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1.
World Neurosurg ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058120

RESUMO

OBJECTIVE: To determine whether TLICS and TL AOSIS have any superiority to each other in terms of the reliability of their recommendations for guiding the treatment strategy of thoracolumbar spine injuries. METHODS: One hundred and ten consecutive patients with thoracolumbar injuries hospitalized from January 2019 to September 2019 were analyzed retrospectively. The TLICS and the TL AOSIS systems were compared based on patients' therapeutic decisions suggested by each system. RESULTS: A total of 110 patients were studied. The TL AOSIS matched treatment decision making in 108 patients (98.18%), and the TLICS matched 96 patients (87.27%). Of the patients without neurological deficit, according to TL AOSIS system, 12 of 62 receivedï¹¥5 points, 12 received 4 or 5 points, and 38 received﹤4 points. While according to TLICS system, 12 of 62 received ≥5 points, 50 received ≤3 points, and nobody received 4 points. The TL AOSIS matched 60 patients (96.77%), and the TLICS matched 48 patients (77.42%). Of the patients with neurological deficits, according to TL AOSIS system, 36 of 48 receivedï¹¥5 points, and 12 received 4 or 5 points. While according to TLICS system, 22 receivedï¹¥4 points, and 26 received 4 points. And the systems achieved agreement. CONCLUSIONS: Recommendations of TL AOSIS might be more reliable than those of TLICS particularly for guiding the surgical management of complete burst fractures.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32006087

RESUMO

Results of a preclinical study suggested that the anticonvulsant drug ethosuximide may elicit ketamine-like rapid-acting antidepressant actions. We evaluated the antidepressant efficacy of ethosuximide versus placebo in non-medicated adult patients with major depressive disorder (MDD). This randomized, double-blind, placebo-controlled trial included patients at three mental health centers in China. Eighty eligible adults (aged 18-65 years) met the DSM-5 criteria for MDD. Patients in the acute single study received three doses (500, 1000, or 1500 mg) of ethosuximide or placebo. Patients in the repeated study received ethosuximide (1500 mg/day) or placebo for 2 weeks. The Hamilton Depression Rating Scale (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Hamilton Anxiety Rating Scale were used to assess antidepressant and antianxiety responses to ethosuximide. No significant reductions in depression and anxiety rating scale scores were observed after a single oral administration of ethosuximide, in comparison with placebo. Furthermore, patients receiving ethosuximide for 2 weeks did not show reductions in depression and anxiety rating scale scores. There were no serious adverse events. Responses to the study's primary and secondary outcome measures, the clinician-rated HAM-D and MADRS, showed no change from baseline to the end of treatment, with either ethosuximide or placebo. These results suggest that ethosuximide does not produce ketamine-like robust antidepressant actions in adult patients with MDD.

3.
Cancer Med ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31991061

RESUMO

BACKGROUND: Defects in DNA damage repair (DDR) system may lead to genomic instability and manifest as increased immunogenicity. DDR deficiency is prevalent in ovarian cancer (OvCa); however, the association of DDR mutation with immune profiles in OvCa remains largely unknown. This knowledge will provide an essential basis to the rational design of biomarker-guided immune combination therapy of OvCa in the future. METHODS: Whole-exome sequencing data of 587 OvCa from The Cancer Genome Atlas (TCGA) were used to determine the expression profiles of 47 immune-related genes and the abundance of tumor-infiltrating immune cells. A Chinese OvCa cohort (n = 220) tested by next-generation sequencing (NGS) was used to validate the association between DDR status and tumor mutation burden (TMB). RESULTS: A total of 19.3% in TCGA cohort and 25.9% in Chinese cohort harbored at least one DDR somatic mutation. DDR deficiency exhibited a distinct immune profile with significant higher expression levels of PTPRCAP, CCL5, IFI16, LAG3, IL15RA, and GBP1 in OvCa in the TCGA cohort. Different DDR pathway deficiency displayed various immune profiles. Increased levels of Th1 cells, TMB, and neoantigen were also observed in DDR-deficient tumors. CONCLUSIONS: DDR deficiency was associated with specific immune signatures in OvCa. Our findings emphasize the urgent need for biomarker-guided rational immune combination therapy to maximize the OvCa patients who could benefit from immunotherapy.

