Search

Your search keyword '"A, Isacchi"' showing total 1,180 results
Start Over Author "A, Isacchi"
1,180 results on '"A, Isacchi"'

1. An experimental methodology to support development of yaw damper prototypes based on a hardware-in-the-loop test bench.

Author

Isacchi, Gioele and Ripamonti, Francesco

Subjects
*HIGH speed trains, *MOTOR vehicle springs & suspension, *VEHICLE models, *PROTOTYPES, *MANUFACTURING industries
Abstract

Research and development of innovative suspension components for rail vehicles have involved huge investments in recent years. Research efforts have focussed on designing and optimising suspension systems to deal with the new challenges introduced in railway dynamics by the continuous increase in vehicle speed. In particular, yaw dampers have been a relevant research topic due to their influence on vehicle stability. In this context, this paper aims to propose a Hardware-In-the-Loop (HIL) methodology for testing yaw dampers under experimental conditions close to real operating scenarios, comparing the influence of different prototypes on the stability of high-speed rail vehicles. A reduced vehicle model is proposed for real-time integration in HIL tests. This model provides a reference stroke to be imposed on the prototype tested, considering the actual damping force provided by the device being analysed. Two yaw damper prototypes are introduced to validate the proposed methodology by means of comparative analysis at different vehicle speeds. The experimental results provided by the HIL test bench are then compared with corresponding analysis done using Multi-Body (MB) simulations. The proposed HIL methodology has proved to be able to test physical prototypes and define guidelines to assist damper manufacturers developing and optimising yaw damper components. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

2. On the implementation of hydraulic-interconnected-suspensions at the primary suspension stage of high-speed rail vehicles.

Author

Isacchi, Gioele and Ripamonti, Francesco

Abstract

In recent years, huge investments have been made to improve the dynamic performance of high-speed trains. Research into innovative suspension components has been part of the development of this transport system for decades. Innovative devices can allow rail vehicles to deal with the constantly increasing speed required by the global market. Among the most innovative suspension layouts proposed in railway dynamics in past years, limited attention has been given to Hydraulic Interconnected Suspensions (HIS). This layout is composed of two hydraulic cylinders with external hydraulic connections. Hydraulic Interconnected Suspensions allow promising tuning capabilities due to their ability to offer different responses based on the specific inputs given to the cylinders. This layout is rarely considered for rail vehicles, and the few previous works related to this topic considered the HIS layout to be applied at the secondary suspension stage. In this context, this paper proposes applying an HIS layout to the primary suspension stage of rail vehicles, in order to overcome the trade-offs between ride comfort, running safety and maximum car body displacement that need to be considered by bogie manufacturers when designing and optimising these mechanical systems. A nonlinear physical model of the HIS is proposed for co-simulation with a Multi-body (MB) model of a high-speed train. The improvement provided implementing an HIS at the primary suspension stage is then compared to similar enhancements that could be made when tuning and varying the standard suspension components of a bogie. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

3. A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response

Author

G. Gambardella, G. Viscido, B. Tumaini, A. Isacchi, R. Bosotti, and D. di Bernardo

Subjects
Science
Abstract

The impact of tumour heterogeneity on drug response in breast cancer is not fully understood. Here, the authors characterise cell lines from all main breast cancer subtypes using single-cell RNA-seq and train a deconvolution algorithm to predict drug responses in heterogeneous tumour cell populations.

Published
2022
Full Text
View/download PDF

7. Molecular Dynamics Simulations of p97 Including Covalent, Allosteric and ATP-competitive Inhibitors

Author

Stefano Rendine, Christian Orrenius, Federico Dapiaggi, Stefano Pieraccini, Ilaria Motto, Roberto D'Alessio, Paola Magnaghi, Antonella Isacchi, Eduard Felder, and Maurizio Sironi

Subjects
Drug design, protein protein interactions, mm-pbsa, molecular dynamics, Chemistry, QD1-999
Abstract

Binary (nucleotide-protein dimer and hexamer complexes) and ternary (nucleotide-protein-inhibitor complexes) p97 complexes were subjected to molecular dynamics simulations in an attempt to further our understanding of the p97 protein oligomer domain stability and, more importantly, of the recently reported diverse molecular mechanisms of inhibition including allosteric, ATP-competitive and covalent inhibitors. Analysis of stable states following equilibration phases indicated a higher intrinsic stability of the homohexamer as opposed to the dimer, and of N-D1 domains as opposed to the D2 domain. The molecular dynamics of the proposed allosteric binding model reproduced important molecular interactions identified experimentally with high frequency throughout the trajectory. Observed conformational changes occurring in the D2 nucleotide binding site provided a novel bind-rearrange-react hypothesis of stepwise molecular events involved in the specific covalent inhibitor mode of action.

