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Laser ablation-inductively coupled plasma-mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma

Tisza, Anna ; Klikovits, Thomas ; Benej, Michal ; Torok, Szilvia ; Szeitz, Beata ; Valko, Zsuzsanna ; Hoda, Mir Alireza ; Hegedus, Balazs ; Bonta, Maximilian and Nischkauer, Winfried , et al. (2023) In British Journal of Clinical Pharmacology 89(11). p.3364-3374
Abstract

Aims: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. Methods: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry and correlated with clinicopathological features. Results: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of... (More)

Aims: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. Methods: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry and correlated with clinicopathological features. Results: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of Pt distribution was seen within the tumourous areas. Pt levels correlated neither with the microvessel area nor with apoptosis rate in the tumourous or nontumourous regions. A significant positive correlation was found between serum and both full tissue section and tumourous area mean Pt levels (r = 0.532, P = 0.006, 95% confidence interval [95% CI] 0.161-0.771 and r = 0.415, P = 0.039, 95% CI 0.011-0.702, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r = −0.474, P = 0.017, 95% CI −0.738-−0.084). Serum Pt levels correlated negatively with overall survival (OS) (P = 0.029). Conclusions: There are major differences in drug distribution between tumourous and nontumourous areas of PM specimens. Serum Pt levels significantly correlate with full section and tumourous area average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.

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type
Contribution to journal
publication status
published
subject
keywords
intratumoural drug distribution, laser ablation-inductively coupled plasma-mass spectrometry, mass spectrometry imaging, neoadjuvant chemotherapy, platinum, pleural mesothelioma
in
British Journal of Clinical Pharmacology
volume
89
issue
11
pages
3364 - 3374
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:37272312
  • scopus:85165206570
ISSN
0306-5251
DOI
10.1111/bcp.15813
language
English
LU publication?
yes
id
c6f26654-e48c-4fb7-b874-32cf1d76d276
date added to LUP
2023-09-25 14:36:17
date last changed
2024-04-19 01:37:33
@article{c6f26654-e48c-4fb7-b874-32cf1d76d276,
  abstract     = {{<p>Aims: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. Methods: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry and correlated with clinicopathological features. Results: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of Pt distribution was seen within the tumourous areas. Pt levels correlated neither with the microvessel area nor with apoptosis rate in the tumourous or nontumourous regions. A significant positive correlation was found between serum and both full tissue section and tumourous area mean Pt levels (r = 0.532, P = 0.006, 95% confidence interval [95% CI] 0.161-0.771 and r = 0.415, P = 0.039, 95% CI 0.011-0.702, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r = −0.474, P = 0.017, 95% CI −0.738-−0.084). Serum Pt levels correlated negatively with overall survival (OS) (P = 0.029). Conclusions: There are major differences in drug distribution between tumourous and nontumourous areas of PM specimens. Serum Pt levels significantly correlate with full section and tumourous area average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.</p>}},
  author       = {{Tisza, Anna and Klikovits, Thomas and Benej, Michal and Torok, Szilvia and Szeitz, Beata and Valko, Zsuzsanna and Hoda, Mir Alireza and Hegedus, Balazs and Bonta, Maximilian and Nischkauer, Winfried and Hoetzenecker, Konrad and Limbeck, Andreas and Schelch, Karin and Laszlo, Viktoria and Megyesfalvi, Zsolt and Dome, Balazs}},
  issn         = {{0306-5251}},
  keywords     = {{intratumoural drug distribution; laser ablation-inductively coupled plasma-mass spectrometry; mass spectrometry imaging; neoadjuvant chemotherapy; platinum; pleural mesothelioma}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{3364--3374}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{British Journal of Clinical Pharmacology}},
  title        = {{Laser ablation-inductively coupled plasma-mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma}},
  url          = {{http://dx.doi.org/10.1111/bcp.15813}},
  doi          = {{10.1111/bcp.15813}},
  volume       = {{89}},
  year         = {{2023}},
}