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Article: ACLP Activates Cancer-Associated Fibroblasts and Inhibits CD8+ T-Cell Infiltration in Oral Squamous Cell Carcinoma.

Sekiguchi, Shohei / Yorozu, Akira / Okazaki, Fumika / Niinuma, Takeshi / Takasawa, Akira / Yamamoto, Eiichiro / Kitajima, Hiroshi / Kubo, Toshiyuki / Hatanaka, Yui / Nishiyama, Koyo / Ogi, Kazuhiro / Dehari, Hironari / Kondo, Atsushi / Kurose, Makoto / Obata, Kazufumi / Kakiuchi, Akito / Kai, Masahiro / Hirohashi, Yoshihiko / Torigoe, Toshihiko /

Kojima, Takashi / Osanai, Makoto / Takano, Kenichi / Miyazaki, Akihiro / Suzuki, Hiromu

Cancers

2023 Volume 15, Issue 17

Abstract: We previously showed that upregulation of adipocyte enhancer-binding protein 1 ( ...

Abstract	We previously showed that upregulation of adipocyte enhancer-binding protein 1 (
Language	English
Publishing date	2023-08-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15174303
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Article ; Online: Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

Kashiro, Ayumi / Kobayashi, Michimoto / Oh, Takanori / Miyamoto, Mitsuko / Atsumi, Jun / Nagashima, Kengo / Takeuchi, Keiko / Nara, Satoshi / Hijioka, Susumu / Morizane, Chigusa / Kikuchi, Shojiro / Kato, Shingo / Kato, Ken / Ochiai, Hiroki / Obata, Daisuke / Shizume, Yuya / Konishi, Hiroshi / Nomura, Yumiko / Matsuyama, Kotone /

Xie, Cassie / Wong, Christin / Huang, Ying / Jung, Giman / Srivastava, Sudhir / Kutsumi, Hiromu / Honda, Kazufumi

Journal of gastroenterology

2024 Volume 59, Issue 3, Page(s) 263–278

Abstract: Background: We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is.: Methods: We established a new enzyme- ... ...

Abstract	Background: We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is. Methods: We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9. Results: The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832-0.925] than for CA19-9 (0.849, 95% CI 0.793-0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 μg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 μg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network. Conclusions: The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.
MeSH term(s)	Humans ; CA-19-9 Antigen ; Biomarkers, Tumor ; Apolipoprotein A-II ; Reproducibility of Results ; Early Detection of Cancer ; Pancreatic Neoplasms/diagnosis ; Protein Isoforms
Chemical Substances	CA-19-9 Antigen ; Biomarkers, Tumor ; Apolipoprotein A-II ; Protein Isoforms
Language	English
Publishing date	2024-01-23
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1186495-3
ISSN	1435-5922 ; 0944-1174
ISSN (online)	1435-5922
ISSN	0944-1174
DOI	10.1007/s00535-023-02072-w
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Article: Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma.

Nakano, Masaya / Ohwada, Kizuku / Shindo, Yuma / Konno, Takumi / Kohno, Takayuki / Kikuchi, Shin / Tsujiwaki, Mitsuhiro / Ishii, Daichi / Nishida, Soshi / Kakuki, Takuya / Obata, Kazufumi / Miyata, Ryo / Kurose, Makoto / Kondoh, Atsushi / Takano, Kenichi / Kojima, Takashi

Cancers

2022 Volume 14, Issue 11

Abstract: Background: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a ... ...

Abstract	Background: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. Methods: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). Results: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. Conclusions: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.
Language	English
Publishing date	2022-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14112584
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Article ; Online: Tracheostomy in Patients With COVID-19: A Single-center Experience.

Obata, Kazufumi / Miyata, Ryo / Yamamoto, Keisuke / Byn-Ya, Naofumi / Kasai, Takehiko / Inoue, Hiroyuki / Narimatsu, Eichi / Takano, Kenichi

In vivo (Athens, Greece)

2020 Volume 34, Issue 6, Page(s) 3747–3751

Abstract: Background/aim: Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide ... ...

