RESUMO
OBJECTIVES: Radiotherapy is the primary treatment for nasopharyngeal carcinoma, but it frequently leads to radiotherapy-induced temporal lobe injury (RTLI). Magnetic resonance imaging (MRI) is the main diagnostic method for RTLI after radiotherapy for nasopharyngeal carcinoma, but it is prone to missed diagnoses. This study aims to investigate the causes of missed diagnoses of RTLI in nasopharyngeal carcinoma patients undergoing MRI after radiotherapy. METHODS: Clinical and MRI data from nasopharyngeal carcinoma patients diagnosed and treated with radiotherapy at Xiangya Hospital of Central South University, from January 2010 to April 2021, were collected. Two radiologists reviewed all head and neck MRIs (including nasopharyngeal and brain MRIs) before and after radiotherapy of identify cases of late delayed response-type RTLI for the first time. If the original diagnosis of the initial RTLI in nasopharyngeal carcinoma patients did not report temporal lobe lesions, it was defined as a missed diagnosis. The first diagnosis of RTLI cases was divided into a missed diagnosis group and a non-missed diagnosis group. Clinical and imaging data were compared between the 2 groups, and multivariate logistic regression analysis was used to identify independent risk factors for MRI missed diagnoses of initial RTLI. RESULTS: A total of 187 nasopharyngeal carcinoma with post-radiotherapy RTLI were included. The original diagnostic reports missed 120 cases and accurately diagnosed 67 cases, with an initial RTLI diagnosis accuracy rate of 35.8% and a missed diagnosis rate of 64.2%. There were statistically significant differences between the missed diagnosis group and the non-missed diagnosis group in terms of lesion size, location, presence of contralateral temporal lobe lesions, white matter high signal, cystic degeneration, hemorrhage, fluid attenuated inversion recovery (FLAIR), and examination site (all P<0.05). Multivariate logistic regression analysis showed that lesions ≤25 mm, non-enhancing lesions, lesions without cystic degeneration or hemorrhage, lesions located only in the medial temporal lobe, and MRI examination only of the nasopharynx were independent risk factors for missed MRI diagnosis of initial RTLI (all P<0.05). CONCLUSIONS: The missed diagnosis of initial RTLI on MRI is mainly related to lesion size and location, imaging characteristics, and MRI examination site.
Assuntos
Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Lobo Temporal , Humanos , Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/efeitos da radiação , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico por imagem , Diagnóstico Ausente , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Background: Intracranial extraventricular ependymoma (IEE) and glioblastoma (GBM) may have similar imaging findings but different prognosis. This study aimed to develop and validate a nomogram based on magnetic resonance imaging (MRI) Visually AcceSAble Rembrandt Images (VASARI) features for preoperatively differentiating IEE from GBM. Methods: The clinical data and the MRI-VASARI features of patients with confirmed IEE (n=114) and confirmed GBM (n=258) in a multicenter cohort were retrospectively analyzed. Predictive models for differentiating IEE from GBM were built using a multivariate logistic regression method. A nomogram was generated and the performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Results: The predictors identified in this study consisted of six VASARI features and four clinical features. Compared with the individual models, the combined model incorporating clinical and VASARI features had the highest area under the curve (AUC) value [training set: 0.99, 95% confidence interval (CI): 0.98-1.00; validation set: 0.97, 95% CI: 0.94-1.00] in comparison to the clinical model. The nomogram was well calibrated with significant clinical benefit according to the calibration curve and decision curve analyses. Conclusions: The nomogram combining clinical and MRI-VASARI characteristics was robust for differentiating IEE from GBM preoperatively and may potentially assist in diagnosis and treatment of brain tumors.
