Treatment for osteosarcoma (OS) involves surgical resection of the primary tumor followed by chemotherapy to eliminate potential metastases. However, the development of chemoresistance remains a key contributor to the poor prognosis of the disease. In this research, we assessed the effects of miR-16, miR-16-1-3p, and miR-16-2-3p on the sensitivity of OS cells to cisplatin using the SRB cell viability method. Overexpression of these miРНКs in U2OS and HOS cells significantly reduced the 50
Breast cancer (BC) is one of the most common and lethal cancers in women. The low predictive value of conventional preclinical models necessitates the creation of more relevant experimental systems. The review presents a comprehensive analysis of the evolution of BC models from simple 2D cultures to complex 3D systems and in vivo models. Key platforms are discussed, including 3D spheroids, patient-derived organoids (PDOs), and organ-on-a-chip technologies. Special attention is given to modern in vivo models, including patient-derived xenografts (PDXs), patient-derived orthotopic xenografts (PDOXs), and humanized mice for studying immunotherapy. Personalized models (PDOs and PDXs), which preserve the heterogeneity of the original tumor, are becoming the gold standard for preclinical screening and the development of individualized therapy. The review details the roles of key cell signaling receptors (ER and HER2) and the PI3K/AKT/mTOR signaling pathway in BC carcinogenesis, as well as the mechanisms of drug resistance. Advanced molecular technologies (CRISPR/Cas9, next-generation sequencing, and multi-omics analyses) are shown to play a crucial role in studying tumor biology and searching for new therapeutic targets. The integration of complex model systems with modern analytical platforms paves the way for personalized oncology and improved clinical outcomes in BC.
RACK1 (Receptor for Activated C Kinase 1) is a ribosomal 40S subunit protein that also functions as a signaling scaffold, playing key roles in synaptic plasticity, cytoskeletal regulation, and neurotransmitter responses in neurons. To investigate RACK1 behavior upon activation of local translation, we examined changes in RACK1 expression and phosphorylation levels in distinct compartments of cortical neurons following NMDA receptor stimulation. Using a porous membrane culture system to physically separate soma and neurites, we performed Phos-tag electrophoresis and Western blotting. RACK1 levels were lower in the neurite fraction compared to the soma. Phos-tag electrophoresis revealed slowly migrating bands corresponding to phosphorylated RACK1 isoforms. NMDA receptor activation reduced the proportion of these phosphorylated forms and increased the non‑phosphorylated RACK1 fraction. These data indicate that NMDA stimulation induces not only RACK1 redistribution but also changes in its post‑translational status within the neurite compartment. The observed electrophoretic mobility shifts likely reflect a transition of RACK1 from a phosphorylated, functionally dimer‑associated state to a predominantly non‑phosphorylated monomeric form, which may regulate its signaling and ribosomal functions.
Severe neurodegenerative disorders, including the most common Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by aggregation of pathological forms of proteins in the brain, nerve cells death, neuroinflammation, and an imbalance of growth factors and neurotrophins. The processes hinder natural regeneration of neural tissue and lead to brain atrophy and severe cognitive and motor impairments. Treating patients with neurodegenerative diseases remains a significant challenge in medicine. Existing drug therapy can slow down disease progression and improve symptoms in AD and PD, but does not stop the neurodegenerative processes in the brain or promote neural tissue regeneration. Gene-cell therapy provides a promising approach to treating such patients. This innovative approach is based on the ability of transduced cells and therapeutic proteins they express to influence the neurodegenerative processes that develop in AD and PD and stimulate neuroregeneration. Genes encoding the vascular endothelial growth factor (VEGF) and neurotrophic factors, such as the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are of greatest interest as therapeutic transgenes for gene-cell therapy of AD and PD. The factors and their effect on neuroregeneration are the most studied. The review describes the specifics of AD and PD pathogenesis in experimental models and considers the clinical studies performed to assess the efficacy of transduced cells expressing VEGF, NGF, and BDNF in the treatment of AD and PD. Various viral vectors can be used for cell transduction; their advantages and disadvantages are discussed in the review. Based on the analysis of experimental and clinical trial results, the most promising drug is proposed for personalized treatment of AD and PD patients.
The adeno-associated vector (AAV) has become a cornerstone in gene therapy, with several approved AAV-based therapeutics successfully used in clinical practice. However, scaling up the production of recombinant AAV (rAAV) remains challenging: the process is still expensive and labor-intensive, which limits the broader availability of gene therapy products. Large-scale rAAV manufacturing can be significantly reduced in cost and simplified by using baculoviruses. Baculovirus expression systems are already employed in the production of at least two approved rAAV-based therapeutics. Baculovirus AAV production platforms continue to improve. Modern systems use a single baculovirus instead of two or three, as well as specialized cell lines. As a result, production efficiency has increased, and the quality of rAAV preparations has improved significantly. This article outlines the history and evolution of various baculovirus systems for rAAV production and describes the most modern and promising platforms for assembling recombinant AAV particles.
