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statin as a therapeutic agent in gastroenterological cancer

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World Journal of Gastrointestinal Oncology 2022年第1期14卷 110-123页

作者： Norio Uemura Hiromitsu Hayashi Hideo Baba Department of Gastroenterological Surgery Graduate School of Medical SciencesKumamoto UniversityKumamoto 860-8556Japan

statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase,the rate-limiting enzyme of the mevalonate pathway,and are widely used as an effective and safe approach handle *** mevalonate pathway is a vital metabolic pathway that uses acetyl-CoA to generate isoprenoids and sterols that are crucial to tumor growth and *** studies have indicated that statins improve patient prognosis in various *** research on the mechanisms underlying the antitumor effects of statins is *** development of new anti-cancer drugs is progressing,but increasing medical costs from drug development have become a major *** available,inexpensive and well-tolerated drugs like statins have not yet been successfully repurposed for cancer *** the cancer patients that may benefit from statins is key to improved patient *** review summarizes recent advances in statin research in cancer and suggests important considerations for the clinical use of statins to improve outcomes for cancer patients.

关键词： statin HMG CoA reductase inhibitor Mevalonate pathway Cancer

Merger of Ezetimibe and statin:a Potential Dual Inhibitor

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Chemical Research in Chinese Universities 2011年第2期27卷 232-236页

作者： HE Xing-lian XU Xian-xiu ZHENG Lian-you BAI Xu Center for Combinatorial Chemistry and Drug Discovery School of Pharmaceutical Sciences Jilin University Changchun 130021 P R. China College of Chemistry Jilin University Changchun 130012 P R. China College of Chemistry Northeast Normal University Changchun 130024 P R. China

A potential dual inhibitor（4） for exogenous absorption and endogenic synthesis of cholesterol was designed based on the conjugation of the β-lactam pharmacophore of ezetimibe and the δ-lactone pharmacophore of statins. The merger of ezetimibe and statin 4 was synthesized from p-hydroxybenzaldehyde through a ten-step route. 1H NMR analysis showed existence of four pairs of enantiomers（5.7：5.7：1：1, molar ratio）. And compound 4 was found to lower total glucose（TG） level in rat serum via a high-cholesterol and high-fat feeding experiment.

关键词： Multi-target drug Ezetimibe statin

Free triiodothyronine level correlates with statin responsiveness in acute myocardial infarction

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Journal of Geriatric Cardiology 2018年第4期15卷 290-297页

作者： Wen-Yao WANG Kuo ZHANG Wei ZHAO A. Martin Gerdes Giorgio Iervasi Yi-Da TANG Departments of Cardiology State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Biomedtcal Sciences New York Institute of Technology-College of Osteopathic Medicine Northern Blvd. Old Westbury New York USA Clinical Physiology Institute Consiglio Nazionale delle Ricerche (CNR) Pisa Italy

Background Although thyroid hormone （TH） has important effects on lipid metabolism, the relationship between TH and statin responsiveness has never been investigated. We hypothesize that TH plays an important role in statin responsiveness in patients with acute myocardial infarction （AMI）. Methods Consecutive 1091 hospitalized AMI patients in Fuwai hospital （Beijing, China） were enrolled into this current study. The study population was divided into three groups based on the intensity of statin treatment： low-intensity （n = 221）, moderate-intensity （n = 712） and high-intensity （n = 158）. Lipid levels were measured after statin therapy lasting for 10-14 days. The association between TH, lipid profile levels and achievement of low-density lipoprotein cholesterol （LDL-C） lowering goals was explored in patients with AMI on statin therapy. Results By general linear analysis, a significant linear trend between free triiodothyronine （FT3） and LDL-C level （linear coefficient r = -0.082, P = 0.001） and FT3 and total cholesterol （TC） level （r = -0.105, P = 0.031） was observed in the moderate-intensity statin group. A more apparent linear trend was detected in the high-intensity statin group （for LDL-C： r = -0.113, P = 0.005; for TC： r = -0.172, P = 0.029, respectively）. However, no significant correlation was observed in the low-intensity statin group. Compared with the low-FT3 group （defined as FT3 〈 1.79 pg/mL）, the OR （95% CI） for attaining a LDL-C 〈 3.0mmol/L was found to be 2.217 （1.001–4.839） in the higher FT3 group （〉 2.95 pg/mL）. The OR （95% CI） for attaining the more intensive goal （LDL-C 〈 1.8mmol/L） was 2.836 （1.014–5.182）. Conclusions Our study reveals that variation in FT3 levels is related to the cholesterol-lowering responsiveness of statins in AMI patients. These findings suggest that low FT3 may be a factor responsible for lack of LDL-C goal attainment and patients’ poor responsiveness to statin treatment.

关键词： Acute myocardial infarction Free triiodothyronine Hypothyroid statin

Anti-tumor effect of statin on pancreatic adenocarcinoma:From concept to precision medicine

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World Journal of Clinical Cases 2021年第18期9卷 4500-4505页

作者： Chung-Tsui Huang Yao-Jen Liang Department of Gastroenterology and Hepatology Far Eastern Memorial HospitalNew Taipei 220Taiwan Graduate Institute of Applied Science and Engineering Department and Institute of Life ScienceFu-Jen UniversityNew Taipei 242Taiwan

A statin is a cholesterol-lowering agent,which inhibits HMG-CoA(3-hydroxy-3-methylglutaryl-coenzyme A)reductase and subsequently reduces the cholesterol precursor,and was first used commercially in *** concept of cholesterol restriction leading to cancer cell dysfunction was proposed in *** interruption of different signaling pathways has been proved in preclinical experiments to elucidate the anti-tumor mechanism of statins in pancreatic *** studies have shown that the clinical use of statins is beneficial in patients with pancreatic adenocarcinoma,including a chemoprevention effect,post-surgical resection follow-up and therapeutic prognosis of advanced cancer *** of the cancer cell cycle by the combined use of gemcitabine and statin was observed in a cell line *** effect of microbiota on the tumor microenvironment of pancreatic adenocarcinoma is a new therapeutic approach as statins can modulate the gut ***,further randomized trials of statins in pancreatic adenocarcinoma treatment will be warranted with application of precision medicine from microbiota-derived,cell cycle-based and signaling pathway-targeted research.

关键词： statin Pancreatic cancer Precision medicine Anti-tumor Pancreatic adenocarcinoma

Intensive vs non-intensive statin pretreatment before percutaneous coronary intervention in Chinese patients:A meta-analysis of randomized controlled trials

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World Journal of Clinical Cases 2022年第5期10卷 1557-1571页

作者： Xian Yang Xi Lan Xin-Lin Zhang Zhong-Lin Han Si-Min Yan Wen-Xiao Wang Biao Xu Wei-Hong Ge Department of Pharmacy Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina Department of Pharmacy Nanjing Medical Center for Clinical PharmacyNanjing 210000Jiangsu ProvinceChina Department of Cardiology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina Department of Pharmacy The Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

BACKGROUND The results of intensive statin pretreatment before percutaneous coronary intervention(PCI)is inconsistent between Chinese and Western populations,and there are no corresponding meta-analyses involving hard clinical endpoints in the available published *** To evaluate the efficacy and safety of high-dose statin loading before PCI in Chinese patients through a *** Relevant studies were identified by searching the electronic databases of PubMed,Embase and Cochrane’s Library to December *** outcomes included an assessment of major adverse cardiovascular event(MACE),non-fatal myocardial infarction(MI),cardiac death,target vessel revascularization(TVR),myalgia/myasthenia and abnormal alanine aminotransferase(ALT)in all enrolled *** effect model and fixed effect model were applied to combine the data,which were further analyzed byχ2 test and I2 *** main outcomes were then analyzed through the use of relative risks(RR)and its 95%confidence interval(95%CI).RESULTS Eleven studies involving 3123 individuals were *** with patients receiving placebo or no statin treatment before surgery,intensive statin treatment was associated with a clear reduction of risk of MACE(RR=0.44,95%CI:0.31-0.61,Pstatin before surgery,no advantage to intensive statin treatment was seen(RR=1.04,95%CI:0.82-1.31,P=0.74).In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR(RR=0.43,95%CI:0.18-1.02,P=0.06),myalgia/myasthenia(RR=1.35,95%CI:0.30-5.95,P=0.69)and abnormal alanine aminotransferase(RR=1.47,95%CI:0.54-4.02,P=0.45)except non-fatal MI(RR=0.54,95%CI:0.33-0.88,P=0.01).CONCLUSION Compared with placebo or no statin pretreatment,intensive statin before PCI displayed reduced incidence of ***,there was no significant benefit between high and moderate-intensity sta

