Identification and therapeutic application of metastasis-related biomarkars in soft tissue sarcomas.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Juntendo University
• Principal Investigator: SAITO TSUYOSHI 順天堂大学, 医学部, 准教授 (80439736)
• Project Period (FY): 2011 – 2013
• Keywords: 軟部肉腫 / 遺伝子異常 / 分子治療標的 / バイオマーカー

Research Abstract

1) We showed a possible role of glutathione peroxidase1(GPX-1) as a biomakar for early recurrence and metastasis in giant cell tumor of bone (GCTB). Inaddition, overexpression of GPX-1 induced by p53 mutation would have an important role in the malignant transformation of GCTB.
2) We showed that fibroblast growth factor receptor(FGFR4) is a trnascriptional target of EWS-WT1 in desmoplastic small round cell tumor, and FGFR4 and as a possible terapeutic target in this tumor.
3) We showed DDX39 and KCTD10 as biomakars for prognosis in gastrointestinal stromal tumor.

Research Products

• [Journal Article] Distinct profile of HIF1α, PTCH, EphB2 or DNA repair protein expression and BRAF mutation in colorectal serrated adenomas (2014)
  • Author(s): Morimoto T, Mitomi H, Saito T, Takahashi M, Murakami T, Sakamoto N, Yao T, Watanabe S.
  • Journal Title: J Gastroenterology and Hepatology Volume: 29 Pages: 1192-1199
• [Journal Article] Downregulation of sFRP-2 by epigenetic silencing activates theβ-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma (2014)
  • Author(s): Saito T, Mitomi H, Imamhasan A, Hayashi T, Mitani K, Takahashi M, Kajiyama Y, Yao T
  • Journal Title: Virchows Arch Volume: 464 Pages: 135-143
• [Journal Article] Desmoplastic fibroma of the rib with cystic change : a case report and literature review (2014)
  • Author(s): Okubo T, Saito T, Takagi T, Suehara Y, Kaneko K
  • Journal Title: Skeletal Radiol Volume: 43 Pages: 703-708
• [Journal Article] An outpatient-based survey about the recognition of locomotive syndrome and the results of the loco-check at a university hospital in Tokyo (2014)
  • Author(s): Okubo T, Suehara Y, Kawasaki T, Akaike K, Toda M, Okubo N, Kubota D, Mukaihara K, Kim Y, Kaketa T, Homma Y, Shimanouchi N, Saito T, Takagi T, Kaneko K
  • Journal Title: Brit J Med Med Res Volume: 4 Pages: 3255-3268
• [Journal Article] A case of dedifferentiated solitary fibrous tumor of thoracic cavity (2014)
  • Author(s): Masuda Y, Kurisaki-Arakawa A, Hara K, Arakawa A, Oh S, Suzuki K, Yao T, Saito T
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 386-393
• [Journal Article] A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary (2014)
  • Author(s): Shiono S, Saito T, Fujii H, Arakawa A, Nakamura T, Yao T
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 394-401
  • DOI: 10.1038/modpathol.2014.41
• [Journal Article] Distinct Wnt/β-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum (2014)
  • Author(s): Murakami T, Mitomi H, Saito T, Takahashi M, Sakamoto N, Fukui N, Yao T, Watanabe S
  • Journal Title: Mod Pathol
• [Journal Article] Possible involvement of p53 genetic alteration associated with protein overexpression in malignant transformation of giant-cell tumor of bone (2013)
  • Author(s): Okubo T, Saito T, Mitomi H, Takagi T, Torigoe T, Suehara Y, Yao T, Kaneko K
