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Article: Relapse of Graves' disease with repetitive depression and dysphagia episodes: A case report.

Sakakura, Koichi

2022 Volume 10, Issue 11, Page(s) e6592

Abstract: Graves' disease is a recurrent syndrome often accompanied by depression. I report a rare case in which dysphagia and bulbar myopathy indicated a relapse of Graves' disease, accompanied by recurrent depression. ...

Abstract	Graves' disease is a recurrent syndrome often accompanied by depression. I report a rare case in which dysphagia and bulbar myopathy indicated a relapse of Graves' disease, accompanied by recurrent depression.
Language	English
Publishing date	2022-11-15
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.6592
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Article ; Online: Immunological features of circulating monocyte subsets in patients with squamous cell carcinoma of the head and neck.

Sakakura, Koichi / Takahashi, Hideyuki / Motegi, Sei-Ichiro / Yokobori-Kuwabara, Yuki / Oyama, Tetsunari / Chikamatsu, Kazuaki

Clinical immunology (Orlando, Fla.)

2021 Volume 225, Page(s) 108677

Abstract: Background: Circulating monocytes are classified into three subsets according to their CD14 and CD16 expressions. Here we investigated all three subsets in patients with squamous cell carcinoma of the head and neck (SCCHN).: Methods: Peripheral blood ...

Abstract	Background: Circulating monocytes are classified into three subsets according to their CD14 and CD16 expressions. Here we investigated all three subsets in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods: Peripheral blood from 54 patients with SCCHN and 24 healthy donors (HDs) was tested for flowcytometry. Immunohistochemical staining of the primary tumor was performed. SCCHN cells were co-cultured with human monocytes in vitro. Results: The level of intermediate monocytes was significantly lower in SCCHN than in HDs. The expression levels of HLA-G, PD-L1, and CD51 on intermediate monocytes was evidently greater in patients with SCCHN. In vitro co-culturing of SCCHN cells with monocytes revealed a significant increase in CD51 expression levels on monocytes. The decrease in expression levels of the maturation markers CX3CR1 and CD68 was significantly correlated to poor clinical outcomes. Conclusion: The level of intermediate monocytes was decreased in cancer patients in favor of immature and expressed immunosuppressive molecules.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/metabolism ; Blood Circulation ; Female ; Flow Cytometry ; HLA-G Antigens ; Head and Neck Neoplasms/immunology ; Humans ; Immunophenotyping ; Lipopolysaccharide Receptors/metabolism ; Male ; Middle Aged ; Monocytes/immunology ; Receptors, IgG/metabolism ; Squamous Cell Carcinoma of Head and Neck/immunology ; Up-Regulation
Chemical Substances	B7-H1 Antigen ; HLA-G Antigens ; Lipopolysaccharide Receptors ; Receptors, IgG
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2021.108677
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Article ; Online: Two Different Tracts and Origin of Pyriform Sinus Fistula.

Sakakura, Koichi / Yasuoka, Yoshihito / Shino, Masato / Toyoda, Minoru / Obi, Kisho / Chikamatsu, Kazuaki

The Annals of otology, rhinology, and laryngology

2020 Volume 130, Issue 6, Page(s) 629–635

Abstract: Objective: Suppurative acute thyroiditis is caused by pyriform sinus fistula (PSF), and PSF frequently elicits deep neck abscess. However, complete fistulectomy is the ideal management of PSF, and studies on surgical findings of PSF are exceedingly rare. ...

Abstract	Objective: Suppurative acute thyroiditis is caused by pyriform sinus fistula (PSF), and PSF frequently elicits deep neck abscess. However, complete fistulectomy is the ideal management of PSF, and studies on surgical findings of PSF are exceedingly rare. This study aimed to reveal the origins of PSF, each route, and clinical presentation. Methods: This is a multicenter study. We have conducted 19 complete fistulectomies of PSF in Japan, analyzed routes of the fistulas, estimated the origins, and investigated their histological and clinical findings. Results: No recurrence was observed in all cases. Five of 12 cases showed thymic and/or parathyroid tissues around the fistulas, passing inside the inferior horn of thyroid cartilage, were regarded as having 3rd pouch origin, and tended to have low frequency of severe deep neck abscess. The remaining 7 cases originated from the 4th pouch running outside of the horn and showed frequent severe infection. Conclusion: PSF have 2 different routes depending on their generation and may present different clinical manifestations.
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Coloring Agents ; Female ; Fistula/pathology ; Fistula/surgery ; Humans ; Infant ; Infant, Newborn ; Male ; Pharyngeal Diseases/pathology ; Pharyngeal Diseases/surgery ; Pyriform Sinus/pathology ; Pyriform Sinus/surgery ; Thymus Gland/pathology ; Thyroid Cartilage/pathology ; Thyroid Gland/pathology ; Young Adult
Chemical Substances	Coloring Agents
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	120642-4
ISSN	1943-572X ; 0003-4894
ISSN (online)	1943-572X
ISSN	0003-4894
DOI	10.1177/0003489420966348
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Article ; Online: AKT3 is a key regulator of head and neck squamous cell carcinoma.

