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The lncRNA BORG: a novel inducer of TNBC metastasis, chemoresistance, and disease recurrence

Journal of Cancer Metastasis and Treatment 2019年第5期4卷 48-61页

作者： Alex J.Gooding Kimberly A.Parker Saba Valadkhan William P.Schiemann Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA Department of Pharmacology Case Western Reserve UniversityClevelandOH 44106USA Department of Molecular Biology and Microbiology Case Western Reserve UniversityClevelandOH 44106USA Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 44106USA

Although greater than 90% of breast cancer-related mortality can be attributed to metastases, the molecular mechanisms underpinning the dissemination of primary breast tumor cells and their ability to establish malignant lesions in distant tissues remain incompletely understood. Genomic and transcriptomic analyses identified a class of transcripts called long noncoding RNA (lncRNA), which interact both directly and indirectly with key components of gene regulatory networks to alter cell proliferation, invasion, and metastasis. We identified a pro-metastatic lncRNA BMP/OP-Responsive Gene (BORG) whose aberrant expression promotes metastatic relapse by reactivating proliferative programs in dormant disseminated tumor cells (DTCs). BORG expression is broadly and strongly induced by environmental and chemotherapeutic stresses, a transcriptional response that facilitates the survival of DTCs. Transcriptomic reprogramming in response to BORG resulted in robust signaling via survival and viability pathways, as well as decreased activation of cell death pathways. As such, BORG expression acts as a (1) marker capable of predicting which breast cancer patients are predisposed to develop secondary metastatic lesions;and (2) unique therapeutic target to maximize chemosensitivity of DTCs. Here we review the molecular and cellular factors that contribute to the pathophysiological activities of BORG during its regulation of breast cancer metastasis, chemoresistance, and disease recurrence.

关键词： BORG chemoresistance disease recurrence dormancy long noncoding RNA metastasis triple-negative breast cancer

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Design and analyses of open-ended pipe piles in cohesionless soils

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Frontiers of Structural and Civil Engineering 2016年第1期10卷 22-29页

作者： Yuan GUO Xiong (Bill) YU Department of Civil Engineering Case Western Reserve University 2104 Adelbert Road Bingham 260 Cleveland OH 44106-7201USA

Large open-ended pipe pile has been found to be advantageous for use in transportation projects. The current design method, however, is not adequately developed. To close this practice gap, this paper first summarized different design methods for open-ended pipe piles in sandy soils. A major factor for all the design codes is to properly account for the formation and effects of soil plug. The comparison indicates that there is a large variation in the base capacity evaluation among different methods due to the complex behaviors of soil plug. To close the knowledge gap, discrete element method （DEM） was used to simulate the soil plugging process and provide insight on the plugging mechanism. The simulation results show that the arching effect significantly increases the internal unit shear resistance along pipe piles. The porosity distribution and particle contact force distribution from DEM model indicate a large stress concentration occurs at the bottom of the soil plug. Besides, nearly 90% of the plug resistance is provided by the bottom half portion of the soil column. The soil-pile friction coefficient has a significant effect on the magnitude of plug resistance, with the major transition occurred for friction coefficient between 0.3 and 0.4.

关键词： open-ended pipe pile soil plug DEM base capacity

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Molecular dynamics simulations of membrane deformation induced by amphiphilic helices of Epsin,Sar1p,and Arf1

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Chinese Physics B 2018年第3期27卷 544-550页

作者： Zhen-Lu Li Department of Physiology and Biophysics Case Western Reserve UniversityCleveland 44106USA Department of Physics Nanjing UniversityNanjing 210093China

The N-terminal amphiphilic helices of proteins Epsin,Sarlp,and Arfl play a critical role in initiating membrane *** interactions of these amphiphilic helices with the lipid membranes are investigated in this study by combining the all-atom and coarse-grained *** the all-atom simulations,the amphiphilic helices of Epsin and Sarlp are found to have a shallower insertion depth into the membrane than the amphiphilic helix of Arfl,but remarkably,the amphiphilic helices of Epsin and Sat lp induce higher asymmetry in the lipid packing between the two monolayers of the *** insertion depth of amphiphilic helix into the membrane is determined not only by the overall hydrophobicity but also by the specific distributions of polar and non-polar residues along the *** directly compare their ability to deform the membrane,the coarse-grained simulations are performed to investigate the membrane deformation under the insertion of multiple helices.

