Faculty Profiles - FUJIWARA Toshiyoshi

MISC - FUJIWARA Toshiyoshi

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Comparison of Tumor Recurrence After Resection of Highly- and Poorly-Metastatic Triple-negative Breast Cancer in Orthotopic Nude-Mouse Models

Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara, Michael Bouvet, Robert M. Hoffman

ANTICANCER RESEARCH 37 ( 1 ) 57 - 60 2017.1

Language：English Publisher：INT INST ANTICANCER RESEARCH

Background: Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2, is a recalcitrant disease in need of effective therapy. We previously isolated highly-metastatic variants of the human TNBC cell line MDA-MB-231 using serial orthotopic implantation in nude mice. Materials and Methods: In the present report, we compared local and metastatic recurrence in lymph nodes in orthotopic nude-mouse models after bright-light surgery (BLS) of tumors from highly-metastatic variants or poorly-metastatic parental MDA-MB-231-RFP cells. Orthotopic tumors from parental MDA-MB-231 or highly-metastatic MDA-MB-231 were resected under bright light similar to an operating room. Results: After resection of primary tumors, local recurrence from highly-metastatic MDA-MB-231 cells grew more rapidly than did parental MDA-MB-231 cells. Lymph-node metastasis from highly-metastatic MDA-MB-231 cells occurred after primary tumor resection much more extensively than after parental MDAMB- 231 tumors were resected. Conclusion: The results of the present report suggest that conventional surgery under bright light was unable to control highly-metastatic compared with poorly-metastatic MDA-MB-231 TNBC.

DOI： 10.21873/anticanres.11288

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Enhanced Oncolytic Activities of the Telomerase-Specific Replication-Competent Adenovirus Expressing Short-Hairpin RNA against Dicer

Mitsuhiro Machitani, Fuminori Sakurai, Keisaku Wakabayashi, Masashi Tachibana, Toshiyoshi Fujiwara, Hiroyuki Mizuguchi

MOLECULAR CANCER THERAPEUTICS 16 ( 1 ) 251 - 259 2017.1

Language：English Publisher：AMER ASSOC CANCER RESEARCH

Oncolytic viruses have been receiving much attention as potential agents for cancer treatment. Among the various types of oncolytic viruses, the telomerase-specific replication-competent adenovirus (TRAD), which carries the tumor-specific promoter- driven E1 gene expression cassette, exhibits efficient antitumor effects. The development of a novel TRAD that shows higher replication efficiency and antitumor activity would be highly beneficial for safer and more efficient cancer therapy. We recently demonstrated that the endoribonuclease Dicer significantly inhibits the replication of wild-type adenovirus (Ad) via the processing of viral-associated (VA)-RNAs, which are Ad-encoded small noncoding RNAs, and that the knockdown of Dicer leads to enhanced VA-RNA expression and Ad replication after infection with wild-type Ad. Based on these findings, we herein developed a novel TRAD expressing shorthairpin RNA against Dicer (shDicer; TRAD-shDicer). After infection, TRAD-shDicer efficiently induced the knockdown of Dicer. TRAD-shDicer showed significantly higher replication efficiency and tumor cell lysis activity compared with the conventional TRAD in tumor cells. The Dicer expression levels and viabilities of normal cells were not altered by infection with TRAD-shDicer. These results indicate that TRAD-shDicer is a potent antitumor reagent by virtue of its enhanced oncolytic activity. (C) 2016 AACR.

DOI： 10.1158/1535-7163.MCT-16-0383

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Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study

Nobuaki Suzuki, Shoichi Hazama, Haruo Iguchi, Kazuhiro Uesugi, Hiroaki Tanaka, Kosei Hirakawa, Atsushi Aruga, Takashi Hatori, Hidenobu Ishizaki, Yuzo Umeda, Toshiyoshi Fujiwara, Tetsuya Ikemoto, Mitsuo Shimada, Kazuhiko Yoshimatsu, Ryoichi Shimizu, Hiroto Hayashi, Koichiro Sakata, Hiroko Takenouchi, Hiroto Matsui, Yoshitaro Shindo, Michihisa Iida, Yasunobu Koki, Hideki Arima, Hiroyuki Furukawa, Tomio Ueno, Shigefumi Yoshino, Yusuke Nakamura, Masaaki Oka, Hiroaki Nagano

CANCER SCIENCE 108 ( 1 ) 73 - 80 2017.1

Language：English Publisher：WILEY-BLACKWELL

We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naive PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.

