Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a relatively newly identified clinical condition that manifests as trismus with a square-shaped mandible. Herein, we report a case of MMATH that was initially misdiagnosed for polymyositis due to trismus and simultaneous lower limb pain, with literature review.

Case presentation

A 30-year-old woman had a history of lower limb pain after exertion for 2 years. Initial physical examination had been performed at the Department of General Medicine in our hospital. There was also redness in the hands and fingers. Although polymyositis was suspected, it was denied. The patient visited our department for right maxillary wisdom tooth extraction.

Clinical examination revealed that the patient had a square-shaped mandible. The maximal mouth opening was 22 mm. There was no temporomandibular joint pain at the time of opening. Furthermore, there was awareness of clenching while working. Panoramic radiography revealed developed square mandibular angles with flattened condyles. Computed tomography showed enlarged masseter muscles with high-density areas around the anterior and lateral fascia. Magnetic resonance imaging also showed thickened tendons and aponeuroses on the anterior surface and inside bilateral masseter muscles. Finally, the patient was diagnosed with MMTAH. Bilateral aponeurectomy of the masseter muscles with coronoidectomy and masseter muscle myotomy was performed under general anesthesia. The maximum opening during surgery was 48 mm. Mouth opening training was started on day 3 after surgery. Histopathological examination of the surgical specimen showed that the muscle fibers were enlarged to 60 μm. Immunohistochemistry testing for calcineurin, which was associated with muscle hypertrophy due to overload in some case reports, showed positive results. Twelve months after surgery, the mouth self-opening and forced opening were over 35 mm and 44 mm, respectively.

Conclusions

Herein, we report a case of MMATH. Lower limb pain due to prolonged standing at work and overload due to clenching were considered risk factors for symptoms onset of MMATH.

File： Masticatory.pdf

DOI： 10.1186/s40902-023-00386-6

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

File： ijms-24-06035.pdf

DOI： 10.3390/ijms24076035

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Pemphigus vulgaris (PV) is a rare autoimmune disease characterized by blisters on the skin and mucous membrane. Since it often appears in the oral mucosa first, it may be diagnosed by oral mucosal cytology. Although the cytologic finding is characterized by acantholytic cells, that is, Tzanck cells, it is important to distinguish PV from neoplastic lesions of the oral mucosal epithelium, including differentiation from atypical parabasal/basal cells, which appear in squamous cell carcinoma (SCC). In this study, we examined the cellular findings in two cases of PV and a case of well-differentiated SCC with loss of epithelial cell cohesion. The samples were prepared using liquid-based cytology, which showed small round-shaped and deeply stained atypical, orangeophilic keratinocytes not only in SCC but also in PV, which made differentiation between the two difficult. However, Tzanck cells found in PV differ from the deep atypical parabasal/basal cells of SCC, suggesting that the cell outline is indistinct and small protrusions and brush-like structures are observed. This feature of Tzanck cells may be useful in cytological judgment.

File： Diagnostic Cytopathology - 2023 - Maruyama - Liquid%E2%80%90based cytology for differentiating two cases of pemphigus vulgaris from.pdf

DOI： 10.1002/dc.25117

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

4歳5ヵ月女児。既往として出生前診断で指摘されていた口底部の嚢胞様病変に対し、生後3日に開窓術が施行され、病理組織学的に類表皮嚢胞と診断された。今回、3歳9ヵ月時に開窓部からの出血を主訴に当科へ受診となった。数日後に出血が治まったため、いったん終診となったが、4歳2ヵ月頃より唾仙痛様症状が出現したため再診した。口腔内所見および画像所見を踏まえて、開窓術後の変化を伴う口底部類表皮嚢胞と診断され、5歳時に全身麻酔下で嚢胞摘出術が行われた。その結果、病理組織学的に異所性胃腸管嚢胞と確定診断された。術後3年経過現在、再発なく、経過良好である。

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Adenosquamous carcinoma (ASC) is an aggressive subtype of squamous cell carcinoma (SCC). Due to its poor prognosis, a precise pathological diagnosis of ASC is essential but challenging because its pathological criteria are still unclear. Here, we present a rare case of oral ASC accompanied by acantholytic features. The tumor was raised in the mandibular gingiva and recurred locally approximately 13 months after the initial surgery with cervical lymph node metastasis. Pathological specimens of the primary lesion showed acantholysis in a large area of the SCC. Mucous cells, the characteristic finding indicating glandular differentiation, were imperceptible in the initial surgical specimen but increased in the locally recurrent and metastatic lymph node specimens. In a comprehensive literature review of oral ASC cases, the present case was the only case of ASC with acantholytic features. We reconfirmed that ASC has poor prognoses, such as low 5-year overall survival and disease-free survival, high locoregional recurrence, and high distant metastasis rates. A precise diagnosis of ASC is required for estimating prognosis and undergoing close follow-up, even if the adenocarcinomatous component is limited to a small area in the lesion.

File： diagnostics-12-02398.pdf

DOI： 10.3390/diagnostics12102398

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Cytology is a simple and non-invasive screening method for oral cancer. However, this method is not yet routinely used by clinicians because of its high false negative rate (FNR) and due to lack of sufficient studies examining the factors for high FNRs. The present retrospective study aimed to compare the screening performance of conventional cytology (CC) and liquid-based cytology (LBC) through histological validation, and to elucidate factors inducing false negative screening in oral cytology. Cytological specimens with histological examination and intraoral digital images of the lesion were retrospectively collected between January 2017 and December 2018 for CC and between October 2019 and September 2021 for LBC. Oral cytological screening was conducted based on the oral Bethesda system for oral cytology. Clinical subtypes were re-evaluated using intraoral digital images. The screening accuracy of oral cytology was calculated considering the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting the malignant transformation of oral lesions. No statistically significant difference was noted in the inadequate rate between CC and LBC groups. For CC and LBC, the sensitivities were 60.9 and 59.2%, the specificities were 87.3 and 79.1%, the PPVs were 85.8 and 76.2%, and the NPVs were 63.9 and 63.2%, respectively. Thus, the screening accuracy was similar between methodologies. Among the clinicopathological factors investigated, histological diagnosis and cellularity contributed to false negative results. Homogeneous findings of oral epithelial dysplasia and the superficial growth of carcinoma in situ/squamous cell carcinoma resulted in false negative findings for CC and LBC. Furthermore, LBC samples with a lower cell number (<2,000 squamous cells) exhibited statistically significantly increased FNRs. The present study found that the cytological methods did not affect the inadequate rate and screening accuracy, whereas clinical subtype and cellularity decreased screening accuracy. Therefore, cytological screening and subsequent follow-up should be performed while considering clinical findings and the cellularity of cytology smears.

File： ol_24_5_13505_PDF.pdf

DOI： 10.3892/ol.2022.13505

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Part of collection (book)  

File： 202200525.pdf

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

File： Oral Science International - 2022 - Kawaharada - Metastasis of pulmonary adenocarcinoma to the oral cavity A case report.pdf

DOI： 10.1002/osi2.1130

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/osi2.1130

Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

File： JOMSMP Ros.pdf

DOI： 10.1016/j.ajoms.2022.02.007

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Most oral squamous cell carcinomas (OSCCs) arise from a premalignant lesion, oral epithelial dysplasia; however, useful markers for the early detection of OSCC are lacking. The present study aimed to establish a novel experimental model to observe changes in the sequential expression patterns of mRNAs and proteins in a rat model of tongue cancer using liquid-based cytology techniques. Cytology specimens were collected at 2, 5, 8, 11, 14, 17 and 21 weeks from rats treated with 4-nitroquinoline 1-oxide to induce tongue cancer. The expression of candidate biomarkers was examined by performing immunocytochemistry and reverse transcription-quantitative PCR. The percentage of positively stained nuclei was calculated as the labeling index (LI). All rats developed OSCC of the tongue at 21 weeks. The mRNA expression levels of bromodomain protein 4 (Brd4), c-Myc and Tp53 were upregulated during the progression from negative for intraepithelial lesion or malignancy to squamous cell carcinoma (SCC). Brd4- and c-Myc-LI increased in low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion and SCC specimens. p53-LI was significantly increased in SCC specimens. This novel experimental model allowed the observation of sequential morphological changes and the expression patterns of mRNAs and proteins during carcinogenesis. Combining immunocytochemistry with cytology-based diagnoses may potentially improve the diagnostic accuracy of OSCC.

File： ol_23_3_13196_PDF.pdf

DOI： 10.3892/ol.2022.13196

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File： 病理と臨床2022.3.pdf

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RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

File： Melanotic_neuroectodermal_tumor_of_infancy_in_the.24.pdf

DOI： 10.1097/MD.0000000000028001

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Objectives: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OI-LPD) have been reported as one of the adverse effects of immunosuppressive therapy. The aim of this study was to describe the clinicopathologic and immunohistochemical features of OI-LPD in the oral cavity. Study Design: Immunohistochemistry was performed to describe the immunohistochemical features in our 4 cases. The results were analyzed along with 62 cases of oral OI-LPD in the English and Japanese literature to define clinical and pathologic characteristic features. Results: In our immunohistochemical analysis, Epstein-Barr virus (EBV)–positive OI-LPD showed a higher percentage of mouse double minute 2–positive cells than EBV-negative samples. A literature survey revealed that OI-LPD (including the present cases) arises primarily in the gingiva, followed by the tongue, and usually occurs with a male-to-female ratio of 1:1.9. The rate of EBV positivity was 93.8%. Further, 31 of 66 patients had osteonecrosis of the jaw and 24 of 31 patients had taken multiple immunosuppressive drugs in combination. Conclusions: We can therefore conclude that the overexpression of mouse double minute 2 in OI-LPD is associated with EBV infection, and the combination of multiple immunosuppressive drugs may be a risk factor for osteonecrosis of the jaw.

File： 1-s2.0-S2212440321004648-main.pdf

DOI： 10.1016/j.oooo.2021.05.015

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Cancer-associated fibroblasts (CAFs) have important roles in promoting cancer development and progression. We previously reported that high expression of sex-determining region Y (SRY)-box9 (SOX9) in oral squamous cell carcinoma (OSCC) cells was positively correlated with poor prognosis. This study developed three-dimensional (3D) in vitro models co-cultured with OSCC cells and CAFs to examine CAF-mediated cancer migration and invasion in vitro and in vivo. Moreover, we performed an immunohistochemical analysis of alpha-smooth muscle actin and SOX9 expression in surgical specimens from 65 OSCC patients. The results indicated that CAFs promote cancer migration and invasion in migration assays and 3D in vitro models. The invading OSCC cells exhibited significant SOX9 expression and changes in the expression of epithelial-mesenchymal transition (EMT) markers, suggesting that SOX9 promotes EMT. TGF-β1 signalling inhibition reduced SOX9 expression and cancer invasion in vitro and in vivo, indicating that TGF-β1-mediated invasion is dependent on SOX9. In surgical specimens, the presence of CAFs was correlated with SOX9 expression in the invasive cancer nests and had a significant impact on regional recurrence. These findings demonstrate that CAFs promote cancer migration and invasion via the TGF-β/SOX9 axis.

File： 1-s2.0-S193652332100228X-main.pdf

DOI： 10.1016/j.tranon.2021.101236

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DOI： 10.1016/j.ijom.2020.11.026

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Spindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis. CASE PRESENTATION: A 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis. CONCLUSION: The presence of neutrophil phagocytosis may be a potent indicator of malignancy.

File： s13256-021-03066-z.pdf

DOI： 10.1186/s13256-021-03066-z

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BACKGROUND: Central mucoepidermoid carcinoma (MEC) is a rare salivary gland tumor that affects the jawbone. Glandular odontogenic cyst (GOC) is also a rare odontogenic developmental cyst with glandular differentiation. GOC shares some histological features with central MEC, and a pre-existing GOC can develop into central MEC. Here, we present a rare case of central MEC developed directly from a pre-existing GOC of the mandible. CASE PRESENTATION: A 67-year-old Japanese man presented with a cystic lesion in the right third molar region. Histologically, the biopsy specimen demonstrated both typical findings of a GOC component lined with non-keratinized squamous epithelium and a recognizable component of central MEC consisting of polycystic nests with mucous cells, intermediate cells, and epidermoid cells in the cyst wall. The results from the immunohistochemistry for cytokeratin (CK) profiling demonstrated that, while both central MEC and GOC expressed CKs 7, 14, 18, and 19, CK13 was interestingly exclusively expressed in GOC. Fluorescence in-situ hybridization (FISH) revealed the rearrangement of the Mastermind like (MAML)-2 gene in both the MEC and GOC components. CONCLUSIONS: Our case suggests that central MEC and GOC may be in the same spectrum of diseases caused by the rearrangement of the MAML-2 gene. However, given that the expression profile of CK13 was completely different between central MEC and GOC, they can be considered as separate tumors. Overall, we demonstrated a rare case in which central MEC may have originated directly from the GOC.

