Daizo Yoshida

Nippon Medical School · Department of Neurosurgery

Background: 5-Aminolevulinic Acid (5-ALA) Photodiagnosis (PD) is an effective method to detect residual tumors during glioma surgery. However, the strength of fluorescence differs in every case even in the most malignant glioma such as glioblastoma. Also, false-negative fluorescence may result in tumor residue. We investigated the effect of ultraso...

Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary a...

Angiogenesis plays a crucial role in tumor growth. Recently, endocan has emerged as a new marker of vascular endothelial cells from cancers in other organs. In this study, we elucidated the relationship between endocan expression and tumor invasion of pituitary adenoma. Tumor tissues were obtained from 70 patients with pituitary adenoma and were ex...

Object: Spinal subdural hematomas (SDHs) are rare and some are concomitant with intracranial SDH. Their pathogenesis and etiology remain to be elucidated although their migration from the intracranial space has been suggested. The authors postulated that if migration plays a major role, patients with intracranial SDH may harbor asymptomatic lumbar...

The incidental detection of thyroid lesions in patients undergoing magnetic resonance (MR) imaging of the cervical spine was prospectively evaluated on 389 MR images. Sagittal images extended from the cranio-cervical junction to the upper thoracic level, and axial images from C3-4 to C7-T1 intervertebral levels. Twenty patients (5.1%) had a total o...

The aim of the present study was to develop a novel transfection method for short interfering RNA (siRNA). A nanotube with surfactant activity, A6K, consisting of six alanine residues and a hydrophilic head, lysine, was compared to the conventional cationic transfectant reagents siFECTOR and Lipofectamine 2000. Cytotoxicity for the human glioblasto...

This study evaluated preliminary findings on the efficacy of polyethylene glycol (PEG) hydrogel dural sealant capping for the prevention of cerebrospinal fluid (CSF) leakage and pneumocephalus during deep brain stimulation (DBS) surgery in the semisupine position. Group A consisted of 5 patients who underwent bilateral subthalamic nucleus (STN)-DBS...

Lumbar puncture is a medical technique that physicians must learn and is, therefore, considered a basic medical procedure. The lumbar puncture simulators Lumbar-Kun (Lumbar Puncture Simulator) and Lumbar-Kun II (Lumbar Puncture Simulator II) (Kyoto Kagaku, Kyoto, Japan) are teaching aids designed for practicing spinal insertions. We describe and re...

Early computed tomography (CT) signs are crucial to predict the onset of hemorrhagic transformation (HT) and are preventive to avoid a fatal hematoma after thrombolysis. In the present study, we retrospectively reviewed the clinical records of patients receiving heparinization to investigate the correlation between early CT signs and the frequency...

BACKGROUND: Transcranial Doppler (TCD) is widely accepted to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH); however, its predictive value remains controversial. OBJECTIVE: To investigate the predictive reliability of an increase in the mean blood flow velocity (mBFV) ratio of the ipsilateral to contralateral middle cerebral arte...

Posterior decompression of the cervical spine is an accepted treatment for patients with cervical canal disease, but some patients experience postoperative axial pain and C5 or C6 palsy that affect their quality of life. Here we describe selective posterior decompression using a spinous process-splitting approach to prevent these complications perf...

A 24-year-old woman presented with concomitant spinal and bilateral intracranial subdural hematomas (SDHs) after hitting her head and lower back in a fall while snowboarding. She developed lower back pain and posture headache. Magnetic resonance imaging revealed bilateral intracranial SDHs and spinal SDH. Her symptoms improved and all hematomas res...

Intractable epilepsy can be divided into the following categories: epilepsy refractory to optimal treatment and epilepsy considered refractory but actually inadequately treated. It is important to assess the individual factors that contribute to making epilepsy refractory, because these factors differ between patients. We report on representative p...

