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Biomedical subjects

Shingo Takano

Publications and source records attributed to Shingo Takano.

At least 19 recordsLinked to original sources

Olfactory ensheathing cell tumor: a case report.

A 31-year-old Japanese woman was referred to our hospital after experiencing a convulsion. Upon radiological examination, a heterogeneously enhanced tumor was found on the anterior skull base. The tumor was surgically removed. On light microscopy, the tumor cells appeared spindle-shaped, forming an interwoven pattern. The nuclei were arranged partially parallel mimicking a palisading pattern. At first, the tumor was thought to be schwannoma. However, it was positive for S-100 and negative for both epithelial membrane antigen (EMA) and Leu7. The final diagnosis was olfactory ensheathing cell (OEC) tumor. OECs are similar to Schwann cells in microscopic appearance and upon immunohistochemical staining. However, the OECs are negative for CD57 (Leu7), while the Schwann cells are positive for it. Our patient's tumor had immunological characteristics identical to those of OEC. In the English and Japanese literature, 21 cases of solitary schwannoma on the anterior skull base have been reported. Although several theories have been suggested, the pathogenesis of subfrontal schwannoma has not been clarified. Also, OECs have never been considered as their origin. However, as in our case, OECs, rather than Schwann cells, are suspected as the origin in some of the cases.

Adult↗

Excision of juvenile pilocytic astrocytoma of the midbrain after radiotherapy.

A 13-year-old girl presented with consciousness disturbance, right hemiparesis, and impairment of hearing, swallowing, and ocular movements. A magnetic resonance image demonstrated marked hydrocephalus due to a large cystic tumor (40 x 40 x 30 mm) in the midbrain. Emergency ventricular drainage and stereotactic cyst puncture dramatically improved her condition. Since her family did not agree to surgery on the brain stem, radiotherapy was performed after ventriculoperitoneal shunting. Conventional radiotherapy of 50.4 Gy was temporarily effective, and the growth of the tumor was stabilized until approximately 8 months later when regrowth was noticed. At this stage, with the consent of her family, the tumor was removed via an infratentorial supracerebellar approach. The pathological diagnosis was juvenile pilocytic astrocytoma. The postoperative course was uneventful. No recurrence has been observed during the follow-up period of more than 6 years. This case study shows that initial excision may be appropriate for some low-grade focal lesions in the midbrain when the histological diagnosis and consent have been obtained.

Adolescent↗

Non-invasive quantification of lactate by proton MR spectroscopy and its clinical applications.

Lactate is an important metabolite in clinical cases indicating the status of metabolic impairment. We applied a clinically relevant simple method for lactate quantification using magnetic resonance spectroscopy (MRS). We used two long in-phase echo time (TE=272,544 ms) to calculate T2 relaxation time and the absolute concentration of lactate. This method was optimized using phantom study and applied to clinical cases. This technique does not require complicated processing and could be applied in daily clinical practice. Moreover, this technique enables lactate quantification in cases (e.g. tumor) where lipid peak is overlapped with the lactate peak at short echo times.

Adult↗

Correlation between choline and MIB-1 index in human gliomas. A quantitative in proton MR spectroscopy study.

BACKGROUND: Choline (Cho) containing compounds are usually evaluated using magnetic resonance spectroscopy (MRS) by relative ratios such as Cho/N-acetylaspartate (NAA) and Cho/creatine (Cre) ratios. To clarify the significance of Cho level in gliomas, we evaluated the quantified Cho level using MRS and compared it with the proliferation activity as determined by MIB-1 immunoreactivity in the histological specimen. METHODS: There were seven benign and seven malignant gliomas. MRS was obtained using a single-voxel proton regional imaging of metabolites (PRIME) sequence with three different TE for T2 compensation. Quantified Cho level was compared with the number of MIB-1 immunopositive positive cells and cell density in surgical specimens. RESULT: A positive correlation was observed between Cho and MIB-1 in benign gliomas, whereas there was a trend to an inverse correlation in malignant gliomas. This inverse correlation became a positive correlation when the necrotic area of the tumor (on the T1-weighted gadolinium enhanced images) was excluded from the voxel of interest (VOI) for MRS, but this correlation did not reach statistical significance. CONCLUSIONS: The quantification data clarified the behavior of Cho in malignant gliomas. The quantification method has the advantage of limiting the influence of other metabolites on Cho determination. In particular, the levels of other commonly measured metabolites, including Cre, may also be altered in glioma, making ratios between metabolites misleading. Heterogeneity in the MRS VOI should be considered when evaluating the proliferative activity of malignant glioma by MRS.

