研究者詳細 - 垣内　慶彦

論文 - 垣内　慶彦

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H.pylori未感染胃粘膜を背景に発生したリンパ節転移を伴う低分化型進行胃癌の一例

倉岡紗樹子, 川野誠司, 小橋真由, 岡上昇太郎, 里見拓也, 稲生祥子, 濱田健太, 河野吉泰, 神崎洋光, 岩室雅也, 河原祥朗, 岡田裕之, 垣内慶彦, 黒田新士, 藤原俊義, 田中健大, 池田宣聖

日本消化器病学会中国支部例会プログラム・抄録集 117回 75 - 75 2022年6月

Surgical technique of suprapancreatic D2 lymphadenectomy focusing on the posterior hepatic plexus for advanced gastric cancer. 査読国際誌

Nobuhiko Kanaya, Shinji Kuroda, Yoshihiko Kakiuchi, Sho Takeda, Satoru Kikuchi, Kazuhiro Noma, Ryuichi Yoshida, Yuzo Umeda, Fuminori Teraishi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Langenbeck's archives of surgery 407 ( 2 ) 871 - 877 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Although D2 lymphadenectomy is currently considered a standard procedure for advanced gastric cancer (GC) worldwide, there is room for discussion about the appropriate range of suprapancreatic D2 lymphadenectomy. Focusing on the posterior hepatic plexus (PHP), which is not well recognized, we developed a surgical technique of suprapancreatic D2 lymphadenectomy, which we have called PHP-D2, and its short-term and long-term efficacies were evaluated in comparison with non-PHP-D2. METHODS: GC patients who underwent distal gastrectomy with D2 lymphadenectomy between July 2006 and May 2013 were enrolled, from which patients who had peritoneal metastasis and/or were peritoneal cytology-positive during surgery were excluded. Their medical records were retrospectively reviewed. RESULTS: Ninety-two patients (non-PHP-D2: 48, PHP-D2: 44) were enrolled. Shorter operation time (330 min vs 275 min, p < 0.0001) and less blood loss (290 mL vs 125 mL, p < 0.0001) were observed in PHP-D2, and no pancreatic fistulas were observed in PHP-D2. More lymph nodes of #11p (1 vs 1.5, p = 0.0328) and #12a lymph nodes (0 vs 1, p = 0.0034) were retrieved in PHP-D2, with no significant differences in #8a and #9 lymph nodes. Lymphatic recurrence was significantly less in PHP-D2 (p = 0.0166), and univariate and multivariate analyses showed that non-PHP-D2 was a significant risk factor for lymphatic recurrence (p = 0.0158), although there were no significant differences between non-PHP-D2 and PHP-D2 in 5-year overall survival and 5-year relapse-free survival. CONCLUSION: PHP-D2 was a safe and feasible procedure that had the potential to reduce lymphatic recurrence, and it can be a standard procedure of D2 lymphadenectomy for advanced GC.

DOI： 10.1007/s00423-022-02437-4

進行・再発胃癌患者に対するNivolumabの実臨床での治療成績の検討(Clinical outcomes of nivolumab in patients with advanced or recurrent gastric cancer)

香川俊輔, 黒田新士, 菊地覚次, 野間和広, 田辺俊介, 重安邦俊, 前田直見, 垣内慶彦, 武田正, 近藤喜太, 寺石文則, 藤原俊義

日本胃癌学会総会記事 94回 425 - 425 2022年3月

腹腔鏡下スリーブ状胃切除術導入から4年間での治療成績

香川俊輔, 菊地覚次, 黒田新士, 垣内慶彦, 武田正, 江口潤, 中司敦子, 山口哲志, 和田淳, 藤原俊義

肥満研究 27 ( Suppl. ) 358 - 358 2022年3月

進行・再発胃癌患者に対するNivolumabの実臨床での治療成績の検討(Clinical outcomes of nivolumab in patients with advanced or recurrent gastric cancer)

