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Atsushi Kawaguchi,
Yasuo Iwadate,
Yoshihiro Komohara,
Masakazu Sano,
Koji Kajiwara,
Naoki Yajima, Naoto Tsuchiya,
Jumpei Homma,
Hiroshi Aoki,
Tsutomu Kobayashi,
Yuko Sakai,
Hiroaki Hondoh,
Yukihiko Fujii,
Tatsuyuki Kakuma,
Ryuya Yamanaka
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ABSTRACT: PURPOSE: Better understanding of the underlying biology of primary central nervous system lymphomas (PCNSL) is critical for the development of early detection strategies, molecular markers, and new therapeutics. This study aimed to define genes associated with survival of patients with PCNSL. EXPERIMENTAL DESIGN: Expression profiling was conducted on 32 PCNSLs. A gene classifier was developed using the random survival forests model. On the basis of this, prognosis prediction score (PPS) using immunohistochemical analysis is also developed and validated in another data set with 43 PCNSLs. RESULTS: We identified 23 genes in which expressions were strongly and consistently related to patient survival. A PPS was developed for overall survival (OS) using a univariate Cox model. Survival analyses using the selected 23-gene classifiers revealed a prognostic value for high-dose methotrexate (HD-MTX) and HD-MTX-containing polychemotherapy regimen-treated patients. Patients predicted to have good outcomes by the PPS showed significantly longer survival than those with poor predicted outcomes (P < 0.0001). PPS using immunohistochemical analysis is also significant in test (P = 0.0004) and validation data set (P = 0.0281). The gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P < 0.0001). Among the genes, BRCA1 protein expressions were most strongly associated with patient survival. CONCLUSION: We have identified gene expression signatures that can accurately predict survival in patients with PCNSL. These predictive genes should be useful as molecular biomarkers and they could provide novel targets for therapeutic interventions. Clin Cancer Res; 18(20); 5672-81. ©2012 AACR.
Clinical Cancer Research 08/2012; 18(20):5672-5681. · 7.74 Impact Factor
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Atsushi Kawaguchi,
Naoki Yajima,
Yoshihiro Komohara,
Hiroshi Aoki, Naoto Tsuchiya,
Jumpei Homma,
Masakazu Sano,
Manabu Natsumeda,
Takeo Uzuka,
Akihiko Saitoh,
Hideaki Takahashi,
Yuko Sakai,
Hitoshi Takahashi,
Yukihiko Fujii,
Tatsuyuki Kakuma,
Ryuya Yamanaka
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ABSTRACT: Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes selected using random survival forests model could be used to define subgroups of gliomas objectively. RNAs from 50 non-treated gliomas were analyzed using the GeneChip Human Genome U133 Plus 2.0 Expression array. We identified 82 genes whose expression was strongly and consistently related to patient survival. For practical purposes, a 15-gene set was also selected. Both the complete 82 gene signature and the 15 gene set subgroup indicated their significant predictivity in the 3 out of 4 independent external dataset. Our method was effective for objectively classifying gliomas, and provided a more accurate predictor of prognosis. We assessed the relationship between gene expressions and survival time by using the random survival forests model and this performance was a better classifier compared to significance analysis of microarrays.
International Journal of Oncology 03/2012; 40(3):721-30. · 2.40 Impact Factor
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Ryuya Yamanaka,
Ken Morii,
Yoshikatsu Shinbo,
Junpei Homma,
Masakazu Sano, Naoto Tsuchiya,
Naoki Yajima,
Tetsuro Tamura,
Hiroaki Hondoh,
Hitoshi Takahashi,
Tatsuyuki Kakuma,
Ryuichi Tanaka
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ABSTRACT: Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found.
One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy.
The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 +/- 4.8% [95% confidence intervals (CI)] and 30.2 +/- 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20-30 Gy WB, and 500 mg/m(2) of MTX dose appeared important determinants of OS.
A modest dose of MTX (500 mg/m(2)) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.
