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Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

World Journal of Clinical Cases 2019年第3期7卷 270-290页

作者： Evaldo Favi Carmelo Puliatti Rajesh Sivaprakasam Mariano Ferraresso federico ambrogi Serena Delbue federico Gervasi Ilaria Salzillo Nicholas Raison Roberto Cacciola Renal Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico Renal Transplantation Barts Health NHS Trust Royal London Hospital Department of Clinical Sciences and Community Health University of Milan Department of Biomedical Surgical and Dental Sciences University of Milan MRC Centre for Transplantation King’s College London

BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also *** To investigate incidence, risk factors, and outcome of BK-virus infection after kidney *** This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and *** BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(< 10000 copies/mL) in 33.3% of these ***-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, P < 0.00001), nephropathy(92.

关键词： Polyomavirus BK virus Kidney transplantation Outcome Risk factors Immunosuppression Human leukocyte antigen Rejection Cytomegalovirus Ethnicity

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Systematic review of ablative therapy for the treatment of renal allograft neoplasms

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World Journal of Clinical Cases 2019年第17期7卷 2487-2504页

作者： Evaldo Favi Nicholas Raison federico ambrogi Serena Delbue Maria Chiara Clementi Luca Lamperti Marta Perego Matteo Bischeri Mariano Ferraresso Renal Transplantation Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilan 20122Italy MRC Centre for Transplantation King’s College LondonLondon WC2R 2LSUnited Kingdom Department of Clinical Sciences and Community Health University of MilanMilan 20122Italy Department of Biomedical Surgical and Dental SciencesUniversity of MilanMilan 20100Italy

BACKGROUND To date,there are no guidelines on the treatment of solid neoplasms in the transplanted ***,allograft nephrectomy has been considered the only reasonable *** recently,nephron-sparing surgery (NSS) and ablative therapy (AT) have been proposed as alternative procedures in selected *** To review outcomes of AT for the treatment of renal allograft *** We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 *** was searched in March 2019 without time restrictions for all papers reporting on radiofrequency ablation (RFA),cryoablation (CA),microwave ablation (MWA),high-intensity focused ultrasound (HIFU),and irreversible electroporation (IRE) of solid tumours of the kidney *** original manuscripts describing actual cases and edited in English were *** relevant articles were accessed in full *** searches included all pertinent *** studies were also assessed for methodological quality using a tool based on a modification of the Newcastle Ottawa *** on recipient characteristics,transplant characteristics,disease characteristics,treatment protocols,and treatment outcomes were extracted and *** the nature and the quality of the studies available (mostly retrospective case reports and small retrospective uncontrolled case series),a descriptive summary was *** Twenty-eight relevant studies were selected describing a total of 100 AT procedures in 92 *** age at diagnosis ranged from 21 to 71 years whereas time from transplant to diagnosis ranged from 0.1 to 312 *** of the neoplasms were asymptomatic and diagnosed incidentally during imaging carried out for screening purposes or for other clinical *** diagnostic modality was Doppler-ultrasound scan followed by computed tomography scan,and magnetic resonance *** tumour types were: pa

关键词： Ablative therapy Cryoablation Radiofrequency ablation Microwave ablation High-intensity focused ultrasonography Irreversible electroporation Neoplasm Kidney transplant Renal allograft Systematic review

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Significance of ipsilateral breast tumor recurrence after breast conserving treatment: role of surgical removal

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Chinese Journal of Cancer Research 2013年第1期25卷 22-31页

作者： Romano Demicheli Ilaria Ardoino federico ambrogi Roberto Agresti Elia Biganzoli Scientific Directorate IRCCS National Cancer Institute Medical Statistics and Biometry University of Milan Breast Surgery IRCCS National Cancer Institute Medical Statistics and Biometry IRCCS National Cancer Institute

Objective： To analyze the pattern over time （dynamics） of further recurrence and death after ipsilateral breast tumor recurrence （IBTR） in breast cancer patients undergoing breast conserving treatment （BCT）. Methods： A total of 338 evaluable patients experiencing IBTR were extracted from a database of 3,293 patients undergoing BCT. The hazard rates for recurrence and mortality throughout 10 years of follow-up after IBTR were assessed and were compared to the analogous estimates associated to the primary treatment. Results： In a time frame with the time origin at the surgical treatment for IBTR, the hazard rate for further recurrence displays a bimodal pattern （peaks at the second and at the sixth year）. Patients receiving mastectomy for IBTR reveal recurrence and mortality dynamics similar to that of node positive （N＋） patients receiving mastectomy as primary surgery, apart from the first two-three years, when IBTR patients do worse. If the patients with time to IBTR longer than 2.5 years are considered, differences disappear. Conclusions： The recurrence and mortality dynamics following IBTR surgical removal is similar to the corresponding dynamics following primary tumor removal. In particular, patients with time to IBTR in excess of 2.5 years behave like N＋ patients following primary tumor removal. Findings may be suitably explained by assuming that the surgical manoeuvre required by IBTR treatment is able to activate a sudden growing phase for tumor foci most of which, as suggested by the systemic model of breast cancer, would have reached the clinical level according to their own dynamics.

