Updated on 2022/06/02

写真a

 
INOKAWA Yoshikuni
 
Organization
Nagoya University Hospital Gastroenterological Surgery 2 Assistant Professor
Graduate School
Graduate School of Medicine
Title
Assistant Professor

Degree 1

  1. 博士(医学) ( 2014.3   名古屋大学 ) 

Research Interests 8

  1. 膵臓癌

  2. 肝細胞癌

  3. 癌抑制遺伝子

  4. 消化器癌

  5. 消化器外科

  6. プロテオミクス

  7. ゲノム編集

  8. DNAメチル化

Research History 3

  1. 名古屋大学医学部附属病院   消化器外科2   助教

    2020.4

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    Country:Japan

  2. Nagoya University   Hospital, Hospital   Assistant professor of hospital

    2019.4

  3. Johns Hopkins University School of Medicine   Department of Otolaryngology, Head and Neck Cancer Research   Postdoctoral Fellow

    2016.5 - 2019.3

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    Country:United States

Professional Memberships 16

  1. Japan Biliary Association

    2020.10

  2. THE JAPAN SOCIETY OF ULTRASONICS IN MEDICINE

  3. 日本臨床外科学会

  4. JAPAN PANCREAS SOCIETY

  5. JAPANESE SOCIETY FOR ABDOMINAL EMERGENCY MEDICINE

  6. 日本胃癌学会

  7. The Japan Society of Hepatology

  8. JAPANESE SOCIETY OF HEPATO-BILIARY-PANCREATIC SURGERY

  9. JAPAN SOCIETY OF CLINICAL ONCOLOGY

  10. The Japanese Society of Gastroenterology

  11. THE JAPANESE SOCIETY OF GASTROENTEROLOGICAL SURGERY

  12. JAPANESE COLLEGE OF SURGEONS

  13. 日本外科学会

  14. 日本内視鏡外科学会

  15. 日本乳癌学会

  16. American Association for Cancer Research (AACR)

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Committee Memberships 1

  1. 日本肝胆膵外科学会   評議員  

    2014.6   

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    Committee type:Academic society

 

Papers 46

  1. Expression of cellular retinoic acid binding protein 1 predicts peritoneal recurrence of gastric cancer

    Sakata Kazuki, Kanda Mitsuro, Shimizu Dai, Nakamura Shunsuke, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Tanaka Chie, Nakayama Goro, Kodera Yasuhiro

    INTERNATIONAL JOURNAL OF ONCOLOGY   Vol. 60 ( 6 )   2022.6

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    Language:Japanese   Publisher:International Journal of Oncology  

    To improve the outcome of gastric cancer, novel markers that predict postoperative prognosis are required. For this purpose, the function of cellular retinoic acid binding protein 1 (CRABP1) in gastric cancer cells was investigated and it was determined whether it serves as a novel biomarker for gastric cancer. Reverse transcription-quantitative (RT-q) PCR and a PCR-array method were used to determine whether the expression of CRABP1 mRNA in gastric cancer cell lines correlated with the expression of cancer-related genes. The correlations of CRABP1 mRNA expression in tissues with clinicopathological factors of 230 patients who underwent radical gastrectomy were further evaluated. CRABP1 mRNA levels varied among gastric cancer cell lines and showed significant positive correlations with numerous epithelial-mesenchymal transition factors. Additionally, CRABP1 knockdown significantly suppressed the proliferation, migration and invasion of gastric cancer cell lines. In a mouse xenograft model of peritoneal metastasis of gastric cancer, it was found that the total weight of disseminated nodules was lower in the group, in which CRABP1 mRNA levels were knocked down compared with those of the untransfected group. Disease-free survival (DFS) was significantly shorter in patients with high expression of CRABP1, and multivariate analysis of DFS revealed that high expression of CRABP1 in the tumor area and lymph node metastasis served as an independent factor associated with poor prognosis. High expression of CRABP1 in cancer tissues was associated with a greater incidence of peritoneal recurrences after curative gastrectomy. These findings indicated that CRABP1 contributes to the malignant phenotype of gastric cancer cells and may serve as a biomarker for prognosing recurrence after curative resection, particularly peritoneal dissemination.

    DOI: 10.3892/ijo.2022.5353

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  2. Lysosomal-associated membrane protein family member 5 promotes the metastatic potential of gastric cancer cells

    Umeda Shinichi, Kanda Mitsuro, Shimizu Dai, Nakamura Shunsuke, Sawaki Koichi, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Tanaka Chie, Nakayama Goro, Kodera Yasuhiro

    GASTRIC CANCER   Vol. 25 ( 3 ) page: 558 - 572   2022.5

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    Language:Japanese   Publisher:Gastric Cancer  

    Background: Metastatic gastric cancer (GC) has a poor prognosis, and elucidating the molecular mechanisms involved in metastasis may lead to the development of novel therapeutic modalities. Methods: Transcriptome analysis of surgically resected metastatic tissue from GC patients and noncancerous tissue was performed to identify novel metastasis-related genes. Analyses of in vitro cell function, apoptosis, the cell cycle and cancer stemness were performed using GC cell lines with a stable knockout of a candidate gene. In vivo percutaneous, peritoneal dissemination and liver metastasis xenograft models were also generated. PCR array and proteome analyses were performed. Expression of the candidate gene was analyzed in GC tissues from 300 patients. Results: Lysosomal Associated Membrane Protein Family Member 5 (LAMP5) was upregulated in the metastatic tissues. LAMP5 knockout significantly suppressed proliferation, invasion, and migration of GC cells and increased apoptosis, cell cycle arrest and cancer stemness. LAMP5 knockout virtually suppressed tumor growth in in vivo percutaneous, peritoneal dissemination and liver metastasis models. EMT- and autophagy-related genes were associated with LAMP5. High LAMP5 mRNA levels were significantly associated with a worse prognosis. Conclusion: LAMP5 plays a vital role in metastasis formation and may be a promising novel target of drug development for metastatic GC in the future.

    DOI: 10.1007/s10120-022-01284-y

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  3. ASO Visual Abstract: Prognostic Value of a Modified Albumin-Bilirubin Grade Designed for Patients with Esophageal Squamous Cell Carcinoma after Radical Resection.

    Shinozuka T, Kanda M, Shimizu D, Tanaka C, Inokawa Y, Hattori N, Hayashi M, Koike M, Kodera Y

    Annals of surgical oncology     2022.4

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    Language:English  

    DOI: 10.1245/s10434-022-11784-x

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  4. Prognostic Value of a Modified Albumin-Bilirubin Score Designed for Patients with Esophageal Squamous Cell Carcinoma After Radical Resection

    Shinozuka Takahiro, Kanda Mitsuro, Shimizu Dai, Tanaka Chie, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Koike Masahiko, Kodera Yasuhiro

    ANNALS OF SURGICAL ONCOLOGY     2022.4

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    Language:Japanese   Publisher:Annals of Surgical Oncology  

    Background: The albumin–bilirubin (ALBI) score was originally developed to assess the severity of liver dysfunction in patients with hepatocellular carcinoma and has subsequently been used as a prognostic marker for that disease. Here, we examined the value of the preoperative ALBI score as a prognostic marker for patients with esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. Methods: We retrospectively analyzed data from 449 patients who underwent curative resection for ESCC. The ALBI score was calculated as (log10 serum bilirubin [μmol/l] × 0.66) + (serum albumin [g/l] × − 0.0852). Receiver operating characteristic curve analysis was used to define a preoperative modified ALBI (mALBI) score for patient stratification. Results: Of the 449 ESCC patients, 232 and 217 were assigned to mALBI Grade 1 or Grade 2 groups based on preoperative ALBI scores of ≤ − 3.33 or > − 3.33, respectively. Preoperative mALBI grade was significantly associated with age, excessive alcohol consumption, squamous cell carcinoma antigen level, and clinical disease stage. The mALBI Grade 2 group had significantly shorter disease-specific and recurrence-free survival than the mALBI Grade 1 group. Multivariate analysis demonstrated that mALBI Grade 2 was an independent prognostic factor for disease-specific survival (hazard ratio 1.86, 95% confidence interval 1.18–2.93, P = 0.0074). In most subgroup analyses, mALBI Grade 2 was associated with a greater risk of disease-specific death. Conclusions: mALBI grade serves as a simple and useful prognostic marker for disease-specific survival in patients with ESCC after radical esophagectomy.

    DOI: 10.1245/s10434-022-11654-6

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  5. Drain Amylase Concentrations at 3 h After Gastrectomy Enhance Early Prediction of Postoperative Peripancreatic Inflammatory Fluid Collection

    Nakanishi Koki, Kanda Mitsuro, Tanaka Chie, Takeda Shigeomi, Tanaka Katsuhito, Shimizu Dai, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Nakayama Goro, Fujiwara Michitaka, Kodera Yasuhiro

    WORLD JOURNAL OF SURGERY   Vol. 46 ( 3 ) page: 648 - 655   2022.3

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    Language:Japanese   Publisher:World Journal of Surgery  

    Background: Despite numerous studies of peripancreatic inflammatory fluid collection (PIFC) that report on the relevance of the drain amylase concentration (D-AMY), early prediction using this assay is problematic. This study aimed to investigate the clinical significance of measuring the D-AMY at 3 h after gastrectomy (POD0) for gastric cancer. Methods: This retrospective analysis included consecutive patients who underwent gastrectomy combined with peripancreatic lymph node dissection. The predictive value of D-AMY on POD0 and postoperative day 1 (POD1) for clinically relevant PIFC was evaluated together or individually. Results: Analyses were performed in 204 patients. Twenty (9.8%) patients experienced PIFC. D-AMY cutoffs of 721 IU/L on POD0 and 1695 IU/L on POD1 were determined using the receiver operating characteristic curve analysis for predicting PIFC. The D-AMY on POD0 had higher sensitivity (80%) but lower specificity (66.3%) for prediction of PIFC, compared with those of D-AMY on POD1 (65%, 89.1%, respectively). When combination marker analysis was performed, the highest risk group (D-AMY ≥ the cutoff values of POD0 and POD1) were associated with an elevated rate of occurrence (44%) and a high positive likelihood ratio (7.36) compared with those of the single cutoff group. The lowest risk group (D-AMY < the cutoff values on POD0 and POD1) was associated with a low rate of occurrence (2.5%) and low negative likelihood ratio (0.24) compared with those of the single cutoff group. Conclusions: Combined measurements of D-AMYs on POD0 and POD1 enhanced early prediction of PIFC after gastrectomy.

