Nonspecific inflammatory pseudotumor of the maxillary and temporal fossa: a study of seven cases.

OBJECTIVE: Inflammatory pseudotumor (IPT) is a rare, locally aggressive, benign neoplasm of unknown etiology. Because of its aggressive clinical behavior and locally destructive or infiltrative features, it may be mistaken for a malignant tumor. Approximately 5%-44% of extrapulmonary IPT occur in the head and neck, primarily affecting the orbit. STUDY DESIGN: Between 2008 and 2021, our hospital received referrals for seven patients (three men and four women, aged 42-73 years) with pain, swelling, mass, and trismus. Computed tomography, magnetic resonance imaging, and biopsy were performed on all patients to diagnose IPT. RESULTS: Of the seven patients, four received low-dose prednisolone (PSL), one underwent surgery, and two were left untreated. The IPT disappeared in one of the two untreated cases, whereas it improved and later deteriorated in the other. The surgical patient had no recurrence. Low-dose PSL was effective in two patients; however, high-dose PSL and immunosuppressants were required in the remaining two cases owing to infiltration into each orbit or brain region. CONCLUSIONS: Low-dose PSL treatment was applicable in IPT cases affecting the maxillary to temporal fossa region, wherein symptoms did not improve without treatment. However, when low-dose PSL was ineffective, high-dose PSL and immunosuppressants were required.

Human antigen R knockdown attenuates the invasive activity of oral cancer cells through inactivation of matrix metalloproteinase-1 gene expression.

Background/purpose: The RNA-binding protein human antigen R (HuR) recognizes AU-rich elements in the 3'-untranslated regions of mRNA. The expression of cytoplasmic HuR is related to the malignancy of many carcinomas. The aim of this study is investigation of effect of HuR knockdown for invasive activity of oral carcinoma. Materials and methods: Proliferation, invasion, real-time PCR, and reporter gene assays were performed to confirm that the knockdown of HuR downregulates the invasive activity of cancer cells. Immunohistochemical staining was performed for high invasive carcinoma, squamous cell carcinoma (SCC) and low invasive carcinoma, verrucous carcinoma (VC), to determine if the localization of cytoplasmic HuR is related to matrix metalloproteinase-1 (MMP-1) expression. Results: Invasive activity was significantly lower in HuR knockdown cancer cells than in control cells. A luciferase assay revealed that HuR knockdown inactivated the promoter activity of the MMP-1 gene. The mRNA levels of the transcription factors required for MMP-1 expression, including c-fos and c-jun, were decreased in HuR knockdown cancer cells. Immunohistochemical analysis revealed the level of cytoplasmic HuR and MMP-1 in invasive carcinoma to be higher than in low invasive cancer. HuR induced MMP-1 expression in the invasive front of most SCC cases. Conclusion: HuR knockdown attenuated the invasive activity of cancer cells by decreasing the expression of the MMP-1, at least partially. HuR localization may help determine the invasive phenotype of cancer cells and inhibit cancer cell invasion. Furthermore, in oral SCC, HuR may be related to invasive activity through the expression of MMP-1.

Significant association of Yamamoto-Kohama classification and pathological depth of invasion with cervical lymph node metastasis in early-stage tongue squamous cell carcinoma (Stage I/II).

Background/purpose: Tongue squamous cell carcinoma (SCC) has a poor prognosis due to a high rate of cervical lymph node metastasis (CLNM). We aimed to determine clinicopathological features related to the prediction of CLNM in tongue carcinomas (Stage Ⅰ/Ⅱ). Materials and methods: Data from 89 patients with tongue SCC (Stage I/II) were analyzed retrospectively. Patients were treated only with partial glossectomy and not with chemotherapy or radiotherapy until CLNM was observed. No cervical lymph node metastasis survival (NCLNMS) was estimated using the Kaplan-Meier method. The difference in NCLNMS between the groups with and without CLNM was compared using the log-rank test. The Cox regression model was used to estimate hazard ratios and the associated 95% confidence interval. Results: Clinical T2, clinical and pathological depth of invasion (cDOI and pDOI, respectively) > 5 mm, Yamamoto-Kohama (YK)-4c, tumor budding ≥5, worst pattern of invasion -4/5, muscle invasion, perineural invasion, and grade of differentiation 3 were found to be significant CLNM risk factors. Conclusion: CLNM was observed in 25.8% of early-stage tongue carcinomas (Stage I/II). YK-4c and pDOI >5 mm were the most important CLNM risk factors identified. Close follow-up is needed after partial glossectomy when patients with tongue SCC have other risk factors, particularly YK-4c and pDOI >5 mm.

Amyloid Variant of Central Odontogenic Fibroma in the Mandible: A Case Report and Literature Review.