DOI： 10.1111/cas.13113

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Sarcopenia predicts postoperative infection in patients undergoing hepato-biliary-pancreatic surgery

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

International Journal of Surgery Open 6 12 - 18 2017

Language：English Publisher：Elsevier Ltd

Background Operative mortality and morbidity rates after hepato-biliary-pancreatic (BILI) surgery remain high. This study evaluated clinical characteristics and surgical outcomes of patients who underwent BILI surgery and investigated predictors of outcomes by focusing on sarcopenia. Materials and methods A prospective observational study was performed for consecutive patients who underwent BILI surgery at our institution between June 2013 and May 2014. Sarcopenia was evaluated using computed tomography. Surgical outcomes and the influence of sarcopenia on outcomes were evaluated. Subsequently, the impact of prognostic factors, including sarcopenia, associated with postoperative infections was assessed using multivariate analyses. Results Total mortality, major complications, and infectious disease rates for all 157 patients were 0%, 9.6%, and 21.7%, respectively. Thirty-eight patients met the criteria for sarcopenia. The sarcopenic group had a significantly higher incidence of infectious complications compared to the non-sarcopenic group (36.8% vs. 17.2%
P = 0.015). During multivariate analyses of prognostic factors, sarcopenia (hazard ratio = 2.44
P = 0.043) and diabetes mellitus (hazard ratio = 3.07
P = 0.01) were detected as independent predictors of postoperative infections. Conclusions Sarcopenia is an independent preoperative predictor of infection after BILI surgery. Earlier diagnosis and therapeutic intervention for patients with sarcopenia could be useful in the development of comprehensive approaches for perioperative care.

DOI： 10.1016/j.ijso.2016.12.002

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Primary pancreatic-type acinar cell carcinoma of the jejunum with tumor thrombus extending into the mesenteric venous system: a case report and literature review

Takagi K, Yagi T, Tanaka T, Umeda Y, Yoshida R, Nobuoka D, Kuise T, Fujiwara T

BMC Surg 17 ( 75 ) doi: 10.1186/s12893-017-0273-3 2017

Management of early gastric cancer that meet the indication for radical lymph node dissection following endoscopic resection: a retrospective cohort analysis

Kikuchi S, Kuroda S, Nishizaki M, Kagawa T, Kanzaki H, Kawahara Y, Kagawa S, Tanaka T, Okada H, Fujiwara T

BMC Surg 17 ( 1 ) doi: 10.1186/s12893-017-0268-0 2017

GFP labeling kinetics of triple-negative human breast cancer by a killer-reporter adenovirus in 3D Gelfoam® histoculture

Yano S, Takehara K, Miwa S, Kishimoto H, Tazawa H, Urata Y, Kagawa S, Bouvet M, Fujiwara T, Hoffman RM

In Vitro Cell Dev Biol Anim 53 ( 6 ) 479 - 482 2017

胃癌術後再発病変に対する複数回の放射線療法が奏功し長期生存が得られた1例

堀直人, 香川俊輔, 菊地覚次, 黒田新士, 渡邉めぐみ, 坂本修一, 香川哲也, 桒田和也, 久保田哲史, 岸本浩行, 西﨑正彦, 片山敬久, 藤原俊義

癌と化学療法 44 ( 2 ) 165 - 167 2017

[Multiple Salvage Radiotherapies for Metachronous Lymph Node Metastasis from Gastric Cancer Contributed to Long-Term Management of Disease].

