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1.
Cancer Sci ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565687

RESUMO

Reliable and noninvasive biomarkers for the early diagnosis of non-small cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. By protein mass spectrometry, urinary MDH2 was found abundant both in lung cancer patients and lung cancer mice compared with controls. Urine samples obtained as retrospective and prospective cohort including 1091 NSCLC patients and 736 healthy controls were measured by ELISA. Compared to healthy controls, patients with stage I NSCLC had higher urinary MDH2. The area under the receiver operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohort for distinguishing stage I cases from controls. Urinary MDH2 level was correlated with gender and smoking history. MDH2 expression was elevated in lung cancer tissues. MDH2 knockdown via shRNA inhibited proliferation of lung cancer cells. Our study demonstrates that the urinary MDH2 concentration is higher in early-stage NSCLC patients than that in controls and may serve as a potential biomarker for the early detection of NSCLC.

2.
eNeuro ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33468538

RESUMO

Excitatory synaptic transmission in many neurons is mediated by two co-expressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in kinetics, ion-selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here we report that the voltage-dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of excitatory postsynaptic potentials (EPSPs) across spatial and voltage domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees revealed that the combined presence of AMPA and NMDA conductances reduce the variability of somatic responses to spatiotemporal patterns of excitatory synaptic input presented at different initial membrane potentials and/or in different dendritic domains. This moderating effect of the NMDA conductance on synaptic integration was robust across a wide range of AMPA-to-NMDA ratios, and results from synergistic interaction of NMDA kinetics (which reduces variability across membrane potential) and voltage-dependence (which favors stabilization across dendritic location). When combined with AMPA conductance, the NMDA conductance compensates for voltage- and impedance-dependent changes in synaptic driving force, and distance-dependent attenuation of synaptic potentials arriving at the axon, to increase the fidelity of synaptic integration and EPSP-spike coupling across both neuron state (i.e., initial membrane potential) and dendritic location of synaptic input. Thus, synaptic NMDA receptors convey advantages for synaptic integration that are independent of, but fully compatible with, their importance for coincidence detection and synaptic plasticity.Significance Statement Glutamate is an excitatory neurotransmitter that, at many synapses, gates two coexpressed receptor subtypes (AMPA and NMDA receptors). Computational simulations reveal that the combined synaptic presence of AMPA and NMDA receptors reduces variability in synaptic integration in response to identical patterns of synaptic input delivered to different dendritic locations and/or at different initial membrane potentials. This results from synergistic interaction of the slower kinetics and voltage-dependence of NMDA receptors, which combine to enhance synaptic currents when synaptic driving forces are otherwise reduced (e.g., at depolarized membrane potentials or in distal, high-impedance dendrites). By stabilizing synaptic integration across dendritic location and initial membrane potential, NMDA receptors provide advantages independent of, but fully compatible with, their well-known contribution to synaptic plasticity.

3.
J Org Chem ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33416327

RESUMO

We developed an electrochemical trifluoromethylation of thiophenols without the use of metal catalysts and oxidants. This reaction features mild reaction conditions, readily available substrate, as well as moderate to good yields. In addition, this protocol can be easily scaled up with moderate efficiency.

4.
Acta Biochim Biophys Sin (Shanghai) ; 53(2): 131-139, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33355638

RESUMO

The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome can be induced by a wide spectrum of activators. This is unlikely achieved by the binding of different activators directly to the NLRP3 protein itself, as the activators found so far show different forms of chemical structures. Previous studies have shown that these activators can induce potassium ion (K+) and chloride ion (Cl-) efflux, calcium (Ca2+) and other ion mobilization, mitochondrial dysfunction, and lysosomal disruption, all of which are believed to cause NLRP3 inflammasome activation; how these events are induced by the activators and how they coordinate with each other in inducing the NLRP3 inflammasome activation are not fully understood. Increasing evidence suggests that the coordinated change of intracellular ion concentrations may be a common mechanism for the NLRP3 activation by different activators. In this mini-review, we present a brief summary of the current knowledge about how different ionic flows (including K+, sodium ion, Ca2+, magnesium ion, manganese ion, zinc ion, iron ion, and Cl-) are involved in regulating the NLRP3 inflammasome activation in macrophages.

