A rare case of thyroid carcinosarcoma arising from recurrent papillary thyroid cancer: Case report and review of the literature.

BACKGROUND: Thyroid carcinosarcoma represents a rare subtype of thyroid cancer, distinguished by its unique histopathology-simultaneous malignant epithelial and mesenchymal cells. The occurrence of thyroid carcinosarcoma arising from recurrent papillary thyroid cancer is exceptionally infrequent. METHODS: Study outlines a patient's thyroid carcinosarcoma journey, covering presentation, recurrence, diagnostics, surgeries, and follow-up. A PubMed search gathered data on pathological features and treatment approaches for thyroid carcinosarcoma. RESULTS: The patient initially diagnosed with papillary thyroid cancer underwent thyroidectomy, neck dissection, and radioactive iodine therapy. Recurrence revealed thyroid carcinosarcoma, featuring papillary carcinoma, squamous cell carcinoma, and spindle cell components. Total laryngectomy followed by adjuvant radiotherapy and chemotherapy. The patient was followed for 17 months with no evidence of disease. CONCLUSIONS: This extraordinary case exemplifies a rare instance of local relapse in form of thyroid carcinosarcoma following an initial diagnosis of papillary thyroid carcinoma. Surgical resection and chemoradiotherapy show promising outcomes in managing this challenging condition.

Surgical approach of laryngofissure combined with epiglottis valley in treating locally-advanced pyriform sinus carcinoma. / å–‰è£‚å¼€è”åˆä¼šåŽŒè°·å ¥è·¯æ‰‹æœ¯æ²»ç–—å±€éƒ¨æ™šæœŸæ¢¨çŠ¶çªç™Œ.

OBJECTIVES: To evaluate feasibility and efficacy of surgical approach of laryngofissure combined with epiglottis valley in treating locally-advanced pyriform sinus carcinoma. METHODS: Clinical data of 216 patients with T3 and T4a pyriform sinus carcinoma, who came from the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University between January 2013 and December 2019, were retrospectively analyzed. Three different types of surgery were used in these patients. Seventy-three patients were performed by approach of laryngofissure combined with epiglottis valley for partial laryngopharyngectomy (Group I); 75 patients were performed by approach of lateral pharynx for piriform fossa resection (Group II); 68 patients were performed by total laryngopharyngectomy (Group III). All patients were treated with radiotherapy and followed up regularly after operation. Kaplan-Meier regression model was used to analyze the overall survival rate. EAT-10 swallowing scale was utilized to evaluate the postoperative swallowing function, while the rate of tracheal tube extubation and the incidence of postoperative complications in each group were compared. RESULTS: There were 76.7% patients with T3 stage in Group I, 100% patients with T3 stage in Group II, and 64.7% patients with T4a stage in Group III. There was significant difference between them (P<0.01). Clinical stage IV patients in the Group I, Group II, and Group III were 74.0%, 54.7%, and 89.7%, respectively, with significant difference (P<0.01). The 3-year overall survival (OS) rate in Group I, Group II, and Group III were 69.9%, 53.3%, and 58.8%, respectively. Patients in the Group I had a better survival outcome than that in the Group II (P<0.05). The median score of EAT-10 swallowing scale was 12.0 in the Group I, 8.0 in Group II, and 5.0 in Group III, with significant difference (P<0.01). There was no significant difference in the rate of tracheal tube extubation and the incidence of complication among the 3 groups (both P>0.05). CONCLUSIONS: Surgical approach of laryngofissure combined with epiglottis valley in the treating locally-advanced piriform sinus carcinoma presents favorable outcome in terms of survival rate and laryngeal function preservation, which deserves to be promoted.

[Retracted] MicroRNA­214 promotes proliferation and inhibits apoptosis via targeting Bax in nasopharyngeal carcinoma cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell apoptotic assay data shown in Figs. 2C and 4B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 6286-6292, 2015; DOI: 10.3892/mmr.2015.4168].

The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse. METHODS: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. RESULTS: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse. CONCLUSIONS: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.

Antifibrotic Role of Nintedanib in Tracheal Stenosis After a Tracheal Wound.

