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171 results on '"Callari M"'

1. Tumour ecosystem and molecular dynamics in clinical triple-negative breast cancer depend on the chemotherapy regimen

Author

Barreca, M, Mariani, M, Dugo, M, Galbardi, B, Valagussa, P, Besozzi, D, Viale, G, Gianni, L, Bianchini, G, Callari, M, Marco Barreca, Marco Mariani, Matteo Dugo, Barbara Galbardi, Pinuccia Valagussa, Daniela Besozzi, Giuseppe Viale, Luca Gianni, Giampaolo Bianchini, Maurizio Callari, Barreca, M, Mariani, M, Dugo, M, Galbardi, B, Valagussa, P, Besozzi, D, Viale, G, Gianni, L, Bianchini, G, Callari, M, Marco Barreca, Marco Mariani, Matteo Dugo, Barbara Galbardi, Pinuccia Valagussa, Daniela Besozzi, Giuseppe Viale, Luca Gianni, Giampaolo Bianchini, and Maurizio Callari

Published
2024

2. Corrigendum to “Mechanisms of responsiveness to and resistance against trabectedin in murine models of human myxoid liposarcoma” [Genomics Volume 113, Issue 5, September 2021, Pages 3439–3448] (Genomics (2021) 113(5) (3439–3448), (S0888754321003062), (10.1016/j.ygeno.2021.07.028))

Author

Mannarino L., Mannarino, L, Craparotta, I, Ballabio, S, Frapolli, R, Meroni, M, Bello, E, Panini, N, Callari, M, Sanfilippo, R, Casali, P, Barisella, M, Fabbroni, C, Marchini, S, D'Incalci, M, Mannarino L., Craparotta I., Ballabio S., Frapolli R., Meroni M., Bello E., Panini N., Callari M., Sanfilippo R., Casali P. G., Barisella M., Fabbroni C., Marchini S., D'Incalci M., Mannarino L., Mannarino, L, Craparotta, I, Ballabio, S, Frapolli, R, Meroni, M, Bello, E, Panini, N, Callari, M, Sanfilippo, R, Casali, P, Barisella, M, Fabbroni, C, Marchini, S, D'Incalci, M, Mannarino L., Craparotta I., Ballabio S., Frapolli R., Meroni M., Bello E., Panini N., Callari M., Sanfilippo R., Casali P. G., Barisella M., Fabbroni C., Marchini S., and D'Incalci M.

Published
2022

3. Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy

Author

Licata, L, Barreca, M, Galbardi, B, Dugo, M, Viale, G, Gyorffy, B, Karn, T, Pusztai, L, Gianni, L, Callari, M, Bianchini, G, Licata, L, Barreca, M, Galbardi, B, Dugo, M, Viale, G, Gyorffy, B, Karn, T, Pusztai, L, Gianni, L, Callari, M, and Bianchini, G

Abstract

Background: Luminal breast cancers with high proliferation (MKShi) and low ER-related signalling (ERSlo) have a poor prognosis. We investigated treatment responses and molecular features of MKShi/ERSlo tumours to inform potential therapies. Methods: Gene expression data from patients who received neoadjuvant chemotherapy (NAC) without (MDACC, N = 199) or with pembrolizumab (I-SPY2, N = 40), or endocrine therapy (NET) without (POETIC, N = 172) or with palbociclib (NeoPalAna, N = 32) were analyzed to assess treatment response by MKS/ERS-subgroups. TCGA was used to assess the mutational landscape and biomarkers associated with palbociclib-resistance (Cyclin-E, RBsig, IRPR) and immunotherapy-response (TMB, TILs, T-cell inflamed) by MKS/ERS-subgroups. Results: Compared to MKShi/ERShi tumours, MKShi/ERSlo tumours had higher pathological response rates to NAC (22% vs 8%, p = 0.06) but a higher recurrence risk (4-year metastasis-free survival 70% vs 94%, p = 0.01). MKShi/ERSlo tumours frequently harboured TP53 (34%) and PIK3CA (33%) mutations, and showed high expression of Cyclin-E, RBsig and IRPR, high TMB and elevated TIL and T-cell inflamed metagene expression. MKShi/ERSlo tumours retained high proliferation after NET with or without palbociclib but had higher pathological complete response rates when pembrolizumab was added to NAC (42% vs 21%, p = 0.07). Conclusions: MKShi/ERSlo tumours have dismal outcomes and are enriched in chemotherapy-sensitive but ET- and palbociclib-resistant tumours. Biomarker analysis and clinical data suggest a potential role for immunotherapy in this group.