5.
Int J Cardiol ; 322: 1-8, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810548

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) participate in angiogenesis and neocollateralization. This study assessed if circulating EPCs can predict long-term improvement of global left ventricular systolic function in patients with coronary chronic total occlusions (CTOs) underwent successful percutaneous coronary intervention (PCI). METHODS: In this single-center, prospective, observational study, 115 consecutive patients with CTOs were evaluated by standard transthoracic echocardiography (ECHO) before and 9-12 months after PCI. Numbers of circulating putative EPCs were determined by flow cytometry analysis of mononuclear cells isolated from peripheral blood samples drawn before and 72 h after PCI. RESULTS: At mean 11.3 ± 2.5 months post vs. before PCI (all P < .05): by SAQ-7 summary scores, angina frequency, physical limitation and quality of life scores were greater; by ECHO, LVEDd decreased and LVEF increased, which were more significant in patients with Rentrop grades 2/3 vs. 0/1. At 72 h post vs. before PCI, CD34+VEGFR-2+CD133- (0.82 ± 0.32 × 106/L vs. 1.00 ± 0.39 × 106/L, P = .003), CD34+VEGFR-2+CD133+ (0.24 ± 0.12 × 106/L vs. 0.27 ± 0.14 × 106/L, P = .028), and CD14+Tie2+VEGFR-2+ (6.60 ± 3.32 × 106/L vs. 7.82 ± 3.91 × 106/L, P = .006) cell numbers were lower. The baseline levels of CD34+VEGFR-2+cells (P = .001) and CD14+Tie2+VEGFR-2+cells (P < .001) were association with the grade of collateralization. In addition, the baseline and peri-procedural decrease of circulating CD34+VEGFR-2+ cells correlated with the increase of LVEF (P < .001, P < .001, respectively) and the decrease of LVEDd (P = .022, P = .029, respectively) at follow-up. CONCLUSIONS: In this small study, the baseline levels of circulating CD34+VEGFR-2+ EPCs and its reduction after successful revascularization of CTOs correlated with long-term improvement in global LV systolic function.

6.
Angiology ; 72(1): 44-49, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32799665

RESUMO

Coronary chronic total occlusions (CTOs) are characterized by a high incidence of severe plaque calcifications, which are associated with a high use of the retrograde approach and a low success rate of percutaneous coronary intervention (PCI). However, the feasibility of rotational atherectomy (RA) in retrograde CTO-PCI remains unknown. The aim of the present study is to examine the safety and efficacy of RA in retrograde CTO-PCI. Consecutive patients (n = 129) who underwent RA during CTO-PCI were categorized into anterograde and retrograde groups according to the CTO crossing approach. The distributions of the baseline characteristics were similar in the 2 groups, but the lesion type was more complex (P = .001), and the starting burr size was smaller (P = .003) in the retrograde group than in the anterograde group. There was a trend of a higher incidence of procedural complications in the retrograde group than in the anterograde group (P = .054). Technical and procedural success and in-hospital outcomes were not significantly different between the 2 groups. In conclusion, RA was feasible in retrograde CTO PCI, but some specific precautions are required before and during the procedure. In addition, further investigation of the long-term outcomes of RA in retrograde CTO PCI is necessary.


Assuntos
Aterectomia Coronária/métodos , Oclusão Coronária/terapia , Aterectomia Coronária/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Estudos Retrospectivos , Stents
8.
Onco Targets Ther ; 13: 12067-12081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262607