OBJECTIVES/HYPOTHESIS: Tracheal stenosis is an obstructive disease of the upper airway that commonly develops as a result of abnormal wound healing. We evaluated the anti-inflammatory and antifibrotic properties of nintedanib on tracheal stenosis both in vitro and in vivo. STUDY DESIGN: Prospective controlled animal study and in vitro comparative study of human cells. METHODS: An animal model of tracheal stenosis was induced via tracheal trauma. Postsurgical rats were orally administered with nintedanib (10 or 20 mg/kg/d) or saline (negative control) for 2 weeks, and tracheal specimens were harvested after 3 weeks. Degree of stenosis, collagen deposition, fibrotic surrogate markers expression, and T-lymphocytic infiltration were evaluated. Human fetal lung fibroblast-1 (HFL-1) cells were cultured to determine the effects of nintedanib on changes of cellular biological function induced by transforming growth factor-ß1 (TGF-ß1). RESULTS: Rat tracheal stenotic tissues exhibited thickened lamina propria with irregular epithelium, characterized by significantly increased collagen deposition and elevated TGF-ß1, collagen I, α-SMA and fibronectin expressions. Nintedanib markedly attenuated the tracheal stenotic lesions, reduced the collagen deposition and the expression of fibrotic marker proteins, and mitigated CD4+ T-lymphocyte infiltration. Additionally, cellular proliferation and migration were decreased dose-dependently in TGF-ß1-stimulated HFL-1 cells when treated with nintedanib. Furthermore, nintedanib inhibited TGF-ß1-induced HFL-1 differentiation and reduced the mRNA levels of the profibrotic genes. TGF-ß1-activated phosphorylation of the TGF-ß/Smad2/3 and ERK1/2 pathways were also blocked by nintedanib. CONCLUSION: Nintedanib effectively prevented tracheal stenosis in rats by inhibiting fibrosis and inflammation. The antifibrotic effect of nintedanib may be achieved by inhibiting fibroblasts' proliferation, migration and differentiation and suppressing the TGF-ß1/Smad2/3 and ERK1/2 signaling pathways. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2496-E2505, 2021.

N6-methyladenosine modification of circCUX1 confers radioresistance of hypopharyngeal squamous cell carcinoma through caspase1 pathway.

Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most common malignant tumors in otolaryngology head and neck surgery and is one of the worst prognostic malignant tumors. Endogenous circular RNA (circRNA) is more stable than mRNA, microRNA (miRNA), and long non-coding RNA (LncRNA) in exosomes, plasma, and urine, and participates in gene expression regulation to perform different functions. Therefore, circRNA is expected to become a biomarker and therapy target for many tumors. However, the expression and function of circRNA regulated by N6-methyladenosine (m6A) are still unclear in HNSCC. In this study, we demonstrated that a specific circRNA, circCUX1, was upregulated in HPSCC patients who are resistant to radiotherapy and predicts poor survival outcome. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circCUX1 and stabilizes its expression. Knockdown circCUX1 promotes the sensitivity of hypopharyngeal cancer cells to radiotherapy. In addition, circCUX1 binds to Caspase1 and inhibits its expression, resulting in a decrease in the release of inflammatory factors, thereby developing tolerance to radiotherapy. Our findings indicate that circCUX1 is a potential therapeutic target for radiotherapy tolerance in HPSCC patients.

ANXA1­derived peptides suppress gastric and colon cancer cell growth by targeting EphA2 degradation.

