and a protein-ligand interaction classification discriminating model using large-scale bioactivity data for a panel of 55 epigenetic targets. Our approach utilizes machine learning techniques to achieve an AUC value of 0.934 for the prior model and 0.830 for the discriminating model, outperforming inverse docking in predicting protein-ligand interactions. When comparing with other open-source target identification tools, it was found that only our tool was able to accurately predict all the targets corresponding to each compound. This further demonstrates the ability of our strategy to take full advantage of molecular-level information as well as protein-level information in molecular activity prediction. Our work highlights the contribution of machine learning in the identification of potential epigenetic targets and offers a novel approach for epigenetic drug discovery and development.Communicated by Ramaswamy H. Sarma.

4.
J Med Chem ; 65(24): 16570-16588, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36480917

RESUMO

Fibroblast growth factor receptors (FGFRs) play key roles in promoting cancer cell proliferation, differentiation, and migration. However, acquired resistance to FGFR inhibitors has become an emerging challenge in long-term cancer therapies, especially for hepatocellular carcinoma (HCC). Gatekeeper (GK) mutations are the main mechanism of resistance. Herein, we describe the discovery of a series of reversible FGFR inhibitors, particularly for GK mutations with the 2-amino-7-sulfonyl-7H-pyrrolo[2,3-d]pyrimidine scaffold. Rational design, optimization, and pharmacokinetic screening provided representative compound 19 with potent FGFR inhibition in vitro, high bioavailability, and an acceptable half-life. GK mutation tolerance was supported by assays against FGFR4V550L and Ba/F3-TEL-FGFR4V550L cells. Moreover, compound 19 exhibited potent antitumor potency in HUH7 xenograft mouse models with no obvious toxicity observed. Compound 19 was identified as a potential candidate for overcoming GK mutations for HCC treatment.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Proliferação de Células , Mutação , Pirimidinas , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral
5.
Radiology ; 298(1): 38-46, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33078996

RESUMO

Background Recognition of salient MRI morphologic and kinetic features of various malignant tumor subtypes and benign diseases, either visually or with artificial intelligence (AI), allows radiologists to improve diagnoses that may improve patient treatment. Purpose To evaluate whether the diagnostic performance of radiologists in the differentiation of cancer from noncancer at dynamic contrast material-enhanced (DCE) breast MRI is improved when using an AI system compared with conventionally available software. Materials and Methods In a retrospective clinical reader study, images from breast DCE MRI examinations were interpreted by 19 breast imaging radiologists from eight academic and 11 private practices. Readers interpreted each examination twice. In the "first read," they were provided with conventionally available computer-aided evaluation software, including kinetic maps. In the "second read," they were also provided with AI analytics through computer-aided diagnosis software. Reader diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis, with the area under the ROC curve (AUC) as a figure of merit in the task of distinguishing between malignant and benign lesions. The primary study end point was the difference in AUC between the first-read and the second-read conditions. Results One hundred eleven women (mean age, 52 years ± 13 [standard deviation]) were evaluated with a total of 111 breast DCE MRI examinations (54 malignant and 57 nonmalignant lesions). The average AUC of all readers improved from 0.71 to 0.76 (P = .04) when using the AI system. The average sensitivity improved when Breast Imaging Reporting and Data System (BI-RADS) category 3 was used as the cut point (from 90% to 94%; 95% confidence interval [CI] for the change: 0.8%, 7.4%) but not when using BI-RADS category 4a (from 80% to 85%; 95% CI: -0.9%, 11%). The average specificity showed no difference when using either BI-RADS category 4a or category 3 as the cut point (52% and 52% [95% CI: -7.3%, 6.0%], and from 29% to 28% [95% CI: -6.4%, 4.3%], respectively). Conclusion Use of an artificial intelligence system improves radiologists' performance in the task of differentiating benign and malignant MRI breast lesions. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Krupinski in this issue.


