|Koshi Mimori||Last modified date：2022.08.15|
Professor / Kyushu University Hospital
Unauthorized reprint of the contents of this database is prohibited.
|Koshi Mimori||Last modified date：2022.08.15|
|1.||Ueo H, Minoura I, Ueo H, Gamachi A, Kai Y, Kubota Y, Doi T, Yamaguchi M, Yamashita T, Tsuda H, Moriya T, Yamaguchi R, Kozuka Y, Sasaki T, Masuda T, Urano Y, Mori M, Mimori K.
, Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements.
, Sci Rep., doi: 10.1038/s41598-022-12614-6., 12, (1), 8520-8520, 2022.05.
|2.||Shimizu D, Taniue K, Matsui Y, Haeno H, Araki H, Miura F, Fukunaga M, Shiraishi K, Miyamoto Y, Tsukamoto S, Komine A, Kobayashi Y, Kitagawa A, Yoshikawa Y, Sato K, Saito T, Ito S, Masuda T, Niida A, Suzuki M, Baba H, Ito T, Akimitsu N, Kodera Y, Mimori K.
, Pan-cancer methylome analysis for cancer diagnosis and classification of cancer cell of origin.
, Cancer Gene Ther. , doi: 10.1038/s41417-021-00401-w., 29, (5), 428-436, 2022.05.
|3.||Masuda T, Mimori K., Artificial intelligence-assisted drug repurposing via "chemical-induced gene expression ranking".
, Patterns (N Y), doi: 10.1016/j.patter.2022.100470., 3, (4), 100470-100470, 2022.04.
|4.||Wang D, Sun L, Okuda S, Yamamoto D, Nakayama M, Oshima H, Saito H, Kouyama Y, Mimori K, Ando T, Watanabe S, Oshima M.
, Nano-scale physical properties characteristic to metastatic intestinal cancer cells identified by high-speed
scanning ion conductance microscope.
, Biomaterials., doi: 10.1016/j.biomaterials.2021.121256. , Epub , Epub , Epub -Epub , 2022.01.
|5.||Takahashi J, Masuda T, Kitagawa A, Tobo T, Nakano Y, Abe T, Ando Y, Kosai K, Kobayashi Y, Matsumoto Y, Yoshizumi T, Mori M, Mimori K.
, Fanconi Anemia Complementation Group E, a DNA Repair-Related Gene, Is a Potential Marker of Poor Prognosis in Hepatocellular Carcinoma.
, Oncology. , doi: 10.1159/000520582. , 100, (2), 101-113, 2022.01.
|6.||Koike K, Masuda T, Sato K, Fujii A, Wakiyama H, Tobo T, Takahashi J, Motomura Y, Nakano T, Saito H, Matsumoto Y, Otsu H, Takeishi K, Yonemura Y, Mimori K, Nakagawa T.
, GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein.
, Cancer Sci., doi: 10.1111/cas.15174., 113, (1), 156-169, 2022.01.
|7.||Sakano Y, Noda T, Kobayashi S, Kitagawa A, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Gotoh K, Asaoka T, Tanemura M, Umeshita K, Mimori K, Doki Y, Eguchi H.
, Clinical Significance of Acylphosphatase 1 Expression in Combined HCC-iCCA, HCC, and iCCA.
, Dig Dis Sci., doi: 10.1007/s10620-021-07266-x., Epub, Epub, Epub-Epub, 2021.10.
|8.||Hirata H, Niida A, Kakiuchi N, Uchi R, Sugimachi K, Masuda T, Saito T, Kageyama SI, Motomura Y, Ito S, Yoshitake T, Tsurumaru D, Nishimuta Y, Yokoyama A, Hasegawa T, Chiba K, Shiraishi Y, Du J, Miura F, Morita M, Toh Y, Hirakawa M, Shioyama Y, Ito T, Akimoto T, Miyano S, Shibata T, Mori M, Suzuki Y, Ogawa S, Ishigami K, Mimori K.
, The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy.
, Cancer Res., doi: 10.1158/0008-5472.CAN-21-0653. , 81, (19), 4926-4938, 2022.07.
|9.||Fukunaga M, Mimori K, Masuda T, Hu Q, Yamada K, Mori M., Postoperative elevation in the plasma CCL2 level is a predictive biomarker of colorectal cancer recurrence.
, Surg Today. , doi: 10.1007/s00595-021-02273-x. , 51, (10), 1671-1681, 2021.10.
|10.||Hu Q, Masuda T, Koike K, Sato K, Tobo T, Kuramitsu S, Kitagawa A, Fujii A, Noda M, Tsuruda Y, Otsu H, Kuroda Y, Ito S, Oki E, Mimori K.
, Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer.
, Sci Rep., doi: 10.1038/s41598-021-98485-9., 11, (1), 19178-19178, 2021.09.
|11.||Takao S, Ushijima Y, Motomura Y, Sakamoto K, Hirakawa M, Nishie A, Mimori K, Yamashita Y, Tsutsumi T, Ishigami K.
, Radiology- and gene-based risk stratification in small renal cell carcinoma: A preliminary study.
, PLoS One., doi: 10.1371/journal.pone.0256471. , 16, (9), e0256471-e0256471, 2021.09.
|12.||Ono H, Arai Y, Furukawa E, Narushima D, Matsuura T, Nakamura H, Shiokawa D, Nagai M, Imai T, Mimori K, Okamoto K, Hippo Y, Shibata T, Kato M.
, Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.
, BMC Biol., doi: 10.1186/s12915-021-01147-5. , 19, (1), 207-207, 2021.09.
|13.||Kuramitsu S, Masuda T, Hu Q, Tobo T, Yashiro M, Fujii A, Kitagawa A, Abe T, Otsu H, Ito S, Oki E, Mori M, Mimori K.
, Cancer-associated Fibroblast-derived Spondin-2 Promotes Motility of Gastric Cancer Cells.
, Cancer Genomics Proteomics., doi: 10.21873/cgp.20277. , 18, (4), 521-529, 2021.07.
|14.||Sakimura S, Nagayama S, Fukunaga M, Hu Q, Kitagawa A, Kobayashi Y, Hasegawa T, Noda M, Kouyama Y, Shimizu D, Saito T, Niida A, Tsuruda Y, Otsu H, Matsumoto Y, Uchida H, Masuda T, Sugimachi K, Sasaki S, Yamada K, Takahashi K, Innan H, Suzuki Y, Nakamura H, Totoki Y, Mizuno S, Ohshima M, Shibata T, Mimori K.
, Impaired tumor immune response in metastatic tumors is a selective pressure for neutral evolution in CRC cases
, PLoS Genet. , doi: 10.1371/journal.pgen., 17, (1), e1009113.-e1009113., 2021.01.
|15.||Masuda T, Niizeki O, Niizeki T, Fujiyoshi K, Ando Y, Niizeki H, Mimori K., Successful Treatment with Hepatic Arterial Infusion Chemotherapy in a Breast Cancer Patient with Multiple Liver Metastases Who Declined Systemic Therapy.
, Case Rep Oncol. , doi: 10.1159/000517854., 14, (3), 1261-1265, 2021.09.
|16.||Sunami K, Bando H, Yatabe Y, Naito Y, Takahashi H, Tsuchihara K, Toyooka S,Mimori K, Kohsaka S, Uetake H, Kinoshita I, Komine K, Takeda M, Hayashida T,
Tamura K, Nishio K, Yamamoto N; Working Group of a Joint Task Force of Three Academic Societies for the Promotion of Cancer Genomic Medicine.
, Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA.
, Cancer Sci., doi: 10.1111/cas.15022. , 112, (9), 3911-3917, 2021.09.
|17.||Kobayashi Y, Masuda T, Fujii A, Shimizu D, Sato K, Kitagawa A, Tobo T, Ozato Y, Saito H, Kuramitsu S, Noda M, Otsu H, Mizushima T, Doki Y, Eguchi H, Mori M, Mimori K., Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer., Cancer Sci, 10.1111/cas.14969., 2021.05.|
|18.||Hu Q, Nonaka K, Wakiyama H, Miyashita Y, Fujimoto Y, Jogo T, Hokonohara K, Nakanishi R, Hisamatsu Y, Ando K, Kimura Y, Masuda T, Oki E, Mimori K, Oda Y, Mori M., Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer., Cancer Med, 10.1002/cam4.3828. , 10, 9, 3129-3138, 2021.05.|
|19.||Fujii A, Masuda T, Iwata M, Tobo T, Wakiyama H, Koike K, Kosai K, Nakano T, Kuramitsu S, Kitagawa A, Sato K, Kouyama Y, Shimizu D, Matsumoto Y, Utsunomiya T, Ohtsuka T, Yamanishi Y, Nakamura M, Mimori K. , The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer. , Cancer Sci, 10.1111/cas.14858., 112, 4, 1655-1668, 2021.04.|
|20.||Fukunaga M, Mimori K, Masuda T, Hu Q, Yamada K, Mori M., Postoperative elevation in the plasma CCL2 level is a predictive biomarker of colorectal cancer recurrence., Surg Today, 10.1007/s00595-021-02273-x. , 2021.04.|
|21.||Sakimura S, Nagayama S, Fukunaga M, Hu Q, Kitagawa A, Kobayashi Y, Hasegawa T, Noda M, Kouyama Y, Shimizu D, Saito T, Niida A, Tsuruda Y, Otsu H, Matsumoto Y, Uchida H, Masuda T, Sugimachi K, Sasaki S, Yamada K, Takahashi K, Innan H, Suzuki Y, Nakamura H, Totoki Y, Mizuno S, Ohshima M, Shibata T, Mimori K. , Impaired tumor immune response in metastatic tumors is a selective pressure for neutral evolution in CRC cases., PLoS Genet, 10.1371/journal.pgen.1009113. , 17, 1, e1009113., 2021.01.|
|22.||Kudo SE, Kouyama Y, Ogawa Y, Ichimasa K, Hamada T, Kato K, Kudo K, Masuda T, Otsu H, Misawa M, Mori Y, Kudo T, Hayashi T, Wakamura K, Miyachi H, Sawada N, Sato T, Shibata T, Hamatani S, Nemoto T, Ishida F, Niida A, Miyano S, Oshima M, Ogino S, Mimori K., Depressed Colorectal Cancer: A New Paradigm in Early Colorectal Cancer., Clin Transl Gastroenterol., 10.14309/ctg.0000000000000269. , 11, 12, e00269., 2020.12.|
