2021/08/17 更新

写真a

アンドウ ミズオ
安藤 瑞生
Ando Mizuo
所属
医歯薬学域 教授
職名
教授
外部リンク

学位

  • 医学博士 ( 東京大学 )

研究キーワード

  • ゲノム医療

  • エピゲノム

  • 頭頸部癌

学歴

  • 東京大学大学院   医学系研究科  

    2010年 - 2014年

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  • 東京大学   医学部   医学科

    1994年 - 2000年

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経歴

  • 岡山大学学術研究院 医歯薬学域   耳鼻咽喉・頭頸部外科学   教授   頭頸部がんセンター 副センター長

    2021年4月 - 現在

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  • 岡山大学大学院 医歯薬学総合研究科   耳鼻咽喉・頭頸部外科学   教授

    2020年

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  • 東京大学大学院 医学系研究科   耳鼻咽喉科・頭頸部外科学   准教授

    2020年

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  • 米国カリフォルニア大学サンディエゴ校(UCSD)   Moores がんセンター   客員研究員

    2016年

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  • 東京大学医学部附属病院   耳鼻咽喉科・頭頸部外科   講師

    2015年

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  • 東京大学医学部附属病院   耳鼻咽喉科・聴覚音声外科   助教

    2008年

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  • 国立がんセンター中央病院   頭頸科

    2005年

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  • 帝京大学   耳鼻咽喉科

    2000年

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▼全件表示

所属学協会

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論文

  • Apocrine Hidrocystoma of the External Auditory Canal in a Child. 国際誌

    Tomoyasu Tachibana, Tomoaki Sasaki, Yoji Wani, Yuto Naoi, Yuko Kataoka, Kazunori Nishizaki, Mizuo Ando

    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/MAO.0000000000003220

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  • Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan. 国際誌

    Chikatoshi Katada, Manabu Muto, Satoshi Fujii, Tetsuji Yokoyama, Tomonori Yano, Akihito Watanabe, Toshiro Iizuka, Shigetaka Yoshinaga, Ichiro Tateya, Hiroki Mitani, Yuichi Shimizu, Akiko Takahashi, Tomoyuki Kamijo, Noboru Hanaoka, Makoto Abe, Akihiro Shiotani, Koichi Kano, Yukinori Asada, Tamotsu Matsuhashi, Hirohito Umeno, Kenji Okami, Kenichi Goda, Shinichiro Hori, Yoichiro Ono, Shuji Terai, Yasuaki Nagami, Kenichi Takemura, Kenro Kawada, Mizuo Ando, Naoto Shimeno, Akihito Arai, Yasutoshi Sakamoto, Masaaki Ichinoe, Tetsuo Nemoto, Masahiro Fujita, Hidenobu Watanabe, Tadakazu Shimoda, Atsushi Ochiai, Takakuni Kato, Ryuichi Hayashi

    Cancer medicine   10 ( 12 )   3848 - 3861   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

    DOI: 10.1002/cam4.3927

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  • A retrospective analysis of radiotherapy in the treatment of external auditory canal carcinoma. 国際誌

    Atsuto Katano, Ryousuke Takenaka, Hideomi Yamashita, Mizuo Ando, Masafumi Yoshida, Yuki Saito, Takahiro Asakage, Osamu Abe, Keiichi Nakagawa

    Molecular and clinical oncology   14 ( 3 )   45 - 45   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    External auditory canal carcinoma (EACC) is a rare disease. The current study aimed to evaluate the clinical outcomes of patients treated with external beam radiotherapy (EBRT) for EACC. The present study retrospectively reviewed 34 consecutive patients treated for EACC with EBRT between February 2001 and January 2019 at the University of Tokyo Hospital. Clinical staging was performed according to the modified Pittsburgh classification. Of all the included patients, seven patients were in the early stages (I or II) and 27 in the advanced stages (III or IV) of EACC. A total of 16 patients underwent EBRT and surgery (S+RT) pre- and/or postoperatively, while 18 patients underwent definitive radiotherapy (dRT). The median prescribed doses for the S+RT and dRT groups were 66 and 70 Gy, respectively. The median follow-up period for all patients was 22.4 months (range, 2-205 months). The 5-year overall survival rates of the S+RT and dRT groups were 66.7 and 45.1%, respectively. The progression-free survival rate at 5-year was 55.6% (95% confidence interval: 36.5-71.1%) for the entire cohort. A total of 14 patients experienced disease relapse after treatment, consisting of 11 locoregional recurrences and three distant metastases. The current study revealed the clinical outcomes of EBRT for EACC.

    DOI: 10.3892/mco.2021.2207

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  • Reciprocal activation of HEY1 and NOTCH4 under SOX2 control promotes EMT in head and neck squamous cell carcinoma. 国際誌

    Takahito Fukusumi, Theresa W Guo, Shuling Ren, Sunny Haft, Chao Liu, Akihiro Sakai, Mizuo Ando, Yuki Saito, Sayed Sadat, Joseph A Califano

    International journal of oncology   58 ( 2 )   226 - 237   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Several comprehensive studies have demonstrated that the NOTCH pathway is altered in a bimodal manner in head and neck squamous cell carcinoma (HNSCC). In a previous study, it was found that the NOTCH4/HEY1 pathway was specifically upregulated in HNSCC and promoted epithelial‑mesenchymal transition (EMT), and that HEY1 activation supported SOX2 expression. However, the interactions in this pathway have not yet been fully elucidated. The present study investigated the NOTCH4/HEY1/SOX2 axis in HNSCC using in vitro models and the Cancer Genome Atlas (TCGA) database. To explore the association, reporter and ChIP RT‑qPCR assays using SOX2‑overexpressing (SOX2‑OE) cells were performed. The association between NOTCH4 and HEY1 was examined in the same manner using HEY1‑overexpressing (HEY1‑OE) cells. The results of the in vitro experiments indicated that HEY1 promoted EMT in the HNSCC cells. Furthermore, the overexpression of HEY1 also promoted sphere formation and increased murine xenograft tumorigenicity. Reporter assays and ChIP RT‑qPCR experiments indicated that SOX2 regulated HEY1 expression via direct binding of the HEY1 promoter. HEY1 expression significantly correlated with SOX2 expression in primary lung SCC and other SCCs using the TCGA database. HEY1 also regulated NOTCH4 expression to create a positive reciprocal feedback loop. On the whole, the present study demonstrates that HEY1 expression in HNSCC is regulated via the promotion of SOX2 and promotes EMT. The NOTCH4/HEY1 pathway is specifically upregulated via a positive reciprocal feedback loop mediated by the HEY1‑medaited regulation of NOTCH4 transcription, and SOX2 correlates with HEY1 expression in SCC from other primary sites.

    DOI: 10.3892/ijo.2020.5156

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  • Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence. 国際誌

    Kenya Kobayashi, Seiichi Yoshimoto, Mizuo Ando, Fumihiko Matsumoto, Naoya Murakami, Go Omura, Yoshitaka Honma, Yoshifumi Matsumoto, Atsuo Ikeda, Azusa Sakai, Kohtaro Eguchi, Akiko Ito, Eigitsu Ryo, Yasushi Yatabe, Taisuke Mori

    Oral oncology   113   105091 - 105091   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023). CONCLUSION: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.

    DOI: 10.1016/j.oraloncology.2020.105091

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  • The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma. 査読 国際誌

    Hideaki Hirai, Yuichiro Tada, Masato Nakaguro, Daisuke Kawakita, Yukiko Sato, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Isaku Okamoto, Soichiro Takase, Takuro Okada, Hiroki Sato, Yorihisa Imanishi, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Natsuki Saigusa, Hideaki Takahashi, Mizuo Ando, Makoto Urano, Toyoyuki Hanazawa, Toshitaka Nagao

    Virchows Archiv : an international journal of pathology   2020年2月

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    記述言語:英語  

    Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)-positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism-related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.

    DOI: 10.1007/s00428-020-02777-w

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  • A novel splice variant of LOXL2 promotes progression of human papillomavirus-negative head and neck squamous cell carcinoma. 国際誌

    Chao Liu, Theresa Guo, Akihiro Sakai, Shuling Ren, Takahito Fukusumi, Mizuo Ando, Sayed Sadat, Yuki Saito, Joseph A Califano

    Cancer   126 ( 4 )   737 - 748   2020年2月

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    記述言語:英語  

    BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently diagnosed cancers worldwide. LOXL2 demonstrates alternative splicing events in patients with human papillomavirus (HPV)-negative HNSCC. The current study explored the role of a dominant LOXL2 variant in HPV-negative HNSCC. METHODS: Expression of the LOXL2 variant was analyzed using The Cancer Genome Atlas cohorts and validated using quantitative reverse transcriptase-polymerase chain reaction in a separate primary tumor set. The authors defined the effect of LOXL2 splice variants in assays for cell proliferation using a cell viability assay and colony formation assay. Cell migration and invasion were examined using a cell scratch assay and transwell cell migration and invasion assay in LOXL2 splice variant gain and loss of expression cells. Western blot analysis and gene set enrichment analysis were used to explore the potential mechanism of the LOXL2 splice variant in HPV-negative HNSCC. RESULTS: Expression of a novel LOXL2 variant was found to be upregulated in The Cancer Genome Atlas HPV-negative HNSCC, and confirmed in the separate primary tumor validation set. Analyses of loss and gain of function demonstrated that this LOXL2 variant enhanced proliferation, migration, and invasion in HPV-negative HNSCC cells and activated the FAK/AKT pathway. A total of 837 upregulated and 820 downregulated genes and 526 upregulated and 124 downregulated pathways associated with LOXL2 variant expression were identified using gene set enrichment analysis, which helped in developing a better understanding of the networks activated by this LOXL2 variant in patients with HPV-negative HNSCC. CONCLUSIONS: The novel LOXL2 variant can promote the progression of HPV-negative HNSCC, in part through FAK/AKT pathway activation, which may provide a new potential therapeutic target among patients with HPV-negative HNSCC.

    DOI: 10.1002/cncr.32610

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  • Cannabinoids promote progression of HPV positive head and neck squamous cell carcinoma via p38 MAPK activation. 査読 国際誌

    Chao Liu, Sayed H Sadat, Koji Ebisumoto, Akihiro Sakai, Bharat A Panuganti, Shuling Ren, Yusuke Goto, Sunny Haft, Takahito Fukusumi, Mizuo Ando, Yuki Saito, Theresa Guo, Pablo Tamayo, Huwate Yeerna, William Kim, Jacqueline Hubbard, Andrew B Sharabi, J Silvio Gutkind, Joseph A Califano

    Clinical cancer research : an official journal of the American Association for Cancer Research   2020年1月

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    記述言語:英語  

    PURPOSE: Human papilloma virus (HPV) related head and neck squamous cell carcinoma (HNSCC) is associated with daily marijuana use and is also increasing in parallel with increased marijuana use in the United States. Our study is designed to define the interaction between cannabinoids and HPV positive HNSCC. EXPERIMENTAL DESIGN: The expression of cannabinoid receptors CNR1 and CNR2 was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data. We used agonists, antagonists, siRNAs or shRNA based models to explore the roles of CNR1 and CNR2 in HPV positive HNSCC cell lines and animal models. Cannabinoid downstream pathways involved were determined by Western blotting and analyzed in a primary HPV HNSCC cohort with single sample gene set enrichment analysis (ssGSEA) and the OncoGenome Positioning System (Onco-GPS). RESULTS: In TCGA cohort, the expression of CNR1 and CNR2 was elevated in HPV positive HNSCC compared with HPV negative HNSCC, and knockdown of CNR1/CNR2 expression inhibited proliferation in HPV positive HNSCC cell lines. Specific CNR1 and CNR2 activation as well as non-selective cannabinoid receptor activation in cell lines and animal models promoted cell growth, migration, and inhibited apoptosis through p38 MAPK pathway activation. CNR1/CNR2 antagonists suppressed cell proliferation and migration, and induced apoptosis. Using whole genome expression analysis in a primary HPV HNSCC cohort, we identified specific p38 MAPK pathway activation signature in tumors from HPV HNSCC patients with objective measurement of concurrent cannabinoid exposure. CONCLUSION: Cannabinoids can promote progression of HPV positive HNSCC through p38 MAPK pathway activation.

