174 results on '"Leone, Biagio Eugenio"'
Search Results
152. Isolation of a Pancreas-Specific Gene Located on Human Chromosome 14q31: Expression Analysis in Human Pancreatic Ductal Carcinomas
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Biunno, Ida, primary, Appierto, Valentina, additional, Cattaneo, Monica, additional, Leone, Biagio Eugenio, additional, Balzano, Gianpaolo, additional, Socci, Carlo, additional, Saccone, Salvatore, additional, Letizia, Andreozzi, additional, Valle, Giuliano Della, additional, and Sgaramella, Vittorio, additional
- Published
- 1997
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153. Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs.
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Sierri, Giulia, Dal Magro, Roberta, Vergani, Barbara, Leone, Biagio Eugenio, Formicola, Beatrice, Taiarol, Lorenzo, Fagioli, Stefano, Kravicz, Marcelo, Tremolizzo, Lucio, Calabresi, Laura, and Re, Francesca
- Subjects
ATP-binding cassette transporters ,ASTROCYTES ,CHOLESTEROL metabolism ,BLOOD-brain barrier ,LIPOPROTEINS ,CHOLESTEROL ,BLOOD cholesterol - Abstract
The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins' synthesis and lipoproteins' assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ
1-42 -induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins' levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs. [ABSTRACT FROM AUTHOR]- Published
- 2022
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154. Nondifferentiated-Type Small Cell Sarcoma of Kidney in a Young Woman
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Taccagni, Gianluca, primary, Terreni, Maria Rosa, additional, Caputo, Valentina, additional, Leone, Biagio Eugenio, additional, and Cantaboni, Angelo, additional
- Published
- 1991
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155. Rapamycin impairs antigen uptake of human dendritic cells1.
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Monti, Paolo, Mercalli, Alessia, Leone, Biagio Eugenio, Valerio, Di Carlo, Allavena, Paola, and Piemonti, Lorenzo
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- 2003
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156. Multicentric CD34 negative epithelioid angiosarcoma of the digestive system.
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Pagni, Fabio, Leone, Biagio Eugenio, Ronchi, Susanna, Sartori, Paola, Corti, Luigi, and Maggioni, Dario
- Published
- 2012
157. b-Catenin as a Morphoimmunohistochemical Marker for the Diagnosis of Papillary Thyroid Carcinoma.
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PAGNI, FABIO, MANZONI, MARCO, BUSCONE, SERENA, and LEONE, BIAGIO EUGENIO
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THYROID gland tumors , *IMMUNOHISTOCHEMISTRY , *LONGITUDINAL method , *TRANSCRIPTION factors , *TUMOR markers , *TISSUE arrays , *DIAGNOSIS - Abstract
A letter to the editor is presented which discusses a study regarding the use of the cytoplasmic protein β-catenin as immunohistochemical (IHC) staining morphologic marker in the diagnosis of papillary thyroid carcinoma (PTC).
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- 2015
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158. The TGF-β pathway is activated by 5-fluorouracil treatment in drug resistant colorectal carcinoma cells
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Biagio Eugenio Leone, Marialuisa Lavitrano, Cristina Garanzini, Maria Rita Giuffrè, Cristina Bugarin, Gabriele Romano, Mariateresa Pettinato, Ludovica Santi, Giuseppe Gaipa, Michele Papa, Roberto Giovannoni, Maria Rosaria Bianco, Silvia Leoni, Emanuela Grassilli, Maria Grazia Cerrito, Leonilde Savarese, Romano, G, Santi, L, Bianco, M, Giuffrè, M, Pettinato, M, Bugarin, C, Garanzini, C, Savarese, L, Leoni, S, Cerrito, M, Leone, B, Gaipa, G, Grassilli, E, Papa, M, Lavitrano, M, Giovannoni, R, Romano, Gabriele, Santi, Ludovica, Bianco, Maria Rosaria, Giuffrã, Maria Rita, Pettinato, Mariateresa, Bugarin, Cristina, Garanzini, Cristina, Savarese, Leonilde, Leoni, Silvia, Cerrito, Maria Grazia, Leone, Biagio Eugenio, Gaipa, Giuseppe, Grassilli, Emanuela, Papa, Michele, Lavitrano, Marialuisa, and Giovannoni, Roberto
- Subjects
