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Adagrasib (MRTX849), an approved and promising KRAS G12C inhibitor, has shown the promising results for treating patients with advanced non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) harboring KRAS-activating mutations. However, emergence of the acquired resistance limits its long-term efficacy and clinical application. Further understanding of the mechanism of the acquired resistance is crucial for developing more new effective therapeutic strategies. Herein, we firstly found a new connection between the acquired resistance to MRTX849 and nuclear factor erythroid 2-related factor 2 (Nrf2). The expression levels of Nrf2 and GLS1 proteins were substantially elevated in different CRC cell lines with the acquired resistance to MRTX849 in comparison with their corresponding parental cell lines. Next, we discovered that RA-V, one of natural cyclopeptides isolated from the roots of Rubia yunnanensis, could restore the response of resistant CRC cells to MRTX849. The results of molecular mechanisms showed that RA-V suppressed Nrf2 protein through the ubiquitin-proteasome-dependent degradation, leading to the induction of oxidative and ER stress, and DNA damage in CRC cell lines. Consequently, RA-V reverses the resistance to MRTX849 by inhibiting the Nrf2/GLS1 axis, which shows the potential for further developing into one of novel adjuvant therapies of MRTX849.
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Neoplasias Colorrectales , Factor 2 Relacionado con NF-E2 , Péptidos Cíclicos , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Línea Celular Tumoral , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Antineoplásicos Fitogénicos/farmacología , Ratones DesnudosRESUMEN
BACKGROUND: Chronic eosinophilic leukemia (CEL) is a rare invasive disease characterized by non-specific cytogenetic abnormalities or elevated mother cells, poor prognosis, and a high risk of conversion to acute leukemia. METHODS: We described the data of a patient with CEL-NOS. RESULTS: This case is a CEL-NOS with four mutations in CSF3R-T618I, DNMT3A Q816, ASXL1, and IDH2. CONCLUSIONS: The patient rapidly evolves into secondary acute myeloid leukemia (AML).
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Síndrome Hipereosinofílico , Leucemia Mieloide Aguda , Leucemia , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Transducción de Señal , Mutación , Células Clonales , Pronóstico , Receptores del Factor Estimulante de Colonias/genéticaRESUMEN
BACKGROUND: The aim of this study was to evaluate the therapeutic regimen of a patient with myelodysplastic syndrome (MDS) who developed invasive fungal infections caused by drug-resistant Candida tropicalis after chemotherapy and to investigate the effect of drug treatment. METHODS: We referred to the Diagnostic Criteria and Treatment Principles of invasive fungal diseases in patients with hematological diseases and malignant tumors (2013, fourth revised edition) and the Expert Consensus on Clinical Application of Posaconazole (2022 Edition). In addition, the drug treatment regimens of drug-resistant Candida tropicalis were reviewed. The doctors in charge were involved in the drug treatment process, and the ra-tional drug use was selected according to evidence-based medicine. RESULTS: After 4 months of use, the nodules around the body disappeared, and there was no further fever during follow-up. After 6 months of use, posaconazole was discontinued, and the patient continued to follow-up for 1 month without further fever or nodules. CONCLUSIONS: The combination of posaconazole, amphotericin B liposome, and micafungin is effective in the treatment of fluconazole-resistant Candida tropicalis infection.
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Anfotericina B , Antifúngicos , Farmacorresistencia Fúngica , Síndromes Mielodisplásicos , Triazoles , Humanos , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/complicaciones , Antifúngicos/uso terapéutico , Triazoles/uso terapéutico , Triazoles/administración & dosificación , Anfotericina B/uso terapéutico , Candida tropicalis/efectos de los fármacos , Masculino , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/microbiología , Micafungina/uso terapéutico , Micafungina/administración & dosificación , Anciano , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 has a relatively favorable prognosis with a high complete remission rate and long disease-free survival. METHODS AND RESULTS: Here we describe a patient who had AML with t(8;21)(q22;q22.1); RUNX1::RUNX1T1. Cooperating mutations including KRAS and ASXL1, and with other abnormal karyotype del(17) and with a myelomonocytic differentiation. CONCLUSIONS: The patient relapsed despite achieving a morphologic complete remission (CR).