香川俊輔, 黒田新士, 菊地覚次, 野間和広, 田辺俊介, 重安邦俊, 前田直見, 垣内慶彦, 武田正, 近藤喜太, 寺石文則, 藤原俊義

日本胃癌学会総会記事 94回 425 - 425 2022年3月

Association between Advanced T Stage and Thick Rectus Abdominis Muscle and Outlet Obstruction and High-Output Stoma after Ileostomy in Patients with Rectal Cancer 査読

Yasuhiro Komatsu, Kunitoshi Shigeyasu, Sho Takeda, Yoshiko Mori, Kazutaka Takahashi, Nanako Hata, Kokichi Miyamoto, Hibiki Umeda, Yoshihiko Kakiuchi, Satoru Kikuchi, Shuya Yano, Shinji Kuroda, Yoshitaka Kondo, Hiroyuki Kishimoto, Fuminori Teraishi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

International Surgery 106 ( 3 ) 102 - 111 2022年

掲載種別：研究論文（学術雑誌）

Objective: This study aimed to identify factors associated with outlet obstruction and high-output stoma (HOS) after ileostomy creation. Summary of background data: Ileostomy creation is effective in preventing leakage among patients undergoing low anterior resection for rectal cancer. However, major complications such as outlet obstruction and HOS can occur after surgery. Moreover, these complications cannot be prevented. Methods: This retrospective study included 34 patients with rectal cancer who underwent low anterior resection and ileostomy creation at Okayama University Hospital from January 2015 to December 2018. Then, the risk factors associated with outlet obstruction and HOS were analyzed. Results: Of 34 patients, 7 (21%) experienced outlet obstruction. In a multivariate logistic regression analysis, advanced T stage (P ¼ 0.10), ileostomy with a short horizontal diameter (P ¼ 0.01), and thick rectus abdominis (RA) muscle (P ¼ 0.0005) were considered independent risk factors for outlet obstruction. There was a significant correlation between outlet obstruction and HOS (P ¼ 0.03). Meanwhile, the independent risk factors of HOS were advanced T stage (P ¼ 0.03) and thick RA muscle (P ¼ 0.04). Conclusions: Thick RA muscle and advanced T stage were the common risk factors of outlet obstruction and HOS. Therefore, in high-risk patients, these complications can be prevented by choosing an appropriate ileostomy location according to RA muscle thickness and by preventing tubing into the ileostomy.

DOI： 10.9738/INTSURG-D-21-00012.1

Accreditation as a qualified surgeon improves surgical outcomes in laparoscopic distal gastrectomy. 査読

Satoru Kikuchi, Tetsuya Kagawa, Shinji Kuroda, Masahiko Nishizaki, Nobuo Takata, Kazuya Kuwada, Ryohei Shoji, Yoshihiko Kakiuchi, Toshiharu Mitsuhashi, Yuzo Umeda, Kazuhiro Noma, Shunsuke Kagawa, Toshiyoshi Fujiwara

Surgery today 51 ( 12 ) 1978 - 1984 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: The Endoscopic Surgical Skill Quantification System for qualified surgeons (QSs) was introduced in Japan to improve surgical outcomes. This study reviewed the surgical outcomes after initial experience performing laparoscopic distal gastrectomy (LDG) and evaluated the improvement in surgical outcomes following accreditation as a QS. METHODS: Eighty-seven consecutive patients who underwent LDG for gastric cancer by a single surgeon were enrolled in this study. The cumulative sum method was used to analyze the learning curve for LDG. The surgical outcomes were evaluated according to the two phases of the learning curve (learning period vs. mastery period) and accreditation (non-QS period vs. QS period). RESULTS: The learning period for LDG was 48 cases. Accreditation was approved at the 67th case. The operation time and estimated blood loss were significantly reduced in the QS period compared to the non-QS period (230 vs. 270 min, p < 0.001; 20.5 vs. 59.8 ml, p = 0.024, respectively). Furthermore, the major complication rate was significantly lower in the QS period than in the non-QS period (0 vs. 10.6%, p = 0.044). CONCLUSIONS: Experience performing approximately 50 cases is required to reach proficiency in LDG. After receiving accreditation as a QS, the surgical outcomes, including the complication rate, were improved.