Published
2023

4. Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Author

Kuett, Laura, Catena, Raúl, Özcan, Alaz, Plüss, Alex, Ali, H. R., Sa’d, M. Al, Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E. S., Bressan, D., Bruna, A., Burger, Marcel, Caldas, C., Callari, M., Cannell, I. G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E. A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G. J., Harris, S., Jauset, C., Joyce, J. A., Karagiannis, E. D., Kovačević, T., Kuett, L., Kunes, R., Yoldaş, A. Küpcü, Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C. M., Nugent, I., O’Flanagan, C. H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A. J., Rueda, O. M., Ruiz, T., Sawicka, K., Sepúlveda, L. A., Shah, S. P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S. L., Walton, N. A., Wassie, A. T., Watson, S. S., Weselak, J., Wild, S. A., Williams, E., Windhager, J., Xia, C., Zheng, P., Zhuang, X., Schraml, Peter, Moch, Holger, de Souza, Natalie, and Bodenmiller, Bernd

Subjects
Cancer Research, Oncology
Abstract

A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

Published
2021
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5. Mechanisms of responsiveness to and resistance against trabectedin in murine models of human myxoid liposarcoma

Author

Mannarino, L, Craparotta, I, Ballabio, S, Frapolli, R, Meroni, M, Bello, E, Panini, N, Callari, M, Sanfilippo, R, Casali, P, Barisella, M, Fabbroni, C, Marchini, S, D'Incalci, M, Mannarino L., Craparotta I., Ballabio S., Frapolli R., Meroni M., Bello E., Panini N., Callari M., Sanfilippo R., Casali P. G., Barisella M., Fabbroni C., Marchini S., D'Incalci M., Mannarino, L, Craparotta, I, Ballabio, S, Frapolli, R, Meroni, M, Bello, E, Panini, N, Callari, M, Sanfilippo, R, Casali, P, Barisella, M, Fabbroni, C, Marchini, S, D'Incalci, M, Mannarino L., Craparotta I., Ballabio S., Frapolli R., Meroni M., Bello E., Panini N., Callari M., Sanfilippo R., Casali P. G., Barisella M., Fabbroni C., Marchini S., and D'Incalci M.

Abstract

Myxoid liposarcoma (MLPS) is a rare soft-tissue sarcoma characterised by the expression of FUS-DDIT3 chimera. Trabectedin has shown significant clinical anti-tumour activity against MLPS. To characterise the molecular mechanism of trabectedin sensitivity and of resistance against it, we integrated genomic and transcriptomic data from treated mice bearing ML017 or ML017/ET, two patient-derived MLPS xenograft models, sensitive to and resistant against trabectedin, respectively. Longitudinal RNA-Seq analysis of ML017 showed that trabectedin acts mainly as a transcriptional regulator: 15 days after the third dose trabectedin modulates the transcription of 4883 genes involved in processes that sustain adipocyte differentiation. No such differences were observed in ML017/ET. Genomic analysis showed that prolonged treatment causes losses in 4p15.2, 4p16.3 and 17q21.3 cytobands leading to acquired-resistance against the drug. The results dissect the complex mechanism of action of trabectedin and provide the basis for novel combinatorial approaches for the treatment of MLPS that could overcome drug-resistance.

