2021/12/09 更新

写真a

アコウ ソウイチロウ
赤穂 宗一郎
AKOU Souichirou
所属
医歯薬学域 助教(特任)
職名
助教(特任)
外部リンク

学位

  • 博士(医学) ( 岡山大学 )

  • 医学博士

 

論文

  • Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer. 国際誌

    Soichiro Ako, Hironari Kato, Kazuhiro Nouso, Hideaki Kinugasa, Hiroyuki Terasawa, Hiroshi Matushita, Saimon Takada, Yosuke Saragai, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Daisuke Nobuoka, Ryuichi Yoshida, Yuzo Umeda, Takahito Yagi, Hiroyuki Okada

    Cancer biology & therapy   1 - 7   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called "liquid biopsy") is recently developed. AIMS: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. METHODS: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. RESULTS: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36-9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). CONCLUSIONS: In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.

    DOI: 10.1080/15384047.2021.1980312

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  • Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells. 国際誌

    Roxanne L Massoumi, Yaroslav Teper, Soichiro Ako, Linda Ye, Elena Wang, O Joe Hines, Guido Eibl

    Pancreas   50 ( 4 )   524 - 528   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic endotoxemia), which is thought to mediate obesity-associated inflammation. However, the direct effects of LPS on PDAC cells are poorly understood. METHODS: The expression of toll-like receptor 4, the receptor for LPS, was confirmed in PDAC cell lines. AsPC-1 and PANC-1 cells were exposed to LPS, and differential gene expression was determined by RNA sequencing. The activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by LPS in PDAC cells was assessed by Western blotting. RESULTS: The expression of toll-like receptor 4 was confirmed in all PDAC cell lines. The exposure to LPS led to differential expression of 3083 genes (426 ≥5-fold) in AsPC-1 and 2584 genes (339 ≥5-fold) in PANC-1. A top canonical pathway affected by LPS in both cell lines was PI3K/Akt/mTOR. Western blotting confirmed activation of this pathway as measured by phosphorylation of the ribosomal protein S6 and Akt. CONCLUSIONS: The exposure of PDAC cells to LPS led to differential gene expression. A top canonical pathway was PI3K/Akt/mTOR, a known oncogenic driver. Our findings provided evidence that LPS can directly induce differential gene expression in PDAC cells.

    DOI: 10.1097/MPA.0000000000001790

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  • Evaluation of Local Recurrence of Pancreatic Cancer by KRAS Mutation Analysis Using Washes from Endoscopic Ultrasound-Guided Fine-Needle Aspiration. 国際誌

    Kazuyuki Matsumoto, Hironari Kato, Kazuhiro Nouso, Soichiro Ako, Hideaki Kinugasa, Shigeru Horiguchi, Yosuke Saragai, Saimon Takada, Shuntaro Yabe, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Hiroyuki Okada

    Digestive diseases and sciences   65 ( 10 )   2907 - 2913   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND AIMS: The sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing the recurrence of pancreatic cancer is usually low because of difficulties in obtaining adequate samples for pathological examinations. We evaluated the efficacy of highly sensitive KRAS mutation analysis using EUS-FNA washes to detect cancer recurrence. METHODS: Nineteen consecutive patients with suspected pancreatic cancer recurrence after surgical resection were enrolled. All underwent EUS-FNA, and samples were obtained for pathological examination. After the first session, the inside of the FNA needle was washed with saline for DNA extraction. KRAS mutations were examined using digital droplet PCR (dPCR). RESULTS: The median needle puncture number used to obtain adequate pathological samples was two (range 1-6). In ten patients pathologically diagnosed with malignant pancreatic cancer, nine patients tested positive for a KRAS mutation. All patients who were not diagnosed with a malignant pancreatic cancer tested negative for a KRAS mutation. About half of surgically resected primary cancers (9/19) showed double KRAS mutations (G12V and G12D); however, all but one wash sample showed a single KRAS mutation, G12D. After including one patient who showed a malignant recurrence during follow-up, the sensitivities of a pathological diagnosis and KRAS analysis to detect recurrence were 90.9% and 81.8%, respectively. CONCLUSIONS: KRAS mutation analysis of needle wash samples using dPCR is a new methodology for the diagnosis of the local recurrence of pancreatic cancer. The diagnostic ability of dPCR with a one-time needle wash sample was comparable to a pathological diagnosis with multiple samplings.

    DOI: 10.1007/s10620-019-06006-6

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  • Gastric Adenocarcinoma and Proximal Polyposis of the Stomach Occurring With Ball Valve Syndrome. 国際誌

    Soichiro Ako, Seiji Kawano, Hiroyuki Okada

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cgh.2020.07.044

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  • Human Telomerase Reverse Transcriptase Gene Promoter Mutation in Serum of Patients with Hepatocellular Carcinoma. 国際誌

    Soichiro Ako, Kazuhiro Nouso, Hideaki Kinugasa, Hiroshi Matsushita, Hiroyuki Terasawa, Takuya Adachi, Nozomu Wada, Yasuto Takeuchi, Mari Mandai, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Shinichi Fujioka, Tetsushige Mimura, Hiroyuki Okada

