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Phase Ⅱ trial of cDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of cDK4/cDKN2A

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5518-5527页

作者： Javier Martin-Broto Jeronimo Martinez-Garcia David SMoura andres Redondo Antonio Gutierrez Antonio Lopez-Pousa Javier Martinez-Trufero Isabel Sevilla Roberto Diaz-Beveridge Maria Pilar Solis-Hernandez Amancio carnero Marco Perez David Marcilla Jesus Garcia-Foncillas Pablo Romero Javier Fernandez-Jara Daniel Lopez-Lopez Ivan Arribas Nadia Hindi Health Research Institute-Fundación Jiménez Díaz University Hospital Universidad Autónoma de Madrid(IIS-FJDUAM)28040MadridSpain Medical Oncology Department Fundación Jimenez Diaz University Hospital28040MadridSpain General de Villalba University Hospital 28400MadridSpain Medical Oncology Department University Hospital Virgen de la Arrixaca30120MurciaSpain Department of Medical Oncology Hospital Universitario La Paz-IdiPAZP.Castellana26128046MadridSpain Hematology Department University Hospital Son Espases07120MallorcaSpain Medical Oncology Department Sant Pau Hospital08025BarcelonaSpain Medical Oncology Department University Hospital Miguel Servet50009ZaragozaSpain Investigación clínica y Traslacional en cáncer/Instituto de Investigaciones Biomédicas de Malaga(IBIMA)/Hospitales Universitarios Regional y Virgen de la Victoria de Malaga MalagaSpain Medical Oncology Department Hospital Universitari i Politècnic La Fe46026ValenciaSpain Medical Oncology Department Central University Hospital of Asturias33011OviedoSpain Instituto de Biomedicina de Sevilla(IBiS HUVRCSICUS)41013SevillaSpain Pathology Department Virgen del Rocio University Hospital41013SevillaSpain Radiology Department Fundación Jimenez Diaz University Hospital28040MadridSpain computational Medicine Platform Fundación progreso y salud(FPS)Hospital Virgen del Rocío41013SevilleSpain Bioinformatics in Rare Diseases(BiER).centro de Investigación Biomédica en Red de Enfermedades Raras(cIBERER) FPSHospital Virgen del RocioSevillaSpain Universitat de València-ERI-cES 46010ValenciaSpain

cyclin-dependent kinases 4 and 6(cDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with cDK4 ***4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for cDK *** investigators of this study found that cDK4 overexpression,while not of cDKN2A,was the most consistent predictive factor for palbociclib efficacy in *** adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed cDK4,but not cDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudracT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this *** was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 cDK4/cDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at *** 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%cI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 *** median PFS and overall survival were 4.2(95%cI 3.6–4.8)and 12(95%cI 8.7–15.4)months,*** research showed a significant correlation between cDK4 mRNA and protein *** was active in a variety of sarcoma subtypes,selected by cDK4/cDKN2A,and deserves further investigation in the sarcoma context.

关键词： cDKN2A sarcoma cDK4

2D organic molecular metallic soft material derived from BEDO-TTF with electrochromic and rectifying properties

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npj Flexible Electronics 2018年第1期2卷 237-243页

作者： Daniel Suarez Eden Steven Elena Laukhina andres Gomez Anna crespi Narcis Mestres concepcio Rovira Eun Sang choi Jaume Veciana Department of Physics National High Magnetic Field Laboratory Florida State University1800 East Paul Dirac DriveTallahasseeFL 32310USA Emmerich Education center Jakarta 14450Indonesia cIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)MadridSpain Institut de ciencia de Materials de Barcelona(IcMAB-cSIc) Campus UABBellaterra 08193Spain

In this article we demonstrate that a migration of iodine species and chemical transformation in a moist environment induced by a voltage-biased Pt electrode is able to alter the color and degree of charge transfer in a layer of the 2D organic molecular metal(BEDO-TTF)_(2.4)I_(3)[BEDO=bis(ethylenedioxy)tetrathiafulvalene]self-assembled at the surface of a polycarbonate *** effects produce a reversible electrochromic behavior of the layer with low operating voltages and fast operation *** with electrochromism,this flexible material exhibits rectifying behavior whose I-V curves are dependent on the voltage sweep *** results open new possibilities for the design and fabrication of organic flexible materials for soft electrochromic and rectifying *** easy working principle ensures reliability,low power consumption,and versatility through its implementation into simple *** working principle has been confirmed by temperature dependent resistance measurements,X-Ray,EDX-SEM,and conducting-AFM studies.

