Ototoxicity in Children Receiving Platinum Chemotherapy: Underestimating a Commonly Occurring Toxicity That May Influence Academic and Social Development

Knight, Keith; Kraemer, Dale F.; Neuwelt, Edward A.

doi:10.1200/jco.2004.00.5355

Cited by 456 publications

(408 citation statements)

References 26 publications

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“…Previous studies have revealed hearing impairments mainly in patients <5 years old (20,24,25). In the adult group, hearing impairments were identified in 6/17 (35.3%) patients.…”

Section: Discussionmentioning

confidence: 99%

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

et al. 2012

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“…Previous studies have revealed hearing impairments mainly in patients <5 years old (20,24,25). In the adult group, hearing impairments were identified in 6/17 (35.3%) patients.…”

Section: Discussionmentioning

confidence: 99%

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

et al. 2012

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“…Cisplatin causes significant permanent hearing loss in 20-80 % of treated patients (Fausti et al 1994;Knight et al 2005;Coradini et al 2007;Lewis et al 2009, reviewed in Neuwelt andBrock 2010). Risk factors that increase the likelihood of cisplatin-induced hearing loss include patient age, gender, cumulative cisplatin dose, certain genetic alleles, and radiation to the base of the skull (Schaefer et al 1985;Schell et al 1989;Li et al 2004;Huang et al 2007;Caronia et al 2009;Ross et al 2009;Yancey et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Baker

Roy

Brandon

et al. 2014

JARO

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Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin treatment include nephrotoxicity and ototoxicity. Cisplatin ototoxicity results from damage to and death of cells in the inner ear, including sensory hair cells. We showed previously that heat shock inhibits cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. Since heat shock protein 70 (HSP70) is the most upregulated HSP in response to heat shock, we investigated the role of HSP70 as a potential protectant against cisplatin-induced hair cell death. Our data using utricles from HSP70 −/− mice indicate that HSP70 is necessary for the protective effect of heat shock against cisplatin-induced hair cell death. In addition, constitutive expression of inducible HSP70 offered modest protection against cisplatin-induced hair cell death. We also examined a second heat-inducible protein, heme oxygenase-1 (HO-1, also called HSP32). HO-1 is an enzyme responsible for the catabolism of free heme. We previously showed that induction of HO-1 using cobalt protoporphyrin IX (CoPPIX) inhibits aminoglycoside-induced hair cell death. Here, we show that HO-1 also offers significant protection against cisplatin-induced hair cell death. HO-1 induction occurred primarily in resident macrophages, with no detectable expression in hair cells or supporting cells. Depletion of macrophages from utricles abolished the protective effect of HO-1 induction. Together, our data indicate that HSP induction protects against cisplatin-induced hair cell death, and they suggest that resident macrophages mediate the protective effect of HO-1 induction.

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“…As reviewed by Rybak (2005), hearing loss occurs in 30 to 100% of patients treated with cisplatin. Hearing loss may occur during treatment (Knight et al, 2005(Knight et al, , 2007Orgel et al, 2012) or after discontinuation of chemotherapy (Al-Khatib et al, 2010;Kolinsky et al, 2010). Furthermore, patients treated with cisplatin exhibit severe difficulty in word recognition (Einarsson et al, 2011), suggesting a central component in their hearing loss.…”

Section: Introductionmentioning

confidence: 99%

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Gopal

Shrestha

et al. 2012

Neurotoxicology and Teratology

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Cisplatin is a platinum-based chemotherapeutic agent widely used for the treatment of various types of cancer. Patients undergoing cisplatin treatment often suffer from a condition known as "chemobrain", ototoxicity, peripheral neuropathy, weight loss, nausea, vomiting, nephrotoxicity, seizures, hearing loss and tinnitus.D-Methionine (D-Met), a sulfur-containing nucleophilic antioxidant, has been shown to prevent cisplatininduced side effects in animals without antitumor interference. In this study, we have used an in vitro model of cortical networks (CNs), enriched in auditory cortex cells; to quantify cisplatin neurotoxicity and the protective effects of D-Met. Dissociated neurons from auditory cortices of mouse embryos were grown on microelectrode arrays with 64 transparent indium-tin oxide electrodes, which enabled continuous optical and electrophysiological monitoring of network neurons. Cisplatin at 0.10-0.25 mM induced up to a 200% increase in spontaneous spiking activity, while concentrations at or above 0.5 mM caused irreversible loss of neuronal activity, accompanied by cell death. Pretreatment with D-Met, at a concentration of 1.0 mM, prevented the cisplatin-induced excitation at 0.10-0.25 mM, caused sustained excitation without occurrence of cell death at 0.5 mM, and delayed cell death at 0.75 mM cisplatin. L-Methionine, the optical isomer, showed lower potency and less efficacy than D-Met, was less protective against 0.1 mM cisplatin, and proved ineffective at a concentration of 0.5 mM cisplatin. Pre-exposure time of D-Met was associated with the protective effects at 0.1 and 0.5 mM cisplatin, with longer pre-exposure times exhibiting better protection. This study quantifies as a function of concentration and time that D-Met protects central nervous system tissue from acute cisplatin toxicity.

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Ototoxicity in Children Receiving Platinum Chemotherapy: Underestimating a Commonly Occurring Toxicity That May Influence Academic and Social Development

Cited by 456 publications

References 26 publications

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

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