Japanese Journal of Clinical Oncology 06/2008; 38(5):373-80. · 1.78 Impact Factor
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Leukemia and Lymphoma 08/2007; 48(7):1429-33. · 2.58 Impact Factor
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Ryuya Yamanaka,
Yoshikatsu Shinbo,
Masakazu Sano,
Jumpei Homma, Naoto Tsuchiya,
Naoki Yajima,
Tetsuro Tamura,
Hiroaki Hondoh,
Hideaki Takahashi,
Ken Morii,
Kiyoshi Onda,
Ryuichi Tanaka
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ABSTRACT: We report the efficacy of salvage therapy with a modified ProMACE-MOPP combined with radiation in patients with primary central nervous system lymphoma (PCNSL). Thirty-two immunocompetent patients were treated with a regimen of pirarubicin, cyclophosphamide, etoposide, vincristin, and methotrexate (MTX: 500 mg/m(2)) administered in 21-day cycles. Patients received 20 Gy of whole-brain radiotherapy after three cycles of chemotherapy. A single cycle of chemotherapy was repeated every four months for two years. Nine patients with CNS relapse were retreated with additional cycles of the ProMACE-MOPP hybrid regimen with a 90% objective response rate. Median complete response (CR) duration was 13.2 months and median survival time (MST) for the nine patients treated after initial relapse was 30 months. One of 17 patients (5.8%) who had less than 20 Gy of whole brain irradiation developed dementia. In contrast, six of seven (85.7%) patients who had more than 30 Gy of whole brain radiotherapy became demented. Maintaining a moderate dose of MTX, while adding chemotherapeutic agents and 20 Gy of whole brain radiation therapy, improved disease control and overall survival and lowered the incidence of delayed neurologic toxicity in patients with PCNSL. Additional treatment with a ProMACE-MOPP hybrid regimen is still effective for relapsed disease.
Leukemia and Lymphoma 07/2007; 48(6):1119-26. · 2.58 Impact Factor
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Leukemia and Lymphoma 06/2007; 48(5):1019-22. · 2.58 Impact Factor
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ABSTRACT: The ECT2 (epithelial cell transforming sequence 2) proto-oncogene encodes a guanine nucleotide exchange factor for Rho GTPases, and regulates cytokinesis. ECT2 plays a critical role in Rho activation during cytokinesis, and thus may play a role in the pathogenesis of glioma. In this study, we investigated relationships between ECT2 expression, tumor histology, and prognosis in glioma patients. ECT2 mRNA expression was examined using quantitative real-time PCR, while its protein expression was examined by immunohistochemistry of 54 glioma tissue samples. Expressions of ECT2 mRNA and protein were markedly increased in high-grade gliomas compared to low-grade gliomas. Patients in whom expression of ECT2 mRNA and protein in tumor tissues was the lowest survived longer than patients who had higher expression. In vitro, ECT2 siRNA inhibited glioma cell proliferation and invasion. These data suggest that increased expression of ECT2 contribute to promotion of tumor invasiveness and progression, implying that evaluation of ECT2 expression is a prognostic marker for glioma patients.
Oncology Reports 12/2006; 16(5):1093-8. · 1.84 Impact Factor
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ABSTRACT: C/EBP beta (CCAAT/enhancer binding protein beta) is a transcriptional factor that belongs to the basic region-leucine zipper class DNA-binding proteins and plays a role in cell differentiation and inflammatory reactions. Although high tissue levels of inflammatory cytokines, such as interleukin (IL)-6, IL-8 and transforming growth factor-beta, have been observed in glioma patients, the mechanisms underlying this phenomenon remain to be elucidated. C/EBP beta induces a variety of cytokines and thus may play a role in the pathogenesis of glioma. In this study, we investigated the relationship between C/EBP beta expression, tumor histology, and prognosis in glioma. The expression of C/EBP beta mRNA was examined with quantitative real-time PCR and protein expression was examined with immunohistochemical techniques in 47 glioma tissue samples. Expression of C/EBP beta mRNA and protein was markedly increased in high grade glioma compared with low grade glioma. Patients whose expression of C/EBP beta mRNA and protein in tumor tissue was lower survived longer than those whose expressions were higher. In vitro, C/EBP beta siRNA inhibited glioma cell proliferation and invasion. Moreover, IL-8 production by glioma cells was inhibited by C/EBP beta siRNA transfection. These data suggest that increased expression of C/EBP beta may contribute to the promotion of tumor invasiveness and progression. The data imply that the comparison of C/EBP beta expression could be a prognostic marker for patients with glioma.
