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5. Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies

Author

Visioli, A, Giani, F, Trivieri, N, Pracella, R, Miccinilli, E, Cariglia, M, Palumbo, O, Arleo, A, Dezi, F, Copetti, M, Cajola, L, Restelli, S, Papa, V, Sciuto, A, Latiano, T, Carella, M, Amadori, D, Gallerani, G, Ricci, R, Alfieri, S, Pesole, G, Vescovi, A, Binda, E, Visioli A., Giani F., Trivieri N., Pracella R., Miccinilli E., Cariglia M. G., Palumbo O., Arleo A., Dezi F., Copetti M., Cajola L., Restelli S., Papa V., Sciuto A., Latiano T. P., Carella M., Amadori D., Gallerani G., Ricci R., Alfieri S., Pesole G., Vescovi A. L., Binda E., Visioli, A, Giani, F, Trivieri, N, Pracella, R, Miccinilli, E, Cariglia, M, Palumbo, O, Arleo, A, Dezi, F, Copetti, M, Cajola, L, Restelli, S, Papa, V, Sciuto, A, Latiano, T, Carella, M, Amadori, D, Gallerani, G, Ricci, R, Alfieri, S, Pesole, G, Vescovi, A, Binda, E, Visioli A., Giani F., Trivieri N., Pracella R., Miccinilli E., Cariglia M. G., Palumbo O., Arleo A., Dezi F., Copetti M., Cajola L., Restelli S., Papa V., Sciuto A., Latiano T. P., Carella M., Amadori D., Gallerani G., Ricci R., Alfieri S., Pesole G., Vescovi A. L., and Binda E.

Abstract

Background: Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings: We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation: Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund: This work was financially supported by grants from “Ministero della Salute Italiano”(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from “Associazione Italiana Cancro” (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

Published
2019

10. Reconnaissance of 2016 Central Italy Earthquake Sequence

Author

Stewart J. P., Zimmaro P., Lanzo G., Mazzoni S., Ausilio E., Aversa S., Bozzoni F., Cairo R., Capatti M. C., Castiglia M., Chiabrando F., Chiaradonna A., D'Onofrio A., Dashti S., De Risi R., De Silva F., Della Pasqua F., Dezi F., Di Domenica A., Di Sarno L., Durante M. G., Falcucci E., Foti S., Franke K. W., Galadini F., Giallini S., Gori S., Kayen R. E., Kishida T., Lingua A., Lingwall B., Mucciacciaro M., Pagliaroli A., Passeri F., Pelekis P., Pizzi A., Reimschiissel B., Santo A., De Magistris F. S., Scasserra G., Sextos A., Sica S., Silvestri F., Simonelli A. L., Spano A., Tommasi P., Tropeano G., DI SARNO, LUIGI, Stewart, J. P., Zimmaro, P., Lanzo, G., Mazzoni, S., Ausilio, E., Aversa, S., Bozzoni, F., Cairo, R., Capatti, M. C., Castiglia, M., Chiabrando, F., Chiaradonna, A., D'Onofrio, A., Dashti, S., De Risi, R., De Silva, F., Della Pasqua, F., Dezi, F., Di Domenica, A., Di Sarno, L., Durante, M. G., Falcucci, E., Foti, S., Franke, K. W., Galadini, F., Giallini, S., Gori, S., Kayen, R. E., Kishida, T., Lingua, A., Lingwall, B., Mucciacciaro, M., Pagliaroli, A., Passeri, F., Pelekis, P., Pizzi, A., Reimschiissel, B., Santo, A., De Magistris, F. S., Scasserra, G., Sextos, A., Sica, S., Silvestri, F., Simonelli, A. L., Spano, A., Tommasi, P., and Tropeano, G.

