The University of Tokyo · Medicine
Professor Hirokazu Takami's research lab specializes in the molecular and pathological characterization of central nervous system germ cell tumors (CNS GCTs) and diffuse gliomas, with a focus on identifying genetic drivers, such as TP53 mutations, and their clinical implications. The lab investigates the molecular heterogeneity, genomic alterations (e.g., 12p gain), and tumor microenvironment influences that shape tumor behavior and treatment response. A key direction involves translating molecular findings into improved diagnostic strategies and personalized therapeutic approaches, particularly for rare and challenging pediatric and adult-onset CNS tumors.
Figures are computed from collected data and may differ slightly.
The association between p53 immunohistochemistry and TP53 mutation status has been controversial. The present study aims to re-evaluate the efficacy of p53 immunohistochemistry to predict the mutational status of TP53. A total of 157 diffuse gliomas (World Health Organization grades II-IV) were assessed by exon-by-exon DNA sequencing from exon 4 through 10 of TP53 using frozen tissue samples. Immunohistochemistry with a p53 antibody (DO-7) on paired formalin-fixed paraffin-embedded materials was
The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.
There appears to be a differential distribution of GCTs by neuroanatomical location between major geographic and national groups. Further study is warranted to better characterize any underlying genomic, epigenetic, or environmental factors that may be driving the phenotypic differences.
Neurohypophyseal iGCTs are insidious tumors that may pose a diagnostic dilemma, as evidenced by the prolonged latency before radiographic confirmation. Serial imaging and close endocrine follow-up are recommended in patients with a characteristic clinical syndrome and negative imaging, due to the propensity for radiographic latency. Pretreatment biochemical abnormalities may indicate higher risk of posttreatment pituitary insufficiency, and all patients should receive careful endocrine follow-up
These results suggested that the pathophysiology of GCTs was less dependent on their site of origin and more dependent on the state of differentiation as well as on the tumor microenvironment balance. This study revealed distinct biological properties of GCTs, which will hopefully lead to future treatment development.
The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.
The central nervous system germ cell tumor (CNS GCT) is a rare and incompletely understood disease. A major outstanding question in the 2015 consensus document for CNS GCT management was the utility and interpretation of the tumor markers human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) in the diagnosis of malignant non-germinomatous GCTs (hereafter NGGCTs) prior to treatment. In the current study, we assembled two geographically and ethnically different clinical cohorts from the M
Preoperative physical status was found to be the most decisive factor in predicting whether patients can tolerate an awake craniotomy without complications, whereas older age and history of psychiatric treatment were not necessarily associated with adverse events. Patients who had intraoperative adverse events often had reduced chances of same-day discharge and discharge to home. Preoperative careful selection of patients who are most likely to tolerate the procedure is the key to success for aw
CNS GCTs are clinically heterogeneous lesions, resulting in numerous opportunities for improved understanding and clinical management via novel diagnostic and therapeutic protocols. Samples from second-look surgeries for recurrent germinomas frequently demonstrate teratomatous tissue, suggesting possible underdiagnosis of mixed GCTs-particularly among pineal lesions. GCT subtypes demonstrate differential cell fraction distributions on CSF analysis, a novel and perhaps diagnostically helpful find
This prospective study will determine the toxicity associated with NaSRS and provide additional quantitative metrics of efficacy for future comparative trials.
Cystic malformations in the posterior cranial fossa result from developmental failure in the paleocerebellum and meninges. The authors present the case of an infant with hydrocephalus associated with cystic dilation of the foramina of Magendie and Luschka. This 7-month-old female infant presented with sudden onset of tonic-clonic seizures. Computed tomography revealed tetraventricular hydrocephalus. Magnetic resonance imaging demonstrated a cyst communicating with the fourth ventricle and projec
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