Assuntos
Inteligência Artificial , Neoplasias da Mama/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Mama/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
6.
Med Sci Monit ; 25: 7527-7537, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31589596

RESUMO

BACKGROUND Osteosarcoma (OS) is a highly aggressive, metastatic bone tumor with a poor prognosis, and occurs more commonly in children and adolescents. Therefore, new drugs and treatments are urgently needed. In this study, we investigated the effect and potential mechanisms of C18H17NO6 on osteosarcoma cells. MATERIAL AND METHODS Human MNNG osteosarcoma cells were treated with different concentrations of C18H17NO6. The proliferation of the MNNG cells was examined via CCK-8 assay. Cell migration and invasion were tested via wound-healing assay and Transwell migration and invasion assays. ELISA was used to detect MMP-2, MMP-9, and VEGF secretion. Finally, Western blotting and qRT-PCR were used to detect protein and mRNA expressions, respectively. RESULTS C18H17NO6 inhibited MNNG proliferation in a dose- and time-dependent manner and inhibited MMP-2, MMP-9, and VEGF secretion. C18H17NO6 treatment significantly downregulated N-cadherin and Vimentin expression levels and upregulated E-cadherin expression levels in vitro and in vivo. C18H17NO6 inhibited tumor growth in a MNNG xenograft. We also found that C18H17NO6 can significantly reduce the phosphorylation of the PI3K/AKT signaling pathway in vivo and in vitro. However, 740Y-P (a PI3K agonist) had the opposite effect on proliferation, migration and invasion of MNNG cells treated with C18H17NO6. LY294002 (a PI3K inhibitor) downregulated p-PI3K and p-AKT could mimic the inhibitory effect of C18H17NO6. CONCLUSIONS Our results suggest that C18H17NO6 can inhibit human MNNG osteosarcoma cell invasion and migration via the PI3K/AKT signaling pathway both in vivo and in vitro. C18H17NO6 may be a highly effective and low-toxicity natural drug for the prevention or treatment of OS.


Assuntos
Benzofuranos/farmacologia , Osteossarcoma/tratamento farmacológico , Usnea/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional Chinesa/métodos , Camundongos , Invasividade Neoplásica , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Usnea/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Chest ; 156(4): 810-811, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31590714
8.
AJR Am J Roentgenol ; 213(2): W66-W75, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31039019

RESUMO

OBJECTIVE. The purpose of this study was to develop a new quantitative image analysis tool for estimating the risk of cancer of the prostate by use of quantitative multiparametric MRI (mpMRI) metrics. MATERIALS AND METHODS. Thirty patients with biopsy-confirmed prostate cancer (PCa) who underwent preoperative 3-T mpMRI were included in the study. Quantitative mpMRI metrics-apparent diffusion coefficient (ADC), T2, and dynamic contrast-enhanced (DCE) signal enhancement rate (α)-were calculated on a voxel-by-voxel basis for the whole prostate and coregistered. A normalized risk value (0-100) for each mpMRI parameter was obtained, with high risk values associated with low T2 and ADC and high signal enhancement rate. The final risk score was calculated as a weighted sum of the risk scores (ADC, 40%; T2, 40%; DCE, 20%). Data from five patients were used as training set to find the threshold for predicting PCa. In the other 25 patients, any region with a minimum of 30 con-joint voxels (≈ 4.8 mm2) with final risk score above the threshold was considered positive for cancer. Lesion-based and sector-based analyses were performed by matching prostatectomyverified malignancy and PCa predicted with the risk analysis tool. RESULTS. The risk map tool had sensitivity of 76.6%, 89.2%, and 100% for detecting all lesions, clinically significant lesions (≥ Gleason 3 + 4), and index lesions, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for PCa detection for all lesions in the sector-based analysis were 78.9%, 88.5%, 84.4%, and 84.1%, respectively, with an ROC AUC of 0.84. CONCLUSION. The risk analysis tool is effective for detecting clinically significant PCa with reasonable sensitivity and specificity in both peripheral and transition zones.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Biópsia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade
9.
Chest ; 156(1): 112-119, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30981723