    DOI: 10.1007/s00268-021-06401-z

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  6. Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy

    Sunagawa Yuki, Hayashi Masamichi, Yamada Suguru, Tanabe Hiroshi, Kurimoto Keisuke, Tanaka Nobutake, Sonohara Fuminori, Inokawa Yoshikuni, Takami Hideki, Kanda Mitsuro, Tanaka Chie, Nakayama Goro, Koike Masahiko, Kodera Yasuhiro

    CLINICAL EPIGENETICS   Vol. 13 ( 1 ) page: 172   2021.12

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    Language:Japanese   Publisher:Clinical Epigenetics  

    Background: Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins. Methods: We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017–2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes. Results: Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352–9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019). Conclusion: Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.

    DOI: 10.1186/s13148-021-01165-8

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  7. Neoadjuvant docetaxel, oxaliplatin plus S-1 for treating clinical stage III squamous cell carcinoma of the esophagus: Study protocol of an open-label phase II trial

    Kanda Mitsuro, Shimizu Dai, Miyata Kazushi, Maeda Osamu, Tanaka Chie, Inokawa Yoshikuni, Hattori Norofumi, Hayashi Masamichi, Ando Masahiko, Kuwatsuka Yachiyo, Murotani Kenta, Nakayama Goro, Koike Masahiko, Ando Yuichi, Ebata Tomoki, Kodera Yasuhiro

    CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS   Vol. 24   page: 100853   2021.12

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    Language:Japanese   Publisher:Contemporary Clinical Trials Communications  

    In Japan, esophagectomy after two courses of 5-fluorouracil plus cisplatin is regarded a standard strategy for treating resectable stage II or III esophageal squamous cell carcinoma (ESCC). However, 5-fluorouracil plus cisplatin does not benefit cohorts with clinical stage III ESCC, suggesting the requirement for a more effective regimen. We are conducting a single-arm phase II study to assess the safety and efficacy of neoadjuvant docetaxel, oxaliplatin plus S-1 (DOS) for treating patients with clinical stage III ESCC. The primary endpoint is the pathological response rate, and the target number is 45 patients. Safety, response rate, R0 resection rate, and survival are secondary endpoints. This trial is registered in the Japan Registry of Clinical Trials as jRCTs041210023. We are conducting a prospective phase II trial to evaluate the safety and efficacy of three courses of neoadjuvant DOS treatment followed by radical esophagectomy for clinical stage III ESCC.

    DOI: 10.1016/j.conctc.2021.100853

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  8. Double common bile duct associated with pancreaticobiliary maljunction

    Yamada Kenta, Ishikawa Takuya, Ohno Eizaburo, Iida Tadashi, Suzuki Hirotaka, Uetsuki Kota, Yashika Jun, Yoshikawa Masakatsu, Takami Hideki, Inokawa Yoshikuni, Uchida Hiroo, Kawashima Hiroki, Fujishiro Mitsuhiro

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 83 ( 3 ) page: 655 - 661   2021.8

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    Language:Japanese   Publisher:Nagoya Journal of Medical Science  

    A 45-year-old female was admitted to the hospital with a diagnosis of acute pancreatitis. A computed tomography scan showed two extrahepatic bile ducts. Magnetic resonance cholangiopancreatography suggested a stone in one of the bile ducts. Endoscopic retrograde cholangiopancreatography revealed two extrahepatic bile ducts joining at the hilum of the liver accompanied with pancreaticobiliary maljunction. Sphincterotomy was performed and a protein plug was drained from the bile duct. Several treatment options were discussed, and the patient was treated with laparoscopic cholecystectomy without extrahepatic bile duct resection and planned to be followed up considering the risk of carcinogenesis in the bile ducts.

    DOI: 10.18999/nagjms.83.3.655

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  9. Different Characteristics of Serum Alfa Fetoprotein and Serum Des-gamma-carboxy Prothrombin in Resected Hepatocellular Carcinoma

    Hayashi Masamichi, Yamada Suguru, Takano Nao, Okamura Yukiyasu, Takami Hideki, Inokawa Yoshikuni, Sonohara Fuminori, Tanaka Nobutake, Shimizu Dai, Hattori Norifumi, Kanda Mitsuro, Tanaka Chie, Nakayama Goro, Koike Masahiko, Kodera Yasuhiro

    IN VIVO   Vol. 35 ( 3 ) page: 1749 - 1760   2021

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    Background/Aim: Hepatocellular carcinoma (HCC) mainly develops in the damaged liver from hepatitis C virus (HCV) or hepatitis B virus (HBV) infection in Japan. On the other hand, the occurrence of HCCs derived from the liver without viral infection has recently been increasing. Our aim was to identify characteristics specific to HCCs with virus-infected liver (HCC-BC) or those with non-B- and non-C-infected liver (HCC-NBNC), Patients and Methods: We collected preoperative serum α-fetoprotein (AFP) and Des-Gamma-Carboxy Prothrombin (DCP), also known as PIVKA-II values from surgically resected HCC cases during 1994-2017 in our department. Results: Preoperative serum AFP values of HCC-BC cases (n=284) were higher compared to HCC-NBNC cases (n=88) (p=0.016), whereas serum DCP values of HCC-NBNC cases were higher compared to HCC-BC cases (p<0.001). Multivariable analyses indicated that abnormal serum AFP [hazard ratio (HR)=1.46, 95% conficdence interval (CI)=1.03-2.07, p=0.035) was one of the significant recurrence-free survival predictors of HCC-BC cases, while abnormal serum DCP (HR=4.99, 95%CI=1.91-13.01, p=0.001) was one of the significant recurrence-free survival predictors of HCC-NBNC cases. Conclusion: HCC-NBNC cases have a different tumor marker profile from HCC-BC cases. Elevated DCP could be both a diagnostic and prognostic marker of HCC-NBNC patients.

    DOI: 10.21873/invivo.12434

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  10. The impact of cancer stem cell markers in the tissues of pancreatic ductal adenocarcinoma for prognosis after surgical resections

    Inokawa Yoshikuni, Yamada Suguru, Hayashi Masamichi, Sunagawa Yuki, Sonohara Fuminori, Takami Hideki, Hattori Norifumi, Kanda Mitsuro, Kobayashi Daisuke, Tanaka Chie, Nakayama Goro, Koike Masahiko, Kodera Yasuhiro

    CANCER RESEARCH   Vol. 80 ( 16 )   2020.8

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  11. Predictive value of the modified systemic inflammation score in patients undergoing curative resection of squamous cell carcinoma of the esophagus

    Kanda Mitsuro, Koike Masahiko, Shimizu Dai, Tanaka Chie, Kobayashi Daisuke, Sonohara Fuminori, Takami Hideki, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Yamada Suguru, Nakayama Goro, Fujiwara Michitaka, Kodera Yasuhiro

    JOURNAL OF CLINICAL ONCOLOGY   Vol. 38 ( 4 )   2020.2

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  12. A case of renal salt-wasting syndrome induced by cisplatin and 5-FU during treatment of esophageal squamous cell carcinoma

    Shimizu Dai, Kanda Mitsuro, Koike Masahiko, Umeda Shinichi, Sonohara Fuminori, Takami Hideki, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Tanaka Chie, Kobayashi Daisuke, Yamada Suguru, Nakayama Goro, Fujiwara Michitaka, Kodera Yasuhiro

    Annals of Cancer Research and Therapy   Vol. 27 ( 2 ) page: 64 - 66   2019

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    Language:Japanese   Publisher:The Japanese Society of Strategies for Cancer Research and Therapy  

    <p>The combination regimen of cisplatin (CDDP) and fluorouracil (5-FU) (FP) is a standard regimen for definitive chemoradiotherapy, neoadjuvant chemotherapy, and for treatment of unresectable or recurrent esophageal squamous cell carcinoma (ESCC). Here, we report a patient with FP-induced renal salt-wasting syndrome (RSWS) who presented with severe hyponatremia with disturbance of consciousness and was admitted to the intensive care unit (ICU). A 66-year-old man with recurrent ESCC was admitted and started on chemotherapy with FP. From day 3 of the first course of FP, he presented with anorexia and vomiting (grade 3). At day 6, he experienced disturbance of consciousness and blood test showed severe hyponatremia (sodium (Na): 119 mmol/L) accompanied with excessive urinary excretion of Na (181 mmol/L). He was diagnosed with RSWS because of CDDP and was transferred to the ICU. Through intensive monitoring and 3% NaCl infusion, serum Na level and symptoms recovered with no sequelae and he was discharged from the ICU after a 4-day stay.</p><p>RSWS is sometimes difficult to diagnose because of its low recognition and is misdiagnosed as the syndrome of inappropriate secretion of antidiuretic hormone. During chemotherapy with platinum-based agents, RSWS should be kept in mind as a disorder that causes hyponatremia.</p>

    DOI: 10.4993/acrt.27.64

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  13. Blockade of CHRNB2 signaling with a therapeutic monoclonal antibody attenuates the aggressiveness of gastric cancer cells. International journal

    Mitsuro Kanda, Dai Shimizu, Shunsuke Nakamura, Koichi Sawaki, Shinichi Umeda, Takashi Miwa, Haruyoshi Tanaka, Yoshikuni Inokawa, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Goro Nakayama, Yohei Iguchi, Masahisa Katsuno, Yasuhiro Kodera

    Oncogene   Vol. 40 ( 36 ) page: 5495 - 5504   2021.9

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    Here, we evaluated the therapeutic potential of antibodies (Abs) targeting cholinergic receptor nicotinic beta 2 subunit (CHRNB2) in gastric cancer. To investigate the effects of these Abs on malignant phenotypes in vitro and in mouse xenograft models, we generated gene knockouts through genome editing, performed RNA interference-mediated knockdown of gene expression, and ectopically expressed CHRNB2 in gastric cancer cells. The effects of anti-CHRNB2 Abs on the proliferation of cancer cells were evaluated both in vitro and in vivo. We determined the effects of Chrnb2 deficiency on mice and the clinical significance of CHRNB2 expression in gastric cancer clinical specimens. Knockdown of CHRNB2 attenuated gastric cancer cell proliferation, whereas forced overexpression of CHRNB2 increased cell proliferation. Knockout of CHRNB2 significantly influenced cell survival and functions associated with metastasis. The effects of polyclonal Abs targeting the C- and N-termini of CHRNB2 guided the development of anti-CHRNB2 monoclonal Abs that inhibited the growth of gastric cancer cells in vitro and in vivo. Pathway analysis revealed that CHRNB2 interfered with signaling through the PI3K-AKT and JAK-STAT pathways. Chrnb2-deficient mice exhibited normal reproduction, organ functions, and motor functions. CHRNB2 regulates multiple oncological phenotypes associated with metastasis, and blockade of CHRNB2 expression using specific Abs shows promise for controlling metastasis in gastric cancer.

