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1.
Surg Neurol Int ; 15: 149, 2024.
Article in English | MEDLINE | ID: mdl-38742004

ABSTRACT

Background: Arteriovenous fistulas (AVFs) of the craniocervical junction (CCJ) and intradural AVFs are often associated with aneurysms and varics, and it is sometimes difficult to identify the ruptured point on radiological images. We report a case in which vessel wall magnetic resonance image (VW-MRI) was useful for identifying the ruptured point at the CCJ AVF. Case Description: A 70-year-old man presented with a sudden onset of headache. He had Glasgow Coma Scale E4V5M6, world federation of neurosurgical societies (WFNS) Grade I. Fisher group 3 subarachnoid hemorrhage and hydrocephalus were found on head computed tomography. Cerebral angiography showed a spinal AVF at the C1 level of the cervical spine. Magnetic resonance image-enhanced motion sensitized driven equilibrium (MSDE-method showed an enhancing effect in part of the AVF draining vein, but the vascular architecture of this lesion was indeterminate. We performed continuous ventricular drainage for acute hydrocephalus and antihypertensive treatment. Cerebral angiography was performed 30days after the onset of the disease, and was revealed an aneurysmal structure in a portion of the AVF draining vein, which VW-MRI initially enhanced. On the 38th day after onset, he underwent direct surgery to occlude the AV fistula and dissect the aneurysmal structure. Histopathology showed that the aneurysmal structure was varices with lymphocytic infiltration, and hemosiderin deposition was observed near the varices. Conclusion: Recently, VW-MRI has been reported to show an association between the enhancement of varices in dural AVF and rupture cases. VW-MRI, especially the enhanced MSDE method, may be useful in estimating the ruptured point in arteriovenous shunt disease.

2.
Surg Neurol Int ; 15: 108, 2024.
Article in English | MEDLINE | ID: mdl-38628517

ABSTRACT

Background: Although mutations in telomerase reverse transcriptase (TERT) promoter (TERTp) are the most common alterations in glioblastoma (GBM), predicting TERTp mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing TERTp mutation status using magnetic resonance imaging (MRI). Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)-wild-type GBM. The apparent diffusion coefficient (ADC) and volume of CELs and FLAIR hyperintense lesions (FHLs) were determined, and the correlation between MRI features and TERTp mutation status was analyzed. In a subset of cases, FHLs were histopathologically analyzed to determine the correlation between tumor cell density and ADC. Results: TERTp mutations were present in 77 (67.5%) patients. The minimum ADC of FHLs was significantly lower in the TERTp-mutant group than in the TERTp-wild-type group (mean, 958.9 × 10-3 and 1092.1 × 10-3 mm2/s, respectively, P < 0.01). However, other MRI features, such as CEL and FHL volumes, minimum ADC of CELs, and FHL/CEL ratio, were not significantly different between the two groups. Histopathologic analysis indicated high tumor cell density in FHLs with low ADC. Conclusion: The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning.

3.
Int J Mol Sci ; 25(7)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38612758

ABSTRACT

The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests that they have unique vulnerabilities that may be therapeutically targeted. We investigated MDM2 expression levels in glioma stem cells and their non-stem cell counterparts and the effects of the genetic and pharmacological inhibition of MDM2 on the viability of these cells as well as downstream molecular pathways. The results obtained showed that MDM2 expression was substantially higher in glioma stem cells than in their non-stem cell counterparts and also that the inhibition of MDM2, either genetically or pharmacologically, induced a more pronounced activation of the p53 pathway and apoptotic cell death in the former than in the latter. Specifically, the inhibition of MDM2 caused a p53-dependent increase in the expression of BAX and PUMA and a decrease in the expression of survivin, both of which significantly contributed to the apoptotic death of glioma stem cells. The present study identified the MDM2-p53 axis as a novel therapeutic vulnerability, or an Achilles' heel, which is unique to glioma stem cells. Our results, which suggest that non-stem, bulk tumor cells are less sensitive to MDM2 inhibitors, may help guide the selection of glioblastoma patients suitable for MDM2 inhibitor therapy.


Subject(s)
Glioblastoma , Glioma , Humans , Tumor Suppressor Protein p53/genetics , Glioma/drug therapy , Glioma/genetics , Apoptosis , Neoplastic Stem Cells , Proto-Oncogene Proteins c-mdm2/genetics
4.
Acta Neurochir (Wien) ; 166(1): 83, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38353806

ABSTRACT

BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.


Subject(s)
Astrocytoma , Glioblastoma , Glioma , Oligodendroglioma , Humans , Cerebellar Nuclei , Glioma/diagnostic imaging , Glioma/surgery , Isocitrate Dehydrogenase
5.
Surg Neurol Int ; 14: 401, 2023.
Article in English | MEDLINE | ID: mdl-38053706

ABSTRACT

Background: Capillary hemangioma is a rare benign hemangioma that occurs in the soft tissues of the skin, orbit, head, and neck. Intracranial cases, especially intraparenchymal cases, are extremely rare. In this study, we report the course of an intracranial parenchymal capillary hemangioma with left mild motor paresis and involuntary movements of the left upper extremity and was successfully treated by surgical resection, including radiological and pathological examinations. Case Description: This is a case of a 60-year-old woman who presented with motor weakness and involuntary movement of the left upper extremity. Computed tomography and magnetic resonance imaging revealed the right frontal hemorrhagic mass lesion without enhancement of contrast medium. Cerebral digital subtraction angiography showed no vascular stain and abnormal arteriovenous shunt. Preoperatively, we diagnosed cavernous hemangioma with a hemorrhagic component located in the right motor cortex. Because this case was symptomatic, we performed a craniotomy and gross total resection of the right frontal lesion. The diagnosis of capillary hemangioma was made by histological examination, including immunohistological study. Conclusion: Because intraparenchymal capillary hemangiomas are difficult to diagnose with preoperative imaging, surgical treatment, and histopathological examination are important.

6.
Cancers (Basel) ; 15(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37686602

ABSTRACT

The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 alone or in combination with MDM2 on inhibition were examined by dye exclusion and/or colony formation assays. The treatment of malignant brain tumor cell lines with CEP-1347 markedly increased MDM2 protein expression, while blocking CEP-1347-induced MDM2 overexpression by genetic knockdown augmented the effects of CEP-1347 on the p53 pathway and cell growth. Blocking the MDM2-p53 interaction using the small molecule MDM2 inhibitor RG7112, but not MDM2 knockdown, reduced MDM4 expression. Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest the combination of CEP-1347-induced MDM2 overexpression with the selective inhibition of MDM2's interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells.

7.
Brain Nerve ; 75(9): 1071-1075, 2023 Sep.
Article in Japanese | MEDLINE | ID: mdl-37691249

ABSTRACT

Chiari malformation type I (CM-1) is a disease in which part of the cerebellum and brainstem invades into the spinal canal beyond the foramen magnum. Patients with CM-1 can present with various symptoms; however, most cases of CM-1 are asymptomatic. Symptomatic cases are distributed bimodally in children and middle-aged adults, but occur very rarely in elderly individuals. We experienced a case of CM-1 onset after the age of 60 years that followed a favorable postoperative course. We report the potential mechanism of asymptomatic CM-1 in elderly patients along with a review of the literature.


Subject(s)
Arnold-Chiari Malformation , Adult , Child , Aged , Middle Aged , Humans , Arnold-Chiari Malformation/surgery , Cerebellum , Brain Stem
8.
Biomedicines ; 11(7)2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37509605

ABSTRACT

A significant proportion of meningiomas are clinically aggressive, but there is currently no effective chemotherapy for meningiomas. An increasing number of studies have been conducted to develop targeted therapies, yet none have focused on the p53 pathway as a potential target. In this study, we aimed to determine the in vitro and in vivo effects of CEP-1347, a small-molecule inhibitor of MDM4 with known safety in humans. The effects of CEP-1347 and MDM4 knockdown on the p53 pathway in human meningioma cell lines with and without p53 mutation were examined by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 were examined in vitro and in a mouse xenograft model of meningioma. In vitro, CEP-1347 at clinically relevant concentrations inhibited MDM4 expression, activated the p53 pathway in malignant meningioma cells with wild-type p53, and exhibited preferential growth inhibitory effects on cells expressing wild-type p53, which was mostly mimicked by MDM4 knockdown. CEP-1347 effectively inhibited the growth of malignant meningioma xenografts at a dose that was far lower than the maximum dose that could be safely given to humans. Our findings suggest targeting the p53 pathway with CEP-1347 represents a novel and viable approach to treating aggressive meningiomas.