RESUMO
BACKGROUND: The three-dimensional chemical exchange saturation transfer (3D CEST) technique is a novel and promising magnetic resonance sequence; however, its application in nasopharyngeal carcinoma (NPC) lacks sufficient evaluation. This study aimed to assess the feasibility of the 3D CEST technique in predicting the short-term treatment outcomes for chemoradiotherapy (CRT) in NPC patients. METHODS: Forty NPC patients and fourteen healthy volunteers were enrolled and underwent the pre-treatment 3D CEST magnetic resonance imaging and diffusion-weighted imaging (DWI). The reliability of 3D CEST was assessed in healthy volunteers by calculating the intra- and inter-observer correlation coefficient (ICC) for amide proton transfer weighted-signal intensity (APTw-SI) and magnetization transfer ratio (MTR) values. NPC patients were divided into residual and non-residual groups based on short-term treatment outcomes after CRT. Whole-tumor regions of interest (ROIs) were manually drawn to measure APTw-SI, MTR and apparent diffusion coefficient (ADC) values. Multivariate analysis and the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of clinical characteristics, APTw-SI, MTR, ADC values, and combined models in predicting short-term treatment outcomes in NPC patients. RESULTS: For the healthy volunteer group, all APTw-SI and MTR values exhibited good to excellent intra- and inter-observer agreements (0.736-0.910, 0.895-0.981, all P > 0.05). For NPC patients, MTR values showed a significant difference between the non-residual and residual groups (31.24 ± 5.21% vs. 34.74 ± 1.54%, P = 0.003) while no significant differences were observed for APTw-SI and ADC values (P > 0.05). Moreover, the diagnostic power of MTR value was superior to APTw-SI (AUC: 0.818 vs. 0.521, P = 0.017) and comparable to ADC values (AUC: 0.818 vs. 0.649, P > 0.05) in predicting short-term treatment outcomes for NPC patients. The prediction performance did not improve even when combining MTR values with APTw-SI and/or ADC values (P > 0.05). CONCLUSIONS: The pre-treatment MTR value acquired through 3D CEST demonstrated superior predictive performance for short-term treatment outcomes compared to APTw-SI and ADC values in NPC patients after CRT.
Assuntos
Neoplasias Nasofaríngeas , Prótons , Humanos , Estudos de Viabilidade , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/terapia , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética , Quimiorradioterapia , Amidas , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/terapiaRESUMO
Introduction: Previous studies have revealed structural, functional, and metabolic changes in brain regions inside the cortico-striatal-thalamo-cortical (CSTC) loop in patients with paroxysmal kinesigenic dyskinesia (PKD), whereas no quantitative susceptibility mapping (QSM)-related studies have explored brain iron deposition in these areas. Methods: A total of eight familial PKD patients and 10 of their healthy family members (normal controls) were recruited and underwent QSM on a 3T magnetic resonance imaging system. Magnetic susceptibility maps were reconstructed using a multi-scale dipole inversion algorithm. Thereafter, we specifically analyzed changes in local mean susceptibility values in cortical regions and subcortical nuclei inside the motor CSTC loop. Results: Compared with normal controls, PKD patients had altered brain iron levels. In the cortical gray matter area involved with the motor CSTC loop, susceptibility values were generally elevated, especially in the bilateral M1 and PMv regions. In the subcortical nuclei regions involved with the motor CSTC loop, susceptibility values were generally lower, especially in the bilateral substantia nigra regions. Conclusion: Our results provide new evidence for the neuropathogenesis of PKD and suggest that an imbalance in brain iron levels may play a role in PKD.
RESUMO
Non-invasive prediction for KIT/PDGFRA status in GIST is a challenging problem. This study aims to evaluate whether CT based sarcopenia could differentiate KIT/PDGFRA wild-type gastrointestinal stromal tumor (wt-GIST) from the mutant-type GIST (mu-GIST), and to evaluate genetic features of GIST. A total of 174 patients with GIST (wt-GIST = 52) were retrospectively identified between January 2011 to October 2019. A sarcopenia nomogram was constructed by multivariate logistic regression. The performance of the nomogram was evaluated by discrimination, calibration curve, and decision curve. Genomic data was obtained from our own specimens and also from the open databases cBioPortal. Data was analyzed by R version 3.6.1 and clusterProfiler ( http://cbioportal.org/msk-impact ). There were significantly higher incidence (75.0% vs. 48.4%) and more severe sarcopenia in patients with wt-GIST than in patients with mu-GIST. Multivariate logistic regression analysis showed that sarcopenia score (fitted based on age, gender and skeletal muscle index), and muscle fat index were independent predictors for higher risk of wt-GIST (P < 0.05 for both the training and validation cohorts). Our sarcopenia nomogram achieved a promising efficiency with an AUC of 0.879 for the training cohort, and 0.9099 for the validation cohort with a satisfying consistency in the calibration curve. Favorable clinical usefulness was observed using decision curve analysis. The additional gene sequencing analysis based on both our data and the external data demonstrated aberrant signal pathways being closely associated with sarcopenia in the wt-GIST. Our study supported the use of CT-based assessment of sarcopenia in differentiating the wt-GIST from the mu-GIST preoperatively.