Published
2019
Full Text
View/download PDF

8. Comprehensive kinome NGS targeted expression profiling by KING-REX

Author

Giovanni Carapezza, Carlo Cusi, Ettore Rizzo, Laura Raddrizzani, Sebastiano Di Bella, Alessio Somaschini, Antonella Leone, Rosita Lupi, Margherita Mutarelli, Vincenzo Nigro, Diego di Bernardo, Paolo Magni, Antonella Isacchi, and Roberta Bosotti

Subjects
Kinome gene expression, NGS RNA targeted panel, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Protein kinases are enzymes controlling different cellular functions. Genetic alterations often result in kinase dysregulation, making kinases a very attractive class of druggable targets in several human diseases. Existing approved drugs still target a very limited portion of the human ‘kinome’, demanding a broader functional knowledge of individual and co-expressed kinase patterns in physiologic and pathologic settings. The development of novel rapid and cost-effective methods for kinome screening is therefore highly desirable, potentially leading to the identification of novel kinase drug targets. Results In this work, we describe the development of KING-REX (KINase Gene RNA EXpression), a comprehensive kinome RNA targeted custom assay-based panel designed for Next Generation Sequencing analysis, coupled with a dedicated data analysis pipeline. We have conceived KING-REX for the gene expression analysis of 512 human kinases; for 319 kinases, paired assays and custom analysis pipeline features allow the evaluation of 3′- and 5′-end transcript imbalances as readout for the prediction of gene rearrangements. Validation tests on cell line models harboring known gene fusions demonstrated a comparable accuracy of KING-REX gene expression assessment as in whole transcriptome analyses, together with a robust detection of transcript portion imbalances in rearranged kinases, even in complex RNA mixtures or in degraded RNA. Conclusions These results support the use of KING-REX as a rapid and cost effective kinome investigation tool in the field of kinase target identification for applications in cancer biology and other human diseases.

Published
2019
Full Text
View/download PDF

9. A Meta-heuristic Optimization Procedure for the Identification of the Nonlinear Model Parameters of Hydraulic Dampers Based On Experimental Dataset of Real Working Conditions

Author

Gioele Isacchi, Francesco Ripamonti, and Matteo Corsi

Subjects
Control and Systems Engineering, Applied Mathematics, Mechanical Engineering, General Medicine
Abstract

Hydraulic dampers are widely implemented in railway vehicle suspension stages, especially in high-speed passenger trains. They are designed to be mounted in different positions to improve comfort, stability, and safety performances. Numerical simulations are often used to assist the design and optimization of these components. Unfortunately, hydraulic dampers are highly nonlinear due to the complex fluid dynamic phenomena taking place inside the chambers and through the by-pass orifices. This requires accurate damper models to be developed to estimate the influence of the nonlinearities of such components during the dynamic performances of the whole vehicle. This work aims at presenting a new parametric damper model based on a nonlinear lumped element approach. Moreover, a new model tuning procedure will be introduced. Differently from the typical sinusoidal characterization cycles, this routine is based on experimental tests of real working conditions. The set of optimal model parameters will be found through a meta-heuristic iterative approach able to minimize the differences between numerical and experimental damper forces. The performances of the optimal model will be compared with the ones of the most common Maxwell model generally implemented in railway multibody software programs.

Published
2023
Full Text
View/download PDF

12. Novel Thienoduocarmycin–Trastuzumab ADC Demonstrates Strong Antitumor Efficacy with Favorable Safety Profile in Preclinical Studies

Author

Valsasina, Barbara, primary, Orsini, Paolo, additional, Caruso, Michele, additional, Albanese, Clara, additional, Ciavolella, Antonella, additional, Cucchi, Ulisse, additional, Fraietta, Ivan, additional, Melillo, Nicola, additional, Fiorentini, Francesco, additional, Rizzi, Simona, additional, Salsa, Matteo, additional, Isacchi, Antonella, additional, and Gasparri, Fabio, additional

Published
2023
Full Text
View/download PDF

14. Establishment and genomic characterization of the new chordoma cell line Chor-IN-1

Author

Roberta Bosotti, Paola Magnaghi, Sebastiano Di Bella, Liviana Cozzi, Carlo Cusi, Fabio Bozzi, Nicola Beltrami, Giovanni Carapezza, Dario Ballinari, Nadia Amboldi, Rosita Lupi, Alessio Somaschini, Laura Raddrizzani, Barbara Salom, Arturo Galvani, Silvia Stacchiotti, Elena Tamborini, and Antonella Isacchi

Subjects
Medicine, Science
Abstract

Abstract Chordomas are rare, slowly growing tumors with high medical need, arising in the axial skeleton from notochord remnants. The transcription factor “brachyury” represents a distinctive molecular marker and a key oncogenic driver of chordomas. Tyrosine kinase receptors are also expressed, but so far kinase inhibitors have not shown clear clinical efficacy in chordoma patients. The need for effective therapies is extremely high, but the paucity of established chordoma cell lines has limited preclinical research. Here we describe the isolation of the new Chor-IN-1 cell line from a recurrent sacral chordoma and its characterization as compared to other chordoma cell lines. Chor-IN-1 displays genomic identity to the tumor of origin and has morphological features, growth characteristics and chromosomal abnormalities typical of chordoma, with expression of brachyury and other relevant biomarkers. Chor-IN-1 gene variants, copy number alterations and kinome gene expression were analyzed in comparison to other four chordoma cell lines, generating large scale DNA and mRNA genomic data that can be exploited for the identification of novel pharmacological targets and candidate predictive biomarkers of drug sensitivity in chordoma. The establishment of this new, well characterized chordoma cell line provides a useful tool for the identification of drugs active in chordoma.