关键词： Breast cancer IBTR recurrence dynamics effects of surgery conservative surgery tumor homeostasis

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Differential expression of genes involved in the epigenetic regulation of cell identity in normal human mammary cell commitment and differentiation

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Chinese Journal of Cancer 2014年第10期33卷 501-510页

作者： Danila Coradini Patrizia Boracchi Saro Oriana Elia Biganzoli federico ambrogi Department of Clinical Sciences and Community Health Medical StatisticsBiometry and BioinformaticsUniversity of MilanVia Vanzetti 5Milan 20133Italy Senology Center Ambrosiana ClinicCesano BosconeMilan 20090Italy

The establishment and maintenance of mammary epithelial cell identity depends on the activity of a group of proteins, collectively called maintenance proteins, that act as epigenetic regulators of gene transcription through DNA methylation, histone modification, and chromatin remodeling. Increasing evidence indicates that dysregulation of these crucial proteins may disrupt epithelial cell integrity and trigger breast tumor initiation. Therefore, we explored in silico the expression pattern of a panel of 369 genes known to be involved in the establishment and maintenance of epithelial cell identity and mammary gland remodeling in cell subpopulations isolated from normal human mammary tissue and selectively enriched in their content of bipotent progenitors, committed luminal progenitors, and differentiated myoepithelial or differentiated luminal cells. The results indicated that, compared to bipotent cells, differentiated myoepithelial and luminal subpopulations were both characterized by the differential expression of 4 genes involved in cell identity maintenance: CBX6 and PCGF2, encoding proteins belonging to the Polycomb group, and SMARCD3 and SMARCE1, encoding proteins belonging to the Trithorax group. In addition to these common genes, the myoepithelial phenotype was associated with the differential expression of HDAC1, which encodes histone deacetylase 1, whereas the luminal phenotype was associated with the differential expression of SMARCA4 and HAT1, which encode a Trithorax protein and histone acetylase 1, respectively. The luminal compartment was further characterized by the overexpression of ALDH1A3 and GATA3, and the down-regulation of NOTCH4 and CCNB1, with the latter suggesting a block in cell cycle progression at the G2 phase. In contrast, myoepithelial differentiation was associated with the overexpression of MYC and the down-regulation of CCNE1, with the latter suggesting a block in cell cycle progression at the G1 phase.

关键词：基因表达差异乳腺细胞分化遗传调控乳腺上皮细胞组蛋白修饰人类表观

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Epithelial cell identity in hyperplastic precursors of breast cancer

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Chinese Journal of Cancer 2015年第3期34卷 121-129页

Introduction:In the adult human breast,hyperplastic enlarged lobular unit(HELU) and atypical ductal hyperplasia(ADH) are two common abnormalities that frequently coexist with ductal carcinoma in situ(DCIS).For this reason,they have been proposed as the early steps in a biological continuum toward breast ***:We investigated in silico the expression of 369 genes experimentally recognized as involved in establishing and maintaining epithelial cell identity and mammary gland remodeling,in HELUs or ADHs with respect to the corresponding patient-matched normal ***:Despite the common luminal origin,HELUs and ADHs proved to be characterized by distinct gene profiles that overlap for 5 genes *** HELUs were associated with the overexpression of progesterone receptor(PGR),ADHs were characterized by the overexpression of estrogen receptor 1(ESR1) coupled with the overexpression of some proliferation-associated ***:This unexpected finding contradicts the notion that in differentiated luminal cells the expression of estrogen receptor(ER) is dissociated from cell proliferation and suggests that the establishing of an ER-dependent signaling is able to sustain cell proliferation in an autocrine manner as an early event in tumor *** clinical evidence indicates that only a fraction of HELUs and ADHs evolve to invasive cancer,present findings warn that exposure to synthetic progestins,frequently administered as hormone-replacement therapy,and estrogens,when abnormally produced by adipose cells and persistently present in the stroma surrounding the mammary gland,may cause these hyperplastic lesions.