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

Gan to kagaku ryoho. Cancer & chemotherapy 44 ( 2 ) 165 - 167 2017

Language：Japanese

A 70-year-old man who underwent gastrectomy for Stage III C gastric cancer developed lymph node(LN)metastasis posterior to the pancreatic head 3 years after the radical surgery.He was first treated with radiotherapy(RT)followed by chemotherapy.The irradiated tumor regressed completely.However, the cancer relapsed in a single para-aortic LN and he was treated with RT to the lesion followed by chemotherapy.Although it completely regressed, later, lung metastasis was observed.The lung lesions were well suppressed by switching to docetaxel; however, the cancer relapsed again in a mediastinal LN, and it was not responsive to docetaxel.The growing mediastinal lesion was irradiated again, which resulted in stable disease.The patient has been treated for 4 years and 7 months with all lesions being well-managed, and chemotherapy is being continued.Recurrent gastric cancer after surgery tends to present as multiple lesions; therefore, the principle therapy is systemic chemotherapy and RT is unlikely to be suitable.However, especially in cases of a solitary lesion that is chemo-resistant, RT could be an optimal option and contribute to long-term survival even in patients with recurrent gastric cancer.

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GFP labeling kinetics of triple-negative human breast cancer by a killer-reporter adenovirus in 3D Gelfoam? histoculture

Shuya Yano, Kiyoto Takehara, Shinji Miwa, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert, M. Hoffman

In Vitro Cellular and Developmental Biology - Plant, In Vitro Cellular and Developmental Biology - Animal 1 - 4 2017

Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging

Shuya Yano, Kiyoto Takehara, Hiroshi Tazawa, Hiroyuki Kishimoto, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara, Robert M. Hoffman

CELL CYCLE 16 ( 5 ) 406 - 414 2017

Language：English Publisher：TAYLOR & FRANCIS INC

We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G(2) phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression.

DOI： 10.1080/15384101.2016.1220461

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Thoracoscopic esophagectomy was effective in a case of lower esophageal stenosis due to recurrence of achalasia after myotomy 40 years previously

Katsura Yuki, Shirakawa Yasuhiro, Tanabe Shunsuke, Maeda Naomi, Noma Kazuhiro, Fujiwara Toshiyoshi

Okayama Igakkai Zasshi (Journal of Okayama Medical Association) 129 ( 1 ) 41 - 44 2017

Language：Japanese Publisher：Okayama Medical Association

When planning surgery for achalasia, it is important to plan for adequate myotomy and prevention of reflux. However, achalasia may recur if the procedure was inadequate or in patients with a long-term course. The present case is a 68-year-old woman who underwent myotomy of the lower esophageal sphincter 40 years ago, but recently reported difficulty in swallowing. Dilatation of the thoracic esophagus and stenosis of the abdominal esophagus were identified by examination, and the patient was diagnosed with recurrence of achalasia. After percutaneous endoscopic gastrostomy was performed to recover nutritional status, thoracoscopic esophagectomy was carried out. The patient's post-operative course was uneventful and oral intake was enabled. At the time of writing, there has been no re-recurrence. There is no standard therapy for post-operative recurrence of achalasia. We believe that thoracoscopic esophagectomy for the recurrence of achalasia is a safe and minimally invasive alternative to conventional surgery.

DOI： 10.4044/joma.129.41

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2017219750

食道胃接合部癌に対する下部食道噴門側胃切除術-腹臥位胸腔鏡・腹腔鏡アプローチによる完全鏡視下手術-

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 71 ( 5 ) 767 - 772 2017

Radiographic sarcopenia predicts postoperative infectious complications in patients undergoing pancreaticoduodenectomy

Takagi K, Yoshida R, Yagi T, Umeda Y, Nobuoka D, Kuise T, Fujiwara T

BMC Surg 17 ( 64 ) DOI: 10.1186/s12893-017-0261-7 2017

A case of long-term survival after surgical resection for solitary adrenal recurrence of esophageal squamous carcinoma

Kanaya N, Noma K, Okada T, Maeda N, Tanabe S, Sakurama K, Shirakawa Y, Fujiwara T

Surg Case Rep 3 ( 61 ) doi: 10.1186/s40792-017-0337-8 2017

Comparison of outcomes between symptomatic and asymptomatic patients with colorectal cancer: a propensity score-matched analysis of surgical invasiveness, medical costs and oncological outcomes. International journal

Ryo Inada, Takeshi Nagasaka, Ayako Watanabe, Tomohiko Yagi, Yoshiko Mori, Yoshitaka Kondo, Hiroyuki Kishimoto, Yuzo Umeda, Toshiyoshi Fujiwara