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Leucemia Mieloide Aguda , Translocación Genética , Humanos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Proteína 1 Compañera de Translocación de RUNX1/genética , Leucemia Mieloide Aguda/genética , MutaciónRESUMEN
OBJECTIVE: To distinguish geniculate ganglion venous malformation (GGVM) from schwannoma (GGS) by using high-resolution CT (HRCT), routine MRI, and dynamic T1-weighted imaging (T1WI) characteristics. METHODS: Surgically confirmed GGVMs and GGSs between 2016 and 2021 were retrospectively included. Preoperative HRCT, routine MR, and dynamic T1WI were performed on all patients. Clinical data, imaging characteristics including lesion size, involvement of facial nerve (FN), signal intensity, enhancement pattern on dynamic T1WI, and bone destruction on HRCT were evaluated. Logistic regression model was developed to identify independent factors for GGVMs, and the diagnostic performance was accessed by receiving operative curve (ROC) analysis. Histological characteristics were explored for both GGVMs and GGSs. RESULTS: Twenty GGVMs and 23 GGSs with mean age of 31 were included. On dynamic T1WI, 18 GGVMs (18/20) showed "pattern A" enhancement (a progressive filling enhancement), while all 23 GGSs showed "pattern B" enhancement (a gradual whole-lesion enhancement) (p < 0.001). Thirteen GGVMs (13/20) showed the "honeycomb" sign whereas all GGS (23/23) showed extensive bone changes on HRCT (p < 0.001). Lesion size, involvement of FN segment, signal intensity on non-contrast T1WI and T2-weighted imaging (T2WI), and homogeneity on enhanced T1WI were obviously differed between two lesions (p < 0.001, p = 0.002, p < 0.001, p = 0.01, p = 0.02, respectively). Regression model showed the "honeycomb" sign and "pattern A" enhancement were independent risk factors. Histologically, GGVM was characterized by interwoven dilated and tortuous veins, while GGS was characterized by abundant spindle cells with dense arterioles or capillaries. CONCLUSIONS: The "honeycomb" sign on HRCT and "pattern A" enhancement on dynamic T1WI are the most promising imaging characteristics for differentiating GGVM from GGS. CLINICAL RELEVANCE STATEMENT: The characteristic sign and enhancement pattern on HRCT and dynamic T1-weighted imaging allow preoperative differentiation of geniculate ganglion venous malformation and schwannoma feasible, which will improve clinical management and benefit patient prognosis. KEY POINTS: ⢠The "honeycomb" sign on HRCT is a reliable finding to differentiate GGVM from GGS. ⢠GGVM typically shows "pattern A" enhancement (focal enhancement of the tumor on early dynamic T1WI, followed by progressive contrast filling of the tumor in the delayed phase), while "pattern B" enhancement (gradual heterogeneous or homogeneous enhancement of the whole lesion) is observed in GGS on dynamic T1WI.
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Neurilemoma , Enfermedades Vasculares , Humanos , Adulto , Ganglio Geniculado/diagnóstico por imagen , Ganglio Geniculado/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Neurilemoma/diagnóstico por imagen , Neurilemoma/patología , Diferenciación CelularRESUMEN
Inflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases.
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Colitis , Enfermedades Inflamatorias del Intestino , Animales , Colitis/tratamiento farmacológico , Colon/metabolismo , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Estrés OxidativoRESUMEN
OBJECTIVE: The objective of this study was to determine the diagnostic value of quantitative border irregularity assessment and apparent diffusion coefficient (ADC) in patients with squamous cell carcinoma of the tongue (SCCT). METHODS: Cervical lymph nodes (n = 192) from 63 patients with SCCT were examined preoperatively by magnetic resonance imaging, including routine head and neck sequences, dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging, ADC, surface regularity (SR), and visually assessed variables, and evaluated pathologically after surgery. RESULTS: Necrosis, lymphatic hilum, unclear margin, higher SR, long to short axis ratio, and ADC were associated with metastasis in cervical lymph nodes (M-cLNs) and extranodal extension (ENE), and thickened nodal rim with ENE alone. Apparent diffusion coefficient, SR, unclear margin, and visible necrosis were strongly associated with M-cLN, whereas SR, unclear margin, and visible necrosis were associated with ENE status on logistic regression analysis. CONCLUSIONS: Quantitative SR and ADC data greatly improved diagnosis of M-cLNs and ENE, relative to visible variables alone in patients with SCCT.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Neoplasias de la Lengua/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imágenes de Resonancia Magnética Multiparamétrica , Cuello , Adulto JovenRESUMEN