Oncology Reports 04/2006; 15(3):595-601. · 1.84 Impact Factor
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Naoto Tsuchiya,
Ryuya Yamanaka,
Naoki Yajima,
Jumpei Homma,
Masakazu Sano,
Tadashi Komata,
Takeshi Ikeda,
Ichiro Fujimoto,
Hitoshi Takahashi,
Ryuichi Tanaka,
Kazuhiro Ikenaka
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ABSTRACT: We have isolated and characterized N-linked oligo-saccharides that are significantly increased in glioblastoma tissue and cell lines. The structures of N-linked oligosaccharides present in 3 human normal brain tissues, 15 patients with glio-blastoma and 3 glioma cell lines were analyzed by partially automated technique for the isolation and fluorescent labeling of N-linked sugar chains from glycoproteins. Characterization of the sugar chains was achieved with the use of a combination of HPLC columns and a highly sensitive fluorescence detector at femtomole levels. By collecting peaks which accounted for 0.1% or more, sixteen different oligosaccharide structures were characterized from glioblastoma tissue and cell lines. The 16 oligosaccharide structures accounted for 48.9% of the total N-linked oligosaccharides present in glioblastoma tissue. The major components of total oligosaccharides were similar to those of normal brain tissue. The amount of a biantennary bigalactosylated structure with one core fucosylation (A2G2F) was present in increased levels in glioblastoma tissue (mean = 2.90%) and glioma cell lines (mean = 5.60%), while being less than 0.1% in normal brain tissue. Expression of highly branched tetra-antennary N-glycans that are usually detected in lungs or hepatocellular cancer was not observed. Tissue glioma cells and cultured cells also displayed strong LCA-lectin binding, which binds to sugar chains with core fucose (including A2G2F), while normal brain tissue did not. Moreover, LCA lectin inhibited proliferation of glioma cells through induction of apoptosis. A2G2F on glioma specimens may provide a novel marker and target for the diagnosis and treatment of glioblastoma, respectively.
International Journal of Oncology 12/2005; 27(5):1231-9. · 2.40 Impact Factor
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Naoki Yajima,
Ryuya Yamanaka,
Takashi Mine, Naoto Tsuchiya,
Jumpei Homma,
Masakazu Sano,
Terukazu Kuramoto,
Yayoi Obata,
Nobukazu Komatsu,
Yoshimi Arima,
Akira Yamada,
Minoru Shigemori,
Kyogo Itoh,
Ryuichi Tanaka
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ABSTRACT: The primary goal of this phase I study was to assess the safety and immunologic responses of personalized peptide vaccination for patients with advanced malignant glioma.
Twenty-five patients with advanced malignant glioma (8 grade 3 and 17 grade 4 gliomas) were evaluated in a phase I clinical study of a personalized peptide vaccination. For personalized peptide vaccination, prevaccination peripheral blood mononuclear cells and plasma were provided to examine cellular and humoral responses to 25 or 23 peptides in HLA-A24+ or HLA-A2+ patients, respectively; then, only the reactive peptides (maximum of four) were used for in vivo administration.
The protocols were well tolerated with local redness and swelling at the injection site in most cases. Twenty-one patients received more than six vaccinations and were evaluated for both immunologic and clinical responses. Increases in cellular or humoral responses specific to at least one of the vaccinated peptides were observed in the postvaccination (sixth) samples from 14 or 11 of 21 patients, respectively. More importantly, significant levels of peptide-specific IgG were detected in the postvaccination tumor cavity or spinal fluid of all of the tested patients who showed favorable clinical responses. Clinical responses were 5 partial responses, 8 cases of stable disease, and 8 cases of progressive disease. The median overall survival for patients with recurrent glioblastoma multiforme in this study (n = 17) was 622 days.
Personalized peptide vaccinations were recommended for the further clinical study to malignant glioma patients.
Clinical Cancer Research 09/2005; 11(16):5900-11. · 7.74 Impact Factor
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Ryuya Yamanaka,
Junpei Homma,
Naoki Yajima, Naoto Tsuchiya,
Masakazu Sano,
Tsutomu Kobayashi,
Seiichi Yoshida,
Takashi Abe,
Miwako Narita,
Masuhiro Takahashi,
Ryuichi Tanaka
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ABSTRACT: To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma.
