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Article ; Online: Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study.

Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

Virchows Archiv : an international journal of pathology

2024

Abstract: Genetic alterations including fusions in fibroblast growth factor receptor 2 (FGFR2) are detected in 10-20% of intrahepatic cholangiocarcinoma (iCCA), and FGFR2 inhibitors are effective for the treatment of iCCA. We examined a prevalence of FGFR2 genetic ...

Abstract	Genetic alterations including fusions in fibroblast growth factor receptor 2 (FGFR2) are detected in 10-20% of intrahepatic cholangiocarcinoma (iCCA), and FGFR2 inhibitors are effective for the treatment of iCCA. We examined a prevalence of FGFR2 genetic alterations and their clinicopathological significance in combined hepatocellular-cholangiocarcinoma (cHCC-CCA). FGFR2 expression, which is a surrogate marker for FGFR2 genetic alterations, was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 35 with small duct-type iCCA, 30 with large duct-type iCCA, and 35 with hepatocellular carcinoma (HCC). FGFR2 genetic alterations were detected by reverse transcription-PCR and direct sequence. An association of FGFR2 expression with clinicopathological features was investigated in cHCC-CCAs. FGFR2 expression was detected in significantly more patients with cHCC-CCA (21.3%) and small duct-type iCCA (25.7%), compared to those with large duct-type iCCA (3.3%) and HCC (0%) (p < 0.05). FGFR2-positive cHCC-CCAs were significantly smaller size (p < 0.05), with more predominant cholangiolocarcinoma component (p < 0.01) and less nestin expression (p < 0.05). Genetic alterations of ARID1A and BAP1 and multiple genes were significantly more frequent in FGFR2-positive cHCC-CCAs (p < 0.05). 5'/3' imbalance in FGFR2 genes indicating exon18-truncated FGFR2 was significantly more frequently detected in FGFR2-positive cHCC-CCAs and small duct iCCAs, compared to FGFR2-negative ones (p < 0.05). FGFR2::BICC fusion was detected in a case of cHCC-CCAs. FGFR2 genetic alterations may be prevalent in cHCC-CCAs as well as small duct-type iCCAs, which suggest cHCC-CCAs may also be a possible therapeutic target of FGFR2 inhibitors.
Language	English
Publishing date	2024-03-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-024-03792-x
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Article ; Online: Clients' and genetic counselors' perceptions of empathy in Japan: A pilot study of simulated consultations of genetic counseling.

Tomozawa, Chikako / Kaneko, Mikiko / Sasaki, Motoko / Miyake, Hidehiko

PloS one

2023 Volume 18, Issue 7, Page(s) e0288881

Abstract: The rapidly increasing availability of genetic testing is driving the acceleration of genetic counseling implementation. Empathy is important in medical encounters in general and forms a core component of a successful genetic counseling session; however, ...

Abstract	The rapidly increasing availability of genetic testing is driving the acceleration of genetic counseling implementation. Empathy is important in medical encounters in general and forms a core component of a successful genetic counseling session; however, empirical evidence on empathy in genetic counseling is minimal. This study aimed to explore the perceptions of empathy in simulated genetic counseling consultations from the perspectives of clients and genetic counselors. Semi-structured interviews and interpersonal process recall were used with participants of simulated genetic counseling consultations to elicit their experiences of empathy. A constructivist grounded theory was used for data analysis. A total of 15 participants, including 10 clients and 5 genetic counselors, participated in 10 simulated counseling sessions. The genetic counselors attempted to demonstrate empathy and were sensitive toward detecting changes in clients. Meanwhile, the clients' perceptions represented their feelings and thoughts elicited through the counselors' empathic approaches. This was the first process study to examine empathy in simulated genetic counseling sessions. Our model of communication of empathy is a process in which counselors try to address implicit aspects of clients, and clients are provided with time and a safe place for introspection, which contributes to discussions on building good relationships with patients. There is also a suggestion of the utility of simulated consultations for healthcare providers to learn empathic communication.
MeSH term(s)	Humans ; Genetic Counseling/psychology ; Counselors ; Pilot Projects ; Empathy ; Japan ; Professional-Patient Relations ; Counseling
Language	English
Publishing date	2023-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0288881
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Article ; Online: Bile duct adenoma and small-sized small duct type intrahepatic cholangiocarcinoma show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components.

Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

Histopathology

2023 Volume 83, Issue 2, Page(s) 298–309

Abstract: Aims: Given that bile duct adenoma was significantly more prevalent in the liver with small duct type intrahepatic cholangiocarcinoma (small duct iCCA), compared to other primary liver carcinomas, we examined the possibility of bile duct adenoma as a ... ...

Abstract	Aims: Given that bile duct adenoma was significantly more prevalent in the liver with small duct type intrahepatic cholangiocarcinoma (small duct iCCA), compared to other primary liver carcinomas, we examined the possibility of bile duct adenoma as a precursor of small duct iCCA by analysing genetic alterations and other features in bile duct adenomas. Methods and results: Subjects included 33 bile duct adenomas and 17 small-sized (up to 2 cm in diameter) small duct iCCAs. Genetic alterations were examined by direct sequencing for hot-spot regions and immunohistochemical staining. The expression of p16 Conclusion: Bile duct adenomas and small-sized small duct iCCAs show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components. There was no evidence suggesting that bile duct adenoma is a precursor of small duct iCCA. Immunohistochemical staining for IMP3, EZH2, p53, ARID1A and MTAP may be useful for differential diagnosis between bile duct adenomas and small duct iCCAs.
MeSH term(s)	Humans ; Adenoma, Bile Duct/pathology ; Bile Duct Neoplasms/metabolism ; Bile Ducts, Intrahepatic/pathology ; Cholangiocarcinoma/pathology ; Tumor Suppressor Protein p53
Chemical Substances	Tumor Suppressor Protein p53 ; EZH2 protein, human (EC 2.1.1.43) ; IGF2BP3 protein, human
Language	English
Publishing date	2023-05-04
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14932
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Article ; Online: Nestin may be a candidate marker for differential diagnosis between small duct type and large duct type intrahepatic cholangiocarcinomas.

Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

Pathology, research and practice

2023 Volume 253, Page(s) 155061

Abstract: Backgrounds/aims: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small and large duct types. These two subtypes show distinct differences in various clinicopathological features and possible cell origin and pathways of carcinogenesis, ... ...

Abstract	Backgrounds/aims: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small and large duct types. These two subtypes show distinct differences in various clinicopathological features and possible cell origin and pathways of carcinogenesis, however, a differential diagnosis may be sometimes difficult. Given the type IV intermediate filament, Nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and small duct type iCCAs, the significance of nestin as a differential diagnostic marker between small and large duct types of iCCAs was addressed in the present study. Methods: Nestin expression was immunohistochemically assessed in the sections from 36 patients with small duct-type iCCA, 30 with large duct-type iCCA, and 27 with extrahepatic cholangiocarcinoma (CCA). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in small duct type iCCAs. Results: Nestin expression was detected in 17 small duct type iCCAs (47.2%), one large duct type iCCA (3.8%) and zero extrahepatic CCA. Nestin expression was significantly more frequent in the patients with small duct type iCCAs than in those with large duct type iCCA and extrahepatic CCA (p < 0.01). In 10 liver biopsies, all samples with nestin expression were small duct type iCCAs. Nestin-positive small duct type iCCAs were characterized by a higher histological grade, compared to Nestin-negative small duct type iCCAs (p < 0.01). Nestin-positive small duct type iCCAs tended to have 2 or more genetic alterations, but there was no statistic difference (p > 0.05). Conclusion: Different nestin expression may reflect differences between small duct type iCCA and large duct type/extrahepatic CCA and may be a useful diagnostic marker for small duct type iCCAs.
MeSH term(s)	Humans ; Diagnosis, Differential ; Nestin ; Cholangiocarcinoma/genetics ; Bile Ducts, Intrahepatic/pathology ; Bile Duct Neoplasms/genetics
Chemical Substances	Nestin
Language	English
Publishing date	2023-12-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.155061
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Article ; Online: An involvement of Hippo-yes-associated protein pathway in biliary epithelial senescence in primary biliary cholangitis.

Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

Clinics and research in hepatology and gastroenterology

2023 Volume 47, Issue 4, Page(s) 102106

Abstract: Background & aims: Accumulating evidence suggest that Hippo-yes-associated protein (YAP) pathway plays important roles in development and repair after injuries in biliary system. We disclosed that senescent biliary epithelial cells (BECs) participate in ...

Abstract	Background & aims: Accumulating evidence suggest that Hippo-yes-associated protein (YAP) pathway plays important roles in development and repair after injuries in biliary system. We disclosed that senescent biliary epithelial cells (BECs) participate in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that dysregulation of Hippo-YAP pathway may be associated with biliary epithelial senescence in pathogenesis of PBC. Approach & results: Cellular senescence was induced in cultured BECs by treatment with serum depletion or glycochenodeoxycholic acid. The expression and activity of YAP1 were significantly decreased in senescent BECs (p<0.01). Cellular senescence and apoptosis were significantly increased (p<0.01) and a proliferation activity and a 3D-cyst formation activity were significantly decreased (p<0.01) by a knockdown of YAP1 in BECs. The expression of YAP1 were immunohistochemically determined in livers taken from the patients with PBC (n = 79) and 79 control diseased and normal livers and its association with senescent markers p16 Conclusion: Dysregulation of Hippo-YAP1 pathway may be involved in the pathogenesis of PBC in association with biliary epithelial senescence.
MeSH term(s)	Humans ; Liver Cirrhosis, Biliary ; YAP-Signaling Proteins ; Cyclin-Dependent Kinase Inhibitor p16 ; Bile Ducts/pathology ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Epithelial Cells/metabolism
Chemical Substances	YAP-Signaling Proteins ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p21
Language	English
Publishing date	2023-02-26
Publishing country	France
Document type	Journal Article
ZDB-ID	2594333-9
ISSN	2210-741X ; 2210-7401
ISSN (online)	2210-741X
ISSN	2210-7401
DOI	10.1016/j.clinre.2023.102106
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Article ; Online: An immunohistochemical panel of insulin-like growth factor II mRNA-binding protein 3 (IMP3), enhancer of zeste homolog 2 (EZH2), and p53 is useful for a diagnosis in bile duct biopsy.

Sasaki, Motoko / Sato, Yasunori

Virchows Archiv : an international journal of pathology

2021 Volume 479, Issue 4, Page(s) 697–703

Abstract: Bile duct biopsy is being increasingly performed in number for a definite diagnosis of cholangiocarcinoma. However, difficulties are associated with a histopathological diagnosis because of the limited small amount of specimen obtained and crash artifact. ...

