Upregulated histamine receptor H3 promotes tumor growth and metastasis in hepatocellular carcinoma.

Histamine receptor H3 (HRH3) is mainly expressed in the central nervous system, where it is involved in the regulation of the release of various neurotransmitters in the brain. Recent studies have demonstrated that the expression of HRH3 is upregulated in several types of cancer. However, the functional effect of HRH3 on tumor progression remains largely unknown, particularly in hepatocellular carcinoma (HCC). In the present study, the expression of HRH3 in 96 HCC patients was first evaluated, and its clinical significance was analyzed. Subsequently, the functional roles of HRH3 in HCC growth and metastasis were systematically explored in vitro and in vivo using its agonist (imetit) or antagonist (clobenpropit). It was observed that HRH3 was significantly upregulated in HCC tissues, while its expression was significantly associated with recurrence­free survival and overall survival in HCC patients. Functional experiments also demonstrated that HRH3 upregulation facilitated the growth and metastasis of HCC cells by inducing the formation of lamellipodia. These findings revealed that HRH3 serves an important role in the growth and metastasis of HCC cells, which provides experimental evidence supporting the application of HRH3 as a potential therapeutic target in HCC treatment.

miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3.

Traditional research modes aim to find cancer-specific single therapeutic target. Recently, emerging evidence suggested that some micro-RNAs (miRNA) can function as oncogenes or tumor suppressors. miRNAs are single-stranded, small noncoding RNA genes that can regulate hundreds of downstream target genes. In this study, we evaluated the miRNA expression patterns in gastric carcinoma and the specific role of miR-223 in gastric cancer metastasis. miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric carcinomas and confirmed in another 20 paired gastric carcinoma tissues. With the 2-fold expression difference as a cutoff level, we identified 22 differential expressed mature miRNAs. Sixteen miRNAs were upregulated in gastric carcinoma, including miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214 and miR-191, and six miRNAs were downregulated in gastric carcinoma, including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p. After examining these miRNAs in several human gastric originated cell lines, we found that miR-223 is overexpressed only in metastatic gastric cancer cells and stimulated nonmetastatic gastric cancer cells migration and invasion. Mechanistically, miR-223, induced by the transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3'-untranslated regions. Significantly, overexpression of miR-223 in primary gastric carcinomas is associated with poor metastasis-free survival. These findings indicate a new regulatory mode, namely, specific miRNA, which is activated by its upstream transcription factor, could suppress its direct targets and lead to tumor invasion and metastasis.

A case-control study of laparoscopy-assisted and open distal gastrectomy for advanced gastric cancer.

BACKGROUND: The application of laparoscopy-assisted gastric surgery has been increasing rapidly for the treatment of early gastric cancer. However, there were few reports of laparoscopic surgery in the management of advanced gastric cancer (AGC), especially with T3 depth of invasion. The aim of this study was to compare the technical feasibility and oncologic efficacy of laparoscopy-assisted distal gastrectomy (LADG) versus open distal gastrectomy (ODG) for advanced gastric cancer. METHODS: A retrospective case-control study was performed comparing LADG and ODG for AGC. Thirty-five consecutive patients with AGC undergoing LADG between August 2005 and December 2007 were enrolled and these patients were compared with 35 AGC patients undergoing ODG during the same period. RESULTS: Forty-two (60.0%) patients were T3 in terms of depth of invasion. Tumor location and histology were similar between the two groups. Operation time was significantly longer in the LADG group than in the ODG group. Estimated blood loss was significantly less in the LADG group. Hospital length of stay after LADG was significantly shorter than in the open group. Postoperative pain was significantly lower for laparoscopic patients. There were no significant differences in postoperative early and late complication and in the number of lymph nodes retrieved between the two groups, and the cumulative survival of the two groups was similar. CONCLUSION: Our data indicate that LADG for AGC, mostly with T3 depth of invasion, yields good oncologic outcomes including the similar early and late complication and the cumulative survival between the two groups after 50 months of follow-up. To be accepted as a choice treatment for advanced distal gastric cancer, well-designed prospective trial to assess long-term outcomes is necessary.