Twenty-four patients with recurrent malignant glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II clinical study of dendritic cell therapy. All patients were resistant to the standard maximum therapy. The patient's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor, plus interleukin 4 with or without OK-432, and pulsed with an autologous tumor lysate. Dendritic cells were injected intradermally, or both intratumorally and intradermally every 3 weeks.
The protocols were well tolerated with only local redness and swelling at the injection site in several cases. Clinical responses were as follows: 1 patient with partial response, 3 patients with minor response, 10 patients with stable disease, and 10 patients with progressive disease. The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation. The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only. Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination. The overall survival of patients with grade 4 glioma was 480 days, which was significantly better than that in the control group.
This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma. Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients.
Clinical Cancer Research 07/2005; 11(11):4160-7. · 7.74 Impact Factor
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ABSTRACT: The aim in this study was the investigation of back pressure in arteries distal to the occlusion site during intraarterial thrombolysis as well as the usefulness of back pressure measurement in combination with diffusion-weighted (DW) magnetic resonance (MR) imaging to predict the occurrence of ischemic lesions following good recanalization.
. Twenty-five consecutive patients with severe hemiparesis caused by embolism of the internal carotid artery (10 patients) and the proximal middle cerebral artery (15 patients) were treated using intraarterial thrombolysis. Systolic back pressure, measured through a microcatheter in the artery just distal to the emboli, ranged from 22 to 78 mm Hg. According to an angiographic inclusion criterion for good recanalization--that is, recanalization of the M2 or more distal arteries at the end of thrombolysis--21 of 25 patients underwent evaluation in this study. In 14 patients volumes of low-density areas on computerized tomography (CT) scans obtained 2 months postthrombolysis were smaller in comparison with volumes of hyperintense areas on DW MR images acquired before treatment, whereas these low-density areas were larger in seven patients. Compared with those on initial DW MR images, the volume of abnormalities on CT scans obtained 2 months posttreatment were significantly reduced in patients with a systolic back pressure greater than 30 mm Hg (16 patients) than in those with a back pressure of 30 mm Hg or less (five patients) (p < 0.05). Systolic back pressures greater than 30 mm Hg were associated with significantly better modified Rankin Scale scores than those 30 mm Hg or less (p < 0.05).
Back pressure measurement in combination with DW MR imaging can be used to predict the occurrence of infarction as demonstrated on CT scans following thrombolysis.
Journal of Neurosurgery 06/2005; 102(5):870-8. · 2.96 Impact Factor
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ABSTRACT: In this study, we demonstrate that tumor lysate-loaded dendritic cells can elicit a specific CD8+ cytotoxic T lymphocyte response against autologous tumor cells in patients with malignant glioma. CTL from three of five patients expressed strong cytolytic activity against autologous glioma cells, did not lyse autologous lymphoblasts and were variably cytotoxic against the LAK-sensitive cell line Daudi. Also, DCs pulsed normal brain lysate failed to induce cytolytic activity against autologous glioma cells, suggesting the lack of autoimmune response. Two of five patients CD8+ T cells expressed a modest cytotoxicity against autologous glioma cells. CD8+ T cells isolated during these ineffective primings secreted large amounts of IL-10, less amounts of IFN-gamma as detected by ELISA, Type 2 bias in the CD8+ T cell response accounts for the lack of cytotoxic effector function from these patients. Cytotoxicity against autologous glioma cells could be significantly inhibited by anti-HLA class I antibody. These data demonstrate that tumor lysate-loaded DC can be an effective tool in inducing glioma-specific CD8+ CTL able to kill autologous glioma cells in vitro. However, high levels of tumor specific tolerance in some patients may account for a significant barrier to therapeutic vaccination. Moreover, cytotoxic responses were augmented by transfecting DC with the gene for IL-18. For all five patients, CD8+T cells treated with IL18 transfected DC produced Th1 response. These results may have important implications for the treatment of malignant glioma patients with immunotherapy. DCs loaded with total tumor lysate and IL-18 may represent a method for inducing Th1 immunoresponses against the entire repertoire of glioma antigens.