RESUMO

Background: Long intergenic non-protein coding RNA 239 (LINC00239) is an oncogenic long non-coding RNA in acute myeloid leukemia. We aimed to determine LINC00239 expression in colorectal cancer (CRC) and examine the influences of LINC00239 on tumor behaviors of CRC cells. Furthermore, the mechanism underlying the actions of LINC00239 in CRC was unveiled in detail. Materials and Methods: Quantitative real-time polymerase chain reaction was used to detect LINC00239 expression in CRC tissues and cell lines. CRC cell proliferation, apoptosis, migration, and invasion were investigated by cell counting kit-8 assays, flow cytometry, and cell migration and invasion assays, respectively. Tumor xenograft experiments were performed to evaluate the tumor growth of CRC cells in vivo. The interactions among LINC00239, microRNA-484 (miR-484), and kruppel-like factor 12 (KLF12) were analyzed by bioinformatics prediction, RNA immunoprecipitation and luciferase reporter assay. Results: LINC00239 was upregulated in CRC tissues and cell lines. LINC00239 knockdown impaired CRC cell proliferation, migration, and invasion and promoted apoptosis in vitro. Additionally, LINC00239 deficiency inhibited CRC growth in vivo. Mechanistically, LINC00239 functioned as a competing endogenous RNA by directly sponging miR-484, thereby enhancing KLF12 expression. Rescue experiments further corroborated that miR-484 inhibition or KLF12 overexpression reversed the inhibitory actions of LINC00239 knockdown in CRC cells. Conclusion: The LINC00239/miR-484/KLF12 pathway executed critical roles in CRC oncogenicity and may provide potential targets for CRC treatments.

9.
Front Endocrinol (Lausanne) ; 11: 566761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362712

RESUMO

Background: Nonfunctioning pituitary neuroendocrine tumor (NF-PitNET) is difficult to resect. Except for surgery, there is no effective treatment for NF-PitNET. MicroRNA-134 (miR-134) has been reported to inhibit proliferation and invasion ability of tumor cells. Herein, the mechanism underlying the effect of miR-134 on alleviating NF-PitNET tumor cells growth is explored. Methods: Mouse pituitary αT3-1 cells were transfected with miR-134 mimics and inhibitor, followed by treatment with stromal cell-derived factor-1α (SDF-1α) in vitro. MiR-134 expression level: we used quantitative real-time PCR (qRT-PCR) to detect the expression of miR-134. Cell behavior level: cell viability and invasion ability were assessed using a cell counting kit-8 (CCK8) assay and Transwell invasion assay respectively. Cytomolecular level: tumor cell proliferation was evaluated by Ki-67 staining; propidium iodide (PI) staining analyzed the effect of miR-134 on cell cycle arrest; western blot analysis and immunofluorescence staining evaluated tumor migration and invasive ability. Additionally, we collected 27 NF-PitNET tumor specimens and related clinical data. The specimens were subjected to qRT-PCR to obtain the relative miR-134 expression level of each specimen; linear regression analysis was used to analyze the miR-134 expression level in tumor specimens and the age of the NF-PitNET population, gender, tumor invasion, prognosis, and other indicators. Results: In vitro experiment, miR-134 was observed to significantly inhibit αT3-1 cells proliferation characterized by inhibited cell viability and expressions of vascular endothelial growth factor A (VEGFA) and cell cycle transition from G1 to S phase (P < 0.01). VEGFA was verified as a target of miR-134. Additionally, miR-134-induced inhibition of αT3-1 cell proliferation and invasion was attenuated by SDF-1α and VEGFA overexpression (P < 0.01). In primary NF-PitNET tumor analysis, miR-134 expression level was negatively correlated with tumor invasion (P = 0.003). Conclusion: The regulation of the SDF-1α/miR-134/VEGFA axis represents a novel mechanism in the pathogenesis of NF-PitNETs and may serve as a potential therapeutic target for the treatment of NF-PitNETs.

