Despite recent improvements in treatment, a significant fraction of patients with diffuse large B-cell lymphoma (DLBCL) still fail therapy. Therefore, new therapeutic modalities are needed to advance the cure rate. Seliciclib (CYC202, R-roscovitine) is a purine analog developed as an inhibitor of CDK2/cyclin E CDK7/cyclin H and CDK9/cyclin T. Seliciclib has been shown to be active in B-cell neoplasms, such as mantle cell lymphoma, chronic lymphocytic leukemia and in multiple myeloma in vitro. The aim of this study was to assess the in vitro activity of seliciclib in DLBCL. The anti-proliferative activity of seliciclib was tested in nine human DLBCL cell lines and six DLBCL primary cell cultures. The effects of seliciclib on the cell cycle and on apoptosis, as well as on transcription-related proteins were assessed. The cell viability of all DLBCL cell lines and primary cells was reduced by seliciclib treatment. The IC50 for the cell lines ranged from 13 - 36 microm. The effect of seliciclib was independent of the genetic aberrations characterizing the cell lines. After seliciclib exposure cells accumulated in G2/M or in G1 phase, with most of the cells showing signs of apoptosis. Despite the clear cytotoxic effect and induction of apoptosis, this study could not identify a unique mechanism of action. The in vitro data suggest that seliciclib is an active agent in DLBCL. Its efficacy is apparently independent of the underlying chromosomal translocations characteristic of DLBCL. The drug might represent a new therapeutic agent in this lymphoma sub-type.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/10428190601026562 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
IFN-γ reprograms cardiac microvascular endothelial cells to mediate doxorubicin transport and influences the sensitivity of mice to doxorubicin-induced cardiotoxicity.
Exp Mol Med
January 2025
Department of Pharmacy at The Second Affiliated Hospital, and Department of Pharmacology at College of Pharmacy (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), Harbin Medical University, Harbin, P. R. China.
Doxorubicin (DOX) is a first-line chemotherapy agent known for its cardiac toxicity. DOX-induced cardiotoxicity (DIC) severely limits the use for treating malignant tumors and is associated with a poor prognosis. The sensitivity to DIC varies among patients, but the precise mechanisms remain elusive.
View Article and Find Full Text PDFLong noncoding RNA DHRS4 antisense RNA 1 suppresses osteosarcoma cell proliferation and promotes apoptosis through a competitive endogenous RNA mechanism.
Sci Rep
January 2025
Department of Spinal Surgery, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue Central Guangzhou, Guangdong510280, Guangzhou, Guangdong510280, China.
Osteosarcoma (OS) is the most common primary malignant bone tumor. Recent evidence suggests that the novel long noncoding RNA DHRS4 antisense RNA 1 (DHRS4-AS1) serves an important role in cancer progression and metastasis. However, its function and molecular mechanism in OS remain largely unknown.
View Article and Find Full Text PDFFirst-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.
Nat Med
January 2025
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing, China.
Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.
View Article and Find Full Text PDFMetal-oxide phase transition of platinum nanocatalyst below fuel cell open-circuit voltage.
Nat Commun
January 2025
ICGM, Univ. Montpellier, CNRS, ENSCM, 34095, Montpellier, France.
The long-term stability of Pt-based catalysts is critical to the reliability of proton exchange membrane fuel cells (PEMFCs), and receives constant attention. However, the current knowledge of Pt oxidation is restricted to unrealistic PEMFC cathode environment or operation, which questions its practical relevance. Herein, Pt oxidation is investigated directly in a PEMFC with stroboscopic operando high energy X-ray scattering.
View Article and Find Full Text PDFSynthesis, HS releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5'-dithioacetates.
Sci Rep
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary.
Hydrogen sulfide (HS) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-HS-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5'-thio metabolites were also produced from uridine and adenosine.
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!