RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma.

OBJECTIVES: RAD51 overexpression has been reported to serve as a marker of poor prognosis in several cancer types. This study aimed to survey the role of RAD51 in oral squamous cell carcinoma and whether RAD51 could be a potential therapeutic target. MATERIALS AND METHODS: RAD51 protein expression, assessed by immunohistochemical staining, was used to examine associations with survival and clinicopathological profiles of patients with oral squamous cell carcinoma. Lentiviral infection was used to knock down or overexpress RAD51. The influence of RAD51 on the biological profile of oral cancer cells was evaluated. Cell viability and apoptosis after treatment with chemotherapeutic agents and irradiation were analyzed. Co-treatment with chemotherapeutic agents and B02, a RAD51 inhibitor, was used to examine additional cytotoxic effects. RESULTS: Oral squamous cell carcinoma patients with higher RAD51 expression exhibited worse survival, especially those treated with adjuvant chemotherapy and radiotherapy. RAD51 overexpression promotes resistance to chemotherapy and radiotherapy in oral cancer cells in vitro. Higher tumorsphere formation ability was observed in RAD51 overexpressing oral cancer cells. However, the expression of oral cancer stem cell markers did not change in immunoblotting analysis. Co-treatment with RAD51 inhibitor B02 and cisplatin, compared with cisplatin alone, significantly enhanced cytotoxicity in oral cancer cells. CONCLUSION: RAD51 is a poor prognostic marker for oral squamous cell carcinoma. High RAD51 protein expression associates with resistance to chemotherapy and radiotherapy. Addition of B02 significantly increased the cytotoxicity of cisplatin. These findings suggest that RAD51 protein may function as a treatment target for oral cancer. TRIAL REGISTRATION: Number: KMUHIRB-E(I)-20190009 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, approved on 20190130, Retrospective registration.

IL17RB expression is associated with malignant cancer behaviors and poor prognosis in oral cancer.

OBJECTIVES: Previously, we demonstrated that IL17RB plays an essential role in lung cancer progression. This study aimed to determine whether IL17RB correlates with oral cancer and promotes oral cancer progression. SUBJECTS AND METHODS: IL17RB expression in oral cancer tissues and normal tissues was determined by immunohistochemistry staining, while the association of IL17RB expression with the clinicopathological characteristics of oral squamous cell carcinoma (OSCC) patients was analyzed and its correlation with progression-free survival and response to radiotherapy and chemotherapy in OSCC patients was also explored. Western blotting was performed to investigate the expression of IL17RB in various OSCC cell lines; moreover, transwell assay was performed to evaluate the effect of IL17RB expression on cell migration ability. RESULTS: In this study, we found that IL17RB was expressed higher in OSCC tissues compared to normal oral mucosa tissues and its expression was positively correlated with tumor size, lymph node metastasis, advanced cancer stage, and poor prognosis. In vitro study showed that IL17RB expression in OSCC cell lines as determined by Western blotting, was positively correlated with their migration ability. CONCLUSION: Clinical and in vitro studies suggest that IL17RB might serve as an independent risk factor and a therapeutic target for oral cancer.

CD44 Mediates Oral Squamous Cell Carcinoma-Promoting Activity of MRE11 via AKT Signaling.

Oral cancer is one of the highest-incidence malignancies worldwide, with the occurrence of oral squamous cell carcinoma (OSCC) being the most frequently diagnosed form. A barrier for oral cancer management may arise from tumor cells that possess properties of cancer stemness, which has been recognized as a crucial factor in tumor recurrence and metastasis. As such, understanding the molecular mechanisms underlying these tumor cells may provide insights for improving cancer treatment. MRE11 is the core protein of the RAD50/MRE11/NBS1 complex with a primary role in DNA damage repair, and it has been diversely associated with tumor development including OSCC. In this study, we aimed to investigate the engagement of CD44, a cancer stemness marker functioning in the control of cell growth and motility, in OSCC malignancy under the influence of MRE11. We found that overexpression of MRE11 enhanced CD44 expression and tumorsphere formation in OSCC cells, whereas knockdown of MRE11 reduced these phenomena. In addition, the MRE11-promoted tumorsphere formation or cell migration ability was compromised in OSCC cells carrying siRNA that targets CD44, as was the MRE11-promoted AKT phosphorylation. These were further supported by analyzing clinical samples, where higher CD44 expression was associated with lymph node metastasis. Additionally, a positive correlation between the expression of MRE11 and CD44, or that of CD44 and phosphorylated AKT, was observed in OSCC tumor tissues. Finally, the expression of CD44 was found to be higher in the metastatic lung nodules from mice receiving tail vein-injection with MRE11-overexpressing OSCC cells compared with control mice, and a positive correlation between CD44 and phosphorylated AKT was also observed in these metastatic lung nodules. Altogether, our current study revealed a previously unidentified mechanism linking CD44 and AKT in MRE11-promoted OSCC malignancy, which may shed light to the development of novel therapeutic strategies in consideration of this new pathway in OSCC.