Takahashi, Hideyuki / Rokudai, Susumu / Kawabata-Iwakawa, Reika / Sakakura, Koichi / Oyama, Tetsunari / Nishiyama, Masahiko / Chikamatsu, Kazuaki

Cancer science

2021 Volume 112, Issue 6, Page(s) 2325–2334

Abstract: The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway plays a vital role in cell proliferation, apoptosis, metabolism, and angiogenesis in various human cancers, including head and neck squamous cell carcinoma (HNSCC). ...

Abstract	The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway plays a vital role in cell proliferation, apoptosis, metabolism, and angiogenesis in various human cancers, including head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to clarify the role of AKT, which is a major downstream effector of the PI3K-AKT-mTOR pathway, in HNSCC. We first investigated the mRNA expression of AKT isoforms using RNA-sequencing data from The Cancer Genome Atlas database. We observed a specific elevation of AKT3 expression in HNSCC tissues when compared with that in normal tissues. Furthermore, AKT3 expression correlated with genes related to the immunosuppressive microenvironment more than the other AKT isoforms and PIK3CA. Accordingly, we focused on AKT3 and performed a knockdown approach using an HNSCC cell line. AKT3 knockdown cells exhibited impaired proliferation, a shift in the cell cycle from G2/M to G1/G0 phase, an increase in apoptotic cells, and downregulation of gene expression related to immunosuppression, as well as the knockdown of its upstream regulator PIK3CA. We also performed immunohistochemistry for both AKT3 and PIK3CA using surgical specimens from 72 patients with HNSCC. AKT3 expression in tumor cells correlated with immune cell infiltration and unfavorable prognosis when compared with PIK3CA. These findings suggested that AKT3 expression is a potential biomarker for predicting the immunoreactivity and prognosis of HNSCC. Furthermore, the isoform-specific inhibition of AKT3 could be developed as a novel cancer therapy that efficiently suppresses the PI3K-AKT-mTOR pathway.
MeSH term(s)	Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Class I Phosphatidylinositol 3-Kinases/genetics ; Class I Phosphatidylinositol 3-Kinases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/metabolism ; Head and Neck Neoplasms/surgery ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Prognosis ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Sequence Analysis, RNA/methods ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Squamous Cell Carcinoma of Head and Neck/surgery ; Survival Analysis ; Tumor Microenvironment ; Up-Regulation
Chemical Substances	Biomarkers, Tumor ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137) ; AKT3 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2021-05-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1347-9032
ISSN (online)	1349-7006
ISSN	1347-9032
DOI	10.1111/cas.14911
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Article: AKT3 Is a Novel Regulator of Cancer-Associated Fibroblasts in Head and Neck Squamous Cell Carcinoma.

Takahashi, Hideyuki / Rokudai, Susumu / Kawabata-Iwakawa, Reika / Sakakura, Koichi / Oyama, Tetsunari / Nishiyama, Masahiko / Chikamatsu, Kazuaki

Cancers

2021 Volume 13, Issue 6

Abstract: Cancer-associated fibroblasts (CAFs) play vital roles in tumor progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and immunosuppression. In the present study, we sought to identify the key regulators of the pro-tumoral functions ...

Abstract	Cancer-associated fibroblasts (CAFs) play vital roles in tumor progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and immunosuppression. In the present study, we sought to identify the key regulators of the pro-tumoral functions of CAFs in head and neck squamous cell carcinoma (HNSCC). mRNA expression data obtained from The Cancer Genome Atlas revealed that CAF-specific mRNA expression correlated with genes that relate to an immunosuppressive microenvironment in a HNSCC cohort. RNA sequencing of CAFs and normal fibroblasts isolated from HNSCC specimens identified 1127 differentially expressed genes (DEGs) and several upregulated pathways in CAFs. Among the 1127 DEGs, we identified 13 immune function-related genes and focused on
Language	English
Publishing date	2021-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13061233
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Article ; Online: Circulating naïve and effector memory T cells correlate with prognosis in head and neck squamous cell carcinoma.