关键词： resistance metallic behavior

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TIPS术后再入院率:最新描述

Gastroenterology Report 2020年第2期8卷 83-84,I0001页

作者： Octavi Basssegoda andres cardenas GI/Liver Unit Institut de Malalties Digestives i MetaboliquesHospital ClinicUniversity of BarcelonaBarcelonaSpain Institut Dinvestigacions Biomediques August Pi I Sunyer(IDIBAPS) Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas(CIBEReHD)BarcelonaSpain

Portal hypertension in patients with cirrhosis is common and can lead to severe complications that are associated with decreased *** these complications,portal hypertensive bleeding and refractory ascites in many cases can be managed with the placement of a transjugular intrahepatic portosystemic shunt(TIPS).current indications of TIPS placement include variceal hemorrhage refractory or recurrent to standard therapy with vasoactive drugs and endoscopic variceal ligation[1].Also,in carefully selected patients(***-Pugh class c cirrhosis with score 10-13 and child Turcotte Pugh(cTP)class B with active bleeding on endoscopy),early TIPS(placed within 72 hours of admission)after vasoactive drugs and endoscopic band ligation improves *** intervention reduces the risk of rebleeding among this group of high-risk patients and is associated with increased survival[2].TIPS is also a treatment of choice in patients bleeding from cardiofundal varices(GOV2 and IGV1)and ectopic varices[1].Refractory ascites is also an indication for TIPS ***,its efficacy is controversial in this *** is clear that TIPS is associated with a better control of ascites than large-volume *** said,TIPS is followed by a greater incidence of hepatic *** results regarding the survival benefits of TIPS have emerged and are still a matter of intense debate[3].In summary,a careful selection of candidates for TIPS placement is necessary if refractory ascites is the indication for ***,TIPS can be detrimental in older patients with cardiopulmonary disease as well as in patients in cTP class c and higher Model for End Stage Liver Disease(MELD)*** has to be noted that most of the randomized trials evaluating survival of TIPS have been performed using bare stents[4].

关键词： refractory indication admission

Investigation of Galactic open cluster remnants： the case of NGc 7193

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Research in Astronomy and Astrophysics 2017年第1期17卷 31-54页

作者： Mateus de Souza Angelo Joao Francisco coelho dos Santos Jr Wagner Jose Barbosa corradi Francisco Ferreira de Souza Maia andres Eduardo Piatti Departamento de Fisica ICEx Universidade Federal de Minas Gerais Av. Antonio Carlos 6627 31270-901 Belo Horizonte MG Brazil Observatorio Astronomico Universidad Nacional de Cordoba Laprida 854 5000 Cordoba Argentina consejo Nacional de Investigaciones cientificas y Tecnicas Av. Rivadavia 1917 C1033AAJ Buenos AiresArgentina

Galactic open clusters （Ocs） that survive the early gas-expulsion phase are gradually de- stroyed over time by the action of disruptive dynamical processes. Their final evolutionary stages are characterized by a poorly populated concentration of stars called an open cluster remnant （OcR）. This study is devoted to assessing the real physical nature of the OcR candidate NGc 7193. GMOS/Gemini spectroscopy of 53 stars in the inner target region were obtained to derive radial velocities and at- mospheric parameters. We also employed photometric and proper motion data. The analysis method consists of the following steps：（i） analysis of the statistical resemblance between the cluster and a set of field samples with respect to the sequences defined in color-magnitude diagrams （cMDs）; （ii） a 5-dimensional iterative exclusion routine was employed to identify outliers from kinematical and posi- tional data; （iii） isochrone fitting to thes× （J - Ks） cMD of the remaining stars and the dispersion of spectral types along empirical sequences in the （J - H） × （H - Ks） diagram were checked. A group of stars was identified for which the mean heliocentric distance is compatible with that obtained via isochrone fitting and whose metallicities are compatible with each other. Fifteen of the member stars observed spectroscopically were identified together with another 19 probable members. Our results indi- cate that NGc 7193 is a genuine OcR, of a once very populous Oc, for which the following parameters were derived： d = 501±46 pc, t = 2.5±1.2 Gyr, （[Fe/H]） = -0.17±0.23 and E（B-V） = 0.05±0.05. Its luminosity and mass functions show depletion of low mass stars, confirming the OcR is in a dynam- ically evolved state.

关键词： open cluster remnants - Galactic open clusters

Effects of omega-3 supplementation on components of the endocannabinoid system and metabolic and inflammatory responses in adipose and liver of peripartum dairy cows

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Journal of Animal Science and Biotechnology 2023年第1期14卷 378-389页

作者： Gitit Kra Jayasimha Rayalu Daddam Uzi Moallem Hadar Kamer Radka Kočvarova Alina Nemirovski Gandres contreras Joseph Tam Maya Zachut Department of Ruminant Science Institute of Animal SciencesARO Volcani InstituteRishon LeZionIsrael. Department of Animal Science The Robert H.Smith Faculty of AgricultureFood and EnvironmentThe Hebrew University of JerusalemRehovotIsrael. Obesity and Metabolism Laboratory The Institute for Drug ResearchSchool of PharmacyFaculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael. Department of Large Animal clinical Sciences College of Veterinary MedicineMichigan State UniversityEast LansingMichiganUSA.