4.
Org Lett ; 22(3): 1213-1216, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31951144

RESUMO

A silylium-ion-promoted ring-opening hydrosilylation of unactivated cyclopropanes is reported. The reaction is facilitated by the γ-silicon effect, and the regioselectivity is influenced by various stabilizing effects on the carbenium-ion intermediates, including the ß-silicon effect. The experimental observations are in accord with the computed reaction mechanism. The work also showcases the ability of silylium ions to isomerize cyclopropyl to allyl groups, and the resulting α-olefins engage in a silylium-ion-mediated disilylation with hexamethyldisilane.

5.
J Food Sci ; 85(2): 340-348, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31957898

RESUMO

Rapeseed meal (RSM) is an important source of protein, but its value is limited due to the poor digestibility and the presence of many antinutritional factors. In this study, a two-step biological method was developed for detoxifying RSM and increasing its protein value. In the first stage, various detoxifying enzymes and proteases were produced by Aspergillus niger during solid-state fermentation (SSF). In the second stage, coordinated enzymatic hydrolysis was employed to further degrade the antinutritional factors and macromolecular proteins in the fermented RSM. Following fermentation at 30 °C for 48 hr and enzymatic hydrolysis at 45 °C for 24 hr, the content of trichloroacetic acid soluble protein (TCA-SP) and glucosinolates (GLS) in RSM was increased by 81.70% and reduced by 30.06%, respectively, compared with that obtained using the SSF process alone. Moreover, to improve the efficiency of enzymatic hydrolysis, the yield of acid protease was increased by optimizing the composition of the medium so that the TCA-SP content was increased to 208.39 mg/g and accounted for 51.62% of the total RSM protein, which was 99.36% and 629.66% higher than that in the fermented RSM and control, respectively. Overall, these results demonstrate that the two-step process could be more effective for the degradation of the antinutritional factors and improvement of the protein quality of RSM compared to use of the SSF method alone, which may improve the utilization of RSM in food and animal feed. PRACTICAL APPLICATION: Rapeseed meal (RSM) is a protein source that provides high-quality nutrition and can be applied to the development of value-added products for humans and animal feed. To improve the utilization of RSM, a combined method of solid-state fermentation and enzymatic digestion was developed. Compared with the traditional solid-state fermentation method, the present method further improves the quality of RSM and demonstrates improved efficacy in increasing the small peptide content while reducing the levels of antinutritional factors.

6.
Sci Total Environ ; 709: 136147, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31905573

RESUMO

Groundwater level is an important variable in the evolution process of ecological environment systems. However, spatiotemporal changes in groundwater level are attributed to the comprehensive influence of natural and anthropogenic activities. Therefore, understanding the major driving forces to changes in spatiotemporal patterns of groundwater level is essential for sustainable utilization of regional groundwater and sustaining healthy ecosystems, especially in arid areas. In this study, based on monthly observations of depth to groundwater table (DTGT) from 67 monitoring wells during 2001-2010 in the Yichang Irrigation Sub-district (YISD) of the Hetao Irrigation District (HID), which is located in Northwest China with an arid climate, the empirical orthogonal function (EOF) method was used to analyze the spatiotemporal variations of DTGT and the major driving forces. The EOF analysis results showed that the first two spatial structures (EOF1 and EOF2) of DTGT were found in this region, which explained over 65% and 8% of the spatial variation of DTGT, respectively. Meteorological factors (evaporation and temperature) were the first leading factors to drive the temporal pattern of the first expansion coefficient (EC1) corresponding to the EOF1 at intra-annual scale as well as inter-annual scale. Particularly, temperature controlled the EC1 pattern during the freezing period from December to March. Soil texture was shown to have good correlations with the spatial patterns of DTGT, although these correlations diminished when the depth exceeded 250 cm. This study provides strong evidence that the principal spatiotemporal variations of groundwater can be effectively extracted by the EOF method, thereby obtaining integrated views of the relationships between the groundwater system and meteorological and anthropogenic factors.