Published
2017
Full Text
View/download PDF

15. Stereoselective synthesis of 3,4‐dihydropyrrolo[1,2‐a]pyrazin‐1(2H)‐one derivatives as PIM kinase inhibitors inspired from marine alkaloids

Author

Francesco Casuscelli, Elena Ardini, Nilla Avanzi, Alessandra Badari, Elena Casale, Teresa Disingrini, Daniele Donati, Antonella Ermoli, Eduard R. Felder, Arturo Galvani, Antonella Isacchi, Maria Menichincheri, Marisa Montemartini, Christian Orrenius, Claudia Piutti, Barbara Salom, and Gianluca Papeo

Subjects
Pharmacology, Structure-Activity Relationship, Alkaloids, Proto-Oncogene Proteins c-pim-1, Cell Line, Tumor, Organic Chemistry, Drug Discovery, Antineoplastic Agents, Stereoisomerism, Protein Kinase Inhibitors, Spectroscopy, Catalysis, Analytical Chemistry
Abstract

We previously demonstrated that natural product-inspired 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-ones derivatives delivered potent and selective PIM kinases inhibitors however with non-optimal ADME/PK properties and modest oral bioavailability. Herein, we describe a structure-based scaffold decoration and a stereoselective approach to this chemical class. The synthesis, structure-activity relationship studies, chiral analysis, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Compound 20c demonstrated excellent potency on PIM1 and PIM2 with exquisite kinases selectivity and PK properties that efficiently and dose-dependently promoted c-Myc degradation and appear to be promising lead compounds for further development.

Published
2022
Full Text
View/download PDF

18. Abstract CT025: NMS-03592088, a novel, potent FLT3, KIT and CSF1R inhibitor with activity in FLT3 positive acute myeloid leukemia patients with prior FLT3 inhibitor experience

Author

Curti, Antonio, primary, Rambaldi, Alessandro, additional, Cattaneo, Chiara, additional, Cairoli, Roberto, additional, Porta, Matteo Della, additional, Chiusolo, Patrizia, additional, Lussana, Federico, additional, Ubezio, Marta, additional, Mancini, Valentina, additional, Cano, Isabel, additional, Besliu, Carmen, additional, Claussen, Christian Hove, additional, Gatto, Rosalinda, additional, Crivori, Patrizia, additional, Colajori, Elena, additional, Somaschini, Alessio, additional, Davite, Cristina, additional, Isacchi, Antonella, additional, Ardini, Elena, additional, Mahnke, Lisa, additional, and Montesinos, Pau, additional

Published
2023
Full Text
View/download PDF

19. Abstract 1615: NMS-812, a novel potent PERK inhibitor that also inhibits GCN2, exhibits strong anti-tumor activity as single agent and in combination in preclinical models

Author

Perrera, Claudia, primary, Pulici, Maurizio, additional, Banfi, Patrizia, additional, Avanzi, Nilla, additional, Carenzi, Davide, additional, Casero, Daniele, additional, Ciavolella, Antonella, additional, Gianellini, Laura, additional, Gasparri, Fabio, additional, Saturno, Grazia, additional, Valsasina, Barbara, additional, Ardini, Elena, additional, Montagnoli, Alessia, additional, Galvani, Arturo P., additional, and Isacchi, Antonella, additional

Published
2023
Full Text
View/download PDF

20. Abstract 4036: NMS-0963 is a novel potent, selective and orally available Syk inhibitor with promising preclinical activity in diffuse large B-cell lymphoma

Author

Saturno, Grazia, primary, Modugno, Michele, additional, Orsini, Paolo, additional, Cervi, Giovanni, additional, Buffa, Laura, additional, Motto, Ilaria, additional, Avanzi, Nilla, additional, Montemartini, Marisa, additional, Gasparri, Fabio, additional, Texido, Gemma, additional, Galvani, Arturo, additional, and Isacchi, Antonella, additional

Published
2023
Full Text
View/download PDF

21. Data from NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies

Author

Valsasina, Barbara, primary, Beria, Italo, primary, Alli, Cristina, primary, Alzani, Rachele, primary, Avanzi, Nilla, primary, Ballinari, Dario, primary, Cappella, Paolo, primary, Caruso, Michele, primary, Casolaro, Alessia, primary, Ciavolella, Antonella, primary, Cucchi, Ulisse, primary, De Ponti, Anna, primary, Felder, Eduard, primary, Fiorentini, Francesco, primary, Galvani, Arturo, primary, Gianellini, Laura M., primary, Giorgini, Maria L., primary, Isacchi, Antonella, primary, Lansen, Jaqueline, primary, Pesenti, Enrico, primary, Rizzi, Simona, primary, Rocchetti, Maurizio, primary, Sola, Francesco, primary, and Moll, Jürgen, primary