Background:Dietary supplementation of omega-3 fatty acids can reduce the activation of the endocannabinoid system(EcS)by decreasing the availability of arachidonic acid,thus lowering endocannabinoids(e cBs)*** EcS is a modulator of energy metabolism,stress response and inflammation in mammals,yet there is little information on the roles of the EcS in transition dairy *** the periparturient period,the adipose tissue and liver are the main metabolic organs that participate in the adaptations of dairy cows to onset of lactation;however,exceeded adipose tissue lipolysis and accumulation of lipids in the liver have adverse effects on cows'*** we aimed to examine whether omega-3 supplementation during the transition period will modulate EcS activation and affect metabolic and inflammatory indices in postpartum dairy cows,by supplementing twenty-eight transition Holstein dairy cows with either saturated fat(cTL)or encapsulated flaxseed oil(FLX).components of the EcS,metabolic and inflammatory markers were measured in blood,liver,and subcutaneous adipose ***:FLX supplementation reduced feed intake by 8.1%(Pced plasma levels of arachidonic acid(by 44.2%;P=0.02)and anandamide(by 49.7%;P=0.03)postpartum compared to *** m RNA transcription levels of the cannabinoid receptor 1(cNR1/cB1)tended to be lower(2.5 folds)in white blood cells of FLX than in cTL(P=0.10),and protein abundance of EcS enzyme monoacylglycerol lipase was higher in peripheral blood mononuclear cells of FLX than in cTL(P=0.04).In adipose tissue,palmitoylethanolamide levels were lower in FLX than in cTL(by 61.5%;P=0.02),relative m RNA transcription of lipogenic genes were higher,and the protein abundance of cannabinoid receptor 2(P=0.08)and monoacylglycerol lipase(P=0.10)tended to be higher in FLX compared to *** 2-arachidonoylglycerol tended to be higher(by 73.1%;P=0.07),and interlukin-6 m RNA transcription level was 1.5 folds lower in liver of FLX

关键词： Adipose Dairy cows Endocannabinoid system Liver Omega-3

二氧化硅纳米颗粒的孔隙率和形貌对（N-异丙基丙烯酰胺）接枝聚合的影响

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二氧化硅纳米颗粒的孔隙率和形貌对（N-异丙基丙烯酰胺）接枝聚合...

作者： Jhair andres Pena Prada（安德鲁）天津大学

学位级别：硕士

通过将纳米颗粒的孔隙率和形貌作为微反应器系统,可以合成高度交联的聚合物,通过一锅反应在二氧化硅纳米颗粒上接枝聚(N-异丙基丙烯酰胺)(PNIPAM)来合成杂化纳米材料。以降低其他众所周知的嫁接程序的复杂性和成本。二氧化硅纳米粒子的... 详细信息

通过将纳米颗粒的孔隙率和形貌作为微反应器系统,可以合成高度交联的聚合物,通过一锅反应在二氧化硅纳米颗粒上接枝聚(N-异丙基丙烯酰胺)(PNIPAM)来合成杂化纳米材料。以降低其他众所周知的嫁接程序的复杂性和成本。二氧化硅纳米粒子的性能可通过模板剂和孔膨胀剂进行调节,从而获得球形和棒状形态,尺寸小于100 nm,孔径最大为3.5 nm。使用不同的引发剂体系和N,N’-亚甲基双丙烯酰胺作为交联剂,在80°c下进行聚合反应4小时。发现引发剂的溶解度及其添加方式显著影响最终材料的聚集和接枝纳米颗粒的尺寸分布。使用扫描电子显微镜(SEM),透射电子显微镜(TEM),物理吸附分析,热重分析(TGA),FTIR光谱,HNMR光谱,差示扫描量热法(DSc)和动态光散射(DLS)对材料进行表征。考察如何通过改变二氧化硅核纳米粒子的性质来修饰聚合物壳,表明该方法可用于药物递送系统的智能材料的简单程序,以及构建更复杂结构的基础材料。

关键词：一锅反应刺激响应性纳米材料接枝机理

Fast and reliable identification of atomically thin layers of TaSe2 crystals

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Nano Research 2013年第3期6卷 191-199页