RESUMO

BACKGROUND: Risk models have been developed that include the subject's pretest risk profile and imaging findings to predict the risk of cancer in an objective way. We assessed the accuracy of the Vancouver Lung Cancer Risk Prediction Model compared with that of trainee and experienced radiologists using a subset of size-matched nodules from the National Lung Screening Trial (NLST). METHODS: One hundred cases from the NLST database were selected (size range, 4-20 mm), including 20 proven cancers and 80 size-matched benign nodules. Three experienced thoracic radiologists and three trainee radiologists were asked to estimate the likelihood of cancer in each case, first independently, and then with knowledge of the model's risk prediction. The results generated by the model alone also were estimated using receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) for each viewing condition was calculated, and statistical significance in their differences was tested by using the Dorfman-Berbaum-Metz method. RESULTS: Human observers were more accurate (AUC value of 0.85 ± 0.05 [SD]) than was the model (0.77 ± 0.06) in estimating the risk of malignancy (P = .0010), and use of the model did not improve their accuracy (0.84 ± 0.06). Experienced radiologists performed better than did trainees. Human observers could distinguish benign from malignant nodule morphology more accurately than could the model, which relies mainly on nodule size for risk estimation. CONCLUSIONS: Experienced and trainee radiologists had superior ability to predict the risk of cancer in size-matched nodules from a screening trial compared with that of the Vancouver model, and use of the model did not improve their accuracy.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Radiologistas , Medição de Risco/métodos , Tomografia Computadorizada por Raios X , Competência Clínica , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Humanos , Masculino
10.
AJR Am J Roentgenol ; 211(2): 452-461, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29792747

RESUMO

OBJECTIVE: The purpose of this study was to compare diagnostic accuracy and interpretation time of screening automated breast ultrasound (ABUS) for women with dense breast tissue without and with use of a recently U.S. Food and Drug Administration-approved computer-aided detection (CAD) system for concurrent read. MATERIALS AND METHODS: In a retrospective observer performance study, 18 radiologists interpreted a cancer-enriched set (i.e., cancer prevalence higher than in the original screening cohort) of 185 screening ABUS studies (52 with and 133 without breast cancer). These studies were from a large cohort of ABUS-screened patients interpreted as BI-RADS density C or D. Each reader interpreted each case twice in a counterbalanced study, once without the CAD system and once with it, separated by 4 weeks. For each case, each reader identified abnormal findings and reported BI-RADS assessment category and level of suspicion for breast cancer. Interpretation time was recorded. Level of suspicion data were compared to evaluate diagnostic accuracy by means of the Dorfman-Berbaum-Metz method of jackknife with ANOVA ROC analysis. Interpretation times were compared by ANOVA. RESULTS: The ROC AUC was 0.848 with the CAD system, compared with 0.828 without it, for a difference of 0.020 (95% CI, -0.011 to 0.051) and was statistically noninferior to the AUC without the CAD system with respect to a margin of -0.05 (p = 0.000086). The mean interpretation time was 3 minutes 33 seconds per case without the CAD system and 2 minutes 24 seconds with it, for a difference of 1 minute 9 seconds saved (95% CI, 44-93 seconds; p = 0.000014), or a reduction in interpretation time to 67% of the time without the CAD system. CONCLUSION: Use of the concurrent-read CAD system for interpretation of screening ABUS studies of women with dense breast tissue who do not have symptoms is expected to make interpretation significantly faster and produce noninferior diagnostic accuracy compared with interpretation without the CAD system.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico por Computador/métodos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação , Competência Clínica , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
11.
Mol Divers ; 21(3): 719-739, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28689235