Abstract	Background/aim: Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide helpful and useful information regarding tracheostomy during the COVID-19 pandemic. Patients and methods: We performed a retrospective analysis on 12 patients with severe COVID-19 who were intubated and underwent tracheostomy in our hospital. Results: Percutaneous tracheostomy was performed in eight cases, and open tracheostomy was performed in four cases. Open tracheostomy in the operating room was performed under a negative pressure closed-space system using a surgical drape to prevent aerosolization. Conclusion: Our experience suggests that bedside percutaneous tracheostomy may be a useful option in patients with COVID-19. In cases where percutaneous tracheostomy is anticipated to be difficult, open tracheostomy using a negative pressure closure may be useful in preventing aerosolization and reducing the risk of infection of healthcare workers.
MeSH term(s)	Adult ; Aged ; Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/pathology ; Coronavirus Infections/therapy ; Coronavirus Infections/virology ; Female ; Humans ; Intubation/methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/pathology ; Pneumonia, Viral/therapy ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Tracheostomy/methods
Keywords	covid19
Language	English
Publishing date	2020-11-03
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.12224
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Article ; Online: Clinical and Prognostic Analysis of Hypopharyngeal Squamous Cell Carcinoma with Synchronous and Metachronous Multiple Malignancies.

Yamamoto, Keisuke / Takano, Kenichi / Kondo, Atsushi / Kurose, Makoto / Obata, Kazufumi / Himi, Tetsuo

In vivo (Athens, Greece)

2018 Volume 32, Issue 1, Page(s) 165–170

Abstract: Background/aim: To analyze the clinical features and prevalence of synchronous and metachronous second primary malignancies (SPMs) in patients with hypopharyngeal squamous cell carcinoma (HSCC), their associated risk factors, and cause-specific ... ...

Abstract	Background/aim: To analyze the clinical features and prevalence of synchronous and metachronous second primary malignancies (SPMs) in patients with hypopharyngeal squamous cell carcinoma (HSCC), their associated risk factors, and cause-specific mortality. Patients and methods: We retrospectively reviewed 136 patients treated with curative intent at our hospital. Statistical analyses were performed to determine factors predictive of SPM and cause-specific mortality. Results: Sixty-three of 136 patients (46.3%) developed SPM; of these, 41 (30.1%) and 42 (30.9%) had synchronous and metachronous SPMs, respectively, with patient overlap. The most common site of synchronous and metachronous SPMs was the oesophagus (65.8% and 24.4%, respectively); the corresponding overall survival rates were 34.1% and 66.5%, respectively. Furthermore, heavy drinking was significantly correlated with synchronous SPM (p<0.001). Conclusion: Oesophageal cancer surveillance is recommended for patients with HSCC, especially heavy drinkers. Our findings may help identify and properly manage HSCC patients at high risk of SPMs.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking ; Carcinoma, Squamous Cell/complications ; Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Hypopharyngeal Neoplasms/complications ; Hypopharyngeal Neoplasms/pathology ; Male ; Middle Aged ; Neoplasms, Multiple Primary/complications ; Neoplasms, Multiple Primary/pathology ; Neoplasms, Second Primary/complications ; Neoplasms, Second Primary/pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Analysis
Language	English
Publishing date	2018-01
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.11220
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Article ; Online: CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma.

Cancer medicine

2022 Volume 12, Issue 5, Page(s) 5953–5963

Abstract: Background: The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor ... ...

Abstract	Background: The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs. Methods: Publicly available single-cell RNA-sequencing (RNA-seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, α-smooth muscle antigen (α-SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co-cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse-transcription PCR. Results: Analysis of the RNA-seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12-positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α-SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co-cultured with OSCC cells. Conclusion: Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction.
MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck ; Carcinoma, Squamous Cell/pathology ; Mouth Neoplasms/pathology ; Tongue Neoplasms/genetics ; Head and Neck Neoplasms ; Tongue ; Muscle, Skeletal/pathology ; Prognosis ; Tumor Microenvironment ; Chemokine CXCL12/genetics ; Chemokine CXCL12/metabolism
Chemical Substances	CXCL12 protein, human ; Chemokine CXCL12
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.5392
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Article ; Online: HDAC inhibitors suppress the proliferation, migration and invasiveness of human head and neck squamous cell carcinoma cells via p63‑mediated tight junction molecules and p21‑mediated growth arrest.