Pituitary adenomas produce the chemokine stromal cell-derived factor (SDF-1α/CXCL12) and its receptor, CXCR4. A recent study indicated that CXCL12 and CXCR4 are concomitantly up-regulated in hypoxia. The objective of this study was to analyze the molecular mechanism of hypoxia-mediated CXCR4 up-regulation and assess the effect of pharmacological in...

The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is known to have a homing effect, recruiting endothelial progenitor cells (EPCs) from the bone marrow to ischemic foci. In this study, we investigated whether SDF-1 is triggered by hypoxia and might be a major driving force for tumor angiogenesis in pituitary adenomas. SDF-1 and microvascul...

Stromal cell-derived factor (SDF)-1 and its receptor, CXCR4, have been identified in both neurones and glia of many brain areas. Previous studies have mainly focused on the role of SDF-1 and CXCR4 in modulating the hypothalamic-pituitary axis and their possible involvement in the development of pituitary adenomas. An alternative SDF-1 receptor, CXC...

A 61-year-old man presented with an extremely rare neoplastic cerebral aneurysm caused by brain metastasis from pleomorphic lung carcinoma manifesting as intracerebral hematoma and sudden onset of semicoma. Computed tomography demonstrated huge intracerebral hemorrhage in the left cerebral hemisphere, which had collapsed into the lateral ventricle....

We describe a 51-year-old woman with a cerebral infarction that showed transient accumulation of thallium-201. On admission, this lesion was well-enhanced by gadolinium injection and gradually expanded, mimicking a malignant brain tumor. A cerebral angiogram, however, did not indicate the presence of a malignant brain tumor. Ethyl cysteinate dimer...

Degradation and remodelling of the extracellular matrix has been investigated, with the main focus on the balance between matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP). Recent reports disclose the presence of a novel MMP-inhibiting cell membrane-anchored glycoprotein designated 'reversion-inducing cysteine-rich p...

Growth hormone-releasing hormone (GHRH) stimulates not only the synthesis and secretion of GH but also the proliferation of normal somatotrophs. The expression of GHRH receptor (GHRHR) is regulated by GHRH, both of which are known to be expressed in human GH-secreting pituitary adenoma cells. Somatic mutations in the subunit of Gsalpha protein (gsp...

Recently, complementary (c) DNA full-length clone transfection and gene silencing with the small interfering (si) RNA method have emerged as new methods for elucidating intracellular signaling pathways in cultured cell lines. However, these methods have rarely been used in the field of neuroendocrinology. Recent reports have shown the presence of a...

The aim of this study is to examine a novel drop culture model using a biologically inspired self-assembling peptide: hydrogel (RAD16-I, also called PuraMatrix), which produces a nanoscale environment similar to native extracellular matrix (ECM) for a cell line weakly adherent to a plastic surface during cell culture. Our work investigates quantita...

The discoidin domain receptor-1 (DDR1) tyrosine kinases are a family of cell surface receptors that bind to several types of collagen and facilitate cell adhesion that is known association with several cancers. However, no previous study has examined the expression and function of DDR1 in pituitary adenoma. Tissue microarray analysis of DDR1 expres...

Pituitary adenoma tissues are hypovascular, and have a lower partial oxygen pressure compared with neighboring normal organs. In this study, we investigated whether hypoxia influences the cell invasiveness of the human pituitary adenoma cell line, HP-75. HP-75 cells were exposed to hypoxic (1-10% oxygen) or normoxic (21% oxygen) conditions for 24 h...

Hypoxia appears to be causatively related to pituitary adenoma. Currently, no biomarkers are available for the postoperative assessment of hypoxia in patient samples. Since the cAMP response element binding protein (CREB) is phosphorylated under hypoxic conditions, we examined whether CREB phosphorylation levels may be exploited as a novel biomarke...

Some studies indicate that pituitary adenoma tissues are hypovascular and have lower oxygen saturation relative to the normal pituitary gland and suggest that this may induce hypoxia. Our previous study showed that laminin β2 mRNA is upregulated under hypoxic conditions (1% oxygen) but not under normoxic conditions (21% oxygen) in the HP-75 cell li...

