Characterization and Magnetic Resonance Imaging of a Rat Model of Human B-Cell Central Nervous System Lymphoma

Soussain, Carole; Muldoon, Leslie L.; Várallyay, Csanád; Jahnke, Kristoph; DePaula, L.P.; Neuwelt, Edward A.

doi:10.1158/1078-0432.ccr-06-2379

Cited by 23 publications

(39 citation statements)

References 36 publications

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“…In order to evaluate PCNSL biology and new treatment approaches, we developed an animal model that closely mimics the clinical situation (Jahnke et al, 2009; Muldoon, Lewin, et al, 2011; Soussain et al, 2007). We implanted MC116 human B-cell lymphoma cells either intracerebrally or intracerebroventricularly in athymic rats.…”

Section: Primary Cns Lymphomamentioning

confidence: 99%

“…MC116 cells were also highly sensitive to MTX in vitro , with most cells killed by a clinically relevant dose of 0.1 μM within 5 days of treatment (Jahnke et al, 2009; Soussain et al, 2007). In contrast, three independent studies demonstrated a lack of responsiveness of the CNSL model to MTX in vivo .…”

Section: Primary Cns Lymphomamentioning

confidence: 99%

“…Based on the safety and efficacy using rituximab in combination with increased delivery to the CNS with BBBD in recurrent PCNSL as well as our translational laboratory studies including the development of a rodent model of human B-cell CNS lymphoma, we treated PCNSL patients with the first-line rituximab in combination with MTX-based chemotherapy and BBBD (Doolittle et al, 2007; Jahnke et al, 2009; Muldoon, Lewin, et al, 2011; Soussain et al, 2007). The rituximab was infused IV approximately 12 h prior to day 1 of monthly BBBD.…”

Section: Primary Cns Lymphomamentioning

confidence: 99%

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Delivery of Chemotherapeutics Across the Blood–Brain Barrier

Doolittle

Muldoon

Culp

et al. 2014

Advances in Pharmacology

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The blood–brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2–26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD.

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Section: Primary Cns Lymphomamentioning

confidence: 99%

Section: Primary Cns Lymphomamentioning

confidence: 99%

Section: Primary Cns Lymphomamentioning

confidence: 99%

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Delivery of Chemotherapeutics Across the Blood–Brain Barrier

Doolittle

Muldoon

Culp

et al. 2014

Advances in Pharmacology

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“…No extracerebral, spinal, or cerebellar metastasis was seen with this model. More recently, Soussain, et al, 25 have described a nude rat model in which MC116 human Blymphoma cells were implanted into the caudate nucleus; infiltrative lymphoma cells were seen in the cortex, meninges, and ventricles. Rats were treated with radiation therapy or methotrexate, and MR images were obtained pre-and posttreatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of celecoxib in the treatment of CNS lymphomas: an in vivo model

Kardosh¹,

Su²,

Schönthal³

et al. 2006

FOC

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Object The incidence of primary central nervous system lymphomas (PCNSLs) has increased over the past several decades. Unfortunately, even with the most effective therapeutic regimen (that is, methotrexate with whole-brain radiation therapy), PCNSL recurs within a few years in more than half of the treated patients and is eventually fatal. Because PCNSL usually occurs in older patients and in those with acquired immunodeficiency syndrome, combination treatments in which both chemo- and radiation therapy are used is often poorly tolerated and results in a significant reduction in the quality of life. Recently, it has been demonstrated that the selective cyclooxygenase-2 inhibitor celecoxib (Celebrex), can block the growth of lymphoma cells in vitro. Methods To create an experimental animal model in vivo for the PCNSL study, the authors intracranially injected a human B-cell lymphoma cell line into nude mice. Their data demonstrate that this experimental model is an excellent one for human PCNSL with brain and leptomeningeal involvement. They also evaluated the feasibility of using celecoxib as a therapeutic agent in the treatment of PCNSL. Nude mice with intracranial lymphomas were treated with celecoxib contained in the animal chow. The treated animals demonstrated significantly prolonged survival times compared with the untreated animals. Conclusions Based on the authors' data, celecoxib may be a promising therapeutic agent for the treatment of PCNSL.

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“…PCNSL Targeting MC116, a CD20-positive systemic B-cell lymphoma cell line, has been used to closely mimic human PCNSL in imaging, histology, and study of treatment sensitivity (25,44). To test the specific targeting of NP-FP to CD20 on the surface of MC116, cells treated with NP-control and NP-FP were analyzed by flow cytometry to detect the green fluorophore conjugated NPs.…”

Section: Peer-review Reportsmentioning

confidence: 99%