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A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan Cuccia Rachael Coates Blake Nassar Ethan Littlefield Elizabeth C.Martin Adam T.Melvin Cain Department of Chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of Chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to *** is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause *** this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and *** device provides a platform to evaluate the effects of FSS on MCF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the *** of the effects of FSS on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk *** single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell *** understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/*** demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were ***,there was no change in p-ERK1/*** is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were *** together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer *** findin

关键词： fluid breast estrogen

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Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management

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Asian Journal of Urology 2024年第1期11卷 42-47页

作者： Randi M.Pose Sophie Knipper Jonas Ekrutt Mara Kölker Pierre Tennstedt Hans Heinzer Derya Tilki Florian Langer Markus Graefen Martini-Klinik Prostate Cancer Centre University Hospital Hamburg-EppendorfGermany Department of Urology University Hospital Hamburg-EppendorfGermany Department of hematology and Oncology University Medical Centre Hamburg-EppendorfHamburgGermany

Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)*** an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in *** increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous ***:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December *** those,patients with factor V Leiden mutation were *** patients received individualised recommendation of haemostaseologists for perioperative *** complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after ***:Overall,85(0.3%)patients with known factor V Leiden mutation were *** age was 65(interquartile range:61-68)*** was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before *** all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after ***:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management *** may reassure patients with this hereditary condition who are counselled for RP.

关键词： Prostatecancer Prostatectomy Factor V Leiden mutation Thromboembolism Thrombophilia

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Update on acute myeloid leukemia stem cells:New discoveries and therapeutic opportunities

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World Journal of Stem Cells 2016年第10期8卷 316-331页

作者： Maximilian Stahl Tae Kon Kim Amer M Zeidan section of hematology Department of Internal MedicineYale School of Medicine

The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.

关键词： Leukemia stem cells Cancer stem cells Acute myeloid leukemia Stem cell niche Xenotransplantation Plerixafor NF-κ B C-X-C chemokine receptor type 4

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Hematological abnormalities in liver cirrhosis

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World Journal of Hepatology 2024年第9期16卷 1229-1244页

作者： Oscar Manuel Fierro-Angulo JoséAlberto González-Regueiro Ariana Pereira-García Astrid Ruiz-Margáin Fernando Solis-Huerta Ricardo Ulises Macías-Rodríguez Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico 14080Mexico Department of hematology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico 14080Mexico

Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological *** have documented a prevalence of thrombocytopenia,leukopenia,and anemia in patients with compensated cirrhosis of 77.9%,23.5%,and 21.1%,*** abnormalities carry significant clinical implications,including considerations for invasive procedures,infection risk,bleeding risk,and ***,cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagula-tion tests such as prothrombin time,partial thromboplastin time,international normalized ratio,and ***,this understanding has evol-ved,and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic *** in cirrhosis patients presents a complex pheno-type,with procoagulant and anticoagulant abnormalities offsetting each *** multifactorial phenomenon is inadequately reflected by routine laboratory *** complications are more prevalent in decompensated cirrhosis and may correlate with disease *** is primarily associated with portal hypertension,endothelial dysfunction,mechanical vessel injury,dissem-inated intravascular coagulation,endotoxemia,and renal *** review comprehensively outlines hematologic index abnormalities,mechanisms of hemostasis,coagulation,and fibrinolysis abnormalities,limitations of laboratory testing,and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

关键词： Cirrhosis Anemia Leukopenia Thrombocytopenia Coagulopathy Bleeding Thrombosis

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Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang

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Cancer Biology & Medicine 2016年第2期13卷 248-259页

作者： Hong-Sheng Zhou Bing Z.Carter Michael Andreeff section of Molecular hematology and Therapy Department of Leukemia The University of Texas M.D.Anderson Cancer Center Department of hematology Nanfang Hospital Southern Medical University

Acute myeloid leukemia （AML） is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow （BM） niche is critical to the maintenance and retention of hematopoietic stem cells （HSC）, including leukemia stem cells （LSC）, and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

关键词： Bone marrow niche leukemia stem cell acute myeloid leukemia Yin and Yang

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Hepatic failure caused by plasma cell infiltration in multiple myeloma

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World Journal of Gastroenterology 2009年第16期15卷 2038-2040页

作者： Fadi E Rahhal Robert R Schade Asha Nayak Teresa A Coleman section of Gastroenterology Department of MedicineMedical College of GeorgiaSchool of Medicine section of hematology/Oncology Department of MedicineMedical College of GeorgiaSchool of Medicine

Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma （MM）, it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stageⅡB. Thalidomide and dexamethasone were initiated. The patient developed a continuous increase in bilirubin that led to severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then rapidly progressed to liver failure and died. Treatment options are limited in MM with significant liver dysfunction. Despite new drug therapies in MM, those patients with rapidly progressive liver failure appear to have a dismal outcome.

