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The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC, n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-ß signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-ß signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-ß signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC.
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Neoplasias Gástricas , Animales , Ratones , Humanos , Neoplasias Gástricas/patología , Transición Epitelial-Mesenquimal/genética , Perfilación de la Expresión Génica , Transcriptoma , Modelos Animales de Enfermedad , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genéticaRESUMEN
PURPOSE: Advancements in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) as a standard care in cancer therapy have been limited. This study is aimed to investigate the clinical availability of 5-aminolevulinic acid (5-ALA)-based PDD and PDT in glioblastoma (GBM) patient-derived tumorspheres (TSs) and mouse orthotopic xenograft model. METHODS: PDT was performed using a 635 nm light-emitting diode (LED). Transcriptome profiles were obtained from microarray data. For knockdown of C5α, siRNA was transfected into tumor mesenchymal stem-like cells (tMSLCs). The invasiveness of TSs was quantified using collagen-based 3D invasion assays. RESULTS: Treatment with 1 mM 5 ALA induced distinct protoporphyrin IX (PpIX) fluorescence in GBM TSs, but not in non-tumor cells or tissues, including tMSLCs. These observations were negatively correlated with the expression levels of FECH, which catalyzes the conversion of accumulated PpIX to heme. Furthermore, the 5-ALA-treated GBM TSs were sensitive to PDT, thereby significantly decreasing cell viability and invasiveness. Notably, the effects of PDT were abolished by culturing TSs with tMSLC-conditioned media. Transcriptome analysis revealed diverse tMSLC-secreted chemokines, including C5α, and their correlations with the expression of stemness- or mesenchymal transition-associated genes. By adding or inhibiting C5α, we confirmed that acquired resistance to PDT was induced via tMSLC-secreted C5α. CONCLUSIONS: Our results show substantial therapeutic effects of 5-ALA-based PDT on GBM TSs, suggesting C5α as a key molecule responsible for PDT resistance. These findings could trigger PDT as a standard clinical modality for the treatment of GBM.
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Glioblastoma , Fotoquimioterapia , Humanos , Animales , Ratones , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/patología , Fotoquimioterapia/métodos , Línea Celular Tumoral , Protoporfirinas/farmacología , Protoporfirinas/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
[This corrects the article on p. 57 in vol. 64.].
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PURPOSE: The positron emission tomography (PET)-magnetic resonance (MR) system is a newly emerging technique that yields hybrid images with high-resolution anatomical and metabolic information. With PET-MR imaging, a definitive diagnosis of breast abnormalities will be possible with high spatial accuracy and images will be acquired for the optimal fusion of anatomic locations. Therefore, we propose a PET-compatible two-channel breast MR coil with minimal disturbance to image acquisition which can be used for simultaneous PET-MR imaging in patients with breast cancer. MATERIALS AND METHODS: For coil design and construction, the conductor loops of the Helmholtz coil were tuned, matched, and subdivided with nonmagnetic components. Element values were optimized with an electromagnetic field simulation. Images were acquired on a GE 600 PET-computed tomography (CT) and GE 3.0 T MR system. For this study, we used the T1-weighted image (volunteer; repetition time (TR), 694 ms; echo time (TE), 9.6 ms) and T2-weighted image (phantom; TR, 8742 ms; TE, 104 ms) with the fast spin-echo sequence. RESULTS: The results of measuring image factors with the proposed radiofrequency (RF) coil and standard conventional RF coil were as follows: signal-to-noise ratio (breast; 207.7 vs. 175.2), percent image uniformity (phantom; 89.22%-91.27% vs. 94.63%-94.77%), and Hounsfield units (phantom; -4.51 vs. 2.38). CONCLUSIONS: Our study focused on the feasibility of proposed two-channel Helmholtz loops (by minimizing metallic components and soldering) for PET-MR imaging and found the comparable image quality to the standard conventional coil. We believe our work will help significantly to improve image quality with the development of a less metallic breast MR coil.