Published
2021

6. EP07.01-004 Long Survivor Epithelioid Pleural Mesotheliomas Are Characterized by Tertiary Lymphoid Structures: An Update to the MATCH Study

Author

Grosso, F., primary, Mannarino, L., additional, Paracchini, L., additional, Pezzuto, F., additional, Moracci, L., additional, Olteanu, G.-E., additional, Delfanti, S., additional, Callari, M., additional, Penpa, S., additional, Maconi, A., additional, De Simone, I., additional, Bosetti, C., additional, Allavena, P., additional, Marchini, S., additional, Calabrese, F., additional, and D'Incalci, M., additional

Published
2022
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8. Immune milieu associated with PD-L1 status in TNBC is dependent on time of biomarker assessment and treatment received: A secondary analysis of the NeoTRIPaPDL1 trial

Author

Callari, M, Huang, C, Egle, D, Bermejo, B, Zamagni, C, Dugo, M, Thill, M, Anton, A, Barreca, M, Russo, S, Ciruelos, E, Greil, R, Zambelli, S, Gyorffy, B, Smart, C, Biasi, O, Valagussa, P, Viale, G, Gianni, L, Bianchini, G, Huang, CS, Ciruelos, EM, Callari, M, Huang, C, Egle, D, Bermejo, B, Zamagni, C, Dugo, M, Thill, M, Anton, A, Barreca, M, Russo, S, Ciruelos, E, Greil, R, Zambelli, S, Gyorffy, B, Smart, C, Biasi, O, Valagussa, P, Viale, G, Gianni, L, Bianchini, G, Huang, CS, and Ciruelos, EM

Published
2022

9. Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Author

Kuett, L, Catena, R, ��zcan, A, Pl��ss, A, Ali, HR, Sa���d, MA, Alon, S, Aparicio, S, Battistoni, G, Balasubramanian, Shankar, Becker, R, Bodenmiller, B, Boyden, ES, Bressan, D, Bruna, A, Burger, M, Caldas, Carlos, Callari, M, Cannell, IG, Casbolt, H, Chornay, N, Cui, Y, Dariush, Aliakbar, Dinh, K, Emenari, A, Eyal-Lubling, Y, Fan, J, Fatemi, A, Fisher, E, Gonz��lez-Solares, EA, Gonz��lez-Fern��ndez, C, Goodwin, D, Greenwood, W, Grimaldi, F, Hannon, GJ, Harris, S, Jauset, C, Joyce, JA, Karagiannis, ED, Kova��evi��, T, Kunes, R, Yolda��, AK, Lai, D, Laks, E, Lee, H, Lee, M, Lerda, G, Li, Y, McPherson, A, Millar, N, Mulvey, CM, Nugent, I, O���Flanagan, CH, Paez-Ribes, M, Pearsall, I, Qosaj, F, Roth, AJ, Rueda, OM, Ruiz, T, Sawicka, K, Sep��lveda, LA, Shah, SP, Shea, A, Sinha, A, Smith, A, Tavar��, S, Tietscher, S, V��zquez-Garc��a, I, Vogl, SL, Walton, NA, Wassie, AT, Watson, SS, Weselak, J, Wild, SA, Williams, E, Windhager, J, Xia, C, Zheng, P, Zhuang, X, Schraml, P, Moch, H, De Souza, N, Ali, Raza [0000-0001-7587-0906], Balasubramanian, Shankar [0000-0002-0281-5815], Caldas, Carlos [0000-0003-3547-1489], Hannon, Gregory [0000-0003-4021-3898], Walton, Nicholas [0000-0003-3983-8778], and Apollo - University of Cambridge Repository

Subjects
Imaging, Three-Dimensional, Tumor Microenvironment, Humans, Breast Neoplasms, Female, Antibodies, Image Cytometry
Abstract