BACKGROUND Odontogenic fibroma is a rare mesenchymal odontogenic tumor. It can be classified as central odontogenic fibroma (COF) or peripheral odontogenic fibroma (POF) based on clinical features. There are several variants of COF, including amyloid, ossifying, and giant cell. It grows slowly and exhibits painless cortical expansion of the jawbone. Radiographically, COF appears as a radiolucent unilocular or multilocular lesion with well-defined borders. COF may be associated with unerupted or displaced teeth and root resorption. CASE REPORT A 35-year-old man was referred to our hospital for submandibular swelling. Panoramic radiography and contrast-enhanced computed tomography revealed a unilocular area of bone resorption with a well-defined border and equal enhancement from the canine to first molar on the right side of the mandible. Root resorption of the first premolar and root separation of the first and second premolars were also evident. The lesion was asymptomatic. Histopathological examination of a biopsy of the lesion was suggestive of OF. Enucleation of the tumor, curettage of the bone around the tumor, and extraction of the premolar were then performed. Histopathological examination of the tumor showed fibrous connective tissue with inactive-looking odontogenic epithelial islands and strands, amyloid deposit, intercalation of Langerhans cells into the tumor epithelium, and no calcification. The final diagnosis of amyloid variant of COF was made. The postoperative course is going well. CONCLUSIONS Herein we describe and discuss the clinical, radiological, and pathological features of the amyloid variant of COF. This report will enhance understanding of this extremely rare variant.

Suramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells.

AU-rich elements (ARE) exist in the 3'-untranslated regions of the mRNA transcribed from cell growth-related genes such as proto-oncogenes, cyclin-related genes, and growth factors. HuR binds and stabilizes ARE-mRNA. HuR is expressed abundantly in cancer cells and related malignant phenotypes. HuR knockdown attenuates the malignant phenotype of oral cancer cells. In this study, we screened 1570 compounds in the approved drug library by differential scanning fluorimetry (DSF) to discover a HuR-targeted compound. Firstly, 55 compounds were selected by DSF. Then, 8 compounds that showed a shift in the melting temperature value in a concentration-dependent manner were selected by DSF. Of them, suramin, an anti-trypanosomal drug, binds to HuR, exhibiting fast-on and fast-off kinetic behavior on surface plasmon resonance (SPR). We confirmed that suramin significantly decreased mRNA and protein expression of cyclin A2 and cyclin B1. The cyclin A2 and cyclin B1 mRNAs were destabilized by suramin. Furthermore, the motile and invasive activities of a tongue carcinoma cell line treated with suramin were markedly lower than those of control cells. The above findings suggest that suramin binds to HuR and inhibits its function. We also showed that the anticancer effects of suramin were caused by the inhibition of HuR function, indicating its potential as a novel therapeutic agent in the treatment of oral cancer. Our results suggest that suramin, via its different mechanism, may effectively suppress progressive oral cancer that cannot be controlled using other anticancer agents.

pp32r1 controls the decay of the RNA-binding protein HuR.

pp32 is a tumor suppressor and is one of the associated proteins of the RNA-binding protein HuR. The pp32-HuR complex is exported to the cytoplasm of cells under stress conditions, and HuR is degraded by caspases in the cytoplasm. In the present study, we examined the role of pp32r1, a member of the pp32 family that has oncogenic properties, in the decay of HuR. pp32r1 was found to be abundantly expressed in cancer cells, and overexpression of pp32r1 induced colony formation in soft-agar. pp32r1 was expressed in both the nucleus and cytoplasm, whereas pp32 was predominantly localized in the nucleus. Even with lethal stress such as staurosporine (STS), HuR in the cytoplasm was never downregulated, and caspase-3 activity was inhibited when cells expressed pp32r1. pp32r1 bound to HuR without interacting with pp32. In cancer cells, HuR survived in the cytoplasm of cells overexpressing pp32r1, although HuR was not expressed in the cytoplasm of pp32-expressing cells, similar to lethal stress conditions. Taken together, these results indicate that pp32r1 binds to HuR to avoid the caspase-mediated decay of HuR in the cytoplasm of cells. We suggest that this function contributes to the oncogenic activity of pp32r1.

HuR knockdown changes the oncogenic potential of oral cancer cells.

HuR binds to AU-rich element-containing mRNA to protect them from rapid degradation. Here, we show that knockdown of HuR changes the oncogenic properties of oral cancer cells. Oral squamous cell carcinoma cell lines, HSC-3 and Ca9.22, which express HuR protein and cytoplasmic AU-rich element mRNA more abundantly than normal cells, were subjected to HuR knockdown. In the HuR-knockdown cancer cells, the cytoplasmic expression of c-fos, c-myc, and COX-2 mRNAs was inhibited compared with those in cells that had been transfected with a control small interfering RNA, and the half-lives of these mRNAs were shorter than those of their counterparts in the control cells. HuR-knockdown cells failed to make colonies in soft agar, suggesting that the cells had lost their ability for anchorage-independent cell growth. Additionally, the motile and invasive activities of the cells decreased remarkably by HuR knockdown. Furthermore, the expression of cell cycle-related proteins, such as cyclin A, cyclin B1, cyclin D1, and cyclin-dependent kinase 1, was reduced in HuR-knockdown cancer cells, and HuR bound to cdk1 mRNA to stabilize it. These findings suggest that HuR knockdown changes the features of oral cancer cells, at least in part, by affecting their cell cycle and shows potential as an effective therapeutic approach.