Adult↗

Anti-angiogenic and immunomodulatory effect of the herbal medicine "Juzen-taiho-to" on malignant glioma.

Juzen-taiho-to (JTT) is known as a Japanese herbal medicine that increases the immune function via the enhancement of phagocytosis, cytokine induction, and antibody production. Anti-neoplastic effects on malignant gliomas have been reported by means of the enhancement of the immune function in both animals and humans. We evaluated whether JTT has anti-angiogenic effects on malignant glioma growth in vitro and in vivo. In vitro, the anti-proliferative effect of JTT on malignant glioma cells and endothelial cells was assessed by cell proliferation assay. In vivo, a subcutaneous model of malignant glioma with different-aged mice (old, 43 weeks; young, 8 weeks) was used. After oral administration of JTT to mice, their immunological function and angiogenic status of tumor tissues were assessed by flow cytometry and immunohistochemistry, respectively. JTT inhibited human endothelial cell, but not glioma cell, proliferation in vitro. In vivo, the NK (natural killer) cell ratio within PBMC (peripheral blood mononuclear cells) and NK activity of fresh splenocytes obtained from JTT-treated old mice were significantly increased compared to the ratio and activity in control mice. In old mice, the vessel area of tumor tissues in JTT treatment groups was significantly decreased. These enhancements of immunological function and the inhibition of angiogenic activity were not observed in young mice. JTT not only increased host immunological function but also exerted anti-angiogenic effects on malignant glioma growth. JTT would be useful as an adjuvant medicine for malignant gliomas through its enhancement of systemic immunological function and its anti-angiogenic action.

Angiogenesis Inhibitors↗

Primary cerebral angiitis containing marked xanthoma cells with massive intraparenchymal involvement--case report--.

A 27-year-old woman was referred to our hospital with mild disorientation, bilateral abducens nerve palsy, and mild left hemiparesis. Magnetic resonance (MR) imaging revealed diffuse mass lesions resembling malignant glioma in the right frontal intraparenchymal region, with enhancement of multiple meningeal and intraparenchymal nodules. Partial resection of the frontal lesion was performed. Histological examination revealed that the specimens consisted of brain tissue, with marked perivascular infiltration of histiocytes and sheets of xanthomatous cells. The diagnosis was primary cerebral angiitis containing marked xanthoma cells. Steroid therapy was administered over 1 week. MR imaging showed that the remaining lesions resolved gradually, and had disappeared 2 years after surgery. No neurological symptoms or recurrence of the tumor has been observed during the 6-year period since the operation.

Abducens Nerve Diseases↗

Anti-angiogenic effects of SN38 (active metabolite of irinotecan): inhibition of hypoxia-inducible factor 1 alpha (HIF-1alpha)/vascular endothelial growth factor (VEGF) expression of glioma and growth of endothelial cells.

PURPOSE: Inhibition of angiogenesis is an important new treatment modality for malignancies, including gliomas. Vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1alpha (HIF-1alpha) have been investigated as potent mediators of tumor angiogenesis. We investigated whether four major chemotherapeutic agents (ACNU, cisplatin, etoposide, and SN38) showed an angiosuppressive effect in vitro. METHOD: The effects of ACNU, cisplatin, etoposide, and SN38 for endothelial cells were assessed by cell growth inhibition assay (WST-8 assay) and vessel formation assay (angiogenesis kit). The inhibitory effects of the HIF-1alpha and VEGF expression of glioma cells after SN38 treatment were assessed by real-time RT-PCR, Western blot, and ELISA. RESULTS: SN38, but not other chemotherapeutic agents, selectively inhibited endothelial cell proliferation and three-dimensional tube formations at the 0.01 microM. Furthermore, SN38 significantly decreased the HIF-1alpha and VEGF expression of glioma cells in a dose- and time-dependent manner under normoxic and hypoxic conditions. SN38 has dual angiosuppressive actions, including both the inhibition of endothelial proliferation and tube formation, and the inhibition of the angiogenic cascade in glioma cells. CONCLUSION: SN38 is an attractive agent as both a direct and indirect angiogenesis inhibitor and provides the anti-glioma agents with an angiosuppressive function.

Angiogenesis Inhibitors↗

Clinical results of proton beam therapy for skull base chordoma.

PURPOSE: To evaluate clinical results of proton beam therapy for patients with skull base chordoma. METHODS AND MATERIALS: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months). RESULTS: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery. CONCLUSION: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy.