关键词：上皮细胞乳腺癌增生性雌激素受体孕激素受体前体细胞增殖过度表达

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Differential Expression of Genes Involved in Cell Polarity, EMT and Cell-Fate in Breast Cancer and Corresponding Normal Tissue

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Advances in Breast Cancer Research 2012年第2期1卷 12-19页

作者： Danila Coradini federico ambrogi Saro Oriana Elia Biganzoli Patrizia Boracchi Department of Clinical and Community Health Sciences Medical Statistics Biometry and Bioinformatics University of Milano Italy Senology Center Casa di Cura Ambrosiana Istituto Sacra Famiglia Cesano Boscone Milano Italy

Objectives: Cell polarity and epithelial morphology are peculiar features of cells forming the terminal ductal lobular unit, and they are early lost during neoplastic transformation because of an epithelial-mesenchymal transition (EMT). To understand these early events we analyzed a set of 125 genes related to cell polarity, EMT and cell-fate decision in 26 breast cancer specimens and corresponding patient-matched normal tissue. Methods: The difference of gene expression was explored by t-paired test. In addition, to evidence latent variables accounting for genes correlations, a Factor Analysis was applied as exploratory technique. Results: Among the 90 differentially expressed genes, those coding for cell polarity complexes, apical-junctional components and luminal cytokeratins were overexpressed in tumor samples (suggesting a terminally differentiated phenotype) whereas those coding for stemness-associated features or related with EMT were expressed in normal tissues but not in tumor samples, suggesting the persistence of stem/progenitor cells. Factor analysis confirmed these findings and indicated that the difference between tumors and normal tissues can be synthesized in three main features representative of specific molecular/morphological alterations. Conclusions: The a priori definition of a selected panel of genes and the application of an exploratory statistical approach, greatly contribute to reduce the intrinsic biological complexity of tumor specimens and to describe the difference between tumor specimens and corresponding histologically normal tissues.

关键词： Breast Cancer Cell-Fate Decision Cell Polarity Epithelial-Mesenchymal Transition Histologically Normal Tissue

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Essential oils as solvents and core materials for the preparation of photo-responsive polymer nanocapsules

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Nano Research 2018年第5期11卷 2783-2795页

作者： Valentina Marturano Valentina Bizzarro Adriana De Luise Anna Calarco Veronica ambrogi Marta Giamberini Bartosz Tylkowski Pierfrancesco Cerruti Department of Chemical Sciences University of Naples "Federico Ⅱ" Via Cynthia 4 Napoli 80125 Italy Institute for Polymers Composites and Biomaterials (IPCB-CNR) Via Campi Flegrei 34 Pozzuoli (NA) 80078 Italy Institute of Agro-Environmental and Forest Biology (IBAF-CNR) Via Pietro Castellino 111 Napoli 80131 Italy Department of Chemical Materials and Production Engineering (DICMAPI) University of Naples "Federico Ⅱ" P. le Tecchio 80 Napoli 80125 Italy Department of Chemical Engineering (DEQ) Universitat Rovira i Virgili Av. Pa'fsos Catalans 26 Tarragona 43007 Spain Chemistry Technology Centre of Catalonia (CTQC) C/Marcel-Ⅱ Domingo Tarragona 43007 Spain

Light-triggered release of active ingredients from polymeric nanosized capsules can be employed in a wide range of applications, such as biomedicine, active packaging, and cosmetics. However, the preparation of core-shell polymeric nanocarriers typically involves the use of toxic organic solvents. To improve the sustainability and safety of nanocapsule applications, we demonstrate that natural essential oils can be used both as solvent and active material in light-responsive nanocapsules synthesized via miniemulsion polycondensation. The documented antimicrobial, anti-inflammatory, and antioxidant activity of essential oils enables the design of multipurpose light-responsive delivery platforms. The photo-responsive behavior of the capsules, achieved by means of photochromic azobenzene segments embedded in the capsule shell, is triggered by UV light irradiation （λmax= 360 nm）. Light-induced release kinetics of the essential oils and a fluorescent probe molecule, coumarin-6, is evaluated via UV-vis spectroscopy and spectrofluorimetry, respectively, demonstrating the efficiency and reliability of the release mechanism. Biological tests prove that the capsules are non-cytotoxic and readily internalized by cells, indicating the suitability of these smart nanocarriers for biological applications.

关键词： light-responsive polymer nanocapsules essential oils azobenzene controlled release cytotoxicity

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