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1.
Medicine (Baltimore) ; 100(16): e25414, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879671

RESUMO

ABSTRACT: Single-cell RNA-seq has become a powerful tool to understand tumor cell heterogenicity. This study tried to screen prognosis-related genes in basal-like breast tumors and evaluate their correlations with cellular states at the single-cell level.Bulk RNA-seq data of basal-like tumor cases from The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and single-cell RNA-seq from GSE75688 were retrospectively reviewed. Kaplan-Meier survival curves, univariate and multivariate analysis based on Cox regression model were conducted for survival analysis. Gene set enrichment analysis (GSEA) and single-cell cellular functional state analysis were performed.Twenty thousand five hundred thirty genes with bulk RNA-seq data in TCGA were subjected to screening. Preliminary screening identified 10 candidate progression-related genes, including CDH19, AQP5, SDR16C5, NCAN, TTYH1, XAGE2, RIMS2, GZMB, LY6D, and FAM3B. By checking their profiles using single-cell RNA-seq data, only CDH19, SDR16C5, TTYH1, and RIMS2 had expression in primary triple-negative breast cancer (TNBC) cells. Prognostic analysis only confirmed that RIMS2 expression was an independent prognostic indicator of favorable progression free survival (PFS) (HR: 0.78, 95%: 0.64-0.95, P  = .015). GSEA analysis showed that low RIMS2 group expression had genes significantly enriched in DNA Repair, and MYC Targets V2. Among the 89 basal-like cells, RIMS2 expression was negatively correlated with DNA repair and epithelial-to-mesenchymal transition (EMT).RIMS2 expression was negatively associated with DNA repair capability of basal-like breast tumor cells and might serve as an independent indicator of favorable PFS.


Assuntos
Neoplasias da Mama/genética , Proteínas de Membrana/genética , Neoplasia de Células Basais/genética , RNA-Seq , Proteínas rab3 de Ligação ao GTP/genética , Adulto , Biomarcadores Tumorais/genética , Simulação por Computador , Reparo do DNA/genética , Bases de Dados Genéticas , Detecção Precoce de Câncer/métodos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/genética
2.
Oncol Rep ; 45(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33786631

RESUMO

Thyroid carcinoma (THCA) is a common type of endocrine system cancer and its current clinical treatment method is surgical resection. Long non­coding RNAs (lncRNAs) have been revealed to serve important roles in a variety of complex human diseases. Therefore, determining the association between lncRNAs and diseases may provide novel insight into disease­related lncRNAs, with the aim of improving disease treatments and diagnoses. Long intergenic non­protein coding RNA 1816 (LINC01816) was identified to be associated with the survival of patients with colorectal cancer using the IDHI­MIRW method. The present study aimed to investigate the role and molecular mechanism of LINC01816 in THCA. Analysis of datasets from The Cancer Genome Atlas database revealed that the upregulation of LINC01816 expression levels was associated with a variety of cancer types. Reverse transcription­quantitative PCR analysis demonstrated that compared with the normal thyroid tissues, the expression levels of LINC01816 were upregulated in THCA tissues. The results of wound healing and Transwell assays, and western blotting demonstrated that the overexpression of LINC01816 could strengthen the invasive and migratory abilities of THCA cells and enhance epithelial­mesenchymal transition progression. Analysis using the starBase website and dual­luciferase reporter assays identified that microRNA (miR)­34c­5p was a target of LINC01816. The overexpression of miR­34c­5p could inhibit the invasive and migratory abilities of THCA cells, in addition to inhibiting the cellular retinoic acid binding protein 2 (CRABP2) overexpression­induced effects on invasion, migration and EMT processes. In conclusion, the findings of the present study indicated that LINC01816 may be capable of sponging miR­34c­5p to upregulate CRABP2 expression levels, which subsequently promoted the invasion, migration and EMT of THCA cells. Therefore, targeting the LINC01816/miR­34c­5p/CRABP2 pathway may be an effective therapeutic approach for patients with THCA.