DOI： 10.1007/s00595-021-02309-2

Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles. 査読国際誌

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

Molecular therapy : the journal of the American Society of Gene Therapy 29 ( 10 ) 2920 - 2930 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. Here, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.

DOI： 10.1016/j.ymthe.2021.05.015

Intracorporeal semi-hand-sewn Billroth I reconstruction in total laparoscopic distal gastrectomy. 査読

Satoru Kikuchi, Shinji Kuroda, Masahiko Nishizaki, Kazuya Kuwada, Nobuo Takata, Yoshihiko Kakiuchi, Shuya Yano, Kazuhiro Noma, Shunsuke Kagawa, Toshiyoshi Fujiwara

Asian journal of endoscopic surgery 14 ( 3 ) 640 - 643 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Intracorporeal Billroth I (B-I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi-hand-sewn (SHS) B-I reconstruction. MATERIALS AND SURGICAL TECHNIQUE: After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B-I anastomosis. All the transection line of the duodenum and one-third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand-sewn technique. DISCUSSION: SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra-abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32-63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill.

DOI： 10.1111/ases.12887

SMAD4 Germline Pathogenic Variant-Related Gastric Juvenile Polyposis with Adenocarcinoma Treated with Laparoscopic Total Gastrectomy: A Case Report. 査読国際誌

Yuya Sakurai, Satoru Kikuchi, Kunitoshi Shigeyasu, Yoshihiko Kakiuchi, Takehiro Tanaka, Hibiki Umeda, Masaki Sakamoto, Sho Takeda, Shuya Yano, Mashu Futagawa, Fumino Kato, Reimi Sogawa, Hideki Yamamoto, Shinji Kuroda, Yoshitaka Kondo, Fuminori Teraishi, Hiroyuki Kishimoto, Masahiko Nishizaki, Shunsuke Kagawa, Akira Hirasawa, Toshiyoshi Fujiwara

The American journal of case reports 22 e932241 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Scientific Information, Inc.

BACKGROUND Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. CASE REPORT A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. CONCLUSIONS JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

DOI： 10.12659/AJCR.932241

Efficacy and safety of short-term (3 days) enoxaparin in preventing venous thromboembolism after gastric cancer surgery: A single-center, prospective cohort study. 査読国際誌

Shinji Kuroda, Satoru Kikuchi, Yoshihiko Kakiuchi, Megumi Watanabe, Kazuya Kuwada, Tomoko Tsumura, Masahiko Nishizaki, Shunsuke Kagawa, Shiro Hinotsu, Toshiyoshi Fujiwara

International journal of surgery (London, England) 89 105946 - 105946 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Pharmacologic prophylaxis such as enoxaparin for venous thromboembolism (VTE) is rarely used in Japan, even following abdominal cancer surgery, for which it is recommended in relevant guidelines (at least 7 days of use) along with mechanical prophylaxis with intermittent pneumatic compression. Reasons for enoxaparin's unpopularity include concerns over postoperative bleeding and its inconvenience in clinical practice. Here, we conducted a prospective clinical study of short-term (3 days) use of enoxaparin, which is considered to minimally impact postoperative management without increasing bleeding risk. METHODS: Gastric cancer patients who underwent gastrectomy received enoxaparin for 3 days from postoperative day (POD) 1-4. The primary endpoint was the incidence of deep vein thrombosis (DVT), which was examined primarily via Doppler ultrasonography of the lower limbs between POD 8 and 14. The planned sample size was 70, which was calculated based on an estimated incidence rate of 9% and an upper limit of incidence rate of 20%, with alpha of 0.05 and beta of 0.2. RESULTS: A total of 70 gastric cancer patients were enrolled, and ultimately, 68 patients received the protocol intervention and DVT evaluation. Sixty-seven patients completed 6 enoxaparin injections, but 1 patient did not complete the course due to abdominal bleeding after initiation. The incidence of DVT was 4.4% (3/68), and the 95% upper confidence interval was 12.2%, lower than the 20% threshold we set as the upper limit of DVT incidence. DVT was detected only in the peripheral veins of the lower extremities in all 3 affected patients. The incidence of bleeding-related complications, which were not severe, was 1.5% (1/68). CONCLUSIONS: Short-term (3 days) use of enoxaparin was shown to be effective and safe for VTE prophylaxis, comparable to regular use (at least 7 days), in postoperative management of gastric cancer surgery.

