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Assessing the response of human primary macrophages to defined fibrous architectures fabricated by melt electrowriting

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Bioactive Materials 2023年第3期21卷 209-222页

作者： Carlotta Mondadori Amit Chandrakar Silvia Lopa Paul Wieringa Giuseppe Tal`o Silvia Perego Giovanni Lombardi Alessandra Colombini Matteo Moretti Lorenzo Moroni IRCCS istituto Ortopedico Galeazzi Cell and Tissue Engineering LaboratoryMilanItaly Complex Tissue Regeneration Department MERLN Institute for Technology-Inspired Regenerative MedicineMaastrichtthe Netherlands IRCCS istituto Ortopedico Galeazzi Laboratory of Experimental Biochemistry and Molecular BiologyMilanItaly Department of Athletics Strength and ConditioningPozna´n University of Physical EducationPozna´nPoland IRCCS istituto Ortopedico Galeazzi Orthopaedic Biotechnology LabMilanItaly Regenerative Medicine Technologies Lab Ente Ospedaliero CantonaleBellinzonaSwitzerland Service of Orthopaedics and Traumatology Department of SurgeryEnte Ospedaliero CantonaleLuganoSwitzerland Euler Institute Faculty of Biomedical SciencesUniversit`a della Svizzera ItalianaLuganoSwitzerland

The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling *** scaf-fold geometry has been proposed as a strategy to influence macrophage behavior and favor the positive host response to ***,we fabricated Polycaprolactone(PCL)scaffolds by Melt Electrowriting(MEW)to investigate the ability of scaffold architecture to modulate macrophage *** human macrophages unpolarized(M0)or polarized into M1,M2a,and M2c phenotypes were cultured on PCL films and MEW scaffolds with pore geometries(square,triangle,and rhombus grid)characterized by different angles.M0,M2a,and M2c macrophages wrapped along the fibers,while M1 macrophages formed clusters with rounded *** bridges were formed only for angles up to 90◦.No relevant differences were found among PCL films and 3D scaffolds in terms of surface ***206 and CD163 were highly expressed by M2a and M2c macrophages,with M2a macrophages presenting also high levels of CD86.M1 macrophages expressed moderate levels of all *** rhombus architecture promoted an increased release by M2a macrophages of IL10,IL13,and sCD163 compared to PCL *** proangiogenic factor IL18 was also upregulated by the rhombus configuration in M0 and M2a macrophages compared to PCL *** interesting findings obtained for the rhombus architecture represent a starting point for the design of scaffolds able to modulate macrophage phenotype,prompting investigations addressed to verify their ability to facilitate the healing process in vivo.

关键词： Macrophage Melt electrowriting Additive manufacturing Scaffold design Scaffold geometry

Is acute dyspnea related to oxaliplatin administration?

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World Journal of Gastroenterology 2006年第36期12卷 5907-5908页

作者： LM Pasetto S Monfardini istituto oncologico Veneto Medical Oncology V. Gattamelata 64 Padua 35128 Italy

The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin. Oxaliplatin improves the efficacy of this combination in patients with stage 111 colon cancer and moreover its toxicity is well tolerable. We describe a rare clinical case of acute dyspnoea probably related to oxaliplatin at one month from the end of the adjuvant treatment. A 74-year-old man developed a locally advanced sigmoid carcinoma （pT3N1M0）. A port a cath attached to an open-ended catheter was implanted in order to administer primary chemotherapy safely according to the FOLFOX4 schedule. One month following the end of the 6^th cycle, the patient referred a persistent cough and moderate dyspnoea. Chest radiography displayed a change in the lung interstitium, chest CT scan confirmed this aspect of adult respiratory distress syndrome, spirometry reported a decreased carbon monoxide diffusion capacity. Antibiotic and corticosteroids were administered for 10 d, then a repeated chest X ray evidenced a progressive pulmonary infiltration. A transbronehial biopsy and cytology did not show an infective process, a CT scan reported radiological abnormalities including linear and nodular densities which were becoming confluents. Antimicotic and antiviral drugs did not evidence any benefit. The antiviral therapy was stopped and high dose metilprednisolone was started. The patient died of pulmonary distress after 10 d.