Subjects
geotechnical, Event (relativity), 0211 other engineering and technologies, 02 engineering and technology, Reconnaissance, earthquake, Italy, central, geotechnical, 010502 geochemistry & geophysics, 01 natural sciences, Geotechnical Engineering and Engineering Geology, Geophysics, damage patterns, Arquata del Tronto, Normal fault, 0105 earth and related environmental sciences, Sequence (medicine), Central Italy EQs, 021110 strategic, defence & security studies, Amatrice, reconnaissance of geotechnical aspects, Central Italy earthquake sequence, Italy, earthquake, central, site effects, Geology, Seismology, Reconnaissance, Central Italy EQs, reconnaissance of geotechnical aspects
Abstract

The Central Italy earthquake sequence nominally began on 24 August 2016 with a M6.1 event on a normal fault that produced devastating effects in the town of Amatrice and several nearby villages and hamlets. A major international response was undertaken to record the effects of this disaster, including surface faulting, ground motions, landslides, and damage patterns to structures. This work targeted the development of high-value case histories useful to future research. Subsequent events in October 2016 exacerbated the damage in previously affected areas and caused damage to new areas in the north, particularly the relatively large town of Norcia. Additional reconnaissance after a M6.5 event on 30 October 2016 documented and mapped several large landslide features and increased damage states for structures in villages and hamlets throughout the region. This paper provides an overview of the reconnaissance activities undertaken to document and map these and other effects, and highlights valuable lessons learned regarding faulting and ground motions, engineering effects, and emergency response to this disaster.

Published
2018

14. Stemness underpinning all steps of human colorectal cancer defines the core of effective therapeutic strategies

Author

Visioli, A., Giani, F., Trivieri, N., Pracella, R., Miccinilli, E., Cariglia, M. G., Palumbo, O., Arleo, A., Dezi, F., Copetti, M., Cajola, L., Restelli, S., Papa, Valerio, Sciuto, A., Latiano, T. P., Carella, M., Amadori, D., Gallerani, G., Ricci, Riccardo, Alfieri, Sergio, Pesole, G., Vescovi, A. L., Binda, E., Papa V. (ORCID:0000-0002-3709-8924), Ricci R. (ORCID:0000-0002-9089-5084), Alfieri S. (ORCID:0000-0002-0404-724X), Visioli, A., Giani, F., Trivieri, N., Pracella, R., Miccinilli, E., Cariglia, M. G., Palumbo, O., Arleo, A., Dezi, F., Copetti, M., Cajola, L., Restelli, S., Papa, Valerio, Sciuto, A., Latiano, T. P., Carella, M., Amadori, D., Gallerani, G., Ricci, Riccardo, Alfieri, Sergio, Pesole, G., Vescovi, A. L., Binda, E., Papa V. (ORCID:0000-0002-3709-8924), Ricci R. (ORCID:0000-0002-9089-5084), and Alfieri S. (ORCID:0000-0002-0404-724X)

Abstract

Background: Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings: We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation: Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund: This work was financially supported by grants from “Ministero della Salute Italiano”(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from “Associazione Italiana Cancro” (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

Published
2019

16. Engineering Reconnaissance following the October 2016 Central Italy Earthquakes. Version 2

Author

Stewart J.P., Lanzo G., Ausilio E., Cairo Bozzoni F., Capatti M.C., della Pasqua F., Dezi F., Di Sarno L., Simonelli L.A., Foti S., Chiabrando F., Dabove P., Di Pietra V., Maschio P., Passeri F., Sgobio A., Teppati Lose' L., Franke K., Reimschiissel B., Galadini F., Falcucci E., Gori, Kayen R.E., Kishida T., Lingwall B., Pagliaroli A., Giallini S., Gogoladze Z., Vessia G., Pizzi A., Di Domenica a., Santo A., De Falco M., Forte G., Pelekis P., Scasserra G., Santucci de Magistris F., Castiglia M., Fierro T., Gautam D., Mignelli F., Staniscia F., Sextos A., De Risi R., Sica S., Mucciacciaro M., Tommasi P., Di Giulio A., Tropeano G., Durante M.G., and Zimmaro P.

Subjects
Structural Damage, Earthquake, Central Italy, Landslide, Site Effect
Abstract

The central Italy earthquakes occurred on 26 and 30 October 2016. The Italy-US GEER team effort combines traditional reconnaissance activities of on-ground recording and mapping of field conditions, with advanced imaging and damage detection routines enabled by state-of-the-art geomatics technology. We describe preliminary findings useful for the broad technical community, emergency responders, and general public. These findings concern attributes of the causative fault system, surface fault rupture, recorded ground motions, landslides and rockfalls, damage to building structures and their spatial patterns, and damage to other types of structures, including bridges.

