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Narrow-band imaging endoscopy to assess mucosal angiogenesis in inflammatory bowel disease: A pilot study

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World Journal of Gastroenterology 2010年第19期16卷 2396-2400页

作者： Silvio Danese Gionata Fiorino Erika Angelucci Stefania Vetrano Nico Pagano Giacomo Rando Antonino Spinelli Alberto Malesci Alessandro Repici Division of Gastroenterology IRCCS Istituto Clinico Humanitas Rozzano Milan 20089 Italy Department of Surgery IRCCS Istituto Clinico Humanitas Rozzano Milan 20089 Italy Department of Translational Medicine Univer-sity of Milan Milan 20100 Italy

AIM: To investigate whether narrow band imaging (NBI) is a useful tool for the in vivo detection of angiogenesis in inflammatory bowel disease (IBD) patients. METHODS: Conventional and NBI colonoscopy was performed in 14 patients with colonic inflammation (8 ulcerative colitis and 6 Crohn’s disease). Biopsy samples were taken and CD31 expression was assayed immuno- histochemically; microvascular density was assessed by vessel count. RESULTS: In areas that were endoscopically normal but positive on NBI, there was a significant (P < 0.05) increase in angiogenesis (12 ± 1 vessels/field vs 18 ± 2 vessels/field) compared with areas negative on NBI. In addition, in areas that were inflamed on white light endoscopy and positive on NBI, there was a significant (P < 0.01) increase in vessel density (24 ± 7 vessels/f ield) compared with NBI-negative ***: NBI may allow in vivo imaging of intestinal angiogenesis in IBD patients.

关键词： Narrow-band imaging Angiogenesis Inflammatory bowel disease Crohn’s disease Ulcerative colitis

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

Early radiological assessment of locally advanced pancreatic cancer treated with electrochemotherapy

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World Journal of Gastroenterology 2017年第26期23卷 4767-4778页

作者： Vincenza Granata Roberta Fusco Sergio Venanzio Setola Mauro Piccirillo Maddalena Leongito Raffaele Palaia Francesco Granata Secondo Lastoria Francesco Izzo Antonella Petrillo Department of Diagnostic Imaging Radiant and Metabolic Therapy'Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli' Department of Surgical Oncology Hepatobiliary Unit'Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli' Departement of Civil and Mechanical Engineering 'University of Cassino and Southern Lazio'Viale dell’Università

To report early imaging assessment of ablated area post electrochemotherapy (ECT) in patients with locally advanced pancreatic cancer (LAPC). METHODSECT was performed in 19 LAPC patients enrolled in an approved ongoing clinical phase I/II study. Before and after ECT, 18 patients underwent computed tomography (CT) scan, 11 patients underwent morphological and functional magnetic resonance (MR) scan (dynamic contrast enhanced-MRI) calculating wash-in slope (WIS) and wash-out slope (WOS); diffusion weighted imaging calculating pseudo-diffusivity (Dp), perfusion fraction (fp) and tissue diffusivity (Dt); 10 patients underwent positron emission tomography (PET). Response evaluation criteria in solid tumour (RECIST) on MR and CT were used to assess tumour therapy response. Choi on CT, PET response criteria in solid tumors (PERCIST) on PET and functional parameters on MR were used to evaluate treatment response. RESULTSFor each patient no significant reduction was measurable by CT and MR using RECIST. According Choi criteria a partial response was obtained in 18/18 (100.0%) patients. According PERCIST criteria 6/10 (60.0%) patients showed a partial response, 3/10 (30.0%) stable disease and 1/10 (10.0%) progression disease. Moreover, using functional MR parameters, a significant reduction of viable tumour after ECT can be observed. According ΔWIS and ΔWOS 9/11 (81.8%) patients exhibited a partial response and 2/11 (18.2%) stable disease; 8/11 (72.7%) patients were considered in partial response by ΔDp evaluation and 3/11 (27.3%) in stable disease; according ΔDt 7/11 (63.6%) patients showed a partial response, 1/11 (9.1%) showed progression of disease and 3/11 (27.3%) were stable. Perfusion fraction fp showed a significant reduction after ECT only in four patients. No significant difference was observed after ECT in signal intensity of T1-weighted images and T2-weighted images, and in equilibrium-phase of contrast study, according to χ2 test was observed. A good c

关键词： Reversible electroporation Response assessment Positron emission tomography/computed tomography Pancreatic cancer Magnetic resonance imaging

Vascular architecture:is it a helpful histopathological biomarker for hepatocellular carcinoma?