Abstract	Bile duct biopsy is being increasingly performed in number for a definite diagnosis of cholangiocarcinoma. However, difficulties are associated with a histopathological diagnosis because of the limited small amount of specimen obtained and crash artifact. The aim of the present study was to identify useful diagnostic immunohistochemical markers in bile duct biopsy that support a histological diagnosis. Fifty-one bile duct biopsy samples, including 26 samples taken from patients with cholangiocarcinoma, 11 with intraductal papillary neoplasm of the bile duct (IPNB), and 14 with benign bile duct lesions, were examined. Histology and the immunohistochemical expression of insulin-like growth factor II mRNA-binding protein 3 (IMP3), enhancer of zeste homolog 2 (EZH2), and p53 were assessed. They were then evaluated for their usefulness as diagnostic markers of malignancy. The diagnostic sensitivity and accuracy of the institutional histological diagnosis were 53.8% and 70.0%, respectively. The diagnostic sensitivity and accuracy of IMP3, EZH2, and p53 were 69.2% and 80.0%, 76.9% and 85.0%, and 50.0% and 67.5%, respectively. Immunohistochemical staining for EZH2; the combination of either 2 of IMP3, EZH2, and p53; or the combination of IMP3, EZH2, and p53 significantly increased sensitivity and accuracy over those of the institutional histological diagnosis (p<0.05). In conclusion, an immunohistochemical panel consisting of IMP3, EZH2, and p53 increases the diagnostic sensitivity and accuracy of bile duct biopsy for the diagnosis of cholangiocarcinoma.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/pathology ; Bile Ducts/metabolism ; Bile Ducts/physiology ; Bile Ducts, Intrahepatic/pathology ; Biomarkers, Tumor/analysis ; Biopsy/methods ; Cholangiocarcinoma/diagnosis ; Cholangiocarcinoma/metabolism ; Data Accuracy ; Diagnosis, Differential ; Enhancer of Zeste Homolog 2 Protein/analysis ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Female ; Humans ; Immunohistochemistry/methods ; Male ; Middle Aged ; RNA, Messenger ; RNA-Binding Proteins/analysis ; RNA-Binding Proteins/metabolism ; Sensitivity and Specificity ; Tumor Suppressor Protein p53/analysis ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Biomarkers, Tumor ; IGF2BP3 protein, human ; RNA, Messenger ; RNA-Binding Proteins ; Tumor Suppressor Protein p53 ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43)
Language	English
Publishing date	2021-06-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-021-03132-3
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Book: Expression profiles of MUC mucins and trefoil factor family (TFF) peptides in the intrahepatic biliary system

Sasaki, Motoko / Ikeda, Hiroko / Nakanuma, Yasuni

physiological distribution and pathological significance

(Progress in histochemistry and cytochemistry ; 42,2)

2007

Author's details	Motoko Sasaki ; Hiroko Ikeda ; Yasuni Nakanuma
Series title	Progress in histochemistry and cytochemistry ; 42,2
Collection
Language	English
Size	S. 61 - 110 : Ill., graph. Darst.
Publisher	Elsevier
Publishing place	Amsterdam u.a.
Publishing country	Netherlands
Document type	Book
HBZ-ID	HT015230278
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
Se 23 -42,2-	verfügbar in Königswinter	Königswinter

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Article ; Online: Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis.

Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

Scientific reports

2021 Volume 11, Issue 1, Page(s) 11413

Abstract: Accumulating studies suggest that senescent biliary epithelial cells (BECs) produce senescence-associated secretory phenotypes (SASPs) and play various roles in the pathogenesis of primary biliary cholangitis (PBC) and other cholangiopathies. We examined ...

Abstract	Accumulating studies suggest that senescent biliary epithelial cells (BECs) produce senescence-associated secretory phenotypes (SASPs) and play various roles in the pathogenesis of primary biliary cholangitis (PBC) and other cholangiopathies. We examined comprehensive profiles of senescent BECs and its contribution to the pathogenesis of PBC taking advantage of microarray analysis. cDNA microarray analysis revealed that 1841 genes including CCL2, IFIT3, CPQ were commonly up-regulated in senescent BECs cultured in serum depleted media or media with glycochenodeoxycholic acid. Knockdown of IFIT3 significantly suppressed cellular senescence (p < 0.01) and significantly increased apoptosis (p < 0.01) in BECs treated with serum depletion or glycochenodeoxycholic acid. Significantly increased expression of IFIT3 was seen in senescent BECs in small bile ducts showing cholangitis and in ductular reactions in PBC, compared to control livers (p < 0.01). An inadequate response to UDCA was inversely correlated to the increased expression of IFIT3 in small bile duct in PBC (p < 0.05). In conclusion, the expression of various genes related to immunity and inflammation including SASPs were increased in senescent BECs. Upregulated IFIT3 in senescent BECs may be associated with the pathogenesis of PBC and may be a possible therapeutic target in PBC.
MeSH term(s)	Animals ; Apoptosis ; Bile Ducts/metabolism ; Bile Ducts/pathology ; Cell Proliferation ; Cells, Cultured ; Cellular Senescence ; Epithelial Cells ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/physiology ; Liver Cirrhosis, Biliary/metabolism ; Liver Cirrhosis, Biliary/pathology ; Mice ; Mice, Inbred BALB C
Chemical Substances	IFIT3 protein, human ; Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2021-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-91016-6
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Article: Hepatic Inflammatory Pseudotumor-Focusing on Its Heterogeneity.