关键词： Acute dyspnea Oxaliplatin Colon cancer

Biosynthetic scaffolds for partial meniscal loss:A systematic review from animal models to clinical practice

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Bioactive Materials 2021年第11期6卷 3782-3800页

作者： F.Veronesi B.Di Matteo N.D.Vitale G.Filardo A.Visani E.Kon M.Fini Complex Structure of Surgical Sciences and Technologies IRCCS Istituto Ortopedico RizzoliBolognaItaly Humanitas University Department of Biomedical SciencesVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly IRCCS Humanitas Research Hospital Via Manzoni 5620089RozzanoMilanItaly Applied and Translational Research Center IRCCS Istituto Ortopedico RizzoliBolognaItaly Orthopaedic and Traumatology Unit Ospedale Regionale di LuganoEOCLuganoSwitzerland Faculty of Biomedical Sciences Universit`a della Svizzera ItalianaLuganoSwitzerland First Moscow State Medical University-Sechenov University Bol’shaya Pirogovskaya Ulitsa19c1119146MoscowRussia

Acute or degenerative meniscus tears are the most common knee *** provides symptomatic relief and functional recovery only in the short-to mid-term follow-up but significantly increases the risk of *** this reason,preserving the meniscus is key,although it remains a *** transplants present many disadvantages,so during the last 20 years preclinical and clinical research focused on developing and investigating meniscal *** aim of this systematic review was to collect and evaluate all the available evidence on biosynthetic scaffolds for meniscus regeneration both in vivo and in clinical *** databases were searched:46 in vivo preclinical studies and 30 clinical ones were *** natural,15 synthetic,and 15 hybrid scaffolds were studied in *** them,only 2 were translated into clinic:the Collagen Meniscus Implant,used in 11 studies,and the polyurethane-based scaffold Actifit®,applied in 19 *** positive outcomes were described in the short-to mid-term,the number of concurrent procedures and the lack of randomized trials are the major limitations of the available clinical *** in vivo studies also combined the use of cells or growth factors,but these augmentation strategies have not been applied in the clinical practice *** solutions offer a significant but incomplete clinical improvement,and the regeneration potential is still *** upon the overall positive results of these“old”technologies to address partial meniscal loss,further innovation is urgently needed in this field to provide patients better joint sparing treatment options.

关键词： Meniscal scaffold Meniscectomy Osteoarthritis Regenerative medicine Collagen Polyurethane

Loss of CDKN1B induces an age-related clonal hematopoietic disorder via Notch2 activity dysregulation

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Cancer Communications 2023年第7期43卷 844-849页

作者： Ilenia Segatto Gian Luca Rampioni Vinciguerra Ilenia Pellarin Alessandra Dall’Acqua Stefania Berton Francesca Citron Sara D’Andrea Giorgia Mungo Davide Viotto Lorena Musco Arianna Di Napoli Maria Antonietta Aloe Spiriti Vincenzo Canzonieri Valter Gattei Andrea Vecchione Barbara Belletti Gustavo Baldassarre Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano(PN)Italy Department of Clinical and Molecular Medicine University of Rome“La Sapienza”Santo Andrea HospitalRomeItaly Division of Pathology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano(PN)Italy Division of Clinical and Experimental Onco-Hematology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano(PN)Italy

Dear Editor,The tumor suppressor gene CDKN1B,encoding for the p27^(Kip1)(p27)protein,defines the smallest region of deletion on chromosome 12p13 described in clonal hematopoietic disorders(CHDs)[1].Among them,myelodysplastic syndromes(MDSs)display typical onset in the elderly and an indolent behavior that may evolve in acute myeloid leukemia(AML)[2].Recent evidences support a model of parallel clonal evolution at the stem or progenitor cell level and implicate the need of more preclinical,translational and clinical research to identify better ways to timely target clones that may evolve toward malignancy[3,4].

关键词： hematopoietic clinical acute

Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

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World Journal of Gastroenterology 2013年第44期19卷 7874-7879页

作者： Antonino Carbone Annunziata Gloghini Department of Pathology Centro di Riferimento Oncologico Aviano Istituto Nazionale Tumori IRCCSAviano and Pordenone Hospital 33081 Aviano Italy Member of WHO IARC Monograph Working Group on Biological Agents 2009 Lyon France Department of Diagnostic Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale dei Tumori 20133 Milano Italy

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns:(1)an independent pattern;(2)a dependent pattern on deregulated interactions;and(3)a dependent pattern on regulated *** examples of the third pattern are hepatitis C virus(HCV)-associated marginal zone lymphomas(MZLs)and mucosa-associated lymphoid tissue *** these lymphomas,a regulated coexistence of the malignant cells and the microenvironmental factors usually *** least initially,however,tumor development and cell growth largely depend on external signals from the microenvironment,such as viral antigens,cytokines,and cell-cell *** association between HCV infection and B-cell lymphomas is not completely defined,although this association has been demonstrated by epidemiological *** and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV *** mechanisms have been proposed for explaining HCV-induced lymphomagenesis;antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell ***,antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent ***,clinically responses were linked to the eradication of the HCV-RNA,providing a strong argument in favor of a causative link between HCV and lymphoproliferation.

