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Dam-break Modeling in Alpine Valleys

Journal of Mountain Science 2014年第6期11卷 1429-1441页

作者： marco pilotti Andrea MARANZONI Luca MILANESI Massimo TOMIROTTI Giulia VALERIO DICATAM Università degli Studi di BresciaVia Branze 43 25123 - Brescia Italy DICATe A Parco Area delle Scienze 181/A43124 - Parma Italy

Dam-break analysis is of great importance in mountain environment,especially where reservoirs are located upstream of densely populated areas and hydraulic hazard should be assessed for land planning ***,there is a need to identify suitable operative tools which may differ from the ones used in flat flood-prone *** paper shows the results provided by a 1D and a 2D model based on the Shallow Water Equations(SWE) for dam-break wave propagation in alpine *** 1D model takes advantage of a topographic toolkit that includes an algorithm for pre-processing the Digital Elevation Model(DEM) and of a novel criterion for the automatic cross-section space *** 2D model is FLO-2D,a commercial software widely used for flood routing in mountain *** order to verify the predictive effectiveness of these numerical models,the test case of the Cancano dam-break has been recovered from the historical study of De Marchi(1945),which provides a unique laboratory data set concerning the consequences of the potential collapse of the former Cancano dam(Northern Italy).The measured discharge hydrograph at the dam also provides the data to test a simplified method recently proposed for the characterization of the hydrograph following a sudden dam-break.

关键词：二维模型溃坝高山峡谷人口稠密地区数字高程模型洪水演进一维模型山地环境

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Experience with peritoneal mesothelioma at the Milan National Cancer Institute

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World Journal of Gastrointestinal Oncology 2010年第2期2卷 76-84页

作者： Marcello Deraco Dario Baratti Antonello Domenico Cabras Nadia Zaffaroni Federica Perrone Raffaella Villa Jenny Jocollè Maria Rosaria Balestra Shigeki Kusamura Barbara Laterza Silvana pilotti Department of Surgery National Cancer Institute Department of Pathology National Cancer Institute Department of Experimental Oncology National Cancer Institute

Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and rapidly fatal *** options have traditionally been limited and *** biologic and molecular events correlated with poor responsiveness to therapy are still poorly *** recent years,an innovative treatment approach involving aggressive cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has reportedly resulted in improved outcome,as compared to historical *** 1995,at the National Cancer Institute (NCI) of Milan (Italy),patients with DMPM have been treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC).In the present paper,clinical experiences and basic science investigations on DMPM at Milan NCI are *** and long-term outcome results with CRS and HIPEC are ***-pathological prognostic factors were investigated by multivariate *** pathologic features and immunohistochemical markers related to DMPM biologic behavior were assessed in a large case-series uniformly treated at our *** prevalence and prognostic role of telomere maintenance mechanisms,which account for the limitless cell replicative potential of many malignancies,were *** dysregulation of the apoptotic pathways may play a role in the relative chemo-resistance of DMPM and a better understanding of apoptosis-related mechanisms could result in novel targeted therapeutic *** this basis,the expression of survivin and other IAP family members (IAP-1,IAP-2,and X-IAP),the pro-apoptotic protein Smac/DIABLO,and antigens associated with cell proliferation (Ki-67) and apoptosis (caspase-cleaved cytokeratin-18) were ***,analyses of EGFR,PDGFRA and PDGFRB were performed to ascertain if deregulation of RTK could offer useful alternative therapeutic targets.

关键词： Peritoneal mesothelioma Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Telomerase Surviving Apoptosis Receptor tyrosin kinase

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The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial-mesenchymal transition, and immune response

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Cancer Communications 2018年第1期38卷 745-758页

作者： Andrea Devecchi Loris De Cecco Matteo Dugo Donata Penso Gianpaolo Dagrada Silvia Brich Silvia Stacchiotti Marialuisa Sensi Silvana Canevari Silvana pilotti Platform of Integrated Biology Department of Applied Research and Technology DevelopmentFondazione IRCCS Istituto Nazionale dei Tumori di Milano2133 MilanItaly Department of Diagnostic Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale dei Tumori di Milano20133 MilanItaly Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori di Milano20133 MilanItaly

Background:Desmoplastic small round cell tumor(DSRCT)is a rare,aggressive,and poorly investigated simple sarcoma with a low frequency of genetic deregulation other than an Ewing sarcoma RNA binding protein 1(EWSR1)-Wilm’s tumor suppressor(WT1)*** used whole-exome sequencing to interrogate six consecutive pretreated DSRCTs whose gene expression was previously ***:DNA libraries were prepared from formalin-fixed,paraffin-embedded archival tissue specimens following the Agilent SureSelectXT2 target enrichment protocol and sequenced on Illumina NextSeq *** sequence data were aligned to the reference genome with Burrows-Wheeler Aligner *** mutations and copy number alterations(CNAs)were identified using MuTect2 and EXCAVATOR2,*** functions associated with altered genes were investigated through Ingenuity Pathway Analysis(IPA)***:A total of 137 unique somatic mutations were identified:133 mutated genes were case-specific,and 2 were mutated in two cases but in different *** the 135 mutated genes,27%were related to two biological categories:DNA damage-response(DDR)network that was also identified through IPA and mesenchymal-epithelial reverse transition(MErT)/epithelial-mesenchymal transition(EMT)already demonstrated to be relevant in *** mutated genes in the DDR network were involved in various steps of transcription and particularly affected *** of these genes encoded RNA-binding proteins or DNA/RNA-binding proteins,which were recently rec-ognized as a new class of DDR *** in genes/gene families,involved in MErT/EMT and DDR,were recurrent across patients and mostly segregated in the MErT/EMT *** addition,recurrent gains of regions in chromosome 1 involving many MErT/EMT gene families and loss of one arm or the entire chromosome 6 affecting relevant immune-regulatory genes were ***:The emerging picture is an extreme inter-tumor heter

