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

DOI： 10.1016/j.oooo.2022.04.042

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OBJECTIVE: The aim of this study was to examine the clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy (IACRT) using cisplatin in combination with oral S-1 (tegafur/gimeracil/oteracil potassium) on stage III and IV oral squamous cell carcinoma. STUDY DESIGN: Thirty patients received infusions of superselective intra-arterial cisplatin 60 mg/m2 by the Seldinger method and conventional external beam radiotherapy (total 40 Gy) combined with oral S-1 on the day of irradiation. Curative surgery and neck dissection were performed 4 to 6 weeks after IACRT. The clinical response of the primary lesion was evaluated approximately 4 weeks after IACRT. The surgically resected specimens were examined for histologic features according to the grading system for histologic evaluation and for residual tumor grade (RGrades). RESULTS: Histopathologic evaluation of the therapeutic effect was grade 2 in 10 patients and grade 3 in 16 patients. According to the distribution of RGrades, the remaining tumor cells were mostly in the central area of the primary lesion, as seen in 24 patients. CONCLUSIONS: These findings indicate that neoadjuvant IACRT with cisplatin and oral S-1 was an effective treatment, suggesting the possibility of reducing the extent of curative surgery based on RGrades.

DOI： 10.1016/j.oooo.2022.04.042

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

Long noncoding RNAs (lncRNAs) are deeply involved in cancer development. We previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is one of the lncRNAs overexpressed in oral squamous cell carcinoma (OSCC) cells, where it exhibits oncogenic activity. In the present study, we further clarified the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that DLEU1 knockdown induced significant changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, DLEU1 knockdown suppressed levels of H3K4me3/ H3K27ac and expression of a number of interferon-stimulated genes (ISGs), including IFIT1, IFI6 and OAS1, while ectopic DLEU1 expression activated these genes. Western blot analysis and reporter assays suggested that DLEU1 upregulates ISGs through activation of JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, was frequently overexpressed in primary OSCC tumors, and its knockdown inhibited OSCC cell proliferation, migration and invasion. These findings suggest that DLEU1 exerts its oncogenic effects, at least in part, through activation of a series ISGs in OSCC cells.

DOI： 10.1038/s41598-021-99736-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research USA Inc.  

BACKGROUND/AIM: The role of tumour-infiltrating CD45Ro+ T-cells in oral squamous cell carcinoma (OSCC) is unclear. This study aimed to evaluate prognostic biomarkers for OSCC. PATIENTS AND METHODS: We determined the density of tumour-infiltrating CD45Ro+ T cells in the parenchyma and stroma at the tumour centre (TCe) and invasive front (IF) and examined the association between the density of these cells and histopathological status in 142 patients. RESULTS: Five-year overall survival (OS) and recurrence-free survival were favourable in patients with high CD45Ro+ T-cell density in the TCe stroma. OS was favourable in patients with high CD45Ro+ T-cell density in the IF stroma. Stepwise Cox regression model analysis indicated that CD45Ro+ T-cells in the stroma of the IF and TCe were an independent prognostic factor for OS. CONCLUSION: CD45Ro+ T-cells in the stroma of the IF and TCe play a role in cancer immune surveillance and may be a useful prognostic factor.

DOI： 10.21873/anticanres.15262

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

Ichushi

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

DOI： 10.1016/j.ajoms.2020.12.012

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

BACKGROUND: Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. METHODS: We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. RESULTS: Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front. CONCLUSIONS: The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4+ cells suppress the function of FoxP3+ T-cells and promote anti-tumor immunity in OSCC.

DOI： 10.1371/journal.pone.0237465

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

Human leukocyte antigen (HLA) class Ⅰ molecules play a central role in anticancer immunity, but their prognostic value in oral squamous cell carcinoma (OSCC) remains unclear. We examined HLA class I expression in 2 distinct tumor compartments, namely, the tumor center and invasive front, and evaluated the association between its expression pattern and histopathological status in 137 cases with OSCC. Human leukocyte antigen class Ⅰ expression was graded semiquantitatively as high, low, and negative. At the invasive front of the tumor, HLA class I expression was high in 72 cases (52.6%), low in 44 cases (32.1%), and negative in 21 cases (15.3%). The HLA class I expression in the tumor center was high in 48 cases (35.0%), low in 58 cases (42.4%), and negative in 31 cases (22.6%). The 5-year overall survival and disease-specific survival rates were good in cases with high HLA class I expression at the invasive front; however, there was no significant difference in survival based on HLA class I expression in the tumor center. In addition, high HLA class I expression was correlated with high CD8+ T cell density, whereas negative HLA class I expression was correlated with low CD8+ T cell density at the invasive front. These results suggest that it is easier for CD8+ T cells to recognize presented peptides in the case of high HLA class Ⅰ expression at the tumor invasive front and could be a prognostic factor for OSCC.

