Publications by authors named "Valentina Z Petukhova"
Mounting evidence shows that tumor growth and progression rely on thioredoxin reductase 1 (TXNRD1)-mediated detoxification of oxidative stress that results from deregulated metabolism and mitogenic signaling in tumors. TXNRD1 levels are significant higher in triple negative breast cancer (TNBC) compared to normal tissue, making TXNRD1 a compelling TNBC therapeutic target. Despite the many attempts to generate TXNRD1 inhibitors, all known and reported compounds inhibiting TXNRD1 are problematic; they interact with TXNRD1 irreversibly and non-specifically resulting in numerous adverse side effects.
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- - Niemann-Pick type C (NPC) disease results from mutations in NPC1 or NPC2 genes, leading to the accumulation of cholesterol in late endosomes/lysosomes, and researchers are exploring LBPA (lysobisphosphatidic acid) as a therapeutic agent to reduce this accumulation.
- - Studies indicate that different stereoisomers of LBPA are effective in reducing cholesterol levels in NPC1-deficient human fibroblast cells, with the presence of an 18:1 acyl chain being particularly significant for enhancing cholesterol clearance.
- - Further experiments suggest that while phosphatidylglycerol (PG) can also reduce cholesterol, it does not convert to LBPA effectively, highlighting that LBPA itself is essential for promoting cholesterol
Pyridine nucleotide-disulfide oxidoreductases are underexplored as drug targets, and thioredoxin reductases (TrxRs) stand out as compelling pharmacological targets. Selective TrxR inhibition is challenging primarily due to the reliance on covalent inhibition strategies. Recent studies identified a regulatory and druggable pocket in thioredoxin glutathione reductase (TGR), a TrxR-like enzyme, and an established drug target for schistosomiasis.
View Article and Find Full Text PDFOnly praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target.
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- Mass spectrometry (MS), particularly MALDI-TOF MS, shows promise in specifically detecting ovarian cancer by analyzing protein patterns in low-concentration cell mixtures.
- The study focuses on using vaginal lavages from a mouse model of high-grade serous ovarian carcinoma (HGSOC) to monitor disease progression.
- Findings indicate that specific protein fingerprints in the 4-20 kDa region consistently correlate with cancer progression and are stable across different test subjects.
Article Synopsis
- MALDI fingerprinting, initially created for microbial identification, has advanced to an automated method used regularly in clinical and environmental fields.
- The technique's application to mammalian cells faces challenges due to their complexity, but recent studies show promise for classifying different cell types and monitoring cell differentiation.
- The optimization of MALDI fingerprinting for mammalian cells demonstrated its effectiveness in identifying cancer cells within mixed populations, achieving a detection level as low as 1% when using specific statistical methods.