Assuntos
Tumores do Estroma Gastrointestinal , Sarcopenia , Humanos , Tumores do Estroma Gastrointestinal/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Estudos Retrospectivos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores Proteína Tirosina Quinases , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: To identify specific imaging and clinicopathological features of a rare potentially malignant epithelioid variant of renal lipid-poor angiomyolipoma (E-lpAML). METHODS: A total of 20 patients with E-lpAML and 43 patients with other lpAML were retrospectively included. Multiphase computed tomography (CT) imaging features and clinicopathological findings were recorded. Independent predictors for E-lpAML were identified using multivariate logistic regression and were used to construct a diagnostic score for differentiation of E-lpAML from other lpAML. RESULTS: The E-lpAML group consisted of 6 men and 14 women (age median ± SD: 39.45 ± 15.70, range: 16.0-68.0 years). E-lpAML tended to appear as hyperdense mass lesions located at the renal sinus (n = 8, 40%) or at the renal cortex (n = 12, 60%), with a "fast-in and slow-out" enhancement pattern (n = 20, 100%), cystic degeneration (n = 18, 90%), "eyeball" sign (n = 11, 55%), and tumor neo-vasculature (n = 15, 75%) on CT. Multivariate logistic regression analysis showed that the independent predictors for diagnosing E-lpAML were cystic degeneration on CT imaging and CT value of the tumor in corticomedullary phase of enhancement. A predictive model was built with the two predictors, achieving an area under the curve (AUC) of 93.5% (95% confidence interval (95%CI): 84.3-98.2%) with a sensitivity of 95.0% (95%CI: 75.1-99.9%) and a specificity of 83.72% (95%CI: 69.3-93.2%). CONCLUSION: We identified specific CT imaging features and predictors that could contribute to the correct diagnosis of E-lpAML. Our findings should be helpful for clinical management of E-lpAML which could potentially be malignant and may require nephron-sparing surgery while other lpAML tumors which are benign require no intervention. KEY POINTS: ⢠It is important to differentiate renal epithelioid lipid-poor angiomyolipoma (E-lpAML) from other lpAML because of differences in clinical management. ⢠E-lpAML tumors tend to be large hyperdense tumors in the renal sinus with cystic degeneration and "fast-in and slow-out" pattern of enhancement. ⢠Our CT imaging-based predictive model was robust in its performance for predicting E-lpAML from other lpAML tumors.
Assuntos
Angiomiolipoma , Carcinoma de Células Renais , Neoplasias Renais , Adolescente , Adulto , Idoso , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/patologia , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/patologia , Lipídeos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
OBJECTIVES: Glioma is the most common intracranial primary tumor in central nervous system. Glioma grading possesses important guiding significance for the selection of clinical treatment and follow-up plan, and the assessment of prognosis. This study aims to explore the feasibility of logistic regression model based on radiomics to predict glioma grading. METHODS: Retrospective analysis was performed on 146 glioma patients with confirmed pathological diagnosis from January, 2012 to December, 2018. A total of 41 radiomics features were extracted from contrast-enhanced T1-weighted imaging (T1WI+C) lesion by manual segmentation. Least absolute shrinkage and selection operator (LASSO) was used to select the most-predictive radiomics features for pathological grading and to calculate radiomics score (Rad-score) of each patient. A logistic regression model was built to explore the correlation between giloma grading and Rad-score. Receiver operating characteristic (ROC) curve was performed to evaluate the model's predictive ability with area under the curve (AUC) for the evaluation index. Hosmer-Lemeshow test was used to measure the model's predictive accuracy. RESULTS: A total of 5 imaging features selected by LASSO were used to establish a logistic regression model for predicting glioma grading. The model showed good discrimination with AUC value of 0.919. Hosmer-Lemeshow test showed no significant difference between the calibration curve and the ideal curve (P=0.808), indicating high predictive accuracy of the model. CONCLUSIONS: The logistic regression model using radiomics exhibits a relatively high accuracy for predicting glioma grading, which may serve as a complementary tool for preoperative prediction of giloma grading.
Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Curva ROC , Estudos RetrospectivosRESUMO
This study aimed to investigate the role of diffusion-weighted imaging (DWI) in predicting tumor consistency, extent of surgical resection, and recurrence in pituitary adenoma (PA). We reviewed a prospectively collected database of surgically treated PA between March 2016 and October 2017. Predictors for extent of resection and recurrence/progression were assessed with logistic and Cox regression analysis. Of the 183 patients, the tumor consistency was found soft in 107 (58.5%) patients, intermediate in 41 (22.4%) patients, and hard in 35 (19.1%) patients. The mean of ADC ratio was 0.92 ± 0.22 for hard tumor, 1.03 ± 0.22 for intermediate tumor, and 1.41 ± 0.62 for soft tumor (P < 0.001). The mean collagen content was 25.86% ± 15.00% for hard tumor, 16.05% ± 9.90% for intermediate tumor, and 5.00% ± 6.00% for soft tumor (P < 0.001). Spearman analysis showed a significant correlation between ADC ratio and collagen content (ρ = - 0.367; P < 0.001). Gross-total resection (GTR) was obtained in 68.3% of patients, and multivariable logistic regression analysis showed that ADC ratio (OR, 12.135; 95% CI, 4.001-36.804; P < 0.001), giant PA (OR, 0.233; 95% CI, 0.105-0.520; P < 0.001), and invasion (OR, 0.459; 95% CI, 0.220-0.960; P = 0.039) were significantly predictive of GTR. Twenty-seven (14.8%) patients suffered recurrence/progression in the mean follow-up of 35.14 months. Invasion (HR, 2.728; 95% CI, 1.262-5.899; P = 0.011) was identified as independent predictors of recurrence/progression. ADC ratio of DWI could be used for preoperative assessment of tumor consistency, tumor collagen content, and extent of surgical resection, which might be useful in preoperative planning for patients with PA.
Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Imagem de Difusão por Ressonância Magnética , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: To describe and evaluate the application of a new 3-D printing-assisted personalized macular buckle for patients with myopic foveoschisis (MFS). METHODS: Twelve eyes of 12 patients with MFS were included in this study. Preoperative MRI images were subsequently measured after marker implantation and imported into the MIMICS software for the 3-D reconstruction of a virtual model of an eyeball and a marker. The virtual eyeball model was designed according to the degree of retinoschisis, which was measured using optical coherence tomography preoperatively. A macular buckle was designed using a titanium stent, assisted by 3-D printing; furthermore, it was surgically placed in combination with pars plana vitrectomy. Visual acuity, axial length and anatomic outcomes were analysed pre- and postoperatively. RESULTS: Macular schisis in all patients was completely resolved after the surgery without any postoperative complications. The mean postoperative best corrected visual acuity (LogMAR) improved significantly from 1.21 to 0.92 during the 6-month follow-up period (p < 0.001) and reached 0.9 (p < 0.001) after 2 years. The axial length was significantly shortened during the 2 years postoperatively follow-up period (p < 0.01). The average axial lengths in all patients decreased from 30.62 mm preoperatively to 29.81 mm 1 month postoperatively and remained around 30.16 mm from 1 year after the surgery. CONCLUSION: The 3-D printing technique is useful to predict the indentation height and position of the macular buckle. The 3D-printing-assisted macular buckle, in combination with vitrectomy, is an effective, safe and accurate treatment modality for MFS.
