Publications by authors named "Weiss-Sadan Tommy"

Article Synopsis
  • Several anticancer drugs increase reactive oxygen species (ROS) levels to induce cell death, but the mechanisms of how ROS affects proteins linked to drug sensitivity and resistance are not well understood.* -
  • Through a study of 11 anticancer drugs, researchers identified unique and common protein targets, including those in ribosomal components, highlighting shared mechanisms related to drug effects on protein translation.* -
  • The study focuses on CHK1, which acts as a sensor for nuclear HO levels, preventing mitochondrial localization of SSBP1 and thereby reducing nuclear HO, indicating a pathway that could be targeted for improving resistance to platinum-based cancer treatments.*
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Multiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator, KEAP1. NRF2 has been studied extensively in KEAP1-mutant cancers; however, the role of this pathway in cancers with wild-type KEAP1 remains poorly understood. To answer this question, we induced NRF2 via pharmacological inactivation of KEAP1 in a panel of 50+ non-small cell lung cancer cell lines.

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Cysteine cathepsin proteases are found under normal conditions in the lysosomal compartments of cells, where they play pivotal roles in a variety of cellular processes such as protein and lipid metabolism, autophagy, antigen presentation, and cell growth and proliferation. As a consequence, aberrant localization and activity contribute to several pathologic conditions such as a variety of malignancies, cardiovascular diseases, osteoporosis, and other diseases. Hence, there is a resurgence of interest to expand the toolkit to monitor intracellular cathepsin activity and better ascertain their functions under these circumstances.

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Stroma-infiltrating immune cells, such as tumor-associated macrophages (TAM), play an important role in regulating tumor progression and chemoresistance. These effects are mostly conveyed by secreted mediators, among them several cathepsin proteases. In addition, increasing evidence suggests that stroma-infiltrating immune cells are able to induce profound metabolic changes within the tumor microenvironment.

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Article Synopsis
  • Cardiovascular diseases remain a major health issue despite the use of lipid-lowering medications, largely due to conditions like atherosclerosis, which involves inflammation and vascular remodeling.
  • Research has identified cysteine protease cathepsins, particularly B, L, and S, as key players in cardiovascular inflammation and disease outcomes.
  • A new non-invasive treatment method using a Photosensitizing quenched Activity-Based Probe (PS-qABP) effectively targets these enzymes and reduces inflammation in atherosclerosis, showing promise for future clinical use.
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Background/aims: Atherosclerosis underlies the majority of cardiovascular events, consequent to non-resolving inflammation. Considerable evidence implicates autophagy dysfunction at the core of this inflammatory condition, but the basis of this dysfunction is not fully understood.

Methods: Using an in vitro model of lipid-laden macrophages, activity-based probes and high-throughput techniques, we studied the role of the cysteine proteases cathepsins in autophagy.

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Rapidly proliferating cells reshape their metabolism to satisfy their ever-lasting need for cellular building blocks. This phenomenon is exemplified in certain malignant conditions such as cancer but also during embryonic development when cells rely heavily on glycolytic metabolism to exploit its metabolic intermediates for biosynthetic processes. How cells reshape their metabolism is not fully understood.

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IRE1, PERK, and ATF6 are the three transducers of the mammalian canonical unfolded protein response (UPR). GSK2606414 is a potent inhibitor of PERK, while KIRA6 inhibits the kinase activity of IRE1. Both molecules are frequently used to probe the biological roles of the UPR in mammalian cells.

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X-ray CT instruments are among the most available, efficient, and cost-effective imaging modalities in hospitals. The field of CT molecular imaging is emerging which relies mainly on the detection of gold nanoparticles and iodine-containing compounds directed to tagging a variety of abundant biomolecules. Here for the first time we attempted to detect enzymatic activity, while the low sensitivity of CT scanners to contrast reagents made this a challenging task.

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Atherosclerosis predisposes patients to cardiovascular diseases, such as myocardial infarction and stroke. Instigation of vascular injury is triggered by retention of lipids and inflammatory cells in the vascular endothelium. Whereas these vascular lesions develop in young adults and are mostly considered harmless, over time persistent inflammatory and remodeling processes will ultimately damage the arterial wall and cause a thrombotic event due to exposure of tissue factors into the lumen.

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Background And Purpose: Atherosclerosis is a leading cause of mortality worldwide, contributing to both strokes and heart attacks. Macrophages are key players in atherogenesis, promoting vascular inflammation and arterial remodeling through cysteine cathepsin proteases. We used a cathepsin-targeted activity-based probe in human carotid plaque to assess its diagnostic potential and evaluate macrophage subtypes ex vivo.

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The caspases are a family of cysteine proteases that are key regulators of apoptosis and their activity may thus serve as a good marker to monitor cell death. We have developed a quenched fluorescent activity-based probe (qABP) that is selective for caspase-3 activity and emits a fluorescent signal after covalently modifying its target. The probe has a wide range of potential applications, in real-time imaging, FACS analysis or biochemical quantification of caspase activity in intact cells.

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