关键词： cell membrane amphiphilic helix membrane deformation molecular simulation

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The association of inherited variation in the CLOCK gene with breast cancer tumor grade

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Family Medicine and Community Health 2017年第2期5卷 103-108页

作者： Neha Gupta Li Li Cheryl L.Thompson Department of Nutrition Case Western Reserve UniversityClevelandOHUSA Department of Family Medicine and Community Health Case Western Reserve UniversityClevelandOHUSA Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOHUSA

Background:Sufficient sleep and maintenance of circadian rhythm are important to *** have shown that short duration of sleep before diagnosis is associated with higher-grade tumors among breast cancer *** studies suggest that genetic variation in the CLOCK gene is associated with risk of cancers,including breast *** of the association of genetic variation,including in CLOCK,and tumor grade,a standard marker of tumor aggressiveness,are ***:We investigated the relationship between single nucleotide polymorphisms(SNPs)in the CLOCK gene and tumor grade and estrogen receptor,progesterone receptor,and human epi-dermal growth factor receptor 2 status in 293 breast cancer *** SNPs were determined by standard TaqMan *** grade,receptor status,and other clinical variables were abstracted from medical ***:Two SNPs were excluded because of poor genotyping *** of the remaining seven variants had a statistically significant association with breast cancer tumor grade or with receptor ***:As with all novel studies,further work is needed to examine the association of CLOCK and other genes in the circadian rhythm pathway with breast cancer tumor grade in other populations.

关键词： Breast cancer SNP tumor grade CLOCK

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Iron oxide nanoparticles promote vascular endothelial cells survival from oxidative stress by enhancement of autophagy

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Regenerative Biomaterials 2019年第4期6卷 221-229页

作者： Jimei Duan Jiuju Du Rongrong Jin Wencheng Zhu Li Liu Li Yang Mengye Li Qiyong Gong Bin Song James MAnderson and Hua Ai National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065P.R.China Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of SciencesShanghai 200031P.R.China Department of Radiology West China HospitalSichuan UniversityChengdu 610041P.R.China Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA Department of Macromolecular Science Case Western Reserve UniversityClevelandOH 44106USA Department of Biomedical Engineering Case Western Reserve UniversityClevelandOH 44106USA

Dextran-coated superparamagnetic iron oxide nanoparticles(Dex-SPIONs)are excellent magnetic resonance imaging contrast agents for disease diagnosis and *** can be delivered to target tissues mainly though vascular endothelium cells,which are major targets of oxidative *** cardiovascular cells,autophagy serves primarily on a pro-survival approach that protects the cells from oxidative stress even some autophagy inducers have been developed for adjuvant therapy of cardiovascular *** study demonstrated that the nanoparticles could be taken up by human umbilical vein endothelial cells(HUVECs)without causing obvious cytotoxicity but triggering ***,our results revealed that Dex-SPIONs could enhance HUVECs survival and reverse the reduction of nitric oxide secretion under the condition of H2O2 ***,these effects could be diminished by the autophagy *** particular,we discovered that Dex-SPIONs evoked autophagy in HUVECs by reducing the phosphorylation of PRAS40,an upstream regulator of autophagy *** results suggested that Dex-SPIONs functions as an autophagic-related antioxidant in HUVECs which may be utilized as an adjuvant therapy to cardiovascular disease associated with oxidative stress.

关键词： human umbilical vein endothelial cells dextran-coated iron oxide nanoparticles autophagy oxidative stress

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Perspectives on “the biology of spinal cord regeneration success and failure”

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Neural Regeneration Research 2018年第8期13卷 1358-1359页

作者： Philippa Mary Warren Amanda Phuong Tran Jerry Silver School of Biomedical Sciences University of Leeds Department of Neurosciences Case Western Reserve University

In our recently co-authored Physiological Reviews manuscript entitled ＂The biology of regeneration failure and success after spinal cord injury＂（Tran et al., 2018b）, we sought to provide a comprehensive and up-to-date de- scription of how the glial scar develops following spinal cord injury （SCI） to chronically inhibit axon regeneration.

