Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of C-methionine in IDH-mutant astrocytoma.

Purpose: The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and C-methionine uptake in astrocytomas with IDH mutations.

Methods: We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent C-methionine positron emission tomography scans prior to surgical resection.

Long-term efficacy and safety of perampanel as an add-on therapy in patients with epilepsy.

Background: Perampanel (PER) is a newly developed amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist that has been globally approved for the treatment of both focal and generalized seizures. The efficacy and safety of PER have only been reported over short periods of treatment so far. This study aims to clarify the long-term efficacy and safety of PER as an add-on therapy.

Long-term prognosis of 452 moyamoya disease patients with and without revascularization under perfusion-based indications.

Objectives: To evaluate the long-term outcomes of patients treated under our perfusion-based strategy and assess whether conservative treatment without surgical treatment under our strategy is acceptable.

Materials And Methods: A total of 315 adult and 137 pediatric MMD patients (follow-up period ≥ 3 years from 2001 to 2020) were included. Follow-up events in each patient group (pediatric or adult, surgically treated or conservatively treated) were evaluated and compared to each other using a log-rank test.

Histone deacetylase inhibitors enhance oncolytic herpes simplex virus therapy for malignant meningioma.

Approximately 20% of meningiomas are not benign (higher grade) and tend to relapse after surgery and radiation therapy. Malignant (anaplastic) meningioma (MM) is a minor subset of high-grade meningioma that is lethal with no effective treatment options currently. Oncolytic herpes simplex virus (oHSV) is a powerful anti-cancer modality that induces both direct cell death and anti-tumor immunity, and has shown activity in preclinical models of MM.

Initial Management of Patients with Suspected Stroke in the SARS-CoV-2 Era: Effects on the Door-to-Picture Time.

Objective: To examine the effectiveness of a newly developed emergency room (ER) protocol to treat patients with stroke and control the spread of SARS-CoV-2 by evaluating the door-to-picture time.

Methods: We retrospectively enrolled 126 patients who were transported to our ER by ambulance with suspected stroke between April 15 and October 31, 2020 (study group). A risk judgment system named the COVID level was introduced to classify the risk of infection as follows: level 0, no infection; I, infection unlikely; II, possible; III, probable; and IV, definite.

Characterization and oncolytic virus targeting of FAP-expressing tumor-associated pericytes in glioblastoma.

Cancer-associated fibroblasts (CAFs) are activated fibroblasts constituting the major stromal components in many types of cancer. CAFs contribute to hallmarks of cancer such as proliferation, invasion and immunosuppressive tumor microenvironment, and are associated with poor prognosis of patients with cancer. However, in glioblastoma (GBM), the most common and aggressive primary malignant brain tumor, our knowledge about CAFs or CAF-like stromal cells is limited.

Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma.

Purpose: Extracellular matrix (ECM) component hyaluronan (HA) facilitates malignant phenotypes of glioblastoma (GBM), however, whether HA impacts response to GBM immunotherapies is not known. Herein, we investigated whether degradation of HA enhances oncolytic virus immunotherapy for GBM.

Experimental Design: Presence of HA was examined in patient and murine GBM.

Preclinical And Clinical Development Of Oncolytic Adenovirus For The Treatment Of Malignant Glioma.

Replication conditional oncolytic human adenovirus has long been considered a promising biological therapeutic to target high-grade gliomas (HGG), a group of essentially lethal primary brain cancer. The last decade has witnessed initiation and some completion of a number of Phase I and II clinical investigations of oncolytic adenovirus for HGG in the US and Europe. Results of these trials in patients are pivotal for not only federal approval but also filling an existing knowledge gap that primarily derives from the stark differences in permissivity to human adenovirus between humans and preclinical mouse models.

IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma.

In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer glioblastoma.

A Monoclonal Antibody Against β1 Integrin Inhibits Proliferation and Increases Survival in an Orthotopic Model of High-Grade Meningioma.

Background: High-grade meningiomas (HGMs; World Health Organization [WHO] classification grade II and III) have high relapse rates and poor clinical outcomes despite surgery and radiation treatments. No effective medical therapy currently exists for HGMs, and developing novel therapeutic strategies depends on the identification of molecular drivers. In cancer, β1 integrin enhances malignant characteristics, including proliferation, invasion, and drug resistance.

Genetically distinct glioma stem-like cell xenografts established from paired glioblastoma samples harvested before and after molecularly targeted therapy.

Intratumoural heterogeneity underlies tumour escape from molecularly targeted therapy in glioblastoma. A cell-based model preserving the evolving molecular profiles of a tumour during treatment is key to understanding the recurrence mechanisms and development of strategies to overcome resistance. In this study, we established a matched pair of glioblastoma stem-like cell (GSC) cultures from patient glioblastoma samples before and after epidermal growth factor receptor (EGFR)-targeted therapy.

PLK1 Inhibition Targets Myc-Activated Malignant Glioma Cells Irrespective of Mismatch Repair Deficiency-Mediated Acquired Resistance to Temozolomide.

Mismatch repair (MMR) deficiency through inactivation has been identified in up to 30% of recurrent high-grade gliomas, and represents a key molecular mechanism underlying the acquired resistance to the alkylating agent temozolomide (TMZ). To develop a therapeutic strategy that could be effective in these TMZ-refractory gliomas, we first screened 13 DNA damage response modulators for their ability to suppress viability of MSH6-inactivated, TMZ-resistant glioma cells. We identified a PLK1 selective inhibitor, Volasertib, as the most potent in inhibiting proliferation of glioblastoma cells.

Syringomyelia due to Lumbar Spinal Fluid Drainage in the Acute Phase of Subarachnoid Hemorrhage: A Case Report.

Lumbar spinal fluid drainage is a common procedure for treating hydrocephalus and alleviating vasospasm by egesting blood in the subarachnoid cavity after subarachnoid hemorrhage. Despite being an effective and safe procedure, cerebrospinal fluid overdrainage might result in serious complications. Here we report the case of a 49-year-old man who suffered from tonsillar herniation with subsequent cervicothoracic syringomyelia in the acute phase of subarachnoid hemorrhage due to vertebral artery dissection.

Blockade of transforming growth factor-β signaling enhances oncolytic herpes simplex virus efficacy in patient-derived recurrent glioblastoma models.

Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized.

Origin, course and distribution of the nerves to the posterosuperior wall of the external acoustic meatus.

Patients with Ramsay Hunt syndrome have various clinical symptoms including vesicular rash of the external acoustic meatus and auricle. In addition to facial nerve paresis, neurological disturbances of various cranial nerves such as the acoustic nerve, glossopharyngeal nerve and vagus nerve are reported in patients of Ramsay Hunt syndrome. To understand the reasons for the clinical symptoms, we observed the nerve branches of the auricle and external acoustic meatus.

Developmental processes and ectodermal contribution to the anal canal in mice.

The anorectal canal has two origins; the upper part is derived from endoderm and the lower part is derived from ectoderm. The process of ectodermal contribution to the canal remains unclear. To understand the development of this area, serial sagittal sections of mouse embryos were made every 12h from embryonic day 13.