0301 basic medicine ,TGF-β ,Pathology ,medicine.medical_specialty ,Xenograft Model Antitumor Assay ,Colorectal cancer ,Angiogenesis ,Antineoplastic Agents ,colorectal cancer ,Drug resistance ,Colorectal Neoplasm ,SMAD3 ,Metastasis ,Antineoplastic Agent ,03 medical and health sciences ,Mice ,In vivo ,Transforming Growth Factor beta ,medicine ,Animals ,Humans ,5-fluorouracil ,Cell Proliferation ,biology ,chemoresistance ,Cell growth ,business.industry ,Animal ,MED/04 - PATOLOGIA GENERALE ,ACVRL1 ,Transforming growth factor beta ,medicine.disease ,HCT116 Cells ,Xenograft Model Antitumor Assays ,TGF-β ,030104 developmental biology ,TGF-β, chemoresistance, 5-fluorouracil, colorectal cancer, SMAD3 ,Oncology ,Drug Resistance, Neoplasm ,HCT116 Cell ,biology.protein ,Cancer research ,Fluorouracil ,business ,Colorectal Neoplasms ,Human ,Research Paper - Abstract
TGF-β pathway is generally associated with the processes of metastasis, angiogenesis and EMT in cancer. Very little is known, however, about the role of TGF-β in cancer drug resistance. In this work, we show a specific activation of the TGF-β pathway in consequence of chemotherapeutic treatment in in vivo and in vitro models of colorectal carcinoma. 5-Fluorouracil (5FU) was able to stimulate the activation of SMAD3 and the transcription of specific genes such as ACVRL1, FN1 and TGFB1. On the other hand, the specific inhibition of TGF-βRI was able to repress the 5FU-induced genes transcription and to restore the sensitivity of chemoresistant cells to the toxic action of the drug, by decreasing the expression of BCL2L1 and ID1 genes. The role of the TGF-β molecule in the chemoresistant colon carcinoma cells' response to 5FU was further demonstrated by conditioned medium (CM) experiments: CM from 5FUtreated chemoresistant cells was able to protect chemosensitive cells against the toxic action of 5FU. In conclusion, these findings showed the pivotal role of TGF-β pathway in colon cancer mechanisms of drug resistance suggesting new possible approaches in diagnosis and treatment of colon cancer patients.
- Published
- 2016
159. Comparison of tumor microenvironment in primary and paired metastatic ER+/HER2- breast cancers: results of a pilot study.
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Zeppellini A, Galimberti S, Leone BE, Pacifico C, Riva F, Cicchiello F, Capici S, Maggioni C, Sala L, and Cazzaniga ME
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- Aged, Aged, 80 and over, Biopsy, Breast immunology, Breast surgery, Breast Neoplasms pathology, Breast Neoplasms therapy, Case-Control Studies, Chemotherapy, Adjuvant, Disease Progression, Female, Follow-Up Studies, Humans, Mastectomy, Middle Aged, Neoplasm Recurrence, Local pathology, Pilot Projects, Prognosis, Receptor, ErbB-2 analysis, Receptor, ErbB-2 metabolism, Receptors, Estrogen analysis, Receptors, Estrogen metabolism, Retrospective Studies, Breast pathology, Breast Neoplasms immunology, Lymphocytes, Tumor-Infiltrating immunology, Neoplasm Recurrence, Local immunology, Tumor Microenvironment immunology
- Abstract
Background: Tumor microenvironment (TME) is a dynamic setting and changes in TILs and their subpopulations are potential candidates to influence the metastatic process. Aim of this pilot study is to describe the changes occurring between primary breast cancers and their paired metastases in terms of TILs composition. To assess if these changes influence the process of metastasis development, we used a control group of patients., Methods: We retrospectively identified 18 Luminal patients, for whom primary and metastatic tissue were available (cases) and 18 paired-matched patients (controls), not relapsed after at least 9 years of follow-up, and we quantified TILs and their composition (i.e. T CD8+ and CD4+/FOXP3+). The presence of TILs was defined as ≥10%., Results: Our results showed that the microenvironment composition of relapsed patients was poor of TILs (median = 5%, I-III quartiles = 0.6-5%), CD8+ (2.5%, 0-5%) and CD4+/FOXP3 + (0%, 0-0.6%) in the primary tumor. Comparable results were observed in their related metastases (TILs 3.8%, 0.6-5%; CD8+ 0%, 0-1.3%; CD4+/FOXP3+ 0%,0-1.9%). On the contrary, the microenvironment in the control group was richer of TILs (5%, 5-17.5%) in comparison to cases, both in primary tumor (p = 0.035) and related metastases (p = 0.018). Although CD8+ in controls were similar to cases at primary tumor (p = 0.6498), but not at metastasis (p = 0.0223), they expressed only one part on the TILs subpopulations (p = 0.0060), while TILs in the cases at primary tumor were almost completely CD8+ (p = 0.5034)., Conclusions: These findings suggest that the lack of activation of immune system in the primary tumor might influence the multifactor process of cancer progression.
- Published
- 2021
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160. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators.