Published
2023
Full Text
View/download PDF

22. Supplementary Figures 1-6 and Tables 1-2 from Entrectinib, a Pan–TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications

Author

Ardini, Elena, primary, Menichincheri, Maria, primary, Banfi, Patrizia, primary, Bosotti, Roberta, primary, De Ponti, Cristina, primary, Pulci, Romana, primary, Ballinari, Dario, primary, Ciomei, Marina, primary, Texido, Gemma, primary, Degrassi, Anna, primary, Avanzi, Nilla, primary, Amboldi, Nadia, primary, Saccardo, Maria Beatrice, primary, Casero, Daniele, primary, Orsini, Paolo, primary, Bandiera, Tiziano, primary, Mologni, Luca, primary, Anderson, David, primary, Wei, Ge, primary, Harris, Jason, primary, Vernier, Jean-Michel, primary, Li, Gang, primary, Felder, Eduard, primary, Donati, Daniele, primary, Isacchi, Antonella, primary, Pesenti, Enrico, primary, Magnaghi, Paola, primary, and Galvani, Arturo, primary

Published
2023
Full Text
View/download PDF

23. Supplementary Figures 1-8 from NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies

Author

Valsasina, Barbara, primary, Beria, Italo, primary, Alli, Cristina, primary, Alzani, Rachele, primary, Avanzi, Nilla, primary, Ballinari, Dario, primary, Cappella, Paolo, primary, Caruso, Michele, primary, Casolaro, Alessia, primary, Ciavolella, Antonella, primary, Cucchi, Ulisse, primary, De Ponti, Anna, primary, Felder, Eduard, primary, Fiorentini, Francesco, primary, Galvani, Arturo, primary, Gianellini, Laura M., primary, Giorgini, Maria L., primary, Isacchi, Antonella, primary, Lansen, Jaqueline, primary, Pesenti, Enrico, primary, Rizzi, Simona, primary, Rocchetti, Maurizio, primary, Sola, Francesco, primary, and Moll, Jürgen, primary

Published
2023
Full Text
View/download PDF

24. Data from Afatinib Is a New Therapeutic Approach in Chordoma with a Unique Ability to Target EGFR and Brachyury

Author

Magnaghi, Paola, primary, Salom, Barbara, primary, Cozzi, Liviana, primary, Amboldi, Nadia, primary, Ballinari, Dario, primary, Tamborini, Elena, primary, Gasparri, Fabio, primary, Montagnoli, Alessia, primary, Raddrizzani, Laura, primary, Somaschini, Alessio, primary, Bosotti, Roberta, primary, Orrenius, Christian, primary, Bozzi, Fabio, primary, Pilotti, Silvana, primary, Galvani, Arturo, primary, Sommer, Josh, primary, Stacchiotti, Silvia, primary, and Isacchi, Antonella, primary

Published
2023
Full Text
View/download PDF

25. Supplementary Methods, Figure Legends 1-8, Tables 1-4 from NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies

Author

Valsasina, Barbara, primary, Beria, Italo, primary, Alli, Cristina, primary, Alzani, Rachele, primary, Avanzi, Nilla, primary, Ballinari, Dario, primary, Cappella, Paolo, primary, Caruso, Michele, primary, Casolaro, Alessia, primary, Ciavolella, Antonella, primary, Cucchi, Ulisse, primary, De Ponti, Anna, primary, Felder, Eduard, primary, Fiorentini, Francesco, primary, Galvani, Arturo, primary, Gianellini, Laura M., primary, Giorgini, Maria L., primary, Isacchi, Antonella, primary, Lansen, Jaqueline, primary, Pesenti, Enrico, primary, Rizzi, Simona, primary, Rocchetti, Maurizio, primary, Sola, Francesco, primary, and Moll, Jürgen, primary

Published
2023
Full Text
View/download PDF

26. Data from Entrectinib, a Pan–TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications

Author

Ardini, Elena, primary, Menichincheri, Maria, primary, Banfi, Patrizia, primary, Bosotti, Roberta, primary, De Ponti, Cristina, primary, Pulci, Romana, primary, Ballinari, Dario, primary, Ciomei, Marina, primary, Texido, Gemma, primary, Degrassi, Anna, primary, Avanzi, Nilla, primary, Amboldi, Nadia, primary, Saccardo, Maria Beatrice, primary, Casero, Daniele, primary, Orsini, Paolo, primary, Bandiera, Tiziano, primary, Mologni, Luca, primary, Anderson, David, primary, Wei, Ge, primary, Harris, Jason, primary, Vernier, Jean-Michel, primary, Li, Gang, primary, Felder, Eduard, primary, Donati, Daniele, primary, Isacchi, Antonella, primary, Pesenti, Enrico, primary, Magnaghi, Paola, primary, and Galvani, Arturo, primary