Adolescent↗

X-irradiation to human malignant glioma cells enhances the cytotoxicity of autologous killer lymphocytes under specific conditions.

PURPOSE: To clarify the effect of combining x-irradiation and human killer lymphocytes against autologous malignant glioma cells, we analyzed not only the alteration of surface antigen expression in irradiated tumor cells, but also the cytotoxic effects of human killer lymphocytes on the autologous tumor cells with and without x-irradiation. METHODS AND MATERIALS: Six malignant glioma cell-lines (MG 1-6) established from each patient with a malignant glioma in our institute, and U87MG, were used as materials. They were irradiated by 0-50 Gy of X-rays, and the alternations of their human histocompatability leukocyte antigen (HLA), HLA-ABC, HLA-DR, -DP, -DQ, and FAS expressions were examined. Then, three sets of autologous natural killer (NK) cells, and autologous tumor-specific T lymphocytes (ATTL) were induced from the peripheral blood mononuclear cells (PBMCs) of three patients, and in vitro cytotoxic effects of these killer cells on the irradiated autologous tumor cells were analyzed. RESULTS: Irradiation-enhanced HLA-DR, -DP, -DQ, and FAS expression in glioma cell lines with low p53 expression. However, there was no correlation between HLA-ABC expression and X-ray dose. After irradiation of the tumor cells, cytotoxicity was enhanced in four of six effectors; in particular, it was significantly elevated in two killer lymphocytes. It was speculated that the enhancing effect was influenced not only by the p53 status of the tumor, but also by the types of killer lymphocytes; the alteration of cytotoxicity in NK cells on irradiated tumor cells may be compensatory for alteration in ATTLs. CONCLUSION: It was indicated that irradiation of malignant tumor cells enhanced killer cell-mediated cytotoxicity in autologous models under specific conditions. These basic data should contribute to clinical trials using local radiotherapy and systemic adoptive immunotherapy with killer lymphocytes.

Cytotoxicity, Immunologic↗

Angiogenesis and antiangiogenic therapy for malignant gliomas.

Angiogenesis is crucial to the growth of malignant gliomas. Therefore, antiangiogenic therapy represents a new, promising therapeutic modality for malignant gliomas. This study was designed to define the malignant glioma cases most suitable for antiangiogenic therapy in humans and to demonstrate the efficacy of antiangiogenic therapy in animals. Protein expression of the most potent angiogenic factor, vascular endothelial growth factor (VEGF), and its specific natural inhibitor, soluble Flt-1, as well as vessel architecture, including vessel density, area, and diameter, was evaluated in human malignant glioma samples (24 glioblastomas, 13 anaplastic astrocytomas). Among these, VEGF >1000ng/ml, VEGF/soluble Fltl ratio >1, vessel density >30, and vessel area >7% were prognostic factors for malignant gliomas. Based on these results, we performed three different antiangiogenic experiments targeted to inhibit VEGF expression in a human malignant glioma (U87) mouse model: anti-VEGF neutralized antibody intraperitoneal injection; interferon-beta intramusclar injection; and transfection of an endogenous nonspecific angiogenesis inhibitor, thrombospondin-1, into glioma cells caused inhibition of VEGF secretion and/or mRNA expression and resulted in glioma growth inhibition of 70%, 84%, and 50%, respectively, compared with control. We conclude that malignant gliomas with high degrees of VEGF expression and vessel areas are good candidates for antiangiogenic therapy, especially that designed to inhibit VEGF expression.

Angiogenesis Inhibitors↗

Intratumoral injection of IL-2-activated NK cells enhances the antitumor effect of intradermally injected paraformaldehyde-fixed tumor vaccine in a rat intracranial brain tumor model.

Combined therapy with a fixed-tumor cell vaccine and intratumoral injection of NK cells induced strong tumor regression of rat glioma. Rat 9L glioma cells were inoculated into syngeneic male rats at the flank (subcutaneous tumor model) or at the basal ganglia of the right hemisphere (intracranial tumor model). Rats were intradermally injected three times with vaccine comprising fixed 9L cells, IL-2- and GMCSF-microparticles, and tuberculin prior to (protective studies) or after (therapeutic studies) challenge with live 9L cells. In the protective studies, the vaccine alone achieved significant tumor growth inhibition and elongation of mean life span in both the subcutaneous and intracranial tumor models. No therapeutic effect was observed in the intracranial tumor model with the vaccine alone. However, intratumoral injection of rat NK cells strongly assisted the therapeutic effect of the vaccine in the brain tumor model and resulted in a statistically significant elongation of life span. We propose that intratumoral injection of NK cells may not only kill brain tumor cells directly, but also trigger a strong immune response in the focal lesion of the brain after vaccination.

