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Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer

World Journal of Gastrointestinal Oncology 2022年第2期14卷 511-524页

作者： Lauren Midthun Sungjin Kim Andrew Hendifar Arsen Osipov Samuel J Klempner Joseph Chao May Cho Michelle Guan veronica r placencio-hickok Alexandra Gangi Miguel Burch De-Chen Lin Kevin Waters Katelyn Atkins Mitchell Kamrava Jun Gong Department of Medicine Division of Hematology and OncologyCedars-Sinai Medical CenterLos AngelesCA 90048United States Biostatistics and Bioinformatics research Center Cedars Sinai Medical CenterLos AngelesCA 90048United States Samuel Oschin Cancer Center Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Beth Israel Deaconess Medical Center/Harvard Medical SchoolBrigham and Women's Hospital/Harvard Medical SchoolBostonMA 02114United States Department of Medical Oncology and Therapeutics research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaIrvineCA 92697United States Department of Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Pathology and Laboratory Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of radiation Oncology Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGrOUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal ***,not all patients with metastatic disease receive *** To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and *** We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without *** A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving *** median follow-up was 69.45 *** median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no *** of diagnosis 2010-2014[odds ratio(Or):1.29,95%confidence interval(CI):1.17-1.43,P value$46000(Or:1.49,95%CI:1.27-1.75,P valuer:1.35,95%CI:1.20-1.52,Pre independent predictors of receiving chemotherapy,while female gender(Or:0.86,95%CI:0.76-0.98,P=0.019),black race(Or:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(Or:0.41,95%CI:0.33-0.52,Prlson Comorbidity Index(CCI)(Or for CCI≥2:0.61,95%CI:0.50-0.74,Predicted for lower odds of receiving *** the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on ***,uninsured status[hazard ratio(Hr):1.20,95%CI:1.09-1.31,Prom the geographic

关键词： Esophageal cancer Metastatic Chemotherapy Predictors Survival

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Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

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World Journal of Gastrointestinal Surgery 2020年第9期12卷 377-389页

作者： Sungjin Kim Timothy P DiPeri Michelle Guan veronica r placencio-hickok Haesoo Kim Jar-Yee Liu Andrew Hendifar Samuel J Klempner ryan Nipp Alexandra Gangi Miguel Burch Kevin Waters May Cho Joseph Chao Katelyn Atkins Mitchell Kamrava richard Tuli Jun Gong Biostatistics and Bioinformatics research Center Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Surgical Oncology Department of SurgerySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Division of Hematology and OncologySamuel Oschin Comprehensive Cancer InstituteCedars Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonMA 02114United States Department of Pathology and Laboratory Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaDavisSacramentoCA 95817United States Department of Medical Oncology and Therapeutics research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Department of radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States

BACKGrOUND Palliative therapy has been associated with improved overall survival(OS)in several tumor *** all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are *** To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving *** The National Cancer Database was used to identify patients between *** with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(rT),pain management,or any combination thereof]were *** with unknown chemotherapy,rT,or nonprimary surgery status were ***-Meier estimates of OS were *** proportional hazards regression models were employed to examine factors influencing *** Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete *** age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic *** majority(72.7%)did not receive other palliative *** both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(Hr)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(Hr 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(Hr 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(Hr 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(Hr 1.17,95%CI:1.03-1.32)were associated with increased *** histologic grade and T-stage were also as

关键词： Esophageal cancer Metastatic Palliative Chemotherapy radiotherapy Survival

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Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

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Neural regeneration research 2025年第10期20卷 2872-2886页

作者： Marta Chierichetti riccardo Cristofani Valeria Crippa veronica Ferrari Marta Cozzi Elena Casarotto Paola Pramaggiore Laura Cornaggia Guglielmo Patelli Ali Mohamed Margherita Piccolella Mariarita Galbiati Paola rusmini Barbara Tedesco Angelo Poletti Laboratory of Experimental Biology Dipartimento di Scienze Farmacologiche e Biomolecolari“Rodolfo Paoletti”(DiSFeB)Universitàdegli Studi di MilanoMilanItaly

