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991.
Elisa Rumi Emanuela Sant'Antonio Chiara Cavalloni Giuditta Comolli Virginia Valeria Ferretti Irene Cassaniti Daniela Pietra Chiara Trotti Michele Ciboddo Milena Furione Daniele Vanni Ilaria Carola Casetti Cristina Favaron Fausto Baldanti Luca Arcaini Mario Cazzola 《Hematological oncology》2020,38(4):554-559
Ruxolitinib is effective in myeloproliferative neoplasms (MPN) but can cause reactivation of silent infections. We aimed at evaluating viral load and T-cell responses to human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in a cohort of 25 MPN patients treated with ruxolitinib. EBV-DNA and HCMV-DNA were quantified monthly using real-time polimerase chain reaction (PCR) on peripheral blood samples, and T-cell subsets were analyzed by flowcytometry. HCMV and EBV-directed T-cell responses were evaluated using the IFN-γ ELISPOT assay. Most patients had CD4+ and/or CD8+ T-cells below the normal range; these reductions were related to the duration of ruxolitinib treatment. In fact, reduced T-lymphocytes' subsets were found in 93% of patients treated for ≥5 years and in 45% of those treated for <5 years (P = .021). The former also had lower median numbers of CD4+ and CD8+ cells. Subclinical reactivation of EBV and HCMV occurred in 76% and 8% of patients. We observed a trend to an inverse relationship between EBV and CMV-specific CD4+ and CD8+ T-cell responses and viral load, and a trend to an inverse correlation with ruxolitinib dose. Therefore, our data suggest that the ruxolitinib treatment may interfere with immunosurveillance against EBV and HCMV. 相似文献
992.
Elena Andreucci Anna Laurenzana Silvia Peppicelli Alessio Biagioni Francesca Margheri Jessica Ruzzolini Francesca Bianchini Gabriella Fibbi Mario Del Rosso Chiara Nediani Simona Serratì Livia Fucci Michele Guida Lido Calorini 《Oncology research》2020,28(9):873-884
Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor
survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of
melanoma rapidly develop resistance to the BRAFV600E inhibitor vemurafenib, with fast tumor dissemination,
a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to
organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenibresistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research
aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma
cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent
experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of
melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant
phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting
and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are
characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and
using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of
VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged
as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid
progression and dissemination of the disease. 相似文献
993.
Hussein Abbouchie Michael Chao Mark Tacey Daryl Lim Joon Huong Ho Mario Guerrieri Michael Ng Farshad Foroudi 《Journal of Medical Imaging and Radiation Oncology》2020,64(2):293-302
Stereotactic body radiotherapy has emerged as one of the preferred treatments for patients with spine metastases, with the potential for long‐term control from lesion irradiation. Post‐treatment vertebral compression fractures are a known complication of this therapy, contributing to worsening pain and reduced quality of life, sometimes requiring surgical intervention. This review explores the current knowledge of post‐radiotherapy fractures, in terms of the rates and associated predictive factors. A search of databases including Medline, Embase and the Cochrane Library was conducted using keywords such as ‘vertebral compression fracture’, ‘stereotactic body radiotherapy’ and ‘spine metastases’. The search was limited to published studies up to March 2019, reporting clinical outcomes including both the post‐treatment fracture rate and statistical identification of associated risk factors. Rates of post‐treatment fractures ranged from 4 to 39%. A variety of factors were found to increase the risk, including the appearance of lytic vertebral disease, degree of pre‐existing compression, spinal malalignment, increased dose per fraction and a Spinal Instability Neoplastic Score >6. This knowledge can enable clinicians to counsel patients when considering management options for spine metastases, maintaining the balance between local tumour control and the risk of subsequent fracture. 相似文献
994.
995.
996.
Samira Chuffi Michele S. Gomes-Gouvêa Luciana V. B. Casadio Ana Catharina S. S. Nastri Mario P. Gonzalez Andr L. F. Cotia Amanda G. D. Aranda Simone B. Tenore Suzane K. Ono Fernanda M. Malta Geraldine Madalosso Paulo R. A. Ferreira Flair J. Carrilho Joo R. R. Pinho 《Viruses》2022,14(1)
Outbreaks of hepatitis A may occur in countries of medium and high socioeconomic levels in which the population generally exhibits an increased susceptibility in young adults to this infection if they are not vaccinated against the hepatitis A virus (HAV). In Europe, an outbreak involved approximately 22 European countries with 4475 cases reported from 2016 to 2018; most of them were men who have sex with men (MSM). This outbreak expanded to North and South America, including Brazil, particularly in São Paulo city with 1547 reported cases from 2016 to 2019. In the present study, we characterized the HAV strains involved in the acute hepatitis A cases identified in the reference centers of São Paulo city during this outbreak. A total of 51 cases with positive anti-HAV IgM were included, 80.4% male, 68.6% of them between 20 and 40 years old and 41.7% MSM. HAV RNA was detected in 92% (47/51) of the cases. Subgenotype IA of HAV was identified and most of the strains were closely related to that isolated in outbreaks that occurred in different European countries in 2016. These results showed the epidemiological relation between these outbreaks and reinforce the need to implement vaccination against hepatitis A for the adult population, particularly for a population with a high-risk behavior. 相似文献
997.
