Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors, but little is known about its presence and role in hematologic neoplasms. Multiple myeloma (MM) is known to involve a deregulated cytokine network with secretion of inflammatory mediators. We thus decided to investigate the involvement of COX-2 in this neoplasm. Western blotting (WB) was used to evaluate 142 bone marrow (BM) specimens, including MM and monoclonal gammopathy of undetermined significance (MGUS). Selected cases under-went further evaluation by WB on purified CD138(+) cells, immunohistochemistry (IC), and real-time polymerase chain reaction (PCR) for mRNA expression. COX-2 was expressed in 11% (2 of 18) of MGUS specimens, 31% (29 of 94) of MM at diagnosis, and 47% (14 of 30) of MM with relapsed/refractory disease. COX-2 positivity was associated with a poor outcome in terms of progression-free (18 vs 36 months; P < .001) and overall survival (28 vs 52 months; P < .05). Real-time PCR showed COX-2 mRNA overexpression. IC and cell separation studies demonstrated COX-2 expression to be restricted to malignant plasma cells. This is the first report of the presence and prognostic role of COX-2 expression in MM. Future studies will assess COX-2 involvement in other hematologic tumors and its potential use as a therapeutic or chemo-preventive target in onco-hematology.
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http://dx.doi.org/10.1182/blood-2004-11-4201 | DOI Listing |
J Exp Clin Cancer Res
December 2024
Institute for Research On Cancer and Aging of Nice (IRCAN), CNRS UMR 7284, INSERM U1081, University Côte d'Azur, Nice, France.
Background: Multiple Myeloma (MM) is the second most common hematological malignancy, characterized by the accumulation of monoclonal plasmocytes in the bone marrow. Despite advancements with proteasome inhibitors, immunomodulatory agents, and CD38-targeting antibodies, MM remains largely incurable due to resistant clones and frequent relapses. The success of the proteasome inhibitor bortezomib (BTZ) in MM treatment highlights the critical role of the ubiquitin-proteasome system (UPS) in this disease.
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December 2024
Hematology Institute, School of Medicine, Northwest University, Xian 710069, Shaanxi, China; Deparment of Hematology, Affiliated Hospital of Northwest University & Xian No. 3 Hospital, Xian 710018, Shaanxi, China. Electronic address:
Despite the improvements in outcomes for patients with multiple myeloma (MM) over the past decade, the disease remains incurable, and even those patients who initially respond favorably to induction therapy eventually suffer from relapse. Consequently, there is an urgent need for the development of novel therapeutic agents and strategies to enhance the treatment outcomes for patients with MM. The proteasome inhibitor bortezomib (BTZ) elicits endoplasmic reticulum (ER) stress and oxidative stress in MM cells, subsequent DNA damage, ultimately inducing cell apoptosis.
View Article and Find Full Text PDFActa Haematol
December 2024
Background: Recent advancements in cellular therapies, particularly CAR-T and T cell engaging bispecific antibodies have significantly altered the therapeutic landscape for Multiple Myeloma. There are two U.S.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
Patients undergoing autologous stem cell transplantation (auto-SCT) face elevated risks of infections. Additionally, patients colonized in the gastrointestinal tract with antibiotic-resistant bacteria (ARB) are at higher risk of infection with ARB and other infections. Therefore, patients colonized with ARB before auto-SCT should present with an exceptionally high incidence of infections.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Faculty of Medical Engineering, National University of Science and Technology Politehnica Bucharest, Gheorghe Polizu 1-7, 011061 Bucharest, Romania; Advanced Polymer Materials Group, University Politehnica of Bucharest, Gheorghe Polizu 1-7, 011061 Bucharest, Romania; ebio-Hub Research Centre, University Politehnica of Bucharest-Campus, Iuliu Maniu 6, 061344 Bucharest, Romania. Electronic address:
Multiple myeloma (MM), a hematological malignancy which affects the monoclonal plasma cells in the bone marrow, is in rising incidence around the world, accounting for approximately 2 % of newly diagnosed cancer cases in the US, Australia, and Western Europe. Despite the progress made in the last few years in the available therapeutic options (e.g.
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