关键词： Intensive Non-intensive statin Percutaneous coronary intervention Chinese Meta-analysis

Factors that contribute to poor adherence to statin therapy in coronary heart disease patients from Chongqing and measures to improve their therapeutic outcomes

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Genes & Diseases 2018年第4期5卷 335-341页

作者： Guiquan Yu Yingjiao Zhang Ying Wang Guanglei Chang Hongmei Tao Dongying Zhang Cardiovascular Department The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Electrocardiogram Room The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

To assess the efficacy and short-term outcomes of adherence to statin therapy among coronary heart disease(CHD)patients following their hospital discharge,we enrolled 615 CHD patients who were prescribed statins from The First Affiliated Hospital of Chongqing Medical University in China between February 1st and October 31st of *** adherence was evaluated by identifying the proportion of patients who remained adherent or became non-adherent to statin therapy over 4e8 months post-discharge from the *** composite outcomes included all-cause mortality and re-hospitalization with cardiovascular *** found that 15.9%patients were non-adherent to their statin therapies and that coronary artery stenosisstatin therapy(36.7%),the treatment being halted at the advice of their doctor(19.4%),and the difficulty in obtaining statins(12.2%).Non-adherence to statin therapy was significantly associated with an increased risk of cardiovascular events(OR Z 1.741,95%CI:1.035e2.929,p Z 0.037).In conclusion,CHD patients with moderate stenosis or adverse effects tended to have poor statin adherence,and this was significantly associated with increased cardiovascular *** should strengthen education of the importance of statin therapy for both patients and doctors and facilitate the ability of patients to obtain their statin medication.

关键词： Adherence Adverse effects Cardiovascular events Coronary heart disease statin

Retrospective cohort study of statin therapy effect on resected colorectal liver metastases

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World Journal of Gastrointestinal Surgery 2020年第2期12卷 34-44页

作者： Edward Alabraba Hussain Ibrahim Adina Olaru Iain Cameron Dhanny Gomez Nottingham HPB Surgery Group Department of Hepatobiliary Surgery and Pancreatic Surgery Queen’s Medical CentreNottingham University Hospitals NHS TrustNottingham NG72UHUnited Kingdom NIHR Nottingham Digestive Disease Biomedical Research Unit University of NottinghamNottingham NG72UHUnited Kingdom 不详

BACKGROUND Above and beyond their role in cardiovascular risk reduction,statins appear to have a chemopreventive role in some gastro-intestinal *** the quest for new chemopreventive agents,some existing established drugs such as statins have shown potential for re-purposing as *** existing drugs,whose pharmacodynamics are familiar,for novel beneficial effects offers a more cost-effective and less time-consuming strategy than establishing brand new drugs whose pharmacodynamic profile is *** studies show statins decrease the risk of developing colorectal cancer but there are no published studies exploring the potential impact of statins on carcinogenesis in colorectal liver metastases(CRLM).AIM To evaluate impact of statins on outcomes of CRLM resection,and secondarily to assess if statins influence CRLM *** We conducted a retrospective cohort study of patients operated for CRLM over a 13-year period from 2005 to *** were identified from a prospective database maintained in our Tertiary care *** 586 patients included the study had undergone resection of CRLM following discussion at multidisclipinary team meeting,some patients requiring neoadjuvant chemotherapy to downstage CRLM prior to *** analysed patient demographics,operative details,CRLM histopathology,Index of Deprivation,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio and chemotherapy use in relation to clinical *** were performed using SPSS version 16.0;significance taken at 5%.RESULTS Liver resection for CRLM was undertaken in 586 patients at a median age of 68(range 19 to 88)*** therapy was used by 181 *** follow-up time was 23(range 12-96)mo and further colorectal cancer metastases developed in 267 patients.A total of 131 patients ***-variate analysis identified 6 independent predictors of poorer disease-free survival:Synchronous presentation,multiple tumours,t

