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使用机器学习的定量冠状动脉CT血管成像对损伤特异性缺血的综合预测:一项多中心研究

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国际医学放射学杂志 2018年第4期 499-500页

作者： D.Dey S.Gaur K.A.Ovrehus P.J.Slomka J.Betancur M.Goeller 吴迪 Biomedical Imaging Research institute Department of Biomedical SciencesCedars-Sinai Medical Center

目的对于是否可以通过有创血流储备分数(FFR)预测的病变特异性缺血,旨在通过冠状动脉CT血管成像(CTA)定量斑块测量的综合机器学习(ML)缺血危险评分实现预测。方法在一项254例病人的多中心试验中,进行了CTA和有创性冠状动脉造影,对484根... 详细信息

目的对于是否可以通过有创血流储备分数(FFR)预测的病变特异性缺血,旨在通过冠状动脉CT血管成像(CTA)定量斑块测量的综合机器学习(ML)缺血危险评分实现预测。方法在一项254例病人的多中心试验中,进行了CTA和有创性冠状动脉造影,对484根血管计算FFR。CTA数据集采用半自动软件进行分析,以量化狭窄和非钙化(NCP),低密度NCP(LD-NCP,<30 HU),钙化和总斑块体积,对比度密度差(CDD,单位面积的最大管腔差异密度)和斑块长度。综合ML包括自动特征选择和从定量CTA与增强型集成算法和十倍分层交叉验证建模。结果 80例病人的100个血管中经FFR(FFR≤0.80)发现局部缺血。CDD(0.172)、LDNCP(0.125)、NCP(0.097)和总斑块体积(0.092)的预测缺血的信息最高。ML比单个CTA测量显示出更高的曲线下面积(0.84),包括狭窄(0.76)、LD-NCP体积(0.77)、总斑块体积(0.74)和预测冠状动脉疾病(CAD)可能性(0.63);P<0.006。结论综合ML缺血危险评分能够改善有创性FFR、过度狭窄、斑块测量和CAD检测前可能性对病变特异性缺血的预测。

关键词：血管成像斑块体积 CT 特异性冠状动脉机器学习

Evaluation of the prevalence and severity of pain in patients with stable chronic heart failure

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World Journal of Cardiology 2012年第8期4卷 250-255页

作者： Dioma U Udeoji Ankit B Shah Parag Bharadwaj Peter Katsiyianis Ernst R Schwarz heart institute of Southern California TemeculaCA 92592United State cedars-sinai Medical Center Los AngelesCA 90048United States University of California Los Angeles Los AngelesCA 90095United States heart institute of Southern California TemeculaCA 92592United State Dioma U Udeoji

AIM: To evaluate the prevalence and severity of pain in patients with chronic stable heart failure (HF) in an outpatient clinic setting. METHODS: This is a cross-sectional study evaluating symptoms of generalized or specific pain in patients with chronic stable heart failure. A standardized questionnaire (Edmonton Symptom Assessment System) was administered during a routine outpatient clinic visit. The severity of pain and other symptoms were assessed on a 10 point scale with 10 being the worst and 0 representing no symptoms. RESULTS: Sixty-two patients [age 56 ± 13 years, 51 males, 11 females, mean ejection fraction (EF) 33% ± 17%] completed the assessment. Thirty-two patients (52%) reported any pain of various character and location such as chest, back, abdomen or the extremities, with a mean pain score of 2.5 ± 3.1. Patients with an EF less than 40% (n = 45, 73%) reported higher pain scores than patients with an EF greater than 40% (n = 17, 27%), scores were 3.1 ± 3.3 vs 1.2 ± 1.9, P heart failure management.

关键词： heart failure Pain Symptoms Therapy Palliative care

Astrocyte elevated gene-1 (AEG-1): a new potential therapeutic target for the treatment of nonalcoholic steatohepatitis (NASH)

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Hepatobiliary Surgery and Nutrition 2018年第1期7卷 44-47页

作者： Qinglan Wang Ekihiro Seki Division of Digestive and Liver Diseases Department of MedicineCedars-Sinai Medical CenterLos AngelesCAUSA E-institute of Shanghai Municipal Education Committee Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Biomedical Sciences Cedars-Sinai Medical CenterLos AngelesCAUSA Division of Gastroenterology Department of MedicineSchool of MedicineUniversity of California San DiegoLa JollaCAUSA Department of Medicine David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCAUSA

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,which affects 25%of the general adult population and 70–80%of individuals with obesity and diabetes(1).

