There is increasing evidence that the expression of microRNA (miRNA) in cancer is associated with chemosensitivity but the mechanism of miRNA-induced chemoresistance has not been fully elucidated. The aim of this study was to examine the role of extracellular miRNA in the response to chemotherapy in esophageal cancer. First, serum expression of miRNAs selected by miRNA array was measured by quantitative reverse transcription-polymerase chain reaction in 68 patients with esophageal cancer who received cisplatin-based chemotherapy to examine the relationship between miRNA expression and response to chemotherapy. The serum expression levels of 18 miRNAs were different between responders and non-responders by miRNA array. Of these, high expression levels of miR-27a/b correlated with poor response to chemotherapy in patients with esophageal cancer. Next, in vitro assays were conducted to investigate the mechanism of miRNA-induced chemoresistance. Although transfection of miR-27a/b to cancer cells had no significant impact on chemosensitivity, esophageal cancer cells cultured in supernatant of miR-27a/b-transfected normal fibroblast showed reduced chemosensitivity to cisplatin, compared with cancer cells cultured in supernatant of normal fibroblast. MiR-27a/b-transfected normal fibroblast showed α-smooth muscle actin (α-SMA) expression, a marker of cancer-associated fibroblasts (CAF) and increased production of transforming growth factor-β (TGF-β). Chemosensitivity recovered after administration of neutralizing antibody of TGF-β to the supernatant transfer experiments. Our results indicated that miR-27a/b is involved in resistance to chemotherapy in esophageal cancer, through miR-27a/b-induced transformation of normal fibroblast into CAF.

A scanning electron microscopic study was made on the morphological changes occurring with age in collagen and elastic fibers in the lamina propria of the human vocal fold. We obtained the specimens from 32 autopsy cases ranging from 20 gestational weeks to 22 postnatal years and submitted them to digestion treatments with 10% sodium hydroxide and 90% formic acid. The vocal folds in fetuses and neonates consisted of sparse and dense areas of collagen and elastic fibers, and the vocal ligament was not found. In subjects 5 years of age, a deep dense area was found in the anterior and posterior maculae flavae, and longitudinal fibers were noted between the maculae. A structure of superficial versus deep layers appeared in children older than 10 years of age. The layered structure of the lamina propria was complete around 17 years of age. The development of the layered structure and the maturity of the fibers appeared to reflect the complexity of phonatory function during adolescence.

The incidence of postoperative infectious complications, in particular pulmonary infection, is associated with unfavorable prognosis in patients with esophageal cancer undergoing preoperative chemotherapy.

High expression of Pink1 is associated with chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant chemotherapy.

The association between the tumor microenvironment (TME) and treatment response or survival has been a recent focus in several types of cancer. However, most study materials are resected specimens that were completely modified by prior chemotherapy; therefore, the unmodified host immune condition has not yet been clarified. The aim of the present study was to evaluate the relationship between TME assessed in pretherapeutic biopsy samples and chemoresistance in esophageal cancer (EC). A total of 86 endoscopic biopsy samples from EC patients who received neoadjuvant chemotherapy (NAC) prior to surgery were evaluated for the number of intratumoral CD4 + lymphocytes (with/without Foxp3 expression), CD8 + lymphocytes (with/without PD-1 expression), monocytes (CD14 + ) and macrophages (CD86 + , CD163 + and CD206 + ) by multiplex immunohistochemistry (IHC). The number of tumor-infiltrating CD206 + macrophages I significantly correlated with cT, cM, cStage and neutrophil/lymphocyte ratio (NLR), whereas the number of lymphocytes (including expression of Foxp3 and PD-1) was not associated with clinico-pathological features. The high infiltration of CD163 + or CD206 + macrophages was significantly associated with poor pathological response to NAC (P = 0.0057 and 0.0196, respectively). Expression of arginase-1 in CD163 + macrophages tended to be higher in non-responders (29.4% vs 18.2%, P = 0.17). In addition, patients with high infiltration of M2 macrophages exhibited unfavorable overall survival compared to those without high infiltration of M2 macrophages (5-year overall survival 57.2% vs 71.0%, P = 0.0498). Thus, a comprehensive analysis of TME using multiplex IHC revealed that M2 macrophage infiltration would be useful in predicting the response to NAC and long-term survival in EC patients. K E Y W O R D Sbiopsy, esophageal cancer, M2 macrophage, multiplex immunohistochemistry, neoadjuvant chemotherapy