|23.||Niida A, Mimori K, Shibata T, Miyano S., Modeling colorectal cancer evolution., J Hum Genet, 10.1038/s10038-021-00930-0. , 2021.05.|
|24.||Morine Y, Utsunomiya T, Saito Y, Yamada S, Imura S, Ikemoto T, Kitagawa A, Kobayashi Y, Takao S, Kosai K, Mimori K, Tanaka Y, Shimada M., Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma., Oncotarget, 10.18632/oncotarget.27852. , 11, 52, 4803-4812, 2021.05.|
|25.||Hu Q, Masuda T, Kuramitsu S, Tobo T, Sato K, Kidogami S, Nambara S, Ueda M, Tsuruda Y, Kuroda Y, Ito S, Oki E, Mori M, Mimori K., Potential association of LOXL1 with peritoneal dissemination in gastric cancer possibly via promotion of EMT. , PLoS One, 10.1371/journal.pone.0241140. , 159, 10, e0241140., 2021.05.|
|26.||Masuda T, Nonami A, Tanaka F, Ando Y, Eto M, Mimori K., A case of a patient receiving combination therapy with paclitaxel plus bevacizumab and adoptive activated αβ T-cell immunotherapy in advanced breast cancer., Breast J, 10.1111/tbj.14108 , 26, 12, 2420-2423, 2020.12.|
|27.||Chen B, Dragomir MP, Fabris L, Bayraktar R, Knutsen E, Liu X, Tang C, Li Y,Shimura T, Ivkovic TC, Cruz De Los Santos M, Anfossi S, Shimizu M, Shah MY, Ling H, Shen P, Multani AS, Pardini B, Burks JK, Katayama H, Reineke LC, Huo L, Syed M, Song S, Ferracin M, Oki E, Fromm B, Ivan C, Bhuvaneshwar K, Gusev Y, Mimori K, Menter D, Sen S, Matsuyama T, Uetake H, Vasilescu C, Kopetz S, Parker-Thornburg J, Taguchi A, Hanash SM, Girnita L, Slaby O, Goel A, Varani G, Gagea M, Li C, Ajani JA, Calin GA., The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling. , Gastroenterology, 10.1053/j.gastro.2020.08.018. , 159, 6, 2146-2162, 2020.12.|
|28.||Nishio M, To Y, Maehama T, Aono Y, Otani J, Hikasa H, Kitagawa A, Mimori K, Sasaki T, Nishina H, Toyokuni S, Lydon JP, Nakao K, Wah Mak T, Kiyono T, Katabuchi H, Tashiro H, Suzuki A., YAP1 Activation Drives Immediate Onset of Cervical Carcinoma In Situ in Mice., Cancer Sci., 10.1111/cas.14581., Epub, Epub, Epub, 2020.07.|
|29.||Masuda T, Noda M, Kitagawa A, Hu Q, Fujii A, Ito S, Kosai K, Ando Y, Matsumoto Y, Ohtsu H, Uchida H, Ohno S, Mimori K., The Expression Level of PD-L1 (CD274) mRNA in Peripheral Blood Is a Potential Biomarker for Predicting Recurrence in Breast Cancer., Anticancer Res., 10.21873/anticanres.14362., 40, 7, 3733-3742, 2020.07.|
|30.||Masuda T, Ueo H, Kai Y, Noda M, Hu Q, Sato K, Fujii A, Hayashi N, Tsuruda Y, Otsu H, Kuroda Y, Eguchi H, Ohno S, Mimori K, Ueo H., N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study., Int J Mol Sci., 10.3390/ijms21020511., 21, 2, 511, 2020.01.|
|31.||Noda M, Masuda T, Ito S, Tobo T, Kitagawa A, Hu Q, Shimizu D, Eguchi H, Etoh T, Ohno S, Inomata M, Mimori K., Circulating PD-1 mRNA in Peripheral Blood is a Potential Biomarker for Predicting Survival of Breast Cancer Patients., Ann Surg Oncol., 10.1245/s10434-020-08375-z., Epub, Epub, Epub, 2020.03.|
|32.||Kitagawa A, Masuda T, Takahashi J, Tobo T, Noda M, Kuroda Y, Hu Q, Kouyama Y, Kobayashi Y, Kuramitsu S, Sato K, Fujii A, Yoshikawa Y, Wakiyama H, Shimizu D, Tsuruda Y, Eguchi H, Doki Y, Mori M, Mimori K. , KIF15 Expression in Tumor-associated Monocytes Is a Prognostic Biomarker in Hepatocellular Carcinoma., Cancer Genomics Proteomics., 10.21873/cgp.20174., 17, 2, 141-149, 2020.03.|
|33.||Sato K, Komune N, Hongo T, Koike K, Niida A, Uchi R, Noda T, Kogo R, Matsumoto N, Yamamoto H, Masuda M, Oda Y, Mimori K, Nakagawa T., Genetic landscape of external auditory canal squamous cell carcinoma., Cancer Sci., 10.1111/cas.14515. , Epub , Epub , Epub , 2020.06.|
|34.||Kidogami S, Iguchi T, Sato K, Yoshikawa Y, Hu Q, Nambara S, Komatsu H, Ueda M, Kuroda Y, Masuda T, Mori M, Doki Y, Mimori K., F3B4 Plays an Oncogenic Role in Esophageal Squamous Cell Carcinoma., Anticancer Res., 10.21873/anticanres.14272. , 40, 5, 2941-2946, 2020.05.|
|35.||Niida A, Hasegawa T, Innan H, Shibata T, Mimori K, Miyano S. , A unified simulation model for understanding the diversity of cancer evolution., PeerJ., 10.7717/peerj.8842., 8, e8842., 2020.04.|
|36.||Ito S, Masuda T, Noda M, Hu Q, Shimizu D, Kuroda Y, Eguchi H, Tobo T, Utsunomiya T, Mimori K. , Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer. , Oncology., 10.1159/000506075., 98, 7, 501-511, 2020.05.|
|37.||Nambara S, Masuda T, Kobayashi Y, Sato K, Tobo T, Koike K, Noda M, Ogawa Y, Kuroda Y, Ito S, Eguchi H, Sugimachi K, Mimori K., GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor-suppressor gene TGFβR2 in colorectal cancer., Cancer Sci., 10.1111/cas.14248., 111, 2, 343-355, 2020.02.|
|38.||Masuda T, Noda M, Kogawa T, Kitagawa D, Hayashi N, Jomori T, Nakanishi Y, Nakayama KI, Ohno S, Mimori K., Phase I dose-escalation trial to repurpose propagermanium, an oral CCL2 inhibitor, in patients with breast cancer., Cancer Sci., 10.1111/cas.14306., 111, 3, 924-931, 2020.02.|
|39.||Omori H, Nishio M, Masuda M, Miyachi Y, Ueda F, Nakano T, Sato K, Mimori K, Taguchi K, Hikasa H, Nishina H, Tashiro H, Kiyono T, Mak TW, Nakao K, Nakagawa T, Maehama T, Suzuki A., YAP1 is a potent driver of the onset and progression of oral squamous cell carcinoma., Sci Adv., 10.1126/sciadv.aay3324., 6, 12, eaay3324, 2020.03.|
|40.||Hu Q, Mimori K., ARL4C and Peritoneal Dissemination in Gastric Cancer., Ann Surg Oncol., 10.1245/s10434-018-7056-7., 26, Suppl 3, 547, 2019.12.|
|41.||Mukohyama J, Isobe T, Hu Q, Hayashi T, Watanabe T, Maeda M, Yanagi H, Qian X, Yamashita K, Minami H, Mimori K, Sahoo D, Kakeji Y, Suzuki A, Dalerba P, Shimono Y., miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells., Cancer Res., 10.1158/0008-5472.CAN-18-3544., 79, 20, 5151-5158, 2020.10.|
|42.||Konno M, Koseki J, Asai A, Yamagata A, Shimamura T, Motooka D, Okuzaki D, Kawamoto K, Mizushima T, Eguchi H, Takiguchi S, Satoh T, Mimori K, Ochiya T, Doki Y, Ofusa K, Mori M, Ishii H., Distinct methylation levels of mature microRNAs in gastrointestinal cancers., Nat Commun., 10.1038/s41467-019-11826-1., 10, (1), 3888, 2019.08.|
|43.||Kouyama Y, Masuda T, Fujii A, Ogawa Y, Sato K, Tobo T, Wakiyama H, Yoshikawa Y, Noda M, Tsuruda Y, Kuroda Y, Eguchi H, Ishida F, Kudo SE, Mimori K.
, Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer.
, Cancer Sci., 10.1111/cas.14163., 110, 10, 3132-3144, 2019.10.
|44.||Masuda T, Tsuruda Y, Matsumoto Y, Uchida H, Nakayama KI, Mimori K., Drug repositioning in cancer: The current situation in Japan., Cancer Sci., 10.1111/cas.14318., 111, 4, 1039-1046, 2020.04.|
|45.||Kohsaka S, Tatsuno K, Ueno T, Nagano M, Shinozaki-Ushiku A, Ushiku T, Takai D, Ikegami M, Kobayashi H, Kage H, Ando M, Hata K, Ueda H, Yamamoto S, Kojima S,Oseto K, Akaike K, Suehara Y, Hayashi T, Saito T, Takahashi F, Takahashi K,Takamochi K, Suzuki K, Nagayama S, Oda Y, Mimori K, Ishihara S, Yatomi Y, NagaseT, Nakajima J, Tanaka S, Fukayama M, Oda K, Nangaku M, Miyazono K, Miyagawa K,Aburatani H, Mano H. , Comprehensive assay for the molecular profiling of cancer by target enrichment from formalin-fixed paraffin-embedded specimens., Cancer Sci., 10.1111/cas.13968., 110, 4, 1464-1479, 2019.05.|
|46.||Sato K, Masuda T, Hu Q, Tobo T, Gillaspie S, Niida A, Thornton M, Kuroda Y, Eguchi H, Nakagawa T, Asano K, Mimori K., Novel oncogene 5MP1 reprograms c-Myc translation initiation to drive malignant phenotypes in colorectal cancer.
, EBioMedicine., 10.1016/j.ebiom., S2352-3964(19)30366-4., 2019.06.
|47.||Yumimoto K, Sugiyama S, Mimori K, Nakayama KI., Potentials of C-C motif chemokine 2-C-C chemokine receptor type 2 blockers including propagermanium as anticancer agents., Cancer Sci., 10.1111/cas.14075., 2019.05.|
|48.||Muto Y, Moroishi T, Ichihara K, Nishiyama M, Shimizu H, Eguchi H, Moriya K, Koike K, Mimori K, Mori M, Katayama Y, Nakayama KI.
, Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.
, Cancer Sci., 10.1111/cas.14075., 2019.05.
