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B cell development is critically dependent on NFATc1 activity

Cellular & Molecular Immunology 2019年第5期16卷 508-520页

作者： sabrina giampaolo Gabriela Wojcik Stefan Klein-Hessling Edgar Serfling Amiya K.Patra Department of Molecular Pathology Institute of PathologyUniversity of WürzburgJosef Schneider-Str.297080 WürzburgGermany Institute of Translational and Stratified Medicine Faculty of Medicine and DentistryUniversity of PlymouthPlymouth PL68BUUK Comprehensive Cancer Center Mainfranken University of WürzburgJosef Schneider-Str.697080 WürzburgGermany

B cell development in bone marrow is a precisely regulated complex *** successive stages of differentiation,which are regulated by a multitude of signaling pathways and an array of lineage-specific transcription factors,the common lymphoid progenitors ultimately give rise to mature B *** to early thymocyte development in the thymus,early B cell development in bone marrow is critically dependent on IL-7 *** this IL-7-dependent stage of differentiation,several transcription factors,such as E2A,EBF1,and Pax5,among others,play indispensable roles in B lineage specification and *** recent studies have implicated several other transcription factors in B cell development,the role of NFATc1 in early B cell developmental stages is not ***,using multiple gene-manipulated mouse models and applying various experimental methods,we show that NFATc1 activity is vital for early B cell *** of NFATc1 activity in pro-B cells suppresses EBF1 expression,impairs immunoglobulin gene rearrangement,and thereby preBCR formation,resulting in defective B cell ***,deficiency in NFATc1 activity arrested the pro-B cell transition to the pre-B cell stage,leading to severe B cell *** findings suggest that,along with other transcription factors,NFATc1 is a critical component of the signaling mechanism that facilitates early B cell differentiation.

关键词： Differentiation EBF1 NFATc1 Pro-B Pre-B

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Metastatic pancreatic cancer: Is there a light at the end of the tunnel?

引用

World Journal of Gastroenterology 2015年第16期21卷 4788-4801页

作者： Vanja Vaccaro Isabella Sperduti sabrina Vari Emilio Bria Davide Melisi Carlo Garufi Carmen Nuzzo Aldo Scarpa giampaolo Tortora Francesco Cognetti Michele Reni Michele Milella Medical Oncology A Regina Elena National Cancer Institute Medical Oncology A and Biostatistics Regina Elena National Cancer Institute Medical Oncology University of VeronaAzienda Ospedaliera Universitaria Integrata ARC-Net Research Centre and Department of Pathology Diagnostics and SurgeryUniversity of Verona Medical Oncology Unit Department of OncologySan Raffaele Scientific Institute

Due to extremely poor prognosis,pancreatic cancer(PDAC)represents the fourth leading cause of cancerrelated death in Western *** more than a decade,gemcitabine(Gem)has been the mainstay of first-line PDAC *** efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing ***,the field of systemic therapy of advanced PDAC is finally moving *** has shown promise over single-agent Gem:regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control,although sometimes at the cost of poor *** PRODIGE 4/ACCORD 11 was the first phaseⅢtrial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX;however the less favorable safety profile and the characteristics of the enrolled population,restrict the use of FOLFIRINOX to young and fit PDAC *** nanoparticle albumin-bound paclitaxel(nab-Paclitaxel)formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer *** of whether or not this is its main mechanisms of action,the combination of nabPaclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary ***,recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC,particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease ***,we provide an overview of recent advances in the systemic treatment of advanced PDAC,mostly focusing on recent findings that have set new standards in metastatic *** avenues for further development in the metastatic setting and current efforts to integratenew effective chemotherapy regimens

关键词： Pancreatic cancer Metastatic disease Chemotherapy Folfirinox nab -Paclitaxel

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