Elevated excitability of primary afferent neurons underlies chronic pain in patients with functional or inflammatory bowel diseases. Recent studies have established an essential role for an enhanced transient receptor potential vanilloid subtype 1 (TRPV1) signaling in mediating peripheral hyperalgesia in inflammatory conditions. Since colocalization of Toll-like receptor 4 (TLR4) and TRPV1 has been observed in primary afferents including the trigeminal sensory neurons and the dorsal root ganglion neurons, we test the hypothesis that TLR4 might regulate the expression and function of TRPV1 in primary afferent neurons in 2,4,6-trinitrobenzene sulfate (TNBS)-induced colitis using the TLR4-deficient and the wild-type C57 mice. Despite having a higher disease activity index following administration of 2,4,6-trinitrobenzene sulfate, the TLR4-deficient mice showed less inflammatory infiltration in the colon than the wild-type mice. Increased expression of TLR4 and TRPV1 as well as increased density of capsaicin-induced TRPV1 current was observed in L4-S2 dorsal root ganglion neurons of the wild-type colitis mice till two weeks post 2,4,6-trinitrobenzene sulfate treatment. In comparison, the TLR4-deficient colitis mice had lower TRPV1 expression and TRPV1 current density in dorsal root ganglion neurons with lower abdominal withdrawal response scores during noxious colonic distensions. In the wild type but not in the TLR4-deficient dorsal root ganglion neurons, acute administration of the TLR4 agonist lipopolysaccharide increased the capsaicin-evoked TRPV1 current. In addition, we found that the canonical signaling downstream of TLR4 was activated in 2,4,6-trinitrobenzene sulfate-induced colitis in the wild type but not in the TLR4-deficient mice. These results indicate that TLR4 may play a major role in regulation of TRPV1 signaling and peripheral hyperalgesia in inflammatory conditions.
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Colitis/patología , Ganglios Espinales/patología , Regulación de la Expresión Génica/fisiología , Neuronas/metabolismo , Canales Catiónicos TRPV/metabolismo , Receptor Toll-Like 4/deficiencia , Regulación hacia Arriba/fisiología , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Capsaicina/farmacología , Colitis/inducido químicamente , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratones Transgénicos , Factor 88 de Diferenciación Mieloide/metabolismo , Neuronas/efectos de los fármacos , Receptor Toll-Like 4/genética , Ácido Trinitrobencenosulfónico/toxicidadRESUMEN
BACKGROUND: Susceptibility weighted imaging (SWI) is helpful for depicting hemorrhage, calcification, and increased vascularity in some neoplasms, which may reflect tumor grade. In this study, we aimed to apply SWI in patients with oral tongue squamous cell carcinomas (OTSCCs) and relate multi-parametric effect to tumor histological grade prediction. METHODS: Preoperative MR examinations were performed on a 1 .5T MRI scanner with T1-, T2- and contrast-enhanced (CE) T1-weighted imaging. In addition to routine head and neck MRI sequences, SWI was performed. Tumor thickness and volume were measured. Intratumoral susceptibility signal intensities (ITSSs), ITSS score and ITSS ratio on SWI were evaluated and recorded. Subjects were sub-grouped into low- and high-grade according to the histological findings post operation. Parameters such as tumor thickness, tumor volume and three ITSS related parameters were compared between low- and high-grade groups. ROC analysis was performed on above parameters to access the capability in predicting tumor histological grade. Different multi-parametric models were run to access multi-parametric combination effect. RESULTS: Thirty patients with OTSCC were finally included in the study. Twenty of them were categorized as low-grade SCC and the other ten subjects were high-grade SCC according to the pathologic findings. No significant difference was seen for tumor thickness or tumor volume between two sub-groups. ITSSs were seen in 23/30 patients. Significant difference of ITSS scores between low- and high-grade OTSCCs was observed, with mean value of 0.95 ± 0.83 and 1.70 ± 0.95, respectively. Univariate ROC analysis demonstrated ITSSs, ITSS score and ITSS ratio were valuable parameters for predicting