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Vergani E, Dugo M, Cossa M, Frigerio S, Di Guardo L, Gallino G, Mattavelli I, Vergani B, Lalli L, Tamborini E, Valeri B, Gargiuli C, Shahaj E, Ferrarini M, Ferrero E, Gomez Lira M, Huber V, Del Vecchio M, Sensi M, Leone BE, Santinami M, Rivoltini L, Rodolfo M, and Vallacchi V
- Subjects
- Cell Line, Tumor, Cyclooxygenase 2 genetics, Extracellular Signal-Regulated MAP Kinases metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Melanoma pathology, MicroRNAs genetics, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases metabolism, Models, Biological, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Proto-Oncogene Proteins B-raf metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction drug effects, Cyclooxygenase 2 metabolism, Drug Resistance, Neoplasm drug effects, Drug Resistance, Neoplasm genetics, Inflammation Mediators metabolism, Melanoma drug therapy, Melanoma genetics, MicroRNAs metabolism, NF-kappa B metabolism, Protein Kinase Inhibitors therapeutic use
- Abstract
Background: Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance., Methods: The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy., Results: miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor., Conclusions: Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. Video Abstract.
- Published
- 2020
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161. Two ultrastaging protocols for the detection of lymph node metastases in early-stage cervical and endometrial cancers.
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Grassi T, Dell'Orto F, Jaconi M, Lamanna M, De Ponti E, Paderno M, Landoni F, Leone BE, Fruscio R, and Buda A
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- Aged, Female, Humans, Middle Aged, Retrospective Studies, Endometrial Neoplasms diagnostic imaging, Lymphatic Metastasis diagnostic imaging, Uterine Cervical Neoplasms diagnostic imaging
- Abstract
Objective: To date, there is no universal consensus on which is the optimal ultrastaging protocol for sentinel lymph node (SLN) evaluation in gynecologic malignancies. To estimate the impact of different ultrastaging methods of SLNs on the detection of patients with nodal metastases in early-stage cervical and endometrial cancers and to describe the incidence of low-volume metastases between two ultrastaging protocols., Methods: We retrospectively compared two ultrastaging protocols (ultrastaging-A vs ultrastaging-B) in patients with clinical stage I endometrial cancer or FIGO stage IA-IB1 cervical cancer who underwent primary surgery including SLN biopsy from October 2010 to December 2017 in our institution. The histologic subtypes and grades of the tumors were evaluated according to WHO criteria. Only SLNs underwent ultrastaging, while other lymph nodes were sectioned and examined by routine hematoxylin and eosin (H&E)., Results: Overall 224 patients were reviewed (159 endometrial cancer and 65 cervical cancer). Lymph node involvement was noted in 15% of patients with endometrial cancer (24/159): 24% of patients (9/38) with the ultrastaging protocol A and 12% (15/121) with the ultrastaging protocol B (p=0.08); while for cervical cancer, SLN metastasis was detected in 14% of patients (9/65): 22% (4/18) in ultrastaging-A and 11% (5/47) in ultrastaging-B (p=0.20). Overall, macrometastasis and low-volume metastases were 50% and 50% for endometrial cancer and 78% and 22% for cervical cancer. Median size of nodal metastasis was 2 (range 0.9-8.5) mm for the ultrastaging-A and 1.2 (range 0.4-2.6) mm for the ultrastaging-B protocol in endometrial cancer (p=0.25); 4 (range 2.5-9.8) mm for ultrastaging-A and 4.4 (range 0.3-7.8) mm for ultrastaging-B protocol in cervical cancer (p=0.64)., Conclusion: In endometrial or cervical cancer patients, the incidence of SLN metastasis was not different between the two different types of ultrastaging protocol., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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162. Detection of TP53 Clonal Variants in Papanicolaou Test Samples Collected up to 6 Years Prior to High-Grade Serous Epithelial Ovarian Cancer Diagnosis.
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Paracchini L, Pesenti C, Delle Marchette M, Beltrame L, Bianchi T, Grassi T, Buda A, Landoni F, Ceppi L, Bosetti C, Paderno M, Adorni M, Vicini D, Perego P, Leone BE, D'Incalci M, Marchini S, and Fruscio R
- Subjects
- Female, Humans, Mass Screening methods, Mass Screening statistics & numerical data, Middle Aged, Sensitivity and Specificity, Time Factors, Carcinoma, Ovarian Epithelial metabolism, Carcinoma, Ovarian Epithelial pathology, Clone Cells pathology, Cystadenocarcinoma, Serous metabolism, Cystadenocarcinoma, Serous pathology, Early Detection of Cancer methods, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Papanicolaou Test methods, Papanicolaou Test statistics & numerical data, Tumor Suppressor Protein p53 analysis
- Abstract
Importance: The low 5-year survival rate of women with high-grade serous epithelial ovarian cancer (HGS-EOC) is related to its late diagnosis; thus, improvement in diagnosis constitutes a crucial step to increase the curability of this disease., Objective: To determine whether the presence of the clonal pathogenic TP53 variant detected in matched primary tumor biopsies can be identified in DNA purified from Papanicolaou test samples collected from women with HGS-EOC years before the diagnosis., Design, Setting, and Participants: This cohort study was conducted among a single-center cohort of women with histologically confirmed diagnosis of HGS-EOC recruited at San Gerardo Hospital, Monza, Italy, from October 15, 2015, to January 4, 2019. Serial dilutions of DNA derived from tumor samples and DNA extracted from healthy women's Papanicolaou test samples were analyzed to define the sensitivity and specificity of droplet digital polymerase chain reaction assays designed to detect the TP53 variants identified in tumors. All available brush-based Papanicolaou test slides performed up to 6 years before diagnosis were investigated at the Mario Negri Institute, Milano, Italy. Data were analyzed from October 2018 to December 2019., Main Outcomes and Measures: The presence of tumor pathogenic TP53 variants was assessed by the droplet digital polymerase chain reaction approach in DNA purified from Papanicolaou test samples obtained from the same patients before diagnosis during cervical cancer screenings., Results: Among 17 included patients (median [interquartile range] age at diagnosis, 60 [53-69] years), Papanicolaou tests withdrawn before diagnosis presented tumor-matched TP53 variants in 11 patients (64%). In 2 patients for whom longitudinal Papanicolaou tests were available, including 1 patient with Papanicolaou tests from 25 and 49 months before diagnosis and 1 patient with Papanicolaou tests from 27 and 68 months before diagnosis, the TP53 clonal variant was detected at all time points., Conclusions and Relevance: These findings suggest that noninvasive early molecular diagnosis of HGS-EOC is potentially achievable through detection of TP53 clonal variants in the DNA purified from Papanicolaou tests performed during cervical cancer screening.
