Radiological findings associated with postoperative wound infection after extraction of impacted mandibular third molar: A retrospective study.

INTRODUCTION: Studies directly relating radiological findings to the risk of postoperative wound infection (PWI) in impacted mandibular third molars (M3) are limited and poorly understood. This study aimed to clarify the radiological risk of PWI. MATERIALS AND METHODS: Twenty-six patients who developed PWI after M3 extraction were retrospectively analyzed using orthopantomography (OPG) and computed tomography (CT) before M3 extraction to determine the association between M3 impaction status and PWI. These were compared with an equal number of non-infected groups. Moreover, the possibility of assessing the same risk in OPG as in CT imaging was examined. RESULTS: Multivariate analysis identified class III and position B of the Pell and Gregory classification system as independent risk factors for PWI. On CT, an axial overlap distance (AOD) >3.5 mm was significantly associated with PWI. Furthermore, the sagittal overlap distance (SOD) and AOD of the OPG were significantly greater in group III-B. A strong positive correlation was observed between SOD and AOD. CONCLUSION: These results indicate that class III, position B, and an AOD >3.5 mm may be novel risk factors for M3 PWI. The strong correlation between SOD and AOD suggests that the risk assessment for PWI can be performed by evaluating OPG alone.

Association between salivary proteases and protease inhibitors linked with viral infections and oral inflammatory diseases.

INTRODUCTION: Despite the role of transmembrane protease, serine 2 (TMPRSS2) in facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the primary cause of the global COVID-19 pandemic, the interaction of extracellular and intracellular proteases in this process remains poorly elucidated. Thus, we monitored the salivary expression concentration (SEC) of TMPRSS2 and its inhibitor, alpha-1 antitrypsin (A1AT), and investigated whether oral inflammatory diseases affected the SEC of both proteins. MATERIALS AND METHODS: We collected saliva samples before and after surgical treatment of inflammatory cystic diseases (radicular and inflammatory dentigerous cysts) in 25 patients. The SEC of TMPRSS2 and A1AT was measured using enzyme-linked immunosorbent assay. SEC in multiple patient status groups and subgroups of each status were investigated. Finally, the correlation between TMPRSS2 and A1AT SEC was analyzed. RESULTS: The TMPRSS2 and A1AT SEC did not significantly change pre- or post-treatment. The TMPRSS2 SEC was significantly higher before and after treatment in patients aged >50 years, patients with radicular cysts, and patients with the basic disease. A1AT SEC was significantly decreased after treatment in the acute inflammation, large-sized, and patients without basic disease groups. No significant correlation was observed between the SEC of either protein before and after treatment. DISCUSSION: Individual-specific SEC for TMPRSS2 may be influenced by age, lesion type, and basic disease; however, oral inflammatory diseases may not have a direct effect. Moreover, the extent of oral inflammatory diseases and the presence of basic diseases may be associated with A1AT SEC. Furthermore, the SEC between the two proteins may be independent.

Analysis of false-negatives in exfoliative cytology in oral potentially malignant disorders: A retrospective cohort study.

INTRODUCTION: Keratinized lesions have been a conceivable false-negative (FN) factor in oral exfoliative cytology (OEC); however, other factors are poorly analyzed. In this study, we aimed to identify the factors influencing the accuracy of OEC and FNs focusing on the lesion characteristics, patient background, and surgeon factors in oral potentially malignant disorders (OPMD). MATERIAL AND METHODS: We retrospectively studied 44 patients who underwent both OEC and histopathological diagnosis. Sensitivity, specificity, FN rate, false-positive (FP) rate, and prevalence of both methods were compared. Similarly, accuracy indices were compared among clinical diagnosis groups (leukoplakia vs. other diagnosis). The association between patient and surgeon-related factors influencing FN OEC results were investigated using Fisher's exact test and a multiple logistic regression analysis. RESULTS: Overall, the sensitivity; specificity; and FN, FP, and prevalence rates of OEC were 31.8%, 82.1%, and 68.8%, 17.9%, and 36.4%, respectively. Leukoplakia was significantly more common in clinical diagnosis (P = 0.007) with sensitivity, specificity, and FN rates of 20.0%, 95.2%, and 80.0%, respectively. Contrarily, non-keratinized lesions had sensitivity, specificity, and FN of 83.3%, 85.7%, and 16.7%, respectively. In the prevalent group, leukoplakia and anucleate squamous cells were significantly associated with FN cases (P = 0.013, P = 0.050). On multivariate analysis in OEC negative patients, age ≤64 (P = 0.050) and location on the tongue (P = 0.047) was independently associated with FNs. CONCLUSION: FN of OEC was conceivable to be due to poor deep-seated cell sampling, which was associated with leukoplakia, age, and location. Therefore, these factors may be considered in the evaluation of OEC results.

Evaluation of anticancer activities of benzo[c]phenanthridine alkaloid sanguinarine in oral squamous cell carcinoma cell line.

While the effects of benzo[c]phenanthridine alkaloids (QBA), known mainly as sanguinarine and chelerythrine, on the inhibition of some kinds of cancer cell proliferation have been established, the effect on oral squamous cell is not known. Here, the antitumor activity of sanguinarine was demonstrated using in vitro assay systems in SAS, a human oral squamous cell carcinoma (OSCC) cell line. The anti-proliferative and -invasive effects were confirmed with IC50 values in the concentration range of 0.75-1.0 µM by MTT assay and invasive assay, respectively. Sanguinarine was also able to suppress cell anchorage-independent growth, whereas it did not affect the cells' adhering capabilities. Finally, sanguinarine induced apoptotic cell death by activating caspase and altering the Bcl-2/Bax ratio. Taken together, these results indicate that sanguinarine is a potential inhibitor of tumorigenesis and suggest that it may be valuable in the development of new anticancer drugs for the treatment of OSCC.