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Artefactos , Mama , Mama/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Fantasmas de Imagen , Tomografía de Emisión de PositronesRESUMEN
RATIONALE AND OBJECTIVES: To compare the diagnostic ability of modified Dixon (mDixon) turbo spin echo (TSE) T1-weighted (T1W) shoulder magnetic resonance arthrography (MRA) with that of conventional shoulder MRA, and evaluate the feasibility of mDixon TSE in-phase (IP) images in measuring the fat fraction and size of rotator cuff muscles. MATERIALS AND METHODS: This retrospective study included 57 patients who underwent 3T shoulder MRA examinations with conventional and mDixon TSE T1W images (mean age: 56.7 years; range: 20-78 years). Two musculoskeletal radiologists independently evaluated the rotator cuff tendons with fat saturated T1W images and mDixon TSE T1W water images. Occupation ratios measured on T1W and mDixon TSE T1W IP images were compared. The fat fraction of the supraspinatus from the mDixon TSE T1W images was calculated and correlated with fatty infiltration of the supraspinatus on T1W images. RESULTS: For tendon pathology, the kappa value for inter-sequence and inter-reader agreement was 0.957 (95% confidence interval [CI]: 0.923-0.990) and 0.839 (95% CI: 0.778-0.899), respectively. For retear, the kappa value for inter-sequence and inter-reader agreement was 0.913 (95% CI: 0.796-1.000) and 0.779 (95% CI: 0.594-0.963), respectively. The intraclass correlation coefficient for both occupation ratios was 0.986 (95% CI: 0.973-0.993). Comparison of mDixon TSE T1W fat fraction with Goutallier grade showed a strong positive linear correlation (râ¯=â¯0.929). CONCLUSIONS: The mDixon TSE T1W sequence is a good alternative to conventional sequences in shoulder MRA for evaluating rotator cuff pathology. Furthermore, this sequence provides information on the size and fat infiltration of rotator cuff muscles.
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Lesiones del Manguito de los Rotadores , Manguito de los Rotadores , Adulto , Anciano , Artrografía , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Persona de Mediana Edad , Estudios Retrospectivos , Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Hombro , Adulto JovenRESUMEN
BACKGROUND: Developing personalized strategies for cancer has shown good efficacies. METHODS: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. RESULTS: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). CONCLUSIONS: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.
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Antígeno B7-H1/biosíntesis , Fosfatidilinositol 3-Quinasa Clase I/genética , Liposarcoma/genética , Liposarcoma/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/inmunología , Fosfatidilinositol 3-Quinasa Clase I/inmunología , Estudios de Cohortes , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica , Liposarcoma/patología , Liposarcoma/cirugía , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To assess the clinical utility of a prototype sequence for metal artifact reduction, the multiacquisition variable-resonance image combination selective (MAVRIC-SL) at 3 T. This sequence allows a surgical prosthesis-dependent reduction in the number of spectral bins. We compared the prototype MAVRIC SL to the conventional two-dimensional fast spin-echo (FSE) sequences and MAVRIC SL images acquired with all spectral bins to those acquired with the optimized number of spectral bins. METHODS: MAVRIC SL images were acquired in 25 image sets from August 2017 to April 2018. For each subject, the optimized number of spectral bins was determined using a short spectral calibration scan. The image sets obtained with magnetic resonance imaging that were used for the analysis consisted of MAVRIC-SL proton density (PD)-weighted or short inversion time inversion recovery (STIR) images acquired with all 24 spectral bins, the corresponding images with the optimized number of spectral bins, and the conventional two-dimensional FSE or STIR PD-weighted images. A musculoskeletal radiologist reviewed and scored the images using a five-point scale for artifact reduction around the prosthesis and visualization of the prosthesis and peri-prosthetic tissues. Quantitative evaluation of the peri-prosthetic tissues was also performed. The Wilcoxon rank-sum test was used to test for significance. RESULTS: The MAVRIC SL images enabled a significantly improved reduction in metallic artifacts compared to the conventional two-dimensional FSE sequences. The optimized number of spectral bins ranged from 6 to 20, depending on the prosthesis susceptibility difference, size, and orientation to the B0 field. The scan times significantly decreased with a reduced number of spectral bins (354.0 ± 139.1 versus 283.0 ± 89.6 s; 20% reduced scan time; p < .05). Compared to the MAVRIC SL images acquired with all 24 bins, the artifact reduction and visualization of the prosthesis and peri-prosthetic tissues on the MAVRIC SL images acquired with calibrated bins were not significantly different. CONCLUSIONS: Compared to the MAVRIC SL images acquired with all 24 spectral bins, those acquired with an optimized number of spectral bins can reduce metallic artifacts with no significant image quality degradation while providing reduced scan time.