RESUMO

Protein-protein interactions (PPIs) have attracted much attention recently because of their preponderant role in most biological processes. The prevention of the interaction between E3 ligase VHL and HIF-1[Formula: see text] may improve tolerance to hypoxia and ameliorate the prognosis of many diseases. To obtain novel potent inhibitors of VHL/HIF-1[Formula: see text] interaction, a series of hydroxyproline-based inhibitors were investigated for structural optimization using a combination of QSAR modeling and molecular docking. Here, 2D- and 3D-QSAR models were developed by genetic function approximation (GFA) and comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods, respectively. The top-ranked models with strict validation revealed satisfactory statistical parameters (CoMFA with [Formula: see text], 0.637; [Formula: see text], 0.955; [Formula: see text], 0.944; CoMSIA with [Formula: see text], 0.649; [Formula: see text], 0.954; [Formula: see text], 0.911; GFA with [Formula: see text], 0.721; [Formula: see text], 0.801; [Formula: see text], 0.861). The selected five 2D-QSAR descriptors were in good accordance with the 3D-QSAR results, and contour maps gave the visualization of feature requirements for inhibitory activity. A new diverse molecular database was created by molecular fragment replacement and BREED techniques for subsequent virtual screening. Eventually, 31 novel hydroxyproline derivatives stood out as potential VHL/HIF-1[Formula: see text] inhibitors with favorable predictions by the CoMFA, CoMSIA and GFA models. The reliability of this protocol suggests that it could also be applied to the exploration of lead optimization of other PPI targets.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Simulação por Computador , Desenho de Fármacos , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Ligação Proteica/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade
12.
AJR Am J Roentgenol ; 207(5): 1159-1166, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27532897

RESUMO

OBJECTIVE: The purposes of this study were to evaluate diagnostic parameters measured with ultrafast MRI acquisition and with standard acquisition and to compare diagnostic utility for differentiating benign from malignant lesions. MATERIALS AND METHODS: Ultrafast acquisition is a high-temporal-resolution (7 seconds) imaging technique for obtaining 3D whole-breast images. The dynamic contrast-enhanced 3-T MRI protocol consists of an unenhanced standard and an ultrafast acquisition that includes eight contrast-enhanced ultrafast images and four standard images. Retrospective assessment was performed for 60 patients with 33 malignant and 29 benign lesions. A computer-aided detection system was used to obtain initial enhancement rate and signal enhancement ratio (SER) by means of identification of a voxel showing the highest signal intensity in the first phase of standard imaging. From the same voxel, the enhancement rate at each time point of the ultrafast acquisition and the AUC of the kinetic curve from zero to each time point of ultrafast imaging were obtained. RESULTS: There was a statistically significant difference between benign and malignant lesions in enhancement rate and kinetic AUC for ultrafast imaging and also in initial enhancement rate and SER for standard imaging. ROC analysis showed no significant differences between enhancement rate in ultrafast imaging and SER or initial enhancement rate in standard imaging. CONCLUSION: Ultrafast imaging is useful for discriminating benign from malignant lesions. The differential utility of ultrafast imaging is comparable to that of standard kinetic assessment in a shorter study time.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Meios de Contraste/farmacocinética , Diagnóstico Diferencial , Feminino , Humanos , Imageamento Tridimensional , Meglumina/análogos & derivados , Meglumina/farmacocinética , Pessoa de Meia-Idade , Compostos Organometálicos/farmacocinética , Estudos Retrospectivos
13.
AJR Am J Roentgenol ; 207(3): 592-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27352026