Anti-tumor activity of dehydroxymethylepoxyquinomicin against human oral squamous cell carcinoma cell lines in vitro and in vivo.

Several reports have indicated that nuclear factor-kappa B (NF-κB) is constitutively activated in a variety of cancer cells including human oral squamous carcinoma cells, and play a key role in their growth and survival. Recent studies report that NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), inhibits proliferation and induces apoptosis in prostate cancer cell lines. However this anti-tumor effects are still unknown in end human oral squamous carcinoma cells. In the present study, we investigated the effects of DHMEQ on oral squamous carcinoma cell (OSCC) lines in vitro and in vivo. Human OSCC cell lines (HSC-3, SAS) were treated with DHMEQ and examined for cell viability by MTT assay, cell cycle distribution by flow-cytometry, apoptosis by TUNEL assay, and protein expression by western blotting, respectively. In vivo activities were also investigated in a mouse xenograft model. DHMEQ inhibited growth of two OSCC cell lines in a dose-dependent manner measured by MTT assay. A flow cytometric analysis demonstrated that treatment with DHMEQ induced accumulation in sub-G1 phase. TUNEL assay showed that DHMEQ induced DNA fragmentation. Protein expression by western blotting analysis revealed that DHMEQ induced nuclear down regulation of Survivin, cIAP-1, and cIAP-2. In nude mice, DHMEQ inhibited growth of OSCC without major toxic side effects. The present results demonstrated that administration of DHMEQ is suggested to be a novel anti-tumor approach to the treatment of OSCC.

Antitumor activity of suberoylanilide hydroxamic acid against human oral squamous cell carcinoma cell lines in vitro and in vivo.

It has been reported recently that histone deacetylase inhibitors (HDACIs) can block the growth of a variety of malignant tumor cells by reversing the silencing of the tumor suppressor genes; these will be the anticancer agents of the next generation. In this study, we evaluated the antitumor effects of the HDACI suberoylanilide hydroxamic acid (SAHA) on oral squamous cell carcinoma (OSCC) and investigated its molecular mechanism. SAHA suppressed the in vitro proliferation of OSCC cell lines in a dose- and time-dependent manner. Flow cytometric analyses showed that treatment with SAHA led to G1 phase cell-cycle arrest of OSCC cells, accompanying a decrease in the percentage of S-phase cells. Western blot analyses demonstrated that the expression of p21 protein was remarkably augmented and hyperacetylation of p53 was induced after SAHA treatment. These results suggest that administration of SAHA suppresses OSCC growth through G1 phase arrest. Additionally, we observed that the growth of xenograft SAS tumors in nude mice was significantly blocked by the administration of SAHA without major adverse effects.

Hypoxia induces resistance to 5-fluorouracil in oral cancer cells via G(1) phase cell cycle arrest.

Malignant tumors are exposed to various levels of hypoxic condition in vivo. It has been known that tumor cells under hypoxia are resistant to chemotherapies. To clarify the mechanism of the hypoxia-induced chemoresistance, we evaluated the effects of hypoxia on the resistance of oral squamous cell carcinoma (OSCC) cell lines to 5-fluorouracil (5-FU). OSCC cells were divided to two groups by the proliferation activity under hypoxic condition; hypoxia-resistant (HR) and hypoxia-sensitive (HS) cells. Growth of HS cells were inhibited by hypoxia and introduced to G(1) arrest in cell cycle. 5-FU effect on HS cell viability was markedly reduced in hypoxic condition without an induction of chemoresistant related protein, P-glycoprotein. However, proliferation, cell cycle, and 5-FU sensitivity of HR cells were not affected by hypoxia. Hypoxia-inducible factor (HIF)-1alpha was induced by hypoxia in all OSCC cell lines, but diminished in HS cells within 48h. Expression of p21 and p27 was strongly augmented and CyclinD expression was reduced by hypoxia in HS cells. However, the expression of these proteins was constitutive in HR cells during 48h hypoxic culture. Phosphorylation of mammalian target of rapamycin (mTOR) was reduced by hypoxia in HS cells. From these findings, we concluded that HS OSCC cells acquire 5-FU resistance under hypoxia by G(1)/S transition through an upregulation of cell cycle inhibitors.

Tumor-specific cytotoxic activity and type of cell death induced by 4-trifluoromethylimidazoles in human oral squamous cell carcinoma cell lines.

Fourteen 4-trifluoromethylimidazole derivatives were investigated for their cytotoxicity against three human normal cells (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF) and four human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, HSC-4 and promyelocytic leukemia HL-60). Among these compounds, 4-trifluoromethyl-1,2-diphenylimidazole (IM5), 1-benzyl-4-trifluoromethyl-2-phenylimidazole (IM7) and 5-[1-ethoxy-2,2,2-trifluoro-1-(trifluoromethyl) ethyl]-1-methyl-2-phenyl-1H-imidazole (IM12) showed much higher cytotoxicity and tumor-specificity than the other compounds. IM5, the most potent compound, induced different types of cell death depending on the target cells. IM5 induced DNA fragmentation of oligonucleosomal units (a biochemical hallmark of apoptosis) in the HL-60 cells, but not in such a clear-cut laddering pattern in the HSC-2 cells. On the other hand, IM5 produced secondary lysosomes digesting broken organelles, without induction of internucleosomal DNA fragmentation and disappearance of cell surface microvilli in the HSC-4 cells, even though the HSC-2 and HSC-4 cells showed comparable sensitivity to IM5. These data suggest that the type of cell death is determined by the type of target cells, but not by the drug-sensitivity of the cells.