Published
2023
Full Text
View/download PDF

27. Supplementary Materials and Methods, Tables S1-S2, and Figures S1-S6 from Afatinib Is a New Therapeutic Approach in Chordoma with a Unique Ability to Target EGFR and Brachyury

Author

Magnaghi, Paola, primary, Salom, Barbara, primary, Cozzi, Liviana, primary, Amboldi, Nadia, primary, Ballinari, Dario, primary, Tamborini, Elena, primary, Gasparri, Fabio, primary, Montagnoli, Alessia, primary, Raddrizzani, Laura, primary, Somaschini, Alessio, primary, Bosotti, Roberta, primary, Orrenius, Christian, primary, Bozzi, Fabio, primary, Pilotti, Silvana, primary, Galvani, Arturo, primary, Sommer, Josh, primary, Stacchiotti, Silvia, primary, and Isacchi, Antonella, primary

Published
2023
Full Text
View/download PDF

28. Supplementary Materials and Methods from Entrectinib, a Pan–TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications

Author

Ardini, Elena, primary, Menichincheri, Maria, primary, Banfi, Patrizia, primary, Bosotti, Roberta, primary, De Ponti, Cristina, primary, Pulci, Romana, primary, Ballinari, Dario, primary, Ciomei, Marina, primary, Texido, Gemma, primary, Degrassi, Anna, primary, Avanzi, Nilla, primary, Amboldi, Nadia, primary, Saccardo, Maria Beatrice, primary, Casero, Daniele, primary, Orsini, Paolo, primary, Bandiera, Tiziano, primary, Mologni, Luca, primary, Anderson, David, primary, Wei, Ge, primary, Harris, Jason, primary, Vernier, Jean-Michel, primary, Li, Gang, primary, Felder, Eduard, primary, Donati, Daniele, primary, Isacchi, Antonella, primary, Pesenti, Enrico, primary, Magnaghi, Paola, primary, and Galvani, Arturo, primary

Published
2023
Full Text
View/download PDF

29. Hydraulic interconnected suspension for rail vehicles: a preliminary analysis

Author

Isacchi, Gioele, Nayir, Fazil Enes, Corsi, Matteo, Ripamonti, Francesco, Isacchi, Gioele, Nayir, Fazil Enes, Corsi, Matteo, and Ripamonti, Francesco

Abstract

This paper aims at analyzing a preliminary layout for a Hydraulic Interconnected Suspension (HIS) for rail vehicles. The device is intended to replace the primary vertical dampers and its design aims at decoupling the heave and roll responses. HIS solution provides additional tuning possibilities to optimize and refine the primary suspension stage of rail vehicles. A physical numerical model is developed, and the influence of three design parameters on the forces generated by the HIS is studied.

Published
2023

30. Ride comfort assessment of high-speed rail vehicles: influence of yaw dampers installation angle

Author

Isacchi, Gioele, Corsi, Matteo, Ripamonti, Francesco, Isacchi, Gioele, Corsi, Matteo, and Ripamonti, Francesco

Abstract

High-speed rail vehicles are equipped with yaw dampers to avoid the arising of hunting motion when running at high-speed. Although these suspension components provide a stabilizing effect on the vehicles, they also influence the ride comfort performances by affecting the accelerations perceived by the passengers. In this context, this paper aims to correlate the installation angle on the vertical plane of such suspension components on the ride comfort performances of a generic high-speed train. The proposed methodology is based on multibody simulations of a model with deformable car body. The modal behavior of the model is aligned to the typical mode shapes and natural frequencies reported in literature.

Published
2023

32. Supplementary Materials and Methods from Entrectinib, a Pan–TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications

Author

Arturo Galvani, Paola Magnaghi, Enrico Pesenti, Antonella Isacchi, Daniele Donati, Eduard Felder, Gang Li, Jean-Michel Vernier, Jason Harris, Ge Wei, David Anderson, Luca Mologni, Tiziano Bandiera, Paolo Orsini, Daniele Casero, Maria Beatrice Saccardo, Nadia Amboldi, Nilla Avanzi, Anna Degrassi, Gemma Texido, Marina Ciomei, Dario Ballinari, Romana Pulci, Cristina De Ponti, Roberta Bosotti, Patrizia Banfi, Maria Menichincheri, and Elena Ardini