Hypoxia-inducible factor-1 (HIF-1) alpha is the major transcription factor involved in the adaptive response to hypoxia. The purpose of this study was to investigate whether HIF 1-alpha protects HP75 cells, pituitary adenoma cell line from hypoxia induced apoptosis. HP75 was transfected with siRNA targeting HIF 1-alpha mRNA sequences or scrambled R...

Some studies indicate that pituitary adenoma tissues are hypovascular and have lower oxygen saturation relative to the normal pituitary gland and suggest that this may induce hypoxia. Our previous study showed that laminin beta2 mRNA is upregulated under hypoxic conditions (1% oxygen) but not under normoxic conditions (21% oxygen) in the HP-75 cell...

Hypoxia inducible factors (HIF) are transcription factors regulating expression of several genes related to oxygen homeostasis in response to hypoxic stress. Although HIF1-alpha and platelet derived growth factor-B (PDGF-B) are expressed in glioma tissue and closely related to tumor angiogenesis mediating vascular endothelial growth factor (VEGF) a...

Hypoxia, the disruption of oxygen homeostasis induced by low oxygen supply, is critical in the development and progression of a large number of tumors. Various solid tumors are basically in a hypoxic condition, when growth exceeds vascular supply. Under such conditions, cellular oxygen concentration redirects cellular biosynthetic pathways to promo...

Hypoxia-inducible factor (HIF)-1alpha is a crucial transcription factor involved in the adaptive response to hypoxia, whereas cathepsin D, which regulates angiostatin in several cancer cell lines, has been reported to be upregulated by HIF-1alpha. In order to determine the involvement of angiogenesis in pituitary adenomas, we studied the expression...

Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor involved in the adaptive response to hypoxia, whereas cathepsin D, which regulates angiostatin in several cancer cell lines, has been reported to be upregulated by HIF-1α. In order to determine the involvement of angiogenesis in pituitary adenomas, we studied the expression of both...

Malignant glioma invasion into the surrounding brain tissue is still a major problem for any therapeutical methods. Matrix metalloproteinases (MMPs) have been implicated as important factors in this pathological process. In this study, one of the non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin was employed to investigate the effect of i...

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor in hypoxia adaptation mechanisms. In malignant tumors, HIF-1alpha upregulates vascular endothelial growth factor (VEGF) expression to induce tumor angiogenesis. Although VEGF and HIF-1alpha are expressed in pituitary adenomas, the relationships of these factors remain unclear. Therefor...

Samples were taken from supratentorial gliomas border and normal brain autopsy which were divided into four groups, these including eight cases normal brain tissues, 30 cases of astrocytomas, 25 cases of anaplastic astrocytomas and 22 cases of glioblastomas. Cathepin B (CB) expression and microvessel density (MVD) were determined with immunohistoch...

Pleomorphic xanthoastrocytoma has been generally conceived to be in a benign nature, showing a relatively favorable prognosis. Apoplectic attack attributable by massive hemorrhage in this distinct form of the supratentorial glioma is an exceedingly rare event. A 61-year-old female presented with a sudden onset of generalized tonic--clonic convulsio...

The matrix metalloproteinase (MMP) inhibitor SI-27 has undergone extensive development because of its effectiveness against glioma invasion and angiogenesis. However, previous studies have been performed in vitro. The present work investigates the potential of SI-27 to inhibit tumor invasion, slow angiogenesis, and prolong survival in rodent brain...

Matrix metalloproteinase (MMP) plays important roles in cell invasion and tumor angiogenesis. SI-27, an anti-MMP agent, has already been shown to possess both in vitro anti-invasive and anti-angiogenic properties against malignant gliomas in non-cytotoxic dose concentrations. However, to the best of our knowledge, the molecular mechanism mediating...