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2007年第4期8卷 217-220页

作者： GRIZZI Fabio FRANCESCHINI Barbara FIAMENGO Barbara RUSSO Carlo DIOGUARDI Nicola Laboratories of Quantitative Medicine Istituto Clinico Humanitas IRCCS20089 RozzanoMilanItaly Department of Pathology Istituto Clinico Humanitas IRCCS20089 RozzanoMilanItaly

Hepatocellular carcinoma(HCC) remains one of the major public health problems throughout the *** originally associated with tumorigenic processes,liver angiogenesis has also been observed in the context of different liver in-flammatory,fibrotic,and ischemic *** we investigate the fractal dimension as a quantitator of non-Euclidean two-dimensional vascular geometry in a series of paired specimens of primary HCC and surrounding non-tumoral tissue,and discuss why this parameter might provide additional information regarding cancer *** application of fractal geometry to the measurement of liver vascularity and the availability of a computer-aided quantitative method can eliminate errors in visual interpretation,and make it possible to obtain closer-to-reality numerals that are compulsory for any measurement process.

关键词： Liver Angiogenesis Cancer Fractals Geometry Biomarkers

Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

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Chinese Journal of Cancer 2016年第10期35卷 546-559页

作者： Vittoria Disciglio Andrea Devecchi Orazio Palumbo Massimo Carella Donata Penso Massimo Milione Giorgio Valle Marco Alessandro Pierotti Marco Vitellaro Lucio Bertario Silvana Canevari Stefano Signoroni Loris De Cecco Department of Experimental Oncology and Molecular Medicine Func-tional Genomics and BioinformaticsFondazione IRCCS Istituto Nazionale dei Tumori20133 MilanItaly. Medical Genetics Unit IRCCS Casa Sollievo della Soferenza71013 San Giovanni Rotondo FGItaly. Department of Pathol-ogy and Laboratory Medicine Fondazione IRCCS Istituto Nazionale Tumori20133 MilanItaly. Department of Biology University of Padova35131 PaduaItaly. Fondazione irccs istituto Nazionale dei Tumori 20133 MilanItaly. Hereditary Digestive Tract Tumors Unit Department of Preventive and Pre-dictive MedicineFondazione IRCCS Istituto Nazionale dei Tumori20133 MilanItaly. Colorectal Surgery Unit Department of SurgeryFondazione IRCCS Istituto Nazionale dei Tumori20133 MilanItaly.

Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been *** presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human ***: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

关键词： Androgen insensitivity syndrome Androgen receptor Colorectal cancer Single nucleotide polymorphism array Testosterone Whole exome sequencing

Sampling variability of computer-aided fractal-corrected measures of liver fibrosis in needle biopsy specimens

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World Journal of Gastroenterology 2006年第47期12卷 7660-7665页

作者： Fabio Grizzi Carlo Russo Barbara Franceschini Mariagrazia Di Rocco Valter Torri Emanuela Morenghi Luigi Rainiero Fassati Nicola Dioguardi Laboralori di Medicina Quanlitativa Islituto Clinico Humanitas IRCCS Rozzano Milan Italy Department of Pathology Istituto ClinicoHumanitas IRCCS Rozzano Milan Italy Laboratory of Clinical Research in Oncology Mario Negri Institute of Pharmacological Research Milan Italy Clinical Research Office Istituto ClinicoHumanitas IRCCS Rozzano Milan Italy Department of General Surgery and Transplantation Ospedale Maggiore IRCCS Milan Italy

AIM： TO assess the sampling variability of computeraided, fractal-corrected measures of fibrosis in liver biopsies. METHODS： Samples were derived from six to eight different parts of livers removed from 12 patients with clinically and histologically proven cirrhosis undergoing orthotopic liver transplantation. Sirius red-stained sections with a thickness of 2 μm were digitized using a computer-aided image analysis system that automatically measures the surface of fibrosis, as well as its outline perimeter, fractal surface and outline dimensions, wrinldedness, and Hurst coefficient. RESULTS： We found a high degree of inter-sample variability in the measurements of the surface [coefficient of variation （CV） = 43% ± 13%] and wrinkledness （CV = 28% ± 9%） of fibrosis, but the inter-sample variability of Hurst＇s exponent was low （CV = 14% ± 2%）. CONCLUSION： This study suggests that Hurst＇s exponent might be used in clinical practice as the best histological estimate of fibrosis in the whole organ, and evidences the fact that biopsy sections, which are fundamental for the qualitative diagnosis of chronic hepatitis, play a key role in the quantitative estimate of architectural changes in liver tissue.