Assuntos
Miopia Degenerativa/complicações , Impressão Tridimensional , Retinosquise/cirurgia , Recurvamento da Esclera/métodos , Cirurgia Assistida por Computador/métodos , Acuidade Visual , Vitrectomia/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/diagnóstico , Retina/patologia , Retina/cirurgia , Retinosquise/diagnóstico , Retinosquise/etiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the image quality of magnetic resonance 3D-sampling perfection with application-optimized contrasts by using different filp angle evolutions (3D-SPACE) sequence combined with different fusion methods in image fusion technology and the application value of fusion technology in preoperative evaluation of pituitary macroadenoma. METHODS: We collected MRI data of 43 patients with pituitary macroadenoma confirmed by Xiangya Hospital of Central South University, including collecting conventional MRI scan+enhancement, 3D-SPACE T2WI, and 3D-SPACE T1WI+C image data. 3D-SPACE sequence fusion was used in 6 combinations of 3D-SPACE T2WI/3D-SPACE T1WI+C, which were normal phase+normal phase, reverse phase+normal phase, normal phase+reverse phase, reverse phase+reverse phase, and normal phase pseudo color+normal phase, normal phase+normal phase pseudo color. Two senior radiologists used semi-quantitative methods to evaluate and compare the image quality of different combinations to obtain the best fusion mode. According to the degree of tumor invasion of the optic chiasma, oculomotor nerve, and cavernous sinus vessels, the MRI enhancement, 3D-SPACE T2WI, 3D-SPACE T1WI+C, and 2 3D-SPACE sequence fusion images were performed according to a three-level score system. Taking the intraoperative observation as the gold standard, Fisher probability exact method was used to compare different sequences to show the difference between the degree of invasion of the pituitary macroadenoma to the surrounding tissue and the intraoperative results. RESULTS: The Kruskal-Wallis H rank sum test showed that among the 6 image fusion modes, 3D-SPACE T1WI+C normal phase pseudo-color and 3D-SPACE T2WI normal phase fusion images had the best quality (P<0.05). No significance was observed among the 4 groups in the evaluation of consistency between the intraoperative findings and the graphically displayed extent of tumor invasion into oculomotor nerve (both level I, II, and III, P>0.05). The 3D-SPACE T2WI/3D-SPACE T1WI+C fusion images and the 3D-SPACE T2WI images showed better performance in the evaluation of consistency between the intraoperative findings and the graphically displayed extent of tumor invasion into optic chiasma (level II and III) than that in other two kinds of imaging data of the MRI enhancement group and 3D-SPACE T1WI+C group (P<0.01, P<0.05, respectively), with no significance being observed in level I. The 3D-SPACE T2WI/3D-SPACE T1WI+C fusion images and the 3D-SPACE T1WI+C images showed better performance in the evaluation of consistency between the intraoperative findings and the graphically displayed extent of tumor invasion into cavernous sinus vessels (level II) than that in other two kinds of imaging data of the MRI enhancement group and 3D-SPACE T2WI group (P<0.01, P<0.05, respectively), with no significance being observed in level I and III. CONCLUSIONS: Magnetic resonance 3D-SPACE sequence combined with image fusion technology is better than conventional magnetic resonance sequence for showing pituitary macroadenoma invasion of skull base vascular nerves. The invasion is better than the 3D-SPACE sequence alone, showing that the relationship between tumor and cavernous sinus vascular grade II better than the 3D-SPACE sequence alone. It has good application prospects for preoperative risk assessment and surgical plan.
Assuntos
Aumento da Imagem , Neoplasias Hipofisárias , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgiaRESUMO
Recent findings have unraveled the critical functions of the long noncoding RNA (lncRNA) SNHG5 in human malignancies. Nevertheless, the role and mechanism of SNHG5 in clear cell renal cell carcinoma (ccRCC) are still elusive. In our study, substantially higher abundance of SNHG5 was observed in ccRCC specimens and cell lines, and increased SNHG5 expression was intimately correlated with tumor size, tumor-node-metastasis (TNM) stage, lymph node invasion, and distant metastases in patients with ccRCC. SNHG5 knockdown obviously suppressed the proliferative, migratory, and invasive capabilities of ccRCC cells, whereas SNHG5 overexpression induced the opposite effects. Mechanistically, SNHG5 activated the transcription of ZEB1, which exerts a pivotal role in modulation of epithelia-mesenchymal transition (EMT) and tumor metastasis. SNHG5 was then shown to act as an endogenous sponge for miR-205-5p, which targets ZEB1 in ccRCC. Moreover rescue experiments revealed that SNHG5 promotes ccRCC cell proliferation, migration, and invasion in a miR-205-5p-dependent manner. Additionally, in vivo assays further indicated that overexpression or silencing of SNHG5 in ccRCC cells promoted or suppressed the tumorigenesis and metastasis, respectively. Altogether, the present data provide the first evidence that the lncRNA SNHG5 has an oncogenic role in ccRCC through the SNHG5/miR-205-5p/ZEB1 signaling axis and represents a novel potential therapeutic regimen against ccRCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genéticaRESUMO
Growth hormone-secreting pituitary adenoma (GHPA), a benign endocrine tumor located in the base of the skull, results in acromegaly. In addition to the mass effect of the tumor itself in the sellar region, GHPA can lead to the overgrowth of almost every organ. Previous findings indicated that the processes underlying acromegaly were partly attributable to hyperactivity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. However, the mechanisms driving this syndrome remains largely unknown. Additionally, the roles of GHPA-derived exosomes, which contain functional microRNAs and proteins that manipulate target cell proliferation and differentiation in distal extremities, are also unknown. In this study, we demonstrated that GHPA exosomes promote bone formation in vitro and trabecula number in vivo. The mechanism of increased trabecula formation may be attributable to GHPA exosome-induced osteoblast proliferation via increased cell viability and DNA replication. We further discovered that exosomal hsa-miR-21-5p plays a distinct role from the GH/IGF-1 axis in these processes. Accordingly, the results of this study provide a novel mechanism whereby GHPA influences distal extremities and a new perspective for treating GHPA.