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Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Artefactos , Calibración , Humanos , Prótesis e ImplantesRESUMEN
A gold nanoparticle-based localized surface plasmon resonance substrate has been developed as nano-sensors for various bio-applications. However, reproducible and robust sensing substrates anchored gold nanoparticles has not yet been explored. In this study, dopamine-coated gold nanorods (DGNRs) were prepared and immobilized onto the micro-grooving PDMS substrates (mgPDMS). Subsequently, HER2-specific aptamers were conjugated with DGNR/mgPDMS for ECD-HER2 detection. By screening of the optimal concentration of DGNR and aptamers, the effective HER2-specific aptasensor was built up. In particular, the real-time binding assay for the evaluation of limit-of-detection (<5 ng ml-1) was conducted. Furthermore, the binding kinetics for ECD-HER2 was investigated under the biological fluid using a rat serum. Our HER2-specific aptasensor demonstrated the effective sensitivity and selectivity for ECD-HER2.
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Aptámeros de Nucleótidos/química , Dopamina/química , Receptor ErbB-2/análisis , Animales , Técnicas Biosensibles , Oro , Límite de Detección , Masculino , Nanopartículas del Metal , Ratas , Receptor ErbB-2/sangre , Resonancia por Plasmón de SuperficieRESUMEN
Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal system defects because of its higher soft-tissue contrast and spatial resolution. With the recent development of MRI-related technology, faster imaging and various image plane reconstructions are possible, enabling better assessment of three-dimensional musculoskeletal anatomy and lesions. Furthermore, the image quality, diagnostic accuracy, and acquisition time depend on the MRI protocol used. Moreover, the protocol affects the efficiency of the MRI scanner. Therefore, it is important for a radiologist to optimize the MRI protocol. In this review, we will provide guidance on patient positioning; selection of the radiofrequency coil, pulse sequences, and imaging planes; and control of MRI parameters to help optimize the MRI protocol for the six major joints of the musculoskeletal system.
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OBJECTIVES: To investigate the feasibility of three-dimensional fast spin echo (3D-FSE) imaging with compressed sensing (CS) and parallel imaging (PI) compared to 3D-FSE imaging with only PI in evaluating ankle joint pathologies. MATERIALS AND METHODS: Twenty consecutive patients underwent ankle magnetic resonance imaging (MRI), including acquisition of image sets of 2D-FSE sequences, and 3D-FSE sequences without and with CS, between June 2016 and November 2017. Three MR image sets were independently rated by two radiologists for the presence/absence of ankle pathology. Quantitative image similarity and subjective image quality were evaluated using 3D-FSE images without CS and those with CS-PI. Inter-sequence agreement between 3D-FSE sequences without CS and with CS-PI in both readers was evaluated. RESULTS: Interobserver agreements were nearly perfect for sprain of the anterior talofibular ligament (ATFL, κ=0.77), osteochondral lesion of the talus (OLT, κ=0.76-0.88), osteochondral lesion of the distal tibia (OLTi, κ=0.74) and os subfibulare (OSF, κ=0.62-0.64). The structural similarity index (mean, 0.996; range, 0.990-0.997) between the 3D-FSE sequences without CS and with CS-PI was acceptable. There was no significant difference in subjective image quality between the two imaging sequences (ATFL, p = 0.317; bone marrow, p = 0.083; cartilage, p = 1.000, tendon, p = 1.000). Intersequence agreement between the 3D-FSE sequences with and without CS was nearly perfect (ATFL and OLTi, κ=1.00; OLT, κ=0.87-0.96; OSF, κ=0.62-0.64) in both readers. CONCLUSIONS: Isotropic 3D-FSE ankle MRI with CS provides acceptable diagnostic performance with reduced scan time. Compressed sensing-related artifacts could be minimized with CS reconstruction enhancement, allowing for better image quality for evaluating ankle joint pathologies.
