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1.
Chem Pharm Bull (Tokyo) ; 68(4): 369-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32238654

RESUMO

Tyrosinase plays important roles in many different disease related processes, and the development of its inhibitors is particularly important in biotechnology. In this study, thirty-nine 3-/4-alkoxyphenylethylidenethiosemicarbazides were synthesized as novel tyrosinase inhibitors based on structure-based molecular design. Our experimental results demonstrated that thirty-one of them possess remarkable tyrosinase inhibitory activities with IC50 value below 1 µM, and 5a, 6e, 6g and 6t did not display any toxicity to 293T cell line at the concentration of 1000 µmol/L. According to the inhibitory activities, several compounds were selected for detail investigation on the structure-activity relationships (SARs), mechanisms of enzyme inhibition, inhibitory kinetics and cytotoxicity. In particular, the interaction between the selected inhibitors and the active center of tyrosinase was considered and discussed in detail based on their structural characteristics. Taken together, the results presented here demonstrated that the newly designed compounds are promising candidates for the treatment of tyrosinase-related disorders and further development of them may have significant contribution in biomedical science.

2.
Clin Cancer Res ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32234760

RESUMO

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

3.
Hepatol Int ; 14(2): 190-201, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32078141

RESUMO

BACKGROUND: Two-dimensional shear wave elastography (2D-SWE) is the latest generation of ultrasound elastography for the non-invasive assessment of liver fibrosis in chronic hepatitis B (CHB). We aimed to identify confounders of 2D-SWE in fibrosis grading. METHODS: A prospective cohort of 440 CHB patients (286 with liver biopsy and 154 with clinical decompensated cirrhosis) was consecutively enrolled from a clinical trial (registration number: ChiCTR-DCD-15006000) aimed at optimizing 2D-SWE assessments from 2015 to 2018. All patients underwent 2D-SWE examination, anthropometric measurement, and serum biomarker assessment. Steatosis was graded by the magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). RESULTS: Overall, the prevalence of incorrect fibrosis staging by 2D-SWE was 26.1% (n = 115), with 43.5% of patients under-staged and 56.5% over-staged. In multivariate analysis, the steatosis degree was an independent predictor of 2D-SWE discordance in the overall cohort, with moderate-severe steatosis for underestimation (odds ratio, [OR] = 4.3, 95% confidence interval [CI] 1.2-18.2, p = 0.049) and overestimation (OR = 8.2, 95% CI 2.9-23.5, p < 0.001), and mild steatosis for overestimation (OR = 3.7, 95% CI 1.5-9.0, p = 0.004). In patients with liver biopsy, both histological inflammation activity over 2 (OR = 5.0, 95% CI 2.0-25.3, p = 0.048) and moderate-severe steatosis (OR = 5.2, 95% CI 2.1-13.4, p < 0.001) were independent factors associated with discordance. For the risk of 2D-SWE mis-staging, a nomogram that integrated these confounders was established and the area under the receiver operating characteristic curve of the model was 0.861. CONCLUSIONS: Steatosis and inflammation activities were confounders for 2D-SWE. The combination of these confounders could predict mis-staging risks of CHB-related fibrosis with 2D-SWE and may be valuable to decision-making on liver biopsy for fibrosis staging.

4.
Leukemia ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080345

RESUMO

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

5.
Soft Robot ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31986109

RESUMO

Soft climbing robots have attracted much attention of researchers for their potential applications on the wall or inside the tube. However, making a soft robot climb on the outer surface of a rod or tube by agile and efficient motion has long been a challenge. Inspired by the winding climbing locomotion of arboreal snakes, a tethered pneumatic-actuated winding-styled soft rod-climbing robot that consists of two winding actuators and a telescopic actuator is proposed in this work. Based on constant curvature assumption, we develop a theoretical model to analyze the linear and bending motion of the actuators. We demonstrate that our robot can perform climbing locomotion similar to snakes, including turning around a corner along a rod, climbing a vertical rod with a maximum speed of 30.85 mm/s (0.193 body length/s), and carrying a larger payload (weight, 500 g, more than 25 times its self-weight) than existing soft climbing robots do on a vertical surface. In addition, the experimental tests exhibit the potential applications of the robot in special environments such as high-voltage cables, nuclear power plants, and underwater sites.