Published
2017
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17. Assessment survey of public school buildings after august 2016 Italy earthquake: preliminary results

Author

Abruzzese, D., Bergami, A., Biondi, S., Camata, G., Canciani, M., Carbonari, S., Cimino, A., Dall'Asta, Andrea, Dezi, F., Dezi, L., Di Fabio, F., Ferracuti, B., Fiorentino, G., Forte, A., Fragiacomo, M., Gara, F., Ianniruberto, U., Imperatore, S., Lavorato, D., Leoni, Graziano, Liberatore, D., Liberatore, L., Mannella, A., Martinelli, A., Mutignani, C., Nuti, C., Paolacci, F., Pagano, E., Rasulo, A., Santini, S., Sorrentino, L., Vanzi, I., and Zucconi, M.

Subjects
ASSESSMENT SURVEY, EARTHQUAKE, SCHOOL BUILDINGS
Abstract

The seismic events which hit Central Italy on 24 August, October 26 and October 30 2016 have caused casualties and major damage mostly to buildings and architectural heritage of the Italian Regions of Abruzzo, Lazio, Marche and Umbria; the most deadly events occurred on August 24, 2016 and caused a total of 298 victims and about 4.600 people evacuated. The mainshock occurred at 3:36 am with epicenter close to Accumoli (Rieti province) and a magnitude Mw 6.0; the aftershock occurred at 4.33 am with epicenter close to Norcia (Perugia province) and a magnitude Mw 5.3. Most of the victims were in the areas of Amatrice (Ri), Accumoli (Ri) and Arquata del Tronto (AP). The earthquakes of October 30 didn't cause any victim but only some injured thanks to the fact that people was already evacuated and also because the Civil Protection was already present on the territory. Nevertheless, the impact of this seismic event was destructive; many small towns and villages, which have survived to the first earthquake, were heavily damaged. In the days following the earthquake of august 24 the Department of Civil Protection and RELUIS started the usability surveys by using the Aedes form (Italian acronym for "accessibility and damage during seismic emergency" [1]) which guides the inspector to rapidly assess the usability of a structure, including the description of damage and all the details of the building.

Published
2017

23. Numerical and Simplified Methods for Soil-pile Interaction Analysis.

Author

Dezi, F., Carbonari, S., Morici, M., and Leoni, G.

Subjects
SEISMIC waves, DYNAMIC stiffness, THEORY of wave motion
Abstract

The paper presents a review of the analytical and numerical procedures developed by the authors for the dynamic analysis of soil-pile foundation systems subjected to the propagation of seismic waves in the soil. Inclined and vertical single piles and groups constituted by piles with a generic inclination are addressed. For the former, an analytical approach based on the beam on dynamic Winkler foundation approach is adopted; the pile is modelled as a Euler-Bernoulli beam and the soil-pile interaction is captured by defining soil impedances relevant to the harmonic vibrations of rigid disks available in the literature. The coupled flexural and axial behaviour of the pile is solved analytically exploiting exponential matrices. The pile group dynamic problem is similarly formulated but the solution is achieved exploiting the finite element approach. Besides numerical models, simplified approaches based on static equivalent methods and simplified formulas are also addressed to estimate the maximum kinematic stress resultants on vertical piles subjected to lateral seismic excitations. The reliability of the presented tools in capturing the dynamic stiffness and the overall kinematic response of pile foundations is shown by comparing results with those available in the literature or achieved through refined finite element models. From an engineering point of view, the proposed approaches assure a sufficient accuracy and may substitute refined computational demanding numerical models. [ABSTRACT FROM AUTHOR]

Published
2020

24. Wnt5a drives an invasive phenotype in human glioblastoma stem-like cells

Author

Binda, E, Visioli, A, Giani, F, Trivieri, N, Palumbo, O, Restelli, S, Dezi, F, Mazza, T, Fusilli, C, Legnani, F, Carella, M, Di Meco, F, Duggal, R, Vescovi, A, TRIVIERI, NADIA, Vescovi, AL, Binda, E, Visioli, A, Giani, F, Trivieri, N, Palumbo, O, Restelli, S, Dezi, F, Mazza, T, Fusilli, C, Legnani, F, Carella, M, Di Meco, F, Duggal, R, Vescovi, A, TRIVIERI, NADIA, and Vescovi, AL

Abstract

Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a.We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5aHigh). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma.