关键词： Colorectal liver metastases statin Liver resection Chemoprevention Tumour biology Survival

statin alternatives or just placebo： an objective review of omega-3, red yeast rice and garlic in cardiovascular therapeutics

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Chinese Medical Journal 2008年第16期121卷 1588-1594页

作者： Hean Teik(Ong) Jin Seng(Cheah) Consultant Cardiologist HT Ong Heart Clinic Penang Malaysia Professor of Medicine National University of Singapore Singapore 119074 Singapore

Objective The aim of this review is to objectively access the trial evidence on the role of omega-3, red yeast rice and garlic in preventing clinical cardiovascular events. Given the large number of clinical trials favoring statin use in cardiovascular disease, it is important to see if evidence is available for these supplements and whether they could replace statin therapy. Data source A PubMed search was conducted using the keywords ＇trial, omega-3, red yeast rice, xuezhikang, garlic, cholesterol, cardiovascular, outcomes＇; the resulting trials were reviewed together with the references quoted in the papers obtained. Study selection The studies selected are prospective, randomized, placebo-controlled studies with predefined clinical cardiovascular end-points recruiting at least 2000 patients, with a follow-up over 2 years. Results Modest dose omega-3 fatty acid has been shown in GISSI-P （11 324 patients, follow-up 3.5 years） to produce a reduction in sudden death of 45%, and in cardiac death of 35%, acting probably via an anti-arrhythmic effect. In JELLS （18 645 patients, follow-up 4.6 years）, high dose omega-3 given to Japanese patients on a high fish diet and already on statin treatment produced further benefit with a 19% reduction of nonfatal cardiovascular outcomes; fatal cardiac events are not affected. CCSPS （4870 patients, follow-up 4 years）, a secondary prevention trial using xuezhikang, a commercial red yeast rice preparation, produced a 46% reduction in nonfatal myocardial infarction and coronary death. There has been no trial to show that garlic reduces clinical cardiovascular outcomes. A rigorous trial with constant assessment of chemicals in the study material in 192 patients found that over a 6-month follow-up, raw garlic and 2 commercial preparations do not significantly affect lipid levels. Conclusions Omega-3 in modest doses reduces cardiac deaths, and in high doses reduces nonfatal cardiovascular events. Red yeast rice reduces adverse cardiac ev

关键词： statin omega-3, red yeast rice garlic cardiovascular therapeutics

Effect of pre-procedural statin therapy on myocardial no-reflow following percutaneous coronary intervention： a meta analysis

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Chinese Medical Journal 2013年第9期126卷 1755-1760页

作者： LI Xiang-dong YANG Yue-jin HAO Yong-chen YANG Ying ZHAO Jing-lin DOU Ke-fei GU Dong-feng Department of Evidence Based Medicine Department of and Cardiology Fuwai Hospital and Cardiovascular Institute Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100037 China

Background Successful revascularization of coronary artery disease, especially ST-elevation myocardial infarction （STEMI）, does not always mean optimal myocardial reperfusion in a portion of patients because of no-reflow phenomenon. We hypothesized that statins might attenuate the incidence of myocardial no-reflow when used before percutaneous coronary intervention （PCI）. The purpose of this study was to summarize the evidence of pre-procedural statin therapy to reduce myocardial no-reflow after PCI. Methods We searched the MEDLINE, Cochrane, and *** databases from inception to October 2012 for clinical trials that examined statin therapy before PCI. We required that studies initiated statins before PCI and reported myocardial no-reflow. A DerSimonian-Laird model was used to construct random-effects summary risk ratios. Results In all, 7 studies with 3086 patients met our selection criteria. The use of pre-procedural statins significantly reduced post-procedural no-reflow by 4.2% in all PCI patients （risk ratio （RR） 0.56, 95% confidence interval （CI） 0.35 to 0.90, P=0.016）, and attenuated by 5.0% in non-STEMI patients （RR 0.41, 95% CI 0.18 to 0.94, P=0.035）. This benefit was mainly observed in the early or acute intensive statin therapy populations （RR 0.43, 95% CI 0.26 to 0.71, P=0.001）. Conclusions Acute intensive statin therapy before PCI significantly reduces the hazard of post-procedural no-reflow phenomenon. The routine use of statins before PCI should be considered.

关键词： statin coronary artery disease percutaneous coronary intervention no-reflow