A rare case of esophageal mucoepidermoid carcinoma successfully treated via endoscopic submucosal dissection.

Esophageal mucoepidermoid carcinoma (EMEC) is a special subtype of esophageal malignancy, accounting for less than 1% of all cases of primary esophageal carcinoma. Pathologically, it consists of a mixture of adenocarcinoma and squamous cell carcinoma with mucin-secreting cells. Special staining for mucicarmine helps to diagnose EMEC. We present a rare case of EMEC successfully treated via endoscopic submucosal dissection (ESD). A 63-year-old man was referred to our tertiary hospital. On esophagogastroduodenoscopy, a 6-mm-sized subtle reddish depressed lesion was identified in the mid-esophagus. Diagnostic ESD was performed with a high suspicion of carcinoma. Histopathologic findings were consistent with EMEC which was confined to the lamina propria without lymphatic invasion. We plan to do a careful follow-up without administering adjuvant chemotherapy or radiotherapy. Due to the small volume of the lesion, establishing a diagnosis was difficult through forceps biopsy alone. However, by using ESD, we could confirm and successfully treat a rare case of early-stage EMEC.

Sensitization of multidrug-resistant cancer cells to Hsp90 inhibitors by NSAIDs-induced apoptotic and autophagic cell death.

NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp), and reversed Hsp90 inhibitor resistance caused by activation of heat shock factor 1 (HSF1) and by up-regulation of heat shock proteins (Hsps) and P-gp. Inhibition of Akt/mTOR and STAT3 pathways by CCB induced autophagy, which promoted the degradation of mutp53, one of Hsp90 client proteins, and subsequently down-regulated HSF1/Hsps and P-gp. Inhibition of autophagy prevented mutp53 degradation and CCB-induced apoptosis, and inhibition of caspase-3-mediated apoptotic pathway by Z-DEVD-FMK did not completely block CCB-induced cell death in MDR cells, suggesting that autophagic and apoptotic cell death may contribute to CCB-induced cytotoxicity in MDR cells. Furthermore, CCB and IBU suppressed Hsp90 inhibitor-induced HSF1/Hsp70/P-gp activity and mutp53 expression in MDR cells. Our results suggest that NSAIDs can be used as potential Hsp90 inhibitor chemosensitizers and reverse resistance of MDR cells to Hsp90 inhibitors via induction of apoptosis and autophagy. These results might enable the use of lower, less toxic doses of Hsp90 inhibitors and facilitate the design of practically applicable, novel combination therapy for the treatment of MDR cancer.