10.
Front Oncol ; 10: 574889, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134173

RESUMO

Background and purpose: To evaluate the feasibility of dose-guided adaptive radiotherapy (ART) based on deformable image registration (DIR) using fractional megavoltage cone-beam CT (MVCBCT) images from Halcyon system that uses identical beams for treatment and imaging and to retrospectively investigate the influence of anatomic changes on target coverage and organ-at-risk (OAR) sparing across various tumor sites. Materials and Methods: Four hundred twenty-two MVCBCT images from 16 patients (three head and neck, seven thoracic, three abdominal, and three pelvic cases) treated in a phase II clinical trial for Halcyon were selected. DIR between the planning CT and daily MVCBCT image was implemented by Velocity software to create pseudo CT. To investigate the accuracy of dose calculation on pseudo CT, three evaluation patients with rescanned CT and adaptive plans were selected. Dose distribution of adaptive plans calculated on pseudo CT was compared with that calculated on the rescanned planning CT on the three evaluation patients. To investigate the impact of inter-fractional anatomic changes on target dose coverage and dose to OARs of the 16 patients, fractional dose was calculated and accumulated incrementally based on deformable registration between planning CT and daily MVCBCT images. Results: Passing rates using 3 mm/3%/10% threshold local gamma analysis were 93.04, 96.00, and 91.68%, respectively, for the three evaluation patients between the reconstructed dose on pseudo CT (MVCBCT) and rescanned CT, where accumulated dose deviations of over 97% voxels were smaller than 0.5 Gy. Planning target volume (PTV) D95% and D90% (the minimum dose received by at least 95/90% of the volume) of the accumulated dose could be as low as 93.8 and 94.5% of the planned dose, respectively. OAR overdose of various degrees were observed in the 16 patients relative to the planned dose. In most cases, OARs' dose volume histogram (DVH) lines of accumulated and planned dose were very close to each other if not overlapping. Among cases with visible deviations, the differences were bilateral without apparent patterns specific to tumor sites or organs. Conclusion: As a confidence building measure, this simulation study suggested the possibility of ART for Halcyon based on DIR between planning CT and MVCBCT. Preliminary clinical data suggested the benefit of patient-specific dose reconstruction and ART to avoid unacceptable target underdosage and OAR overdosage.

11.
Stress Health ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33251689

RESUMO

Exposure to prenatal maternal stress (PNMS) has been implicated as a risk factor for a range of psychiatric disorders in children. However, there have been a few studies showing inconsistent associations between PNMS and offspring autistic-like behaviours. We therefore aimed to examine whether trimester-specific PNMS exposure might be related to an increased risk of autistic-like behaviours among preschoolers. Using data from Longhua Children Cohort Study, mothers of 65,931 preschool children were asked to recall their level of PNMS in each of the three trimesters of pregnancy, while children's current autistic-like behaviours were assessed using the Autism Behaviour Checklist. A series of Cox regression models were fitted to assess the association between PNMS exposure and autistic-like behaviours. After adjusting for potential confounders, the Cox regression models showed that PNMS exposure, especially during the second pregnant trimester, was significantly and positively associated with the presence of children's autistic-like behaviours. The strength of these associations was enhanced with the increase of PNMS exposure level. Furthermore, based on different permutations of exposure versus no exposure in each trimester, the participants were divided into eight groups. A cross-over analysis confirmed the aforementioned finding that the second pregnant trimester might be the sensitive period for PNMS exposure increasing the risk of autistic-like behaviours. Our findings supported the hypothesis of an association between PNMS exposure and autistic-like behaviours among preschoolers. Preventive interventions should be trialled to examine whether minimizing maternal psychological stress during pregnancy, especially the second trimester, may reduce the risk of offspring autistic-like behaviours.

12.
NPJ Sci Food ; 4: 14, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083546

RESUMO

This paper explores how food safety and nutrition organisations can harness the power of search engines, games, apps, social media, and digital analytics tools to craft broad-reaching and engaging digital communications. We start with search engines, showing how organisations can identify popular food safety and nutrition queries, facilitating the creation of timely and in-demand content. To ensure this content is discoverable by search engines, we cover several non-technical aspects of search engine optimisation (SEO). We next explore the potential of games, apps, social media, and going viral for reaching and engaging the public, and how digital data-based tools can be used to optimise communications. Throughout, we draw on examples not only from Europe and North America, but also China. While we are enthusiastic about the benefits of digital communications, we recognise that they are not without their drawbacks and challenges. To help organisations evaluate whether a given digital approach is appropriate for their objectives, we end each section with a discussion of limitations. We conclude with a discussion of General Data Protection Regulation (GDPR) and the practical, philosophical, and policy challenges associated with communicating food safety and nutrition information digitally.