RESUMO

OBJECTIVE: The objective of our study was to evaluate the role of a hybrid T2-weighted imaging-DWI sequence for prostate cancer diagnosis and differentiation of aggressive prostate cancer from nonaggressive prostate cancer. MATERIALS AND METHODS: Twenty-one patients with prostate cancer who underwent preoperative 3-T MRI and prostatectomy were included in this study. Patients underwent a hybrid T2-weighted imaging-DWI examination consisting of DW images acquired with TEs of 47, 75, and 100 ms and b values of 0 and 750 s/mm(2). The apparent diffusion coefficient (ADC) and T2 were calculated for cancer and normal prostate ROIs at each TE and b value. Changes in ADC and T2 as a function of increasing the TE and b value, respectively, were analyzed. A new metric termed "PQ4" was defined as the percentage of voxels within an ROI that has increasing T2 with increasing b value and has decreasing ADC with increasing TE. RESULTS: ADC values were significantly higher in normal ROIs than in cancer ROIs at all TEs (p < 0.0001). With increasing TE, the mean ADC increased 3% in cancer ROIs and increased 12% in normal ROIs. T2 was significantly higher in normal ROIs than in cancer ROIs at both b values (p ≤ 0.0002). The mean T2 decreased with increasing b value in cancer ROIs (ΔT2 = -17 ms) and normal ROIs (ΔT2 = -52 ms). PQ4 clearly differentiated normal ROIs from prostate cancer ROIs (p = 0.0004) and showed significant correlation with Gleason score (ρ = 0.508, p < 0.0001). CONCLUSION: Hybrid MRI measures the response of ADC and T2 to changing TEs and b values, respectively. This approach shows promise for detecting prostate cancer and determining its aggressiveness noninvasively.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Gradação de Tumores , Projetos Piloto , Prostatectomia , Neoplasias da Próstata/cirurgia
14.
Arthritis Rheumatol ; 68(11): 2740-2751, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27159593

RESUMO

OBJECTIVE: In lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ adaptive immune cell networks that amplify local tissue damage. Since conventional therapy appears ineffective for severe TII, and these patients often progress to renal failure, understanding in situ mechanisms might reveal new therapeutic targets. This study was undertaken to assess whether dysregulated apoptotic regulators maintain local adaptive immunity and drive inflammation in TII. METHODS: This study utilized novel computational approaches that, when applied to multicolor confocal images, quantified apoptotic regulator protein expression in selected lymphocyte subsets. This approach was validated using laser-capture microdissection (LCM) coupled to quantitative polymerase chain reaction (qPCR). Furthermore, the consequences of dysregulated apoptotic mediator expression were explored in a murine model of lupus nephritis. RESULTS: Analyses of renal biopsy tissue from patients with lupus nephritis and those with mixed cellular renal allograft rejection revealed that the B cell lymphoma 2 protein (Bcl-2) was frequently expressed in infiltrating lymphocytes, whereas expression of myeloid cell leukemia 1 was low. In contrast, the reciprocal pattern of expression was observed in tonsil germinal centers. These results were consistent with RNA expression data obtained using LCM and qPCR. Bcl-2 was also highly expressed in tubulointerstitial infiltrates in (NZB × NZW)F1 (NZB/NZW) mice. Furthermore, treatment of NZB/NZW mice with ABT-199, a selective oral inhibitor of Bcl-2, prolonged survival and prevented proteinuria and development of TII in a lupus prevention model. Interestingly, glomerular immune complexes were partially ameliorated by ABT-199 treatment, and serum anti-double-stranded DNA antibody titers were unaffected. CONCLUSION: These data demonstrate that Bcl-2 is an attractive therapeutic target in patients with lupus nephritis who manifest TII.


Assuntos
Apoptose , Nefrite Lúpica/metabolismo , Linfócitos/metabolismo , Nefrite Intersticial/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Imunidade Adaptativa/imunologia , Animais , Complexo Antígeno-Anticorpo/efeitos dos fármacos , Complexo Antígeno-Anticorpo/imunologia , Complexo Antígeno-Anticorpo/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Feminino , Centro Germinativo/metabolismo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Inflamação , Rim/efeitos dos fármacos , Rim/imunologia , Rim/metabolismo , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/imunologia , Glomérulos Renais/metabolismo , Transplante de Rim , Microdissecção e Captura a Laser , Nefrite Lúpica/imunologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos NZB , Microscopia Confocal , Microscopia de Fluorescência , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Nefrite Intersticial/imunologia , Tonsila Palatina , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Sulfonamidas/farmacologia
15.
AJR Am J Roentgenol ; 206(6): 1341-50, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27043979

