記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Acute-on-chronic liver failure (ACLF), a disease with poor prognosis, is reportedly caused by cellular senescence due to mitochondrial dysfunction. In this study, we described and analyzed the underlying mechanism of a novel approach for ACLF using ABT263/navitoclax (Navi) that selectively eliminates senescent cells. METHODS: Irradiation-induced senescent hepatocytes were used for in vitro evaluation of the effects of Navi on ACLF (n = 6 for each group). Lipopolysaccharide- and carbon tetrachloride-induced ACLF mouse model was used for in vivo evaluation of the effects of Navi administration compared with the control using one-way or two-way analysis of variance, followed by Student's t-test or Kruskal-Wallis test. The effects on the senescence-associated secretory phenotype (n = 8 for each group) and mitochondrial functions, including adenosine triphosphate concentration and membrane potential (n = 8 for each group), were investigated using real-time polymerase chain reaction, immunohistochemistry, and enzyme analysis. RESULTS: Navi eliminated irradiation-induced senescent hepatocytes in vitro, leading to non-senescent hepatocyte proliferation. Navi eliminated senescent cells in the liver in vivo, resulting in downregulation of mRNA expression of senescence-associated secretory phenotype factors, a decrease of liver enzymes, and upregulated proliferation of non-senescent cells in the liver. Regarding mitochondrial functional assessment in the liver, adenosine triphosphate concentration and membrane potential were upregulated after Navi administration in vitro and in vivo. CONCLUSIONS: Navi may ameliorate ACLF damage by eliminating senescent cells in the liver, downregulating senescence-associated secretory phenotype factors, and upregulating mitochondrial functions. We believe that this novel approach using Navi will pave the way for ACLF treatment.

DOI： 10.1111/hepr.13879

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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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: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

DOI： 10.1002/jgh3.12789

PubMed

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本再生医療学会  

肝硬変症に対する治療として、2003年実施した臨床研究:自己骨髄細胞投与療法により、肝線維化改善とそれに引き続く肝再生の誘導、それに伴う肝機能の改善効果を確認してきた。その後、2017年より、肝硬変症に対する他家脂肪組織由来間葉系幹細胞投与療法の企業治験、現在軽症の肝硬変に対する他家脂肪組織由来間葉系幹細胞の医師主導治験を2021年より実施している。さらに2020年よりHMGB1ペプチドを用いた医師主導治験を実施しており、より効率のいい再生療法の開発を行っている。さらに次のステップとして間葉系幹細胞由来エクソソームを用いた治療の準備を行っている。本稿では、現時点における我々の肝硬変症に対するアプローチを紹介する。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.

DOI： 10.1371/journal.pone.0263464

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

＜文献概要＞本稿では,肝疾患領域の細胞を用いた再生医療の現状について概説する。2000年から基礎研究成果を基盤に,2003年から開始された肝硬変症に対する自己骨髄細胞投与療法,その後,血管内皮細胞投与療法,さらに自己脂肪組織細胞投与療法が実施されてきた。また,英国エジンバラ大学のForbesらは,肝硬変症に対して自己マクロファージ細胞投与療法を実施し,一方でSokalらは,代償性肝硬変症から急激に肝不全状態になるacute on chronic liver failure(ACLF)に対する,肝臓から採取した肝前駆細胞の投与療法を実施している。さらに,自己間葉系幹細胞を用いた治験も実施されてきた。日本では2017年より他家間葉系幹細胞投与療法の肝硬変症に対する治験を進めてきた(PhaseI,II)。また,2019年よりES細胞由来の肝臓様細胞を門脈より投与する先天性の尿素酵素欠損症に対する医師主導治験が進んでいる。本稿では,現在進んでいる細胞を用いた肝臓疾患に対する細胞を用いた再生療法を俯瞰し紹介する(図1)。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01750&link_issn=&doc_id=20211223100008&doc_link_id=issn%3D0289-5803%26volume%3D39%26issue%3D12%26spage%3D37&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-5803%26volume%3D39%26issue%3D12%26spage%3D37&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

症例は50代の女性.30代でC型肝炎ウイルスへの感染を指摘されていたが治療に至らず,継続的な受診も行っていなかった.腹痛と意識消失を主訴に救急搬送され,脾動脈瘤破裂による出血性ショックと診断された.当院で脾動脈瘤塞栓術を施行し,術後経過は良好であった.外来にて直接作用型抗ウイルス薬を導入し,ウイルス学的著効を達成した.CT検査の普及により,脾動脈瘤の偶然の発見も増加していると報告されていて,今後本例のように肝臓以外の疾患での受診を契機に,ウイルス性肝炎や肝硬変の診断から治療に至る症例もある.C型肝炎の未治療者や未受検者,非認識受検者は国内に未だ数多く存在しており,脾動脈瘤に関する文献的考察と,新潟県で実施している肝炎患者の拾い上げの試みについても併せて記載し報告する.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00263&link_issn=&doc_id=20211111030008&doc_link_id=1390852945233297152&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390852945233297152&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (Trem2+Cd9+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages.