9.
BMC Med Imaging ; 23(1): 81, 2023 06 13.
Article in English | MEDLINE | ID: mdl-37312030

ABSTRACT

BACKGROUND: Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [123I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) accumulation in the volume of interest (VOI) by CSF area dilatation on the specific binding ratio (SBR) calculated using the Southampton method. We assessed the effect of CSF area mask correction on the SBR for idiopathic normal pressure hydrocephalus (iNPH) characterized by CSF area dilatation. METHODS: We enrolled 25 patients with iNPH who were assessed using 123I-FP-CIT single-photon emission computed tomography (SPECT) before shunt surgery or the tap test. The SBRs with and without CSF area mask correction were calculated, and changes in quantitative values were verified. Additionally, the number of voxels in the striatal and background (BG) VOI before and after CSF area mask correction were extracted. The number of voxels after correction was subtracted from that before correction, and the volume removed by the CSF area mask correction was calculated. The volumes removed from each VOI were compared to verify their effect on SBR. RESULTS: The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF area mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively than those in the striatal region. CONCLUSIONS: The SBR before and after CSF area mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results suggest that CSF area mask correction is effective in patients with iNPH. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826. 11/07/2021.


Subject(s)
Hydrocephalus, Normal Pressure , Humans , Hydrocephalus, Normal Pressure/diagnostic imaging , Hydrocephalus, Normal Pressure/surgery , Iodine Radioisotopes , Tomography, Emission-Computed, Single-Photon
10.
Surg Neurol Int ; 14: 98, 2023.
Article in English | MEDLINE | ID: mdl-37025542

ABSTRACT

Background: Aqueduct of Sylvius stenosis/obstruction interferes with cerebrospinal fluid (CSF) flow and leads to the non-communicating hydrocephalus. Acquired non-neoplastic causes of aqueduct of Sylvius stenosis/ obstruction include simple stenosis, gliosis, slit-like stenosis, and septal formation, but the detailed mechanisms are not clear. In the present study, we experienced a case of late-onset aqueductal membranous occlusion (LAMO) successfully treated by neuroendoscopic procedure, which allowed us to examine the pathology of the membranous structures of the aqueduct of Sylvius occlusion. Case Description: A 66-year-old woman presented with gradually progressive gait disturbance, cognitive dysfunction, and urinary incontinenc. Brain magnetic resonance imaging (MRI) showed enlargement of the bilateral lateral ventricles and the third ventricle without dilatation of fourth ventricle, and heavily T2-weighted images showed an enlarged aqueduct of Sylvius and a membranous structure at its caudal end. Gadolinium contrast-enhanced T1-weighted images showed no neoplastic lesions. We diagnosed this case that the hydrocephalus due to late-onset idiopathic aqueductal stenosis or LAMO and the patient underwent endoscopic third ventriculostomy and endoscopic aqueduct oplasty. Membranous tissue specimens were obtained from the occluded aqueduct of Sylvius at the time of treatment. Histopathological examination revealed gliosis, and inside the gliosis, there were cell clusters that appeared to be ependymal cells and were corpora amylacea. We confirmed CSF flow at the site of obstruction of the aqueduct of Sylvius and the stoma of the third ventricle floor by MRI images. Her symptoms were improved immediately. Conclusion: We experienced a case of LAMO successfully treated by neuroendoscopic procedure, which allowed us to examine the pathology of the membranous structure of the aqueduct of Sylvius. The pathological study of LAMO is rare, and we report it, including a review of the literature.

