Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

Introduction: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL.

Methods And Analysis: Forty-five elderly patients will be included.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

Objective: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV.

Methods: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration.

Anticonvulsant and antioxidant effects of lamotrigine on pilocarpine-induced status epilepticus in mice.

Objectives: The anticonvulsant and antioxidant effects of lamotrigine on status epilepticus (SE) are incompletely understood. We assessed these effects of lamotrigine on pilocarpine (Pilo)-induced SE in mice.

Methods: Male C57BL/J6 mice were assigned to three groups: the control group, Pilo (400 mg/kg, s.

Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C.

Background: The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.

Methods: An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenance TMZ for 2 years (arm B).

Mathematical Modeling and Mutational Analysis Reveal Optimal Therapy to Prevent Malignant Transformation in Grade II IDH-Mutant Gliomas.

Isocitrate dehydrogenase-mutant low-grade gliomas (IDHmut-LGG) grow slowly but frequently undergo malignant transformation, which eventually leads to premature death. Chemotherapy and radiotherapy treatments prolong survival, but can also induce genetic (or epigenetic) alterations involved in transformation. Here, we developed a mathematical model of tumor progression based on serial tumor volume data and treatment history of 276 IDHmut-LGGs classified by chromosome 1p/19q codeletion (IDH/1p19q and IDH/1p19q) and performed genome-wide mutational analyses, including targeted sequencing and longitudinal whole-exome sequencing data.

Perfusion Parameter Obtained on 3-Tesla Magnetic Resonance Imaging and the Ki-67 Labeling Index Predict the Overall Survival of Glioblastoma.

Background: Pulsed arterial spin-labeling, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) are useful for predicting glioma survival. We performed a comparative review of multiple parameters obtained using these pulse sequences on 3-Tesla magnetic resonance imaging (MRI) including the molecular status and Ki-67 labeling index in newly diagnosed supratentorial glioblastomas.

Methods: A total of 35 patients with glioblastomas underwent pulsed arterial spin-labeling, DTI, and MRS studies using 3-Tesla MRI preoperatively.

Sialic acid-binding immunoglobulin-like lectin-15 expression on peritumoral macrophages is a favorable prognostic factor for primary central nervous system lymphoma patients.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) is a new immune checkpoint molecule and its role of primary central nervous system lymphoma (PCNSL) tumor microenvironment has been unclear. We explored the Siglec-15 and programed death-ligand 1 (PD-L1) expression in tumor tissues and analyzed the association between the expression of these molecules and overall survival in newly diagnosed PCNSL. A total of 60 patients diagnosed with diffuse large B-cell lymphoma in PCNSL were included in this study.

Well-differentiated Astroblastoma with Both Focal Anaplastic Features and a Meningioma 1 Gene Alteration.

A 6-year-old female was incidentally found to have a brain tumor. Magnetic resonance imaging (MRI) demonstrated a gadolinium-enhanced mass in the left parietal lobe. We performed gross total resection with the assistance of fluorescent guidance by 5-aminolevulinic acid (5-ALA).

Recurrence of Biphenotypic Sinonasal Sarcoma With Cerebral Hemorrhaging.

Biphenotypic sinonasal sarcoma (BSNS) is a newly classified tumor that is characterized by neural and myogenic differentiation. The authors herein report a rare patient of the recurrence of BSNS with intracranial hemorrhaging and a review of the literature. A 70-year-old man presented with disturbance of consciousness and vomiting blood.

Prognostic relevance of genetic alterations in diffuse lower-grade gliomas.

Background: Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown.

Methods: Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308).

A Single Oral Dose of Geranylgeranylacetone Upregulates Vascular Endothelial Growth Factor and Protects against Kainic Acid-Induced Neuronal Cell Death: Involvement of the Phosphatidylinositol-3 Kinase/Akt Pathway.

Background: Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein inducer, against ischemic insult or kainic acid (KA)-induced neuronal cell death. Phosphatidylinositol-3 kinase (PI3K)/Akt is thought to be an important factor that mediates neuroprotection. However, the signaling pathways in the brain in vivo after oral GGA administration remain unclear.

Dedifferentiated chordoid meningioma with rhabdomyosarcomatous differentiation on the middle cranial fossa.

A 46-year-old woman presented with headache and right hemiparesis. MRI demonstrated a mass in the left middle fossa. Total resection was performed.

Venous air embolism (VAE) associated with stereotactic biopsies.

Background: Venous air embolism (VAE) is a serious potential complication of neurosurgical procedures. Stereotactic biopsies can also cause VAE; therefore, we evaluated VAE patients to call attention to the risk of VAE associated with stereotactic biopsies.

Methods: In this report, symptomatic VAE was defined as paroxysmal coughing with associated symptoms.

Stereotactic biopsy with electrical monitoring for deep-seated brain tumors.

Objective: The stereotactic biopsy is widely integrated into clinical practice as an efficient and safe procedure for histologic diagnoses. However, the surgical risk increases when the lesions are close to the eloquence of the adjacent brain. The present report describes two patients with deep-seated brain tumors who underwent a stereotactic biopsy with electrical monitoring and demonstrates the importance of this technique.

Malignant fibrous histiocytosis after high-dose proton radiation therapy for anaplastic astrocytoma.

This report presents a 70-year-old male who presented with a rare malignant fibrous histiocytosis after high-dose proton radiation therapy for anaplastic astrocytoma. To our knowledge, malignant fibrous histiocytosis caused by proton therapy has not been reported, therefore the clinical features of this complication are described and previous cases are reviewed.

Functional motor recovery of an infant after a huge ependymoma resection.

Huge supratentorial ependymomas are rarely encountered tumors, even in the infant population. A recovery from complete hemiplegia following a tumor resection including the primary motor cortex was observed. A 5-month-old girl presented with a conjugate deviation to the right and a head circumference that had gradually expanded since birth.

p73gamma transactivates the p21 promoter through preferential interaction with the p300/CBP-associated factor in human prostate cancer cells.

Several p73 variants have been reported with different carboxy-terminal structures and transcriptional activities. We showed that p73gamma had stronger transactivation activity than the other splicing variants such as alpha, beta and delta by analysing p21 promoter activity in human prostate cancer PC3 cells. The transactivation activity of p73gamma was similar to that of p53 and was enhanced by co-transfection with p300/CBP-associated factor (PCAF).

Gamma Knife surgery for primary central nervous system lymphoma: usefulness as palliative local tumor control.

Object: Although there is no established treatment for primary central nervous system lymphoma (PCNSL), therapeutic protocols involving high-dose methotrexate therapy followed, in some cases, by whole-brain radiotherapy (WBRT) have generally been adopted, and they have yielded relatively favorable results. Gamma Knife surgery (GKS) is a stopgap measure to treat patients with PCNSL. The authors summarize the results of their cases and evaluate the efficacy and usefulness of GKS.

Transcription factors and drug resistance.

Intrinsic or acquired resistance to anticancer agents is a major obstacle to the success of chemotherapy. Anticancer agents are known to modulate signal transduction pathways and alter expression of genes that play an important role in drug resistance. Emerging evidence suggests that the complexity of genomic response against anticancer agents arise from elaborate gene expression by multiple transcription factors.

Cisplatin resistance and transcription factors.

Cisplatin is one of the most potent and widely used anti-cancer agents in the treatment of various solid tumors. However, the development of resistance to cisplatin is a major obstacle in clinical treatment. Several mechanisms are thought to be involved in cisplatin resistance, including decreased intracellular drug accumulation, increased levels of cellular thiols, increased nucleotide excision-repair activity and decreased mismatch-repair activity.