Glioblastoma Multiforme (GBM) is the most malignant type of all brain tumors. Current GBM treatment options include surgery, followed by radiation and chemotherapy. However, GBM can become resistant to therapy, resulting in tumor recurrence. GBM cells develop resistance to treatments by either downregulating cell death pathways (CD95) or upregulating cell survival pathways (NF-κB (p65)). Healthy tissues can be affected by the increased therapeutic dose. Therefore, it is important to develop a method that can only target GBM tumor cells, thereby reducing the non-specific uptake which will reduce the side effects. Here we demonstrate an application of novel priori activation of apoptosis pathways of tumor technology (AAAPT), which has been used to demonstrate the effect of targeted tumor sensitizers to make chemotherapy work at lower doses in breast, lung and prostate cancers. Treatment of GBM spheroids with AAAPT in 3D PEGDA microwells, showed an increase in cell death, an upregulation of cell death pathways, and a downregulation of cell survival pathways, in comparison to Temozolomide (TMZ), an oral alkylating agent, which is a commonly used chemotherapy in the treatment of GBM. The dose of AAAPT sensitizers may provide a promising method to increase treatment efficacy and reduce off-target toxicity, as an alternative to existing methods which cause significant off-target damage.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776093PMC
http://dx.doi.org/10.1109/OJEMB.2023.3336181DOI Listing

Publication Analysis

Top Keywords

cell death
12
glioblastoma multiforme
8
death pathways
8
cell survival
8
survival pathways
8
treatment gbm
8
gbm
7
cell
5
pathways
5
targeted sensitization
4

Similar Publications

This study evaluates the oncolytic potential of the Moscow strain of reovirus against human metastatic melanoma and glioblastoma cells. The Moscow strain effectively infects and replicates within human melanoma cell lines and primary glioblastoma cells, while sparing non-malignant human cells. Infection leads to the selective destruction of neoplastic cells, mediated by functional viral replication.

View Article and Find Full Text PDF

Achieving the precise targeting of lentiviral vectors (LVs) to specific cell populations is crucial for effective gene therapy, particularly in cancer treatment where the modulation of the tumor microenvironment can enhance anti-tumor immunity. Programmed cell death protein 1 (PD-1) is overexpressed on activated tumor-infiltrating T lymphocytes, including regulatory T cells that suppress immune responses via FOXP3 expression. We developed PD1-targeted LVs by incorporating the anti-PD1 nanobody nb102c3 into receptor-blinded measles virus H and VSV-G glycoproteins.

View Article and Find Full Text PDF

Numerous host factors function as intrinsic antiviral effectors to attenuate viral replication. MARCH8 is an E3 ubiquitin ligase that has been identified as a host restriction factor that inhibits the replication of various viruses. This study elucidated the mechanism by which MARCH8 restricts respiratory syncytial virus (RSV) replication through selective degradation of the viral small hydrophobic (SH) protein.

View Article and Find Full Text PDF

During virus infection, the activation of the antiviral endoribonuclease, ribonuclease L (RNase L), by a unique ligand 2'-5'-oilgoadenylate (2-5A) causes the cleavage of single-stranded viral and cellular RNA targets, restricting protein synthesis, activating stress response pathways, and promoting cell death to establish broad antiviral effects. The immunostimulatory dsRNA cleavage products of RNase L activity (RL RNAs) recruit diverse dsRNA sensors to activate signaling pathways to amplify interferon (IFN) production and activate inflammasome, but the sensors that promote cell death are not known. In this study, we found that DEAH-box polypeptide 15 (DHX15) and retinoic acid-inducible gene I (Rig-I) are essential for apoptosis induced by RL RNAs and require mitochondrial antiviral signaling (MAVS), c-Jun amino terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) for caspase-3-mediated intrinsic apoptosis.

View Article and Find Full Text PDF

Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis.

Viruses

November 2024

Laboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, Argentina.

, commonly named Canine distemper virus (CDV), is a morbillivirus implicated in several signs in the family. In dogs (), common signs of infection include conjunctivitis, digital hyperkeratosis and neuropathologies. Even with vaccination, the canine distemper disease persists worldwide so the molecular pathways implicated in the infection processes have been an interesting and promising area in new therapeutic drugs research in recent years.

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!