甲胺通过内质网膜压力-CHOP通路使AML细胞对venetoclax敏感
Lei Hua1, Nianhui Yang1, Yue Li1
1Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
British journal of haematology
|July 6, 2023
概括
甲福明与venetoclax结合,通过诱导急性髓性白血病 (AML) 细胞中的亡和内分泌网膜应激,显示出协同作用的抗白血病效应. 这种组合策略为AML患者提供了增强的疗效和可接受的安全性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 威尼托克拉克斯针对BCL-2治疗急性髓性白血病 (AML),但耐药性和复发仍然是一个重大挑战.
- 梅特福明通过诱导亡而表现出抗癌性质,但其与AML中的venetoclax的协同作用潜力尚未得到充分证实.
研究的目的:
- 研究甲胺和venetoclax对AML细胞生长的协同作用.
- 阐明甲胺诱导的亡的潜在机制与venetoclax结合使用.
主要方法:
- 使用AML细胞系 (Molm13,THP-1) 进行体外研究,以评估扩散和亡.
- 在体内异种移植模型和患者骨髓样本的分析.
- 研究了内质网膜 (ER) 压力标志物CHOP的作用,包括CHOP敲击实验.
主要成果:
- 甲胺和venetoclax协同抑制了AML细胞系中的增殖和诱导的亡.
- 组合治疗显著增加了CHOP表达,这是ER压力诱导的亡的关键调解者.
- 在CHOP中,Knockdown减弱了结合的apoptotic效应,证实了其在机制中的作用.
- 该组合在体内和患者样本中表现出强烈的抗白血病活性.
结论:
- 甲胺和venetoclax的组合显示出针对AML的增强抗白血病活性.
- 由CHOP介导的内质网膜应激是协同效应背后的一个关键机制.
- 这种组合方法为AML治疗提供了一个有希望的新策略,具有可接受的安全性,需要进一步的临床研究.
相关概念视频
Combination Therapies and Personalized Medicine
4.9K
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...
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...
4.9K
Treatment Resistant Cancers
3.3K
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...
3.3K
Targeted Cancer Therapies
7.7K
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...
There are several types of targeted therapies against...
7.7K
Oral Hypoglycemic Agents: Biguanides and Glitazones
238
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
238
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Electron Transport Chain: Complex I and II
14.6K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.6K


