相关实验视频

Updated: Jan 16, 2026

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

瘤 - 骨髓交叉驱动局部膀癌的治疗耐药性

Filipe Lf Carvalho, Jihyun Lee, Nikolaos Kalavros

bioRxiv : the preprint server for biology

|September 26, 2025

概括

在肌肉侵入性膀癌 (MIBC) 中,化疗耐药性涉及癌细胞和巨细胞. 抑制巨细胞中的PARP14可以使瘤对思丁重新敏感,为膀癌提供了一种新的治疗方法.

科学领域:

在瘤学瘤学.
癌症免疫学癌症免疫学
基因组学就是基因组学.

背景情况:

新辅助性思普拉丁化疗在肌肉侵入性膀癌 (MIBC) 中提供了有限的病理完整反应率.
驱动化疗耐药性的机制和化疗对MIBC瘤微环境的影响尚未完全理解.

研究的目的:

为了研究肌肉侵入性膀癌中基底的细胞和分子机制,在肌肉侵入性膀癌中对西斯普拉丁的耐药性.
确定潜在的治疗点,以克服MIBC中的化疗耐药性.

主要方法:

来自MIBC患者的癌症和免疫细胞的单细胞和空间转录组分析,这些患者对基于西斯的化疗有极端反应.
对抗性癌细胞中的表皮细胞转化为介质细胞转化 (EMT) 程序的分析.
在瘤中研究巨细胞透和基因表达 (PARP14).
涉及对巨细胞中PARP14抑制的功能性研究,以评估瘤对西斯丁的敏感性.

主要成果:

化疗后持续的MIBC显示癌细胞具有激活的上皮细胞到介质细胞程序,与更差的存活率相关.
抗西斯普拉丁的瘤被表达瘤允许程序的巨细胞透,其特征是PARP14的升高.
在巨细胞中抑制PARP14将它们重新编程,降低癌细胞中抗药性途径的调节,并使瘤对思丁敏感.

结论:

癌细胞和巨细胞在肌肉侵入性膀癌中协同促进西斯普拉丁耐药性.
巨相关的PARP14是西斯普拉丁耐药性的关键媒介.
向巨细胞PARP14代表了一种有前途的治疗策略,以提高MIBC中西斯丁的疗效.

更多相关视频

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

Published on: December 1, 2013

Culture of Bladder Cancer Organoids as Precision Medicine Tools

Culture of Bladder Cancer Organoids as Precision Medicine Tools

Published on: December 28, 2021

相关概念视频

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...

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...

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...

Cancer Stem Cells and Tumor Maintenance

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...

The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.