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  1. Article ; Online: Genetic Analyses of Primary Liver Cancer Cell Lines: Correspondence With Morphological Features of Original Tumors.

    Akiba, Jun / Ogasawara, Sachiko / Yano, Hirohisa

    Cancer genomics & proteomics

    2024  Volume 21, Issue 3, Page(s) 260–271

    Abstract: Background/aim: Advancements in genetic analysis technologies have led to establishment of molecular classifications systems for primary liver cancers. The correlation between pathological morphology and genetic mutations in hepatocellular carcinoma ( ... ...

    Abstract Background/aim: Advancements in genetic analysis technologies have led to establishment of molecular classifications systems for primary liver cancers. The correlation between pathological morphology and genetic mutations in hepatocellular carcinoma (HCC) is becoming increasingly evident. To construct appropriate experimental models, it is crucial to select cell lines based on their morphology and genetic mutations. In this study, we conducted comprehensive genetic analyses of primary liver cancer cell lines and examined their correlations with morphology.
    Materials and methods: Thirteen primary liver cancer cell lines established in our Department were investigated. Eleven cell lines were HCC cell lines, whereas 2 were combined hepatocellular-cholangiocarcinoma (CHC) cell line characteristics. Whole exome sequencing and fusion gene analyses were conducted using a next generation sequencing platform. We also examined correlations between cell mutations and morphological findings and conducted experiments to clarify the association between morphological findings and genetic alterations.
    Results: Mutations in TP53, HMCN1, PCLO, HYDIN, APOB, and EYS were found in 11, 5, 4, 4, 3, and 3 cell lines, respectively. CTNNB1 mutation was not identified in any cell line. The original tumor of four cell lines (KYN-1, KYN-2, KYN-3, and HAK-6) showed morphologically macrotrabecular massive patterns and these cell lines harbor TP53 mutations. Two cell lines (KYN-2 and KMCH-2) showed an extremely high tumor mutation burden. These two cell lines possess ultra-mutations associated with DNA repair and/or DNA polymerase.
    Conclusion: The study identified correlations between morphological findings and genetic mutations in several HCC cell lines. Cell lines with unique genetic mutations were found. This information will be a valuable tool for the selection of suitable experimental models in HCC research.
    MeSH term(s) Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Mutation ; Cell Line, Tumor ; Male ; Female ; Middle Aged ; Aged ; Exome Sequencing ; High-Throughput Nucleotide Sequencing/methods
    Language English
    Publishing date 2024-04-26
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 2144517-5
    ISSN 1790-6245 ; 1109-6535
    ISSN (online) 1790-6245
    ISSN 1109-6535
    DOI 10.21873/cgp.20445
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Endotheliopathy of liver sinusoidal endothelial cells in liver disease.

    Kondo, Reiichiro / Iwakiri, Yasuko / Kage, Masayoshi / Yano, Hirohisa

    Pathology international

    2023  Volume 73, Issue 9, Page(s) 381–393

    Abstract: Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We ... ...

    Abstract Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic factors produced by the endothelial cells. In the setting of inflammation, injured endothelial cells lose these functions, defined as inflammatory endotheliopathy. In chronic hepatitis C, inflammatory endotheliopathy in LSECs contributes to platelet accumulation in the liver tissue, and the improvement of thrombocytopenia by splenectomy is attenuated in cases with severe hepatic inflammation. In COVID-19, LSEC endotheliopathy induced by interleukin (IL)-6 trans-signaling promotes neutrophil accumulation and platelet microthrombosis in the liver sinusoids, resulting in liver injury. IL-6 trans-signaling promotes the expression of intercellular adhesion molecule-1, chemokine (C-X-C motif) ligand (CXCL1), and CXCL2, which are the neutrophil chemotactic mediators, and P-selectin, E-selectin, and von Willebrand factor, which are involved in platelet adhesion to endothelial cells, in LSECs. Restoring LSECs function is important for ameliorating liver injury. Prevention of endotheliopathy is a potential therapeutic strategy in liver disease.
    MeSH term(s) Humans ; Endothelial Cells ; COVID-19 ; Liver Diseases ; Hepatic Veins
    Language English
    Publishing date 2023-08-17
    Publishing country Australia
    Document type Journal Article ; Review
    ZDB-ID 1194850-4
    ISSN 1440-1827 ; 1320-5463
    ISSN (online) 1440-1827
    ISSN 1320-5463
    DOI 10.1111/pin.13361
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: US Dispersion Slope in Patients with Varying Liver Pathology.

