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1.
BMC Cancer ; 24(1): 418, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580939

RESUMO

BACKGROUND: This study aimed to develop and validate a machine learning (ML)-based fusion model to preoperatively predict Ki-67 expression levels in patients with head and neck squamous cell carcinoma (HNSCC) using multiparametric magnetic resonance imaging (MRI). METHODS: A total of 351 patients with pathologically proven HNSCC from two medical centers were retrospectively enrolled in the study and divided into training (n = 196), internal validation (n = 84), and external validation (n = 71) cohorts. Radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images and screened. Seven ML classifiers, including k-nearest neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forest (RF), linear discriminant analysis (LDA), naive Bayes (NB), and eXtreme Gradient Boosting (XGBoost) were trained. The best classifier was used to calculate radiomics (Rad)-scores and combine clinical factors to construct a fusion model. Performance was evaluated based on calibration, discrimination, reclassification, and clinical utility. RESULTS: Thirteen features combining multiparametric MRI were finally selected. The SVM classifier showed the best performance, with the highest average area under the curve (AUC) of 0.851 in the validation cohorts. The fusion model incorporating SVM-based Rad-scores with clinical T stage and MR-reported lymph node status achieved encouraging predictive performance in the training (AUC = 0.916), internal validation (AUC = 0.903), and external validation (AUC = 0.885) cohorts. Furthermore, the fusion model showed better clinical benefit and higher classification accuracy than the clinical model. CONCLUSIONS: The ML-based fusion model based on multiparametric MRI exhibited promise for predicting Ki-67 expression levels in HNSCC patients, which might be helpful for prognosis evaluation and clinical decision-making.


Assuntos
Neoplasias de Cabeça e Pescoço , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Teorema de Bayes , Antígeno Ki-67/genética , Radiômica , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Aprendizado de Máquina , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem
2.
Eur Radiol ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39414655

RESUMO

OBJECTIVES: We evaluated the value of dual-energy computed tomography (DECT) parameters derived from pancreatic ductal adenocarcinoma (PDAC) to discriminate between high- and low-grade tumors and predict overall survival (OS) in patients. METHODS: Data were retrospectively collected from 169 consecutive patients with pathologically confirmed PDAC who underwent third-generation dual-source DECT enhanced dual-phase scanning before surgery between January 2017 and March 2023. Patients with prior treatments, other malignancies, small tumors, or poor-quality scans were excluded. Two radiologists evaluated three clinical and seven radiological features and measured sixteen DECT-derived parameters. Univariate and multivariate analyses were applied to select independent predictors. A prediction model and a corresponding nomogram were developed, and the area under the curve (AUC), calibration, and clinical applicability were assessed. The correlations between factors and OS were evaluated using Kaplan-Meier survival and Cox regression analyses. RESULTS: One hundred sixty-nine patients were randomly divided into training (n = 118) and validation (n = 51) cohorts, among which 43 (36.4%) and 19 (37.3%) had high-grade PDAC confirmed by pathology, respectively. The vascular invasion, normalized iodine concentration in the venous phase, and effective atomic number in the venous phase were independent predictors for histological grading. A nomogram was constructed to predict the risk of high-grade tumors in PDAC, with AUCs of 0.887 and 0.844 in the training and validation cohorts, respectively. The nomogram exhibited good calibration and was more beneficial than a single parameter in both cohorts. Pathological- and nomoscore-predicted high-grade PDACs were associated with poor OS (all p < 0.05). CONCLUSIONS: The nomogram, which combines DECT parameters and radiological features, can predict the histological grade and OS in patients with PDAC before surgery. KEY POINTS: Question Preoperative determination of histological grade in PDAC is crucial for guiding treatment, yet current methods are invasive and limited. Findings A DECT-based nomogram combining vascular invasion, normalized iodine concentration, and effective atomic number accurately predicts histological grade and OS in PDAC patients. Clinical relevance The DECT-based nomogram is a reliable, non-invasive tool for predicting histological grade and OS in PDAC. It provides essential information to guide personalized treatment strategies, potentially improving patient management and outcomes.