关键词： the biology of spinal cord regeneration success and failure SCI

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Neuronal failure in Alzheimer's disease: a view through the oxidative stress looking-glass

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Neuroscience Bulletin 2014年第2期30卷 243-252页

作者： David J. Bonda Xinglong Wang Hyoung-Gon Lee Mark A. Smith George Perry Xiongwei Zhu Department of Pathology Case Western Reserve University UTSA Neurosciences Institute and Department of Biology University of Texas at San Antonio

Considerable debate and controversy surround the cause（s） of AIzheimer＇s disease （AD）. To date, several theories have gained notoriety, however none is universally accepted. In this review, we provide evidence for the oxidative stress-induced AD cascade that posits aged mitochondria as the critical origin of neurodegeneration in AD.

关键词： Alzheimer's disease amyloid-beta free radicals mitochondria mitochondrial dynamics oxidativestress

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Future challenges in the in vitro and in vivo evaluation of biomaterial biocompatibility

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Regenerative Biomaterials 2016年第2期3卷 73-77页

作者： James M.Anderson Case western reserve University 2103 Cornell RoadWRB 5105ClevelandOH 44106-7288USA

As the science and engineering of biomaterials continues to expand with increased emphasis on the development of nanomaterials and tissue engineering scaffolds,emphasis also must be placed on appropriate and adequate approaches to the in vivo and in vitro evaluation of biomaterial biocompatibility/biological response *** article presents six topic areas that should be addressed by investigators as they move forward in the development of new systems for regenerative *** certainly,there are other areas that require attention to detail and a more complete understanding of the strengths and weaknesses of various experimental approaches to biomaterial/biological response *** small number of issues addressed in this article is only meant to bring to the attention of prospective investigators and authors,the importance of the development of adequate and appropriate evaluation techniques that address the unique features of biomaterials utilized in the development of new medical devices.

关键词： biomaterials nanomaterials tissue engineering

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A facile and sensitive method of quantifying glutaminase binding to its ninhibitor CB-839 in tissues

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Journal of Genetics and Genomics 2020年第7期47卷 389-395页

作者： Yicheng Chen Yiqing Zhao David L.Bajor Zhenghe Wang J.Eva Selfridge Department of Genetics and Genome Sciences Case Western Reserve University10900 Euclid AvenueClevelandOH44106USA Department of Medicine Case Western Reserve University10900 Euclid AvenueClevelandOH.44106USA Case Comprehensive Cancer Center Case Western Reserve University10900 Euclid AvenueClevelandOH44106USA Seidman Cancer Center University Hospitals Cleveland Medical CenterWOO Euclid AvenueClevelandOH44106USA

Many cancer types reprogram their metabolism to become addicted to *** of the critical enzymes in the utilization of glutamine in these cells is ***-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine *** its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical ***,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft ***,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical *** assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.

关键词： Glutaminase Method Cancer

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Modeling challenges and potential solutions for integration of emerging DERs in DMS applications: power flow and short-circuit analysis

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Journal of Modern Power Systems and Clean Energy 2019年第6期7卷 1365-1384页

作者： Luka V.STREZOSKI Nikola R.VOJNOVIC Vladimir C.STREZOSKI Predrag M.VIDOVIC Marija D.PRICA Kenneth A.LOPARO Case School of Engineering Case Western Reserve UniversityClevelandUSA Faculty of Technical Sciences University of Novi SadNovi SadSerbia

We aim to systematically review challenges imposed by emerging distributed energy resources(DERs)to model in two basic distribution management system(DMS)online applications—power flow and short-circuit analysis,as well as to offer a systematic review of potential *** the last decade,electronically coupled DERs became increasingly *** can employ a wide range of control strategies for power,current,or voltage control,in both normal and faulted ***,DERs cannot be modeled with the traditional PQ(load or generator bus)or PV(generator bus)bus types used for modeling synchronous and induction machines in online power flow ***,since fault currents of DERs are limited to predefined maximal values,electronically coupled DERs cannot be represented with traditional voltage source behind impedance models for online short-circuit calculation(SCC).However,most of the DMS software packages still use the traditional models to represent all DER types,including those that are electronically *** paper shows that there will be large calculation errors in such practice,which make the system model an inadequate representation of the *** will lead to serious errors in the management,control,and operation of distribution ***,potential solutions to the challenges are systematically ***,the calculation results on a distribution test system with all DER types are used to prove the claim.

关键词： Distributed energy resources(DERs) Distribution management system(DMS) Power flow modeling Short-circuit modeling

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