    Sugimoto, Katsutoshi / Yano, Hirohisa / Itoi, Takao

    Radiology

    2023  Volume 307, Issue 3, Page(s) e222251

    MeSH term(s) Humans ; Liver/pathology ; Abdomen
    Language English
    Publishing date 2023-02-28
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 80324-8
    ISSN 1527-1315 ; 0033-8419
    ISSN (online) 1527-1315
    ISSN 0033-8419
    DOI 10.1148/radiol.222251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Intraductal papilloma with atypical ductal hyperplasia and neuroendocrine differentiation as a possible precursor lesion of solid papillary carcinoma.

    Mihara, Yutaro / Yamaguchi, Rin / Takahashi, Ryuji / Yano, Yuta / Yano, Hirohisa

    Medical molecular morphology

    2023  Volume 56, Issue 3, Page(s) 227–232

    Abstract: Breast papillary neoplasms include a wide range of tumor types, and their pathological diagnosis is sometimes difficult. Furthermore, the etiology of these lesions is still not fully understood. We report the case of a 72-years-old woman referred to our ... ...

    Abstract Breast papillary neoplasms include a wide range of tumor types, and their pathological diagnosis is sometimes difficult. Furthermore, the etiology of these lesions is still not fully understood. We report the case of a 72-years-old woman referred to our hospital with bloody discharge from the right nipple. An imaging study detected a cystic lesion, including a solid component contiguous with the mammary duct, in the subareolar region. The lesion was then removed by segmental mastectomy. Pathological examination of the resected specimen revealed an intraductal papilloma with atypical ductal hyperplasia. Moreover, the atypical ductal epithelial cells expressed neuroendocrine markers. The presence of an intraductal papillary lesion with neuroendocrine differentiation suggests solid papillary carcinoma. Thus, this case suggests that intraductal papilloma could be a precursor of solid papillary carcinoma.
    MeSH term(s) Female ; Humans ; Aged ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/surgery ; Carcinoma, Intraductal, Noninfiltrating/surgery ; Papilloma, Intraductal/diagnostic imaging ; Papilloma, Intraductal/surgery ; Carcinoma, Papillary/diagnostic imaging ; Carcinoma, Papillary/surgery ; Mastectomy ; Cell Differentiation ; Hyperplasia/diagnosis ; Hyperplasia/surgery
    Language English
    Publishing date 2023-06-07
    Publishing country Japan
    Document type Case Reports ; Journal Article
    ZDB-ID 2190059-0
    ISSN 1860-1499 ; 1860-1480
    ISSN (online) 1860-1499
    ISSN 1860-1480
    DOI 10.1007/s00795-023-00357-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Squamous cell carcinoma of the tongue: subtypes and morphological features affecting prognosis.

    Matsuo, Katsuhisa / Akiba, Jun / Kusukawa, Jingo / Yano, Hirohisa

    American journal of physiology. Cell physiology

    2022  Volume 323, Issue 6, Page(s) C1611–C1623

    Abstract: Squamous cell carcinoma (SCC) is the most common histological type of mobile tongue carcinoma. The incidence of mobile tongue carcinoma is decreasing in some countries owing to decreasing exposure to risk factors, but it has been reported to be ... ...

