研究者詳細 - 香川　俊輔

論文 - 香川　俊輔

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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年10月

p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. 査読国際誌

Koji Demiya, Hiroshi Tazawa, Hiroya Kondo, Miho Kure, Yusuke Mochizuki, Tadashi Komatsubara, Aki Yoshida, Koji Uotani, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Molecular therapy. Oncology 32 ( 3 ) 200845 - 200845 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

DOI： 10.1016/j.omton.2024.200845

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間質のコラーゲン産生は胃癌における腫瘍融解ウイルス療法の治療抵抗性を増強する(Stromal collagen type 1 deposition promotes resistance to oncolytic virotherapy in gastric cancer)

大倉友博, 田澤大, 菊地覚次, 黒田新士, 大原利章, 野間和広, 大塚旬子, 大木理恵子, 浦田泰生, 香川俊輔, 藤原俊義, 藤原俊義

日本癌学会総会記事 83回 P - 2252 2024年9月

Comprehensive geriatric assessment as an indicator of postoperative recovery in older patients with colorectal cancer. 査読国際誌

Fuminori Teraishi, Ryohei Shoji, Yoshitaka Kondo, Shunsuke Kagawa, Rie Tamura, Yoshikazu Matsuoka, Hiroshi Morimatsu, Toshiharu Mitsuhashi, Toshiyoshi Fujiwara

Journal of geriatric oncology 101837 - 101837 2024年7月

BRAF-mutant microsatellite-stable rectal cancer with acquired KRAS mutation leading to drug resistance in liver metastasis. 査読国際誌

Kunitoshi Shigeyasu, Hideki Yamamoto, Toshiaki Takahashi, Kazuya Moriwake, Masashi Kayano, Sho Takeda, Yuki Matsumi, Yuzo Umeda, Yoshitaka Kondo, Fuminori Teraishi, Kazuya Yasui, Tomokazu Fuji, Shunsuke Kagawa, Toshiyoshi Fujiwara

International cancer conference journal 13 ( 3 ) 189 - 192 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BRAF-mutant microsatellite-stable colorectal cancer (CRC), metastasized to distant sites, is associated with a poor prognosis. However, the BEACON CRC regimen, comprising a BRAF inhibitor, MEK inhibitor, and anti-EGFR antibody, offered a prolonged prognosis. Nonetheless, resistance to this regimen may occur, as observed in our reported case of CRC, where a KRAS mutation was identified in addition to the BRAF V600E mutation. Here, we present a case of 74-year-old woman with rectal cancer (pT4bN1bM0 Stage IIIc) harboring the BRAF V600E mutation. After resection of the primary tumor and during adjuvant chemotherapy using CAPOX (capecitabine and oxaliplatin), liver and lung metastases became apparent, and a companion diagnosis test revealed the presence of a BRAF V600E mutation. The new lesions were deemed resistant to the CAPOX regimen, and we decided to introduce encorafenib and cetuximab. After resection of liver metastases, encorafenib and cetuximab were reintroduced, but a new lesion appeared in hepatic S7, indicating resistance to the encorafenib and cetuximab regimen. The resistant liver metastasis was subsequently resected. To elucidate the resistance mechanism, we conducted a comprehensive analysis using the FoundationOne CDx cancer gene panel test, revealing the presence of a KRAS Q61H mutation alongside the BRAF V600E mutation. Subsequent liquid biopsy after liver recurrence confirmed the persistence of the KRAS Q61H mutation. Our results highlight the significance of cancer genome profiling tests (CGP tests) and liquid biopsies in guiding treatment strategies for BRAF-mutant colorectal cancer. Therefore, CGP testing offers valuable information for treatment, even if it does not lead to new drug administrations.

DOI： 10.1007/s13691-024-00678-2

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私が目指すScientific Surgeonとその現状と未来

金谷信彦, 黒田新士, 近藤喜太, 坂本真樹, 垣内慶彦, 菊地覚次, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 668 - 668 2024年7月

上部消化管上部消化管癌に対する更なる低侵襲・機能温存治療観音開き法再建後の吻合部狭窄および狭窄症状のリスク因子分析から見えた再建手技の理想型

黒田新士, 垣内慶彦, 菊地覚次, 賀島肇, 田辺俊介, 野間和広, 楳田祐三, 寺石文則, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 573 - 573 2024年7月

Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer. 査読国際誌

Motoyasu Tabuchi, Satoru Kikuchi, Hiroshi Tazawa, Tomohiro Okura, Toshihiro Ogawa, Ema Mitsui, Yuta Une, Shinji Kuroda, Hiroki Sato, Kazuhiro Noma, Shunsuke Kagawa, Toshiaki Ohara, Junko Ohtsuka, Rieko Ohki, Yasuo Urata, Toshiyoshi Fujiwara