RESUMO

OBJECTIVE: The objective of our study was to assess and compare, in a reader study, radiologists' performance in the detection of breast cancer using full-field digital mammography (FFDM) alone and using FFDM with 3D automated breast ultrasound (ABUS). MATERIALS AND METHODS: In this multireader, multicase, sequential-design reader study, 17 Mammography Quality Standards Act-qualified radiologists interpreted a cancer-enriched set of FFDM and ABUS examinations. All imaging studies were of asymptomatic women with BI-RADS C or D breast density. Readers first interpreted FFDM alone and subsequently interpreted FFDM combined with ABUS. The analysis included 185 cases: 133 noncancers and 52 biopsy-proven cancers. Of the 52 cancer cases, the screening FFDM images were interpreted as showing BI-RADS 1 or 2 findings in 31 cases and BI-RADS 0 findings in 21 cases. For the cases interpreted as BI-RADS 0, a forced BI-RADS score was also given. Reader performance was compared in terms of AUC under the ROC curve, sensitivity, and specificity. RESULTS: The AUC was 0.72 for FFDM alone and 0.82 for FFDM combined with ABUS, yielding a statistically significant 14% relative improvement in AUC (i.e., change in AUC = 0.10 [95% CI, 0.07-0.14]; p < 0.001). When a cutpoint of BI-RADS 3 was used, the sensitivity across all readers was 57.5% for FFDM alone and 74.1% for FFDM with ABUS, yielding a statistically significant increase in sensitivity (p < 0.001) (relative increase = 29%). Overall specificity was 78.1% for FFDM alone and 76.1% for FFDM with ABUS (p = 0.496). For only the mammography-negative cancers, the average AUC was 0.60 for FFDM alone and 0.75 for FFDM with ABUS, yielding a statistically significant 25% relative improvement in AUC with the addition of ABUS (p < 0.001). CONCLUSION: Combining mammography with ABUS, compared with mammography alone, significantly improved readers' detection of breast cancers in women with dense breast tissue without substantially affecting specificity.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Mamografia , Ultrassonografia Mamária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Adulto Jovem
16.
AJR Am J Roentgenol ; 206(3): 559-65, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26901012

RESUMO

OBJECTIVE: The objective of our study was to investigate associations between quantitative image features of multiparametric MRI of the prostate and PTEN expression of peripheral zone prostate cancer. MATERIALS AND METHODS: A total of 45 peripheral zone cancer foci from 30 patients who had undergone multiparametric prostate MRI before prostatectomy were identified by a genitourinary pathologist and a radiologist who reviewed histologic findings and MR images. Histologic sections of cancer foci underwent immunohistochemical analysis and were scored according to the percentage of tumor-positive cells expressing PTEN as negative (0-20%), mixed (20-80%), or positive (80-100%). Average and 10th percentile apparent diffusion coefficient (ADC) values, skewness of T2-weighted signal intensity histogram, and quantitative perfusion parameters (i.e., forward volume transfer constant [K(trans)], extravascular extracellular volume fraction [ve], and reverse reflux rate constant between the extracellular space and plasma [k(ep)]) from the Tofts model were calculated for each cancer focus. Associations between the quantitative image features and PTEN expression were analyzed with the Spearman rank correlation coefficient (r). RESULTS: Analysis of the 45 cancer foci revealed that 21 (47%) were PTEN-positive, 12 (27%) were PTEN-negative, and 12 (27%) were mixed. There was a weak but significant negative correlation between Gleason score and PTEN expression (r = -0.30, p = 0.04) and between k(ep) and PTEN expression (r = -0.35, p = 0.02). There was no significant correlation between other multiparametric MRI features and PTEN expression. CONCLUSION: This preliminary study of radiogenomics of peripheral zone prostate cancer revealed weak-but significant-associations between the quantitative dynamic contrast-enhanced MRI feature k(ep) and Gleason score with PTEN expression. These findings warrant further investigation and validation with the aim of using multiparametric MRI to improve risk assessment of patients with prostate cancer.