    DOI: 10.1158/1078-0432.CCR-18-3301

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  • Spinal solitary fibrous tumor of the neck: Next-generation sequencing-based analysis of genomic aberrations. 査読 国際誌

    Mizuo Ando, Hiroshi Kobayashi, Aya Shinozaki-Ushiku, Hirotaka Chikuda, Yoshitaka Matsubayashi, Masafumi Yoshida, Yuki Saito, Shinji Kohsaka, Katsutoshi Oda, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Tatsuya Yamasoba

    Auris, nasus, larynx   2019年12月

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    記述言語:英語  

    A solitary fibrous tumor (SFT) is a rare neoplasm with recurrent NAB2-STAT6 gene fusion. An SFT may develop almost anywhere throughout the body, including the head and neck region, and is characterized by a broad spectrum of malignancy. Here we present a case involving a 57-year-old male with a dumbbell-shaped SFT in the cervical spine that mimicked schwannoma. Repeated fine-needle aspiration cytology failed to establish a definitive diagnosis. Given that the tumor size increased significantly over a 10-month period, open biopsy was then performed. Though the biopsy result was inconclusive, a nonepithelial tumor, including sclerosing epithelioid fibrosarcoma or ossifying fibromyxoid tumor, was suspected. The tumor was then completely removed together with adjacent parts of C2 and C3 vertebrae and left vertebral artery via combined anterior and posterior approaches. Histologically, the tumor consisted of round cells with prominent stromal hyalinization and was immunohistochemically positive for STAT6, CD34, and cytokeratin. Finally, Todai OncoPanel, a next-generation sequencing-based molecular profiling system using formalin-fixed paraffin-embedded samples, demonstrated fusion transcript in which NAB2 exon 6 was fused to STAT6 exon 16 supporting the diagnosis of SFT, while whole-exome sequencing analysis detected no somatic mutations which were known to be oncogenic.

    DOI: 10.1016/j.anl.2019.12.001

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  • Rational genomic optimization of DNA detection for human papillomavirus type 16 in head and neck squamous cell carcinoma. 国際誌

    Yuki Saito, Alexander V Favorov, Michael Forman, Shuling Ren, Akihiro Sakai, Takahito Fukusumi, Chao Liu, Sayed Sadat, Mizuo Ando, Guorong Xu, Zubair Khan, John Pang, Alex Valsamakis, Kathleen M Fisch, Joseph A Califano

    Head & neck   2019年12月

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    記述言語:英語  

    BACKGROUND: We aimed to use genomic data for optimizing polymerase chain reaction (PCR) primer/probe sets for detection of human papillomavirus (HPV)-16 in body fluids of patients with HPV-related head and neck squamous cell carcinoma (HPV-HNSCC). METHODS: We used genomic HPV-HNSCC sequencing data from a single institutional and a TCGA cohort. Optimized primer/probe sets were designed and tested for analytical performance in CaSki HPV-16 genome and confirmed in salivary rinse samples from patients with HPV-HNSCC. RESULTS: The highest read density was observed between E5 and L2 regions. The E1 region contained a region that was universally present. Among candidate PCR primer/probe sets created, six reliably detected 30 HPV-16 copy number. In a CLIA certified laboratory setting, the combination of two novel primer/probe with E7 sets improved performance in salivary rinse samples with a sensitivity of 96% and specificity of 100%. CONCLUSIONS: PCR-based detection of HPV-16 DNA in HPV-HNSCC can be improved using rational genomic design.

    DOI: 10.1002/hed.26041

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  • Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma: Proposal of a Novel Histologic Risk Stratification Model. 査読 国際誌

    Masato Nakaguro, Yukiko Sato, Yuichiro Tada, Daisuke Kawakita, Hideaki Hirai, Makoto Urano, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Soichiro Takase, Takuro Okada, Hiroki Sato, Yorihisa Imanishi, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Natsuki Saigusa, Hideaki Takahashi, Mizuo Ando, Toyoyuki Hanazawa, Toshitaka Nagao

    The American journal of surgical pathology   2019年11月

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    記述言語:英語  

    Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.

    DOI: 10.1097/PAS.0000000000001413

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  • Mutation of chromatin regulators and focal hotspot alterations characterize human papillomavirus-positive oropharyngeal squamous cell carcinoma. 査読 国際誌

    Sunny Haft, Shuling Ren, Guorong Xu, Adam Mark, Kathleen Fisch, Theresa W Guo, Zubair Khan, John Pang, Mizuo Ando, Chao Liu, Akihiro Sakai, Takahito Fukusumi, Joseph A Califano

    Cancer   125 ( 14 )   2423 - 2434   2019年7月

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    記述言語:英語  

    BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal cancer is a disease clinically and biologically distinct from smoking-related head and neck squamous cell carcinoma (HNSCC). Despite its rapidly increasing incidence, the mutational landscape of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) remains understudied. METHODS: This article presents the first mutational analysis of the 46 HPV+ OPSCC tumors within the newly expanded cohort of 530 HNSCC tumors from The Cancer Genome Atlas. A separate exome sequencing analysis was also performed for 46 HPV+ OPSCCs matched to their normal lymphocyte controls from the Johns Hopkins University cohort. RESULTS: There was a strikingly high 33% frequency of mutations within genes associated with chromatin regulation, including mutations in lysine methyltransferase 2C (KMT2C), lysine methyltransferase 2D (KMT2D), nuclear receptor binding SET domain protein 1 (NSD1), CREB binding protein (CREBBP), E1A-associated protein p300 (EP300), and CCCTC-binding factor (CTCF). In addition, the commonly altered genes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) and fibroblast growth factor receptor 3 (FGFR3) showed distinct domain-specific hotspot mutations in comparison with their HPV- counterparts. PIK3CA showed a uniquely high rate of mutations within the helicase domain, and FGFR3 contained a predominance of hotspot S249C alterations that were not found in HPV- HNSCC. CONCLUSIONS: This analysis represents one of the largest studies to date of HPV+ OPSCC and lends novel insight into the genetic landscape of this biologically distinct disease, including a high rate of mutations in histone- and chromatin-modifying genes, which may offer novel therapeutic targets.

    DOI: 10.1002/cncr.32068

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  • Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa. 査読

    Iwamura H, Kondo K, Kikuta S, Nishijima H, Kagoya R, Suzukawa K, Ando M, Fujimoto C, Toma-Hirano M, Yamasoba T

    Cell and tissue research   2019年6月

  • Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers. 査読 国際誌

    Mizuo Ando, Yuki Saito, Guorong Xu, Nam Q Bui, Kate Medetgul-Ernar, Minya Pu, Kathleen Fisch, Shuling Ren, Akihiro Sakai, Takahito Fukusumi, Chao Liu, Sunny Haft, John Pang, Adam Mark, Daria A Gaykalova, Theresa Guo, Alexander V Favorov, Srinivasan Yegnasubramanian, Elana J Fertig, Patrick Ha, Pablo Tamayo, Tatsuya Yamasoba, Trey Ideker, Karen Messer, Joseph A Califano

    Nature communications   10 ( 1 )   2188 - 2188   2019年5月

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    記述言語:英語  

    Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine DNA methylation, chromatin marks, and transcriptional alterations to define the relationship between transcriptional modulation and spatial changes in chromatin structure. Using human papillomavirus-related oropharyngeal carcinoma as a model, we show aberrant enrichment of repressive H3K9me3 at the transcriptional start site (TSS) with methylation-associated, tumor-specific gene silencing. Further analysis identifies a hypermethylated subtype which shows a functional convergence on MYC targets and association with CREBBP/EP300 mutation. The tumor-specific shift to transcriptional repression associated with DNA methylation at TSSs was confirmed in multiple tumor types. Our data may show a common underlying epigenetic dysregulation in cancer associated with broad enrichment of repressive chromatin marks and aberrant DNA hypermethylation at TSSs in combination with MYC network activation.

    DOI: 10.1038/s41467-019-09937-w

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  • 4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer. 査読

    Wang Z, Feng X, Molinolo AA, Martin D, Vitale-Cross L, Nohata N, Ando M, Wahba A, Amornphimoltham P, Wu X, Gilardi M, Allevato M, Wu V, Steffen DJ, Tofilon P, Sonenberg N, Califano J, Chen Q, Lippman SM, Gutkind JS

    Cancer research   79 ( 7 )   1438 - 1450   2019年4月

  • Comprehensive assay for the molecular profiling of cancer by target enrichment from formalin-fixed paraffin-embedded specimens. 査読 国際誌

    Shinji Kohsaka, Kenji Tatsuno, Toshihide Ueno, Masaaki Nagano, Aya Shinozaki-Ushiku, Tetsuo Ushiku, Daiya Takai, Masachika Ikegami, Hiroshi Kobayashi, Hidenori Kage, Mizuo Ando, Keisuke Hata, Hiroki Ueda, Shogo Yamamoto, Shinya Kojima, Kumiko Oseto, Keisuke Akaike, Yoshiyuki Suehara, Takuo Hayashi, Tsuyoshi Saito, Fumiyuki Takahashi, Kazuhisa Takahashi, Kazuya Takamochi, Kenji Suzuki, Satoshi Nagayama, Yoshinao Oda, Koshi Mimori, Soichiro Ishihara, Yutaka Yatomi, Takahide Nagase, Jun Nakajima, Sakae Tanaka, Masashi Fukayama, Katsutoshi Oda, Masaomi Nangaku, Kohei Miyazono, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano

    Cancer science   110 ( 4 )   1464 - 1479   2019年4月

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    記述言語:英語  

    Tumor molecular profiling is becoming a standard of care for patients with cancer, but the optimal platform for cancer sequencing remains undetermined. We established a comprehensive assay, the Todai OncoPanel (TOP), which consists of DNA and RNA hybridization capture-based next-generation sequencing panels. A novel method for target enrichment, named the junction capture method, was developed for the RNA panel to accurately and cost-effectively detect 365 fusion genes as well as aberrantly spliced transcripts. The TOP RNA panel can also measure the expression profiles of an additional 109 genes. The TOP DNA panel was developed to detect single nucleotide variants and insertions/deletions for 464 genes, to calculate tumor mutation burden and microsatellite instability status, and to infer chromosomal copy number. Clinically relevant somatic mutations were identified in 32.2% (59/183) of patients by prospective TOP testing, signifying the clinical utility of TOP for providing personalized medicine to cancer patients.

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  • All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma. 査読

    Kobayashi K, Yoshimoto S, Matsumoto F, Ando M, Murakami N, Omura G, Fukasawa M, Matsumoto Y, Matsumura S, Akamatsu M, Hiraoka N, Eigitsu R, Mori T

    Annals of surgical oncology   2019年3月

  • Discovery and development of differentially methylated regions in human papillomavirus-related oropharyngeal squamous cell carcinoma. 査読 国際誌

    Shuling Ren, Daria Gaykalova, Jennifer Wang, Theresa Guo, Ludmila Danilova, Alexander Favorov, Elana Fertig, Justin Bishop, Zubair Khan, Emily Flam, Piotr T Wysocki, Peter DeJong, Mizuo Ando, Chao Liu, Akihiro Sakai, Takahito Fukusumi, Sunny Haft, Sayed Sadat, Joseph A Califano

    International journal of cancer   143 ( 10 )   2425 - 2436   2018年11月

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    記述言語:英語  

    Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) exhibits a different composition of epigenetic alterations. In this study, we identified differentially methylated regions (DMRs) with potential utility in screening for HPV-positive OPSCC. Genome wide DNA methylation was measured using methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) in 50 HPV-positive OPSCC tissues and 25 normal tissues. Fifty-one DMRs were defined with maximal methylation specificity to cancer samples. The Cancer Genome Atlas (TCGA) methylation array data was used to evaluate the performance of the proposed candidates. Supervised hierarchical clustering of 51 DMRs found that HPV-positive OPSCC had significantly higher DNA methylation levels compared to normal samples, and non-HPV-related head and neck squamous cell carcinoma (HNSCC). The methylation levels of all top 20 DNA methylation biomarkers in HPV-positive OPSCC were significantly higher than those in normal samples. Further confirmation using quantitative methylation specific PCR (QMSP) in an independent set of 24 HPV-related OPSCCs and 22 controls showed that 16 of the 20 candidates had significant higher methylation levels in HPV-positive OPSCC samples compared with controls. One candidate, OR6S1, had a sensitivity of 100%, while 17 candidates (KCNA3, EMBP1, CCDC181, DPP4, ITGA4, BEND4, ELMO1, SFMBT2, C1QL3, MIR129-2, NID2, HOXB4, ZNF439, ZNF93, VSTM2B, ZNF137P and ZNF773) had specificities of 100%. The prediction accuracy of the 20 candidates rang from 56.2% to 99.8% by receiver operating characteristic analysis. We have defined 20 highly specific DMRs in HPV-related OPSCC, which can potentially be applied to molecular-based detection tests and improve disease management.

