2001 Fiscal Year Annual Research Report

遺伝子解析による悪性グリオーマの再分類とそれに基づく治療体系の確立

Research Project

Project/Area Number	11307025
Research Institution	KUMAMOTO UNIVERSITY
Principal Investigator	生塩之敬熊本大学, 医学部, 教授 (20028583)
Co-Investigator(Kenkyū-buntansha)	河内正人熊本大学, 医学部, 助教授 (70178218) 佐谷秀行熊本大学, 医学部, 教授 (80264282)
Keywords	glioblastoma / gene analysis / p53 / p16 / EGFR / LOH10 / prognosis / classification
Research Abstract	これまでに約240例のグリオーマを解析し、以下の知見を得ている。 1)p53のmutation =出芽酵母を利用して解析した結果、diffuse astrocytomaの約25%、anaplastic astrocytoma(AA)の約50%、glioblastoma multiforme (GBM)の約35%にmutationを認めた。mutationの有無とtime to tumor progression (TTP)および生存期間との間に有意な相関はなかった。一般的に、AAを経て段階的に悪性化したGBMはsecondary glioblastomaと呼ばれ、p53のmutationに特徴付けられるが、今回の解析ではAAとGBMとでmutationの部位に差があり、P53にmutationを持つGBMが必ずしもsecondary glioblastomaではない事が示唆された。 2)p16のhomozygous deletion (HD) =multiplex PCR法を用いて解析した結果、AAの約10%、GBMの約30%にHDを認めた。男性のGBMにおいてHDは有意な予後不良因子であった。 3)Epidermal Growth Factor Receptor (EGFR)のamplification =Southern blotting法を用いて解析した結果、AAの約10%、GBMの約30%にamplificationを認めた。GBMにおいてamplificationは有意な予後不良因子であった。 4)10番染色体のloss of heterozygosity (LOH) =microsatellite markerを利用して解析した結果、AAの約30%、GBMの約60%にLOHを認めた。GBMにおいてPTEN遺伝子領域のLOHは有意な予後不良因子であった。なおLOH10とEGFR増幅の共存例は、特に予後不良であった。

Research Products
(14 results)

All Other

All Publications (14 results)

[Publications] K.Yamada, Y.Ushio: "Symptomatic solitary xanthogranuloma occupying the cavernous sinus"J.Neurosurg.. 94. 322-326 (2001)
[Publications] H.Takeshima, Y.Ushio: "Metastatic Brain Tumours from Oesophageal Carcinoma : Neuro-Imaging and Clinicopathological Characteristics in Japanese Patients"Acta Neurochir (Wien). 143. 31-36 (2001)
[Publications] M.Murakami, Y.Ushio: "The invasive features of glial and non-central nervous system tumor cells are different on organotypic brain slices from newborn rats"International J.Oncology. 18. 721-727 (2001)
[Publications] H.Tsuiki, Y.Ushio, H.saya: "Mechanism of hyperploid cell formation induced by microtubule inhibiting drug in glioma cell lines"Oncogene. 20. 420-429 (2001)
[Publications] M.Murakami, M.Kochi, Y.Ushio: "The inhibitory effect of simvastatin on growth in malignant gliomas-with special reference to its local application with fibrin glue spray in vivo"International J.Oncology. 19. 525-531 (2001)
[Publications] J.Kuratsu, Y.Ushio: "Trends in the incidence of primary intracranial tumors in Kumamoto, Japan"Int.J.Clin.Oncol.. 6. 183-191 (2001)
[Publications] K.Koga, Y.Ushio: "Expression of Angiopoietin-2 in Human Glioma Cells and Its Role for Angiogenesis"Cancer Research. 61. 6248-6254 (2001)
[Publications] K.Tada, M.Kochi, Y.Ushio: "Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors : correlation with patients age and survival"J.Neurosurg.. 95. 651-659 (2001)
[Publications] T.Kino, M.Kochi, Y.Ushio: "Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma"Genes to Cells. 6. 441-454 (2001)
[Publications] T.Goto, M.Kochi, Y.Ushio: "Suprasellar Hemangioblastoma in a patient with von hippel-lindau disease confirmed by germline mutation study. case report and review of the literature"Surgical Neurology. 56. 22-26 (2001)
[Publications] T.Tamura, Y.Ushio: "Intratumoral Delivery of Interleukin 12 Expression Plasmids with In Vivo Electroporation Is Effective for Colon and Renall Cancer"Human Gene Therapy. 12. 1265-1276 (2001)
[Publications] Y.Kai, Y.Ushio: "Appropriate Interval between Embolization and Surgery in Patients with Meningioma"Am.J.Neuroradiol.. 23. 139-142 (2002)
[Publications] T.Kamiryo, M.Kochi, H.Saya, Y.Ushio: "Analysis of Homozygous Deletion of p16 Gene in Patients with Glioblastoma and its Correlation with Patient Survival"J.Neurosurg.. (in press). (2002)
[Publications] S.Shiraishi, M.Kochi, H.Saya, Y.Ushio: "Influence of p53 Mutations on Prognosis of Patients with Glioblastoma"Cancer. (in press). (2002)

