Faculty Profiles - FUJIWARA Toshiyoshi

MISC - FUJIWARA Toshiyoshi

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Suppression of Oncolytic Adenovirus-Mediated Hepatotoxicity by Liver-Specific Inhibition of NF-κB. International journal

Mitsuhiro Machitani, Fuminori Sakurai, Keisaku Wakabayashi, Kosuke Nakatani, Masashi Tachibana, Nobuyuki Kato, Toshiyoshi Fujiwara, Hiroyuki Mizuguchi

Molecular therapy oncolytics 7 76 - 85 2017.12

Language：English

Telomerase-specific replication-competent adenoviruses (Ads), i.e., TRADs, which possess an E1 gene expression cassette driven by the human telomerase reverse transcriptase promoter, are promising agents for cancer treatment. However, even though oncolytic Ads, including TRAD, are intratumorally administered, they are disseminated from the tumor to systemic circulation, causing concern about oncolytic Ad-mediated hepatotoxicity (due mainly to leaky expression of Ad genes in liver). We reported that inhibition of nuclear factor-κB (NF-κB) leads to the suppression of replication-incompetent Ad vector-mediated hepatotoxicity via reduction of the leaky expression of Ad genes in liver. Here, to develop a TRAD with an improved safety profile, we designed a TRAD that carries a liver-specific promoter-driven dominant-negative IκBα (DNIκBα) expression cassette (TRAD-DNIκBα). Compared with a conventional TRAD, TRAD-DNIκBα showed hepatocyte-specific inhibition of NF-κB signaling and significantly reduced Ad gene expression and replication in the normal human hepatocyte cell line. TRAD-induced hepatotoxicity was largely suppressed in mice following intravenous administration of TRAD-DNIκBα. However, the replication profiles and oncolytic activities of TRAD-DNIκBα were comparable with those of the conventional TRAD in human non-hepatic tumor cells. These results indicate that oncolytic Ads containing the liver-specific DNIκBα expression cassette have improved safety profiles without inhibiting oncolytic activities.

DOI： 10.1016/j.omto.2017.10.003

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Iron depletion is a novel therapeutic strategy to target cancer stem cells. International journal

Takayuki Ninomiya, Toshiaki Ohara, Kazuhiro Noma, Yuki Katsura, Ryoichi Katsube, Hajime Kashima, Takuya Kato, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Fumiaki Kimura, Ling Chen, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara

Oncotarget 8 ( 58 ) 98405 - 98416 2017.11

Language：English

Adequate iron levels are essential for human health. However, iron overload can act as catalyst for the formation of free radicals, which may cause cancer. Cancer stem cells (CSCs), which maintain the hallmark stem cell characteristics of self-renewal and differentiation capacity, have been proposed as a driving force of tumorigenesis and metastases. In the present study, we investigated the role of iron in the proliferation and stemness of CSCs, using the miPS-LLCcm cell model. Although the anti-cancer agents fluorouracil and cisplatin suppressed the proliferation of miPS-LLCcm cells, these drugs did not alter the expression of stemness markers, including Nanog, SOX2, c-Myc, Oct3/4 and Klf4. In contrast, iron depletion by the iron chelators deferasirox and deferoxamine suppressed the proliferation of miPS-LLCcm cells and the expression of stemness markers. In an allograft model, deferasirox inhibited the growth of miPS-LLCcm implants, which was associated with decreased expression of Nanog and Sox2. Altogether, iron appears to be crucial for the proliferation and maintenance of stemness of CSCs, and iron depletion may be a novel therapeutic strategy to target CSCs.

