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Vincenzo Nasillo Giovanni Riva Ambra Paolini Fabio Forghieri Luca Roncati Beatrice Lusenti Monica Maccaferri Andrea Messerotti Valeria Pioli Andrea Gilioli Francesca Bettelli Davide Giusti Patrizia Barozzi Ivana Lagreca Rossana Maffei Roberto Marasca Leonardo Potenza Patrizia Comoli Rossella Manfredini Antonino Maiorana Enrico Tagliafico Mario Luppi Tommaso Trenti 《International journal of molecular sciences》2021,22(4)
The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches. 相似文献
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Viola Alesi Maria Lisa Dentici Silvia Genovese Sara Loddo Emanuele Bellacchio Valeria Orlando Silvia Di Tommaso Giorgia Catino Chiara Calacci Giusy Calvieri Daniele Pompili Graziamaria Ubertini Bruno Dallapiccola Rossella Capolino Antonio Novelli 《International journal of molecular sciences》2021,22(2)
We report on a patient born to consanguineous parents, presenting with Growth Hormone Deficiency (GHD) and osteoporosis. SNP-array analysis and exome sequencing disclosed long contiguous stretches of homozygosity and two distinct homozygous variants in HESX1 (Q6H) and COL1A1 (E1361K) genes. The HESX1 variant was described as causative in a few subjects with an incompletely penetrant dominant form of combined pituitary hormone deficiency (CPHD). The COL1A1 variant is rare, and so far it has never been found in a homozygous form. Segregation analysis showed that both variants were inherited from heterozygous unaffected parents. Present results further elucidate the inheritance pattern of HESX1 variants and recommend assessing the clinical impact of variants located in C-terminal propeptide of COL1A1 gene for their potential association with rare recessive and early onset forms of osteoporosis. 相似文献
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Paolo Romania Alice Bertaina Giorgia Bracaglia Franco Locatelli Doriana Fruci Rossella Rota 《International journal of molecular sciences》2012,13(12):16554-16579
Gene expression control mediated by microRNAs and epigenetic remodeling of chromatin are interconnected processes often involved in feedback regulatory loops, which strictly guide proper tissue differentiation during embryonal development. Altered expression of microRNAs is one of the mechanisms leading to pathologic conditions, such as cancer. Several lines of evidence pointed to epigenetic alterations as responsible for aberrant microRNA expression in human cancers. Rhabdomyosarcoma and neuroblastoma are pediatric cancers derived from cells presenting features of skeletal muscle and neuronal precursors, respectively, blocked at different stages of differentiation. Consistently, tumor cells express tissue markers of origin but are unable to terminally differentiate. Several microRNAs playing a key role during tissue differentiation are often epigenetically downregulated in rhabdomyosarcoma and neuroblastoma and behave as tumor suppressors when re-expressed. Recently, inhibition of epigenetic modulators in adult tumors has provided encouraging results causing re-expression of anti-tumor master gene pathways. Thus, a similar approach could be used to correct the aberrant epigenetic regulation of microRNAs in rhabdomyosarcoma and neuroblastoma. The present review highlights the current insights on epigenetically deregulated microRNAs in rhabdomyosarcoma and neuroblastoma and their role in tumorigenesis and developmental pathways. The translational clinical implications and challenges regarding modulation of epigenetic chromatin remodeling/microRNAs interconnections are also discussed. 相似文献
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Silvia Pisani Ida Genta Rossella Dorati Paraskevi Kavatzikidou Despoina Angelaki Aleka Manousaki Kanelina Karali Anthi Ranella Emmanuel Stratakis Bice Conti 《应用聚合物科学杂志》2020,137(40):49223
This work reports a preliminary biological study performed on nanofibrous biocompatible polylactidecopolycaprolactone (PLA-PCL) scaffolds intended for tissue regeneration. The aim was to evaluate how matrix surface topography affects cell adhesion and proliferation. Scaffolds prepared by electrospinning either equipped with plane or rotating mandrel collectors, were characterized for their surface topography and nanofiber size. Cell culture studies were carried out using mouse embryonic fibroblast cells lines (NIH-3T3), as model for skin, murine neuroblastoma neuro-2α cell line, as model for neuronal tissue, and mouse mesenchymal stem cells (MSCs), because of their differentiation ability. Imaging analysis by scanning electron microscope and laser scanning confocal microscopy together with cell viability (MTT, L 3-(4,5-dymethiltiazol-2-y)-2,5 diphenyltetrazolium bromide) test, were performed on cell cultures at fixed time laps. The results showed that electrospun nanofibers supported growth and proliferation of the tested cell lines, but electrospun matrices obtained with rotating mandrel showed significantly higher cell viability that follows the orientation of electrospun nanofibers. 相似文献
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Giosuè Scognamiglio Anna De Chiara Maurizio Di Bonito Fabiana Tatangelo Nunzia Simona Losito Annamaria Anniciello Rossella De Cecio Crescenzo D’Alterio Stefania Scala Monica Cantile Gerardo Botti 《International journal of molecular sciences》2016,17(5)
In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. 相似文献
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