    Abstract Squamous cell carcinoma (SCC) is the most common histological type of mobile tongue carcinoma. The incidence of mobile tongue carcinoma is decreasing in some countries owing to decreasing exposure to risk factors, but it has been reported to be increasing in younger people. The majority of mobile tongue cancers are conventional SCCs. Pathological diagnosis of conventional SCC is relatively easy. However, mobile tongue SCCs involve several subtypes that have distinct pathological features and biological behaviors. Some subtypes are relatively rare, and the pathological subtype influences treatment decision-making. Therefore, the recognition of SCC subtypes is crucial for proper treatment. In this review, we summarize nine SCC subtypes, including conventional SCC and highlight their pathological characteristics. We also report some morphological factors, such as the pattern of invasion, budding, desmoplastic reaction, lymphovascular invasion, and perineural invasion, which could be predictive of prognosis. As some morphological factors are closely associated with prognosis, pathologists may need to evaluate additional factors in pathological reports of near features. In summary, we highlight the basic knowledge of mobile tongue SCC with an emphasis on pathological subtypes, morphological features, and their relationship. We provide information to further elucidate SCC in the oral region.
    MeSH term(s) Humans ; Tongue Neoplasms/pathology ; Carcinoma, Squamous Cell/diagnosis ; Carcinoma, Squamous Cell/pathology ; Tongue/pathology ; Risk Factors
    Language English
    Publishing date 2022-10-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00098.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: [Minimally Invasive Conversion Hepatectomy for Advanced Hepatocellular Carcinoma].

    Sakai, Hisamune / Goto, Yuichi / Shimose, Shigeo / Niizeki, Takashi / Kawaguchi, Takumi / Akiba, Jun / Yano, Hirohisa / Akagi, Yoshito / Fujita, Fumihiko / Hisaka, Toru

    Gan to kagaku ryoho. Cancer & chemotherapy

    2024  Volume 50, Issue 13, Page(s) 1572–1574

    Abstract: Some cases of advanced hepatocellular carcinoma(HCC)diagnosed as unresectable(UR)have been reported to undergo conversion surgery following systemic therapy. Furthermore, the combination of atezolizumab plus bevacizumab(Atez/Bev) shows potential ... ...

    Abstract Some cases of advanced hepatocellular carcinoma(HCC)diagnosed as unresectable(UR)have been reported to undergo conversion surgery following systemic therapy. Furthermore, the combination of atezolizumab plus bevacizumab(Atez/Bev) shows potential therapeutic effects in conversion surgery for UR-HCC. At our hospital, neoadjuvant chemotherapy(NAC) using New-FP therapy(hepatic arterial infusion chemotherapy: HAIC)has been performed for borderline resectable HCC. New-FP therapy for advanced HCC with macrovascular invasion has a high response rate of 70%. For hepatectomy after NAC, a high response rate is required as a pretreatment, and New-FP therapy may be useful as the initial treatment. Limited reports exist of the laparoscopic approach in conversion surgery for advanced HCC. However, 14 cases of minimally invasive liver resection, including 10 cases after New-FP therapy and 4 cases after Atez/Bev therapy, have been safely performed conversion surgery for advanced HCC. In selected patients with advanced HCC, minimally invasive liver resection may be safely performed if the tumor shows shrinkage with various treatments.
    MeSH term(s) Humans ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/surgery ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/drug therapy ; Liver Neoplasms/surgery ; Liver Neoplasms/pathology ; Hepatectomy ; Infusions, Intra-Arterial ; Bevacizumab/therapeutic use
    Chemical Substances Bevacizumab (2S9ZZM9Q9V)
    Language Japanese
    Publishing date 2024-02-01
    Publishing country Japan
    Document type English Abstract ; Journal Article
    ZDB-ID 604842-0
    ISSN 0385-0684
    ISSN 0385-0684
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: CXCR4 Expression and Cancer-associated Fibroblasts May Play an Important Role in the Invasion of Low-grade Endometrioid Carcinoma.

    Fukumitsu, Chihiro / Sanada, Sakiko / Ogasawara, Sachiko / Tsuda, Naotake / Murotani, Kenta / Akao, Mayuka / Ushijima, Kimio / Akiba, Jun / Yano, Hirohisa

    International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

    2024  

    Abstract: Well-differentiated endometrioid carcinoma (EC) is a low-grade cancer with relatively indolent behavior. However, even with well-differentiated histology, it sometimes tends to invade extensively and shows metastatic potential, suggesting that this is a ... ...