File： maruyama.pdf

DOI： 10.1186/s13000-021-01124-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Objectives</title>
This study aimed to clarify the accuracy of intraoral ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) in preoperative image depth of invasion (DOI) measurement of T1/T2 tongue cancer through comparison with histopathological measurements.


</sec><sec>
<title>Methods</title>
Imaging of the primary lesions was performed at our hospital; the lesions were classified into T1 and T2 based on the 8th edition of the AJCC/UICC, and surgery performed. There was histopathological confirmation of lesions as squamous cell carcinoma in 48 patients with tongue cancer. T3 and T4 cases, cases in which preoperative chemotherapy and radiation therapy were performed, and cases where biopsy was performed before imaging were excluded. The radiological DOI in US, CT, and MRI and the histopathological DOI as base were comparatively investigated and statistical analyses were performed by Bland–Altman analysis and Spearman's rank correlation coefficient.


</sec><sec>
<title>Results</title>
Bland–Altman analysis showed that the US radiological DOI was overestimated by an average of 0.2 mm compared to the histopathological DOI, while CT and MRI radiological DOI were overestimated by an average of 2–3 mm. The comparison of CT and MRI revealed that the difference between the MRI and histopathological DOI, as well as the 95% limit of agreement, were smaller than those of the CT radiological DOI.


</sec><sec>
<title>Conclusions</title>
US is the most accurate preoperative diagnostic tool for T1 and T2 squamous cell carcinoma; CT and MRI tend to have an overestimation of about 2–3 mm and so caution is required.


</sec>

File： Takamura2021_Article_AComparativeStudyBetweenCTMRIA.pdf

DOI： 10.1007/s11282-021-00533-7

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R2TP is a well-conserved molecular chaperone complex, composed of Pontin, Reptin, RPAP3, and PIH1D, in eukaryotes. Recent studies have suggested an involvement of R2TP in cancer development. However, it remains unclear if it is related to the development of oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer. Here, we identify and investigate the function of R2TP in OSCC development. Immunohistochemical analysis reveals that all of the R2TP components are strongly expressed in normal oral epithelia and OSCC tissues, where actively proliferating cells are abundant. Co-immunoprecipitation assay identifies that R2TP components form a protein complex in OSCC-derived HSC4-cells. Knockdown experiments show that all R2TP components, except for RPAP3, are required for the cell proliferation and migration of HSC-4 cells. Furthermore, we reveal that Pontin contributes to a gain-of-function (GOF) activity of mutp53-R248Q in HSC-4 cells by regulating phosphorylation levels of mutp53 at Ser15 and Ser46. To our knowledge, this study is the first to report the functional involvement of R2TP and its components in the malignant characteristics of OSCC cells.

DOI： 10.1016/j.bbrc.2021.02.074

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File： 診断病理.pdf

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

We describe a case of low-grade myofibroblastic sarcoma (LGMS) on the dorsum of the tongue. A 41-year-old Japanese man noticed that a mass on the dorsal surface of the tongue had been present for 8 months. Computed tomography showed a homogeneously enhancing mass measuring 16 x 14 mm in the midline of the tongue. Magnetic resonance imaging showed a homogeneously enhancing mass with an almost clear margin on post-contrast T1-weighted imaging. The lesion was homogeneous with high signal intensity on T2-weighted imaging. The patient underwent excisional biopsy. Histologically, the tumor had an indistinct margin and was composed of spindle-shaped cells arranged in cellular fascicles. The cell nuclei showed signs of mild atypia. Positive staining for desmin and less strong staining for a-smooth muscle actin revealed that the tumor cells were myofibroblasts or smooth muscle cells. The tumor cells were negative for h-caldesmon. The MIB-1 labeling index of the tumor was 4.9 %. Thus, based on the histopathological, immunohistochemical and imaging findings, the tumor was finally diagnosed as LGMS. We reviewed the literature on the immunohistochemistry of LGMS. We suggest that immunohistochemistry is helpful in the differential diagnosis of LGMS.

File： kawaharada.pdf

DOI： 10.1016/j.ajoms.2020.07.011

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (other academic)  

File： 検査士会.pdf

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Language：Japanese   Publisher：新潟歯学会  

線維性異形成症(FD)は正常な骨組織が線維性結合組織で置換され増殖することを特徴とする非腫瘍性骨病変である。骨格成長後にはFDの増殖が静止するとされているが、成人期でも増大をきたすことがある。今回、上顎骨FDの減量手術後再増大をきたし、再び減量手術が必要となった症例を経験したので報告する。患者は42歳の男性。25歳の時に上顎骨FDの減量手術を施行されるも受診が途絶え、再増大による顔面非対称をきたしたため17年後に当科初診となった。顔面非対称改善と病変増大による機能障害の予防のため、右側上顎骨頬側と口蓋側の2回に分けて減量手術を行った。削除量の目安としてCT画像から3次元実体モデルを利用してサージカルガイドを制作し、術中の対称性確認と手術時間の短縮を行った。術後3年経過した現在、明らかな再増大はない。今回もあくまで減量手術であり、病巣の残遺に伴う病態変化の可能性についての患者教育とともに長期の経過管理が重要と考えられた。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called “ribosomopathies,” including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions −248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 (n = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis (p &lt; 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.

File： cells-09-02409-v2.pdf

DOI： 10.3390/cells9112409

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

52歳女。舌の違和感を主訴に近医を受診し、右側舌腫瘍を指摘された。他院のMRIで腫瘍性病変を認められ、当科での加療を勧められて来院した。右側舌下面粘膜下に15×15×15mm大の比較的境界明瞭な弾性硬の腫瘤を認めた。画像所見からは腺系腫瘍が示唆され、良悪性を含めた病理組織学的診断目的に生検を行ったが、組織型の確定には至らず、舌癌の診断のもと全身麻酔下に舌部分切除術を施行した。切除標本の病理組織所見は、淡明細胞の胞巣状増殖が主体ながら、粘液産生を示す二相性腺管がわずかに混在していたことから、鑑別疾患として筋上皮癌、上皮筋上皮癌、多型腺癌、明細胞癌が挙げられた。免疫染色によって筋上皮癌、上皮筋上皮癌、多型腺癌は否定され、EWSR1遺伝子のFISH解析によって明細胞癌も否定されたため腺癌NOS(not otherwise specified)と診断した。術後4年の現在まで再発・転移は認めていない。

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Language：English   Publishing type：Research paper (scientific journal)  

Apoptotic cell death frequently occurs in human cancer tissues including oral squamous cell carcinoma (SCC), wherein apoptotic tumor cells are phagocytosed not only by macrophages but also by neighboring tumor cells. We previously reported that the engulfment of apoptotic SCC cells by neighboring SCC cells frequently occurs at the invading front. Therefore, we hypothesized that the phagocytosis of these apoptotic cells by tumor cells contributes to disease progression. Herein, using cultured oral SCC cells, we aimed to confirm whether tumor cells actually phagocytose apoptotic cells and to examine whether cellular activities are regulated by the phagocytosis of apoptotic cells. Co-culture experiments showed that living cells could ingest apoptotic cells into phagolysosomes. NSC23766, an inhibitor of Rac1, which is a key regulator of phagocytic cup formation in professional phagocytes, dramatically suppressed the phagocytosis of apoptotic cells by living cells. Additionally, cell migration and the secretion of DKK1, a tumor-promoting protein, were enhanced by co-culture with apoptotic cells, whereas NSC23766 inhibited these effects. These results show that tumor cells can actively phagocytose apoptotic neighbors in a Rac1-dependent manner and that such activity increases their migration. The regulation of apoptotic cell phagocytosis thus represents new directions for therapeutic intervention for oral cancer.

File： 1-s2.0-S0014482720302354-main.pdf

DOI： 10.1016/j.yexcr.2020.112013

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Ectomesenchymal chondromyxoid tumour (ECT) is an extremely rare intraoral mesenchymal tumour. Most of these tumours have been identified on the anterior aspect of the dorsal surface of the tongue. ECT is difficult to diagnose because of its rarity. We report a case of ECT arising on the lateral border of the tongue in a 67-year-old woman. The tumour, measuring 20 × 10 mm in size, was surgically removed. Histopathologically, the tumour was composed of small polygonal cells arranged in sheets, with a myxoid or hyalinized stroma. The tumour boundary was clear; however, the tumour showed a multinodular structure expanding along the tongue surface without obvious capsule. Careful examination revealed the tumour nodule to be spreading in a skip lesion-like fashion away from the main part of the tumour in the striated muscle layer. Although there was no evidence of recurrence at 18 months after the surgery, our observations suggest that surgery for ECT resection with a safety margin is more appropriate than enucleation.

File： 1-s2.0-S0901502720301399-main.pdf

DOI： 10.1016/j.ijom.2020.04.010

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Authorship：Lead author   Publishing type：Research paper (scientific journal)  

File： 新潟歯学会.pdf

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Masseter muscle hypertrophy is defined as the unilateral or bilateral expansion of the masseter muscle, and little is known about its etiology. Here we report a case of masseter muscle hypertrophy in a female patient in her 20 s who complained of facial asymmetry. Because of the hemifacial overgrowth of the right-side maxillofacial region from birth, she was thought to have congenital hemifacial hyperplasia. After orthodontic treatment and osteotomy, the patient underwent debulking of the right masseter muscle. Histologically, the surgical specimens exhibited thick masseter muscle fibers arranged irregularly. Masseter muscle cells exhibited diameters in the range of 20-60 mu m.

File： 1-s2.0-S2212555819301905-main.pdf

DOI： 10.1016/j.ajoms.2019.08.005

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Transcription factor SRY‑box 9 (SOX9) is a key regulator of chondrocyte differentiation and sex determination, and it is also involved in the progression of various types of human cancer. However, its putative association with oral squamous cell carcinoma (OSCC) remains elusive. The aim of the present study was to investigate the expression profiles of SOX9 in various oral epithelial lesions, including OSCC. We performed immunohistochemical analysis of SOX9 expression in surgical specimens of OSCC, which simultaneously exhibited different grades of epithelial lesions, and analyzed the correlation between SOX9 expression and several clinicopathological factors. Moreover, we performed immunofluorescent staining, western blot analysis and real‑time reverse transcription‑polymerase chain reaction to assess SOX9 expression in OSCC HSC‑3 (a metastatic cell line) and HSC‑4 (a non‑metastatic cell line) cell lines. In surgical specimens, SOX9 expression was detected in the nuclei of proliferating cells in areas with epithelial dysplasia and carcinoma in situ, but not in areas with normal epithelia. Nuclear SOX9 expression was observed in most SCC cells. Notably, cytoplasmic SOX9 expression was confirmed only in some SCC cells; however, cytoplasmic SOX9 expression was significantly and positively correlated with poor clinical outcomes. Both protein and mRNA expression of SOX9 were significantly higher in the HSC‑3 cell line than that in the HSC‑4 line. Notably, however, only HSC‑3 cells exhibited cytoplasmic localization of SOX9 expression. Our findings indicate that SOX9 may be involved in the tumorigenesis and progression of OSCC. Furthermore, its cytoplasmic expression represents a potential predictive biomarker for tumor aggressiveness and OSCC prognosis.

File： 2018SOX9 oncology report.pdf

DOI： 10.3892/or.2018.6665

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Language：Japanese   Publishing type：Research paper (scientific journal)  

File： 2019田沼.pdf

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Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)  

File： BD Oral Cytology Report Vol.1.pdf

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Language：Japanese   Publisher：新潟歯学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

Gorham-Stout disease (GSD) is an extremely rare massive osteolytic bone disease, and the pathogenesis and etiology are unknown. It is characterized by the uncontrolled proliferation of distended, thin-walled vascular and lymphatic channels within bone, which leads to resorption and replacement of the bone with angiomas and/or fibrosis.A 35-year-old man had complained of masticatory disturbance caused by mandibular teeth mobility and mandibular swelling for several years. He suffered from an eating disorder because of the severe mobility of his mandibular teeth, and he presented at our hospital for consultation. He had swelling and grade III mobility without pain
his skin was normal in color with a 70 mm × 50 mm lesion of elastic and firm texture at the submental region. The ill-defined mandibular bone destruction was seen radiographically. Magnetic resonance imaging (MRI) showed that the lesion occupied the submental region and inside the mandibular bone, and these lesions were isolated. The biopsy results suggested a diagnosis of lymphangioma. The patient received radical surgery, and histological examination suggested lymphangioma. We diagnosed GSD because massive osteolysis of the mandible associated with lymphangioma was seen in the lesion. The postoperative course was uneventful, with no local recurrence 36 months after surgery. Given the rarity of this disease entity, there is no standard therapy. The details of this case are presented, and diagnostic and management considerations are described.

