Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus ...are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.
Steroid has recently been reported as a treatment for new coronavirus disease (COVID-19). The incidence of oropharyngeal candidiasis due to the inhaled steroid ciclesonide is lower than that due to ...other inhaled steroids. We report the first case of oral candidiasis with COVID-19 pneumonia using ciclesonide. A 75-year-old man was hospitalized for COVID-19 pneumonia. After admission, an oral combination of lopinavir/ritonavir was administered, and ciclesonide was inhaled for 7 days. On the 14th day of hospitalization, white plaque was found in his oral mucosa. Candida albicans was identified by oral bacterial tests, and amphotericin B was initiated. On the 35th hospital day, negative result for C. albicans was confirmed. Intraoral monitoring and intervention by dental care workers are considered important for the prevention of infectious complications induced by corticosteroids.
Preoperative intra-arterial chemoradiotherapy (IACRT) can improve the outcome and reduce the extent of surgery in patients with advanced oral cancer. However, the response to this regimen varies ...among patients, which may be related to the immune status of the tumor. We investigated the effects of proteins involved in tumor immunity on the outcomes of combined IACRT and surgery for oral cancer. We examined CD8 + and FoxP3 + tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on immune cells and tumor cells in pretreatment biopsy samples from 69 patients diagnosed with oral cancer treated with IACRT at our institution during 2000–2020. Patients with abundant CD8 + TILs had significantly better 5-year disease-specific survival (DSS) compared to that of patients with less infiltration of these cells (
P
= 0.016). Patients with higher FoxP3 + T-cells invasion had significantly better DSS compared to that of less FoxP3 (
P
= 0.005). Patients with high PD-L1 expression in tumor cells and immune cells had significantly better DSS than that of patients with low PD-L1 expression in these cells (
P
= 0.009 and
P
= 0.025, respectively). Collectively, these results suggest that the tumor immune microenvironment could affect outcomes of IACRT treatment in oral cancer.
Colorectal cancer consists of a small number of cancer stem cells (CSC) and many non-CSCs. Although rare in number, CSCs are a target for cancer therapy, because they survive conventional chemo- and ...radiotherapies and perpetuate tumor formation
In this study, we conducted an HLA ligandome analysis to survey HLA-A24 peptides displayed by CSCs and non-CSCs of colorectal cancer. The analysis identified an antigen, ASB4, which was processed and presented by a CSC subset but not by non-CSCs. The
gene was expressed in CSCs of colorectal cancer, but not in cells that had differentiated into non-CSCs. Because
was not expressed by normal tissues, its peptide epitope elicited CD8
cytotoxic T-cell (CTL) responses, which lysed CSCs of colorectal cancer and left non-CSCs intact. Therefore, ASB4 is a tumor-associated antigen that can elicit CTL responses specific to CSCs and can discriminate between two cellular subsets of colorectal cancer. Adoptively transferred CTLs specific for the CSC antigen ASB4 could infiltrate implanted colorectal cancer cell tumors and effectively prevented tumor growth in a mouse model. As the cancer cells implanted in these mice contained very few CSCs, the elimination of a CSC subset could be the condition necessary and sufficient to control tumor formation
These results suggest that CTL-based immunotherapies against colorectal CSCs might be useful for preventing relapses.
.
Cystadenoma is a rare salivary gland benign tumor and consists of monolocular or multilocular cysts in the tumor. This type of tumor accounts for 2–4.7％ of all minor salivary gland tumors and it ...usually occurs on the lip, palate, and buccal mucosa, but rarely in the retro-molar region. We present a case of cystadenoma arising from the left retro-molar region in an 83-year-old male patient. The clinical evaluation showed a solitary mass of 15×18mm which was elastic soft, with a smooth surface, partially purply blue color, and a clear border. The MRI findings revealed that the tumor was well defined with rim-enhanced mass. The clinical diagnosis was a benign tumor. The lesion was resected under general anesthesia, and the histopathological diagnosis was cystadenoma. There was no evidence of recurrence 3 years after resection.
Background
During tumor development, cells are exposed to a hypoxic microenvironment. Tumor hypoxia also has a profound influence on the sensitivity of cancer chemotherapy.
The objective of this ...study was to investigate the mechanism of cisplatin (CDDP) resistance of oral squamous cell carcinoma (OSCC) cells under hypoxia by analyzing gene expression profiles to identify key genes and factors involved.
Methods
Cell viability was measured following culture of the cells in the presence or absence of CDDP, under normoxic or hypoxic conditions, using a CCK‐8 assay. Analysis of the expression of HIF target genes in hypoxia‐treated cells was performed using an HIF‐regulated cDNA plate array. Changes in the mRNA expression of selected HIF target genes were analyzed using RT‐PCR, and changes in the protein levels of these genes were analyzed by Western blotting. Tumor cell apoptosis was assessed by flow cytometry.