A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

Published
2022

10. Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response

Author

Georgopoulou, Dimitra, Callari, Maurizio, Rueda, Oscar M., Shea, Abigail, Martin, Alistair, Giovannetti, Agnese, Qosaj, Fatime, Dariush, Ali, Chin, Suet-Feung, Carnevalli, Larissa S., Provenzano, Elena, Greenwood, Wendy, Lerda, Giulia, Esmaeilishirazifard, Elham, O’Reilly, Martin, Serra, Violeta, Bressan, Dario, Mills, Gordon B., Ali, H. Raza, Cosulich, Sabina S., Hannon, Gregory J., Bruna, Alejandra, Caldas, Carlos, Ali, H. R., Al Sa’d, M., Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E. S., Bressan, D., Bruna, A., Burger, Marcel, Caldas, C., Callari, M., Cannell, I. G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E. A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G. J., Harris, O., Harris, S., Jauset, C., Joyce, J. A., Karagiannis, E. D., Kovačević, T., Kuett, L., Kunes, R., Küpcü, Yoldaş A., Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C. M., Nugent, F., O’Flanagan, C. H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A. J., Rueda, O. M., Ruiz, T., Sawicka, K., Sepúlveda, L. A., Shah, S. P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S. L., Walton, N. A., Wassie, A. T., Watson, S. S., Weselak, J., Wild, S. A., Williams, E., Windhager, J., Whitmarsh, T., Xia, C., Zheng, P., Zhuang, X., Rueda, Oscar M. [0000-0003-0008-4884], Giovannetti, Agnese [0000-0001-5207-7243], Chin, Suet-Feung [0000-0001-5697-1082], Carnevalli, Larissa S. [0000-0001-7432-0195], Provenzano, Elena [0000-0003-3345-3965], Serra, Violeta [0000-0001-6620-1065], Bressan, Dario [0000-0003-3592-699X], Mills, Gordon B. [0000-0002-0144-9614], Ali, H. Raza [0000-0001-7587-0906], Caldas, Carlos [0000-0003-3547-1489], and Apollo - University of Cambridge Repository

Subjects
13/1, 13/105, article, 13/106, 38/39, 45/23, 631/67/1347, 631/67/2329
Abstract

Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289, Funder: AstraZeneca; doi: https://doi.org/10.13039/100004325, The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.

Published
2021
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11. Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems

Author

Alon, Shahar, Goodwin, Daniel R., Sinha, Anubhav, Wassie, Asmamaw T., Chen, Fei, Daugharthy, Evan R., Bando, Yosuke, Kajita, Atsushi, Xue, Andrew G., Marrett, Karl, Prior, Robert, Cui, Yi, Payne, Andrew C., Yao, Chun-Chen, Suk, Ho-Jun, Wang, Ru, Yu, Chih-Chieh (Jay), Tillberg, Paul, Reginato, Paul, Pak, Nikita, Liu, Songlei, Punthambaker, Sukanya, Iyer, Eswar P. R., Kohman, Richie E., Miller, Jeremy A., Lein, Ed S., Lako, Ana, Cullen, Nicole, Rodig, Scott, Helvie, Karla, Abravanel, Daniel L., Wagle, Nikhil, Johnson, Bruce E., Klughammer, Johanna, Slyper, Michal, Waldman, Julia, Jané-Valbuena, Judit, Rozenblatt-Rosen, Orit, Regev, Aviv, Church, George M., Marblestone, Adam H., Boyden, Edward S., Ali, H. R., Al Sa’d, M., Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E. S., Bressan, D., Bruna, A., Burger, Marcel, Caldas, C., Callari, M., Cannell, I. G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E. A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G. J., Harris, O., Harris, S., Jauset, C., Joyce, J. A., Karagiannis, E. D., Kovačević, T., Kuett, L., Kunes, R., Küpcü Yoldaş, A., Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C. M., Nugent, F., O'Flanagan, C. H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A. J., Rueda, O. M., Ruiz, T., Sawicka, K., Sepúlveda, L. A., Shah, S. P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S. L., Walton, N. A., Wassie, A. T., Watson, S. S., Weselak, J., Wild, S. A., Williams, E., Windhager, J., Whitmarsh, T., Xia, C., Zheng, P., and Zhuang, X.