Published
2017

27. Linee di indirizzo per interventi su edifici industriali monopiano colpiti dal terremoto della Pianura Padana Emiliana del maggio 2012 non progettati con criteri antisismici: aspetti geotecnici

Author

Maugeri M., Abate G., Aversa S., Boldini D., Dezi F., Fioravante V., Ghinelli A., Massimino M. R., Santucci de Magistris F., Sica S., Silvestri F., Vannucchi G., Maugeri, M., Abate, G., Aversa, S., Boldini, D., Dezi, F., Fioravante, V., Ghinelli, A., Massimino, M. R., Santucci de Magistris, F., Sica, S., Silvestri, F., and Vannucchi, G.

Published
2013

28. Earthquake Geotechnical Engineering aspects: the 2012 Emilia-Romagna earthquake (Italy)

Author

Fioravante V., Giretti D., Abate G., Aversa S., Capilleri P. P., Cavallaro A., Chamlagain D., Crespellani T., Dezi F., Facciorusso J., Ghinelli A., Grasso S., Lanzo G., Madiai C., Massimino M. R., Maugeri M., Pagliaroli A., Ranieri C., Tropeano G., Santucci De Magistris F., Sica S., Silvestri F., Vannucchi G., BOLDINI, DANIELA, Shamsher Prakash, Fioravante V., Giretti D., Abate G., Aversa S., Boldini D., Capilleri P. P., Cavallaro A., Chamlagain D., Crespellani T., Dezi F., Facciorusso J., Ghinelli A., Grasso S., Lanzo G., Madiai C., Massimino M. R., Maugeri M., Pagliaroli A., Ranieri C., Tropeano G., Santucci De Magistris F., Sica S., Silvestri F., and Vannucchi G.

Subjects
remedial measures, geotechnical engineering, Emilia-Romagna earthquake, liquefaction, damage to industrial buildings, damage to industrial building
Abstract

On May 20, 2012 an earthquake of magnitude ML=5.9 struck the Emilia Romagna Region of Italy and a little portion of Lombardia Region. Successive earthquakes occurred on May 29, 2012 with ML=5.8 and ML=5.3. The earthquakes caused 27 deaths, of which 13 on industrial buildings. The damage was considerable. 12,000 buildings were severely damaged; big damages occurred also to monuments and cultural heritage of Italy, causing the collapse of 147 campaniles. The damage is estimated in about 5-6 billions of euro. To the damage caused to people and buildings, must be summed the indirect damage due to loss of industrial production and to the impossibility to operate for several months. The indirect damage could be bigger than the direct damage caused by the earthquake. The resilience of the damaged cities to the damage to the industrial buildings and the lifelines was good enough, because some industries built a smart campus to start again to operate in less of one month and structural and geotechnical guidelines were edited to start with the recovering the damage industrial buildings. In the paper a damage survey is presented and linked with the ground effects. Among these, soil amplification and liquefaction phenomena are analyzed, basing on the soil properties evaluation by field and laboratory tests. Particular emphasis is devoted to the damaged suffered by the industrial buildings and to the aspects of the remedial work linked with the shallow foundation inadequacy and to the liquefaction mitigation effects.