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14388

DOI： 10.1111/cas.14388

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

DOI： 10.1016/j.oraloncology.2019.104509

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

The most important prognostic factor in oral squamous cell carcinoma (OSCC) is neck metastasis, which is treated by neck dissection. Although selective neck dissection (SND) is a useful tool for clinically node-negative OSCC, its efficacy for neck node-positive OSCC has not been established. Sixty-eight OSCC patients with pN1–3 disease who were treated with curative surgery using SND and/or modified-radical/radical neck dissection (MRND/RND) were retrospectively reviewed. The neck control rate was 94% for pN1–3 patients who underwent SND. The five-year overall survival (OS) and disease-specific survival (DSS) in pN1-3 OSCC patients were 62% and 71%, respectively. The multivariate analysis of clinical and pathological variables identified the number of positive nodes as an independent predictor of SND outcome (OS, hazard ratio (HR) = 4.98, 95% confidence interval (CI): 1.48–16.72, p < 0.01; DSS, HR = 6.44, 95% CI: 1.76–23.50, p < 0.01). The results of this retrospective study showed that only SND for neck node-positive OSCC was appropriate for those with up to 2 lymph nodes that had a largest diameter ≤3 cm without extranodal extension (ENE) of the neck and adjuvant radiotherapy. However, the availability of postoperative therapeutic options for high-risk OSCC, including ENE and/or multiple positive lymph nodes, needs to be further investigated.

DOI： 10.3390/cancers11020269

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

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved survival in head and neck squamous cell carcinoma. However, the prognostic value of TILs remains unclear in oral squamous cell carcinoma (OSCC). METHODS: We evaluated the associations between tumor-infiltrating CD8+ T-cell density and survival in five distinct compartments in 139 OSCC cases. RESULTS: There was a significant association between increased tumor-infiltrating CD8+ T cells and their distribution. High parenchymal CD8+ T-cell density at the invading tumor edge was associated with improved overall survival (OS) and disease-specific survival (DSS; P < 0.01 and P < 0.01, respectively). High stromal CD8+ T-cell density at the tumor periphery was also associated with improved recurrence-free survival (RFS; P < 0.01). Cox regression analysis revealed that high stromal CD8+ T-cell density at the tumor periphery and high parenchymal CD8+ T-cell density at the invading edge were independent prognostic makers (hazard ratio: 0.38 and 0.19, 95% confidence interval, 0.18-0.80 and 0.05-0.72, P = 0.01 and 0.01, respectively) for RFS and OS, respectively. CONCLUSIONS: Assessment of CD8+ T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis.

DOI： 10.1002/cam4.1889

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

Other Link： http://link.springer.com/article/10.1186/s12903-018-0572-9/fulltext.html

DOI： 10.1186/s12903-018-0572-9

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：IOS Press  

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/1010428318800180

DOI： 10.1177/1010428318800180

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

DOI： 10.1038/s41419-018-0893-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 (24%) had pathologically proven regional metastasis. The mode of invasion (p<0.01) and tumor budding (p<0.01) were associated with regional metastasis as well as lymphovascular invasion (p = 0.04) in univariate analysis. In logistic regression analysis, however, tumor budding was the only independent predictor of regional metastasis (hazard ratio (HR) = 3.05, 95% confidence interval (CI) = 0.29-5.30, p<0.01). All three invasive patterns, the mode of invasion, WPOI, and tumor budding, were found to be significant predictors of 5-year disease-free survival (p<0.01, p = 0.03, and p<0.01, respectively) as well as lymphovascular invasion (p = 0.02) and perineural invasion (p = 0.02). A final model for Cox multivariate analysis identified the prognostic advantage of the intensity of tumor budding (HR = 2.19, 95% CI = 1.51-3.18, p<0.01) compared with the mode of invasion and WPOI in disease-free survival. Our results indicate that the intensity of tumor budding may be a novel diagnostic biomarker, as well as a therapeutic tool, for regional metastasis in patients with cT1,2N0M0 OSCC. If the pancytokeratin-based immunohistochemical features of more than five buds, and a grade 4C or 4D mode of invasion are identified, careful wait-and-see follow-up in a short period with the use of imaging modalities is desirable. If there are more than ten buds, a grade 4D mode of invasion, or WPOI-5 in the same section, wide resection of the primary tumor with elective neck dissection should be recommended.

