Yukiko Nakahara

The development of potent and selective therapeutic approaches to glioblastoma (GBM) requires the identification of molecular pathways that critically regulate the survival and proliferation of GBM. Glioblastoma stem-like cells (GSCs) possess stem-cell-like properties, self-renewal, and differentiation into multiple neural cell lineages. From a clinical point of view, GSCs have been reported to resist radiation and chemotherapy. GSCs are influenced by the microenvironment, especially the hypoxic condition. N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress the proliferation, invasion, and migration of cancer cells. Previous studies have reported that deregulated expression of NDRG1 affects tumor growth and clinical outcomes of patients with GBM. This literature review aimed to clarify the critical role of NDRG1 in tumorigenesis and acquirement of resistance for anti-GBM therapies, further to discussing the possibility and efficacy of NDRG1 as a novel target of treatment for GBM. The present review was conducted by searching the PubMed and Scopus databases. The search was conducted in February 2022. We review current knowledge on the regulation and signaling of NDRG1 in neuro-oncology. Finally, the role of NDRG1 in GBM and potential clinical applications are discussed.

Meningiomas are the most common type of intracranial brain tumors in adults. The majority of meningiomas are benign with a low risk of recurrence after resection. However, meningiomas defined as grades II or III, according to the 2016 World Health Organization (WHO) classification, termed high-grade meningiomas, frequently recur, even after gross total resection with or without adjuvant radiotherapy. Boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) are novel treatment modalities for malignant brain tumors, represented by glioblastomas. Although BNCT is based on a nuclear reaction and PDT uses a photochemical reaction, both of these therapies result in cellular damage to only the tumor cells. The aim of this literature review is to investigate the possibility and efficacy of BNCT and PDT as novel treatment modalities for high-grade meningiomas. The present review was conducted by searching PubMed and Scopus databases. The search was conducted in December 2019. Early clinical studies of BNCT have demonstrated activity for high-grade meningiomas, and a phase II clinical trial is in progress in Japan. As for PDT, studies have investigated the effect of PDT in malignant meningioma cell lines to establish PDT as a treatment for malignant meningiomas. Further laboratory research combined with proper controlled trials investigating the effects of these therapies is warranted.

Dopamine agonists are the standard first-line medical therapy for prolactinoma. We report a rare case of giant prolactinoma with a first epileptic seizure due to rapid reduction of the tumor as a complication of dopamine agonist therapy. A 27-year-old Japanese man presented to our institution with a history of visual disturbance for 1 year and general fatigue for 3 months. Magnetic resonance imaging showed a tumor that arose from the pituitary and extended to the bilateral anterior skull base, the clivus, and the cavernous sinus, with compression of the optic chiasm and the bilateral frontal and temporal lobes. On the basis of the patient’s serum concentration of prolactin, we diagnosed a prolactinoma and started dopamine agonist therapy with cabergoline. The patient had a general seizure immediately after starting dopamine agonist therapy and required general anesthetic treatment following the rapid reduction of the tumor. We speculated that the rapid reduction of the tumor resulted in the retraction of the surrounding brain structure, and the epileptic seizure was then induced by dopamine agonist therapy. We report a rare case of giant prolactinoma with a first epileptic seizure immediately after the initiation of dopamine agonist therapy. Clinicians need to be aware that the rapid reduction of a giant prolactinoma by dopamine agonist therapy may cause an epileptic seizure.

The brain tumor cells can survive regardless of hypoxia and undernutrition. Hypoxia is known to be causes of resistance to radio-chemotherapy, increased recurrent and poor prognosis. Recent reports demonstrated that cancer stem cells (CSCs) exist in hypoxic lesion of the tumor. In this study, we examined the mechanism of drug resistance under hypoxic condition in vitro and in vivo. Most of brain tumor patients are treated by temozolomide (TMZ) as chemotherapy. The efficiency and resistance of TMZ are associated with the O6-methylguanine-DNA methyltransferase (MGMT) gene. In addition, MGMT expression is induced by hypoxia, and regulated by N-myc downstream regulated gene 1 (NDRG1). We investigated the expression of these genes in glioma cell lines (GCs), glioma stem cells (GSCs), and clinical specimens detected by molecular hypoxia imaging, 18F-FRP170 PET. Some hypoxic clinical specimens showed the increased expression of MGMT and NDGR1 genes. However, GBM cell lines and GSCs showed increased expression of NDRG1 and decreased expression of MGMT. These data suggest that a hypoxic microenvironment in vivo might play an important role in molecular and phenotypic profile of tumor cells including cancer stem cells.

In the surgeries of the upper part of the cerebellopontine angle (CPA), the petrosal vein (PV) is an obstacle, and the resection of the PV sometimes causes postoperative complications such as cerebellar hemorrhagic infarction. On the other hand, it can be an anatomical landmark during the surgery. We have used three-dimensional (3D) CT images for preoperative evaluation. We, herein, report 4 cases of CPA lesions. The PV was imaged with neighboring structures using CT and a workstation. We paid attention especially to the vein of the cerebellopontine fissure (VCPF). The four cases include one case of trigeminal neuralgia, two meningiomas and one case of acoustic schwannoma. 3D CT images showed (1) the anatomical formation such as course of the PV, (2) relationship to the neighboring structures of the tumors, (3) expectation of complications after sacrificing the PV. By observing the preoperative 3D CT images, we were able to plan safety operative approaches and procedures. 3D CT images of the PV are very useful for preoperative evaluation of surgery in CPA lesions.