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Cardiac differentiation is modulated by anti-apoptotic signals in murine embryonic stem cells

World Journal of Stem cells 2024年第5期16卷 551-559页

作者： Amani Yehya Joseph Azar Mohamad Al-Fares Helene boeuf Wassim Abou-Kheir Dana Zeineddine Ola Hadadeh Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Inserm BiotisU1026University BordeauxBordeaux F-33000France Rammal Rammal Lab Physio-Toxicity Environmental TeamFaculty of SciencesLebanese UniversityNabatieh 0000Lebanon

bACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage *** exhibit a unique combination of self-renewal potency,unlimited proliferation,and *** latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ *** regulatory networks guide ESCs,directing their self-renewal and lineage-specific ***,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic ***-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly *** To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-b-cell lym-phoma 2(bCL-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes bcl-2,Pim-2,and Met-1,*** mESC-T2(wild-type),mESC-bCL-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac *** hanging drop method was adopted to generate embryoid bodies(Ebs)and induce terminal differentiation of *** size of the generated Ebs was measured in each condition compared to the wild *** the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the *** the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and ***,troponin T protein expression was evaluated through immunofluorescence and western blot *** Our findings showed that the upregulation of bcl-

关键词： Mouse embryonic stem cells Self-renewal Apoptosis Cardiac differentiation b-cell lymphoma 2 PIM-2 Metallothionein-1

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MiR-503 regulates cisplatin resistance of human gastric cancer cell lines by targeting IGF1R and bCL2

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Chinese Medical Journal 2014年第12期127卷 2357-2362页

作者： Wang Tongshan Ge Gaoxia Ding Yin Zhou Xin Huang Zebo Zhu Wei Shu Yongqian Liu Ping Department of Oncology First Affiliated Hospital of Nanjing Medical University NanjingJiangsu 210029China Department of Clinical Laboratory First Affiliated Hospital of Nanjing Medical University NanjingJiangsu 210029China State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjingJiangsu 210093China Department of Oncology Jiangsu Province HospitalNanjingJiangsu 210029China

background Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs （miRNAs）.We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell *** MiR-503 expression was measured by quantitative real-time *** （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA.A dual-luciferase activity assay was used to verify target genes of ***,Western blotting analysis,and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer *** MiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell ***,downregulation of miR-503 in the cisplatin （DDP）-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor （IGF1R） and b-cell lymphoma 2 （bCL2） expression compared with the parental SGC7901 cell *** in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to *** luciferase activity of reporters driven by IGF1R and bCL2 3＇-untranslated regions in SGC7901/DDP cells suggested that IGF1R and bCL2 were both direct target genes of *** miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins,inhibited proliferation,and sensitized the cells to DDP-induced *** Our findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and bCL2.

关键词： miR-503 cisplatin resistance insulin-like growth factor-1 receptor b-cell lymphoma 2 gastric cancer

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Promises and pitfalls of targeted agents in chronic lymphocytic leukemia

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Cancer Drug Resistance 2020年第3期3卷 415-444页

作者： Thomas E.Lew Mary Ann Anderson John F.Seymour Department of Clinical Haematology The Royal Melbourne Hospital and Peter MacCallum Cancer CentreParkville 3050Australia. blood cells and blood Cancer Division Walter and Eliza Hall Institute of Medical ResearchParkville 3050Australia. Faculty of Medicine Dentistry and Health SciencesThe University of MelbourneParkville 3050Australia.

Targeted agents have significantly improved outcomes for patients with chronic lymphocytic leukemia,particularly high-risk subgroups for whom chemoimmunotherapy previously offered limited *** classes of agent in particular,the bruton tyrosine kinase inhibitors(e.g.,ibrutinib)and the b-cell lymphoma 2 inhibitor,venetoclax,induce high response rates and durable remissions in the relapsed/refractory and frontline ***,maturing clinical data have revealed promises and pitfalls for both *** drugs induce remissions and disease control in the majority of patients,often in situations where modest efficacy would be expected with traditional chemoimmunotherapy ***,in the relapsed and refractory setting,both agents appear to be associated with an inevitable risk of disease relapse and *** patterns of resistance are being described for both agents but a common theme appears to be multiple sub-clonal drivers of disease *** these mechanisms and developing effective and safe methods to circumvent the emergence of resistance will determine the longer-term utility of these agents to improve patients’quality and length of *** drug combinations,optimised scheduling and sequencing of therapy will likely hold the key to achieving these important goals.

关键词： Chronic lymphocytic leukemia drug resistance venetoclax b-cell lymphoma 2 ibrutinib bruton tyrosine kinase idelalisib phosphatidylinositol 3-kinase

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