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Articulación del Tobillo/patología , Artropatías/patología , Adulto , Artefactos , Estudios de Factibilidad , Femenino , Humanos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Presión , Sensibilidad y Especificidad , Astrágalo/patologíaRESUMEN
Herein, we report a de novo synthesis approach to produce bandgap-controlled polyaniline (PAni) nanostructure via Mn-mediated oxidative polymerization at the catalytic nanoreactor. To achieve systemic nanoconfined polymerization, manganese oxide (MnOx) nanoparticles coated with silica were used as the sacrificial nanotemplate. Interestingly, the catalytic nanoreactor simultaneously allowed the nanoconfined oxidative polymerization and controlling of the bandgap. MnOx could be reduced by the addition of aniline monomers and consecutive redox reaction at the nanoreactor. Furthermore, core cavity was generated, and ionized Mn could control the bandgap by coordination at the nanostructures.
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OBJECTIVES: To investigate the agreement between double-inversion recovery (DIR) with synthetic magnetic resonance imaging (MRI) and T1-weighted contrast-enhanced (CE)-MRI for the assessment of knee synovitis. METHODS: T1-weighted CE-MRI and synthetic MRI of 30 patients were compared. Synthetic DIR image reconstruction was performed with two inversion times (280-330 ms and 2800-2900 ms). Subjective image quality, visibility of synovium, detection of synovitis, and total synovitis score in the knee joint were evaluated on both MR images. The relative signal intensity (SI) and relative contrast of synovium, joint effusion, and bone marrow for two imaging were assessed. Differences in data between two imaging were assessed by using Wilcoxon's signed-rank test and chi-square test/Fisher's exact test. Interobserver agreement was expressed as weighted kappa value. Accuracy of synthetic DIR image was calculated by using CE-MRI as reference standard. RESULTS: T1-weighted CE-MRI yielded better image quality than synthetic DIR imaging (p < 0.001). Interobserver agreements for detecting synovitis diagnosis/sum of the synovitis score were moderate to almost perfect (κ = 0.58/0.44, synthetic DIR; κ = 0.83/0.65, T1-weighted CE-MRI). There were no statistical differences in visibility of synovium (p = 0.058-0.190), detection of synovitis (p < 0.001), and relative SI of structures between two imaging (p = 0.086-0.360). Synovium-to-effusion contrast was higher in synthetic DIR (p = 0.003) and synovium-to-bone marrow contrast was higher in CE-MRI (p < 0.001). CONCLUSION: Synthetic DIR imaging showed a moderate degree of interobserver agreement and good accuracy for detecting synovitis. Though it has limitations, it may play a role in imaging of degenerative joint disease or larger cohort scientific studies where gadolinium application is not feasible. KEY POINTS: ⢠Synthetic double-inversion recovery (DIR) imaging avoids the use of contrast agent. ⢠There was no significant difference between T1-weighted CE-MRI and synthetic DIR imaging in evaluating presence of synovitis in knee joint. ⢠Synthetic DIR imaging showed moderate degree of interobserver agreement and good accuracy for detecting synovitis compared to CE-MRI, and it may facilitate evaluation of some regions of peripatellar synovitis.
