MicroRNA-184 Modulates Human Central Nervous System Lymphoma Cells Growth and Invasion by Targeting iASPP

Abstract Background: High-dose methotrexate and whole brain radiation therapy (WBRT) is the recommended treatment for primary central nervous system lymphoma (PCNSL). Although the initial treatment is successful, the recurrence rate is high and the prognosis is poor. Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation that occurs when non-radioactive boron-10 is irradiated with neutrons to produce α particles (10B [n, α] 7Li). In this study, we conducted a basic research to explore the possibility of BNCT as a treatment option for PCNSL. Methods: Cellular uptake of boron using human lymphoma cell-lines after exposure to boronophenylalanine (BPA) were evaluated. The cytotoxicity of lymphoma cells by photon irradiation or neutron irradiation with BPA were also evaluated. The lymphoma cells were implanted into the mouse brain and the bio-distribution of boron after administration of BPA were measured. In neutron irradiation studies, the therapeutic effect of BNCT on mouse CNSL models were evaluated in terms of survival time. Results: The boron concentration in lymphoma cells after BPA exposure was sufficiently high, and lymphoma cells showed cytotoxicity by photon irradiation, and also by BNCT. In in vivo bio-distribution study, lymphoma cells showed enough uptake of BPA with well contrasted to the brain. In the neutron irradiation experiment, the BNCT group showed a significant prolongation in their survival time compared to the control group. Conclusions: In our study, BNCT showed its effectiveness for PCNSL in a mouse brain tumor model. PCNSL is a radio-sensitive tumor with a extremely good response rate, but it also has a high recurrence rate / a high rate of adverse events, so there is no effective treatment for recurrence after treatment. Our translational study showed that BNCT is possibly have an important role against PCNSL during the therapy lines as a new treatment option for PCNSL patients.

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Efficacy of Boron Neutron Capture Therapy in Primary Central Nervous System Lymphoma: In Vitro and In Vivo Evaluation

Cells ◽

10.3390/cells10123398 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3398

Author(s):

Kohei Yoshimura ◽

Shinji Kawabata ◽

Hideki Kashiwagi ◽

Yusuke Fukuo ◽

Koji Takeuchi ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neutron Irradiation ◽

Central Nervous System Lymphoma ◽

Neutron Capture Therapy ◽

Lymphoma Cells ◽

Boron Neutron Capture ◽

Human Lymphoma

Background: Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation method. High-dose methotrexate and whole-brain radiation therapy (WBRT) are the recommended treatments for primary central nervous system lymphoma (PCNSL). This tumor responds well to initial treatment but relapses even after successful treatment, and the prognosis is poor as there is no safe and effective treatment for relapse. In this study, we aimed to conduct basic research to explore the possibility of using BNCT as a treatment for PCNSL. Methods: The boron concentration in human lymphoma cells was measured. Subsequently, neutron irradiation experiments on lymphoma cells were conducted. A mouse central nervous system (CNS) lymphoma model was created to evaluate the biodistribution of boron after the administration of borono-phenylalanine as a capture agent. In the neutron irradiation study of a mouse PCNSL model, the therapeutic effect of BNCT on PCNSL was evaluated in terms of survival. Results: The boron uptake capability of human lymphoma cells was sufficiently high both in vitro and in vivo. In the neutron irradiation study, the BNCT group showed a higher cell killing effect and prolonged survival compared with the control group. Conclusions: A new therapeutic approach for PCNSL is urgently required, and BNCT may be a promising treatment for PCNSL. The results of this study, including those of neutron irradiation, suggest success in the conduct of future clinical trials to explore the possibility of BNCT as a new treatment option for PCNSL.

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