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Biomedical subjects

Hideo Takeshima

Publications and source records attributed to Hideo Takeshima.

At least 19 recordsLinked to original sources
PubMed2006

Sellar repair with resorbable polyglactin acid sheet and fibrin glue in endoscopic endonasal transsphenoidal surgery.

BACKGROUND: Cerebrospinal fluid leakage after transsphenoidal surgery represents a serious problem. Various methods to prevent postoperative CSF leakage are available, but immediate and tight dural closure is still difficult. The efficacy of a novel sellar repair was described. METHODS: The sellar repair using absorbable PGA sheet and fibrin glue was applied to 18 consecutive patients with sellar tumors that include 13 pituitary adenomas, 2 craniopharyngiomas, 2 Rathke's cleft cysts, and 1 meningioma within 135 patients who were treated with endoscopic endonasal transsphenoidal approach. The reaction speed and strength between PGA sheets and fibrin glue were examined in vitro. RESULTS: Polyglactin acid sheets were adhered to the rabbit skin with fibrin glue within 3 minutes and withstood a pressure of more than 220 mm Hg. Postoperative CSF leakage of the patients was not observed in any patients, and excellent adhesion of the PGA sheets to surrounding mucosa was estimated by endoscopic observation after the surgery. CONCLUSIONS: Repair of the sellar floor with PGA sheet and fibrin glue is a safe and effective method to prevent postoperative CSF leakage, which decreases the necessity for lumbar drainage after the operation.

Absorbable Implants↗
PubMed2006

Rising incidence of primary central nervous system lymphoma in Kumamoto, Japan.

BACKGROUND: Primary central nervous system lymphoma is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL is reportedly on the increase in some parts of the world in the last 2 decades. METHODS: We surveyed 4007 patients diagnosed with PIT between 1989 and 2004, with histologic diagnosis being obtained in 70% of the patients. Of these, the PCNSL cases were reviewed. RESULTS: Of 4007, 136 (3.4%) carried a diagnosis of PCNSL. At 0.41 per 100,000 per year, the age-adjusted incidence rate for that period was higher than that for the period from 1989 to 1998 (0.29 per 100,000 per year). Moreover, the number of patients with PCNSL doubled from 45 (1989-1996) to 91 (1997-2004). CONCLUSIONS: Our findings point to an increase in the incidence of PCNSL among immunocompetent individuals in Kumamoto Prefecture.

Age Distribution↗
PubMed2006

Recurrent intracranial germinoma outside the initial radiation field: a single-institution study.

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.

Adolescent↗
PubMed2006

Low-grade astroblastoma recurring with extensive invasion.

A 17-year-old male presented with morning headache and double vision. Neuroimaging revealed a lobulated enhanced mass lesion with a blurred margin and remarkable peritumoral edema, and high uptake of methionine. The gray, soft, well-circumscribed mass was grossly totally resected. Histological examination showed the tumor cells were well differentiated with the perivascular pseudorosette pattern with broad, non-tapering processes radiating towards a central vessel without anaplastic features such as necrosis and endothelial proliferation. The histological diagnosis was low-grade astroblastoma. Follow-up magnetic resonance imaging demonstrated local recurrence 5 months later. Second surgery was followed by adjuvant radiotherapy and combination chemotherapy. Histological examination disclosed wide invasion by tumor cells into the subpial and perivascular space of the surrounding brain tissue. Follow-up magnetic resonance imaging demonstrated further recurrence around the tumor cavity. Surgical removal followed by six courses of combination chemotherapy (ifosfamide, cisplatin, and etoposide) resulted in complete remission of the tumor. Although gross total resection of astroblastoma usually results in long-term survival, some of these yet unfamiliar tumors may develop a more malignant character.

Adolescent↗
PubMed2005

C-kit expression in germinoma: an immunohistochemistry-based study.

In our immunohistochemical study of 25 human primary intracranial germinomas and germinomas with syncytiotrophoblastic giant cells (STGC), we stained the same sections for c-kit and placental alkaline phosphatase (PLAP). Immunohistochemical expression was graded using a semi-quantitative scoring system where 3+ =51-75%, and 4+ =76-100%. Of the 25 cases, 7 (28%) were graded 3+ and 18 (72%) 4+ for c-kit; 8 (32%) were 3+ or 4+ for PLAP. All 3 cases negative for PLAP-staining were strongly positive and all embryonal carcinomas, immature teratomas, and yolk sac tumors were negative for c-kit staining. The soluble isoform of c-kit (s-kit) is reportedly detectable in cerebral spinal fluid of patients with germinomas and germinomas with STGC. C-kit and s-kit may be powerful tumor markers for germinomas with or without STGC.