Decreased Circulating Melatonin with Loss of Age-Related Biphasic Change in Patients with Oral Squamous Cell Carcinoma.

BACKGROUND: Melatonin, produced by the pineal gland, is known for its antioxidant, oncostatic, and anti-inflammatory properties. However, studies on serum melatonin levels in different cancer types have yielded conflicting results, and little is known about the clinical significance of serum melatonin in oral squamous cell carcinoma (OSCC) in the Southern Asian population. Therefore, we explored its role in OSCC in this study. METHODS: A total of 67 male OSCC patients and 78 healthy controls were enrolled in this case-control study. The serum levels of melatonin were determined by enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. RESULTS: The serum melatonin levels were significantly lower in OSCC patients compared with healthy controls (mean ± standard deviation, 15.0 ± 4.6 vs. 18.5 ± 11.8 pg/mL, p = 0.02). In the subgroup of age less than 55 years (mean age of OSCC), OSCC patients had a significantly decreased melatonin level than healthy controls (mean melatonin, 15.7 ± 12.6 vs. 20.8 ± 3.9 pg/mL, p = 0.02). Decreased serum melatonin (odds ratio (OR): 0.95, 95%CI: 0.91-0.99), alcohol consumption (OR: 29.02, 95%CI: 11.68-72.16), betel quid chewing (OR:136.44, 95%CI: 39.17-475.27), and cigarette smoking (OR:29.48, 95%CI: 11.06-78.60) all increased the risk of OSCC under univariate analyses of logistic regression. Betel quid chewing (OR: 45.98, 95%CI: 10.34-204.49) and cigarette smoking (OR:6.94, 95%CI: 1.60-30.16) were the independent risk factors for OSCC in Taiwan. In addition, a negative correlation between age and melatonin level was observed in healthy controls (Pearson r = -0.24, p = 0.03). However, the negative correlation was lost in patients with OSCC. Melatonin concentration had no association with the severity of OSCC. CONCLUSION: Overall, our study provides evidence that serum melatonin levels decreased in OSCC patients in Taiwan and the decreased level is much significant in young populations and suggests that the decreased melatonin was associated with OSCC, especially in young populations. Further studies are warranted to investigate whether melatonin can be a useful non-invasive screening tool for OSCC.

Excision repair cross-complementing group 2 upregulation is a potential predictive biomarker for oral squamous cell carcinoma recurrence.

Oral cancer is the fourth most common type of cancer among males in Taiwan, and the prognosis for patients with advanced-stage oral squamous cell carcinoma (OSCC) remains poor. The present study investigated the prognostic value of three DNA repair genes, namely excision repair cross-complementing group 1 (ERCC1), ERCC2 and X-ray repair cross-complementing group 1 (XRCC1) in OSCC. The protein expression levels of XRCC1, ERCC1 and ERCC2 in oral cell lines were analyzed via western blotting and immunohistochemistry using samples from 98 patients with biopsy-proven OSCC, while the χ2 test was used to analyze the clinicopathological association. Kaplan-Meier estimates were used to determine the prognostic value of XRCC1, ERCC1 and ERCC2 for overall survival, and the log-rank test was used to evaluate the significance of differences. Multivariate analysis revealed a positive association between ERCC2 expression and OSCC recurrence (19.64-fold; 95% CI, 5.00-77.1; P<0.001). In addition, the high protein expression levels of XRCC1, ERCC1 and ERCC2 were associated with poor disease-free and overall survival rates. Therefore, the present study suggested that high ERCC2 expression may be a risk factor for OSCC recurrence.

Clinicopathological study of 13 cases of intraoral soft tissue metastatic carcinomas.

