11-epi-Sinulariolide Acetate-induced Apoptosis in Oral Cancer Cells Is Regulated by FOXO Through Inhibition of PI3K/AKT Pathway.

BACKGROUND/AIM: Oral cancer is a general term for carcinomas that occur around the oral tissues, and most are squamous cell carcinoma. Oral cancer is a common disease among Taiwanese males and poses a great threat to national health owing to its high mortality rate. In this study, we used the CAL-27 oral cancer cell lines as in vitro models to investigate the pathways involved in 11-epi-sinulariolide acetate (11-epi-SA)-induced apoptosis. MATERIALS AND METHODS: There have been no previous studies of the anticancer activity of 11-epi-SA isolated from Sinularia flexibilis against oral cancer. We used MTT assay, cell morphologic analysis, DNA fragmentation, TUNEL/DAPI assay, and JC-1 fluorescence staining to analyze the inhibitory effect of 11-epi-SA against the CAL-27 oral cancer cell line and assessed the potential molecular mechanism of apoptosis using western blot. RESULTS: Our results showed that 11-epi-SA inhibited CAL-27 cell proliferation, and its effect on cell growth was mediated through an apoptotic pathway mechanism. 11-epi-SA inhibited the PI3K/AKT pathway, allowing downstream FOXO to separate from 14-3-3 and return to the nucleus. We also observed that 11-epi-SA disrupted mitochondrial Bcl family protein homeostasis and activated caspase-3 and caspase-9, which led to apoptosis. CONCLUSION: A low concentration of 11-epi-SA can effectively induce apoptosis in oral cancer cells through the PI3K/AKT/FOXO pathway. 11-epi-SA has great potential as a new drug for the treatment of oral cancer.

4-Carbomethoxyl-10-Epigyrosanoldie E Extracted from Cultured Soft Coral Sinularia sandensis Induced Apoptosis and Autophagy via ROS and Mitochondrial Dysfunction and ER Stress in Oral Cancer Cells.

Oral cancer is a malignant neoplasia that is more common in Asian than other regions, and men are at higher risk than women. Currently, clinical treatment for oral cancer consists of radiation therapy combined with chemotherapy. Therefore, it is important to find a drug that can inhibit the growth of cancer cells more effectively and safely. In this study, we examined the cytotoxicity of 4-carbomethoxyl-10-epigyrosanoldie E extracted from cultured soft coral Sinularia sandensis towards oral cancer cells. MTT cell proliferation and colony formation assays were used to evaluate cell survival, and immunofluorescence staining and Western blotting were employed to analyze the effects of 4-carbomethoxyl-10-epigyrosanoldie E on apoptosis and autophagy. 4-Carbomethoxyl-10-epigyrosanoldie E treatment also induced the formation of reactive oxygen species (ROS), which are associated with 4-carbomethoxyl-10-epigyrosanoldie E-induced cell death. In addition, the 4-carbomethoxyl-10-epigyrosanoldie E-induced antiproliferation effects on Ca9-22 and Cal-27 cells were associated with the release of cytochrome c from mitochondria, activation of proapoptotic proteins (such as caspase-3/-9, Bax, and Bad), and inhibition of antiapoptotic proteins (Bcl-2, Bcl-xl, and Mcl-1). 4-Carbomethoxyl-10-epigyrosanoldie E treatment also triggered endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/ATF4/CHOP apoptotic pathway. Moreover, increased expressions of Beclin-1, Atg3, Atg5, Atg7, Atg12, Atg 16, LC3-I, and LC3-II proteins indicated that 4-carbomethoxyl-10-epigyrosanoldie E triggered autophagy in oral cancer cells. In conclusion, our findings demonstrated that 4-carbomethoxyl-10-epigyrosanoldie E suppressed human oral cancer cell proliferation and should be further investigated with regard to its potential use as a chemotherapy drug for the treatment of human oral cancer.

Learning Curve of Upper Aerodigestive Tract Foreign Body Management for Otorhinolaryngology Residents.