Assuntos
Acromegalia/patologia , Exossomos/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , MicroRNAs/metabolismo , Osteogênese , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Meios de Cultivo Condicionados/farmacologia , Endocitose/efeitos dos fármacos , Exossomos/ultraestrutura , Proteínas da Matriz Extracelular/metabolismo , Humanos , Masculino , Camundongos , MicroRNAs/genética , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Ratos Sprague-Dawley , Proteína Smad7/metabolismo , Fator de Transcrição AP-1/metabolismoRESUMO
BACKGROUND: Artificial mutagenesis not only provides a new approach to increase the diversity of desirable traits for breeding new varieties but are also beneficial for characterizing the genetic basis of functional genes. In recent decades, many mutation genes have been identified which are responsible for phenotype changes in mutants in various species including Arabidopsis and rice. However, the mutation feature in induced mutants and the underlying mechanisms of various types of artificial mutagenesis remain unclear. RESULTS: In this study, we adopted a transcriptome sequencing strategy to characterize mutations in coding regions in a barley dwarf mutant induced by gamma-ray radiation. We detected 1193 genetic mutations in gene transcription regions introduced by gamma-ray radiation. Interestingly, up to 97% of the gamma irradiation mutations were concentrated in certain regions in chromosome 5H and chromosome 7H. Of the 26,745 expressed genes, 140 were affected by gamma-ray radiation; their biological functions included cellular and metabolic processes. CONCLUSION: Our results indicate that mutations induced by gamma-ray radiation are not evenly distributed across the whole genome but located in several concentrated regions. Our study provides an overview of the feature of genetic mutations and the genes affected by gamma-ray radiation, which should contribute to a deeper understanding of the mechanisms of radiation mutation and their application in gene function analysis.
Assuntos
Raios gama , Hordeum/genética , Mutagênese , Mutação , Genes de Plantas , Genoma de Planta , Hordeum/efeitos da radiação , Mutação INDEL , Polimorfismo de Nucleotídeo Único , RNA-SeqRESUMO
OBJECTIVE: To explore the feasibility and efficacy of artificial neural network for differentiating high-grade glioma and low-grade glioma using image information.â© Methods: A total of 130 glioma patients with confirmed pathological diagnosis were selected retrospectively from 2012 to 2017. Forty one imaging features were extracted from each subjects based on 2-dimension magnetic resonance T1 weighted imaging with contrast-enhancement. An artificial neural network model was created and optimized according to the performance of feature selection. The training dataset was randomly selected half of the whole dataset, and the other half dataset was used to verify the performance of the neural network for glioma grading. The training-verification process was repeated for 100 times and the performance was averaged.â© Results: A total of 5 imaging features were selected as the ultimate input features for the neural network. The mean accuracy of the neural network for glioma grading was 90.32%, with a mean sensitivity at 87.86% and a mean specificity at 92.49%. The area under the curve of receiver operating characteristic curve was 0.9486.â© Conclusion: As a technique of artificial intelligence, neural network can reach a relatively high accuracy for the grading of glioma and provide a non-invasive and promising computer-aided diagnostic process for the pre-operative grading of glioma.
