Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 might induce the invasion, migration, and epithelial–mesenchymal transition (EMT) process of breast cancer. In this research, human breast cancer MCF‐7 and MDA‐MB‐231cells were treated with CCL19 and small‐interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 mediated cell invasion and migration by inducing the EMT, with downregulation of E‐cadherin and up‐regulation of N‐cadherin and vimentin levels. On the other hand, knockdown of CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits CCL19‐induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT. Moreover, we demonstrated that CCL19‐induced AKT phosphorylation; however, CCR7 siRNA suppressed CCL19‐induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL19/CCR7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR7 may regard as a therapeutic target for the breast cancer treatment.

Ghrelin accelerates delayed GE and IT but has no effect on CT in diabetic mice. Ghrelin may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.

strips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION:Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system. © 2008 WJG . All rights reserved.Key words: Gastric emptying; Ghrelin; Growth hormone releasing peptide 6; Growth hormone secretagogue receptor; Diabetic mice INTRODUCTIONDelayed gastric emptying occurs in more than 50% of patients with chronic diabetes mellitus (DM) and is always associated with impaired quality of life and diabetic control. While this delay is not always clinically apparent, the range of gastrointestinal symptoms may include nausea, vomiting, regurgitation, fullness, and bloating [1] . Diabetic patients with poor gastric emptying have a number of possible metabolic consequences, including poor glycemic control, increased risk of postprandial hypoglycemia and variable drug absorption. At its worst, gastroparesis can lead to intractable vomiting and an inability to feed, and carries a poor prognosis [2] . Present management of diabetic gastroparesis involves empirical use of prokinetic drugs such as domperidone, metoclopramide, cisapride [2,3] and erythromycin [4] . The effects of these drugs, however, are unpredictable. One possible explanation for this lack of sustained response to treatment is that gastroparesis may be originally associated with progressive autonomic neuropathy [5,6] . Ghrelin, a 28-amino acid peptide with an octanoyl moiety at Ser Abstract AIM: To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS:A diabetic mouse model was established by intraperitoneal (ip ) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, N G -nitro-L-arginine methyl ester hydrochloride (L-N AME) or D -Lys 3 -GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro , in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS:We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys 3 -GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-indu...

Bovine herpesvirus 1 (BoHV-1) is a promising oncolytic virus with broad antitumor spectrum; however, its oncolytic effects on human lung adenocarcinoma in vivo have not been reported. In this study, we report that BoHV-1 can be used as an oncolytic virus for human lung adenocarcinoma, and elucidate the underlying mechanism of how BoHV-1 suppresses tumor cell proliferation and growth. First, we examined the oncolytic activities of BoHV-1 in human lung adenocarcinoma A549 cells. BoHV-1 infection reduced the protein levels of histone deacetylases (HDACs), including HDAC1-4 that are promising anti-tumor drug targets. Furthermore, the HDAC inhibitor Trichostatin A (TSA) promoted BoHV-1 infection and exacerbated DNA damage and cytopathology, suggesting a synergy between BoHV-1 and TSA. In the A549 tumor xenograft mouse model, we, for the first time, showed that BoHV-1 can infect tumor and suppressed tumor growth with a similar high efficacy as the treatment of TSA, and HDACs have potential effects on the virus replication. Taken together, our study demonstrates that BoHV-1 has oncolytic effects against human lung adenocarcinoma in vivo.