Assuntos
Imageamento por Ressonância Magnética/métodos , PTEN Fosfo-Hidrolase/genética , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Idoso , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/biossíntese , Projetos Piloto , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
17.
Nucl Med Commun ; 37(1): 50-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26426969

RESUMO

OBJECTIVES: The objective of this study was to test the hypothesis that the metabolic tumor volume (MTV) of primary non-small-cell lung cancer is not sensitive to differences in F-fluorodeoxyglucose (F-FDG) uptake time, and to compare this consistency of MTV measurements with that of standardized uptake value (SUV) and total lesion glycolysis (TLG). METHODS: Under Institutional Review Board approval, 134 consecutive patients with histologically proven non-small-cell lung cancer underwent F-FDG PET/computed tomography scanning at about 1 h (early) and 2 h (delayed) after intravenous injection of F-FDG. MTV, SUV, and TLG of the primary tumor were all measured. Student's t-test and Wilcoxon's signed-rank test for paired data were used to compare MTV, SUV, and TLG between the two scans. The intraclass correlation coefficient (ICC) was used to assess agreement in PET parameters between the two scans and between the measurements made by two observers. RESULTS: MTV was not significantly different (P=0.17) between the two scans. However, SUVmax, SUVmean, SUVpeak, and TLG increased significantly from the early to the delayed scans (P<0.0001 for all). The median percentage change between the two scans in MTV (1.65%) was smaller than in SUVmax (11.76%), SUVmean(10.57%), SUVpeak(13.51%), and TLG (14.34%); the ICC of MTV (0.996) was greater than that of SUVmax (0.933), SUVmean (0.952), SUVpeak (0.928), and TLG (0.982). Interobserver agreement between the two radiologists was excellent for MTV, SUV, and TLG on both scans (ICC: 0.934-0.999). CONCLUSION: MTV is not sensitive to common clinical variations in F-FDG uptake time, its consistency is greater than that of SUVmax, SUVmean, SUVpeak, and TLG, and it has excellent interobserver agreement.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Carga Tumoral , Idoso , Transporte Biológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Fluordesoxiglucose F18/metabolismo , Glicólise , Humanos , Cinética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prognóstico
18.
J Magn Reson Imaging ; 42(6): 1733-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25946664

RESUMO

PURPOSE: To determine whether prostate-specific antigen (PSA) levels adjusted by prostate and zonal volumes estimated from magnetic resonance imaging (MRI) improve the diagnosis of prostate cancer (PCa) and differentiation between patients who harbor high-Gleason-sum PCa and those without PCa. MATERIALS AND METHODS: This retrospective study was Health Insurance Portability and Accountability Act (HIPAA)-compliant and approved by the Institutional Review Board of participating medical institutions. T2 -weighted MR images were acquired for 61 PCa patients and 100 patients with elevated PSA but without PCa. Computer methods were used to segment prostate and zonal structures and to estimate the total prostate and central-gland (CG) volumes, which were then used to calculate CG volume fraction, PSA density, and PSA density adjusted by CG volume. These quantities were used to differentiate patients with and without PCa. Area under the receiver operating characteristic curve (AUC) was used as the figure of merit. RESULTS: The total prostate and CG volumes, CG volume fraction, and PSA density adjusted by the total prostate and CG volumes were statistically significantly different between patients with PCa and patients without PCa (P ≤ 0.007). AUC values for the total prostate and CG volumes, and PSA density adjusted by CG volume, were 0.68 ± 0.04, 0.68 ± 0.04, and 0.66 ± 0.04, respectively, and were significantly better than that of PSA (P < 0.02), for differentiation of PCa patients from patients without PCa. CONCLUSION: The total prostate and CG volumes estimated from T2 -weighted MR images and PSA density adjusted by these volumes can improve the effectiveness of PSA for the diagnosis of PCa and differentiation of high-Gleason-sum PCa patients from patients without PCa.