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Procesamiento de Imagen Asistido por Computador , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Membrana Sinovial/patología , Sinovitis/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Curva ROC , Adulto JovenRESUMEN
BACKGROUND: We retrospectively investigated the treatment outcomes of second-line treatment with pazopanib or gemcitabine/docetaxel in patients with advanced soft tissue sarcoma (STS). METHODS: Ninety-one patients who were treated with pazopanib or gemcitabine/docetaxel for advanced STS between 1995 and 2015 were analyzed. RESULTS: Forty-six and 45 patients received pazopanib and gemcitabine/docetaxel, respectively. The median progression-free survival for the group treated with pazopanib was 4.5 months compared with 3.0 months for the gemcitabine/docetaxel group (p = 0.593). The median overall survival for the group treated with pazopanib was 12.6 months compared with 14.2 months for the gemcitabine/docetaxel group (p = 0.362). The overall response rates (ORRs) were 6.5 and 26.7% in the pazopanib and gemcitabine/docetaxel groups, respectively. The following parameters had ORRs favoring gemcitabine/docetaxel: age ≥50 years (31.6 vs. 2.9%, p = 0.006), histologic grade 1-2 (40.9 vs. 0%, p = 0.001), and poor first-line treatment response (23.3 vs. 3.0%, p = 0.022). Gemcitabine/docetaxel was associated with better ORRs for the following histologic subtypes: leiomyosarcoma (p = 0.624), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (p = 0.055), and angiosarcoma (p = 0.182). However, the ORR of synovial sarcoma favored pazopanib (p = 0.99). CONCLUSIONS: The efficacies of pazopanib and gemcitabine/docetaxel as second-line treatments after doxorubicin or ifosfamide failure differed among clinical and histologic subgroups and appeared to facilitate a more personalized treatment approach for advanced STS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Docetaxel/administración & dosificación , Docetaxel/efectos adversos , Femenino , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Pirimidinas/efectos adversos , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/patología , Sulfonamidas/efectos adversos , Adulto Joven , GemcitabinaRESUMEN
The objectives of this study were to compare the ultrashort T2* relaxation time with the T2* relaxation time using the 3 dimensional (3D) cones sequence in 3 groups of patients with normal, degenerated, and torn knee menisci, and to demonstrate the additional effect of the ultrashort echo time (UTE) signal intensity.Following institutional review board approval, 42 knee magnetic resonance imaging (MRI) scans of 42 patients who presented with knee pain and underwent knee MRIs, with the 3D Cones of UTE sequence (minimum TEs: 32âµs) and a 3T MRI scanner (Discovery 750, GE Healthcare, Waukesha, WI), were analyzed. The enrolled patients were classified into 3 subgroups:normal meniscus on conventional MRI, with no positive meniscus-related physical examination in medical records;meniscal degeneration with signal changes on conventional MRI; andmeniscal tear.For the quantitative assessment, the mean values inside user-drawn regions of interest (ROIs) of the medial menisci were drawn on UTE T2* map and T2* map. For statistical analyses, 1-way analysis of variance (ANOVA) with post-hoc analysis using the Tukey HSD test was conducted to compare groups, and effect size was used to compare the discrimination power.The ultrashort T2* relaxation times were higher in patients with meniscal tear than in those with normal and degeneration groups (Pâ<.05, respectively) whereas T2* relaxation times were not statistically significantly different. The ultrashort T2* relaxation times showed higher effect sizes than the T2* times between tear and normal/degeneration.The ultrashort T2* relaxation times showed better delineation of meniscal degeneration or tears than T2* relaxation times. The ultrashort T2* relaxation times could be more sensitive at differentiating between normal and pathologic meniscal conditions in patients.
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Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Menisco/diagnóstico por imagen , Relajación/fisiología , Lesiones de Menisco Tibial/diagnóstico por imagen , Adolescente , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Masculino , Menisco/fisiopatología , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Lesiones de Menisco Tibial/fisiopatología , Factores de Tiempo , Adulto JovenRESUMEN
Biophysical properties are intimately connected to metastatic functions and aggressiveness in cancers. Especially, cellular stiffness is regarded as a biomarker for the understanding of metastatic potential and drug sensitivity. Here, protease-mediated changes of cortical stiffness are identified due to the deformation of cytoskeleton alignment at a cortex. For the past few decades, membrane type 1-matrix metalloproteinase (MT1-MMP) has been well known as a kernel protease enriched in podosomes during metastasis for extracellular matrix degradation. However, the biophysical significance of MT1-MMP expressing cancer cells is still unknown. Therefore, the nanomechanics of cancer cells is analyzed by a nanoindentation using a microsphere-attached cantilever of atomic force microscopy (AFM). In conclusion, the results suggest that MT1-MMP has contributed as a key regulator in cytoskeletal deformation related with cancer metastasis. Particularly, the AFM-based nanoindentation system for the monitoring of cortical nanomechanics will be crucial to understand molecular networks in cancers.
