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

BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

DOI： 10.1007/s00464-024-10762-6

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

Objectives

The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)–encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs.

Materials and Methods

Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR.

Results

Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA, in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA, which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC, which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA, HULC, or CA19-9 alone.

Conclusions

Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

DOI： 10.1097/mpa.0000000000002315

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Language：English   Publisher：(一社)日本病理学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, and developing an efficient and reliable approach for its early-stage diagnosis is urgently needed. Precancerous lesions of PDAC, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), arise through multiple steps of driver gene alterations in KRAS, TP53, CDKN2A, SMAD4, or GNAS. Hallmark mutations play a role in tumor initiation and progression, and their detection in bodily fluids is crucial for diagnosis. Recently, liquid biopsy has gained attention as an approach to complement pathological diagnosis, and in addition to mutation signatures in cell-free DNA, cell-free RNA, and extracellular vesicles have been investigated as potential diagnostic and prognostic markers. Integrating such molecular information to revise the diagnostic criteria for pancreatic cancer can enable a better understanding of the pathogenesis underlying inter-patient heterogeneity, such as sensitivity to chemotherapy and disease outcomes. This review discusses the current diagnostic approaches and clinical applications of genetic analysis in pancreatic cancer and diagnostic attempts by liquid biopsy and molecular analyses using pancreatic juice, duodenal fluid, and blood samples. Emerging knowledge in the rapidly advancing liquid biopsy field is promising for molecular profiling and diagnosing pancreatic diseases with significant diversity.

DOI： 10.1007/s00535-023-02024-4

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Language：Japanese   Publisher：医学図書出版(株)  

膵管内乳頭粘液性腫瘍(IPMN)は膵癌の高リスク群として位置付けられる膵癌の前駆病変の一つである。IPMNにおいても他の前駆病変と同様KRAS遺伝子変異が高頻度にみられる。近年,KRAS経路を軸としつつGNAS変異を含むIPMNに特徴的なドライバー遺伝子の異常により,IPMNの上皮亜型や異型度の成り立ちが説明可能となってきた。さらに,IPMNが有するKRAS,GNASおよび癌抑制遺伝子異常の組み合わせや量的バランスが浸潤癌への進展や予後と関連することが明らかになりつつある。これらの知見に基づいた高感度な分子診断は,IPMN患者に対する外科切除の時期を適切に判断するための精密サーベイランスに役立つと期待される。(著者抄録)

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Digital PCR (dPCR) allows for highly sensitive quantification of low-frequency mutations and facilitates early detection of cancer. However, low-throughput targeting of single hotspots in dPCR hinders variant specification when multiple probes are used. We developed a dPCR method to simultaneously identify major variants related to pancreatic carcinogenesis. Using a two-dimensional plot of droplet fluorescence under the optimized concentration of two fluorescent probe pools, we determined the absolute quantification of different KRAS and GNAS variants. Successful detection of the multiple driver mutations was verified in 24 surgically resected tumor samples from 19 patients and 22 fine-needle aspiration samples from patients with pancreatic ductal adenocarcinoma. Precise quantification of the variant allele frequency was optimized by using template DNA at a concentration as low as 1 to 10 ng. Furthermore, amplicons targeting multiple hotspots were successfully enriched with fewer false-positive findings using high-fidelity polymerase, allowing for the detection of various KRAS and GNAS mutations with high probability in small cell/tissue specimens. Using this target enrichment, mutations at a rate of 90% in small residual tissues, such as the fine-needle aspiration needle flush and microscopic lesions in resected specimens, were successfully identified. The proposed method allows for low-cost, accurate detection of driver mutations to diagnose cancers, even with minimal tissue collection.

DOI： 10.1016/j.jmoldx.2023.02.007

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

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

早期の膵癌や小膵癌の拾い上げは膵癌の予後向上に必須である.治癒可能な病変の確実な拾い上げには,画像診断を基盤とする診断体系に,膵発癌に重要なゲノム・分子異常に関わる情報を統合する必要がある.KRAS,TP53,SMAD4,CDKN2Aをはじめとした遺伝子変異の検出に加え,細胞外小胞に含まれるRNAやタンパク質の発現を定量する技術に期待が寄せられている.低侵襲かつ高精度な診断の確定を実現するために,次世代シーケンサーを用いた解析のみならず,デジタルPCRを用いた高感度・低コストな検出系を確立することにより,がんゲノム医療を膵癌の早期診断においても拡大・適応できると期待される.本稿では,膵発癌に関与する分子異常を解説し,膵癌患者より採取可能な様々な生体試料を用いた次世代の遺伝子診療に対する取り組みを紹介する.(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J02025&link_issn=&doc_id=20220307300005&doc_link_id=%2Fcq0pancr%2F2022%2F003701%2F006%2F0029-0039%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq0pancr%2F2022%2F003701%2F006%2F0029-0039%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