3.
Sci Total Environ ; 774: 145553, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-33611006

RESUMO

Sustainability concerns are increasing globally. Besides, in Pakistan, these concerns are increasing day by day due to lack of education as well as redundancy among human capital, depletion of natural resources and economic growth can lead to pose severe threats to the environment. To address this concern, this study examines the phenomena that in what way natural resources, human capital, and economic growth affect two important indicators i.e., ecological footprint and carbon emission in Pakistan from 1985 to 2018 by using the dynamic autoregressive distribution lag (DARDL) approach. The outcomes of the analysis indicate that in the long run human capital and natural resource has a negative link with carbon emission whereas economic growth has a positive link with carbon emission. On the other side, in the short run, human capital and economic growth have a positive link with carbon emission while natural resources have a negative link with carbon emission. Moreover, in the long and short-run human capital and economic growth has a positive link with ecological footprint whereas natural resources have a negative link with the ecological footprint. However, the results of this study also revealed the presence of the environmental Kuznets curve (EKC) in Pakistan. Moreover, creating awareness among the citizens together with governmental regulatory pressures might help in solving the problems related to the environment resulting in preserving the sustainability of future generations in Pakistan.

4.
BMC Surg ; 21(1): 53, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482804

RESUMO

BACKGROUND: To investigate the association between postoperative lymph nodes (LNs) recurrence and distinct serum thyroglobulin (Tg) levels in patients with papillary thyroid carcinoma (PTC). METHODS: This study included PTC patients who underwent total thyroidectomy (TT) with at least central neck dissection and then re-operated due to recurrence of LNs between January 2013 and June 2018. These patients were grouped by negative or positive serum Tg levels according to the American Thyroid Association guidelines. RESULTS: Of the 60 included patients, 49 underwent radioactive iodine (RAI) treatment. Maximum unstimulated Tg (uTg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs (P = 0.027), and higher rate of metastatic LNs (P < 0.001). Serum-stimulated Tg (off-Tg) ≥ 1 ng/mL (P = 0.047) and unstimulated Tg (on-Tg) ≥ 0.2 ng/Ml (P = 0.013) were associated with larger diameter of recurrent LNs. Number of metastatic LNs ≥ 8 was an independent predictor for postoperative maximum uTg ≥ 0.2 ng/mL (OR = 8.767; 95% CI = 1.392-55.216; P = 0.021). Ratio of metastatic LNs ≥ 25% was an independent predictor for off-Tg ≥ 1 ng/mL (OR = 20.997; 95% CI = 1.649-267.384; P = 0.019). CONCLUSION: Postoperative Tg-positive status was associated with larger size of recurrent LNs. Number of metastatic LNs ≥ 8 and ratio of metastatic LNs ≥ 25% were independent predicators for uTg-positive and off-Tg-positive status, respectively.


Assuntos
Recidiva Local de Neoplasia , Tireoglobulina/sangue , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Adulto , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
5.
J Clin Endocrinol Metab ; 106(4): 988-998, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33428730

RESUMO

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. METHODS: Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. RESULTS: The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. CONCLUSIONS: This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33481200

RESUMO

One of humanity's most significant problems in the twenty-first century revolves around how to balance the mitigation of environmental pollution while achieving sustainable economic development. Despite increased awareness and dedication to climate change, the planet is still seeing a drastic decrease in the volume of pollutant emissions. This study explores the long-run and causal impact of economic growth, financial development, urbanization, and gross capital formation on Malaysia's CO2 emissions based on the STIRPAT framework. The current paper employs recently developed econometric techniques such as Maki co-integration, auto-regressive distribution lag (ARDL), fully modified OLS (FMOLS), dynamic ordinary least square (DOLS), and wavelet coherence and gradual shift causality tests to investigate these interconnections. The advantage of the gradual shift causality test is that it can capture the causality in the presence of a structural break(s). The findings from the Maki co-integration and ARDL bounds tests reveal evidence of cointegration among the variables. The ARDL test reveals that economic growth, gross capital formation, and urbanization exert a positive impact on CO2 emissions. Furthermore, the wavelet coherence test reveals that there is a significant dependency between CO2 emissions and economic growth, gross capital formation, and urbanization. The Toda Yamamoto and Gradual shift causality tests reveal that there is a (a) unidirectional causality from urbanization to CO2 emissions, (b) unidirectional causality from economic growth to CO2 emissions, and (c) unidirectional causality from gross capital formation to CO2 emissions.