6.
J Hazard Mater ; 385: 121552, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31733996

RESUMO

A high-efficiency hollow BiOCl@CeO2 heterostructured microspheres with type-II staggered-gap type was successfully synthesized by precipitation-hydrothermal process loaded with BiOCl nanoparticles on CeO2 microspheres. XRD, FT-IR, EDS, SEM, HRTEM and XPS results show that the prepared materials have good crystallization, morphology and retain hollow spherical structure of CeO2. Batch experiments indicate that the photocatalytic performance of BiOCl@CeO2 towards Tetracycline (TC) is superior to pure BiOCl or CeO2 owing to the distinctive hollow structures and the formed heterostructure between BiOCl and CeO2. Cyclic experiment exhibits that the optimal BiOCl@CeO2 photocatalyst can still photodegrade more than 80% of TC in 120 min after 4 cycles. Additionally, the reactive oxidation species (ROS) trapping experiments reveal that the critical ROS include photogenerated holes (h+) and superoxide radical anions (O2-). Finally, the possible degradation pathways of TC and enhanced photodegradation mechanism was systematically discussed. On this basis, the hollow BiOCl@CeO2 heterostructured microspheres provide a new alternative with great potential in efficient visible-light-driven photodegradation of persistent organic pollutants.

7.
Biosens Bioelectron ; 148: 111832, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706173

RESUMO

Fluorescence-activated cell sorting (FACS) has rarely been applied to screening of microorganisms because of poor detection resolution, which is compromised by poor stability, toxicity, or interference from background fluorescence of the fluorescence sensors used. Here, a fluorescence-based rapid high-throughput cell sorting method was first developed using a fluorescence resonance energy transfer (FRET) fluorescent nanoprobe NP-RA, which was constructed by coating a silica nanoparticle with Rhodamine B and methyl-red (an azo dye). Rhodamine B (inner layer) is the FRET donor and methyl-red (outer layer) is the acceptor. This ready-to-use NP-RA is non-fluorescent, but fluoresces once the outer layer is degraded by microorganisms. In our experiment, NP-RA was ultrasensitive to model strain Shewanella decolorationis S12, showing a broad detection range from 8.0 cfu/mL to 8.7 × 108 cfu/mL under confocal laser scanning microscopy, and from 1.1 × 107 to 9.36 × 108 cfu/mL under a fluorometer. In addition, NP-RA bioimaging can clearly identify other azo-respiring cells in the microbial community, including Bosea thiooxidans DSM 9653 and Lysinibacillus pakistanensis NCCP-54. Furthermore, the fluorescent probe NP-RA is compatible with downstream FACS so that azo-respiring cells can be rapidly sorted out directly from an artificial microbial community. To our knowledge, no fluorescent nanoprobe has yet been designed for tracking and sorting azo-respiration functional microorganisms.

8.
Materials (Basel) ; 12(24)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818046

RESUMO

In this work, polyamide 6 (PA6) composites with improved flame retardancy and thermal conductivity were prepared with different thermal conductive fillers (TC fillers) such as aluminum nitride (AlN) and boron nitride (BN) in a PA6 matrix with aluminum diethylphosphinate (AlPi) as a fire retardant. The resultant halogen-free flame retardant (HFFR) and thermal conductive (TC) PA6 (HFFR-TC-PA6) were investigated in detail with a mechanical property test, a limiting oxygen index (LOI), the vertical burning test (UL-94), a cone calorimeter, a thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). The morphology of the impact fracture surface and char residue of the composites were analyzed by scanning electron microscopy (SEM). It was found that the thermal conductivity of the HFFR-TC-PA6 composite increased with the amount of TC fillers. The TC fillers exerted a positive effect for flame retardant PA6. For example, the HFFR-TC-PA6 composites with the thickness of 1.6 mm successfully passed the UL-94 V-0 rating with an LOI of more than 29% when the loading amount of AlN-550RFS, BN-SW08 and BN-NW04 was 30 wt%. The morphological structures of the char residues revealed that TC fillers formed a highly integrated char layer surface (without holes) during the combustion process, as compared to that of flame retardant PA6/AlPi composites. In addition, the thermal stability and crystallization behavior of the composites were studied.