    Abstract Well-differentiated endometrioid carcinoma (EC) is a low-grade cancer with relatively indolent behavior. However, even with well-differentiated histology, it sometimes tends to invade extensively and shows metastatic potential, suggesting that this is a group of cancers with heterogeneous behavior. In contrast, due to its tendency for younger onset, the treatment strategy for EC frequently considers fertility preservation, highlighting the need for a more accurate evaluation of myometrial invasion through biopsy and imaging diagnostics. We previously reported the involvement of the CXCR4-CXCL12 and CXCL14 axes in EC invasion. Accordingly, we investigated whether CXCR4 expression could reflect invasive potential and explored its interaction with cancer-associated fibroblasts that produce chemokines in the tumor microenvironment. Immunohistochemical expression of CXCR4 was assessed in 71 cases of EC (14 of EC confined to the endometrium and 57 of myoinvasive EC), 6 cases of endometrial intraepithelial neoplasia, and 42 cases of noncarcinomatous conditions. CXCR4 expression was significantly higher in myoinvasive EC than in noncancerous conditions, endometrial intraepithelial neoplasia, and endometrium-confined EC. By univariate and multivariate analysis, CXCR4 expression significantly reflected myometrial invasion. CXCR4 expression in the biopsied and resected specimens correlated weakly positively. Invasion and wound-healing assays were performed culturing an EC cell line in a cancer-associated fibroblast-conditioned medium. The invasion and wound-healing potentials were dependent on CXCR4 and cancer-associated fibroblast. Our study demonstrated that CXCR4 expression is an independent factor in myometrial invasion and can support diagnostic evaluation before treatment in the biopsy sample.
    Language English
    Publishing date 2024-01-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604859-6
    ISSN 1538-7151 ; 0277-1691
    ISSN (online) 1538-7151
    ISSN 0277-1691
    DOI 10.1097/PGP.0000000000001015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Fatty Liver Does Not Increase the Risk of Postoperative Liver Damage Following Hepatectomy.

    Nomura, Yoriko / Akiba, Jun / Yano, Hirohisa / Akagi, Yoshito / Hisaka, Toru

    Anticancer research

    2022  Volume 42, Issue 8, Page(s) 4159–4164

    Abstract: Background/aim: The number of patients with fatty liver due to alcohol consumption, metabolic syndrome, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis is increasing. Since there is no consensus on the risk of hepatectomy for ... ...

    Abstract Background/aim: The number of patients with fatty liver due to alcohol consumption, metabolic syndrome, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis is increasing. Since there is no consensus on the risk of hepatectomy for patients with fatty liver, this study examined the clinical outcomes of hepatectomy for fatty liver patients via evaluation of transaminase.
    Patients and methods: Patients (n=164) who underwent hepatectomy for primary liver tumors from January 2014 to March 2019 were included in the study. Patients were divided into steatohepatitis (n=19), steatosis (n=20), and control (n=30) groups. Serum values of aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TB), prothrombin time (PT), white blood cells, and platelets were compared before and immediately after surgery, and on postoperative days 1-5, 7, and 10. And their rates of change were compared using the preoperative value as a reference value.
    Results: Overall, AST and ALT elevation rates were higher in the control group than in the steatosis and steatohepatitis groups from postoperative days 2-7. There was no difference in postoperative hepatic dysfunction between the steatosis and steatohepatitis groups. Univariate analysis revealed significant differences in liver stiffness, operative time, mobilization, and Pringle time. Multivariate analysis indicated low liver stiffness and longer Pringle time as independent risk factors. Postoperative change in TB, PT, and albumin levels did not differ between the groups. There was no difference in postoperative complications and hospital stay between the groups.
    Conclusion: Fatty liver does not increase the risk of postoperative liver damage following hepatectomy.
    MeSH term(s) Alanine Transaminase ; Aspartate Aminotransferases ; Bilirubin ; Hepatectomy/adverse effects ; Humans ; Liver/surgery ; Non-alcoholic Fatty Liver Disease/complications ; Postoperative Complications/etiology
    Chemical Substances Aspartate Aminotransferases (EC 2.6.1.1) ; Alanine Transaminase (EC 2.6.1.2) ; Bilirubin (RFM9X3LJ49)
    Language English
    Publishing date 2022-07-27
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 604549-2
    ISSN 1791-7530 ; 0250-7005
    ISSN (online) 1791-7530
    ISSN 0250-7005
    DOI 10.21873/anticanres.15915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Recent Topics Concerning Combined Hepatocellular Cholangiocarcinoma.