- Published
- 2020
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163. ki67 nuclei detection and ki67-index estimation: a novel automatic approach based on human vision modeling.
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Barricelli BR, Casiraghi E, Gliozzo J, Huber V, Leone BE, Rizzi A, and Vergani B
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- Algorithms, Animals, Bayes Theorem, Cell Nucleus chemistry, Humans, Mice, Software, Image Processing, Computer-Assisted methods, Ki-67 Antigen analysis, Neoplasms chemistry
- Abstract
Background: The protein ki67 (pki67) is a marker of tumor aggressiveness, and its expression has been proven to be useful in the prognostic and predictive evaluation of several types of tumors. To numerically quantify the pki67 presence in cancerous tissue areas, pathologists generally analyze histochemical images to count the number of tumor nuclei marked for pki67. This allows estimating the ki67-index, that is the percentage of tumor nuclei positive for pki67 over all the tumor nuclei. Given the high image resolution and dimensions, its estimation by expert clinicians is particularly laborious and time consuming. Though automatic cell counting techniques have been presented so far, the problem is still open., Results: In this paper we present a novel automatic approach for the estimations of the ki67-index. The method starts by exploiting the STRESS algorithm to produce a color enhanced image where all pixels belonging to nuclei are easily identified by thresholding, and then separated into positive (i.e. pixels belonging to nuclei marked for pki67) and negative by a binary classification tree. Next, positive and negative nuclei pixels are processed separately by two multiscale procedures identifying isolated nuclei and separating adjoining nuclei. The multiscale procedures exploit two Bayesian classification trees to recognize positive and negative nuclei-shaped regions., Conclusions: The evaluation of the computed results, both through experts' visual assessments and through the comparison of the computed indexes with those of experts, proved that the prototype is promising, so that experts believe in its potential as a tool to be exploited in the clinical practice as a valid aid for clinicians estimating the ki67-index. The MATLAB source code is open source for research purposes.
- Published
- 2019
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164. Clinical-pathological issues in thyroid pathology: study on the routine application of NIFTP diagnostic criteria.
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Canini V, Leni D, Pincelli AI, Scardilli M, Garancini M, Villa C, Di Bella C, Capitoli G, Cimini R, Leone BE, and Pagni F
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- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Preoperative Care, Thyroid Gland metabolism, Thyroid Gland pathology, Thyroid Neoplasms diagnosis, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology
- Abstract
In 2017, the WHO classification of tumours of the endocrine organs established the criteria for a NIFTP diagnosis. The present paper considers some aspects that are still debated or unresolved: the real incidence and clinical meaning of multifocal/multinodular lesions, the biological behaviour of micro-NIFTP, the sprinkling phenomenon and the corresponding modifications to the FNA reporting systems based on changes to the ROM. Moreover, the paper suggests possible scenarios for the clinical-pathological management of this entity. From the initial 1470 cases, a group of 68 NIFTPs was recruited in a 9 year-long period. The average age at diagnosis was 55 years. The average diameter of the lesion was 1.7 cm (0.1 cm-10 cm). In 41 cases (60.1%), the lesion was inserted in the context of a multinodular background. In 12 cases, the diagnosis was incidental and the pre- operative FNA was performed on a different target. In 10 out of 68 cases, there was a multifocal NIFTP; in 14.7% of patients, PTC-like nuclear features showed sprinkling phenomenon. The cytological revision allocated 21 cases (49%) to the SIAPEC TIR3 indeterminate class and a nuclear score 2 or 3 were identified in 25 smears. Multifocality is part of the spectrum of NIFTPs, that can arise in a multinodular background with variable sizes from microscopic lesions to very large ones. Cytopathological criteria such as an evaluation of the nuclear score may help the pathologists in promoting a NIFTP diagnosis in the preoperative setting.
