scholarly journals Activating Transcription Factor 5 (ATF5) Promotes Tumorigenic Capability and Activates the Wnt/b-Catenin Pathway in Bladder Cancer

Author(s):  
Junhao Zhou ◽  
Hu Tian ◽  
Xi Zhi ◽  
Zhuoyu Xiao ◽  
Taoyi Chen ◽  
...  

Abstract Background In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. Methods Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. Results ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/β-catenin pathway. Conclusions This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junhao Zhou ◽  
Hu Tian ◽  
Xi Zhi ◽  
Zhuoyu Xiao ◽  
Taoyi Chen ◽  
...  

Abstract Background In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. Methods Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. Results ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/β-catenin pathway. Conclusions This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4084-4084
Author(s):  
Andrew X. Zhu ◽  
Josep M Llovet ◽  
Masahiro Kobayashi ◽  
Masafumi Ikeda ◽  
Marc Pracht ◽  
...  

4084 Background: In a phase 1b trial (NCT03006926), L + P had promising antitumor activity as first-line (1L) therapy in uHCC. We present exploratory biomarker analyses of circulating angiogenic factors and cytokines/chemokines related to the mechanism of action of L + P (ie, pharmacodynamic [PD] biomarkers), as well as biomarker correlations with clinical outcomes in patients (pts) with uHCC, from this trial. Methods: Pts received lenvatinib 12 mg/d (bodyweight [BW] >60 kg) or 8 mg/d (BW < 60 kg) PO + pembrolizumab 200 mg IV Q3W. Tumors were assessed using mRECIST or RECIST v1.1 per independent imaging review. Peripheral blood samples were collected before administration of study drug at baseline, cycle (C) 2, day (D) 1, C3D1, C4D1, and off-treatment. 43 Biomarkers were assayed in serum from 100 1L uHCC pts (excluding 4 pts from the dose-limiting toxicity part of the trial with prior sorafenib). Of these 43, 31 biomarkers (for which ≤20% of samples had measurements above/below the quantification limit of the assay) were included in the analyses. Changes in biomarker levels from baseline were evaluated via 1-sample Wilcoxon signed-rank test. Associations were explored between changes in biomarker levels and maximum tumor shrinkage (MTS) via the Spearman’s rank correlation test, objective response (OR; complete response + partial response) via the Wilcoxon rank sum test, and PFS via Cox regression analysis and log rank test. Data cutoff date for clinical endpoints was 7 August 2020. Results: Levels of PD biomarkers related to angiogenic signaling (VEGF increase/ANG2 decrease), FGF signaling (increase in FGF23/FGF19), and IFNγ signaling (increase in IFNγ, CXCL9/10/11) were changed significantly (adjusted P< 0.05) with L + P (C2D1–C4D1; except for FGF19 at C3D1). Significant decreases of TIMP1 and increases of MCP1 were observed at C4D1 during treatment; these were associated with greater MTS. Greater decreases in TIMP1 and greater increases in MCP1 were observed in pts with OR vs others. Changes in levels of the PD biomarkers ANG2, IL10, and VEGFR2 were found to be associated with PFS by dichotomized analysis. With tertile 2 cutoff, median PFS for pts in the group with greater decreases of ANG2 was 13.9 months vs 9.6 months for pts in the group with lesser decreases of ANG2 (unadjusted P= 0.002; HR 2.65, 95% CI 1.39–5.08). Conclusions: These are the first exploratory biomarker analyses for the single-arm study of L + P in pts with uHCC. Changes in serum biomarkers associated with angiogenic-, FGF-, and IFNγ-signaling pathways indicated target engagement of L + P. Decreases in TIMP1 and increases in MCP1 were associated with MTS and OR. Associations were found between longer PFS and a greater decrease in levels of ANG2. Angiogenesis inhibition and modulation of cancer immune response were observed with L + P. Further validation from independent studies is warranted. Clinical trial information: NCT03006926.


2012 ◽  
Vol 37 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Prasath Jayakaran ◽  
Gillian M Johnson ◽  
S John Sullivan

Background and Aim: The physical asymmetries associated with a prosthesis raises the question of validity of the Sensory Organization Test (SOT) measures (equilibrium score (ES) and strategy score (SS)) in lower limb amputees. This study explores the validity of these measures in transtibial amputees by correlating with their corresponding centre of pressure (COP) excursion/velocity measures. Technique: Fifteen transtibial amputees (69.5 ± 6.5 years) completed three trials for each of the six SOT conditions. Discussion: The Spearman’s rank correlation coefficients between ESs and global COP excursion/velocity measures ranged from 0.52 to 0.71 for Conditions 1, 4 and 5, 0.79 to 0.85 for Conditions 2 and 3, and 0.39 to 0.43 for Condition 6. The coefficients for SSs ranged between 0.78 and 0.97 for Conditions 1 to 5 and 0.55 to 0.67 for Condition 6. The corresponding sound and prosthetic side COP variables demonstrated varying strengths of association with ES and SS. Clinical relevance Of the two clinical measures examined, the SSs are strongly reflective of COP excursion/velocity measures and these findings have application in the interpretation of SOT when evaluating balance in transtibial amputees.


2017 ◽  
Author(s):  
Ming Kei Chung ◽  
Kurunthachalam Kannan ◽  
Germaine M. Buck Louis ◽  
Chirag J. Patel

AbstractBACKGROUND:Along with time, variation in the exposome is dependent on the location and sex of study participants. One specific factor that may influence exposure co-variations is a shared household environment.OBJECTIVES:To examine the influence of shared household and partner’s sex in relation to the variation in 128 endocrine disrupting chemical (EDC) exposures among couples.METHODS:In a cohort comprising 501 couples trying for pregnancy, we measured 128 (13 chemical classes) persistent and non-persistent EDCs and estimated 1) sex-specific differences; 2) variance explained by shared household; and 3) Spearman’s rank correlation coefficients (rs) for females, males, and couples’ exposures.RESULTS:Sex was correlated with 8 EDCs including polyfluoroalkyl substances (PFASs) (p< 0.05). Shared household explained 43% and 41% of the total variance for PFASs and blood metals, respectively, but less than 20% for the remaining 11 EDC classes. Co-exposure patterns of the exposome were similar between females and males, with within-classrs higher for persistent and lower for non-persistent chemicals. Medianrss of polybrominated compounds and urine metalloids were 0.45 and 0.09, respectively, for females (0.41 and 0.08 for males), whereas lowerrss for these 2 classes were found for couples (0.21 and 0.04).CONCLUSIONS:Overall, sex did not significantly affect EDC levels in couples. Individual, rather than shared environment, could be a major factor influencing the co-variation of 128 markers of the exposome. Correlations between exposures are lower in couples than in individual partners and have important analytical and sampling implications for epidemiological study.


2021 ◽  
Vol 30 (2) ◽  
pp. 211-223
Author(s):  
IC Travnik ◽  
AC Sant'Anna

This study into the behaviour of domestic cats (Feliscatus) aimed to assess the relationship between behavioural expressions obtained via the Qualitative Behaviour Assessment (QBA) and quantitative outcomes of temperament tests. Four behavioural tests were used: Unfamiliar person (UP); Novel object (NO); Conspecific reaction (CR); and Food offering (FO) tests. Tests were filmed and assessed using an ethogram that included 25 discrete behavioural categories, generating quantitative information (coding method) on the existing temperament dimensions. Videos were also assessed by another observer using the QBA method, based on a list of 20 adjectives rated in visual analogue scales (rating method). Data were analysed using Principal Component Analysis. Spearman's rank correlation coefficients were used to relate the principal components (PC) of QBA to the temperament dimensions obtained with the coding method. The QBA allowed us to identify three PC, explaining 76.63% of the total variance. PC1 ranged from 'calm/relaxed/friendly' to 'tense/fearful/alert', reflecting the valence of cats' behavioural and emotional expressions towards the stimuli tested. PC2 ranged from 'indifferent' to 'agitated/active', indicating the level of emotional arousal, and PC3 ranged from 'aggressive' to 'suspicious' and could be interpreted as an axis of 'aggressiveness — caution' in response to the stimuli. The first PC obtained for each test by using the coding method was significantly correlated with the PC1 of QBA, suggesting that the variations in cats' behavioural and emotional expressions identified by QBA were correlated with the main quantitative outcomes of temperament tests traditionally applied for domestic cats. QBA could be a promising tool for identifying and differentiating cat temperament profiles. Further research is required to assess the potential use of QBA as a feasible and practical method for use in shelters.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xuan Zhao ◽  
Wei Lin ◽  
Jiawei Li ◽  
Yunhui Chen ◽  
Anamica Patel ◽  
...  

Dosage is essential for studying the compatibility and effectiveness of traditional Chinese medicine. Danggui and Chuanxiong are widely used in traditional Chinese medicine for ailments and treatment of various disorders. 628 traditional Chinese medicine prescriptions containing Danggui and Chuanxiong were extracted from the self-built prescription database and screened for the three groups of prescriptions, i.e., irregular menstruation, sores, and stroke. We processed and tested the dosage of Danggui and Chuanxiong and selected the optimal copula function, Gumbel copula function, from the Archimedes function family and elliptical copula function family to establish the data model. To establish the presence of a correlation between the dose of Danggui and Chuanxiong, a graph of the joint distribution function of rank correlation coefficients, Kendall’s rank correlation coefficient and Spearman’s rank correlation coefficient, was used. Our results suggest that the model using the Gumbel copula function better reflects the correlation between the dose of Danggui and Chuanxiong. For irregular menstruation, sores, and strokes, Kendall’s rank correlation coefficients were 0.6724, 0.5930, and 0.7757, respectively, and Spearman’s correlation coefficients were 0.8536, 0.7812, and 0.9285, respectively. In all three prescription groups, the dose of Danggui and Chuanxiong was positively correlated, implying that, as the dosage of one drug increases, the dosage of the other increases as well. From the perspective of data mining and mathematical statistics, the use of the copula function model to evaluate the correlation between the prescribed dosage of the two drugs was innovative and provided a new model for the scientific interpretation of the compatibility of traditional drugs. This might also serve to guide the clinical use of traditional Chinese medicine.


2019 ◽  
Vol 32 ◽  
Author(s):  
Daniel Vicentini de Oliveira ◽  
Amanda Mansano de Souza ◽  
Áurea Gonçalves Ferreira ◽  
Mateus Dias Antunes ◽  
Natália Serra Lovato ◽  
...  

Abstract Introduction: Despite the importance of appropriate levels of muscular strength to maintain the functional capacity and a healthy life in old age, the current literature still lacks studies that investigate the profile of elderly women who practice Mat Pilates regarding these variables. Objective: This study aimed to analyze muscular strength, functional capacity, and risk of sarcopenia in elderly women who practiced Mat Pilates. Method: This is a cross-sectional study carried out with 50 elderly women who practice Mat Pilates in the city of Maringá, Paraná. Sociodemographic and health questionnaires were used, in addition to tests created by a Latin American development group for maturity called Grupo de Desenvolvimento Latino Americano para a Maturidade (GDLAM), sitting-rising test, arm curl test, and SARC-F questionnaire. For data analysis, Shapiro-Wilk and Mann-Whitney U tests, as well as Spearman’s Rank Correlation Coefficients, were used. The level of significance was p < 0.05. Results: The 70-79-year-old elderly women showed worse results in the functional capacity and muscular strength tests of the upper limbs and a higher risk of sarcopenia than the individuals who were under 70 years of age. Muscular strength was inversely related to the reduction of the risk of sarcopenia, and functional capacity was directly associated with this risk. Conclusion: A good functional capacity seems to be related to the reduction of the risk of sarcopenia. Age seems to be an intervening factor for reducing muscular strength levels and functional capacity and increasing the risk of sarcopenia.


2018 ◽  
Vol 64 (No. 10) ◽  
pp. 464-475 ◽  
Author(s):  
Hoang Viet

This paper aims to investigate the agricultural trade complementarity of the Association of Southeast Asian Nations (ASEAN) countries on the global agricultural market over the period 1997–2015 by employing the trade complementarity index (TCI), the export similarity index (ESI), and Spearman’s rank correlation coefficients for competitiveness indicators. The results indicate that: (i) the ASEAN countries’ agricultural export patterns are weakly complementary in matching the regional import demands; while (ii) they are relatively complementary in exporting agricultural products to the world market; (iii) the countries’ agricultural competitiveness patterns are more affected by and benefited from the global integration than the regional integration; and (iv) the countries, moreover, tend to become more substitutable over time. The research results suggest that the ASEAN countries should cooperate and utilise the internal markets to enhance the competitiveness and predominantly focus on the external global markets.


2020 ◽  
Vol 23 (18) ◽  
pp. 3295-3303
Author(s):  
Yiyang Yue ◽  
Joshua Petimar ◽  
Walter C Willett ◽  
Stephanie A Smith-Warner ◽  
Changzheng Yuan ◽  
...  

AbstractObjective:To evaluate the validity and reproducibility of a 152-item semi-quantitative FFQ (SFFQ) for estimating flavonoid intakes.Design:Over a 1-year period, participants completed two SFFQ and two weighed 7-d dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQHarvard) and Phenol-Explorer (SFFQPE) food composition databases. 7DDR flavonoid intakes were derived using the Phenol-Explorer database (7DDRPE). Validity was assessed using Spearman’s rank correlation coefficients deattenuated for random measurement error (rs), and reproducibility was assessed using rank intraclass correlation coefficients.Setting:This validation study included primarily participants from two large observational cohort studies.Participants:Six hundred forty-one men and 724 women.Results:When compared with two 7DDRPE, the validity of total flavonoid intake assessed by SFFQPE was high for both men and women (rs = 0·77 and rs = 0·74, respectively). The rs for flavonoid subclasses ranged from 0·47 for flavones to 0·78 for anthocyanins in men and from 0·46 for flavonols to 0·77 for anthocyanins in women. We observed similarly moderate (0·4–0·7) to high (≥0·7) validity when using SFFQHarvard estimates, except for flavonesHarvard (rs = 0·25 for men and rs = 0·19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0·69 (flavonolsPE) to 0·80 (proanthocyanidinsPE) in men and from 0·67 (flavonolsPE) to 0·77 (flavan-3-ol monomersHarvard) in women.Conclusions:SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women.


2017 ◽  
Vol 31 (07) ◽  
pp. 670-676
Author(s):  
Dongzhe Li ◽  
Yu Liang ◽  
Kunlong Ma ◽  
Chang Zou ◽  
Yue Fang

AbstractThe aim is to assess the association between computed tomography (CT) findings and clinical outcomes in posterior tibial plateau fractures (TPF). This is a retrospective analysis of the records of 23 patients with posterior TPF treated at our institution between 2004 and 2011. Two indices of residual articular displacement of posterior TPF (gap and step-off) were measured from CT images, and clinical outcomes were assessed using the Short Musculoskeletal Function Assessment (SMFA) questionnaire. Spearman's rank correlation coefficient analysis was used to evaluate the correlations between the postoperative posterior TPF radiological findings and the clinical outcomes. Both the intraobserver and the interobserver correlation coefficients were high (0.90 and 0.92, respectively), indicating excellent agreement between the reviewers for the assessment of residual displacement via CT scans. Additionally, residual articular step displacement showed a strongly negative correlation with clinical outcomes (R = 0.700, p = 0.036), whereas the residual gap displacement did not (R = 0.400, p = 0.505). More importantly, the medial posterior step displacement was significantly correlated with the clinical outcomes (p = 0.040), whereas the lateral posterior step displacement was not (p = 0.618). Based on the data of this study, the higher the step-off deformity of the medial posterior tibial plateau, the worse the SMFA. More attention should be paid to this factor when treating medial posterior TPF.


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