关键词： Hepatic failure Multiple myeloma Cell infiltration

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Determination of the Mineral Composition of the Pulp and Evaluation of the Acute Toxicity of the Seeds of Carica papaya L. Consumed in Lubumbashi and Kinshasa in the Democratic Republic of the Congo

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Journal of Biosciences and Medicines 2024年第9期12卷 266-279页

作者： Guelord Inkalaba Janvier Arnauld Kiza Magain Mihatano Mathilde Bushiri Furaha Arthur Duki Olivier Nzingula Armelle Naniwambote Maguy Luvandu Nicole Misengabu Désiré Musuyu Fridolin Kodondi Kule-Koto Laboratory of Biochemistry Nutrition and Hematology Faculty of Pharmaceutical Sciences University of Kinshasa Kinshasa Democratic Republic of the Congo Faculty of Pharmaceutical Sciences University of Lubumbashi Lubumbashi Democratic Republic of the Congo Food Technology and Food Analysis Laboratory Faculty of Pharmaceutical Sciences University of Kinshasa Kinshasa Democratic Republic of the Congo Higher Institute of Medical Techniques Nutrition and Dietetics Section Kinshasa Democratic Republic of the Congo Laboratory of the National Institute of Biomedical Research (NIBR) Kinshasa Democratic Republic of the Congo

This work aimed, on the one hand, to determine the mineral and phytochemical composition of Carica papaya in order to guarantee the food safety of consumers and on the other hand, to evaluate the acute toxicity of papaya seeds. The papayas were bought at the Mzée market in Lubumbashi and Selembao in Kinshasa. Fruit sampling was done according to the ISO 7002 standard on agricultural and food products;the papayas were firm, mature, and without stains or physical damage. The analysis results of the papaya pulp showed both for the samples from the city of Lubumbashi and for the city province of Kinshasa that it contains respectively 85.87% and 84.46% water, 0.59% and 0.53% ash content. The mineral evaluation of our two samples presented a potassium content of 200 ± 8 mg, magnesium 13.12 ± 3 mg, calcium 22.15 ± 2 mg, sodium 3 mg ± 0.5 for the sample from Lubumbashi and 192.32 ± 8 mg of potassium, 14.458 ± 3 mg of magnesium, 20.58 ± 2 mg of calcium and 3.58 ± 0.5 mg of sodium for the sample from Kinshasa in macroelements. Concerning the trace elements, after analysis, we found zinc content (0.29 ± 0.1 mg and 0.12 ± 0.1 mg), copper (0.02 ± 0.01 mg and 0.14 ± 0.01 mg), and iron (2.22 ± 0.5 mg and 2.04 ± 0.5 mg) respectively for Lubumbashi and Kinshasa. The chemical screening indicates the presence of alkaloids, saponosides, tannins catechics, flavonoids and anthocyanins in the palm wine and ethanolic extract of the seeds of Carica papaya and an absence of cyanogenic glycosides and gallic tannins. With mild toxicity, the seeds of the fruit of Carica papaya L. can be used with moderate risk by the population.

关键词： Carica papaya Mineral Composition Acute Toxicity

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Past,present,and future perspectives of ultrasound-guided ablation of liver tumors:Where could artificial intelligence lead interventional oncology?

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Artificial Intelligence in Cancer 2024年第1期5卷 1-12页

作者： Paola Tombesi Andrea Cutini Valentina Grasso Francesca Di Vece Ugo Politti Eleonora Capatti Florence Labb Stefano Petaccia Sergio Sartori Department of Internal Medicine Section of Interventional UltrasoundSt.Anna HospitalFerrara 44100Italy Esaote S.p.A. Genova 16100Italy

The first ablation procedures for small hepatocellular carcinomas were percutaneous ethanol injection under ultrasound(US)***,radiofrequency ablation was shown to achieve larger coagulation areas than percutaneous ethanol injection and became the most used ablation technique *** the past decade,microwave ablation systems have achieved larger ablation areas than radiofrequency ablation,suggesting that the 3-cm barrier could be broken in the treatment of liver ***,US techniques to guide percutaneous ablation have seen important ***-enhanced US(CEUS)can define and target the tumor better than US and can assess the size of the ablation area after the procedure,which allows immediate retreatment of the residual tumor ***,fusion imaging fuses real-time US images with computed tomography or magnetic resonance imaging with significant improvements in detecting and targeting lesions with low conspicuity on ***,software powered by artificial intelligence has been developed to allow three-dimensional segmentation and reconstruction of the anatomical structures,aiding in procedure planning,assessing ablation completeness,and targeting the residual viable foci with greater precision than ***,this could lead to the ablation of tumors up to 5-7 cm in size.