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  • Characterization of Alternative Splicing Events in HPV-Negative Head and Neck Squamous Cell Carcinoma Identifies an Oncogenic DOCK5 Variant. 査読 国際誌

    Chao Liu, Theresa Guo, Guorong Xu, Akihiro Sakai, Shuling Ren, Takahito Fukusumi, Mizuo Ando, Sayed Sadat, Yuki Saito, Zubair Khan, Kathleen M Fisch, Joseph Califano

    Clinical cancer research : an official journal of the American Association for Cancer Research   24 ( 20 )   5123 - 5132   2018年10月

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    記述言語:英語  

    Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, and alternative splicing is considered to play important roles in tumor progression. Our study is designed to identify alternative splicing events (ASEs) in human papillomavirus (HPV)-negative HNSCC.Experimental Design: RNA sequencing data of 407 HPV-negative HNSCC and 38 normal samples were obtained from The Cancer Genome Atlas (TCGA), and splice junctions were discovered using MapSplice. Outlier analysis was used to identify significant splicing junctions between HPV-negative HNSCC and normal samples. To explore the functional role of the identified DOCK5 variant, we checked its expression with qRT-PCR in a separate primary tumor validation set and performed proliferation, migration, and invasion assays.Results: A total of 580 significant splicing events were identified in HPV-negative HNSCC, and the most common type of splicing events was an alternative start site (33.3%). The prevalence of a given individual ASE among the tumor cohort ranged from 9.8% and 64.4%. Within the 407 HPV-negative HNSCC samples in TCGA, the number of significant ASEs differentially expressed in each tumor ranged from 17 to 290. We identified a novel candidate oncogenic DOCK5 variant confirmed using qRT-PCR in a separate primary tumor validation set. Loss- and gain-of-function experiments indicated that DOCK5 variant promoted proliferation, migration, and invasion of HPV-negative HNSCC cells, and patients with higher expression of DOCK5 variant showed decreased overall survival.Conclusions: Analysis of ASEs in HPV-negative HNSCC identifies multiple alterations likely related to carcinogenesis, including an oncogenic DOCK5 variant. Clin Cancer Res; 24(20); 5123-32. ©2018 AACR.

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  • Postoperative mechanical bowel obstruction after pharyngolaryngectomy for hypopharyngeal cancer: Retrospective analysis using a Japanese inpatient database. 査読 国際誌

    Sayaka Suzuki, Hideo Yasunaga, Hiroki Matsui, Kiyohide Fushimi, Mizuo Ando, Tatsuya Yamasoba

    Head & neck   40 ( 7 )   1548 - 1554   2018年7月

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    記述言語:英語  

    BACKGROUND: Data have been limited on donor-site mechanical bowel obstruction after pharyngolaryngectomy with free jejunum graft reconstruction. METHODS: Using a nationwide Japanese inpatient database, we extracted data on patients who underwent pharyngolaryngectomy for hypopharyngeal cancer between July 2007 and March 2014. A Cox proportional hazard model was used to determine the association between background characteristics and the occurrence of mechanical bowel obstruction. RESULTS: Among the 3320 eligible patients from 332 hospitals, 108 patients (3.3%) developed mechanical bowel obstruction after a median 88 (interquartile range 26-217) postoperative days. Multivariable Cox regression analysis revealed that older age (≥60 years old) was independently associated with an increased risk of mechanical bowel obstruction, whereas sex, body mass index [BMI], smoking status, comorbidity at admission, blood transfusion, history of surgery, and hospital type were not. CONCLUSION: In pharyngolaryngectomy, careful attention should be paid to the risk of abdominal complications and, thus, to the graft choice, especially in elderly patients.

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  • Radiotherapy alone and with concurrent chemotherapy for nasopharyngeal carcinoma 査読

    Atsuto Katano, Wataru Takahashi, Hideomi Yamashita, Kentaro Yamamoto, Mizuo Ando, Masafumi Yoshida, Yuki Saito, Osamu Abe, Keiichi Nakagawa

    Medicine (United States)   97 ( 18 )   e0502   2018年5月

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    掲載種別:研究論文(学術雑誌)  

    Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. We sought to evaluate clinical outcomes and toxicities of radiation therapy (RT) alone compared to RT with concurrent chemotherapy (CCT) for nasopharyngeal carcinoma (NPC) treatment. We conducted a retrospective review of consecutive patients with biopsy-proven nonmetastatic NPC who underwent RT at our institution. From May 2001 to April 2015; 62 newly diagnosed NPC patients were treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with or without CCT. The patients were classified as follows: 8% stage I, 15% stage II, 32% stage III, and 45% stage IVA/IVB. A total of 76% of tumors were World Health Organization types II or III. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) were analyzed. The median follow-up period for living patients was 53 months. The median actual delivered dose was 70 Gy with a range of 28 to 70 Gy in fraction sizes of 2 Gy. The estimated 5-year OS, PFS, LRPFS, and DMFS rates were 72.7%, 59.8%, 77.9%, and 84.2%, respectively. The use of CCT was a predictive factor of significantly better OS and PFS, whereas stage IV was a significant predictor of poor OS and PFS. The most severe acute toxicities included Grade 3 mucositis in 56% and Grade 3 dermatitis in 8%. Subset analysis revealed that Grade 2 xerostomia was significantly lower in the IMRT (23%) group than in the 3D-CRT (52%) group (P = .02). RT yielded favorable outcomes. CCT was associated with longer PFS and OS than RT alone.

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  • The NOTCH4-HEY1 Pathway Induces Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma. 査読 国際誌

    Takahito Fukusumi, Theresa W Guo, Akihiro Sakai, Mizuo Ando, Shuling Ren, Sunny Haft, Chao Liu, Panomwat Amornphimoltham, J Silvio Gutkind, Joseph A Califano

    Clinical cancer research : an official journal of the American Association for Cancer Research   24 ( 3 )   619 - 633   2018年2月

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    記述言語:英語  

    Purpose: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood.Experimental Design: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell-cycle assays. We also compared the relationships among NOTCH4, HEY1, and epithelial-mesenchymal transition (EMT)-related genes using the TCGA data set and in vitro assays.Results:HEY1 is specifically upregulated in HNSCC compared with normal tissues in the TCGA data set. NOTCH4 is more significantly related to HEY1 activation in HNSCC in comparison with other NOTCH receptors. NOTCH4 promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell-cycle dysregulation. Furthermore, NOTCH4 and HEY1 upregulation resulted in decreased E-cadherin expression and increased Vimentin, Fibronectin, TWIST1, and SOX2 expression. NOTCH4 and HEY1 expression was associated with an EMT phenotype as well as increased invasion and cell migration.Conclusions: In HNSCC, the NOTCH4-HEY1 pathway is specifically upregulated, induces proliferation and cisplatin resistance, and promotes EMT. Clin Cancer Res; 24(3); 619-33. ©2017 AACR.

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  • Prognostic and histogenetic roles of gene alteration and the expression of key potentially actionable targets in salivary duct carcinomas. 査読 国際誌

    Tomotaka Shimura, Yuichiro Tada, Hideaki Hirai, Daisuke Kawakita, Satoshi Kano, Kiyoaki Tsukahara, Akira Shimizu, Soichiro Takase, Yorihisa Imanishi, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Yukiko Sato, Chihiro Fushimi, Hideaki Takahashi, Takuro Okada, Hiroki Sato, Kuninori Otsuka, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Mizuo Ando, Shinji Kohsaka, Toyoyuki Hanazawa, Hideaki Chazono, Yoshiyuki Kadokura, Hitome Kobayashi, Toshitaka Nagao

    Oncotarget   9 ( 2 )   1852 - 1867   2018年1月

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    記述言語:英語  

    The molecular characteristics of therapeutically-relevant targets and their clinicopathological implications in salivary duct carcinomas (SDCs) are poorly understood. We investigated the gene alterations and the immunoexpression of crucial oncogenic molecules in 151 SDCs. The mutation rates that were identified, in order of frequency, were as follows: TP53, 68%; PIK3CA, 18%; H-RAS, 16%; BRAF, 4%; and AKT1, 1.5%. PIK3CA/H-RAS/BRAF mutations were more common in de novo SDC than in SDC ex-pleomorphic adenoma. Furthermore, these mutations were mutually exclusive for HER2 overexpression/amplification. TP53 mutations were frequently detected in cases with the aberrant p53 expression, and TP53 missense and truncating mutations were associated with p53-extreme positivity and negativity, respectively. DISH analysis revealed no cases of EGFR amplification. The rates of PI3K, p-Akt, and p-mTOR positivity were 34%, 22%, and 66%, respectively; PTEN loss was observed in 47% of the cases. These expressions were correlated according to the signaling axis. Cases with PI3K negativity and PTEN loss appeared to show a lower expression of androgen receptor. In the multivariate analysis, patients with SDC harboring TP53 truncating mutations showed shorter progression-free survival. Conversely, p-Akt positivity was associated with a favorable outcome. This study might provide information that leads to advances in personized therapy for SDC.

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  • The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma 査読

    Go Omura, Mizuo Ando, Yasuhiro Ebihara, Yuki Saito, Kenya Kobayashi, Osamu Fukuoka, Ken Akashi, Masafumi Yoshida, Takahiro Asakage, Tatsuya Yamasoba

    BMC Cancer   17 ( 1 )   898   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BioMed Central Ltd.  

    Background: TP53 is the most frequently mutated gene in human cancers. Previous studies reported that TP53 mutations correlated with poor prognoses in patients with head and neck squamous cell carcinoma (HNSCC). However, the relationship between TP53 mutations and hypopharyngeal squamous cell carcinoma (HPSCC) is not known. The current study aimed to evaluate TP53 mutation status as a predictive biomarker in patients with HPSCC. Methods: We retrospectively reviewed the clinical charts of 57 HPSCC patients treated with initial surgery between 2008 and 2014. TP53 mutation status was determined by Sanger sequencing, and patients were classified into wild-type, missense mutation, and truncating mutation groups. Additionally, p53 expression was determined using immunohistochemistry in surgical specimens. Results: TP53 mutations were identified in 39 (68%) patients. The 3-year disease-specific survival (DSS) rate of wild-type, missense mutation, and truncating mutation group were 94%, 61%, and 43%, respectively. The TP53 mutation group displayed significantly worse DSS and overall survival rates than the wild-type group (P = 0.01 and P = 0.007, respectively). Multivariate analyses revealed that the presence of TP53 mutations and ≥4 metastatic lymph nodes were independent adverse prognostic factors for HPSCC. p53 immunopositivity was detected in 22 patients, including 5 (28%) and 17 (71%) patients in the wild-type and missense mutation groups, whereas none of the patients with truncating mutation exhibited p53 immunopositivity (P = 0.0001). Conclusion: The TP53 mutation status correlated with poor prognosis in surgically treated HPSCC patients. Specifically, truncating mutations which were not detected by p53 immunohistochemistry were predictive of worst survival.

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  • Prognostic value of ALDH2 polymorphism for patients with oropharyngeal cancer in a Japanese population 査読

    Hirotaka Shinomiya, Hitomi Shinomiya, Mie Kubo, Yuki Saito, Masafumi Yoshida, Mizuo Ando, Masanori Teshima, Naoki Otsuki, Naomi Kiyota, Ryohei Sasaki, Kenichi Nibu

    PLOS ONE   12 ( 12 )   e0187992   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background
    Half of Japanese possess a polymorphism of aldehyde dehydrogenase 2(ALDH2), while few white individuals possess this mutation. The purpose of this study was to investigate the possibility of ALDH2 polymorphism as a prognostic factor for oropharyngeal cancer (OPC) among Japanese population.
    Methods
    We analyzed 82 Japanese patients with OPC treated between 2006 and 2011. The median observation period was 50 months. P16-staining and ALDH2 polymorphisms were investigated. To examine the frequencies of second primary pharyngeal and esophageal cancers (SPPEC), 37 Japanese patients with OPC treated at Tokyo University Hospital were included for statistical analysis.
    Results
    Statistically significant differences were noted in OS among sex, age, N classification, and p16 (p = 0.045, 0.024, 0.020, 0.007, respectively). In addition, OS and DSS rates of the patients with heterozygous ALDH2 tended to be worse than those of the patients with homozygous ALDH2 (p = 0.21, 0.086, respectively). Of note, OS and DSS of the patients with p16-negative OPC and heterozygous ALDH2 was significant poorer than those of the patients with p16-positive OPC (p = 0.002, 0.006, respectively), while there was no significant difference in OS and DSS between patients with p16-positive OPC and patients with p16-negative OPC and homozygous ALDH2.
    Conclusions
    ALDH2 polymorphism might be a promising prognostic factor for Japanese patients with p16-negative OPC.

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  • The impact of elevated C-reactive protein level on the prognosis for oro-hypopharynx cancer patients treated with radiotherapy 査読

    Atsuto Katano, Wataru Takahashi, Hideomi Yamashita, Kentaro Yamamoto, Mizuo Ando, Masafumi Yoshida, Yuki Saito, Osamu Abe, Keiichi Nakagawa

    SCIENTIFIC REPORTS   7 ( 1 )   17805   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    The purpose of this study was to investigate an association between the prognosis for oro-hypopharynx squamous cell carcinoma treated with radiation therapy and the pre-therapeutic level of C-reactive protein (CRP). Patient with oro-hypopharyngeal squamous cell carcinoma who underwent definitive radiotherapy in our institution from January 2002 to August 2016 were enrolled. The patient were divided into elevated CRP (over 0.3 mg/dl) group and normal CRP groups, according to pre-treatment serum levels. There were 276 evaluable patients, and the median follow up was 41 months, ranging from 2 to 171 months. The 3-year OS and CSS for all enrolled patients were 67.0% and 72.8%, respectively. The OS and CSS rates were significantly worse in the elevated CRP group than in the normal CRP group, according to Kaplan-Meier survival curves analysed by a Log-rank test (p = 0.005 and p &lt; 0.001, respectively). Multivariate analyses indicated that serum CRP levels remained independent predictors for both OS (HR: 1.588, p = 0.022) and CSS (HR: 1.989, p = 0.005). The pre-treatment CRP level is an independent predictor of treatment prognosis in patients with oro-hypopharyngeal cancer who underwent definitive radiotherapy. Especially, it is curious that an elevated CRP serum level is a significant predictor of loco-regional recurrence.