Assuntos
Neoplasias Encefálicas , Glioma/diagnóstico por imagem , Glioma/patologia , Gradação de Tumores , Redes Neurais de Computação , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Humanos , Imageamento por Ressonância Magnética , Curva ROC , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: EBV-encoded latent membrane protein 1 (EBV-LMP1) is an important oncogenic protein for nasopharyngeal carcinoma (NPC) and has been shown to engage a plethora of signaling pathways. Correspondingly, an LMP1-targeted DNAzyme was found to inhibit the growth of NPC cells both in vivo and in vitro by suppressing cell proliferation and inducing apoptosis. However, it remains unknown whether an LMP1-targeted DNAzyme would affect the vasculature of NPC. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been applied in the clinical trials of anti-angiogenic drugs for more than ten years, and Ktrans has been recommended as a primary endpoint. Therefore, the objective of the current study was to use DCE-MRI to longitudinally study the effect of an EBV-LMP1-targeted DNAzyme on the vasculature of patients with NPC. METHODS: Twenty-four patients were randomly divided into two groups: a combined treatment group (radiotherapy + LMP1-targeted DNAzyme) and a radiotherapy alone group (radiotherapy + normal saline). DCE-MRI scans were conducted 1 ~ 2 days before radiotherapy (Pre-RT), during radiotherapy (RT 50 Gy), upon completion of radiotherapy (RT 70 Gy), and three months after radiotherapy (3 months post-RT). Parameters of vascular permeability and intra- and extravascular volumes were subsequently obtained (e.g., Ktrans, kep, ve) using nordicICE software. RESULTS: Both Ktrans and kep values for NPC tumor tissues decreased for both groups after treatment. Moreover, a statistically significant difference in Ktrans values at the pre-therapy and post-therapy timepoints emerged earlier for the combined treatment group (RT 50 Gy, P =0.045) compared to the radiotherapy alone group (3 months post-RT, P = 0.032). For the kep values, the downward trend observed for both the combined treatment group and the radiotherapy alone group were similar. In contrast, ve values for all of the tumor tissues increased following therapy. CONCLUSIONS: The EBV-LMP1-targeted DNAzyme that was tested was found to accelerate the decline of Ktrans values for patients with NPC. Correspondingly, the LMP1-targeted DNAzyme treatments were found to affect the angiogenesis and microvascular permeability of NPC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01449942. Registered 6 October 2011.
Assuntos
DNA Catalítico/administração & dosagem , DNA Catalítico/genética , Imageamento por Ressonância Magnética/métodos , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , Neovascularização Patológica/genética , Proteínas da Matriz Viral/genética , Adulto , Carcinoma , Estudos de Coortes , Terapia Combinada , DNA Catalítico/efeitos adversos , Regulação para Baixo , Feminino , Regulação da Expressão Gênica , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Estadiamento de Neoplasias , Neovascularização Patológica/diagnóstico , Radioterapia/efeitos adversos , Resultado do TratamentoRESUMO
A novel dual-activatable fluorescence/MRI bimodal platform is designed for tumor cell imaging by using a redoxable manganese dioxide (MnO2) nanosheet-aptamer nanoprobe. The redoxable MnO2 nanosheet acts as a DNA nanocarrier, fluorescence quencher, and intracellular glutathione (GSH)-activated MRI contrast agent. In the absence of target cells, neither fluorescence signaling nor MRI contrast of the nanoprobe is activated. In the presence of target cells, the binding of aptamers to their targets weakens the adsorption of aptamers on the MnO2 nanosheets, causing partial fluorescence recovery, illuminating the target cells, and also facilitating the endocytosis of nanoprobes into target cells. After endocytosis, the reduction of MnO2 nanosheets by GSH further activates the fluorescence signals and generates large amounts of Mn(2+) ions suitable for MRI. This platform should facilitate the development of various dual-activatable fluorescence/MRI bimodalities for use in cells or in vivo.