Journal of Neuro-Oncology 05/2005; 72(2):107-13. · 3.21 Impact Factor
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ABSTRACT: Mechanical disruption of a clot with a microcatheter and a guidewire has not been detailed in conjunction with intra-arterial thrombolysis in patients with acute ischemic stroke. The purpose of this study was to evaluate the efficacy of mechanical disruption of an embolus in the carotid artery distribution.
We analyzed clinical and radiologic findings and functional outcomes 3 months after thrombolysis with mechanical disruption. Outcomes were classified as good for modified Rankin scale (mRS) scores of 0-2, moderate for mRS scores of 3, and poor for death and mRS scores of 4 or 5.
Twenty-three consecutive patients with severe hemispheric symptoms were treated with several methods of mechanical embolus disruption during the intra-arterial administration of urokinase. Twelve patients had occlusions of the proximal middle cerebral artery (MCA), and 11 had occlusions of the distal internal carotid artery (ICA). Recanalization was observed in all patients with MCA occlusions and in 10 (91%) with ICA occlusions. Outcomes were good in nine patients (75%) with MCA occlusions and in four (36.4%) with ICA occlusions. Early management of vessel perforation, caused by a microguidewire tip in two patients, resulted in early hemostasis. Neither patient had a major deficit attributable to the complication.
A high incidence of recanalization and clinical improvement can be observed in patients with occlusions of not only the proximal MCA but also the distal ICA. This method might be an effective additional option to intra-arterial thrombolysis for acute distal ICA and proximal MCA occlusions.
American Journal of Neuroradiology 10/2004; 25(8):1391-402. · 2.93 Impact Factor
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ABSTRACT: The authors report on two patients in whom an increased signal on T1-weighted magnetic resonance images and a high-density signal on computerized tomography scans of the striatum were demonstrated, both of which were associated with nonketotic hyperglycemia. Involuntary movements, which have been present in all previously reported cases, were not observed in either patient at any time during the entire course of illness. One patient displayed hemiparesis, whereas the other had dementia, gait disturbance, and urinary incontinence. Clinical and radiological abnormalities improved on control of blood glucose levels. Invasive studies, including biopsy procedures, should be avoided on encountering this disease given the good prognosis that results from simple medical treatment.
Journal of Neurosurgery 09/2004; 101(2):343-6. · 2.96 Impact Factor
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Ryuya Yamanaka,
Shigeru Akutagawa,
Fumiko Taguchi,
Naoki Yajima, Naoto Tsuchiya,
Takeo Uzuka,
Ken Morii,
Hideaki Takahashi,
Ryuichi Tanaka,
Nagahiro Saijo,
Kazuto Nishio
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ABSTRACT: Primary central nervous system lymphomas (PCNSLs) are extra nodal B-cell non-Hodgkin's lymphomas with primary manifestation in the brain, and their incidence has been increasing among both immunocompetent and immunocompromised populations. Samples of oligodendroglioma (n=5), glioblastoma (n=7), PCNSL (n=6), and normal brain (n=3) were studied (total of 21 samples) using cDNA array technology. The hierarchical clustering algorithm was used to obtain a phylogenetic tree, and it revealed a striking feature: PCNSL was clearly separated. The genes encoding laminin receptor 2, thioredoxin peroxidase, and elongation factor-1 were selected as specific genes in PCNSL by principal component analysis (PCA). When Mann-Whitney tests were performed to identify genes responsible for the differences between responders and non-responders to the treatment schedule for PCNSL, 76 known genes were found to show significantly different expression patterns between the two groups at the P<0.01 level. The two groups were clearly separated by the re-clustering method using the selected genes related to response to chemo-radiotherapy. This is the first report describing the gene expression profiles of PCNSL. In conclusion, accumulation of data with respect to the expression profiles of PCNSL specimens, clinicopathological data, susceptibility to treatment, and outcome will provide information for identifying optimal therapeutic modalities for individual patients and novel therapeutic targets.