tumor histological grade and ITSSs was superior to the other two parameters, with an area under ROC curve of 0.790. Multi-parametric model using combination of ITSSs and tumor thickness would greatly improve the predictive capability in comparison with a univariate approach, yielding the area under ROC curve of 0.84(0.69,0.99). On contrast-enhanced SWI (CE-SWI), ITSSs were shown more clearly delineated in comparison with non-contrast enhanced SWI. CONCLUSIONS: In conclusion, SWI was superior in depiction of internal characteristics of OTSCCs, which would potentially provide more diagnostic information. Multi-parametric model using combination of ITSSs and tumor thickness would be valuable in predicting tumor histological grade.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Imagen por Resonancia Magnética/métodos , Neoplasias de la Lengua/diagnóstico por imagen , Neoplasias de la Lengua/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Carga Tumoral , Adulto JovenRESUMEN
Malignant gliomas are the most common primary brain tumors and are associated with aggressive growth, high morbidity, and mortality. Aberrant mesenchymal-epithelial transition factor (MET) activation occurs in approximately 30% of glioma patients and correlates with poor prognosis, elevated invasion, and increased drug resistance. Therefore, MET has emerged as an attractive target for glioma therapy. In this study, we developed a novel nanoinhibitor by conjugating MET-targeting cMBP peptides on the G4 dendrimer. Compared to the binding affinity of the free peptide ( KD = 3.96 × 10-7 M), the binding affinity of the nanoinhibitor to MET increased 3 orders of magnitude to 1.32 × 10-10 M. This nanoinhibitor efficiently reduced the proliferation and invasion of human glioblastoma U87MG cells in vitro by blocking MET signaling with remarkably attenuated levels of phosphorylated MET ( pMET) and its downstream signaling proteins, such as pAKT and pERK1/2. Although no obvious therapeutic effect was observed after treatment with free cBMP peptide, in vivo T2-weighted magnetic resonance imaging (MRI) showed a significant delay in tumor growth after intravenous injection of the nanoinhibitor. The medium survival in mouse models was extended by 59%, which is similar to the effects of PF-04217903, a small molecule MET inhibitor currently in clinical trials. Immunoblotting studies of tumor homogenate verified that the nanoinhibitor restrained glioma growth by blocking MET downstream signaling. pMET and its downstream proteins pAKT and pERK1/2, which are involved in the survival and invasion of cancer cells, decreased in the nanoinhibitor-treated group by 44.2%, 62.2%, and 32.3%, respectively, compared with those in the control group. In summary, we developed a peptide-functionalized MET nanoinhibitor that showed extremely high binding affinity to MET and effectively inhibited glioma growth by blocking MET downstream signaling. To the best of our knowledge, this is the first report of therapeutic inhibition of glioma growth by blocking MET signaling with a novel nanoinhibitor. Compared to antibodies and chemical inhibitors in clinical trials, the nanoinhibitor blocks MET signaling and provides a new approach for the treatment of glioma with the advantages of high efficiency, affordability, and, most importantly, potentially reduced drug resistance.
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Neoplasias Encefálicas/tratamiento farmacológico , Dendrímeros/uso terapéutico , Glioma/tratamiento farmacológico , Nanoconjugados/uso terapéutico , Péptidos/uso terapéutico , Proteínas Proto-Oncogénicas c-met/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dendrímeros/química , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Glioma/metabolismo , Glioma/patología , Humanos , Ratones , Nanoconjugados/química , Nylons/química , Péptidos/químicaRESUMEN
An efficient design for a quarter-wave (λ/4) retardation plate (QWP) operating at microwave frequencies has been designed and manufactured using dual head fused deposition modelling (FDM) 3D printing. Exploiting a bespoke composite material feedstock filament with high dielectric permittivity ϵr = 10.8, the resulting 3D-printed QWP comprising alternative layers of high and low permittivity had a high artificial double refraction of Δϵ = 2.9. The QWP provided broadband conversion of linear to circular polarization and phase modulation of an incident plane electromagnetic wave at 12-18 GHz, and demonstrated the potential for optical devices via additive manufacture for use in the microwave frequency range.