DOI： 10.1371/journal.pone.0195451

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Impact Journals, LLC  

DOI： 10.18632/oncotarget.19262

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/jop.12606

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Cleft Palate Craniofacial Association  

DOI： 10.1597/14-329

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

DOI： 10.1016/j.oooo.2016.06.008

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Impact Journals, LLC  

DOI： 10.18632/oncotarget.11366

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Language：English  

DOI： 10.1158/1538-7445.AM2016-3707

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Ichushi

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

DOI： 10.1016/j.ajoms.2015.08.006

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Language：Japanese  

Other Link： http://ir.cc.sapmed.ac.jp/dspace/handle/123456789/6606

DOI： 10.15114/smj.84.7

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

Carcinoma ex pleomorphic adenoma mainly occurs in the major salivary gland, and a tissue type of myoepithelial carcinoma is extremely rare in the minor salivary gland.<br>We report a case of myoepithelial carcinoma ex pleomorphic adenoma of the hard palate in a 65-year-old man. At presentation, a tumor measuring 23 × 16 mm, which had a painless elastic hard, smooth surface and clear border, was found in the right side of the hard palate. Computed tomographic scanning and magnetic resonance imaging indicated the suspicion of malignancy. Histological examination suggested a myoepithelial carcinoma. A partial maxillectomy combined with a supraomohyoid neck dissection was performed. The histological diagnosis of the resected specimen was a myoepithelial carcinoma ex pleomorphic adenoma. There has been no sign of recurrence as of 2 years postoperatively.

Other Link： https://jlc.jst.go.jp/DN/JLC/20009068474?from=CiNii

DOI： 10.5794/jjoms.61.173

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/jop.12028

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Language：Japanese   Publisher：(一社)日本癌治療学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Ichushi

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

DOI： 10.1074/jbc.m111.321828

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Language：Japanese   Publisher：(一社)日本癌治療学会  

Ichushi

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

We examined the clinical features of bisphosphonate(BP)-related osteonecrosis of the jaws(BRONJ), a serious complication resulting from intravenous BP treatment for multiple myeloma and malignant tumors with bone metastasis. We retrospectively reviewed the medical records of 36 patients who received intravenous BP therapy for the above-mentioned conditions, at Sapporo Medical University Hospital between July 2006 and October 2008. BP therapy caused BRONJ in 7 of 24 patients, but did not affect the bones of the other 17 patients. The other 12 of the 36 patients involved in the study were prescribed BP only after they had undergone an oral examination and treatment for dental inflammation. Of these patients, 7 developed BRONJ with BP treatment, after tooth extraction or acute dental inflammation. Treating dental inflammation before prescribing BP prevented the development of BRONJ. BRONJ is highly intractable and does not resolve with the standard treatment for osteomyelitis. Therefore, preventive therapy, which can be achieved by cooperation between medical doctors and dentists, is currently the most effective strategy for BRONJ. Conservative treatment with antibiotics may also be useful for maintaining or improving the quality of life of BRONJ patients.

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Language：Japanese   Publisher：(一社)日本癌治療学会  

Ichushi

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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

Ichushi

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

DOI： 10.1016/j.ccr.2007.05.006

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Language：Japanese   Publisher：(一社)日本癌学会  

Ichushi

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Language：English  

BACKGROUND: Antitumor effects of chemotherapeutic agents are commonly associated with the induction of apoptosis. Bax belongs to the Bcl-2 family and induces apoptosis. The present study was conducted to investigate the relationship between enhanced Bax expression in oral squamous cell carcinoma (SCC; cell lines and clinical cases) and the antitumor effects of chemotherapy. METHODS: In three oral SCC cell lines, Bax expression before and after treatment with chemotherapeutic agents [docetaxel (TXT), cisplatin and 5-fluorouracil] was examined by reverse transcriptase-polymerase chain reaction and immunoblotting. The effects of treatment were assessed by counting the number of viable cells and determining sub-G1 cells. Tissue samples (both biopsy specimens before chemotherapy and surgically excised specimens after chemotherapy) from nine patients with oral SCC who underwent neoadjuvant chemotherapy were immunostained for Bax. The relationship between enhancement of Bax expression and chemotherapeutic effects was established. RESULTS: Two of three cell lines did not express Bax mRNA or protein before treatment. After treatment, Bax expression was enhanced only by TXT in one cell line, but by all chemotherapeutic agents in the other two cell lines. In three of nine patients, Bax expression was not found before chemotherapy. Two of these three patients showed enhanced Bax expression after chemotherapy including TXT, but one still failed to express Bax. Both in cell lines and clinical cases, enhancement of Bax after chemotherapy was associated with antitumor effects. CONCLUSION: Certain chemotherapeutic agents enhance Bax expression in oral SCC, and it is suggested that this contributes to the antitumor effects of chemotherapy.