EphA2 (EPH receptor A2) (erythropoietin­producing hepatocellular receptor tyrosine kinase subtype A2) plays a crucial role in human cancers, and is a promising target for the development of new anticancer drugs. In this study, we showed that the interaction of Annexin A1 (ANXA1) and EphA2 increased EphA2 stability by inhibiting its proteasome degradation in gastric cancer (GC) and colon cancer (CC) cells, and the amino acid residues 20­30 and 28­30 of ANXA1 N terminal were responsible for binding and stabilizing EphA2. Based on the amino acid residues of ANXA1 responsible for binding EphA2, we developed ANXA1­derived 3 amino acid­long (SKG) and 11 amino acid­long peptides (EYVQTVKSSKG) in fusion to cell­penetrating peptide, named as A1(28­30) and A1(20­30) respectively, and found that A1(28­30) and A1(20­30) blocked the binding of ANXA1 with EphA2, targeted EphA2 degradation, and suppressed the growth of GC and CC cells in vitro and in mice. Our data demonstrated that ANXA1 was able to bind and stabilize EphA2 in GC and CC cells, and disruption of ANXA1­EphA2 interaction by the two ANXA1­derived peptides inhibited the growth of GC and CC cells by targeting EphA2 degradation, presenting a potential strategy for treating GC and CC with these peptides.

Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2/Erk-1/2 signaling pathway.

EphA2 is an important oncogenic protein and emerging drug target, but the oncogenic role and mechanism of ligand-independent phosphorylation of EphA2 at tyrosine 772 (pY772-EphA2) is unclear. In this study, we established nasopharyngeal carcinoma (NPC) cell lines with stable expression of exogenous EphA2 and EphA2-Y772A (phosphorylation inactivation) using endogenous EphA2-knockdown cells, and observed that pY772A EphA2 was responsible for EphA2-promoting NPC cell proliferation and anchorage-independent and in vivo growth in mice. Mechanistically, EphA2-Y772A mediated EphA2-activating Shp2/Erk-1/2 signaling pathway in the NPC cells, and Gab1 (Grb2-associated binder 1) and Grb2 (growth factor receptor-bound protein 2) were involved in pY772-EphA2 activating this signaling pathway. Our results further showed that Shp2/Erk-1/2 signaling mediated pY772-EphA2-promoting NPC cell proliferation and anchorage-independent growth. Moreover, we observed that EphA2 tyrosine kinase inhibitor ALW-II-41-27 inhibited pY772-EphA2 and EphA2-Y772A decreased the inhibitory effect of ALW-II-41-27 on NPC cell proliferation. Collectively, our results demonstrate that pY772-EphA2 is responsible for EphA2-dependent NPC cell growth in vitro and in vivo by activating Shp2/Erk-1/2 signaling pathway, and is a pharmacologic target of ALW-II-41-27, suggesting that pY772-EphA2 can serve as a therapeutic target in NPC and perhaps in other cancers.

ANXA1 Binds and Stabilizes EphA2 to Promote Nasopharyngeal Carcinoma Growth and Metastasis.

Overexpression of ANXA1 and EphA2 has been linked to various cancers and both proteins have attracted considerable attention for the development of new anticancer drugs. Here we report that ANXA1 competes with Cbl for binding EphA2 and increases its stability by inhibiting Cbl-mediated EphA2 ubiquitination and degradation in nasopharyngeal carcinoma (NPC). Binding of ANXA1 to EphA2 promoted NPC cell growth and metastasis in vitro and in vivo by elevating EphA2 levels and increasing activity of EphA2 oncogenic signaling (pS897-EphA2). Expression of ANXA1 and EphA2 was positively correlated and both were significantly higher in NPC tissues than in the normal nasopharyngeal epithelial tissues. Patients with high expression of both proteins presented poorer disease-free survival and overall survival relative to patients with high expression of one protein alone. Furthermore, amino acid residues 20-30aa and 28-30aa of the ANXA1 N-terminus bound EphA2. An 11 amino acid-long ANXA1-derived peptide (EYVQTVKSSKG) was developed on the basis of this N-terminal region, which disrupted the connection of ANXA1 with EphA2, successfully downregulating EphA2 expression and dramatically suppressing NPC cell oncogenicity in vitro and in mice. These findings suggest that ANXA1 promotes NPC growth and metastasis via binding and stabilization of EphA2 and present a strategy for targeting EphA2 degradation and treating NPC with a peptide. This therapeutic strategy may also be extended to other cancers with high expression of both proteins. SIGNIFICANCE: These findings show that EphA2 is a potential target for NPC therapeutics and an ANXA1-derived peptide suppresses NPC growth and metastasis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/20/4386/F1.large.jpg.

HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis.

HDAC7 plays a crucial role in cancers, and is the main drug target of several HDAC inhibitors. However, the role and mechanism of HDAC7 in nasopharyngeal carcinoma (NPC) are still unclear. In this study, we observed that HDAC7 was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM) tissues, HDAC7 expression levels were positively correlated with NPC progression and negatively correlated with patient prognosis, and HDAC7 knockdown dramatically inhibited the in vitro proliferation, migration, and invasion of NPC cells, and the growth of NPC xenografts in mice, indicating the HDAC7 promotes the oncogenicity of NPC. Mechanistically, HDAC7 promoted the in vitro proliferation, migration, and invasion of NPC cells by upregulating EphA2, in which miR-4465 mediated HDAC7-regulating EphA2, a direct target gene of miR-4465. We further showed that miR-4465 was significantly downregulated in the NPC tissues relative to NNM tissues, and inhibited the in vitro proliferation, migration, and invasion of NPC cells by targeting EphA2 expression. Moreover, we observed that the expressions of HDAC7, miR-4465, and EphA2 in NPC tissues were correlated. The results suggest that HDAC7 promotes the oncogenicity of NPC by downregulating miR-4465 and subsequently upregulating EphA2, highlighting HDAC7 as a potential therapeutic target for NPC.

Heterozygous p53-R280T Mutation Enhances the Oncogenicity of NPC Cells Through Activating PI3K-Akt Signaling Pathway.

A heterozygous point mutation of p53 gene at codon 280 from AGA to ACA (R280T) frequently occurs in nasopharyngeal carcinoma (NPC) cell lines, and about 10% NPC tissues. However, the role of this mutation in the pathogenesis of NPC remains unclear. In this study, we generated p53 knockout (KO) NPC cell lines from CNE2 cells carrying heterozygous p53 R280T (p53-R280T) mutation and C666-1 cells carrying wild-type p53 by CRISPR-Cas9 gene editing system, and found that KO of heterozygous p53-R280T significantly decreased NPC cell proliferation and increased NPC cell apoptosis, whereas KO of wild-type p53 had opposite effects on NPC cell proliferation and apoptosis. Moreover, KO of heterozygous p53-R280T inhibited the anchorage-independent growth and in vivo tumorigenicity of NPC cells. mRNA sequencing of heterozygous p53-R280T KO and control CNE2 cells revealed that heterozygous p53-R280T mutation activated PI3K-Akt signaling pathway. Moreover, blocking of PI3K-Akt signaling pathway abolished heterozygous p53-R280T mutation-promoting NPC cell proliferation and survival. Our data indicate that p53 with heterozygous R280T mutation functions as an oncogene, and promotes the oncogenicity of NPC cells by activating PI3K-Akt signaling pathway.

Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1.

Laryngeal squamous cell carcinoma (LSCC) arises from the squamous epithelium of the larynx and is associated with a high incidence of cervical lymph node metastasis. MicroRNAs (miRNAs) play a crucial role in the epigenetic regulation of cellular biological processes, including cancer metastasis. However, the molecular mechanisms of specific miRNAs responsible for LSCC metastasis and their clinical significance have yet to be fully elucidated. In this study, LSCC cohort datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were downloaded and examined by comprehensive bioinformatics analysis, which revealed that upregulation of mRNA SERPINE1 and downregulation of miR-181c-5p were associated with unfavorable overall survival. Our analysis showed that SERPINE1 expression negatively correlated with the expression level of miR-181c-5p in our LSCC patient samples. Silencing of miR-181c-5p expression promoted cell migration and invasion in cell lines, whereas the overexpression of miR-181c-5p suppressed cell migration and epithelial-to-mesenchymal transition (EMT) through the downregulation of SERPINE1. Further analysis showed that the enhancement effect on EMT and metastasis induced by silencing miR-181c-5p could be rescued through knockdown of SERPINE1 expression in vitro. Collectively, our findings indicated that miR-181c-5p acted as an EMT suppressor miRNA by downregulation of SERPINE1 in LSCC and offers novel strategies for the prevention of metastasis in LSCC.

