Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(1), P. 32 - 32

Published: Jan. 6, 2025

Proteasome inhibitors (PIs) constitute the most common type of induction treatment for multiple myeloma. Interactions between proteasome, autophagy, and reactive oxygen species (ROS) have been shown in past, thus emphasizing need a better understanding underlying pathophysiology. For this study, bone marrow mononuclear cells from 110 myeloma patients were collected at different disease stages. PSMB5 LC3I/II protein levels determined using Western blot, proteasome proteolytic activity (PPA) with spectrofluorometry, ROS flow cytometry. accumulation was found to diminish after PI (p-value = 0.014), same pattern observed PPA < 0.001). Conversely, LC3II elevated both remission relapse compared baseline 0.041). Patients lower than 1.06 units had longer disease-free survival those values above (12.0 ± 6.7 vs. 36 12.1 months; p-value Median plasma significantly higher 0.001), implying poor prognosis. Overall, post-treatment reduction could indicate shift proteasomal autophagic degradation as main proteostatic mechanism, explaining resistance. The oxidative stress PI-treated possibly serve an additional compensatory mechanism.

Language: Английский

Therapy resistance in prostate cancer: mechanism, signaling and reversal strategies

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2024, Volume and Issue: 5(5), P. 1110 - 1134

Published: Aug. 29, 2024

Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in treatment and diverse clinical trajectories. Even advances modern strategies, spectrum of resistance therapies continues be significant challenge. This review comprehensively examines underlying mechanisms therapy occurred PC, focusing on both tumor microenvironment signaling pathways implicated resistance. Tumor comprises stromal epithelial cells, which influences growth, response progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression stimulation angiogenesis results Moreover, dysregulation including androgen receptor (AR), mammalian target rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair Janus kinase/signal transducers activators transcription (JAK/STAT) drive by promoting survival proliferation. Understanding these molecular is important for developing targeted therapeutic interventions overcomes In conclusion, complete grasp medication PC development individualized plans enhancements outcomes. By studying understanding complex factors contributing resistance, this study focuses aims guide innovative approaches effectively overcome progression improve rate patients.

Language: Английский