Assuntos
Corantes Fluorescentes/química , Imageamento por Ressonância Magnética , Compostos de Manganês/química , Nanoestruturas/química , Neoplasias/patologia , Óxidos/química , Adsorção , Linhagem Celular Tumoral , Meios de Contraste/química , DNA/química , Endocitose , Glutationa/química , Glutationa/metabolismo , Humanos , Íons , Ligantes , Manganês/química , Microscopia Eletrônica de TransmissãoAssuntos
Catatonia/etiologia , Hipersensibilidade Tardia/complicações , Mordeduras e Picadas de Insetos/complicações , Transtornos dos Movimentos/etiologia , Venenos de Vespas , Vespas , Adulto , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Creatina/sangue , Eletrocardiografia , Eletroencefalografia , Globo Pálido/patologia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Rigidez Muscular/etiologia , Exame Neurológico , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To analyze HSP70/HSP27 protein expression in the nasopharyngeal carcinoma (NPC) primary tissues and the residual lesion, and to explore its predictive value. METHODS: Immunohistochemical experiment was performed to detect the expression of HSP70 and HSP27 in 58 NPC primary tissues: 28 were in the experimental group with the local residual lesion and 30 in the control group without recurring and metastasis within 5 years by conventional radiotherapy. RESULTS: The positive expression of HSP70 and HSP27 in the experimental group was 92.9%(26/28) and 53.6%(15/28), while that in the control group was 53.3%(16/30) and 53.3%(16/30),respectively. There was significant difference in the 2 groups. The common positive expression of HSP70 and HSP27 between the 2 groups had significant difference, 50.0% (14/28) in the experimental group and 16.7% (5/30) in the control group, respectively. There was no significant difference in the negative ratio of HSP70 and HSP27 common expression between the 2 groups, 3.6% (1/28) in the experimental group and 10.0% (3/30) in the control group, respectively. CONCLUSION: HSP70 may have an important role in the radioresistance of NPC, and may predict the residual lesion after radiotherapy.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/radioterapia , Feminino , Proteínas de Choque Térmico , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Neoplasias Nasofaríngeas/radioterapia , Adulto JovemRESUMO
OBJECTIVE: To study the clinical and radiological characteristics of levamisole-induced leukoencephalopathy (LILE) in patients with recurrent aphthous ulcers (RAU) or infected with Ascaris. METHODS: The medical histories of 16 patients with LILE were analyzed, including clinical manifestations, brain magnetic resonance imaging (MRI) characteristics, cerebrospinal fluid, and brain biopsy findings. RESULTS: The main clinical manifestations of LILE were motor weakness (75.0%), dysphasia or aphasia (50.0%), cognitive disorder (50.0%), and facial palsy (43.8%). The MRI of 16 cases showed plaque and round or oval demyelinating lesions in white matter, which revealed a signal hypointensity on T1-weighted and diffusion-weighted images (DWI), and demonstrated hyperintensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. The MRI revealed peripheral ring-type enhancement about the focus after Gd-DTPA administration and edema around some lesions, without mass effect. T2-weighted and FLAIR images were highly sensitive to the lesions. Brain biopsy in 1 patient showed multifocal demyelinating lesions without perivascular cuffing by lymphocytes. Treatment generally consisted of steroids and hyperbaric oxygen therapy, and patients recovered to normal condition. CONCLUSIONS: A single normal dose of levamisole can induce leukoencephalopathy in patients with RAU or Ascaris. The diagnosis depends on the clinical features and imaging appearances. Steroid therapy might be a good choice of treatment.
Assuntos
Adjuvantes Imunológicos/efeitos adversos , Antinematódeos/efeitos adversos , Encéfalo/patologia , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/patologia , Levamisol/efeitos adversos , Adolescente , Adulto , Ascaríase/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Criança , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/patologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estomatite Aftosa/tratamento farmacológicoRESUMO
OBJECTIVE: To study the value of proton magnetic resonance spectroscopy ((1)H-MRS) with two-dimensional (2D) chemical-shift imaging (CSI) in evaluating brain gliomas. METHODS: Thirty-six patients with gliomas received examinations with 2D-CSI. The VOI of MRS included the tumor, peritumoral edematous and nonedematous areas, and the contralateral normal tissue. The changes of the metabolites in different areas were determined using 2D-CSI (1)H-MRS with SE sequence and the metabolite ratios were calculated. RESULTS: Significant differences were found in the ratios of NAA/Cr, Cho/Cr and NAA/Cho between low-grade gliomas and contralateral normal brain tissue, and between high-grade gliomas and the contralateral normal tissue (P<0.01). The low-grade gliomas and high-grade gliomas differed significantly in the ratios of NAA/Cr, Cho/Cr and NAA/Cho (P<0.05). These ratios also showed significant differences between peritumoral edematous area and the glioma tissue, between the peritumoral edematous area and contralateral normal brain tissue (P<0.05), and between the peritumoral nonedematous area and the glioma tissue (P<0.05). Between the peritumoral nonedematous area and contralateral normal brain tissue, NAA/Cr and NAA/Cho ratios were significantly different (P<0.05) but the Cho/Cr ratio was similar (P>0.05). CONCLUSIONS: MRS with 2D-CSI can provide precise and effective evidences with high time resolution for glioma grading, assessment of peritumoral involvement and glioma therapies.