File： 1-s2.0-S2212555815002008-main-2.pdf

DOI： 10.1016/j.ajoms.2015.09.007

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Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis.

File： 1-s2.0-S0099239915008316-main.pdf

DOI： 10.1016/j.joen.2015.09.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive neoplasm of the paranasal sinuses. SNUC is characterized by rapid expansion with high rates of recurrence and metastasis to cervical lymph nodes and distant sites. The patient was a 65-year-old woman who complained of persistant pain at the right maxilla. She had undergone endodontic therapy at the right first molar by her primary dentist. Imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI), showed a lesion occupying the right maxillary sinus and extending into the nasal cavity and ethmoid sinus. A malignant tumor of the maxillary sinus was suspected, and a biopsy was performed. The lesion was diagnosed as sinonasal undifferentiated carcinoma. The patient was treated with chemoradiation therapy. After 4 cycles of chemoradiation therapy, CT and MRI showed shrinkage of the lesion and changes consistent with necrosis. Histological examination of a repeat biopsy specimen after the 4 cycles of chemoradiation did not contain tumor cells. 2 more cycles of chemoradiation therapy were added. Six months after the initial diagnosis, CT finding suggested residual tumor in the ethmoid sinus. We performed another biopsy and the histopathological analysis was negative for tumor. The patient has been followed for 33 months since completing chemoradiation therapy, and there has not been any further evidence of disease.

File： 1-s2.0-S2212555813001828-main.pdf

DOI： 10.1016/j.ajoms.2013.10.001

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Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

DOI： 10.1538/expanim.14-0072

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Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

DOI： 10.1538/expanim.14-0072

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Language：English   Publisher：OXFORD UNIV PRESS INC  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOURNAL HARD TISSUE BIOLOGY  

Dens invaginatus (DI) is one of the rare developmental tooth anomaly, and generally resulting from invagination of the inner enamel epithelium into the dental papilla before calcification. However, it remains unclear whether the invaginated enamel mineralizaion is lower than outer enamel, the association with the resistance to invaginated enamel caries and the inflammatory lesions mediated their invagination. Because of the difficulties of treating and the tendency of their inflammatory lesions mediated their malformed structures, teeth extracted from the patients with DI, were collected in our hospital and analyzed by three-dimensional micro-focusing computed tomography (mu CT) to clarify the differences of the invaginated enamel in mineral density (MD), and to find their pathogenesis of tooth anomaly and associated inflammatory lesions by histological analysis. The teeth were fixed with 10% formaldehyde and analyzed by mu CT, decalcified specimens were performed to histological (HE) and immunohistochemistry for cytokeratin AE1/AE3. All invaginated teeth enamel showed extremely lower MD than did the outer enamel. Interestingly there were no carious lesions in the invaginated enamel. HE showed thin reduced enamel epithelium on the surface of invaginated enamel and cytokeratin AE1/AE3 markedly showed positive their cellular matrix. The persistent reduced enamel epithelium of the invaginated enamel indicates delayed or inhibited maturation after tooth eruption. This failure of maturation results in lower MD but resistance to enamel caries. However, the structural abnormalities of DI teeth may allow bacteria to enter the interior of the tooth through the invagination, causing pulpitis or apical periodontitis. (243 words)

File： 23_449.pdf

DOI： 10.2485/jhtb.23.449

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Susceptibly to the induction of rat tongue cancer (TC) by oral 4-nitroquinoline 1-oxide (4NQO) exposure is a polygenic trait. Among several quantitative trait loci identified by crosses between TC-susceptible Dark Agouti (DA) rats and TC-resistant Wistar-Furth (WF) rats, we focused on tongue cancer susceptibility locus (Tcas3) of chromosome 4. We examined tongue carcinogenesis in the reciprocal congenic strains DA.WF-Tcas3 and WF.DA-Tcas3 and in their parental strains. The Tcas3DA allele, and not the Tcas3WF allele, significantly favored tumor latency, incidence and TC number/size. In genomic DNA of TCs induced in (DA x WF) F1 rats, the resistant Tcas3WF allele was frequently and selectively lost, particularly in larger tumors. Thus, we searched the possible candidate genes in the Tcas3 region using microarray analysis of TCs in F1 rats and revealed significant upregulation of 2 cancer-related genes, parathyroid hormone-like hormone (Pthlh) and Kras2. The relevance of the WF allele of Pthlh as a cancer modifier was indicated by 3 single nucleotide polymorphisms specific to this strain. In contrast, no consistent strain-specific variations were found in Kras2. Moreover, the plasma Ca2+ level was consistently higher in DA rats when compared to the level in WF rats bearing TCs; moreover, the Pthlh-mRNA expression level was >30-fold higher in TCs when compared to this level in the normal tongue mucosa. Immunostaining experiments showed strong PTHrP protein expression in TCs of DA rats, and the signal was intensified in larger TCs. Kras2 was also upregulated in TCs, but to a lesser degree than PTHrP. Thus, Pthlh is a promising candidate modifier gene in the development and progression of rat TCs.

DOI： 10.3892/or.2013.2859

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DOI： 10.1111/pin.12121

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DOI： 10.3353/omp.15.117

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The genotype of the fibroblast growth factor receptor 4 (FGFR4) gene and TP53 mutation have been reported as prognostic factors for cancers of the head and neck, bladder, breast and colon. To determine whether they are applicable for oral squamous cell carcinoma (OSCC), we investigated these two genes in OSCC samples from 150 patients who had undergone radical surgery and in 100 cancer-free individuals. In OSCC, the FGFR4 Gly388Arg polymorphism and the presence or absence of mutation in TP53 did not show a significant association with the clinicopathological features of the tumors at surgery. However, the FGFR4 Arg388 allele, as well as mutations in TP53, was found to be closely associated with poor prognosis. Moreover, these two parameters synergistically affected the survival of OSCC patients. During 60 months of observation after radical surgery, a majority of patients with homozygous Arg388 FGFR4 plus mutated TP53 died of cancer, whereas >90% patients carrying homozygous Gly388 FGFR4 plus wild-type TP53 survived. Therefore, the FGFR4 Gly388Arg polymorphism and TP53 mutations, as well as their combinations, are excellent predictors of the prognosis for OSCC patients.

DOI： 10.3892/or-00000692

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BACKGROUND: Lymphatic vessel density (LVD) and microvessel density (MVD) are important parameters for assessing the malignant potential of tumors and patient survival. In this report, the authors defined LVD as the density of D2-40-positive lymphatic vessels and MVD as the density of CD105-positive microvessels per unit area of tissue. It was reported previously that vascular endothelial growth factor C (VEGF-C) is a major modulator of LVD and MVD. The objectives of this study were to clarify the clinical and prognostic significance of both LVD and MVD in oral squamous cell carcinoma (OSCC) and to elucidate the lymphangiogenic and angiogenic activities of VEGF-C in cancer tissues. METHODS: In total, 110 OSCC tissue samples were evaluated for LVD, MVD, and expression of VEGF-C using immunohistochemistry. Correlations among these parameters and clinicopathologic factors were examined. RESULTS: LVD was significantly higher in tumors that had very high expression of VEGF-C compared with tumors that had no/weak expression of VEGF-C. LVD correlated well with lymph node metastasis (P < .001). MVD was correlated significantly with positive lymph node metastasis (P < .001) but not with VEGF-C expression. In contrast, high expression of VEGF-C was correlated significantly with advanced tumor status (P = .041). Survival rates were lower in patients who had higher LVD (P < .001), higher MVD (P = .0028), and strong VEGF-C expression (P = .048). CONCLUSIONS: Lymphangiogenesis predominantly influenced metastasis-free survival. The current results suggested that LVD is a more useful tool than MVD and VEGF-C for deciding on therapeutic strategies in patients with OSCC.

DOI： 10.1002/cncr.22900

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BRITISH INST RADIOLOGY  

We report an unusual case of pleomorphic adenoma of the submandibular gland in a 48-year-old female. The present case appeared as a relatively homogeneous, low to intermediate signal-intensity on the T-2 weighted magnetic resonance (MR) images. To our knowledge, the MR feature of low T-2 signal-intensity of pleomorphic adenoma has not been reported in the literature.

DOI： 10.1259/dmfr/21157218

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We previously reported that susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer in Dark-Agouti (DA) and Wistar/Furth (WF) rats was determined by a number of quantitative trait loci. In this article, we further scrutinized one of the quantitative trait loci at a suggestive level on rat chromosome 5. Analyzing a DNA panel of 130 (DAxWF) F2 rats treated with 4NQO showed a quantitative trait loci, containing p15INK4B and p16INK4A. To study the possible relevance of these genes in the development of tongue cancer, we examined 45 4NQO-induced tongue cancers in 100 (DAxWF) F1 rats for loss of heterozygosity. The incidence of loss of heterozygosity at p15INK4B and p16INK4A genes in large advanced tongue cancers was 37.8% and 40.0%, respectively, and the WF allele was selectively lost. Accumulation of loss of heterozygosity and methylation of the promoter regions in the tumour suppressor genes in advanced tumours suggests that they may play a role in tongue cancer progression.

DOI： 10.1016/j.oraloncology.2005.11.011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

BACKGROUND: Oral squamous cell carcinoma develops through a multistep of genetic mutations, and the process can be morphologically recognized as oral epithelial dysplasia. To evaluate the hypothesis that distributional alterations of proliferating and stem cells may be a useful index to estimate the grading and development of epithelial dysplasia, we examined the distribution patterns according to stratified cell layers.
METHODS: Sixty-two oral dysplasia cases according to the histological grades were immunohistologically examined and the nuclear expression of Ki-67 and p63 antigens was counted according to epithelial layers as labeling index.
RESULTS: The Ki-67 labeling index in the basal and suprabasal layers and that of p63 in the basal layer showed a significant difference between low- and high-grade groups of epithelial dysplasia.
CONCLUSION: The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias.

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BACKGROUND: Oral squamous cell carcinoma develops through a multistep of genetic mutations, and the process can be morphologically recognized as oral epithelial dysplasia. To evaluate the hypothesis that distributional alterations of proliferating and stem cells may be a useful index to estimate the grading and development of epithelial dysplasia, we examined the distribution patterns according to stratified cell layers. METHODS: Sixty-two oral dysplasia cases according to the histological grades were immunohistologically examined and the nuclear expression of Ki-67 and p63 antigens was counted according to epithelial layers as labeling index. RESULTS: The Ki-67 labeling index in the basal and suprabasal layers and that of p63 in the basal layer showed a significant difference between low- and high-grade groups of epithelial dysplasia. CONCLUSION: The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias. © Blackwell Munksgaard 2006 · All rights reserved.

DOI： 10.1111/j.1600-0714.2006.00444.x

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We previously reported that Dark-Agouti (DA) rats are highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer (TC), whereas Wistar/Furth (WF) rats are barely susceptible. Linkage analysis of reciprocal (DAxWF)F2 rats demonstrated five quantitative trait loci, Tongue squamous cell carcinoma 1-5 (Tscc1-5) determining the size and number of the TCs. The major susceptibility locus Tscc1 is mapped on rat chromosome 19. In the present study, we used a marker-assisted speed congenic procedure to construct WF.DA-Tscc1 (WF-T1D) rats, i.e. WF rats carrying a DA-derived Tscc1 chromosomal segment, and evaluated the effect of a single Tscc1 on 4NQO-induced tongue carcinogenesis. In WF-T1D rats, the incidence, number and size of 4NQO-induced TCs were significantly higher than those in WF rats, indicating that the introgressed segment contains one of the susceptibility loci for 4NQO-induced TCs from DA rats. Detection of a single nucleotide polymorphism in NQO1, one of the Tscc1 candidate genes, enabled us to map NQO1 in the Tscc1 segment between D19Wox8 and D19Wox7 on chromosome 19. Possible relevance of NQO1 polymorphism to TC susceptibility is discussed.