DOI： 10.1016/j.ijsu.2021.105946

Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody. 査読国際誌

Nobuhiko Kanaya, Shinji Kuroda, Yoshihiko Kakiuchi, Kento Kumon, Tomoko Tsumura, Masashi Hashimoto, Toshiaki Morihiro, Tetsushi Kubota, Katsuyuki Aoyama, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Hiroyuki Mizuguchi, Yasuo Urata, Toshiyoshi Fujiwara

Molecular therapy : the journal of the American Society of Gene Therapy 28 ( 3 ) 794 - 804 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs.

DOI： 10.1016/j.ymthe.2020.01.003

Short-term and long-term comparisons of laparoscopy-assisted proximal gastrectomy with esophagogastrostomy by the double-flap technique and laparoscopy-assisted total gastrectomy for proximal gastric cancer. 査読国際誌

Tomoko Tsumura, Shinji Kuroda, Masahiko Nishizaki, Satoru Kikuchi, Yoshihiko Kakiuchi, Nobuo Takata, Atene Ito, Megumi Watanabe, Kazuya Kuwada, Shunsuke Kagawa, Toshiyoshi Fujiwara

PloS one 15 ( 11 ) e0242223 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Although proximal gastrectomy (PG) is a recognized surgical procedure for early proximal gastric cancer, total gastrectomy (TG) is sometimes selected due to concern about severe gastroesophageal reflux. Esophagogastrostomy by the double-flap technique (DFT) is an anti-reflux reconstruction after PG, and its short-term effectiveness has been reported. However, little is known about the long-term effects on nutritional status and quality of life (QOL). METHODS: Gastric cancer patients who underwent laparoscopy-assisted PG (LAPG) with DFT or laparoscopy-assisted TG (LATG) between April 2011 and March 2014 were retrospectively analyzed. Body weight (BW), body mass index (BMI), and prognostic nutritional index (PNI) were reviewed to assess nutritional status, and the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 was used to assess QOL. RESULTS: A total of 36 patients (LATG: 17, LAPG: 19) were enrolled. Four of 17 LATG patients (24%) were diagnosed with Stage ≥II after surgery, and half received S-1 adjuvant chemotherapy. BW and PNI were better maintained in LAPG than in LATG patients until 1-year follow-up. Seven of 16 LATG patients (44%) were categorized as "underweight (BMI<18.5 kg/m2)" at 1-year follow-up, compared to three of 18 LAPG patients (17%; p = 0.0836). The PGSAS-45 showed no significant difference in all QOL categories except for decreased BW (p = 0.0132). Multivariate analysis showed that LATG was the only potential risk factor for severe BW loss (odds ratio: 3.03, p = 0.0722). CONCLUSIONS: LAPG with DFT was superior to LATG in postoperative nutritional maintenance, and can be the first option for early proximal gastric cancer.

DOI： 10.1371/journal.pone.0242223

PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer. 査読国際誌

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

Scientific reports 9 ( 1 ) 4633 - 4633 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.

DOI： 10.1038/s41598-019-41177-2

Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer. 査読国際誌

Shuichi Sakamoto, Shunsuke Kagawa, Kazuya Kuwada, Atene Ito, Hiroki Kajioka, Yoshihiko Kakiuchi, Megumi Watanabe, Tetsuya Kagawa, Ryuichi Yoshida, Satoru Kikuchi, Shinji Kuroda, Hiroshi Tazawa, Toshiyoshi Fujiwara

Oncoimmunology 8 ( 12 ) e1671760 2019年

記述言語：英語掲載種別：研究論文（学術雑誌）

A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC.

