Cardiotoxicity of cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

Demkow, Urszula; Stelmaszczyk-Emmel, Anna

doi:10.1016/j.resp.2013.03.013

Cited by 45 publications

(31 citation statements)

References 33 publications

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“…In this sense, experimental studies directed to the identification and understanding of the mechanisms involved in this particular toxicity could be useful to the scientific community. In the present study, the experimental conditions used provoked in the animals, cardiovascular alterations similar to those described in humans treated with cycles of cisplatin (Demkow and Stelmaszczyk-Emmel, 2013; Haugnes et al, 2015; Herrmann et al, 2016), being a useful tool for this purpose. However, further investigations are needed to identify early signs of cardiac and vascular damage in order to optimize the clinical management of cardiotoxicity in cisplatin treatments.…”

Section: Resultsmentioning

confidence: 85%

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

et al. 2017

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In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

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Section: Resultsmentioning

confidence: 85%

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

et al. 2017

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“…Increases in 99m Tc-duramycin uptake were observed in tissues known to be susceptible to cisplatin toxicity. The known susceptible tissues for cisplatin toxicity are listed in Supplementary Table S2 (43)(44)(45)(46)(47). According to the net uptake of 99m Tc-duramycin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Whole-body Imaging of Cell Death Provides a Systemic, Minimally Invasive, Dynamic, and Near-real Time Indicator for Chemotherapeutic Drug Toxicity

Johnson

Ugolkov²,

Haney

et al. 2019

Clinical Cancer Research

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Purpose: Response to toxicity in chemotherapies varies considerably from tissue to tissue and from patient to patient. An ability to monitor the tissue damage done by chemotherapy may have a profound impact on treatment and prognosis allowing for a proactive management in understanding and mitigating such events. For the first time, we investigated the feasibility of using whole-body imaging to map chemotherapeutic drug-induced toxicity on an individual basis.Experimental Design: In a preclinical proof-of-concept, rats were treated with a single clinical dose of cyclophosphamide, methotrexate, or cisplatin. In vivo whole-body imaging data were acquired using 99m Tc-duramycin, which identifies dead and dying cells as an unambiguous marker for tissue injury in susceptible organs. Imaging results were cross-validated using quantitative ex vivo measurements and histopathology and compared with standard blood and serum panels for toxicology.Results: The in vivo whole-body imaging data detected widespread changes, where spatially heterogeneous toxic effects were identified across different tissues, within substructures of organs, as well as among different individuals. The signal changes were consistent with established toxicity profiles of these chemotherapeutic drugs. Apart from generating a map of susceptible tissues, this in vivo imaging approach was more sensitive compared with conventional blood and serum markers used in toxicology. Also, repeated imaging during the acute period after drug treatment captured different kinetics of tissue injury among susceptible organs in males and females.Conclusions: This novel and highly translational imaging approach shows promise in optimizing therapeutic decisions by detecting and managing drug toxicity on a personalized basis.Toxicity to normal tissues is a significant limitation in chemotherapies. This work demonstrated an in vivo imaging-based approach for characterizing toxicity-induced tissue injury in a systemic, dynamic, and near-real time fashion. This novel approach shows promise in optimizing therapeutic decisions by monitoring drug toxicity on a personalized basis. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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“…Apoptosis is also responsible for the typical nephrotoxicity, ototoxicity and other cytotoxicities. Cisplatin-induced cytotoxicity in endothelial cells has been linked to increased generation of procoagulant endothelial micro-particles and free radicals [66,67]. For example, testicular cancer patients treated with orchiectomy showed a decrease in plasma levels of the endothelial pro-thrombotic markers PAI-1 (plasminogen activator inhibitor-1) and vWF (Von Willebrand factor) compared to those patients treated with cisplatin [68].…”

Section: Vascular Damage Caused By Chemotherapymentioning

confidence: 99%

Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond

Lisi

Madonna

Zito

et al. 2017

International Journal of Cardiology

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Cardiotoxicity of cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

Cited by 45 publications

References 33 publications

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

Whole-body Imaging of Cell Death Provides a Systemic, Minimally Invasive, Dynamic, and Near-real Time Indicator for Chemotherapeutic Drug Toxicity

Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond

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