Laryngeal Diffuse Large B-Cell Lymphoma Presenting as Laryngeal Stenosis.

BACKGROUND: Laryngeal stenosis is challenging for treatment due to uncertain etiology. Primary laryngeal lymphoma as the initial clinical manifestation of laryngeal stenosis has been rarely reported. Primary diffuse large B-cell lymphoma as an underlying etiology has not been reported. CASE REPORT: A 79-year-old male presented with dyspnea, stridor and dysphonia of 6 months' duration. Computed tomography scans and flexible laryngoscopic examination revealed vocal cord mobility with bilaterally limited abduction and a subglottic stenosis up to 50%. The laryngeal mucosa was smooth. Laryngeal biopsy showed atypical lymphoid infiltrates, predominantly large sized B-cells, in the submucosa with crush/cauterized artifacts. The tumor cells were positive for B-lymphocyte antigen CD20, paired-box 5 (PAX5), B-cell lymphoma 2 (BCL2), BCL6 and multiple myeloma oncogene 1 (MUM1). They were negative for CD10, CD30, cyclin D1 (CCND1), SRY-box 11 (SOX11), activin-receptor like kinase 1 (ALK1), CD138 and c-MYC, and negative for kappa/lambda light chain and Epstein-Barr virus-encoded small RNA by in situ hybridization. The pathologic diagnosis was diffuse large B-cell lymphoma. Fluorescent in situ hybridization (FISH) for MYC was negative. Next-generation sequencing using a 175-gene panel was performed and no pathologic mutations were identified. No lymphadenopathy elsewhere was identified. The patient was treated with chemotherapy and was doing well at the 5-month follow-up. CONCLUSION: To the best of our knowledge, this is the first documented case of primary laryngeal diffuse large B-cell lymphoma presenting as increasing laryngeal stenosis. The rarity, diagnosis and treatment of this entity are discussed.

Targeted Inhibitory Effect of Nasopharyngeal Carcinoma Cells by Hre2.Grp78 Chimeric Promoter Regulating Fusion Gene TK/VP3.

OBJECTIVE: To construct plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3 and elaborate the effects of overexpressed TK/VP3 on nasopharyngeal carcinoma cells. METHODS: Four plasmids were constructed, including pcDNA3.1-CMV-TK/VP3, pcDNA3.1-Hre2.TK/VP3, pcDNA3.1-Grp78.TK/VP3, and pcDNA3.1-Hre2.Grp78.TK/VP3. The human nasopharyngeal carcinoma cell line HNE1 cells were transfected with the 4 plasmids, respectively. Cell viabilities were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was conducted using flow cytometry analysis. The expression of TK, VP3, Grp78, and hypoxia-inducible factor 1α and apoptosis-related proteins was determined by real-time quantitative polymerase chain reaction and Western blotting. RESULTS: The recombinant plasmids that could steadily overexpress TK and VP3 were successfully constructed. Expression of TK and VP3 in cells transfected with pcDNA3.1-Hre2.TK/VP3 and pcDNA3.1-Grp78.TK/VP3 was significantly higher than pcDNA3.1-CMV-TK/VP3, and expression in cells transfected with pcDNA3.1-Hre2.Grp78.TK/VP3 was the highest. Under glucose deprivation or hypoxia condition, Grp78 or hypoxia-inducible factor 1α was overexpressed so that expression of TK and VP3 was significantly upregulated, which could further inhibit cell proliferation and enhance cell apoptosis. CONCLUSION: We successfully constructed 4 plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3, which could significantly inhibit the proliferation as well as enhance the apoptosis of nasopharyngeal carcinoma cells under glucose deprivation or hypoxia condition.

Alcohol consumption, tobacco smoking, betel quid chewing and oral health associations with hypopharyngeal cancer among men in Central South China: a case-control study.

