Pharmacologic and genetic inhibition of cholesterol esterification enzymes reduces tumour burden: a systematic review and meta-analysis of preclinical models

2021 ◽  
pp. 114731
Author(s):  
Alex Websdale ◽  
Yi Kiew ◽  
Philip Chalmers ◽  
Xinyu Chen ◽  
Giorgia Cioccoloni ◽  
...  
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.


2020 ◽  
Vol 29 (19) ◽  
pp. 1247-1265
Author(s):  
Gabriela Maciel Lopes ◽  
Patrícia Bencke Grudzinski ◽  
Nance Beyer Nardi ◽  
Natalia Motta Leguisamo

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Emanuel L. Peter ◽  
Andrew G. Mtewa ◽  
Prakash B. Nagendrappa ◽  
Anita Kaligirwa ◽  
Crispin Duncan Sesaazi

Abstract Background Studies on several preclinical models of type 2 diabetes mellitus have been conducted to establish the hypoglycemic activity of Momordica charantia L. Concerned with appropriateness of these models, we designed a systematic review to establish the efficacy and safety of M. charantia L. in preclinical models of type 2 diabetes mellitus. Methods Review authors will search without language restriction in MEDLINE/PubMed, Web of Science, Embase, Scopus, and CINAHL databases through April 2019. Search filters will be applied to enhance search efficiency. The authors will search for gray literature in Google and Google Scholar, OpenGrey, and ProQuest Dissertations & Theses. Two authors will evaluate full texts, extract data, and asses risk of bias independently. The review will include randomized or non-randomized studies that assessed the efficacy or safety of M. charantia L. with vehicle control group. The primary endpoint will be fasting blood glucose level. We will use Egger’s test to assess publication biases. Chi-square test and I2 will be used to assess heterogeneity in effect size of the primary outcome. Using RevMan software version 5.3, the authors will perform a meta-analysis of quantitative data. Discussion The strength of evidence will be rated as high, moderate, low, or very low using GRADE framework for animal studies. This systematic review will potentially improve research practice by identifying risks of bias and design features that compromise translatability and contribute to evidence-based clinical trial design. Systematic review registration PROSPERO CRD42019119181


2021 ◽  
Author(s):  
Yali Wei ◽  
Yan Meng ◽  
Na Li ◽  
Qian Wang ◽  
Liyong Chen

The purpose of the systematic review and meta-analysis was to determine if low-ratio n-6/n-3 long-chain polyunsaturated fatty acid (PUFA) supplementation affects serum inflammation markers based on current studies.


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