DOI： 10.1186/s41232-021-00177-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The liver is a highly regenerative organ; however, its regeneration potential is reduced by chronic inflammation with fibrosis accumulation, leading to cirrhosis. With an aim to tackle liver cirrhosis, a life-threatening disease, trials of autologous bone marrow cell infusion (ABMi) therapy started in 2003. Clinical studies revealed that ABMi attenuated liver fibrosis and improved liver function in some patients; however, this therapy has some limitations such as the need of general anesthesia. Following ABMi therapy, studies have focused on specific cells such as mesenchymal stromal cells (MSCs) from a variety of tissues such as bone marrow, adipose tissue, and umbilical cord tissues. Particularly, studies have focused on gaining mechanistic insights into MSC distribution and effects on immune cells, especially macrophages. Several basic studies have reported the use of MSCs for liver cirrhosis models, while a number of clinical studies have used autologous and allogeneic MSCs; however, there are only a few reports on the obvious substantial effect of MSCs in clinical studies. Since then, studies have analyzed and identified the important signals or components in MSCs that regulate immune cells, such as macrophages, under cirrhotic conditions and have revealed that MSC-derived exosomes are key regulators. Researchers are still seeking the best approach and filling the gap between basic and clinical studies to treat liver cirrhosis. This paper highlights the timeline of basic and clinical studies analyzing ABMi and MSC therapies for cirrhosis and the scope for future studies and therapy.

DOI： 10.1186/s41232-021-00178-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The number of patients with non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD) is increasing. This study elucidates the effect of both NASH and IBD on hepatocellular carcinoma (HCC) using a mouse model combining NASH and IBD. The melanocortin 4 receptor-deficient (Mc4r-KO) mice were divided into four groups with or without a high-fat diet (HFD) and with or without dextran sulfate sodium (DSS) to induce colitis, and the differences in liver damage and occurrence of HCC were analyzed. In the HFD + DSS group, the body weight, liver weight/body weight ratio, and serum levels of albumin and alanine aminotransferase were significantly lower than those in the HFD group. We further found that steatosis was significantly lower and lobular inflammation was significantly higher in the HFD + DSS group than those in the HFD group, and that individual steatosis and lobular inflammation state in the HFD + DSS mice varied. We detected HCC only in the HFD + DSS group, and mice with severe steatosis and mild colitis were found to be at high risk of HCC. Presently, the prediction of HCC is very difficult. In some cases, severe colitis reverses the fat accumulation due to appetite loss. Our findings clearly showed that severe steatohepatitis and mild colitis are simultaneously essential for the occurrence of HCC in patients with NASH and IBD.

DOI： 10.1016/j.bbrc.2021.05.097

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) colitis are opportunistic infections that occur during immunosuppressive treatments for ulcerative colitis (UC). The prognosis of PJP and CMV colitis is very poor. We herein report a rare case of a 74-year-old UC patient with PJP and CMV colitis that was successfully treated with intensive therapy. PJP progresses rapidly, so the timing and choice of treatment are critical. Furthermore, a literature review of similar cases suggested that prophylactic therapy for opportunistic infections might be important, especially in the elderly. This case will serve as a reference for successful treatment in future cases.

DOI： 10.2169/internalmedicine.7953-21

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>Situs inversus abdominus is a congenital abnormality characterized by the mirror image positioning of the abdominal organs, making it difficult to diagnosis and treatment of many diseases. Here, we report a rare case of gastric varices in situs inversus abdominus patient. A 55-year-old man was diagnosed with F2-shaped gastric varices associated with alcoholic cirrhosis. Abdominal dynamic computed tomography showed situs inversus abdominus, and gastric varices with a gastrorenal shunt. Due to the complex anatomy, emergency interventional radiology during bleeding was extremely difficult. Therefore, after thorough consultation, we decided to treat gastric varices prophylactically by balloon-occluded retrograde transvenous obliteration. After treatment, the patient’s clinical course was generally good, with no adverse events, and the gastric varices disappeared. It is important to assess anatomical positioning using three-dimensional reconstruction computed tomography images before treatment, to adequately prepare, including selecting appropriate devices (i.e., catheters and sheath). Although preventive treatment of gastric varices is controversial, in cases with anatomical complexity, preventive treatment with sufficient preparation would be recommended. To the best of our knowledge, there are no reports of treatment for gastric varices in situs inversus abdominus patient. This case will serve as a reference for successful treatment in future cases.