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  • Current status of superficial pharyngeal squamous cell carcinoma in Japan 査読

    Ryoko Rikitake, Mizuo Ando, Yuki Saito, Seiichi Yoshimoto, Tatsuya Yamasoba, Takahiro Higashi

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   22 ( 5 )   826 - 833   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    To investigate the status and treatment of superficial pharyngeal squamous cell carcinoma in Japan.
    We analyzed all cases diagnosed between 2011 and 2013, as recorded in the national database of hospital-based cancer registries. We extracted data on patient sex, age, tumor locations, histology, presentation routes, initial treatments, and TNM stages. Additionally, we compared the characteristics of pharyngeal carcinoma to those of esophageal cancer.
    A total of 16,521 oropharyngeal and hypopharyngeal cancers from 409 institutions were included. Diagnosis of Tis tumors was infrequent, and both cancers were likely to be diagnosed at an advanced stage (n = 866, 5.3%). Tis diseases were the most commonly detected during follow-up examinations for other diseases (n = 608, 70%). While more oropharyngeal Tis patients were men compared to T1-4 patients (88 vs 82%, respectively), hypopharyngeal cancer patients comprised an equally high proportion of men (94 vs 92%, respectively). The most common location of oropharyngeal Tis tumors was the posterior wall (32%), whereas T1-4 tumors were most commonly found on the lateral wall (36%). In hypopharyngeal cancer, both Tis and T1-4 were most commonly located in the pyriform sinus (62%). The proportion of Tis tumors diagnosed at individual institutions showed a positive correlation with the number of endoscopic treatments (r = 0.32, P &lt; 0.001) and the number of esophageal cancer cases (r = 0.37, P &lt; 0.001).
    Our national database study elucidated the current characteristics of superficial pharyngeal squamous cell carcinoma patients in Japan. Further improvements in early diagnosis and standardized treatments are warranted.

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  • Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy 査読

    Yuki Saito, Go Omura, Kazuo Yasuhara, Ryoko Rikitake, Ken Akashi, Osamu Fukuoka, Masafumi Yoshida, Mizuo Ando, Takahiro Asakage, Tatsuya Yamasoba

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   39 ( 8 )   1535 - 1543   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Background. We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma.
    Methods. Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases.
    Results. We reviewed 135 records (120 men and 15 women; age range, 36-84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, &gt;3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS.
    Conclusion. Vascular invasion is a strong prognostic biomarker for advanced hypopharyngeal carcinoma. (C) 2017 Wiley Periodicals, Inc.

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  • Prolonged denervation induces remodeling of nasal mucosa in rat model of posterior nasal neurectomy 査読

    Hironobu Nishijima, Kenji Kondo, Makiko Toma-Hirano, Shu Kikuta, Mizuo Ando, Rumi Ueha, Tatsuya Yamasoba

    INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY   7 ( 7 )   670 - 678   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Background: The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) induces denervation of the nasal mucosa and relieves the nasal symptoms of intractable rhinitis. PNN depletes nerve fibers, choline acetyltransferase, and neuropeptides in nasal respiratory mucosa, and reduces nasal secretion. However, the histological and symptomatic changes over an extended period after PNN remain unknown.
    Methods: Using a rat model of PNN via the transorbital approach, we investigated chronological changes of nasal morphology, innervation, and secretion over a 48-week postoperative period after PNN.
    Results: The respiratory nasal mucosa exhibited squamous metaplasia, lymphocyte and plasma cell infiltration, basement membrane thickening, loss of cilia, and hyperplasia of the mucus gland in thickened epithelium with increased connective tissue from24 weeks after PNN. These changes resemble the characteristics of remodeling in chronic rhinosinusitis. DNA microarray and quantitative polymerase chain reaction analysis revealed that mucin 5ac, interleukin 13, and brain-derived neurotrophic factor messenger RNA ( mRNA) were upregulated in PNN-treatedmucosa compared to untreated mucosa. During this period, nerve fibers including sensory, sympathetic, and parasympathetic fibers gradually reinnervated the mucosa from 12 weeks after PNN. However, nasal secretion was decreased even at 48 weeks after PNN probably due to the prolonged absence of choline acetyltransferase.
    Conclusion: Prolonged denervation induces remodeling of the nasal mucosa. Although the depleted nerves were partially reinnervated a few months after PNN, nasal secretion was still suppressed, partly due to a sustained deficiency of acetylcholine synthesis. (C) 2017 ARS-AAOA, LLC.

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  • Survival impact of local extension sites in surgically treated patients with temporal bone squamous cell carcinoma 査読

    Go Omura, Mizuo Ando, Yuki Saito, Osamu Fukuoka, Ken Akashi, Masafumi Yoshida, Akinobu Kakigi, Takahiro Asakage, Tatsuya Yamasoba

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   22 ( 3 )   431 - 437   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Objectives Temporal bone squamous cell carcinoma (TSCC) is a rare malignancy. Due to its low incidence rate, studies involving TSCC treatment are limited. The aim of this study is to define the prognostic factors of surgery for TSCC by evaluating our clinical experience.
    Methods We reviewed the clinical charts of patients presenting at the University of Tokyo Hospital between 2001 and 2014 and identified 33 patients with TSCC who had been treated with surgery as initial curative treatment.
    Results Lateral and subtotal temporal bone resections were performed in 17 and 16 patients, respectively. The 5-year disease-specific and overall survival rate were 71 and 62%, respectively. The significant poor prognostic factors were pathological T4 (P = 0.03), dural invasion (P = 0.008), temporomandibular joint invasion (P = 0.04), and a positive surgical margin (P = 0.009).
    Conclusion We demonstrated that the outcome of curative surgery for TSCC as initial treatment was favorable. However, because of the difficulty to ensure an adequate or clear surgical margin due to anatomical complexity, the surgical indication for T4 TSCC with temporomandibular joint invasion should be reconsidered.

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  • Association between ear-picking habits and carcinoma of external auditory canal 査読

    Ryohei Ishiura, Takuya Iida, Akinobu Kakigi, Mizuo Ando, Masafumi Yoshida, Yuki Saito, Tatsuya Yamasoba, Isao Koshima

    Japanese Journal of Head and Neck Cancer   43 ( 1 )   76 - 78   2017年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Society for Head and Neck Cancer  

    Carcinoma of the external auditory canal (EAC) is a very rare disease. Although a relationship between frequent ear-picking and EAC carcinoma has been suspected, no statistical analysis has been reported. We retrospectively reviewed ear-picking habit in patients with carcinoma of EAC and in healthy Japanese people and statistically analyzed the data. As a result, in the“ younger ( under 50 years old)” group, both“ frequency” and“ materials” showed a significant difference between the patients and the healthy population( p=0.0021 and p=0.0012, respectively). Ear-picking more than once a day and with hard materials might be risk factors for carcinoma of EAC in the younger generation.

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  • Association of the upregulated expression of focal adhesion kinase with poor prognosis and tumor dissemination in hypopharyngeal cancer 査読

    Go Omura, Mizuo Ando, Yuki Saito, Kenya Kobayashi, Masafumi Yoshida, Yasuhiro Ebihara, Kaori Kanaya, Chisato Fujimoto, Takashi Sakamoto, Kenji Kondo, Takahiro Asakage, Tatsuya Yamasoba

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   38 ( 8 )   1164 - 1169   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BackgroundFocal adhesion kinase (FAK) plays an important role in tumor metastasis. The purpose of this study was to evaluate the significance of FAK expression in surgically treated patients with hypopharyngeal cancer.
    MethodsWe retrospectively reviewed the clinical charts of patients treated at our institution between 2004 and 2012 and identified 87 patients with hypopharyngeal cancer. FAK expression status was retrospectively evaluated using immunohistochemistry.
    ResultsFAK-positive patients displayed significantly worse disease-specific survival than FAK-negative patients (p=.001). Multivariate analyses revealed that FAK positivity and extracapsular spread (ECS) were independent, significant adverse prognostic factors. Furthermore, FAK positivity significantly correlated with the number of metastatic lymph nodes (p=.048), and FAK-positive patients displayed a higher incidence of distant metastases (p=.009).
    ConclusionThe current study demonstrated that upregulated FAK expression correlates with poor prognosis and tumor dissemination in surgically treated patients with hypopharyngeal cancer. (c) 2016 Wiley Periodicals, Inc. Head Neck 38:1164-1169, 2016

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  • Induction Chemotherapy for p16 Positive Oropharyngeal Squamous Cell Carcinoma. 査読

    Saito Y, Ando M, Omura G, Yasuhara K, Yoshida M, Takahashi W, Yamasoba T

    Laryngoscope investigative otolaryngology   1 ( 2 )   28 - 32   2016年4月

  • Mutational Landscape and Antiproliferative Functions of ELF Transcription Factors in Human Cancer 査読

    Mizuo Ando, Masahito Kawazu, Toshihide Ueno, Daizo Koinuma, Koji Ando, Junji Koya, Keisuke Kataoka, Takahiko Yasuda, Hiroyuki Yamaguchi, Kazutaka Fukumura, Azusa Yamato, Manabu Soda, Eirin Sai, Yoshihiro Yamashita, Takahiro Asakage, Yasushi Miyazaki, Mineo Kurokawa, Kohei Miyazono, Stephen D. Nimer, Tatsuya Yamasoba, Hiroyuki Mano

    CANCER RESEARCH   76 ( 7 )   1814 - 1824   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    ELF4 (also known as MEF) is a member of the ETS family of transcription factors. An oncogenic role for ELF4 has been demonstrated in hematopoietic malignancies, but its function in epithelial tumors remains unclear. Here, we show that ELF4 can function as a tumor suppressor and is somatically inactivated in a wide range of human tumors. We identified a missense mutation affecting the transactivation potential of ELF4 in oral squamous cell carcinoma cells. Restoration of the transactivation activity through introduction of wild-type ELF4 significantly inhibited cell proliferation in vitro and tumor xenograft growth. Furthermore, we found that ELF1 and ELF2, closely related transcription factors to ELF4, also exerted anti-proliferative effects in multiple cancer cell lines. Mutations in ELF1 and ELF2, as in ELF4, were widespread across human cancers, but were almost all mutually exclusive. Moreover, chromatin immunoprecipitation coupled with high-throughput sequencing revealed ELF4-binding sites in genomic regions adjacent to genes related to cell-cycle regulation and apoptosis. Finally, we provide mechanistic evidence that the antiproliferative effects of ELF4 were mediated through the induction of HRK, an activator of apoptosis, and DLX3, an inhibitor of cell growth. Collectively, our findings reveal a novel subtype of human cancer characterized by inactivating mutations in the ELF subfamily of proteins, and warrant further investigation of the specific settings where ELF restoration may be therapeutically beneficial.

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  • Comorbidity as predictor poor prognosis for patients with advanced head and neck cancer treated with major surgery 査読

    Go Omura, Mizuo Ando, Yuki Saito, Kenya Kobayashi, Tatsuya Yamasoba, Takahiro Asakage

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   38 ( 3 )   364 - 369   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BackgroundThe impact of comorbidities on patients with advanced head and neck cancer treated with major surgery has not been reported before.
    MethodsWe retrospectively reviewed clinical charts between 2004 and 2011 at our institution and identified 185 patients with clinical stage III to IV head and neck cancer treated with major surgery. Comorbidities were scored using the Adult Comorbidity Evaluation-27 (ACE-27) index manual.
    ResultsPatients with ACE-27 2 had significantly worse overall survival (OS) and disease-specific survival (DSS) than those with ACE-27 1 (p&lt;.0001 and p=.0047, respectively). Multivariate analyses revealed that ACE-27 2 and extracapsular spread (ECS) were independently significant adverse prognostic factors for OS and DSS. In addition, patients with ACE-27 2 had a higher incidence of distant metastases (p=.0057).
    ConclusionThe current study suggests that comorbidities may predict poor prognosis and development of distant metastases for patients with advanced head and neck cancer treated with major surgery. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: 364-369, 2016

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  • Clinical Value of the Epstein-Barr Virus and p16 Status in Patients with Nasopharyngeal Carcinoma: A Single-Centre Study in Japan 査読

    Yuki Saito, Tetsuo Ushiku, Go Omura, Kazuo Yasuhara, Masafumi Yoshida, Wataru Takahashi, Mizuo Ando, Masashi Fukayama, Tatsuya Yamasoba

    ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY HEAD AND NECK SURGERY   78 ( 6 )   334 - 343   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Background: The clinical significance of the Epstein-Barr virus (EBV) status and p16 expression was unknown in nasopharyngeal carcinoma (NPC). Methods: We retrospectively studied our pathology database for 13 years to determine the prevalence of EBV and p16 expression and their association with prognosis in cases of NPC. We performed immunohistochemistry for the p16 protein and in situ hybridization (ISH) for EBV-encoded small RNAs and human papillomavirus (HPV) DNA. Results: Of the 43 patients with NPC, 27 (63%), 6 (14%), and 10 (23%) cases were EBV positive, EBV negative with keratinization, and EBV negative without keratinization, respectively. No cases were HPV positive by ISH. Among the 21 EBV-positive tumours that were tested for p16, only 2 tumours were p16 positive. The keratinization-positive group included only males, typically &gt; 60 years of age (5 of 6) and with T4 tumours (3 of 6). In contrast, the EBV-positive cohort tended to be younger (&lt; 60 years, 13 of 27) and have progressive N-stage tumours (N2-3, 14 of 27). The keratinization and EBV-negative cohort included predominantly males (9 of 10) who were likely p16 negative (4 of 10) and smokers (7 of 10). Multivariate analysis confirmed that keratinization was an independent prognostic factor for progression-free survival. Conclusion: In areas, such as Japan, that are nonendemic for both EBV and HPV, the causality of NPC appears to be more heterogeneous. (C) 2017 S. Karger AG, Basel

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  • Human Papillomavirus 16 Physical Status and the TP53 Codon 72 Polymorphism in Japanese HPV-Positive Oropharyngeal Cancer Patients 査読

    Yuki Saito, Mizuo Ando, Chisato Fujimoto, Go Omura, Kenya Kobayashi, Takahiro Asakage, Tatsuya Yannasoba

    ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY HEAD AND NECK SURGERY   78 ( 1 )   46 - 54   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Background: In human papillomavirus (HPV)-induced carcinogenesis, the arginine (Arg) allele of the TP53 codon 72 polymorphism binds more efficiently to the HPV E6 oncoprotein than the proline (Pro) allele. We investigated the physical status of HPV-16 DNA and the TP53 codon 72 polymorphism in oropharyngeal squamous cell carcinoma (OPSCC). Methods: Tumor samples from 70 p16-positive OPSCC patients were tested for HPV-16 physical status by examining the E2 and E6 open reading frames. The TP53 codon 72 polymorphism was screened by direct sequencing. Results: Of 70 patients, 53 were E6 positive, 29 had integrated forms of HPV-16 DNA, and 24 had mixed or episomal forms. Furthermore, 44 carried the Arg/Arg or Arg/Pro genotype, 3 carried the Pro/Pro genotype, and in 6 patients we were unable to obtain sequencing data. Conclusions: HPV-16 physical status was heterogeneous in our OPSCC patients. Most OPSCC patients had the TP53 Arg/Arg or Arg/Pro genotype. (C) 2016 S. Karger AG, Basel

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  • Maxillary carcinosarcoma: Identification of a novel MET mutation in both carcinomatous and sarcomatous components through next generation sequencing 査読

    Mizuo Ando, Yuki Saito, Teppei Morikawa, Go Omura, Kenya Kobayashi, Ken Akashi, Masafumi Yoshida, Yasuhiro Ebihara, Chisato Fujimoto, Masashi Fukayama, Tatsuya Yamasoba, Takahiro Asakage

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   37 ( 12 )   E179 - E185   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background. Carcinosarcoma is a rare tumor with biphasic growth of the carcinomatous and sarcomatous components. Prognosis is generally poor and characterization of the molecular mechanisms may provide information for the development of novel antitumor agents and biomarkers.
    Methods and Results. We present the case of 66-year-old man with a complaint of nasal obstruction. He was diagnosed with maxillary carcinosarcoma and coexisting papilloma. He underwent multimodal treatment but died of uncontrolled local disease 10 months after the initial presentation. Genetic testing using next-generation sequencing (NGS) revealed that both the carcinomatous and sarcomatous components carried a somatic mutation in the conserved domain of the mesenchymal-epithelial transition factor (MET) proto-oncogene.
    Conclusion. Our observation highlighted the importance of the MET gene in the oncogenesis of maxillary carcinosarcoma and is indicative of the common clonal origin of both malignant components. This suggested a possibility of treating MET mutation-positive carcinosarcomas with c-MET inhibitors. (C) 2015 Wiley Periodicals, Inc.

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  • Retrospective study of induction chemotherapy and concurrent chemoradiation therapy for oropharyngeal cancer 査読

    Takahiro Asakage, Mizuo Ando, Masafumi Yoshida, Yuki Saito, Go Omura, Tatsuya Yamasoba

    Journal of Otolaryngology of Japan   118 ( 10 )   1226 - 1232   2015年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oto-Rhino-Laryngological Society of Japan Inc.  

    We carried out this study to clarify the treatment outcomes and problems associated with induction chemotherapy (using taxotere, cisplatin and 5-FU [TPF therapy]) and chemoradiotherapy in patients with oropharyngeal cancer. The data of 44 patients receiving their initial treatment for oropharyngeal cancer (including 2, 9 and 33 patients with stage II, stage III and stage IV disease, respectively, and 31, 8 and 3 patients with side wall, front wall and upper wall (soft palate and uvula) involvement) were examined. Of the 44 patients, 33 received induction chemotherapy and 11 received chemoradiotherapy. The feasibility, incidence of neutropenia, response rate, and 3 year disease-specific survival rate in the induction chemotherapy group vs. chemoradiotherapy group were 70%, 88%, 82% and 73%, respectively, vs. 63%, 91%, 82% and 55%, respectively. A statistically significant difference in the 3-year disease-specific survival rate was seen between the p16-positive and p16-negative patients in the induction chemotherapy group: while the rate was 100% in the p16-positive patients, it was only 51% in the p16-negative patients (p = 0.004). Of the patients undergoing chemoradio-therapy, 3 developed mandibular osteomyelitis, which was considered as one of the important problems associated with this therapy.

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  • Retrospective study of laryngeal preservation treatment for hypopharyngeal carcinoma with transoral resection or induction chemotherapy 査読

    Takahiro Asakage, Mizuo Ando, Masafumi Yoshida, Yuki Saito, Go Omura, Tatsuya Yamasoba

    Journal of Otolaryngology of Japan   118 ( 9 )   1118 - 1123   2015年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oto-Rhino-Laryngological Society of Japan Inc.  

    We have performed transoral surgical resection for patients with T1/T2 hypopharyngeal cancer and induction chemotherapy with docetaxel for patients with T2/T3 disease. The patients were analyzed in order to determine the current situation of larynx preservation in patients with hypopharyngeal cancer. The data of a total of 83 patients with hypopharyngeal cancer were analyzed retrospectively. The primary subsites were: pyriform sinus (PS) in 61 patients, posterior wall (PW) in 13 patients, and postcricoid (PC) in 9 patients. The number of patients classified as having T1, T2, T3 and T4 disease were 14, 29, 23 and 17, respectively. The main therapies employed in the patients were as follows: transoral surgical resection plus radiation therapy for Tl disease, radiation therapy, induction chemotherapy, and partial resection for T2 disease, induction chemotherapy, radiation therapy, and pharyngo-laryngoesophagectomy for T3 disease, and pharyngo-laryngoesophagectomy plus induction chemotherapy for T4 disease. The 5-year larynx preservation rates in the patients with T1, T2, T3 and T4 disease were 100%, 73%, 39% and 35%, respectively. Our method was able to improve the larynx preservation rate without having any adverse effect on the survival rate. However, the strength of treatment for T 3 disease needs to be improved, because a large number of recurrences and deaths due to the primary disease were encountered in this patient group.

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  • Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma 査読

    Yuki Saito, Masafumi Yoshida, Go Omura, Kenya Kobayashi, Chisato Fujimoto, Mizuo Ando, Takashi Sakamoto, Takahiro Asakage, Tatsuya Yamasoba

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   45 ( 9 )   828 - 836   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    In a previous study, we reported the value of p16 expression and alcohol consumption in oropharyngeal carcinoma in Japan. We now report the clinical significance of human papillomavirus status and p16 expression in oropharyngeal carcinoma in Japan.
    Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify tumor samples of oropharyngeal carcinoma. We performed immunohistochemistry for the p16 protein, in situ hybridization for human papillomavirus-deoxyribonucleic acid and polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 in oropharyngeal carcinoma in Japanese patients. We evaluated the human papillomavirus status in patients with oropharyngeal carcinoma to determine its prevalence and association with prognosis. We defined human papillomavirus(+) and human papillomavirus(-) oropharyngeal carcinoma cohorts as those with and without polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 or in situ hybridization-human papillomavirus.
    In oropharyngeal carcinoma, the prevalences of p16(+)human papillomavirus(+), p16(+)human papillomavirus(-), p16(-)human papillomavirus(+) and p16(-)human papillomavirus(-) were 32% (48/150), 7% (10/150), 2% (3/150) and 59% (89/150), respectively. Low tobacco and alcohol consumption, tonsil or base of tongue localization, but not age, were associated with p16(+)human papillomavirus(+). Low alcohol consumption was associated with p16(+)human papillomavirus(-). There was a significant difference in overall survival between p16(+)human papillomavirus(-) and p16(-)human papillomavirus(-) (P = 0.03). In multivariate Cox regression models, p16 was the independent prognostic factor, regardless of human papillomavirus status.
    p16 expression was a reliable prognostic biomarker regardless of human papillomavirus status.

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  • Nerve Growth Factor Signals as Possible Pathogenic Biomarkers for Perineural Invasion in Adenoid Cystic Carcinoma 査読

    Kenya Kobayashi, Mizuo Ando, Yuki Saito, Kenji Kondo, Go Omura, Aya Shinozaki-Ushiku, Masashi Fukayama, Takahiro Asakage, Tatsuya Yamasoba

    OTOLARYNGOLOGY-HEAD AND NECK SURGERY   153 ( 2 )   218 - 224   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE PUBLICATIONS LTD  

    Objective The molecular mechanisms underlying perineural invasion (PNI)a characteristic pathological feature of adenoid cystic carcinoma (ACC)remain largely unclear. Recently, nerve growth factor (NGF) has been implicated in perineural invasion in certain malignancies. Overexpression of Myb related to the MYB-NFIB fusion gene in ACC has also been correlated with perineural invasion and survival. However, this concept is controversial. The aim of this study was to examine the expression of NGF together with its receptors, tropomyosin receptor kinase A (TrkA) and p75NRT, and Myb in ACC and assess their relationship with perineural invasion and survival.
    Study Design Case series with chart review.
    Setting The University of Tokyo Hospital.
    Subjects and Methods We retrospectively analyzed 37 patients with ACC surgically treated from 1991 to 2011. We examined expression levels of NGF, TrkA, p75NRT, and Myb in the ACC specimens and their correlations with PNI and prognosis.
    Results NGF, TrkA, p75NRT, and Myb overexpression rates were 65%, 65%, 30%, and 62%, respectively. Pearson product-moment correlation coefficient revealed a strong correlation between NGF/TrkA immunostaining and PNI (NGF: r = 0.68, P &lt; .0001; TrkA: r = 0.53, P = .0007). Moreover, NGF overexpression was significantly associated with worse 8-year local control rate (27% vs 80%, P = .005). However, p75NRT and Myb expression was related to neither perineural invasion nor survival.
    Conclusion Our findings demonstrated that NGF and TrkA overexpression, but not Myb and p75NRT overexpression, may contribute to PNI and thus cause local recurrence in patients with ACC.

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  • Disease control and clinicopathological prognostic factors of total pharyngolaryngectomy for hypopharyngeal cancer: a single-center study 査読

    Go Omura, Mizuo Ando, Yuki Saito, Kenya Kobayashi, Tatsuya Yamasoba, Takahiro Asakage

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   20 ( 2 )   290 - 297   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Total pharyngolaryngectomy (TPL) is a conventional and standard surgical method for locoregional control of advanced hypopharyngeal cancer (HPC). This study aimed to define the clinicopathological prognostic factors of TPL by evaluating our surgical experience of TPL in the treatment of HPCs.
    We retrospectively reviewed the clinical charts of patients with HPC who were treated between 1995 and 2011 at the University of Tokyo Hospital and enrolled 119 patients who underwent TPL as an initial curative treatment.
    The mean follow-up period was 46 months (range, 2-164 months). The 5-year overall survival (OS), disease-specific survival (DSS), locoregional control rates, and relapse-free survival for all patients were 44, 53, 76, and 50 %, respectively. In multivariate analysis, the number of a parts per thousand yen4 metastatic lymph nodes (LNs) was a significant poor prognostic factor for both OS and DSS (p = 0.03 and p = 0.01). Patients with moderate to severe comorbidities had poor prognoses for OS (p = 0.002). In addition, patients with the number of a parts per thousand yen4 metastatic LNs had a higher incidence of distant metastases (p &lt; 0.0001).
    The locoregional control rate following TPL was acceptable and the number of metastatic LNs was associated with the incidence of distant metastases.