|49.||Toyoki Maeda, Koshi Mimori, Sadao Suzuki, Takahiko Horiuchi, Naoki Makino, Preventive and promotive effects of habitual hot spa-bathing on the elderly in Japan, Scientific Reports, 10.1038/s41598-017-18488-3, 8, 1, 2018.12, Although body-warming with hot spa-bathing has been proposed to exert medical therapeutic effects on certain diseases, whether body-warming has preventive and promotive effects remains unknown. To clarify this issue, an epidemiological questionnaire study regarding personal hot spa-bathing habits and disease history was carried out in Japan, where individuals engage in daily warm water bathing. Questionnaires regarding hot spa-bathing habits and disease history were randomly sent to 20,000 residents aged ≥65 years living in Beppu, a city in Japan that has the highest concentration of hot spa sources in the world. The results showed that habitual hot spa-bathing exerts preventive or promotive effects on the occurrence of certain diseases, such as hypertension (preventive) and collagen disease (promotive) in women, and cardiovascular diseases (preventive) and colon cancer survival (promotive) in men. These findings suggest that habitual body warming is an effective and economical method with beneficial preventive and promotive effects on various diseases..|
|50.||Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori, Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling, Cancer Science, 10.1111/cas.13510, 109, 4, 884-892, 2018.04, Cancer is composed of multiple cell populations with different genomes. This phenomenon called intratumor heterogeneity (ITH) is supposed to be a fundamental cause of therapeutic failure. Therefore, its principle-level understanding is a clinically important issue. To achieve this goal, an interdisciplinary approach combining genome analysis and mathematical modeling is essential. For example, we have recently performed multiregion sequencing to unveil extensive ITH in colorectal cancer. Moreover, by employing mathematical modeling of cancer evolution, we demonstrated that it is possible that this ITH is generated by neutral evolution. In this review, we introduce recent advances in a research field related to ITH and also discuss strategies for exploiting novel findings on ITH in a clinical setting..|
|51.||Eri Sakai, Mizuho Nakayama, Hiroko Oshima, Yuta Kouyama, Atsushi Niida, Satoshi Fujii, Atsushi Ochiai, Keiichi Nakayama, Koshi Mimori, Yutaka Suzuki, Chang Pyo Hong, Chan Young Ock, Seong Jin Kim, Masanobu Oshima, Combined mutation of Apc, Kras, and Tgfbr2 effectively drives metastasis of intestinal cancer, Cancer Research, 10.1158/0008-5472.CAN-17-3303, 78, 5, 1334-1346, 2018.03, Colorectal cancer is driven by the accumulation of driver mutations, but the contributions of specific mutations to different steps in malignant progression are not fully understood. In this study, we generated mouse models harboring different combinations of key colorectal cancer driver mutations (Apc, Kras, Tgfbr2, Trp53, Fbxw7) in intestinal epithelial cells to comprehensively investigate their roles in the development of primary tumors and metastases. Apcδ716 mutation caused intestinal adenomas and combination with Trp53R270 mutation or Tgfbr2 deletion induced submucosal invasion. The addition of KrasG12D mutation yielded epithelial-mesenchymal transition (EMT)-like morphology and lymph vessel intravasation of the invasive tumors. In contrast, combinations of Apcδ716 with KrasG12D and Fbxw7 mutation were insufficient for submucosal invasion, but still induced EMT-like histology. Studies using tumor-derived organoids showed that KrasG12D was critical for liver metastasis following splenic transplantation, when this mutation was combined with either Apcδ716 plus Trp53R270H or Tgfbr2 deletion, with the highest incidence of metastasis displayed by tumors with a Apcδ716 KrasG12D Tgfbr2-/- genotype. RNA sequencing analysis of tumor organoids defined distinct gene expression profiles characteristic for the respective combinations of driver mutations, with upre-gulated genes in Apcδ716 KrasG12D Tgfbr2-/- tumors found to be similarly upregulated in specimens of human metastatic colorectal cancer. Our results show how activation of Wnt and Kras with suppression of TGFβ signaling in intestinal epithelial cells is sufficient for colorectal cancer metastasis, with possible implications for the development of metastasis prevention strategies..|
|52.||Qingjiang Hu, Takaaki Masuda, Kuniaki Sato, Taro Tobo, Sho Nambara, Shinya Kidogami, Naoki Hayashi, Yohsuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Koshi Mimori, Identification of ARL4C as a Peritoneal Dissemination-Associated Gene and Its Clinical Significance in Gastric Cancer, Annals of Surgical Oncology, 10.1245/s10434-017-6292-6, 25, 3, 745-753, 2018.03, Background: In gastric cancer (GC), peritoneal dissemination (PD) occurs frequently and is incurable. In this study, we aimed to identify PD-associated genes in GC. Methods: We identified a PD-associated gene using three GC datasets: highly disseminated peritoneal GC cell lines, the Singapore dataset and The Cancer Genome Atlas (TCGA) dataset. We assessed the clinicopathological significance of the gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and performed immunohistochemical analysis for the gene in our patient cohort. We also performed survival analyses of the gene in our patient cohort, the Singapore dataset and the GSE62254 datasets. Moreover, gene set enrichment analysis (GSEA) was performed using the Singapore and TCGA datasets. Finally, in vitro experiments such as invasion/migration assays, immunofluorescence staining of actin filaments, epidermal growth factor (EGF) treatment analysis, and gene expression analysis were conducted using three gene-knockdown GC cell lines (AGS, 58As9, MKN45). Results: ADP-ribosylation factor-like 4c (ARL4C) was identified as a PD-associated gene, and immunohistochemical analysis showed that ARL4C was overexpressed in GC cells. High ARL4C expression was associated with the depth of invasion (p < 0.01) and PD (p < 0.05) and was a poor prognostic factor (p < 0.05) in our patient cohort, the Singapore dataset and the GSE62254 dataset. ARL4C expression positively correlated with the epithelial–mesenchymal transition (EMT) gene set in GSEA. Moreover, ARL4C knockdown reduced invasion/migration capacity, SLUG expression, and the formation of lamellipodia or filopodia in AGS and 58As9 cells. Finally, EGF treatment increased ARL4C expression in MKN45 cells. Conclusions: ARL4C was associated with PD and was a poor prognostic factor in GC, possibly through promoting invasive capacity by activation of both EMT and motility..|
|53.||Yuki Kiyozumi, Masaaki Iwatsuki, Junji Kurashige, Yoko Ogata, Kohei Yamashita, Yuki Koga, Tasuku Toihata, Yukiharu Hiyoshi, Takatsugu Ishimoto, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Kazuyoshi Yanagihara, Koshi Mimori, Hideo Baba, PLOD2 as a potential regulator of peritoneal dissemination in gastric cancer, International Journal of Cancer, 10.1002/ijc.31410, 2018.01, Peritoneal dissemination is the most common metastatic pattern in advanced gastric cancer (GC) and has a very poor prognosis. However, its molecular mechanism has not been elucidated. Our study investigated genes associated with peritoneal dissemination of GC. We performed combined expression analysis of metastatic GC cell lines and identified Procollagen-lysine, 2-oxoglutarate 5-dioxygenase2 (PLOD2) as a potential regulator of peritoneal dissemination. PLOD2 is regulated by hypoxia-inducible factor-1 (HIF-1) and mediates extracellular matrix remodeling, alignment, and mechanical properties. We analyzed PLOD2 expression immunohistochemically in 179 clinical samples, and found high PLOD2 expression to be significantly associated with peritoneal dissemination, leading to poor prognosis. In an in vivo-collected metastatic cell line, downregulation of PLOD2 by siRNA reduced invasiveness and migration. Hypoxia upregulated PLOD2 mediated by HIF-1, and promoted invasiveness and migration. After exposure to hypoxia, a cell line transfected with siPLOD2 exhibited significantly suppressed invasiveness and migration, despite high HIF-1 expression. These findings indicate that PLOD2 is a regulator of, and candidate therapeutic target for peritoneal dissemination of GC. Although peritoneal dissemination of GC has a very poor prognosis, its molecular mechanism has not been elucidated. We identified PLOD2 regulated by HIF-1 as a potential regulator of peritoneal dissemination of GC. Finally, we showed that PLOD2 promotes cell invasiveness and migration in GC under hypoxia and lead to peritoneal dissemination of GC..|
|54.||Shuhei Ito, Yuichiro Kai, Takaaki Masuda, Fumiaki Tanaka, Toshifumi Matsumoto, Yukio Kamohara, Hiroshi Hayakawa, Hiroaki Ueo, Hideki Iwaguro, Marc H. Hedrick, Koshi Mimori, Masaki Mori, Long-term outcome of adipose-derived regenerative cell-enriched autologous fat transplantation for reconstruction after breast-conserving surgery for Japanese women with breast cancer, Surgery Today, 10.1007/s00595-017-1544-4, 47, 12, 1500-1511, 2017.12, Purpose: More effective methods are needed for breast reconstruction after breast-conserving surgery for breast cancer. The aim of this clinical study was to assess the perioperative and long-term outcomes of adipose-derived regenerative cell (ADRC)-enriched autologous fat grafting. Methods: Ten female patients who had undergone breast-conserving surgery and adjuvant radiotherapy for breast cancer were enrolled. An ADRC-enriched fat graft prepared from the patient’s adipose tissue was implanted at the time of adipose tissue harvest. The perioperative and long-term outcomes of the grafts, which included safety, efficacy, and questionnaire-based patient satisfaction, were investigated. Results: The mean operation time was 188 ± 30 min, and the mean duration of postoperative hospitalization was 1.2 ± 0.4 days. No serious postoperative complications were associated with the procedure. Neither recurrence nor metastatic disease was observed during the follow-up period (7.8 ± 1.5 years) after transplantation. Of 9 available patients, “more than or equal to average” satisfaction with breast appearance and overall satisfaction were reported by 6 (66.7%) and 5 (55.6%) patients, respectively. Conclusions: ADRC-enriched autologous fat transplantation is thus considered to be safe perioperatively, with no long-term recurrence, for patients with breast cancer treated by breast-conserving surgery, and it may be an option for breast reconstruction, even after adjuvant radiotherapy..|
|55.||Tomoya Sudo, Ryosuke Nishida, Akihiko Kawahara, Kouhei Saisho, Koshi Mimori, Akira Yamada, Atsuhi Mizoguchi, Kazutaka Kadoya, Satoru Matono, Naoki Mori, Toshiaki Tanaka, Yoshito Akagi, Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma, Annals of Surgical Oncology, 10.1245/s10434-017-5796-4, 24, 12, 3763-3770, 2017.11, Background: Recently, several immune checkpoint inhibitors have been developed and are being used to treat malignant melanoma, lung cancer, and other cancers. Several reports have indicated that tumor-infiltrating lymphocytes (TILs) are associated with clinical and histopathologic risk factors in various cancers. However, the role of TILs in esophageal squamous cell carcinoma (ESCC) has not been well studied. This study aimed to investigate the perilesional status of TILs in ESCC and to show associations between TILs and clinical variables. Methods: The study enrolled 277 ESCC patients. Evaluation of TILs was performed according to the criteria of the International TILs Working Group 2014, and associations between TIL and clinicopathologic variables were examined. Results: Most of the clinicopathologic factors were not statistically associated with TIL status. The number of patients who received adjuvant therapy was significantly larger in the TIL-negative group. Cancer-specific survival (CSS) of patients in the TIL-positive group was significantly better than in the TIL-negative group. Among the patients who received adjuvant therapy, CSS was significantly better in the TIL-positive group than in the TIL-negative group. Uni- and multivariate analyses identified tumor depth and TIL status as independent prognostic factors for CSS. Among the other clinicopathologic variables, TIL status was the strongest CSS indicator. Conclusion: Tumor-infiltrating lymphocyte status is a strong predictor of good prognosis for ESCC patients..|
|56.||Yusuke Takahashi, Keishi Sugimachi, Ken Yamamoto, Atsushi Niida, Teppei Shimamura, Tetsuya Sato, Masahiko Watanabe, Junichi Tanaka, Shinei Kudo, Kenichi Sugihara, Kazuo Hase, Masato Kusunoki, Kazutaka Yamada, Yasuhiro Shimada, Yoshihiro Moriya, Yutaka Suzuki, Satoru Miyano, Masaki Mori, Koshi Mimori, Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14, Cancer Science, 10.1111/cas.13391, 108, 11, 2239-2247, 2017.11, Genome-wide association studies are a powerful tool for searching for disease susceptibility loci. Several studies identifying single nucleotide polymorphisms (SNP) connected intimately to the onset of colorectal cancer (CRC) have been published, but there are few reports of genome-wide association studies in Japan. To identify genetic variants that modify the risk of CRC oncogenesis, especially in the Japanese population, we performed a multi-stage genome-wide association study using a large number of samples: 1846 CRC cases and 2675 controls. We identified 4 SNP (rs7912831, rs4749812, rs7898455 and rs10905453) in chromosome region 10p14 associated with CRC; however, there are no coding or non-coding genes within this region of fairly extensive linkage disequilibrium (a 500-kb block) on 10p14. Our study revealed that the 10p14 locus is significantly correlated with susceptibility to CRC in the Japanese population, in accordance with the results of multiple studies in other races..|
|57.||Shuhei Ito, Takaaki Masuda, Noboru Harada, Ayumi Matsuyama, Motoharu Hamatake, Takashi Maeda, Shinichi Tsutsui, Hiroyuki Matsuda, Koshi Mimori, Teruyoshi Ishida, Diagnostic laparoscopy for pneumatosis intestinalis in a very elderly patient
A case report, Annals of Medicine and Surgery, 10.1016/j.amsu.2017.07.058, 21, 109-113, 2017.09, Introduction Pneumatosis intestinalis is rare but may be associated with life-threatening intra-abdominal conditions such as intestinal ischemia or perforation. However, it can be difficult, particularly in the very elderly, to identify candidates for immediate surgical intervention. Presentation of case A 94-year-old man with abdominal distension underwent abdominal computed tomography, which demonstrated accumulation of air bubbles within the intestinal wall and some free intraperitoneal air, suggestive of pneumatosis intestinalis. His vital signs showed evidence of systemic inflammatory response syndrome, and laboratory examination revealed inflammation and hypoxia. As the patient was frail, with his age and concomitant conditions which may have masked the symptoms and severity of his illness, immediate diagnostic laparoscopy was performed, which confirmed the diagnosis of pneumatosis intestinalis, with multiple gas-filled cysts seen within the subserosa of the small intestine. No additional surgical procedure was performed. His symptoms improved postoperatively. Discussion Optimal management of pneumatosis intestinalis in a timely manner requires a comprehensive evaluation of factors in each individual. In patients with severe symptoms, PI might be a sign of a life-threatening intra-abdominal emergency. Despite the contrast-enhanced CT and prediction markers in previous reports, it considered to be difficult to completely rule out these fatal conditions without surgery, especially in very elderly patients with poor performance status. Conclusion Diagnostic laparoscopy may be a useful option for definitively ruling out the lethal conditions associated with pneumatosis intestinalis in frail elderly patients with severe conditions in the emergency setting..
