Quantitative imaging of platinum based on laser ablation-inductively coupled plasma-mass spectrometry to investigate toxic side effects of cisplatin

Köppen, Christina; Reifschneider, Olga; Castanheira, Isabel; Sperling, Michael; Kärst, Uwe; Ciarimboli, Giuliano

doi:10.1039/c5mt00226e

Cited by 32 publications

(28 citation statements)

References 36 publications

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“…The glomerulus at the right side of the image corresponds to the dark blue zone, indicating very low cisplatin accumulation, which is in agreement with the findings of Moreno-Gordaliza et al [36], who indicated cisplatin was absent in glomeruli. In contrast to our results based on a single dose administration, Köppen et al [35] reported the presence of significant amounts of cisplatin in the glomeruli of mice kidneys after cisplatin administration of eight doses of …”

Section: Articlecontrasting

confidence: 55%

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High-resolution laser ablation-inductively coupled plasma-mass spectrometry imaging of cisplatin-induced nephrotoxic side effects

Acker

Malderen

Heerden

et al. 2016

Analytica Chimica Acta

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Two-dimensional elemental mapping (bioimaging) via laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was performed on 5 µm thick formalin-fixed, paraffin-embedded kidney tissue sections from Cynomolgus monkeys administered with increasing pharmacological doses of cisplatin. Laterally resolved pixels of 1 µm were achieved, enabling elemental analysis on a (sub-)cellular level.Zones of high Pt response were observed in the renal cortex, where proximal tubules are present, the epithelium of which is responsible for partial reabsorption of cisplatin. Histopathological evaluation, of hematoxylin and eosin-stained serial sections, adjacent to the sections probed via LA-ICP-MS, revealed minimal to mild cisplatin-related lesions (< 100 µm) in the renal cortex. Necrotic proximal tubules with sloughed epithelial cells in their lumen could be linked directly to the areas with the highest accumulation of cisplatin, indicating a direct link between cellular concentration and toxicity, thereby providing more insight into the mechanisms through which renal damage occurs.

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Section: Articlecontrasting

confidence: 55%

“…Different tubular structures can be recognized in the Pt distribution map and as expected, cisplatin is mainly present in the epithelial cells of proximal and distal tubules. Previous studies [35,36] on this topic also indicate the accumulation of cisplatin in tubular epithelial cells. The lumens of these tubular segments are low in cisplatin.…”

Section: Articlementioning

confidence: 94%

High-resolution laser ablation-inductively coupled plasma-mass spectrometry imaging of cisplatin-induced nephrotoxic side effects

Acker

Malderen

Heerden

et al. 2016

Analytica Chimica Acta

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“…In addition, recent studies35–37 using cancer cell lines, Hep3B, HepJ5, ES-2, SKOV-3, OVCAR-3, MCF-7, revealed significant decreases in cell viability after DXR exposure. On the other hand, the same degree of sensitivity from the 2D system did not translate to a 3D culture system, resulting in higher IC50 values than the 2D system 38.…”

Section: Introductionmentioning

confidence: 91%

“…On the other hand, the same degree of sensitivity from the 2D system did not translate to a 3D culture system, resulting in higher IC50 values than the 2D system 38. Greatly reduced cell viabilities from DXR treatments were observed from uterus/endometrium cancer (KLE) and colon carcinoma (HCT116), osteogenic sarcoma (Saos-2), and bone osteosarcoma (HOS), which were cultured in 3D system 33–35,39. In addition, a significant effect of DXR towards 3D-spheroid forms of Ishikawa human endometrial cancer cells (RL95-2) was revealed by measuring cell viability 40.…”

