Faculty Profiles - FUJIWARA Toshiyoshi

Papers - FUJIWARA Toshiyoshi

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Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity. International journal

Tomoko Ohtani, Shinji Kuroda, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Kento Kumon, Masashi Hashimoto, Chiaki Yagi, Ryoma Sugimoto, Satoru Kikuchi, Shunsuke Kagawa, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara

Cancer immunology, immunotherapy : CII 74 ( 1 ) 12 - 12 2024.11

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

Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect.

DOI： 10.1007/s00262-024-03849-5

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Gastro-tracheal fistula following esophageal cancer surgery through the retrosternal route: a case report. International journal

Seitaro Nishimura, Kazuhiro Noma, Kento Kawasaki, Masashi Hashimoto, Takuya Kato, Naoaki Maeda, Shunsuke Tanabe, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

Surgical case reports 10 ( 1 ) 252 - 252 2024.11

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

BACKGROUND: Gastro-tracheal fistula is a rare but serious complication after esophageal surgery, often requiring long-term treatment and invasive procedures. Gastro-tracheal fistula usually occurs through the posterior mediastinal route and rarely through the retrosternal route. No previous reports have described gastro-tracheal fistula after retrosternal route reconstruction was cured by conservative treatment. CASE PRESENTATION: A 70-year-old man with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy in the prone position and gastric tube reconstruction through the retrosternal route with neck anastomosis after neoadjuvant chemotherapy. Despite anastomotic leakage on postoperative day 10, his general condition was stable, and he was managed conservatively with antibiotics and gastric tube decompression. On day 29, he presented with high fever and a gastro-tracheal fistula was observed by esophagography. Conservative management was continued because the patient remained stable. On day 48, esophagography showed that the fistula was undetectable. The patient was able to take fluids orally. He progressed well on an oral diet and was transferred to a different hospital. CONCLUSIONS: A gastro-tracheal fistula, although rare, can occur after retrosternal route reconstruction. When a patient is stable, gastro-tracheal fistula after retrosternal route reconstruction may be cured by conservative treatment.

DOI： 10.1186/s40792-024-02052-z

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Risk model for predicting failure to rescue after hepatectomy: Cohort study of 1371 consecutive patients. International journal

Jiro Kimura, Kosei Takagi, Yuzo Umeda, Tomokazu Fuji, Kazuya Yasui, Motohiko Yamada, Takeyoshi Nishiyama, Yasuo Nagai, Noriyuki Kanehira, Toshiyoshi Fujiwara

Hepatology research : the official journal of the Japan Society of Hepatology 2024.11

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

AIM: Although hepatectomy is a complex surgical procedure, its incidence among older patients has increased due to global aging. However, few studies have focused on the association between age and failure to rescue (FTR) posthepatectomy. This study aimed to investigate the association between age and FTR and develop a risk model for FTR following hepatectomy. METHODS: We analyzed a total of 1371 consecutive patients who underwent primary hepatectomy between July 2003 and September 2022. The patients were divided into three groups according to their age: young-old (<65 years), pre-old (65-74 years), and old group (≥75 years). Additionally, the associations among age, FTR, and risk factors for FTR were investigated. Subsequently, a risk model was developed to predict the FTR. RESULTS: Of the 1371 patients, 373 (27.2%) experienced major complications, and FTR occurred in 15 patients. The older group showed a higher FTR rate (8.4%) than the young-old (1.3%) and pre-old (4.3%) groups (p = 0.03). Multivariate analyses indicated that older age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.00-1.15; p = 0.045) and American Society of Anesthesiologists Physical Status score ≥3 (OR 4.35; 95% CI 1.24-15.2; p = 0.02) were independent predictive factors for FTR. The risk model exhibited an accuracy with an area under the curve of 0.80 (95% CI 0.69-0.92). Calibration plots of the model revealed a concordance index of 0.73. CONCLUSIONS: This study identified an association between age, FTR, and risk factors for FTR posthepatectomy. Together, our risk model is a clinically relevant, internally validated, and useful tool for predicting FTR posthepatectomy.

DOI： 10.1111/hepr.14134

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Primary ileal myeloid sarcoma presenting with bowel obstruction: a case report. International journal

Hitoshi Minagi, Nobuhiko Kanaya, Yoshitaka Kondo, Yoshihiko Kakiuchi, Shinji Kuroda, Ryohei Shoji, Hajime Kashima, Yuki Matsumi, Satoru Kikuchi, Kunitoshi Shigeyasu, Fuminori Teraishi, Shunsuke Kagawa, Toshiyoshi Fujiwara

Surgical case reports 10 ( 1 ) 229 - 229 2024.10

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

BACKGROUND: Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement. CASE REPRESENTATION: A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital. CONCLUSIONS: Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical.

