PMID- 36778300
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240506
DP  - 2023 Jan 30
TI  - Alleviating iatrogenic effects of paclitaxel via anti-inflammatory treatment.
LID - rs.3.rs-2487922 [pii]
LID - 10.21203/rs.3.rs-2487922/v1 [doi]
AB  - BACKGROUND: Paclitaxel is touted as an essential medicine due to its extensive 
      use as a chemotherapeutic for various cancers and an antiproliferative agent for 
      restenosis. Due to recent concerns related to long-term mortality, paclitaxel 
      (PTX)-based endovascular therapy is now surrounded by controversies. OBJECTIVE: 
      Examine the inflammatory mediators driven by the systemic administration of PTX 
      and explore the means to suppress these effects. METHODS: RNAseq analysis, cell 
      and mouse models. RESULTS: RNAseq analysis of primary human endothelial cells 
      (ECs) treated with PTX demonstrated transcriptional perturbations of a set of 
      pro-inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1) 
      and CD137, which were validated in EC lysates. These perturbations were abrogated 
      with dexamethasone, a prototypic anti-inflammatory compound. The media of ECs 
      pre-treated with PTX showed a significant increase in MCP-1 levels, which were 
      reverted to baseline levels with DEX treatment. A group of mice harvested at 
      different time points after PTX injection were analyzed for immediate and delayed 
      effects of PTX. A 3-fold increase in MCP-1 was noted in blood and aortic ECs 
      after 12 hours of PTX treatment. Similar changes in CD137 and downstream 
      mediators such as tissue factor, VCAM-1 and E-selectin were noted in aortic ECs. 
      CONCLUSIONS: Our study shows that systemic PTX exposure upregulates 
      atherothrombotic markers, and co-delivery of DEX can subdue the untoward toxic 
      effects. Long-term studies are needed to probe the mechanisms driving systemic 
      complications of PTX-based therapies and evaluate the clinical potential of DEX 
      to mitigate risk.
FAU - Zhang, Mengwei
AU  - Zhang M
AD  - Boston University.
FAU - Lotfollahzadeh, Saran
AU  - Lotfollahzadeh S
AD  - Boston University.
FAU - Elzinad, Nagla
AU  - Elzinad N
AD  - Boston University.
FAU - Yang, Xiaosheng
AU  - Yang X
AD  - Boston University.
FAU - Elsadawi, Murad
AU  - Elsadawi M
AD  - Boston University.
FAU - Gower, Adam
AU  - Gower A
AD  - Boston University.
FAU - Belghasem, Mostafa
AU  - Belghasem M
AD  - Boston University.
FAU - Shazly, Tarek
AU  - Shazly T
AD  - University of South Carolina.
FAU - Kolachalama, Vijaya B
AU  - Kolachalama VB
AUID- ORCID: 0000-0002-5312-8644
AD  - Boston University.
FAU - Chitalia, Vipul
AU  - Chitalia V
AD  - Boston University.
LA  - eng
GR  - RF1 AG062109/AG/NIA NIH HHS/United States
GR  - R01 HL159620/HL/NHLBI NIH HHS/United States
GR  - R21 CA253498/CA/NCI NIH HHS/United States
GR  - R21 DK119740/DK/NIDDK NIH HHS/United States
GR  - UL1 TR001430/TR/NCATS NIH HHS/United States
PT  - Preprint
DEP - 20230130
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
UIN - Vasc Med. 2024 Apr 16;:1358863X241231942. PMID: 38623630
PMC - PMC9915804
OTO - NOTNLM
OT  - Peripheral artery disease
OT  - dexamethasone
OT  - drug coated balloon
OT  - inflammation
OT  - paclitaxel
COIS- Competing interests: None
EDAT- 2023/02/14 06:00
MHDA- 2023/02/14 06:01
PMCR- 2023/02/10
CRDT- 2023/02/13 03:46
PHST- 2023/02/14 06:00 [pubmed]
PHST- 2023/02/14 06:01 [medline]
PHST- 2023/02/13 03:46 [entrez]
PHST- 2023/02/10 00:00 [pmc-release]
AID - rs.3.rs-2487922 [pii]
AID - 10.21203/rs.3.rs-2487922/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Jan 30:rs.3.rs-2487922. doi: 10.21203/rs.3.rs-2487922/v1.