DOI： 10.1111/j.1600-0714.2004.00257.x

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Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin-ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, we analyzed the pattern of CHFR expression in a number of human cancer cell lines and primary tumors. We found CpG methylation-dependent silencing of CHFR expression in 45% of cancer cell lines, 40% of primary colorectal cancers, 53% of colorectal adenomas, and 30% of primary head and neck cancers. Expression of CHFR was precisely correlated with both CpG methylation and deacetylation of histones H3 and H4 in the CpG-rich regulatory region. Moreover, CpG methylation and thus silencing of CHFR depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3b, as their genetic inactivation restored CHFR expression. Finally, cells with CHFR methylation had an intrinsically high mitotic index when treated with microtubule inhibitor. This means that cells in which CHFR was epigenetically inactivated constitute loss-of-function alleles for mitotic checkpoint control. Taken together, these findings shed light on a pathway by which mitotic checkpoint is bypassed in cancer cells and suggest that inactivation of checkpoint genes is much more widespread than previously suspected.

DOI： 10.1073/pnas.1337066100

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1158/1538-7445.AM2015-4905

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Language：Japanese   Publisher：(一社)国際個別化医療学会  

Ichushi

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

Solitary fibrous tumor (SFT) is a rare benign tumor that occurs mainly in the pleura; however, it can also arise in other extrapleural sites, including the oral cavity. In 2002, the World Health Organization classified SFT as a tumor of intermediate malignancy characterized by metastases to the lung, bone and, rarely, liver. We report a case of SFT in the left side of the buccal region. A 52-year-old woman visited our hospital in June 2005 because of a painless swelling on the left side of the buccal region. A CT scan and MRI showed awell-defined solid tumor in the left side of the buccal region. The tumor was surgically resected, and histopathological examination revealed a SFT. There has been no recurrence ofthe tumor for 18 months since the operation. We review the literature with regard to the clinicopathologic features of SFT.

DOI： 10.5794/jjoms.54.54

J-GLOBAL

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Language：Japanese  

DOI： 10.5843/jsot.15.191

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Language：Japanese   Publisher：(一社)日本癌学会  

Ichushi

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Language：Japanese   Publisher：Japan Society for Oral Tumors  

Clinical examination of 24 N0 cases of squamous cell carcinoma of the tongue (10 cases), the floor of the mouth (10 cases), and mandibular gingiva (4 cases), which received unilateral supraomohyoid neck dissection, was retrospectively performed.&lt;BR&gt;Pathologically, lymph node metastasis was recognized in 8 cases (33.3%) of which prognoses are good. Among the 16 patients in which pathologically lymph node metastasis was not recognized, 1 patient had died of cervical lymph node metastasis, found after surgery, and the other 15 patients were surviving without recurrence or metastasis.&lt;BR&gt;Three metastatic lymph nodes (LNs) were recognized in 1 case, and 1&#039; LN in 7 cases. LNs were located in level 1 in 6 cases, and in level 2 in 2 cases. An extracapsular metastatic lesion was found in level 1 in 1 case. Histopathological malignancy of the primary lesion was relatively high in most of the cases examined.&lt;BR&gt;From the results, it is suggested that supraomohyoid neck dissection may be effective not only for diagnosis but also for therapy, considering the histopathological malignancy of the primary lesion.

DOI： 10.5843/jsot.13.Suppliment_319

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Language：Japanese  

DOI： 10.5843/jsot.13.23

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

We clinically examined 29 patients with squamous cell carcinoma of tongue, floor of the mouth, and maxillary gingiva who received unilateral functional neck dissection with preservation of the sternocleidmastoid muscle, internal jugular vein, and/or accessory nerve.&lt;BR&gt;The 5-year cumulative survival rate of all patients was 80.4%, that of 19 pN (+) patients was 68.6%, and that of 10 pN (-) patients was 100%. Pathologically, 4 metastatic lymph nodes (LNs) were found in 1 patient, 3 LNs in 3 patients, 2 LNs in 6 patients, and 1 LN in 9 patients. LNs were located in level 1 in 5 paitents, level 2 in 12, and level 4 in 2. Extranodular metastatic lesions were found in level 1 in 1 patient and in level 2 in 4. Among the patients with a poor prognosis, 2 LNs were found in 2 patients, 3 LNs in 1, and 4 LNs in 1, extranodular lesions were found in 2 patients, and LNs were located in level 2 in all patients.&lt;BR&gt;Our results suggest that functional neck dissection is indicated for patients who have single and movable nodular metastatic lymph node.

DOI： 10.5794/jjoms.46.655

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