Hepatocellular carcinoma (HCC) is a common and rapidly progressing malignancy. Current treatment options for advanced HCC are limited. This clinical study of dendritic cell (DC)-based immunotherapy for HCC enrolled 31 patients with advanced HCC. DCs, propagated from peripheral blood monocytes, were pulsed with autologous tumor lysates to treat HCC. The first 14 patients underwent pulsed therapy with five courses of DC vaccination intravenously at weekly intervals. The other 17 patients underwent monthly boost vaccinations after the initial pulsed therapy. Among the 31 patients, 4 (12.9%) exhibited partial response to DC vaccination. Seventeen patients (54.8%) had stable disease. Ten patients (32.3%) had progressive disease. The overall 1-year survival rate of all 31 patients was 40.1 +/- 9.1%. The patients treated with pulsed and boosted therapy had better 1-year survival rates than those treated by pulsed therapy alone (63.3 +/- 12.0% vs. 10.7 +/- 9.4%; P < 0.001). In this trial, DC vaccinations for advanced HCC were safe. Liver function tests showed no difference before and after DC vaccinations. The results of this clinical trial indicate that DC vaccination is a safe treatment for HCC. Pulsed DC vaccination followed by boosters can provide better clinical survival for advanced HCC patients than pulsed DC vaccination only. Further studies are needed to increase the efficacy of this therapeutic approach.
The molecular mechanisms underlying the pathophysiology of heat stress in the small intestine remain undefined. Furthermore, little information is available concerning changes in microRNA (miRNA) expression following heat stress. The present study sought to evaluate miRNA and mRNA expression profiles in the rat small intestine in response to heat stress. Male Sprague-Dawley rats were subjected to 2 h of heat stress daily for ten consecutive days. Rats were sacrificed at specific time points immediately following heat treatment, and morphological changes in the small intestine were determined. The miRNA and mRNA expression profiles from sample of small intestine were evaluated by microarray analysis. Heat stress caused pronounced morphological damage in the rat small intestine, most severe within the jejunum after 3 days of heat treatment. A mRNA microarray analysis found 270 genes to be up-regulated and 122 genes down-regulated (P ≤ 0.01, ≥2.0-fold change) in the jejunum after heat treatment. A miRNA microarray analysis found 18 miRNAs to be up-regulated and 11 down-regulated in the jejunum after heat treatment (P ≤ 0.05). Subsequent bioinformatic analyses of the differentially expressed mRNAs and miRNAs were carried out to integrate miRNA and mRNA expression and revealed that alterations in mRNA following heat stress were negatively correlated with miRNA expression. These findings significantly advance our understanding of the regulatory mechanisms underlying the pathophysiology of heat stress-induced injury in the small intestine, specifically with regard to miRNAs.
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