Published
2013

29. Earthquake geotechnical engineering aspects of the 2012 Emilia-Romagna Earthquake (Italy)

Author

Fioravante V., Abate G., Giretti D., Aversa S., Boldini D., Crespellani T., Dezi F., Facciorusso J., Ghinelli A., Grasso S., Lanzo G., Madiai C., Massimino M. R., Maugeri M., Tropeano G., Santucci de Magistris F., Sica S., Vannucchi G., SILVESTRI, FRANCESCO, Fioravante, V., Abate, G., Giretti, D., Aversa, S., Boldini, D., Crespellani, T., Dezi, F., Facciorusso, J., Ghinelli, A., Grasso, S., Lanzo, G., Madiai, C., Massimino, M. R., Maugeri, M., Tropeano, G., Santucci de Magistris, F., Sica, S., Silvestri, Francesco, and Vannucchi, G.

Published
2013

37. Earthquake Geotechnical Engineering Aspects: The 2012 Emilia Romagna Earthquake (Italy)

Author

Fioravante V. 1, Giretti D. 2, Abate G. 3, Aversa S. 4, Boldini D. 5, Capilleri P. P. 6, Cavallaro A. 7, Chamlagain D. 8, Crespellani T. 9, Dezi F. 10, Facciorusso J. 11, Ghinelli A. 12, Grasso S. 13, Lanzo G. 14, Madiai C. 15, Massimino M. R. 16, Maugeri M. 17, Pagliaroli A. 18, Ranieri C. 19, Tropeano G. 20, Santucci De Magistris F. 21, Sica S. 22, Silvestri F. 23, and Vannucchi G. 24

Abstract

On May 20, 2012 an earthquake of magnitude ML=5.9 struck the Emilia Romagna Region of Italy and a little portion of Lombardia Region. Successive earthquakes occurred on May 29, 2012 with ML=5.8 and ML=5.3. The earthquakes caused 27 deaths, of which 13 on industrial buildings. The damage was considerable. 12,000 buildings were severely damaged; big damages occurred also to monuments and cultural heritage of Italy, causing the collapse of 147 campaniles. The damage is estimated in about 5-6 billions of euro. To the damage caused to people and buildings, must be summed the indirect damage due to loss of industrial production and to the impossibility to operate for several months. The indirect damage could be bigger than the direct damage caused by the earthquake. The resilience of the damaged cities to the damage to the industrial buildings and the lifelines was good enough, because some industries built a smart campus to start again to operate in less of one month and structural and geotechnical guidelines were edited to start with the recovering the damage industrial buildings. In the paper a damage survey is presented and linked with the ground effects. Among these, soil amplification and liquefaction phenomena are analyzed, basing on the soil properties evaluation by field and laboratory tests. Particular emphasis is devoted to the damaged suffered by the industrial buildings and to the aspects of the remedial work linked with the shallow foundation inadequacy and to the liquefaction mitigation effects.

Published
2013

40. Earthquake geotechnical engineering aspects: the 2012 Emilia-Romagna earthquake (Italy)

Author

Fioravante V., Giretti D., Abate, G., Aversa, S., Boldini, D., Capilleri, P., Cavallaro, A., Chamlagain, D., Crespellani T. Dezi ., F, Facciorusso, J., Ghinelli, A., Grasso, S., Lanzo, Giuseppe, Madiai, C., Massimino, M. R., Maugeri, M., Pagliaroli, A., Ranieri, C., Tropeano, G., Santucci de Magistris, F., Sica, S., and Silvestri, F.

Subjects
remedial measures, geotechnical engineering, Emilia-Romagna earthquake, liquefaction, damage to industrial buildings
Published
2013

41. EARTHQUAKE GEOTECHNICAL ENGINEERING ASPECTS OF THE 2012 EMILIA-ROMAGNA EARTHQUAKE (ITALY)

Author

Fioravante, V., Giretti, D., Abate, G., Aversa, S., Boldini, D., Capilleri, P., Cavallaro, A., Chamlagaind, Crespellani, T., Dezi, F., Facciorusso, J., Ghinelli, A., Grasso, Salvatore, Lanzo, G., Madiai, C., Massimino, MARIA ROSSELLA, Maugeri, M., Pagliaroli, A., Rainieri, C., Tropeano, G., Santucci De Magistric, F., Sica, S., Silvestri, F., and Vannucchi, G.

Subjects
Liquefaction, Ground motion, Industrial building foundation
Published
2013

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