ET-743 (Yondelis(TM), Trabectedin) isolated from the tunicate Ecteinascidia turbinata, is being tested in phase II clinical trials in Europe and the United States of America (USA). Studies with different solid tumours have shown antitumour activity in advanced, pre-treated sarcomas as well as in drug-resistant breast and ovarian cancer. The primary mechanism of action for ET-743 has not been fully elucidated and different models have been suggested to explain its molecular mechanism of action. ET-743 binds tightly to the minor groove of DNA and previous data have suggested that ET-743 acts by interfering with RNA transcription. To further investigate the mechanism of in vitro drug resistance, we evaluated the gene expression profile in ovarian and chondrosarcoma cell lines selected for resistance to ET-743. We found 70 genes whose expression was modulated in both drug-resistant cell lines when compared with their respective parental drug-sensitive cell lines. This pattern of gene expression seems to be selective for ET-743-resistant cells, since ovarian cancer cells resistant to paclitaxel did not share the same gene expression changes. Data presented in this study reveal different molecular pathways that could be involved in the cellular mechanism of ET-743 resistance.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejca.2004.10.021 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evaluation of Jaundice in Adults.
Am Fam Physician
January 2025
University of Florida College of Medicine, Gainesville.
Jaundice is an indication of hyperbilirubinemia and is caused by derangements in bilirubin metabolism. It is typically apparent when serum bilirubin levels exceed 3 mg/dL and can indicate serious underlying disease of the liver or biliary tract. A comprehensive medical history, review of systems, and physical examination are essential for differentiating potential causes such as alcoholic liver disease, biliary strictures, choledocholithiasis, drug-induced liver injury, hemolysis, or hepatitis.
View Article and Find Full Text PDFThe nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.
PLoS Pathog
January 2025
Integrative Cell Biology Graduate Program, Loyola University Chicago, Maywood, Illinois, United States of America.
The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting.
View Article and Find Full Text PDFFBXW7 metabolic reprogramming inhibits the development of colon cancer by down-regulating the activity of arginine/mToR pathways.
PLoS One
January 2025
Center of Gene Sequencing, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, P. R. China.
FBXW7 is a tumor suppressor gene that regulates metabolism and is associated with the onset and progression of colorectal cancer (CRC)), however, the precise mechanism whereby FBXW7 participates in the metabolic reprogramming of CRC remains unclear. Here, the research aims to reveal the association between the expression of FBXW7 and clinical variables and to investigate the molecular mechanism by which FBXW7 plays a critical role in the development of CRC. The clinical importance of FBXW7 in CRC was determined by immunohistochemistry.
View Article and Find Full Text PDFToll-like receptor 2/6-stimulated HMC-1 mast cells promote keratinocyte migration in wound healing.
PLoS One
January 2025
Departments of Microbiology, College of Medicine, Ewha Womans University, Seoul, Korea.
Mast cells, immune sentinels that respond to various stimuli in barrier organs, provide defense by expressing pattern recognition receptors, such as Toll-like receptors (TLRs). They may affect inflammatory responses and wound healing. Here, we investigated the effect of TLR2/6-stimulated mast cells on wound healing in keratinocytes.
View Article and Find Full Text PDFSquamocin Suppresses Tumor Growth through Triggering an Endoplasmic Reticulum Stress-Associated Degradation of EZH2/MYC Axis.
Adv Sci (Weinh)
January 2025
School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!