A 20-year-old male presented with an osteosarcoma in the right parieto-occipital bone occurring as a painless occipital lump which had rapidly enlarged in the 6 months prior to admission. The neuroimaging appearance resembled intraosseous meningioma. Gross total resection of the tumor was achieved. The final histological diagnosis was osteosarcoma....

We aimed to analyze the anti-invasive effect of the anti-matrix metalloproteinase (anti-MMP) agent SI-27 by quantitative tracking of enhanced green fluorescent protein (EGFP)-labeled human malignant glioma cell lines in a brain slice model. Persistent expression of EGFP in human malignant glioma cell clones (U87MG, U251MG, and U373MG) was establish...

Matrix metalloproteinases (MMPs) have been implicated to play a critical role in glioma invasiveness. In this study, we aimed to investigate the expression of MMP-2 and MMP-9 in human gliomas of different degrees of malignancy, and evaluated the correlation between MMP-2 and MMP-9 expression in gliomas. The samples from 65 cases of glioma were divi...

We have elucidated the pharmacological action of the anti-matrix metalloproteinase inhibitor BE16627B on glioma cells. The study was limited to the noncytotoxic dose range. The aim of the study was to investigate whether the cytotoxicity of BE16627B, an anti-MMP agent, is related to apoptosis in the human malignant glioma cell lines U87MG, U251MG,...

OBJECTIVE: We aimed to analyze the anti-invasive effect of the anti-matrix metalloproteinase (anti-MMP) agent SI-27 by quantitative tracking of enhanced green fluorescent protein (EGFP)-labeled human malignant glioma cell lines in a brain slice model. METHODS: Persistent expression of EGFP in human malignant glioma cell clones (U87MG, U251MG, and U...

OBJECTIVE We aimed to analyze the anti-invasive effect of the anti-matrix metalloproteinase (anti-MMP) agent SI-27 by quantitative tracking of enhanced green fluorescent protein (EGFP)-labeled human malignant glioma cell lines in a brain slice model. METHODS Persistent expression of EGFP in human malignant glioma cell clones (U87MG, U251MG, and U3...

We report a girl who was diagnosed with choroid plexus carcinoma at the age of 7 and has had an active daily life in the 11 years after onset. She underwent two tumor excision operations and received radiotherapy followed by intensive chemotherapy using cisplatin, carboplatin, and etoposide. In general, the prognosis of choroid plexus carcinoma is...

We have previously reported on the anti-invasive and angiosuppressive effects of SI-27, an anti-matrix metalloproteinase (MMP) agent. The molecular mechanism of its anti-MMP action, however, has not yet been determined. The purpose of this study was to investigate the effects of SI-27 on MMP- 1, -2, -3, -9, and TIMP-1, -2 secreted by human glioma c...

Degradation of basement membrane is one the of crucial steps in tumor angiogenesis and is performed by matrix metalloproteinases (MMPs). This study was designed to investigate the suppression of tumor angiogenesis by SI-27, an MMP inhibitor. SI-27 was applied at noncytotoxic concentrations (1-100 micromol/L), and its effect on nonmitogenic vascular...

OBJECTIVE : Degradation of basement membrane is one the of crucial steps in tumor angiogenesis and is performed by matrix metalloproteinases (MMPs). This study was designed to investigate the suppression of tumor angiogenesis by SI-27, an MMP inhibitor. METHODS : SI-27 was applied at noncytotoxic concentrations (1–100 μmol/L), and its effect on non...

Persistent expression of green fluorescent protein (GFP) in human malignant glioma cell clones (U87MG, U251MG, and U373MG) was established using the pEGFP-Cl vector. Tumor spheroid was implanted into the caudate nucleus-putamen of a severely compromised immunodeficient (SCID) mouse brain slice. To allow quantitative assessment of tumor cell invasio...

Estramustine phosphate (EMP) is an anti-microtubule agent that induces apoptosis of glioma cells. We investigated whether EMP caused apoptosis through the alkylating effect of its nitrogen mustard component or by phosphorylation of bcl-2 like other anti-microtubule agents in normal human astrocyte and human malignant glioma cell lines. Apoptosis wa...