Abstract

Supplementary experimental procedures are described

Published
2023
Full Text
View/download PDF

33. Supplementary Methods, Figure Legends 1-8, Tables 1-4 from NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies

Author

Jürgen Moll, Francesco Sola, Maurizio Rocchetti, Simona Rizzi, Enrico Pesenti, Jaqueline Lansen, Antonella Isacchi, Maria L. Giorgini, Laura M. Gianellini, Arturo Galvani, Francesco Fiorentini, Eduard Felder, Anna De Ponti, Ulisse Cucchi, Antonella Ciavolella, Alessia Casolaro, Michele Caruso, Paolo Cappella, Dario Ballinari, Nilla Avanzi, Rachele Alzani, Cristina Alli, Italo Beria, and Barbara Valsasina

Abstract

PDF file - 213K

Published
2023
Full Text
View/download PDF

34. Supplementary Figures 1-8 from NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies

Author

Jürgen Moll, Francesco Sola, Maurizio Rocchetti, Simona Rizzi, Enrico Pesenti, Jaqueline Lansen, Antonella Isacchi, Maria L. Giorgini, Laura M. Gianellini, Arturo Galvani, Francesco Fiorentini, Eduard Felder, Anna De Ponti, Ulisse Cucchi, Antonella Ciavolella, Alessia Casolaro, Michele Caruso, Paolo Cappella, Dario Ballinari, Nilla Avanzi, Rachele Alzani, Cristina Alli, Italo Beria, and Barbara Valsasina

Abstract

PDF file - 1.2MB

Published
2023
Full Text
View/download PDF

35. Data from Afatinib Is a New Therapeutic Approach in Chordoma with a Unique Ability to Target EGFR and Brachyury

Author

Antonella Isacchi, Silvia Stacchiotti, Josh Sommer, Arturo Galvani, Silvana Pilotti, Fabio Bozzi, Christian Orrenius, Roberta Bosotti, Alessio Somaschini, Laura Raddrizzani, Alessia Montagnoli, Fabio Gasparri, Elena Tamborini, Dario Ballinari, Nadia Amboldi, Liviana Cozzi, Barbara Salom, and Paola Magnaghi

Abstract

Chordomas are rare bone tumors with no approved therapy. These tumors express several activated tyrosine kinase receptors, which prompted attempts to treat patients with tyrosine kinase inhibitors. Although clinical benefit was observed in phase II clinical trials with imatinib and sorafenib, and sporadically also with EGFR inhibitors, therapies evaluated to date have shown modest activity. With the goal of identifying new drugs with immediate therapeutic potential for chordoma patients, we collected clinically approved drugs and other advanced inhibitors of MET, PDGFRβ, and EGFR tyrosine kinases, and assessed their antiproliferative activity against a panel of chordoma cell lines. Chordoma cell lines were not responsive to MET and PDGFRβ inhibitors. U-CH1 and UM-Chor1 were sensitive to all EGFR inhibitors, whereas the remaining cell lines were generally insensitive to these drugs. Afatinib was the only EGFR inhibitor with activity across the chordoma panel. We then investigated the molecular mechanisms behind the responses observed and found that the antiproliferative IC50s correlate with the unique ability of afatinib to promote degradation of EGFR and brachyury, an embryonic transcription factor considered a key driver of chordoma. Afatinib displayed potent antitumor efficacy in U-CH1, SF8894, CF322, and CF365 chordoma tumor models in vivo. In the panel analyzed, high EGFR phosphorylation and low AXL and STK33 expression correlated with higher sensitivity to afatinib and deserve further investigation as potential biomarkers of response. These data support the use of afatinib in clinical trials and provide the rationale for the upcoming European phase II study on afatinib in advanced chordoma. Mol Cancer Ther; 17(3); 603–13. ©2017 AACR.

Published
2023
Full Text
View/download PDF

36. Supplementary Figures 1-6 and Tables 1-2 from Entrectinib, a Pan–TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications

Author

Arturo Galvani, Paola Magnaghi, Enrico Pesenti, Antonella Isacchi, Daniele Donati, Eduard Felder, Gang Li, Jean-Michel Vernier, Jason Harris, Ge Wei, David Anderson, Luca Mologni, Tiziano Bandiera, Paolo Orsini, Daniele Casero, Maria Beatrice Saccardo, Nadia Amboldi, Nilla Avanzi, Anna Degrassi, Gemma Texido, Marina Ciomei, Dario Ballinari, Romana Pulci, Cristina De Ponti, Roberta Bosotti, Patrizia Banfi, Maria Menichincheri, and Elena Ardini

Abstract

Supplementary Figure 1. Efficacy of entrectinib on KM12 xenograft model using the scheduling 4 days on/ 3 days off. Supplementary Figure 2. Mechanism of action of entrectinib compared to crizotinib in ALK-dependent Ba/F3 cells. Supplementary Figure 3. Cell cycle distrivbution of Karpas-299 and SR-786 cells treated with entrectinib for different periods of time Supplementary Figure 4. Mechanism of action studies of entrectinib in additional ALK-dependent ALCL models Supplementary Figure 5. In vivo efficacy of entrectinib on NCI-H2228 xenograft model using the scheduling 4 days on/ 3 days off Supplementary Figure 6. Representative magnetic resonance images of mice bearing intracranial tumors treated with vehicle, entrectinib or crizotinib Supplementary Table 1. List of human tumor cell lines treated with entrectinib Supplementary Table 2. Pharmacokinetic paramenters of entrectinib evaluated after repeated administration of compound in CD1 mice.