DOI： 10.18632/oncotarget.21846

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The characteristics and outcomes of small bowel adenocarcinoma: a multicentre retrospective observational study

Hiroyuki Sakae, Hiromitsu Kanzaki, Junichiro Nasu, Yutaka Akimoto, Kazuhiro Matsueda, Masao Yoshioka, Masahiro Nakagawa, Shinichiro Hori, Masafumi Inoue, Tomoki Inaba, Atsushi Imagawa, Masahiro Takatani, Ryuta Takenaka, Seiyu Suzuki, Toshiyoshi Fujiwara, Hiroyuki Okada

BRITISH JOURNAL OF CANCER 117 ( 11 ) 1607 - 1613 2017.11

Language：English Publisher：NATURE PUBLISHING GROUP

Background: Small bowel adenocarcinoma (SBA) is a rare malignancy that accounts for 1-2% of gastrointestinal tumours. We investigated the clinical characteristics, outcomes, and prognostic factors of primary SBA.
Methods: We retrospectively analysed the characteristics and clinical courses of 205 SBA patients from 11 institutions in Japan between June 2002 and August 2013.
Results: The primary tumour was in the duodenum and jejunum/ileum in 149 (72.7%) and 56 (27.3%) patients, respectively. Sixty-four patients (43.0%) with duodenal adenocarcinoma were asymptomatic and most cases were detected by oesophagogastroduodenoscopy (EGD), which was not specifically performed for the detection or surveillance of duodenal tumours. In contrast, 47 patients (83.9%) with jejunoileal carcinoma were symptomatic. The 3-year survival rate for stage 0/I, II, III, and IV cancers was 93.4%, 73.1%, 50.9%, and 15.1%, respectively. Multivariate analysis revealed performance status 3-4, high carcinoembryonic antigen, high lactate dehydrogenase (LDH), low albumin, symptomatic at diagnosis, and stage III/IV disease were independent factors for overall survival (OS). Ten patients (18.5%) with stage IV disease were treated with a combination of resection of primary tumour, local treatment of metastasis, and chemotherapy; this group had a median OS of 36.9 months.
Conclusions: Although most SBA patients were diagnosed with symptomatic, advanced stage disease, some patients with duodenal carcinoma were detected in early stage by EGD. High LDH and symptomatic at diagnosis were identified as novel independent prognostic factors for OS. The prognosis of advanced SBA was poor, but combined modality therapy with local treatment of metastasis might prolong patient survival.

DOI： 10.1038/bjc.2017.338

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Novel therapeutic strategy for human epidermal growth factor receptor 2-positive gastric cancer

Nobuhiko Kanaya, Shinji Kuroda, Tetsushi Kubota, Toshiaki Morihiro, Satoru Kikuchi, Masahiko Nishizaki, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara

Japanese Journal of Cancer and Chemotherapy 44 ( 10 ) 883 - 885 2017.10

Language：Japanese Publishing type：Book review, literature introduction, etc. Publisher：Japanese Journal of Cancer and Chemotherapy Publishers Inc.

Trastuzumab (Tmab), a humanized monoclonal antibody that selectively targets human epidermal growth factor receptor 2 (HER2), is currently used in the clinical setting for the treatment of both breast and gastric cancer. While Tmab has shown improvements in patient prognoses, acquired resistance to this agent remains an issue. While some novel HER2-targeted agents have been approved for clinical use in breast cancer, no such agent has shown treatment efficacy for gastric malignancies with Tmab-resistance. Nanotechnology, which has progressed rapidly, has been applied to medical fields in recent years. Gold nanopartides, which are characterized by their in vivo stability and ease of surface modification, have been reported to show efficacy as the carriers of therapeutic agents, such as drugs, antibodies, peptides, and nucleic acids. In this work, we developed Tmab-conjugated gold nanopartides and demonstrate their efficacy for the treatment of HER2-positive, Tmab-resistant gastric cancer cell lines. Our findings demonstrate that Tmab-conjugated gold nanopartides have the potential to be a novel HER2-targeted therapeutic agent.

Scopus

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食道胃接合部癌に対する胸腔鏡下下縦隔郭清・腹腔鏡下下部食道噴門側胃切除 (特集食道胃接合部癌の手術) -- (経裂孔アプローチ)

野間和広, 白川靖博, 田辺俊介, 黒田新士, 西﨑正彦, 藤原俊義

手術 = Operation 71 ( 11 ) 1525 - 1529 2017.10

Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system

Katsuyuki Aoyama, Shinji Kuroda, Toshiaki Morihiro, Nobuhiko Kanaya, Tetsushi Kubota, Yoshihiko Kakiuchi, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

SCIENTIFIC REPORTS 7 ( 1 ) 1 - 8 2017.10

Language：English Publisher：NATURE PUBLISHING GROUP

Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery was investigated. Lipo-pTS, which has a diameter of 40-50 nm, showed potent antitumor effects on HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS reduced production of adenovirus-neutralizing antibodies (AdNAbs) after intravenous administration into immune-competent mice compared to TelomeScan, and even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent suitable for systemic delivery with the characteristics of CAR-independent antitumor activity and a stealth effect on the immune system.