9.
Artif Cells Nanomed Biotechnol ; 47(1): 3585-3597, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31497998

RESUMO

Increasing evidences have revealed that long noncoding RNAs (lncRNAs) are frequently involved in various cancers. However, the expression and function of lncRNA DRAIC in nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that DRAIC was significantly increased in NPC tissues. Increased expression of DRAIC was positively correlated with advanced clinical stages of NPC patients. Functional assays revealed that ectopic expression of DRAIC enhances NPC cell growth, migration and invasion. DRAIC knockdown represses NPC cell growth, migration and invasion. Mechanistically, we identified two miR-122 binding sites on DRAIC. RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays confirmed the binding of DRAIC to miR-122. Via binding of miR-122, DRAIC upregulated the expression of miR-122 target SATB1, which was abolished by the mutation of miR-122 binding sites on SATB1. Moreover, the oncogenic roles of DRAIC on NPC were reversed by the mutation of miR-122 binding sites on SATB1, simultaneous overexpression of miR-122, or depletion of SATB1. In addition, the expression of SATB1 was also increased and positively associated with that of DRAIC in NPC tissues. In conclusion, these findings revealed the important roles of DRAIC-miR-122-SATB1 axis in NPC and suggested that DRAIC may be a potential therapeutic target for NPC.


Assuntos
Movimento Celular/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , RNA Longo não Codificante/genética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Técnicas de Silenciamento de Genes , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/deficiência , Invasividade Neoplásica
10.
Bioresour Technol ; 289: 121734, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323713

RESUMO

From the perspective of waste utilization, the invasive species, Eupatorium adenophorum was used to prepare biochar, which was then loaded with iron/nickel bimetals. Compared with pure biochar, the biochar-loaded nano-iron/nickel bimetals have a significant effect on the removal of 2,4,6-trichlorophenol (2,4,6-TCP) from water, and their degradation rate can be increased by 39.7%-71.6% under different conditions. Several factors can influence the removal of 2,4,6-TCP, including the load ratio, pH of the solution, concentration of 2,4,6-TCP, and coexisting ions in water (HCO3-, SO42-, NO3-). Based on the density functional model (DET), Ni can activate H2 (produced in the reaction between nano-Fe and H2O) to convert to H*, which can then substitute Cl. The activation energy is 109.5 kJ/mol, indicating the reaction is easy to take place.


Assuntos
Ageratina , Poluentes Químicos da Água , Purificação da Água , Carvão Vegetal , Clorofenóis , Ferro , Níquel , Água
11.
Abdom Radiol (NY) ; 44(7): 2409-2417, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31093728

RESUMO

PURPOSE: Intraductal papillary neoplasms of the bile duct (IPNBs) are a group of rare lesions with uncertain clinical findings and imaging features. We aim to investigate the clinicopathological features and imaging findings of IPNBs on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT). METHODS: From February 2005 to March 2018, 30 patients with pathologically confirmed IPNBs were retrospectively identified in our hospital. Demographic, clinical, and pathological data, CEUS and CECT features and surgical strategies were analyzed. RESULTS: The most common clinical manifestations were abdominal pain (53.3%), jaundice (23.3%), and acute cholangitis (10.0%). Among all lesions, 5/30 (16.7%) lesions presented as dilated bile ducts only, while 13/30 (43.3%) lesions presented as dilated bile ducts with intraductal papillary masses, and 12/30 (40.0%) presented as solid masses with dilated bile ducts. For the 20 patients who underwent both CEUS and CECT, 18 lesions were hyperenhanced on CEUS, and 17 lesions were hyperenhanced on CECT in the arterial phase. In total, 16 and 18 lesions showed washout in the portal and late phases on CEUS, while the corresponding number of lesions that showed washout in the portal and late phases on CECT were 11 and 13. Twelve lesions (40.0%) showed atypical hyperplasia, while 16/30 (53.3%) lesions underwent malignant transformations. CONCLUSIONS: There are 3 major forms of IPNBs on grayscale ultrasound, including diffusely dilated bile ducts without visible mass; focal dilated bile duct with intraductal papillary masses; and solid mass surrounded by dilated bile ducts. The enhancement patterns of IPNBs on CEUS and on CECT were consistent. IPNB has a high malignant potential, and patients should be treated with surgical resection after the diagnosis is established.