|58.||Takaaki Masuda, Naoki Hayashi, Yohsuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori, MicroRNAs as biomarkers in colorectal cancer, Cancers, 10.3390/cancers9090124, 9, 9, 2017.09, MicroRNAs (miRs) are small RNAs that repress mRNA translation, resulting in the degradation of mRNAs and regulation of the expression levels of various genes. Recent studies have shown that aberrant miR expression has a functional role in the initiation and progression of various malignancies, including colorectal cancer (CRC), which is one of the leading causes of cancer-related death worldwide. miRs have also been shown to have applications as diagnostic, prognostic, and predictive biomarkers because of their high tissue specificity, stability, and altered expression in tumor development. In this report, we examined the role of miRs as biomarkers in CRC through a review of meta-analyses and large-scale analyses having strong statistical confidence in the study outcomes. We also discuss current issues in the clinical application of these miRs..|
|59.||Keishi Sugimachi, Miki Nishio, Shinichi Aishima, Yohsuke Kuroda, Tomohiro Iguchi, Hisateru Komatsu, Hidenari Hirata, Shotaro Sakimura, Hidetoshi Eguchi, Yuki Bekki, Kenji Takenaka, Yoshihiko Maehara, Akira Suzuki, Koshi Mimori, Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma, Oncology, 10.1159/000463390, 93, 1, 67-74, 2017.07, Objective: MOB1, a core component of the Hippo signaling pathway, suppresses cell proliferation, and MOB1 liver conditional knockout mice develop intrahepatic cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not been established. The aim of this study was to characterize protein levels and the role of Hippo and TGF pathways in ICCs. Methods: The protein levels of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFβ2 in 88 ICC cases were analyzed. Protein level was graded by a scoring system; then, the clinicopathological factors, including prognosis, were analyzed based on protein level. Results: Nuclear overexpression of YAP1 was seen in 28 cases (31.8%), and it was significantly associated with a poor overall survival rate (p = 0.01). MOB1 expression decreased in 42 cases (47.7%) and was associated with a poor overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly correlated with a high YAP1 level independent of TGFβ2. Multivariate analysis revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were independent risk factors for overall survival. Conclusions: These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC..|
|60.||Kohei Otsubo, H. Goto, M. Nishio, K. Kawamura, S. Yanagi, W. Nishie, T. Sasaki, T. Maehama, H. Nishina, Koshi Mimori, T. Nakano, H. Shimizu, T. W. Mak, K. Nakao, Yoichi Nakanishi, A. Suzuki, MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation, Oncogene, 10.1038/onc.2017.58, 36, 29, 4201-4211, 2017.07, Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO) 7-Cre/Mob1a flox/flox/Mob1b-/- termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth. Their alveolar epithelial cells showed increased proliferation, impaired YAP1/TAZ-dependent differentiation and decreased surfactant protein production, all features characteristic of human respiratory distress syndrome. Intriguingly, mutant mice that received Dox postnatally (luMob1DKO (P21-41) mice) did not develop spontaneous lung adenocarcinomas, and urethane treatment-induced lung tumour formation was decreased (rather than increased). Lungs of luMob1DKO (P21-41) mice exhibited increased detachment of bronchiolar epithelial cells and decreased numbers of the bronchioalveolar stem cells thought to initiate lung adenocarcinomas. YAP1/TAZ-NKX2.1-dependent expression of collagen XVII, a key hemidesmosome component, was also reduced. Thus, a MOB1-YAP1/TAZ-NKX2.1 axis is essential for normal lung homeostasis and expression of the collagen XVII protein necessary for alveolar stem cell maintenance in the lung niche..|
|61.||Sho Nambara, Tomohiro Iguchi, Eiji Oki, Patrick Tan, Yoshihiko Maehara, Koshi Mimori, Overexpression of CXCR7 Is a novel prognostic indicator in gastric cancer, Digestive Surgery, 10.1159/000452977, 34, 4, 312-318, 2017.07, Background: Among several candidate genes that promote peritoneal dissemination extracted by comprehensive expression analysis of both in vivo selected metastatic cell lines and patients with gastric cancer, we focused on the chemokine (C-X-C motif) receptor (CXCR7) and explored its clinicopathological significance in gastric cancer. Methods:CXCR7 expression was evaluated by microarray data in the Singapore cohort (n = 196) and by immunohistochemistry and reverse transcription quantitative real-time polymerase chain reaction in the Japanese cohort (n = 195). The biological function of CXCR7 in gastric cancer was explored using gene set enrichment analysis (GSEA). Results: CXCR7 expression was upregulated in tumor tissues compared to normal tissues. High CXCR7 mRNA expression was associated with peritoneal dissemination and poor prognosis in the Singapore cohort. Consistent with this, the high CXCR7 mRNA expression group showed significantly poorer prognosis and a more aggressive disease course than the low expression group in the Japanese cohort. High CXCR7 mRNA expression and peritoneal dissemination were clinically relevant. GSEA revealed that CXCR7 was significantly enriched in gene expression signatures associated with tumor progression. Conclusions:CXCR7 may be a prognostic indicator and therapeutic target for gastric cancer with peritoneal dissemination..|
|62.||Sho Takano, Qingjiang Hu, Takaki Amamoto, Paulo Refinetti, Koshi Mimori, Takashi Funatsu, Masaru Kato, Extraction of cell-free DNA from urine, using polylysine-coated silica particles, Fresenius Zeitschrift fur Analytische Chemie, 10.1007/s00216-017-0345-3, 409, 16, 4021-4025, 2017.06, DNA analysis is used for a variety of purposes, including disease diagnosis and DNA profiling; this involves extracting DNA from living organisms. In this study, we prepared polycationic silica particles to extract DNA that has the negatively charged phosphate backbone from solution. The coated particles were prepared by mixing conventional silica gel particles and poly-Lys; these particles could efficiently extract 1.3 μg of cell-free DNA from 50 mL of (male) urine. It is expected that these easily prepared particles (just a mixture of two commercially available chemicals) can be used as a noninvasive diagnostic tool for genetic disorders such as cancer, diabetes, and hypertension. [Figure not available: see fulltext.]..|
|63.||Shin Sasaki, Masami Ueda, Tomohiro Iguchi, Manabu Kaneko, Hiroshi Nakayama, Toshiyuki Watanabe, Atsuhiko Sakamoto, Koshi Mimori, DDR2 expression is associated with a high frequency of peritoneal dissemination and poor prognosis in colorectal cancer, Anticancer Research, 10.21873/anticanres.11603, 37, 5, 2587-2591, 2017.05, Background: We previously identified discoidindomain receptor 2 (DDR2) as a promising driver gene of peritoneal dissemination (PD) in gastric cancer. In the present study we explored the clinical significance of DDR2 expression in colorectal cancer (CRC). Materials and Methods: We examined DDR2 expression in CRC specimens by immunohistochemistry. We analyzed the association of DDR2 expression with clinicopathological factors in CRC. We divided 63 CRC cases into two groups according to their level of DDR2 expression and compared several clinicopathological factors and their overall survival. Results: The group with high DDR2 expression had significantly higher frequencies of T4, lymph node metastasis, and PD compared to the group with low DDR2 expression. Furthermore, the prognosis of the group with high DDR2 expression was significantly poorer than the group with low DDR2. Conclusion: DDR2 is a powerful biomarker that can predict poor prognosis as well as PD, and might be an effective therapeutic target for CRC..|
|64.||Sho Nambara, Koshi Mimori, MicroRNA in various aspects of cancer development, Japanese Journal of Cancer and Chemotherapy, 44, 5, 362-366, 2017.05, MicroRNAs (miRNAs) are small (18-25 nucleotides) noncoding RNA molecules that bind to partially complementary mRNA sequences, resulting in target degradation or translation inhibition. A single miRNA can influence the expression of hundreds of target genes, and miRNAs have been implicated as key molecules in various diseases, including cancer. Many studies have shown that the miRNAs play an important role in cancer cells and tumor microenvironment and may be biomarkers for early detection and therapeutic targets for various cancers. Recently, relationships between miRNAs and immunocheckpoint molecules have been focused on as new tumor progression associated mechanisms. As for biomarkers, cell-free miRNAs detected in body fluids (circulating miRNAs) have attached the attention of researchers due to their potential as tumor-specific and non-invasive biomarkers. In terms of strategies to use miRNAs as therapeutic targets, developments of tissue specific delivery systems, including lipid nanoparticles or exosome vectors, are progressing. Here we will review the mechanisms and clinical uses of miRNAs in cancer..|
|65.||Kuniaki Sato, Takaaki Masuda, Qingjiang Hu, Taro Tobo, Shinya Kidogami, Yushi Ogawa, Tomoko Saito, Sho Nambara, Hisateru Komatsu, Hidenari Hirata, Shotaro Sakimura, Ryutaro Uchi, Naoki Hayashi, Tomohiro Iguchi, Hidetoshi Eguchi, Shuhei Ito, Takashi Nakagawa, Koshi Mimori, Phosphoserine phosphatase is a novel prognostic biomarker on chromosome 7 in colorectal cancer, Anticancer Research, 10.21873/anticanres.11574, 37, 5, 2365-2371, 2017.05, Background/Aim: Amplification of chromosome 7p (Ch.7p) is common in colorectal cancer (CRC). The aim of this study was to identify potential driver genes on Ch.7p that are overexpressed due to DNA copy number amplification and determine their clinical significance in CRC. Materials and Methods: We identified phosphoserine phosphatase (PSPH) as a potential driver gene using a CRC dataset from The Cancer Genome Atlas (TCGA) using a bioinformatics approach. The expression of PSPH in 124 primary CRCs was examined by quantitative reverse transcription polymerase chain reaction (PCR) and immunohistochemistry. The biological effect of PSPH expression was explored by Gene Set Enrichment Analysis (GSEA) using the TCGA dataset. Results: PSPH was overexpressed in tumor tissues and PSPH positively correlated with depth of invasion and distant metastasis. On multivariate analysis, high PSPH expression was an independent poor prognostic factor. These results were supported by GSEA. Conclusion: PSPH could be a novel prognostic biomarker with malignant potential on Ch.7p in CRC..|
|66.||Masami Ueda, Tomohiro Iguchi, Takaaki Masuda, Hisateru Komatsu, Sho Nambara, Shotaro Sakimura, Hidenari Hirata, Ryutaro Uchi, Hidetoshi Eguchi, Shuhei Ito, Keishi Sugimachi, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Koshi Mimori, Up-regulation of SLC9A9 promotes cancer progression and is involved in poor prognosis in colorectal cancer, Anticancer Research, 10.21873/anticanres.11562, 37, 5, 2255-2263, 2017.05, Background/Aim: SLC9A9 plays an oncogenic role in esophageal squamous carcinoma and glioblastoma. Herein, we showed an oncogenic function of SLC9A9 in colorectal cancer (CRC). Materials and Methods: We examined SLC9A9 expression in CRC specimens by immunohistochemistry. In CRC tissues, the relationship between SLC9A9 expression and clinicopathological factors was further elucidated by quantitative real-time polymerase chain reaction (qRT-PCR) and gene set enrichment analysis (GSEA). In vitro, we performed knockdown and overexpression experiments. Results: SLC9A9 was overexpressed in CRC specimens. In clinicopathological analysis of our cohort, high SLC9A9 expression increased liver metastasis and was correlated with worse prognoses in two cohorts. A significantly positive relationship between SLC9A9 and EGFR was revealed. While knockdown of SLC9A9 suppressed proliferation and anchorageindependent growth, up-regulation of SLC9A9 promoted proliferation and anchorage-independent growth in vitro. Conclusion: SLC9A9 has an oncogenic function by being related to EGFR signaling, suggesting SLC9A9 may be a novel prognostic indicator and a therapeutic target in CRC..|
|67.||Yusuke Matsui, Atsushi Niida, Ryutaro Uchi, Koshi Mimori, Satoru Miyano, Teppei Shimamura, phyC
Clustering cancer evolutionary trees, PLoS Computational Biology, 10.1371/journal.pcbi.1005509, 13, 5, 2017.05, Multi-regional sequencing provides new opportunities to investigate genetic heterogeneity within or between common tumors from an evolutionary perspective. Several state-of-the-art methods have been proposed for reconstructing cancer evolutionary trees based on multi-regional sequencing data to develop models of cancer evolution. However, there have been few studies on comparisons of a set of cancer evolutionary trees. We propose a clustering method (phyC) for cancer evolutionary trees, in which sub-groups of the trees are identified based on topology and edge length attributes. For interpretation, we also propose a method for evaluating the sub-clonal diversity of trees in the clusters, which provides insight into the acceleration of sub-clonal expansion. Simulation showed that the proposed method can detect true clusters with sufficient accuracy. Application of the method to actual multi-regional sequencing data of clear cell renal carcinoma and non-small cell lung cancer allowed for the detection of clusters related to cancer type or phenotype. phyC is implemented with R(≥3.2.2) and is available from https://github.com/ymatts/phyC..