BACKGROUND: Hypopharyngeal cancer has relatively high incidence rates in China, especially in high-risk areas. However, data on the role of major risk factors in these areas of China are still limited. METHODS: We have evaluated the roles of alcohol, tobacco and betel quid consumption, and oral health, based on 278 hypopharyngeal cancer cases and 693 controls from two centers in Central South China. The odds ratio (OR) and 95% confidence interval (CI) values were estimated using logistic regression. RESULTS: We found that alcohol drinkers had a risk of hypopharyngeal cancer that was up to seven times higher than that for those who had never drunk. A very strong effect of traditional liquor as compared to other alcohol types was observed, with the OR reaching 11.26 (CI 6.53-19.41) for this cancer. Tobacco smokers were up to four times more likely to develop hypopharyngeal cancer than never smokers. The OR for betel quid chewing was 1.86 (CI 1.26-2.75) as compared to never users. Poor oral hygiene had a risk of hypopharyngeal cancer that was two times higher than that for normal oral hygiene. CONCLUSION: In this study, we have shown for what is believed to be the first time the association of increased hypopharyngeal cancer incidence with alcohol, tobacco, betel quid and oral hygiene in China. Alcohol may play a larger role for hypopharyngeal cancer in this population than in populations in other areas.

Primary Extracranial Meningioma of Mastoid in a Patient With History of Skin Squamous Cell Carcinoma, Lung Adenocarcinoma and Prostatic Carcinoma.

BACKGROUND: Meningiomas are the most common benign intracranial tumors and frequently develop in the parasagittal region, but can also present extracranially. Rarely, meningiomas may involve the middle ear and mastoid, resulting from contiguous spread of adjacent intracranial tumor, or extremely rarely, as an isolated primary tumor, which is frequently misdiagnosed and unrecognized, resulting in inappropriate clinical management. CASE REPORT: Herein we report such a case of an 80-year-old man with history of multiple cancer who presented with ear pain, vertigo and hearing loss. Audiometry demonstrated bilateral sensorineural hearing loss. Contrast-enhanced temporal bone computed tomography revealed a soft-tissue mass in the right epitympanum without bone erosion or any intracranial involvement. Radiological and operative findings were suspicious for cholesteatoma. Histological examination showed an epithelial neoplasm arranged in nests and whorls with intranuclear inclusions. No psammoma bodies, mitotic figures, or tumor necrosis were identified. The tumor cells were positive for epithelial membrane antigen, vimentin, progesterone receptor and CD56; and negative for synaptophysin, chromogranin, pancytokeratin (AE1/AE3), cytokeratin 7, prostate-specific antigen, inhibin, S100, P63, and P40. Ki67 highlighted about 2% of the tumor cells. Based on the morphological features and immunohistochemical profile, the tumor was diagnosed as primary extracranial meningioma of the mastoid, meningothelial subtype, World Health Organization grade 1. CONCLUSION: To the best of our knowledge, primary mastoid meningioma clinically mimicking a cholesteatoma presenting in a patient with a history of multiple primary carcinomas has not been previously reported. The pathogenesis, diagnosis and treatment of this entity are discussed.

Warthin-like Mucoepidermoid Carcinoma of the Parotid Gland: Unusual Morphology and Diagnostic Pitfalls.

BACKGROUND: Warthin-like mucoepidermoid carcinoma is a newly recognized rare entity and could be misdiagnosed as a benign Warthin tumor. We report such a case of a 36-year-old male who presented with a left parotid gland mass. CASE REPORT: Fine-needle aspiration showed features suggestive of Warthin tumor. Following parotidectomy, grossly there was a 1.6 cm well-circumscribed multilobular mass with focal areas of cystic change. Microscopically, at low magnification it had histological features resembling Warthin tumor, while lining with squamoid cells with scattered mucocytes demonstrating mild cytologic atypia was observed at high magnification. Immunohistochemically, the tumor cells were positive for p40, p63, cytokeratin 5/6, cytokeratin 7, and cancer antigen 125, but negative for discovered on GIST-1 (DOG1). Mucicarmine stain highlighted intracellular mucin within mucocytes. Rearrangement of mastermind like transcriptional coactivator 2 (MAML2) (11q21) gene was shown to be present in tumor cells by fluorescence in situ hybridization, supporting the diagnosis of a low-grade Warthin-like mucoepidermoid carcinoma. The patient was disease-free 12 months after surgery. CONCLUSION: Warthin-like mucoepidermoid carcinoma has not been widely recognized and can be misdiagnosed as Warthin tumor. Testing for MAML2 rearrangement provides essential support for diagnosis in difficult cases.

