Effects of Long‐Term Exposure of Intermediate Frequency Magnetic Fields (20 kHz, 360 µT) on the Development, Pathological Findings, and Behavior of Female Mice

Abstract INTRODUCTION: The tumor treatment field induces apoptosis of tumor cells by providing a low intensity, intermediate frequency, alternating current electric field via a transducer array. TTFields is based on Phase 3 EF-11 and EF-14 trials for glioblastoma in the US FDA and Japan PMDA. Therefore, I will report the statistics of TTFields use in Japan along with recent papers. METHODS: 410 patients were treated with TTFields in Japan (December 2017-), of which 17 were at Tokyo Women’s Medical University. We also referred to papers about global post-marketing surveillance and recent studies. RESULTS: Of the 410 patients, 409 (99.8%) were diagnosed with ndGBM(male: female, 66.8%: 33.2%). As of June 2020, 222 patients (54.1%) were on treatment and 188 (45.9%) were discontinued. In 17 cases at TWMU, the average age was 46.3 years. The average treatment period was 218 days, with 6 patients (35%) continuing treatment, 6 patients (35%) discontinuing due to patient wishes, and 5 patients (30%) discontinuing treatment due to recurrence. Side effects were contact dermatitis under the array in 9 patients (57%) and mild malaise in 7 patients (43%). We experienced long-term progression-free cases with TTF use of 25 months (survival 30 months after surgery) with a glioma partially resected and 21 months (survival 27 months after surgery) with a biopsied glioma. In the biopsy case, bevacizumab was used in combination during the treatment. Conclusion: In global surveillance, use for rGBM accounts for 39%, but Japan is limited to use for ndGBM due to insurance coverage. In terms of side effects, it showed a good safety profile comparable to previous trials. Long-term progression-free cases have been observed, and it is necessary to examine the characteristics of patients who respond to treatment and the effect of concomitant use with bevacizumab by prospective studies

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Activation of Glutamate Transporter-1 (GLT-1) Confers Sex-Dependent Neuroprotection in Brain Ischemia

Brain Sciences ◽

10.3390/brainsci11010076 ◽

2021 ◽

Vol 11 (1) ◽

pp. 76

Author(s):

Flavia A. Tejeda-Bayron ◽

David E. Rivera-Aponte ◽

Christian J. Malpica-Nieves ◽

Gerónimo Maldonado-Martínez ◽

Héctor M. Maldonado ◽

...

Keyword(s):

Infarct Size ◽

Glutamate Transporter ◽

Triphenyltetrazolium Chloride ◽

Stroke Outcomes ◽

Female Mice ◽

Protein Levels ◽

Translational Activator ◽

Glutamate Transporter 1 ◽

Sensorimotor Performance

Stroke is one of the leading causes of long-term disability. During ischemic stroke, glutamate is released, reuptake processes are impaired, and glutamate promotes excitotoxic neuronal death. Astrocytic glutamate transporter 1 (GLT-1) is the major transporter responsible for removing excess glutamate from the extracellular space. A translational activator of GLT-1, LDN/OSU 0212320 (LDN) has been previously developed with beneficial outcomes in epileptic animal models but has never been tested as a potential therapeutic for ischemic strokes. The present study evaluated the effects of LDN on stroke-associated brain injury. Male and female mice received LDN or vehicle 24 h before or 2 h after focal ischemia was induced in the sensorimotor cortex. Sensorimotor performance was determined using the Rung Ladder Walk and infarct area was assessed using triphenyltetrazolium chloride staining. Males treated with LDN exhibited upregulated GLT-1 protein levels, significantly smaller infarct size, and displayed better sensorimotor performance in comparison to those treated with vehicle only. In contrast, there was no upregulation of GLT-1 protein levels and no difference in infarct size or sensorimotor performance between vehicle- and LDN-treated females. Taken together, our results indicate that the GLT-1 translational activator LDN improved stroke outcomes in young adult male, but not female mice.

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