BACKGROUND: Mutations in GNAS drive pancreatic tumorigenesis and frequently occur in intraductal papillary mucinous neoplasm (IPMN); however, their value as a therapeutic target is yet to be determined. This study aimed at evaluating the involvement of mutant GNAS in tumor aggressiveness in established pancreatic cancer. METHODS: CRISPR/Cas9-mediated GNAS R201H silencing was performed using human primary IPMN-associated pancreatic cancer cells. The role of oncogenic GNAS in tumor maintenance was evaluated by conducting cell culture and xenograft experiments, and western blotting and transcriptome analyses were performed to uncover GNAS-driven signatures. RESULTS: Xenografts of GNAS wild-type cells were characterized by a higher Ki-67 labeling index relative to GNAS-mutant cells. Phenotypic alterations in the GNAS wild-type tumors resulted in a significant reduction in mucin production accompanied by solid with massive stromal components. Transcriptional profiling suggested an apparent conflict of mutant GNAS with KRAS signaling. A significantly higher Notch intercellular domain (NICD) was observed in the nuclear fraction of GNAS wild-type cells. Meanwhile, inhibition of protein kinase A (PKA) induced NICD in GNAS-mutant IPMN cells, suggesting that NOTCH signaling is negatively regulated by the GNAS-PKA pathway. GNAS wild-type cells were characterized by a significant invasive property relative to GNAS-mutant cells, which was mediated through the NOTCH regulatory pathway. CONCLUSIONS: Oncogenic GNAS induces mucin production, not only via MUC2 but also via MUC5AC/B, which may enlarge cystic lesions in the pancreas. The mutation may also limit tumor aggressiveness by attenuating NOTCH signaling; therefore, such tumor-suppressing effects must be considered when therapeutically inhibiting the GNAS pathway.

DOI： 10.1007/s00535-021-01846-4

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

The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies' datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells.

DOI： 10.3390/ijms23010496

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Language：Japanese   Publisher：医学図書出版(株)  

近年、体液を使用した液体生検(liquid biopsy)が、腫瘍の質的診断や病勢把握に重要な位置を得つつある。膵癌における代表的なドライバー遺伝子であるKRAS、CDKN2A、TP53、SMAD4変異や、IPMNで多くみられるGNAS変異など、血中遊離DNA(cell-free DNA)を用いたliquid biopsyは、通常型膵癌のみならず、IPMNの悪性度評価にも大きく寄与する可能性がある。一方で、体液中のcell-free RNAや細胞外小胞(extracellular vesicles: EVs)内に発現するRNAも、liquid biopsyの重要な標的となる。本稿ではIPMNの発生・進展における分子異常に触れるとともに、体液中の遺伝子変異やRNA発現解析による診断、悪性度評価に関するこれまでの報告をまとめ、診療への応用が期待されるliquid biopsyの最新の動向について、われわれが得た知見と併せて概説する。(著者抄録)

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

MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA-protein systems in cancer progression and its future applications in cancer treatment.

DOI： 10.3390/ijms222212303

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

Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor-derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have been studied, less is known about the contributions of normal, nontransformed cells. We examined the impact of EVs within the cellular secretome from nonmalignant cells on transformed cell growth and behavior in cholangiocarcinoma cells. These effects were enhanced in the presence of the pro-fibrogenic mediator TGF-β. We identified miR-195 as a TGF-β responsive miRNA in normal cells that can be transferred via EV to tumor cells and regulate cell growth, invasion, and migration. The effects of miR-195 involve modulation of the epithelial-mesenchymal transition through direct effects on the transcription factor Snail. These studies provide in vitro and in vivo evidence for the impact of normal cellular secretome on transformed cell growth, show the importance of EV RNA transfer, and identify mechanisms of EV-mediated transfer of miRNA as a contributor to tumor development, which may provide new therapeutic opportunities for targeting human cholangiocarcinoma.

DOI： 10.1002/2211-5463.13294

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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J-GLOBAL

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J-GLOBAL

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

Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.

DOI： 10.3389/fmolb.2021.717890

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial-mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA-HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC.

DOI： 10.3389/fonc.2020.01013

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Language：Japanese   Publisher：(株)メディカルアイ  

昨今の画像・動画処理技術の進歩により、フルフォーカスが可能となった。造影超音波検査での精密検査では音圧とフォーカスの設定が重要であるが、フルフォーカス技術を用いることで通常の造影超音波のみならず造影3D超音波においても、深部病変から浅部病変まで高精度な評価が可能なことが確認されたため、初期使用経験について報告する。(著者抄録)

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

The role of long noncoding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) is unclear. Some lncRNAs can be transferred by extracellular vesicles (EVs) and have potential as biomarkers. Here, we identify an lncRNA that could serve as a biomarker for PDAC and show the functional roles of the lncRNA. Expression profiling of lncRNAs revealed that highly upregulated in liver cancer (HULC) was highly expressed, and induced, by transforming growth factor-β in PDAC cells and their EVs. Knockdown of HULC decreased PDAC cell invasion and migration by inhibiting the EMT. Thus, HULC could be transferred by EVs, and promote EMT, invasion, and migration in recipient PDAC cells. To assess the roles of HULC, PDAC cell xenografts in nude mice were established. Knockdown of HULC in PDAC cells implanted in mice inhibited tumor growth. Moreover, microRNA-133b suppressed PDAC cell invasion and migration by inhibiting the EMT through targeting HULC. Furthermore, serum samples were obtained from 20 PDAC and 22 intraductal papillary mucinous neoplasm (IPMN) patients, as well as 21 healthy individuals. Analysis of serum EV HULC expression by digital PCR showed that HULC expression was significantly increased in PDAC patients compared to healthy individuals or IPMN patients. Additionally, HULC showed good predictive performance for discriminating PDAC, suggesting that the analysis of EV-encapsulated HULC would contribute to the diagnosis for human PDAC. Extracellular vesicle-transported HULC promotes cell invasion and migration by inducing the EMT, and microRNA-133b suppresses the EMT by targeting HULC. Extracellular vesicle-encapsulated HULC could be a potential circulating biomarker for human PDAC.

DOI： 10.1111/cas.14232

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 26-year-old man was admitted to our hospital due to upper abdominal pain. He had previously been diagnosed with gastroduodenal ulcer at 23 and 25 years old and had been treated with proton-pump inhibitors. Endoscopic hemostasis and a biopsy were performed on the hemorrhagic gastroduodenal ulcers. Laboratory and pathologic examinations demonstrated elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into the gastroduodenal tissues. Based on the clinicopathologic findings and after excluding other causes, he was diagnosed with IgG4-related gastroduodenal ulcer. We herein report a rare case of IgG4-related disease manifesting as a gastroduodenal ulcer diagnosed by an endoscopic biopsy.

DOI： 10.2169/internalmedicine.4483-20

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：Japanese   Publisher：(株)メディカルアイ  

肝限局性結節性過形成(FNH)に特徴的な造影3D超音波像としてSpiral patternを報告した。Spiral patternは螺旋状に走行するFNHの栄養動脈をあらわしており、病態を反映する画像所見の一つと考えられた。(著者抄録)

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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

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Language：Japanese   Publisher：(株)メディカルアイ  

症例は59歳女性。造影CTにて肝S8に47mm大の動脈血豊富な腫瘍を認め、MRIでは内部に脂肪成分の存在が示唆された。造影3D超音波血管相のMPR像ではearly venous returnが検出された。以上より、肝血管筋脂肪腫(AML)が疑われたが、脂肪化を伴う肝細胞癌を否定できず外科的切除を施行し、病理学的にAMLと診断された。AMLは肝細胞癌との鑑別に苦慮する場合があるが、特徴的なearly venous returnの検出に造影3D超音波は有用と考えられた。(著者抄録)

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Language：English   Publisher：WILEY  

Web of Science

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.isci.2018.03.004

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Authorship：Corresponding author   Language：English  

Early-staged cholangiocarcinoma (CCA) is difficult to diagnose due to its high potential for invasion and metastasis. Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor-β (TGF-β) in a process thought to be important for invasion and metastasis in several cancers, including CCA. Although microRNAs (miRNAs) have been implicated in the pathogenesis of several malignancies, their roles to CCA are not clearly understood. Some miRNAs were reported to be included in extracellular vesicles (EVs) and transferred from their donor cells to other cells, modulating recipient cell behaviors. In this study, the involvement and functional roles of EV-contained miRNAs during EMT in human CCA were determined. Expression profiling identified a subset of miRNAs that were reduced by TGF-β in CCA cells. Among these, miR-30e was highly downregulated by TGF-β and predicted to target Snail, which is an EMT-inducible transcription factor. MiR-30e overexpression suppressed cell invasion and migration via inhibiting EMT, whereas miR-30e inhibition promoted EMT, cell invasion and migration. Moreover, miR-30e was enriched in EVs derived from CCA cells after miR-30e overexpression, and miR-30e intercellular transfer through EVs suppressed EMT, cell invasion and migration in recipient CCA cells. Together, our results suggest that EV-mediated miR-30e transfer could inhibit EMT via directly targeting Snail, which subsequently suppresses CCA cell invasion and migration. These findings provide several new insights into regulatory mechanisms of tumor invasion and metastasis in human CCA.