Estramustine phosphate (EMP) is an anti-microtubule agent that depolymerizes microtubules and also causes apoptosis of glioma cells. Both of these pharmacological actions have been previously studied within the same cytotoxic range of EMP concentrations. The purpose of this study was to investigate which of these two phenomena occurred before the o...

Degradation of basement membrane by metalloproteinases (MMP) is a critical step in tumor angiogenesis. To evaluate in vitro angiogenesis, several models have been employed, including bovine cornea, fenestrated rat brain, Matrigel, and others. These models did not provide quantitative analysis of capillary formation. The current study aimed for a no...

Cell invasion is a nature of malignant gliomas, demeriting to many efforts of the treatment. Matrix metalloproteinase (MMP) is acknowledged as a key factor in this complicated process. The aim of this study was to investigate whether inhibition of MMP activity in malignant glioma cells could be achieved by a novel agent, BE16627B (BE). Malignant gl...

Matrix metalloproteinase (MMP) has come to be highlighted by its close relation to the cell invasion of gliomas. Suppression of MMP activity in malignant glioma cells would be meriting to local delivery of genes or chemotherapeutic agents. In this study, we employed a novel MMP inhibitor, SI-27 to investigate inhibition of cell invasiveness in huma...

A thirty-year-old male with an intracranial malignant meningioma, first diagnosed 9 years ago, with three recurrences was admitted with a hypoglycemic shock. The blood glucose level was 17 mg/dl, requiring treatment with high doses of intravenous and oral dextrose for improvement. A large metastatic tumor in the liver was noted. All hormones and pe...

The drug effect of estramustine phosphate (EMP), an anti-microtubule agent on human glioma cells has been studied with the focus being mainly its cytotoxity or its targeting of organelles. However, the pharmacological knowledge of estramustine with respect to its cytotoxity and mechanism is limited. To acquire such knowledge, the present study inve...

Cavernous hemangiomas rarely occur in the calvarium and most commonly present in middle-age. Although a congenital vascular disorder can theoretically cause a diploic lesion in any age group, a calvarial cavernous hemangioma has not been reported in newborn. A 4-month-old male infant presented with a large left parietal mass that had been present s...

Malignant fibrous histiocytomas (MFHs) are mesenchymal tumors, usually arising in soft tissue of the extremities and are remarkably resistant to radiation and chemotherapy. A 45-year-old female presented with a rare case of MFH originating in the cranial bone manifesting as a lump in the left parietal region with no neurological abnormality. Neuroi...

Malignant fibrous histiocytomas (MFHs) are mesenchymal tumors, usually arising in soft tissue of the extremities and are remarkably resistant to radiation and chemotherapy. A 45-year-old female presented with a rare case of MFH originating in the cranial bone manifesting as a lump in the left parietal region with no neurological abnormality. Neuroi...

Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that the depolymerizing effect of an antimicrotubule agent, estramustine, on glioma microtubules would modulate cell invasiveness. To determine whether matrix metalloproteinases, key factors in cell invasion, are affected by expos...

This report presents a summary of preclinical data concerning the use of estramustine, an antimicrotubule agent against human glioblastoma cells. The strategy for the investigation of estramustine is predicated on the unique affinity of this agent for microtubule-associated proteins (MAPs). A series of laboratory investigations were used to demonst...

Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma. However, a significant amount of preclinical investigation has been directed toward estramustine's activity against human malignant glioma. These studies have demonstrated that estramusti...

Several determinants of cell motility are highly dependent on the cytoskeleton, in particular, microtubules. To our knowledge, there have been no previous reports regarding the anti-invasive ability by an antimicro-tubule agent, estramustine phosphate (EMP), on glioblastoma cell lines. We investigated the modulated cell proliferation and invasivene...

