Purpose: MicroRNAs are f22 nucleotide noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was (a) to determine a role of microRNA-21 in esophageal squamous cell carcinoma and (b) to elucidate the regulation of the programmed cell death 4 (PDCD4) gene by microRNA-21. Experimental Design: MicroRNA-21 expression was investigated in 20 matched normal esophageal epitheliums and esophageal squamous cell carcinomas and seven esophageal squamous cell carcinoma cell lines (TE6, TE8, TE10, TE11, TE12, TE14, KYSE30) by TaqMan quantitative real-time PCR and in situ hybridization. To evaluate the role of microRNA-21, cell proliferation and invasion were analyzed with anti^microRNA-21^transfected cells. In addition, the regulation of PDCD4 by microRNA-21 was elucidated to identify the mechanisms of this regulation. Results: Of 20 paired samples, 18 cancer tissues overexpressed microRNA-21 in comparison with matched normal epitheliums. Specifically, patients with lymph node metastasis or venous invasion showed significantly high expression of microRNA-21. In situ hybridization for microRNA-21 showed strong positive staining in paraffin-embedded esophageal squamous cell carcinoma tissues. All seven esophageal squamous cell carcinoma cell lines also overexpressed microRNA-21, and anti^microRNA-21^transfected cells showed significant reduction in cellular proliferation and invasion. The PDCD4 protein levels in esophageal squamous cell carcinoma cells have an inverse correlation with microRNA-21expression. Anti^microRNA-21^transfected cells increased PDCD4 protein expression without changing the PDCD4 mRNA level and increased a luciferase-reporter activity containing the PDCD4-3 ¶ untranslated region construct. Conclusions: MicroRNA-21 targets PDCD4 at the posttranscriptional level and regulates cell proliferation and invasion in esophageal squamous cell carcinoma. It may serve as a novel therapeutic target in esophageal squamous cell carcinoma.Esophageal cancer occurs worldwide with a variable geographic distribution and ranks eighth in order of occurrence and the sixth leading cause of cancer mortality, affecting men more than women (1). It has two main forms, each with distinct etiologic and pathologic characteristics, esophageal squamous cell carcinoma and adenocarcinoma. Esophageal squamous cell carcinoma is the most frequent subtype of esophageal cancer, although the incidence of adenocarcinoma in the Western world is increasing faster than other esophageal malignancies.

The alternative CPCR demonstrated an improvement in the incidence of good recovery. Based upon these findings, randomized studies of this hypothermia are needed.

Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients, and asphyxic newborns, recent randomized controlled trials (RCTs) have equally shown good neurological outcome between targeted temperature management at 33 °C versus 36 °C, and have not shown consistent benefits in patients with traumatic brain injury (TBI). We aimed to determine the effect of therapeutic hypothermia, while avoiding some limitations of earlier studies, which included patient selection based on Glasgow coma scale (GCS), delayed initiation of cooling, short duration of cooling, inter-center variation in patient care, and relatively rapid rewarming. We conducted a multicenter RCT in patients with severe TBI (GCS 4-8). Patients were randomly assigned (2:1 allocation ratio) to either therapeutic hypothermia (32-34 °C, n = 98) or fever control (35.5-37 °C, n = 50). Patients with therapeutic hypothermia were cooled as soon as possible for ≥ 72 h and rewarmed at a rate of <1 °C/day. All patients received tight hemodynamic monitoring under intensive neurological care. The Glasgow Outcome Scale was assessed at 6 months by physicians who were blinded to the treatment allocation. The overall rates of poor neurological outcomes were 53% and 48% in the therapeutic hypothermia and fever control groups, respectively. There were no significant differences in the likelihood of poor neurological outcome (relative risk [RR] 1.24, 95% confidence interval [CI] 0.62-2.48, p = 0.597) or mortality (RR 1.82, 95% CI 0.82-4.03, p = 0.180) between the two groups. We concluded that tight hemodynamic management and slow rewarming, together with prolonged therapeutic hypothermia (32-34 °C) for severe TBI, did not improve the neurological outcomes or risk of mortality compared with strict temperature control (35.5-37 °C).

Abstract. The clinical significance of isolated tumor cells (ITC) circulating in the blood of patients with colorectal cancer is unclear. In this study, we investigated the relationship between the presence of ITC that express carcinoembryonic antigen (CEA) and/or cytokeratin 20 (CK20) transcripts in the blood and the clinicopathological findings and prognosis using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. We studied peripheral blood and tumor drainage blood from 167 patients with colorectal cancer. Quantitative real-time RT-PCR assay was able to detect one tumor cell in 3x10 6 peripheral blood mononuclear cells. Applying a cut-off value, CEA and/or CK20 (CEA/CK20) were detected in 10.2% (17/167) of the patients' preoperative peripheral blood samples and 34.1% (57/167) of the patients' tumor drainage blood samples. In the relationship between the CEA/CK20 of the blood and the clinicopathological factors, a significant correlation was demonstrated between the positivity of marker genes and the depth of invasion, venous invasion, lymph node metastasis, liver metastasis or stage. The disease-free and overall survival of patients with CEA/CK20-positive peripheral or tumor drainage blood was significantly shorter than that of marker gene-negative patients. CEA/CK20 transcripts in tumor drainage blood were independent factors for prognosis in disease-free survival and overall survival. These results suggest that detecting CEA/CK20 mRNA in tumor drainage blood by real-time RT-PCR has prognostic value in patients with colorectal cancer. Large scale and longterm clinical studies are needed to confirm the prognostic value of genetically detecting ITC in the peripheral blood.

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