关键词： Artificial intelligence Fusion imaging Percutaneous thermal ablation Microwave ablation Radiofrequency ablation Ultrasound Contrast-enhanced ultrasound

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Effects of insulin and pathway inhibitors on the PI3K-Akt- mTOR phosphorylation profile in acute myeloid leukemia cells

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Signal Transduction and Targeted Therapy 2019年第1期4卷 504-515页

作者： Ina Nepstad Kimberley Joanne Hatfield Ida Sofie Grønningsæter Elise Aasebø Maria Hernandez-Valladares Karen Marie Hagen Kristin Paulsen Rye Frode SBerven Frode Selheim Håkon Reikvam Øystein Bruserud section for hematology Department of Clinical ScienceUniversity of BergenBergenNorway Department of Immunology and Transfusion Medicine Haukeland University HospitalBergenNorway Department of Biomedicine Faculty of Medicine and DentistryUniversity of BergenJonas Lies vei 915009 BergenNorway section for hematology Department of MedicineHaukeland University HospitalBergenNorway

The phosphatidylinositol 3-kinase(PI3K)-Akt-mechanistic target of rapamycin(mTOR)pathway is constitutively activated in human acute myeloid leukemia(AML)cells and is regarded as a possible therapeutic *** is an agonist of this pathway and a growth factor for AML *** characterized the effect of insulin on the phosphorylation of 10 mediators in the main track of the PI3K-Akt-mTOR pathway in AML cells from 76 consecutive *** overall results showed that insulin significantly increased the phosphorylation of all investigated ***,insulin effects on the pathway activation profile varied among patients,and increased phosphorylation in all mediators was observed only in a minority of patients;in other patients,insulin had divergent *** gene expression profiling and proteomic/phosphoproteomic comparisons suggested that AML cells from these two patient subsets differed with regard to AML cell differentiation,transcriptional regulation,RNA metabolism,and cellular *** insulin-induced phosphorylation was associated with weakened antiproliferative effects of metabolic ***3K,Akt,and mTOR inhibitors also caused divergent effects on the overall pathway phosphorylation profile in the presence of insulin,although PI3K and Akt inhibition caused a general reduction in Akt pT308 and 4EBP1 pT36/pT45 *** Akt inhibition,the phosphorylation of upstream mediators was generally increased or *** contrast,mTOR inhibition reduced mTOR pS2448 and S6 pS244 phosphorylation but increased Akt pT308 *** conclusion,the effects of both insulin and PI3K-Akt-mTOR inhibitors differ between AML patient subsets,and differences in insulin responsiveness are associated with differential susceptibility to metabolic targeting.

关键词： metabolism myeloid mTOR

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MicroRNAs in cancer biology and therapy:Current status and perspectives

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Genes & Diseases 2014年第1期1卷 53-63页

作者： Colles Price Jianjun Chen section of hematology/Oncology Department of MedicineUniversity of ChicagoChicagoIL 60637USA

The study of a class of small non-coding RNA molecules,named microRNAs(miRNAs),has advanced our understanding of many of the fundamental processes of cancer biology and the molecular mechanisms underlying tumor initiation and *** research has become more and more attractive as evidence is emerging that miRNAs likely play important regulatory roles virtually in all essential *** at this field over the past decade it becomes evident that our understanding of miRNAs remains rather *** research continues to reveal the mechanisms underlying cancer therapy efficacy,it is clear that miRNAs contribute to responses to drug therapy and are themselves modified by drug *** important area for miRNA research is to understand the functions of miRNAs and the relevant signaling pathways in the initiation,progression and drug-resistance of tumors to be able to design novel,effective targeted therapeutics that directly target pathologically essential miRNAs and/or their target *** area of increasing importance is the use of miRNA signatures in the diagnosis and prognosis of various types of *** the study of noncoding RNAs is increasingly more popular and important,it is without doubt that the next several years of miRNA research will provide more fascinating results.

关键词： Cancer biology Drug therapy miRNAs Nanoparticles Oncogene Tumor suppressor

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