关键词： elevated liver NAFLD

Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond

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World Journal of Gastroenterology 2018年第25期24卷 2686-2697页

作者： Emily M Lin Jun Gong Samuel J Klempner Joseph Chao Department of Internal Medicine Harbor-UCLA Medical CenterTorranceCA 90509United States Department of Medical Oncology and Developmental Therapeutics City of Hope Comprehensive Cancer CenterDuarteCA 91010United States The Angeles Clinic and Research institute Los AngelesCA 90404United States Samuel Oschin Comprehensive Cancer institute Cedars-Sinai Medical CenterLos AngelesCA 90048United States

Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.

关键词： Immunotherapy programmed cell death 1 programmed death ligand 1 microsatellite instablility Gastric cancer

Trading in your spindles for blebs： the amoeboid tumor cell phenotype in prostate cancer

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Asian Journal of Andrology 2014年第4期16卷 530-535页

作者： Samantha Morley Martin H Hager Sara G Poilan Beatrice Knudsen Dolores Di Vizio Michael R Freeman Division of Cancer Biology and Therapeutics Departments of Surgery Medicine and Biomedical Sciences and The Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center Los Angeles CA Urological Diseases Research Center Boston Children's Hospital Boston MA Department of Surgery Harvard Medical School Boston MA Department of Medicine David Geffen School of Medicine University of California Los Angeles CA USA.

Prostate cancer （PCa） remains a principal cause ofmortalityin developed *** no clinical interventions overcome resistance to androgen ablation therapy, management of castration resistance and metastatic disease remains largely untreatable. Metastasis is a multistep process in which tumor cells lose cell-cell contacts, egress from the primary tumor, intravasate, survive shear stress within the vasculature and extravasate into tissues to colonize ectopic sites. Tumor ceils reestablish migratory behaviors employed during nonneoplastic processes such as embryonic development, leukocyte trafficking and wound healing. While mesenchymal motility is an established paradigm of dissemination, an alternate, ＇amoeboid＇ phenotype is increasingly appreciated as relevant to human cancer.

关键词： SIGNALING COOPERATE RHO GTPASES INVASION MOTILITY MIGRATION TRANSITION PLASTICITY ROCK METASTASIS ACTIVATION

A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1042-1049页

作者： Jieling Xiao Cheng-Han Ng Yip-Han Chin Darren Jun Hao Tan Wen-Hui Lim Grace Lim Jingxuan Quek Ansel Shao Pin Tang Kai-En Chan Rou-Yi Soong Nicholas Chew Benjamin Tay Daniel Q.Huang Nobuharu Tamaki Roger Foo Mark Y.Chan Mazen Noureddin Mohammad Shadab Siddiqui Arun J.Sanyaland Mark D.Muthiah Yong Loo Lin School of Medicine National University of SingaporeSingapore Lee Kong Chian School of Medicine Nan-yang Technological UniversitySingapore Department of Cardiology National University Heart CenterNational University HospitalSingapore Division of Gastroenterology and Hepatology Department of MedicineNational University HospitalSingaporeSingapore National University Center for Organ Transplantation National University Health SystemSingapore NAFLD Research Center Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of California at San DiegoLa JollaCAUSA Department of Gastroenterology and Hepatology Musashino Red Cross HospitalTokyoJapan cedars-sinai Fatty Liver Program Division of Digestive and Liver DiseasesDepartment of MedicineComprehen-sive Transplant CenterCedars-Sinai Medical CenterLos AngelesCAUSA Division of Gastroenterology Hepatology and NutritionDepartment of Internal MedicineVirginia Commonwealth UniversityRichmondVAUSA

Background and Aims:Pharmaceutical therapy for NASH is associated with lipid modulation,but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness.A network meta-analysis was conducted to compare NASH drug classes in lipid ***:Online databases were searched for randomized controlled trails(RCTs)evaluating NASH treatments in biopsy-proven NASH *** were classified into four groups:(1)inflammation,(2)energy,(3)bile acids,and(4)fibro-sis based on the mechanism of action.A Bayesian network analysis was conducted with outcome measured by mean difference(MD)with credible intervals(Crl)and surface un-der the cumulative ranking curve(SUCRA).Results:Forty-four RCTs were included in the *** acid modulat-ing treatments(MD:0.05,Crl:0.03-0.07)were the best treatment for improvement in high-density lipid(HDL)cho-lesterol,followed by treatments modulating energy(MD:0.03,Crl:0.02-0.04)and fibrosis(MD:0.01,Crl:−0.12 to 0.14)compared with *** top three treatments for reduction in triglycerides were treatments modulating energy(MD:−0.46,Crl:−0.49 to−0.43),bile acids(MD:−0.22,Crl:−0.35 to−0.09),and inflammation(MD:−0.08,Crl:−0.13 to−0.03)compared with *** found treatment modulating fibrosis(MD:−1.27,Crl:−1.76 to−0.79)was the best treatment for reduction in low-density lipid(LDL)cholesterol followed by treatment modulating in-flammation(MD:−1.03,Crl:−1.09 to−0.97)and energy(MD:−0.37,Crl:−0.39 to−0.34)compared with placebo,but LDL cholesterol was worsened by treatments modulat-ing bile ***:Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of athero-genic *** studies are required to evaluate the cardiovascular outcomes.

