Faculty Profiles - Ando Mizuo

Papers - Ando Mizuo

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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. Reviewed International journal

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 378 ( 2 ) 175 - 193 2019.6

Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers. Reviewed International journal

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 2019.5

4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer. Reviewed International journal

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 2019.4

Comprehensive assay for the molecular profiling of cancer by target enrichment from formalin-fixed paraffin-embedded specimens. Reviewed International journal

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 2019.4

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

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 26 ( 7 ) 2294 - 2303 2019.3

Discovery and development of differentially methylated regions in human papillomavirus-related oropharyngeal squamous cell carcinoma. Reviewed International journal

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 2018.11

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1002/ijc.31778

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Characterization of Alternative Splicing Events in HPV-Negative Head and Neck Squamous Cell Carcinoma Identifies an Oncogenic DOCK5 Variant. Reviewed International journal

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 2018.10

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1158/1078-0432.CCR-18-0752

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Postoperative mechanical bowel obstruction after pharyngolaryngectomy for hypopharyngeal cancer: Retrospective analysis using a Japanese inpatient database. Reviewed International journal

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

Head & neck 40 ( 7 ) 1548 - 1554 2018.7

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1002/hed.25139

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Radiotherapy alone and with concurrent chemotherapy for nasopharyngeal carcinoma Reviewed

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

Medicine (United States) 97 ( 18 ) e0502 2018.5

The NOTCH4-HEY1 Pathway Induces Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma. Reviewed International journal

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 2018.2

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1158/1078-0432.CCR-17-1366

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Prognostic and histogenetic roles of gene alteration and the expression of key potentially actionable targets in salivary duct carcinomas. Reviewed International journal

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 2018.1

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.18632/oncotarget.22927

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The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma Reviewed

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 2017.12

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

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 2017.12

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

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

SCIENTIFIC REPORTS 7 ( 1 ) 17805 2017.12

Current status of superficial pharyngeal squamous cell carcinoma in Japan Reviewed

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

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 22 ( 5 ) 826 - 833 2017.10

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

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 2017.8

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

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

INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY 7 ( 7 ) 670 - 678 2017.7

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

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 2017.6

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

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

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

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 2016.8

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Papers - Ando Mizuo