Adolescent↗
PubMed2005

The environment of increased concentration of docosahexaenoic acid in glioblastoma may suppress the anti-tumor effect of macrophages.

Regarding glioblastoma, there has been controversy over whether a large number of infiltrating macrophages act as anti-tumor effectors or not. It has been exhibited that intratumoral lipid environments have a possible influence on anti-tumor immunity. Necrosis of glioblastoma and non-necrotic tissues of astrocytic tumors were analyzed to compare the amount of free docosahexaenoic acid (DHA) content. The apoptosis inducible effects of DHA on macrophages derived from peripheral blood monocytes and cultured glioma cells were evaluated by flow cytometry. The influence of DHA on the anti-tumor effects of macrophages was assessed at 0, 30, 60, and 90 mM of DHA by (51)Cr releasing assay and MTT assay. The mean concentration of free DHA in necrotic tissues (757.6 mmol/kg) was 5 times higher than that in non-necrotic tissues (147.2 mmol/kg). The DHA concentration of 30 mM induced apoptosis in macrophages, however, glioma cells were not affected even at a DHA concentration of 60 mM. Macrophages pre-exposed to DHA for 24 h decreased the cytotoxicity to U251MG cells as shown by (51)Cr releasing assay. Total viability of co-cultured macrophages and U251MG cells showed an increase at high concentrations of DHA (60 and 90 mM) according to 24 h MTT assay, although each separate culture did not. The DHA concentration in necrosis of glioblastoma was sufficient for macrophages to cause apoptosis and suppress their anti-tumor effects. The results suggest that liberated DHA in necrosis can induce apoptosis in macrophages and inhibit their functions.

Apoptosis↗
PubMed2004

Integrin-linked kinase (ILK) regulation of the cell viability in PTEN mutant glioblastoma and in vitro inhibition by the specific COX-2 inhibitor NS-398.

We report the increased activity and expression of the ILK protein in human glioblastomas and demonstrate that ILK activity is regulated by PTEN. The transfection of wild type-PTEN into the glioblastoma cell line U-251 MG altered the localization of ILK in the cell membrane; transfection with PTEN down-regulated PKB/Akt-Ser-473 phosphorylation via the inhibition of ILK-signaling. Our results suggest that ILK is critical for the PTEN-sensitive regulation of PKB/Akt-dependent cell survival. The selective COX-2 inhibitor NS-398 was found capable of down-regulating ILK and PKB/Akt phosphorylation. Our data indicate that inhibition of ILK signaling may be beneficial in the treatment of PTEN-deficient glioblastoma.

Brain↗
PubMed2004

Expression and distribution of c-kit receptor and its ligand in human CNS germ cell tumors: a useful histological marker for the diagnosis of germinoma.

We previously reported the expression of protooncogene c-kit in CNS germ cell tumors and suggested that the soluble form of c-kit (s-kit) may represent a specific clinical marker for germinoma-containing tumors. Here we investigated the expression of stem cell factor (SCF), a specific ligand of c-kit, in CNS germ cell tumor samples from 16 patients, using immunohistochemical methods to assay the expression of c-kit and SCF protein. The immunostaining patterns of c-kit and SCF were almost identical. In all germinoma-containing tumors, c-kit and SCF were diffusely expressed on the surface of germinoma cells; lymphocytes and interstitial cells were negatively stained. In immature teratomas, only some mature components, e.g., cartilage and gland, were immunoreactive for c-kit and SCF. Syncytiotrophoblastic giant cells (STGCs) were negative for both SCF and c-kit, suggesting that germinoma cells primarily coexpress SCF and c-kit. The coexpression of c-kit and SCF may be an important immunohistochemical marker for the diagnosis of CNS germinoma, and the SCF/c-kit pathway may be an alternative molecular target for the treatment of human CNS germinomas.

Biomarkers, Tumor↗
PubMed2004

Combination electro-gene therapy using herpes virus thymidine kinase and interleukin-12 expression plasmids is highly efficient against murine carcinomas in vivo.