Takahashi, Hideyuki / Sakakura, Koichi / Ida, Shota / Kawabata-Iwakawa, Reika / Matsuyama, Toshiyuki / Tada, Hiroe / Mito, Ikko / Chikamatsu, Kazuaki

Cancer science

2021 Volume 113, Issue 1, Page(s) 53–64

Abstract: T-cell memory is an important mechanism for long-term protection against diverse pathogens. Generation and persistence of memory T cells are vital components of anti-tumor immunity, given their ability to persist for prolonged durations, as well as ... ...

Abstract	T-cell memory is an important mechanism for long-term protection against diverse pathogens. Generation and persistence of memory T cells are vital components of anti-tumor immunity, given their ability to persist for prolonged durations, as well as activate and migrate rapidly. In the present study, we investigated the clinical and prognostic significance of T-cell subsets in the peripheral circulation of patients with head and neck squamous cell carcinoma (HNSCC). Moreover, we calculated the enrichment scores of T-cell subsets in primary tumor tissues and compared their clinical characteristics using a public database. Multivariate survival analyses of circulating T-cell parameters revealed that clinical parameters, except M factor, were not independent prognostic factors, whereas proportions of CD8
MeSH term(s)	Biomarkers, Tumor/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/virology ; High-Throughput Nucleotide Sequencing ; Humans ; Memory T Cells/metabolism ; Neoplasm Staging ; Papillomavirus Infections/genetics ; Papillomavirus Infections/immunology ; Papillomavirus Infections/pathology ; Prognosis ; Sequence Analysis, RNA ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/pathology ; Squamous Cell Carcinoma of Head and Neck/virology
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2021-11-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1347-9032
ISSN (online)	1349-7006
ISSN	1347-9032
DOI	10.1111/cas.15195
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Article ; Online: Prognostic significance and population dynamics of peripheral monocytes in patients with oropharyngeal squamous cell carcinoma.

Takahashi, Hideyuki / Sakakura, Koichi / Tada, Hiroe / Kaira, Kyoichi / Oyama, Tetsunari / Chikamatsu, Kazuaki

Head & neck

2019 Volume 41, Issue 6, Page(s) 1880–1888

Abstract: Background: Several inflammatory biomarkers are considered potential prognostic factors in various cancers. This study aimed to investigate the prognostic significance and population dynamics of pretreatment inflammatory biomarker levels in patients ... ...

Abstract	Background: Several inflammatory biomarkers are considered potential prognostic factors in various cancers. This study aimed to investigate the prognostic significance and population dynamics of pretreatment inflammatory biomarker levels in patients with oropharyngeal squamous cell carcinoma (OPSCC). Methods: The influence of neutrophil counts, lymphocyte counts, monocyte counts, platelet counts, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on progression-free survival (PFS), and overall survival (OS) was analyzed. We also analyzed the peripheral blood mononuclear cells collected from patients and healthy donors (HDs). Results: Elevated monocyte count was an independent prognostic factor for PFS. Low LMR was an independent prognostic factor for OS. The proportion of intermediate monocytes was lower, and that of classical monocytes was higher in patients than in HDs. Furthermore, PD-L1 expression on monocytes was higher in patients than in HDs. Conclusions: We showed the prognostic significance and population dynamics of peripheral monocytes in patients with OPSCC.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/blood ; Carcinoma, Squamous Cell/blood ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Monocytes/physiology ; Neutrophils ; Oropharyngeal Neoplasms/blood ; Oropharyngeal Neoplasms/mortality ; Oropharyngeal Neoplasms/pathology ; Platelet Count ; Retrospective Studies ; Survival Rate
Chemical Substances	B7-H1 Antigen ; CD274 protein, human
Language	English
Publishing date	2019-01-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645165-2
ISSN	1097-0347 ; 0148-6403 ; 1043-3074
ISSN (online)	1097-0347
ISSN	0148-6403 ; 1043-3074
DOI	10.1002/hed.25625
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Article ; Online: Transitional imaging of bone destruction in invasive sinus aspergillosis masquerading as idiopathic optic neuropathy.

Shibata, Makoto / Iwazaki, Osamu / Fujita, Yukio / Nagashima, Kazuaki / Sakakura, Koichi / Hirato, Junko / Ikeda, Yoshio

Journal of the neurological sciences

2018 Volume 391, Page(s) 61–63

MeSH term(s)	Aged ; Aspergillosis/diagnostic imaging ; Aspergillosis/drug therapy ; Diagnosis, Differential ; Humans ; Male ; Optic Nerve Diseases/diagnosis ; Paranasal Sinuses ; Skull/diagnostic imaging
Language	English
Publishing date	2018-06-01
Publishing country	Netherlands
Document type	Case Reports ; Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2018.05.026
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Article ; Online: Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy.