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  • Frequent copy gain of the MET gene in hypopharyngeal and laryngeal cancer in Japanese population. 査読

    Journal of Cancer Therapy   ( 6 )   1093 - 1102   2015年

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  • Salvage Surgery for Local Residual or Recurrent Pharyngeal Cancer After Radiotherapy or Chemoradiotherapy 査読

    Go Omura, Yuki Saito, Mizuo Ando, Kenya Kobayashi, Yasuhiro Ebihara, Tatsuya Yamasoba, Takahiro Asakage

    LARYNGOSCOPE   124 ( 9 )   2075 - 2080   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Objectives/Hypothesis: Local residual or recurrent pharyngeal cancer after definitive radiotherapy (RT) or chemoradiotherapy (CRT) is correlated to poor prognosis. We analyzed the efficacy of salvage surgery for patients with local residual or recurrent pharyngeal cancer after RT or CRT.
    Study Design: Retrospective clinical study with chart review.
    Methods: Between 2001 and 2011, we treated 207 patients with resectable pharyngeal cancer, including 98 patients with oropharyngeal cancer (OPC) and 109 patients with hypopharyngeal cancer (HPC) who received definitive RT or CRT. Local residual or recurrence developed in 59 patients (23 with OPC; 36 with HPC), of whom 42 (18 with OPC; 24 with HPC) underwent salvage surgery. These 42 patients were investigated in this study.
    Results: The initial treatments were RT; RT with induction chemotherapy (IC); and concurrent CRT in 12, 9, and 21 patients, respectively. The median radiation dose was 70 Gy. The 3-year disease-specific survival rate after salvage surgery was 40% (median, 26 months). The significant prognostic factors were stage IV prior to initial therapy (P=.049), development of concurrent local and regional relapse (P=.02), and OPC (P=.04).
    Conclusions: The efficacy of salvage surgery for local residual or recurrent pharyngeal cancer was limited. Oropharynx origin, stage IV prior to initial therapy, and concurrent regional relapses were significantly poor prognostic factors. Salvage surgery for HPC is worth challenging aggressively. Conversely, the indication of salvage surgery for OPCs should be carefully considered because of its low cure rate.

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  • Negative Human Papillomavirus Status and Excessive Alcohol Consumption are Significant Risk Factors for Second Primary Malignancies in Japanese Patients with Oropharyngeal Carcinoma 査読

    Yuki Saito, Yasuhiro Ebihara, Tetsuo Ushiku, Go Omura, Kenya Kobayashi, Mizuo Ando, Takashi Sakamoto, Masashi Fukayama, Tatsuya Yamasoba, Takahiro Asakage

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   44 ( 6 )   564 - 569   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    To determine the clinical significance of human papillomavirus subclinical infection in patients with oropharyngeal squamous cell carcinoma in Japan.
    Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify samples of oropharyngeal squamous cell carcinoma. We performed in situ hybridization for human papillomavirus-DNA to identify subclinical human papillomavirus infections among patients with oropharyngeal squamous cell carcinoma. Second primary malignancies were classified as synchronous, if identified within 6 months of the diagnosis of the first tumor, or metachronous, if identified after this 6-month period. Univariate and multivariate analyses using logistic stepwise regression models were performed to identify factors associated with synchronous and metachronous second primary malignancy.
    Of the 150 patients with oropharyngeal squamous cell carcinoma, 14% (21/150) and 20.7% (31/150) developed synchronous and metachronous second primary malignancies, respectively. Esophageal carcinoma was the most frequent second primary malignancy (10/21 for synchronous and 10/31 for metachronous second primary malignancies). The prevalence of oropharyngeal squamous cell carcinoma positive for human papillomavirus was 31% (47/150). Multivariate analysis identified alcohol consumption as a significant unfavorable risk factor for the occurrence of synchronous second primary malignancy, and either a human papillomavirus-negative status or N0 classification was a significant unfavorable risk factor for the occurrence of metachronous second primary malignancy.
    Evaluation of the human papillomavirus status may help identify patients at risk for metachronous second primary malignancy. Upper gastrointestinal endoscopy is very important in the diagnosis of oropharyngeal squamous cell carcinoma among heavy drinkers in Japan.

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  • Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation 査読

    T. Yasuda, T. Ueno, K. Fukumura, A. Yamato, M. Ando, H. Yamaguchi, M. Soda, M. Kawazu, E. Sai, Y. Yamashita, M. Murata, H. Kiyoi, T. Naoe, H. Mano

    LEUKEMIA   28 ( 2 )   426 - 428   2014年2月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

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  • Clinical Features of Human Papilloma Virus-Related Head and Neck Squamous Cell Carcinoma of an Unknown Primary Site 査読

    Kenya Kobayashi, Yuki Saito, Go Omura, Mizuo Ando, Takashi Sakamoto, Tatsuya Yamasoba, Takahiro Asakage

    ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY HEAD AND NECK SURGERY   76 ( 3 )   137 - 146   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Purpose: Head and neck squamous cell carcinoma of an unknown primary site (HNSCCUP) is a heterogeneous group of tumors that includes the human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. To investigate the relationship between HNSCCUP and HPV, we reviewed p16 overexpression and HPV DNA in lymph node metastases and examined their correlation with the primary site and clinical features. Materials and Methods: Thirty-three patients with HNSCCUP were retrospectively studied. Dissected neck metastases were analyzed for p16 overexpression by immunohistochemistry, and the presence of HPV DNA was investigated by in situ hybridization. Results: Of the 33 patients, 8 (24%) exhibited p16 overexpression. p16-positive lymph node metastases contained significantly more HPV DNA and were most frequently associated with occult primary lesions in the oropharynx and a favorable prognosis. Patients with a lower alcohol consumption, only level II/III metastasis, and cystic lymph node metastasis tended to have p16 overexpression. Conclusions: This is the first report on the relationship of HNSCCUP with p16 and HPV DNA status in Asian patients. In total, 24% of the HNSCCUP patients were p16 positive. p16 overexpression in neck metastasis was predictive of both an occult primary lesion in the oropharynx and an association with HPV infection. Alcohol consumption, location, and features of neck metastasis were correlated with p16 expression. (C) 2014 S. Karger AG, Basel

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  • High incidence of null-type mutations of the TP53 gene in Japanese patients with head and neck squamous cell carcinoma 査読

    Ebihara Y, Iwai M, Ito T, Omura G, Saito Y, Yoshida M, Ando M, Asakage T, Yamasoba T, Murakami Y

    Journal of Cancer Therapy   5   664 - 671   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • STK10 missense mutations associated with anti-apoptotic function 査読

    Kazutaka Fukumura, Yoshihiro Yamashita, Masahito Kawazu, Eirin Sai, Shin-Ichiro Fujiwara, Naoya Nakamura, Kengo Takeuchi, Mizuo Ando, Kohei Miyazono, Toshihide Ueno, Keiya Ozawa, Hiroyuki Mano

    Oncology Reports   30 ( 4 )   1542 - 1548   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:4  

    Peripheral T-cell lymphoma (PTCL) is an aggressive lymphoma with a 5-year overall survival rate of &lt
    30%. To identify carcinogenesis-related genes in PTCL, we conducted high-throughput resequencing of target-captured cDNA in a PTCL specimen, revealing a total of 19 missense mutations among 18 independent genes. One of such substitutions, c.2201G&gt
    A in STK10 cDNA, replaces an arginine residue to a histidine (R634H) in the encoded protein. Of note, while wild-type STK10 suppresses NF-κ
    B activity and potentiates dexamethasone-induced apoptosis, the R634H change significantly decreases such pro-apoptotic activity. This c.2201G&gt
    A change of STK10 was also identified in another PTCL specimen, but now registered as a single nucleotide polymorphism in the latest dbSNP database. Furthermore, other somatic mutations of STK10 have been reported, and we now reveal that some of them (L85P and K277E) have more profound anti-apoptotic effects compared to R634H. These results suggest that STK10 functions as a tumor suppressor gene, and that dysfunction of STK10 activity either through polymorphism or somatic mutations may confer anti-apoptotic effects contributing to carcinogenesis.

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  • Cancer-associated missense mutations of caspase-8 activate nuclear factor-kappa B signaling 査読

    Mizuo Ando, Masahito Kawazu, Toshihide Ueno, Kazutaka Fukumura, Azusa Yamato, Manabu Soda, Yoshihiro Yamashita, Young L. Choi, Tatsuya Yamasoba, Hiroyuki Mano

    CANCER SCIENCE   104 ( 8 )   1002 - 1008   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a 5-year survival rate of similar to 50%. With the use of a custom cDNA-capture system coupled with massively parallel sequencing, we have now investigated transforming mechanisms for this malignancy. The cDNAs of cancer-related genes (n = 906) were purified from a human HNSCC cell line (T3M-1 Cl-10) and subjected to high-throughput resequencing, and the clinical relevance of non-synonymous mutations thus identified was evaluated with luciferase-based reporter assays. A CASP8 (procaspase-8) cDNA with a novel G-to-C point mutation that results in the substitution of alanine for glycine at codon 325 was identified, and the mutant protein, CASP8 (G325A), was found to activate nuclear factor-kappa B (NF-kappa B) signaling to an extent far greater than that achieved with the wild-type protein. Moreover, forced expression of wild-type CASP8 suppressed the growth of T3M-1 Cl-10 cells without notable effects on apoptosis. We further found that most CASP8 mutations previously detected in various epithelial tumors also increase the ability of the protein to activate NF-kappa B signaling. Such NF-kappa B activation was shown to be mediated through the COOH-terminal region of the second death effector domain of CASP8. Although CASP8 mutations associated with cancer have been thought to promote tumorigenesis as a result of attenuation of the proapoptotic function of the protein, our results now show that most such mutations, including the novel G325A identified here, separately confer a gain of function with regard to activation of NF-kappa B signaling, indicating another role of CASP8 in the transformation of human malignancies including HNSCC.

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  • Cancer-associated missense mutations of caspase-8 activate nuclear factor-κB signaling. 査読

    Ando M, Kawazu M, Ueno T, Fukumura K, Yamato A, Soda M, Yamashita Y, Choi YL, Yamasoba T, Mano H

    Cancer science   104 ( 8 )   1002 - 1008   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:8  

    DOI: 10.1111/cas.12191

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  • Transforming mutations of RAC guanosine triphosphatases in human cancers 査読

    Masahito Kawazu, Toshihide Ueno, Kenji Kontani, Yoshitaka Ogita, Mizuo Ando, Kazutaka Fukumura, Azusa Yamato, Manabu Soda, Kengo Takeuchi, Yoshio Miki, Hiroyuki Yamaguchi, Takahiko Yasuda, Tomoki Naoe, Yoshihiro Yamashita, Toshiaki Katada, Young Lim Choi, Hiroyuki Mano

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   110 ( 8 )   3029 - 3034   2013年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL ACAD SCIENCES  

    Members of the RAS superfamily of small guanosine triphosphatases (GTPases) transition between GDP-bound, inactive and GTP-bound, active states and thereby function as binary switches in the regulation of various cellular activities. Whereas HRAS, NRAS, and KRAS frequently acquire transforming missense mutations in human cancer, little is known of the oncogenic roles of other small GTPases, including Ras-related C3 botulinum toxin substrate (RAC) proteins. We show that the human sarcoma cell line HT1080 harbors both NRAS(Q61K) and RAC1(N92I) mutant proteins. Whereas both of these mutants were able to transform fibroblasts, knockdown experiments indicated that RAC1(N92I) may be the essential growth driver for this cell line. Screening for RAC1, RAC2, or RAC3 mutations in cell lines and public databases identified several missense mutations for RAC1 and RAC2, with some of the mutant proteins, including RAC1(P29S), RAC1(C157Y), RAC2(P29L), and RAC2(P29Q), being found to be activated and transforming. P29S, N92I, and C157Y mutants of RAC1 were shown to exist preferentially in the GTP-bound state as a result of a rapid transition from the GDP-bound state, rather than as a result of a reduced intrinsic GTPase activity. Activating mutations of RAC GTPases were thus found in a wide variety of human cancers at a low frequency; however, given their marked transforming ability, the mutant proteins are potential targets for the development of new therapeutic agents.

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  • Salvage surgery for recurrence of hypopharyngeal carcinoma after definitive radiotherapy or chemoradio-therapy 査読

    Go Omura, Yuki Saito, Masahumi Yoshida, Mizuo Ando, Yasuhiro Ebihara, Takahiro Asakage

    Japanese Journal of Head and Neck Cancer   39 ( 1 )   55 - 59   2013年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Society for Head and Neck Cancer  

    The aim of this study was to analyze the efficacy of salvage surgery for patients with recurrent hypopharyngeal carcinoma after definitive radiotherapy (RT) or chemoradiotherapy (CRT). From April 2001 to August 2010, 101 patients with hypopharyngeal carcinoma underwent definitive RT or CRT at the University of Tokyo Hospital. Local recurrence developed in 35 patients (35%), of whom 24 patients underwent salvage surgery. The types of surgical procedures were as follows: total pharyngolaryngectomy: 20, partial pharyngectomy: 3, and endoscopic pharyngo-laryngo surgery (ELPS): 1. Three-year overall survival after salvage surgery was 60%. The median survival period was 38 months. Among these patients, postoperative complications occurred in 11 patients (46%). Salvage surgery for recurrent hypopharyngeal carcinoma after definitive RT or CRT is effective for not only for the patients' quality of life, but also for the improvement of prognosis.