作者： andres castellanos-Gomez Efren Navarro-Moratalla Guillermo Mokry Jorge Quereda Elena Pinilla-cienfuegos Nicolas Agrait Herre S. J. van der Zant Eugenio coronado Gary A. Steele Gabino Rubio-Bollinger Kavli Institute of Nanoscience Delft University of Technology Lorentzweg 1 2628 CJ Delft The Netherlands Instituto ciencia Molecular (IcMol) Univ. Valencia C/Catedrdtico Jose Beltrdn 2 E-46980 Paterna Spain Departamento de Fisica de la Materia condensada (c-III). UniversidadAutonoma de Madrid Campus de Cantoblanco 28049 Madrid Spain Instituto Madrileno de Estudios Avanzados en Nanociencia IMDEA-Nanociencia E-28049 Madrid Spain

Deposition of clean and defect-free atomically thin two-dimensional crystalline flakes on surfaces by mechanical exfoliation of layered bulk materials has proven to be a powerful technique, but it requires a fast, reliable and non-destructive way to identify the atomically thin flakes among a crowd of thick flakes. In this work, we provide general guidelines to identify ultrathin flakes of TaSe2 by means of optical microscopy and Raman spectroscopy. Additionally, we determine the optimal substrates to facilitate the optical identification of atomically thin TaSe2 crystals. Experimental realization and isolation of ultrathin layers of TaSe2 enables future studies on the role of the dimensionality in interesting phenomena such as superconductivity and charge density waves.

关键词：光谱识别超薄层原子晶体光学显微镜电荷密度波超薄片散装物料

In <i>Silico</i>Analysis of cross Reactivity between Lipocalin of Domestic Animals

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Open Journal of Immunology 2018年第4期8卷 97-106页

作者： Múnera Marlon Sanchez andres Sanchez Jorge Emiliani Yuliana Medical Research Group (GINUMED) Universitary Corporation Rafael Nu&ntilde ez Cartagena Colombia Group of clinical and Experimental Allergy (GAcE) IPS Universitaria University of Antioquia Medellín Colombia

Lipocalins are one of the groups of allergens derived from domestic animals with clinical importance for the development of allergic responses. They have been characterized in different animals. With allergenic capacity characterized, little is known about the epitopes involved in allergic responses. Here, potential antigenic regions involved in cross-reactivity among lipocalins were explored through bioinformatics tools. The amino acid sequences of several lipocalins from different domestic animals (mouse, dog, cat, bull, hamster, horse and pig) were used to determine the degree of kinship by phylogenetic studies. Groups with highest phylogenetic relation were obtained by using MEGA software. 3D models of lipocalins not reported in the protein data bank were modeled by homology to identify potential antigenic regions compromised in the cross-reactivity of this group of allergens. The alignment of the entire database of allergenic lipocalins and the inferred maximum likelihood tree segregate lipocalins into five monophyletic clades (referenced here as A, B, c, D and E). According to the multiple pairing analyzes, group c (Fel d 4, Rat n 1 and Equ c 1) showed the highest degree of identity among their amino acid sequences (58%). The analysis of conserved and exposed residues showed that group c shares three antigenic regions that could potentially contribute to its cross-reactivity. Potential antigenic sites were identified for the generation of cross-reactivity between the different lipocalins analyzed in this study. These studies support the need to carry out directed mutagenesis tests to confirm their relevance in the allergenic capacity of lipocalins.

关键词： Bioinformatics Immunology Prediction Epitope Allergen Antigen

Lactic Acidosis and Atrial Tachycardia: Unusual Presentations of Disseminated Burkitt-Like Lymphoma

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Journal of cancer Therapy 2012年第5期3卷 589-594页

作者： Hazem El-Osta Abdulrahman Abdulbaki Prakash Peddi Amol Takalkar James cotelingam Diana Veillon andres Vargas Nuri Akkus Gerhard c. Hildebrandt Department of Medicine Division of Cardiology Louisiana State University Health Sciences Center Shreveport USA Department of Medicine Division of Hematology oncology Louisiana State University Health Sciences Center Shreveport USA Department of Medicine Division of internal medicine Louisiana State University Health Sciences Center Shreveport USA Department of Nuclear Medicine Louisiana State University Health Sciences Center Shreveport USA Department of Pathology Louisiana State University Health Sciences Center Shreveport USA

Lactic acidosis is a rare complication of malignancies and is seen more frequently in high grade lymphoma and leukemia. Although, its pathogenesis is not well understood, it remains a surrogate of poor prognosis. Herein, we present a case of Burkitt-like lymphoma presenting with metabolic abnormalities including lactic acidosis and hypoglycemia along with atrial tachycardia. We will discuss the different mechanisms involved in these metabolic disturbances and we will provide insight on novel therapeutic strategies based on our understanding of the underlying pathophysiology.

关键词： Atrial Tachycardia Burkitt-Like Lymphoma B-cell Lymphoma Intra-cardiac Tumor Hypoglycemia Lactic Acidosis