相关实验视频

Updated: Jun 16, 2025

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development

Published on: October 30, 2013

通过工程向OIP5,通过TRIP12-PPP1CB-YBX1轴使膀癌对化疗耐药性敏感

Xianteng Wang^1,2, Ting Guo^3,4,5, Liman Niu¹

¹Department of Urology, Shenzhen Institute of Translational Medicine, Medical Innovation Technology Transformation Center, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, International Cancer Center of Shenzhen University, Shenzhen, China.

|August 18, 2024

概括

吉姆西塔加西斯治疗触发了涉及OIP5和YBX1的信号通路,导致膀癌的化学抵抗. 通过基因电路准这种途径,有望改善癌症治疗结果.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症遗传学癌症遗传学

背景情况:

化疗抵抗显著导致膀癌的治疗失败.
识别药物耐药性背后的分子机制对于开发新型治疗策略至关重要.

研究的目的:

为了阐明gemcitabine加 cisplatin (GEM/DDP) 在膀癌中诱导化学抵抗的分子机制.
调查OIP5在赋予化学抗性的作用及其与患者预后的关联.
评估基于CRISPR/Cas9的基因电路的治疗潜力,以此途径为目标.

主要方法:

研究了GEM/DDP对NF-κB信号传递和OIP5表达的影响.
使用分子生物学技术研究蛋白质相互作用和转录调节 (OIP5,TRIP12,PPP1CB,YBX1,IKKβ).
开发并测试了一种CRISPR/Cas9工程基因电路,用于实时监测和干预体内化学抵抗.

主要成果:

GEM/DDP疗法激活NF-κB信号,导致OIP5上调.
OIP5通过招募TRIP12来降解PPP1CB,增强YBX1活动和耐药基因表达,促进化学抵抗.
一个涉及PPP1CB降解和IKKβ酸化的负反循环进一步放大NF-κB信号和OIP5表达.
提高OIP5表达与膀癌患者的化学抵抗和不良预后相关.
在体内,CRISPR/Cas9基因电路通过诱导OIP5淘汰赛来有效抑制瘤生长.

结论:

通过OIP5介导的途径是膀癌中GEM/DDP化学抵抗的关键驱动因素.
OIP5表达作为膀癌的预后生物标志物.
针对这种途径的工程基因电路为克服化学抵抗和增强癌症治疗提供了一个有希望的战略.

更多相关视频

Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model

Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model

Published on: May 29, 2015

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

Published on: December 1, 2013

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...