    DOI: 10.5981/jjhnc.39.55

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  • Oncogenic MAP2K1 mutations in human epithelial tumors 査読

    Young Lim Choi, Manabu Soda, Toshihide Ueno, Toru Hamada, Hidenori Haruta, Azusa Yamato, Kazutaka Fukumura, Mizuo Ando, Masahito Kawazu, Yoshihiro Yamashita, Hiroyuki Mano

    CARCINOGENESIS   33 ( 5 )   956 - 961   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    The scirrhous subtype of gastric cancer is a highly infiltrative tumor with a poor outcome. To identify a transforming gene in this intractable disorder, we constructed a retroviral complementary DNA (cDNA) expression library from a cell line (OCUM-1) of scirrhous gastric cancer. A focus formation assay with the library and mouse 3T3 fibroblasts led to the discovery of a transforming cDNA, encoding for MAP2K1 with a glutamine-to-proline substitution at amino acid position 56. Interestingly, treatment with a MAP2K1-specific inhibitor clearly induced cell death of OCUM-1 but not of other two cells lines of scirrhous gastric cancer that do not carry MAP2K1 mutations, revealing the essential role of MAP2K1(Q56P) in the transformation mechanism of OCUM-1 cells. By using a next-generation sequencer, we further conducted deep sequencing of the MAP2K1 cDNA among 171 human cancer specimens or cell lines, resulting in the identification of one known (D67N) and four novel (R47Q, R49L, I204T and P306H) mutations within MAP2K1. The latter four changes were further shown to confer transforming potential to MAP2K1. In our experiments, a total of six (3.5%) activating mutations in MAP2K1 were thus identified among 172 of specimens or cell lines for human epithelial tumors. Given the addiction of cancer cells to the elevated MAP2K1 activity for proliferation, human cancers with such MAP2K1 mutations are suitable targets for the treatment with MAP2K1 inhibitors.

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  • High-throughput resequencing of target-captured cDNA in cancer cells 査読

    Toshihide Ueno, Yoshihiro Yamashita, Manabu Soda, Kazutaka Fukumura, Mizuo Ando, Azusa Yamato, Masahito Kawazu, Young Lim Choi, Hiroyuki Mano

    CANCER SCIENCE   103 ( 1 )   131 - 135   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    The recent advent of whole exon (exome)-capture technology, coupled with second-generation sequencers, has made it possible to readily detect genomic alterations that affect encoded proteins in cancer cells. Such target resequencing of the cancer genome, however, fails to detect most clinically-relevant gene fusions, given that such oncogenic fusion genes are often generated through intron-to-intron ligation. To develop a resequencing platform that simultaneously captures point mutations, insertions-deletions (indels), and gene fusions in the cancer genome, we chose cDNA as the input for target capture and extensive resequencing, and we describe the versatility of such a cDNA-capture system. As a test case, we constructed a custom target-capture system for 913 cancer-related genes, and we purified cDNA fragments for the target gene set from five cell lines of CML. Our target gene set included Abelson murine leukemia viral oncogene homolog 1 (ABL1), but it did not include breakpoint cluster region (BCR); however, the sequence output faithfully detected reads spanning the fusion points of these two genes in all cell lines, confirming the ability of cDNA capture to detect gene fusions. Furthermore, computational analysis of the sequence dataset successfully identified non-synonymous mutations and indels, including those of tumor protein p53 (TP53). Our data might thus support the feasibility of a cDNA-capture system coupled with massively parallel sequencing as a simple platform for the detection of a variety of anomalies in protein-coding genes among hundreds of cancer specimens. (Cancer Sci 2012; 103: 131-135)

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  • High-throughput resequencing of target-captured cDNA in cancer cells 査読

    Toshihide Ueno, Yoshihiro Yamashita, Manabu Soda, Kazutaka Fukumura, Mizuo Ando, Azusa Yamato, Masahito Kawazu, Young Lim Choi, Hiroyuki Mano

    Cancer Science   103 ( 1 )   131 - 135   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:1  

    The recent advent of whole exon (exome)-capture technology, coupled with second-generation sequencers, has made it possible to readily detect genomic alterations that affect encoded proteins in cancer cells. Such target resequencing of the cancer genome, however, fails to detect most clinically-relevant gene fusions, given that such oncogenic fusion genes are often generated through intron-to-intron ligation. To develop a resequencing platform that simultaneously captures point mutations, insertions-deletions (indels), and gene fusions in the cancer genome, we chose cDNA as the input for target capture and extensive resequencing, and we describe the versatility of such a cDNA-capture system. As a test case, we constructed a custom target-capture system for 913 cancer-related genes, and we purified cDNA fragments for the target gene set from five cell lines of CML. Our target gene set included Abelson murine leukemia viral oncogene homolog 1 (ABL1), but it did not include breakpoint cluster region (BCR)
    however, the sequence output faithfully detected reads spanning the fusion points of these two genes in all cell lines, confirming the ability of cDNA capture to detect gene fusions. Furthermore, computational analysis of the sequence dataset successfully identified non-synonymous mutations and indels, including those of tumor protein p53 (TP53). Our data might thus support the feasibility of a cDNA-capture system coupled with massively parallel sequencing as a simple platform for the detection of a variety of anomalies in protein-coding genes among hundreds of cancer specimens. © 2011 Japanese Cancer Association.

    DOI: 10.1111/j.1349-7006.2011.02105.x

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  • Genetic analysis of the TP53 and EGFR genes in head and neck cancers 査読

    Yasuhiro Ebihara, Miwako Iwai, Masafumi Yoshida, Mizuo Ando, Takahiro Asakage, Tatsuya Yamasoba, Yoshinori Murakami

    Japanese Journal of Head and Neck Cancer   37 ( 1 )   1 - 6   2011年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    To identify useful molecular markers for the treatment of head and neck cancers (HNCs), mutations of the TP53 and EGFR genes were analyzed in 56 HNCs, including 39 head and neck squamous cell carcinomas (HNSCCs). No EGFR mutation was observed in the fragments of exons 18-21. By contrast, 17 of 39 (44%) HNSCCs, as well as 3 of 6 cases (50%) with salivary gland carcinoma showed TP53 mutation in the fragments of exons 5-9. The incidence of nonsense mutation was 47%, which was higher than that in previous reports in other countries, suggesting the presence of etiological factors characteristic to Japanese patients. Further clinical assessment, including drug response and prognosis, is required in HNSCCs carrying the null-type mutation of TP53.

    DOI: 10.5981/jjhnc.37.1

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  • Metastases to the lingual nodes in tongue cancer: A pitfall in a conventional neck dissection 査読

    Mizuo Ando, Masao Asai, Takayuki Ono, Yukihiro Nakanishi, Takahiro Asakage, Tatsuya Yamasoba

    AURIS NASUS LARYNX   37 ( 3 )   386 - 389   2010年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Some classical textbooks of anatomy provided a detailed description of the lingual nodes, which are small inconstant lymph nodes in the floor-of-mouth and the upper neck. The clinical importance of these lymph nodes in cancer therapy. however, has been underestimated so far. We previously reported an extremely poor prognosis of oral tongue cancer patients who had lesions at the root of the lingual artery and assumed that metastases in occult lingual nodes might be responsible for such lesions. This case report clearly demonstrates the distinctive draining course of the lateral lingual nodes, which may potentially be left untreated by a neck dissection. A 63-year-old Japanese male with T2 squamous cell carcinoma of the oral tongue showed multiple metastatic involvements of the lateral lingual nodes; three nodes in close contact with the sublingual gland, and one node at the root of the lingual artery. A systematic inspection of lymph nodes along the draining course of the lateral lingual nodes should be included, because a neck dissection in continuity with the primary tumor (a pull-through approach) is still inadequate for the removal of the lymph nodes at the root of the lingual artery. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.anl.2009.10.001

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  • A clinical study of glottic carcinoma 査読

    Kazuki Miyano, Mizuo Ando, Masafumi Yoshida, Yasuhiro Ebihara, Takahiro Asakage, Atsuro Terahara, Kazuki Miyano

    Toukeibu Gan   36 ( 3 )   322 - 326   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A clinical study was made of 179 patients with previously untreated glottic carcinoma registered in our department between 1998 and 2004. In our facility, T1 glottic cancer was treated by radiotherapy, T2 glottic cancer by radiotherapy or chemoradiotherapy using low-dose CDDP, and T3 and T4 glottic cancer by laryngectomy. The five-year cause-specific survival rate for glottic carcinoma was 95.1%, 96.5% for stage I, 96.6% for stage II, 92.9% for stage III, and 68.6% for stage IV. The five-year local control rate for early glottic carcinoma treated by radiotherapy was 83.1% for T1a, 60.7% for T1b, and 62.5% for T2. In T2 cases, the local control rate was 49.2% for treatment by radiotherapy, and 83.6% for low-dose CDDP with radiotherapy. Low-dose CDDP with radiotherapy contributes to high local control rate in T2 cases. © 2010, Japan Society for Head and Neck Cancer. All rights reserved.

    DOI: 10.5981/jjhnc.36.322

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  • Metastatic Neck Disease Beyond the Limits of a Neck Dissection: Attention to the &apos;Para-hyoid&apos; Area in T1/2 Oral Tongue Cancer 査読

    Mizuo Ando, Masao Asai, Takahiro Asakage, Waichiro Oyama, Masahisa Saikawa, Mitsuo Yamazaki, Masakazu Miyazaki, Toru Ugumori, Hiroyuki Daiko, Ryuichi Hayashi

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   39 ( 4 )   231 - 236   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    We evaluated patients with small oral tongue cancer suffering from recurrence, which develops in the intervening area between the primary site and the neck. Lesions in the area around the cornu of the hyoid bone (&apos;para-hyoid&apos; area) often involve the hypoglossal nerve and the root of the lingual artery, resulting in treatment failure and death.
    A 10-year retrospective chart review was conducted of 248 oral tongue cancer patients with small primary tumors (T1/2). No patients who underwent postoperative radiotherapy (PORT) were included.
    After excluding those who had local failure or developed new primary lesions, 6.3% of the patients were noted to have a para-hyoid lesion. A similar incidence was observed between the patients with and without previous neck dissection, 6.9% and 5.7%, respectively. All but one patient died due to uncontrolled neck disease.
    Recurrent para-hyoid lesions could occur, irrespective of a previous neck dissection. In other words, the para-hyoid area is beyond the limits of a neck dissection. Once a para-hyoid lesion becomes clinically evident, it seems difficult to salvage. Therefore, a careful inspection of the area should be included intraoperatively in any type of neck dissection (i.e. elective or therapeutic) for patients with oral tongue cancer. This may be the key to improving the regional control rate of patients with small oral tongue cancer. We believe that some patients will benefit from more aggressive treatment of the neck, although PORT seems unnecessary for the majority of the patients with limited neck disease.

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  • Recurrent Cancer of the Parotid Gland: How Well Does Salvage Surgery Work for Locoregional Failure? 査読

    Kenya Kobayashi, Kazunari Nakao, Masafumi Yoshida, Mizuo Ando, Yasuhiro Ebihara, Takahiro Asakage, Tatsuya Yamasoba

    ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES   71 ( 5 )   239 - 243   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Purpose: Many articles have discussed the clinical features of previously untreated parotid cancer, but the clinical characteristics and treatment of recurrent parotid cancer have not yet been fully described. Materials: We retrospectively reviewed 20 patients with recurrent parotid cancer and analyzed the therapeutic strategies and the prognostic factors. Results: Twelve patients (60%) underwent definitive surgery, including 3 who underwent skull base surgery. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) in the surgery group were 66.7 and 64.1%. In the definitive surgery group, the presence of lymph node metastasis and high-grade malignant histopathology were associated with a poor prognosis (p &lt; 0.01). On the other hand, the presence of facial palsy at presentation, the surgical margin, the time of relapse and the T stage did not affect the DFS in our series. Conclusions: The results suggest that aggressive definitive surgery may be justified for the treatment of recurrent parotid cancer. The presence of lymph node metastasis and the histopathological malignancy grade are poor prognostic factors for OS and DFS. Copyright (C) 2009 S. Karger AG, Basel

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  • Mucoepidermoid carcinoma of the thyroid gland showing marked ciliation suggestive of its pathogenesis 査読

    Mizuo Ando, Yukihiro Nakanishi, Masao Asai, Akiko Maeshima, Yoshihiro Matsuno

    PATHOLOGY INTERNATIONAL   58 ( 11 )   741 - 744   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Mucoepidermoid carcinoma of the thyroid gland is a rare tumor first described by Rhatigan et al. in 1977. Its pathogenesis is still controversial. With regard to its most likely origin, some authors have suggested that it arises directly from follicular epithelium whereas others have proposed that it arises from ultimobranchial body (diverticulum from the fourth pharyngeal pouch) remnants, also known as solid cell nests (SCN). Herein is reported a unique case of thyroid mucoepidermoid carcinoma. The patient, a 67-year-old man, presented with a non-tender thyroid mass and vocal cord fixation. The tumor was poorly defined, necessitating subtotal thyroidectomy with composite resection of the adjacent structures. Pathologically, the tumor cells had characteristics of mucoepidermoid carcinoma, along with layers of columnar cells showing marked ciliation resembling respiratory-type epithelium, suggesting that this rare tumor had originated from SCN. p63 immunopositivity in the tumor provided additional evidence for the pathogenesis.

