title: Application of chemokine receptor antagonist with stents reduces local inflammation and suppresses cancer growth.
abstract: Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients' condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth.
authors.affiliation: Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, 410008, China.|Interventional Center, St. Luke's Hospital of Jiaotong University School of Medicine, 786 Yuyuan Road, Shanghai, 200050, China.
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Mao
authors.affiliation: Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, 410008, China.|Interventional Center, St. Luke's Hospital of Jiaotong University School of Medicine, 786 Yuyuan Road, Shanghai, 200050, China.
authors.forename: Ting-Hui
authors.initials: TH
authors.lastname: Jiang
authors.affiliation: Interventional Center, St. Luke's Hospital of Jiaotong University School of Medicine, 786 Yuyuan Road, Shanghai, 200050, China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, 410008, China. aiwu_mao@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D001596:Benzylamines; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000235:genetics*; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015607:Stents / Q000009:adverse effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: Inflammation; Pancreatic cancer; Stents; Stromal cell-derived factor 1 (SDF-1)