DOI： 10.18632/oncotarget.24711

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Language：Japanese   Publisher：(公財)日本膵臓病研究財団  

膵癌は早期より局所浸潤、遠隔転移を伴う事が多く、早期診断に寄与する新規バイオマーカーの同定及び、浸潤転移制御機構の解明が急務である。一方で上皮間葉形質転換(EMT)が、膵癌の浸潤転移に大きく関わる事が知られている。そのため、EMTを介した癌浸潤、転移のメカニズムを明らかにする事は、膵癌治療成績を向上させる突破口となる可能性が高い。近年、長鎖の機能性RNAであるlong non-coding RNA(lncRNA)が、種々の疾患の病態成立に関わる事が明らかにされつつあるが、膵癌の発癌や進展と関連したlncRNAの報告は数少ない。また、lncRNAのいくつかは細胞外小胞(Extracellular vesicle(EV))に内包され細胞間伝達される事がわかっている。EVは体液中を循環している事から、EV中のRNAの発現変化は疾患早期診断のLiquid biopsyとして有用である。本研究では、膵癌早期診断、進展予測に寄与する血清EV中の新規lncRNAを同定し、膵癌における浸潤、転移を含めた進展制御機構とEVを介した情報伝達機構を解明する事を目的とした。DNA microarrayの結果から、膵癌患者血清中EVに高発現する4つの新規lncRNAを同定した。その内の2つ、lncRNA(A)とlncRNA(B)は正常膵管上皮細胞に比べて、膵癌細胞において高発現が認められた。さらにLncRNA(A)は健常者、IPMN患者と比べて膵癌患者血清中EVに有意に高発現している事から、膵癌の新規バイオマーカーとして、特にIPMN由来膵癌や併存癌の拾い上げに寄与する可能性が考えられた。この遺伝子の膵癌進展に関わる詳細なメカニズムは現在解析中であり、今後さらに検討を重ね、新規癌遺伝子、バイオマーカーとしての有用性を提唱し、膵癌新規診断、治療法開発基盤の確立に繋げて行く事を最終的な目標とする。(著者抄録)

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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Language：Japanese   Publisher：(株)メディカルアイ  

肝腫瘍診断における造影Smart Sensor 3Dの有用性について検討した。造影Smart Sensor 3DはAmplitude modulationを用いたMPR像の作成が可能であり、その診断精度は造影3Dメカニカルプローブ法と同等であることが示唆された。(著者抄録)

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Language：English   Publisher：WILEY  

Web of Science

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

Stem cell-based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. Therapeutic effects of bone-marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d-galactosamine/tumor necrosis factor-α (TNF-α). Systemically administered EV derived from MSC accumulated within the injured liver following systemic administration, reduced hepatic injury, and modulated cytokine expression. Moreover, survival was dramatically increased by EV derived from either murine or human MSC. Similar results were observed with the use of cryopreserved mMSC-EV after 3 months. Y-RNA-1 was identified as a highly enriched noncoding RNA within hMSC-EV compared to cells of origin. Moreover, siRNA mediated knockdown of Y-RNA-1 reduced the protective effects of MSC-EV on TNF-α/ActD-mediated hepatocyte apoptosis in vitro. These data support a critical role for MSC-derived EV in mediating reparative responses following hepatic injury, and provide compelling evidence to support the therapeutic use of MSC-derived EV in fulminant hepatic failure. Stem Cells Translational Medicine 2017;6:1262-1272.

