The prognosis of esophageal squamous cell carcinoma is poor. In order to find out appropriate treatment for each group of patients, we aim to examine the prognostic factors influencing survival for esophageal cancer patients in Taiwan. Data were obtained from the Taiwan Society of Cancer Registry. There were 14,394 esophageal cancer patients analyzed between 2008 and 2014 in this retrospective review. The impact of the clinicopathologic factors on overall survival was assessed. The following clinic‐pathologic factors were included to analyses: age, sex, tumor location, tumor length, histologic grade, clinical T, clinical N, clinical M, clinical stage, and all therapeutic methods within 3 months after diagnosis. The 5‐year survival rate was 16.8%, with a median survival of 343 days. The distribution of patients by their clinical stage is as follows: stage 0 (n = 162; 1.1%); stage I (n = 964; 6.7%); stage II (n = 2392; 16.6%); stage III (n = 6636; 46.1%); and stage IV (n = 3661; 25.4%). In the multivariate analysis, age, sex, tumor location, tumor length, clinical T, clinical N, clinical M, and treatment remained independent prognostic factors. Our data indicated that age, sex, tumor location, tumor length, clinical T, clinical N, clinical M, and treatment remained independent prognostic factors. Patients who could receive surgery had significantly better outcomes.

Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important therapeutic target in future cancer therapy. Previous studies reported that hinokitiol exhibits an anti-cancer activity against murine tumor cells through the induction of autophagy. The current research revealed that hinokitiol suppressed the self-renewal capabilities of human breast CSCs (BCSCs) and inhibited the expression of BMI1 at protein level without suppressing its mRNA. Treatment of hinokitiol in mammospheres induced the expression of miR-494-3p and inhibition of miR-494-3p expression in BCSCs. This treatment abolished the suppressive effects of hinokitiol in mammosphere formation and BMI1 expression. BMI1 is a target of miR-494-3p by luciferase-based 3′UTR reporter assay. Overexpression of miR-494-3p in BCSCs caused the down-regulation of BMI1 protein, inhibition of mammosphere forming capability, and suppression of their tumorigenicity. Moreover, miR-494-3p expression was significantly and inversely correlated with patient survival in two independent public database sets. Furthermore, treatment of hinokitiol in vivo suppressed the growth of xenograft human breast tumors as well as the expression of BMI1 and ALDH1A1 in xenograft tumors. In conclusion, these data suggest that hinokitiol targets BCSCs through the miR-494-3p-mediated down-modulation of BMI1 expression.

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Compared with surgery alone, adjuvant chemoradiation provides a survival benefit to ESCC patients, especially those with pT3/4 stage, N+ tumors, larger tumor size, poorly differentiated tumors, and R1/2 resections.

Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. Through immunoprecipitation analysis, we found that BMI1 did not interact with Hsp90α and that the downregulation of BMI1 by 17-DMAG was mediated by the inhibition of c-Myc and enhancement of zeste homolog 2 (EZH2) expression. The transcriptional and BMI1 promoter-binding activities of c-Myc in BCSCs were inhibited by 17-DMAG treatment. The overexpression of EZH2 attenuated the inhibitory effect of 17-DMAG on BMI1 and c-Myc expression. Furthermore, Hsp90α could be co-immunoprecipitated with c-Myc and EZH2 and bind to the BMI1 promoter. Treatment with 17-DMAG decreased the nuclear expression of EZH2 and c-Myc but not that of Hsp90α. In conclusion, our data suggested that Hsp90α could positively regulate the self-renewal of BCSCs by facilitating the nuclear translocation of c-Myc and EZH2 to maintain BMI1 expression.