12.
Chemosphere ; 228: 656-667, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31063913

RESUMO

A novel blocking wall was synthesized using fly ash and bentonite with strong adsorption capability. The optimized material ratio of the blocking wall was determined by penetration tests, shear tests and adsorption tests. The morphologies and stabilities of blocking wall samples with optimized material ratio were investigated by scanning electron microscopy (SEM), energy spectrum analysis (EDS), and erosion tests, the adsorption capability of blocking wall with optimized material ratio was investigated by adsorption kinetic and isotherm tests, the migration and penetration time of Cd pollutants in blocking wall with optimized material ratio were investigated by penetration tests and numerical simulations. Results indicated that the optimized fly ash/bentonite ratio (in mass) of blocking wall was 5:1. The permeability coefficient was 1.11 × 10-8 m s-1 and the maximum adsorption rate was 98.38%. Meanwhile, Cd2+ adsorbed on the blocking wall homogeneously; the alkali corrosion resistance of the blocking wall was higher than its acid corrosion resistance, and its resistance to organic pollutants and solutions with high Cd2+ concentrations were high. The adsorption process can be described by the Quasi-first-order kinetics and the Freundlich equation. Specifically, the overall adsorption efficiency was simultaneously affected by liquid membrane diffusion and particle diffusion and the adsorption process is an endothermic one dominated by physical adsorption. Additionally, Cd2+ penetration through the wall was dominated by molecular diffusion. The variation of permeability coefficient was inversely proportional to the initial concentration of Cd2+. The penetration of Cd2+ at initial concentration of 500 mg L-1 through the blocking wall needs 40 years.


Assuntos
Bentonita/química , Cádmio/química , Cinza de Carvão/química , Poluentes Químicos da Água/química , Poluição Química da Água/prevenção & controle , Adsorção , Compostos de Cádmio/química , Água Subterrânea , Concentração de Íons de Hidrogênio , Cinética , Microscopia Eletrônica de Varredura , Permeabilidade , Sulfatos/química
13.
J Biol Chem ; 294(25): 9959-9972, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31092598

RESUMO

Mesoderm development is a finely tuned process initiated by the differentiation of pluripotent epiblast cells. Serine/threonine kinase 40 (STK40) controls the development of several mesoderm-derived cell types, its overexpression induces differentiation of mouse embryonic stem cells (mESCs) toward the extraembryonic endoderm, and Stk40 knockout (KO) results in multiple organ failure and is lethal at the perinatal stage in mice. However, molecular mechanisms underlying the physiological functions of STK40 in mesoderm differentiation remain elusive. Here, we report that Stk40 ablation impairs mesoderm differentiation both in vitro and in vivo Mechanistically, STK40 interacts with both the E3 ubiquitin ligase mammalian constitutive photomorphogenesis protein 1 (COP1) and the transcriptional regulator proto-oncogene c-Jun (c-JUN), promoting c-JUN protein degradation. Consequently, Stk40 knockout leads to c-JUN protein accumulation, which, in turn, apparently suppresses WNT signaling activity and impairs the mesoderm differentiation process. Overall, this study reveals that STK40, together with COP1, represents a previously unknown regulatory axis that modulates the c-JUN protein level within an appropriate range during mesoderm differentiation from mESCs. Our findings provide critical insights into the molecular mechanisms regulating the c-JUN protein level and may have potential implications for managing cellular disorders arising from c-JUN dysfunction.