INTRODUCTION: Foreign body ingestion is the most common reason for otolaryngology specialist consultations in emergency departments. Among the different types of foreign bodies, fish bones are the most common, particularly in Asian populations. In Taiwan, upper aerodigestive tract foreign bodies (UADT-FBs) are mostly managed by residents in the otorhinolaryngology (ORL) department. Considering the learning curve required for all procedures, different management types between residents, and possible resulting safety issues, this study explored the outcomes of UADT-FB management by residents in different years of ORL training. MATERIALS AND METHODS: The medical records of 2,283 patients who visited Kaohsiung Veterans General Hospital's Emergency Department for UADT-FB during June 2013-August 2019 were retrospectively reviewed. The reviewed data included the demographic data of enrolled patients, outcomes of foreign body management, and follow-up chart records of the patients. RESULTS: Among the 2,283 patients, 1,324 (58%) were found to be negative for foreign bodies, and foreign bodies in 951 (41.7%) were removed immediately. In the negative finding (NF) group, 2 (4.9%) patients were later found to be positive for foreign bodies during follow-up in the outpatient department. One (2.4%) patient developed a deep neck infection and esophageal perforation. The percentage of NFs decreased from 62.58% in residents in the first half of their first year (R1a) to 54% for third-year residents (R3). Comparing R1a with R3, the number needed to harm for retained UADT-FBs after patients visited the emergency department was 12.2. DISCUSSION/CONCLUSION: This study provides data from 1 referral center regarding the management of UADT-FBs. With increasing resident training, the percentage of NFs declined from 62.58 to 54%. Young residents, especially those in the first 6 months of their training, should have senior residents perform a second examination if UADT-FBs are not found in suspected cases.

Sarcopenia results in poor survival rates in oral cavity cancer patients.

OBJECTIVE: This study aimed to determine the impact or survival of low skeletal muscle mass (SMM) among patients with oral squamous cell carcinoma (OSCC) undergoing primary surgery. DESIGN: This study was a retrospective cohort study. SETTING: Oral squamous cell carcinoma patients treated at our referral centre from April 2005 to March 2014 were examined. PARTICIPANTS: The cohort comprised 276 patients with OSCC undergoing primary surgery. MAIN OUTCOME MEASURES: Estimated SMM was measured by calculating the cervical skeletal muscle mass from a CT scan of the head and neck. The 5-year overall survival (OS) and disease-specific survival (DSS) were analysed using a multivariable Cox regression model. RESULTS: There were 276 patients with a male-to-female ratio of 12:1. A low SMM (<47.5 cm2 /m2 ) was associated with worse survival. After adjustment for other factors, the result remained robust for OS (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.14-2.67) and disease-specific survival (HR 1.67, 95% CI 1.04-2.67). In the subgroup analysis, worse OS and DSS were particularly noted in male patients (HR = 1.90, 95% CI 1.22-2.97; HR = 1.91, 95% CI 1.27-3.19) and in those younger than 60 years of age (HR = 1.91, 95% CI 1.14-3.22; HR = 2.12, 95% CI 1.23-3.64) with low SMM. CONCLUSIONS: Low SMM was a significant independent factor that was associated with lower survival in patients who have oral cavity cancers and are undergoing primary surgery. Preoperative CT scans of the head and neck could be utilised to evaluate SMM, predict treatment outcomes and facilitate nutrition management.

Transnasal endoscopic orbital decompression: 15-year clinical experience in Southern Taiwan.

BACKGROUND/PURPOSE: To present the results and evaluate the efficacy of endoscopic transnasal orbital decompression for dysthyroid orbitopathy. METHODS: Retrospective chart review of patients who underwent endoscopic transnasal orbital decompression from 1996 to 2010 in one institution. We included 42 orbits of 25 patients. Preoperative and postoperative examinations included visual acuity, Hertel exophthalmometry, tonometry, exposure keratitis, and diplopia. The measurements of outcome depend on proptosis reduction, intraocular pressure reduction, and visual acuity improvement of 42 orbits of 25 patients. RESULTS: There were no surgical complications for the 42 orbital decompressions except one patient experienced cerebrospinal fluid leak during the operation. Mean proptosis reduction in all orbits was 1.93 ± 0.25 (mean ± standard deviation, p < 0.01) after 1 month postoperatively and 2.07 ± 0.29 (p < 0.01) after 3 months postoperatively. An average reduction of intraocular pressure was 4.40 ± 0.72 (p < 0.01) and 4.38 ± 0.80 (p < 0.01) respectively after 1 and 3 months postoperatively. Visual acuity increased from a preoperative average of 0.45 ± 0.34 to 0.66 ± 0.36 and 0.70 ± 0.35 after 1 and 3 months postoperatively. In addition, postoperative relief of exposure keratitis is also noted. CONCLUSION: The transnasal orbital decompression procedure has statistically significant improvements in proptosis, intraocular pressure, and visual acuity. The procedure has obvious benefit in relieving exposure keratitis. Furthermore, there are favorable cosmetic results and rare complications.