    DOI: 10.1038/s41388-021-01945-9

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  14. A Possible Definition of Oligometastasis in Pancreatic Cancer and Associated Survival Outcomes. International journal

    Masaya Yamanaka, Masamichi Hayashi, Suguru Yamada, Fuminori Sonohara, Hideki Takami, Yoshikuni Inokawa, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Anticancer research   Vol. 41 ( 8 ) page: 3933 - 3940   2021.8

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    BACKGROUND: Oligometastatic cancer (OM) is possibly associated with relatively better survival outcomes. We attempted to identify cases in line with this OM concept. PATIENTS AND METHODS: A total of 130 cases with unresectable metastatic pancreatic cancer underwent non-curative surgery from April 2001 to December 2019. Sites of metastasis, clinicopathological information, and surgical outcomes were collected to formulate a better definition of OM. RESULTS: OM criteria were defined as having metastasis to a single organ, few countable lesions and low serum cancer antigen 19-9 level. The median overall survival after non-curative surgery of OM cases was 13.0 months and was significantly better than that of non-OM cases (8.4 months, p=0.003). CONCLUSION: We propose single-organ metastasis of limited tumor volume (H1 or P1/2 by the Japanese Society of Cancer of the Colon and Rectum classification) and low serum cancer antigen 19-9 level (<2,000 U/ml) as new criteria for defining OM pancreatic cancer.

    DOI: 10.21873/anticanres.15189

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  15. High Serum Uric Acid Levels Could Be a Risk Factor of Hepatocellular Carcinoma Recurrences. International journal

    Masamichi Hayashi, Suguru Yamada, Hiroshi Tanabe, Hideki Takami, Yoshikuni Inokawa, Fuminori Sonohara, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera

    Nutrition and cancer   Vol. 73 ( 6 ) page: 996 - 1003   2021.7

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    BACKGROUND: The Apolipoprotein-related MORtality RISk (AMORIS) study in Sweden revealed that serum uric acid (SUA) was significantly associated with hepatobiliary cancer occurrence. However, the association with postoperative hepatocellular carcinoma (HCC) recurrence has not been reported. METHODS: A total of 256 surgically resected HCC patients were included (from January 2003 to December 2017) in this study. Comparisons in terms of clinicopathologic factors and long-term outcomes were made between patients with high SUA (>6.1 mg/dl) at the time of hepatectomy and low SUA. Besides, SUA data at one postoperative year (1POY) of the same cohort were collected and analyzed in the same manner. RESULTS: About 88.8% of tumor relapse sites were the remnant liver. High SUA levels were associated with male and well-differentiated HCCs. Recurrence-free survival (RFS) of high SUA patients was significantly inferior to low SUA patients [median survival time (MST): 22.7 vs. 28.5 mo, P = 0.033], whereas no difference was observed in overall survival (MST: both not reached, P = 0.771). RFS of high SUA patients at 1POY also showed significantly poorer outcomes than low SUA patients (MST: 29.3 vs. 57.0 mo, P = 0.049). CONCLUSIONS: High SUA implies a significant risk factor of activating hepatocarcinogenesis. Keeping the SUA level low may be recommended after HCC resections.

    DOI: 10.1080/01635581.2020.1779758

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  16. The impact of early tumor shrinkage on conversion surgery and the survival in patients with unresectable locally advanced pancreatic cancer.

    Nao Takano, Suguru Yamada, Fuminori Sonohara, Yoshikuni Inokawa, Hideki Takami, Masamichi Hayashi, Masahiko Koike, Tsutomu Fujii, Yasuhiro Kodera

    Surgery today   Vol. 51 ( 7 ) page: 1099 - 1107   2021.7

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    PURPOSES: Owing to recent advances in induction chemo(radio)therapy, patients with unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) are sometimes indicated for conversion surgery (CS). However, the predictors for proceeding to CS are unclear. We investigated the predictive factors for CS, especially at the early stage of induction therapy, and evaluated the impact of CS on the survival. METHODS: We analyzed 49 UR-LA PDAC patients retrospectively and investigated the predictive factors for proceeding to CS, including early tumor shrinkage (ETS). ETS in this study was defined as shrinkage of tumors by ≥ 15% at 8-12 weeks after the induction of treatment. RESULTS: CS was performed in 21 patients (43%). In a multivariate logistic regression analysis, ETS was an independent predictive factor for successfully proceeding to CS (P = 0.046). The median overall survival (OS) was not reached in the CS group but was 17.2 months in the non-CS group (P < 0.0001). A multivariate analysis by the Cox proportional hazard model identified CS as the only significant independent determinant of the OS (hazard ratio: 0.26, 95% confidence interval: 0.07-0.94, P = 0.004). CONCLUSIONS: ETS by induction therapy is a significant predictor of proceeding to CS among patients with UR-LA PDAC. CS was the only independent prognostic factor for this population.

    DOI: 10.1007/s00595-020-02220-2

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  17. Novel prognostic implications of YTH domain family 2 in resected hepatocellular carcinoma. International journal

    Nobuhiko Nakagawa, Fuminori Sonohara, Katsuhito Tanaka, Yuki Sunagawa, Yoshikuni Inokawa, Hideki Takami, Masamichi Hayashi, Suguru Yamada, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Oncology letters   Vol. 22 ( 1 ) page: 538 - 538   2021.7

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    N6-methyladenosine (m6A), the most abundant internal RNA modification, serves a critical role in cancer development. However, the clinical implications of m6A in hepatocellular carcinoma (HCC) remain unclear. The present study sought to reveal the potential roles of m6A readers, which recognize m6A, in HCC. A total of 177 HCC and paired non-cancerous liver tissues from patients who underwent hepatectomy were analysed using quantitative PCR for the expression of m6A readers: YT521-B homology domain family 1 (YTHDF1) and YT521-B homology domain family 2 (YTHDF2). The expression levels of both YTHDF1 and YTHDF2 were not significantly different between tumour and non-cancerous tissues (P=0.93 and P=0.7, respectively). Analysis of the association between clinical features and m6A reader expression revealed that YTHDF1 expression was associated with formation of capsule (P=0.02), whereas low YTHDF2 expression was associated with septal formation (P=0.02). Furthermore, high YTHDF1 expression and high YTHDF2 expression were significantly associated with shorter recurrence-free survival (RFS) [YTHDF1: Mean survival time (MST), 34.0 vs. 19.0 months, P=0.014; YTHDF2: MST, 30.1 vs. 12.9 months, P=0.0032], whereas YTHDF1 and YTHDF2 expression was not significantly associated with overall survival (OS) (YTHDF1: MST, 99.4 vs. 70.2 months, P=0.74; YTHDF2: MST, 98.4 vs. 64.1 months, P=0.28). According to multivariate analysis, serosal invasion [hazard ratio (HR), 2.39; 95% CI 1.30-4.42; P=0.005), portal vein or hepatic vein invasion (HR, 2.82; 95% CI 1.26-6.28; P=0.01) and YTHDF2 expression in HCC tissues (HR, 1.85; 95% CI 1.09-3.15; P=0.02) were identified as significant independent prognostic factors for RFS. α-fetoprotein (HR, 1.79; 95% CI 1.10-2.92; P=0.02), serosal invasion (HR, 1.99; 95% CI 1.17-3.34; P=0.01) and portal vein or hepatic vein invasion (HR, 3.02; 95% CI 1.38-6.61; P=0.006) were identified as significant independent prognostic factors for OS. In conclusion, the present study revealed that high YTHDF2 expression, an m6A reader, in HCC tissues was associated with cancer recurrence.

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  18. BRA膵癌に対する治療戦略 BR-A膵癌に対する集学的治療の術後成績

    猪川 祥邦, 田中 伸孟, 園原 史訓, 高見 秀樹, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: O34 - 5   2021.7

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  19. 膵癌に対する術前AGRと臨床病理学的因子や予後に関する検討

    小林 大悟, 林 真路, 加藤 吉康, 栗本 景介, 田中 伸孟, 砂川 祐輝, 園原 史訓, 猪川 祥邦, 高見 秀樹, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: P129 - 4   2021.7

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  20. 膵癌におけるEat me signalの関与

    林 真路, 高見 秀樹, 猪川 祥邦, 園原 史訓, 田中 伸孟, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: P186 - 1   2021.7

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  21. 後期高齢者肝細胞癌における肝切除術の安全性と妥当性に関する検討

    田中 伸孟, 林 真路, 園原 史訓, 猪川 祥邦, 高見 秀樹, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: P163 - 7   2021.7

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  22. 右側肝円索に合併した胆嚢癌の1例

    鈴木 雄之典, 猪川 祥邦, 栗本 景介, 田中 伸孟, 園原 史訓, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: P126 - 6   2021.7

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  23. UR膵癌に対するConversion surgeryの適応 当科におけるUnresectable膵癌治療症例の検討 非切除例も含めた全コホート解析

    加藤 吉康, 高見 秀樹, 林 真路, 園原 史訓, 猪川 祥邦, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤井 努, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: PD6 - 4   2021.7

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  24. IPMN診断と治療のUpdate IPMN国際診療ガイドライン2017の手術適応の検証