Subjects
In situ, Cell type, Dendritic spine, Sequence analysis, Dendritic Spines, Breast Neoplasms, Computational biology, Biology, Biochemistry, Article, Transcriptome, Mice, 03 medical and health sciences, Animals, Humans, splice, Molecular Biology, Gene, Visual Cortex, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Sequence Analysis, RNA, Gene Expression Profiling, Computational Biology, RNA, Cell Biology, Molecular Imaging, Female, Single-Cell Analysis, Biotechnology
Abstract

Identifying transcript location in cells Identifying where specific RNAs occur within a cell or tissue has been limited by technology and imaging capabilities. Expansion microscopy has allowed for better visualization of small structures by expanding the tissues with a polymer- and hydrogel-based system. Alon et al. combined expansion microscopy with long-read in situ RNA sequencing, resulting in a more precise visualization of the location of specific transcripts. This method, termed “ExSeq” for expansion sequencing, was used to detect RNAs, both new transcripts and those previously demonstrated to localize to neuronal dendrites. Unlike other in situ sequencing methods, ExSeq does not target sets of genes. This technology thus unites spatial resolution, multiplexing, and an unbiased approach to reveal insights into RNA localization and its physiological roles in developing and active tissue. Science , this issue p. eaax2656

Published
2021

12. LBA12 Predictive value of gene-expression profiles (GEPs) and their dynamics during therapy in the NeoTRIPaPDL1 trial

Author

Bianchini, G., primary, Dugo, M., additional, Huang, C-S., additional, Egle, D., additional, Bermejo, B., additional, Seitz, R.S., additional, Nielsen, T.J.J., additional, Zamagni, C., additional, Thill, M., additional, Anton, A., additional, Russo, S., additional, Ciruelos, E.M., additional, Schweitzer, B.L., additional, Greil, R., additional, Semiglazov, V., additional, Gyorffy, B., additional, Valagussa, P., additional, Viale, G., additional, Callari, M., additional, and Gianni, L., additional

Published
2021
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13. 141P Gene-expression pathways and dynamics during neoadjuvant chemo-free therapy predict pathologic complete response in ER+/HER2+ breast cancer (BC)

Author

Dugo, M., primary, Gyorffy, B., additional, Bisagni, G., additional, Colleoni, M.A., additional, Mansutti, M., additional, Zamagni, C., additional, Del Mastro, L., additional, Zambelli, S., additional, Frassoldati, A., additional, Licata, L., additional, Galbardi, B., additional, Biasi, O.M., additional, Viganò, L., additional, Locatelli, A., additional, Viale, G., additional, Valagussa, P., additional, Callari, M., additional, Gianni, L., additional, and Bianchini, G., additional

Published
2021
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15. 11P BioItaLEE: Comparative biomarker analysis of liquid biopsies and paired tissue samples of patients treated with ribociclib and letrozole as first-line therapy for advanced breast cancer (aBC)

Author

Bianchini, G., primary, De Laurentiis, M., additional, Arpino, G., additional, Zambelli, A., additional, Puglisi, F., additional, Del Mastro, L., additional, Colleoni, M.A., additional, Montemurro, F., additional, Bianchi, G.V., additional, Paris, I., additional, Allegrini, G., additional, Amaducci, L., additional, Cazzaniga, M.E., additional, Orditura, M., additional, Zamagni, C., additional, Bianchetti, S., additional, Castelletti, D., additional, Benelli, M., additional, Callari, M., additional, and Malorni, L., additional

Published
2020
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16. PATRI, a Genomics Data Integration Tool for Biomarker Discovery