  • Journal Title: Virchows Archiv Volume: 63 Pages: 67-77
• [Journal Article] Tissue Sample Preparation for Biomarker Discovery (2013)
  • Author(s): Suehara Y, Kubota D, Saito T
  • Journal Title: Methods Mol Biol Volume: 1002 Pages: 13-23
• [Journal Article] Protein expression and methylation of DNA repair genes hMLH1, hMSH2, MGMT and BRCA1 and their correlation with clinicopathological parameters and prognosis in basal-like breast cancer (2013)
  • Author(s): Alkam Y, Mitomi H, Nakai K, Himuro T, Saito T, Takahashi M, Arakawa A, Yao T, Saito M
  • Journal Title: Histopathology Volume: 63 Pages: 713-725
• [Journal Article] Alteration in the Wnt/β-catenin signaling pathway in gastric neoplasias of fundic gland (chief cell predominant) type (2013)
  • Author(s): Hidaka Y, Mitomi H, Saito T, Takahashi M, Lee SY, Matsumoto K, Yao T, Watanabe S
  • Journal Title: Human Pathol Volume: 44 Pages: 2438-2448
• [Journal Article] Galectin-4, a novel predictor for lymph node metastasis in lung adenocarcinoma : A proteomic study (2013)
  • Author(s): Hayashi T, Saito T, Fujimura T, Hara K, Takamochi K, Mitani K, Mineki R, Kazuno S, Oh S, Suzuki K, Ueno T, Suzuki K, Yao T
  • Journal Title: PLoS One Volume: 8 Pages: e81883
• [Journal Article] Infiltrative angiolipoma of the thoracic wall : A case report (2013)
  • Author(s): Hamano A, Suzuki T, Saito T, Kuwatsuru R, Oh S, Suzuki K
  • Journal Title: Open J Clin Diag. Volume: 3 Pages: 19-22
• [Journal Article] Low-grade myofibroblastic sarcoma of the distal femur (2013)
  • Author(s): Saito T, Mitomi H, Kurisaki A, Torigoe T, Takagi T, Suehara Y, Okubo T, Kaneko K, Yao T
  • Journal Title: Int J Surg Case Rep. Volume: 4 Pages: 195-199
• [Journal Article] A combined integrated genomics / functional genomics strategy to dissect the biology of a cancer-associated, aberrant transcription factor, the ASPSCR1-TFE3 fusion oncoprotein (2013)
  • Author(s): Kobos R, Nagai M, Tsuda M, Lui MY, Saito T, Laé M, Mo Q, Olshen A, Lianoglou S, Leslie C, Shao Y, Antczak C, Djaballah H, Ladanyi M
  • Journal Title: J Pathol Volume: 229 Pages: 743-754
• [Journal Article] Gene expression network analysis of ETV1 reveals KCTD10 as a novel prognostic biomarker in gastrointestinal stromal tumor (2013)
  • Author(s): Kubota D, Yoshida A, Tsuda H, Suehara Y, Okubo T, Saito T, Orita H, Sato K, Taguchi T, Yao T, Kaneko K, Katai H, Kawai A, Kondo T
  • Journal Title: PLoS One Volume: 8 Pages: e73896
• [Journal Article] The prognostic value of pfetin : a validation study in gastrointestinal stromal tumors using a commercially available antibody (2013)
  • Author(s): Kubota D, Mukaihara K, Yoshida A, Suehara Y, Saito T, Okubo T, Gotoh M, Orita H, Tsuda H, Kaneko K, Kawai A, Kondo T, Sato K, Yao T
  • Journal Title: Jpn J Clin Oncol Volume: 43 Pages: 669-675
• [Journal Article] A case of myxoid liposarcoma of the breast (2013)
  • Author(s): Saito T, Ryu M, Fukumura Y, Asahina M, Arakawa A, Nakai K, Miura H, Saito M, Yao T
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 1432-1436
• [Journal Article] Desmoplastic fibroma of the scapula with uptake of FDG-PET : A case report with review of literature (2013)