    山中 雅也, 高見 秀樹, 園原 史訓, 猪川 祥邦, 林 真路, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本消化器外科学会総会   Vol. 76回   page: RS22 - 7   2021.7

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  25. miR-23b-3p Plays an Oncogenic Role in Hepatocellular Carcinoma. International journal

    Masamichi Hayashi, Suguru Yamada, Keisuke Kurimoto, Hiroshi Tanabe, Sho Hirabayashi, Fuminori Sonohara, Yoshikuni Inokawa, Hideki Takami, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Annals of surgical oncology   Vol. 28 ( 6 ) page: 3416 - 3426   2021.6

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    BACKGROUND: Reports show miR-23b to be a cancer-related biomarker in various cancer types. Interestingly, it has a dual role of oncogenic and tumor-suppressive functions, depending on the cancer type. This study focused on the unknown association of miR-23b-3p with hepatocellular carcinoma (HCC). METHODS: Expression of miR-23b-3p was measured in nine HCC cell lines and 125 resected human HCC samples by TaqMan microRNA assays. To detect its downstream target, miR-23b-3p mimic and inhibitor constructs were transfected and analyzed. RESULTS: HepG2, a high miR-23b-3p-expressing cell line, was transfected with a miR-23b-3p inhibitor construct, whereas SK-Hep1, a low miR-23b-3p-expressing cell line, was transfected with a mimic construct. Proliferation of HCC cells was activated by miR-23b-3p overexpression and diminished by its knockdown. Then, 125 clinical HCC samples were examined to measure miR-23b-3p expression. Tumor expression of miR-23b-3p was upregulated in 48 cases (38%) and downregulated in 77 cases (62%). The upregulated cases were correlated with elderly patients (P = 0.015). These patients also showed significantly poor overall survival [hazard ratio (HR), 3.10; 95% conflidence interval (CI), 1.57-6.29; P = 0.001] in a multivariate analysis. Furthermore, mitochondrial metabolism-related genes (MICU3 and AUH) were detected as specific binding targets. CONCLUSION: The study showed that miR-23b-3p functions as an oncogenic microRNA in HCC cell lines. Its overexpression in resected HCC tissues was a significant prognostic factor of overall survival. Both MICU3 and AUH may be candidate gene targets of miR-23b-3p.

    DOI: 10.1245/s10434-020-09283-y

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  26. Genome-wide identification and characterization of circular RNA in resected hepatocellular carcinoma and background liver tissue. International journal

    Yuki Sunagawa, Suguru Yamada, Fuminori Sonohara, Keisuke Kurimoto, Nobutake Tanaka, Yunosuke Suzuki, Yoshikuni Inokawa, Hideki Takami, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Scientific reports   Vol. 11 ( 1 ) page: 6016 - 6016   2021.3

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    Circular RNA (circRNA) is a type of non-coding RNA known to affect cancer-related micro RNAs and various transcription factors. circRNA has promise as a cancer-related biomarker because its circular structure affords high stability. We found using high-throughput sequencing that seven candidate circRNAs (hsa_circ_0041150, hsa_circ_0025624, hsa_circ_0001020, hsa_circ_0028129, hsa_circ_0008558, hsa_circ_0036683, hsa_circ_0058087) were downregulated in HCC. The expression of these circRNAs was examined by quantitative PCR in 233 sets of HCC and matched background normal liver tissues, and correlations between candidate circRNA expression and prognosis were evaluated. The results of quantitative PCR showed that expression of hsa_circ_0041150, hsa_circ_0001020 and hsa_circ_0008558 was significantly lower in HCC than in background normal liver tissues. Kaplan-Meier analysis revealed that low expression of hsa_circ_0001020, hsa_circ_0036683, and hsa_circ_0058087 was associated with poor recurrence-free (RFS) and overall survival (OS) in HCC. Additionally, multivariate analysis revealed that low hsa_circ_0036683 expression was a significant prognostic factor, independent from other clinicopathological features, for inferior RFS and OS. There was no significant association between the expression of these circRNAs and hepatitis B/C status or cirrhosis. This study therefore identified circRNAs as potential prognostic markers for patients who undergo curative surgery for HCC and highlighted hsa_circ_0036683 as the most useful biomarker.

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  27. Tissue <i>RNFT2</i> Expression Levels Are Associated With Peritoneal Recurrence and Poor Prognosis in Gastric Cancer.

    Sasahara M, Kanda M, Shimizu D, Tanaka C, Inokawa Y, Hattori N, Hayashi M, Nakayama G, Kodera Y

    Anticancer research   Vol. 41 ( 2 ) page: 609 - 617   2021.2

  28. Tissue RNFT2 Expression Levels Are Associated With Peritoneal Recurrence and Poor Prognosis in Gastric Cancer

    Sasahara Masahiro, Kanda Mitsuro, Shimizu Dai, Tanaka Chie, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Nakayama Goro, Kodera Yasuhiro

    ANTICANCER RESEARCH   Vol. 41 ( 2 ) page: 609 - 617   2021.2

  29. Tissue RNFT2 Expression Levels Are Associated With Peritoneal Recurrence and Poor Prognosis in Gastric Cancer

    Sasahara Masahiro, Kanda Mitsuro, Shimizu Dai, Tanaka Chie, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Nakayama Goro, Kodera Yasuhiro

    ANTICANCER RESEARCH   Vol. 41 ( 2 ) page: 609 - 617   2021.2

  30. Tissue RNFT2 expression levels are associated with peritoneal recurrence and poor prognosis in gastric cancer

    Sasahara M.

    Anticancer Research   Vol. 41 ( 2 ) page: 609 - 617   2021.2

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    DOI: 10.21873/ANTICANRES.14812

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  31. Age-Related Differences in the Prognosis of Pancreatic Cancer According to Perioperative Systemic Therapy. International journal

    Fuminori Sonohara, Suguru Yamada, Keisuke Kurimoto, Yoshikuni Inokawa, Hideki Takami, Masamichi Hayashi, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Tsutomu Fujii, Yasuhiro Kodera

    Pancreas   Vol. 50 ( 1 ) page: 37 - 46   2021.1

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    OBJECTIVES: In this study, we retrospectively assessed the feasibility and prognostic efficacy of perioperative chemo(radio)therapy for pancreatic cancer (PC) patients according to age. METHODS: A total of 556 consecutive patients who underwent curative-intent pancreatectomy for PC between 2000 and 2018 were enrolled. RESULTS: Of the 556 patients who underwent resection, 95 (17%) were elderly (age, ≥75 years). Postoperative complications did not significantly differ between the 2 age groups, and postoperative prognoses were also similar (recurrence-free survival [RFS], P = 0.68; overall survival [OS], P = 0.28). In this cohort, 103 patients (19%) underwent preoperative chemo(radio)therapy, and 417 (77%) underwent postoperative chemotherapy. Perioperative therapy was found to be significantly beneficial for younger patients (preoperative therapy: RFS, P = 0.006; OS, P < 0.001; postoperative therapy: RFS, P < 0.001; OS, P < 0.001). Conversely, no significant survival benefit of perioperative therapy was found for the elderly (preoperative therapy: RFS, P = 0.28; OS, P = 0.44; postoperative therapy: RFS, P = 0.77; OS, P = 0.08). CONCLUSIONS: This study demonstrated that, although perioperative therapy is feasible for selected elderly patients with PC, this approach might not be as beneficial as it is for younger PC patients.

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  32. Perioperative assessment of indocyanine green elimination rate accurately predicts postoperative liver failure in patients undergoing hepatectomy.

    Yuki Sunagawa, Suguru Yamada, Yoshiyasu Kato, Fuminori Sonohara, Hideki Takami, Yoshikuni Inokawa, Masamichi Hayashi, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Journal of hepato-biliary-pancreatic sciences   Vol. 28 ( 1 ) page: 86 - 94   2021.1

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    BACKGROUND: This study aimed to evaluate the usefulness of perioperative indocyanine green elimination rate (ICG-K) as a predictive factor of posthepatectomy liver failure (PHLF). METHODS: This study enrolled 193 patients who underwent hepatectomy between 2013 and 2019. We analyzed the relationship between estimated ICG-K (ICG-Krem) calculated by the preoperative ICG-K and the residual liver volume ratio, ICG-K at days 1 and 7 after hepatectomy (ICG-Kpod1, ICG-Kpod7), and grade B or C PHLF. RESULTS: Grade B and C PHLF were observed in eight and two patients, respectively. ICG-Krem and ICG-Kpod1 were highly correlated (correlation coefficient [CC] 0.715), and ICG-Krem and ICG-Kpod7 were moderately correlated (CC 0.653). Receiver-operating characteristic curve analyses indicated that ICG-Krem and ICG-Kpod1 had moderate diagnostic value, while ICG-Kpod7 had high diagnostic value (area under the curve 0.703, 0.845 and 0.937, respectively). Multivariate analysis demonstrated that ICG-Kpod7 (relative risk [RR] 26.04, P = .012) and postoperative bile leakage (PBL) (RR 226.0, P < .001) were independent predictive factors for PHLF. PBL induced PHLF in seven patients, respectively. CONCLUSIONS: ICG-Krem correlated well with postoperative ICG-K, having moderate accuracy as a predictor of PHLF. However, the clinical relevance of postoperatively measuring ICG-K is limited because PHLF is greatly affected by surgical and postoperative factors.

    DOI: 10.1002/jhbp.833

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  33. AMIGO2 Expression as a Potential Prognostic Biomarker for Gastric Cancer. International journal

    Shunsuke Nakamura, Mitsuro Kanda, Dai Shimizu, Chie Tanaka, Yoshikuni Inokawa, Norifumi Hattori, Masamichi Hayashi, Suguru Yamada, Goro Nakayama, Kenji Omae, Masahiko Koike, Yasuhiro Kodera

    Anticancer research   Vol. 40 ( 12 ) page: 6713 - 6721   2020.12

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    BACKGROUND/AIM: Although our understanding of the molecular mechanisms of gastric cancer (GC) development and progression is steadily deepening, the clinical outcome of GC patients remains inadequate. The identification of molecules associated with GC will help improve prognosis. We aimed to identify the molecules involved in GC progression and metastasis. MATERIALS AND METHODS: Transcriptome analysis was performed on surgically resected gastric tissue from patients with hepatic metastasis. Fourteen cell lines and 230 pairs of primary GC tissues and their corresponding normal adjacent tissues were included in the mRNA expression analysis. RESULTS: Adhesion molecule with Ig like domain 2 (AMIGO2) was identified as a gene of interest. The levels of AMIGO2 mRNA positively correlated with those encoding FOXC2, NODAL, GEMIN2 and negatively correlated with TFPI2. Patients with high AMIGO2 expression experienced significantly shorter disease-free survival and overall survival. High levels of AMIGO2 were associated with poor prognosis. CONCLUSION: Patients with GC with high AMIGO2 mRNA levels experienced significantly shorter survival, suggesting that AMIGO2 may serve as a prognostic biomarker for GC.