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BACKGROUND: The overlap of morphological feature and mean ADC value restricted clinical application of MRI in the differential diagnosis of orbital lymphoma and idiopathic orbital inflammatory pseudotumor (IOIP). In this paper, we aimed to retrospectively evaluate the combined diagnostic value of conventional magnetic resonance imaging (MRI) and whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in the differentiation of the two lesions. METHODS: In total, 18 patients with orbital lymphoma and 22 patients with IOIP were included, who underwent both conventional MRI and diffusion weighted imaging before treatment. Conventional MRI features and histogram parameters derived from ADC maps, including mean ADC (ADCmean), median ADC (ADCmedian), skewness, kurtosis, 10th, 25th, 75th and 90th percentiles of ADC (ADC10, ADC25, ADC75, ADC90) were evaluated and compared between orbital lymphoma and IOIP. Multivariate logistic regression analysis was used to identify the most valuable variables for discriminating. Differential model was built upon the selected variables and receiver operating characteristic (ROC) analysis was also performed to determine the differential ability of the model. RESULTS: Multivariate logistic regression showed ADC10 (P = 0.023) and involvement of orbit preseptal space (P = 0.029) were the most promising indexes in the discrimination of orbital lymphoma and IOIP. The logistic model defined by ADC10 and involvement of orbit preseptal space was built, which achieved an AUC of 0.939, with sensitivity of 77.30% and specificity of 94.40%. CONCLUSIONS: Conventional MRI feature of involvement of orbit preseptal space and ADC histogram parameter of ADC10 are valuable in differential diagnosis of orbital lymphoma and IOIP.
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Interpretación de Imagen Asistida por Computador/métodos , Linfoma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neoplasias Orbitales/diagnóstico por imagen , Seudotumor Orbitario/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The neuroprotective effect of ceria nanoparticles in the context of brain disorders has been explained by their antioxidant effect. However, the in-depth mechanism remains unknown. As resident immune cells in the brain, microglia exert a variety of functional reprogramming termed as polarization in response to stress stimuli. Herein, custom-made ceria nanoparticles were developed and found to scavenge multiple reactive oxygen species with extremely high efficiency. These nanoparticles drove microglial polarization from a pro-inflammatory phenotype to an anti-inflammatory phenotype under pathological conditions. Pretreatment of these nanoparticles changed the microglial function from detrimental to protective for the neuronal cells by blocking the pro-inflammatory signaling. This work not only helps to elucidate the mechanism of ceria-nanoparticle-mediated neuroprotection but also provides a new strategy to rebalance the immuno-environment by switching the equilibrium of the phenotypic activation of microglia.
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Microglía/efectos de los fármacos , Nanopartículas/química , Fármacos Neuroprotectores/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Ratones , Microglía/inmunología , Microglía/metabolismo , Fármacos Neuroprotectores/química , Tamaño de la Partícula , Fenotipo , Especies Reactivas de Oxígeno/metabolismo , Propiedades de SuperficieRESUMEN
BACKGROUND: Our aim was to identify the preoperative computed tomographic (CT) characteristics most efficient in predicting overall survival (OS) of patients with maxillary cancer (MC). METHODS: A retrospective review of CT images was performed in 115 patients with histopathologically confirmed primary MC from January 2005 to December 2013, who were classified into 2 subtypes (epithelial and non-epithelial) according to tissue of origin. The prognostic value of CT characteristics for OS was determined firstly through univariate Kaplan-Meier survival estimates with log-rank tests. Significant predictors were further tested with multivariable Cox proportional hazard models. RESULTS: CT characteristics predictive of OS in univariate survival analysis were long and short diameter of the mass, long and short diameter of the largest cervical lymph node and adjacent soft tissue infiltration (P < 0.05). In the multivariable Cox analyses, the significantly independent predictors were long diameter of mass ≥ 4.2 cm (hazard ratio [HR] 1.8; 95 % confidence interval [CI] 1.1-3.0) and short diameter of the largest lymph node ≥ 7 mm (HR 1.9; 95 % CI 1.0-3.6) for all MC patients, as well as for non-epithelial MC patients (HR 3.1; 95 % CI 1.2-8.0; HR 3.3; 95 % CI 1.3-8.7, respectively). CONCLUSIONS: Preoperative CT characteristics of tumor size, lymph node size and adjacent structure infiltration are predictive of the OS time of MC patients. The information brought up in this study could be used in clinical practice to inform about the possible prognosis, and be beneficial to clinical decision making.