DOI： 10.1038/s41598-017-14717-x

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Living Donor Liver Transplantation for Acute Liver Failure: Comparing Guidelines on the Prediction of Liver Transplantation

Kazuhiro Yoshida, Yuzo Umeda, Akinobu Takaki, Takeshi Nagasaka, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Kosei Takagi, Tetsuya Yasunaka, Hiroyuki Okada, Takahito Yagi, Toshiyoshi Fujiwara

ACTA MEDICA OKAYAMA 71 ( 5 ) 381 - 390 2017.10

Language：English Publisher：OKAYAMA UNIV MED SCHOOL

Determining the indications for and timing of liver transplantation (LT) for acute liver failure (ALF) is essential. The King's College Hospital (KCH) guidelines and Japanese guidelines are used to predict the need for LT and the outcomes in ALF. These guidelines' accuracy when applied to ALF in different regional and etiological backgrounds may differ. Here we compared the accuracy of new (2010) Japanese guidelines that use a simple scoring system with the 1996 Japanese guidelines and the KCH criteria for living donor liver transplantation (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub-acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the accuracies of the 3 guidelines' criteria for ALF. The overall 1-year survival rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new Japanese guidelines could identify 13 acute-type ALF patients for LT, based on the timing of encephalopathy onset. Using the previous Japanese guidelines, although the same 13 acute-type ALF patients (72%) had indications for LT, only 4 patients were indicated at the 1st step, and it took an additional 5 days to decide the indication at the 2nd step in the other 9 cases. Our findings showed that the new Japanese guidelines can predict the indications for LT and provide a reliable alternative to the previous Japanese and KCH guidelines.

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Preoperative Controlling Nutritional Status (CONUT) Score for Assessment of Prognosis Following Hepatectomy for Hepatocellular Carcinoma

Kosei Takagi, Takahito Yagi, Yuzo Umeda, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Hiroyuki Araki, Toshiyoshi Fujiwara

WORLD JOURNAL OF SURGERY 41 ( 9 ) 2353 - 2360 2017.9

Language：English Publisher：SPRINGER

Immune-nutritional status has been recently reported as a prognostic factor in hepatocellular carcinoma (HCC). The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to investigate the efficacy of the CONUT score as a prognostic factor in patients undergoing hepatectomy for HCC.
A total of 295 patients who underwent curative hepatectomy for HCC between January 2007 and December 2014 were retrospectively analyzed. Patients were divided into two groups according to the CONUT score. The impact of the CONUT score on clinicopathological, surgical, and long-term outcomes was evaluated. Subsequently, the impact of prognostic factors, including the CONUT score, associated with outcomes was assessed using multivariate analyses.
Of 295 patients, 118 (40%) belonged to the high CONUT group (CONUT score 3). The high CONUT group had a significantly lower 5-year recurrence-free survival rate than the low CONUT group (27.9 vs. 41.4%, p = 0.011) and a significantly lower 5-year overall survival rate (61.9 vs. 74.9%, p = 0.006). In multivariate analyses of prognostic factors, the CONUT score was an independent predictor of recurrence-free survival (hazard ratio = 1.64, p = 0.006) and overall survival (hazard ratio = 2.50, p = 0.001).
The CONUT score is a valuable preoperative predictor of survival in patients undergoing hepatectomy for HCC.

DOI： 10.1007/s00268-017-3985-8

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IS POOR OUTCOME OF LIVING DONOR LIVER TRANSPLANTATION FOR PRIMARY SCLEROSING CHOLANGITIS THE NATURE OF THE DISEASE ITSELF OR INSUFFICIENT IMMUNOSUPPRESSION?