|68.||Ｋｏｍａｔｓｕ Ｈ, Iguchi T, Takaaki Masuda, Ｈｉｒａｔａ Ｈ, Ｕｅｄａ Ｍ, Ｋｉｄｏｇａｍｉ Ｓ, Ｏｇａｗａ Ｙ, Ｓａｔｏ Ｋ, Ｈｕ Ｑ, Ｎａｍｂａｒａ Ｓ, Ｓａｉｔｏ Ｔ, Ｓａｋｉｍｕｒａ Ｓ, Ｕｃｈｉ Ｒ, Ito S, Eguchi H, Sugimachi K, Ｅｇｕｃｈｉ Ｈ, Ｄｏｋｉ Ｙ, Ｍｏｒｉ Ｍ, Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma., Ann Surg Oncol., 10.1245/s10434-016-5573-9., ２４, ３, 850-859, 2017.03.|
|69.||Hisateru Komatsu, Tomohiro Iguchi, Takaaki Masuda, Hidenari Hirata, Masami Ueda, Shinya Kidogami, Yushi Ogawa, Kuniaki Sato, Qingjiang Hu, Sho Nambara, Tomoko Saito, Shotaro Sakimura, Ryutaro Uchi, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori, Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma, Annals of Surgical Oncology, 10.1245/s10434-016-5573-9, 24, 3, 850-859, 2017.03, Background: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). Methods: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520. Gene set enrichment analysis (GSEA) was also conducted. Finally, knockdown experiments were performed using small interfering RNA (siRNA) in vitro. Results: In all cohorts, RND1 expression was decreased as cancer progressed, and was affected by promoter methylation. In our HCC cases, the 5-year overall survival (OS) and recurrence-free survival of patients with low RND1 expression was significantly poorer than those of patients with high RND1 expression. TCGA and GSE14520 analyses provided similar results for OS. Multivariate analysis indicated that RND1 expression was an independent prognostic factor for OS in all three cohorts. Additionally, GSEA showed an inverse correlation between RND1 expression and the Ras signaling activity. In vitro, knockdown of RND1 expression resulted in significant increases in proliferation, invasion, and chemoresistance to cisplatin in HCC cells. Conclusions: Reduced RND1 expression in HCC was associated with cancer progression, likely through regulation of the Ras signaling pathway, and may serve as a novel clinical biomarker for predicting prognosis in patients with HCC..|
|70.||Ｎａｍｂａｒａ Ｓ, Iguchi T, Oki E, Ｔａｎ Ｐ, Ｍａｅｈａｒａ Ｙ, Mimori K, Overexpression of CXCR7 Is a Novel Prognostic Indicator in Gastric Cancer., Dig Surg, 10.1159/000452977, 2016.12.|
|71.||Iguchi T, Nambara S, Takaaki Masuda, Komatsu H, Ｕｅｄａ Ｍ, Ｋｉｄｏｇａｍｉ Ｓ, Ogawa Y, Hu Q, Sato K, Hirata H, Ｓａｋｉｍｕｒａ Ｓ, Ｕｃｈｉ Ｒ, Hayashi N, Ito S, Eguchi H, Sugimachi K, Ｍｅｈａｒａ Ｙ, Mimori K, miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients' Susceptibility to Liver Metastasis., PLoS One, 10.1371/journal.pone.0165912, １１, １１, e0165912-e0165912, 2016.11.|
|72.||Sugimachi K, Yamaguchi R, Eguchi H, Ueda M, Niida A, Sakimura S, Hirata H, Uchi R, Shinden Y, Iguchi T, Morita K, Yamamoto K, Miyano S, Mori M, Marhara Y, Mimori K, 8q24 Polymorphisms and Diabetes Mellitus Regulate Apolipoprotein A-IV in Colorectal Carcinogenesis, Ann Surg Oncol., 10.1245/s10434-016-5374-1, ２３, ４, 546--551, 2016.08.|
|73.||Hirata H, Sugimachi K, Komatsu H, Ueda M, Uchi R, Sakimura S, Nambara S, Saito T, Shinden Y, Iguchi T, Eguchi H, Ito S, Terashima K, Sakamoto K, Hirakawa M, Honda H, Mimori K, Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma., Cancer Res, 10.1158/0008-5472.CAN-15-2601, 76, 11, 3265-3276, 2016.06.|
|74.||Sugimachi K, Ｍａｔｓｕｍｕｒａ Ｔ, Shimamura T, Hirata H, Uchi R, Ueda M, Sakimura S, IguchiT, Eguchi H, Takaaki Masuda, Morita K, Takenaka K, Maehara Y, Mori M, Mimori K, Aberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer., Ann Surg Oncol, 10.1245/s10434-016-5289-x, 23, 12, 3948-3955, 2016.06.|
|75.||Komatsu H, Iguchi T, Takaaki Masuda, Ueda M, Kidogami S, Ogawa Y, Nambara S, Sato K, Hu Q, Saito T, Hirata H, Sakimura S, Uchi R, Hayashi N, Ito S, Eguchi H, Sugimachi K, Doki Y, Mori M, HOXB7 Expression is a Novel Biomarker for Long-term Prognosis After Resection of Hepatocellular Carcinoma., Anticancer Res., 36, 6, 2767-2773, 2016.06.|
|76.||Shinden Y, Ueo H, Tobo T, Gamachi A, Utou M, Komatsu H, Nambara S, Saito T, Ueda M, Hirata H, Sakimura S, Takano Y, Uchi R, Kurashige J, Akiyoshi S, Iguchi T, Eguchi H, Sugimachi K, Kubota Y, Rapid diagnosis of lymph node metastasis in breast cancer using a new fluorescent method with γ-glutamyl hydroxymethyl rhodamine green, Sci Rep., 10.1038/srep27525., ９, ６, 27525-27525, 2016.06.|
|77.||Hisateru Komatsu, Iguchi Tomohiro, Masami Ueda, Sho Nanbara, Tomoko Saito, Hidenari Hirata, Shotaro Sakimura, Yuki Takano, Ryutaro Uchi, Shinden Yoshiaki, Hidetoshi Eguchi, Takaaki Masuda, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori, Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma., Oncol Rep, 10.3892/or.2016.4593., 35, 4, 2073-2080, 2016.04.|
|78.||Genta Sawada, Atsushi Niida, HIdenari Hirata, Hisateru Komatsu, Ryutaro Uchi, Teppei Shimamura, Yusuke Takahashi, Junji Kurashige, Tae Matsumura, Hiroki Ueo, Yuki Takano, Masami Ueda, Shotaro Sakimura, Shinden Yoshiaki, Hidetoshi Eguchi, Sudo Tomoya, Keishi Sugimachi, Koshi Mimori, An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma., PLoS One., 10.1371/journal.pone.0139808., 10, 10, e0139808, 2015.10.|
|79.||Keishi Sugimachi, Shotaro Sakimura, Akira Tomokuni, Ryutaro Uchi, Hidenari Hirata, Hisateru Komatsu, Shinden Yoshiaki, Iguchi Tomohiro, Hidetoshi Eguchi, Takaaki Masuda, Kazutoyo Morita, Ken Shirabe, Hidetoshi Eguchi, Yoshihiko Maehara, Masaki Mori, Koshi Mimori, Identification of Recurrence-Related microRNAs from Bone Marrow in Hepatocellular Carcinoma Patients., J Clin Med., 10.3390/jcm4081600., 4, 8, 1600-1611, 2015.08.|
|80.||Tae Matsumura, Keishi Sugimachi, Hisae Iinuma, Yusuke Takahashi, Junji Kurashige, Genta Sawada, Masami Ueda, Ryutaro Uchi, Hiroki Ueda, Yuki Takano, Shinden Yoshiaki, Hidetoshi Eguchi, Hirofumi Yamamoto, Yuichiro Doki, Takahiro Ochiya, Koshi Mimori, Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer., Br J Cancer, 10.1038/bjc.2015.201., 113, 2, 275-281, 2015.07.|
|81.||Shinden Yoshiaki, Iguchi Tomohiro, Akiyoshi Sayuri, Hiroki Ueo, Masami Ueda, Hidenari Hirata, Shotaro Sakimura, Ryutaro Uchi, Yuki Takano, Hidetoshi Eguchi, Keishi Sugimachi, Yuko Kijima, Shoji Natsugoe, Koshi Mimori, miR-29b is an indicator of prognosis in breast cancer patients., Mol Clin Oncol., 10.3892/mco.2015.565, 3, 4, 919-923, 2015.07.|
|82.||Masami Ueda, Iguchi Tomohiro, Sho Nanbara, Tomoko Saito, Hisateru Komatsu, Shotaro Sakimura, Hidenari Hirata, Ryutaro Uchi, Yuki Takano, Shinden Yoshiaki, Hidetoshi Eguchi, Takaaki Masuda, Keishi Sugimachi, Hirofumi Yamamoto, Yuichiro Doki, Koshi Mimori, Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer., Ann Surg Oncol. , 10.1245/s10434-015-4652-7., 3, S1490.-S1498, 2015.06.|
|83.||Hiroki Ueo, Shinden Yoshiaki, Taro Tobo, Ayako Gamachi, Mitsuaki Udo, Hisateru Komatsu, Sho Nanbara, Tomoko Saito, Masami Ueda, Hidenari Hirata, Shotaro Sakimura, Yuki Takano, Ryutaro Uchi, Junji Kurashige, Akiyoshi Sayuri, Iguchi Tomohiro, Hidetoshi Eguchi, Keishi Sugimachi, Rapid intraoperative visualization of breast lesions with γ-glutamyl hydroxymethyl rhodamine green., Sci Rep., 10.1038/srep12080., 13, 5, 12080, 2015.06.|
|84.||Iguchi Tomohiro, Ryutaro Uchi, Sho Nanbara, Tomoko Saito, Hisateru Komatsu, Hidenatri Hitara, Masami Ueda, Shotaro Sakimura, Yuki Takano, Junji Kurashige, Shinden Yoshiaki, Hidetoshi Eguchi, Keishi Sugimachi, Yoshihiko Maehara, Koshi Mimori, A long noncoding RNA, lncRNA-ATB, is involved in the progression and prognosis of colorectal cancer., Anticancer Res., ３５, 3, １３８５-１３８８, 2015.05, BACKGROUND/AIM:
A long noncoding RNA (lncRNA) activated by transforming growth factor (TGF)-β (lncRNA-ATB) was recently described to promote the invasion-metastasis cascade in hepatocellular carcinoma. The aim of the present study was to clarify the clinicopathological role and prognostic relevance of lncRNA-ATB in colorectal cancer (CRC).