We report the use of plasmid DNA-mediated combination gene therapy for tumor-bearing mice using in vivo electroporation, also called electro-gene therapy (EGT), that resulted in uncomplicated and complete cures in more than 90% of the mice. Subcutaneously inoculated CT26 tumors in syngeneic BALB/c mice were subjected to repeated EGT treatments consisting of intratumoral co-injection of naked plasmids encoding the cytokine interleukin-12 (IL-12) (p35 and p40 subunits) and the suicide gene herpes simplex virus thymidine kinase (HSV-tk), followed by in vivo electroporation. The early anti-tumor effect was always stronger, and the rate of cure, as seen in the long-term follow-up, was always greater in the groups treated with combination EGT than in those treated with IL-12 or HSV-tk EGT alone. Systemic levels of IL-12 and IFN-gamma increased in both combination and IL-12-alone EGT-treated groups. Moreover, combination EGT for established subcutaneous tumors strongly reduced hematogenous lung metastases and increased survival time when live CT26 tumor cells were injected through the tail vein. Limited experiments on C57/B16 mice with murine melanoma also showed very similar trends. These results suggest that this simple and safe method of plasmid-mediated combination EGT may provide a potentially effective gene therapy for cancer.

Animals↗
PubMed2004

Multiple meningeal tuberculomas recurring after 18-month anti-tuberculous chemotherapy--case report.

A 26-year-old man with multiple intracranial masses widely attached to the dura presented with hypopituitarism and sexual impotence. Magnetic resonance imaging showed the lesions were isointense on the T1-weighted and hypointense on the T2-weighted images, and involved the bilateral sphenoid ridges, the convexity, and tentorial incisura. The lesion was partially removed via the right pterional approach. Histological examination identified tuberculoma associated with giant cells and caseous necrosis. Although his neurological and radiological signs worsened paradoxically during anti-tuberculosis therapy, he recovered spontaneously upon continuation of the anti-tuberculous treatment. However, he suffered recurrence as tuberculous meningitis, after administration of anti-tuberculous therapy for 18 months. Additional anti-tuberculous treatment for 12 months stabilized the disease. Tuberculoma should be included in the differential diagnosis of enhanced intracranial mass lesions. Anti-tuberculous therapy may require extended periods of up to 36 months to stabilize the disease.

Adult↗
PubMed2004

Expression of interleukin-6 in human craniopharyngiomas: a possible inducer of tumor-associated inflammation.

The total removal of craniopharyngiomas can be difficult because of their tendency to adhere to surrounding vital structures. Frequently, adjacent brain tissue is infiltrated by leukocytes and cytokine(s) produced by tumor cells may play a pivotal role in tissue reaction. To elucidate the molecular mechanism(s) underlying such local inflammation, we investigated the expression of interleukin (IL)-1alpha, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha in 15 craniopharyngiomas using a combination of RT-PCR, immunoblots, and immunohistochemistry. Although RT-PCR detected the expression of IL-1alpha, IL-6, and TNF-alpha, immunoblots demonstrated remarkable protein expression only for IL-6. Immunohistochemical study found that the epithelial cell layer was strongly immunoreactive for IL-6. Tumor cell layers stained weakly or negatively for IL-1alpha and TNF-alpha. Sandwich ELISA showed that levels of IL-1alpha and TNF-alpha were significantly higher in the cyst fluid than in cerebrospinal fluid (CSF) but lower than 10-fold. As the concentration of IL-6 in cyst fluid was >50,000 times that in CSF, we suggest that IL-6 plays an important role in the inflammatory reaction that occurs in the interface between the craniopharyngioma and the brain parenchyma.

Craniopharyngioma↗
PubMed2003

A review of soluble c-kit (s-kit) as a novel tumor marker and possible molecular target for the treatment of CNS germinoma.