关键词： Desmoplastic small round cell tumor Whole-exome sequencing Somatic mutations Copy number alterations Chromosome imbalance DNA damage response Genomic stability Mesenchymal-epithelial reverse transition/epithelial-mesenchymal transition Immune response

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可手术乳腺癌CMF辅助化疗随机研究的30年随访:队列研究

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英国医学杂志中文版 2005年第3期8卷 148-151页

作者： Gianni Bonadonna Angela Moliterni Milvia Zambetti Maria Grazia Daidone Silvana pilotti Luca Gianni Pinuccia Valagussa 樊英 Istituto Nazionale Tumori 20133 Milano Italy

目的根据1973年6月至1980年12月期间的3项连续随机试验和1项观察研究,评价有复发风险的可手术乳腺癌患者使用环磷酰胺、甲氨蝶呤和氟尿嘧啶(CMF)辅助治疗的长期有效性。设计队列研究。地点意大利米兰国家肿瘤研究所。主要结局指标无复... 详细信息

目的根据1973年6月至1980年12月期间的3项连续随机试验和1项观察研究,评价有复发风险的可手术乳腺癌患者使用环磷酰胺、甲氨蝶呤和氟尿嘧啶(CMF)辅助治疗的长期有效性。设计队列研究。地点意大利米兰国家肿瘤研究所。主要结局指标无复发生存和总生存,采用单变量和多变量分析。结果在首项研究随访平均28.5年后,发现辅助CMF能显著降低复发的相对危险度(危险比为0.71,95%可信区间0.56～0.91,P=0.005)并减少死亡(0.79,0.63～0.98,P=0.04)。12个周期的CMF似乎并不优于6个周期的相对短期治疗。在淋巴结和雌激素受体阴性的研究中,平均随访20年后,静脉使用CMF能显著降低疾病复发的相对危险度(0.65,0.47～0.90,P=0.009)以及死亡的相对危险度(0.65,0.470.92,P=0.01)。结论如应用适当,CMF方案能使具有远处复发风险的患者获益,没有证据显示它对任何研究亚组有不良影响。

关键词：队列研究随访随机研究辅助化疗手术相对危险度雌激素受体阴性复发风险 1980年乳腺癌患者意大利米兰多变量分析 CMF方案观察研究随机试验环磷酰胺辅助治疗氟尿嘧啶甲氨蝶呤结局指标可信区间短期治疗

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KIT ATP袋结构域的一个新突变导致胃肠间质肿瘤患者对伊马替尼获得性耐药

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世界核心医学期刊文摘（胃肠病学分册） 2005年第2期1卷 28-28页

作者： Tamborini E. Bonadiman L. Greco A. S. pilotti 翟惠虹 U.of Exp. Molecular Pat hology Department of PathologyIst. Naz. Stud. e Al Cura dei Tumori Milan Ita ly

Background &Aims: Imatinib, a tyrosine kinase inhibitor of BCR-ABL, KIT, and platelet-derived growth factor receptor, is used in patients with chronic myel ogenous leukemia (CML)and gastrointestinal stromal tumors (GIST). Primary and ac quired resistance to the drug can occur in both diseases. Molecular mechanisms h ave been reported in CML and GIST for primary resistance, whereas extensive stud ies on the mechanisms responsible for secondary resistance have been almost excl usively reported for CML. Methods: In a patient with advanced GIST undergoing im atinib therapy,an isolated progressing peritoneal mass was excised, along with 2 still-responding lesions. Complementary DNA and genomic DNA were analyzed by s equencing for c-Kit gene mutations. KIT receptor expression and phosphorylation status were assessed by immunoprecipitation and Western blot. Transient-transf ection experiments were performed with mutagenized KIT constructs, and their act ivation status was assessed. Results: In addition to an exon11 mutation, shared among all of the analyzed lesions, a novel point mutation in c-Kit exon 14 resu lting in T670I substitution was found only in the progressing lesion, which harb ored aphosphorylated receptor, as opposed to the finding of an inactive receptor in responding lesions. Functional analyses showed that KIT/T670I is insensitive to imatinib and that T670I mutation,introduced in a receptor responding to imat inib, subverted its sensitivity to the drug. Conclusions: This new mutation was confined to the progressing lesion; the resulting amino acidic substitution, T67 0I, affecting the ATP/imatinib pocket of KIT,makes it insensitive to the drug. I nterestingly, this substitution is a homologue to the T315I mutation already rep orted in CML,where it is responsible for acquired resistance to imatinib.

关键词：间质肿瘤 KIT ATP 伊马替尼获得性耐药结构域肾上腺素注射慢性髓性白血病免疫沉淀法消化性溃疡出血胶圈套扎

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