DOI： 10.1007/s12328-020-01332-z

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その他リンク： http://link.springer.com/article/10.1007/s12328-020-01332-z/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed. METHODS: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment. RESULTS: Kaplan-Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293-12.054, p = 0.016 and HR 6.040, 95% CI 1.969-18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231-88.936, p = 0.032 and HR 10.824, 95% CI 1.252-93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008-1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919-0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098-12.128, p = 0.035) at the time of diagnosis. CONCLUSIONS: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients.

DOI： 10.1007/s12072-021-10163-0

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記述言語：日本語   出版者・発行元：(株)アークメディア  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-甲信越支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-甲信越支部  

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

＜文献概要＞近年開発された抗ウイルス薬によりウイルス性肝炎の治療法は確立されつつあるが,依然として肝硬変患者は世界中に多く存在している.肝硬変に対する根治治療は肝移植が唯一の治療法であるが,実施できるのは一部の患者に限られるため再生医療による低侵襲な新規治療法が嘱望されている.ここ数年で肝臓の分野で再生医療は著しく進歩しており,今回はおもに最近の研究成果を中心に細胞や細胞外小胞による有望な肝再生治療の現状について述べる.これらの研究は使用する細胞や小胞の安全性の確保,大量生産における均一性や品質保持など一般化に向けてクリアすべき課題も存在するが,新たな肝再生治療開発に向けて努力を継続していく必要がある.

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担当区分：筆頭著者  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 69-year-old man consulted a local doctor because of a chief complaint of fever and anorexia. CT showed a giant liver mass of the right hepatic lobe and multiple pulmonary nodules. The patient was admitted to our hospital. We punctured the liver mass, obtaining pus, and as gram-negative bacilli were detected from both blood and pus cultures, a liver abscess with septic pulmonary embolism was diagnosed. Following a positive string test, we identified the pathogenic bacteria as hypermucoviscous Klebsiella pneumoniae, which is highly invasive to the tissues. The patient showed improvement following the administration of an antimicrobial agent (Meropenem) and multiple abscess drainage procedures.

DOI： 10.11405/nisshoshi.117.437

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.

DOI： 10.1186/s41232-020-00121-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Inflammatory bowel diseases (IBDs) are sometimes refractory to current therapy or associated with severe adverse events during immunosuppressive therapy; thus, new therapies are urgently needed. Recently, mesenchymal stem cells (MSCs) have attracted attention based on their multitude of functions including anti-inflammatory effects. However, proper timing of MSC therapy and the mechanisms underlying the therapeutic effects of MSCs on colitis are not fully elucidated. Human adipose tissue-derived mesenchymal stem cells (hAdMSCs; 1 × 106) were administrated via the tail vein on day 3 (early) or 11 (delayed) using a 7-day dextran sulfate sodium (DSS)-induced mouse model of colitis. The effects were evaluated based on colon length, disease activity index (DAI) and histological score. Cytokine-encoding mRNA levels T cells and macrophages were evaluated by real-time PCR and flow cytometry. Regarding the timing of administration, early (day 3) injection significantly ameliorated DSS-induced colitis in terms of both DAI and histological score, compared to those parameters with delayed (day 11) injection. With early cell injection, the tissue mRNA levels of anti-inflammatory cytokine genes (Il10, Tgfb) increased, whereas those of inflammatory cytokine genes (Il6, Tnfa and Il17a) decreased significantly. Regarding the associated mechanism, hAdMSCs suppressed T cell proliferation and activation in vitro, increased the number of regulatory T cells in vivo and changed the polarity of macrophages (into the anti-inflammatory M2 phenotype) in vitro. Timing of injection is critical for the effective therapeutic effects of hAdMSCs. Furthermore, part of the associated mechanism includes T cell activation and expansion and altered macrophage polarization.

DOI： 10.1007/s00441-018-02981-w

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記述言語：英語  

DOI： 10.1097/MPA.0000000000001267

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatocellular carcinomas (HCCs), which often arise from chronic liver damage, have poor conditional 5-year survival and are recognized as heterogeneous tumors. Considering the heterogeneity of HCCs, diverse perspectives need to be addressed for treating such tumors, besides the findings of conventional imaging modalities and tumor markers. Data from the latest technologies, such as liquid biopsy, and the detection of the presence of cancer cells with stem/progenitor cell markers, gene mutations and diverse pathways, crosstalk with immune cells and cancer-associated fibroblasts, and mechanisms of epithelial-mesenchymal transition provide diverse lines of information. Integration of these data with clinical data might be necessary to develop effective therapies for precision medicine. Here, we review several aspects of dealing with the complexity of heterogeneous HCCs.

