New cancer treatment focusing on genetic instability of the cancer stem cell

新的癌症治疗重点关注癌症干细胞的遗传不稳定性

• 批准号: 24659614
• 负责人: MAEHARA Yoshihiko
• 金额: $ 2.41万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659614/
• 关键词: 染色体不安定性; 酸化ストレス; BuBR1; p53; がん幹細胞; LgR5; LGR5; 遺伝子不安定性; 癌幹細胞; CD44

The cancer stem cell remains to be resistant to the treatment such as chemotherapy or the radiation. We can propose a new treatment to reduce recurrence and metastasis by targetting the cancer stem cell. Because a cancer is exposed to hypoxia and chemical irritation partially, some cells become a stem like cell and become to generate genetic instability.In our experiment,oxidative stress (OS) causes DNA damage and chromosome instability that may lead to carcinogenesis. OS is also suggested to contribute to an increase in aneuploid cells. However, it is not clear how OS is involved in the regulation of SAC and contributes to carcinogenesis associated with aneuploidy. Here we show that an oxidant (KBrO3) activated the p53 signaling pathway and suppressed the expression of SAC factors, BubR1, and Mad2, in human diploid fibroblast MRC5 cells. This suppression was dependent on functional p53 and reactive oxygen species.

癌症干细胞仍然对化疗或放射等治疗具有抵抗力。我们可以提出一种新的治疗方法，通过靶向肿瘤干细胞来减少复发和转移。由于癌症部分暴露在低氧和化学刺激下，一些细胞成为干细胞并产生遗传不稳定性。在我们的实验中，氧化应激(OS)导致DNA损伤和染色体不稳定，可能导致癌症发生。OS也被认为是导致非整倍体细胞增加的原因。然而，目前尚不清楚OS如何参与SAC的调控，以及与非整倍体相关的致癌作用。在这里，我们发现氧化剂(KBrO_3)激活了P53信号通路，并抑制了SAC因子BubR1和MAD2在人二倍体成纤维细胞MRC5细胞中的表达。这种抑制依赖于功能上的P53和活性氧物种。

项目成果

Hepatic vein waveform and splenomegaly predict improvement of prothrombin time after splenectomy in hepatitis C virus-related cirrhotic patients.

肝静脉波形和脾肿大可预测丙型肝炎病毒相关肝硬化患者脾切除术后凝血酶原时间的改善。

• DOI: 10.1111/hepr.12040
• 发表时间: 2012
• 期刊: Hepatol Res.
• 作者: Kinjo N;Nagao Y;Akahoshi T;Masahiro K;Hashimoto N;Uehara H;Kawanaka H;Tomikawa M;Shirabe K;Hashizume M;Maehara Y.
• 通讯作者: Maehara Y.

Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: a multicenter study in Japan.

二线及后续含西妥昔单抗治疗和 KRAS 基因型对转移性结直肠癌患者的影响：日本的一项多中心研究。

• DOI: 10.1007/s00595-013-0716-0
• 发表时间: 2014
• 期刊: Surg Today.
• 作者: Saeki H;Emi Y;Kumashiro R;Otsu H;Kawano H;Ando K;Ida S;Kimura Y;Tokunaga E;Oki E;Morita M;Shimokawa M;Maehara Y
• 通讯作者: Maehara Y

Hepatic interferon‐gamma‐induced protein‐10 expression is more strongly associated with liver fibrosis than interleukin‐28B single nucleotide polymorphisms in hepatocellular carcinoma resected patients with chronic hepatitis C

• DOI: 10.1111/hepr.12070
• 发表时间: 2013-11
• 期刊: Hepatology Research
• 影响因子: 4.2
• 作者: H. Konishi;K. Shirabe;S. Yoshiya;T. Ikeda;T. Ikegami;T. Yoshizumi;Ayae Ikawa-Yoshida;T. Motomura;T. Fukuhara;Y. Maehara

Contribution of BubR1 to oxidative stress-induced aneuploidy in p53-deficient cells.

• DOI: 10.1002/cam4.101
• 发表时间: 2013-08
• 期刊: CANCER MEDICINE
• 影响因子: 4
• 作者: Ikawa-Yoshida, Ayae;Ando, Koji;Oki, Eiji;Saeki, Hiroshi;Kumashiro, Ryuichi;Taketani, Kenji;Ida, Satoshi;Tokunaga, Eriko;Kitao, Hiroyuki;Morita, Masaru;Maehara, Yoshihiko
• 通讯作者: Maehara, Yoshihiko

Impact of GATA-3 and FOXA1 expression in patients with hormone receptor-positive/HER2-negative breast cancer

• DOI: 10.1007/s12282-013-0515-x
• 发表时间: 2015-09-01
• 期刊: BREAST CANCER
• 影响因子: 4
• 作者: Hisamatsu, Yuichi;Tokunaga, Eriko;Maehara, Yoshihiko
• 通讯作者: Maehara, Yoshihiko