  • Author(s): Okubo T, Saito T, Takagi T, Torigoe T, Suehara Y, Akaike K, Yao T, Kaneko K
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 2230-2236
• [Journal Article] A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 (2013)
  • Author(s): Kurisaki-Arakawa A, Saito T, Takahashi M, Mitani K, Fukumura Y, Nagashima Y, Argani P, Yao T
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 2585-2590
• [Journal Article] Review : SYT-SSX fusion protein and histological epithelial differentiation in synovial sarcoma : relationship with extracellular matrix remodeling (2013)
  • Author(s): Saito T
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 2272-2279
• [Journal Article] Reconstruction using frozen autograft bone treated by liquid nitrogen for malignant bone tumor in the forearm : A new technique of pedicle freezing (2012)
  • Author(s): Torigoe T, Tomita Y, Iwase Y, Aritomi K, Suehara Y, Oukubo T, Sakurai A, Terakado A, Takagi T, Kaneko K, Saito T, Yazawa Y
  • Journal Title: J Ortho Surg Volume: 20 Pages: 98-102
• [Journal Article] Synovial sarcoma of the cauda equina (2012)
  • Author(s): Yonezawa I, Saito T, Nakahara D, Won J, Wada T, Kaneko K
  • Journal Title: J Neurosurg Spine Volume: 16 Pages: 187-190
• [Journal Article] Clear cell variant of squamous cell carcinoma originating in the esophagus : Report of a case with immunohistochemical and oncogenetic analyses (2012)
  • Author(s): Imamhasan A, Mitomi H, Saito T, Arakawa A, Yao T
  • Journal Title: Pathol Int. Volume: 62 Pages: 137-143
• [Journal Article] Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor (2012)
  • Author(s): Kikuta K, Kubota D, Saito T, Orita H, Yoshida A, Tsuda H, Suehara Y, Katai H, Shimada Y, Toyama Y, Sato K, Yao T, Kaneko K, Beppu Y, Murakami Y, Kawai A, Kondo T
  • Journal Title: J Proteomics Volume: 75 Pages: 1089-1098
• [Journal Article] Intraneural lipomatous tumor of median nerve : Report of 3 cases with literature review (2012)
  • Author(s): Okubo T, Saito T, Mitomi H, Takagi T, Torigoe T, Suehara Y, Katagiri H, Murata H, Takahashi M, Ito I, Yao T, Kaneko K
  • Journal Title: Int J Surg Case Rep. Volume: 3 Pages: 407-411
• [Journal Article] Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas (2012)
  • Author(s): Imamhasan A, Mitomi H, Saito T, Hayashi T, Takahashi M, Kajiyama Y, Yao T
  • Journal Title: Human Pathol Volume: 43 Pages: 2012-2023
• [Journal Article] MUC5AC/β-catenin expression and K-ras gene altered in laterally spreading colorectal tumors (2012)
  • Author(s): Nakae K, Mitomi H, Saito T, Takahashi M, Morimoto T, Hidaka Y, Sakamoto N, Yao T, Watanabe S
  • Journal Title: World J Gastroenterol Volume: 18 Pages: 5551-5559
• [Journal Article] Uterine angiosarcoma associated with lymphangioleiomyomatosis in a patient with tuberous sclerosis complex:An autopsy case report with immunohistochemical and genetic analysis (2012)
  • Author(s): Hayashi T, Koike K, Kumasaka T, Saito T, Mitani K, Terao Y, Ogishima D, Yao T, Takeda S, Takahashi K, Seyama K
  • Journal Title: Human Pathol Volume: 43 Pages: 1777-1784
• [Journal Article] Validation Study on Pfetin and ATP-dependent RNA helicase DDX39 as Prognostic Biomarkers in Gastrointestinal Stromal Tumor (2012)