BACKGROUND: Although germinomas are the most common central nervous system (CNS) germ cell tumors (GCTs), no specific tumor marker(s) has been identified. In the absence of such a marker, effective treatment planning requires surgical intervention to obtain a histologic diagnosis. The proto-oncogene c-kit is a transmembrane tyrosine kinase receptor that plays a crucial role in the development of germ cells and is aberrantly expressed in a variety of neoplasms. A soluble form of the c-kit (s-kit), composed of only the extracellular domain, has been identified as a functional molecule. METHODS: We immunohistochemically analyzed the distribution of c-kit to determine its expression profile in various histologic subtypes of CNS GCTs. To examine whether s-kit represents a novel clinical marker, its concentration in cerebrospinal fluid (CSF) was assayed by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: On the cell surface of germinomas, c-kit was diffusely positive. Some mature teratoma components were weakly immunoreactive for c-kit; syncytiotrophoblastic giant cells were negative. The level of s-kit was significantly higher in germinoma-containing tumors. The CSF concentration of s-kit was correlated with the clinical course; it was markedly higher in patients with subarachnoid dissemination. CONCLUSIONS: We found that s-kit could be a novel tumor marker for CNS germinomas. In addition, the diffuse expression of c-kit suggests that it may serve as a possible molecular target in the treatment of CNS germinomas.

Biomarkers, Tumor↗
PubMed2003

Postoperative regression of desmoplastic infantile gangliogliomas: report of two cases.

OBJECTIVE AND IMPORTANCE: Desmoplastic infantile gangliogliomas (DIGs) are extremely rare tumors that respond well to treatment. However, their biological behavior remains to be clarified. We describe two patients whose DIGs spontaneously regressed after surgery, without adjuvant therapy. CLINICAL PRESENTATION: A 9-month-old girl presented with left hemiparesis, and a 6-month-old boy presented with increasing head circumference. For both patients, neuroimaging demonstrated a huge cystic tumor that included a solid portion and was widely attached to the dura. Gadolinium-diethylenetriamine penta-acetic acid produced strong enhancement. INTERVENTION: One patient underwent partial and the other subtotal tumor removal. Histologically, both tumors were diagnosed as DIGs. Postoperatively, the residual tumors were monitored without adjuvant therapy, and both regressed in several months. CONCLUSION: Our experience suggests that DIGs may include a subgroup of tumors with a tendency for spontaneous regression, possibly attributable to the induction of apoptosis.

Apoptosis↗
PubMed2003

Pineal xanthogranuloma.

A 64-year-old man presented a large pineal cystic lesion manifesting as headache and exhibiting unusual neuroradiological findings. Magnetic resonance imaging showed a cystic lesion appearing as hyperintense on both T1- and T2-weighted images, and a nodular lesion which was hypointense on T1-and mixed intensity on T2-weighted images. The cystic mass was removed via a right occipital transtentorial approach. Histological examination disclosed that the inner surface of the cystic part consisted of bi-layered epithelial lining, portions of which had changed to stratified squamous epithelium. The solid part showed the characteristics of xanthogranuloma such as cholesterol clefts, hemosiderin-laden macrophages, and foreign body giant cells.

Brain Diseases↗
PubMed2003

Tumefactive myelinoclastic diffuse sclerosis--case report.

A 6-year-old boy presented with mental disturbance and progressive left hemiparesis. Magnetic resonance imaging demonstrated large intracranial mass lesions with ring-like enhancement. His neurological condition deteriorated rapidly. Open biopsy via craniotomy was performed under the suspicion of tumor. Histological examination showed massive demyelination and axon preservation, but no tumor cells. The diagnosis was myelinoclastic diffuse sclerosis (MDS). He was treated with high-dose methylprednisolone and improved dramatically. MDS is a rare demyelinating disorder of the central nervous system that affects mainly children and may mimic a brain tumor. MDS must be included in the differential diagnosis in young patients with a brain tumor with atypical radiological appearance.

Brain Neoplasms↗
PubMed2002

Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase (FAK).

To investigate the biological effect of cerivastatin on glioblastoma cells, we exposed them to various concentrations of cerivastatin. Cerivastatin exhibited dual effects on glioblastoma cells in a dose-dependent manner. Immunofluorescence microscopy showed disruption of actin stress fibers and focal adhesion plaques even at nanomolar concentrations. Matrigel assay demonstrated marked inhibition of glioblastoma cell invasion. Immunoblot analysis using a phosphospecific antibody against focal adhesion kinase (FAK) showed that inhibition of migration was associated with the down-regulation of tyrosine phosphorylation of FAK. Our data suggest that cerivastatin may be beneficial for combination therapy with conventional anti-cancer drugs by inhibiting the invasion of glioblastoma.

Brain Neoplasms↗