DOI： 10.1002/sctm.16-0226

PubMed

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Language：Japanese   Publisher：(株)メディカルアイ  

肝癌診断における造影3Dの有用性について検討した。造影3Dによる腫瘍血管評価は肝内胆管癌と転移性肝腫瘍の鑑別診断に寄与する可能性が示唆された。また、造影3D後血管像における腫瘍の輪郭評価は肝癌の悪性度診断に寄与する可能性が示唆された。さらに、ドプラ法を応用した造影Smart 3Dは従来のハーモニックイメージングを補完する上で有用と考えられた。(著者抄録)

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Language：Japanese   Publisher：(株)メディカルアイ  

Superb Micro-vascular Imaging(SMI)は高分解能、高フレームレートでの微細血流観察を可能にしたカラードプラ法であり、本法は血流と組織を分離して評価することも可能である。また、Smart 3DはSMIに対応した三次元モードであり、血流と組織を一体化させた高精細3D画像を短時間で作成することができる。これらの新たな造影ドプラ法は、肝癌の精密病態診断に寄与することが期待される。(著者抄録)

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Language：English   Publisher：WILEY  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(株)インナービジョン  

近年の画像処理技術の向上により、ソナゾイド造影エコー法(以下、造影US)は飛躍的に進歩した。それは、従来の造影ハーモニック法の画質向上にとどまらず、高精細な血流診断を可能にする"Micro Flow Imaging(MFI)"や、高速・高画質な造影三次元エコー法(以下、造影3D)など多くの新技術を生み出している。さらに最近、ドプラ法を応用した新規撮像法が開発され、造影USにおいて空間分解能とリアルタイム性を両立しながら、組織と血流の信号を分離して表示できるようになった。こうした背景から現在、造影USには複数の撮像法が存在し、それに伴ってさまざまな条件下での臨床応用が試みられている。そこで、本稿では東芝メディカルシステムズ社製「Aplio 500」における造影USについて、造影二次元エコー法(以下、造影2D)、造影3D、造影ドプラ法に分けて概説し、肝腫瘍診断における造影USの臨床応用について議論したい。(著者抄録)

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Language：Japanese   Publisher：日本膵臓学会  

近年、長鎖の機能性RNAであるlong non-coding RNA(lncRNA)が、癌を含めた疾患の病態成立に寄与する事が明らかとなっている。また、lncRNAの中には細胞外小胞(extracellular vesicle;EV)によって細胞間輸送されるものがあり、伝達先の細胞においてシグナルや機能に影響を与える事が分かっている。これらlncRNAとEVの膵発癌、進展における機能解析はほとんどなされていないのが現状であるが、いくつかのlncRNAが膵癌浸潤、転移に重要なプロセスであるepithelial-mesenchymal transition(EMT)を制御する事が示唆されている。膵癌におけるlncRNAの核酸本体としてのエピジェネティックな制御機構及び、EVを介した情報伝達機構を解明する事が、新たな膵癌診断、治療法の開発につながる可能性がある。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J02025&link_issn=&doc_id=20160304110005&doc_link_id=%2Fcq0pancr%2F2016%2F003101%2F006%2F0032-0040%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq0pancr%2F2016%2F003101%2F006%2F0032-0040%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(株)メディカルアイ  

肝癌切除例を中心に造影3D画像と病理像との関連について検討した。造影3D後血管像は肝癌の組織分化度が低下するにつれて明瞭な欠損像を呈した。造影3Dは肝癌の腫瘍形態診断および組織分化度診断に有用性が示唆される。(著者抄録)

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Language：Japanese   Publisher：(株)メディカルアイ  

肝癌診断における造影USの有用性について造影CTと比較検討した。造影USは肝癌における総合画像診断の1つとして、造影CTなど他のモダリティを補完する役目を持つとともに、肝癌の腫瘍血管評価や腫瘍形態評価など精密診断には極めて有用と考えられる。(著者抄録)

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

The contributions of mesenchymal stem cells (MSCs) to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs). We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell-derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell-derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell-derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can "educate" MSCs to induce local microenvironmental changes that enhance tumour cell growth.

DOI： 10.3402/jev.v4.24900

PubMed

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Language：Japanese   Publisher：(株)メディカルアイ  

症例は72歳女性、病理学的に肝原発平滑筋肉腫と診断された。本例のソナゾイド造影超音波所見は血管相で不整な腫瘍血管と腫瘍濃染を呈し、後血管相では境界鮮明な欠損像を呈した。さらに造影3D超音波(造影3D)では肝癌に類似したNetwork Patternを認めた。造影3Dは本腫瘍の血管構築を検討する上で有用な手法と考えられた。(著者抄録)