Author

Ukmar, G, Melloni, G, Raddrizzani, L, Rossi, P, Di Bella, S, Pirchio, M, Vescovi, M, Leone, A, Callari, M, Cesarini, M, Somaschini, A, Della Vedova, G, Daidone, M, Pettenella, M, Isacchi, A, Bosotti, R, Ukmar G., Melloni G. E. M., Raddrizzani L., Rossi P., Di Bella S., Pirchio M. R., Vescovi M., Leone A., Callari M., Cesarini M., Somaschini A., Della Vedova G., Daidone M. G., Pettenella M., Isacchi A., Bosotti R., Ukmar, G, Melloni, G, Raddrizzani, L, Rossi, P, Di Bella, S, Pirchio, M, Vescovi, M, Leone, A, Callari, M, Cesarini, M, Somaschini, A, Della Vedova, G, Daidone, M, Pettenella, M, Isacchi, A, Bosotti, R, Ukmar G., Melloni G. E. M., Raddrizzani L., Rossi P., Di Bella S., Pirchio M. R., Vescovi M., Leone A., Callari M., Cesarini M., Somaschini A., Della Vedova G., Daidone M. G., Pettenella M., Isacchi A., and Bosotti R.

Abstract

The availability of genomic datasets in association with clinical, phenotypic, and drug sensitivity information represents an invaluable source for potential therapeutic applications, supporting the identification of new drug sensitivity biomarkers and pharmacological targets. Drug discovery and precision oncology can largely benefit from the integration of treatment molecular discriminants obtained from cell line models and clinical tumor samples; however this task demands comprehensive analysis approaches for the discovery of underlying data connections. Here we introduce PATRI (Platform for the Analysis of TRanslational Integrated data), a standalone tool accessible through a user-friendly graphical interface, conceived for the identification of treatment sensitivity biomarkers from user-provided genomics data, associated with information on sample characteristics. PATRI streamlines a translational analysis workflow: first, baseline genomics signatures are statistically identified, differentiating treatment sensitive from resistant preclinical models; then, these signatures are used for the prediction of treatment sensitivity in clinical samples, via random forest categorization of clinical genomics datasets and statistical evaluation of the relative phenotypic features. The same workflow can also be applied across distinct clinical datasets. The ease of use of the PATRI tool is illustrated with validation analysis examples, performed with sensitivity data for drug treatments with known molecular discriminants

Published
2018

17. Crosslinking of self-assembled protein-polymer conjugates with divanillin

Author

Li, Z ; https://orcid.org/0000-0002-1723-5047, Jiang, Y, Wust, K, Callari, M, Stenzel, MH ; https://orcid.org/0000-0002-6433-4419, Li, Z ; https://orcid.org/0000-0002-1723-5047, Jiang, Y, Wust, K, Callari, M, and Stenzel, MH ; https://orcid.org/0000-0002-6433-4419

Abstract

Protein-based materials are widely used in biomedical applications. Often the proteins need to be crosslinked in order to be stable for application. Here, we explored the use of 5, 50-bisvanillin as a potentially non-toxic crosslinker that can react with lysine residues on proteins. To demonstrate the success of the crosslinking reaction, polymer-protein conjugates based on bovine serum albumin (BSA) and poly(N-isopropyl acrylamide) (PNIPAM) were employed. The BSA-PNIPAM conjugate is water soluble at room temperature, but heated above the cloud point, BSA-PNIPAM forms nanoparticles of around 70 nm that can again disassemble at lower temperatures. Reaction with 5, 50-bisvanillin prevented disassembly resulting in stable BSA nanoparticles of 50 nm in size. The formed nanoparticles were observed to be rather stable and were not easily cleaved in acidic conditions. The crosslinker 5, 50-bisvanillin was measured to have lower toxicity against A2780 lung cancer cell lines compared with the commonly applied crosslinker glutaraldehyde.