7.
Entropy (Basel) ; 22(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33287002

RESUMO

Functional brain network (FBN) is an intuitive expression of the dynamic neural activity interaction between different neurons, neuron clusters, or cerebral cortex regions. It can characterize the brain network topology and dynamic properties. The method of building an FBN to characterize the features of the brain network accurately and effectively is a challenging subject. Entropy can effectively describe the complexity, non-linearity, and uncertainty of electroencephalogram (EEG) signals. As a relatively new research direction, the research of the FBN construction method based on EEG data of fatigue driving has broad prospects. Therefore, it is of great significance to study the entropy-based FBN construction. We focus on selecting appropriate entropy features to characterize EEG signals and construct an FBN. On the real data set of fatigue driving, FBN models based on different entropies are constructed to identify the state of fatigue driving. Through analyzing network measurement indicators, the experiment shows that the FBN model based on fuzzy entropy can achieve excellent classification recognition rate and good classification stability. In addition, when compared with the other model based on the same data set, our model could obtain a higher accuracy and more stable classification results even if the length of the intercepted EEG signal is different.

8.
Diabetes Metab Syndr Obes ; 13: 4661-4667, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299334

RESUMO

Background: Previous studies have reported that diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD). Vascular cell adhesion molecule-1 (VCAM-1) plays an important role in the pathological process of atherosclerosis. The aim was to elucidate the relationship between serum VCAM-1 and early AD in DM patients. Methods: Serum samples for VCAM-1 were tested in 208 DM patients. All included DM patients were followed up for a median of 36 months prospectively. The prognostic value of serum VCAM-1 for predicting AD events was analyzed by using Cox proportional hazard. Results: Serum VCAM-1 was independently associated with AD history after adjusting for related confounding factors in patients with DM at baseline by using the logistic regression analysis (OR=1.861; 95% CI, 1.435-2.539; P trend=0.020). The Cox proportional hazard model suggested that VCAM-1 was a prognostic factor for AD events in the DM patients (HR=2.728; 95% CI, 1.785-5.439; P trend<0.001). Stratified analysis showed that the significant association between AD event and serum VCAM-1 in DM patients was not affective by CVD history. Conclusion: Our results showed that higher VCAM-1 levels were significantly related to a higher risk of AD events in DM patients. The serum biomarker might be beneficial to predict AD early. Serum VCAM-1 might be a good biochemical parameter for predicting AD in DM.

9.
EMBO J ; : e104532, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33215753

RESUMO

Metabolic fitness of T cells is crucial for immune responses against infections and tumorigenesis. Both the T cell receptor (TCR) signal and environmental cues contribute to the induction of T cell metabolic reprogramming, but the underlying mechanism is incompletely understood. Here, we identified the E3 ubiquitin ligase Peli1 as an important regulator of T cell metabolism and antitumor immunity. Peli1 ablation profoundly promotes tumor rejection, associated with increased tumor-infiltrating CD4 and CD8 T cells. The Peli1-deficient T cells display markedly stronger metabolic activities, particularly glycolysis, than wild-type T cells. Peli1 controls the activation of a metabolic kinase, mTORC1, stimulated by both the TCR signal and growth factors, and this function of Peli1 is mediated through regulation of the mTORC1-inhibitory proteins, TSC1 and TSC2. Peli1 mediates non-degradative ubiquitination of TSC1, thereby promoting TSC1-TSC2 dimerization and TSC2 stabilization. These results establish Peli1 as a novel regulator of mTORC1 and downstream mTORC1-mediated actions on T cell metabolism and antitumor immunity.