DOI： 10.1016/j.canlet.2005.01.043

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A functional Gly388Arg variation in the FGFR4 gene has been reported to be associated with breast and colorectal cancer prognostic parameters. To further examine the functional role of this genetic polymorphism at the population level, we assessed the presence of the Arg388 allele in 142 breast carcinoma patients, 179 colorectal carcinoma patients and 220 general population controls with respect to an association with cancer prognosis and/or risk. No significant association with cancer risk, survival or any other prognostic parameters was observed in either breast or colorectal cancer. A pooled analysis of the present and published data on nodal status by FGFR4 genotypes revealed no association in either breast cancer [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.7-1.4; 702 subjects] or colorectal cancer (OR, 1.4; 95% CI, 0.6-3.4; 260 cases). Thus, the FGFR4 polymorphism may not be relevant in predicting nodal involvement of breast cancer or colon cancer patients.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Objective: This study aims to elucidate the genetic basis of predisposition to 4-nitroquinoline1-oxide (4NQO)-induced tongue cancers (TCs). Materials and Methods: We have reported that inbred Dark-Agouti (DA) strain rats were highly susceptible to 4NQO-induced TCs, whereas Wistar/Furth (WF) rats were resistant to tongue squamous cell carcinomas induced by oral administration of 4NQO. Using size and number of the tumours as quantitative parameters, responsible host loci were analysed by an interval mapping of F-2 intercross of DA and WF given carcinogenic regimen. Also, loss of heterozygosity (LOH) at these loci was analysed in tongue cancers in (DA x WF) F-1. Results: We identified and mapped 5 significant quantitative trait loci (QTL), the Tongue squamous cell carcinoma 1-5 (Tscc1-5), and several other suggestive QTL that determine susceptibility to 4NQO-induced TC. Study of TCs induced in (DA x WF)F-1 rats revealed a high frequency of LOH in the chromosomal regions of Tscc2, 3, and 4 and also of suggestive QTL on chromosomes 5 and 6. The fact that LOH was found only in larger TCs indicates that LOH occurred in the process of tumour progression. In most LOH, the allele of the resistant WF strain was lost, suggesting that these loci may encode tumour suppressor genes. In larger TCs, in addition to LOH, point mutations and the methylation of possible candidate genes were accumulated. Conclusion: These observations indicate that the 4NQO-induced TC in the rat is a multifactorial disease of a polygenic trait. This model will be useful to understand the complicated genetic basis of predisposition to oral cancers. Copyright (C) 2005 S. Karger AG, Basel.

DOI： 10.1159/000086926

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To explore a possible role for viral genes as determinants of virulence, portions of the UL144 tumor necrosis factor-like receptor gene and the UL55 envelope glycoprotein B gene from 42 patients with congenital human cytomegalovirus (HCMV) infection or other diseases were sequenced. Of the 42 patients, 16 (38%) had UL144 group 1 [group 1A, 15 of 16 (94%); group 1B, 1 of 16 (6%); group 1C, 0 of 16 (0%)], 5 patients (12%) had UL144 group 2, and 21 patients (50%) had UL144 group 3. Although group 1C was not found in Japan strains (0%), it was found in USA strains (22%). Other HCMV polymorphisms should be further evaluated for their potential relevance to neonatal infection, and acquired immunodeficiency syndrome-associated HCMV diseases.

DOI： 10.1159/000081749

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Objective: This study aims to elucidate the genetic basis of predisposition to 4-nitroquinoline1-oxide (4NQO)-induced tongue cancers (TCs). Materials and Methods: We have reported that inbred Dark-Agouti (DA) strain rats were highly susceptible to 4NQO-induced TCs, whereas Wistar/Furth (WF) rats were resistant to tongue squamous cell carcinomas induced by oral administration of 4NQO. Using size and number of the tumours as quantitative parameters, responsible host loci were analysed by an interval mapping of F-2 intercross of DA and WF given carcinogenic regimen. Also, loss of heterozygosity (LOH) at these loci was analysed in tongue cancers in (DA x WF) F-1. Results: We identified and mapped 5 significant quantitative trait loci (QTL), the Tongue squamous cell carcinoma 1-5 (Tscc1-5), and several other suggestive QTL that determine susceptibility to 4NQO-induced TC. Study of TCs induced in (DA x WF)F-1 rats revealed a high frequency of LOH in the chromosomal regions of Tscc2, 3, and 4 and also of suggestive QTL on chromosomes 5 and 6. The fact that LOH was found only in larger TCs indicates that LOH occurred in the process of tumour progression. In most LOH, the allele of the resistant WF strain was lost, suggesting that these loci may encode tumour suppressor genes. In larger TCs, in addition to LOH, point mutations and the methylation of possible candidate genes were accumulated. Conclusion: These observations indicate that the 4NQO-induced TC in the rat is a multifactorial disease of a polygenic trait. This model will be useful to understand the complicated genetic basis of predisposition to oral cancers. Copyright (C) 2005 S. Karger AG, Basel.

DOI： 10.1159/000086926

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

Activator protein-1 (AP-1) is a transcription factor activated in many tumors. Using 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue cancers (TC), the present study investigated the expression levels of genes that encode the components of AP-1, the jun gene family (c-jun, junB and junD) and the fos gene family (c-fos, fra-1, fra-2 and fosB). Expression levels of junB and c-fos mRNAs in TC were significantly elevated compared with those in epithelial tissue of control rat tongue, although only c-fos mRNA levels tended to be elevated in dysplastic tongue epithelium. Histologically, all 4NQO-induced rat TC were well-differentiated squamous cell carcinomas. Immunostaining for JunB and c-Fos proteins was positive in the nuclei of tumor cells of all TC. It is noteworthy that JunB was negative, but c-Fos was positive in the dysplastic tongue epithelium of the 4NQO-treated rats. Immunostaining for both proteins was negative in tongue mucosal epithelium of control rats. There were no mutations in the coding regions of either junB or c-fos in all the TC examined. These results suggest the possibility that the expressions of junB and c-fos were enhanced stepwise in 4NQO-induced carcinogenesis of rat tongue, and that the coexpression of JunB and c-Fos might play an important role in the establishment of TC.

DOI： 10.1046/j.1440-1827.2003.01587.x

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Activator protein-1 (AP-1) is a transcription factor activated in many tumors. Using 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue cancers (TC), the present study investigated the expression levels of genes that encode the components of AP-1, the jun gene family (c-jun, junB and junD) and the fos gene family (c-fos, fra-1, fra-2 and fosB). Expression levels of junB and c-fos mRNAs in TC were significantly elevated compared with those in epithelial tissue of control rat tongue, although only c-fos mRNA levels tended to be elevated in dysplastic tongue epithelium. Histologically, all 4NQO-induced rat TC were well-differentiated squamous cell carcinomas. Immunostaining for JunB and c-Fos proteins was positive in the nuclei of tumor cells of all TC. It is noteworthy that JunB was negative, but c-Fos was positive in the dysplastic tongue epithelium of the 4NQO-treated rats. Immunostaining for both proteins was negative in tongue mucosal epithelium of control rats. There were no mutations in the coding regions of either junB or c-fos in all the TC examined. These results suggest the possibility that the expressions of junB and c-fos were enhanced stepwise in 4NQO-induced carcinogenesis of rat tongue, and that the coexpression of JunB and c-Fos might play an important role in the establishment of TC.

DOI： 10.1046/j.1440-1827.2003.01587.x

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Rats of the DA strain are highly susceptible to 4NQO-induced TCs, whereas WF rats are barely susceptible. In (DA x WF)F2 rats, 5 QTL, Tscc1-5, are responsible for most of the phenotypic variations, though they do not account for all of the phenotypic differences between WF and DA rats. Analysis of 40 tongue tumors >5 mm in diameter from (DA x WF)F1 rats for LOH at the Tscc loci revealed a high frequency of LOH in chromosomal regions where the Tscc2, -3 and -4 loci map. In most cases of LOH, the allele of the barely susceptible WF strain was lost, suggesting that these loci in the WF strain encode tumor-suppressor genes. Analysis of the same tumors for somatic mutations in oncogenes indicated frequent alteration of Ha-ras, which maps in the Tscc3 region, but rare mutation of the p15(INK4B) and p16(INK4A) genes or the p53 and Msh2 genes. Frequent LOH was also found on rat chromosomes 5 (RNO5) and 6 (RNO6). Tumors of large size accumulated LOH at multiple loci, suggesting the involvement of Tscc loci in tumor progression.

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Rats of the DA strain are highly susceptible to 4NQO-induced TCs, whereas WF rats are barely susceptible. In (DA x WF)F2 rats, 5 QTL, Tscc1-5, are responsible for most of the phenotypic variations, though they do not account for all of the phenotypic differences between WF and DA rats. Analysis of 40 tongue tumors >5 mm in diameter from (DA x WF)F1 rats for LOH at the Tscc loci revealed a high frequency of LOH in chromosomal regions where the Tscc2, -3 and -4 loci map. In most cases of LOH, the allele of the barely susceptible WF strain was lost, suggesting that these loci in the WF strain encode tumor-suppressor genes. Analysis of the same tumors for somatic mutations in oncogenes indicated frequent alteration of Ha-ras, which maps in the Tscc3 region, but rare mutation of the p15(INK4B) and p16(INK4A) genes or the p53 and Msh2 genes. Frequent LOH was also found on rat chromosomes 5 (RNO5) and 6 (RNO6). Tumors of large size accumulated LOH at multiple loci, suggesting the involvement of Tscc loci in tumor progression.

DOI： 10.1002/ijc.10751

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING ASIA  

Solitary fibrous tumor (SFT) is a rare, benign, soft tissue tumor that most commonly occurs in the pleura; however, it has recently been described in other sites of the body. To date, eight examples of oral SFT have been reported. This paper is a description of the first case of an SFT occurring as a soft tissue tumor in the mental region. Histologically, the tumor was composed predominantly of rather uniform spindle-shaped fibroblastic cells arranged in vague fascicles or in a haphazard fashion, intermingled with abundant collagen fibers. Immunohistochemically, the tumor cells were positive for CD34 and vimentin, and weakly positive for muscle actin and alpha -smooth muscle actin. The diagnosis of SFT may be difficult as this tumor shares a number of histological features with other soft tissue tumors. Awareness of its occurrence in the oral cavity is important so that confusion with other spindle cell neoplasms can be avoided.

DOI： 10.1046/j.1440-1827.2001.01290.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BUSINESS CENTER ACADEMIC SOCIETIES JAPAN  

In our previous study, Dark-Agouti (DA) rats were found to be highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue carcinoma (TC), whereas Wistar/Furth (WF) rats were barely susceptible. Interval mapping analysis of reciprocal backcross rats showed two quantitative trait loci (QTL) on rat chromosomes (RNO) 1 and 19, In the present study, a composite interval mapping analysis was applied to 4NQO-induced TC in 130 (DAxWF) F2 rats, demonstrating five independent QTL, Tongue squamous cell carcinoma 1-5 (Tscc1-5), responsible for phenotypic differences in the size and number of TCs in the two strains. Two of these QTL were mapped on RNO1, and the others were mapped on RNO4, 14, and 19. The DA allele at these loci consistently yielded semidominant susceptibility to TC, Out of the five loci detected in this F2 generation, Tscc1 and 2 were identical to Stc1 and Rtc1 described in our previous study, but the other three were novel. We propose a new nomenclature consistent with their function. Genome-nide screening of the F2 progeny also suggested the presence of three additional QTL on RNO5, 6, and 10, The possible roles of these loci in tongue carcinogenesis are discussed.