Kakiuchi, Akito / Kakuki, Takuya / Ohwada, Kizuku / Kurose, Makoto / Kondoh, Atsushi / Obata, Kazufumi / Nomura, Kazuaki / Miyata, Ryo / Kaneko, Yakuto / Konno, Takumi / Kohno, Takayuki / Himi, Tetsuo / Takano, Ken-Ichi / Kojima, Takashi

Oncology reports

2021 Volume 45, Issue 4

Abstract: In human head and neck squamous cell carcinoma (HNSCC), the invasion and metastatic properties of cancer cells are promoted by junctional adhesion molecule‑A (JAM‑A) and claudin‑1; these are epithelial tight junction molecules regulated by histone ... ...

Abstract	In human head and neck squamous cell carcinoma (HNSCC), the invasion and metastatic properties of cancer cells are promoted by junctional adhesion molecule‑A (JAM‑A) and claudin‑1; these are epithelial tight junction molecules regulated by histone deacetylases (HDACs) and transcription factor p63. HDAC expression is reportedly upregulated in HNSCC, and HDAC inhibitors suppress cancer cell proliferation by initiating proliferative arrest or apoptosis. However, little is known of the anti‑cancer mechanisms of HDAC inhibitors in HNSCC. Thus, in the present study, the HNSCC Detroit 562 cell line and primary cultured HNSCC cells were treated with HDAC inhibitors to investigate their effects in HNSCC. Higher expression of p63, HDAC1, JAM‑A and claudin‑1 was observed in HNSCC tissues compared with the adjacent dysplastic regions. In Detroit 562 cells, treatment with trichostatin A (TSA), an inhibitor of HDAC1 and 6, downregulated the expression of p63, JAM‑A and claudin‑1, and upregulated that of acetylated tubulin; conversely, p63 knockdown resulted in the downregulation of JAM‑A and claudin‑1. Collectively, inhibiting HDAC suppressed the migration and invasiveness of cancer cells. In addition, treatment with TSA suppressed cancer cell proliferation via G
MeSH term(s)	Aged ; Apoptosis/drug effects ; Cell Adhesion Molecules/metabolism ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Claudin-1/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Female ; G2 Phase Cell Cycle Checkpoints/drug effects ; Gene Knockdown Techniques ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Male ; Middle Aged ; Receptors, Cell Surface/metabolism ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/pathology ; Tight Junctions/drug effects ; Tight Junctions/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	CDKN1A protein, human ; CLDN1 protein, human ; Cell Adhesion Molecules ; Claudin-1 ; Cyclin-Dependent Kinase Inhibitor p21 ; F11R protein, human ; Histone Deacetylase Inhibitors ; Receptors, Cell Surface ; TP63 protein, human ; Transcription Factors ; Tumor Suppressor Proteins
Language	English
Publishing date	2021-03-02
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2021.7997
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Article: Tracheostomy in Patients With COVID-19: A Single-center Experience

Obata, Kazufumi / Miyata, Ryo / Yamamoto, Keisuke / Byn-Ya, Naofumi / Kasai, Takehiko / Inoue, Hiroyuki / Narimatsu, Eichi / Takano, Kenichi

In Vivo

Abstract: BACKGROUND/AIM: Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide ... ...

Abstract	BACKGROUND/AIM: Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide helpful and useful information regarding tracheostomy during the COVID-19 pandemic. PATIENTS AND METHODS: We performed a retrospective analysis on 12 patients with severe COVID-19 who were intubated and underwent tracheostomy in our hospital. RESULTS: Percutaneous tracheostomy was performed in eight cases, and open tracheostomy was performed in four cases. Open tracheostomy in the operating room was performed under a negative pressure closed-space system using a surgical drape to prevent aerosolization. CONCLUSION: Our experience suggests that bedside percutaneous tracheostomy may be a useful option in patients with COVID-19. In cases where percutaneous tracheostomy is anticipated to be difficult, open tracheostomy using a negative pressure closure may be useful in preventing aerosolization and reducing the risk of infection of healthcare workers.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #910226
Database	COVID19

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Article ; Online: Common carotid artery rupture during treatment with lenvatinib for anaplastic thyroid cancer.