MATERIALS AND METHODS:
lncRNA-ATB expression was evaluated by real-time reverse transcription polymerase chain reaction in 124 patients with CRC. Patients were divided into two groups based on the median lncRNA-ATB expression.
High lncRNA-ATB expression was significantly associated with greater tumor size, depth of tumor invasion, lymphatic invasion, vascular invasion, and lymph node metastasis. Patients of the high-lncRNA-ATB expression group had significantly poorer outcomes than those of the low-expression group. Additionally, levels of lncRNA-ATB expression were significantly higher in patients with hematogenous metastases.
lncRNA-ATB may be involved in the progression of CRC and be a novel indicator of poor prognosis in patients with CRC.
Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Long noncoding RNA; TGF-β; colorectal cancer; prognosis; progression.
|85.||Tomoko Saito, Junji Kurashige, Sho Nanbara, Hisateru Komatsu, Hidenari Hirata, Masami Ueda, Shotaro Sakimura, Ryutaro Uchi, Yuki Takano, Shinden Yoshiaki, Iguchi Tomohiro, Hidetoshi Eguchi, Shogo Ehata, Kazunari Murakami, Keishi Sugimachi, Koshi Mimori, A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer., Ann Surg Oncol., 10.1245/s10434-015-4554-8, 2015.05, BACKGROUND:
A recent study reported that long non-coding RNA activated by TGF-β (lncRNA-ATB) induced epithelial-mesenchymal transition (EMT) through the transforming growth factor-β (TGF-β)/miR-200s/ZEB axis in hepatocellular carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in gastric cancer (GC) patients.
MATERIALS AND METHODS:
Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183). Patients were divided into high and low lncRNA-ATB expression groups using a cutoff of lncRNA-ATB/GAPDH ≥0.60 or <0.60 to determine the clinicopathological significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF-β, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines were treated by recombinant TGF-β1 or TGF-β receptor inhibitor to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype.
The high lncRNA-ATB group experienced a lower overall survival rate compared with the low lncRNA-ATB group, and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (hazard ratio 3.50; 95 % CI 1.73-7.44; p = 0.0004). miR-200c levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than in the low lncRNA-ATB group. Treatment with TGF-β in GC cell lines resulted in morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression.
LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-β/miR-200s/ZEB axis, resulting in a poor prognosis in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis in GC patients..
|86.||Hidekazu Takahashi, Junichi Nishimura, Yoshinori Kagawa, Yoshihiro Kano, Yusuke Takahashi, Xin Wu, Masayuki Hiraki, Atsushi Hamabe, Masamitsu Konno, Naotsugu Haraguchi, Ichiro Takemasa, Tsunekazu Mizushima, Masaru Ishii, Koshi Mimori, Hideshi Ishii, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto, Significance of Polypyrimidine Tract-Binding Protein 1 Expression in Colorectal Cancer., Molecular Cancer Therapeutics, 10.1158/1535-7163, 2015.04, Polypyrimidine tract-binding protein (PTBP1) is an RNA-binding protein with various molecular functions related to RNA metabolism and a major repressive regulator of alternative splicing, causing exon skipping in numerous alternatively spliced pre-mRNAs. Here, we have investigated the role of PTBP1 in colorectal cancer. PTBP1 expression levels were significantly overexpressed in cancerous tissues compared with corresponding normal mucosal tissues. We also observed that PTBP1 expression levels, c-MYC expression levels, and PKM2:PKM1 ratio were positively correlated in colorectal cancer specimens. Moreover, PTBP1 expression levels were positively correlated to poor prognosis and lymph node metastasis. In analyses of colorectal cancer cells using siRNA for PTBP1, we observed that PTBP1 affects cell invasion, which was partially correlated to CD44 splicing, and this correlation was also confirmed in clinical samples. PTBP1 expression also affected anchorage-independent growth in colorectal cancer cell lines. PTBP1 expression also affected cell proliferation. Using time-lapse imaging analysis, PTBP1 was implicated in prolonged G2-M phase in HCT116 cells. As for the mechanism of prolonged G2-M phase in HCT116 siPTBP1 cells, Western blotting revealed that PTBP1 expression level was correlated to CDK11p58 expression level, which was reported to play an important role on progression to complete mitosis. These findings indicated that PTBP1 is a potential therapeutic target for colorectal cancer. Mol Cancer Ther; 14(7); 1-12. ©2015 AACR..|
|87.||Yumimoto Kanae, Akiyoshi Sayuri, Ueo Hiroki, Sagara Yasuaki, Onoyama Ichiro, Ueo Hiroaki, Ohno, Shinji, Mori, Masaki, Koshi Mimori, Keiichi Nakayama, F-box protein FBXW7 inhibits-cancer metastasis in a non-cell-autonomous manner, JOURNAL OF CLINICAL INVESTIGATION, 10.1172/JCI78782, 125, 2, 621-635, 2015.02, The gene encoding F-box protein FBXW7 is frequently mutated in many human cancers. Although most previous studies have focused on the tumor-suppressive capacity of FBXW7 in tumor cells themselves, we determined that FBXW7 in the host microenvironment also suppresses cancer metastasis. Deletion of Fbxw7 in murine BM-derived stromal cells induced accumulation of NOTCH and consequent transcriptional activation of Ccl2. FBXW7-deficient mice exhibited increased serum levels of the chemokine CCL2, which resulted in the recruitment of both monocytic myeloid-derived suppressor cells and macrophages, thereby promoting metastatic tumor growth. Administration of a CCL2 receptor antagonist blocked the enhancement of metastasis in FBXW7-deficient mice. Furthermore, in human breast cancer patients, FBXW7 expression in peripheral blood was associated with serum CCL2 concentration and disease prognosis. Together, these results suggest that FBXW7 antagonizes cancer development in not only a cell-autonomous manner, but also a non-cell-autonomous manner, and that modulation of the FBXW7/NOTCH/CCL2 axis may provide a potential approach to suppression of cancer metastasis. .|
|88.||Shotaro Sakimura, Keishi Sugimachi, Junji Kurashige, Msasami Ueda, Hidenari Hirata, Sho Nanbara, Hisateru Komatsu, Tomoko Saito, Yuki Takano, Ryutaro Uchi, Etsuko Sakimura, Shinden Yoshiaki, Iguchi Tomohiro, Hidetoshi Eguchi, Yugo Oba, Sumio Hoka, Koshi Mimori, The miR-506-Induced Epithelial-Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer., Ann Surg Oncol. , 10.1245/s10434-015-4418-2, 2015.02, BACKGROUND:
MicroRNAs have roles in the regulation of the epithelial-mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer.
In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3' untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines.
Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3'UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells.
The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent..
|89.||Junji Kurasige, Koshuke Mima, Genta Sawada, Yusuke Takahashi, Hidetoshi Eguchi, Keishi Sugimachi, Masaki Mori, Kazuyoshi Yanagihara, Masakazu Yashiro, Kosei Hirakawa, Hideo Baba, Koshi Mimori, Epigenetic modulation and repression of miR-200b by cancer-associated fibroblasts contribute to cancer invasion and peritoneal dissemination in gastric cancer, CARCINOGENESIS, 10.1093/carcin/bgu232, 36, 1, 133-141, 2015.01, Cancer-associated fibroblasts (CAFs) have recently been linked to the invasion and metastasis of gastric cancer. In addition, the microRNA (miR)-200 family plays a central role in the regulation of the epithelial-mesenchymal transition process during cancer metastasis, and aberrant DNA methylation is one of the key mechanisms underlying regulation of the miR-200 family. In this study, we clarified whether epigenetic changes of miR-200b by CAFs stimulate cancer invasion and peritoneal dissemination in gastric cancer. We evaluated the relationship between miR-200b and CAFs using a coculture model. In addition, we established a peritoneal metastasis mouse model and investigated the expression and methylation status of miR-200b. We also investigated the expression and methylation status of miR-200b and CAFs expression in primary gastric cancer samples. CAFs (CAF-37 and CAF-50) contributed to epigenetic changes of miR-200b, reduced miR-200b expression and promoted tumor invasion and migration in NUGC3 and OCUM-2M cells in coculture. In the model mice, epigenetic changes of miR-200b were observed in the inoculated high-frequency peritoneal dissemination cells. In the 173 gastric cancer samples, the low miR-200b expression group demonstrated a significantly poorer prognosis compared with the high miR-200b expression group and was associated with peritoneal metastasis. In addition, downregulation of miR-200b in cancer cells was significantly correlated with alpha-smooth muscle actin expression. Our data provide evidence that CAFs reduce miR-200b expression and promote tumor invasion through epigenetic changes of miR-200b in gastric cancer. Thus, CAFs might be a therapeutic target for inhibition of gastric cancer. .|
|90.||Junji Kurasige, Koshuke Mima, Genta Sawada, Yusuke Takahashi, Hidetoshi Eguchi, Keishi Sugimachi, Masaki Mori, Kazuyoshi Yanagihara, Masakazu Yashiro, Kosei Hirakawa, Hideo Baba, Koshi Mimori, Epigenetic modulation and repression of miR-200b by cancer-associated fibroblasts contribute to cancer invasion and peritoneal dissemination in gastric cancer, CARCINOGENESIS, 10.1093/carcin/bgu232, 36, 1, 133-141, 2015.01, Cancer-associated fibroblasts (CAFs) have recently been linked to the invasion and metastasis of gastric cancer. In addition, the microRNA (miR)-200 family plays a central role in the regulation of the epithelial-mesenchymal transition process during cancer metastasis, and aberrant DNA methylation is one of the key mechanisms underlying regulation of the miR-200 family. In this study, we clarified whether epigenetic changes of miR-200b by CAFs stimulate cancer invasion and peritoneal dissemination in gastric cancer. We evaluated the relationship between miR-200b and CAFs using a coculture model. In addition, we established a peritoneal metastasis mouse model and investigated the expression and methylation status of miR-200b. We also investigated the expression and methylation status of miR-200b and CAFs expression in primary gastric cancer samples. CAFs (CAF-37 and CAF-50) contributed to epigenetic changes of miR-200b, reduced miR-200b expression and promoted tumor invasion and migration in NUGC3 and OCUM-2M cells in coculture. In the model mice, epigenetic changes of miR-200b were observed in the inoculated high-frequency peritoneal dissemination cells. In the 173 gastric cancer samples, the low miR-200b expression group demonstrated a significantly poorer prognosis compared with the high miR-200b expression group and was associated with peritoneal metastasis. In addition, downregulation of miR-200b in cancer cells was significantly correlated with alpha-smooth muscle actin expression. Our data provide evidence that CAFs reduce miR-200b expression and promote tumor invasion through epigenetic changes of miR-200b in gastric cancer. Thus, CAFs might be a therapeutic target for inhibition of gastric cancer. .|
|91.||Shinden Yoshiaki, Akiyoshi Sayuri, Ueo Hiroki, Sho Nanbara, Tomoko Saito, Hisateru Komatsu, Masami Ueda, Hidenari Hirata, Shotaro Sakimura, Ryutaro Uchi, Yuki Takano, Iguchi Tomohiro, Hidetoshi Eguchi, Keishi Sugimachi, Y Kijima, Hiroaki Ueo, Shoji Natsugoe, Koshi Mimori, Diminished Expression of MiR-15a Is an Independent Prognostic Marker for Breast Cancer Cases, ANTICANCER RESEARCH, 35, 1, 123-127, 2015.01, BACKGROUND/AIM:
MiR-15a targets Cyclin E1 (CCNE1), which regulates the cell cycle and promotes cell proliferation and progression. Herein, we investigated the clinicopathological significance of miR-15a as a prognostic marker in breast cancer (BC) cases.