关键词： Cirrhosis Hepatitis C virus Inter-sample variability Extra-cellular matrix Image analysis

Anxiety,depression,and quality of life in Parkinson's disease:the implications of multidisciplinary treatment

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Neural Regeneration Research 2021年第3期16卷 587-590页

作者： Viviana Lo Buono Rosanna Palmeri Simona De Salvo Matteo Berenati Agata Greco Rosella Ciurleo Chiara Sorbera Vincenzo Cimino Francesco Corallo Placido Bramanti Silvia Marino Giuseppe Di Lorenzo Lilla Bonanno Department of Neurobioimaging Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Centro Neurolesi Bonino-PulejoMessinaItaly

Anxiety and depression in Parkinson's disease(PD)reduce well-being of the *** alterations influence motor skills and cognitive performance;moreover,they contribute significantly and independently to worsen rehabilitative treatment *** investigated anxiety,depression,and quality of life in PD patients subjected to multidisciplinary rehabilitative *** self-controlled study included 100 PD patients(49 males and 51 females with the mean age of 64.66 years)admitted to 60 days hospitalization rehabilitative program,between January 2017 and December ***,cognitive,linguistic abilities,and functional independence were evaluated at admission(T0 baseline visit)and 60 days after(T1)the multidisciplinary rehabilitation including motor exercises,speech therapies,and cognitive *** multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood,motor abilities,autonomy in the activities of daily life,perception of quality of life,cognitive performance and speech ***-motor symptoms may worsen severe disability and reduce quality of *** are often poorly recognized and inadequately ***,multidisciplinary rehabilitative training represents an optimal strategy to improve disease *** study was approved by Istituito di Ricovero e Cura a Carattere Scientifico(irccs)Centro Neurolesi"Bonino-Pulejo"Ethical Committee(approval No.6/2016)in June 2016.

关键词： anxiety depression multidisciplinary rehabilitation Parkinson's disease

Specific contribution of mannose-binding lectin murine isoforms to brain ischemia/reperfusion injury

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Cellular & Molecular Immunology 2020年第3期17卷 218-226页

作者： Laura Neglia Marco Oggioni Domenico Mercurio Maria-Grazia De Simoni Stefano Fumagalli1 istituto di Ricerche Farmacologiche Mario Negri irccs Department of NeuroscienceMilanItaly

Mannose-binding lectin(MBL),an initiator of the lectin pathway(LP)of complement activation,is detrimental in ischemic stroke,as shown in clinical studies and rodent *** humans have one functional MBL protein,rodents have two isoforms,MBL-A and MBL-C,whose functions relative to that of human MBL are *** permit the clinical translation of preclinical data,we aimed to define the specific contributions of MBL-A and MBL-C to brain *** subjected mice with double(MBL^(−/−))or single(MBL-A^(−/−)or MBL-C^(−/−))MBL isoform depletion to transient middle cerebral artery occlusion(tMCAo).MBL^(−/−) mice had fewer neurological deficits and smaller ischemic lesions than WT ***-A^(−/−) mice had smaller lesions than WT mice and exhibited no significant behavioral defects,whereas MBL-C^(−/−) mice did not differ from WT *** induction of Mbl1 and Mbl2(the MBL-A and MBL-C genes)expression 48 h after tMCAo was similar across *** time course of Mbl1 and Mbl2 expression in WT ischemic mice showed that Mbl1 activation occurred earlier(24 h)than Mbl2 activation(48 h).The plasma levels of MBL-A and MBL-C in MBL-C^(−/−) and MBL-A^(−/−) mice,respectively,were similar to those in WT mice both at baseline and at 48 h after *** 48 h,MBL-A^(−/−)ischemic mice showed higher MBL-C levels in the brain than WT *** and MBL-C^(−/−) ischemic mice had higher LP activity in plasma and,accordingly,higher levels of C3 deposition in the brain than MBL-A^(−/−) and MBL^(−/−) *** conclusion,mice with depletion of both MBL isoforms exhibited strong protection from ischemia/reperfusion ***-A was the main contributor to injury,likely owing to its earlier activation after ischemia and more efficient activation of the complement system than MBL-C.

关键词： injury depletion likely

CHK2 kinase in the DNA damage response and beyond

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Journal of Molecular Cell Biology 2014年第6期8卷 442-457页

作者： Laura Zannini Domenico Delia Giacomo Buscemi Department of Experimental Oncology Fondazione IRCCS Istituto Nazionale dei Tumori Via Amadeo 42 20133 Milan Italy

The serine/threonine kinase CHK2 is a keycomponent of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates 〉20 proteins to induce the appropriate cellular response, which, depending on the extent of damage, the cell type, and other factors, could be cell cycle checkpoint activation, induction of apoptosis or senescence, DNA repair, or tolerance of the damage. Recently, CHK2 has also been found to have cellular functions independent of the presence of nuclear DNA lesions. In par- ticular, CHK2 participates in several molecular processes involved in DNA structure modification and cell cycle progression. In this review, we discuss the activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells. These activities are also considered in relation to a possible role of CHK2 in tumorigenesis and, as a consequence, as a target of cancer therapy.

关键词： DNA damage checkpoints apoptosis genomic stability