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The chemokine receptors CXCR4 and CCR5 are considered to be potential targets for the inhibition of HIV-1 replication. We have reported that T134 and T140 inhibited X4 HIV-1 infection specifically because they acted as CXCR4 antagonists. In the present study, we have generated a T134-resistant virus (trHIV-1NL4-3) in a cell culture with gradually increasing concentrations of the compound. The EC50 of T134 against trHIV-1NL4-3 recovered after 145 passages was 15 times greater than that against wild-type HIV-1NL4-3. This adapted virus was resistant to other CXCR4 antagonists, T140, AMD3100, and ALX40-4C, and SDF-1
from 10 to 145 times greater than that against wild-type HIV-1NL4-3. On the other hand, T134, T140, and ALX40-4C were still active against AMD3100-resistant viruses (arHIV-1018A). The trHIV-1NL4-3 contained the following mutations in the V3 loop of gp120: N269K, Q278T, R279K, A284V, F285L, V286Y, I288T, K290E, N293D, M294I, and Q296K
an insertion of T at 290
and Δ274-275 (SI). In addition, many other mutations were recognized in the V1, V2, and V4 domains. Thus, resistance to T134 may be the consequence of amino acid substitutions in the envelope glycoprotein of X4 HIV-1. The trHIV-1NL4-3 could not utilize CCR5 as an HIV infection coreceptor, although many amino acid substitutions were recognized. The trHIV-1NL4-3 acquired resistance to vMIP II, which could inhibit both X4 and R5 HIV-1 infection. However, neither the ligands of CCR5, RANTES, and MIP-1α, nor a CCR5 low molecular antagonist, TAK-779, were able to influence the infection of trHIV-1NL4-3. Those results indicated that alternation of coreceptor usage of trHIV-1NL4-3 was not induced.

DOI： 10.1089/088922201300119716

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DOI： 10.1046/j.1440-1827.2001.01290.x

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Urban und Fischer Verlag Jena  

Oral administration of 4-nitroquinoline 1-oxide (4NQO) to rats induced a high incidence of tongue carcinomas (TCs). The inbred Dark-Agouti (DA) strain of rats showed much higher susceptibility to 4NQO-induced TCs than the Wistar-Furth (WF) strain. Our previous study on crosses between the two strains postulated a semidominant susceptibility gene in DA and a semidominant resistance gene in WF rats. This hypothesis was confirmed by the genetic analysis of the backcrosses to either parent with PCR-based microsatellite assay. Using the number of TCS with &gt
5 mm diameter as a quantitative parameter, we mapped a quantitative trait locus Stc1 (Susceptibility to TC) favouring TC development near the locus D19Mit9 on Chr. 19 with a peak LOD scare of 6.08. Two other regions in Chr. 3 and Chr. 14 showed weak linkage for susceptibility, but were not statistically significant. On the other hand, another quantitative trait locus Rtc1 (Resistance to TC) providing resistance to TCs was mapped on Chr. 1 between the loci of D1Mit1 and D1Mit3 with a peak LOD score of 3.30. Quantitative parameters such as the number of tumours in the tongue or upper alimentary tract, the frequency of larger tumours and their maximum size were closely correlated and principally determined by Stc1 and Rtc1. Therefore the susceptibility to 4NQO-induced TCs in crosses between DA and WF is explained by the combinations of genotypes at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.

DOI： 10.1016/S0939-8600(00)80034-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Churchill Livingstone  

Oral administration of propylnitrosourea (PNU) in drinking water induces high incidence of lympho-haemopoietic malignancies in rats. Previously we reported that F344 strain rats were highly susceptible to T-lymphomas, and LE/Stm rats, to erythro- or myeloid leukaemias. For analysis of the genetic factors determining types of diseases, we have established LEXF recombinant inbred strains of rats comprising 23 substrains, each derived from intercross between F344 and LE/Stm rats. Rats of 23 LEXF substrains were given PNU, and the development of tumours was observed. The overall incidence of haemopoietic tumours ranged from 100% to 66.7%, and the fractions of T-lymphomas, from 100% to 4%, showing a continuous spectrum. Based on the genetic profile published as a strain distribution pattern table for the LEXF, we screened the potential quantitative trait loci involved in determination of the types of disease and length of the latency period. Statistical calculation was performed using the Map Manager QT software developed by Manly. Four loci, on chromosome 4, 7, 10 and 18, were suggested to associate with the T-lymphoma susceptibility and three loci, on chromosome 1, 5 and 16, with the length of the latency period. These putative loci were further examined in backcross (F344 x LE)F1 x LE. Among seven loci suggested by the recombinant inbred study, three loci, on chromosome 5, 7 and 10, were significantly associated with T-lymphomas and another locus on chromosome 1, just weakly. These observations indicate that PNU-induced lymphomagenesis is a multifactorial genetic process involving a number of loci linked with susceptibility and resistance.

DOI： 10.1038/sj.bjc.6690432

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estro en receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.

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Language：English   Publishing type：Doctoral thesis  

The incidence of tongue carcinomas (TCs) induced by oral administration of 4-nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA) strain showed a much higher susceptibility to large mass-forming infiltrative TCs than did the Wistar-Furth (WF) strain. Our previous study (M. Kitano et al, Jpn. J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains postulated a dominant susceptibility gene in DA and a dominant resistance gene in WF rats. The present study mapped these loci by analyzing the backcrosses to each parent with simple sequence repeat polymorphisms. Five quantitative parameters were analyzed: (a) the number of TCs &gt; 5 mm in diameter; (b) the total number of TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number of non-TC cancers per rat; and (e) and the number of cancers of any site per rat. All of these parameters were closely correlated (P &lt; 0.0001). DA rats had a semidominant gene (Stc1) favoring the development of 4-nitroquinoline 1-oxide-induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of 5.72 for

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A new set of rat RI strains consisting of 11 independent strains and 13 of their substrains was established by inbreeding F2 rats between F344/DuCrj and LE/Stm. The strain distribution pattern was examined for 66 microsatellite loci, 8 biochemical genetic markers, 2 histocompatibility loci, and 2 coat color genes. A rat salivary protein gene Spe1 was newly mapped on Chr 1.

DOI： 10.1007/s003359900432

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Seven cases of endometrial adenocarcinoma patients who had experienced long-term tamoxifen treatments as adjuvant therapy of breast carcinoma, were investigated with respect to estrogen receptor (ER) status. Four cases of endometrial adenocarcinoma without tamoxifen treatment but with a previous history of breast carcinoma were investigated for comparison. One of the 7 and two of the 4 cases were positive for ER immunohistochemically. Thus, the frequency of ER positivity in secondary endometrial adenocarcinoma seemed to be at random among tamoxifen-treated and non-treated br east cancer patients. These results suggest that tamoxifen-mediated human endometrial carcinogenesis may not involve estrogenic pathway(s) but may involve other carcinogenic mechanisms such as DNA adduct formation as shown in rat liver tumorigenesis.

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Expression of ras p21 oncoproteins in human ovarian carcinomas was examined immunohistochemically by using a monoclonal antibody(clone RAS 10) with respect to the degree of their histological differentiation. To achieve this, the intensity of staining for the protein was compared between undifferentiated and well differentiated carcinomas, i.e. extreme subtypes of common epithelial carcinomas. The former was composed of 8 'solid' carcinomas and the latter
11 serous, 8 mucinous, 4 endometrioid and 4 clear cell carcinomas. All the cases examined, including both undifferentiated and well-differentiated carcinomas, showed a positive reaction to this antibody. Staining intensity and the number of positive cells somewhat varied among the cases. Additionally, 2 cases of ovarian epithelial tumors of low malignant potential (I,MP) were stained with this antibody. Both the cases were positive, but the number of positive cells seemed to be rather less than than that found in the carcinoma groups. Thus, no differences in ras p21 expression were observed between the cases examined in spite of the differences in the degree of differentiation of the epithelial ovarian carcinomas. However
the possibility remained that the number of positive cells could be an indicator of malignant potential, enabling us to distinguish LMPs from carcinomas. Thus immunodetection of ras p21 could not provide an additional means for the histological differentiation of ovarian cancer although the evaluation of basement membrane integrity and cell proliferation kinetics as reported previously was useful in differential diagnosis and in understanding the biology of ovarian undifferentiated carcinomas.

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Responsible for pages：62-106, 195-213, 332-354   Language：Japanese Book type：Scholarly book

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

かかりつけ歯科医院での長期メインテナンス中、下顎埋伏智歯の歯冠部に関連して生じたと考えられる高齢者の原発性骨内癌を経験したので報告する。症例は74歳の男性、右側下唇の知覚異常と右側下顎臼歯部の咬合痛を主訴に当科紹介初診となった。右側下顎第二大臼歯は挺出し、動揺度2、頬側歯肉に軽度の腫脹を認めたが排膿はなかった。パノラマX線写真で右側下顎智歯は骨性に逆生埋伏しており、単純CTで埋伏智歯の歯冠部に連続した境界不明瞭で辺縁不整な35×25mm大の腫瘤性病変を認めた。生検にて扁平上皮癌(原発性骨内癌疑い)の診断を得て、顎下部郭清術、下顎骨区域切除術、金属プレートによる顎骨再建術を行った。一般的に原発性骨内癌は嚢胞様病変から悪性転化するとされるが、本症例は当科初診の8ヵ月前に紹介元で撮影されたパノラマX線写真では異常所見は観察されず、明白な嚢胞様変化を辿ることなく悪性転化し、急速に増大したと推察された。症状のない下顎埋伏智歯は経過観察されることが多いが、発育性嚢胞や歯周炎などのリスクが低いと判断される高齢者の下顎埋伏智歯においても、多様な変化の可能性も念頭に置いた経過観察が肝要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02382&link_issn=&doc_id=20201221280014&doc_link_id=10.5843%2Fjsot.32.243&url=https%3A%2F%2Fdoi.org%2F10.5843%2Fjsot.32.243&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：新潟歯学会  

近年普及した液状化検体細胞診(LBC)法による口腔細胞診の現状と応用について述べた。LBC法では、Papanicolaou染色の標本背景が鮮明であり、さらに免疫染色用標本を複数作製することが可能である。LBC法のボトルからのDNA・RNAの抽出は容易で、量的・質的にも十分であるため、多くの遺伝子解析の検索が可能である。今後、口腔癌検診へのLBC法の利用が期待される。

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本小児口腔外科学会  

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Language：English   Publisher：日本癌学会  

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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DOI： 10.5794/jjoms.64.577

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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歯科インプラント治療症例における高度の骨吸収や骨欠損に対し、骨再生療法が行われている。骨再生療法としては骨再生誘導法（Guided Bone Regeneration: GBR）としてメンブレンテクニックが応用されているが骨造成量が多く必要な場合には、自家骨を始めとする骨補填剤が応用される。自家骨を応用する場合はその採取のための手術侵襲や、手術時間の延長などの問題があるため、人工骨補填材料が臨床応用されている3）。人工骨補填材としてはハイドロキシアパタイト（HA）やβ-TricalciumPhosphate（β-TCP）等のリン酸カルシウム系材料が応用されてきた5）しかし、HAは生体親和性に優れるが材料吸収性ではないため、 生体内に残存する6）。また、β-TCPは生体内で吸収され、骨と置換する材料であるが7-9）、含有されている成分の中には生体親和性において問題が指摘されている。このような問題点を改善すべく、DoiらとElliesは生体親和性に優れ、吸収性材料である炭酸含有アパタイト（Carbonated Apatite, CA）を開発した12-13）。そして、その優れた特性を活かした生体応用研究がこれまでに報告されてきた14）。本研究では、 ラット大腿骨を用いた動物実験モデルにおいて焼成温度の異なる（700℃ /500℃）CA顆粒を人工骨補填材料として填入し、組織学的に評価し、さらに、吸着徐放性の検討も併せて行った。実験結果では、500℃焼成と700℃焼成のCAの臨床応用を考慮すると、500℃では生体における材料吸収性が良い反面、骨形成開始や骨成熟に至る期間やCA顆粒の臨床的操作性においては700℃の方が良好であった。以上の結果から臨床応用には700℃焼成のCA顆粒に、骨吸収や骨欠損部に対する人工骨補填材料としての期待ができる。また、CA顆粒とFGF2の併用は、至適濃度等の検討が必要ではあるが、骨形成や骨成熟を促進させることが示されたことから、同様に他の成長因子の併用による有用性も期待される。For severe bone resorption and bone defects at dental implant treatment sites, bone augmentation treatment is required. For bone augmentation treatments such as guided bone regeneration(GBR), the membrane technique is most commonly applied, but bone substitute materials including autogenous bone are used when large quantities of bone are required. However, the collection of autogenous bone requires increased surgical invasiveness, and artificial bone substitute materials have therefore been applied clinically. Calcium phosphate-based materials such as hydroxyapatite(HA) or β-tricalcium phosphate(β-TCP) have been applied as artificial bone substitute materials. Although HA has superior biocompatibility, it remains in the living bone because it is not resorbable. In contrast, β-TCP is resorbable in vivo, as it is replaced with bone, but it has lower biocompatibility. Doi and Ellies reportedly developed Carbonated Apatite(CA), which shows superior biocompatibility and is resorbable, and preliminary studies have reported superior characteristics in the living. In the present animal experiment using rat femur to evaluate differences in sintered temperature (700℃ / 500℃), CA granules were used as an artificial bone substitute material, and were observed histologically for their absorption and controlled release characteristics. The resorbability in the living body was good at 500°C, which we considered to be suitable for clinical application of CA, but 700°C was apparently better for early bone formation and maturity, as well as the clinical maneuverability of CA granules. Based on these results, we concluded that for clinical application of CA granules, preparation at 700℃ is optimal for severe bone resorption and bone defects at the dental implant treatment sites. In addition, the combination of CA granules and FGF-2 requires further study to determine optimal concentrations, and their usefulness in combination with other growth factors is expected because CA granules were shown topromote bone formation and bone maturity.