DOI： 10.1186/s40792-024-02030-5

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大腸癌に対する樹状細胞ワクチン療法と腫瘍融解アデノウイルスの併用効果

岡田尚大, 田澤大, 山田元彦, 陶守貫人, 菊地覚次, 黒田新士, 野間和広, 浦田泰生, 香川俊輔, 藤原俊義

癌と化学療法 51 ( 10 ) 1035 - 1037 2024.10

Language：Japanese Publisher：(株)癌と化学療法社

樹状細胞(DC)ワクチン療法は,細胞傷害性Tリンパ球を強力に誘導する癌免疫療法として広く研究されている。しかし臨床における有効性は十分確立されていない。著者らは,癌抑制遺伝子p53を搭載した腫瘍融解アデノウイルス製剤OBP-702を開発し,p53誘導を介した抗腫瘍効果や腫瘍免疫の活性化を明らかにしてきた。本研究では,大腸癌に対するp53導入DCワクチンとOBP-702の併用効果について検討した。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J00296&link_issn=&doc_id=20241023220015&doc_link_id=%2Fab8gtkrc%2F2024%2F005110%2F016%2F1035-1037%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2024%2F005110%2F016%2F1035-1037%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Endoscopic lavage for an infected pelvic hematoma in a patient with pelvic sepsis after anterior pelvic exenteration.

Ryohei Shoji, Fuminori Teraishi, Yoshitaka Kondo, Toshihiro Inokuchi, Hideaki Kinugasa, Toshiyoshi Fujiwara

Asian journal of endoscopic surgery 17 ( 4 ) e13384 2024.10

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

Anastomotic leakage and subsequent pelvic sepsis are serious complications after surgery for pelvic malignancies, particularly challenging due to the large pelvic cavity dead space post-exenteration. We report a 47-year-old man treated for a severely infected pelvic hematoma and sepsis following anastomotic leakage after anterior pelvic exenteration. Post robot-assisted exenteration for locally advanced sigmoid colon cancer treated with neoadjuvant chemotherapy, a pelvic abscess from anastomotic dehiscence was identified. Initial CT-guided drainage and subsequent laparoscopic drainage were performed. On postoperative day 22, a bleeding left internal iliac pseudoaneurysm required embolization. Despite these efforts, the sepsis worsened due to an enlarged, infected hematoma. Endoscopic lavage, in collaboration with skilled endoscopists, successfully removed the hematoma, leading to an improved inflammatory response, and the patient was discharged. Endoscopic lavage proved to be the safest and most effective treatment for pelvic sepsis with an infected hematoma after various attempted interventions.

DOI： 10.1111/ases.13384

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[Combined Efficacy of Dendritic Cell Vaccine and Oncolytic Adenovirus in Colorectal Cancer].

Naohiro Okada, Hiroshi Tazawa, Motohiko Yamada, Kanto Suemori, Satoru Kikuchi, Shinji Kuroda, Kazuhiro Noma, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

Gan to kagaku ryoho. Cancer & chemotherapy 51 ( 10 ) 1035 - 1037 2024.10

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

Dendritic cell(DC)vaccine therapy has been widely studied as cancer immunotherapy that potently induces cytotoxic T lymphocytes. However, their efficacy in clinical practice has not yet been established. We have developed an oncolytic adenovirus OBP-702 carrying the tumor suppressor gene p53 and have demonstrated its therapeutic potential to induce cytopathic effect and activate antitumor immunity via p53 induction. In this study, we investigated the combined effect of p53-transduced DC vaccine and OBP-702 in colorectal cancer.

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RNA編集酵素ADAR1に基づく大腸癌肝転移の残肝再発リスク層別化の検討