3.
Exp Cell Res ; 425(1): 113525, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36841324

RESUMO

Gastric cancer is a serious malignant tumor in the world, accounting for the third cause of cancer death worldwide. The pathogenesis of gastric cancer is very complex, in which epigenetic inheritance plays an important role. In our study, we found that DZIP3 was significantly up-regulated in gastric cancer tissues as compared to adjacent normal tissue, which suggested it may be play a crucial part in gastric cancer. To clarify the mechanism of it, we further analyzed the interacting proteome and transcriptome of DZIP3. An association between DZIP3 and some epigenetic regulators, such as CUL4B complex, was verified. We also present the first proteomic characterization of the protein-protein interaction (PPI) network of DZIP3. Then, the transcriptome analysis of DZIP3 demonstrated that knockdown DZIP3 increased a cohort of genes, including SETD7 and ZBTB4, which have essential role in tumors. We also revealed that DZIP3 promotes proliferation and metastasis of gastric cancer cells. And the higher expression of DZIP3 is positively associated with the poor prognosis of several cancers. In summary, our study revealed a mechanistic role of DZIP3 in promoting proliferation and metastasis in gastric cancer, supporting the pursuit of DZIP3 as a potential target for gastric cancer therapy.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Proteômica , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Metástase Neoplásica , Histona-Lisina N-Metiltransferase/genética , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Culina/metabolismo
4.
J Nanobiotechnology ; 22(1): 478, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135099

RESUMO

PURPOSE OF REVIEW: Atherosclerosis, a highly pathogenic and lethal disease, is difficult to locate accurately via conventional imaging because of its scattered and deep lesions. However, second near-infrared (NIR-II) nanomaterials show great application potential in the tracing of atherosclerotic plaques due to their excellent penetration and angiographic capabilities. RECENT FINDINGS: With the development of nanotechnology, among many nanomaterials available for the visual diagnosis and treatment of cardiovascular diseases, optical nanomaterials provide strong support for various biomedical applications because of their advantages, such as noninvasive, nondestructive and molecular component imaging. Among optical nanomaterials of different wavelengths, NIR-II-range (900 ~ 1700 nm) nanomaterials have been gradually applied in the visual diagnosis and treatment of atherosclerosis and other vascular diseases because of their deep biological tissue penetration and limited background interference. This review explored in detail the prospects and challenges of the biological imaging and clinical application of NIR-II nanomaterials in treating atherosclerosis.


Assuntos
Aterosclerose , Nanoestruturas , Aterosclerose/diagnóstico por imagem , Humanos , Nanoestruturas/química , Animais , Raios Infravermelhos , Placa Aterosclerótica/diagnóstico por imagem , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos
5.
J Stroke Cerebrovasc Dis ; 33(6): 107677, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38460777

RESUMO

OBJECTIVES: To investigate the relationship between baseline computed tomography perfusion deficit volumes and functional outcomes in patients with basilar artery occlusion (BAO) undergoing endovascular therapy. METHODS: This was a single-center study in which the data of 64 patients with BAO who underwent endovascular therapy were retrospectively analyzed. All the patients underwent multi-model computed tomography on admission. The posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score was applied to assess the ischemic changes. Perfusion deficit volumes were obtained using Syngo.via software. The primary outcome of the analysis was a good functional outcome (90-day modified Rankin Scale score ≤ 3). Logistic regression and receiver operating characteristic curves were used to explore predictors of functional outcome. RESULTS: A total of 64 patients (median age, 68 years; 72 % male) were recruited, of whom 26 (41 %) patients achieved good functional outcomes, while 38 (59 %) had poor functional outcomes. Tmax > 10 s, Tmax > 6 s, and rCBF < 30 % volume were independent predictors of good functional outcomes (odds ratio range, 1.0-1.2; 95 % confidence interval [CI], 1.0-1.4]) and performed well in the receiver operating characteristic curve analyses, exhibiting positive prognostic value; the areas under the curve values were 0.85 (95 % CI, 0.75-0.94), 0.81 (95 % CI, 0.70-0.90), and 0.78 (95 % CI, 0.67-0.89). CONCLUSION: Computed tomography perfusion deficit volume represents a valuable tool in predicting high risk of disability and mortality in patients with BAO after endovascular treatment.