Metformin Suppresses Hypopharyngeal Cancer Growth by Epigenetically Silencing Long Non-coding RNA SNHG7 in FaDu Cells.

Local recurrence after therapy remains a challenging problem for hypopharyngeal cancer (HPC) due to the chemotherapy resistance. Metformin is associated with reduced cancer risk through promoting global DNA methylation in cancer cells by controlling S-adenosylhomocysteine (SAHH) activity. However, the mechanisms by which metformin inhibits HPC remain elusive. In this study, we aim to investigate the role of metformin in HPC and illustrate the mechanism by which metformin regulates long non-coding RNAs (lncRNAs) expression. CCK-8 and annexin-V/PI double staining were performed to analyze the cell viability and apoptosis. LncRNA microarray analysis, QPCR, methylation specific PCR, Western blot and RNA Immunoprecipitation were performed to analyze the molecular mechanism, Here, we report that metformin inhibits FaDu cell proliferation in time- and dose-dependent manner by suppressing lncRNA SNHG7. Further investigations revealed that SNHG7 interacted with SAHH and metformin decreased SNHG7 expression by activating SAHH activity. Increased SAHH activity resulted in upregulating DNMT1 expression, leading to hypermethylation of SNHG7 promotor. In addition, upregulation of SNHG7 was associated with advanced stage. The patients with high SNHG7 have lower overall survival than that of with low SNHG7. Interestingly, SNHG7 levels were higher in taxol resistant patients than in taxol sensitive patients. Metformin sensitizes FaDu cells to taxol and irradiation through decreasing SNHG7. In conclusion, our recent study demonstrates that metformin inhibits FaDu cell proliferation by decreasing SNHG7 expression via SAHH-mediated DNA methylation. These findings indicate that combined metformin with paclitaxel or irradiation would be a novel therapeutic strategy to overcome resistance and prevent recurrence in HPC.

[Corrigendum] ANXA1­derived peptides suppress gastric and colon cancer cell growth by targeting EphA2 degradation.

Following the publication of the above article, the authors have realized that one of the data panels featured in Fig. 5D was selected incorrectly. Specifically, the wrong image was selected for the A1 (28­30), HCT116 experiment. The authors have revisited their original sources to identify the correct data panel, and can confirm that the error arose unintentionally during the process of compiling the figure. The correct version of Fig. 5, featuring corrected data panel for Fig. 5D, is shown on the next page. The authors confirm that this error did not affect the conclusions reported in this study, and are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. Furthermore, the authors apologize to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Oncology 57: 1203­1213, 2020; DOI: 10.3892/ijo.2020.5119].

Rapid detection of quantum dot immune chromatography nasopharyngeal carcinoma EBNA1 antibody.

This study explored the 605 nm carboxyl of water-soluble quantum dots to assess the practicability of the nasopharyngeal carcinoma marker EBNA1 antibody. We used 605 nm carboxyl water-soluble quantum dots and nasopharyngeal carcinoma EBNA1 antigen in 1-(3-dimethylaminopropyl-3-2-ethylcarbonimine hydrochloride to generate quantum dot-labeled antigen. Gel imaging system showed that serum group and 60 patients with nasopharyngeal carcinoma had significant differences in 30 cases of normal adult serogroup brightness, Levene test in the two groups ELISA absorbance value was P<0.001, namely the nasopharyngeal carcinoma group and the normal adult serum group measured absorbance value difference was obvious. The statistical significance, and the detection technology were of high specificity and sensitivity. In conclusion, this study adopted double antigen clip combining immune chromatography test EBNA1 antibody in serum, compared with the traditional enzyme-linked immunoassays this method is more rapid, with simpler operation, rapid detection for developing quantum dot immune chromatography technology the EBNA1 antibody kit provides a theoretical basis.