Animals↗

Effects of local injection of ex vivo expanded autologous tumor-specific T lymphocytes in cases with recurrent malignant gliomas.

PURPOSE: The aim of this report was to indicate both the advantages and disadvantages of local cell transfer therapy using ex vivo expanded autologous tumor-specific T lymphocytes (ATTLs) for recurrent cases of malignant gliomas. EXPERIMENTAL DESIGN: Subjects are 10 cases of malignant gliomas consisting of 7 cases of glioblastoma multiforme, 2 cases of anaplastic astrocytoma, and 1 case of anaplastic oligoastrocytoma. All cases were recurrences. ATTLs were induced by coculturing peripheral blood mononuclear cells with autologous tumor cells in medium containing interleukin-1, -2, -4, and -6 and administered into the local tumor site in total numbers of 3-247 x 10(7) cells. As end points, tumor response and survival time were analyzed observing clinical state. RESULTS: Five cases responded to this therapy (namely, one case showed complete remission, and four cases had a partial response). There were three cases of no change, and two cases of progressive disease. The overall tumor response rate was 50%. No complications were noticed, except for two cases of minor local hemorrhage and eight cases of temporary fever. Nine cases died of further tumor progression, and one case died of aspiration pneumonia, and the cause-specific survival analysis indicates that the median survival time was 5 months from the initial ATTL injection. CONCLUSIONS: The results suggest that local administration of ATTLs is effective in recurrent malignant gliomas in that it demonstrated a high benefit:risk ratio with minor side effects. Although its antitumor effect may be temporary in some advanced cases, it is highly possible that the tumor could be stabilized when conditions are optimal.

Adult↗

Primary small cell carcinoma of the common bile duct, in which surgical treatment was performed after neoadjuvant chemotherapy: report of a case.

Primary small cell carcinoma of the hepatobiliary tract is rare. Most cases occur in the gallbladder or in the ampulla of Vater, and such cases in the common bile duct (CBD) are extremely rare. We herein report a case of small cell carcinoma arising in the CBD. In this case, neoadjuvant chemotherapy followed by pylorus-preserving pancreaticoduodenectomy showed an excellent response. To our knowledge, this is the first reported case of small cell carcinoma of the CBD in which a radical resection was performed after successful neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Anti-vascular endothelial growth factor antibody and nimustine as combined therapy: effects on tumour growth and angiogenesis in human glioblastoma xenografts.

We evaluated the effectiveness of vascular endothelial growth factor (VEGF) blockade alone and in combination with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU, nimustine), a cytotoxic agent commonly used in the treatment of malignant gliomas, to eradicate tumors of human glioblastoma cell lines implanted in SCID (severe combined immunodeficiency) mice. ACNU, but not cisplatin and etoposide, elevated VEGF expression in a glioma cell line in vitro. VEGF antibody alone inhibited glioma growth in vivo as a result of angiogenesis inhibition. The combination with ACNU resulted in an additive effect for inhibition of glioma growth. ACNU also induced VEGF up-regulation in glioma tissues, which was decreased with VEGF antibody treatment. One of the mechanisms of the additive effect of the VEGF antibody and ACNU combination is the blockade of VEGF up-regulation induced by ACNU. As such, the combination of antiangiogenic therapy with conventional therapy is promising for glioma treatment in the future.

Animals↗

Cervical intramedullary gliofibroma in a child: a case report and review of the literature.

A rare case of intramedullary gliofibroma in a 12-year-old girl is reported. MRI revealed an intramedullary tumor with two different intensities, and these portions showed different staining patterns after gadolinium contrast enhancement, with faint enhancement at the periphery and strong enhancement in the central portion. Intraoperatively, the tumor had a relatively clear margin to the spinal cord and was composed of two portions of different consistencies, one soft in the periphery and the other elastic and firm in the central portion. This tumor was grossly, totally removed. The patient made a full recovery and there was no recurrence 2 years and 9 months after operation. There have only been 7 previous case reports of spinal intramedullary gliofibroma. Gliofibroma is usually a relatively benign astroglial variant. Recognition of such a variant is clinically important in considering the extent of the operation and postoperative adjuvant therapy.

Astrocytoma↗