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Neoplasias Maxilares/diagnóstico , Neoplasias Maxilares/mortalidad , Tomografía Computarizada por Rayos X , Adulto , Anciano , Terapia Combinada , Estudios Transversales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Neoplasias Maxilares/terapia , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the feasibility of using magnetic resonance (MR) imaging and single photon emission computed tomography (SPECT)/computed tomography (CT) to visualize the in vivo recruitment of iron oxide-labeled macrophages and indium 111 ((111)In)-labeled macrophages in inflammatory bowel disease (IBD) and to monitor disease activity. MATERIALS AND METHODS: This study had institutional animal care and use committee approval. Twenty-seven C57/B6 mice with dextran sodium sulfate (DSS)-induced IBD and control mice were included. Peritoneal macrophages were harvested from seven thioglycollate-treated mice and were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Macrophage iron content was determined by using inductively coupled plasma mass spectrometry. SPIO nanoparticle-labeled macrophages (5 × 10(6)) were intravenously administered. Mice with DSS-induced IBD (n = 8) and control mice (n = 6) were imaged with a 9.4-T MR imaging unit at 0, 5, and 24 hours after macrophage administration. Percentage normalized enhancement (NE) was calculated for the intestinal wall and liver 24 hours after injection. Six mice with IBD coinjected with SPIO nanoparticles and (111)In oxine-labeled macrophages were imaged with MR imaging and SPECT/CT after 24 hours. The pharmacokinetics and biodistribution of the implanted macrophages were determined. Correlation between percentage NE and IBD scores was calculated. RESULTS: Ex vivo mass spectrometry revealed strong SPIO nanoparticle uptake (7.4 pg iron per cell). R2* correlated with cell number (r = 0.9813, P < .05). Percentage NE correlated with both clinical (r = 0.924) and pathologic (r = 0.795) IBD score. Cell circulation half-life in the first and second phases was 0.32 hour and 10.2 hours, respectively. SPECT/CT showed that approximately 3% of the injected dose was present in the intestines 24 hours after injection; this was confirmed at MR imaging and histologic examination. Indium 111-labeled cells were present in all tissue associated with the reticuloendothelial system or mononuclear phagocyte system at 24 hours. CONCLUSION: SPIO nanoparticles and (111)In-labeled macrophages could be observed in vivo at MR imaging and SPECT/CT in mice with IBD. Percentage NE at MR imaging correlates with disease activity.
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Enfermedades Inflamatorias del Intestino/patología , Macrófagos/patología , Imagen Multimodal , Animales , Medios de Contraste , Dextranos , Modelos Animales de Enfermedad , Radioisótopos de Indio , Cloruro de Magnesio , Imagen por Resonancia Magnética , Nanopartículas de Magnetita , Ratones , Ratones Endogámicos C57BL , Nanopartículas , Fantasmas de Imagen , Proyectos Piloto , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: This study aimed to develop machine learning models to predict phosphorylated mesenchymal-epithelial transition factor (p-MET) expression in oral tongue squamous cell carcinoma (OTSCC) using magnetic resonance imaging (MRI)-derived texture features and clinical features. METHODS: Thirty-four patients with OTSCC were retrospectively collected. Texture features were derived from preoperative MR images, including T2WI, apparent diffusion coefficient mapping, and contrast-enhanced (ce)-T1WI. Dimension reduction was performed consecutively with reproducibility analysis and an information gain algorithm. Five machine learning methods-AdaBoost, logistic regression (LR), naïve Bayes (NB), random forest (RF), and support vector machine (SVM)-were adopted to create models predicting p-MET expression. Their performance was assessed with fivefold cross-validation. RESULTS: In total, 22 and 12 cases showed low and high p-MET expression, respectively. After dimension reduction, 3 texture features (ADC-Minimum, ce-T1WI-Imc2, and ce-T1WI-DependenceVariance) and 2 clinical features (depth of invasion [DOI] and T-stage) were selected with good reproducibility and best correlation with p-MET expression levels. The RF model yielded the best overall performance, correctly classifying p-MET expression status in 87.5% of OTSCCs with an area under the receiver operating characteristic curve of 0.875. CONCLUSION: Differences in p-MET expression in OTSCCs can be noninvasively reflected in MRI-based texture features and clinical parameters. Machine learning can potentially predict biomarker expression levels, such as MET, in patients with OTSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Proyectos Piloto , Estudios Retrospectivos , Carcinoma de Células Escamosas/diagnóstico por imagen , Teorema de Bayes , Reproducibilidad de los Resultados , Neoplasias de la Lengua/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Fine needle aspiration biopsy is usually performed to evaluate thyroid lesions. The purpose of