  • Author(s): Kubota D, Okubo T, Saito T, Suehara Y, Yoshida A, Kikuta K, Tsuda H, Katai H, Shimada Y, Kaneko K, Kawai A, Kondo T
  • Journal Title: Jpn J Clin Oncol Volume: 42 Pages: 730-741
• [Journal Article] Malignant granular cell tumor with unusual long clinical course. An autopsy case with review of literatures (2012)
  • Author(s): Saito T, Mitomi H, Torigoe T, Takagi T, Suehara Y, Okubo T, Kaneko K, Yao T
  • Journal Title: J Cancer Sci Ther Volume: 4 Pages: 260-263
• [Journal Article] EWS-WT1 chimeric protein in desmoplastic small round cell tumor is a potent transactivator of FGFR4 (2012)
  • Author(s): Saito T, Yokotsuka M, Motoi T, Iwasaki H, Nagao T, Ladanyi M, Yao T
  • Journal Title: J Cancer Sci Ther Volume: 4 Pages: 335-340
• [Journal Article] PDGFRA is an alternative mediator of Rapamycin-Induced Akt Activation in Synovial Sarcoma : implications for combination targeted therapy (2012)
  • Author(s): Ho AL, Vasudeva SD, Barbashina V, Laé M, Saito T, Antonescu C, Ladanyi M, Schwartz GK
  • Journal Title: Cancer Res Volume: 72 Pages: 4515-4525
• [Journal Article] Overexpression of HER2 signaling to WAVE2–Arp2/3 complex activates MMP-independent migration in breast cancer (2011)
  • Author(s): Yokotsuka M, Iwaya K, Saito T, Pandiella A, Tsuboi R, Kohno N, Matsubara O, Mukai K
  • Journal Title: Breast Cancer Res Treat Volume: 126 Pages: 311-318
• [Journal Article] A case of secondary malignant giant-cell tumor of bone with p53 mutation after long-time follow-up (2011)
  • Author(s): Saito T, Mitomi H, Izumi H, Suehara Y, Torigoe T, Takagi T, Kaneko K, Sato K, Matsumoto T, Yao T
  • Journal Title: Human Pathol Volume: 42 Pages: 727-733
• [Journal Article] Abnormalities of Wnt/β-catenin signaling pathway induce tumor progression in sporadic desmoids tumors : correlation betweenβ-catenin widespread nuclear expression and VEGF overexpression (2011)
  • Author(s): Matono H, Tamiya S, Yokoyama R, Saito T, Iwamoto Y, Tsuneyoshi M, Oda Y
  • Journal Title: Histopathology Volume: 59 Pages: 368-375
• [Journal Article] Cluster analysis of claudin-1 and -4, E-cadherin andβ-catenin expression in colorectal cancers (2011)
  • Author(s): Matsuoka T, Mitomi H, Fukui N, Kanazawa H, Saito T, Hayashi T, Yao T
  • Journal Title: J Surg Oncol Volume: 103 Pages: 674-686
• [Journal Article] Role for p16(INK4a) in progression of gastrointestinal stromal tumors of the stomach : alteration of p16(INK4a) network members (2011)
  • Author(s): Mitomi H, Fukui N, Kishimoto I, Tanabe S, Kikuchi S, Saito T, Hayashi T, Yao T
  • Journal Title: Human Pathol Volume: 42 Pages: 1505-1513
• [Journal Article] Oncocytic mucoepidermoid carcinoma of the parotid gland with CRTC1-MAML2 fusion transcript : report of a case with review of literature (2011)
  • Author(s): Fujimaki M, Fukumura Y, Saito T, Mitani K, Uchida S, Yokoyama J, Yao T, Ikeda K
  • Journal Title: Human Pathol Volume: 42 Pages: 2052-2055
• [Journal Article] A case of de novo secondary malignant giant-cell tumor of bone with loss of heterozygosity of p53 gene that transformed within a short-term follow-up (2011)
  • Author(s): Saito T, Mitomi H, Suehara Y, Okubo T, Torigoe T, Takagi T, Kaneko K, Yao T
