[Role of CXCL16/CXCR6 axis in the metastasis of human prostate cancer].

OBJECTIVE: To explore the roles of chemokine CXCL16 and its receptor CXCR6 in the directional invasion of human prostate cancer (PCa). METHODS: The expression of CXCL16/CXCR6 in PCa samples and osseous tissues was determined by immunohistochemistry. The expression of CXCR6 in PC3 and LNCap cells was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. Then the effects of CXCL16 upon the migration and invasion of human PC3 and LNCap cells were examined by Matrigel invasion assay. RESULTS: The expression of CXCR6 protein was detected in all clinical PCa samples. But no CXCL16 protein was detected. Positive CXCL16 expression was observed in human osseous tissues. Both PC3 and LNCap cells expressed CXCR6 mRNA (0.38+/-0.054 vs 0.41+/-0.019 respectively) and protein. In addition, CXCL16 could promote the in vitro migration and invasion of PC3 and LNCap cell lines (invading cells 211.50+/-5.60 vs 89.25+/-3.31 respectively). Such a promoting effect of CXCL16 could not be blocked influenced by antiCXCL12 or antiCXCR4. CONCLUSION: CXCL16/CXCR6 axis may be another independent chemokine factor playing a significant role in the metastasis of prostate cancer.

Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: Results of a randomized controlled clinical trial.

AIM: To study the effects of perioperative administration of cimetidine (CIM) on peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODS: Forty-nine GI cancer patients were randomized into treatment group, who took CIM in perioperative period, and control group, who did not take the drug. The treatment was initiated 7 days before operation and continued for 10 days after surgery. At baseline examination before operation, on the 2nd and 10th postoperative days, total T lymphocytes, T helper cells, T suppressor cells, and NK cells in peripheral blood were measured respectively by immunocytochemical method using mouse-anti human CD(3), CD(4), CD(8) and CD(57) monoclonal antibodies. Blood samples from 20 healthy volunteers were treated in the same way as normal controls. Surgical specimens were examined during routine histopathological evaluation for the presence of TIL in tumor margin. Immunohistochemical study was performed to measure the proportion of T and B lymphocytes in TIL population. T and B lymphocytes were detected respectively using mouse-anti-human CD(3) and CD(20) monoclonal antibodies. RESULTS: In comparison with normal controls, both the treatment and control groups had decreased T cells, T helper cells and NK cells at baseline. In control group, total T cells, T helper cells and NK cells declined continuously with the disease progression and the decrease became more obvious after operation. From baseline to the 2nd postoperative day, the proportion of total T cells, T helper cells, and NK cells went down from 60.5+/-4.6% to 56.2+/-3.8%, 33.4+/-3.7% to 28.1+/-3.4%, and 15.0+/-2.8% to 14.2+/-2.2%, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative day, the treatment group had significantly higher percentages of total T cells, T helper cells and NK cells than control group. Moreover, CIM treatment also boosted TIL response, as was reflected by findings that 68% (17/25) of the patients in treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL responses (P<0.01). CONCLUSION: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity induced by tumor burden and surgical maneuver. The drug could also boost TIL responses to tumor. These effects suggest that the drug be used as an immunomodulator for GI cancer patients.