2001 Fiscal Year Annual Research Report

遺伝子解析による悪性グリオーマの再分類とそれに基づく治療体系の確立

Principal Investigator

生塩 之敬 熊本大学, 医学部, 教授 (20028583)

Research Products

[Publications] K.Yamada, Y.Ushio: "Symptomatic solitary xanthogranuloma occupying the cavernous sinus"J.Neurosurg.. 94. 322-326 (2001)

[Publications] H.Takeshima, Y.Ushio: "Metastatic Brain Tumours from Oesophageal Carcinoma : Neuro-Imaging and Clinicopathological Characteristics in Japanese Patients"Acta Neurochir (Wien). 143. 31-36 (2001)

[Publications] M.Murakami, Y.Ushio: "The invasive features of glial and non-central nervous system tumor cells are different on organotypic brain slices from newborn rats"International J.Oncology. 18. 721-727 (2001)

[Publications] H.Tsuiki, Y.Ushio, H.saya: "Mechanism of hyperploid cell formation induced by microtubule inhibiting drug in glioma cell lines"Oncogene. 20. 420-429 (2001)

[Publications] M.Murakami, M.Kochi, Y.Ushio: "The inhibitory effect of simvastatin on growth in malignant gliomas-with special reference to its local application with fibrin glue spray in vivo"International J.Oncology. 19. 525-531 (2001)

[Publications] J.Kuratsu, Y.Ushio: "Trends in the incidence of primary intracranial tumors in Kumamoto, Japan"Int.J.Clin.Oncol.. 6. 183-191 (2001)

[Publications] K.Koga, Y.Ushio: "Expression of Angiopoietin-2 in Human Glioma Cells and Its Role for Angiogenesis"Cancer Research. 61. 6248-6254 (2001)

[Publications] K.Tada, M.Kochi, Y.Ushio: "Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors : correlation with patients age and survival"J.Neurosurg.. 95. 651-659 (2001)

[Publications] T.Kino, M.Kochi, Y.Ushio: "Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma"Genes to Cells. 6. 441-454 (2001)

[Publications] T.Goto, M.Kochi, Y.Ushio: "Suprasellar Hemangioblastoma in a patient with von hippel-lindau disease confirmed by germline mutation study. case report and review of the literature"Surgical Neurology. 56. 22-26 (2001)

[Publications] T.Tamura, Y.Ushio: "Intratumoral Delivery of Interleukin 12 Expression Plasmids with In Vivo Electroporation Is Effective for Colon and Renall Cancer"Human Gene Therapy. 12. 1265-1276 (2001)

[Publications] Y.Kai, Y.Ushio: "Appropriate Interval between Embolization and Surgery in Patients with Meningioma"Am.J.Neuroradiol.. 23. 139-142 (2002)

[Publications] T.Kamiryo, M.Kochi, H.Saya, Y.Ushio: "Analysis of Homozygous Deletion of p16 Gene in Patients with Glioblastoma and its Correlation with Patient Survival"J.Neurosurg.. (in press). (2002)

[Publications] S.Shiraishi, M.Kochi, H.Saya, Y.Ushio: "Influence of p53 Mutations on Prognosis of Patients with Glioblastoma"Cancer. (in press). (2002)

生塩之敬熊本大学, 医学部, 教授 (20028583)