14.
Ecotoxicol Environ Saf ; 180: 366-373, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31102844

RESUMO

Fluoride removal from aqueous solution by adsorption using fly ash cenospheres (FAC) modified with paper mill lime mud (LM) as composite adsorbent had been investigated. The characterization of FAC and composite adsorbent were analyzed by Scanning electron spectroscope (SEM), Energy dispersive spectrometer (EDS), Brunauer emmett teller (BET) and Fourier transform infrared (FTIR), which demonstrated that the porous structure of composite adsorbent was obtained after surface modification. Adsorption of fluoride on modified fly ash cenospheres was fitted with pseudo-second-order model and Langmuir model. Response surface methodology (RSM) was employed to investigate the effects of F- concentration, pH, adsorbent dosage and temperature on the removal efficiency. Analysis of variance (ANOVA) was used to test the adequacy of the mathematical models. The Nonelectrostatic model of modified fly ash cenospheres adsorbing fluoride was built through the Generalized composite method, indicating that two inner-spherical complexes, ≡SF and ≡SOHF-, were formed in the adsorption process by means of the ligand exchange and surface complexation. Optimization of the adsorption conditions enabled the realization of the practical needs for fluoride contaminated water.


Assuntos
Compostos de Cálcio/química , Cinza de Carvão/química , Fluoretos/análise , Modelos Teóricos , Óxidos/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Temperatura
15.
Leukemia ; 33(10): 2454-2465, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.


Assuntos
MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão/métodos
16.
Future Oncol ; 15(17): 2009-2018, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30931608

RESUMO

Aim: To study the expression of EIF5A2 in urinary tract urothelial carcinoma and its clinicopathological features and prognosis. Methods: EIF5A2 expression was detected via immunohistochemistry in 101 patients. Results: Kaplan-Meier analysis showed that the EIF5A2 low expression group had significantly longer overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001) than the EIF5A2 high expression group. The high expression of EIF5A2 significantly predict poor OS and PFS in the subset patients (p < 0.05). EIF5A2 was an independent prognostic factor for OS and PFS (p = 0.003 and p = 0.001). The established nomogram model and its calibration curve predicted the probability of survival accurately. Conclusion: EIF5A2 is a potential molecular marker of poor prognosis in urinary tract urothelial carcinoma.


Assuntos
Carcinoma de Células de Transição/patologia , Neoplasias Renais/patologia , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Ureterais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Pelve Renal/patologia , Pelve Renal/cirurgia , Masculino , Pessoa de Meia-Idade , Nefroureterectomia , Prognóstico , Intervalo Livre de Progressão , Ureter/patologia , Ureter/cirurgia , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/cirurgia
17.
Curr Treat Options Neurol ; 21(5): 24, 2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31030283

RESUMO

PURPOSE OF REVIEW: Brachial plexopathies (BPs) are a heterogeneous group of diseases which can profoundly affect person's function and quality of life. This review targets current approaches to treatment of different BP types. RECENT FINDINGS: Although there are multiple BP etiologies, non-traumatic causes are particularly unrecognized by clinicians, leading to misdiagnoses and delay in appropriate therapies. Recent data suggests that idiopathic neuralgic amyotrophy may be 50-fold more common than previously thought, with poorer outcomes than reported unless rapid diagnosis is followed by a multidisciplinary approach to treatment, including surgery for refractory cases. Advances in diagnostic imaging reduce time to treatment, if proper recognition by primary providers leads to rapid referral to neurologists. Due to rarity, heterogeneity, and overlap of different BP syndromes, development of treatment strategies is still based on case series and retrospective studies. Despite advances in surgical therapies, there are no randomized trials to guide optimal approaches to treatment in either traumatic or non-traumatic cases. Recent advances in imaging and surgical therapies may significantly improve clinical outcomes for patients with BPs, if rapid diagnosis of these often under-recognized conditions can be substantially improved to optimize approach to management. Controlled trials are still needed to optimize therapeutic strategies.

