Faculty Profiles - FUJIWARA Toshiyoshi

MISC - FUJIWARA Toshiyoshi

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Visualization of epithelial-mesenchymal transition in inflammatory microenvironment-colorectal cancer network in vitro and in vivo

Hiroshi Tazawa, Takeshi Ieda, Shuya Yano, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Hiroyuki Kishimoto, Masahiko Nishizaki, Shunsuke Kagawa, Takashi Saitou, Takeshi Imamura, Toshiyoshi Fujiwara

CANCER RESEARCH 78 ( 13 ) 2018.7

Dual-targeting photoimmunotherapy (NIR-PIT) for esophageal cancer cells and cancer-associated fibroblasts (CAFs)

Hiroaki Sato, Kazuhiro Noma, Toru Narusaka, Satoshi Komoto, Yuki Katsura, Takuya Kato, Takayuki Ninomiya, Toshiaki Ohara, Hiroshi Tazawa, Yasuhiro Shirakawa, Hisataka Kobayashi, Toshiyoshi Fujiwara

CANCER RESEARCH 78 ( 13 ) 2018.7

Iron depletion suppress the stemness markers and functions of cancer stem cells

Toshiaki Ohara, Yuki Katsura, Kazuhiro Noma, Toru Narusaka, Takuya Kato, Hiroaki Sato, Satoshi Komoto, Yasuko Tomono, Takayuki Ninomiya, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

CANCER RESEARCH 78 ( 13 ) 2018.7

Development of near-infrared photoimmunotherapy targeting GD2-positive neuroblastoma

Hiroshi Nouso, Hiroshi Tazawa, Terutaka Tanimoto, Morimichi Tani, Takanori Oyama, Hiroaki Sato, Kazuhiro Noma, Shunsuke Kagawa, Hisataka Kobayashi, Takuo Noda, Toshiyoshi Fujiwara

CANCER RESEARCH 78 ( 13 ) 2018.7

Transforming growth factor-b-induced epithelial-mesenchymal transition is attenuated by telomerase-specific oncolytic virotherapy in human esophageal cancer

Tomoya Masuda, Hiroshi Tazawa, Takeshi Ieda, Yuuri Hashimoto, Shunsuke Tanabe, Kazuhiro Noma, Yasuo Urata, Shunsuke Kagawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

CANCER RESEARCH 78 ( 13 ) 2018.7

Cancer-associated fibroblasts regulate intratumoral CD8(+)/FoxP3(+) T cells via interleukin 6 in the tumor immune microenvironment

Takuya Kato, Kazuhiro Noma, Yuki Katsura, Hiroaki Sato, Satoshi Kohmoto, Toshiaki Ohara, Hiroshi Tazawa, Yasuhiro Shirakawa, Masaru Inagaki, Toshiyoshi Fujiwara

CANCER RESEARCH 78 ( 13 ) 2018.7

【膵癌に挑む】膵癌に対するウイルス療法の実用化に向けて

國府島健, 田澤大, 杭瀬崇, 吉田龍一, 楳田祐三, 藤原俊義

消化器外科 41 ( 6 ) 931 - 938 2018.5

腫瘍融解ウイルス併用放射線療法による食道癌治療成績向上への取り組み

田辺俊介, 白川靖博, 前田直見, 二宮卓之, 黒田新士, 野間和広, 楳田祐三, 田澤大, 香川俊輔, 藤原俊義

日本外科学会定期学術集会抄録集 118回 944 - 944 2018.4

A multi-institution phase II study of docetaxel and S-1 in combination with trastuzumab for HER2-positive advanced gastric cancer (DASH study)

Shunsuke Kagawa, Atsushi Muraoka, Takeshi Kambara, Hiroshi Nakayama, Ryosuke Hamano, Norimitsu Tanaka, Kazuhiro Noma, Kohji Tanakaya, Hiroyuki Kishimoto, Kunitoshi Shigeyasu, Shinji Kuroda, Satoru Kikuchi, Kazuya Kuwada, Masahiko Nishizaki, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

Cancer Chemotherapy and Pharmacology 81 ( 2 ) 387 - 392 2018.2

Language：English Publisher：Springer Verlag

Background: Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated. Methods: This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m2 on day 1 of each cycle. S-1 was administered at a dosage based on body surface area for 14 days in a 3-weekly cycle. The primary endpoint was progression-free survival (PFS). Results: A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1–10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3–4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%). Conclusion: Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC.

DOI： 10.1007/s00280-017-3505-4

Tumour-infiltrating lymphocytes (TILs)-related genomic signature predicts chemotherapy response in breast cancer

Mariko Kochi, Takayuki Iwamoto, Naoki Niikura, Giampaolo Bianchini, Shinobu Masuda, Taeko Mizoo, Tomohiro Nogami, Tadahiko Shien, Takayuki Motoki, Naruto Taira, Yutaka Tokuda, Hiroyoshi Doihara, Junji Matsuoka, Toshiyoshi Fujiwara

Breast Cancer Research and Treatment 167 ( 1 ) 39 - 47 2018.1

Language：English Publisher：Springer New York LLC

Purpose: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. Methods: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS. The TILs-GS were compared with breast cancer subtype and were evaluated predictive values for prognosis and response to therapies. Results: Higher TILs-GS expressions were observed for triple-negative and human epidermal growth factor receptor 2 (HER2) positive (+) breast cancers, compared to the luminal types (P &lt
0.001). With the exception of HER2+, the TILs-GS had no prognostic value in subtypes of breast cancers. The Wilcoxon test revealed significantly different TILs-GS levels between the cases with pathological complete response (pCR) and residual disease after anthracycline and taxane-based neoadjuvant chemotherapy, with the exception of the luminal-low proliferation subtype. In the multivariate analysis, pCR was independently associated with smaller tumour size, higher histological grade, ER negativity, HER2 positivity and higher TILs-GS scores (OR 2.02, 95% CI 1.30–3.14, P = 0.025). Conclusions: TILs-GS was associated with stromal and intra-tumour TILs levels, as evaluated using HE, which predicted prognosis and chemotherapy response in several breast cancer subtypes. Further studies are needed to perform stratification according to TILs-GS levels and the conventional breast cancer subtypes.

DOI： 10.1007/s10549-017-4502-3

Molecular radiosensitization of p53-armed telomerase-dependent oncolytic adenovirus against human soft-tissue sarcoma

Tadashi Komatsubara, Hiroshi Tazawa, Yusuke Mochizuki, Kazuhisa Sugiu, Toshinori Omori, Yasuaki Yamakawa, Syuhei Osaki, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER SCIENCE 109 454 - 454 2018.1

Detection of circulating tumor cells in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells. International journal

Masahiro Takakura, Takeo Matsumoto, Mitsuhiro Nakamura, Yasunari Mizumoto, Subaru Myojyo, Rena Yamazaki, Jyunpei Iwadare, Yukiko Bono, Shunsuke Orisaka, Takeshi Obata, Takashi Iizuka, Kyosuke Kagami, Kentaro Nakayama, Hideki Hayakawa, Fuminori Sakurai, Hiroyuki Mizuguchi, Yasuo Urata, Toshiyoshi Fujiwara, Satoru Kyo, Toshiyuki Sasagawa, Hiroshi Fujiwara

Cancer science 109 ( 1 ) 231 - 240 2018.1

Language：English

Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (-) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.

DOI： 10.1111/cas.13449

Novel evidence for AZIN1 RNA editing-mediated oncogenic role in colorectal cancer

Kunitoshi Shigeyasu, Sho Takeda, Yoshinaga Okugawa, Yuji Toiyama, Takeshi Nagasaka, Hiroshi Tazawa, Shunsuke Kagawa, Ajay Goel, Toshiyoshi Fujiwara

CANCER SCIENCE 109 529 - 529 2018.1

Focusing on the antitumor effect of iron chelator, specifically suppressing the stemness of cancer stem cell.

Yuki Katsura, Toshiaki Ohara, Hajime Kashima, Hiroaki Sato, Takuya Kato, Takayuki Ninomiya, Kazuhiro Noma, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

CANCER SCIENCE 109 87 - 87 2018.1

Cancer-associated fibroblasts (CAFs) promote to tumor immunosuppression via IL-6 secretion.

Takuya Kato, Kazuhiro Noma, Hajime Kashima, Yuki Katsura, Hiroaki Sato, Takayuki Ninomiya, Toshiaki Ohara, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER SCIENCE 109 299 - 299 2018.1

Novel theranostic strategy: combination of fluorescence oncolytic virus and chemotherapy for scirrhous gastric cancer

Wataru Ishikawa, Satoru Kikuchi, Hiroshi Tazawa, Shinji Kuroda, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER SCIENCE 109 912 - 912 2018.1

Fluorescence-guided live cell imaging system of EMT-tumor microenvironment network in gastrointestinal cancer

Takeshi Ieda, Hiroshi Tazawa, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Takeshi Imamura, Toshiyoshi Fujiwara

CANCER SCIENCE 109 557 - 557 2018.1

Liposomally formulated indocyanine green derivative encapsulating anticancer drugs for photoinduced immunotherapy

Tetsuya Kagawa, Hiroyuki Kishimoto, Yuki Matsumi, Hiroshi Tazawa, Toshiaki Ohara, Takeshi Nagasaka, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER SCIENCE 109 755 - 755 2018.1

骨肉腫に対するp53誘導性腫瘍融解ウイルス療法による免疫原性細胞死の誘導効果

出宮光二, 田澤大, 田澤大, 望月雄介, 小松原将, 長谷井嬢, 中田英二, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 92 ( 8 ) 2018

軟部肉腫に対するp53発現腫瘍融解アデノウイルスによるアポトーシス抑制遺伝子発現の制御を介した放射線感受性増感作用の検討

小松原将, 出宮光二, 望月雄介, 長谷井嬢, 吉田晶, 中田英二, 国定俊之, 浦田泰生, 田澤大, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 92 ( 8 ) 2018

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