13.
Water Res ; 186: 116358, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898788

RESUMO

In this work, the ozonation properties of 2,2',3',4,5-pentachlorodiphenyl sulfide (PeCDPS) was systematically studied, with special emphasis on the underlying mechanism for the effects of inorganic ions. Kinetic experiments show that common ions can significantly reduce the oxidative properties of ozone, except for SO32- and Cu2+. The inhibition effect of anions has been explained through the scavenging effect of free radicals and the generation of other free radicals with weaker oxidation potentials, but no research has reported on the effect of free radicals generated by anions on the degradation pathway. However, SO32- and Cu2+ exerted a promoting effect through enhanced formation of ·OH via the hydrolysis effect and the catalyzed decomposition of O3, respectively. According to the intermediate products identified by high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) analysis, direct oxidation of S atom, substitution of Cl atom with -OH group, and hydroxylation of the benzene ring were commonly observed. The addition of NO2- and SO32- produced new free radicals like ·NO2, ·SO3 and ·SO4-, which would attack the parent compound or its primary product, thus influencing the degradation efficiency and pathways. The radicals initiated reactions and the structures of the corresponding products were further rationalized by density functional theory (DFT) calculations. These findings provide new insights into the effects of common anions on ozone oxidation of organic compounds.


Assuntos
Ozônio , Poluentes Químicos da Água , Cinética , Oxirredução , Sílica Gel , Sulfetos , Espectrometria de Massas em Tandem
14.
Thorac Cancer ; 11(11): 3234-3242, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32989915

RESUMO

BACKGROUND: Circulating genetically abnormal cells (CACs) with specific chromosome variations have been confirmed to be present in non-small cell lung cancer (NSCLC). However, the diagnostic performance of CAC detection remains unclear. This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC. METHODS: In this prospective study, a total of 339 participants (261 lung cancer patients and 78 healthy volunteers) were enrolled. An antigen-independent fluorescence in situ hybridization was used to enumerate the number of CACs in peripheral blood. RESULTS: Patients with early-stage NSCLC were found to have a significantly higher number of CACs than those of healthy participants (1.34 vs. 0.19; P < 0.001). The CAC test displayed an area under the receiver operating characteristic (ROC) curve of 0.76139 for discriminating stage I NSCLC from healthy participants with 67.2% sensitivity and 80.8% specificity, respectively. Compared with serum tumor markers, the sensitivity of CAC assays for distinguishing early-stage NSCLC was higher (67.2% vs. 48.7%, P < 0.001), especially in NSCLC patients with small nodules (65.4% vs. 36.5%, P = 0.003) and ground-glass nodules (pure GGNs: 66.7% vs. 40.9%, P = 0.003; mixed GGNs: 73.0% vs. 43.2%, P < 0.001). CONCLUSIONS: CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC. KEY POINTS: What this study adds: This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC. Significant findings of the study: CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC.

15.
Front Pharmacol ; 11: 1286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973517

RESUMO

Advanced drug carriers for the controlled release of chemotherapeutics in the treatment of malignant tumors have drawn significant notice in recent years. In the current study, microspheres (MPs) loaded with docetaxel (DTX) were prepared using polylactic-co-glycolic acid copolymer (PLGA). The double emulsion solvent evaporation method is simple to perform, and results in high encapsulation efficiency. Electron micrographs of the MPs showed that controlling the shear rate can effectively control the size of the MPs. At present, most DTX sustained-release carriers cannot maintain stable and long-term local drug release. The 1.68 µm DTX-loaded microspheres (MP/DTX) with elastase was completely degraded in 14 d. This controlled degradation period is similar to a course of treatment for most cancers. The drug release profile of all kinds of MP/DTX demonstrated an initial rapid release, then slower and stable release to the end. The current study demonstrates that it is possible to create drug-loaded MPs with specific degradation times and drug release curves, which may be useful in achieving optimal treatment times and drug release rates for different diseases, and different drug delivery routes. The initial burst release reaches the effective concentration of the drug at the beginning of release, and then the drug concentration is maintained by stable release to reduce the number of injections and improve patient compliance.