Results
The OSCC cell lines responded differently to CDDP under normoxic and hypoxic conditions. The expression of glucose transporter protein‐1 (GLUT‐1) was up‐regulated in human squamous cell carcinoma of mouth (HSC‐2) cells under hypoxia. Furthermore, there was little correlation between the cisplatin sensitivity of human squamous cell carcinoma of tongue (SAS) in normoxia and hypoxia. After GLUT‐1 knockdown, CDDP treatment resulted in increased rates of apoptosis under hypoxia as compared with normoxia in cell lines HSC‐2, Ca9‐22, and SAS (P = 0.025).
Conclusion
The results of this study suggest that knockdown of GLUT‐1 inhibits sensitization of oral squamous cells to CDDP during hypoxia in HSC‐2, Ca9‐22, and SAS cells.
Objectives
We evaluated the accuracy of estimating the cross-sectional area (CSA) at the third lumbar vertebra (L3) based on the CSA at the third cervical vertebra (C3) using computed tomographic ...images, and we identified the sources of error and bias using the evaluation of absolute reliability in 89 Japanese patients with oral squamous cell carcinoma.
Methods
Skeletal muscle CSA was measured at the C3 and L3 on pretreatment computed tomographic images. We used the CSA at the C3 to estimate CSA at the L3 in an existing prediction formula. Correlation coefficients were used to evaluate the relative reliability of the estimate, and Bland–Altman analysis and minimum detectable change (MDC) were used to evaluate its absolute reliability.
Results
Estimated and actual CSAs at L3 were strongly correlated (
r
= 0.885,
p
< 0.001). The mean difference between the estimated and actual CSAs was − 1.0887 cm
2
, the 95% confidence interval was − 4.09 to 1.91 cm
2
(
p
= 0.472), and the 95% limits of agreement were − 29.0 and 26.8 cm
2
. The MDC at the 95% level of confidence in estimated and actual CSAs was 27.9 cm
2
.
Conclusions
The estimation of CSA at the L3 from the existing prediction formula with the CSA at the C3 had no systematic biases, but it did have random errors. Random errors resulted from measurement errors and biological variation. Usefulness of the existing formula is limited by physical differences in populations.
Background
Aberrant Notch signaling pathway has been related with the tumorigenesis in head and neck region, involving oral cavity. Here, we report the correlation between mutations in the Notch ...signaling pathway and CD8+ T‐cell infiltration via PD‐L1, which lead to enhanced antitumor immunity and may target for immune‐checkpoint inhibitors (ICIs) therapy.
Methods
This retrospective study analyzed the results of immunohistochemical staining for PD‐L1 and CD8+ T‐cell infiltration in 10 patients and whole‐exome sequencing (WES) was conducted on five of these patients to identify frequently mutated genes.
Results
Four of 10 patients were positive for PD‐L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of ICI therapy with CD8+ T‐cell infiltration via PD‐L1 expression for oral squamous cell carcinoma patients with mutations in Notch signaling pathway.
Intravascular papillary endothelial hyperplasia is an unusual benign lesion of vascular origin. A 56-year-old man presented with a mass in the right side of the lower lip. Before visiting our ...hospital, he had undergone 3 surgical procedures for recurrence of the mass in a short period of time. Clinical examination revealed a painless, soft, elastic, dark purple obscure mass measuring 17 × 11 mm in the right lower lip. Ultrasonography and magnetic resonance imaging suggested a hemangioma-like lesion. The possibility of malignant transformation could not be ruled out because of the clinical course up to that point, even though it had been histopathologically diagnosed as hemangioma. The lesion was surgically resected and the defect was reconstructed using a vermilion advancement flap combined with a V-Y advancement flap. The histopathological diagnosis was intravascular papillary endothelial hyperplasia. The patient has had no symptoms or any evidence of recurrence in the 4 years since the operation. His postoperative progress has been favorable both functionally and aesthetically.
We report that the reactivity of a novel monoclonal antibody LpMab-23 for human cancer-type podoplanin (PDPN) is a predictor for a poor prognosis of tongue cancer.
The association between ...LpMab-23-recognizing cancer-type PDPN expression and clinical/pathological features were analyzed on 60 patients with stage I and II tongue cancer treated with transoral resection of the primary tumor.
In the mode of invasion, the LpMab-23-dull/negative cases were significantly larger in cases with low-grade malignancies and without late cervical lymph node metastasis, than in cases with high-grade malignancies and the metastasis. In the high-grade malignant cases, LpMab-23-positive cases were significantly larger than LpMab-23-dull/negative cases. The Kaplan-Meier curves of the five-year metastasis-free survival rate (MFS) were significantly lower in the LpMab-23 positive patients than in LpMab-23 dull/negative patients. The LpMab-23-dull/negative cases showed the highest MFS in all of the clinical/pathological features and particularly, the MFS of the LpMab-23 positive cases decreased to less than 60% in the first year. In the Cox proportional hazard regression models a comparison of the numbers of LpMab-23 dull/negative with positive cases showed the highest hazard ratio with statistical significance in all of the clinical/pathological features.
LpMab-23 positive cases may be considered to present a useful predictor of poor prognosis for early stage tongue cancer.
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