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

UNLABELLED: Hepatocellular cancer (HCC) is a highly treatment-refractory cancer and is also highly resistant to adverse cellular stress. Although cell behavior can be modulated by noncoding RNAs (ncRNA) within extracellular vesicles (EV), the contributions of long noncoding RNAs (lncRNAs) are largely unknown. To this end, the involvement and functional roles of lncRNAs contained within EVs during chemotherapeutic stress in human HCC were determined. Expression profiling identified a subset of lncRNAs that were enriched in tumor cell-derived vesicles released from two different cell lines. Of these, lincRNA-VLDLR (linc-VLDLR) was significantly upregulated in malignant hepatocytes. Exposure of HCC cells to diverse anticancer agents such as sorafenib, camptothecin, and doxorubicin increased linc-VLDLR expression in cells as well as within EVs released from these cells. Incubation with EVs reduced chemotherapy-induced cell death and also increased linc-VLDLR expression in recipient cells. RNAi-mediated knockdown of linc-VLDLR decreased cell viability and abrogated cell-cycle progression. Moreover, knockdown of VLDLR reduced expression of ABCG2 (ATP-binding cassette, subfamily G member 2), whereas overexpression of this protein reduced the effects of VLDLR knockdown on sorafenib-induced cell death. Here, linc-VLDLR is identified as an EV-enriched lncRNA that contributes to cellular stress responses. IMPLICATIONS: These findings provide new insight into the role of EVs and demonstrate the capacity of lncRNAs to mediate chemotherapeutic stress response in HCC.

DOI： 10.1158/1541-7786.MCR-13-0636

PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

UNLABELLED: The identification of the presence of large RNA transcripts that do not code for proteins but that may have biological functions has provided an important new perspective in gene regulation. These long noncoding RNAs (lncRNAs) are being increasingly recognized to contribute to many biological processes through diverse mechanisms. The roles of these emerging genes are being recognized across kingdoms. These findings are profoundly altering our understanding of disease pathobiology and leading to the emergence of new biological concepts underlying human diseases. Strategies for the discovery and characterization of lncRNAs are highlighted. Several lncRNAs have been described in liver disease, and in liver cancers in particular. Their molecular mechanisms of action, function, and contributions to disease pathophysiology are reviewed. LncRNA genes associated with liver diseases have potential roles as biomarkers of disease diagnosis, prognosis, or therapeutic response as well as direct targets for therapeutic intervention. CONCLUSION: The emerging knowledge in this rapidly advancing field offers promise for new fundamental knowledge and clinical applications that will be relevant for human liver diseases.

DOI： 10.1002/hep.27043

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

DOI： 10.3389/fonc.2014.00129

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Resistance to adverse environmental conditions, such as hypoxia, contributes to the reduced efficacy of anticancer therapies and tumor progression. Although deregulated expression of many long noncoding RNA (lncRNA) occurs in human cancers, the contribution of such RNA to tumor responses to hypoxia are unknown. RNA expression profiling identified several hypoxia-responsive lncRNAs, including the long intergenic noncoding RNA, regulator of reprogramming (linc-RoR), which is also increased in expression in malignant liver cancer cells. Linc-RoR expression was increased in hypoxic regions within tumor cell xenografts in vivo. Tumor cell viability during hypoxia was reduced by small interfering RNA (siRNA) to linc-RoR. Compared with controls, siRNA to linc-RoR decreased phosphorylation of p70S6K1 (RPS6KB1), PDK1 and HIF-1α protein expression and increased expression of the linc-RoR target microRNA-145 (miR-145). Linc-RoR was highly expressed in extracellular RNA released by hepatocellular cancer (HCC) cells during hypoxia. Incubation with extracellular vesicle preparations containing extracellular RNA increased linc-RoR, HIF-1α expression and cell survival in recipient cells. These studies show that linc-RoR is a hypoxia-responsive lncRNA that is functionally linked to hypoxia signaling in HCC through a miR-145-HIF-1α signaling module. Furthermore, this work identifies a mechanistic role for the extracellular transfer of linc-RoR in intercellular signaling to promote cell survival during hypoxic stress.