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock ***8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and ***8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective *** line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and *** cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under ***,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar *** note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other *** is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial *** review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its ***-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

关键词： aggregation autophagy cancer chaperone chaperone-assisted selective autophagy cognitive impairment HSPB8 neuroinflammation neuromuscular diseases therapy

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Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems

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Neural regeneration research 2025年第9期20卷 2591-2593页

作者： Alena Salasova Anders Nykjær Danish research Institute of Translational Neuroscience DANDrITE-Nordic EMBL Partnership for Molecular Medicine and Centre of Excellence PROMEMODepartment of BiomedicineAarhus UniversityAarhusDenmark

The formation of the mammalian nervous system and its maturation into sensory,motor,cognitive,and behavioral circuits is a complex process that begins during early embryogenesis and lasts until young *** neurodevelopm... 详细信息

关键词： progr jointly CS2

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Axonal tuning by GABA_(A) receptor unveils novel tricks from an old dog

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Neural regeneration research 2023年第3期18卷 533-534页

作者： veronica Bonalume Valerio Magnaghi Department of Pharmacological and Biomolecular Sciences Universitàdegli Studi di MilanoMilanItaly

In the last years,axonal conductance of action potential trains became a novel subject of study,changing the view of axons,from a static cable-like compartment to a more complex and dynamic system(Debanne et al.,2011).Axonal computation,indeed,is canonically constituted by the action of voltage-gated ion channels,such as the classic Na+and K+channels,but recent studies demonstrated that it can be modulated by the action of other ion channel pumps,and metabolic factors(Byczkowicz et al.,2019;Zang and Marder.

关键词： tuning action classic

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Antisense oligonucleotides provide optimism to the therapeutic landscape for tauopathies

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Neural regeneration research 2025年第3期20卷 803-804页

作者： Glenn A.Harris Lauren r.Hirschfeld rainwater Charitable Foundation Fort WorthTXUSA

Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3r) or 4-repeat(4r) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.

关键词： tau metabolism diseases

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Sensitivity of a solid Eu(Ⅲ) complex towards acetonitrile vapor:Structural and spectroscopic characterization

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Journal of rare Earths 2020年第5期38卷 571-576页

作者： Fabio Piccinelli veronica Paterlini Magda Monari Marco Bettinelli Luminescent Materials Laboratory DBUniversita di Veronaand INSTMUdR VeronaStrada Le Grazie 1537134VeronaItaly Dipartimento di Chimica"G.Ciamician" Universita di BolognaVia Selmi 240126BolognaItaly

The Eu(Ⅲ)nitrate complex of the meso-N,N’-bis(2-pyridylmethylene)-1,2-(r,S)-cyclohexanediamine ligand was synthesized and characterized by single crystal and powder X-ray *** crystal lattice of the complex is capable of absorbing and desorbing selectively acetonitrile molecules,at 293 K upon an acetonitrile vapor pressure of^0.1×10^5 *** process,which is partially reversible,can be easily followed by both powder X-ray diffraction(P-XrD)and Eu(III)luminescence *** acetonitrile molecule,located in the outer coordination sphere of the metal ion,does not affect the radiative transition probability of 5 D0 level of Eu(Ⅲ)and also it does not activate further non-radiative channels from this *** the other hand,this molecule is capable of affecting the energy position and intensities of the crystal field components of the 5 D0→7 F2 *** complex in solid form can be considered a promising material for the optical sensing of acetonitrile vapors.