    Oncology   98 ( 5 )   311 - 317   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Mutations in the human telomerase reverse transcriptase (hTERT) gene promoter have been reported in hepatocellular carcinoma (HCC); however, analyses of these mutations in liquid biopsies have been technically difficult because of the high GC content of the regions of interest within this promoter. We evaluated the feasibility and prognostic value of hTERT promoter mutations identified in circulating cell-free DNA (cfDNA) from the serum of patients with HCC. OBJECTIVE: A cohort of HCC patients (n = 36) who were curatively treated by surgical resection between June 2003 and September 2014 were enrolled in this study. METHODS: The presence of hTERT promoter mutations in cfDNA from the patients' serum was analyzed via modified droplet digital polymerase chain reaction, and associations were sought between specific promoter mutations and patients' disease-free survival (DFS). RESULTS: The G>A hTERT mutation at -124 bp was detected in the serum of 25 patients (69%). Although no marked differences were observed between the characteristics of the serum mutation-positive and serum mutation-negative patient groups, the DFS of patients with the mutation was significantly shorter than that of the serum mutation-negative patients (p = 0.02). Among 18 clinicopathologic and background liver factors examined, the presence of the -124 bp G>A mutation was an independent and significant predictor of patients' DFS (hazard ratio = 3.01, 95% confidence interval 1.11-10.5, p = 0.03) in multivariate analyses. CONCLUSIONS: The -124 bp G>A hTERT promoter mutation was observed in the serum of 69% of HCC patients who underwent surgical resection and was an independent predictor of disease progression in HCC.

    DOI: 10.1159/000506135

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  • Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular Carcinoma before Radiofrequency Ablation.

    Soichiro Ako, Shinichiro Nakamura, Kazuhiro Nouso, Chihiro Dohi, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Tetsuya Yasunaka, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    Acta medica Okayama   72 ( 1 )   47 - 52   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Transcatheter arterial chemoembolization (TACE) is often performed before radiofrequency ablation (RFA) for the treatment of early-stage hepatocellular carcinoma (HCC). TACE prior to RFA can expand the ablated area and reduce the tumor size, facilitating complete ablation. However, the factors correlated with size reduction remain uncertain. The aim of this study was to identify the factors associated with size reduction by TACE and develop a formula to predict the reduction rate. A total of 100 HCC patients treated with TACE followed by RFA at least 20 days later were enrolled. The tumor size was measured at the time of TACE and RFA, and correlations between the reduction rate and 13 clinical factors were examined. A formula to predict the reduction rate was built using the factors obtained by the analysis. Reduction in the tumor size was observed in 69 nodules, and the median reduction rate was 16.2%. A multivariate regression analysis revealed that a large tumor size (p< 0.01) and a long interval between the therapies (p= 0.01) were factors for a high tumor reduction rate, with tumor size more strongly related to the degree of reduction. A size reduction of more than 10% can be expected by waiting 20 days after TACE when the size of the tumor at TACE is over 25 mm in diameter. The tumor size.

    DOI: 10.18926/AMO/55662

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  • Liquid biopsy of bile for the molecular diagnosis of gallbladder cancer. 国際誌

    Hideaki Kinugasa, Kazuhiro Nouso, Soichiro Ako, Chihiro Dohi, Hiroshi Matsushita, Kazuyuki Matsumoto, Hironari Kato, Hiroyuki Okada

    Cancer biology & therapy   19 ( 10 )   934 - 938   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Tissue sampling of gallbladder cancer (GBCa) is challenging because of the anatomy of the gallbladder. The aim of this study is to investigate the possibility of diagnosing GBCa patients by performing a liquid biopsy of bile in addition to current diagnostic methods. METHODS: Thirty patients with GBCa were enrolled in this study. Cytological examination was performed in all patients. Using next generation sequencing (NGS), DNA isolated from the bile and tumor tissue was analyzed for mutations in 49 oncogenes. We also compared these mutations with cytology results. RESULTS: 57.1% of DNA samples from tumor tissue were positive for a mutation. In these patients, 87.5% of the bile circulating tumor DNA (ctDNA) samples had the same mutation. The concordance rate between bile ctDNA and tissue DNA samples was 85.7%, and the mutation frequencies detected in ctDNA were approximately half of what was detected in tumor tissue DNA. On the other hand, the sensitivity of the cytological and bile ctDNA analyses was 45.8% and 58.3%, respectively. The concordance rate between cytology and bile ctDNA analyses was 87.5%. CONCLUSIONS: Mutated tumor DNA could be detected in bile by NGS. Liquid biopsy of bile might help us to diagnose GBCa because of higher sensitivity and positive predict value compared to cytology with ERCP.