Kim, Soo Ryang / Kim, Soo Ki / Koma, Yu-Ichiro / Sasaki, Motoko / Asai, Akira / Nishikawa, Hiroki

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 17

Abstract: Hepatic inflammatory pseudotumors (IPTs) are defined as benign, non-malignant, non-metastasizing tumors characterized by the presence of myofibroblastic spindle cells, hetorogenous populations of inflammatory cells, particularly plasma cells, lymphocytes ...

Abstract	Hepatic inflammatory pseudotumors (IPTs) are defined as benign, non-malignant, non-metastasizing tumors characterized by the presence of myofibroblastic spindle cells, hetorogenous populations of inflammatory cells, particularly plasma cells, lymphocytes and macrophages, as well as locations of fibrosis and necrosis without cellular anaplasia or atypical mitoses. Despite subsequent reports in the references, hepatic IPT remains difficult to diagnose; while posing major issues specifically for its differential diagnosis compared with that of other various benign diseases and malignant hepatic tumors. Histopathological findings are always a requisite for confirming the diagnosis, particularly given that the pathogenesis of IPT remains ambiguous to date. Hepatic IPT is a heterogeneous entity in terms of its clinical features, pathological findings, and pathogenesis. Once the diagnosis is confirmed, however, needless surgery such as wedge resection and lobectomy should be avoided. Here, we discuss the heterogeneity of hepatic IPT, its clinical features, pathological findings, and pathogenesis, and describe its differential diagnosis.
Language	English
Publishing date	2023-09-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13172857
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Article ; Online: Medical Needs of Adults with Down Syndrome Presenting at a Regional Medical and Rehabilitation Center in Japan.

Kanbara, Yoko / Takeuchi, Chisen / Mochizuki, Yoko / Osako, Miho / Sasaki, Motoko / Miyake, Hidehiko

Journal of Nippon Medical School = Nippon Ika Daigaku zasshi

2023 Volume 90, Issue 2, Page(s) 210–219

Abstract: Background: Down syndrome (DS) is the most frequent chromosomal aberration; however, knowledge of associated health issues in adulthood is inadequate. We analyzed health data from Japanese adults with DS.: Methods: We conducted a retrospective chart ... ...

Abstract	Background: Down syndrome (DS) is the most frequent chromosomal aberration; however, knowledge of associated health issues in adulthood is inadequate. We analyzed health data from Japanese adults with DS. Methods: We conducted a retrospective chart review of 151 patients with DS who visited the Internal Medicine Outpatient Department of the Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled. Results: Endocrine disorders such as obesity, hyperlipidemia, and hyperuricemia were most common in adulthood (≤40 years) and senescence (>40 years); neurological diseases were more prevalent in senescence. Multimorbidity was noted even patients with DS who were younger than 30 years, and the prevalence increased with age. Only 21 patients (13.9%) with DS visited our hospital with referral letters from pediatricians; 94 patients (62.3%) visited without such referrals from other medical institutions. Patients without a referral letter had a mean of 3.1 comorbidities per patient. Moreover, medical care for some people with DS was interrupted during childhood. Conclusions: Prevention and detection of comorbidities in patients with DS requires continuous medical care from childhood through adulthood. Recently, DS has been diagnosed by chromosome testing and genetic counseling. Clinical geneticists and genetic counselors can help patients with DS, and their caregivers, to obtain appropriate health care and achieve well-being on their own by seamlessly engaging them throughout childhood and adulthood.
MeSH term(s)	Humans ; Adult ; Down Syndrome/epidemiology ; Japan/epidemiology ; Retrospective Studies ; Chromosome Aberrations ; Rehabilitation Centers
Language	English
Publishing date	2023-02-21
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2091563-9
ISSN	1347-3409 ; 1345-4676
ISSN (online)	1347-3409
ISSN	1345-4676
DOI	10.1272/jnms.JNMS.2023_90-211
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