  • Journal Title: Pathol Res Pract Volume: 207 Pages: 664-669
• [Journal Article] Pfetin mutations in gastrointestinal stromal tumor
  • Author(s): Okubo T, Suehara Y, Mitomi H, Mitani K, Takahashi M, Kubota D, Kondo T, Taguchi T, Kawai A, Kaneko K, Yao T, Saito T
  • Journal Title: Am J Pathol Volume: (in submission)
• [Journal Article] Giant-cell tumor of bone arising in the anterior chest wall with positive expressions of GPX-1: a case report with review of literature
  • Author(s): Toda M, Suehara Y, Akaike K, Okubo T, Kubota D, Mukaihara K, Kaneko K, Yao T, Takagi T, Saito T
  • Journal Title: Int Canc Conf J Volume: (in press)
• [Journal Article] Review : Proteomic technologies to develop biomarkers and functional analyses in the bone and soft tissue tumors
  • Author(s): Suehara Y, Kohsaka S, Kubota D, Mukaihara K, Akaike K, Mineki R, Fujimura T, Ladanyi M, Saito T, Kondo T
  • Journal Title: J Proteo Bioinf Volume: (in press)
• [Journal Article] PTCH1 mutation is a frequent event in esophageal basaloid squamous cell carcinoma
  • Author(s): Saito T, Mitomi H, Imamhasan A, Hayashi H, Kurisaki-Arakawa A, Mitani K, Takahashi M, Kajiyama Y, Yao T
  • Journal Title: Mutagenesis Volume: (in press)
• [Journal Article] Eggshell-like mineralized recurrent lesion in the popliteal region after treatment of giant cell tumor of bone with denosumab
  • Author(s): Akaike K, Suehara Y, Takagi T, Kaneko K, Saito T
  • Journal Title: Skeletal Radiol Volume: (in press)
• [Journal Article] A case of ^123I-MIBG scintigram-negative functioning pheochromocytoma : Immunohistochemical and molecular analysis with review of literature
  • Author(s): Kurisaki-Arakawa A, Saito T, Takahashi M, Mitani K, Yao T
  • Journal Title: Int J Clin Exp Pathol Volume: (in press)
• [Journal Article] A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation
  • Author(s): Kurisaki-Arakawa A, Akaike K, Hara K, Arakawa A, Takahashi M, Mitani K, Yao T, Saito T
  • Journal Title: Virchows Archiv Volume: (in press)
• [Presentation] 脱分化成分にTP53 mutationを認めた脱分化型孤在性線維性腫瘍の一例 (2014)
  • Author(s): 栗崎-荒川愛子, 赤池慶祐, 原貴恵子, 福村由紀, 荒川敦, 八尾隆史, 齋藤剛
  • Organizer: 日本病理学会
  • Place of Presentation: 広島
  • Year and Date: 20140428-30
• [Presentation] 123I-MIBGシンチグラフィ陰性褐色細胞腫の一例—免疫組織学的, 遺伝学的, 統計学的検討を加えて-- (2014)
  • Author(s): 栗崎-荒川愛子, 齋藤剛, 三谷恵子, 荒川敦, 八尾隆史
  • Organizer: 日本病理学会
  • Place of Presentation: 広島
  • Year and Date: 20140428-30
• [Presentation] 肺腺癌ではGalectin-4とTTF-1の発現は逆相関する (2014)
  • Author(s): 原貴恵子, 齋藤剛, 林大久生, 三谷恵子, 八尾隆史
  • Organizer: 日本病理学会
  • Place of Presentation: 広島
  • Year and Date: 20140428-30
• [Presentation] 胃底腺型胃癌におけるGNAS遺伝子解析 (2014)
  • Author(s): 野村亮介, 齋藤剛, 李世容, 日高康博, 渡辺純夫, 八尾隆史
  • Organizer: 日本病理学会
  • Place of Presentation: 広島
  • Year and Date: 20140428-30
• [Presentation] Solitary fibrous tumorにおけるNAB2-STAT6融合遺伝子のタイプと臨床病理像 (2014)
  • Author(s): 赤池慶祐, 原貴恵子, 栗崎-荒川愛子, 三谷恵子, 八尾隆史, 齋藤剛
  • Organizer: 日本病理学会
  • Place of Presentation: 広島
  • Year and Date: 20140428-30
• [Presentation] IPMNにおけるGNAS変異と組織像の関連 (2014)
  • Author(s): Osman Mamat, 福村由紀, 高橋路子, 三谷恵子, 倉林功, 齋藤剛, 八尾隆史
  • Organizer: 日本病理学会
  • Place of Presentation: 広島
  • Year and Date: 20140428-30