    DOI: 10.1080/15384047.2018.1456604

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  • Comparing reduced-dose sodium phosphate tablets to 2 L of polyethylene glycol: A randomized study. 国際誌

    Soichiro Ako, Koji Takemoto, Eriko Yasutomi, Chihiro Sakaguchi, Mayu Murakami, Tomoko Sunami, Shohei Oka, Hamada Kenta, Noriko Okazaki, Yuki Baba, Yasushi Yamasaki, Toshiyuki Asato, Daisuke Kawai, Ryuta Takenaka, Hirohumi Tsugeno, Sakiko Hiraoka, Jun Kato, Shigeatsu Fujiki

    World journal of gastroenterology   23 ( 24 )   4454 - 4461   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: To compare the tolerability and quality of bowel cleansing between 2 L polyethylene glycol (PEG) and reduced-dose sodium phosphate (NaP) tablets as a preparation for colonoscopy. METHODS: Two hundred patients were randomly assigned to the PEG or NaP groups at the same ratio. The NaP group patients took 30 tablets with 2 L of clear liquid, while the PEG group patients took 2L of PEG. Tolerability was assessed by a questionnaire about taste, volume, and the overall impression. The bowel cleansing quality was evaluated by colonoscopists. RESULTS: Although NaP showed better tolerability in terms of taste, volume and overall impression (P < 0.01, P < 0.01 and P = 0.02, respectively), the overall cleansing quality was better in the PEG group (P < 0.01). A subgroup analysis, stratified by sex and age, indicated that NaP was associated with better tolerability and equivalent bowel cleansing quality in females of < 50 years of age. CONCLUSION: Despite the better tolerability, the use of 30 NaP tablets with 2 L of clear liquid should be limited due to its lower cleansing quality; however, in certain cases the regimen may deserve consideration, particularly in cases involving young women.

    DOI: 10.3748/wjg.v23.i24.4454

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  • Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma. 国際誌

    Kazuhiro Nouso, Kazuya Kariyama, Shinichiro Nakamura, Ayano Oonishi, Akiko Wakuta, Atsushi Oyama, Soichiro Ako, Chihiro Dohi, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

    Journal of gastroenterology and hepatology   32 ( 3 )   695 - 700   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND AIM: Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC. METHODS: Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching. RESULTS: About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (>30 mm, hazard ratio = 1.685, P = 0.043), high des-γ-carboxyprothrombin (>100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group. CONCLUSIONS: RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

    DOI: 10.1111/jgh.13586

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  • The effect of long-term supplementation with branched-chain amino acid granules in patients with hepatitis C virus-related hepatocellular carcinoma after radiofrequency thermal ablation. 国際誌

    Hiroki Nishikawa, Yukio Osaki, Eriko Iguchi, Yorimitsu Koshikawa, Soichiro Ako, Tadashi Inuzuka, Haruhiko Takeda, Jun Nakajima, Fumihiro Matsuda, Azusa Sakamoto, Shinichiro Henmi, Keiichi Hatamaru, Tetsuro Ishikawa, Sumio Saito, Akihiro Nasu, Ryuichi Kita, Toru Kimura

    Journal of clinical gastroenterology   47 ( 4 )   359 - 66   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    GOALS: To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ≤3.5 g/dL. BACKGROUND: Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear. STUDY: We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS. RESULTS: The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively. CONCLUSIONS: BCAA treatment may improve OS and RFS after RFA in patients with HCV-related HCC≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL.

    DOI: 10.1097/MCG.0b013e31826be9ad

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  • [A case of diffuse cystic malformation in which submucosal tumor-like advanced gastric cancer was identified during 10-year follow-up].

    Soichiro Ako, Takehiko Tsumura, Yoshihiro Okabe, Akira Sekikawa, Takashi Kanesaka, Tomoko Wakasa, Masayuki Shintaku, Takanori Maruo, Toru Kimura, Yukio Osaki

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology   109 ( 11 )   1910 - 9   2012年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 66-year-old man with giant gastric folds had been followed up since February 2000. In March 2010, a submucosal tumor of 35mm was identified with endoscopy and a low echoic mass was identified with endoscopic ultrasonography. After histologic diagnosis by endosonography-guided fine needle aspiration biopsy, he underwent a total gastrectomy. Histologic examination of the resected specimen revealed a tumor 20mm in diameter consisting of well-to-moderately differentiated tubular adenocarcinoma in the thickened wall of the gastric greater curvature, which contained small cystic lesions in the lamina propria. Immunohistochemical staining showed thick gastric wall consisting of not only multiple cysts but also smooth muscle, elastic and collagen fibers. The histologic diagnosis was advanced gastric cancer accompanied by diffuse cystic malformation (DCM). Although it is a rare condition, DCM should be considered in the differential diagnosis of giant gastric folds and as a pre-cancerous lesion.

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  • The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients. 国際誌

    Hiroki Nishikawa, Eriko Iguchi, Yorimitsu Koshikawa, Soichiro Ako, Tadashi Inuzuka, Haruhiko Takeda, Jun Nakajima, Fumihiro Matsuda, Azusa Sakamoto, Sinichiro Henmi, Keiichi Hatamaru, Tetsuro Ishikawa, Sumio Saito, Ryuichi Kita, Toru Kimura, Yukio Osaki

    BMC research notes   5   135 - 135   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients. The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged < 65 years and 108 elderly patients aged ≥ 65 years. We also examined the factors contributing to a sustained virological response. RESULTS: There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; P = 0.378). There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively). However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040- 0.330, P < 0.001). CONCLUSIONS: The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.

    DOI: 10.1186/1756-0500-5-135

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