Assuntos
Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Estado Funcional , Imagem de Perfusão , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Insuficiência Vertebrobasilar , Humanos , Masculino , Feminino , Idoso , Procedimentos Endovasculares/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/fisiopatologia , Insuficiência Vertebrobasilar/terapia , Imagem de Perfusão/métodos , Avaliação da Deficiência , Idoso de 80 Anos ou mais , Fatores de Tempo , Angiografia Cerebral , Fatores de Risco , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/fisiopatologia , Tomografia Computadorizada Multidetectores , Curva ROC
6.
Cancer Cell Int ; 22(1): 65, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135548

RESUMO

BACKGROUND: Tumor microenvironments are characterized by resistance to chemotherapeutic agents and radiotherapy. Hypoxia plays an important role in the development of tumor resistance, as well as the generation of metastatic potential. YAP also participates in the regulation of hypoxia-mediated chemoresistance, and is negatively regulated by protein tyrosine phosphatase non-receptor type 14 (PTPN14). METHODS: The PTPN14 expression in hepatocellular carcinoma (HCC) tissues were evaluated by qRT-PCR, western blot and tissue microarrays. The effect of PTPN14 on HCC progression was investigated in vitro and in vivo. RESULTS: Here, we report that PTPN14 expression was downregulated in HCC tissues and cell lines. Silencing PTPN14 significantly enhanced proliferation, migration, invasion of HepG2 cells in vitro and tumor growth and metastasis in vivo, whereas overexpression of PTPN14 significantly inhibited these abilities in SK-Hep1 cells. We also found that hypoxia-induced nuclear translocation and accumulation of PTPN14 led to resistance to sorafenib in HCC cells. Further mechanistic studies suggested that NPM1 regulates PTPN14 localization, and that NPM1 regulates YAP by retaining PTPN14 in the nucleus under hypoxic conditions. CONCLUSIONS: These data suggest that a therapeutic strategy against chemoresistant HCC may involve disruption of NPM1-mediated regulation of YAP by retaining PTPN14 in the nucleus under hypoxic conditions.

7.
J Sci Food Agric ; 102(11): 4802-4812, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35229291

RESUMO

BACKGROUND: Prebiotics, such as algal polysaccharides, can be used to manage metabolic diseases by modulating gut microbiota. However, the effect of Pyropia yezoensis porphyran (PYP), a red algal polysaccharide, on gut microbiota has not been reported. Thus, the objective of this study was to determine effects of PYP on metabolic disorders caused by high sucrose (HS) and underlying mechanisms involved in such effects. RESULTS: Biochemical analysis demonstrated that an HS diet increased triglyceride and circulating sugar contents (metabolic abnormalities) in Drosophila larvae. It also increased the relative abundance of harmful microbiota within the larvae as identified by 16S ribosomal DNA analysis. PYP supplementation at 25 and 50 g kg-1 equivalently reduced metabolic abnormalities in the HS group. Therefore, 25 g kg-1 PYP was selected to investigate its effects on the metabolic pathway and gut microbiota of larvae in the HS group. The activity of PYP in ameliorating metabolic abnormalities by reverse transcription quantitative real-time polymerase chain reaction analysis was consistent with the expression trend of key factors involved in metabolism regulation. PYP reduced the relative abundance of bacteria causing metabolic abnormalities, such as Escherichia-Shigella and Fusobacterium, but increased the relative abundance of beneficial bacteria such as Bacillus and Akkermansia. However, PYP had no effect on triglyceride and circulating sugar contents in HS-fed larvae treated with a mixture of antibiotics designed to remove gut microbiota. CONCLUSION: PYP exhibits anti-metabolic disorder activity by modulating gut microbiota, thereby supporting the development of PYP as a functional prebiotic derived from red algae food. Copyright © 2022 John Wiley & Sons, Ltd. © 2022 Society of Chemical Industry.


Assuntos
Microbioma Gastrointestinal , Doenças Metabólicas , Rodófitas , Animais , Dieta Hiperlipídica , Drosophila melanogaster/genética , Doenças Metabólicas/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/farmacologia , Prebióticos , Sefarose/análogos & derivados , Sacarose , Triglicerídeos
8.
J Nanobiotechnology ; 19(1): 132, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971910