    DOI: 10.21873/anticanres.14694

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  34. Novel Prognostic Implications of Methylated RNA and Demethylases in Resected HCC and Background Liver Tissue. International journal

    Nobuhiko Nakagawa, Katsuhito Tanaka, Fuminori Sonohara, Raju Kandimalla, Yuki Sunagawa, Yoshikuni Inokawa, Hideki Takami, Masamichi Hayashi, Suguru Yamada, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

    Anticancer research   Vol. 40 ( 12 ) page: 6665 - 6676   2020.12

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    BACKGROUND/AIM: N6-Methyladenosine (m6A), the most abundant internal modification of RNA, plays a critical role in cancer development. However, the clinical implications of m6A in hepatocellular carcinoma (HCC) remain unclear. MATERIALS AND METHODS: We analyzed 177 HCC and paired noncancerous liver tissues from patients who underwent hepatectomy according to global m6A quantification and expression of m6A demethylases fat mass and obesity-associated protein (FTO) and alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5). RESULTS: The global m6A quantification revealed no significant difference between HCC and non-cancerous tissue. The expression of m6A demethylases FTO and ALKBH5, was significantly lower in HCC than in non-cancerous tissues (both p<0.001). Furthermore, low ALKBH5 expression in non-cancerous tissues was significantly correlated with worse recurrence-free survival (median of 16.3 vs. 38.9 months, p=0.001). CONCLUSION: m6A in HCC and its demethylase in surrounding non-cancerous liver tissues might be involved in inherent mechanisms for HCC development and affect malignant potential after HCC resection.

    DOI: 10.21873/anticanres.14690

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  35. Concurrent Targeting of Potential Cancer Stem Cells Regulating Pathways Sensitizes Lung Adenocarcinoma to Standard Chemotherapy. International journal

    Masahiro Shibata, Akira Ooki, Yoshikuni Inokawa, Pritam Sadhukhan, M Talha Ugurlu, Evgeny Izumchenko, Enrico Munari, Giuseppe Bogina, Charles M Rudin, Edward Gabrielson, Anju Singh, Mohammad O Hoque

    Molecular cancer therapeutics   Vol. 19 ( 10 ) page: 2175 - 2185   2020.10

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    Cancer stem cells (CSC) are highly resistant to conventional chemotherapeutic drugs. YAP1 and STAT3 are the two transcription factors that facilitate the therapeutic resistance and expansion of CSCs. The objective of this study was to understand the cross-talk between YAP1 and STAT3 activities and to determine the therapeutic efficacy of targeting dual CSC-regulating pathways (YAP1 and STAT3) combined with chemotherapy in lung adenocarcinoma. Here, we showed that YAP1 contributes to CSC regulation and enhances tumor formation while suppressing apoptosis. Mechanistically, YAP1 promotes phosphorylation of STAT3 by upregulating IL6. In lung adenocarcinoma clinical specimens, YAP1 expression correlated with that of IL6 (P < 0.01). More importantly, YAP1 and phosphorylated STAT3 (pSTAT3) protein expressions were significantly correlated (P < 0.0001) in primary lung adenocarcinoma as determined by IHC. Immunoblotting of 13 lung adenocarcinoma patient-derived xenografts (PDX) showed that all YAP1-expressing PDXs also exhibited pSTAT3. Additional investigations revealed that chemotherapy resistance and malignant stemness were influenced by upregulating NANOG, OCT4, and SOX2, and the expression of these targets significantly attenuated by genetically and pharmacologically hindering the activities of YAP1 and STAT3 in vivo and in vitro Therapeutically, the dual inhibition of YAP1 and STAT3 elicits a long-lasting therapeutic response by limiting CSC expansion following chemotherapy in cell line xenograft and PDX models of lung adenocarcinoma. Collectively, these findings provide a conceptual framework to target the YAP1 and STAT3 pathways concurrently with systemic chemotherapy to improve the clinical management of lung adenocarcinoma, based on evidence that these two pathways expand CSC populations that mediate resistance to chemotherapy.

    DOI: 10.1158/1535-7163.MCT-20-0024

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  36. 予定残肝ICG消失率(ICG-Krem)の術後肝不全発症予測因子としての有用性

    砂川 祐輝, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本癌治療学会学術集会抄録集   Vol. 58回   page: O60 - 4   2020.10

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  37. GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma. International journal

    Masamichi Hayashi, Elisa Guida, Yoshikuni Inokawa, Rachel Goldberg, Leonardo O Reis, Akira Ooki, Manohar Pilli, Pritam Sadhukhan, Juhyung Woo, Woonyoung Choi, Evgeny Izumchenko, Leonel Maldonado Gonzalez, Luigi Marchionni, Alex Zhavoronkov, Mariana Brait, Trinity Bivalacqua, Alexander Baras, George J Netto, Wayne Koch, Anju Singh, Mohammad O Hoque

    Science signaling   Vol. 13 ( 645 )   2020.8

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    Disruption of the KEAP1-NRF2 pathway results in the transactivation of NRF2 target genes, consequently inducing cell proliferation and other phenotypic changes in cancer cells. Here, we demonstrated that GULP1 was a KEAP1-binding protein that maintained actin cytoskeleton architecture and helped KEAP1 to sequester NRF2 in the cytoplasm. In urothelial carcinoma of the bladder (UCB), silencing of GULP1 facilitated the nuclear accumulation of NRF2, led to constitutive activation of NRF2 signaling, and conferred resistance to the platinum drug cisplatin. Knockdown of GULP1 in UCB cells promoted tumor cell proliferation in vitro and enhanced tumor growth in vivo. In primary UCB, GULP1 silencing was more prevalent in muscle-invasive UCB compared to nonmuscle-invasive UCB. GULP1 knockdown cells showed resistance to cisplatin treatment. In parallel with decreased GULP1 expression, we observed increased expression of NRF2, HMOX1, and other candidate antioxidant genes in cisplatin-resistant cells. Furthermore, low or no expression of GULP1 was observed in most cisplatin nonresponder cases. Silencing of GULP1 was associated with GULP1 promoter hypermethylation in cell lines and primary tumors, and a high frequency of GULP1 promoter methylation was observed in multiple sets of primary clinical UCB samples. Together, our findings demonstrate that GULP1 is a KEAP1-binding protein that regulates KEAP1-NRF2 signaling in UCB and that promoter hypermethylation of GULP1 is a potential mechanism of GULP1 silencing.

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  38. Novel Prognostic Implications of DUPAN-2 in the Era of Initial Systemic Therapy for Pancreatic Cancer. Reviewed International journal

    Yuki Sunagawa, Suguru Yamada, Yusuke Sato, Daishi Morimoto, Fuminori Sonohara, Hideki Takami, Yoshikuni Inokawa, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Daisuke Kobayashi, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Tsutomu Fujii, Yasuhiro Kodera

    Annals of surgical oncology   Vol. 27 ( 6 ) page: 2081 - 2089   2020.6

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    BACKGROUND: This study aimed to explore the impact of serum tumor markers on survival for patients with pancreatic cancer (PC) who received initial systemic therapy (IST) followed by surgery. METHODS: Between April 2010 and July 2018, 285 consecutive patients who underwent curative intent surgery for PC were enrolled in the study. The relation between carbohydrate antigen 19-9 and duke pancreatic monoclonal antigen type 2 (DUPAN-2) after IST was analyzed as well as PC prognosis. RESULTS: The study identified 95 patients who underwent systemic chemotherapy with or without radiotherapy as IST from the our prospectively maintained database at the Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. Survival analysis of the 95 patients showed significant differences in recurrence-free survival (RFS) and overall survival (OS) between the DUPAN-2-normalized (D-normalized) and DUPAN-2-unnormalized (D-unnormalized) groups (median RFS, 24.1 vs. 14.2 months, p = 0.003; median OS, not reached vs. 29.6 months, p = 0.003). In addition, a tendency of differences in survival was observed between the D-normalized and D-unnormalized groups with borderline resectable PC (RFS, 20.1 vs. 14.2 months, p = 0.052; OS, not reached vs. 29.6 months, p = 0.081), and significant differences in survival were observed between the D-normalized and D-unnormalized groups with unresectable PC (RFS, 25.1 vs. 12.1 months, p < 0.001; OS, not reached vs. 11.4 months, p < 0.001). Furthermore, multivariate analysis demonstrated that normalized DUPAN-2 independently predicted survival of resected PC [RFS: hazard ratio (HR) 2.180; 95% confidence interval (CI) 1.16-4.08, p = 0.015; OS: HR 2.806; 95% CI 1.19-6.62, p = 0.018]. CONCLUSIONS: During IST, DUPAN-2 normalization may potentially predict prolonged survival for PC patients and optimal timing for conversion surgery in IST.