MATERIALS AND METHODS:
We collected primary tumor samples of 230 BC cases, including 68 triple-negative cases. The expression levels of miR-15a in primary tumors were measured by qRT-PCR assay.
Low expression of miR-15a in primary tumors was significantly correlated with shorter disease-free survival (p=0.0012) and overall survival (p=0.005) compared to the high miR-15a expression in triple-negative BC cases. Multivariate analysis indicated that low miR-15a expression was an independent prognostic factor for overall survival [RR=2.56(1.03-7.18), p=0.04].
MiR-15a expression levels could be a promising biological and prognostic marker for overall survival especially in triple-negative BC cases.
Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
breast cancer; miR-15a; prognosis.
|92.||Masami Ueda, Iguchi Tomohiro, Sho Nanbara, Tomoko Saito, Hisateru Komatsu, Shotaro Sakimura, Hidenari Hirata, Ryutaro Uchi, Yuki Takano, Shinden Yoshiaki, Hidetoshi Eguchi, Takaaki Masuda, Keishi Sugimachi, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori, Koshi Mimori, Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer., Ann Surg Oncol., 10.1245/s10434-015-4652-7, 2015.01, BACKGROUND:
RNA polymerase 1 transcription termination factor (TTF1) mediates the transcription of ribosomal RNA (rRNA). In the current study, we investigated the clinical and biological significance of the TTF1 gene in colorectal cancer (CRC).
The expression of TTF1 messenger RNA (mRNA) in tumor and normal tissues from 136 patients with CRC was examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We also performed in vitro cell proliferation and migration assays in TTF1-expressing CRC cells. The biological role of TTF1 in CRC was further elucidated using gene set enrichment analysis (GSEA) with CRC samples.
TTF1 expression was significantly higher in tumor tissues than in corresponding normal tissues (p = 0.016). In clinicopathological analysis, the high-TTF1 expression group showed a higher incidence of liver metastasis and lymphatic invasion than the low-TTF1 expression group (p < 0.05), and tended to have more frequent venous invasion than the low-TTF1 expression group. Furthermore, the high-TTF1 expression group had a significantly poorer prognosis than the low-TTF1 expression group (p = 0.011). Moreover, overexpression of TTF1 enhanced the proliferation and migration capacity of CRC cells in vitro. GSEA revealed that TTF1 was significantly associated with the RAS and MYC pathways, and this observation was confirmed in samples from 136 patients with CRC.
TTF1 was involved in cancer progression via the RAS and MYC pathways in CRC, suggesting that TTF1 may be a prognostic indicator and therapeutic target in CRC.
|93.||Genta Sawada, Yusuke Takahashi, Atsushi Niida, Teppei Shimamura, Junji Kurashige, Tae Matsumura, Hiroki Ueo, Ryutaro Uchi, Yuki Takano, Masami Ueda, Hidernari Hirata, Shotaro Sakimura, Shinden Yoshiaki, Hidetoshi Eguchi, Sudo Tomoya, Keishi Sugimachi, Satoru Miyano, Yuichiro Doki, Masaki Mori, Koshi Mimori, Loss of CDCP1 Expression Promotes Invasiveness and Poor Prognosis in Esophageal Squamous Cell Carcinoma, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-014-3740-4, 21, S640-S647, 2014.12, BACKGROUND:
Human CDCP1 gene, located on chromosome 3p21.3, is a transmembrane glycoprotein widely expressed in epithelial tissues, and its role in cancer remains to be understood.
Using microarray profiles of gene expression and copy number data from 69 esophageal squamous cell carcinoma (ESCC) samples, we performed informatics analyses to reveal the significance of CDCP1 expression. We also performed migration and invasion assays of siRNA-targeted CDCP1-transfected cells and CDCP1-overexpressing cell in vitro. Moreover, we evaluated the clinical magnitude of CDCP1 expression in esophageal squamous cell cancer cases.
Allelic loss of chromosome 3p was confirmed by copy number analysis. The expression level of CDCP1 in tumor tissue was significantly lower than that in corresponding normal tissue. siRNA targeting of CDCP1 promoted the migratory and invasive abilities of esophageal cancer cell lines, whereas both abilities were reduced in CDCP1-overexpressing cells. Gene set enrichment analysis showed that expression levels of CDCP1 were associated with tumor differentiation and metastasis, consistent with the result of clinicopathologic analyses. Finally, multivariate analysis revealed that the expression level of CDCP1 was an independent prognostic factor for survival.
Loss of CDCP1 expression may be a novel indicator for biological aggressiveness in ESCC..
|94.||Tae Matsumura, Keishi Sugimachi, Yusuke Takahashi, Ryutaro Uchi, Genta Sawada, Masami Ueda, Hidenari Hirata, Shotaro Sakimura, Hiroki Ueo, Yuki Takano, Junji Kurashige, Shinden Yoshiaki, Hidetoshi Eguchi, Sudo Tomoya, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori, Koshi Mimori, Clinical Significance of GAB2, a Scaffolding/Docking Protein Acting Downstream of EGFR in Human Colorectal Cancer, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-014-3889-x, 21, S743-S749, 2014.12.|
|95.||Hidenari Hirata, Keishi Sugimachi, Yusuke Takahashi, Masami Ueda, Shotaro Sakimura, Ryutaro Uchi, Junji Kurashige, Yuki Takano, Sho Nanbara, Hisateru Komatsu, Tomoko Saito, Shinden Yoshiaki, Iguchi Tomohiro, Hidetoshi Eguchi, Kazushige Atsumi, Katsumi Sakamoto, Toshio Doi, Masakazu Hirakawa, Hiroshi Honda, Koshi Mimori, Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma., Ann Surg Oncol., 10.1245/s10434-014-4242-0, 2014.11, BACKGROUND:
Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC).
The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated.
Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation.
Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties..
|96.||Masami Ueda, Yusuke Takahashi, Shinden Yoshiaki, Shotaro Sakimura, Hidenari Hirata, Ryutaro Uchi, Yuki Takano, Junji Kurashige, Iguchi Tomohiro, Hidetoshi Eguchi, Keishi Sugimachi, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori, Koshi Mimori, Prognostic Significance of High Mobility Group Box 1 (HMGB1) Expression in Patients with Colorectal Cancer, ANTICANCER RESEARCH, 34, 10, 5357-5362, 2014.10.|
|97.||Atsushi Hamabe, Masamitsu Konno, Nobuhiro Tanuma, Hiroshi Shima, Kenta Tsunekuni, Koichi Kawamoto, Naohiro Nishida, Jun Koseki, Koshi Mimori, Noriko Gotoh, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori, Hideshi Ishii, Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial-mesenchymal transition, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 10.1073/pnas.1407717111, 111, 43, 15526-15531, 2014.10, Pyruvate kinase M2 (PKM2) is an alternatively spliced variant of the pyruvate kinase gene that is preferentially expressed during embryonic development and in cancer cells. PKM2 alters the final rate-limiting step of glycolysis, resulting in the cancer-specific Warburg effect (also referred to as aerobic glycolysis). Although previous reports suggest that PKM2 functions in nonmetabolic transcriptional regulation, its significance in cancer biology remains elusive. Here we report that stimulation of epithelial-mesenchymal transition (EMT) results in the nuclear translocation of PKM2 in colon cancer cells, which is pivotal in promoting EMT. Immunoprecipitation and LC-electrospray ionized TOF MS analyses revealed that EMT stimulation causes direct interaction of PKM2 in the nucleus with TGF-β-induced factor homeobox 2 (TGIF2), a transcriptional cofactor repressor of TGF-β signaling. The binding of PKM2 with TGIF2 recruits histone deacetylase 3 to the E-cadherin promoter sequence, with subsequent deacetylation of histone H3 and suppression of E-cadherin transcription. This previously unidentified finding of the molecular interaction of PKM2 in the nucleus sheds light on the significance of PKM2 expression in cancer cells. .|
|98.||Hiroyuki Kida, Yuki Takano, Ken Yamamoto, Masaki Mori, Katsuhiko Yanaga, Jun-Ichi Tanaka, Shin-Ei Kudo, Koshi Mimori, A single nucleotide polymorphism in fibronectin 1 determines tumor shape in colorectal cancer., Oncol Rep. , 10.3892/or.2014.3251, 32, 2, 548-552, 2014.08, Depressed and flat surface lesions are not easy to identify with routine colonoscopies during screening for colorectal cancer (CRC). Identifying clinically relevant genes that influence tumor shape could be useful when screening for the presence of depressed lesions. Total RNA was extracted from tumor cells collected by laser microdissection from the primary lesions of 146 CRC cases. Microarray analysis was performed to identify genes that were differentially expressed between depressed and elevated tumors. Single nucleotide polymorphism (SNP) analysis of genomic DNA from the peripheral blood of 67 CRC patients was then used to associate polymorphisms with the occurrence of depressed tumors. Microarray analysis revealed significantly higher expression of the fibronectin 1 (FN1) gene in 129 depressed-type tumors and lesions compared to 17 elevated-type tumors. FN1-abundant CRC tumors were large with a significantly higher incidence of lymphatic permeation. SNP analysis indicated that 44 tumors with a GG genotype at SNP rs6707530 showed significantly higher FN1 expression than did 23 tumors with GT/TT genotypes (p<0.05). The product of the FN1 gene (located at 2q34) is involved in cell adhesion, migration and metastasis in mesenchymal tumors. Abundant expression of FN1 may allow cancer cells to invade deeper layers, which would eventually define tumor shape. Identification of this SNP in blood samples may facilitate disease diagnosis and allow prediction of the presence of depressed tumors in the colorectal epithelium before a colon fiberscope examination..|
|99.||Koshi Mimori, Aberrant Expression of Plastin-3 Via Copy Number Gain Induces the Epithelial-Mesenchymal Transition in Circulating Colorectal Cancer Cells., ANNALS OF SURGICAL ONCOLOGY, 2014.01.|
|100.||Koshi Mimori, Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers., Br J Cancer. 2014 Jan 7;110(1):164-71. doi: 10.1038/bjc.2013.698. Epub 2013 Nov 5., 2014.01, We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.