Melanin concentration maps by label-free super-resolution photo-thermal imaging on melanoma biopsies
Margaux Bouzin Mario Marini Giuseppe Chirico Francesca Granucci Francesca Mingozzi Roberto Colombo Laura DAlfonso Laura Sironi Maddalena Collini 《Biomedical optics express》2022,13(3):1173
Surgical excision followed by histopathological examination is the gold standard for melanoma screening. However, the color-based inspection of hematoxylin-and-eosin-stained biopsies does not provide a space-resolved quantification of the melanin content in melanocytic lesions. We propose a non-destructive photo-thermal imaging method capable of characterizing the microscopic distribution and absolute concentration of melanin pigments in excised melanoma biopsies. By exploiting the photo-thermal effect primed by melanin absorption of visible laser light we obtain label-free super-resolution far-infrared thermal images of tissue sections where melanin is spatially mapped at sub-diffraction 40-μm resolution. Based on the finite-element simulation of the full 3D heat transfer model, we are able to convert temperature maps into quantitative images of the melanin molar concentration on B16 murine melanoma biopsies, with 4·10-4 M concentration sensitivity. Being readily applicable to human melanoma biopsies in combination with hematoxylin-and-eosin staining, the proposed approach could complement traditional histopathology in the characterization of pigmented lesions ex-vivo. 相似文献
998.
Francois Rheault Kurt G. Schilling Alex ValcourtCaron Antoine Thberge Charles Poirier Gabrielle Grenier Guido I. Guberman John Begnoche Jon Haitz Legarreta Leon Y. Cai Maggie Roy Manon Edde Marco Perez Caceres Mario OcampoPineda Noor AlSharif Philippe Karan Pietro Bontempi Sami Obaid Sara Bosticardo Simona Schiavi Viljami Sairanen Alessandro Daducci Laurie E. Cutting Laurent Petit Maxime Descoteaux Bennett A. Landman 《Human brain mapping》2022,43(7):2134
The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White‐matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach. Moreover, the complex shape of WM pathways and their representation using tractography (streamlines) make the design and evaluation of dissection protocols difficult and time‐consuming. The first iteration of Tractostorm quantified the variability of a pyramidal tract dissection protocol and compared results between experts in neuroanatomy and nonexperts. Despite virtual dissection being used for decades, in‐depth investigations of how learning or practicing such protocols impact dissection results are nonexistent. To begin to fill the gap, we evaluate an online educational tractography course and investigate the impact learning and practicing a dissection protocol has on interrater (groupwise) reproducibility. To generate the required data to quantify reproducibility across raters and time, 20 independent raters performed dissections of three bundles of interest on five Human Connectome Project subjects, each with four timepoints. Our investigation shows that the dissection protocol in conjunction with an online course achieves a high level of reproducibility (between 0.85 and 0.90 for the voxel‐based Dice score) for the three bundles of interest and remains stable over time (repetition of the protocol). Suggesting that once raters are familiar with the software and tasks at hand, their interpretation and execution at the group level do not drastically vary. When compared to previous work that used a different method of communication for the protocol, our results show that incorporating a virtual educational session increased reproducibility. Insights from this work may be used to improve the future design of WM pathway dissection protocols and to further inform neuroanatomical definitions. 相似文献
999.
1000.
Alessandro Cama Fabio Verginelli Lavinia Vittoria Lotti Francesco Napolitano Annalisa Morgano Andria D’Orazio Michele Vacca Silvia Perconti Felice Pepe Federico Romani Francesca Vitullo Filippo di Lella Rosa Visone Massimo Mannelli Hartmut P. H. Neumann Giancarlo Raiconi Carlo Paties Antonio Moschetta Roberto Tagliaferri Angelo Veronese Mario Sanna Renato Mariani-Costantini 《Acta neuropathologica》2013,126(4):575-594
Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The “NOTCH signaling pathway” was the most significantly enriched term in the list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunohistochemistry in 47 head and neck paraganglioma cases. There were no relationships between level and pattern of NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes, implicated in paraganglioma predisposition, or the presence/absence of immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly, NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of this pathway. To address this issue we performed microarray-based microRNA expression analyses. Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most downregulated in the tumors, correlated to NOTCH signaling and directly targeted NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore, lentiviral transduction of miR-200s and miR-34s in patient-derived primary tympano-jugular paraganglioma cell cultures was associated with NOTCH1 downregulation and increased levels of markers of cell toxicity and cell death. Taken together, our results provide an integrated view of common molecular alterations associated with head and neck paraganglioma and reveal an essential role of NOTCH pathway deregulation in this tumor type. 相似文献