Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	The Combination of Panobinostat and Melphalan for the Treatment of Patients with Multiple Myeloma
Δημιουργός/Συγγραφέας:	Gkotzamanidou, Maria Terpos, Evangelos Dimopoulos, Meletios A. [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L.
Ημερομηνία:	2022-12-10
Γλώσσα:	Αγγλικά
ISSN:	1422-0067
DOI:	10.3390/ijms232415671
Άλλο:	36555311
Περίληψη:	Histone deacetylase inhibitors show synergy with several genotoxic drugs. Herein, we investigated the biological impact of the combined treatment of panobinostat and melphalan in multiple myeloma (MM). DNA damage response (DDR) parameters and the expression of DDR-associated genes were analyzed in bone marrow plasma cells (BMPCs) and peripheral blood mononuclear cells (PBMCs) from 26 newly diagnosed MM patients. PBMCs from 25 healthy controls (HC) were examined in parallel. Compared with the ex vivo melphalan-only treatment, combined treatment with panobinostat and melphalan significantly reduced the efficiency of nucleotide excision repair (NER) and double-strand-break repair (DSB/R), enhanced the accumulation of DNA lesions (monoadducts and DSBs), and increased the apoptosis rate only in patients’ BMPCs (all p < 0.001); marginal changes were observed in PBMCs from the same patients or HC. Accordingly, panobinostat pre-treatment decreased the expression levels of critical NER (DDB2, XPC) and DSB/R (MRE11A, PRKDC/DNAPKc, RAD50, XRCC6/Ku70) genes only in patients’ BMPCs; no significant changes were observed in PBMCs from patients or HC. Together, our findings demonstrate that panobinostat significantly increased the melphalan sensitivity of malignant BMPCs without increasing the melphalan sensitivity of PBMCs from the same patients, thus paving the way for combination therapies in MM with improved anti-myeloma efficacy and lower side effects.
Τίτλος πηγής δημοσίευσης:	International journal of molecular sciences
Τόμος/Κεφάλαιο:	23
Τεύχος:	24
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Βιοχημεία[EN] Biochemistry [EL] Χημική Βιολογία[EN] Chemical Biology [EL] Κυτταρολογία[EN] Cytology [EL] Γενετική[EN] Genetics
Λέξεις-Κλειδιά:	DNA damage response Clinical response Combination therapy Melphalan Multiple myeloma Panobinostat
EU Grant identifier:	2014-AACR -Aflac
Κάτοχος πνευματικών δικαιωμάτων:	© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/1422-0067/23/24/15671
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο