scholarly journals Pharmacologic and genetic inhibition of cholesterol esterification reduces tumour burden: a pan-cancer systematic review and meta-analysis of preclinical models

2021 ◽  
Author(s):  
Alex Websdale ◽  
Yi Kiew ◽  
Philip Chalmers ◽  
Xinyu Chen ◽  
Giorgia Cioccoloni ◽  
...  

Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, and Web of Science for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p<0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p≤0.002). SOAT inhibition increased tumour apoptosis (p=0.007), CD8+ lymphocyte infiltration and cytotoxicity (p≤0.05), and reduced proliferation (p=0.0003) and metastasis (p<0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size was overestimated. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.

2019 ◽  
Vol 20 (2) ◽  
pp. 293 ◽  
Author(s):  
Milad Bastami ◽  
Jalal Choupani ◽  
Zahra Saadatian ◽  
Sepideh Zununi Vahed ◽  
Yaser Mansoori ◽  
...  

Recently extensive focus has been concentrated on the role of miRNAs in the initiation and progression of cardio-cerebrovascular diseases (CCDs) which constitute a range of conditions including cardiovascular diseases (CVDs, especially coronary artery disease (CAD)), congenital heart disease (CHD) and cerebrovascular diseases (CBVDs, especially the ischemic stroke (IS)). An increasing number of studies are evaluating the association between different miRNA polymorphisms and risk of CCDs, but results have been inconclusive. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and risk of CCDs. PubMed, Embase, Scopus, and Web of Science were queried to identify eligible articles. Odds ratios and 95% confidence intervals were used to assess the association of miRNA polymorphisms with CCD susceptibility. A total of 51 eligible articles evaluating the association of 31 miRNA polymorphisms were identified. Meta-analysis was performed for six miRNA polymorphisms. miR-146a rs2910164 (30 studies: 13,186 cases/14,497 controls), miR-149 rs2292832 (Nine studies: 4116 cases/3511 controls), miR-149 rs71428439 (Three studies: 1556 cases/1567 controls), miR-196a2 rs11614913 (20 studies: 10,144 cases/10,433 controls), miR-218 rs11134527 (Three studies: 2,322 cases/2,754 controls) were not associated with overall CCD. miR-499 rs3746444 was associated with CCD (20 studies: 9564 cases/8876 controls). In the subgroups, rs2910164 and rs3746444 were only associated with CVDs, especially CAD. In conclusion, the results support the existence of a role for miR-146a rs2910164 and miR-499 rs3746444 in determining susceptibility to CCDs, especially CAD.


2020 ◽  
Vol 11 ◽  
Author(s):  
Xue Zhao ◽  
Xiaokun Gang ◽  
Guangyu He ◽  
Zhuo Li ◽  
You Lv ◽  
...  

Since December 2019, COVID-19 has aroused global attention. Studies show the link between obesity and severe outcome of influenza and COVID-19. Thus, we aimed to compare the impacts of obesity on the severity and mortality of influenza and COVID-19 by performing a meta-analysis. A systematic search was performed in MEDLINE, EMASE, ClinicalTrials.gov, and Web of Science from January 2009 to July 2020. The protocol was registered onto PROSPERO (CRD42020201461). After selection, 46 studies were included in this meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed. We found obesity was a risk factor for the severity and mortality of influenza (ORsevere outcome = 1.56, CI: 1.28-1.90; ORmortality = 1.99, CI: 1.15-3.46). For COVID-19, obesity was a significant risk factor only for severe outcome (OR = 2.07, CI: 1.53-2.81) but not for mortality (OR = 1.57, CI: 0.85-2.90). Compared with obesity, morbid obesity was linked with a higher risk for the severity and mortality of both influenza (OR = 1.40, CI: 1.10-1.79) and COVID-19 (OR = 3.76, CI: 2.67-5.28). Thus, obesity should be recommended as a risk factor for the prognosis assessment of COVID-19. Special monitoring and earlier treatment should be implemented in patients with obesity and COVID-19.


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Haoran Liu ◽  
Tao Ye ◽  
Xiaoqi Yang ◽  
Peng Lv ◽  
Xiaoliang Wu ◽  
...  

Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma (UC). To evaluate the predictive and prognostic value of PD-L1 on response and survival in UC patients after cystectomy, chemotherapy, or anti-PD-1/PD-L1 therapy, a systematic review of PubMed, Embase, Web of Science, and the Cochrane Library was performed. A total of 2154 patients from 14 published studies were included. In all UC patients after cystectomy, tumour cell (TC) PD-L1 expression was not associated with the OS or PFS. For the subset of patients with organ-confined disease, TC PD-L1 expression significantly predicted OS after cystectomy (P=0.0004). There was no significant evidence of an association between TC PD-L1 status and ORR or OS for UC patients treated with platinum-based chemotherapy. For UC patients treated with anti-PD-1/PD-L1 therapy, TC PD-L1 expression≥5% could predict the response (P=0.005), but not for the 1% cut-off (P≥0.05). As for PD-L1 expression in tumour-inflating immune cells (TIICs), both subsets with IC2/3 vs. IC0/1 and IC1/2/3 vs. IC0 were associated with ORR to anti-PD-1/PD-L1 therapy. In the TIIC subset, IC2/3 vs. IC0/1 of PD-L1 was associated with higher CR (P=0.002), PR (P=0.04), and PD (P=0.007). Further, higher TIIC PD-L1 status benefited from longer PFS (P<0.001), but was not associated with OS in UC patients with anti-PD-1/PD-L1 therapy. Our study suggested that TIIC PD-L1 expression with 5% cut-off was valuable as a predictive and prognostic biomarker for ORR and PFS in UC patients with anti-PD-1/PD-L1 therapy.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yung-Chi Hsieh ◽  
Li-Shiu Chou ◽  
Ching-Hua Lin ◽  
Hung-Chi Wu ◽  
Dian-Jeng Li ◽  
...  

Abstract Background Bipolar disorder (BD) is a major psychiatric illness, however its physiopathology is unclear. The role of folate in the physiopathology of BD is controversial. We conducted this systematic review and meta-analysis to investigate the effect of folate in BD patients. Methods We performed a thorough literature study of the PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, and ClinicalTrials.gov databases until December 21st, 2018. Random effects meta-analysis was conducted. Results Six articles involving 481 patients with BD and 760 controls were included. The meta-analysis results suggested that serum folate levels in the patients with BD were significantly lower than those in the controls (Hedges’ g = − 0.211, 95% confidence interval = − 0.391 to − 0.031, p = 0.021). Conclusion The current meta-analysis show it might be association between lower serum folate levels and patient with BD. However, we could not distinguish the potentially confounding effects of mood states on the folate levels. Further prospective studies including subjects with different mood states and possible physiopathology are warranted to investigate the association between folate deficiency and the etiology of BD.


Thrita ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Nasrin Hosseini ◽  
Shabnam Nadjafi ◽  
Leila Janani ◽  
Zahra Faraji ◽  
Behnaz Ashtari ◽  
...  

Context: Alzheimer’s disease (AD) is a neurodegenerative disease affecting many people around the world. Recently, it has been reported that toll-like receptors (TLRs) play a role in AD; therefore, the present study aimed to systematically review the studies and to meta-analyze the role of toll-like receptor 9 (TLR9) in AD. Methods: Seven main electronic databases, including PubMed/MEDLINE, Web of Science, Embase, Scopus, CINAHL, Cochrane, and Google Scholar, will be considered with no language restrictions. Full texts of articles will be prepared by a determined search strategy. Studies including the assessment of TLR9 function in adults with AD, published before June 15 2020, will be considered. Hence, this protocol will be presented based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements for protocols. The related results and data analyses will be provided in the final review. This paper plans the protocol for a systematic review identifying TLR9 up-regulation and down-regulation in adults with AD. Conclusions: The meta-analysis of TLR9 may subsequently provide attractive therapeutic tools for AD.


2020 ◽  
Author(s):  
Hossein Dabiriyan Tehrani ◽  
Sara Yamini

This systematic review aimed to find attitudes toward Altruistic and Game-playing love styles across individualistic and collectivistic cultures. Addressing major moderators concerning Altruistic and Game-playing love styles are the secondary objectives of this review. This review included 102 articles comprising samples from 37 countries (N = 41997). The findings of this meta-analysis show that there is a collectivistic and individualistic difference in Game-playing but not in the Altruistic love style. Collectivistic and individualistic cultures, on average, demonstrate the same perception concerning the Altruistic love style, whereas collectivistic culture shows the Game-playing love style more strongly. To explain the role of moderators in key measures, the subgroup analysis and meta-regression show that both Game-playing and Altruistic love styles decline by increasing the length of the relationship. Likewise, having children affects these love styles such that the Altruistic love style is improved, and the Game-playing love style is reduced by the presence of children in families.


Sign in / Sign up

Export Citation Format

Share Document