Pathologic Correlates of Primary Central Nervous System Lymphoma Defined in an Orthotopic Xenograft Model
Cigall Kadoch,Eduard B. Dinca,Ramona Voicu,Lingjing Chen,Diana Nguyen,Seema Parikh,Juliana Karrim,Marc A. Shuman,Clifford A. Lowell,Patrick A. Treseler,C. David James,James L. Rubenstein +11 more
TLDR
Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents.Abstract:
Purpose: The prospect for advances in the treatment of patients with primary central nervous system lymphoma (PCNSL) is likely dependent on the systematic evaluation of its pathobiology. Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics. Experimental Design: We characterized the molecular pathology of CNS lymphoma tumors generated by the intracerebral implantation of Raji B lymphoma cells in athymic mice. Lymphoma cells were modified for bioluminescence imaging to facilitate monitoring of tumor growth and response to therapy. In parallel, we identified molecular features of lymphoma xenograft histopathology that are evident in human PCNSL specimens. Results: Intracerebral Raji tumors were determined to faithfully reflect the molecular pathogenesis of PCNSL, including the predominant immunophenotypic state of differentiation of lymphoma cells and their reactive microenvironment. We show the expression of interleukin-4 by Raji and other B lymphoma cell lines in vitro and by Raji tumors in vivo and provide evidence for a role of this cytokine in the M2 polarization of lymphoma macrophages both in the murine model and in diagnostic specimens of human PCNSL. Conclusion: Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents. We also show for the first time the feasibility and accuracy of tumor bioluminescence in the monitoring of a highly infiltrative brain tumor.read more
Citations
More filters
Journal ArticleDOI
Emerging insights into origin and pathobiology of primary central nervous system lymphoma.
TL;DR: It is concluded that there is a lack of a genetic/transgenic model that adequately mimics pathogenesis of the disease and contribution of the tumor microenvironment in tumorigenesis and aggressiveness of PCNSL remains understudied.
Journal ArticleDOI
Mouse models of primary central nervous system lymphomas: tools for basing funding and therapeutic strategies.
Rym Ben Abdelwahed Bagga,Sabrina Donnou,Sabrina Donnou,Jérémie Cosette,Jérémie Cosette,Catherine Sautès-Fridman,Catherine Sautès-Fridman,Catherine Sautès-Fridman,Mahjoub Aouni,Sylvain Fisson,Sylvain Fisson +10 more
TL;DR: The B-and T-cell PCNSL mouse models that are used to improve the understanding of the lymphoma microenvironment, tropism and migration and to investigate novel therapeutic strategies are compiled.
Journal ArticleDOI
A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement
Rosa Bosch,Maria J. Moreno,Rebeca Dieguez-Gonzalez,María Virtudes Céspedes,Alberto Gallardo,Manuel Trias,Albert Grañena,Jorge Sierra,Isolda Casanova,Ramon Mangues +9 more
TL;DR: E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement.
Journal ArticleDOI
Blood Coagulation Factor Fibrinogen in Tumor Pathogenesis of Central Nervous System B-Cell Lymphoma.
Justin P. Chan,Mario Merlini,Hua-Xin Gao,Andrew S. Mendiola,Katerina Akassoglou,James L. Rubenstein,Jae K. Ryu +6 more
TL;DR: In this paper, abundant deposition of the blood coagulation protein fibrinogen around B-cell lymphoma was detected in CNS lymphoma patients and in the CNS parenchyma in an orthotopic mouse model.
References
More filters
Journal ArticleDOI
MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
Monika E. Hegi,Annie-Claire Diserens,Thierry Gorlia,Marie-France Hamou,Nicolas de Tribolet,Nicolas de Tribolet,Michael Weller,Johan M. Kros,Johannes A. Hainfellner,Warren P. Mason,Luigi Mariani,Jacoline E C Bromberg,Peter Hau,René O. Mirimanoff,J. Gregory Cairncross,Robert C. Janzer,Roger Stupp +16 more
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Journal ArticleDOI
Alternative activation of macrophages
TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
Journal ArticleDOI
Monocyte and macrophage heterogeneity
Siamon Gordon,Philip R. Taylor +1 more
TL;DR: Recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues.
Journal ArticleDOI
Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes
Alberto Mantovani,Silvano Sozzani,Silvano Sozzani,Massimo Locati,Paola Allavena,Antonio Sica +5 more
TL;DR: These functionally polarized cells, and similarly oriented or immature dendritic cells present in tumors, have a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression.
Journal ArticleDOI
Macrophage activation and polarization.
TL;DR: The main functions of polarized macrophages are reviewed and the perspectives of this field are discussed, which include high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion.