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ABSTRACT: Glioblastoma multiforme (GBM) cells invade along the existing normal capillaries in brain. Normal capillary endothelial cells function as the blood-brain barrier (BBB) that limits permeability of chemicals into the brain. To investigate whether GBM cells modulate the BBB function of normal endothelial cells, we developed a new in vitro BBB model with primary cultures of rat brain endothelial cells (RBECs), pericytes, and astrocytes. Cells were plated on a membrane with 8 μm pores, either as a monolayer or as a BBB model with triple layer culture. The BBB model consisted of RBEC on the luminal side as a bottom, and pericytes and astrocytes on the abluminal side as a top of the chamber. Human GBM cell line, LN-18 cells, or lung cancer cell line, NCI-H1299 cells, placed on either the RBEC monolayer or the BBB model increased the transendothelial electrical resistance (TEER) values against the model, which peaked within 72 h after the tumor cell application. The TEER value gradually returned to baseline with LN-18 cells, whereas the value quickly dropped to the baseline in 24 h with NCI-H1299 cells. NCI-H1299 cells invaded into the RBEC layer through the membrane, but LN-18 cells did not. Fibroblast growth factor 2 (FGF-2) strengthens the endothelial cell BBB function by increased occludin and ZO-1 expression. In our model, LN-18 and NCI-H1299 cells secreted FGF-2, and a neutralization antibody to FGF-2 inhibited LN-18 cells enhanced BBB function. These results suggest that FGF-2 would be a novel therapeutic target for GBM in the perivascular invasive front.
Cellular and Molecular Neurobiology 02/2013; · 1.97 Impact Factor
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ABSTRACT: Ultrasonography has become a common method for evaluation of the central nervous system. We present our experience with ultrasonography monitoring with a burr-hole transducer for investigation of intracranial lesions. Common indications for this technique included guidance for placement of catheters, localization of masses, aspiration of cystic lesion, and confirmation of removal. Postoperative computed tomography (CT) was obtained to corroborate the appropriate procedures performed under ultrasonography guidance. Intraoperative ultrasonography provided immediate real-time information about the anatomy and pathological location of lesions. Postoperative CT findings were consistent with intraoperative ultrasonography findings. No procedure-related complication was noted and problems were minimal. Intraoperative ultrasonography using a burr-hole transducer has proved to be useful in burr-hole surgery.
Neurologia medico-chirurgica 01/2012; 52(3):165-8. · 0.61 Impact Factor
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Kenta Ujifuku, Takayuki Matsuo,
Keisuke Toyoda,
Shiro Baba,
Tomohiro Okunaga,
Yukishige Hayashi,
Kensaku Kamada,
Minoru Morikawa,
Kazuhiko Suyama,
Izumi Nagata,
Nobuyuki Hayashi
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ABSTRACT: A 63-year-old woman presented with right hearing disturbance and vertigo. Magnetic resonance (MR) imaging revealed the presence of right vestibular schwannoma (VS). Stereotactic radiosurgery (SRS) was performed with a tumor marginal dose of 14 Gy using two isocenters. She was followed up clinically and neuroradiologically using three-dimensional spoiled gradient-echo MR imaging. She experienced temporal neurological deterioration due to peritumoral edema in her right cerebellar peduncle and pons for a few months beginning 1.5 years after SRS, when she experienced transient right facial dysesthesia and hearing deterioration. Ten years after SRS, the patient presented with sudden onset of vertigo, gait disturbance, diplopia, dysarthria, and nausea. MR imaging demonstrated a new lesion in the right cerebellar peduncle, which was diagnosed as radiation-induced stroke. The patient was followed up conservatively and her symptoms disappeared within a few months. Multiple delayed onset radiation injuries are possible sequelae of SRS for VS.
Neurologia medico-chirurgica 01/2012; 52(12):933-6. · 0.61 Impact Factor
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ABSTRACT: We describe a rare case of multinodular cerebral neuroepithelial tumor with ependymal differentiation. A 65-year-old man experienced loss of consciousness with an obscure episode of seizure attack. Magnetic resonance images disclosed a lesion located in the left temporal lobe and the insular cortex. The tumor was partially removed. Histologically, the tumor showed infiltrating multinodular tumor nodules in the cerebrum. Each nodule was well demarcated and composed of clear cells with perinuclear halos, intermingled fibrillary cells, and poorly differentiated neuroepithelial cells with mitotic activity. Immunohistochemically, clear cells showed dot-like positivity for epithelial membrane antigen. Fibrillary cells were positive for vimentin and nestin, whereas only a few glial fibrillary acidic protein-immunopositive cells were seen. We conclude that this tumor, being microscopically characterized by multinodular tumor nodules, was a high-grade neuroepithelial tumor with ependymal differentiation.
Brain Tumor Pathology 04/2011; 28(3):253-7. · 1.19 Impact Factor
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ABSTRACT: The steel scalpel and scalp clips have been commonly used for scalp incision in many neurosurgical procedures. Electrocautery is used mainly for subcutaneous and deep-layer dissection. The use of electrocautery on scalp incision has been avoided because of possible adverse events such as wound dehiscence and infection. We report our experience in Colorado-microdissection needle electrocautery for scalp incisions performed in our institution between November, 2006 and March, 2009. The rate of wound infection was compared in patients using the microdissection needle (100 procedures, n=93) and those using the steel scalpel/clips (n=261) during the same period. In patients using the microdissection needle, wound healing delay was not observed. Wound infection developed in only one procedure (1.0%) with the microdissection needle, and it developed in 6 procedures (2.2%) with the steel scalpel/clips, although this did not reach statistical significance (p=0.34). The use of electrocautery tended to cause little tissue distortion during fine dissection and it reduced blood loss. In conclusion, Colorado-microdissection needle electrocautery for scalp incisions could be safe and quite useful in neurosurgical procedures.
No shinkei geka. Neurological surgery 06/2010; 38(6):539-44. · 0.13 Impact Factor
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Kenta Ujifuku,
Norisato Mitsutake,
Shu Takakura,
Michiko Matsuse,
Vladimir Saenko,
Keiji Suzuki,
Kentaro Hayashi, Takayuki Matsuo,
Kensaku Kamada,
Izumi Nagata,
Shunichi Yamashita
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ABSTRACT: To identify microRNAs (miRNAs) specifically involved in the acquisition of temozolomide (TMZ) resistance in glioblastoma multiforme (GBM), we first established a resistant variant, U251R cells from TMZ-sensitive GBM cell line, U251MG. We then performed a comprehensive analysis of miRNA expressions in U251R and parental cells using miRNA microarrays. miR-195, miR-455-3p and miR-10a( *) were the three most up-regulated miRNAs in the resistant cells. To investigate the functional role of these miRNAs in TMZ resistance, U251R cells were transfected with miRNA inhibitors consisting of DNA/LNA hybrid oligonucleotides. Suppression of miR-455-3p or miR-10a( *) had no effect on cell growth, but showed modest cell killing effect in the presence of TMZ. On the other hand, knockdown of miR-195 alone displayed moderate cell killing effect, and combination with TMZ strongly enhanced the effect. In addition, using in silico analysis combined with cDNA microarray experiment, we present possible mRNA targets of these miRNAs. In conclusion, our findings suggest that those miRNAs may play a role in acquired TMZ resistance and could be a novel target for recurrent GBM treatment.
Cancer letters 05/2010; 296(2):241-8. · 4.86 Impact Factor
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ABSTRACT: Granulocytic sarcoma consists of neoplastic granulocytic precursors and myeloblasts. It is a focal lesion seen in 2-10.9% of acute myelogenous leukaemia (AML) patients. It usually develops either concurrently with the AML or after a remission. On rare occasions, it may be an initial manifestation of AML. Most common involvement sites are bone, periostium, soft tissue, lymph nodes and skin. Intracranial granulocytic sarcoma rarely occurs in meningeal or parenchymal form. We present an extremely rare case of intracranial granulocytic sarcoma extending from the posterior fossa to the carotid space via the jugular foramen in a 69 year old female. This form of involvement has not been previously reported. On MRI, the lesion appears isointense compared with normal grey matter in T1 and T2 weighted images and shows homogeneous contrast enhancement. With these findings, it is difficult to differentiate the lesion from other extraaxial tumours such as meningioma, paraganglioma, schwannoma, carcinoma, metastatic tumor, malignant lymphoma. However, granulocytic sarcoma, densely increased tumour cells restrict diffusion and reduce the extracellular volume fraction, tends to be markedly hyperintense on diffusion-weighted MR images and exhibits a marked decrease in ADC values. Therefore, DWI may be helpful in differentiating granulocytic sarcoma from other intracranial lesions.
No shinkei geka. Neurological surgery 01/2010; 38(1):53-9. · 0.13 Impact Factor
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ABSTRACT: A 32-year-old man presented with malignant craniopharyngioma associated with moyamoya syndrome manifesting as right visual disturbance. Magnetic resonance (MR) imaging revealed a parasellar mass lesion diagnosed as adamantinomatous craniopharyngioma. He underwent three surgical procedures and repeated courses of radiotherapy, and was able to resume his daily life. MR imaging demonstrated tumor regrowth and bilateral occlusions of the internal carotid arteries (ICAs) with basal moyamoya phenomenon, which might have been induced by irradiation and/or tumor compression, 10 years after the initial manifestations. Sufficient debulking was safely achieved via the transsphenoidal route and histological examination revealed squamous cell carcinoma, indicating malignant transformation of craniopharyngioma. The tumor relapsed after only one month, so transsphenoidal tumor debulking was tried again. However, the postoperative course was unfavorable because of intraoperative bleeding from the right ICA. Malignant transformation of craniopharyngioma may be included in moyamoya syndrome. The treatment strategy should be carefully considered in such a complicated situation.
Neurologia medico-chirurgica 01/2010; 50(7):599-603. · 0.61 Impact Factor
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ABSTRACT: To analyses the result of linac radiosurgery (LRS) for the treatment of intracranial benign lesions and to assess possible factors related to complications.
The authors retrospectively reviewed 204 patients treated with LRS between May, 1993 and December, 2003. The study determined the correlation between radiosurgical complications including imaging changes after LRS and multiple factors such as radiosurgical parameters, location, volume and shape. We divided the patients into three groups by MRI imaging changes and clinical symptoms. Group 1 (Gr. 1): Imaging change only. Group 2 (Gr. 2): Imaging change with transient symptoms. Group 3 (Gr.3): Imaging change with permanent symptoms.
Ninty-three patient with AVM: Gr. 1, 8 cases (8.6%), Gr. 2, 1 case (1.1%), Gr. 3, 2 cases (2.1%). A significantly higher incidence of imaging change was noted in patients with arteriovenous malformation (AVM) volumes greater than 10 cc, irregular shape of the nidus and deep location. Fifty-eight patients with vestibulan schwannoma (VS): Gr. 1, 6 cases (10.3%), Gr. 2, 1 case (1.8%), Gr. 3, 2 cases (3.4%). Imaging changes were seen mostly in cases with tumor volume greater than 5 cc. Fifty-three patients with meningioma: Gr. 1, 4 cases (7.5%), Gr.2, 2 cases (3.7%), Gr.3, 0 case. Imaging changes were seen mostly in convexity, parasaggital, and falx meningiomas that were deeply embedded in the cortex. The symptom continued the until last serial observation in four cases. We used various interventions in these patients including steroid, anticoagulant, surgical removal, and hyperbaric oxygen therapy; but these therapies were not effective.
LRS for each disease seems to be a safe and effective treatment. However, once serious radiation injuries occur there is no effective therapy, so it is important to make appropriate selection of patients for radiosurgery.
No shinkei geka. Neurological surgery 12/2009; 37(12):1201-6. · 0.13 Impact Factor
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ABSTRACT: NAGASAKI IS LOCATED on the western edge of Japan, closer to the Asian continent. Because of this geographical proximity, Nagasaki became a gateway for the introduction of continental culture and civilization to Japan. After the port of Nagasaki was opened for trade with the Portuguese in 1571, Nagasaki had a central role in cultural exchange with the West and China until the latter half of the 19th century. As a result of the political situation, students came to Nagasaki from all over Japan to obtain information on Western science, especially in medicine, turning Nagasaki into a hub for modern academic studies. The first medical facility in Japan educating doctors in the Western style was founded in Nagasaki in 1857. Despite the tragedy of World War II, the medical school arose again. More than 10 000 physicians have completed their studies at the medical school since its founding. The Department of Neurosurgery at Nagasaki University had its origins within the Second Department of Surgery and became an independent department in 1973. The post of professor was assumed by Kazuo Mori and succeeded in 1991 by Shobu Shibata and in 2003 by Izumi Nagata, who holds the post at the time of this writing. Neurosurgery is dynamic and constantly changing at Nagasaki University with work in progress on technological, diagnostic, and surgical innovations that permit the treatment of highly complex cases. In 2007, the 150th anniversary of the founding of Nagasaki University School of Medicine was celebrated with a number of commemorative events.
Neurosurgery 10/2009; 65(3):595-9; discussion 599-600. · 2.79 Impact Factor
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ABSTRACT: A case of nonfunctioning suprasellar ectopic pituitary adenoma in a 49-year-old man is reported. The patient was refered to us with a partial visual field defect of the right eye. Neuroendocrinological examinations showed slightly higher levels of adrenocorticotrophic hormone and prolactin. MR imagings revealed an enhancing suprasellar tumor and a normal pituitary gland in the sella turcica. The patient underwent a craniotomy and the tumor was partially removed, although it was firmly attached to the pituitary stalk. The tumor was diagnosed histologically as a nonfunctioning pituitary adenoma. Cases of nonfunctioning suprasellar ectopic pituitary adenoma have rarely been reported. The pathophysiology of such tumors is discussed.
No shinkei geka. Neurological surgery 01/2009; 36(12):1121-5. · 0.13 Impact Factor
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ABSTRACT: Dehydroepiandrosterone (DHEA) modulates sensitivity to radiation-induced injury in human neuroglioma cells (H4) through effects on Akt signalling by glutathione (GSH)-dependent redox regulation. Previous treatment of H4 cells with DHEA for 18 h reduced the gamma-ray-induced phosphorylation of Akt, activated p21(waf1) synthesis and up-regulated phosphorylation of Rb independent of p53. These reactions were followed by a decrease in cell number and an increase in apoptosis and G(2)/M checkpoint arrest. The suppression of phosphorylation of Akt by DHEA was due to regulation of the dephosphorylation by protein phosphatase 2A (PP2A). DHEA up-regulated the expression of gamma-glutamylcysteine synthetase, a rate-limiting enzyme of glutathione (GSH) synthesis, and the levels of GSH to maintain PP2A activity. The results suggested that DHEA increases the sensitivity of cells to gamma-ray irradiation by inducing apoptosis and cell cycle arrest through GSH-dependent regulation of the reduced form of PP2A to down-regulate the Akt signalling pathway.
Free radical research 12/2008; 42(11-12):957-65. · 2.22 Impact Factor
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ABSTRACT: Ultrasound imaging has become a common method for evaluation of the central nervous system. In this report, we present our novel experience with ultrasonography monitoring conducted through a burr-hole for investigation of intracranial lesions. A portable ultrasound scanner and a small transducer with a straight, untapered head were used. After opening a standard burr-hole, the transducer was inserted through the burr-hole and the intracranial lesion was examined. Intraoperative ultrasonography provides immediate ongoing information about the anatomy and pathological lesions. Distance and trajectory to the best location for the catheter were determined and the catheter was inserted with ultrasound monitoring. The final position of the catheter placed accurately into the intended compartment of the ventricular system. No procedure related complication was noted and pitfalls were minimal. Furthermore, a postoperative CT scan was obtained in each case to confirm the appropriateness of the procedure with ultrasonography. In conclusion, intraoperative ultrasonography using a burr-hole transducer has proved useful in neurological surgery.
No shinkei geka. Neurological surgery 11/2008; 36(10):879-83. · 0.13 Impact Factor
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Yoichi Morofuji,
Shunsuke Ishizaka,
Tomonori Takeshita,
Keisuke Toyoda,
Kenta Ujifuku,
Makoto Hirose,
Tsuyoshi Izumo,
Keishi Tsunoda,
Kentaro Hayashi, Takayuki Matsuo,
Naoki Kitagawa,
Kazuhiko Suyama,
Izumi Nagata
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ABSTRACT: It is reported that antimicrobial prophylaxis (AMP) reduces the incidence of surgical site infection (SSI) in neurological surgery. However, a great deal of variation exists regarding the type of antibiotics, dose, timing and duration. In this study, the authors analyzed the incidence of SSI comparing two different AMP protocols.
Five hundred and fifty patients who had undergone neurosurgeries at our institute between April 2005 and August 2007 were reviewed retrospectively. They were divided into the protocol F (309 patients with two or more days AMP) and the protocol P (241 patients with one-day AMP).
Baseline characteristics were not statistically different between two protocols. The overall rate of SSI was 1.5%. Although SSI showed a trend of low SSI incidence in the protocol P (0.8%), this was not statistically significant compared with that in the protocol F (1.9%).
The one-day (< 24 hours) administration of AMP is enough to prevent SSI in neurological surgery.
No shinkei geka. Neurological surgery 10/2008; 36(9):769-74. · 0.13 Impact Factor
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Plastic and reconstructive surgery 08/2008; 122(2):79e-80e. · 2.74 Impact Factor
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ABSTRACT: We present a case of a meningioma in which photodynamic diagnosis (PDD) using 5-aminolevulinic acid was very useful in identifying the cranial involvement.
An 83-year-old woman presented with a bony, hard, immobile bulge in her left forehead. Computed tomographic scans showed a thickening in the left frontal bone with a flat mass underneath. Magnetic resonance imaging scans revealed that enhancing lesions spread to the dura mater and subcutaneous tissue around the thickened frontal bone, reaching the upper margin of the left orbit.
Intraoperative PDD using 5-aminolevulinic acid indicated the optimal extent of the excision by showing clear fluorescence of affected tissues. The tumor was totally resected and diagnosed as an atypical meningioma. Histopathological examination confirmed the consistency of the extent of tumor invasion with affected lesions on PDD.
To the best of our knowledge, this is the first case demonstrating the efficacy of PDD using 5-aminolevulinic acid for a meningioma with cranial invasion. Additional studies are warranted, as shown in cases of malignant gliomas.
Neurosurgery 04/2008; 62(3 Suppl 1):102-3; discussion 103-4. · 2.79 Impact Factor
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ABSTRACT: There have been no studies on photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) in patients with metastatic skull tumors. Here, we present a case of skull metastasis of hepatocellular carcinoma (HCC) successfully treated by intraoperative PDD using 5-ALA. A 63-year-old man with HCC presented with a subcutaneous mass in the left occipital region. CT showed a hyperdensity mass and severe osteolytic change in the left side of the occipital bone. MRI revealed an extra-axial enhanced mass that compressed the left occipital lobe and enhancement was spreading to the adjacent subcutaneous soft tissue. In order to intraoperatively evaluate the extent of tumor invasion, PDD using 5-ALA was performed. Intraoperative PDD comfirmed that the tumor itself was highly fluorescent. Surgery was completed after comfirming the absence of residual fluorescence in the surgical field. The tumor was diagnosed HCC. Histopathological analysis confirmed that PDD accurately assessed the extent of tumor invasion. The patient was discharged home at 10 days after surgery. PDD using 5-ALA is convenient and inexpensive, and because adverse reactions are minimal, it may be useful in not only malignant glioma, but also other brain tumors.