Assuntos
Biomarcadores Tumorais/sangue , Diagnóstico por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Lung Cancer ; 89(1): 43-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25936471

RESUMO

OBJECTIVES: Whole-body metabolic tumor volume (MTVWB) has been shown of prognostic value for non-small cell lung cancer (NSCLC) beyond that of TNM stage, age, gender, performance status, and treatment selection. The current TNM staging system does not incorporate tumor volumetric information. We propose a new PET/CT volumetric prognostic (PVP) index that combines the prognostic value of MTVWB and TNM stage. MATERIALS AND METHODS: Based on 328 consecutive NSCLC patients with a baseline PET/CT scan before treatment, from which MTVWB was measured semi-automatically, we estimated hazard ratios (HRs) for ln(MTVWB) and TNM stage from a Cox proportional hazard regression model that consisted of only ln(MTVWB) and TNM stage as prognostic variables of overall survival. We used the regression coefficients, which gave rise to the HRs, as weights to formulate the PET/CT volumetric prognostic (PVP) index. We also compared the prognostic value of the PVP index against that of TNM stage alone and ln(MTVWB) alone with univariate and multivariate survival analyses and C-statistics. RESULTS: Univariate analysis C-statistic for the PVP index (C=0.71) was statistically significantly greater than those for TNM stage alone (C=0.67, p<0.01) and for ln(MTVWB) alone (C=0.69, p=0.033). Multivariate analyses showed that the PVP index yielded significantly greater discriminatory power (C=0.74) than similar models based on either TNM stage (C=0.72, p<0.01) or ln(MTVWB) (C=0.73, p<0.01). Lower values of the PVP index were associated with significantly better overall survival (adjusted HR=2.70, 95%CI [2.16, 3.37]). CONCLUSION: The PVP index provides a practical means for clinicians to combine the prognostic value of MTVWB and TNM stage and offers significantly better prognostic accuracy for overall survival of NSCLC patients than the current TNM staging system or metabolic tumor burden alone.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Imagem Corporal Total , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Taxa de Sobrevida , Carga Tumoral
20.
Nucl Med Commun ; 36(8): 782-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25888358

RESUMO

PURPOSE: Metabolic tumor burden (MTB) measurements including metabolic tumor volume and total lesion glycolysis have been shown to have prognostic value in non-small-cell lung cancer (NSCLC). The calculation of MTB typically utilizes software to semiautomatically draw volumes of interest around the tumor, which are subsequently manually adjusted by the radiologist to include the entire tumor. The manual adjustment step can be time-consuming and observer-dependent. We compared the agreement of MTB values obtained using the semiautomatic method with and without manual adjustment in NSCLC patients. METHODS: This IRB-approved prospective study included 134 patients with histologically proven NSCLC who underwent fluorine-18 fluorodeoxyglucose PET/computed tomography. The MTB of the primary tumor was measured with a semiautomatic gradient-based method without manual adjustment (the semiautomatic gradient method) and with manual adjustment (the manually adjusted semiautomatic gradient method) by two radiologists using the MIM PETedge tool. The paired t-test, Wilcoxon signed-rank test, and concordance correlation coefficient (CCC) were calculated to evaluate the agreement between MTB measures obtained with these two methods, as well as agreement between the two radiologists for each method. RESULTS: Maximum standardized uptake value was identical between the two methods. No statistically significant difference was present for peak standardized uptake value, metabolic tumor volume, and total lesion glycolysis values between the two methods (P=0.23, 0.45, and 0.37, respectively). Excellent agreement between the two methods was found in terms of CCC (CCC>0.98 for all measures). Interobserver reliability was excellent for all measures (CCC>0.90). CONCLUSION: The semiautomatic gradient-based tumor-segmentation method can be used without the additional manual adjustment step for MTB quantification of primary NSCLC tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico , Imagem Multimodal , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Software , Tomografia Computadorizada por Raios X , Adulto Jovem
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