11.
Neurol Med Chir (Tokyo) ; 63(3): 111-115, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36682790

ABSTRACT

Serum soluble interleukin-2 receptor (sIL-2R) is a practical tumor marker that is elevated in hematogenous tumors. The purpose of this study was to determine the usefulness of serum sIL-2R for differentiating among malignant brain tumors, including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL). This study retrospectively investigated the sIL-2R levels in 130 patients with various types of malignant brain tumors, including PCNSL patients (n = 48) and SCNSL (n = 8); metastatic brain tumors (MTs, n = 16); and glioblastoma (GBM, n = 58). The median sIL-2R level (U/mL) of the PCNSL, SCNSL, MTs, and GBM groups were 489.7, 1024.8, 413.3, and 332.7 respectively. The sIL-2R level was significantly higher in the SCNSL group than in the PCNSL or other groups. The area under the ROC curve generated from the sIL-2R level was 0.826 (sensitivity: 0.875, specificity: 0.667, cutoff value: 521 U/mL) for differentiating SCNSL from PCNSL and 0.685 (sensitivity: 0.667, specificity: 0.707, cutoff value: 342 U/mL) for differentiating PCNSL from GBM. Measurement of sIL-2R level was convenient and useful to differentiate between SCNSL and PCSNL, both of which demand different treatment strategies.


Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , Lymphoma , Humans , Retrospective Studies , Lymphoma/diagnosis , Central Nervous System Neoplasms/pathology , Brain Neoplasms/diagnosis , Receptors, Interleukin-2
12.
J Radiat Res ; 64(2): 428-437, 2023 Mar 23.
Article in English | MEDLINE | ID: mdl-36610798

ABSTRACT

This study investigated the effectiveness and safety of low-dose salvage craniospinal irradiation (CSI) for recurrent germinoma. We retrospectively reviewed long-term tumor control and late adverse effects in 15 recurrent germinoma patients treated at our hospital between 1983 and 2019. Following the first recurrence of germinoma, seven were treated with 24-30 Gy of salvage CSI, three underwent non-CSI, and five were treated with only chemotherapy. CSI achieved a significantly better recurrence-free survival rate after the first recurrence compared to other strategies (100% vs 33%, p < 0.001: log-rank test). To evaluate the safety of salvage CSI, we assessed the outcomes at the final follow-up of seven patients who received salvage CSI at first recurrence and three patients who received salvage CSI at second recurrence. The median follow-up period was 220 months after initial treatment. Five patients who received 40-50 Gy of radiation therapy or underwent multiple radiation therapy before salvage CSI were classified into Group A, whereas five patients treated with platinum-based chemotherapy and 24-32 Gy of radiation therapy to the primary site, whole ventricle, or whole brain were classified into Group B. In Group A, one had endocrine dysfunction and the other had visual dysfunction. None were socially independent. Meanwhile, in Group B, no endocrine or visual dysfunction was found, and three patients were socially independent. Salvage CSI achieved excellent tumor control in recurrent germinoma and was safe in patients initially treated with low-dose radiation therapy and chemotherapy.


Subject(s)
Brain Neoplasms , Craniospinal Irradiation , Germinoma , Humans , Retrospective Studies , Germinoma/radiotherapy , Germinoma/drug therapy , Germinoma/pathology , Brain Neoplasms/drug therapy , Brain/pathology , Radiotherapy Dosage , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/pathology , Follow-Up Studies
13.
J Nucl Med Technol ; 51(1): 44-48, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36351801

ABSTRACT

Previous reports suggest that a headrest made of carbon significantly influences cerebral blood flow in the anterior and posterior regions by image reconstruction and attenuation correction (AC). The present study aimed to develop a headrest that reduces the influence of the AC process on human brain SPECT. Methods: To validate the performance of a headrest made of extruded polystyrene (XPS), 10 healthy controls and 43 patients with cerebrovascular disease underwent 99mTc-ethyl cysteinate dimer SPECT using a carbon headrest and an XPS headrest. We evaluated the anterior-to-posterior and middle-to-posterior ratio of the brain regions in filtered backprojection (FBP) Chang AC, ordered-subset expectation maximization (OSEM) Chang AC, and OSEM CT-based AC. Results: The anterior-to-posterior ratio was significantly higher with the carbon headrest than with the XPS headrest in FBP Chang AC and OSEM Chang AC (P < 0.001). There was no significant difference between the materials in OSEM CT-based AC. The middle-to-posterior ratio did not differ to a statistically significant extent in any correction process. Conclusion: Acquisition of brain SPECT images with an XPS headrest and processing by the FBP or OSEM Chang AC method enables the influence of the headrest to be reduced, especially in anterior and posterior brain regions.