关键词： Hepatitis C virus-infection B-cell lymphomas Marginal zone lymphoma Mucosa-associated lymphoid tissue lymphomas Diffuse large B-cell lymphomas Microenvironment

Aggressive behaviour of solid-pseudopapillary tumor of the pancreas in adults:A case report and review of the literature

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World Journal of Gastroenterology 2008年第6期14卷 960-965页

作者： Cosimo Sperti Mattia Berselli Claudio Pasquali Davide Pastorelli Sergio Pedrazzoli Department of Medical and Surgical Sciences Clinica Chirurgica Ⅳ University of Padua Padua 35128 Italy Department of Oncology Istituto Oncologico Veneto Padua Italy

Solid-pseudopapillary tumor (SPT) is a rare neoplasm of the pancreas that usually occurs in young females. It is generally considered a low-grade malignant tumor that can remain asymptomatic for several years. The occurrence of infiltrating varieties of SPT is around 10%-15%. Between 1986 and 2006, 282 cystic tumors of the pancreas were observed. Among them a SPT was diagnosed in 8 patients (2.8%) with only one infiltrating variety. This was diagnosed in a 49-year-old female 13 years after the sonographic evidence of a small pancreatic cystic lesion interpreted as a pseudocyst. The tumor invaded a long segment of the portal- mesenteric vein confluence, and was removed with a total pancreatectomy, resection of the portal vein and reconstruction with the internal jugular vein. Histological examination confirmed the R-0 resection of the primary SPT, although a vascular invasion was demonstrated. The postoperative course was uneventful, but 32 mo after surgery the patient experienced diffuse liver metastases. Chemotherapy with different drugs was started. The patient is alive and symptom-free, with stable disease, 75 mo after surgery. Twenty-five patients with invasion of the portal vein and/or of mesenteric vessels were retrieved from the literature, 16 recent patients with tumor relapse after potentially curative resection were also retrieved. The best treatment remains a radical resection whenever possible, even in locally advanced or metastatic disease. The role of chemotherapy, and/or radiotherapy, is still to be defined.

关键词： Solid-pseudopapillary tumor Pancreatectomy Vascular resection Liver metastases Follow-up

Colorectal cancer and 18FDG-PET/CT:What about adding the T to the N parameter in loco-regional staging?

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World Journal of Gastroenterology 2011年第11期17卷 1427-1433页

作者： Pier Paolo Mainenti Delfina Iodice Sabrina Segreto Giovanni Storto Mario Magliulo Giovanni Domenico De Palma Marco Salvatore Leonardo Pace istituto di Biostrutture e Bioimmagini Consiglio Nazionale delle Ricerche Naples 80131Italy Department of Biomorphological and Functional Sciences University of Naples"Federico II"Naples 80131Italy Istitituto di Ricovero e Cura a carattere scientifico Centro di Riferimento Oncologico della BasilicataRionero in Vulture 85028 PZItaly Department of General Surgery Geriatry and EndoscopyUniversity of Naples"Federico II"Naples 80131Italy

AIM:To evaluate whether FDG-positron emission tomography(PET)/computed tomography(CT)may be an accurate technique in the assessment of the T stage in patients with colorectal ***:Thirty four consecutive patients(20 men and 14 women;mean age:63 years)with a histologically proven diagnosis of colorectal adenocarcinoma and scheduled for surgery in our hospital were enrolled in this *** patients underwent FDG-PET/CT *** primary tumor site and extent were evaluated on PET/CT *** wall invasion was analysed according to a modified T classification that considers only three stages(≤T2,T3,T4).Assessment of accuracy was carried out using 95%confidence intervals for ***:Thirty five/37(94.6%)adenocarcinomas were identified and correctly located on PET/CT ***/CT correctly staged the T of 33/35 lesions identified showing an accuracy of 94.3%(95%CI:87%-100%).All T1,T3 and T4 lesions were correctly staged,while two T2 neoplasms were overstated as ***:Our data suggest that FDG-PET/CT may be an accurate modality for identifying primary tumor and defining its local extent in patients with colorectal cancer.

