6 results on '"Federico Caligaris-Cappio"'
Search Results
2. Ex-vivo dynamic 3-D culture of human tissues in the RCCS™ bioreactor allows the study of Multiple Myeloma biology and response to therapy.
- Author
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Marina Ferrarini, Nathalie Steimberg, Maurilio Ponzoni, Daniela Belloni, Angiola Berenzi, Stefania Girlanda, Federico Caligaris-Cappio, Giovanna Mazzoleni, and Elisabetta Ferrero
- Subjects
Medicine ,Science - Abstract
Three-dimensional (3-D) culture models are emerging as invaluable tools in tumor biology, since they reproduce tissue-specific structural features and cell-cell interactions more accurately than conventional 2-D cultures. Multiple Myeloma, which depends on myeloma cell-Bone Marrow microenvironment interactions for development and response to drugs, may particularly benefit from such an approach. An innovative 3-D dynamic culture model based on the use of the RCCS™ Bioreactor was developed to allow long-term culture of myeloma tissue explants. This model was first validated with normal and pathological explants, then applied to tissues from myeloma patients. In all cases, histological examination demonstrated maintenance of viable myeloma cells inside their native microenvironment, with an overall well preserved histo-architecture including bone lamellae and vessels. This system was then successfully applied to evaluate the cytotoxic effects exerted by the proteasome inhibitor Bortezomib not only on myeloma cells but also on angiogenic vessels. Moreover, as surrogate markers of specialized functions expressed by myeloma cells and microenvironment, β2 microglobulin, VEGF and Angiopoietin-2 levels, as well as Matrix Metalloproteases activity, were evaluated in supernatants from 3D cultures and their levels reflected the effects of Bortezomib treatment. Notably, determination of β2 microglobulin levels in supernatants from Bortezomib-treated samples and in patients'sera following Bortezomib-based therapies disclosed an overall concordance in the response to the drug ex vivo and in vivo. Our findings indicate, as a proof of principle, that 3-D, RCCS™ bioreactor-based culture of tissue explants can be exploited for studying myeloma biology and for a pre-clinical approach to patient-targeted therapy.
- Published
- 2013
- Full Text
- View/download PDF
3. Correction: Dynamic 3-D Culture of Human Tissues in the RCCS™ Bioreactor Allows the Study of Multiple Myeloma Biology and Response to Therapy.
- Author
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Marina Ferrarini, Nathalie Steimberg, Maurilio Ponzoni, Daniela Belloni, Angiola Berenzi, Stefania Girlanda, Federico Caligaris-Cappio, Giovanna Mazzoleni, and Elisabetta Ferrero
- Subjects
Medicine ,Science - Published
- 2013
- Full Text
- View/download PDF
4. Correction: Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line
- Author
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Paolo Ghia, Gabriella Leone, Lorenza Pecciarini, Lydia Scarfò, Maurilio Ponzoni, Andreas Agathangelidis, Cristina Scielzo, Maria Teresa Sabrina Bertilaccio, Federico Caligaris-Cappio, Pamela Ranghetti, Valeria De Pascali, Federica Barbaglio, and Benedetta Apollonio
- Subjects
Gene Rearrangement ,Multidisciplinary ,Lymphocytic leukaemia ,ZAP-70 Protein-Tyrosine Kinase ,business.industry ,Science ,Correction ,CD5 Antigens ,Leukemia, Lymphocytic, Chronic, B-Cell ,Mice ,Phenotype ,Cell culture ,Cell Line, Tumor ,Cancer research ,Medicine ,Animals ,Humans ,CD5 ,business ,Neoplasm Transplantation - Abstract
Immortalized cell lines representative of chronic lymphocytic leukemia (CLL) can assist in understanding disease pathogenesis and testing new therapeutic agents. At present, very few representative cell lines are available. We here describe the characterization of a new cell line (PCL12) that grew spontaneously from the peripheral blood (PB) of a CLL patient with progressive disease and EBV infection. The CLL cell origin of PCL12 was confirmed after the alignment of its IGH sequence against the "original" clonotypic sequence. The IGH gene rearrangement was truly unmutated and no CLL-related cytogenetic or genetic lesions were detected. PCL12 cells express CD19, CD20, CD5, CD23, low levels of IgM and IgD and the poor-outcome-associated prognostic markers CD38, ZAP70 and TCL1. In accordance with its aggressive phenotype the cell line is inactive in terms of LYN and HS1 phosphorylation. BcR signalling pathway is constitutively active and anergic in terms of p-ERK and Calcium flux response to α-IgM stimulation. PCL12 cells strongly migrate in vitro in response to SDF-1 and form clusters. Finally, they grow rapidly and localize in all lymphoid organs when xenotrasplanted in Rag2-/-γc-/- mice. PCL12 represents a suitable preclinical model for testing pharmacological agents.
- Published
- 2015
5. Ex-vivo dynamic 3-D culture of human tissues in the RCCS™ bioreactor allows the study of Multiple Myeloma biology and response to therapy
- Author
-
Nathalie Steimberg, Elisabetta Ferrero, Maurilio Ponzoni, Angiola Berenzi, Daniela Belloni, Marina Ferrarini, Stefania Girlanda, Federico Caligaris-Cappio, Giovanna Mazzoleni, Ferrarini, M, Steimberg, N, Ponzoni, Maurilio, Belloni, D, Berenzi, A, Girlanda, S, Caligaris Cappio, F, Mazzoleni, G, and Ferrero, E.