BMJ open gastroenterology 4 ( 1 ) doi: 10.1136/bmjgast-2017-000146 2017

Language：English

BACKGROUND AND AIMS: Whether asymptomatic patients with colorectal cancer (CRC) who are treated in hospitals show better outcomes than symptomatic patients with CRC still remains unknown. The aim of this study was to evaluate differences in clinical benefits following treatment in asymptomatic and symptomatic patients with CRC. METHODS: This study was a retrospective cohort analysis with data obtained from records. A cohort of 145 asymptomatic and 123 symptomatic patients who underwent CRC surgery between January 2009 and December 2011 was enrolled. To reduce bias in comparing outcomes, propensity score (PS) analysis was used for matching of patients in the symptomatic and asymptomatic groups based on clinicopathological factors. Surgical invasiveness, medical costs and oncological outcomes were examined by unadjusted and PS-matched analysis. RESULTS: Tumours in the symptomatic group were more often diagnosed in advanced stages compared with tumours in the asymptomatic group. Therefore, fewer symptomatic group patients underwent minimally invasive surgery. Short-term outcomes, including amount of blood loss, duration of postoperative hospital stay and perioperative medical costs, were significantly better in the asymptomatic group. Although overall survival was significantly better in the asymptomatic group, there was no significant difference between the groups when the patients were adjusted on the basis of PS. CONCLUSIONS: Though this study was limited by the retrospective nature and small sample size, favourable outcomes in asymptomatic patients were due to the higher proportion of patients in this group who were diagnosed with CRC in earlier stages, due to participation in CRC screening programmes.

DOI： 10.1136/bmjgast-2017-000146

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Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer

Tazawa H, Kuroda S, Hasei J, Kagawa S, Fujiwara T

Int J Mol Sci 18 ( 7 ) doi:10.3390/ijms18071479 2017

Eradication of melanoma in vitro and in vivo via targeting with a Killer-Red-containing telomerase-dependent adenovirus

Kiyoto Takehara, Shuya Yano, Hiroshi Tazawa, Hiroyuki Kishimoto, Nobuhiro Narii, Hiroyuki Mizuguchi, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara, Robert, M. Hoffman

Cell Cycle 1 - 7 2017

A novel intestinal rotation method for digestive reconstruction after combined pancreaticoduodenectomy and extended right hemicolectomy: A case report and surgical technique

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

International Journal of Surgery Case Reports 39 51 - 55 2017

Language：English Publisher：Elsevier Ltd

Introduction Pancreaticoduodenectomy (PD) combined with extended right hemicolectomy (RH) is a challenging procedure for locally advanced malignancies. However, information concerning the reconstruction method of the digestive system is limited. Here, we present a case and surgical technique of a novel intestinal rotation method for digestive reconstruction after PD combined with RH. Presentation of case A 62-year-old man with locally advanced pancreatic cancer received conversion surgery combined with PD and RH after preoperative chemotherapy. With respect to the reconstruction of the digestive system, the entire intestinal mesentery was rotated 180° forward counterclockwise around the axis of the superior mesenteric artery, and then the reconstruction, according to Child's method, was performed. The patient recovered without problems in gastroenterological functions after the operation. Discussion With respect to the reconstruction of the digestive system in patients undergoing combined PD and RH, practitioners should pay close attention to twisting of the intestinal mesentery when bringing up the proximal jejunum for pancreatojejunostomy and hepatojejunostomy and the distal ileum for ileocolic anastomosis. This intestinal rotation method enables a smooth and uneventful reconstruction of the digestive system. Conclusion This is the first detailed description of an intestinal rotation method for digestive reconstruction after combined PD and extended RH. The intestinal rotation method can be an alternative and helpful technical option for digestive reconstruction in patients with combined PD and RH.

DOI： 10.1016/j.ijscr.2017.07.063

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Role of zoledronic acid in oncolytic virotherapy

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, Japanese Journal of Cancer Research, Gann, The Japanese Journal of Cancer Research 149 - 160 2017

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MISC - FUJIWARA Toshiyoshi