Research Project
Grant-in-Aid for Scientific Research (C)
Novel molecular targeted therapy for peritoneal dissemination of gastric cancer was examined in this study.1, The purpose of this study was to evaluate the efficacy of double-stranded decoy oligonucleotides targeting ets-1-binding cis elements for the suppression of ets-1 in treatment of a peritoneal dissemination model of gastric cancer. We have demonstrated that intra-peritoneal injection of ets-1 decoy inhibited the peritoneal dissemination of gastric cancer through suppression of tumor angiogenesis in a nude mice model. These results indicate that the decoy strategy for ets-1 can offer a promising therapy for patients with incurable peritoneal dissemination of gastric cancers.2, The transcription factor nuclear factor-kB (NF-kB) plays important roles in tumor invasion, metastasis, and chemoresistance. Aberrant NF-kB expression correlates with aggressive tumor behavior and poor prognosis in patients with various malignancies. This study evaluated the sesquiterpene lactone parthenolide, an inhibitor of NF-kB, in the treatment of gastric cancer. Parthenolide significantly inhibited cell growth in three gastric cancer cell lines. It downregulated the phosphorylation of NF-kB, and acted synergistically with chemotherapeutic drugs, paclitaxel and cisplatin. In the peritoneal dissemination model, parthenolide as a single agent significantly suppressed the formation of disseminated nodules, and enhanced chemosensitivity to paclitaxel when used in combination. Furthermore, the combined parthenolide and paclitaxel therapy significantly prolonged survival. Parthenolide, a selective NF-□B inhibitor, seems to enhance the chemosensitivity of paclitaxel and cisplatin in the incurable peritoneal dissemination of gastric cancers.
All 2007 2006
All Journal Article (17 results) (of which Peer Reviewed: 6 results) Presentation (2 results)
International Journal of Cancer 121
Pages: 1609-1617
Gastric Cancer 10
Pages: 197-204
Int J Oncol 28(2)
Pages: 375-381
Clin Cancer Res 12(1)
Pages: 117-122
Gastric Cancer 9(1)
Pages: 44-49
J Surg Oncol 93
Pages: 477-484
Eur J Cancer 42
Pages: 1897-1903
J Surg Oncol 932