- Published
- 2019
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165. APOA-1Milano muteins, orally delivered via genetically modified rice, show anti-atherogenic and anti-inflammatory properties in vitro and in Apoe -/- atherosclerotic mice.
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Romano G, Reggi S, Kutryb-Zajac B, Facoetti A, Chisci E, Pettinato M, Giuffrè MR, Vecchio F, Leoni S, De Giorgi M, Avezza F, Cadamuro M, Crippa L, Leone BE, Lavitrano M, Rivolta I, Barisani D, Smolenski RT, and Giovannoni R
- Subjects
- Administration, Oral, Animals, Atherosclerosis metabolism, Atherosclerosis pathology, Dose-Response Relationship, Drug, Food, Genetically Modified, Male, Mice, Mice, Knockout, Plaque, Atherosclerotic metabolism, Plaque, Atherosclerotic pathology, Anti-Inflammatory Agents administration & dosage, Apolipoprotein A-I administration & dosage, Apolipoproteins E deficiency, Atherosclerosis drug therapy, Oryza genetics, Plaque, Atherosclerotic drug therapy
- Abstract
Background: Atherosclerosis is a slowly progressing, chronic multifactorial disease characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue that drives to the formation of asymmetric focal thickenings in the tunica intima of large and mid-sized arteries. Despite the high therapeutic potential of ApoA-1 proteins, the purification and delivery into the disordered organisms of these drugs is still limited by low efficiency in these processes., Methods and Results: We report here a novel production and delivery system of anti-atherogenic APOA-1Milano muteins (APOA-1M) by means of genetically modified rice plants. APOA-1M, delivered as protein extracts from transgenic rice seeds, significantly reduced macrophage activation and foam cell formation in vitro in oxLDL-loaded THP-1 model. The APOA-1M delivery method and therapeutic efficacy was tested in healthy mice and in Apoe
-/- mice fed with high cholesterol diet (Western Diet, WD). APOA-1M rice milk significantly reduced atherosclerotic plaque size and lipids composition in aortic sinus and aortic arch of WD-fed Apoe-/- mice as compared to wild type rice milk-treated, WD-fed Apoe-/- mice. APOA-1M rice milk also significantly reduced macrophage number in liver of WD-fed Apoe-/- mice as compared to WT rice milk treated mice., Translational Impact: The delivery of therapeutic APOA-1M full length proteins via oral administration of rice seeds protein extracts (the 'rice milk') to the disordered organism, without any need of purification, might overcome the main APOA1-based therapies' limitations and improve the use of this molecules as therapeutic agents for cardiovascular patients., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2018
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166. HER2 status of gastric carcinoma and corresponding lymph node metastasis.
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Pagni F, Zannella S, Ronchi S, Garanzini C, and Leone BE
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- Aged, Female, Humans, Immunohistochemistry, Lymph Nodes chemistry, Lymphatic Metastasis, Male, Lymph Nodes pathology, Receptor, ErbB-2 chemistry, Stomach Neoplasms enzymology, Stomach Neoplasms pathology
- Abstract
Our goal is to verify HER2 status variability between primary tumor and metastatic site. Our second intention is to identify the most reliable criteria for pathological HER2 status assessment in gastric cancer node metastases since, at present, there is not a validated standard. 3 independent pathologists evaluated HER2 immunohistochemical and gene status (for IHC 2+ cases) in 34 gastric carcinoma metastatic lymph nodes and in their corresponding primary tumors. For primary gastric cancers, we followed the current HER2 assessment guidelines and for nodal metastases, we applied two immunohistochemical scoring systems with different cut-offs. The immunohistochemical inter-pathologists mean agreement was 71.4 % (κ = 0.45); a final score for each case was defined after collegial revision. By applying the two immunohistochemical criteria, we found 2 discordant cases, which can imply different pathological management. Moreover, a significantly different HER2 status between lymph node metastasis and primary tumor was obtained in 4 cases (concordance ratio 87.5 %). None of the patients would have undergone a different therapeutic pathway despite the scoring method applied. On the other hand we also detected a subset of patients who could have their therapeutic management changed, according to the differences between HER2 status in lymph nodes metastases and primary tumor.
- Published
- 2013
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167. Application of the British National Health Service Breast Cancer Screening Programme classification in 226 breast core needle biopsies: correlation with resected specimens.