10.
Clin Cosmet Investig Dermatol ; 13: 789-794, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149651

RESUMO

Background: The available treatments for refractory hyperkeratotic eczema are inadequate with frustrating results. We, therefore, incorporated Calcipotriol and Betamethasone Dipropionate (Daivobet®), and Viaminate into the mainstay treatment to improve the clinical symptoms. The study aimed to evaluate the efficacy of Daivobet ® and Viaminate as a potential treatment alternative for refractory hyperkeratotic eczema. Patients and Methods: Between 2013 and 2015, 61 patients diagnosed with refractory hyperkeratotic eczema (RHE) who had shown inadequate response to conventional therapies were pooled from a single center. Besides, they were all treated with Daivobet ® , Viaminate, and an occlusive dressing mixture containing 5% salicylic acid ointment and 25% zinc oxide paste following inadequate response to conventional therapies (corticosteroids plus 25% zinc oxide paste and 5% salicylic acid ointment). Investigators Global Assessment (IGA) and Patient-Oriented Eczema Measure (POEM) assessed baseline and outcome measures for the degree of hyperkeratinization (0-clear; 3-moderate; 4-severe). Results: Of the 61 patients, 49 (80.3%) patients presented with moderate RHE and 12 (19.7%) with severe RHE. After 24 weeks of treatment, the period for loss of keratinization was significantly lower in patients with moderate RHE (3.9±1.9 weeks) than those with severe RHE (10.8±1.0 weeks) with a P-value <0.01. Furthermore, they required a significantly shorter total treatment duration (10.6 ± 4.3 weeks) than those with severe RHE (20.3±3.6 weeks) with a P-value of <0.01. However, there were no significant differences in post hoc analysis at week 36 with P-values of 0.46 and 1.00 for IGA and POEM, respectively. Conclusion: Our results showed that the incorporation of Viaminate and Daivobet® into mainstay treatment was effective and safe for the long-term management of RHE.

11.
J Magn Reson Imaging ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075178

RESUMO

BACKGROUND: MRI-based finite element analysis (MRI-FEA) is the only method able to assess microstructural and whole-bone mechanical properties of the hip in vivo. PURPOSE: To examine whether MRI-FEA is capable of discriminating age-related changes in whole-bone mechanical performance and micromechanical behavior of the proximal femur, particularly considering the most common hip fracture-related sideways fall loading. STUDY TYPE: Retrospective. SUBJECTS: A total of nine younger (27 ± 3.2 years) and nine elderly (61 ± 3.9 years) healthy volunteers. FIELD STRENGTH/SEQUENCE: 3T; 3D fast field echo sequence. ASSESSMENT: The left proximal femurs were scanned and FE models created. FEA was performed to simulate sideways fall and stance loading for each femoral model. Apparent stiffness and high-risk (90th percentile) tensile and compressive strains of the proximal femur as well as the average strains within cubic regions of the femoral neck and greater trochanter were assessed. STATISTICAL TESTS: Paired and unpaired t-tests. RESULTS: Compared to the young group, the femoral stiffness of the elderly decreased by 39% and 40% (both P < 0.05) under the sideways fall and stance conditions, respectively. Accordingly, the high-risk tensile and compressive stains were elevated with aging (40% and 23% for sideways fall, 23% and 11% for stance conditions; all P < 0.05). However, the loading configuration-induced difference was only observed in the elderly group for the high-risk strains (22% for tension and 12% for compression; both P < 0.05). Additionally, compared to the stance condition, the sideways fall increased the average tensile (young: 108%, elderly: 123%; both P < 0.05) and compressive strains (young: 631%, elderly: 617%, both P < 0.05) within the greater trochanter rather than the femoral neck region. DATA CONCLUSION: In vivo MRI-FEA is capable of capturing age-related changes in both apparent-level stiffness and tissue-level micromechanical behavior of the proximal femur. However, the effect of sideways fall loading might be better reflected by tissue-level micromechanics rather than apparent stiffness. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

12.
Materials (Basel) ; 13(20)2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33076495

RESUMO

The oral cavity harbors complex microbial communities, which leads to biomaterial-associated infections (BAI) during dental and orthopedic treatments. Conventional antibiotic treatments have met great challenges recently due to the increasing emergency of drug-resistant bacteria. To tackle this clinical issue, antibacterial surface treatments, containing surface modification and coatings, of dental and orthopedic materials have become an area of intensive interest now. Among various antibacterial agents used in surface treatments, metallic agents possess unique properties, mainly including broad-spectrum antibacterial properties, low potential to develop bacterial resistance, relative biocompatibility, and chemical stability. Therefore, this review mainly focuses on underlying antibacterial applications and the mechanisms of metallic agents in dentistry and orthopedics. An overview of the present review indicates that much work remains to be done to deepen the understanding of antibacterial mechanisms and potential side-effects of metallic agents.