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Metaloproteinasa 14 de la Matriz/química , Microesferas , Citoesqueleto/química , Microscopía de Fuerza AtómicaRESUMEN
The aim of this study was the development of a human epidermal growth factor receptor 2 (HER2)-targetable contrast agent for magnetic resonance imaging (MRI) with a high magnetic sensitivity. An anti-HER2 aptamer-modified magnetic nanosensitizer (AptHER2-MNS) was prepared by conjugation with 5'-thiol-modified aptamers and maleimidylated magnetic nanocrystals (MNCs). The physicochemical characteristics and targeting ability of AptHER2-MNS were confirmed, and the binding affinity (Kd) onto HER2 protein of AptHER2-MNS was 0.57 ± 0.26 nM. In vivo MRI contrast enhancement ability was also verified at HER2+ cancer cell (NIH3T6.7)-xenograft mouse models (n = 3) at 3T clinical MRI instrument. The control experiment was carried out using non-labeled MNCs. The results indicated that up to 150% contrast enhancement was achieved at the tumor region in the T2-weighted MR images after the injection of the AptHER2-MNS agent in mice that received the NIH3T6.7 cells.
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We investigated the water contents in several organ tissues such as the liver, spleen, kidney, and brain tissue of rats using the terahertz spectroscopic imaging technique. The water contents of the tissues were determined by using a simple equation containing the absorption coefficients of fresh and lyophilized tissues and water. We compared the measured water contents with the difference in mass of tissues before and after lyophilization. All results showed a good match except for the kidney, which has several Bowman's capsules.
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Objective: To evaluate the feasibility of synthetic magnetic resonance imaging (MRI) compared to conventional MRI for the diagnosis of internal derangements of the knee at 3T. Materials and Methods: Following Institutional Review Board approval, image sets of conventional and synthetic MRI in 39 patients were included. Two musculoskeletal radiologists compared the image sets and qualitatively analyzed the images. Subjective image quality was assessed using a four-grade scale. Interobserver agreement and intersequence agreement between conventional and synthetic images for cartilage lesions, tears of the cruciate ligament, and tears of the meniscus were independently assessed using Kappa statistics. In patients who underwent arthroscopy (n = 8), the sensitivity, specificity, and accuracy for evaluated internal structures were calculated using arthroscopic findings as the gold standard. Results: There was no statistically significant difference in image quality (p = 0.90). Interobserver agreement (κ = 0.649- 0.981) and intersequence agreement (κ = 0.794-0.938) were nearly perfect for all evaluated structures. The sensitivity, specificity, and accuracy for detecting cartilage lesions (sensitivity, 63.6% vs. 54.6-63.6%; specificity, 91.9% vs. 91.9%; accuracy, 83.3-85.4% vs. 83.3-85.4%) and tears of the cruciate ligament (sensitivity, specificity, accuracy, 100% vs. 100%) and meniscus (sensitivity, 50.0-62.5% vs. 62.5%; specificity, 100% vs. 87.5-100%; accuracy, 83.3-85.4% vs. 83.3-85.4%) were similar between the two MRI methods. Conclusion: Conventional and synthetic MRI showed substantial to almost perfect degree of agreement for the assessment of internal derangement of knee joints. Synthetic MRI may be feasible in the diagnosis of internal derangements of the knee.
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Traumatismos de la Rodilla/diagnóstico , Imagen por Resonancia Magnética , Lesiones de Menisco Tibial/diagnóstico , Adulto , Anciano , Artroscopía , Estudios de Factibilidad , Femenino , Humanos , Traumatismos de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Ligamentos Articulares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Lesiones de Menisco Tibial/diagnóstico por imagen , Adulto JovenRESUMEN
The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitative MRI (QRAPMASTER) sequence for the quantitative assessment of knee cartilage. The T2 values from the phantom study showed excellent correlation between the two techniques (r2 = 0.998). The cartilage T2 values exhibited strong correlations (r2 = 0.867-0.982). Quantitative MRI (qMRI) T2 mapping can be used as an alternative to multi-echo T2 mapping, with relatively short scan time.