DOI： 10.1016/j.heliyon.2019.e01325

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a case of inferior vena cava (IVC) thrombosis caused by compression by a giant liver cyst. A 68-year-old man with a 1-day history of abdominal pain was referred to another hospital. Ultrasonography (US) and enhanced computed tomography (CT) showed a multilobular cyst on the right liver lobe that had increased to 300 mm in diameter from 90 mm 18 months earlier. Thrombosis was detected in the IVC, which was compressed by the cyst. Percutaneous transhepatic cyst drainage achieved no significant change in size. Cytological analysis from the percutaneous drainage tube fluid showed no evidence of malignancy. He was referred to our hospital for further assessment and treatment. Enhanced US using perfluorobutane, CT, and magnetic resonance imaging showed no tumorous lesions in the cyst. Thus, we diagnosed it as a multilobular cyst with no evidence of malignancy. A 3-week course of heparin resulted in the successful resolution of the thrombosis. Cystectomy was subsequently performed and pathological examination showed a multifocal cyst consisting of central suppurative inflammatory exudation and hemorrhagic material, with no malignancy. This case demonstrates that giant, expanding, non-tumorous cysts can cause IVC thrombosis. Careful treatment using heparin successfully resolved the thrombosis and allowed successful cystectomy.

DOI： 10.1007/s12328-018-0885-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.0611-17

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Our case highlights the need for caution during vascular endothelial growth factor pathway inhibitor (VPI) therapy and for the occurrence of aortic dissection. If Stanford classification type A aortic dissection occurs during VPI therapy, surgical intervention should be considered to prevent cardiac tamponade if the patient's clinical condition permits it.

DOI： 10.1002/ccr3.1674

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The high heterogeneity of hepatocellular carcinomas (HCCs) complicates stratification of HCC patients for treatment. Therefore, it is necessary to establish a comprehensive panel of HCC biomarkers related to tumour behaviour and cancer prognosis. Resected HCCs from 251 patients were stained for hepatic progenitor cell (HPC) markers epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), delta-like 1 homolog (DLK1), and cytokeratin 19 (CK19). Staining patterns were analysed for their prognostic association with relapse-free survival and overall survival. α-Fetoprotein (AFP), lectin-reactive α-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin (DCP) were assessed as indicators of HPC protein expression. Expression pattern of HPC markers correlated with tumour malignancy indicated by high AFP/AFP-L3 serum levels, more frequent vascular invasion, and poorer tumour differentiation. EpCAM expression, DCP ≥300 mAU/ml, age ≥60, and Child-Pugh score grade B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation. Expression of two or more HPC markers was a significant predictor of poor HCC outcome and serum levels of AFP/AFP-L3 correlated with the expression of HPC proteins. Our study paved the way for further elucidation of the association among HPC markers, serum tumour markers, and HCC clinical outcome for precision medicine.

DOI： 10.18632/oncotarget.25074

PubMed

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記述言語：英語   出版者・発行元：WILEY  

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mesenchymal stem cell (MSC) therapies have been used in clinical trials in various fields. These cells are easily expanded, show low immunogenicity, can be acquired from medical waste, and have multiple functions, suggesting their potential applications in a variety of diseases, including liver disease and inflammatory bowel disease. MSCs help prepare the microenvironment, in response to inflammatory cytokines, by producing immunoregulatory factors that modulate the progression of inflammation by affecting dendritic cells, B cells, T cells, and macrophages. MSCs also produce a large amount of cytokines, chemokines, and growth factors, including exosomes that stimulate angiogenesis, prevent apoptosis, block oxidation reactions, promote remodeling of the extracellular matrix, and induce differentiation of tissue stem cells. According to ClinicalTrials.gov, more than 680 clinical trials using MSCs are registered for cell therapy of many fields including liver diseases (more than 40 trials) and inflammatory bowel diseases (more than 20 trials). In this report, we introduce background and clinical studies of MSCs in liver disease and inflammatory bowel diseases.

DOI： 10.1186/s41232-017-0045-6

PubMed

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記述言語：英語   出版者・発行元：WILEY  

Web of Science

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担当区分：筆頭著者  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：新潟医学会  

CiNii Article

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2016166709

記述言語：日本語   出版者・発行元：(株)医薬ジャーナル社  

限局性結節性過形成(focal nodular hyperplasia:FNH)は血管腫に次いで多い、基本的には非慢性障害肝に生じる、悪性に変化することのない良性結節である。典型的には中心瘢痕を持つこと、中心瘢痕から放射状に分布する中隔内に拡張する動脈(車軸様血管)を持つことが特徴とされる。近年の画像の進歩により、大きな結節での診断能は向上しているが、小結節では鑑別診断が難しいケースもある。特に臨床的には同じ多血性病変である肝細胞癌との鑑別が最も重要なポイントになる。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)アークメディア  

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