高橋利明, 重安邦俊, 中村峻輔, 高橋政史, 萱野真史, 新田薫, 森分和也, 安井和也, 松三雄騎, 藤智和, 近藤喜太, 寺石文則, 田澤大, 藤原俊義

日本癌治療学会学術集会抄録集 62回 P80 - 2 2024.10

潰瘍性大腸炎においてRNA編集解析が発癌予測バイオマーカーとなりうる

森分和也, 重安邦俊, 萱野真史, 新田薫, 中村峻輔, 高橋利明, 高橋政史, 金谷信彦, 松三雄騎, 近藤喜太, 寺石文則, 田澤大, 藤原俊義

日本癌治療学会学術集会抄録集 62回 P43 - 2 2024.10

膵癌が誘導する癌関連線維芽細胞サブタイプは腫瘍融解ウイルスに異なる感受性を示す

永井康雄, 田澤大, 藤田修斗, 高橋洋祐, 菊地覚次, 黒田新士, 大原利章, 野間和広, 浦田泰生, 香川俊輔, 藤原俊義

日本癌治療学会学術集会抄録集 62回 O66 - 4 2024.10

マクロピノサイトーシスは膵癌関連膵星細胞の腫瘍融解ウイルスへの感受性を増強する

西山岳芳, 田澤大, 永井康雄, 庄司良平, 菊地覚次, 黒田新士, 大原利章, 野間和広, 田中啓祥, 狩野光伸, 浦田泰生, 香川俊輔, 藤原俊義

日本癌治療学会学術集会抄録集 62回 O66 - 6 2024.10

食道扁平上皮癌オルガノイドの樹立と個別化治療のための薬剤耐性実験モデル

竹田泰茂, 野間和広, 賀島肇, 清水彰人, 松本祐, 高橋達也, 前田直見, 田邊俊介, 大原利章, 田澤大, 中川裕, 藤原俊義

日本癌治療学会学術集会抄録集 62回 O75 - 6 2024.10

FAPを標的とした近赤外線光免疫療法によるCAF-rich腫瘍への化学療法抵抗性の克服

西村星多郎, 野間和広, 松本佑, 竹田泰茂, 高橋達也, 松本聖, 河崎健人, 國友知義, 賀島肇, 加藤卓也, 菊地覚次, 大原利章, 田澤大, 藤原俊義

日本癌治療学会学術集会抄録集 62回 O76 - 2 2024.10

高齢がん患者に対するがん診療高齢大腸癌患者における主観的包括的栄養評価(SGA)の有用性単施設前向き観察研究

寺石文則, 吉田有佑, 庄司良平, 松三雄騎, 重安邦俊, 近藤喜太, 香川俊輔, 田村利枝, 松岡義和, 藤原俊義

日本癌治療学会学術集会抄録集 62回 CCWS1 - 6 2024.10

発生部位からみた肉腫の適切な外科的切除縁とは?-領域横断的な認識の統合- 後腹膜脂肪肉腫に対する外科的切除縁の最適化

近藤喜太, 金谷信彦, 庄司良平, 松三雄騎, 垣内慶彦, 重安邦俊, 菊地覚次, 黒田新士, 田辺俊介, 野間和広, 寺石文則, 香川俊輔, 藤原俊義

日本癌治療学会学術集会抄録集 62回 OWS3 - 2 2024.10

NTRK融合遺伝子とERBB2 amplificationが合併したマイクロサテライト安定型大腸癌

重安邦俊, 高橋利明, 山本英喜, 垣内慶彦, 松三雄騎, 近藤喜太, 寺石文則, 黒田新士, 香川俊輔, 藤原俊義

日本癌治療学会学術集会抄録集 62回 ICCJ3 - 6 2024.10

食道癌の集学的治療～高齢化社会とICI時代の先鞭をつける～高齢者食道癌患者に対する免疫チェックポイント阻害薬+化学療法

橋本将志, 野間和広, 松本聖, 河崎健人, 國友知義, 田上幸憲, 前田直見, 菊地覚次, 重安邦俊, 田辺俊介, 近藤喜太, 黒田新士, 寺石文則, 香川俊輔, 藤原俊義

日本癌治療学会学術集会抄録集 62回 OSY8 - 7 2024.10

膵癌の更なる早期発見、早期診断に向けて Ct-DNA内KRAS mutation profileとCA19-9値による膵癌予後予測診断と治療戦略

安井和也, 吉田龍一, 宮本耕吉, 重安邦俊, 高木弘誠, 藤智和, 黒田新士, 藤原俊義

日本癌治療学会学術集会抄録集 62回 OSY9 - 4 2024.10

RNA編集酵素ADAR1に基づく大腸癌肝転移の残肝再発リスク層別化の検討

高橋利明, 重安邦俊, 中村峻輔, 高橋政史, 萱野真史, 新田薫, 森分和也, 安井和也, 松三雄騎, 藤智和, 近藤喜太, 寺石文則, 田澤大, 藤原俊義

日本癌治療学会学術集会抄録集 62回 P80 - 2 2024.10

CA19-9高値悪性腫瘍へのプレシジョン中性子捕捉療法(BNCT)

金平典之, 寺石文則, 田嶋智之, 大曽根達則, 後藤和義, 櫻井良憲, 近藤夏子, 森原聡, 高口豊, 北松瑞生, 宝田剛士, 重安邦俊, 鈴木実, 藤原俊義, 道上宏之

日本癌治療学会学術集会抄録集 62回 O55 - 5 2024.10

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Papers - FUJIWARA Toshiyoshi