DOI： 10.1242/jcs.141069

PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Hepatocellular cancers (HCC) are highly resistant to chemotherapy. TGFβ has been associated with chemoresistance in some human cancers but the mechanisms involved are unknown. We explored how TGFβ might contribute to altered responses to therapy by assessing the involvement and mechanistic contribution of extracellular vesicle long non-coding RNA (lncRNA) in mediating TGFβ-dependent chemoresistance. TGFβ reduced the sensitivity of HCC cells to sorafenib or doxorubicin and altered the release of both extracellular vesicles and of selected lncRNA within these vesicles. Amongst these, lincRNA-ROR (linc-ROR), a stress-responsive lncRNA was highly expressed in HCC cells and enriched within extracellular vesicles derived from tumor cells. Incubation with HCC-derived extracellular vesicles increased linc-ROR expression and reduced chemotherapy-induced cell death in recipient cells. Sorafenib increased linc-ROR expression in both tumor cells and extracellular vesicles, whereas siRNA to linc-ROR increased chemotherapy-induced apoptosis and cytotoxicity. Tumor-initiating cells that express CD133 have an increased resistance to therapy. TGFβ increased expression of CD133+ cells and colony growth in limiting dilution assays, both of which were attenuated by linc-ROR knockdown. These data provide mechanistic insights into primary chemoresistance in HCC by showing that: (a) TGFβ selectively enriches linc-RoR within extracellular vesicles, which has a potential role in intercellular signaling in response to TGFβ; (b) expression and enrichment of linc-ROR during chemotherapeutic stress plays a functional role in chemoresistance; and (c) the effects of TGFβ on chemoresistance in HCC may involve linc-RoR-dependent effects on tumor-initiating cells. These findings implicate extracellular vesicle lncRNA as mediators of the chemotherapeutic response, and support targeting linc-ROR to enhance chemosensitivity in HCC.

DOI： 10.1016/j.fob.2014.04.007

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

The microRNAs (miRNAs) are small noncoding RNAs that are potent regulators of gene expression and can regulate several diverse biological functions. This minireview provides an overview of recent studies that have examined the role and involvement of miRNAs in cholangiocarcinomas. These studies provide evidence for deregulated expression of miRNA and are providing new insights into the potential contribution of these in the pathogenesis of cholangiocarcinoma.

DOI： 10.3727/105221614X13919976902174

PubMed

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Language：English   Publisher：WILEY-BLACKWELL  

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Authorship：Lead author   Language：English  

There is a need to identify effective biomarkers for diagnosis, prognosis and prediction of treatment efficacy for many liver diseases such as hepatocellular cancer, and chronic viral hepatitis. The identification of disease-specific alterations in microRNA expression and the ability to detect microRNAs in the circulation provide the basis for identifying novel clinically effective treatments and biomarkers. Knowledge regarding miRNA in human liver disease may eventually lead to serum or tissue biomarkers with clinical utility. A selection of relevant studies is reviewed. There are major challenges that need to be addressed prior to clinical application such as the need for careful validation of diagnostic miRNA candidates in well described clinical cohorts, and technical issues such as quantitation and standardization of assays. The rapid progress in therapeutic interventions using miRNA based strategies for chronic hepatitis C and hepatocellular cancer provides optimism for novel approaches that will build on the existing and emerging knowledge regarding miRNA in liver diseases.

DOI： 10.1016/j.clinbiochem.2013.01.025

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Objectives:: Homeobox gene caudal related homeobox gene 2 (CDX2) is an intestine-specific tumor suppressor gene. This study is intended to investigate the effect of CDX2 expression on cell proliferation and cyclin D1 expression in pancreatic cancer cells. Methods:: Four pancreatic ductal adenocarcinoma cell lines (PancQGO-1, BxPC-3, MIAPaCa-2, CFPAC-1), 1 islet carcinoma cell line (QGP-1), and 1 adenosquamous carcinoma cell line (KP-3) were analyzed for CDX1 and CDX2 expression using real-time reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of pancreatic cancer cells was analyzed using WST-1 assay after CDX2 transfection. Luciferase assay was performed to examine the effects of CDX2 on cyclin D1 transcriptional activity. Results:: CDX2 was expressed at a significantly higher level in QGP-1 cells than in KP-3 cells. Moreover, CDX2 was expressed at a middle level in 4 pancreatic ductal adenocarcinoma cells. Cell proliferation and cyclin D1 mRNA level were inhibited significantly after CDX2 transfection in pancreatic cancer cells. Furthermore, CDX2 inhibited exogenous nuclear factor κB-p65-induced luciferase gene expression in a dose-dependent manner. In addition, CDX2 inhibited pGL2HIVD1κB2-luciferase activity. Conclusions:: CDX2 might play a role in inhibiting cell proliferation and repressing cyclin D1 transcriptional activity through the proximal nuclear factor κB binding site in pancreatic cancer cells. Copyright © 2008 by Lippincott Williams &amp
Wilkins.

