Yugo Kishida

Publications (6)20.81 Total impact

• Article: Quality of life in nonfunctioning pituitary macroadenoma patients before and after surgical treatment.

  Eriko Tanemura, Tetsuya Nagatani, Yuri Aimi, Yugo Kishida, Kazuhito Takeuchi, Toshihiko Wakabayashi
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  ABSTRACT: Nonfunctioning pituitary macroadenoma (NFMA) is a benign neoplasm that causes visual function disturbances and headaches and can be treated by transsphenoidal surgery (TSS). It is unclear how quality of life (QOL) changes with surgery and which QOL factors are affected by treatment. The aim is to assess the temporal transition of QOL in NFMA patients undergoing TSS and to identify influential factors. The QOL of NFMA patients who underwent endoscopic TSS was investigated with the short-form 36 (SF-36) health survey questionnaire, general health questionnaire 30 (GHQ30), and numerical rating scale (NRS) of pain at the following three time points: immediately before, 1 month after, and 6 months after surgery. Twenty-four of 30 patients had visual deterioration. The SF-36 baseline value of visual function-impaired NFMA patients was lower than that of the normal population. SF-36 results showed that physical summary scores decreased at 1 month after the operation, but recovered up to the normal population level by 6 months. Mental summary scores generally increased at 1 month after surgery and remained stable until 6 months later. The GHQ30 results were similar to the SF-36 mental summary scores. The strongest factor related to the QOL was visual function. The amount of pain and the necessity of hormonal replacement were also influencing factors. The QOL of NFMA patients is affected both physically and mentally by surgical treatment and symptoms. This QOL assessment is important for planning treatment strategies.
  Acta Neurochirurgica 08/2012; 154(10):1895-902. · 1.52 Impact Factor
• Article: Correlation between quantified promoter methylation and enzymatic activity of O6-methylguanine-DNA methyltransferase in glioblastomas.

  Yugo Kishida, Atsushi Natsume, Hiroshi Toda, Yuki Toi, Kazuya Motomura, Hiroko Koyama, Keiji Matsuda, Osamu Nakayama, Makoto Sato, Masaaki Suzuki, Yutaka Kondo, Toshihiko Wakabayashi
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  ABSTRACT: The DNA repair protein O (6)-methylguanine-DNA methyltransferase (MGMT, AGT) is a determinant of the resistance of tumor cells to alkylating anticancer agents that target the O(6) position of guanine. MGMT promoter methylation in tumors is regarded as the most common predictor of the responsiveness of glioblastoma to alkylating agents. However, MGMT promoter methylation status has been investigated mainly by methylation-specific PCR, which is a qualitative and subjective assay. In addition, the actual enzymatic activities associated with the methylation status of MGMT have not been explored. In the present study, MGMT promoter methylation in glioblastomas was quantified by bisulfite pyrosequencing, and its correlation with enzymatic activity was determined using a novel quantitative assay for studying the functional activity of MGMT. MGMT enzymatic activity was assessed using fluorometrically labeled oligonucleotide substrates containing MGMT-specific DNA lesions and capillary electrophoresis to detect and quantify these lesions. In comparison with existing traditional assays, this assay was equally sensitive but less time consuming and easier to perform. MGMT promoter methylation was assessed in 41 glioblastomas by bisulfite pyrosequencing, and five samples with different values were chosen for comparison with enzymatic assays. Bisulfite pyrosequencing using primers designed to work in the upstream promoter regions of MGMT demonstrated high quantitative capability and reproducibility in triplicate measurements. In comparative studies, MGMT promoter methylation values obtained by bisulfite pyrosequencing were inversely proportional to the measured enzymatic activity. The present results indicate that the quantification of MGMT methylation by bisulfite pyrosequencing represents its enzymatic activity and thus, its therapeutic responsiveness to alkylating agents.
  Tumor Biology 04/2012; 33(2):373-81. · 1.94 Impact Factor
• Article: Epigenetic subclassification of meningiomas based on genome-wide DNA methylation analyses.

  Yugo Kishida, Atsushi Natsume, Yutaka Kondo, Ichiro Takeuchi, Byonggu An, Yasuyuki Okamoto, Keiko Shinjo, Kiyoshi Saito, Hitoshi Ando, Fumiharu Ohka, Yoshitaka Sekido, Toshihiko Wakabayashi
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  ABSTRACT: Meningiomas are among the most common intracranial tumors and are mostly curable by surgical resection. However, some populations of meningiomas with benign histological profiles show malignant behavior. The reasons for this inconsistency are yet to be ascertained, and novel diagnostic criteria other than the histological one are urgently needed. The aim of the present study is to subclassify meningiomas from the viewpoint of gene methylation and to determine the subgroup with malignant characteristics. Thirty meningiomas were analyzed using microarrays for 6157 genes and were classified into three clusters on the basis of their methylation status; these were found to be independent of the histological grading. One of the clusters showed a high frequency of recurrence, with a marked accumulation of methylation in a subset of genes. We hypothesized that the aggressive meningiomas universally share characteristic methylation in certain genes; therefore, we chose the genes that strongly contributed to cluster formation. The quantified methylation values of five chosen genes (HOXA6, HOXA9, PENK, UPK3A and IGF2BP1) agreed well with microarray findings, and a scoring system consisting of the five genes significantly correlated with a high frequency of recurrence in an additional validation set of 32 patients. Of particular note is that three cases with malignant transformation already showed hypermethylation at histologically benign stage. In conclusion, a subgroup of meningiomas is characterized by aberrant hypermethylation of the subset of genes in the early stage of tumorigenesis, and our findings highlight the possibility of speculating potential malignancy of meningiomas by assessing methylation status.
  Carcinogenesis 11/2011; 33(2):436-41. · 5.70 Impact Factor
• Article: Benefits of interferon-β and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter: A multicenter study.