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Pagni F, Bosisio FM, Salvioni D, Colombo P, Leone BE, and Di Bella C
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- Biopsy, Needle, Breast Neoplasms pathology, Breast Neoplasms surgery, Female, Humans, National Health Programs, Retrospective Studies, Sensitivity and Specificity, State Medicine, United Kingdom, Breast Neoplasms classification, Early Detection of Cancer
- Abstract
A retrospective study correlating the diagnosis made on core needle breast biopsy (CNB) with the diagnosis made on the final surgical specimen was done using the British National Health Service Breast Cancer Screening Programme (NHSBSP) classification for CNB on 226 patients during a period of 15 months. Statistical analysis was used to evaluate sensitivity, specificity, and positive and negative predictive values of the NHSBSP diagnostic categories. Cohen κ was used to evaluate the agreement between the diagnosis on CNB and the final pathologic diagnosis in "clinically positive cases." Finally, a comparative analysis between the CNB method and fine needle aspiration biopsy was made. The distribution of our cases for each diagnostic category reflects the literature guidelines, with minor differences in the B2 and B4 groups. Statistical data about the patients' follow-up revealed a small number of false-negative cases in the B1 and B2 categories and no false-positive cases in the B4 and B5 groups. Uncertain malignant lesions (B3 category) were divided into 3 major areas (papillary lesions, fibroepithelial proliferations with cellular stroma, and intraepithelial atypical lesions such as ductal intraepithelial neoplasia grade 1/lobular intraepithelial neoplasia grade 1). Of the 29 patients in the B3 category, 26 underwent surgery. Cohen κ analysis showed a strong statistical correlation (κ = 0.77; Z = 4.3; significance >1.96; α = .05) between CNB diagnosis and surgical pathology final results in the subgroup of high-risk patients (diagnosis, ≥ductal intraepithelial neoplasia grade 1 on CNB). Global diagnostic power of CNB in all 226 cases revealed high sensitivity (88.3%) and slightly lower specificity (72.8%). In 42 "doubtful" cases, synchronous fine needle aspiration biopsy and CNB were performed, showing a complementary role in the diagnostic phase of breast lesions. Core needle breast biopsy represents the criterion standard method in the diagnostic phase of many breast tumors; the NHSBSP classification is a useful reporting system that provides a good standardization of the pathologic diagnosis and provides a clear guideline for the correct management of the patient., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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168. The black color in pathology.
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Pagni F, Di Bella C, Ronchi S, and Leone BE
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- Pathology, Color, Diagnosis, Differential, Pigmentation
- Published
- 2011
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169. Interleukin-2 immunotherapy action on innate immunity cells in peripheral blood and tumoral tissue of pancreatic adenocarcinoma patients.
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Degrate L, Nobili C, Franciosi C, Caprotti R, Brivio F, Romano F, Leone BE, Trezzi R, and Uggeri F
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- Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Carcinoma, Pancreatic Ductal surgery, Chemotherapy, Adjuvant, Combined Modality Therapy, Dose-Response Relationship, Drug, Eosinophils drug effects, Eosinophils immunology, Female, Humans, Injections, Subcutaneous, Interleukin-2 adverse effects, Interleukin-2 therapeutic use, Killer Cells, Natural drug effects, Killer Cells, Natural immunology, Leukocyte Count, Male, Middle Aged, Neoadjuvant Therapy, Pancreatectomy, Pancreatic Neoplasms surgery, Pancreaticoduodenectomy, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Antineoplastic Agents therapeutic use, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal immunology, Immunity, Innate drug effects, Immunity, Innate immunology, Immunotherapy methods, Interleukin-2 analogs & derivatives, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms immunology
- Abstract
Background and Aims: Innate immunity cells play a crucial role in host anticancer defense: cancer patients with high levels of natural killer (NK) cells and eosinophils have a better prognosis. Recombinant interleukin-2 (rIL-2) immunotherapy stimulates innate immunity cells. This study aims to evaluate the toxicity of pre- and postoperative rIL-2 treatment and the effects on innate immunity both in peripheral blood and in cancer tissue of patients with resectable pancreatic adenocarcinoma., Materials and Methods: Seventeen patients received high dose rIL-2 preoperative subcutaneous administration and two low dose postoperative cycles. We evaluated NK cell and eosinophil count in blood and in pancreatic surgical specimens., Results: Toxicity was moderate. In the early postoperative period, blood NK cells and eosinophils significantly increased compared to basal values (p < 0.02). Histopathological analysis did not find significant intratumoral infiltration of NK cells nor of eosinophils., Conclusions: Preoperative high dose rIL-2 administration is able to counteract surgery-induced deficiency of NK cells and eosinophils in peripheral blood in the early postoperative period, although it cannot overcome local mechanisms of immune tumor escape in cancer tissue. The amplification of innate immunity, induced by immunotherapy, may improve the control of metastatic cells spreading in the perioperative period.
- Published
- 2009
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170. Malignant epidermoid cyst of the pineal region with lumbar metastasis.
