The ubiquitin-proteasome pathway is implicated in the pathogenesis of many haematologic malignancies, including multiple myeloma. Under conditions of rapid cell turnover and growth rate, proteasomes are returned into circulation. The measurement of their levels or activity could offer a new approach to diagnosis, prognosis and monitoring of anticancer treatment in carcinoma patients. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in the plasma of 64 patients with a newly diagnosed multiple myeloma and 30 healthy volunteers. The values were found to be significantly higher in the studied patients and advanced disease stages compared to the control group, and decreased significant after chemotherapy. Both proteasome concentration and ChT-L activity correlated with adverse prognostic factors, such as lactate dehydrogenase and β2-macroglobulin. We also showed that proteasome concentration positively correlates with IL-6 level, as opposed to proteasome ChT-L activity. Of note, higher proteasome ChT-L activity, unlike the concentration, was proved to be an indicator of a shorter progression free survival, constituting thereby an important prognostic marker.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2014.05.008DOI Listing

Publication Analysis

Top Keywords

proteasome concentration
16
cht-l activity
16
multiple myeloma
12
concentration chymotrypsin-like
8
activity plasma
8
plasma patients
8
patients newly
8
newly diagnosed
8
diagnosed multiple
8
proteasome cht-l
8

Similar Publications

Artemisinin is a sesquiterpene lactone derived from the plant L., renowned for its antimalarial activity. Based on this compound, various derivatives and analogues have been obtained that exhibit diverse biological activities, including clinically approved drugs.

View Article and Find Full Text PDF

Itaconate drives pro-inflammatory responses through proteasomal degradation of GLO1.

Biochem Biophys Res Commun

January 2025

2nd Ward of Oncology Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130031, China. Electronic address:

Itaconate is a small-molecule metabolite generated by the enzyme aconitate decarboxylase 1 (ACOD1), which is upregulated during inflammation. Traditionally, itaconate has been recognized for its anti-inflammatory properties; however, this study reveals a pro-inflammatory mechanism of itaconate in macrophages. We demonstrate that itaconate promotes the proteasomal degradation of glyoxalase 1 (GLO1) via Cys139.

View Article and Find Full Text PDF

Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations, leading to enhanced lipid peroxidation. In neurological disorders, both oxidative stress and mitochondrial damage can contribute to ferroptosis, resulting in nerve cell dysfunction and death. The ubiquitin-proteasome system (UPS) refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.

View Article and Find Full Text PDF

The rearranged during transfection (RET) mutation such as the G810C mutation has significantly restricted the clinical application of selective RET inhibitors in the treatment of RET-driven cancers. This study designed and evaluated RET proteolysis targeting chimeras (PROTACs) based on selpercatinib (LOXO-292), identifying as a potent and selective RET PROTAC. effectively inhibited the proliferation of BaF3 cells with various RET mutations, showing IC values of 2.

View Article and Find Full Text PDF

Boanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma.

Biol Direct

January 2025

Department of Hematology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, 518172, China.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells and is currently incurable. Despite advancements in therapeutic strategies, resistance to proteasome inhibitors, particularly bortezomib (BTZ), poses a substantial challenge to disease management. This study aimed to explore the efficacy of boanmycin, a novel antitumor antibiotic, in overcoming resistance to BTZ in MM.

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!