相关实验视频

Updated: Jan 13, 2026

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Published on: April 26, 2012

白细胞内在的ER应激反应有助于化疗诱导的外周神经病变

Miriam M Fonseca¹, Oriana Gelblung¹, Sarah D Pennypacker¹

¹Pain Mechanisms Laboratory, Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Science translational medicine

|October 29, 2025

概括

帕克利塔塞尔化学疗法通过激活免疫细胞中的IRE1α压力传感器,导致神经损伤 (CIPN). 在白细胞中准IRE1α可能会预防或减少癌症患者的CIPN.

科学领域:

神经科学是一个神经科学.
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

化疗诱导的周围神经病变 (CIPN) 是帕克利塔塞尔的主要剂量限制副作用.
CIPN涉及神经炎症,但免疫细胞在感知帕克利塔塞尔中的作用尚未完全理解.

研究的目的:

研究免疫细胞如何感知帕克利塔塞尔并为CIPN做出贡献.
探索内细胞网膜 (ER) 压力传感器 IRE1α 在帕克利塔塞尔诱导的神经炎症中的作用.

主要方法:

在小鼠中服用帕克利塔塞尔来诱导CIPN.
在髓状细胞和巨细胞中IRE1α激活的分析.
在白细胞中,IRE1α的遗传移除或药理抑制.
评估神经炎症和疼痛行为.
在癌症患者中,IRE1α激活与CIPN严重性的相关性.

主要成果:

帕克利塔塞尔激活了髓状细胞和巨细胞中的IRE1α,导致ER压力和ROS产生.
IRE1α激活促进了炎症性巨细胞的表型,产生像TNF-α和IL-1β这样的细胞因子.
在白细胞中抑制 IRE1α 改善了小鼠的神经炎症和疼痛行为.
循环白细胞中的IRE1α激活与妇科癌症患者的CIPN严重程度相关.

结论:

白细胞内在的IRE1α是CIPN的关键调解者.
针对 IRE1α 激活提供了一个潜在的治疗策略,以减轻 paclitaxel 治疗患者的 CIPN.

更多相关视频

Modeling Chemotherapy Resistant Leukemia In Vitro

Modeling Chemotherapy Resistant Leukemia In Vitro

Published on: February 9, 2016

相关概念视频

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...

Psychoneuroimmunology: Diabetes and Cancer

Psychoneuroimmunology: Diabetes and Cancer

Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

Cells of the Innate Immune Response

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...

Disorders of Leukocytes

Disorders of Leukocytes

Leukocyte disorders can lead to either leukopenia, characterized by an abnormally low leukocyte count, or leukocytosis, marked by a very high leukocyte number.
Leukopenia may result from bone marrow disorders, autoimmune diseases, and infectious diseases. For example, conditions such as multiple myeloma and aplastic anemia can impair the bone marrow's ability to produce adequate leukocytes. Similarly, autoimmune diseases like lupus and viral infections such as HIV can prompt the immune...