Subject(s)
Polystyrenes , Tomography, Emission-Computed, Single-Photon , Humans , Tomography, Emission-Computed, Single-Photon/methods , Image Processing, Computer-Assisted , Brain , Phantoms, Imaging , Algorithms
14.
Surg Neurol Int ; 13: 481, 2022.
Article in English | MEDLINE | ID: mdl-36324967

ABSTRACT

Background: The vascular supply to nonfunctioning pituitary adenomas (NFPAs) differs compared with that of the anterior lobe of the normal pituitary gland. In this study, we aimed to identify feeding arteries and flow dynamics using 3.0 T magnetic resonance imaging (MRI) in NFPAs. Methods: We divided 77 cases of NFPA into three groups according to the time-intensity curve (TIC) pattern by dynamic MRI. We also investigated the presence of feeder arteries as a flow void signal on T2-weighted imaging (T2WI). Results: According to the TIC, 39 cases demonstrated an ascending pattern, 10 cases demonstrated a descending pattern, and 28 cases demonstrated a monophasic pattern. Tumor size in the ascending group was larger compared with the descending group (P = 0.0036). Flow void signals were identified in 51 of 77 cases (66.2%) on T2WI. Tumor size was larger in tumors with a flow void signal compared with those without (P < 0.0001). Flow void signals were more frequently observed in the group of ascending pattern compared with the group of monophasic and descending pattern (P = 0.032 and P = 0.003, respectively). Particularly on the caudal side, the difference between the ascending group and the monophasic and descending groups was remarkable (P = 0.0035 and P < 0.0001, respectively). Conclusion: We successfully evaluated the blood supply pattern by the TIC analysis and identified flow voids using 3.0 T MRI. Blood supply pattern was significantly associated with NFPA size. These results suggested that NFPA hemodynamics changes during tumor growth.

15.
Anticancer Res ; 42(10): 4727-4733, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36192008

ABSTRACT

BACKGROUND/AIM: The development of pharmacological inhibitors targeting negative regulators of p53, such as murine double minute (MDM) 2 and, more recently, MDM4, has been actively pursued as a potential strategy to treat cancers with wild-type p53. We previously showed that CEP-1347, a small molecule kinase inhibitor originally developed for the treatment of Parkinson's disease, suppressed MDM4 expression and activated wild-type p53 in retinoblastoma cells. However, it remains unknown whether CEP-1347 acts as an MDM4 inhibitor and as such activates p53 in other types of human cancer cells. MATERIALS AND METHODS: The effects of CEP-1347 and MDM4 knockdown on the mRNA and protein expression of components of the p53 pathway, including MDM4, in human glioma cell lines with and without p53 mutation were examined by RT-PCR and western blot analyses. Trypan blue dye exclusion was used to examine the effect of CEP-1347 on cell growth. RESULTS: CEP-1347 decreased the expression of MDM4, increase that of p53, and activated the p53 pathway in glioma cells with wild-type p53. Knockdown-mediated inhibition of MDM4 expression in a glioma cell line with wild-type p53 that overexpresses MDM4 resulted in increased p53 expression and activation of the p53 pathway. CEP-1347 preferentially inhibited the growth of glioma cells with wild-type p53 without showing toxicity to normal cells at clinically relevant concentrations. CONCLUSION: Our findings suggest CEP-1347 is a novel inhibitor of MDM4 protein expression and as such activates p53 to inhibit the growth of cancer cells with wild-type p53, including retinoblastoma and glioblastoma.