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  • Clinical analysis of lateral wall oropharyngeal carcinoma - A retrospective study of 32 cases 査読

    Yasuhiro Ebihara, Masafumi Yoshida, Mizuo Ando, Kazunari Nakao, Takahiro Asakage, Atsurou Terahara, Isao Koushima

    Toukeibu Gan   34 ( 4 )   526 - 529   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We analyzed 32 cases of lateral wall oropharyngeal carcinoma treated at our institution retrospectively. Five-year overall and disease-specific survival rates were 50% and 62%, respectively. The 5-year locoregional control rate was 57%, and including salvage therapy it was improved up to 62%. It was difficult to control locoregional tumor with surgery in far-advanced cases where the tumor had invaded the nasopharynx or larynx. There is a possibility of salvage if the recurrence is solitary, but a case with multiple recurrence is difficult to salvage. © 2008, Japan Society for Head and Neck Cancer. All rights reserved.

    DOI: 10.5981/jjhnc.34.526

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  • Mucosa-associated lymphoid tissue lymphoma presented as diffuse swelling of the parotid gland 査読

    M Ando, M Matsuzaki, T Murofushi

    AMERICAN JOURNAL OF OTOLARYNGOLOGY   26 ( 4 )   285 - 288   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO  

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct subtype of lymphoma. Parotid MALT lymphoma is a rare tumor that is hard to diagnose by fine-needle aspiration cytology. Therefore, partial parotidectomy is often required for a pathological diagnosis. We report a case of MALT lymphoma presented as unilateral diffuse swelling of the parotid gland, who was diagnosed by partial parotidectomy and underwent radiotherapy. (c) 2005 Elsevier Inc. All rights reserved.

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MISC

  • 唾液腺導管癌における脂質関連蛋白発現の臨床病理学的意義

    平井 秀明, 多田 雄一郎, 中黒 匡人, 川北 大介, 佐藤 由紀子, 志村 智隆, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 伏見 千宙, 清水 顕, 高瀬 総一郎, 岡田 拓朗, 佐藤 宏樹, 今西 順久, 大塚 邦憲, 渡部 佳弘, 酒井 昭博, 戎本 浩史, 富樫 孝文, 植木 雄志, 太田 久幸, 三枝 奈津季, 高橋 秀聡, 安藤 瑞生, 浦野 誠, 花澤 豊行, 長尾 俊孝

    日本唾液腺学会誌   60   24 - 25   2019年11月

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    記述言語:日本語   出版者・発行元:日本唾液腺学会  

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  • 唾液腺導管癌における脂質関連蛋白発現の臨床病理学的意義 査読

    平井 秀明, 多田 雄一郎, 中黒 匡人, 川北 大介, 佐藤 由紀子, 志村 智隆, 塚原 清彰, 加納 里志, 小澤 宏之, 大上 研二, 佐藤 雄一郎, 伏見 千宙, 清水 顕, 高瀬 総一郎, 岡田 拓朗, 佐藤 宏樹, 今西 順久, 大塚 邦憲, 渡部 佳弘, 酒井 昭博, 戎本 浩史, 富樫 孝文, 植木 雄志, 太田 久幸, 三枝 奈津季, 高橋 秀聡, 安藤 瑞生, 浦野 誠, 花澤 豊行, 長尾 俊孝

    日本唾液腺学会誌   60   24 - 25   2019年11月

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    記述言語:日本語   出版者・発行元:日本唾液腺学会  

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  • 外耳道癌と耳かき頻度の相関性の検討

    石浦 良平, 飯田 拓也, 柿木 章伸, 安藤 瑞生, 吉田 昌史, 齊藤 祐毅, 山岨 達也, 光嶋 勲

    頭頸部癌   43 ( 1 )   76 - 78   2017年4月

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    記述言語:日本語   出版者・発行元:(一社)日本頭頸部癌学会  

    外耳道癌は稀かつ予後不良な疾患である。その危険因子として過剰な耳かきが臨床上推測されているが、統計学的に検討した報告は少ない。今回、我々は当科で加療を行った外耳道癌患者14例を対象とし年齢、性別、耳かき頻度、耳かきに使用する道具の材質、罹患側、病理組織について検討した。また、本研究に同意を得た健常人69名を対象とし、年齢、性別、耳かき頻度、耳かきに使用する道具の材質について調査し患者群と比較検討した。その結果、50歳未満の若年群における患者群と健常人群間において、有意に耳かき頻度、および硬質素材を用いる率が高かった。今回の結果から、過剰な刺激の耳かきが外耳道癌発生を誘発する可能性が示唆された。(著者抄録)

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  • 【頭頸部癌学-診断と治療の最新研究動向-】 頭頸部癌の疫学 頭頸部癌の危険因子 ウイルス、その他の危険因子

    安藤 瑞生

    日本臨床   75 ( 増刊2 頭頸部癌学 )   66 - 69   2017年2月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • 【中咽頭癌-HPVの視点からみた大きな変化】 治療 HPV陽性T3/4N(+)の治療方針は?

    安藤 瑞生

    JOHNS   32 ( 3 )   351 - 354   2016年3月

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

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  • 【耳鼻咽喉科診療におけるリスクマネージメント-患者トラブルを防ぐために】 セカンドオピニオンのリスクマネージメント

    安藤 瑞生

    JOHNS   31 ( 10 )   1451 - 1453   2015年10月

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

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  • 【よくわかる遺伝子】 遺伝子検査 次世代シーケンサーによる遺伝子検査

    安藤 瑞生

    JOHNS   30 ( 6 )   691 - 694   2014年6月

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

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  • 当院における中咽頭前壁癌に対する治療成績の検討

    吉田 昌史, 安藤 瑞生, 蝦原 康宏, 朝蔭 孝宏, 山岨 達也, 井垣 浩

    頭頸部癌   37 ( 2 )   209 - 209   2011年5月

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    記述言語:日本語   出版者・発行元:日本頭頸部癌学会  

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  • 当科における上咽頭癌放射線化学療法(IMRT+TPF)施行例に関する短期報告

    蝦原 康宏, 井垣 浩, 安藤 瑞生, 吉田 昌史, 朝蔭 孝宏

    頭頸部癌   37 ( 2 )   208 - 208   2011年5月

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    記述言語:日本語   出版者・発行元:日本頭頸部癌学会  

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  • 下咽頭・頸部食道癌の種々の切除様式に対する再建の治療戦略

    飯田 拓也, 三原 誠, 成島 三長, 荒木 淳, 大島 梓, 平井 林太郎, 光嶋 勲, 朝蔭 孝宏, 蝦原 康宏, 吉田 昌史, 安藤 瑞生, 瀬戸 泰之

    頭頸部癌   37 ( 1 )   121 - 125   2011年4月

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    記述言語:日本語   出版者・発行元:(一社)日本頭頸部癌学会  

    下咽頭・頸部食道癌は上部消化管の悪性腫瘍を合併することが多く、通常の咽頭喉頭頸部食道全摘では対応できず、全食道を合併切除する必要がある症例も存在する。一方で、根治性を損なわない範囲内で可及的に機能温存を図る手術の広がりに伴い、下咽頭部分切除が施行される症例も増えてきている。今回、われわれはこうした種々の下咽頭癌・頸部食道癌切除法に対応した再建法について検討した。対象は下咽頭・頸部食道癌の切除・再建術のうち、TPLEに加え食道全切除も必要であった拡大切除5例と、下咽頭部切などの縮小切除5例である。再建方法は拡大手術では、延長胃管、遊離空腸+胃管等で、縮小手術では遊離空腸パッチ、遊離前腕皮弁であった。各種の再建方法にはそれぞれ長所、短所があるが、再建法を決める際には耳鼻科や食道外科と切除・郭清範囲、温存される血管、侵襲の程度などについて事前に十分に打ち合わせ、総合的に検討する必要があると考えられた。(著者抄録)

    DOI: 10.5981/jjhnc.37.121

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  • 【ここまで変わった頸部郭清術】 特殊領域の頸部リンパ節郭清 適応と手技 舌骨傍領域リンパ節

    安藤 瑞生

    JOHNS   27 ( 2 )   209 - 214   2011年2月

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    記述言語:日本語   出版者・発行元:(株)東京医学社  

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  • 舌癌における「舌骨傍領域 (para-hyoid area)」の制御を目指して 査読

    安藤 瑞生, 浅井 昌大, 吉田 昌史, 蝦原 康宏, 中尾 一成, 朝蔭 孝宏, 山岨 達也

    頭頸部癌 = Head and neck cancer   36 ( 3 )   303 - 308   2010年

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    記述言語:英語   出版者・発行元:Japan Society for Head and Neck Cancer  

    われわれは,舌癌において制御困難な再発をきたし得る部位として「舌骨傍領域」に注目している。同領域は舌癌における原発巣と頸部の継ぎ目に位置し,口腔からのアプローチは困難で,かつ通常の頸部郭清術の郭清範囲外である。病巣は舌下神経の深部で舌動脈を巻き込むように出現し,やがて副咽頭間隙に広く進展して根治困難となりうる。このような再発は,舌動脈に沿って出現する小リンパ節への転移によるものであろうと考えている。臨床的に明らかな再発病巣として発見される時点では既に周囲へ浸潤していることが多く,治癒切除を施行するためには遊離皮弁が必要となる場合がある。病巣は可能な限り早期に発見されるべきだが,舌骨傍領域の画像診断には限界があるため,頸部郭清術を施行する際には必ず同領域の組織を摘出するようにしている。治療後の機能温存が強く求められる部位であるので,合併症のより少ない治療を選択すべきである。

    DOI: 10.5981/jjhnc.36.303

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  • Clinical inspection of metastasis to the mesenteric lymph nodes in patients with hypopharyngeal cancer after pharyngolaryngectomy with free jejunal graft-136 cases

    Sayaka Suzuki, Masato Mochiki, Kazunari Nakao, Takashi Sakamoto, Mizuo Ando, Masashi Sugasawa

    Journal of Otolaryngology of Japan   109 ( 1 )   19 - 23   2006年

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    記述言語:日本語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:Oto-Rhino-Laryngological Society of Japan Inc.  

    Single-stage reconstruction of the pharyngoesophagus with a free jejunal graft is considered standard surgical treatment for hypopharyngeal cancer. We reviewed postoperative cervical CTs in 72 of 136 consecutive patients (1982-2002) undergoing this therapy in our department. Of these, 29 (40%) showed mesenteric lymph node swelling (&gt
    10mm) in grafts. Most swelling is considered reactive, but 1 patient showed pathological metastasis in fine-needle aspiration cytology (FNA). When metastasis is clinically suspected in imaging study and other examinations, FNA should be done carefully with guided ultrasound echo-imaging, to avoid damaging vascular grafts and necrosis of the jejunal graft.

    DOI: 10.3950/jibiinkoka.109.19

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共同研究・競争的資金等の研究

  • 唾液腺導管癌の個別化治療へ向けた癌ゲノム解析研究

    2018年 - 2021年

    文部科学省  科学研究補助金(基盤研究C) 

    安藤瑞生

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    担当区分:研究代表者  資金種別:競争的資金

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  • 患者由来腫瘍異種移植片モデルを用いた腺様嚢胞癌の進展機序の解明

    2016年 - 2019年

    文部科学省  科学研究費補助金(国際共同研究強化) 

    安藤瑞生

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    担当区分:研究代表者  資金種別:競争的資金

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  • 患者由来腫瘍異種移植片モデルを用いた腺様嚢胞癌の進展機序の解明

    2015年 - 2018年

    文部科学省  科学研究費補助金(若手研究B) 

    安藤瑞生

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    担当区分:研究代表者  資金種別:競争的資金

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  • 頭頸部癌における癌関連遺伝子のターゲット変異解析と発癌メカニズム解明

    研究課題/領域番号:26893058  2014年 - 2015年

    文部科学省  科学研究費補助金(研究活動スタート支援)  研究活動スタート支援

    安藤 瑞生

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:1430000円 ( 直接経費:1100000円 、 間接経費:330000円 )

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  • 乳頭腫が癌肉腫へ悪性転化する発がん分子機構の解明

    2014年 - 2015年

    GSKジャパン  2014年度研究助成金 

    安藤瑞生

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    担当区分:研究代表者  資金種別:競争的資金

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担当授業科目

  • 感覚器系(臓器・系別統合講義) (2021年度) 特別  - その他

  • 病態機構学演習 (2021年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学I(演習・実習) (2021年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学I(講義・演習) (2021年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学II(演習・実習) (2021年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学II(講義・演習) (2021年度) 特別  - その他

  • 耳鼻咽喉科学(基本臨床実習) (2021年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学I(演習・実習) (2020年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学I(講義・演習) (2020年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学II(演習・実習) (2020年度) 特別  - その他

  • 耳鼻咽喉・頭頸部外科学II(講義・演習) (2020年度) 特別  - その他

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