16.
Gynecol Oncol ; 159(2): 365-372, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32933759

RESUMO

OBJECTIVE: High-dose-rate (HDR) afterloading brachytherapy using Iridium-192 source involves large radiation activity varieties due to fast decay. It was unknown but clinically desirable to evaluate its impacts on patient outcomes to support more informed decisions. METHODS: Data of 510 cervical carcinoma (CC) patients were retrospectively included. High-radioactive (HR) and low-radioactive (LR) groups were statistically defined per patient-specific average mean-dose-rate (MDR) of all fractions. The cutoffs were calculated using R-3.6.1 packages based on significance of correlation with binary outcome or survival time. Categorized 1-month and 3-month follow-up results were analyzed as short-term outcomes. Long-term outcomes were evaluated using local recurrence-free survival (LRFS) and metastatic recurrence-free survival (MRFS). Propensity-score-matched (PSM) pairs were generated to reduce bias. RESULTS: The median follow-up time was 47.1 months (interquartile range: 33.9 months-66.4 months), involving MDR varieties of up to 9 folds ranging from 6059.99 cGy/h to 54013.66 cGy/h due to 17 source replacements at intervals ranging from 93 days-199 days. Both short-term (1-month: p = 0.22; 3-month: p = 0.79) and long-term (LRFS: p = 0.10; MRFS: p = 0.46) outcomes showed no significant difference between HR and LR. Subgroup analysis displayed significantly better results in LR for stage I-II (3-month, p = 0.02) and stage II (LRFS, p = 0.04) patients. Both LRFS and MRFS of LR were significantly non-inferior to HR (p ≤ 0.02). CONCLUSIONS: LR is clinically non-inferior or partially superior to HR for CC treatment using HDR, which dispels concerns of potentially undermined patient outcomes when source replacement is delayed.

17.
Transl Lung Cancer Res ; 9(4): 1187-1201, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953497

RESUMO

Background: The genomic profile of non-small cell lung cancer (NSCLC) in Asians is distinct from that of Caucasians, but comprehensive genetic profiling reports have been limited for Asian patients. We aimed to elucidate genomic characteristics of Chinese NSCLC patients and develop potential model including genomic characteristics to predict postoperative prognosis. Methods: Resected tumor samples from 511 patients with stage I-IV lung cancer were subjected to targeted sequencing using a panel of 295 cancer-related genes. Based on the molecular profiles and clinical features, we established nomogram models with predictors consisting of integrated clinical and genomic characteristics to provide post-operative risk stratification. Results: Compared to the TCGA population (mainly Caucasians), there was a significantly higher frequency of EGFR (53.7% vs. 14.4%) and NOTCH3 (8.4% vs. 1.3%) mutations and less mutated KRAS (11.0% vs. 32.6%), KEAP1 (4.4% vs. 17.4%) and LRP1B (16.3% vs. 29.6%) in Chinese lung adenocarcinomas (LUAD). Distinct patterns of mutually exclusive and co-occurring mutations were identified between LUAD and lung squamous cell carcinoma (LUSC), indicating the unique histology-specific tumorigenesis mechanism of each subtype. We observed alterations in pathways correlated with clinical characteristics. Additionally, we constructed nomogram model with predictors consisting of clinical and genomic characteristics, which were more accurate than models with clinical characteristics or TNM staging only both in stage I-IIIA patients and T1-2N0M0 sub-cohort. Conclusions: This study revealed Chinese NSCLC patients have unique genomic profile. Furthermore, the nomogram model combining clinical features with genomic characteristics could improve risk stratification in early-stage NSCLC.

18.
Medicine (Baltimore) ; 99(31): e21210, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756098

RESUMO

RATIONALE: Procalcitonin (PCT) has been identified as a tumor biomarker in medullary thyroid carcinoma. Other neuroendocrine carcinomas with elevated PCT levels are relatively rare, and are mainly reported in the lung, digestive tract, and pancreas. No studies in the literature have reported a case of primary hepatic carcinoma complicated with unexpectedly elevated PCT levels. PATIENT CONCERNS: A 78-year-old man with persistent fatigue and mild fever was complicated with an extremely high PCT level. Radiological examination revealed a single hypodense lesion in the left lobe of the liver with a "rapid enhancement and rapid washout" pattern. Pathological analysis showed a poorly differentiated neuroendocrine carcinoma (grade 3) with multiple genetic mutations. DIAGNOSIS: Primary hepatic neuroendocrine carcinoma. INTERVENTIONS: The patient received antibiotic therapy and subsequent transcatheter hepatic arterial chemoembolization; a PCT assessment and computed tomography were performed during the follow-up. OUTCOMES: The PCT level did not decline after antibiotic therapy but greatly declined in response to effective transcatheter hepatic arterial chemoembolization. The patient survived and is still being followed up. LESSONS: An extremely elevated PCT level may raise a suspicion of a neuroendocrine carcinoma and plays an indicative role as a biomarker during therapy.