关键词： Cancer Colorectal Positron emission tomography/computed tomography Staging

Adaptive nanopores:A bioinspired label-free approach for protein sequencing and identification

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Nano Research 2021年第1期14卷 328-333页

作者： Andrea Spitaleri Denis Garoli Moritz Schutte Hans Lehrach Walter Rocchia Francesco De Angelis CONCEPT Lab Istituto Italiano di TecnologiaVia Morego 30Genova1-16163Italy Center for Omics Sciences IRCCS San Raffaele Scientific InstituteMilanVia Olgettina 58Milano1-20132Italy Plasmon Nanotechnology Unit Istituto Italiano di TecnologiaVia Morego 30Genova1-16163Italy AB ANALITICA s.r.l Via Svizzera 161-35127 PadovaItaly Alacris Theranostics GmbH Max-Planck-Strasse 3D-12489 BerlinGermany Max Planck Institute for Molecular Genetics Ihnestrasse 63-73D-14195 BerlinGermany

Single molecule protein sequencing would tremendously impact in proteomics and human biology and it would promote the development of novel diagnostic and therapeutic ***,its technological realization can only be envisioned,and huge challenges need to be *** difficulties are inherent to the structure of proteins,which are composed by several different *** long standing efforts,only few complex techniques,such as Edman degradation,liquid chromatography and mass spectroscopy,make protein sequencing ***,these techniques present significant limitations in terms of amount of sample required and dynamic range of *** is known that proteins can distinguish closely similar ***,several proteins can work as biological nanopores in order to perform single molecule detection and ***,while DNA sequencing by means of nanopores is demonstrated,very few examples of nanopores able to perform reliable protein-sequencing have been reported ***,we investigate,by means of molecular dynamics simulations,how a re-engineered protein,acting as biological nanopore,can be used to recognize the sequence of a translocating peptide by sensing the MshapeH of individual *** our simulations we demonstrate that it is possible to discriminate with high fidelity,9 different amino-acids in a short peptide translocating through the engineered *** method,here shown for fluorescence-based sequencing,does not require any labelling of the peptidic *** results can pave the way for a new and highly sensitive method of sequencing.

关键词： nanopores single molecule sequencing protein sequencing luorescence resonance energy transfer(FRET) amino-acids fluorescence

Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma:A Rare Cancer Network study

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Chinese Journal of Cancer Research 2017年第6期29卷 521-532页

作者： Alessandra Franzetti Pellanda Berardino De Bari Elisabeth Deniaud-Alexandre MarcoKrengli Paul Van Houtte Antonella Riehetti Salvador Villa Hadassah Goldberg EwaSzutowiez-Zielifiska Michel Bolla Heidi Rutten Marc Van Eijkeren Philip Poortmans Guido Henke Yavuz Anaeak Steve Chan Christine Landmann Carine Kirkove LueianoScandolaro Jacques Bernier Rene-Olivier Mirimanof Mahmut Ozsahin Centre Hospitalier Universitaire Vaudois(CHUV) 1011 LausanneSwitzerland Clinica Luganese Moncucco 6903 LuganoSwitzerland Centre Hospitalier R6gional Universitaire"Jean Minjoz" INSERMUMR109825030 BesangonFrance Hopital Tenon 75970 ParisFrance Centre Hospitalier Departemental 85925 VendeeFrance degli Studi del Piemonte Orientale e Ospedale Maggiore della Carifi 28100 NovaraItaly University Institut Jules Bordet 1000 BrusselsBelgium 8Ospedale di Circolo 21100 VareseItaly Ospedale di Circolo 21100 VareseItalyt istituto oncologico della svizzera italiana EOC6500 BellinzonaSwitzerland Catalan Institute of Oncology Universitat Autbnoma de Barcelona08916 Barcelona 08916Spain Rambam Medical Center 31096 HaifaIsrael Medical University 80210 GdanskPoland Hopital Michallon BP21738043Grenoble cedex 09France Radboud University Medical Center 6525 NijmegenThe Netherlands Ghent University Hospital 9000 GentBelgium Institute Verbeeten 90120 TilburgThe Netherlands Kantonsspital St.Gallen 9007St.GallenSwitzerland Karadeniz Technical University 61080 TrabzonTurkey Nottingham University Hospital NHS trustNG5 1PB NottinghamUnited Kingdom Kantonsspital Basel 4031 BaselSwitzerland UCL St.Luc 1200 BrusselsBelgium presidio Ospedaliero Sant'Anna 22100 ComoItaly Ospedale San Giovanni 6500 BellinzonaSwitzerland Clinique de Genolier Genolier1272 Switzerland Department of Radiation Oncology Centre Hospitalier Universitaire Vaudois(CHUV)University of LausanneSwitzerland

Objective： Primary uterine leiomyosarcomas （ULMS） are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. Methods： We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network （RCN）. Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics （FIGO） stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control （LC） and locoregional control （LRC）, overall survival （OS） and disease-free survival （DFS） rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. Results： All patients underwent surgery. Seventy-five patients （68%） received adjuvant radiotherapy （RT）, including brachytherapy in 18 （I 6%）. Seventeen patients （15 %） received adjuvant chemotherapy. Median follow-up was 58 （range, 6-240） months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. Conclusions： In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim p

关键词： Uterine leiomyosarcoma prognostic factors radiotherapy overall survival local control