Molecular therapy. Oncology 32 ( 2 ) 200806 - 200806 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Intraperitoneal tumor-associated macrophages (TAMs) are involved in evading anti-tumor immunity and promoting the peritoneal metastasis (PM) of gastric cancer (GC). Oncolytic viruses are known to induce the activation of host anti-tumor immunity in addition to tumor lysis. This study investigated whether a wild-type p53-loading telomerase-specific oncolytic adenovirus (OBP-702) could elicit the remodeling of intraperitoneal macrophages and enhance the efficacy of immune therapy. Increased numbers of CD163 TAMs and few CD8+ lymphocytes were immunohistochemically observed in clinical samples with PM, which suggested that TAMs were associated with the suppression of anti-tumor immunity. OBP-702 induced immunogenic cell death and upregulated PD-L1 expression in human and murine GC cell lines. Intraperitoneal administration of OBP-702 increased recruitment of CD8+ lymphocytes into the PM via the functional remodeling of intraperitoneal macrophages from TAM toward a pro-inflammatory phenotype, resulting in significantly suppressed tumor growth for the in vivo model. Furthermore, the combination of intraperitoneal OBP-702 with anti-programmed cell death-1 antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC.

DOI： 10.1016/j.omton.2024.200806

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Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8-mediated Crosstalk. 査読国際誌

Yuncheng Li, Hiroshi Tazawa, Yasuo Nagai, Shuto Fujita, Tomohiro Okura, Ryohei Shoji, Motohiko Yamada, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Anticancer research 44 ( 6 ) 2497 - 2509 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIM: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. MATERIALS AND METHODS: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α-smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. RESULTS: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor-β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. CONCLUSION: sCAFs promote peritoneal metastasis of DGC via IL-8-mediated crosstalk.

DOI： 10.21873/anticanres.17056

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局所環境とがん免疫膵臓癌のMHC低発現を改善するエピジェネティック制御剤の同定と樹状細胞併用p53ウイルス免疫療法への応用

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

日本がん免疫学会総会・日本バイオセラピィ学会学術集会総会合同大会プログラム・抄録集 28回・37回 78 - 78 2024年6月

A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study). 査読

Shinji Kuroda, Michihiro Ishida, Yasuhiro Choda, Atsushi Muraoka, Shinji Hato, Tetsuya Kagawa, Norimitsu Tanaka, Toshiharu Mitsuhashi, Yoshihiko Kakiuchi, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Annals of gastroenterological surgery 8 ( 3 ) 374 - 382 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. METHODS: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. RESULTS: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien-Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). CONCLUSION: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.

DOI： 10.1002/ags3.12783

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「多様な外科医が活躍する社会」の実現に向けて Academic daddy surgeonを目指した一外科医の試み

金谷信彦, 黒田新士, 坂本真樹, 垣内慶彦, 近藤喜太, 竹原裕子, 香川俊輔, 藤原俊義

日本外科系連合学会誌 49 ( 3 ) 276 - 276 2024年5月

p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression. 査読

Tadashi Komatsubara, Hiroshi Tazawa, Joe Hasei, Toshinori Omori, Kazuhisa Sugiu, Yusuke Mochizuki, Koji Demiya, Aki Yoshida, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Acta medica Okayama 78 ( 2 ) 151 - 161 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.

DOI： 10.18926/AMO/66924

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Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus. 査読国際誌

Masashi Hashimoto, Shinji Kuroda, Nobuhiko Kanaya, Daisuke Kadowaki, Yusuke Yoshida, Masaki Sakamoto, Yuki Hamada, Ryoma Sugimoto, Chiaki Yagi, Tomoko Ohtani, Kento Kumon, Yoshihiko Kakiuchi, Kazuya Yasui, Satoru Kikuchi, Ryuichi Yoshida, Hiroshi Tazawa, Shunsuke Kagawa, Takahito Yagi, Yasuo Urata, Toshiyoshi Fujiwara

British journal of cancer 130 ( 7 ) 1187 - 1195 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Pancreatic cancer is an aggressive, immunologically "cold" tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). METHODS: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). RESULTS: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. CONCLUSION: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.

DOI： 10.1038/s41416-024-02583-0

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高齢者大腸癌における周術期リハビリテーションの個別化を目指した術前機能評価の有用性の検証

寺石文則, 庄司良平, 賀島肇, 松三雄騎, 近藤喜太, 黒田新士, 野間和広, 香川俊輔, 藤原俊義

日本外科学会定期学術集会抄録集 124回 PS - 8 2024年4月

術後障害の評価と対策術後継続的な栄養指導による胃切除術後障害の軽減効果

菊地覚次, 半澤俊哉, 賀島肇, 庄司良平, 松三雄騎, 垣内慶彦, 黒田新士, 田辺俊介, 野間和広, 香川俊輔, 藤原俊義

日本胃癌学会総会記事 96回 175 - 175 2024年2月

Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy. 査読国際誌

Shunya Hanzawa, Satoru Kikuchi, Shinji Kuroda, Ryohei Shoji, Hajime Kashima, Yuki Matsumi, Ayako Takahashi, Yoshihiko Kakiuchi, Kosei Takagi, Shunsuke Tanabe, Kazuhiro Noma, Shunsuke Kagawa, Kenichi Shikata, Toshiyoshi Fujiwara

Nutrition and cancer 76 ( 6 ) 476 - 485 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (-7.98% vs. -12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL.