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Language：Japanese   Publisher：岐阜歯科学会  

歯科インプラント治療症例における高度の骨吸収や骨欠損に対し、骨再生療法が行われている。骨再生療法としては骨再生誘導法(Guided Bone Regeneration:GBR)としてメンブレンテクニックが応用されているが骨造成量が多く必要な場合には、自家骨を始めとする骨補填剤が応用される。自家骨を応用する場合はその採取のための手術侵襲や、手術時間の延長などの問題があるため、人工骨補填材料が臨床応用されている。人工骨補填材としてはハイドロキシアパタイト(HA)やβ-TricalciumPhosphate(β-TCP)等のリン酸カルシウム系材料が応用されてきた しかし、HAは生体親和性に優れるが材料吸収性ではないため、生体内に残存する。また、β-TCPは生体内で吸収され、骨と置換する材料であるが、含有されている成分の中には生体親和性において問題が指摘されている。このような問題点を改善すべく、DoiらとElliesは生体親和性に優れ、吸収性材料である炭酸含有アパタイト(Carbonated Apatite、CA)を開発した。そして、その優れた特性を活かした生体応用研究がこれまでに報告されてきた。本研究では、ラット大腿骨を用いた動物実験モデルにおいて焼成温度の異なる(700℃/500℃)CA顆粒を人工骨補填材料として填入し、組織学的に評価し、さらに、吸着徐放性の検討も併せて行った。実験結果では、500℃焼成と700℃焼成のCAの臨床応用を考慮すると、500℃では生体における材料吸収性が良い反面、骨形成開始や骨成熟に至る期間やCA顆粒の臨床的操作性においては700℃の方が良好であった。以上の結果から臨床応用には700℃焼成のCA顆粒に、骨吸収や骨欠損部に対する人工骨補填材料としての期待ができる。また、CA顆粒とFGF2の併用は、至適濃度等の検討が必要ではあるが、骨形成や骨成熟を促進させることが示されたことから、同様に他の成長因子の併用による有用性も期待される。(著者抄録)

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Language：Japanese   Publisher：新潟歯学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：岐阜歯科学会  

難治性である慢性の根尖性歯周炎に対して、歯科用顕微鏡やCT画像診断を駆使した歯内療法が施行されているが、歯科臨床では依然として完全に治癒しない根尖性歯周炎に遭遇することが多い。この原因にはオーラルバイオフィルムの細菌構成の違いや根尖病巣の急速な拡大とともに症状を示すという宿主の因子も考えられる。周知の如く、慢性の根尖性歯周炎では、口腔常在菌の根管内から根尖孔外への感染に伴う根尖部歯周組織の細胞が産生する種々の炎症性サイトカインや成長因子が放出され、炎症細胞の浸潤が多く認められる。しかし、根管内の無菌化(細菌除去)後においても、完全治癒しない症例が多いのも事実であり、根尖歯周組織に持続的な炎症細胞が存在していることが考えられる。そこで、本研究では難治性の慢性根尖性歯周炎100症例における病変部の検索、根管内細菌、免疫担当細胞、炎症性サイトカイン、細胞増殖因子とそのレセプターの検出を行った。さらに、これら慢性根尖性歯周炎において炎症細胞の浸潤・増殖が見られるp16遺伝子産物(抗p16抗体と抗Ki-67抗体の陽性反応)におけるエピジェネティクスな変化、すなわち、DNAのメチル化等の化学修飾による遺伝子発現の制御伝達による可能性について、免疫組織学的に検索を行った。まず、研究に用いた症例は難治性の慢性根尖性歯周炎100症例でHE染色による病理組織学的観察に基づく分類を行った結果、40症例が歯根肉芽腫、45症例が歯根嚢胞、15症例が慢性化膿性根尖性歯周炎で、ほとんどの病巣は幼若から成熟した肉芽組織から構成されていた。根管内からの細菌の侵襲により根尖周囲に細菌が認められた症例は、慢性化膿性根尖性歯周炎に3例、歯根嚢胞に1例だけであった。免疫担当細胞の検出ではCD68陽性のマクロファージの浸潤が最も多く見られ、リンパ球は少なかった。炎症性サイトカインの検出ではマクロファージを中心に多くの炎症細胞が認められ、これらのレセプターは主に線維芽細胞と血管内皮細胞に認められた。細胞増殖因子のbFGF、PDGF、TGF-βはマクロファージ、線維芽細胞、血管内皮細胞に発現し、これらのレセプターは線維芽細胞と血管内皮細胞に多く認められた。エピジェネティクスな変化の解析結果では幼若肉芽組織におけるマクロファージや線維芽細胞にp16陽性を多く認め、成熟または瘢痕化した線維組織では陰性を示した。また、歯根嚢胞では裏装上皮細胞にp16陽性が多く認められたが、細胞増殖を示すKi-67は全ての症例で陽性率が低く、これは炎症刺激による炎症細胞の反応性増殖とみなした。以上の結果から、難治性の慢性根尖性歯周炎の病変は免疫応答を生じ、線維芽細胞と血管内皮細胞がマクロファージとの間でサイトカインネットワークを形成し、これにエピジェネティクスな変化が加わることで根尖性歯周炎に存在する肉芽組織の形成と線維化の維持に繋がることが示唆された。(著者抄録)

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Language：Japanese   Publisher：松本歯科大学学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：English   Publisher：INT PRESS EDITING CENTRE INC  

Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosonnal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

DOI： 10.1538/expanim.14-0072

Web of Science

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(一社)日本口腔内科学会  

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Language：Japanese   Publisher：岐阜歯科学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(公社)日本矯正歯科学会  

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Language：English   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

Glomangiomyomaは爪甲下に好発するGlomus腫瘍の亜型の一つであるが、口腔領域では極めて稀で、上唇正中部に多くみられ無症状の経過を示す。治療は外科的切除が推奨されており、再発は少なく予後も良好である。患者は61歳の男性。約2ヵ月前から上唇正中部の腫脹を自覚していたが、緩徐な増大傾向を示したため精査を目的に当科を受診した。正常粘膜下に直径5mmの境界明瞭で弾性硬の小腫瘤を認め、翌週には直径10mmまで急速に拡大した。MRIおよび超音波画像検査にて上唇の粘膜下の領域に境界明瞭な10mmの病巣を認めた。小唾液腺腫瘍の臨床診断にて切除生検を施行した。病理組織学的検査と免疫組織化学的検査にてGlomangiomyomaと確定診断した。(著者抄録)

DOI： 10.5843/jsot.26.25

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Other Link： http://search.jamas.or.jp/link/ui/2014192139

Language：Japanese   Publisher：岐阜歯科学会  

緒言:上顎洞粘液嚢胞は、比較的無症状で緩慢に発育することから、画像検査で偶然に発見されることが多い。時に上顎洞とは別に嚢胞病変が存在することがあり、顎嚢胞も考慮しなければならない。また術後性上顎嚢胞と鑑別する必要もある。今回、臨床所見から顎嚢胞を疑われたが、組織像および既往歴から上顎洞粘液嚢胞と診断した1例を経験したので報告する。症例:57歳の女性。2013年6月に上顎左側臼歯部の欠損を主訴に近歯科医院を受診した。画像検査から上顎左側顎骨内にエックス線透過所見を認め、当院を紹介された。20年前に左側上顎洞炎に対し鼻腔洗浄の既往があった。CT画像で、左側歯槽突起内に直径35mmの境界明瞭な透過性病変を認め、上顎洞との間には菲薄な骨を認めた。病変部のCT値から液体と軟組織の混在が示唆された。歯肉部から開窓して骨を含む病巣の生検を施行した。同時に創部より排出した茶褐色成分含み透明感のあるゼリー状の内容物を採取し、口腔に開窓した。細胞所見:内容物の細胞診では、背景は炎症性細胞が目立たず、粘液成分を主体に少数の線毛を有する円柱上皮を僅かに認めた。組織所見:嚢胞壁は僅かな瘢痕組織を伴う浮腫性の線維性結合組織が主体を占め、粘液を分泌する線毛上皮で覆われていた。診断:上顎洞粘液嚢胞 まとめ:今回、顎嚢胞が疑われた上顎洞粘液嚢胞の一例を経験した。上顎洞粘液嚢胞は、顎嚢胞と類似する点があり、診断には慎重を要することが示唆された。(著者抄録)

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Language：English   Publisher：岐阜歯科学会  

重層扁平上皮は高度に分化した組織であるが、これを発生由来とする扁平上皮癌ではその分化程度により、本来の組織形態とは異なる形質を発現することが知られている。本研究はこれらの形質発現の変化の中で上皮間葉転換の一つとして知られる扁平上皮から紡錘形の間葉系への分化の可能性とその癌細胞の浸潤性への関連を探るため、超微細構造を含む形態的な変化や細胞間接着因子のカドヘリンとカテニン、細胞外基質のヒアルロン酸と大きく関わり、また腫瘍の浸潤や細胞活性にも関わると言われているCD44ファミリーについて免疫組織化学的に検索した。歯肉に生じた扁平上皮癌で頸部リンパ節転移を示した一例を材料にその検索を行ったところ、原発巣における紡錘形を示す癌細胞は超微細形態的にも紡錘形を示すがトノフィラメントやデスモゾーム構造を有した上皮細胞としての性格を維持しており、また免疫染色においても、ケラチン発現の維持とEMAの減少に加えて間葉成分のビメンチン発現を認めたが、細胞間接着に関する異常は認めなかった。一方、CD44ファミリーのバリアント6(CD44v6)は紡錘形を示す癌細胞に強い発現を示し、この発現と癌細胞の浸潤が強く示唆された。(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2015007439

Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(一社)日本口腔内科学会  

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Language：Japanese   Publisher：(一社)日本口腔内科学会  

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：WILEY-BLACKWELL  

DOI： 10.1111/pin.12121

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Language：English   Publisher：日本癌学会  

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：岐阜歯科学会  

粘液線維腫は比較的に稀な顎骨に発生する歯原性良性腫瘍の1つで、WHOの組織学的分類(2005)では、間葉性あるいは歯原性外胚葉性間葉組織由来で、歯原性上皮をみるもの、あるいはみないものに分類される。同じカテゴリーに分類されているものに歯原性線維腫があり、その組織成分から両者の鑑別がしばしば困難となる場合が多い。今回、我々は一般的に顎骨への強い侵襲性を示す歯原性粘液腫とは明らかに異なり、病理組織標本では比較的線維成分の多い粘液線維腫と考えられる1例を経験した。その臨床態度との関係が重視されることから、若干の考察を加えたところ、本症例のような線維成分の多いタイプでは、軽度な骨侵襲性があり、その病理組織像からは、粘液基質成分を背景としながらも、線維成分が豊富なため粘液線維腫と診断した。本症の治療は従来の歯原性粘液腫とは異なり、骨侵襲性が低いと判断し、患者のQOLを考慮した掻爬による治療選択を行ったが、術後2年経過後も再発は認められない。(著者抄録)

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Language：Japanese   Publisher：岐阜歯科学会  

疣贅状黄色腫(Verruciform Xanthoma, VX)はShaferによって初めて報告された中高年成人の歯肉歯槽粘膜に好発する比較的まれな良性の病変である。今回、我々は下顎歯肉前歯部に生じた疣贅状黄色腫の1例を経験し、その概要に考察を加えて報告する。患者は58歳の男性。右側下顎前歯部歯肉に5×5mm程度の腫瘤に気付き、精査のため朝日大学附属病院を紹介来院した。口腔内所見では、右側下顎側切歯部に乳頭状の腫瘤と同部歯肉の発赤・腫脹を認めたが、圧痛や硬結は認めなかった。良性腫瘍の臨床診断の下、摘出生検を施行した。組織診では、乳頭状に肥厚した角化を伴う重層扁平上皮の増生がみられ、上皮脚の延長と歯肉固有層の乳頭部に限局した多数の泡沫細胞を認めた。これらの泡沫細胞は免疫組織化学的にCD68に陽性を示し、一方S-100タンパクには陰性を示したことから、炎症性細胞由来のマクロファージの集簇による疣贅状黄色腫と診断した。現在、経過観察中であるが、再発は認められない。(著者抄録)