Published
2020

18. Abstract GS3-06: Dynamics of breast cancer relapse reveal molecularly defined late recurring ER-positive subgroups: Results from the METABRIC study

Author

Curtis, C, primary, Rueda, OM, additional, Sammut, S-J, additional, Chin, S-F, additional, Caswell-Jin, JL, additional, Seoane, JA, additional, Callari, M, additional, Batra, R, additional, Pereira, B, additional, Bruna, A, additional, Ali, HR, additional, Provenzano, E, additional, Liu, B, additional, Parisien, M, additional, Gillett, C, additional, McKinney, S, additional, Green, A, additional, Murphy, L, additional, Purushotham, A, additional, Ellis, I, additional, Pharoah, P, additional, Rueda, C, additional, Aparicio, S, additional, and Caldas, C, additional

Published
2019
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19. PATRI, a Genomics Data Integration Tool for Biomarker Discovery

Author

Ukmar, G., primary, Melloni, G. E. M., additional, Raddrizzani, L., additional, Rossi, P., additional, Di Bella, S., additional, Pirchio, M. R., additional, Vescovi, M., additional, Leone, A., additional, Callari, M., additional, Cesarini, M., additional, Somaschini, A., additional, Della Vedova, G., additional, Daidone, M. G., additional, Pettenella, M., additional, Isacchi, A., additional, and Bosotti, R., additional

Published
2018
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23. Drug induced self-assembly of triblock copolymers into polymersomes for the synergistic dual-drug delivery of platinum drugs and paclitaxel

Author

Callari, M, Wong, S, Lu, H, Aldrich-Wright, J, de Souza, P, and Stenzel, MH

Subjects
0303 Macromolecular and Materials Chemistry, 0307 Theoretical and Computational Chemistry
Abstract

Co-delivery of two drugs in one nanoparticle is increasingly used to overcome, for example, multi-drug resistance in cancer therapy and therefore suitable drug carriers need to be developed. In this work, a well-known polymer based on poly(glutamic acid) (PGA) and poly(ethylene glycol) (PEG), PGA-PEG-PGA, was employed as a reactive scaffold for the attachment of paclitaxel (Ptx) and platinum(iv) prodrugs. While the polymer itself is water-soluble, the chemical conjugation of both drugs induces self-assembly into polymersomes with a high drug loading content of 28 wt% of Ptx and 11 wt% of the platinum drug. These polymersomes were found to be stable against enzymatic degradation, yet allowed the release of the platinum drugs in a reductive environment. Twenty-two percent of platinum was released after 48 hours, suggesting a two-step model where Pt-drugs are released within a few days, while Ptx has a slower, prolonged, release. Using traditional A549 and LNCap cell lines in 2D culture to test cytotoxicity, the free Ptx drug performed better than Ptx delivered in nanoparticles, as expected, due to the slow cleavage of the drug. However, experiments in 3D cell culture models with A549 spheroids revealed that the drug carrier enabled a higher accumulation of Pt-drugs inside the cells, and after 14 days incubation, the drug-loaded carrier performed slightly better than the free drugs over the longer timeframe. Further, Chou-Talalay analysis confirmed the synergistic effect of the combination of platinum drug and Ptx in the nanoparticle system.

Published
2017

25. PEGylated Albumin based Polyion Complex Micelles for protein delivery

Author

Jiang, Y, Lu, H, Chen, F, Callari, M, Pourgholami, M, Morris, DL, and Stenzel, MH

Subjects
Maleimides, Drug Carriers, Polymers, Enzyme Stability, MCF-7 Cells, Humans, Methacrylates, Nanoparticles, Muramidase, Serum Albumin, Bovine, 03 Chemical Sciences, 06 Biological Sciences, 09 Engineering, Micelles, Polyethylene Glycols
Abstract