7.
Sci Total Environ ; 711: 135141, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31822401

RESUMO

Water supply safety of riverbank filtration wells (RBFWs) have attracted a great deal of attention in recent years as their role in water supply is increasingly valued. In this study, this issue was revealed from the perspective of water level, quality and supply capacity of RBFWs based on an interference-pumping test with three pumping wells near the Songhua River in Northeast China followed by a recovery test. The results showed that a stable cone of depression of groundwater level in the riverbank filtration (RBF) formed after pumping for about five days with the maximum drawdown of the groundwater level of 10.42 m. The corresponding water capacity of the well group maintained 2.78 × 104 m3/d from then until the end of the test, 60% of which were captured directly from the river. The groundwater level could return to the level before the pumping test after the pumping test stopped for one day. The RBF could provide turbidity, trace organic substances and major cations and anions (except for Ca2+ and Mg2+) pre-treatment of the river water with the removal rates of 29%-95% for some water quality indicators. However, limited improvement of water quality was observed with respect to some inorganic contaminants (Fe, Mn and NH4+-N) because the background concentrations of them in the groundwater were higher than in the river water. When compared with the impact on water level and supply capacity, the impact of the surface water-groundwater interaction on the mechanisms of water quality evolution was more complicated. Taken together, the results of this study indicate that RBFWs can ensure a sustainable water supply of stable quality, which can also simplify the post-treatment processes of waterworks and reduce costs.

8.
Sci Total Environ ; 707: 135601, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767320

RESUMO

The composition and distribution of microplastics in surface water of the Yellow River lower reach near estuary were investigated in this work. The major shape types of microplastics can be classified to fibers, fragments and particles, and 93.12% of microplastics in the surface water were fibers. The microplastics <200 µm were most abundant at all sample sites, which accounted for 87.94% of microplastics. The composition of microplastics was identified as polyethylene, polypropylene, and polystyrene according to infrared spectrometer analysis. The amounts of primary microplastics accounted for approximately three-fourths according to scanning electron microscope and microscope photo observing. The microplastics at different weathering processes could be also observed. The average abundances of microplastics in the dry and wet seasons were 930 and 497 item/L, respectively. The abundances of microplastics in the dry season all higher than that in the wet season. The microplastic concentrations in the surface water decreased linearly with the distances from the estuary of Yellow River with rather high positive correlation coefficients at wet season (r = 0.8104, p < .01) and at dry season (r = 0.8333, p < .01). The distribution of microplastics in the river section and the density of microplastics may be the primary factors to influence the microplastic concentrations in the surface water. The researches about distribution of microplastics in the river section might provide useful information that could be used for calculating either mass fluxes or inventories of microplastics.

9.
J Immunother Cancer ; 7(1): 341, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801636

RESUMO

BACKGROUND: Deciphering the correlation between immune-related adverse events (irAEs) categorized by organ system class and clinical benefit of immunotherapy is critical for clinical practice. The aim of this study is to investigate the incidence rates of irAEs and their correlations with objective response rate (ORR) in patients with advanced solid tumours treated with nivolumab (NIVO) or nivolumab plus ipilimumab (NIVO+IPI). METHODS: PubMed, Embase and Cochrane library were searched for eligible studies from January 1st, 2000 to May 1st 2019. Published clinical trials on NIVO or NIVO+IPI with reported irAEs were included. Logit transformation of the irAE incidences was applied for the generation of pooled estimate and Pearson correlation coefficient was calculated to evaluate the correlation between irAE and ORR. RESULTS: 48 clinical trials involving 7936 patients treated with NIVO or NIVO+IPI were included. Compared to NIVO, NIVO+IPI led to more all-grade and grade 3 or higher irAEs categorized by system organ class (P < 0.05). The ORR of NIVO was positively correlated with the incidence rate of skin (r = 0.79, P < 0.001), gastrointestinal (r = 0.56, P = 0.006) and endocrine irAEs (r = 0.44, P = 0.05), but not hepatic, pulmonary and renal irAEs. The ORR of NIVO+IPI was positively correlated with the incidence rate of skin (r = 0.54, P = 0.04), and gastrointestinal irAEs (r = 0.60, P = 0.02), but not endocrine, hepatic, pulmonary and renal irAEs. CONCLUSION: This meta-analysis summarizes the incidence rates of irAEs in patients with advanced solid tumours treated with NIVO or NIVO+IPI, and uncovers their correlations with ORR across multiple neoplasms. These findings highlight the potential of irAE to reflect response to NIVO or NIVO+IPI.

10.
JAMA Oncol ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31876895

RESUMO

Importance: Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice. Objective: To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types. Data Sources: Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed. Study Selection: All randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups. Data Extraction and Synthesis: Three investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis. Main Outcomes and Measures: Differences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Results: Nineteen randomized clinical trials involving 11 379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P < .001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P = .02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies. Conclusions and Relevance: Comprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.

11.
J Thorac Oncol ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843683

RESUMO

INTRODUCTION: Blood-based tumor mutational burden (bTMB) has been studied to differentiate non-small cell lung cancer (NSCLC) patients who would benefit from anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. However, it failed to predict overall survival (OS) benefits, which warrants further exploration. METHODS: Three independent cohorts of NSCLC patients treated with immunotherapy were used in this study. A new bTMB algorithm was first developed in the two independent cohorts (POPLAR, N=211 and OAK, N=462) and further validated in the third National Cancer Center cohort (NCC, N=64). RESULTS: bTMB-H (bTMB≥cut-off point) was not associated with favorable OS following immunotherapy regardless of the cut-off points in either the POPLAR and OAK or the NCC cohorts (P>0.05) due to its correlation with the circulating tumor DNA (ctDNA) amount, which was associated with poor OS. In the POPLAR and OAK cohorts, upon allele frequency (AF) adjustment, a high allele frequency bTMB (HAF-bTMB, mutation counts with an AF>5%) was strongly correlated with the ctDNA amount (Pearson's r=0.65), while a low allele frequency bTMB (LAF-bTMB, mutation counts with an AF≤5%) was not (Pearson's r=0.09). LAF-bTMB-H was associated with favorable OS (hazard ratio [[HR], 0.70; 95% confidence interval [CI], 0.52-0.95; P=0.02), progression-free survival (PFS) (HR, 0.62; 95% CI, 0.47-0.80; P<0.001), and the objective response rate (ORR) (P<0.001) following immunotherapy but not chemotherapy, with a cut-off point of 12 trained in the POPLAR cohort and validated in the OAK cohort. The LAF-bTMB algorithm was further validated in the NCC cohort in which LAF-bTMB-H was associated with OS (HR, 0.20; 95% CI, 0.05-0.84; P=0.02), PFS (HR, 0.30; 95% CI, 0.13-0.70; P=0.003), and the ORR (P=0.001). CONCLUSIONS: We developed and validated a new LAF-bTMB algorithm as a feasible predictor of OS, PFS, and the ORR following anti-PD-1/PD-L1 therapies in NSCLC patients, which needs to be prospectively validated.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31781258

RESUMO

In traditional Chinese medicine theory, blood stasis syndrome (BSS), characterized by blood flow retardation and blood stagnation, is one of the main pathologic mechanisms and clinical syndromes of cardiovascular diseases (CVDs). Rhodiola wallichiana var. cholaensis injection (RWCI) is made from dry roots and stems of RWC via the processes of decoction, alcohol precipitation, filtration, and dilution. Studies indicated the extracts of RWC could alleviate CVDs; however, the mechanism had not been illustrated. In the present study, the acute blood stasis rat model was established to investigate the pathogenesis of BSS and the therapeutic mechanism of RWCI against BSS. Hemorheological parameters (whole blood viscosity and plasma viscosity) and inflammatory factors (TNF-α and IL-6) were used to evaluate the success of the BSS rat model and RWCI efficacy. 14 and 33 differential metabolites were identified from plasma and urine samples using the metabolomics approach based on ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The results of multivariate analysis displayed that there were significant separations among model, control, and treatment groups, but the high-dose RWCI treatment group was closer to the control group. 9 perturbed metabolic pathways were related to BSS's development and RWCI intervention. 5 metabolic pathways (arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, retinol metabolism, and steroid hormone biosynthesis) showed apparent correlations. These differential metabolites and perturbed metabolic pathways might provide a novel view to understand the pathogenesis of BSS and the pharmacological mechanism of RWCI.

13.
Sensors (Basel) ; 19(23)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775382

RESUMO

The remarkable development of various sensor equipment and communication technologies has stimulated many application platforms of automation. A drone is a sensing platform with strong environmental adaptability and expandability, which is widely used in aerial photography, transmission line inspection, remote sensing mapping, auxiliary communication, traffic patrolling, and other fields. A drone is an effective supplement to the current patrolling business in road traffic patrolling with complex urban buildings and road conditions and a limited ground perspective. However, the limited endurance of patrol drones can be directly solved by vehicles that cooperate with drones on patrolling missions. In this paper, we first proposed and studied the traffic patrolling routing problem with drones (TPRP-D) in an urban road system. Considering road network equations and the heterogeneity of patrolling tasks in the actual patrolling process, we modeled the problem as a double-layer arc routing problem (DL-ARP). Based on graph theory and related research work, we present the mixed integer linear programming formulations and two-stage heuristic solution approaches to solve practical-sized problems. Through analysis of numerical experiments, the solution method proposed in this paper can quickly provide an optimal path planning scheme for different test sets, which can save 9%-16% of time compared with traditional vehicle patrol. At the same time, we analyze several relevant parameters of the patrol process to determine the effect of coordinated traffic patrol. Finally, a case study was completed to verify the practicability of the algorithm.

14.
Clin Chem ; 65(12): 1543-1553, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672853

RESUMO

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS: Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-l-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS: In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908-0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875-0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929-0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909-0.953)]. CONCLUSIONS: Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB. CLINICALTRIALSGOV IDENTIFIER: NCT03047603.

15.
Mol Med Rep ; 20(5): 4551-4557, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702026

RESUMO

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of various types of cancer. The lncRNA deleted in lymphocytic leukemia 1 (DLEU1) has been reported to be dysregulated in cancer cells and thus associated with tumor development; however, the role of DLEU1 in renal cell carcinoma (RCC) remains unclear. In the present study, DLEU1 was knocked down using small interfering RNA in the RCC cell lines KETR3 and 786­O to determine the role of DLEU1. Cell Counting Kit­8, colony formation, Transwell and flow cytometry assays were performed to assess the effects of DLEU1 on cell proliferation, migration, invasion and apoptosis in KETR3 and 786­O cells. The protein expression levels of factors associated with apoptosis and epithelial­mesenchymal transition (EMT) were examined by western blot. The results demonstrated that silencing DLEU1 decreased the growth capacity, migration and invasion of KETR3 and 786­O cells. Additionally, loss of DLEU1 was observed to stimulate the mitochondrial pathway of cell apoptosis via regulation of the expression of Bcl­2/Bax, cleaved caspase­3 and cleaved caspase­9 in KETR3 and 786­O cells. Furthermore, DLEU1 knockdown significantly inhibited the protein kinase B (Akt) pathway by downregulating the expression of phosphorylated­Akt, cyclin  D1 and P70S6 kinase. In addition, depletion of DLEU1 was observed to impair the process of EMT in RCC cells via the upregulation of E­cadherin, and downregulation of N­cadherin and vimentin. Collectively, these results indicated a pro­oncogenic role of DLEU1 in the progression and development of RCC via modulation of the Akt pathway and EMT phenotype.

16.
J Cancer ; 10(22): 5315-5323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632476

RESUMO

Purpose: The aim of this study was to evaluate the diagnostic value of S100A9 and tenascin-c (TNC) levels as colorectal cancer (CRC) biomarkers in several ways, including through screening tests, differentiation tests, combination with existing biomarkers (CEA and CA19-9), and serum level measurements before and after surgery. Materials and Methods: In this case-control study, S100A9 and TNC serum levels were measured in 460 participants: 258 CRC patients, 99 patients with benign colonic disease (BCD) and 103 healthy donors (HD). Results: The serum levels of S100A9 were 22.32 (14.88-29.55) ng/ml, 10.02 (5.83-14.15) ng/ml and 10.05 (7.68-15.34) ng/ml in the CRC, BCD and HD groups, respectively. The serum levels of TNC were 4.30 (2.12-6.04) ng/ml, 1.60 (1.06-2.30) ng/ml and 2.00 (1.37-3.00) ng/ml in the CRC, BCD and HD groups, respectively. Significantly higher levels of both biomarkers (S100A9 and TNC) were found in CRC patients (both p<0.001). Both S100A9 and TNC levels were superior to CEA and CA19-9 levels as CRC diagnostic biomarkers; the combination of S100A9, TNC and CEA levels was an excellent biomarker with 79.8% sensitivity and 89.6% specificity. The serum levels of S100A9 and TNC in CRC patients were significantly lower after surgery than before surgery (p<0.01). Conclusion: S100A9 and TNC levels could serve as diagnostic biomarkers of colorectal cancer.

17.
J Cancer ; 10(21): 5108-5113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602263

RESUMO

Background: Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate new therapeutic strategies in cancer. However, RECIST fails to assess the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as the maximum percentage change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods: Advanced NSCLC patients harboring EGFR driver mutation (L858R or exon 19 deletion) treated with EGFR-TKI from August 2014 to July 2017 from two sites were retrospetively collected for analysis. Patients were divided into four groups by DepOR (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS against DepOR and the hazard ratio (HR) was determined through univariable and multivariable cox regression models. Results: In total, 265 patients were included for analysis. The number of patients in Group Q1-Q4 were 91 (34.3%), 73 (27.5%), 65 (24.5%) and 36 (13.6%), respectively. A greater DepOR was significantly associated with a longer PFS (Log-rank P<0.0001). The HRs (95% CI) for PFS comparing patients with different DepOR status were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3, and 0.33 (0.22-0.50) for Q4, all compared with patients in Q1. DepOR as a continuous variable was also associated with prolonged PFS (HR, 0.20; 95% CI, 0.13-0.33; P<0.001). Additionally, in the multivariable cox regression model, abnormal LDH, brain metastasis and male were found to be associated with worse PFS outcomes (P<0.05). Conclusion: A greater DepOR is significantly associated with PFS benefit in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to evaluate the response of targeted therapy.

18.
Sci Rep ; 9(1): 13315, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527664

RESUMO

A major challenge in regenerative medicine is the repair of injured neurons. Regeneration of laser-cut C. elegans neurons requires early action of core apoptosis activator CED-4/Apaf1 and CED-3/caspase. While testing models for CED-4 as a candidate calcium-sensitive activator of repair, we unexpectedly discovered that amino acid substitutions affecting alpha-helix-6 within the CED-4 caspase recruitment domain (CARD) confer a CED-4 gain-of-function (gf) activity that increases axonal regrowth without disrupting CED-4 apoptosis activity. The in vivo caspase reporter CA-GFP reveals a rapid localized increase in caspase activity upon axotomy, which is absent in ced-4 and ced-3 loss-of-function mutants but present in the ced-4(gf) mutant. The ced-3 loss-of-function mutation can significantly suppress the axonal regrowth of the ced-4(gf) mutant, indicating that CED-4(gf) regeneration depends on CED-3 caspase. Thus, we identified a subdomain within the CED-4 CARD that regulates the dynamic and controlled caspase activity required for efficient regeneration.

19.
Cancer Med ; 8(12): 5544-5553, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385461

RESUMO

BACKGROUND: Previous case reports have shown the promising antitumor activity of everolimus in solid tumors containing molecular aberrations in PI3K/ATK/mTOR pathway, however, whether it is effective in patients with breast cancer remains unknown. Therefore, we conducted this retrospective cohort study to compare the efficacy of molecularly matched targeted therapy with everolimus to conventional therapy in refractory breast cancer patients harboring PI3K/ATK/mTOR pathway activating mutations. METHODS: Refractory metastatic breast cancer patients who have received molecular screening using next-generation sequencing (NGS) between September 8, 2015 and October 30, 2017 in two sites were screened for this study. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety profile. RESULTS: A total of 78 patients were screened for analysis, amongst all, 52 (66.7%) had at least one gene mutation in PI3K/AKT/mTOR pathway. The most common mutation fell in PIK3CA (76.9%, 40/52) with a mutational prevalence of 51.3%. Of the 32 patients who were eligible for efficacy analysis, patients in the everolimus group (n = 19) exhibited shorter PFS than those in the conventional group (n = 13) (median, 1.9 vs 6.1 months; HR, 3.6; 95% CI, 1.48-8.81; P = .0005). ORR was 15.4% (2/13) in the everolimus group and 23.1% (3/13) in the conventional group (P = 1.000), and DCR was 30.8% (4/13) and 100% (13/13) for each group, respectively (P = .000). The incidence of grade 3-5 adverse events was relatively higher in the conventional group (38.5%, 5/13) than that in the everolimus group (26.3%, 5/19). CONCLUSIONS: Our findings suggested that everolimus might not be effective for cancer patients harboring mutations in PI3K/ATK/mTOR pathway and physicians should be cautious about its off-label use in clinical practice.

20.
Front Chem ; 7: 557, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31448263

RESUMO

The detailed mechanism of the AuCN-catalyzed annulation of salicylaldehyde (SA) and phenyl acetylene leading to isoflavanone-type complexes has been investigated via density functional theory (DFT) calculations. Reaction pathways and possible stationary points are obtained with the combined molecular dynamics and coordinate driving (MD/CD) method. Our calculations reveal that the cyanide ion promoted umpolung hydroacylation/intramolecular oxa-Michael addition mechanism is more favorable than the Au(I)/Au(III) redox mechanism proposed previously. In the umpolung mechanism, the hydroxyl of SA is found to strongly stabilize the cyanide ion involved intermediates and transition states via hydrogen bond interactions, while the Au(I) ion always acts as a counter cation. The overall reaction is exergonic by 41.8 kcal/mol. The hydroacylation of phenyl acetylene is the rate-determining step and responsible for the regioselectivity with a free energy barrier of 27.3 kcal/mol. These calculated results are in qualitative accord with the experimental findings.

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