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  39. FGFR1は胃癌細胞のEMTを促進し腹膜播種形成に関連する

    清水 大, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 三森 功士, 小寺 泰弘

    日本胃癌学会総会記事   Vol. 92回   page: 393 - 393   2020.3

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  40. 高齢者胃切除手術症例における自立度の転帰

    田中 千恵, 神田 光郎, 猪川 祥邦, 清水 大, 園原 史訓, 小林 大介, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本胃癌学会総会記事   Vol. 92回   page: 251 - 251   2020.3

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  41. 今後の胃癌バイオマーカー 胃癌腹膜播種再発を予測する腹膜洗浄液中の分子バイオマーカー(Upcoming biomarkers for gastric cancer Molecular biomarkers in peritoneal lavages to predict the peritoneal recurrences of gastric cancer)

    Kanda Mitsuro, Nakanishi Koki, Tanaka Chie, Kobayashi Daisuke, Shimizu Dai, Sonohara Fuminori, Takami Hideki, Inokawa Yoshikuni, Hattori Norifumi, Hayashi Masamichi, Yamada Suguru, Nakayama Goro, Koike Masahiko, Fujiwara Michitaka, Kodera Yasuhiro

    日本胃癌学会総会記事   Vol. 92回   page: 233 - 233   2020.3

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  42. 日本のAYA世代のがん対策の方向性を読み解く Reviewed

    栗本 景介, 堀部 敬三, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 神田 光郎, 小林 大介, 田中 千恵, 山田 豪, 中山 吾郎, 小池 聖彦, 清水 千佳子, 高橋 義行, 小寺 泰弘

    日本癌治療学会学術集会抄録集   Vol. 57回   page: P166 - 5   2019.10

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  43. Prognostic Value of Long Non-Coding RNA HULC and MALAT1 Following the Curative Resection of Hepatocellular Carcinoma. Reviewed International journal

    Fuminori Sonohara, Yoshikuni Inokawa, Masamichi Hayashi, Suguru Yamada, Hiroyuki Sugimoto, Tsutomu Fujii, Yasuhiro Kodera, Shuji Nomoto

    Scientific reports   Vol. 7 ( 1 ) page: 16142 - 16142   2017.11

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    Long non-coding RNAs (lncRNAs) were shown to be the crucial regulators of the many diseases. In this study, the expressions of lncRNAs were investigated in resected 158 hepatocellular carcinomas (HCCs) to evaluate the effects of their expression levels on prognosis. The expression levels of HULC and MALAT1 were shown to be significantly higher in the normal background tissue of HCC than those in the normal liver tissue of metastatic liver tumor without hepatitis (HULC: fold change 14.9, P = 1.7e-06; MALAT1: fold change 17.5, P = 1.2e-06. The formation of capsule was shown to be correlated with the increased expression of HULC (P = 0.041), while the size of HCC under 2 cm was correlated with a decrease in MALAT1 expression (P = 0.019). The levels of serum alpha-fetoprotein above 20 ng/mL indicated a decreased expression of both HULC and MALAT1 (HULC: P = 0.017; MALAT1: P = 0.0036). The increase in the expression levels of MALAT1 in HCC tissues was significantly correlated with better overall survival (HULC: P = 0.099, MALAT1: P = 0.028). Thus, the expression of these lncRNAs in HCC potentially correlates with the HCC malignancy and they represent potential prognostic biomarkers of the resected HCC.

    DOI: 10.1038/s41598-017-16260-1

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  44. Epigenetic modulation associated with carcinogenesis and prognosis of human gastric cancer. Reviewed International journal

    Fuminori Sonohara, Yoshikuni Inokawa, Masamichi Hayashi, Yasuhiro Kodera, Shuji Nomoto

    Oncology letters   Vol. 13 ( 5 ) page: 3363 - 3368   2017.5

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    Gastric cancer (GC) is a leading cause of cancer-related death, particularly in Asia. Epidemiological and other clinical studies have identified an association between a number of risk factors, including Helicobacter pylori, and GC. A number of studies have also examined genetic changes associated with the development and progression of GC. When considering the clinical significance of the expression of a specific gene, its epigenetic modulation should be considered. Epigenetic modulation appears to be a primary driver of changes in gastric tissue that promotes carcinogenesis and progression of GC and other neoplasms. The role of epigenetic modulation in GC carcinogenesis and progression has been widely studied in recent years. In the present review, recent results of epigenetic modulation associated with GC and their effects on clinical outcome are examined, with particular respect to DNA methylation, histone modulation and non-coding RNA. A number of studies indicate that epigenetic changes in the expression of specific genes critically affect their clinical significance and further study may reveal epigenetic changes as the basis for targeted molecular therapy or novel biomarkers that predict GC prognosis or extension of this often fatal disease.

    DOI: 10.3892/ol.2017.5912

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  45. Search for useful biomarkers in hepatocellular carcinoma, tumor factors and background liver factors (Review). Reviewed International journal

    Dai Shimizu, Yoshikuni Inokawa, Fuminori Sonohara, Kenichi Inaoka, Shuji Nomoto

    Oncology reports   Vol. 37 ( 5 ) page: 2527 - 2542   2017.5

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    Hepatocarcinogenesis is a complex and multistep process that involves the accumulation of genetic and epigenetic alterations in regulatory genes. To understand the development of hepatocellular carcinoma (HCC), current research has utilized improved array technologies. The identification of cancer-related molecules could lead to the development of novel molecular targets for treatment and biomarkers for predicting prognosis. However, prognostic prediction is insufficient when considering only tumor factors, since hepatocarcinogenesis is also greatly influenced by the status of the background liver. Clinical background liver factors, such as the presence of chronic active hepatitis or cirrhosis, are well known as risk factors for developing HCC. In contrast, genetic or epigenetic background liver factors remain unknown, albeit those are important to understand the developing process of HCC. Investigating background liver factors could contribute to the development of carcinogenic markers of HCC and to the prevention of the development of HCC. In the present study, we review the currently identified tumor factors and background liver factors from a molecular biological viewpoint and also introduce our combination array analysis.

    DOI: 10.3892/or.2017.5541

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  46. Association of Inflammasome Components in Background Liver with Poor Prognosis After Curatively-resected Hepatocellular Carcinoma. Reviewed International journal

    Fuminori Sonohara, Yoshikuni Inokawa, Mitsuro Kanda, Yoko Nishikawa, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Yasuhiro Kodera, Shuji Nomoto

    Anticancer research   Vol. 37 ( 1 ) page: 293 - 300   2017.1

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    BACKGROUND/AIM: Inflammasomes are multiprotein complexes that evoke key inflammatory cascades. The present study evaluated the influence of inflammasome component expression in non-tumorous tissue on postsurgical hepatocellular carcinoma (HCC) prognosis. MATERIALS AND METHODS: The expressions of candidate genes were investigated using real-time quantitative reverse-transcription polymerase chain reaction in resected HCC cases. In order to identify potential prognostic factors, statistical analyses were performed for each gene. RESULTS: The expression of nod-like receptor family, pyrin domain containing 3 (NLRP3), nod-like receptor family, CARD domain containing 4 (NLRC4), and absent in melanoma 2 (AIM2) was significantly higher in corresponding normal tissue (CN) compared to those in HCC. High expression of NLRP3, NLRC4, and caspase 1 (CASP1) in CN was significantly correlated with worse overall survival. Furthermore, multivariate analysis revealed that NLRP3 expression in CN greater than the median was an independent prognostic factor for poorer overall survival. CONCLUSION: High expression of NLRP3, NLRC4, and CASP1 in background non-tumorous liver is significantly correlated with poor prognosis of patients after resection of HCC.

    DOI: 10.21873/anticanres.11320

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MISC 77

  1. 十二指腸肉腫の1例

    山中 雅也, 高見 秀樹, 園原 史訓, 猪川 祥邦, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 82 ( 5 ) page: 1023 - 1023   2021.5

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  2. GAD1の食道扁平上皮癌根治的切除後予後予測バイオマーカーとしての意義

    岸田 貴喜, 神田 光郎, 清水 大, 田中 千恵, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: PS - 4   2021.4

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  3. 肝胆膵領域癌におけるサルコペニアの臨床的意義と当教室の周術期対策

    猪川 祥邦, 山田 豪, 横山 幸浩, 薮崎 紀充, 二宮 豪, 田中 伸孟, 園原 史訓, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 3   2021.4

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  4. 片側肝動脈合併切除を伴う膵頭十二指腸切除後の肝動脈血流の評価と早期合併症に関する検討

    鈴木 雄之典, 山田 豪, 猪川 祥邦, 田中 伸孟, 園原 史訓, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: PS - 1   2021.4

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  5. 当教室における膵頭十二指腸切除術後出血に対する対策と治療効果の検討

    田中 伸孟, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 4   2021.4

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  6. 切除肝細胞癌におけるYTH domain family 2の臨床的意義

    中川 暢彦, 園原 史訓, 田中 克仁, 砂川 祐輝, 猪川 祥邦, 高見 秀樹, 林 真路, 山田 豪, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 7   2021.4

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  7. 切除可能境界膵癌に対する至適術前治療確立をめざして 当教室の治療成績とランダム化比較試験によるエビデンスの構築

    山田 豪, 園原 史訓, 田中 伸孟, 高見 秀樹, 猪川 祥邦, 林 真路, 中山 吾郎, 小池 聖彦, 藤井 努, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 6   2021.4

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  8. パンデミック下における外科卒前教育の工夫

    高見 秀樹, 小池 聖彦, 鈴木 雄之典, 栗本 景介, 田中 伸孟, 柴田 雅央, 園原 史訓, 武内 大, 猪川 祥邦, 服部 憲史, 林 真路, 神田 光郎, 田中 知恵, 山田 豪, 中山 吾郎, 菊森 豊根, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SP - 7   2021.4

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  9. ゲノム編集技術を用いたLAMP5遺伝子の胃癌転移巣形成における役割の検討

    梅田 晋一, 神田 光郎, 清水 大, 田中 千恵, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, Fujiwara Michitaka, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 5   2021.4

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  10. UR-M膵癌に対するconversion surgeryの課題

    加藤 吉康, 山田 豪, 田中 伸孟, 園原 史訓, 高見 秀樹, 猪川 祥邦, 林 真路, 服部 憲史, 清水 大, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 6   2021.4

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  11. 胃癌における組織中RNFT2遺伝子発現と予後の関連性の検討

    笹原 正寛, 神田 光郎, 清水 大, 田中 千恵, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: PS - 4   2021.4

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  12. 食道扁平上皮癌術後長期生存例における多重癌発生状況

    清水 大, 小池 聖彦, 神田 光郎, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 田中 千恵, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 1   2021.4

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  13. 転移性肝腫瘍に対する至適治療戦略 術前化学療法の可否につき考える