No shinkei geka. Neurological surgery 10/2007; 35(9):913-8. · 0.13 Impact Factor
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ABSTRACT: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Although it was considered to be a poor prognostic disease, modern treatment protocols (aggressive chemotherapy and prophylactic cranial irradiation) have resulted in dramatically improved survival rates. In a group of low-risk ALL patients, the 5-year survival rate is estimated to be 85%. However, ALL patients who undergo this treatment are at risk of developing secondary neoplasms related to treatment, which has become an increasingly recognized problem.
A 3-year-old boy with ALL was successfully treated with chemotherapy (vincristine, prednisolone, mercaptopurine and methotrexate) and prophylactic cranial irradiation (total 18 Gy). At the age of 23, he was admitted to our hospital for weakness in the right leg. Computed tomography and magnetic resonance imaging revealed a parasagittal tumor of the left frontoparietal lobe with perifocal edema. The tumor was completely removed surgically and pathohistologically diagnosed as atypical meningioma.
Long-term survivors who received radiotherapy for ALL in childhood are at risk for late complications, including radiation-induced meningioma. Therefore, careful follow-up neurological examinations, for example magnetic resonance imaging, are indicated in these patients. In addition, late complications should be taken into account during the initial planning of prophylactic radiotheraphy dosage, which has implications for informed consent of the patient.
Pediatric Neurosurgery 02/2007; 43(1):36-41. · 0.70 Impact Factor
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ABSTRACT: Cranioplasty of cranial bone defects can generally be accomplished with autogeneous bones as well as with nonbiological materials. Autologous living-bone grafts are ideal but require sacrifice of donor bone, and synthetic materials might have possible exposure of the materials, delayed infection, and/or allergic reaction. The authors report cranioplasty with a bone graft after auto-purification by subcutaneous preservation of the contaminated bone fragment. A 47-year-old man was given a frontal cranioplasty with a split parietal bone and rib. Epidural abscess ensued, and debridement was performed to control the infection. The largest bone fragment was subcutaneously preserved in the chest wall and reused for cranioplasty. Subcutaneous preservation of bone is a promising strategy for cranioplasty after neurosurgery. The condition of the bone fragment can be inferred from the condition of the site at which it is preserved. If the bone flap is contaminated, it can be purified by the patient's immune system.
Journal of Craniofacial Surgery 12/2006; 17(6):1076-9. · 0.82 Impact Factor
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ABSTRACT: Radiotherapy is the primary and most important adjuvant therapy for malignant gliomas. Although the mechanism of radiation resistance in gliomas has been studied for decades, it is still not clear how the resistance is related with functions of molecular chaperones in the endoplasmic reticulum. Calreticulin (CRT) is a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum. Recently, it was reported that changes in intracellular Ca(2+) homeostasis play a role in the modulation of apoptosis. In the present study, we found that the level of CRT was higher in neuroglioma H4 cells than in glioblastoma cells (U251MG and T98G), and was well correlated with the sensitivity to gamma-irradiation. To examine the role of CRT in the radiosensitivity of malignant gliomas, the CRT gene was introduced into U251MG cells, which express low levels of CRT, and the effect of overexpression of CRT on the radiosensitivity was examined. The cells transfected with the CRT gene exhibited enhanced radiation-induced apoptosis compared with untransfected control cells. In CRT-overexpressing cells, cell survival signaling via Akt was markedly suppressed. Furthermore, the gene expression of protein phosphatase 2Ac alpha (PP2Ac alpha), which is responsible for the dephosphorylation and inactivation of Akt, was up-regulated in CRT-overexpressing cells, and the regulation was dependent on Ca(2+). Thus, overexpression of CRT modulates radiation-induced apoptosis by suppressing Akt signaling through the up-regulation of PP2Ac alpha expression via altered Ca(2+) homeostasis. These results show the novel mechanism by which CRT is involved in the regulation of radiosensitivity and radiation-induced apoptosis in malignant glioma cells.
Cancer Research 10/2006; 66(17):8662-71. · 7.86 Impact Factor