RESUMO

Molecular imaging technology enables us to observe the physiological or pathological processes in living tissue at the molecular level to accurately diagnose diseases at an early stage. Optical imaging can be employed to achieve the dynamic monitoring of tissue and pathological processes and has promising applications in biomedicine. The traditional first near-infrared (NIR-I) window (NIR-I, range from 700 to 900 nm) imaging technique has been available for more than two decades and has been extensively utilized in clinical diagnosis, treatment and scientific research. Compared with NIR-I, the second NIR window optical imaging (NIR-II, range from 1000 to 1700 nm) technology has low autofluorescence, a high signal-to-noise ratio, a high tissue penetration depth and a large Stokes shift. Recently, this technology has attracted significant attention and has also become a heavily researched topic in biomedicine. In this study, the optical characteristics of different fluorescence nanoprobes and the latest reports regarding the application of NIR-II nanoprobes in different biological tissues will be described. Furthermore, the existing problems and future application perspectives of NIR-II optical imaging probes will also be discussed.


Assuntos
Raios Infravermelhos , Imagem Molecular/métodos , Imagem Óptica/métodos , Animais , Tecnologia Biomédica , Liberação Controlada de Fármacos , Fluorescência , Humanos , Neoplasias/diagnóstico por imagem , Razão Sinal-Ruído , Células-Tronco , Cirurgia Assistida por Computador/métodos
9.
Nanomedicine ; 32: 102342, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33253922

RESUMO

Acute kidney injury (AKI) is a life-threatening disease without effective treatment. The utilization of curcumin (Cur) for the treatment of AKI is still facing challenges due to its poor water-solubility and low bioavailability. Herein, kidney-targeted octenyl succinic anhydride-grafted fucoidan loaded with Cur (OSA-Fucoidan/Cur) was fabricated for synergistic treatment of AKI. It was found that OSA-Fucoidan/Cur micelles had a sustained drug release behavior and excellent physicochemical stability. Cellular uptake studies demonstrated that the specific binding between fucoidan and P-selectin overexpressed on H2O2-stimulated HUVECs contributed to the higher internalization of OSA-Fucoidan/Cur micelles by the cells. In addition, OSA-Fucoidan micelles exhibited an ideal kidney-targeted characteristic in lipopolysaccharide (LPS)-induced AKI mice. In vivo studies showed that the combination of Cur and OSA-Fucoidan endowed the OSA-Fucoidan/Cur micelles with synergistically anti-inflammatory and antioxidant abilities, thereby largely enhancing the therapeutic efficacy of AKI. Therefore, OSA-Fucoidan/Cur micelles may represent a potential kidney-targeted nanomedicine for effective treatment of AKI.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Portadores de Fármacos/química , Micelas , Selectina-P/antagonistas & inibidores , Polissacarídeos/química , Injúria Renal Aguda/patologia , Animais , Antioxidantes/farmacologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Meia-Vida , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos ICR , Anidridos Succínicos/química , Distribuição Tecidual/efeitos dos fármacos
10.
Ecotoxicol Environ Saf ; 225: 112739, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481351

RESUMO

The incidence of metabolic diseases is increasing every year, and several studies have highlighted the activity of persistent organic pollutants (POPs) in causing hyperlipidemia and diabetes, and these compounds are considered to be endocrine disrupting chemicals (EDCs). Chlordane is classified as an endocrine disruptor, but the mechanism of how it functions is still unclear. This study investigates the effects of chlordane exposure on Drosophila larvae. Drosophila was cultured in diet containing 0.01 µM, 0.1 µM, 1 µM, 5 µM, and 10 µM chlordane, and the toxicity of chlordane, the growth and development of Drosophila, the homeostasis of glucose and lipid metabolism and insulin signaling pathway, lipid peroxidation-related indicators and Nrf2 signaling pathway were evaluated. We here found that exposure to high concentrations of chlordane decreased the survival rate of Drosophila and that exposure to low concentrations of chlordane caused disruption of glucose and lipid metabolism, increased insulin secretion and impairment of insulin signaling. Notably, it also led to massive ROS production and lipid peroxidation despite of the activation of Nrf2 signaling pathway, an important pathway for maintaining redox homeostasis. Collectively, chlordane causes lipid peroxidation and disrupts redox homeostasis, which may be a potential mechanism leading to impaired insulin signaling and the metabolism of glucose and lipid, ultimately affects Drosophila development.