Subject(s)
Glioma , Retinal Neoplasms , Retinoblastoma , Carbazoles , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Gene Expression Regulation, Neoplastic , Glioma/drug therapy , Glioma/genetics , Humans , Nuclear Proteins/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , RNA, Messenger/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
16.
Cancers (Basel) ; 14(17)2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36077758

ABSTRACT

Glioblastoma (GBM) inevitably recurs due to a resistance to current standard therapy. We showed that the antidiabetic drug metformin (MF) can induce the differentiation of stem-like glioma-initiating cells and suppress tumor formation through AMPK-FOXO3 activation. In this study, we design a phase I/II study to examine the clinical effect of MF. We aim to determine a recommended phase II MF dose with maintenance temozolomide (TMZ) in patients with newly diagnosed GBM who completed standard concomitant radiotherapy and TMZ. MF dose-escalation was planned using a 3 + 3 design. Dose-limiting toxicities (DLTs) were assessed during the first six weeks after MF initiation. Three patients were treated with 1500 mg/day MF and four patients were treated with 2250 mg/day MF between February 2021 and January 2022. No DLTs were observed. The most common adverse effects were appetite loss, nausea, and diarrhea, all of which were manageable. Two patients experienced tumor progression at 6.0 and 6.1 months, and one died 12.2 months after initial surgery. The other five patients remained stable at the last follow-up session. The MF dose of up to 2250 mg/day combined with maintenance TMZ appeared to be well tolerated, and we proceeded to a phase II study with 2250 mg/day MF.

17.
Clin Case Rep ; 10(9): e6257, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36110331

ABSTRACT

Headache is one of the most common symptoms encountered during the postpartum period. The cause may be unknown, or the following illnesses are possible: cervical artery dissection (CAD), reversible posterior cerebral encephalopathy syndrome (PRES), and reversible cerebral vasoconstrictor syndrome (RCVS). It is suggested that they are interrelated and share a similar mechanism such as small vessel endothelial dysfunction, deficiencies in self-regulation, and decreased sympathetic innervation of the posterior circulation. However, there are few reports of neuroradiological findings. We experienced a rare case of multiple postpartum vascular disease occurring at the same time. A 38-year-old woman suddenly developed thunderclap headache after giving birth. She was clear and had no neuropathy. Computed tomography revealed subarachnoid hemorrhage, including the cortical surface of the frontal lobe. Magnetic resonance image fluid-attenuated inversion recovery revealed high-intensity area in the bilateral basal ganglia and right occipital cortex. Angiography showed "string sausage" and extracranial left vertebral artery stenosis, but no aneurysm. Based on the clinical course and neuroradiological findings, we diagnosed her as postpartum vascular disease including CAD, PRES, RCVS, and cortical subarachnoid hemorrhage (SAH). Three-dimensional black blood T1-weighted images using a motion-sensitized driven equilibrium three-dimensional turbo spin echo (MSDE) sequencing method revealed an intramural hematoma consistent with the extracranial vertebral artery. After 3 months, MSDE lost its abnormal signal. Our case was rare in that multiple phenomena of postpartum vascular disease occurred at the same time. In particular, we could reveal that this speculation was reversible in the MRI MSDE sequencing.

18.
Surg Neurol Int ; 13: 209, 2022.
Article in English | MEDLINE | ID: mdl-35673670

ABSTRACT

Background: Hemifacial spasm (HFS) is most often caused by blood vessels touching a facial nerve. In particular, responsible vessels compress the root exit zone (REZ) of the facial nerve. Although we recognize these causes of HFS, it is difficult to evaluate the findings of precise lesion in radiological imaging when vessels compress REZ. Hence, we tried to obtain precise images of pre- and postoperative neuroradiological findings of HFS by creating a fusion image of MR angiography and the REZ of facial nerve extracted by magnetic resonance imaging (MRI) diffusion tensor image (DTI). Case Description: A 52-year-old woman had a 2-year history of HFS on the left side of her face. It was confirmed that the left vertebral artery and anterior inferior cerebellar artery were presented near the facial nerve on MRI. REZ of the facial nerve was visualized using DTI and fusion image was created with vascular components, making it possible to recognize the relationship between compression vessels and REZ of the facial nerve in detail. She underwent microvascular decompression and her HFS completely disappeared. We confirmed that the REZ of the facial nerve was decompressed by MRI imaging, in the same way as before surgery. Conclusion: We describe that the REZ of facial nerve and compressive vessels was delineated in detail on MRI and this technique is useful for pre- and postoperative evaluation of HFS.

