Publications by authors named "M Kmieciak"
Article Synopsis
- Researchers studied how combining ATR inhibitors (like BAY1895344) with MEK1/2 inhibitors (like cobimetinib) enhances the effectiveness of treating multiple myeloma (MM) by increasing cell death in MM cell lines.
- The combination works by inactivating and downregulating STAT3, a protein linked to cell survival, leading to reduced levels of its targets, c-Myc and BCL-X, even in drug-resistant MM cells.
- This combined treatment not only showed effectiveness against primary MM cells but also improved survival in MM models with low toxicity, highlighting its potential as a new therapeutic strategy for multiple myeloma patients.
Here we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma (NCT01817751). Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%).
View Article and Find Full Text PDFThe purpose of this study is to establish the recommended phase 2 dose for regorafenib in combination with sildenafil for patients with advanced solid tumors. Secondary outcomes included identification of antitumor effects of regorafenib and sildenafil, toxicity of the combination, determination of PDE5 expression in tumor samples, and the impact of sildenafil on the pharmacokinetics of regorafenib. This study was a phase 1, open-label single-arm dose-escalation trial using a 3 + 3 design.
View Article and Find Full Text PDFPurpose: The goal of this study was to characterize the relationship between ATR and STAT3 interactions in human multiple myeloma (MM) cells.
Methods: Various MM cell lines, including IL-6-dependent cells were exposed to ATR inhibitors and effects on STAT3 Tyr705 and Ser727 were monitored by WB analysis and ImageStream analysis. Parallel studies examined induction of cell death, STAT3 DNA binding activity, and expression of STAT3 downstream targets (BCL-X, MCL-1, c-MYC).
Purpose: Belinostat is an intravenous histone deacetylase inhibitor with approval for T-cell lymphomas. Adavosertib is a first in class oral Wee1 inhibitor. Preclinical studies of the combination demonstrated synergy in various human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models.
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