Assuntos
Disruptores Endócrinos , Doenças Metabólicas , Animais , Clordano , Drosophila melanogaster , Insulina
11.
J Magn Reson Imaging ; 52(2): 499-509, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31950573

RESUMO

BACKGROUND: The poor prognosis of cardiac sarcoidosis (CS) underscores the need for risk stratification. PURPOSE: To investigate the prognostic significance of ventricular/myocardial remodeling features in sarcoidosis. STUDY TYPE: Retrospective. POPULATION: In all, 132 biopsy-proven sarcoidosis patients imaged from 2008 to 2018. The primary endpoint was a composite of cardiac mortality, new onset arrhythmias, hospitalization for heart failure, and device implantation. FIELD STRENGTH/SEQUENCE: No field strength or sequence restrictions. ASSESSMENT: Global and regional ventricular/myocardial remodeling features were assessed by standard volumetric measurements and automated function imaging postprocessing analysis. STATISTICAL TESTS: Student's t-test or Mann-Whitney test (chi2 test or Fisher's exact test for categorical variables) were used for comparisons. Cox-proportional hazards regression model, univariate /multivariate analyses, and receiver operating characteristic were performed to relate clinical/lab data, imaging parameters to the endpoints. RESULTS: Over a median follow-up of 40.7 (interquartile range 18.8-60.5) months, 41 (31.1%) patients developed adverse cardiac events. Abnormal left ventricular (LV) geometric remodeling alterations (measured by LV mass index and relative wall thickness) occurred 3.66-fold more frequently in patients with endpoints than patients without. The ratio of patients with endpoints increased as ventricular remodeling phenotype progressed. In patients with endpoints, regional myocardial wall thickness (RMWT) was significantly (P = 0.022) increased in six clustered LV segments located in the middle interventricular septum and basal/middle anterolateral walls. In all of the abnormal ventricular remodeling stages, patients with endpoints constantly had higher mean RMWT than those without. Among clinical, electrocardiographic, and imaging parameters, LV mass index (hazard ratio [HR] 1.010 95% confidence interval [CI] 1.002-1.018, P = 0.017) and mean RMWT (HR 3.482 95% CI 1.679-7.223, P = 0.001) were independently associated with endpoints. Sarcoidosis patients without this RMWT distribution pattern were significantly (P < 0.001) more likely to be free of the occurrence of subsequent cardiac events. DATA CONCLUSION: Regional myocardial remodeling characteristics are associated with subsequent adverse cardiac events in sarcoidosis. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:499-509.


Assuntos
Sarcoidose , Função Ventricular Esquerda , Humanos , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcoidose/diagnóstico por imagem , Remodelação Ventricular
12.
Cell Commun Signal ; 18(1): 165, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092596

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

13.
Cell Commun Signal ; 18(1): 174, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115468

RESUMO

BACKGROUND: In this study, we comprehensively analyzed genes related to ferroptosis and iron metabolism to construct diagnostic and prognostic models and explore the relationship with the immune microenvironment in HCC. METHODS: Integrated analysis, cox regression and the least absolute shrinkage and selection operator (LASSO) method of 104 ferroptosis- and iron metabolism-related genes and HCC-related RNA sequencing were performed to identify HCC-related ferroptosis and iron metabolism genes. RESULTS: Four genes (ABCB6, FLVCR1, SLC48A1 and SLC7A11) were identified to construct prognostic and diagnostic models. Poorer overall survival (OS) was exhibited in the high-risk group than that in the low-risk group in both the training cohort (P < 0.001, HR = 0.27) and test cohort (P < 0.001, HR = 0.27). The diagnostic models successfully distinguished HCC from normal samples and proliferative nodule samples. Compared with low-risk groups, high-risk groups had higher TMB; higher fractions of macrophages, follicular helper T cells, memory B cells, and neutrophils; and exhibited higher expression of CD83, B7H3, OX40 and CD134L. As an inducer of ferroptosis, erastin inhibited HCC cell proliferation and progression, and it was showed to affect Th17 cell differentiation and IL-17 signaling pathway through bioinformatics analysis, indicating it a potential agent of cancer immunotherapy. CONCLUSIONS: The prognostic and diagnostic models based on the four genes indicated superior diagnostic and predictive performance, indicating new possibilities for individualized treatment of HCC patients. Video Abstract.