    林 真路, 山田 豪, 高見 秀樹, 猪川 祥邦, 園原 史訓, 田中 伸孟, 栗本 景介, 砂川 祐輝, 加藤 吉康, 中川 暢彦, 鈴木 雄之典, 山中 雅也, 清水 大, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 5   2021.4

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  14. 膵癌における術前治療中の腫瘍マーカーの比較・検討

    砂川 祐輝, 山田 豪, 田中 伸孟, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: PS - 4   2021.4

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  15. 膵癌におけるオリゴメタスタシスの臨床的意義

    山中 雅也, 山田 豪, 林 真路, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: SF - 5   2021.4

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  16. 胃癌切除後予後と原発巣組織中CRABP1発現の相関性の検討

    坂田 和規, 神田 光郎, 清水 大, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 田中 千恵, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: PS - 5   2021.4

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  17. 胃癌に対する腹腔鏡下手術でのIndocyanine Green蛍光法を用いたマーキング法の成績

    佐藤 敏, 田中 千恵, 園原 史訓, 清水 大, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 神田 光郎, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 121回   page: PS - 6   2021.4

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  18. ETNK2のアポトーシス調整を介した胃癌肝転移形成との関連性(ETNK2 promotes hepatic metastasis of gastric cancer via the p53-Bcl-2 related apoptosis)

    三輪 高嗣, 神田 光郎, 田中 千恵, 清水 大, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本胃癌学会総会記事   Vol. 93回   page: 244 - 244   2021.3

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  19. 当科におけるUnresectable/Borderline resectable膵癌に対する集学的治療の検討

    加藤 吉康, 山田 豪, 田中 伸孟, 園原 史訓, 高見 秀樹, 猪川 祥邦, 林 真路, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: P290 - 3   2020.12

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  20. 当教室におけるStage I膵癌切除例の検討

    中川 暢彦, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: P303 - 5   2020.12

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  21. 尿中cell free DNAを用いた膵癌診断法の開発

    林 真路, 山田 豪, 高見 秀樹, 猪川 祥邦, 園原 史訓, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: P276 - 5   2020.12

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  22. ゲノムワイドアプローチによる肝細胞癌関連circRNAの探索

    砂川 祐輝, 山田 豪, 園原 史訓, 栗本 景介, 猪川 祥邦, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: P219 - 4   2020.12

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  23. DAA時代のHCV治療がもたらす切除可能HCCへの臨床的影響の検討

    園原 史訓, 山田 豪, 高見 秀樹, 猪川 祥邦, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: O12 - 3   2020.12

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  24. 膵全摘術における長期予後と栄養・炎症指標についての検討

    猪川 祥邦, 山田 豪, 園原 史訓, 高見 秀樹, 林 真路, 小林 大介, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: RS18 - 1   2020.12

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  25. 膵頭十二指腸切除術における胆管空腸吻合部狭窄に関する検討

    鈴木 雄之典, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: P308 - 4   2020.12

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  26. 膵神経内分泌腫瘍における再発予測因子と再発患者に対する治療戦略

    田中 伸孟, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 小池 聖彦, 藤井 努, 小寺 泰弘

    日本消化器外科学会総会   Vol. 75回   page: RS17 - 3   2020.12

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  27. 劇症型A群β溶連菌感染症による原発性腹膜炎の1例

    砂川 祐輝, 猪川 祥邦, 山田 豪, 園原 史訓, 高見 秀樹, 林 真路, 服部 憲史, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 81 ( 11 ) page: 2399 - 2399   2020.11

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  28. 胃 診断

    中村 俊介, 神田 光郎, 清水 大, 澤木 康一, 田中 千恵, 服部 憲史, 園原 史訓, 高見 秀樹, 猪川 祥邦, 林 真路, 山田 豪, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会雑誌   Vol. 53 ( Suppl.2 ) page: 296 - 296   2020.11

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  29. 膵臓 化学療法

    砂川 祐輝, 山田 豪, 山中 雅也, 鈴木 雄之典, 中川 暢彦, 加藤 吉康, 田中 伸孟, 栗本 景介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器外科学会雑誌   Vol. 53 ( Suppl.2 ) page: 311 - 311   2020.11

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  30. 膵臓 悪性

    山田 豪, 高見 秀樹, 園原 史訓, 猪川 祥邦, 林 真路, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤井 努, 小寺 泰弘

    日本消化器外科学会雑誌   Vol. 53 ( Suppl.2 ) page: 316 - 316   2020.11

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  31. 予定残肝ICG消失率(ICG-Krem)の術後肝不全発症予測因子としての有用性

    砂川 祐輝, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本癌治療学会学術集会抄録集   Vol. 58回   page: O60 - 4   2020.10

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  32. 膵癌における術前治療中のSpan-1の臨床的意義

    砂川 祐輝, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 清水 大, 服部 憲史, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 81 ( 増刊 ) page: 463 - 463   2020.10

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  33. 膵癌に対する術前治療の現状 膵癌術前治療時代における放射線療法の意義を考える メリットとデメリット及び今後の展望

    山田 豪, 園原 史訓, 横山 幸浩, 高見 秀樹, 山口 淳平, 猪川 祥邦, 尾上 俊介, 林 真路, 藤井 努, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 81 ( 増刊 ) page: 223 - 223   2020.10

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  34. Initial systemic therapy時代における高齢者膵癌集学的治療の意義と限界

    園原 史訓, 山田 豪, 高見 秀樹, 猪川 祥邦, 林 真路, 清水 大, 服部 憲史, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 藤井 努, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 6   2020.8

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  35. 当科におけるUnresectable膵癌治療の検討

    加藤 吉康, 山田 豪, 高見 秀樹, 園原 史訓, 猪川 祥邦, 林 真路, 服部 憲史, 神田 光郎, 小林 大介, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 4   2020.8

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  36. 大腸癌初回肝転移手術後の早期再発予測因子の検討

    林 真路, 山田 豪, 高見 秀樹, 猪川 祥邦, 園原 史訓, 砂川 祐輝, 田中 伸孟, 栗本 景介, 加藤 吉康, 中川 暢彦, 鈴木 雄之典, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 4   2020.8

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  37. 切除不能胃癌に対する集学的治療としてのconversion surgeryの適応について

    小林 大介, 神田 光郎, 田中 千恵, 清水 大, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 3   2020.8

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  38. 傾向スコアマッチングを用いた後期高齢者における食道亜全摘術の短期成績と術前免疫栄養因子の検討

    神田 光郎, 小池 聖彦, 清水 大, 田中 千恵, 小林 大介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 4   2020.8

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  39. 膵癌に対する膵頭十二指腸切除術の分子生物学的なsurgical marginの評価

    砂川 祐輝, 山田 豪, 林 真路, 高見 秀樹, 猪川 祥邦, 園原 史訓, 栗本 景介, 田中 伸孟, 加藤 吉康, 中川 暢彦, 鈴木 雄之典, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 2   2020.8

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  40. 高齢者胃切除手術症例における前向き高齢者機能評価

    田中 千恵, 神田 光郎, 猪川 祥邦, 小林 大介, 清水 大, 園原 史訓, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 4   2020.8

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  41. 食道癌術前化学療法中にRenal Salt-Wasting Syndromeを生じた1例

    山本 周平, 神田 光郎, 小池 聖彦, 高見 秀樹, 清水 大, 田中 千恵, 小林 大介, 園原 史訓, 猪川 祥邦, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: RS - 4   2020.8

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  42. 食道扁平上皮癌の術後長期予後因子としてのmodified systemic inflammation scoreの意義

    清水 大, 神田 光郎, 小池 聖彦, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 田中 千恵, 小林 大介, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 5   2020.8

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  43. 食道扁平上皮癌におけるKCNJ15遺伝子の機能解析と、その組織中発現における臨床的意義の検討

    中村 俊介, 神田 光郎, 小池 聖彦, 清水 大, 小林 大介, 田中 千恵, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 8   2020.8

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  44. 食道亜全摘術後肺炎予測因子に関する検討

    澤木 康一, 神田 光郎, 小池 聖彦, 清水 大, 田中 千恵, 小林 大介, 園原 史訓, 服部 憲史, 猪川 祥邦, 高見 秀樹, 林 真路, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 4   2020.8

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  45. 長期成績からみた膵癌術前治療の評価 病理学的腫瘍消失率は予後因子となり得るか?

    山田 豪, 横山 幸浩, 園原 史訓, 山口 淳平, 高見 秀樹, 猪川 祥邦, 林 真路, 尾上 俊介, 藤井 努, 梛野 正人, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 1   2020.8

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  46. 術前CT画像を利用した膵内脂肪量と体組成による膵液瘻予測因子の検討

    田中 克仁, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 1   2020.8

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  47. 膵頸部癌における臨床病理学的特徴

    栗本 景介, 山田 豪, 鈴木 雄之典, 中川 暢彦, 加藤 吉康, 田中 伸孟, 砂川 祐輝, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 3   2020.8

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  48. 膵頭部癌における周術期輸血の長期予後に対する影響

    田中 伸孟, 山田 豪, 栗本 景介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 3   2020.8

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  49. 膵頭十二指腸切除術施行膵癌患者における周術期メインおよびリパクレオン投与の安全性と有用性

    中川 暢彦, 山田 豪, 多代 充, 栗本 景介, 園原 史訓, 清水 大, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 5   2020.8

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  50. 膵頭十二指腸切除術における胆管空腸吻合部狭窄のリスクファクターに関する検討

    鈴木 雄之典, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 小林 大介, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 4   2020.8

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  51. 膵癌集学的治療における放射線治療の意義 放射線治療投入タイミングを考慮した「共存」

    高見 秀樹, 山田 豪, 横山 幸浩, 園原 史訓, 猪川 祥邦, 林 真路, 尾上 俊介, 山口 淳平, 藤井 努, 梛野 正人, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: SF - 7   2020.8

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  52. 膵癌組織における癌幹細胞マーカー発現が切除後予後に与える影響についての検討

    猪川 祥邦, 山田 豪, 林 真路, 砂川 祐輝, 園原 史訓, 高見 秀樹, 服部 憲史, 神田 光郎, 小林 大介, 田中 千恵, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 120回   page: DP - 5   2020.8