关键词： Lipid modulation NASH Dyslipidemia

mRNA delivery in cancer immunotherapy

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1348-1357页

作者： Yichen Zhong Shi Du Yizhou Dong Division of Pharmaceutics&Pharmacology College of PharmacyThe Ohio State UniversityColumbusOH 43210USA Department of Radiation Oncology Department of Biomedical EngineeringCenter for Clinical and Translational ScienceComprehensive Cancer CenterDorothy M.Davis Heart&Lung Research InstituteCenter for Cancer EngineeringCenter for Cancer MetabolismPelotonia Institute for Immune-OncologyThe Ohio State UniversityColumbusOH 43210USA Icahn Genomics institute Precision Immunology InstituteDepartment of Oncological SciencesTisch Cancer InstituteFriedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA

Messenger RNA(mRNA)has drawn much attention in the medical *** various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic strategy for ***,delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular ***,in addition to mRNA modification,efforts have been devoted to developing nanoparticles for mRNA *** this review,we introduce four categories of nanoparticle platform systems:lipid,polymer,lipid-polymer hybrid,and protein/peptide-mediated nanoparticles,together with their roles in facilitating mRNA-based cancer *** also highlight promising treatment regimens and their clinical translation.

关键词： Cancer immunotherapy Lipid nanoparticles Lipid—polymer hybrid nanoparticles Messenger RNA mRNA delivery Polymeric nanoparticles Protein/peptide-mediated nanoparticles

Clinical development of reovirus for cancer therapy:An oncolytic virus with immune-mediated antitumor activity

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World Journal of Methodology 2016年第1期6卷 25-42页

作者： Jun Gong Esha Sachdev Alain C Mita Monica M Mita Department of Medical Oncology City of Hope National Medical Center Division of Experimental Therapeutics Program Samuel Oschin Com-prehensive Cancer Institute Cedars-Sinai Medical Center

Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirusmediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus（Reolysin） across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed.

关键词： Reovirus Type 3 Dearing Oncolytic virus Ras Epidermal growth factor receptor Clinical trial Preclinical Immune modulation

Involvement of BMP Signaling in Proliferation of Human Coronary Artery Endothelial Cells

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South China Journal of Cardiology 2008年第2期9卷 81-87页

作者：郭素珍 Terence M Doherty 徐军 Andres J.Espinoza The Atherosclerosis Research Center Division of Cardiology Department of Medicineand The Burns and Allen Research Institute Cedars-Sinai Medical Centerand David Geffen School of Medicine at UCLA Los Angeles

Objectives To test the hypotheses that bone morphogenetic protein（BMP） signaling pathway components are expressed in arterial endothelial cells （ECs） and that BMP signaling influences endothelial cell（EC） proliferation. Methods We used cell culture and RT-PCR to determined mRNA expression of BMP receptors （BMPR）-IA, -IB, and II, Smads 1,4, 5, 6, and 7, and in cultured human coronary artery ECs at baseline and after stimulation with BMP2 （300 ng/mL for 6 hr）, non-radioactive cell proliferation to examine cell proliferation. Results Proteasome inhibition has been previously shown to enhance BMP signaling by preventing degradation of BMP pathway components. Therefore, identical experiments were also performed in the presence of the proteasome inhibitor epoxomicin. ECs expressed mRNA for BMPRs IA and II, Smads 1,4, 5, 6, 7, and stimulation with either BMP2 or epoxomicin resulted in a significant increase in EC proliferation measured after 48 hours in a dose-dependent fashion. Proliferation was accompanied by a marked increase in proliferating cell nuclear antigen （PCNA） expression. Toxicity was observed at high doses of epoxomicin. Conclusions All major BMP signaling molecules are expressed by vascular ECs and expression of these are affected by both BMP2 and epoxomicin. BMP2 may regulate EC proliferation, suggesting a possible role in vascular homeostasis and vascular pathologies involving EC denudation or proliferation.

关键词： bone morphogenetic proteins bone morphogenetic protein receptors endothelial cells