DOI： 10.1097/MPA.0b013e31817fa2ba

Scopus

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(株)メディカルアイ  

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Language：Japanese   Publisher：(一社)日本インターベンショナルラジオロジー学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00534-006-1205-2

CiNii Books

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Other Link： http://link.springer.com/article/10.1007/s00534-006-1205-2/fulltext.html

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

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(株)メディカルアイ  

52歳男性。C型慢性肝炎であったが、6年経過して腹部膨満感が出現した。造影CTにより肝表面の凹凸不整、その周囲の腹水貯留を認めた。肝門部には内部に淡い造影効果を伴う低吸収域が存在し、それに接した門脈内にthread and streaks signを認めた。以上よりC型肝硬変症に合併した門脈腫瘍塞栓を伴う進行肝細胞癌と診断した。造影前カラードプラ検査所見より門脈右枝完全閉塞の診断で、attenuation differenceも認められた。Sonazoidを用いて低音圧Harmonic Imagingによる肝細胞癌門脈腫瘍塞栓の血流評価を行った結果、肝内の肝動脈より分岐して門脈腫瘍塞栓に流入している栄養動脈が観察された。さらにMicro Flow Imagingを用いて再度観察を行ったところ、その一部始終はより明瞭化し、いわゆるthread and streaks signがリアルタイムに映像化されたことを確認できた。さらにParametric Imagingによる血流速度評価にて正確さを証明できた。Sonazoid造影超音波はリアルタイム性の良さと空間分解能の高さを兼ね備えており、肝細胞癌門脈腫瘍塞栓の腫瘍内血流評価に大変有用であると考えられた。

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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J-GLOBAL

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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J-GLOBAL

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：旭川医科大学  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J03513&link_issn=&doc_id=20160930310017&doc_link_id=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3Df1601030&url=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3Df1601030&type=%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%81F%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%90%AC%89%CA%83%8A%83%7C%83W%83g%83%8A_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese  

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Language：Japanese  

CiNii Books

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Language：Japanese  

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Event date： 2023.7

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：博多  

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Event date： 2023.7

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：博多  

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Event date： 2023.7

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：博多  

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Event date： 2023.4

Language：English   Presentation type：Poster presentation  

Venue：Orlando, FL, USA  

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Event date： 2022.11

Language：English   Presentation type：Oral presentation (general)  

Venue：Austin, TX USA  

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Event date： 2022.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：博多  

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Event date： 2022.9 - 2022.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜  

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Event date： 2022.9

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Boston, MA, USA  

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Event date： 2022.7

Language：English   Presentation type：Oral presentation (general)  

Venue：Kyoto  

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Event date： 2022.7

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Kyoto  

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Event date： 2022.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京  

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Event date： 2022.3

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：札幌  

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Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜  

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Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜  

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Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜  

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Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜  

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Event date： 2021.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京  

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Event date： 2021.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京  

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Event date： 2021.1

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：神戸  

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Event date： 2020.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：神戸  

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Event date： 2020.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：札幌  

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Event date： 2020.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：広島  

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Event date： 2020.6

Language：English   Presentation type：Poster presentation  

Venue：大阪(web発表)  

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Event date： 2019.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：金沢  

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Event date： 2018.8

Language：English   Presentation type：Poster presentation  

Venue：広島  

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Event date： 2018.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：大阪  

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Event date： 2018.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京  

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Event date： 2018.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京  

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Event date： 2017.8 - 2017.9

Language：English   Presentation type：Poster presentation  

Venue：広島  

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Event date： 2017.7

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：京都  

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Event date： 2016.10

Language：English   Presentation type：Oral presentation (general)  

Venue：横浜  

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Event date： 2016.8 - 2016.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：広島  

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Event date： 2016.8

Language：English   Presentation type：Poster presentation  

Venue：仙台  

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Event date： 2016.8

Language：English   Presentation type：Poster presentation  

Venue：仙台  

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Event date： 2016.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：幕張  

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Event date： 2015.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：名古屋  

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Event date： 2015.5

Language：English   Presentation type：Poster presentation  

Venue：Washington, DC, USA  

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Event date： 2014.4

Language：English   Presentation type：Poster presentation  

Venue：Chicago, IL, USA  

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Presentation type：Oral presentation (general)  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (invited, special)  

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Presentation type：Poster presentation  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Poster presentation  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (invited, special)  

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Presentation type：Oral presentation (general)  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Symposium, workshop panel (public)  

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Presentation type：Poster presentation  

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Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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Award type：Award from international society, conference, symposium, etc.  Country：United States

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Award type：International academic award (Japan or overseas)  Country：Japan

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Award type：Award from international society, conference, symposium, etc.  Country：Japan

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Award type：Award from international society, conference, symposium, etc.  Country：United States

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Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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Award type：Award from international society, conference, symposium, etc.  Country：United States

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Award type：International academic award (Japan or overseas)  Country：Japan

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Award type：Award from international society, conference, symposium, etc.  Country：United States

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Award type：Award from international society, conference, symposium, etc.  Country：United States

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Award type：Award from international society, conference, symposium, etc.  Country：France

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