Assuntos
Carcinoma Hepatocelular/genética , Ferroptose/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ferro/metabolismo , Neoplasias Hepáticas/genética , Microambiente Tumoral/imunologia , Animais , Carcinogênese/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Nomogramas , Piperazinas/química , Piperazinas/farmacologia , Prognóstico , Análise de Regressão , Reprodutibilidade dos Testes , Fatores de Risco , Microambiente Tumoral/genética
14.
Cell Commun Signal ; 18(1): 97, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576292

RESUMO

BACKGROUND: Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients. METHODS: Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models. RESULTS: Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvß3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvß3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN. CONCLUSIONS: Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC. Video Abstract.


Assuntos
Carcinoma Hepatocelular/genética , Glicólise/genética , Neoplasias Hepáticas/genética , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfaVbeta3/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Osteopontina/metabolismo , Prognóstico , Transdução de Sinais , Efeito Warburg em Oncologia
15.
Nanomedicine ; 14(7): 2167-2178, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30017962

RESUMO

Effective treatment and real-time monitoring of hepatic cancer are essential. A multifunctional calcium phosphate nanoparticles loading chemotherapeutic agent doxorubicin and magnetic resonance imaging contrast agent diethylenetriaminepentaacetic acid gadolinium (A54-CaP/Gd-DTPA/DOX) was developed for visual targeted therapy of hepatic cancer via T1-weighted MRI in real-time. A54-CaP/Gd-DTPA/DOX exhibited a higher longitudinal relaxivity (6.02 mM-1 s-1) than commercial MR contrast agent Gd-DTPA (3.3765 mM-1 s-1). The DOX release from the nanoparticles exhibited a pH dependent behavior. The cellular uptake results showed that the internalization of A54-CaP/Gd-DTPA/DOX into BEL-7402 cells was1.9-fold faster than that of HepG2 cells via A54 binding. In vivo experiments presented that A54-CaP/Gd-DTPA/DOX had higher distribution and longer retention time in tumor tissue than CaP/Gd-DTPA/DOX and free DOX, and also displayed great antitumor efficacy (95.38% tumor inhibition rate) and lower toxicity. Furthermore, the Gd-DTPA entrapped in the nanoparticles could provide T1-weighted MRI for real-time monitoring the progress of tumor treatment.


Assuntos
Fosfatos de Cálcio/química , Doxorrubicina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Nanopartículas/administração & dosagem , Fragmentos de Peptídeos/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Contraste , Doxorrubicina/administração & dosagem , Feminino , Gadolínio DTPA/química , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular , Nanopartículas/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Tumour Biol ; 39(5): 1010428317701656, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28475013

RESUMO

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Quimioembolização Terapêutica , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/secundário , Intervalo Livre de Doença , Óleo Etiodado/administração & dosagem , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Compostos Radiofarmacêuticos/uso terapêutico
17.
Cardiovasc Ultrasound ; 15(1): 26, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-29187206

RESUMO

BACKGROUND: Integrated bedside and sophisticated cardiac imaging techniques help characterize the discrepancy between myocardial injury and mechanic dysfunction in acute myocardial infarction. CASE PRESENTATION: A 57 year-old woman presented with sudden onset chest pain and ventricular fibrillation after hearing of her brother's death. The electrocardiography indicated "anterior wall ST segment elevation myocardial infarction". Coronary angiography ruled out obstructive lesion in the major coronary arteries, but revealed fibromuscular dysplasia of the distal left anterior descending artery. The ventriculography showed remarkable ventricular dilation, which affected much broader myocardium than the culprit vessel supplied. In a subsequent cardiac magnetic resonance study, delayed contrast (gadolinium) image revealed a focal left ventricular (LV) apical infarction. Her LV systolic function normalized within 1 week, except for a residual apical hypokinesis. She developed recurrent chest pain and LV dilation when she was laid off 9 months later. After supportive therapy, her symptoms improved and LV dysfunction normalized again. CONCLUSIONS: "Tako-tsubo" syndrome can occur recurrently in the heart with pre-existing localized myocardial infarction. Its molecular mechanism and clinical significance warrants further investigation.