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Pagni F, Brenna A, Leone BE, Vergani F, and Isimbaldi G
- Subjects
- Aged, Carcinoma, Squamous Cell complications, Female, Humans, Hydrocephalus etiology, Intracranial Hypertension etiology, Pinealoma complications, Spinal Cord Neoplasms complications, Carcinoma, Squamous Cell secondary, Cell Transformation, Neoplastic pathology, Epidermal Cyst pathology, Pinealoma pathology, Spinal Cord Neoplasms secondary
- Abstract
This report describes a malignant neoplasia of the pineal region in a 65-year-old woman who presented with symptoms of intracranial hypertension and dissemination to CSF with radiologically documented lumbar intradural localizations. The histological examination of the lesion showed fragments of a cystic malignant neoplasia with epithelial elements resembling squamous cell carcinoma. We excluded the possibility of a cerebral metastasis from a squamous cell carcinoma arising in the genital or gastrointestinal tract, lung and skin. We propose this unique report for cyto- histological correlation and, as suggested in the American and Japanese literature, we discuss the hypothesis of the development of a squamous cell carcinoma arising from the malignant degeneration of a cerebral epidermoid cyst and we show by cytological examination of the CSF the exceptional presence of malignant cells and by lumbar MRI their intradural localizations.
- Published
- 2007
- Full Text
- View/download PDF
171. Selective reduction of extracellular signal-regulated protein kinase (ERK) phosphorylation in squamous cell carcinoma of the larynx.
- Author
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Garavello W, Nicolini G, Aguzzi A, Maggioni D, Leone BE, Viganò P, Gaini RM, and Tredici G
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Squamous Cell pathology, Cell Proliferation, Female, Humans, Laryngeal Neoplasms pathology, Larynx enzymology, Larynx pathology, Male, Middle Aged, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 12 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Mitogen-Activated Protein Kinase 8 metabolism, Phosphorylation, Prognosis, Signal Transduction, p38 Mitogen-Activated Protein Kinases metabolism, Carcinoma, Squamous Cell enzymology, Extracellular Signal-Regulated MAP Kinases metabolism, Laryngeal Neoplasms enzymology
- Abstract
Mitogen-activated protein kinase (MAPK) cascades transmit and amplify signals involved in cell proliferation as well as in cell death. In this study, the potential derangement of MAPK pathways has been evaluated in human squamous cell carcinomas (SCC) of the larynx. The expression and activity of the MAPK p38, ERK1/2p44/p42 and JNK/SAPKp46/p54 have been investigated by immunoblot analysis of tissue homogenates in 27 samples of primary laryngeal cancer and in 27 paired non-neoplastic laryngeal mucosa. On the same tissues, the activation of MAPK JNK/SAPKp46/p54 was also analyzed by an ELISA assay. The results obtained showed that both total and phosphorylated levels of JNK/SAPKp46/p54 and p38 were not different between tumor and normal samples. Conversely, while total protein levels for both ERK1p44 and ERK2p42 were not statistically different between tumor and normal samples, the analysis of the level of the activated forms of ERK1/2 showed a statistically significant decreased phosphorylation of both isoforms in the tumor samples compared to the control tissues. The rate of reduction was similar for both isoforms. Immunohistochemical analysis of all the activated MAPK (p38, JNK/SAPKp46/p54 and ERK1/2p44/p42) in both laryngeal SCC and normal mucosa demonstrated no difference of cellular localization. Activated ERK1/2p44/p42 and activated p38 demonstrated a nucleo-cytoplasmic distribution whereas activated JNK/SAPKp46/p54 were localized into the cytoplasmic membrane. The decreased activity of ERK1/2p44/42 in laryngeal SCC might reflect alterations in tumor suppressing activity or might derive from the interplay among various transduction pathways.
- Published
- 2006
172. Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets.
- Author
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Sordi V, Malosio ML, Marchesi F, Mercalli A, Melzi R, Giordano T, Belmonte N, Ferrari G, Leone BE, Bertuzzi F, Zerbini G, Allavena P, Bonifacio E, and Piemonti L
- Subjects
- Animals, Base Sequence, Cell Separation, Cells, Cultured, Chemokines genetics, Chemokines physiology, Chemotaxis physiology, DNA genetics, Gene Expression, Humans, In Vitro Techniques, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Bone Marrow Cells cytology, Bone Marrow Cells physiology, Islets of Langerhans cytology, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells physiology, Receptors, Chemokine genetics, Receptors, Chemokine physiology
- Abstract
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are stromal cells with the ability to proliferate and differentiate into many tissues. Although they represent powerful tools for several therapeutic settings, mechanisms regulating their migration to peripheral tissues are still unknown. Here, we report chemokine receptor expression on human BM-MSCs and their role in mediating migration to tissues. A minority of BM-MSCs (2% to 25%) expressed a restricted set of chemokine receptors (CXC receptor 4 [CXCR4], CX3C receptor 1 [CX3CR1], CXCR6, CC chemokine receptor 1 [CCR1], CCR7) and, accordingly, showed appreciable chemotactic migration in response to the chemokines CXC ligand 12 (CXCL12), CX3CL1, CXCL16, CC chemokine ligand 3 (CCL3), and CCL19. Using human pancreatic islets as an in vitro model of peripheral tissue, we showed that islet supernatants released factors able to attract BM-MSCs in vitro, and this attraction was principally mediated by CX3CL1 and CXCL12. Moreover, cells with features of BM-MSCs were detected within the pancreatic islets of mice injected with green fluorescent protein (GFP)-positive BM. A population of bona fide MSCs that also expressed CXCR4, CXCR6, CCR1, and CCR7 could be isolated from normal adult human pancreas. This study defines the chemokine receptor repertoire of human BM-MSCs that determines their migratory activity. Modulation of homing capacity may be instrumental for harnessing the therapeutic potential of BM-MSCs.