Assuntos
Carcinoma Neuroendócrino/diagnóstico , Neoplasias Hepáticas/diagnóstico , Pró-Calcitonina/sangue , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/terapia , Quimioembolização Terapêutica , Diagnóstico Diferencial , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Masculino , Tomografia Computadorizada por Raios X
19.
Thorac Cancer ; 11(10): 2887-2895, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32856417

RESUMO

BACKGROUND: This study aimed to identify an efficient, simple, and specific method of detecting mutations in the epidermal growth factor receptor (EGFR) gene in isolated lung cancer circulating tumor cells (CTCs) and to improve the ability to obtain tumor tissue clinically. METHODS: EGFR peptide lipid magnetic spheres (EG-P-LMB) were prepared by reverse evaporation, and characterization and cell capture efficiency assessed. The peripheral blood samples of 30 lung cancer patients were isolated and identified with the EG-P-LMB using 20 healthy volunteers as controls. Finally, the isolated CTCs were tested for EGFR gene mutations, and the tissue samples selected for comparison. RESULTS: The prepared magnetic spheres had a smaller particle size and higher stability according to the particle size potential test. Their morphology was homogeneous by atomic force observation, and the UV test showed that there were peptides on the surface. The separation efficiency of EG-P-LMB was greater than 90% in PBS and greater than 80% in the blood simulation system. Compared with the tissue sample results, the positive rate of EGFR gene mutations was 94%. The CTC test results of 27 patients were consistent with the tissue test results of the corresponding patients, and the consistency with the tissue comparison test results was 90% (27/30). CONCLUSIONS: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice. WHAT THIS STUDY ADDS: This study added EGFR peptide lipid magnetic spheres to capture CTCs in the blood. Genetic testing was performed and compared with tissues. It solves the problem of clinically difficult tumor tissue sampling.

20.
Oncol Lett ; 20(3): 3024-3034, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782620

RESUMO

Glioma is one of the most prevalent types of malignancy in the central nervous system worldwide, and the prognosis of patients with late stage glioma remains poor. Thus, the development of promising therapeutic strategies against glioma is essential. Long non-coding RNAs (lncRNAs) are functional RNA molecules involved in the initiation and progression of tumors, including glioma. Investigation on the regulatory roles of lncRNAs may facilitate the development of effective treatments. lncRNA NBAT1 is associated with the growth and metastasis of cancer; however, its underlying molecular mechanisms remain unknown. Thus, the present study aimed to investigate the effects of NBAT1 in glioma. The expression levels of NBAT1, microRNA (miRNA/miR)-21 and SOX7 in patients with glioma, and healthy donors using reverse transcription-quantitative PCR analysis. Human glioma cells (A172 and AM138) and normal astrocytes were used to establish the NBAT1-knockdown and overexpression models. Cell Counting Kit-8 and Transwell assays were performed to determine whether NBAT1 exerted effects on cell proliferation, migration and invasion. The results demonstrated that NBAT1 expression decreased in glioma tissues compared to normal samples. Additionally, downregulation of NBAT1 was detected in human glioma cells compared with normal astrocytes. Overexpression of NBAT1 inhibited glioma cell proliferation, migration and invasion. In addition, miR-21 was identified as a potential target of NBAT1, and the effects of miR-21-induced cell proliferation and metastasis were reversed following overexpression of NBAT1. Furthermore, SOX7 was predicted as the potential target of miR-21, and its expression was upregulated in glioma cells by overexpression of NBAT1 compared with the vehicle only control. Taken together, the results of the present study provide novel insight into the functions of NBAT1 in glioma, suggesting that the NBAT1/miR-21/SOX7 axis may act as a potential therapeutic target for the treatment of patients with glioma.

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