  Kazuya Motomura, Atsushi Natsume, Yugo Kishida, Hiroyuki Higashi, Yutaka Kondo, Yoko Nakasu, Tatsuya Abe, Hiroki Namba, Kenji Wakai, Toshihiko Wakabayashi
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  ABSTRACT: The aim of the current study was to catalog genomic and epigenomic abnormalities in newly diagnosed glioblastoma patients and determine the correlation among clinical, genetic, and epigenetic profiles and clinical outcome. This study retrospectively included 68 consecutive patients who underwent surgical treatment and received standard radiotherapy with temozolomide (TMZ)-based chemotherapy. Of a total of 68 patients, 39 patients (57.4%) received interferon (IFN)-β in combination of TMZ. The genetic and epigenetic alterations frequently observed were EGFR amplification (51.5%), TP53 mutation (33.8%), CDKN2A loss (32.4%), TP53 loss (16.2%), methylation of the MGMT promoter (33.8%) and IDH1 mutation (5.9%). Multivariate analysis revealed that methylated MGMT promoter and the combination of TMZ and IFN-β were independent prognostic factors associated with survival. The median survival time (MST) of the patients who received the combination of IFN-β and TMZ was significantly greater with 19.9 months as compared to the TMZ alone group (12.7 months). Notably, in even patients whose tumors had unmethylated MGMT promoter, the MST prolonged to 17.2 months when receiving TMZ with IFN-β, compared to 12.5 months in those receiving TMZ without IFN-β. Taken together, addition of IFN-β for newly diagnosed primary GBM achieved a favorable outcome, particularly in patients with unmethylated MGMT promoter.
  Cancer 04/2011; 117(8):1721-30. · 4.77 Impact Factor
• Source

  Available from: PubMed Central

  Article: The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.

  Fumiharu Ohka, Atsushi Natsume, Kazuya Motomura, Yugo Kishida, Yutaka Kondo, Tatsuya Abe, Yoko Nakasu, Hiroki Namba, Kenji Wakai, Takashi Fukui, Hiroyuki Momota, Kenichiro Iwami, Sayano Kinjo, Maki Ito, Masazumi Fujii, Toshihiko Wakabayashi
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  ABSTRACT: Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4) have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ), and even low grade gliomas (LGGs, WHO grade 2) eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP) in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1) IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2) LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3) LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4) higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.
  PLoS ONE 01/2011; 6(8):e23332. · 4.09 Impact Factor
• Article: Magnetically guided 3-dimensional virtual neuronavigation for neuroendoscopic surgery: technique and clinical experience.

  Eiji Ito, Masazumi Fujii, Yuichiro Hayashi, Jiang Zhengang, Tetsuya Nagatani, Kiyoshi Saito, Yugo Kishida, Kensaku Mori, Toshihiko Wakabayashi
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  ABSTRACT: The authors have developed a novel intraoperative neuronavigation with 3-dimensional (3D) virtual images, a 3D virtual navigation system, for neuroendoscopic surgery. The present study describes this technique and clinical experience with the system. Preoperative imaging data sets were transferred to a personal computer to construct virtual endoscopic views with image segmentation software. An electromagnetic tracker was used to acquire the position and orientation of the tip of the neuroendo-scope. Virtual endoscopic images were interlinked to an electromagnetic tracking system and demonstrated on the navigation display in real time. Accuracy and efficacy of the 3D virtual navigation system were evaluated in a phantom test and on 5 consecutive patients undergoing neuroendoscopic surgery. Virtual navigation views were consistent with actual endoscopic views and trajectory in both phantom testing and clinical neuroendoscopic surgery. Anatomic structures that can affect surgical approaches were adequately predicted with the virtual navigation system. The virtual semitransparent view contributed to a clear understanding of spatial relationships between surgical targets and surrounding structures. Surgical procedures in all patients were performed while confirming with virtual navigation. In neurosurgery with a flexible neuroscope, virtual navigation also demonstrated anatomic structures in real time. The interactive method of intraoperative visualization influenced the decision-making process during surgery and provided useful assistance in identifying safe approaches for neuroendoscopic surgery. The magnetically guided navigation system enabled navigation of surgical targets in both rigid and flexible endoscopic surgeries.
  Neurosurgery 06/2010; 66(6 Suppl Operative):342-53; discussion 353. · 2.79 Impact Factor