Obata, Kazufumi / Sugitani, Iwao / Ebina, Aya / Sugiura, Yoshiya / Toda, Kazuhisa / Takahashi, Shunji / Kawabata, Kazuyoshi

International cancer conference journal

2016 Volume 5, Issue 4, Page(s) 197–201

Abstract: Anaplastic thyroid cancer is a fatal disease for which no effective therapeutic strategies exist. Lenvatinib, a tyrosine-kinase inhibitor that targets vascular endothelial growth factor receptor, has recently been approved in Japan for the treatment of ... ...

Abstract	Anaplastic thyroid cancer is a fatal disease for which no effective therapeutic strategies exist. Lenvatinib, a tyrosine-kinase inhibitor that targets vascular endothelial growth factor receptor, has recently been approved in Japan for the treatment of patients with unresectable thyroid cancer including anaplastic thyroid cancer. Although lenvatinib, like the other tyrosine-kinase inhibitors, sunitinib and sorafenib, might also confer a risk of bleeding, fatal bleeding as a result of lenvatinib treatment for anaplastic thyroid cancer has not been described. A 61-year-old woman presented with a 7-cm mass in the right lobe of the thyroid, lymph node metastases to the neck and multiple lung metastases. Fine needle aspiration revealed that the tumor was anaplastic thyroid cancer. The TNM classification was T4aN1bM1, stage IVC. Shortly after local curative surgery, a tumor recurred in her neck that was treated with lenvatinib (24 mg/day). Nineteen days later, the common carotid artery ruptured and the lenvatinib was stopped. She received the best possible supportive care but died 40 days after stopping the lenvatinib. Autopsy findings showed that the tumor had invaded the adventitia of the common carotid artery at the region of the neck surgery, and an aneurysm had developed. However, the adventitia of the common carotid artery was preserved at the non-dissected area. Lenvatinib might confer risk for fatal bleeding in patients with recurrent anaplastic thyroid cancer after neck surgery, particularly with dissection around the common carotid artery.
Language	English
Publishing date	2016-07-27
Publishing country	Singapore
Document type	Case Reports
ISSN	2192-3183
ISSN (online)	2192-3183
DOI	10.1007/s13691-016-0257-7
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Article ; Online: A Clinical Review of Thyroid Cancer at Sapporo Medical University Hospital.

Koizumi, Junichi / Takano, Kenichi / Obata, Kazufumi / Yamamoto, Keisuke / Murayama, Kosuke / Himi, Tetsuo

Advances in oto-rhino-laryngology

2016 Volume 77, Page(s) 88–91

Abstract: Thyroid cancer is a disease that affects 8,000 new individuals a year, a number that has increased approximately 3-fold in the past 30 years. The increase in the incidence of thyroid cancer can be related to various factors. The evolution of diagnostic ... ...

Abstract	Thyroid cancer is a disease that affects 8,000 new individuals a year, a number that has increased approximately 3-fold in the past 30 years. The increase in the incidence of thyroid cancer can be related to various factors. The evolution of diagnostic technology has distinctly occurred in the fields of diagnostic imaging, cytology and immunochemistry. For example, liquid-based cytology, developed to assess gynecological lesions, has improved diagnostic accuracy over conventional smear cytology. This technique can also be positively applied to cytological analyses of thyroid cancer. In the field of tumor biomarkers, thyroglobulin and trefoil factor-1 are well known and useful. On the other hand, a new specific biomarker of thyroid cancer has been developed. Furthermore, definitive diagnosis of follicular thyroid tumors is extremely difficult or impossible with current tumor biomarkers and cytological methods. Although the standard treatment for thyroid cancer is a basic surgical resection, iodine adjuvant therapy after surgery is a well-known treatment. Here we present a treatment strategy for thyroid cancer according to the statistics obtained at our facility.
MeSH term(s)	Combined Modality Therapy ; Disease-Free Survival ; Hospitals, University ; Humans ; Incidence ; Japan/epidemiology ; Survival Rate/trends ; Thyroid Neoplasms/diagnosis ; Thyroid Neoplasms/epidemiology ; Thyroid Neoplasms/therapy
Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	1662-2847 ; 0065-3071
ISSN (online)	1662-2847
ISSN	0065-3071
DOI	10.1159/000441880
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