DOI： 10.1080/01635581.2024.2340782

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Clinical Impact of Prehabilitation on Elective Laparoscopic Surgery in Frail Octogenarians With Colorectal Cancer. 査読国際誌

Fuminori Teraishi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Shunsuke Kagawa, Rie Tamura, Yoshikazu Matsuoka, Hiroshi Morimatsu, Toshiyoshi Fujiwara

Anticancer research 43 ( 12 ) 5597 - 5604 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIM: The aim of the present study was to clarify the clinical impact of prehabilitation by the perioperative management center (PERIO) at our hospital in severely frail octogenarians with colorectal cancer. PATIENTS AND METHODS: We compared the clinicopathological characteristics of octogenarians who underwent surgery for colorectal cancer before the establishment of PERIO intervention (Control group) with those who received prehabilitation (PERIO group). All patients were classified as American Society of Anesthesiologists (ASA) class 3 or higher. The primary outcome was the incidence of postoperative complications. RESULTS: There were 21 patients in the Control group and 19 patients in the PERIO group. Operative time was significantly longer in the PERIO group (Control group, 200 min vs. PERIO group, 230 min; p=0.03) and blood loss was significantly higher in the PERIO group (Control group, 5 ml vs. PERIO group, 30 ml; p=0.02). Postoperative complications occurred in 10 patients (47.6%) in the Control group and 3 patients (15.8%) in the PERIO group and were significantly lower in the PERIO group (p=0.03). Postoperative hospital stay was 13 days (range=7-31 days) in the Control group and 11 days (range=8-70 days) in the PERIO group (p=0.39). The rate of discharge directly to home was 81% in the Control group and 93.3% in the PERIO group (p=0.29). CONCLUSION: In frail octogenarians with colorectal cancer of ASA class 3 or higher, the incidence of postoperative complications was significantly lower after PERIO intervention.

DOI： 10.21873/anticanres.16762

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Intraperitoneal Administration of p53-armed Oncolytic Adenovirus Inhibits Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells. 査読国際誌

Naoto Hori, Hiroshi Tazawa, Yuncheng Li, Tomohiro Okura, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Masahiko Nishizaki, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

Anticancer research 43 ( 11 ) 4809 - 4821 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIM: Diffuse-type gastric cancer (GC) frequently exhibits peritoneal metastasis, leading to poor prognosis. However, efforts to develop antitumor strategies for preventing the peritoneal metastasis of GC have been unsuccessful. As diffuse-type GC cells often carry a genetic alteration in the tumor suppressor p53 gene, p53 restoration may be a potent strategy for preventing peritoneal metastasis of GC. In this study, we investigated the therapeutic potential of p53-expressing adenoviral vectors against peritoneal metastasis of diffuse-type GC cells. MATERIALS AND METHODS: Three diffuse-type human GC cell types with different p53 statuses (p53-wild type NUGC-4, p53-mutant type GCIY, and p53-null type KATOIII) were used to evaluate the therapeutic potential of p53 activation induced by the p53-expressing, replication-deficient adenovirus Ad-p53 and oncolytic adenovirus OBP-702. Viability, apoptosis, and autophagy of virus-treated GC cells were analyzed under normal and sphere-forming culture conditions using the XTT assay and western blot analysis. The in vivo antitumor effects of OBP-702 and Ad-p53 were assessed using xenograft tumor models involving peritoneal metastasis of NUGC-4 and GCIY cells. RESULTS: Under normal and sphere-forming culture conditions, OBP-702 induced a significantly greater antitumor effect in GC cells compared with Ad-p53 by strongly inducing p53-mediated apoptosis and autophagy and receptor tyrosine kinase suppression. In vivo experiments demonstrated that intraperitoneal administration of OBP-702 significantly suppressed the peritoneal metastasis of NUGC-4 and GCIY cells compared with Ad-p53, leading to prolonged survival of mice. CONCLUSION: Intraperitoneal administration of OBP-702 inhibits the peritoneal metastasis of GC cells by inducing p53-mediated cytopathic activity.

DOI： 10.21873/anticanres.16678

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米国留学中に経験した出産育児と共稼ぎから見えた外科医のワークライフバランスへの提言

金谷信彦, 黒田新士, 竹原裕子, 皆木仁志, 垣内慶彦, 近藤喜太, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S65 - S65 2023年10月

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