- Published
- 2005
- Full Text
- View/download PDF
173. The CC chemokine MCP-1/CCL2 in pancreatic cancer progression: regulation of expression and potential mechanisms of antimalignant activity.
- Author
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Monti P, Leone BE, Marchesi F, Balzano G, Zerbi A, Scaltrini F, Pasquali C, Calori G, Pessi F, Sperti C, Di Carlo V, Allavena P, and Piemonti L
- Subjects
- Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal therapy, Cell Division physiology, Cell Line, Tumor, Chemokine CCL2 metabolism, Chemokine CCL2 pharmacology, Disease Progression, Humans, Macrophages pathology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms therapy, Prognosis, Carcinoma, Pancreatic Ductal metabolism, Chemokine CCL2 biosynthesis, Pancreatic Neoplasms metabolism
- Abstract
The aim of this study was to discover whether MCP-1/CCL2, a CC chemokine able to attract macrophages, is expressed in human pancreatic cancer and how it modulates cancer progression. All primary tumors were tested, and 6 of 14 pancreatic cancer cell lines were constitutively secreted CCL2. Analysis of the regulation demonstrated that the expression of CCL2 was significantly elevated and in a synergistic manner by IFN-gamma, tumor necrosis factor alpha, and interleukin 1beta. By immunohistochemistry and in situ hybridization, CCL2 production was confirmed in neoplastic ducts from surgical specimens. Serum levels of CCL2 in pancreatic cancer patients were significantly higher than in normal healthy subjects (P < 0.0001). Patients with high circulating levels of CCL2 had significantly higher survival rate than low CCL2 producers. Serum CCL2 levels positively correlated with tumor macrophage infiltration and inversely correlated with tumor proliferative activity (Ki67 expression). A direct effect of CCL2 on tumor cells is to be excluded, either because primary tumors as well as cell lines have no detectable CCL2 receptor (CCR2) and because addition of CCL2 on tumor cells in vitro did not modify cell cycle progression or apoptosis. In vitro, a model of tumor microenvironment showed a direct antiproliferative and proapoptotic activity of monocytes toward pancreatic cancer cell, which is mediated at least in part by interleukin 1beta. Moreover, other proinflammatory cytokines such as tumor necrosis factor alpha and IFN-gamma appeared able to induce apoptosis and to reduce the proliferative rate of pancreatic cancer. On the whole, the results presented in our investigation suggest that CCL2 could be a relevant negative regulator of pancreatic cancer progression.
- Published
- 2003
174. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation.
- Author
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Piemonti L, Leone BE, Nano R, Saccani A, Monti P, Maffi P, Bianchi G, Sica A, Peri G, Melzi R, Aldrighetti L, Secchi A, Di Carlo V, Allavena P, and Bertuzzi F
- Subjects
- Adult, Blotting, Northern, Cells, Cultured, Chemokine CCL2 metabolism, Chemokine CCL2 pharmacology, Chemotaxis, Leukocyte drug effects, Cytokines pharmacology, Diabetic Nephropathies surgery, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Humans, Immunosuppression Therapy, Insulin Secretion, Kidney Transplantation, Male, Middle Aged, Monocytes physiology, Chemokine CCL2 genetics, Diabetes Mellitus, Type 1 surgery, Insulin metabolism, Islets of Langerhans metabolism, Islets of Langerhans Transplantation physiology
- Abstract
We investigated the capacity of human islets to produce monocyte chemoattractant protein-1 (MCP-1). Primary cultures of pancreatic islets expressed and secreted MCP-1, as determined by Northern blot, immunohistochemistry, in situ hybridization, and enzyme-linked immunosorbent assay. The produced MCP-1 was biologically active as it attracted monocytes in chemotaxis assay, and chemotactic activity was almost abrogated by a neutralizing anti-MCP-1 monoclonal antibody. Expression of MCP-1 was increased by primary inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha) and lipopolysaccharide at both the mRNA and protein levels but not by glucose. However, MCP-1 did not modulate insulin secretion. MCP-1 secreted by pancreatic islets plays a relevant role in the clinical outcome of islet transplant in patients with type 1 diabetes. In fact, low MCP-1 secretion resulted as the most relevant factor for long-lasting insulin independence. This finding opens new approaches in the management of human islet transplantation. Finally, the finding that MCP-1 appears constitutively present in normal human islet beta-cells (immunohistochemistry and in situ hybridization), in the absence of an inflammatory infiltrate, suggests that this chemokine could have functions other than monocyte recruitment and opens a new link between the endocrine and immune systems.
- Published
- 2002
- Full Text
- View/download PDF
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