    Akiba, Jun / Fujita, Naoya / Yano, Hirohisa

    The Kurume medical journal

    2020  Volume 66, Issue 1, Page(s) 29–36

    Abstract: Combined hepatocellular-cholangiocarcinoma (CHC) is a relatively rare tumor with an incidence range of 1.0-4.7%. CHC is defined as a tumor containing unequivocal, intimately mixed components of both hepatocellular carcinoma and intrahepatic ... ...

    Abstract Combined hepatocellular-cholangiocarcinoma (CHC) is a relatively rare tumor with an incidence range of 1.0-4.7%. CHC is defined as a tumor containing unequivocal, intimately mixed components of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The recent development of biochemical methodologies and cancer stem cell theory have paved the way for a clearer understanding of the histogenesis of CHC. The latest edited WHO classification published in 2010 adopted the concept of stem cell/hepatic progenitor cells in the pathological classification of CHC. Although this classification includes novel and unique concepts of histogenesis and facilitates the recognition of CHC, there are several problems with it in practice. To reduce confusion, an international group of hepatic pathologists, radiologists, surgeons, and clinicians formulated a nomenclature for CHC and issued a consensus article in 2018. In this review article, we discuss the problems with the latest WHO classification and introduce recent topics concerning CHC from pathologic and genetic points of view.
    MeSH term(s) Bile Duct Neoplasms ; Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Humans ; Liver Neoplasms ; Neoplastic Stem Cells ; Terminology as Topic
    Language English
    Publishing date 2020-05-01
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 603905-4
    ISSN 1881-2090 ; 0023-5679
    ISSN (online) 1881-2090
    ISSN 0023-5679
    DOI 10.2739/kurumemedj.MS661014
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  10. Article ; Online: Histopathological findings of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    Kage, Masayoshi / Aishima, Shinichi / Kusano, Hironori / Yano, Hirohisa

    Journal of medical ultrasonics (2001)

    2020  Volume 47, Issue 4, Page(s) 549–554

    Abstract: Nonalcoholic fatty liver disease (NAFLD) is based on the concept of pathological morphology as well as clinical findings, and is broadly categorized into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The differential diagnosis ... ...

    Abstract Nonalcoholic fatty liver disease (NAFLD) is based on the concept of pathological morphology as well as clinical findings, and is broadly categorized into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The differential diagnosis between NAFL and NASH is important because NASH has the potential to progress to cirrhosis and hepatocellular carcinoma. NAFL is simple hepatic steatosis without hepatocellular injury, while NASH is characterized by macrovesicular steatosis, inflammation, and ballooning hepatocytes with a predominantly centrilobular (zone 3) distribution. Liver biopsy is a useful test for diagnosing NAFLD, but it is invasive. Therefore, various noninvasive methods including diagnostic imaging have been developed in recent years. To verify their usefulness, it is necessary to clarify in detail how the pathological findings are reflected in the image findings as imaging and histopathological findings are closely related. We describe the main histological features of NAFLD, i.e., steatosis, inflammation, ballooning hepatocytes, Mallory-Denk bodies, and fibrosis, as well as the evolutional process to liver cirrhosis.
    MeSH term(s) Biopsy ; Diagnosis, Differential ; Disease Progression ; Humans ; Liver/pathology ; Liver/ultrastructure ; Non-alcoholic Fatty Liver Disease/pathology
    Language English
    Publishing date 2020-11-02
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 1396630-3
    ISSN 1613-2254 ; 0287-0592 ; 1346-4523
    ISSN (online) 1613-2254
    ISSN 0287-0592 ; 1346-4523
    DOI 10.1007/s10396-020-01061-3
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