Section: Introductionmentioning

confidence: 99%

Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time

Baek¹,

Seo²,

Kim³

et al. 2016

OTT

109

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Recently, increasing numbers of cell culture experiments with 3D spheroids presented better correlating results in vivo than traditional 2D cell culture systems. 3D spheroids could offer a simple and highly reproducible model that would exhibit many characteristics of natural tissue, such as the production of extracellular matrix. In this paper numerous cell lines were screened and selected depending on their ability to form and maintain a spherical shape. The effects of increasing concentrations of doxorubicin (DXR) on the integrity and viability of the selected spheroids were then measured at regular intervals and in real-time. In total 12 cell lines, adenocarcinomic alveolar basal epithelial (A549), muscle (C2C12), prostate (DU145), testis (F9), pituitary epithelial-like (GH3), cervical cancer (HeLa), HeLa contaminant (HEp2), embryo (NIH3T3), embryo (PA317), neuroblastoma (SH-SY5Y), osteosarcoma U2OS, and embryonic kidney cells (293T), were screened. Out of the 12, 8 cell lines, NIH3T3, C2C12, 293T, SH-SY5Y, A549, HeLa, PA317, and U2OS formed regular spheroids and the effects of DXR on these structures were measured at regular intervals. Finally, 5 cell lines, A549, HeLa, SH-SY5Y, U2OS, and 293T, were selected for real-time monitoring and the effects of DXR treatment on their behavior were continuously recorded for 5 days. A potential correlation regarding the effects of DXR on spheroid viability and ATP production was measured on days 1, 3, and 5. Cytotoxicity of DXR seemed to occur after endocytosis, since the cellular activities and ATP productions were still viable after 1 day of the treatment in all spheroids, except SH-SY5Y. Both cellular activity and ATP production were halted 3 and 5 days from the start of the treatment in all spheroids. All cell lines maintained their spheroid shape, except SHSY-5, which behaved in an unpredictable manner when exposed to toxic concentrations of DXR. Cytotoxic effects of DXR towards SH-SY5Y seemed to cause degradation of the extracellular matrix, since all cells were dismantled from the spheroid upon cell death. On the other hand, 293T spheroids revealed retarded cellular activity and ATP productions upon DXR treatment throughout the experiment. Since 293T was the embryonic kidney cells, the fast clearance or neutralizations could have made them resistant towards DXR. In conclusion, the same degree of sensitivity from the 2D system did not translate to a 3D culture system, resulting in higher IC50 values than the 2D system. The varying sensitivities and tolerances to drugs could be better understood with a 3D cell culture system.

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“…Sections of explants treated with cisplatin were subjected to Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to produce elemental maps showing the spatial distribution of platinum in tissue sections (25). The method is described in Supplementary Fig.…”

Section: Laser Ablation Inductively Coupled Plasma Mass Spectrometrymentioning

confidence: 99%

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

et al. 2017

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To improve treatment outcomes in non-small cell lung cancer (NSCLC), preclinical models that can better predict individual patient response to novel therapies are urgently needed. Using freshly resected tumor tissue, we describe an optimized ex vivo explant culture model that enables concurrent evaluation of NSCLC response to therapy while maintaining the tumor microenvironment. We found that approximately 70% of primary NSCLC specimens were amenable to explant culture with tissue integrity intact for up to 72 hours. Variations in cisplatin sensitivity were noted with approximately 50% of cases responding ex vivo. Notably, explant responses to cisplatin correlated significantly with patient survival (P ¼ 0.006) irrespective of tumor stage. In explant tissue, cisplatin-resistant tumors excluded platinum ions from tumor areas in contrast to cisplatin-sensitive tumors. Intact TP53 did not predict cisplatin sensitivity, but a positive correlation was observed between cisplatin sensitivity and TP53 mutation status (P ¼ 0.003). Treatment of NSCLC explants with the targeted agent TRAIL revealed differential sensitivity with the majority of tumors resistant to single-agent or cisplatin combination therapy. Overall, our results validated a rapid, reproducible, and low-cost platform for assessing drug responses in patient tumors ex vivo, thereby enabling preclinical testing of novel drugs and helping stratify patients using biomarker evaluation.

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Quantitative imaging of platinum based on laser ablation-inductively coupled plasma-mass spectrometry to investigate toxic side effects of cisplatin

Cited by 32 publications

References 36 publications

High-resolution laser ablation-inductively coupled plasma-mass spectrometry imaging of cisplatin-induced nephrotoxic side effects

High-resolution laser ablation-inductively coupled plasma-mass spectrometry imaging of cisplatin-induced nephrotoxic side effects

Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

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