Assuntos
Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Displasia Fibromuscular/diagnóstico , Imagem Cinética por Ressonância Magnética/métodos , Imagem Multimodal , Ventriculografia com Radionuclídeos/métodos , Cardiomiopatia de Takotsubo/diagnóstico , Vasos Coronários/fisiopatologia , Diagnóstico Diferencial , Ecocardiografia/métodos , Feminino , Displasia Fibromuscular/complicações , Displasia Fibromuscular/fisiopatologia , Humanos , Pessoa de Meia-Idade , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/fisiopatologia
18.
Abdom Imaging ; 40(5): 1164-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25316564

RESUMO

PURPOSE: The purpose of this study was to evaluate the computed tomography (CT) imaging characteristics of gastric schwannoma. METHODS: Eight cases of gastric schwannomas confirmed by surgery and pathology were retrospectively analyzed by CT. We reviewed the CT findings of gastric schwannomas for the following characteristics: tumor location, size, contour, margin, growth pattern, enhancement pattern, the presence or absence of necrosis, and perigastric lymph nodes. RESULTS: The tumors were located in the lesser curvature of gastric body (n = 5) and greater curvature of the gastric antrum (n = 3) with a median size of 4.8 cm (range 1.7-11.4 cm). Gastric schwannomas appeared as submucosal tumors with CT features of ovoid (7/8 patients), well-defined (8/8) and exophytic (4/8) or mixed (3/8) growth patterns. On dynamic CT examination, the tumors displayed homogeneous enhancement in seven cases and heterogeneous enhancement in one case. Solid parts of eight tumors demonstrated mild enhancement during the arterial phase and strengthened progressive enhancement during the venous and delayed phases. Two cases had perigastric lymph nodes. CONCLUSIONS: Gastric schwannomas typically manifested as ovoid, well-defined, exophytic, or mixed growth pattern masses on CT. Homogeneous progressive enhancement on dynamic CT is a characteristic finding of gastric schwannoma.


Assuntos
Neurilemoma/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Estômago/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologia , Estudos Retrospectivos , Estômago/patologia , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X
19.
World J Surg Oncol ; 13: 156, 2015 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-25896915

RESUMO

Primary ectopic meningiomas occurring in the mediastinal region are extremely rare. So far, only five cases of primary mediastinal meningioma have been reported in the literatures. The imaging characteristics and the clinicopathological significance of mediastinal psammomatous meningioma have not been detailed. Here, we report the case of a 42-year-old male with primary posterior mediastinal psammomatous meningioma. The clinical features, imaging, and pathological findings are carefully analyzed, and the relevant literatures were reviewed.


Assuntos
Neoplasias do Mediastino/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Adulto , Humanos , Masculino , Prognóstico , Tomografia Computadorizada por Raios X
20.
Zhonghua Yi Xue Za Zhi ; 95(7): 541-3, 2015 Feb 17.
Artigo em Zh | MEDLINE | ID: mdl-25916934

RESUMO

OBJECTIVE: To evaluate the diagnostic values of computed tomographic angiography (CTA) for liver VX2 tumor in rabbits. METHODS: A total of 40 New Zealand white rabbits were employed by implanting tumor fragment into left liver by computed tomography (CT)-guided percutaneous puncture. And successful modeling was established in 38 rabbits. Plain and three-phase enhanced CT scan and its CTA reconstruction were performed in different stages (14, 21 and 28 days) after tumor implantation, followed by digital subtraction angiography (DSA) via femoral artery and hepatic artery. Dynamic observations of tumor growth characteristics were recorded by plain and enhanced CT and comparing CTA and DSA images. And comparisons of CTA and DSA were made for identifying the origin, course and blood supply of transplanted tumors. RESULTS: (1) Multi-slice computed tomography (MSCT) could dynamically monitor the growth transfer characteristics. And all tumors became strengthened obviously in arterial phase and washed out in venous and delayed phases. (2) CTA showed that the feeding artery of transplanted tumor was hepatic artery. (3) No obvious differences existed in the display of feeding artery of transplanted tumor between CTA and DSA.However CTA was superior to DSA in displaying three-dimensional structure. CONCLUSION: Liver VX2 tumors are hypervascular in rabbits. CT enhanced scanning may dynamically monitor the growth patterns of tumors and CTA is a better method than DSA in visualizing the feeding arteries of tumors. Before and after interventions, CTA may replace DSA in evaluating liver VX2 tumors in rabbits.


Assuntos
Angiografia Digital , Neoplasias Hepáticas , Animais , Artéria Hepática , Coelhos , Tomografia Computadorizada por Raios X
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