We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR.
CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-β signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients.
PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients..
|101.||Koshi Mimori, Up-regulation of NEK2 by MicroRNA-128 Methylation is Associated with Poor Prognosis in Colorectal Cancer, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-013-3264-3, 21, 1, 205-212, 2014.01.|
|102.||Koshi Mimori, Contrasting Expression Patterns of Histone mRNA and microRNA 760 in Patients with Gastric Cancer, CLINICAL CANCER RESEARCH, 10.1158/1078-0432.CCR-12-3186, 19, 23, 6438-6449, 2013.12.|
|103.||Koshi Mimori, Cell Cycle-Dependent Rho GTPase Activity Dynamically Regulates Cancer Cell Motility and Invasion In Vivo, PLOS ONE, 10.1371/journal.pone.0083629, 8, 12, 2013.12.|
|104.||Koshi Mimori, PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression, BRITISH JOURNAL OF CANCER, 10.1038/bjc.2013.561, 109, 8, 2199-2206, 2013.10.|
|105.||Koshi Mimori, EGFR gets in the way of microRNA biogenesis, CELL RESEARCH, 10.1038/cr.2013.87, 23, 10, 1157-1158, 2013.10.|
|106.||Koshi Mimori, CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer, GENOME RESEARCH, 10.1101/gr.152942.112, 23, 9, 1446-1461, 2013.09.|
|107.||Koshi Mimori, Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis, Cancer Res, 73, 7, 2059-2069, 2013.04.|
|108.||Iwaya Takeshi, Yokobori Takehiko, Nishida, Naohiro, Sudo Tomoya, Fumiaki Tanaka, Shibata Kohei, Sawada, Genta, Takahashi, Yusuke, Ishibashi, Masahisa, Wakabayashi, Go, Mori, Masaki, Koshi Mimori, Downregulation of miR-144 is associated with colorectal cancer progression via activation of mTOR signaling pathway, CARCINOGENESIS, 10.1093/carcin/bgs288, 33, 12, 2391-2397, 2012.12.|
|109.||Nishida, Naohiro, Yamashita, Shinya, Koshi Mimori, Sudo Tomoya, Fumiaki Tanaka, Shibata Kohei, Yamamoto, Hirofumi, Ishii, Hideshi, Doki, Yuichiro, Mori, Masaki, MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-012-2246-1, 19, 9, 3065-3071, 2012.09.|
|110.||Ishimaru, Shinya, Koshi Mimori, Ken Yamamoto, Hiroshi Inoue, Imoto, Seiya, Shuichi; Yamaguchi, Rui; Sato, Sato Tetsuya, Toh, Hiroyuki, Iinuma, Hisae, Toyoki Maeda, Ishii, Hideshi, Suzuki, Sadao, Tokudome, Shinkan, Watanabe, Masahiko, Tanaka, Jun-ichi, Kudo, Shin-ei, Sugihara, Ken-ichi, Hase, Kazuo, Mochizuki, Hidetaka, Increased Risk for CRC in Diabetic Patients with the Nonrisk Allele of SNPs at 8q24, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-012-2278-6, 19, 9, 2853-2858, 2012.09.|
|111.||Yokobori, Takehiko, Koshi Mimori, Iwatsuki, Masaaki, Ishii, Hideshi, Fumiaki Tanaka, Sato Tetsuya, Toh, Hiroyuki, Sudo Tomoya, Iwaya, Takeshi, Tanaka, Yoichi, Onoyama, Ichiro, Kuwano, Hiroyuki, Nakayama, Keiichi I., Mori, Masaki, Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma, INTERNATIONAL JOURNAL OF ONCOLOGY, 10.3892/ijo.2012.1436, 41, 1, 253-259, 2012.07.|
|112.||Nishida N, Nagahara M, Sato T, Mimori K, Sudo T, Tanaka F, Shibata K, Ishii H, Sugihara K, Doki Y, Mori M., Microarray Analysis of Colorectal Cancer Stromal Tissue Reveals Upregulation of Two Oncogenic miRNA Clusters., Clin Cancer Res, 18, 11, 3054-70, 2012.06, Cancer stroma plays an important role in the progression of cancer. Although alterations in miRNA expression have been explored in various kinds of cancers, the expression of miRNAs in cancer stroma has not been explored in detail.
Using a laser microdissection technique, we collected RNA samples specific for epithelium or stroma from 13 colorectal cancer tissues and four normal tissues, and miRNA microarray and gene expression microarray were carried out. The expression status of miRNAs was confirmed by reverse transcriptase PCR. Furthermore, we investigated whether miRNA expression status in stromal tissue could influence the clinicopathologic factors.
Oncogenic miRNAs, including two miRNA clusters, miR-17-92a and miR-106b-25 cluster, were upregulated in cancer stromal tissues compared with normal stroma. Gene expression profiles from cDNA microarray analyses of the same stromal tissue samples revealed that putative targets of these miRNA clusters, predicted by Target Scan, such as TGFBR2, SMAD2, and BMP family genes, were significantly downregulated in cancer stromal tissue. Downregulated putative targets were also found to be involved in cytokine interaction and cellular adhesion. Importantly, expression of miR-25 and miR-92a in stromal tissues was associated with a variety of clinicopathologic factors.
Oncogenic miRNAs were highly expressed in cancer stroma. Although further validation is required, the finding that stromal miRNA expression levels were associated with clinicopathologic factors suggests the possibility that miRNAs in cancer stroma are crucially involved in cancer progression. Clin Cancer Res; 18(11); 3054-70. ©2012 AACR..
|113.||Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, Tanaka F, Shibata K, Suzuki A, Komune S, Miyano S, Mori M., Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers., Cancer Res, 71, 20, 6320-6, 2011.08, The functional impact of recently discovered long noncoding RNAs (ncRNAs) in human cancer remains to be clarified. One long ncRNA which has attracted attention is the Hox transcript antisense intergenic RNA termed HOTAIR, a long ncRNA expressed from the developmental HOXC locus located on chromosome 12q13.13. In cooperation with Polycomb complex PRC2, the HOTAIR long ncRNA is reported to reprogram chromatin organization and promote breast cancer metastasis. In this study, we examined the status and function of HOTAIR in patients with stage IV colorectal cancer (CRC) who have liver metastases and a poor prognosis. HOTAIR expression levels were higher in cancerous tissues than in corresponding noncancerous tissues and high HOTAIR expression correlated tightly with the presence of liver metastasis. Moreover, patients with high HOTAIR expression had a relatively poorer prognosis. In a subset of 32 CRC specimens, gene set enrichment analysis using cDNA array data revealed a close correlation between expression of HOTAIR and members of the PRC2 complex (SUZ12, EZH2, and H3K27me3). Our findings suggest that HOTAIR expression is associated with a genome-wide reprogramming of PRC2 function not only in breast cancer but also in CRC, where upregulation of this long ncRNA may be a critical element in metastatic progression..|
|114.||Nishida N, Mimori K, Fabbri M, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Mori M., MicroRNA-125a-5p is an independent prognostic factor in gastric cancer,and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab., Clin Cancer Res., 17, 9, 2725-33, 2011.05.|
|115.||Nishida N, Mimori K, Fabbri M, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Mori M., MicroRNA-125a-5p is an independent prognostic factor in gastric cancer,and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab., Clin Cancer Res., 17, 9, 2725-33, 2011.05.|
|116.||Miyoshi N, Ishii H, Nagano H, Haraguchi, Dewi DL, Kano Y Nishikawa S, Tanemura T, Mimori K, Tanaka F, Saito T, Nishimura J; Takemasa I, Mizusima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. , Reprogramming of mouse and human cells to pluripotency using mature microRNAs. , Cell Stem Cell, 2011.05.|
|117.||Mimori K*, Tahara K*, Iinuma H, Iwatsuki M, Yokobori T, Ishii H, Anai H, Kitano S,Mori M, Serum Matrix-Metalloproteinase-1 is a Bona Fide Prognostic Marker for Colorectal Cancer., Ann Surg Oncol , 17, 12, 3362-9., 2011.05.|
|118.||Kogo R , Mimori K, Tanaka F, Komune S, Mori M, Clinical significance of miR-146a in gastric cancer cases. , Clin Cancer Res, 2011.05.|
|119.||Kogo R , Mimori K, Tanaka F, Komune S, Mori M, Clinical significance of miR-146a in gastric cancer cases. , Clin Cancer Res, 2011.05.|
|120.||Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, Nozawa K, Ishihara Matsuda KN, Fukushima R, Okinaga K, Sasako M, Mori M, Reply to B Faltas et al., J Clin Oncol, 2011.05.|
|121.||Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, Matsuda K, Fukushima R, Okinaga K, Sasako M, Mori M., Clinical Significance of Circulating Tumor Cells Including Cancer Stem-like Cells in Peripheral Blood for Recurrence and Prognosis in Colorectal Cancer Patients with Dukes stage B and C., J Clin Oncol, 29, 1547-55, 2011.05.|
|122.||Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, Itoh B, Wangjia J, Komatsu Y, Yang YR, Hikasa H, Horie Y, Yamashita T, Kamijo T, Zhang Y, Prives C, Nakano T, Mak TW, Sasaki T, Maehama T, Mori M, Suzuki A. , Regulation of the MDM2-p53 Pathway and Tumor Growth by PICT1/GLTSCR2 via Nucleolar RPL11., Nat Med, 2011.04.|
|123.||Mimori K*, Ota D*, Yokobori T, Iwatsuki M, Kataoka A, Masuda N, Ishii H, Ohno S,Mori S, Identification of Recurrence-Related microRNAs in the Bone Marrow of Breast Cancer Patients. , Int J Oncol , 2010.05.|
|124.||Mimori K, Coexpression of MMP-7 and EGF receptor in colorectal cancer: an EGF receptor tyrosine kinase inhibitor is effective against MMP-7-expressing cancer cells, Clin Cancer Res, 10.1158/1078-0432.CCR-04-0849, 10, 24, 8243-8249, 2004.12.|
|125.||Mimori K, Druck T, Inoue H, Hansjuerg A, Berk L, Mori M, Huebner K, Croce CM. , Cancer-specific chromosome alterations in the constitutive fragile region FRA3B., Proc Natl Acad Sci (USA), 10.1073/pnas.96.13.7456, 96, 13, 7456-7461, 1999.06.|
|126.||Mimori K, Druck T, Inoue H, Alder H, Berk L, Mori M, Huebner K and Croce CM, Cancer-specific chromosome alterations in the constitutive fragile region FRA3B.
, Proc Natl Acad Sci (U.S.A) , 10.1073/pnas.96.13.7456, 96, 13, 7456-7461, 96: 7456-61, 1999, 1999.06.