DOI： 10.1080/2162402X.2019.1671760

HER2-targeted gold nanoparticles potentially overcome resistance to trastuzumab in gastric cancer. 査読国際誌

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

Nanomedicine : nanotechnology, biology, and medicine 14 ( 6 ) 1919 - 1929 2018年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

An issue of concern is that no current HER2-targeted therapeutic agent is effective against Trastuzumab (Tmab)-resistant gastric cancer. Gold nanoparticles (AuNPs) are promising drug carriers with unique characteristics of a large surface area available for attachment of materials such as antibodies. Here, we created HER2-targeted AuNPs (T-AuNPs) and examined their therapeutic efficacy and cytotoxic mechanisms using HER2-postive Tmab-resistant (MKN7) or Tmab-sensitive (NCI-N87) gastric cancer cell lines. In vitro, T-AuNPs showed stronger cytotoxic effects than controls against MKN7 and NCI-N87 cells although Tmab had no effect on MKN7 cells. Autophagy played an important role in T-AuNP cytotoxic mechanisms, which was considered to be driven by internalization of T-AuNPs. Finally, T-AuNPs displayed potent antitumor effects against NCI-N87 and MKN7 subcutaneous tumors in in vivo mouse models. In conclusion, HER2-targeted AuNPs with conjugated Tmab is a promising strategy for the development of novel therapeutic agents to overcome Tmab resistance in gastric cancer.

DOI： 10.1016/j.nano.2018.05.019

Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system. 査読国際誌

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 ) 14177 - 14177 2017年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

A small intestine volvulus caused by strangulation of a mesenteric lipoma: a case report. 査読国際誌

Yoshihiko Kakiuchi, Hiroaki Mashima, Naoto Hori, Hirotoshi Takashima

Journal of medical case reports 11 ( 1 ) 68 - 68 2017年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BioMed Central Ltd.

BACKGROUND: An emergency department encounters a variety of cases, including rare cases of the strangulation of a mesenteric lipoma by the greater omentum band. CASE PRESENTATION: A 67-year-old Japanese man presented with nausea, vomiting, and upper abdominal pain. There were no abnormalities detected by routine blood tests other than a slight rise in his white cell count. A contrast-enhanced computed tomography scan of his abdomen revealed a dilated intestine, a small intestine volvulus, and a well-capsulated homogeneous mass. He was suspected of having a small intestine volvulus that was affected by a mesenteric lipoma; therefore, single-port laparoscopic surgery was performed. Laparoscopy revealed a small intestine volvulus secondary to the strangulation of a mesenteric lipoma. The band and tumor were removed. He had no postoperative complications and was discharged on postoperative day 6. CONCLUSIONS: Although this case was an emergency, it showed that single-port laparoscopic surgery can be a safe, useful, and efficacious procedure.

DOI： 10.1186/s13256-017-1232-4

食道胃接合部へ達する胃大型GISTに対して腹腔鏡下胃局所切除術を施行した1例査読

垣内慶彦, 真島宏聡, 堀直人, 高嶌寛年, 西崎正彦

日鏡外会誌 22 ( 4 ) 531 - 637 2017年

[A Patient with Gastric Cancer with Peritoneal Dissemination Who Survived for Five Years after Sequential Chemotherapy with S-1 Followed by Paclitaxel].

Shinichi Urano, Yoshihiko Kakiuchi, Hirotoshi Takashima

Gan to kagaku ryoho. Cancer & chemotherapy 43 ( 2 ) 251 - 4 2016年2月

記述言語：日本語掲載種別：研究論文（学術雑誌）

A 76-year-old man complained of hematemesis and melena, and consulted the doctor. An endoscopic examination revealed type 3 advanced gastric cancer and a gastric ulcer with a visible vessel. We performed total gastrectomy with peritoneal metastasis dissection. After surgery, he received sequential chemotherapy with S-1 followed by paclitaxel. He continued the adjuvant chemotherapy without severe adverse events. He was treated successfully in spite of risk factors such as old age and postoperative body weight loss. We report herein a rare case of gastric cancer with peritoneal dissemination who achieved 5- year survival after surgery along with the literature review.

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