BACKGROUND/PURPOSE: Oral metastatic carcinomas are rarely found in oral soft tissues. This study reported the clinicopathological features of 13 intraoral soft tissue metastatic carcinomas. MATERIALS AND METHODS: A total of 13 intraoral soft tissue metastatic carcinomas were included in this study. The clinicopathological features of the 13 cases including the primary cancer site, metastatic intraoral soft tissue region, clinical presentation, and histopathological diagnoses were examined and reported. RESULTS: The 13 intraoral soft tissue metastatic carcinomas occurred in 13 patients (11 males and 2 females) with a mean age of 59.4 (range, 39-78) years. Nine cases originated from the liver (69.2%), and one each from the colon (7.7%), pancreas (7.7%), thyroid (7.7%), and kidney (7.7%). The histopathological diagnoses of the metastatic lesions were hepatocellular carcinoma in 9 cases, adenocarcinomas in 2 cases (one each from the colon and pancreas), clear cell carcinoma of the kidney in one case, and follicular thyroid carcinoma in one case. The gingiva and alveolar mucosa were the major metastatic sites (10 cases, 76.9%), followed by the buccal mucosa (two cases, 15.4%), and soft palate (one case, 7.7%). Twelve metastatic lesions manifested as ulcerated, easy-bleeding, and pyogenic granuloma-like lesions. CONCLUSION: The results of our series of 13 cases indicate that intraoral soft tissue metastatic carcinomas have a male predilection with a male to female ratio of 11:2, are commonly found in the gingiva and alveolar mucosa (76.9%), present frequently as an easy-bleeding pyogenic granuloma-like lesion (92.3%). In addition, the most common primary cancer site is the liver.

Silencing of FOXA2 decreases E-cadherin expression and is associated with lymph node metastasis in oral cancer.

OBJECTIVES: FOXA2 gene methylation links to the progression of cancers, but has not been documented in oral cancer. Herein, we explore the role of FOXA2 in the migration of oral cancer cells. MATERIAL AND METHODS: Methylation-specific PCR was applied for gene methylation. Wound healing and transwell experiments were tested for cell migration. FOXA2 expression in oral cancer tissues was addressed by immunohistochemistry, followed by statistical analysis of its association with clinical manifestations and patient survival. RESULTS: FOXA2 bound to the promoter of CDH1 and enhanced the expression of its gene product E-cadherin, and decreased the cancer cell migration activity. High FOXA2 expression in oral cancer tissues was associated with high E-cadherin expression, decreased lymph node metastasis, and increased patient survival. CONCLUSION: FOXA2-E-cadherin link is involved in regulation of oral cancer cell metastasis and provides a new insight for the tumor suppressor activity of FOXA2 in oral cancer.

MnO2 prepared by hydrothermal method and electrochemical performance as anode for lithium-ion battery.

Two α-MnO2 crystals with caddice-clew-like and urchin-like morphologies are prepared by the hydrothermal method, and their structure and electrochemical performance are characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), galvanostatic cell cycling, cyclic voltammetry, and electrochemical impedance spectroscopy (EIS). The morphology of the MnO2 prepared under acidic condition is urchin-like, while the one prepared under neutral condition is caddice-clew-like. The identical crystalline phase of MnO2 crystals is essential to evaluate the relationship between electrochemical performances and morphologies for lithium-ion battery application. In this study, urchin-like α-MnO2 crystals with compact structure have better electrochemical performance due to the higher specific capacity and lower impedance. We find that the relationship between electrochemical performance and morphology is different when MnO2 material used as electrochemical supercapacitor or as anode of lithium-ion battery. For lithium-ion battery application, urchin-like MnO2 material has better electrochemical performance.

N,N-Bis(2-pyrid-yl)formamidine.

In the crystal structure of the title compound, C(11)H(10)N(4), the dihedral angle between the two pyridyl rings is 36.1 (1)°. The mol-ecules are connected via two strong N-H⋯N and two weak C-H⋯N hydrogen bonds into dimers, which are located on centers of inversion. This compound adopts the s-trans-anti-s-cis conformation in the solid state.

N,N-Bis(6-methyl-2-pyrid-yl)formamidine.

In the crystal structure of the title mol-ecule, C(13)H(14)N(4), the two pyridyl rings are not coplanar but twisted about the C-N bond with an inter-planar angle of 71.1 (1)°. In the crystal, the mol-ecules form dimers, situated on crystallographic centres of inversion, which are connected via a pair of N-H⋯N hydrogen bonds. C-H⋯π-electron ring inter-actions are also present in the crystal structure. The title mol-ecule adopts an s-cis-anti-s-cis conformation in the solid state.