Novel molecular targeted therapy for peritoneal dissemination of gastric cancer

胃癌腹膜播散的新型分子靶向治疗

• 批准号: 18591463
• 负责人: FUJIWARA Yoshiyuki
• 金额: $ 2.57万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591463/
• 关键词: gastric cancer; peritonitis carcinomatosa; molecular targeted therapy; ets-1; parthenolide; NFkappaB

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.

本研究探讨了针对胃癌腹膜播散的新型分子靶向治疗。1，本研究的目的是评估靶向 ets-1 结合顺式元件的双链诱饵寡核苷酸在抑制 ets-1 治疗胃癌腹膜播散模型中的功效。我们在裸鼠模型中证明，腹腔注射 ets-1 诱饵可通过抑制肿瘤血管生成来抑制胃癌的腹膜播散。这些结果表明，ets-1的诱饵策略可以为无法治愈的腹膜播散性胃癌患者提供一种有希望的治疗方法。2、转录因子核因子-kB（NF-kB）在肿瘤侵袭、转移和化疗耐药中发挥重要作用。异常的 NF-kB 表达与各种恶性肿瘤患者的侵袭性肿瘤行为和不良预后相关。本研究评估了倍半萜内酯小白菊内酯（一种 NF-kB 抑制剂）在胃癌治疗中的作用。小白菊内酯显着抑制三种胃癌细胞系的细胞生长。它下调NF-kB的磷酸化，并与化疗药物紫杉醇和顺铂协同作用。在腹膜播散模型中，小白菊内酯作为单一药物可显着抑制播散性结节的形成，并在联合使用时增强对紫杉醇的化疗敏感性。此外，小白菊内酯和紫杉醇联合治疗显着延长了生存期。小白菊内酯是一种选择性 NF-□B 抑制剂，似乎可以增强紫杉醇和顺铂在无法治愈的腹膜播散性胃癌中的化疗敏感性。

项目成果

Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site

• DOI: 10.1016/j.ejca.2006.04.007
• 发表时间: 2006-08-01
• 期刊: EUROPEAN JOURNAL OF CANCER
• 影响因子: 8.4
• 作者: Motoori, Masaaki;Takemasa, Ichiro;Kato, Kikuya
• 通讯作者: Kato, Kikuya

Expression of hepatoma-derived growth factor is correlated with lymph nodemetastasis and prognosis of gastric carcinoma.

肝细胞源性生长因子的表达与胃癌淋巴结转移及预后相关。

• 发表时间: 2006
• 期刊: Clin Cancer Res 12(1)
• 作者: Yamamoto S.;Tomita Y.;Hoshida Y.;Takiguchi S.;Fujiwara Y.;Yasuda T.;Doki Y.;Yoshida K.;Aozasa K.;Nakamura H.;Monden M.
• 通讯作者: Monden M.

Gene therapy using ets-1 transcription factor decoy for peritoneal dissemination of gastric cancer.

使用 ets-1 转录因子诱饵进行胃癌腹膜播散的基因治疗。

• 发表时间: 2007
• 期刊: International Journal of Cancer 121
• 作者: Taniguchi H;Fujiwara Y
• 通讯作者: Fujiwara Y

A prospective trial for avoiding cervical lymph node dissection for thoracic esophageal cancers, based on infra-operative genetic diagosis of micrometastasis in recurrent laryngeal nerve chain nodes.

基于喉返神经链淋巴结微转移的术中遗传学诊断，避免胸段食管癌颈淋巴结清扫的前瞻性试验。

• 发表时间: 2006
• 期刊: J Surg Oncol 93
• 作者: Miyata H.;Yano M.;Doki Y.;Yasuda T.;Yoshioka S.;Sugita Y.;Takiguchi S.;Fujiwara Y.;Monden M.
• 通讯作者: Monden M.

Parthenolide, a selective NF-kB inhibitor, suppreses tumor growth and enhances response to chemotherapy in gastric cancer

小白菊内酯是一种选择性 NF-kB 抑制剂，可抑制肿瘤生长并增强胃癌化疗反应

• 发表时间: 2007
• 作者: Miyata H.;Yano M.;Doki Y.;Yasuda T.;Yoshioka S.;Sugita Y.;Takiguchi S.;Fujiwara Y.;Monden M.;Fujiwara Y
• 通讯作者: Fujiwara Y