Evidence map›Paper›PMID 36555311›Full record

ArticleInternational journal of molecular sciences2022

The Combination of Panobinostat and Melphalan for the Treatment of Patients with Multiple Myeloma.

Maria Gkotzamanidou, Evangelos Terpos, Meletios A Dimopoulos, Vassilis L Souliotis

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.4field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. DNA Damage, DNA Repair, and Cancer: Second Edition.International journal of molecular sciences · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Maria GkotzamanidouOncology Department, 251 Hellenic Air-Force General Hospital, 155 61 Athens, Greece.
Evangelos TerposDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 115 28 Athens, Greece.ORCID 0000-0001-5133-1422
Meletios A DimopoulosDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 115 28 Athens, Greece.ORCID 0000-0001-8990-3254
Vassilis L SouliotisInstitute of Chemical Biology, National Hellenic Research Foundation, 116 35 Athens, Greece.ORCID 0000-0002-2945-1329
National and Kapodistrian University of Athens · GRHellenic Air Force · GRNational Hellenic Research Foundation · GR

Funding

This work was supported from the 2014-AACR -Aflac, Incorporated Scholar-in-Training Awards for AACR to Maria Gkotzamanidou 2014-AACR -Aflac
6 · The paper itself

Abstract

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.

Indexed as

MelphalanMultiple MyelomaDNA RepairHumansLeukocytes, MononuclearPanobinostatMelphalanPanobinostatclinical responsecombination therapyDNA damage responsemelphalanmultiple myelomapanobinostat

Identifiers

PMID36555311
PMCPMC9778728
OpenAlexW4312123494

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.