13.
Oncol Rep ; 44(6): 2443-2454, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33125141

RESUMO

Flap endonuclease­1 (FEN1), a structure­specific nuclease participating in DNA replication and repair processes, has been confirmed to promote the proliferation and drug resistance of tumor cells. However, the biological functions of FEN1 in cancer cell migration and invasion have not been defined. In the present study, using online database analysis and immunohistochemistry of the specimens, it was found that FEN1 expression was associated with a highly invasive triple­negative breast cancer (TNBC) subtype in both breast cancer samples from the Oncomine database and from patients recruited into the study. Furthermore, FEN1 was an important biomarker of lymph node metastasis and poor prognosis in patients with TNBC. FEN1 promoted migration of TNBC cell lines and FEN1 knockdown reduced the number of spontaneous lung metastasis in vivo. Ingenuity Pathway Analysis of FEN1­related transcripts in 198 patients with TNBC demonstrated that the polo­like kinase family may be the downstream target of FEN1. PLK4 was further identified as a critical target of FEN1 mediating TNBC cell migration, by regulating actin cytoskeleton rearrangement. The results of the present study validate FEN1 as a therapeutic target in patients with TNBC and revealed a new role for FEN1 in regulating TNBC invasion and metastasis.

14.
Clin Breast Cancer ; 20(5): e540-e550, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32773343

RESUMO

PURPOSE: To investigate the relationship between dietary habits and breast cancer (BC) risk in Chinese women. PATIENTS AND METHODS: We performed a hospital-based matched case-control study that included 654 BC cases and 654 healthy controls matched by age and residence. A qualified structured questionnaire was used to collect detailed sociodemographic factors and information about dietary habits. The odds ratios (ORs) and 95% confidence intervals were calculated with unconditional logistic regression analysis; the patients were grouped according to their estrogen receptor (ER) status and analyzed separately. The propensity score analysis was performed according to different postmenopause status. RESULTS: ER-negative BC participants with intake of cured foods had increased BC risk (adjusted OR, 2.72, P = .017). Participants diagnosed as having ER-positive BC with intake of grilled foods had increased BC risk compared to those who did not consume such foods (adjusted OR, 2.14, P = .026). After propensity score analysis, fried (OR, 3.19, P = .001) and grilled (OR, 1.77, P = .031) food were considered to be risk factors for BC in premenopausal women; and fried (OR, 1.61, P = .006), grilled (OR, 4.62, P = .001), and smoked foods (OR, 2.28, P = .001) are considered risk factors for BC in postmenopausal women. CONCLUSION: Chinese women who ate cured, grilled, and fried foods had higher BC risk. Consumption of smoked food might contribute to increased BC risk in Chinese women.

15.
Thorac Cancer ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32841514

RESUMO

BACKGROUND: Exosomes have significant implications in cancer progression via transferring various modulatory molecules. Long non-coding RNAs (lncRNAs) play essential biological roles in lung cancer. In this report, we unlock the functional mechanism of tumor protein P73 antisense RNA 1 (TP73-AS1) in lung cancer. METHODS: The expression analyses of TP73-AS1, microRNA-216a-5p (miR-216a-5p) and Cullin 4B (CUL4B) were performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion were assessed using wound healing and transwell assays. Flow cytometry was applied to determine cell apoptosis. Colony formation assay was performed for cell survival to evaluate the effect on radiosensitivity. The intergenic interaction was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Western blot was used for associated protein determination. An in vivo experiment was conducted by establishing xenograft models in mice. RESULTS: TP73-AS1 was conspicuously overexpressed in lung cancer tissues and cells. Silencing TP73-AS1 restrained cell migration and invasion while it enhanced apoptosis and radiosensitivity of lung cancer. TP73-AS1 could bind to miR-216a-5p as well as miR-216a-5p and CUL4B. The function of TP73-AS1 downregulation in lung cancer was achieved by miR-216a-5p/CUL4B axis. Inhibition of TP73-AS1 also exerted an inhibitory effect on tumor growth and radioresistance in vivo potentially via regulating miR-216a-5p/CUL4B axis. Moreover, exosomes from lung cancer cells downregulated TP73-AS1 could repress tumor evolution and radioresistance. CONCLUSIONS: Collectively, TP73-AS1 acted as a sponge of miR-216a-5p to regulate CUL4B in order to promote tumor progression and radioresistance in lung cancer cells with the implication of exosomes, which presents a novel mechanism of tumor action and radioresistance in lung cancer. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: TP73-AS1 silence inhibits migration and invasion while elevates apoptosis and radiosensitivity in lung cancer cells TP73-AS1 targets miR-216a-5p and miR-216a-5p targets CUL4B WHAT THIS STUDY ADDS: Downregulation of TP73-AS1 reduces tumor growth and radioresistance in vivo via the miR-216a-5p/CUL4B axis Exosomes from si-TP73-AS1-transfected cells inhibits lung cancer progression and radioresistance.

16.
Turk J Orthod ; 33(2): 85-91, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32637188

RESUMO

Objective: This study aims to quantitatively compare cephalogram and cone-beam computed tomography (CBCT) when evaluating maxillary central incisor alveolar bone thickness. Methods: We used 30 sets of lateral cephalograms and CBCT images that were recorded at the same time. Labial, buccal, and overall alveolar bone thicknesses were measured on three measurement lines of the forward-most incisor in lateral cephalograms and four maxillary incisors in CBCT images. Paired t-test, interclass correlation coefficient analysis, one-way analysis of variance (ANOVA), and Bland-Altman analysis were used to assess cephalometrically measured alveolar bone thickness of maxillary incisors and compare these measurements with those made using CBCT images. Results: Significant differences were observed between cephalometric and CBCT-based measurements of maxillary incisor alveolar bone thickness; most values showed mild or moderate correlation between the two methods. In most cases, cephalometric measurements were greater than CBCT-based measurements. Bland-Altman plots and ANOVA revealed that measurement bias increased when measurement lines moved apically. Alveolar bone thickness was always overestimated on cephalograms. Conclusion: Maxillary incisor alveolar bone thickness is always overestimated on cephalograms compared with CBCT-based measurements, with the overestimations ranging from 0.3 to 1.3 mm. Cephalometric measurement bias increases when measurement lines move apically. Thus, CBCT should be recommended when the accurate evaluation of alveolar bone thickness is warranted.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32655662

RESUMO

Objective: To elucidate the pharmacological mechanisms of Qubi Formula (QBF), a traditional Chinese medicine (TCM) formula which has been demonstrated as an effective therapy for psoriasis in China. Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, BATMAN-TCM database, and literature search were used to excavate the pharmacologically active ingredients of QBF and to predict the potential targets. Psoriasis-related targets were obtained from Therapeutic Target Database (TTD), DrugBank database (DBD), MalaCards database, and DisGeNET database. Then, we established the network concerning the interactions of potential targets of QBF with well-known psoriasis-related targets by using protein-protein interaction (PPI) data in String database. Afterwards, topological parameters (including DNMC, Degree, Closeness, and Betweenness) were calculated to excavate the core targets of Qubi Formula in treating psoriasis (main targets in the PPI network). Cytoscape was used to construct the ingredients-targets core network for Qubi Formula in treating psoriasis, and ClueGO was used to perform GO-BP and KEGG pathway enrichment analysis on these core targets. Results: The ingredient-target-disease core network of QBF in treating psoriasis was screened to contain 175 active ingredients, which corresponded to 27 core targets. Additionally, enrichment analysis suggested that targets of QBF in treating psoriasis were mainly clustered into multiple biological processes (associated with nuclear translocation of proteins, cellular response to multiple stimuli (immunoinflammatory factors, oxidative stress, and nutrient substance), lymphocyte activation, regulation of cyclase activity, cell-cell adhesion, and cell death) and related pathways (VEGF, JAK-STAT, TLRs, NF-κB, and lymphocyte differentiation-related pathways), indicating the underlying mechanisms of QBF on psoriasis. Conclusion: In this work, we have successfully illuminated that Qubi Formula could relieve a wide variety of pathological factors (such as inflammatory infiltration and abnormal angiogenesis) of psoriasis in a "multicompound, multitarget, and multipathway" manner by using network pharmacology. Moreover, our present outcomes might shed light on the further clinical application of QBF on psoriasis treatment.

18.
Aging (Albany NY) ; 12(11): 11042-11060, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32516753

RESUMO

Signal transducer and activator of transcription-1 (STAT1) is an important factor in various cellular processes. The cancer stem cell (CSC) is considered as a tumor-initiating cell that drives the inner hierarchy in many cancers including epithelial ovarian cancer (EOC). Here, we explored for the first time the regulation of STAT1 on stemness properties in chemoresistant EOC cells. The paclitaxel (PTX)-resistant EOC cell line (OV3R-PTX) was derived from PTX-sensitive OVCAR-3 cells treated by the PTX regimen. A single cell clone OV3R-PTX-B4 was selected by fluorescence-activated cell sorting. PTX-resistant cells grew slowly in conventional 2D and 3D cultures, but tumor xenograft with PTX-resistant cells grew fast in nude mice. Interestingly, OV3R-PTX-B4 cells shared the characteristics of CSCs and stemness properties were found to be increased in the non-adherent spheroid culture system. The PTX-resistant cells had a high expression of CSC-related markers and low expression of STAT1 that had a high methylation level of CpG in its promoter region. Overexpressed STAT1 suppressed stemness properties, cell proliferation, and colony formation and favored the overall survival of patients with EOC. In summary, these data indicate a regulatory mechanism of STAT1 underlying drug resistance and provide a potential therapeutic application for EOC patients with PTX resistance.

19.
J Surg Oncol ; 122(5): 897-905, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32596828

RESUMO

BACKGROUND: Easily accessible, generalized, and inexpensive methods are expected to differentiate anaplastic thyroid carcinoma (ATC) from advanced differentiated thyroid cancer (aDTC). We aimed to explore potential diagnostic and prognostic value of systematic inflammatory markers (SIMs) in ATC and aDTC. METHODS: About 22 ATC, 101 aDTC, and 100 matched early DTC patients were analyzed retrospectively. SIMs included the comprehensive index, neutrophil-monocyte-platelet-to-lymphocyte ratio (NMPLR) and the previously reported ones. Receiver operating characteristic, Kaplan-Meier, and COX regression analyses were mainly conducted. RESULTS: NMPLR exhibited the highest area under the curve value 0.806 (P < .0001) to diagnose ATC from aDTC. NMPLR was identified as an independent risk factor for overall survival (OS) (hazard ratio [HR]: 47.821, 95% confidence interval [CI], 2.863-798.765, P = .007) in ATC, as well as for OS (HR: 7.360, 95% CI, 1.620-33.430, P = .010) and recurrence-free survival (HR: 4.172, 95% CI, 1.139-15.286, P = .031) in aDTC. Taken both refractory types (ATC and aDTC) together, NMPLR could independently predict OS (HR: 6.470; 95% CI, 2.134-19.616; P = .001). CONCLUSION: NMPLR is a generalized index. It showed excellent potential in differential diagnosis and survival prediction in refractory thyroid cancer. However, it needs to be validated in larger cohort and clinical practice.

20.
Front Oncol ; 10: 695, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32435620

RESUMO

Background: Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) is an E3 ubiquitin-protein ligase and a signal-transducing adaptor protein involved in the development and progression of cancer. Despite the known functions of Cbl-b, its role in breast cancer remains unclear. The aim of this study is to explore the prognostic value of Cbl-b in breast cancer. Methods: Cbl-b expression was analyzed by immunohistochemistry in 292 breast cancer patients from the First Hospital of China Medical University between 1999 and 2008. Kaplan-Meier curve and Cox proportional hazards regression were used to analyze the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Nomogram was constructed based on these prognostic factors. Results: Cbl-b expression was detected in 54.1% (158/292) breast cancer tissue samples. Cbl-b expression was correlated with DFS (p = 0.033), but was not significantly associated with the known clinic-pathological factors in this study. Log-rank analysis indicated that Cbl-b expression was correlated with better OS (p = 0.013) and DFS (p = 0.016). Multivariate analysis showed that Cbl-b expression was an independent prognostic factor in breast cancer. The nomogram we built for predicting OS was integrated with Cbl-b expression, age, tumor size, lymph node metastasis and histological grade. Except tumor size, all the above factors and date of diagnosis were used to construct the DFS nomogram. The C-indexes of the nomograms were 0.735 and 0.678, respectively. Our new clinical model was superior to the TNM staging for prediction of OS. Conclusion: Cbl-b expression independently predicts favorable prognosis in breast cancer. Cbl-b expression, combined with other variables could be more precise clinical predictive models for predicting OS and DFS in patients with breast cancer.

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