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  53. 膵癌のconversion surgery:課題と展望 当教室におけるConversion Surgeryの現状 再発予測因子からみた至適手術適応の検討

    山田 豪, 高見 秀樹, 園原 史訓, 猪川 祥邦, 林 真路, 田中 伸孟, 藤井 努, 小寺 泰弘

    膵臓   Vol. 35 ( 3 ) page: A240 - A240   2020.7

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  54. 進行膵癌におけるオリゴメタスタシス症例の検討

    林 真路, 山田 豪, 高見 秀樹, 園原 史訓, 猪川 祥邦, 田中 伸孟, 加藤 吉康, 中川 暢彦, 栗本 景介, 鈴木 雄之典, 山中 雅也, 小寺 泰弘

    膵臓   Vol. 35 ( 3 ) page: A304 - A304   2020.7

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  55. 集学的治療による病勢コントロール後に外腸骨リンパ節転移を切除しえた膵NETの1例

    鈴木 雄之典, 山田 豪, 高見 秀樹, 園原 史訓, 猪川 祥邦, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本消化器病学会東海支部例会プログラム抄録集   Vol. 132回   page: 55 - 55   2020.6

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  56. 切除HCCにおける非侵襲的肝線維化モデル PALBI,FIB-4,APRIの臨床的有用性の検討

    山田 豪, 園原 史訓, 高見 秀樹, 猪川 祥邦, 林 真路

    肝臓   Vol. 61 ( Suppl.1 ) page: A463 - A463   2020.4

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  57. FGFR1は胃癌細胞のEMTを促進し腹膜播種形成に関連する

    清水 大, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 三森 功士, 小寺 泰弘

    日本胃癌学会総会記事   Vol. 92回   page: 393 - 393   2020.3

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  58. 高齢者胃切除手術症例における自立度の転帰

    田中 千恵, 神田 光郎, 猪川 祥邦, 清水 大, 園原 史訓, 小林 大介, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本胃癌学会総会記事   Vol. 92回   page: 251 - 251   2020.3

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  59. 食道亜全摘術後の肺炎発生予測因子の検討

    神田 光郎, 小池 聖彦, 清水 大, 田中 千恵, 小林 大介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本消化管学会雑誌   Vol. 4 ( Suppl. ) page: 303 - 303   2020.1

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  60. ミラーイメージはカメラを180度回転させると操作が容易になる

    砂川 祐輝, 山田 豪, 園原 史訓, 猪川 祥邦, 高見 秀樹, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本内視鏡外科学会雑誌   Vol. 24 ( 7 ) page: SF029 - 4   2019.12

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  61. 腹腔鏡下手術による膵体尾部切除術後の門脈・脾静脈血栓症に対する影響

    山田 豪, 園原 史訓, 高見 秀樹, 猪川 祥邦, 林 真路, 神田 光郎, 小林 大介, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本内視鏡外科学会雑誌   Vol. 24 ( 7 ) page: MO180 - 5   2019.12

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  62. 食道癌FP療法によるRenal Salt-Wasting Syndromeの2例

    梅田 晋一, 神田 光郎, 小池 聖彦, 清水 大, 田中 千恵, 小林 大介, 園原 史訓, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 80 ( 12 ) page: 2312 - 2312   2019.12

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  63. 妊娠を契機に急速増大を来したMCNと術前診断した膵リンパ管腫の一切除例

    加藤 吉康, 山田 豪, 高見 秀樹, 園原 史訓, 猪川 祥邦, 林 真路, 服部 憲史, 神田 光郎, 小林 大介, 田中 千恵, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本消化器病学会東海支部例会プログラム抄録集   Vol. 131回   page: 75 - 75   2019.11

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  64. 胃原発mixed adenoneuroendocrine carcinomaの1例

    荘加 道太, 清水 大, 栗本 景介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 神田 光郎, 田中 千恵, 小林 大介, 山田 豪, 中山 吾郎, 小池 聖彦, 小寺 泰弘

    日本消化器病学会東海支部例会プログラム抄録集   Vol. 131回   page: 59 - 59   2019.11

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  65. Conversion Surgery施行例の予後因子から検討した切除不能胃癌に対する集学的治療戦略

    小林 大介, 神田 光郎, 田中 千恵, 清水 大, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本癌治療学会学術集会抄録集   Vol. 57回   page: RT21 - 5   2019.10

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  66. 神経内分泌腫瘍Up to Date 膵神経内分泌腫瘍における再発予測因子と至適管理の検討

    山田 豪, 園原 史訓, 高見 秀樹, 猪川 祥邦, 林 真路, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本癌治療学会学術集会抄録集   Vol. 57回   page: SY13 - 2   2019.10

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  67. 切除不能進行再発胃癌に対するnivolumab療法における好中球/リンパ球比の臨床的意義

    小林 大介, 清水 大, 神田 光郎, 田中 千恵, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 80 ( 増刊 ) page: 506 - 506   2019.10

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  68. トランスレーショナルリサーチについて考える:臨床現場のアイデアをどう生かすか 消化器外科医ならではの創薬シーズを求めて

    神田 光郎, 清水 大, 田中 千恵, 小林 大介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 80 ( 増刊 ) page: 360 - 360   2019.10

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  69. 胃癌根治切除術後S-1補助化学療法の忍容性予測因子の検討

    三輪 高嗣, 神田 光郎, 田中 千恵, 小林 大介, 園原 史訓, 高見 秀樹, 服部 憲史, 猪川 祥邦, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 80 ( 増刊 ) page: 570 - 570   2019.10

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  70. 開腹・開胸手術のメリット・デメリットについて考える 開胸アプローチを活用する食道癌治療戦略 開胸のメリットは再建にあり?

    小池 聖彦, 佐藤 雄介, 園原 史訓, 清水 大, 高見 秀樹, 猪川 祥邦, 服部 憲史, 林 真路, 神田 光郎, 小林 大介, 田中 千恵, 山田 豪, 中山 吾郎, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 80 ( 増刊 ) page: 351 - 351   2019.10

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  71. 長期予後が得られた症例1(上部消化管) HER2陽性切除不能進行胃癌に対するtrastuzumab療法とconversion surgeryによる集学的治療

    佐藤 敏, 小林 大介, 清水 大, 神田 光郎, 田中 千恵, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 80 ( 増刊 ) page: 404 - 404   2019.10

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  72. 英文論文について考える:方法論・重要性を中心に 臨床外科医が英文論文を書く際の最初のハードルを越える 定型化と剽窃回避

    神田 光郎, 清水 大, 田中 千恵, 小林 大介, 園原 史訓, 猪川 祥邦, 高見 秀樹, 服部 憲史, 林 真路, 山田 豪, 中山 吾郎, 小池 聖彦, 藤原 道隆, 小寺 泰弘

    日本臨床外科学会雑誌   Vol. 80 ( 増刊 ) page: 346 - 346   2019.10

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  73. 腫瘍生物学的な要素を考慮した膵癌切除可能性分類の検討

    加藤 吉康, 山田 豪, 園原 史訓, 高見 秀樹, 猪川 祥邦, 林 真路, 小寺 泰弘

    日本癌治療学会学術集会抄録集   Vol. 57回   page: O49 - 2   2019.10

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  74. 尿路上皮癌におけるGULP1遺伝子によるKEAP1-NRF2シグナルの調節

    猪川 祥邦, 林 真路, 山田 豪, 園原 史訓, 高見 秀樹, 小寺 泰弘, Hoque Mohammad

    日本外科学会定期学術集会抄録集   Vol. 119回   page: PS - 011   2019.4

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  75. 尿路上皮癌におけるGULP1遺伝子によるKEAP1-NRF2シグナルの調節

    猪川 祥邦, 林 真路, 山田 豪, 園原 史訓, 高見 秀樹, 小寺 泰弘, Hoque Mohammad

    日本外科学会定期学術集会抄録集   Vol. 119回   page: PS - 7   2019.4

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  76. 肝細胞癌切除後・予後予測マーカーとしてのLong non-coding RNA発現

    園原 史訓, 猪川 祥邦, 林 真路, 山田 豪, 杉本 博行, 藤井 努, 野本 周嗣, 小寺 泰弘

    日本消化器外科学会総会   Vol. 73回   page: 777 - 777   2018.7

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  77. 門脈合併切除膵癌における脾静脈再建-するvsしない- しない

    藤井 努, 服部 正嗣, 山田 豪, 猪川 祥邦, 神田 光郎, 高見 秀樹, 吉岡 伊作, 渋谷 和人, 奥村 知之, 中尾 昭公, 小寺 泰弘

    日本外科学会定期学術集会抄録集   Vol. 118回   page: 743 - 743   2018.4

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KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. 膵癌における低酸素応答性エレメントのターゲット遺伝子群の同定

    Grant number:22K08797  2022.4 - 2025.3

    科学研究費助成事業  基盤研究(C)

    猪川 祥邦

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  2. 膵癌腹膜播種に対する新規バイオマーカー: 臨床応用に向けた検証と新規治療法開発

    Grant number:21K07188  2021.4 - 2025.3

    科学研究費助成事業  基盤研究(C)

    末永 雅也, 林 真路, 高見 秀樹, 猪川 祥邦

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    Authorship:Coinvestigator(s) 

    膵癌の腹膜播種は予後を規定する重要な因子である。近年、膵癌手術患者の腹腔腔洗浄液
    中から高感度測定法を用いて検出される腫瘍DNAが腹膜播種の有望なバイオマーカーとなる可能性を報告した。本研究ではこの手法の臨床応用を目的として、前向き臨床試験によって有用性を検証する。さらに、本研究で得られた腹腔洗浄液を用いて、将来的な治療ターゲットに応用可能な新規バイオマーカーの探索する。

  3. Possible treatment strategy of one-carbon metabolism on pancreatic cancer management

    Grant number:21K07147  2021.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Coinvestigator(s) 

  4. 膵癌における骨髄由来免疫抑制細胞(MDSC)を調節する新規遺伝子同定の試み

    2019.9 - 2020.8

    公益信託外科学研究助成金 

    猪川祥邦

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    Authorship:Principal investigator  Grant type:Competitive