this study was to evaluate the usefulness of diffusion weighted imaging to differentiate malignancy of thyroid lesions. METHODS: The study was approved by ethics committee of Shanghai Changzheng Hospital.Forty-two patients, 10 men and 32 women (range: 20-72 years, mean age 42.4 years) with thyroid lesions were included in the study. Routine neck MR and diffusion-weighted MR imaging was performed using multiple b-values. ADC values were computed for the different b-values. Histological results of the thyroidectomy samples were obtained for all the patients. ADC values of benign and malignant thyroid lesions were compared with the pathology results. Logistic regression analysis was used to detect independent parameters for differentiating benign and malignancy of lesions. RESULT: Based on the histology results there were 28 benign and 14 malignant cases. The difference of ADC value between benign and malignant thyroid lesions was significant for ADC values obtained using b-values of 0 and 300 s/mm(2) (p < 0.001). The ADC values were significantly higher in benign lesions (benign ADC: 2.37 ± 0.47 × 10-3 mm(2)/s vs. malignant: 1.49 ± 0.60 × 10-3 mm(2)/s). ADC values obtained with b-values of 0 and 300 mm(2)/s and max nodular diameter was regarded as the two most discriminative parameters for differentiating malignancy. Using the pathology results as a standard reference, area under ROC curve was found to be 0.876 for an ADC cutoff value of 2.17 × 10-3 mm(2)/s that corresponded to an acquisition with b-values of 0 and 300 mm(2)/s. CONCLUSION: Diffusion-weighted MR imaging is a promising non-invasive method to differentiate malignancy in thyroid lesions.
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Imagen de Difusión por Resonancia Magnética/métodos , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/patología , Adulto , Anciano , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Nódulo Tiroideo/cirugía , Adulto JovenRESUMEN
OBJECTIVE: To explore the value of apparent diffusion coefficient (ADC) ratio in the diagnosis of bladder cancer pre-operation by analyzing its differences among different grades of bladder cancer. METHODS: A total of 52 cases of bladder cancer were all definitely diagnosed with histological results.Routine examinations of magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) were performed preoperatively on each patient. ADC map was constructed in work station and ADC values of tumor and internal obturator muscle were measured (b = 800 s/mm(2)).Ratio of ADC was calculated with internal obturator muscle as reference site. Then the relationship between ADC ratio and bladder cancer grade was analyzed. RESULTS: Mean ratio of ADC of all tumors was 0.98±0.35, G1 (1.12±0.21) and G2 (0.67±0.29), the sensitivity and specificity of ADC ratio was 90.2% and 85.3% respectively with an optimal threshold of 0.96. The ratios of ADC of low-grade group were significantly higher than those of high-grade group while the values of non-muscle-invasive group were significantly higher than those of muscle-invasive group. The ratios of ADC of tumor were inversely associated with the malignancy degree of bladder cancer (r = -0.845, P < 0.05). CONCLUSION: The ratio of ADC of bladder cancer reflects the lesion tissue properties. And its measurement plays an important role in the diagnosis of bladder cancer grading pre-operation.
Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del TumorRESUMEN
Objective: Primary Trigeminal Neuralgia (PTN) is a common and refractory neurological disease. Conventional vascular compression theory could not completely explain the etiology and pathogenesis of PTN. This study used diffusion tensor imaging (DTI) to demonstrate the microstructural changes of root entry zone (REZ) region in PTN patients. Materials and methods: DTI sequences was performed on PTN patients and healthy controls (HCs). Clinical data included affected side, disease course and visual analogue scale (VAS) were collected. Quantitative DTI variables such as FA, MD, AD and RD of the root entry/Exit zone (REZ) were measured and compared in PTN/HCs, affected/unaffected side, and pre/post operation groups. The PCoA was established to conduct overall differences between PTN group and the HCs. Results: A total of 17 patients with PTN (mean age 59.29 ± 8.53; 5 men) and 34 HCs (mean age 57.70 ± 6.37; 10 men) were included. Lower FA value of the affected side of PTN group was observed compared to the unaffected side and the HCs (p = 0.001), whereas the values of MD, AD and RD were significantly increased (p < 0.001). Moreover, the decrease of FA value was recovered post operation. PCoA results of the comprehensive indexes can significantly distinguish PTN group from HCs (r = 0.500, p < 0.001). Conclusion: Quantitative variables derived from DTI in REZ had significantly different profiles between PTN patients and HCs, which were associated with VAS situation and the disease course of PTN. The comprehensive index established on DTI variables were of great potential to reveal the microstructure changes in PTN patients and predict the therapeutic effect.