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Pathology ,Cell Culture Techniques ,Cancer Treatment ,Cell Communication ,Plasma Cell Disorders ,Bortezomib ,Rats, Sprague-Dawley ,Hematologic Cancers and Related Disorders ,Tissue culture ,Bioreactors ,Engineering ,hemic and lymphatic diseases ,Tumor Cells, Cultured ,Multiple myeloma ,Multidisciplinary ,Neovascularization, Pathologic ,Hematology ,Middle Aged ,Boronic Acids ,Immunohistochemistry ,Oncology ,Pyrazines ,Medicine ,Female ,Antiangiogenesis Therapy ,Multiple Myeloma ,Proteasome Inhibitors ,Research Article ,Biotechnology ,medicine.drug ,Adult ,Genetic Markers ,medicine.medical_specialty ,Histology ,Science ,Bone Marrow Cells ,Bioengineering ,Biology ,Bone and Bones ,Angiopoietin-2 ,In vivo ,medicine ,Animals ,Humans ,Aged ,Tibia ,Beta-2 microglobulin ,Chemotherapy and Drug Treatment ,medicine.disease ,Rats ,Cell culture ,Proteasome inhibitor ,Cancer research ,beta 2-Microglobulin ,Ex vivo - Abstract
Three-dimensional (3-D) culture models are emerging as invaluable tools in tumor biology, since they reproduce tissue-specific structural features and cell-cell interactions more accurately than conventional 2-D cultures. Multiple Myeloma, which depends on myeloma cell-Bone Marrow microenvironment interactions for development and response to drugs, may particularly benefit from such an approach. An innovative 3-D dynamic culture model based on the use of the RCCS™ Bioreactor was developed to allow long-term culture of myeloma tissue explants. This model was first validated with normal and pathological explants, then applied to tissues from myeloma patients. In all cases, histological examination demonstrated maintenance of viable myeloma cells inside their native microenvironment, with an overall well preserved histo-architecture including bone lamellae and vessels. This system was then successfully applied to evaluate the cytotoxic effects exerted by the proteasome inhibitor Bortezomib not only on myeloma cells but also on angiogenic vessels. Moreover, as surrogate markers of specialized functions expressed by myeloma cells and microenvironment, β2 microglobulin, VEGF and Angiopoietin-2 levels, as well as Matrix Metalloproteases activity, were evaluated in supernatants from 3D cultures and their levels reflected the effects of Bortezomib treatment. Notably, determination of β2 microglobulin levels in supernatants from Bortezomib-treated samples and in patients'sera following Bortezomib-based therapies disclosed an overall concordance in the response to the drug ex vivo and in vivo. Our findings indicate, as a proof of principle, that 3-D, RCCS™ bioreactor-based culture of tissue explants can be exploited for studying myeloma biology and for a pre-clinical approach to patient-targeted therapy.
- Published
- 2013
6. Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line
- Author
-
Pamela Ranghetti, Maria Teresa Sabrina Bertilaccio, Gabriella Leone, Benedetta Apollonio, Federica Barbaglio, Cristina Scielzo, Maurilio Ponzoni, Lydia Scarfò, Andreas Agathangelidis, Paolo Ghia, Lorenza Pecciarini, Valeria De Pascali, Federico Caligaris-Cappio, Agathangelidis, A, Scarfò, L, Barbaglio, F, Apollonio, B, Bertilaccio, Mt, Ranghetti, P, Ponzoni, M, Leone, G, De Pascali, V, Pecciarini, L, Ghia, PAOLO PROSPERO, Caligaris Cappio, F, Scielzo, C., Agathangelidis, A., Scarfo', L., Barbaglio, F., Apollonio, B., Bertilaccio, M. T., Ranghetti, P., Ponzoni, M., Leone, G., De Pascali, V., Pecciarini, L., Ghia, P., and Caligaris-Cappio, F.
- Subjects
Chronic lymphocytic leukemia ,lcsh:Medicine ,Biology ,CD5 Antigens ,CD19 ,Mice ,immune system diseases ,Cell Line, Tumor ,hemic and lymphatic diseases ,Calcium flux ,medicine ,Animals ,Humans ,lcsh:Science ,Gene Rearrangement ,CD20 ,ZAP-70 Protein-Tyrosine Kinase ,Multidisciplinary ,ZAP70 ,lcsh:R ,hemic and immune systems ,Gene rearrangement ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Phenotype ,biology.protein ,Cancer research ,lcsh:Q ,CD5 ,Immortalised cell line ,Neoplasm Transplantation ,Research Article - Abstract
Immortalized cell lines representative of chronic lymphocytic leukemia (CLL) can assist in understanding disease pathogenesis and testing new therapeutic agents. At present, very few representative cell lines are available. We here describe the characterization of a new cell line (PCL12) that grew spontaneously from the peripheral blood (PB) of a CLL patient with progressive disease and EBV infection. The CLL cell origin of PCL12 was confirmed after the alignment of its IGH sequence against the “original” clonotypic sequence. The IGH gene rearrangement was truly unmutated and no CLL-related cytogenetic or genetic lesions were detected. PCL12 cells express CD19, CD20, CD5, CD23, low levels of IgM and IgD and the poor-outcome-associated prognostic markers CD38, ZAP70 and TCL1. In accordance with its aggressive phenotype the cell line is inactive in terms of LYN and HS1 phosphorylation. BcR signalling pathway is constitutively active and anergic in terms of p-ERK and Calcium flux response to α-IgM stimulation. PCL12 cells strongly migrate in vitro in response to SDF-1 and form clusters. Finally, they grow rapidly and localize in all lymphoid organs when xenotrasplanted in Rag2-/-γc-/- mice. PCL12 represents a suitable preclinical model for testing pharmacological agents.
- Published
- 2015
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