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Genetic Risk Factors for Bortezomib-induced Neuropathic Pain in an Asian Population: A Genome-wide Association Study in South Korea.
J Pain
September 2024
Department of Internal Medicine, Seoul National University Hospital, Biomedical Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Article Synopsis
- Bortezomib-induced neuropathic pain (BINP) complicates treatment for multiple myeloma (MM), and this study investigates genetic factors associated with BINP specifically in Korean patients, rather than focusing solely on Caucasian populations.
- Researchers collected clinical data and samples from 185 MM patients receiving bortezomib, conducting a genome-wide association study to identify genetic risk factors and relevant biological pathways relating to neuropathic pain.
- The study found that 16 out of the top 20 genetic variants associated with BINP were replicated in the Korean cohort, providing new insights into personalized risk assessment and expanding the understanding of BINP mechanisms in diverse populations.
New insights into the Bortezomib-induced cytotoxic and resistance mechanisms in a primary effusion lymphoma mouse model.
Hematol Oncol
March 2024
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
JQ-1/bortezomib combination strongly impairs MM and PEL survival by inhibiting c-Myc and mTOR despite the activation of prosurvival mechanisms.
Exp Hematol
March 2023
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. Electronic address:
Multiple myeloma (MM) and primary effusion lymphoma (PEL) are two aggressive hematologic cancers against which bortezomib and JQ-1, proteasome and bromodomain and extraterminal domain (BET) inhibitors, respectively, have been shown to have a certain success. However, the combination of both seems to be more promising than the single treatments against several cancers, including MM. Indeed, in the latter, proteasome inhibition upregulated nuclear respiratory factor 1 (NRF1), and such a prosurvival effect was counteracted by BET inhibitors.
View Article and Find Full Text PDFISG20L2 suppresses bortezomib antimyeloma activity by attenuating bortezomib binding to PSMB5.
JCI Insight
October 2022
Department of Hematology, Institute of Hematology, West China Hospital/State Key Laboratory of Biotherapy and Cancer Center and.
The proteasome inhibitors (PIs) bortezomib and carfilzomib, which target proteasome 20S subunit beta 5 (PSMB5) in cells, are widely used in multiple myeloma (MM) treatment. In this study, we demonstrated the role of interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2) in MM PI resistance. Gain- and loss-of-function studies showed that ISG20L2 suppressed MM cell sensitivity to PIs in vitro and in vivo.
View Article and Find Full Text PDFThe molecular and cellular insight into the toxicology of bortezomib-induced peripheral neuropathy.
Biomed Pharmacother
October 2021
Department of Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:
The proteasome inhibitor bortezomib (BTZ) is a first-line antitumor drug, mainly used for multiple myeloma treatment. However, BTZ shows prominent toxicity in the peripheral nervous system, termed BTZ-induced peripheral neuropathy (BIPN). BIPN is characterized by neuropathic pain, resulting in a dose reduction or even treatment withdrawal.
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