International Journal of Oncology 11/2003; 23(4):913-23. · 2.40 Impact Factor
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ABSTRACT: In this study, we demonstrate that tumor mRNA-loaded dendritic cells can elicit a specific CD8(+) cytotoxic T-lymphocyte (CTL) response against autologous tumor cells in patients with malignant glioma. CTLs from three patients expressed strong cytolytic activity against autologous glioma cells, did not lyse autologous lymphoblasts or EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Also, DCs-pulsed normal brain mRNA failed to induce cytolytic activity against autologous glioma cells, suggesting the lack of autoimmune response. Two patients' CD8(+) T cells expressed a modest cytotoxicity against autologous glioma cells. CD8(+) T cells isolated during these ineffective primings secreted large amounts of IL-10 and smaller amounts of IFN-gamma as detected by ELISA. Type 2 bias in the CD8(+) T-cell response accounts for the lack of cytotoxic effector function from these patients. Cytotoxicity against autologous glioma cells could be significantly inhibited by anti-HLA class I antibody. These data demonstrate that tumor mRNA-loaded DC can be an effective tool in inducing glioma-specific CD8(+) CTLs able to kill autologous glioma cells in vitro. However, high levels of tumor-specific tolerance in some patients may account for a significant barrier to therapeutic vaccination. These results may have important implications for the treatment of malignant glioma patients with immunotherapy. DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of glioma antigens.
Cancer Immunology and Immunotherapy 11/2003; 52(10):632-7. · 3.70 Impact Factor
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ABSTRACT: The aim of this study was to investigate further immunogene treatment of malignant brain tumor to improve its therapeutic efficacy.
Intratumoral dendritic cells pulsed with Semliki Forest virus (SFV)-interleukin-18 (IL-18) and/or systemic IL-12 were injected into mice bearing the B16 brain tumor. To study the immune mechanisms involved in tumor regression, we monitored the growth of implanted B16 brain tumor cells in T cell-depleted mice and IFNgamma-neutralized mice. To analyze the protective immunity created by tumor inoculation, B16 cells were injected into the left thighs of mice that had received an inoculation, and tumor growth was monitored. The local delivery of dendritic cells pulsed with IL-18 bound by SFV combined with the systemic administration of IL-12 enhanced the induction of the T helper type 1 response from tumor-specific CD4+ and CD8+ T cells and natural killer cells as well as antitumor immunity. Interferon-gamma is partly responsible for this IL-18-mediated antitumor immunity. Furthermore, the protective immunity is mediated mainly by CD8+ T cells.
Immunogene therapy that combines the local administration of dendritic cells pulsed with IL-18 bound by SFV and the systemic administration of IL-12 may be an excellent candidate for the development of a new treatment protocol. A self-replicating SFV system may therefore open a novel approach for the treatment of malignant brain tumor.
Journal of Neurosurgery 10/2003; 99(4):746-53. · 2.96 Impact Factor
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ABSTRACT: Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Among the new treatments currently being investigated for malignant glioma, immunotherapy is theoretically very attractive, since it offers the potential for high tumor-specific cytotoxicity. There are increasing reports demonstrating that systemic immunotherapy using dendritic cells is capable of inducing an antiglioma response. Therefore, dendritic cell-based immunotherapy could be a new treatment modality for patients with glioma. Dendritic cell-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and increase survival in patients with glioma. The development of methods for manipulating dendritic cells for the purpose of vaccination will enhance the clinical usefulness of these cells for biotherapy for malignant glioma.
Nō to shinkei = Brain and nerve 09/2003; 55(9):771-80.
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ABSTRACT: Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Among the new treatments currently being investigated for malignant glioma, immunotherapy is theoretically very attractive, since it offers the potential for high tumor-specific cytotoxicity. There are increasing reports demonstrating that systemic immunotherapy using dendritic cells is capable of inducing an antiglioma response. Therefore, dendritic cell-based immunotherapy could be a new treatment modality for patients with glioma. In this review, we will discuss the implications of these findings for glioma therapy. A literature review of dendritic cell-based glioma immunotherapy was used to overview the dendritic cell in immunobiology, in the central nervous system and in tumor immunology, glioma-associated antigens, dendritic cell therapy in animal glioma model, dendritic cell therapy in clinical trials and future directions in dendritic cell therapy. Dendritic cell-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and increase survival in patients with glioma. Dendritic cell therapy of glioma seems to be safe and without major side effects. Its efficacy should be further determined in randomized, controlled clinical trials. The development of methods for manipulating dendritic cells for the purpose of vaccination will enhance the clinical usefulness of these cells for biotherapy for malignant glioma.
International Journal of Oncology 08/2003; 23(1):5-15. · 2.40 Impact Factor