关键词： Eu(Ⅲ) X-ray diffraction Crystal structure Luminescence spectroscopy rare earths

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Surrogate potency assays:Comparison of binding profiles complements dose response curves for unambiguous assessment of relative potencies

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Journal of Pharmaceutical Analysis 2018年第2期8卷 138-146页

作者： robert Karlsson veronica Fridh Asa Frostell Purification and Analysis GE Healthcare Life SciencesUppsalaSweden

Surface plasmon resonance(SPr) systems are widely used for detailed characterization of antibody activities including antigen and Fc-receptor binding. During the later stages of development, where the focus is to ensure that established critical quality attributes(CQAs) are maintained during cell culture,purification and formulation processes, analysis is simplified, and relative potencies are often determined. Here, simulation of binding data revealed that relative potency values, determined via parallel line analysis(PLA) and half maximal effective concentration(EC50) analysis accurately reflect changes in active concentration only if binding kinetics remain unchanged. Changes in the association rate constant shifted dose response curves, and therefore relative potencies, in the same way as changes in analyte concentration do. However, for interactions characterized by stable binding, changes in the dissociation rate constant did not result in any shift, suggesting that this type of change may go unnoticed in the dose response curve. Thus, EC50 and PLA analyses of dose response curves obtained with an anti-TNF-α antibody were complemented with the Biacore functionality for sensorgram comparison analysis, whereby changes in antigen and Fc-receptor binding profiles could be detected. Next, analysis of temperature stressed TNF-α antibody revealed that calibration free concentration analysis(CFCA) data correlated perfectly with relative potency values. Together, these results demonstrate that combinations of SPr based dose response curves, sensorgram comparison and CFCA can be used to strengthen the confidence in relative potency assessments, and suggest that SPr can potentially be used as a surrogate potency assay in the quality control of biotherapeutic medicines.

关键词： Surface plasmon resonance EC50 Sensorgram comparison Calibration free concentration analysis Surrogate potency assay TNF-a

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Interactions between Axillary Branches of Arabidopsis

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Molecular Plant 2008年第2期1卷 388-400页

作者： veronica Ongaro Katherine Bainbridge Lisa Williamson Ottoline Leyser Department of Biology University of York PO Box 373--Area 11York YO10 5YW UK Present address: Institute of Plant Sciences University of Bern CH-3013 Bern Switzerland

Studies of apical dominance have benefited greatly from two-branch assays in pea and bean, in which the shoot system is trimmed back to leave only two active cotyledonary axillary branches. In these two-branch shoots, a large body of evidence shows that one actively growing branch is able to inhibit the growth of the other, prompting studies on the nature of the inhibitory signals, which are still poorly understood. Here, we describe the establishment of two-branch assays in Arabidopsis, using consecutive branches on the bolting stem. As with the classical studies in pea and bean, these consecutive branches are able to inhibit one another＇s growth. Not only can the upper branch inhibit the lower branch, but also the lower branch can inhibit the upper branch, illustrating the bi-directional action of the inhibitory signals. Using mutants, we show that the inhibition is partially dependent on the MAX pathway and that while the inhibition is clearly transmitted across the stem from the active to the inhibited branch, the vascular connectivity of the two branches is weak, and the MAX pathway is capable of acting unilaterally in the stem.

关键词： shoot branching auxin MAX vascularization.

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Micromechanical adaptation as a treatment for spinal cord injury

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Neural regeneration research 2019年第11期14卷 1909-1911页

作者： veronica estrada Hans werner Müller Molecular Neurobiology Laboratory Department of Neurology Heinrich-Heine-University Medical Center Düsseldorf

Spinal cord injury: Thus far injury of the spinal cord is incurable and, in the majority of cases, a devastating and life-changing event. The worldwide incidence rate of spinal cord injury (SCI) ranges from 250,000 to 900,000 (***, 2013;Kumar et al., 2018) new cases per year. SCI outcome includes the damage of axons, demyelination of axons, loss of signal transduction, and consequential long-lasting motor and sensory deficits. Additionally, the non-use of muscles can lead to atrophy and joint contractures, thereby further reducing the possibility of recovery. Depending on the spinal level and the severity of the injury, the extent of the damage can vary and spontaneous recovery is possible to varying degrees.

关键词： Micromechanical adaptation spinal cord injury spinal cord injury(SCI)

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