Takahashi, Hideyuki / Sakakura, Koichi / Mito, Ikko / Ida, Shota / Chikamatsu, Kazuaki

Cancer science

2016 Volume 107, Issue 8, Page(s) 1065–1071

Abstract: Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been revealed in peripheral blood as well as within tumors. In the present study, we first investigated the ... ...

Abstract	Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been revealed in peripheral blood as well as within tumors. In the present study, we first investigated the proportion and activation status of peripheral immune regulatory cells and CD8(+) T-cell subsets in patients with head and neck squamous cell carcinoma (HNSCC) using a multicolor flow cytometer, and then evaluated how therapy with docetaxel, cisplatin, and 5-fluorouracil modulated the immune cell profile in peripheral blood. The proportion of naïve T cells was lower and that of effector memory T cells (TEM ) was higher in HNSCC patients than in healthy donors. Moreover, the proportions of activated TEM cells and effector T cells (TEFF ) were dramatically increased in patients with advanced stage disease. The proportion of regulatory T cells and CD14(+) HLA-DR(-) myeloid-derived suppressor cells was elevated in HNSCC patients. Of note, after therapy, in addition to the transient reduction in immune regulatory cells, decreases in central memory T cells and increases in TEFF cells were observed among CD8(+) T-cell subsets, suggesting differentiation from central memory T cells into TEFF cells. Our results suggested that, despite the immunosuppressive status in HNSCC patients, tumor-specific immune responses mediated by CD8(+) T cells might be induced and maintained. Moreover, chemotherapy can trigger not only a transient reduction in immune regulatory cells but also further activation of CD8(+) T cells.
MeSH term(s)	Aged ; Aged, 80 and over ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; Carcinoma, Squamous Cell/blood ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/immunology ; Cisplatin/pharmacology ; Docetaxel ; Female ; Fluorouracil/pharmacology ; Head and Neck Neoplasms/blood ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/immunology ; Humans ; Immunologic Memory/drug effects ; Lymphocyte Activation/drug effects ; Male ; Middle Aged ; Squamous Cell Carcinoma of Head and Neck ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; Taxoids/pharmacology
Chemical Substances	Taxoids ; Docetaxel (15H5577CQD) ; Cisplatin (Q20Q21Q62J) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2016-06-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1347-9032
ISSN (online)	1349-7006
ISSN	1347-9032
DOI	10.1111/cas.12976
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Article ; Online: Immunological and Clinicopathological Significance of MFG-E8 Expression in Patients with Oral Squamous Cell Carcinoma.

Okamoto, Ayako / Sakakura, Koichi / Takahashi, Hideyuki / Motegi, Sei-Ichiro / Kaira, Kyoichi / Yokobori-Kuwabara, Yuki / Ishikawa, Osamu / Chikamatsu, Kazuaki

Pathology oncology research : POR

2019 Volume 26, Issue 2, Page(s) 1263–1268

Abstract: Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein secreted by the activated macrophages and acts as a bridge between apoptotic cells and phagocytes. Aside from macrophages, a variety of malignant cells also express MFG-E8. The ... ...

Abstract	Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein secreted by the activated macrophages and acts as a bridge between apoptotic cells and phagocytes. Aside from macrophages, a variety of malignant cells also express MFG-E8. The objective of this study is to elucidate the clinical relevance and significance of MFG-E8 in the tumor microenvironment (TME) of patients with oral squamous cell carcinoma (OSCC). We investigated MFG-E8 expression in 74 patients with OSCC by immunohistochemistry and evaluated the relationship between MFG-E8 expression and various clinicopathological factors including immune cell infiltration. MFG-E8 expression was detected in 34 of 74 (45.9%) patients with OSCC and a significant correlation was observed with levels of infiltrating T cells, macrophages, and immunosuppressive M2 macrophages. Furthermore, MFG-E8 expression was also associated with clinical stage, lymphatic/vascular invasion, and Ki-67+ tumor cells but not with survival. Our results suggest that MFG-E8 may play an important role in shaping the immune suppressive network in TME as well as tumor progression.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antigens, Surface/biosynthesis ; Biomarkers, Tumor/analysis ; Female ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/pathology ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Middle Aged ; Milk Proteins/biosynthesis ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/pathology ; Tumor Microenvironment/immunology
Chemical Substances	Antigens, Surface ; Biomarkers, Tumor ; MFGE8 protein, human ; Milk Proteins
Language	English
Publishing date	2019-06-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1375979-6
ISSN	1532-2807 ; 1219-4956
ISSN (online)	1532-2807
ISSN	1219-4956
DOI	10.1007/s12253-019-00692-3
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