An increasing amount of therapeutic agents are based on proteins. However, proteins as drug have intrinsic problems such as their low hydrolytic stability. Delivery of proteins using nanoparticles has increasingly been the focus of interest with polyion complex micelles, prepared from charged block copolymer and the oppositely charged protein, as an example of an attractive carrier for proteins. Inspired by this approach, a more biocompatible pathway has been developed here, which replaces the charged synthetic polymer with an abundant protein, such as albumin. Although bovine serum albumin (BSA) was observed to form complexes with positively charged proteins directly, the resulting protein nanoparticle were not stable and aggregated to large precipitates over the course of a day. Therefore, maleimide functionalized poly(oligo (ethylene glycol) methyl ether methacrylate) (MI-POEGMEMA) (Mn = 26000 g/mol) was synthesized to generate a polymer-albumin conjugate, which was able to condense positively charged proteins, here lysozyme (Lyz) as a model. The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio. The activity of the encapsulated protein was tested using Sprouty 1 (C-12; Spry1) proteins, which can act as an endogenous angiogenesis inhibitor. Condensation of Spry1 with the PEGylated albumin could improve the anticancer efficacy of Spry1 against the breast cancer cells lowering the IC50 value of the protein. Furthermore, the high anticancer efficacy of the POEGMEMA-BSA/Spry1 complex micelle was verified by effectively inhibiting the growth of three-dimensional MCF-7 multicellular tumor spheroids. The PEGylated albumin complex micelle has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals.

Published
2016

27. Direct Correlation Between Zeta Potential and Cellular Uptake of Poly(methacrylic acid) Post-Modified with Guanidinium Functionalities

Author

Khine, YY, Callari, M, Lu, H, Stenzel, MH, Khine, YY, Callari, M, Lu, H, and Stenzel, MH

Abstract

Cellular uptake is identified as one of the key parameters to the successful delivery of drugs into cancer cells. In this study, the effect of the ratio of negative and positive charges on a polymer on the amount of uptake is studied. Poly(methacrylic acid), prepared by RAFT polymerization, is post-functionalized with agmatine in water to various degrees. When agmatine ratio is increased to 1, the conjugation efficiency is observed to be ≈63% indicating potentially some steric hindrance or excessive repulsion by the positive charged guanidinium functionality. The resulting zeta potential, ranging from −40 to −14 mV, is in linear correlation with the degree of functionalization. The resulting polymers are found to be non-toxic to A2780 ovarian cancer cells. The cellular uptake is subsequently studied by laser scanning confocal fluorescent microscopy, flow cytometry, and by analysis of the fluorescence intensity of the remaining solution after incubation with A2780 ovarian cancer cells. An almost linear relationship between zeta potential and cellular uptake is observed. (Figure presented.).

Published
2016

28. Dynamics of relapse in breast cancer

Author

Rueda, O.M., primary, Sammut, S.J., additional, Chin, S.F., additional, Pereira, B., additional, Batra, R.N., additional, Callari, M., additional, Provenzano, E., additional, Curtis, C., additional, and Caldas, C., additional

Published
2016
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45. miR-205 regulates basement membrane deposition in human prostate: implications for cancer development

Author

Gandellini, P, primary, Profumo, V, additional, Casamichele, A, additional, Fenderico, N, additional, Borrelli, S, additional, Petrovich, G, additional, Santilli, G, additional, Callari, M, additional, Colecchia, M, additional, Pozzi, S, additional, De Cesare, M, additional, Folini, M, additional, Valdagni, R, additional, Mantovani, R, additional, and Zaffaroni, N, additional

Published
2012
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48. Molecular heterogeneity in breast carcinoma cells with increased invasive capacities

Author

Negro Giulia, Aschenbrenner Bertram, Brezar Simona Kranjc, Cemazar Maja, Coer Andrej, Gasljevic Gorana, Savic Dragana, Sorokin Maxim, Buzdin Anton, Callari Maurizio, Kvitsaridze Irma, Jewett Anahid, Vasileva-Slaveva Mariela, Ganswindt Ute, Skvortsova Ira, and Skvortsov Sergej

Subjects
breast cancer cells, cancer stem cells, invasiveness, migration, metastasis, molecular profiling, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes.

Published
2020
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