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Language：Japanese   Publisher：岐阜歯科学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(NPO)日本歯周病学会  

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Language：Japanese  

43歳の女性。右側口蓋粘膜の12×10mmの黒色斑を主訴に来院した。黒色斑の境界はやや滲んだ様相で、CT検査において口蓋の骨や上顎洞は健常であった。悪性黒色腫と臨床診断し、腫瘍辺縁より最低10mmの安全域を設定して骨膜を含めて切除した。切除標本の病理組織所見で、切除辺縁は陰性であったが、腫瘍細胞の固有層への浸潤は2mmをわずかに超えており皮膚の悪性黒色腫のpT3aN0M0、StageⅡAに相当すると病期分類した。術後早期にDAV-Feron免疫・化学療法を開始し、１年間に3クール施行した。術後2年半経過した現在、局所再発、領域リンパ節転移および遠隔転移は認めず良好に経過している。

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Language：Japanese   Publisher：岐阜歯科学会  

43歳の女性。右側口蓋粘膜の12×10mmの黒色斑を主訴に来院した。黒色斑の境界はやや滲んだ様相で、CT検査において口蓋の骨や上顎洞は健常であった。悪性黒色腫と臨床診断し、腫瘍辺縁より最低10mmの安全域を設定して骨膜を含めて切除した。切除標本の病理組織所見で、切除辺縁は陰性であったが、腫瘍細胞の固有層への浸潤は2mmをわずかに超えており皮膚の悪性黒色腫のpT3aN 0 M0、Stage II Aに相当すると病期分類した。術後早期にDAV-Feron免疫・化学療法を開始し、1年間に3クール施行した。術後2年半経過した現在、局所再発、領域リンパ節転移および遠隔転移は認めず良好に経過している。(著者抄録)

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Language：Japanese   Publisher：岐阜歯科学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：Japanese Society of Oral Oncology  

Glomangiomyoma is a subtype of glomus tumors, which usually occur in the subungual layer. Such tumors localized to the oral cavity are very rare, and are most commonly in the center of the upper lip. The clinical symptoms are solitary swelling without pain, and excision of the tumor is recommended for treatment. Recurrence is rare and the prognosis is good.&lt;br&gt;A 61-year-old man was referred to the Department of Oral Surgery at our institution in March 2012 complaining of swelling of his upper lip. He had noticed the swelling two months earlier and had been left untreated. Intraoral examination revealed a marked small swelling without inflammatory symptoms in the center of the upper lip. The lesion was a well-defined submucosal mass. The size of the lesion was 5 mm and also showed mobility. One week later the lesion expanded rapidly. We performed imaging examination, including magnetic resonance imaging (MRI) and ultrasonography (US). The lesion had developed in the submucosal layer of the upper lip and measured approximately 10 mm in size. A minor salivary gland tumor was suspected and excisional biopsy was performed. The mass was well circumscribed, was excised completely, and the surgical site was closed. The removed specimen was placed in 10% formalin and submitted for histological examination. Histological and immunohistochemical studies were performed, and a diagnosis of glomangiomyoma was made.

DOI： 10.5843/jsot.26.25

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：岐阜歯科学会  

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(公社)日本歯科医師会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：岐阜歯科学会  

歯原性線維腫、粘液腫はともに間葉性あるいは歯原性外胚葉性間葉組織で歯原性上皮をみるもの、あるいはみないもので歯原性上皮性間葉組織に由来する比較的まれな腫瘍であるが、その発育形式や予後は著しく異なり、治療方針決定のためにも鑑別診断が重要と考えられる。今回、我々は歯原性線維腫様変化を呈する歯原性粘液腫の1例を経験したので、その概要に考察を加えて報告する。患者は12歳の男子。下顎左側のエックス線透過像の精査を求めて、2004年6月に紹介来院した。初診時、顔貌に特記すべき異常はなく、下顎左側第二乳臼歯部には抜歯窩が認められるが歯肉の異常は特に認めなかった。エックス線所見で水平に埋伏した第二小臼歯を含む境界明瞭な単胞性の嚢胞様透過像を認めた。同日、抜歯窩から生検を行い、透明感のあるゼリー状の組織を採取した。生検組織の病理組織像は豊富な粘液基質と散在性の紡錘形や星状の腫瘍細胞からなり、歯原性粘液腫と診断した。反復掻爬療法を計画し、2004年9月に摘出掻爬術を施行し、摘出物の病理組織所見では線維組織の増生が大部分を占め、それらの間に粘液基質が認められたが、最終的に歯原性線維腫様変化を呈する歯原性粘液腫と診断した。2005年3月に瘢痕組織の再掻爬術を施行し、その際に得られた標本には腫瘍を疑う組織は認められなかった。再掻爬後約1年を経過した現在、再発の徴候は認められない。(著者抄録)

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

DOI： 10.5795/jjscc.51.295

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：岐阜歯科学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：English   Publisher：岐阜歯科学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：English   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(一社)歯科基礎医学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本歯科薬物療法学会  

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

20歳女。右側耳介下部皮下に示指頭大で可動性のある骨様硬の孤在性腫瘤を触知した。X線およびCTでは右側耳介下部皮下に境界明瞭なX線不透過像を認め、右側耳介下部良性腫瘍と診断し、全身麻酔下に腫瘍摘出術を施行した。腫瘍は容易に摘出され、術後1年6ヵ月現在、創部治癒の経過は良好である。摘出標本は20×13mm大で、石灰化組織を含んでおり、割面は黄白色調であった。軟X線写真では、二つの結節が癒合したようなダンベル状であり、内部に明瞭な不透過像の混在がみられた。病理組織学的には好塩基性を示す石灰化した腫瘍実質周囲に著明な骨形成がみられ、明らかな好塩基性細胞や好酸性陰影細胞は認められなかった。好塩基性を示す石灰化した実質辺縁に破骨細胞様多核巨細胞がみられ、その細胞直下の実質は好酸性に変化していた。実質辺縁には骨形成がみられ、一部では骨芽細胞が骨組織辺縁にみられた。間質は疎で脂肪細胞を含み、脂肪髄に類似していた。間質には膠原線維が増生し、硝子化した部分には好塩基性を示す顆粒状石灰化がみられた。

DOI： 10.5794/jjoms.53.499

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

27歳女。1997年に近医歯科を受診した際、左下顎乳犬歯晩期残存、X線検査にて左下顎犬歯に埋伏歯の残存を指摘されたが放置していた。2004年10月の口腔内所見で開口障害はなく、左下顎乳犬歯晩期残存を認め、下顎右犬歯〜左犬歯部唇側歯肉から移行部の皮膜粘膜はほぼ正常で骨様硬の膨隆を認めた。2005年1月に全身麻酔下腫瘍摘出術および左下顎犬歯抜歯術を行った。腫瘍は被膜で覆われ、周囲からの剥離は容易で左下顎3番を含み一塊として摘出した。本症例は腺様歯原性腫瘍の組織像中にcalcifying epithelial odontogenic tumorの組織像を含んでいたことから、病理組織学的にcombined epithelial odontogenic tumorと診断された。術後9ヵ月経過した現在、創部経過は良好である。

DOI： 10.5794/jjoms.52.498

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Language：Japanese   Publisher：日本癌学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Language：Japanese   Publisher：Higashikyushu Junior College  

Previously we reported that Dark-Agouti (DA) rat strain is highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer (TC), whereas Wistar-Furth (WF) rat strain is resistant. Linkage analysis of reciprocal (DAxWF) F2 rats demontstrated five quantitative trait loci (QTLs), named &#039;Tongue squamous cell carcinoma 1-5 (Tscc1-5)&#039;, determining the size and number of the TCs. The major susceptibility locus Tscc1 is mapped on rat chromosome 19. In the present study, we used a marker-assisted speed congenic procedure to construct a special congenic strain of rats, i.e., WF rats carrying a DA-derived Tscc1 chromosomal segment between D19Wox8 and D19Wox7 on chromosome 19. We, now, call it &#039;WF.DA-Tscc1 (WF-T1D) strain of rats&#039;. Using this newly established rat strain we evaluated the effect of a single Tscc1 on 4NQO-induced tongue carcinogenesis. In WF-T1D rats the incidence, number and size of 4NQO-induced TCs were significantly higher than those in WF rats. It is appropriate to consider that the introgressed segment contains one of the susceptibility loci for 4NQO-induced TCs in the rats. Otherwise, we found out a single nucleotide-polymorphism between the DA and WF rats in NQO1, which is one of the candidate genes of Tscc1, and subsequently we mapped NQO1 in the Tscc1 segment on chromosome 19. NQO1-polymorphism should be considered possible relevance to TC susceptibility.

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(公財)化学療法研究会  

4-nitroquinoline 1-oxide(4NQO)誘発舌癌に感受性の強いDark-Agouti系ラットと抵抗性を示すWistar/Furth系ラットを2世代交配させて作成したF2ラットの検索から,5つのQTLを見出した.第5染色体のsuggestiveなレベルに達しているQTLの近辺に癌抑制遺伝子であるP15INK4BおよびP16INK4Aが座位を占めることがわかっている.今回,この2つの遺伝子に注目し,これらの遺伝子の発癌にかかわる重要性について検討した.遺伝子P15INK4BおよびP16INK4AのLOHや点突然変異などの遺伝子の変化がラットの舌癌の進展に寄与していることが推定された.このことから,遺伝子P15INK4BおよびP16INK4Aが4NQO誘発舌癌発生ラットモデルにおいて,治療面に応用すべきターゲット修飾遺伝子である強い可能性が示唆された

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Language：Japanese   Publisher：日本癌学会  

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Language：Japanese   Publisher：(公財)化学療法研究会  

Quantitative trait loci(QTL)解析を行って,推計学的に有意水準に達した5つのQTLs[Tongue squamous cell carcinoma 1〜5(Tscc1〜5)]および推計学的にsuggestive levelの3つのQTLsを見出した.Tscc2,Tscc3およびTscc4の3つのQILsは癌抑制型遺伝子として機能している可能性が指摘された.推計学的にsuggestive levelの3つのQTLsについては,それぞれの最大の候補遺伝子として癌抑制遺伝子のp15/p16,Msh2,Tp53が考えられた.それに対応するかのごとく,LOHの頻度はやや高かった.反対にTscc3は癌抑制遺伝子の可能性が云々されたにもかかわらず,マップ上の位置からは,Ha-ras遺伝子が候補遺伝子として最有力の一つであり,さらに本遺伝子のLOHの頻度がこの領域では最大であった.Ha-ras,p15/p16,Msh2,Tp53における点突然変異の有無とその頻度について検索を行った.腫瘍のサイズが大きくなるにしたがって各領域におけるLOHと上記の諸遺伝子の変異の発生頻度が高くなることがわかった

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Language：Japanese   Publisher：(一社)日本小児口腔外科学会  

5歳男児.口腔内より出血が認められた.顔貌は左右非対称で,左頬部にクルミ大の骨様硬の膨隆が認められた.エックス線所見等から根尖性歯周炎,上顎歯槽骨炎を疑った.局所麻酔下に歯肉部を試験切除を施行した.試験切除組織の病理組織学的診断は上顎骨血管腫であった.出血の頻度と出血重の増加がみられるようになり,上顎骨にかけての膨隆も増大傾向を示した.全身麻酔下に血管造影施行し,腫瘍は顎動脈,顔面動脈の分枝各2本により栄養され,顎動脈の支配領域が大きいことを確認した.又,出血量の減少,顔面の成長,皮膚の壊死防止を考慮して,顎動脈の枝2本に対して塞栓術を施行した.依然持続的に出血があるため,全身麻酔下に左上顎腫瘍切除術,頬脂肪体移植を行った.術後経過は順調で,上顎骨欠損部の縮小と上皮化が認められたため,退院した

DOI： 10.11265/poms1991.13.2_36

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J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Reasons for early onset skin cancer are poorly understood. Microarray analysis revealed overexpression of the Scca2 gene in the 12-O-tetradecanoylphorbol-13-acetate-treated skin of Car-S mice, or line phenotypically selected for high susceptibility to two-stage skin carcinogenesis, as compared with 12-O-tetradecanoylphorbol-13-acetate-treated skin of Car-R mice, which is resistant. A human skin squamous cell carcinoma cell line (NCI-H520) transfected with mouse Scca2 or a related gene, Scca2-rs1, both expressed in the skin, showed significantly increased tumor growth as compared with controls when injected in nude mice. Immunohistochemical analysis of samples from two independent series of Italian and Korean patients with squamous cell carcinoma of the skin indicated a significant association between SCCA2 protein expression and younger age at tumor onset. These findings provide evidence that SCCA2-like serpins mediate genetic predisposition to skin cancer in a mouse model and in humans.