18.
Lancet Oncol ; 20(4): 591-600, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30880070

RESUMO

BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

19.
Eur Radiol ; 29(9): 4648-4659, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30689032

RESUMO

OBJECTIVES: Preoperative prediction of microvascular invasion (MVI) in patients with hepatocellular cancer (HCC) is important for surgery strategy making. We aimed to develop and validate a combined intratumoural and peritumoural radiomics model based on gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in primary HCC patients. METHODS: This study included a training cohort of 110 HCC patients and a validating cohort of 50 HCC patients. All the patients underwent preoperative Gd-EOB-DTPA-enhanced MRI examination and curative hepatectomy. The volumes of interest (VOIs) around the hepatic lesions including intratumoural and peritumoural regions were manually delineated in the hepatobiliary phase of MRI images, from which quantitative features were extracted and analysed. In the training cohort, machine-learning method was applied for dimensionality reduction and selection of the extracted features. RESULTS: The proportion of MVI-positive patients was 38.2% and 40.0% in the training and validation cohort, respectively. Supervised machine learning selected ten features to establish a predictive model for MVI. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity of the combined intratumoural and peritumoural radiomics model in the training and validation cohort were 0.85 (95% confidence interval (CI), 0.77-0.93), 88.2%, 76.2%, and 0.83 (95% CI, 0.71-0.95), 90.0%, 75.0%, respectively. CONCLUSIONS: We evaluate quantitative Gd-EOB-DTPA-enhanced MRI image features of both intratumoural and peritumoural regions and provide an effective radiomics-based model for the prediction of MVI in HCC patients, and may therefore help clinicians make precise decisions regarding treatment before the surgery. KEY POINTS: • An effective radiomics model for prediction of microvascular invasion in HCC patients is established. • The radiomics model is superior to the radiologist in prediction of MVI. • The radiomics model can help clinicians in pretreatment decision making.


Assuntos
Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Microvasos/patologia , Cuidados Pré-Operatórios/métodos , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Talanta ; 194: 164-170, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609517

RESUMO

Fluorescein has been found as an efficient visible-light-induced oxidase mimic and its catalytic performance is group-dependent. Herein, a facile colorimetric strategy for ß-galactosidase (ß-gal) was developed using fluorescein di ß-D-galactopyranoside (FDG) as a probe based on the analyte induced change in oxidase mimicking activity of fluorescein derivatives. FDG doesn't possess any visible-light-induced oxidase activity and can generate fluorescein and fluorescein mono ß-D-galactopyranoside (FMG) in the presence of ß-gal. The in situ generated fluorescein and FMG possess high oxidase-like activities under visible-light illumination and could catalyze the oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) upon short irradiation by light-emitting diode (LED) lamp. Thus, the ß-gal activity can be selectively detected in linear range from 0.10 to 12.9 µg mL-1 with a limit of detection (LOD) of 0.04 µg mL-1. We further integrated with the visual detection of α-fetoprotein antigen (AFP) based on the corresponding colorimetric signal induced by ß-gal-linked colorimetric immunoassay, a LOD of 0.08 ng mL-1 could be achieved. Significantly, our proposed assay provides a facile sensing platform based on the change in enzyme mimicking activity induced by analytes. In addition, this optical method works without complex synthesis procedure and efficiently avoids participation of unstable H2O2 as an oxidant. Therefore, the present work not only shows the excellent assay performance in ß-gal and tumor biomarker detection, but also opens up a new avenue for its application in practical optical sensing.


Assuntos
Materiais Biomiméticos/química , Colorimetria/métodos , Fluoresceína/química , Oxirredutases/metabolismo , alfa-Fetoproteínas/metabolismo , beta-Galactosidase/metabolismo , Animais , Benzidinas/química , Catálise , Bovinos , Estudos de Viabilidade , Humanos , Imunoensaio , Oxirredução
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