Published
2023
Full Text
View/download PDF

37. Supplementary Materials and Methods, Tables S1-S2, and Figures S1-S6 from Afatinib Is a New Therapeutic Approach in Chordoma with a Unique Ability to Target EGFR and Brachyury

Author

Antonella Isacchi, Silvia Stacchiotti, Josh Sommer, Arturo Galvani, Silvana Pilotti, Fabio Bozzi, Christian Orrenius, Roberta Bosotti, Alessio Somaschini, Laura Raddrizzani, Alessia Montagnoli, Fabio Gasparri, Elena Tamborini, Dario Ballinari, Nadia Amboldi, Liviana Cozzi, Barbara Salom, and Paola Magnaghi

Abstract

Supplementary Table S1: Short Tandem Repeat (STR) fingerprinting; Supplementary Table S2: Anti-proliferative activity of MET and PDGFR inhibitors in chordoma cell lines; Supplementary Figure S1: Live-cell kinetic analysis of afatinib activity in U-CH1 cell line; Supplementary Figure S2: Effect of dacomitinib on EGFR and brachyury proteins; Supplementary Figure S3: Effect of EGFR and brachyury siRNA on U-CH1 cell viability and target proteins levels; Supplementary Figure S4: Analysis of the mechanism of afatinib-induced EGFR and brachyury down-modulation in U-CH1 chordoma cell line; Supplementary Figure S5: EGFR localization and phosphorylation in the different chordoma cell lines; Supplementary Figure S6: Short term pharmaco-dynamic response to afatinib.

Published
2023
Full Text
View/download PDF

40. Supplementary Figure S1 from NMS-E973, a Novel Synthetic Inhibitor of Hsp90 with Activity against Multiple Models of Drug Resistance to Targeted Agents, Including Intracranial Metastases

Author

Fogliatto, Gianpaolo, primary, Gianellini, Laura, primary, Brasca, Maria G., primary, Casale, Elena, primary, Ballinari, Dario, primary, Ciomei, Marina, primary, Degrassi, Anna, primary, De Ponti, Anna, primary, Germani, Massimiliano, primary, Guanci, Marco, primary, Paolucci, Mauro, primary, Polucci, Paolo, primary, Russo, Micaela, primary, Sola, Francesco, primary, Valsasina, Barbara, primary, Visco, Carlo, primary, Zuccotto, Fabio, primary, Donati, Daniele, primary, Felder, Eduard, primary, Pesenti, Enrico, primary, Galvani, Arturo, primary, Mantegani, Sergio, primary, and Isacchi, Antonella, primary

Published
2023
Full Text
View/download PDF

41. Supplementary Methods from NMS-E973, a Novel Synthetic Inhibitor of Hsp90 with Activity against Multiple Models of Drug Resistance to Targeted Agents, Including Intracranial Metastases

Author

Fogliatto, Gianpaolo, primary, Gianellini, Laura, primary, Brasca, Maria G., primary, Casale, Elena, primary, Ballinari, Dario, primary, Ciomei, Marina, primary, Degrassi, Anna, primary, De Ponti, Anna, primary, Germani, Massimiliano, primary, Guanci, Marco, primary, Paolucci, Mauro, primary, Polucci, Paolo, primary, Russo, Micaela, primary, Sola, Francesco, primary, Valsasina, Barbara, primary, Visco, Carlo, primary, Zuccotto, Fabio, primary, Donati, Daniele, primary, Felder, Eduard, primary, Pesenti, Enrico, primary, Galvani, Arturo, primary, Mantegani, Sergio, primary, and Isacchi, Antonella, primary

Published
2023
Full Text
View/download PDF

42. Supplementary Table S1 from NMS-E973, a Novel Synthetic Inhibitor of Hsp90 with Activity against Multiple Models of Drug Resistance to Targeted Agents, Including Intracranial Metastases

Author

Fogliatto, Gianpaolo, primary, Gianellini, Laura, primary, Brasca, Maria G., primary, Casale, Elena, primary, Ballinari, Dario, primary, Ciomei, Marina, primary, Degrassi, Anna, primary, De Ponti, Anna, primary, Germani, Massimiliano, primary, Guanci, Marco, primary, Paolucci, Mauro, primary, Polucci, Paolo, primary, Russo, Micaela, primary, Sola, Francesco, primary, Valsasina, Barbara, primary, Visco, Carlo, primary, Zuccotto, Fabio, primary, Donati, Daniele, primary, Felder, Eduard, primary, Pesenti, Enrico, primary, Galvani, Arturo, primary, Mantegani, Sergio, primary, and Isacchi, Antonella, primary