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Language：English   Publisher：Japanese Society for Oral Pathology  

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J-GLOBAL

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In our previous study, Dark-Agouti (DA) rats were found to be highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue carcinoma (TC), whereas Wistar/Furth (WF) rats were barely susceptible. Interval mapping analysis of reciprocal backcross rats showed two quantitative trait loci (QTL) on rat chromosomes (RNO) 1 and 19. In the present study, a composite interval mapping analysis was applied to 4NQO-induced TC in 130 (DAxWF) F2 rats, demonstrating five independent QTL, Tongue squamous cell carcinoma 1-5 (Tsccl-5), responsible for phenotypic differences in the size and number of TCs in the two strains. Two of these QTL were mapped on RNO1, and the others were mapped on RNO4, 14, and 19. The DA allele at these loci consistently yielded semidominant susceptibility to TC. Out of the five loci detected in this F2 generation, Tscc1 and 2 were identical to Stc1 and Rtc1 described in our previous study, but the other three were novel. We propose a new nomenclature consistent with their function. Genome-wide screening of the F2 progeny also suggested the presence of three additional QTL on RNO5, 6, and 10. The possible roles of these loci in tongue carcinogenesis are discussed.

DOI： 10.1111/j.1349-7006.2001.tb01138.x

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Language：Japanese   Publisher：(一社)日本病理学会  

J-GLOBAL

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Language：English   Publisher：Urban und Fischer Verlag Jena  

Oral administration of 4-nitroquinoline 1-oxide (4NQO) to rats induced a high incidence of tongue carcinomas (TCs). The inbred Dark-Agouti (DA) strain of rats showed much higher susceptibility to 4NQO-induced TCs than the Wistar-Furth (WF) strain. Our previous study on crosses between the two strains postulated a semidominant susceptibility gene in DA and a semidominant resistance gene in WF rats. This hypothesis was confirmed by the genetic analysis of the backcrosses to either parent with PCR-based microsatellite assay. Using the number of TCS with &gt
5 mm diameter as a quantitative parameter, we mapped a quantitative trait locus Stc1 (Susceptibility to TC) favouring TC development near the locus D19Mit9 on Chr. 19 with a peak LOD scare of 6.08. Two other regions in Chr. 3 and Chr. 14 showed weak linkage for susceptibility, but were not statistically significant. On the other hand, another quantitative trait locus Rtc1 (Resistance to TC) providing resistance to TCs was mapped on Chr. 1 between the loci of D1Mit1 and D1Mit3 with a peak LOD score of 3.30. Quantitative parameters such as the number of tumours in the tongue or upper alimentary tract, the frequency of larger tumours and their maximum size were closely correlated and principally determined by Stc1 and Rtc1. Therefore the susceptibility to 4NQO-induced TCs in crosses between DA and WF is explained by the combinations of genotypes at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.

DOI： 10.1016/S0939-8600(00)80034-6

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：English   Publisher：AMER ASSOC CANCER RESEARCH  

The incidence of tongue carcinomas (TCs) induced by oral administration of 4-nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA) strain showed a much higher susceptibility to large mass-forming infiltrative TCs than did the Wistar-Furth (WF) strain, Our previous study (M. Kitano et at, Jpn. J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains postulated a dominant susceptibility gene in DA and a dominant resistance gene in WF rats. The present study mapped these loci by analyzing the backcrosses to each parent with simple sequence repeat polymorphisms. Five quantitative parameters were analyzed: (a) the number of TCs &gt; 5 mm in diameter; (b) the total number of TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number of non-TC cancers per rat; and (e) and the number of cancers of any site per rat. All of these parameters were closely correlated (P &lt; 0.0001). DA rats had a semidominant gene (Stc1) favoring the development of il-nitroquinoline 1-oxide-induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of 5.72 for the number of large TCs and 6.08 for the DTCmax. On the other hand, WF rats had a semidominant gene (Rtc1) mapped between D1Mit1 and D1Mit3, similar to 20 cM from D1Mit1, with a peak lod score of 3.30 for both the number of large TCs and the DTCmax. The main effect of Rtc1 seemed to be to reduce the size of the TCs. The action of these genes was dose dependent and cooperative. The final incidence of TC in DA, WF, Fl, and backcross rats seemed to be explained by combinations of genotype at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.

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Language：English   Publisher：Lippincott Williams and Wilkins  

In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estrogen receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and -untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.

DOI： 10.1097/00004347-199804000-00007

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Language：English   Publisher：INT INST ANTICANCER RESEARCH  

Correlation between expression status of bcl-2 products and cell growth fraction (estimated by immunostaining for Ki-67 antigen) was analyzed in human endometrial adenocarcinoma tissue in situ. For this, serial sections, 2 micrometers thick, from formalin-fixed and paraffin-embedded tissue samples of 10 cases of the carcinoma were examined. Nine out of 10 carcinomas contained both bcl-2 positive and negative nests when examined immunohistochemically. In the remaining one case no positive reaction for bcl-2 was observed In general bcl-2 positive nests tended to contain quiescent (Ki-67 negative) carcinoma cells, and bcl-2 negative nests, on the contrary, a large fraction of proliferating (Ki-67 positive) cells. However; this correlation was not strict, and in a few nests, the level of growth fraction was observed to be similar in irrespective of bcl-2 positivity. These results show the complex function(s) of bcl-2 products, when considering their apoptosis-suppressing effects, cell cycle dependence and influence on cell proliferation status. Further the results suggest an altered regulation of oncogene products in human solid tumor tissue in vivo.

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Language：English   Publisher：INT INST ANTICANCER RESEARCH  

In situ estimation of DNA fragmentation by the nick end labelling (NEL) method, and immunohistochemical examination of Ki-67 proliferative antigen and bcl-2 products in human endometrial adenocarcinoma tissues were performed to provide answers to the following two questions; a) does apoptotic DNA fragmentation occur specifically in quiescent cells or in proliferating cells or randomly in both?, b) does the bcl-2 product exert its apoptosis-suppressing effects differentially on carcinoma cells depending on their cell cycle condition?. Serial sections, one micrometer in thickness, from formalin-fixed and paraffinembedded tissues of 9 cases of human endometrial adenocarcinoma were examined. Apoptotic DNA fragmientation was observed in both quiescent (Ki-67 negative) and proliferating (Ki-67 positive) cells. Bcl-2 product-positive tumor cell islands tended to be NEL negative, although a few but non-negligeable number of carcinoma cells, including both Ki-67 positive and negaitive ones, were NEL positive. These results indicate chat, at least in human endometrial adenocarcinomas, apoptotic DNA fragmentation and bcl-2 product-independent (DNA) fragmentation occurs non-specifically with respect to the cell proliferation status. Further, the results suggest an altered regulation of cell death processes in human solid tumor tissue in vivo.

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Language：English   Publisher：INT INST ANTICANCER RESEARCH  

Seven cases of endometrial adenocarcinoma patients who had experienced long-term tamoxifen treatments as adjuvant therapy of breast carcinoma, were investigated with respect to estrogen receptor (ER) status. Four cases of endometrial adenocarcinoma without tamoxifen treatment but with a previous history of breast carcinoma were investigated for comparison. One of the 7 and two of the 4 cases were positive for ER immunohistochemically. Thus, the frequency of ER positivity in secondary endometrial adenocarcinoma seemed to be at random among tamoxifen-treated and non-treated br east cancer patients. These results suggest that tamoxifen-mediated human endometrial carcinogenesis may not involve estrogenic pathway(s) but may involve other carcinogenic mechanisms such as DNA adduct formation as shown in rat liver tumorigenesis.

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Language：English   Publisher：INT INST ANTICANCER RESEARCH  

Immunohistochemical detection of bcl-2 products and in situ estimation of DNA fragmentation during apoptosis by the nick end labelling method were performed to establish any correlation between these two apparently opposing processes in human solid tumors. Serial sections, one micrometer in thickness, from formalin-fixed and paraffin-embedded tissues of 10 cases of human endometrial adenocarcinoma were examined using the two techniques. A significant fraction of carcinoma cells were found to be stained by both methods, although there existed a general tendency for bcl-2 expression to be negatively correlated with DNA fragmentation in carcinoma tissue. The results thus suggest that bcl-2 expression doses not always block apoptosis, and that simultaneous application of bcl-2 immunostaining and DNA nick end labeling is useful for showing the complex nature of apoptosis in histologic slides, especially in gynecological cancers.

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Language：English   Publisher：INT INST ANTICANCER RESEARCH  

In situ estimation of DNA fragmentation by the nick end labeling method and immunohistochemical detection of cell surface carbohydrate Le(y) were performed to establish correlation between the results of these two apoptosis-detecting techniques in human solid tumor tissues. Formalin-fixed and paraffin-embedded tissue samples from 10 cases of human endometrial adenocarcinoma were examined adn compared by using the two techniques. A substantial fraction of carcinoma cells was found to be definitely stained by both methods, although Le(y) expression did not seem to be positively correlated with DNA fragmentation in the carcinooma tissue. These results suggest that Le(y) expression does not necessarily reflect apoptotic DNA fragmentation, at least in human endometrial adenocarcinomas, and simultaneous application of DNA nick end labeling and Le(y) immunostaining is necessary to show the relevant signs of apoptosis in histologic slides, especially gynecological cancers.

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Language：English   Publisher：Japanese Cancer Association  

We analyzed the incidence of infiltrative mass-type tongue carcinomas (IMTC) induced in 550 rats by continuous oral administration of 0.001% 4-nitroquinoline 1-oxide solution for 180 days. The study included various crosses of susceptible Dark-Agouti rats (DA) and resistant Wistar/Furth rats (WF). DA showed a 93.6% incidence of IMTC measuring more than 5 mm in their largest diameter, while WF showed only a 4% incidence. Reciprocal F1 and F2 hybrids mated by DA and WF showed 47.5% and 45.8% incidences, respectively. Meanwhile, reciprocal backcrossed hybrids to DA and WF showed 73.7%, and 24.6% incidences, respectively. Segregation of the incidences suggests that there are two autosomal dominant genes, one linked to the susceptibility of DA and the other to the resistance of WF.

DOI： 10.1111/j.1349-7006.1996.tb03116.x

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Expression of ras p21 oncoproteins in human ovarian carcinomas was examined immunohistochemically by using a monoclonal antibody(clone RAS 10) with respect to the degree of their histological differentiation. To achieve this, the intensity of staining for the protein was compared between undifferentiated and well differentiated carcinomas, i.e. extreme subtypes of common epithelial carcinomas. The former was composed of 8 'solid' carcinomas and the latter
11 serous, 8 mucinous, 4 endometrioid and 4 clear cell carcinomas. All the cases examined, including both undifferentiated and well-differentiated carcinomas, showed a positive reaction to this antibody. Staining intensity and the number of positive cells somewhat varied among the cases. Additionally, 2 cases of ovarian epithelial tumors of low malignant potential (I,MP) were stained with this antibody. Both the cases were positive, but the number of positive cells seemed to be rather less than than that found in the carcinoma groups. Thus, no differences in ras p21 expression were observed between the cases examined in spite of the differences in the degree of differentiation of the epithelial ovarian carcinomas. However
the possibility remained that the number of positive cells could be an indicator of malignant potential, enabling us to distinguish LMPs from carcinomas. Thus immunodetection of ras p21 could not provide an additional means for the histological differentiation of ovarian cancer although the evaluation of basement membrane integrity and cell proliferation kinetics as reported previously was useful in differential diagnosis and in understanding the biology of ovarian undifferentiated carcinomas.

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Language：English   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：English   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：English   Presentation type：Oral presentation (invited, special)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Language：English   Presentation type：Oral presentation (invited, special)  

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Language：English   Presentation type：Oral presentation (invited, special)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (invited, special)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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