Takahito Yagi, Daisuke Nobuoka, Yuzo Umeda, Ryuichi Yoshida, Takashi Kuise, Kosei Takagi, Kenjiro Kumano, Toshiyoshi Fujiwara

TRANSPLANT INTERNATIONAL 30 288 - 289 2017.9

SURGICAL OUTCOMES OF LIVING DONOR LIVER SURGERY: TECHNICAL KNACK FOR ZERO MORBIDITY

Takashi Kuise, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Kenjiro Kumano, Takeshi Koujima, Kosei Takagi, Toshiyoshi Fujiwara, Takahito Yagi

TRANSPLANT INTERNATIONAL 30 128 - 129 2017.9

PREDICTION OF SALVAGE LIVER TRANSPLANTATION FOR HCC RECURRENCE: WHEN AND WHICH PATIENT SHOULD WE DECIDE TRANSPLANT?

Yuzo Umeda, Takahito Yagi, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Kenjiro Kumano, Takeshi Koujima, Kosei Takagi, Takeshi Nagasaka, Toshiyoshi Fujiwara

TRANSPLANT INTERNATIONAL 30 180 - 180 2017.9

ANALYSIS OF PROGNOSTIC FACTORS OF PEDIATRIC LIVING DONOR LIVER TRANSPLANTATION: A SINGLE CENTER EXPERIENCE OF MORTALITY ZERO TRANSPLANTATION FOR CHOLESTATIC DISEASE

Takahito Yagi, Kosei Takagi, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Kenjiro Kumano, Mari Yoshida, Toshiyoshi Fujiwara

TRANSPLANT INTERNATIONAL 30 158 - 159 2017.9

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction

Yasuaki Yamakawa, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER SCIENCE 108 ( 9 ) 1870 - 1880 2017.9

Language：English Publisher：WILEY

Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP-301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP-301 and ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor-mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation.

DOI： 10.1111/cas.13316

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SNORA21 - An Oncogenic Small Nucleolar RNA, with a Prognostic Biomarker Potential in Human Colorectal Cancer

Kazuhiro Yoshida, Shusuke Toden, Wenhao Weng, Kunitoshi Shigeyasu, Jinsei Miyoshi, Jacob Turner, Takeshi Nagasaka, Yanlei Ma, Tetsuji Takayama, Toshiyoshi Fujiwara, Ajay Goel

EBIOMEDICINE 22 68 - 77 2017.8

Language：English Publisher：ELSEVIER SCIENCE BV

Background: Emerging evidence indicates that small nucleolar RNAs (snoRNAs) play a central role in oncogenesis. Herein, we systematically evaluated expression profiles of snoRNAs in colorectal cancer (CRC) and investigated their clinical and functional role in this malignancy.
Methods: We compared expression levels of snoRNAs between cancer and normal tissues using publicly available datasets and identified the most differentially expressed and commonly upregulated snoRNAs in CRC. These results were examined in 489 colorectal tissues to assess their clinical significance, followed by a series of in vitro and in vivo experiments to evaluate the functional role of candidate snoRNAs.
Results: Usingmultiple RNA profiling datasets, we identified consistent overexpression of SNORA21 in CRC. In the clinical validation cohorts, the expression level of SNORA21was upregulated in colorectal adenomas and cancers. Furthermore, elevated SNORA21 emerged as an independent factor for predicting poor survival. Both in vitro and in vivo experiments revealed that CRISPR/Cas9-mediated inhibition of SNORA21 expression resulted in decreased cell proliferation and invasion through modulation of multiple cancer related pathways.
Conclusions: Wesystematically identified SNORA21 as a key oncogenic snoRNA in CRC, which plays an important role in cancer progression, and might serve as an important prognostic biomarker in CRC. (C) 2017 The Authors. Published by Elsevier B.V.