Published
2023
Full Text
View/download PDF

43. Supplementary Data from Transcriptional Analysis of an E2F Gene Signature as a Biomarker of Activity of the Cyclin-Dependent Kinase Inhibitor PHA-793887 in Tumor and Skin Biopsies from a Phase I Clinical Study

Author

Locatelli, Giuseppe, primary, Bosotti, Roberta, primary, Ciomei, Marina, primary, Brasca, Maria G., primary, Calogero, Raffaele, primary, Mercurio, Ciro, primary, Fiorentini, Francesco, primary, Bertolotti, Matteo, primary, Scacheri, Emanuela, primary, Scaburri, Angela, primary, Galvani, Arturo, primary, Pesenti, Enrico, primary, De Baere, Thierry, primary, Soria, Jean-Charles, primary, Lazar, Vladimir, primary, and Isacchi, Antonella, primary

Published
2023
Full Text
View/download PDF

44. Supplementary Data from Dual Targeting of CDK and Tropomyosin Receptor Kinase Families by the Oral Inhibitor PHA-848125, an Agent with Broad-Spectrum Antitumor Efficacy

Author

Albanese, Clara, primary, Alzani, Rachele, primary, Amboldi, Nadia, primary, Avanzi, Nilla, primary, Ballinari, Dario, primary, Brasca, Maria Gabriella, primary, Festuccia, Claudio, primary, Fiorentini, Francesco, primary, Locatelli, Giuseppe, primary, Pastori, Wilma, primary, Patton, Veronica, primary, Roletto, Fulvia, primary, Colotta, Francesco, primary, Galvani, Arturo, primary, Isacchi, Antonella, primary, Moll, Jurgen, primary, Pesenti, Enrico, primary, Mercurio, Ciro, primary, and Ciomei, Marina, primary

Published
2023
Full Text
View/download PDF

46. Supplementary Table 1 from Crystal Structure of the T315I Abl Mutant in Complex with the Aurora Kinases Inhibitor PHA-739358

Author

Modugno, Michele, primary, Casale, Elena, primary, Soncini, Chiara, primary, Rosettani, Pamela, primary, Colombo, Riccardo, primary, Lupi, Rosita, primary, Rusconi, Luisa, primary, Fancelli, Daniele, primary, Carpinelli, Patrizia, primary, Cameron, Alexander D., primary, Isacchi, Antonella, primary, and Moll, Jürgen, primary

Published
2023
Full Text
View/download PDF

47. Supplementary Figures 1-14, Tables 1-4, Methods, References from Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase

Author

Colombo, Riccardo, primary, Caldarelli, Marina, primary, Mennecozzi, Milena, primary, Giorgini, Maria Laura, primary, Sola, Francesco, primary, Cappella, Paolo, primary, Perrera, Claudia, primary, Depaolini, Stefania Re, primary, Rusconi, Luisa, primary, Cucchi, Ulisse, primary, Avanzi, Nilla, primary, Bertrand, Jay Aaron, primary, Bossi, Roberto Tiberio, primary, Pesenti, Enrico, primary, Galvani, Arturo, primary, Isacchi, Antonella, primary, Colotta, Francesco, primary, Donati, Daniele, primary, and Moll, Jürgen, primary

Published
2023
Full Text
View/download PDF

48. Data from Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase

Author

Colombo, Riccardo, primary, Caldarelli, Marina, primary, Mennecozzi, Milena, primary, Giorgini, Maria Laura, primary, Sola, Francesco, primary, Cappella, Paolo, primary, Perrera, Claudia, primary, Depaolini, Stefania Re, primary, Rusconi, Luisa, primary, Cucchi, Ulisse, primary, Avanzi, Nilla, primary, Bertrand, Jay Aaron, primary, Bossi, Roberto Tiberio, primary, Pesenti, Enrico, primary, Galvani, Arturo, primary, Isacchi, Antonella, primary, Colotta, Francesco, primary, Donati, Daniele, primary, and Moll, Jürgen, primary

Published
2023
Full Text
View/download PDF

50. Supplementary Data from Transcriptional Analysis of an E2F Gene Signature as a Biomarker of Activity of the Cyclin-Dependent Kinase Inhibitor PHA-793887 in Tumor and Skin Biopsies from a Phase I Clinical Study

Author

Antonella Isacchi, Vladimir Lazar, Jean-Charles Soria, Thierry De Baere, Enrico Pesenti, Arturo Galvani, Angela Scaburri, Emanuela Scacheri, Matteo Bertolotti, Francesco Fiorentini, Ciro Mercurio, Raffaele Calogero, Maria G. Brasca, Marina Ciomei, Roberta Bosotti, and Giuseppe Locatelli

Abstract

Supplementary Data from Transcriptional Analysis of an E2F Gene Signature as a Biomarker of Activity of the Cyclin-Dependent Kinase Inhibitor PHA-793887 in Tumor and Skin Biopsies from a Phase I Clinical Study

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results