Co-transduction of p27Kip1 strongly augments Fas ligand- and caspase-8-mediated apoptosis in U-373MG glioma cells.

Anticancer Res

Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, Tokyo, Japan.

Published: March 2002

Background: p27Kip1 is a potential tumor suppressor gene. As malignant gliomas express Fas at high levels, the relationship between Fas-mediated apoptosis and p27Kip1 expression may improve therapeutic approaches for treating gliomas.

Materials And Methods: In this study, we transduced U-373MG glioma cells with the Fas ligand or caspase-8 genes using adenovirus vectors after transduction of the p27Kip1 gene to induce cell cycle arrest in U-373MG cells, and evaluated the degree of apoptosis.

Results: The results demonstrate that expression of p27Kip1 enhanced Fas ligand- or caspase-8-mediated apoptosis in U-373MG cells. Expression of apoptosis-related genes such as Bax, Bcl-X(L), Bcl-2 or caspase-8 were reduced by p27Kip1 transduction compared with that of beta-actin, whereas p27Kip1 transduction did not affect the expression level of Fas or the Fas ligand.

Conclusion: Combined transduction of p27Kip1 with Fas ligand or caspase-8 would overide the resistance mechanism to apoptosis in malignant gliomas.

Download full-text PDF

Source

Publication Analysis

Top Keywords

fas ligand-
8
ligand- caspase-8-mediated
8
caspase-8-mediated apoptosis
8
apoptosis u-373mg
8
u-373mg glioma
8
glioma cells
8
malignant gliomas
8
fas ligand
8
ligand caspase-8
8
transduction p27kip1
8

Similar Publications

The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B cell malignancies. The classic form of follicular lymphoma (FL) is a prototypic GC-derived B cell malignancy, characterized by the t(14;18)(q32;q21)IGH::BCL2 translocation and overexpression of antiapoptotic BCL2.

View Article and Find Full Text PDF

Death ligands (DLs), particularly tumor necrosis factor alpha (TNF-α), FAS ligand (FASL), and TNF-related apoptosis-inducing ligand (TRAIL), collectively termed TFT, are pivotal members of the TNF superfamily. While traditionally linked to apoptosis, TFT proteins have emerged as key regulators of various non-apoptotic processes. This review summarizes the non-apoptotic functions of TFT in cancer and explores the intricate crosstalk signaling pathways and their impact on nuclear factor kappa B (NF-κB) signaling, inflammation, and pro-tumorigenic function.

View Article and Find Full Text PDF

An engineered Palivizumab IgG2 subclass for synthetic gp130 and fas mediated signaling.

J Biol Chem

January 2025

Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany. Electronic address:

Recently, we phenocopied Interleukin (IL-)6 signaling using the dimerized single-chain variable fragment (scFv) derived from the respiratory syncytial virus (RSV) IgG1-antibody Palivizumab (PLHFc) to activate a Palivizumab anti-idiotypic nanobody (AIP)-gp130 receptor fusion protein. Palivizumab was unable to activate STAT3 signaling, so we aimed to create a similar ligand capable of triggering this pathway. Here, we created three variants of the ligand called PLH0Fc, PLH4Fc and PLH8Fc by shortening the spacer region connecting PLH and Fc from 23 amino acids in PLHFc to 0 amino acids or expanding it by rigid linkers of 4 or 8 alpha helical loops, respectively.

View Article and Find Full Text PDF

Objectives: To investigate the expression of soluble factor-related apoptosis ligand (sFasL) in peripheral blood and microRNA-147b (miR-147b) in monocytes in children with sepsis and their value in assessing prognosis.

Methods: A prospective study was conducted on 124 children with sepsis (sepsis group), 60 children with common infections (infection group), and 60 healthy children undergoing physical examinations (healthy control group). The independent risk factors for poor prognosis in children with sepsis were analyzed, and the value of serum sFasL and monocyte miR-147b in predicting poor prognosis in children with sepsis was assessed.

View Article and Find Full Text PDF

Focal Adhesion Regulation as a Strategy against Kidney Fibrosis.

ACS Chem Biol

January 2025

Department of Pediatric Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, and Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Shandong Provincial Clinical Research Center for Oral Diseases, Jinan 250012, China.

Chronic kidney fibrosis poses a significant global health challenge with effective therapeutic strategies remaining elusive. While cell-extracellular matrix (ECM) interactions are known to drive fibrosis progression, the specific role of focal adhesions (FAs) in kidney fibrosis is not fully understood. In this study, we investigated the role of FAs in kidney tubular epithelial cell fibrosis by employing precise nanogold patterning to modulate integrin distribution.

View Article and Find Full Text PDF

Want 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!