A 39-year-old female presented with acute intraventricular hemorrhage manifesting as sudden onset of headache associated with gradually progressing somnolence and left oculomotor nerve paresis. Intraventricular hemorrhage occurred from a meningioma of the lateral ventricle. Computed tomography and magnetic resonance (MR) imaging revealed intraventr...

To investigate the effects of copper (Cu)-depletion diet and D-penicillamine treatment (CDPT) on both tumor growth and angiogenesis, we studied Fischer-344 rats in which 9L gliosarcoma cells had been subcutaneously implanted. We focused primarily on the alteration of Cu contents and the vascular density. Compared with the normal diet group, the CDP...

The effect of copper (Cu) depletion on the growth of tumors was investigated in a rat brain tumor model. 9L gliosarcoma cells were injected subcutaneously in 5-week-old male Fischer-344 rats. The control group (n = 18) received a normal diet throughout the experiment and the depletion group (n = 18) received a Cu-deficient diet starting 3 weeks pri...

Estramustine is an estradiol-based agent that accumulates in cells containing estramustine binding protein. Previous studies have shown that this binding site is expressed in human glioblastoma cells and that estramustine accumulates in glioma cells, resulting in a concentration-dependent inhibition of proliferation. We have shown that estramustine...

Estramustine is an estradiol-based antimicrotubule agent that accumulates in malignant glioma cells, resulting in a concentration-dependent inhibition of proliferation. This agent has been shown to synchronize human glioma cells at G2-M consistent with its known effects on the mitotic spindle and potentially could be used as a radiation enhancer. W...

A 78-year-old female presented with swelling and severe pain in the left forehead secondary to a simple head injury received 1 month previously. On admission, neurological examination was normal. Plain skull x-ray films and computed tomography showed an osteolytic and well-defined mass in the left frontal bone. Bone scintigraphy showed high-uptake...

Trace element such as Cu and Zn have important chemical and biological properties. Recently, tissue Cu and Zn concentrations have been correlated with prognosis in selected malignancies. In addition, depletion of trace metals has suppressive effects on tumor growth in experimental rat models. We measured tissue levels of Cu and Zn and investigated...

Serum copper and zinc concentrations and copper/zinc ratios have been shown to be increased in several types of human malignancies, including human brain tumors. In this study, copper and zinc levels and copper/zinc ratios were determined by atomic absorption analysis in tissue and serum from 29 primary and metastatic brain tumor patients. Metastat...

A case of an intracerebral fibromyxoma in a 4-year-old female with a developing left hemiplegia is described. Primary intracranial benign fibrous tumors are rare. A review of the relevant patients in the literature revealed 12 other cases. The management of this patient and an analysis of reported cases are presented.

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's ea...

Two cases of postoperative enterocolitis due to methicillin-resistant Staphylococcus aureus (MRSA) after gastrectomy were experienced. Case 1: A 59-year-old male underwent subtotal gastrectomy for advanced gastric cancer. Diffuse peritonitis progressed after the first operation, so reoperation for drainage was required. Two days after the second op...

A form of disseminated necrotizing leukoencephalopathy and the shaping process of calcification was observed by CT scan in a 9-year-old boy with intracranial germ cell tumor who had received systemic combined chemotherapy, brain radiation, and intraventricular administration of methotrexate and bleomycin for the meningeal involvement of tumor cells...

The purpose of this study is to present the results of a clinical trial of local administration for malignant gliomas based upon anti-cancer agents, mainly on adriamycin. Ommaya devices, tube and reservoir were prepared, which had been chosen and improved. The following techniques were employed for implantation and local chemo-therapy. (1) Implanta...

The concentration of antibiotics in cerebrospinal fluid is of great interest in therapeutics, especially for the treatment of the central nervous system. We studied the penetration of mezlocillin (MZPC) in 3 cases with V-P shunt and 7 cases after neurosurgical operation. After intravenous injection of 4 g MZPC in the 3 cases with V-P shunt, a peak...