DOI： 10.1016/j.ebiom.2017.07.009

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Training system for laparoscopy-assisted distal gastrectomy

Shinji Kuroda, Satoru Kikuchi, Naoto Hori, Shuichi Sakamoto, Tetsuya Kagawa, Megumi Watanabe, Tetsushi Kubota, Kazuya Kuwada, Michihiro Ishida, Hiroyuki Kishimoto, Futoshi Uno, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

SURGERY TODAY 47 ( 7 ) 802 - 809 2017.7

Language：English Publisher：SPRINGER

Purpose Laparoscopy-assisted distal gastrectomy (LADG) is likely to become a standard procedure for gastric cancer, which highlights the importance of establishing a training system in which even inexperienced surgeons can perform this procedure safely. This study assesses our training system for LADG based on short-term surgical outcomes.
Methods We evaluated retrospectively the short-term outcomes of 100 consecutive LADGs with curative D1/D1+ lymph node dissection. Our training system was assessed based on the learning curve of trainees, and factors related to achieving good-quality operations were analyzed statistically.
Results Overall, postoperative complications developed in 10 patients (10%), and included one case of anastomotic leakage (1%) and one case of pancreatic fistula (1%). The learning curve of the trainees plateaued after 10 operator cases in terms of operation time. The importance of the trainer's position was also confirmed by the result that the operation time was significantly longer when trainees with <= 10 operator cases performed LADG with a trainer as scopist vs. a trainer as the first assistant. Univariate and multivariate analyses revealed that > 10 operator cases were the most important factor for achieving good-quality operations.
Conclusion These results show that our current LADG procedure and training system are appropriate and effective.

DOI： 10.1007/s00595-016-1439-9

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Circular RNA ciRS-7-A Promising Prognostic Biomarker and a Potential Therapeutic Target in Colorectal Cancer

Wenhao Weng, Qing Wei, Shusuke Toden, Kazuhiro Yoshida, Takeshi Nagasaka, Toshiyoshi Fujiwara, Sanjun Cai, Huanlong Qin, Yanlei Ma, Ajay Goel

CLINICAL CANCER RESEARCH 23 ( 14 ) 3918 - 3928 2017.7

Language：English Publisher：AMER ASSOC CANCER RESEARCH

Purpose: Colorectal cancer is one of themost common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. As miR-7, a putative tumor-suppressor, regulates the expression of several important drivers of colorectal cancer, we analyzed the clinical significance of ciRS-7 in colorectal cancer patients.
Experimental Design: Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary colorectal cancer tissues and 44 matched normal mucosae. We subsequently confirmed its clinical relevance in an independent validation cohort (n = 165), and evaluated the effect of ciRS-7 on miR-7, and its target genes EGFR and RAF1. Functional analyses were performed in cell lines and an animal model to support clinical findings.
Results: Our data revealed that ciRS-7 was significantly upregulated in colorectal cancer tissues compared with matched normal mucosae (P = 0.0018), and its overexpression was associated with poor patient survival (P = 0.0224 and 0.0061 in the training and validation cohorts, respectively). Multivariate survival analysis revealed that ciRS-7 emerged as an independent risk factor for overall survival (P = 0.0656 and 0.0324 in the training and validation cohorts, respectively). Overexpression of ciRS-7 in HCT116 and HT29 cells led to the blocking of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted the inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes.
Conclusions: CiRS-7 is a promising prognostic biomarker in colorectal cancer patients and may serve as a therapeutic target for reducing EGFR-RAF1 activity in colorectal cancer patients. (C) 2017 AACR.

DOI： 10.1158/1078-0432.CCR-16-2541

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Gene expression profiles in BRAF V600E mutant colorectal cancer and association with SFRP2 methylation status

Kazuya Yasui, Takeshi Nagasaka, Toshiaki Toshima, Takashi Kawai, Kunitoshi Shigeyasu, Yoshiko Mori, Junko Haraga, Keiichiro Nakamura, Yuzo Umeda, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

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

Kunitoshi Shigeyasu, Shusuke Toden, Yoshinaga Okugawa, Jinsei Miyoshi, Takeshi Nagasaka, Toshiyoshi Fujiwara, Leilei Chen, Ajay Goel

CANCER RESEARCH 77 2017.7

Tumorigenesis of murine iPS cell is prevented by iron depletion with downregulation of stemness markers

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 RESEARCH 77 2017.7

Cancer-associated fibroblasts contribute to tumor immunosuppression by regulating tumor-infiltrating lymphocytes

Takuya Kato, Kazuhiro Noma, Hajime Kashima, Yuki Katsura, Hiroaki Sato, Takayuki Ninomiya, Toshiaki Ohara, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

CANCER RESEARCH 77 2017.7

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MISC - FUJIWARA Toshiyoshi