19.
J Neurol Sci ; 437: 120266, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35486971

ABSTRACT

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is primarily characterized by cognitive impairment and gait disturbance. Our objective was to evaluate the clinical characteristics of iNPH and the association between cerebral blood flow (CBF), measured using single-photon emission computed tomography (SPECT), and both cognitive and gait disturbances in iNPH patients. METHODS: We compared cognitive and motor functions and neuroimaging findings between 29 iNPH patients and 35 age-matched Parkinson's disease (PD) patients. We examined the associations between cognitive and motor dysfunctions and CBF in iNPH patients using 99mTc-ECD SPECT subtraction imaging data from a database of healthy control subjects. RESULTS: The cognitive function of iNPH patients, as measured by the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB), was significantly poorer than that of PD patients; however motor function of the legs based on the Unified PD Rating Scale (UPDRS) part III was similar across groups. Impairment in cognitive function based on the MMSE and FAB was significantly correlated with motor dysfunction of the legs on the UPDRS part III and the 3-m Timed Up and Go test. Furthermore, 99mTc-ECD SPECT subtraction imaging revealed lower CBF in the bilateral lingual gyrus of iNPH patients with severely impaired cognitive and motor functions than healthy control subjects. CONCLUSION: Patients with iNPH have severely impaired cognitive function; however, motor dysfunction of the legs is similar to PD patients. The cognitive and gait disturbances of iNPH are significantly interrelated, which may be associated with an impaired brain network that includes the bilateral lingual gyrus.


Subject(s)
Cognitive Dysfunction , Hydrocephalus, Normal Pressure , Parkinson Disease , Cerebrovascular Circulation , Cognitive Dysfunction/complications , Cognitive Dysfunction/etiology , Gait , Humans , Hydrocephalus, Normal Pressure/complications , Hydrocephalus, Normal Pressure/diagnostic imaging , Occipital Lobe , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Postural Balance , Time and Motion Studies
20.
Brain Tumor Pathol ; 39(3): 139-150, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35312904

ABSTRACT

Clinicopathological risk factors for a poor prognosis were investigated in elderly patients with malignant lymphoma of the central nervous system. A total of 82 pathologically confirmed, CD20-positive, diffuse large B-cell lymphoma patients aged 71 years or older who underwent therapeutic intervention in the Tohoku and Niigata area in Japan were retrospectively reviewed. A univariate analysis was performed by the log-rank test using the Kaplan-Meier method. A Cox proportional hazards model was used for multivariate analysis of risk factors. Of the 82 patients, 39 were male and 43 were female, and their median age at onset was 75 years. At the end of the study, there were 34 relapse-free patients (41.5%), 48 relapse cases (58.5%), median progression-free survival was 18 months, and median overall survival (OS) was 26 months; there were 41 deaths and 41 survivors. Multivariate analysis of median OS showed that Karnofsky Performance Status less than 60% 3 months after treatment (p = 0.022, hazard ratio (HR) = 2.591) was the clinical risk factor, and double expressor lymphoma (p = 0.004, HR = 3.163), expression of programmed death-ligand 1 in tumor infiltrating lymphocytes or tumor-associated macrophages (p < 0.001, HR = 5.455), and Epstein-Barr virus infection (p = 0.031, HR = 5.304) were the pathological risk factors.


Subject(s)
Brain Neoplasms , Epstein-Barr Virus Infections , Lymphoma, Large B-Cell, Diffuse , Aged , Central Nervous System/pathology , Cohort Studies , Female , Herpesvirus 4, Human , Humans , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Prognosis , Retrospective Studies , Risk Factors
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