Publications by authors named "Robert Tressler"
Article Synopsis
- - The study focuses on a new small molecule, GRN510, that activates telomerase and shows promise in treating diseases like pulmonary fibrosis and aplastic anemia, especially in mouse models.
- - In experiments, GRN510 significantly activated telomerase in different tissue types and reduced fibrosis caused by bleomycin, highlighting its potential therapeutic effects.
- - The protective impact of GRN510 appears to be cell-type specific, as it promoted telomerase activity and cellular lifespan mainly in small airway epithelial cells, suggesting targeted treatment strategies for lung fibrosis.
Purpose: Recent studies have revealed that the majority of pediatric low-grade astrocytomas (PLGA) harbor the BRAF-KIAA1549 (B-K) fusion gene resulting in constitutive activation of the RAS/MAPK pathway. However, the clinical significance of this genetic alteration is yet to be determined. We aimed to test the prognostic role of the B-K fusion in progression of incompletely resected PLGA.
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- Cancer recurrence is a major issue in oncology, and targeting telomerase, which helps maintain telomeres in tumor cells, could be a potential treatment, but it may also harm normal stem cells.
- The study investigated telomerase activity in glioma tumors and found it was mainly present in tumor-initiating cells (TIC) with short telomeres, while normal stem cells had longer telomeres and showed resistance to telomerase inhibition.
- Results showed that inhibiting telomerase in TIC led to their rapid loss of self-renewal and significant survival benefits in a xenograft model, indicating that this approach could effectively target neural tumors without harming normal stem cells.
Article Synopsis
- Cancer stem cells (CSCs) are rare but drug-resistant cancer cells linked to cancer recurrence and metastasis, making them a key target for treatment.
- Imetelstat (GRN163L) is a telomerase inhibitor that has shown efficacy in reducing telomerase activity in both bulk tumor cells and CSCs in breast and pancreatic cancer cell lines.
- The study found that imetelstat treatment not only decreased the CSC populations and their self-renewal capability but also hindered cancer growth in animal models, indicating its potential as an effective cancer therapy.
Article Synopsis
- Plasma cells are the main tumor cells in multiple myeloma but don’t grow indefinitely, while clonotypic B cells act like cancer stem cells and can regenerate the disease in mice.
- The study focused on using imetelstat, a telomerase inhibitor, to target these myeloma cancer stem cells, demonstrating that treatment reduced telomere length and inhibited tumor growth.
- Findings showed that both long and short-term telomerase inhibition affected cancer stem cell characteristics, indicating that telomerase plays a crucial role in their growth and could be a therapeutic target in treating multiple myeloma.
Differential regulation of telomerase activity in normal and tumor cells provides a rationale for the design of new classes of telomerase inhibitors. The telomerase enzyme complex presents multiple potential sites for the development of inhibitors. GRN163L, a telomerase enzyme antagonist, is a lipid-modified 13-mer oligonucleotide N3' --> P5'-thio-phosphoramidate, complementary to the template region of telomerase RNA (hTR).
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