Browsing by Subject "peripheral neuropathy"

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    Adverse Health Outcomes among U.S. Testicular Cancer Survivors after Cisplatin-Based Chemotherapy vs. Surgical Management
    (Oxford, 2019-10) Agrawal, Vaibhav; Dinh, Paul C., Jr.; Fung, Chunkit; Monahan, Patrick O.; Althouse, Sandra K.; Norton, Kelli; Cary, Clint; Einhorn, Lawrence; Fossa, Sophie D.; Adra, Nabil; Travis, Lois B.; Medicine, School of Medicine
    We evaluated for the first time adverse health outcomes (AHOs) among U.S. testicular cancer survivors (TCS) given chemotherapy (n = 381) vs. surgery-only patients (n = 98) managed at a single institution, accounting for non-treatment-related risk factors to delineate chemotherapy’s impact. Chemotherapy consisted largely of bleomycin-etoposide-cisplatin (BEP) administered in 3 or 4 cycles (BEPX3, n = 235; BEPX4, n = 82). Incidence of ≥ 3 AHOs was lowest in surgery-only TCS and increased with BEPX3, BEPX4 and other cisplatin-based regimens (12.2%, 40.8%, 52.5%, 54.8%; P<0.0001). Multivariate modeling assessed associations of risk factors and treatment with hearing impairment, tinnitus, peripheral neuropathy, and Raynaud phenomenon. Risk for each AHO significantly increased with both increasing chemotherapy burden (P < 0.0001) and selected modifiable risk factors (P < 0.05): hypertension (OR = 2.40) and noise exposure (OR ≥ 2.3) for hearing impairment; noise exposure for tinnitus (OR ≥ 1.69); peripheral vascular disease for neuropathy (OR = 8.72), and current smoking for Raynaud phenomenon (OR = 2.41). Clinicians should manage modifiable risk factors for AHOs among TCS.
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    Paclitaxel inhibits the activity and membrane localization of PKCα and PKCβI/II to elicit a decrease in stimulated calcitonin gene-related peptide release from cultured sensory neurons
    (Elsevier, 2017) Darby, Lisa M.; Meng, Hongdi; Fehrenbacher, Jill C.; Department of Pharmacology and Toxicology, IU School of Medicine
    Peripheral neuropathy is a dose-limiting and debilitating side effect of the chemotherapeutic drug, paclitaxel. Consequently, elucidating the mechanisms by which this drug alters sensory neuronal function is essential for the development of successful therapeutics for peripheral neuropathy. We previously demonstrated that chronic treatment with paclitaxel (3–5 days) reduces neuropeptide release stimulated by agonists of TRPV1. Because the activity of TRPV1 channels is modulated by conventional and novel PKC isozymes (c/nPKC), we investigated whether c/nPKC mediate the loss of neuropeptide release following chronic treatment with paclitaxel (300 nM; 3 and 5 days). Release of the neuropeptide, calcitonin gene-related peptide (CGRP), was measured as an index of neuronal sensitivity. Following paclitaxel treatment, cultured dorsal root ganglia sensory neurons were stimulated with a c/nPKC activator, phorbol 12,13-dibutyrate (PDBu), or a TRPV1 agonist, capsaicin, in the absence and presence of selective inhibitors of conventional PKCα and PKCβI/II isozymes (cPKC). Paclitaxel (300 nM; 3 days and 5 days) attenuated both PDBu- and capsaicin-stimulated release in a cPKC-dependent manner. Under basal conditions, there were no changes in the protein expression, phosphorylation or membrane localization of PKC α, βI or βII, however, paclitaxel decreased cPKC activity as indicated by a reduction in the phosphorylation of cPKC substrates. Under stimulatory conditions, paclitaxel attenuated the membrane translocation of phosphorylated PKC α, βI and βII, providing a rationale for the attenuation in PDBu- and capsaicin-stimulated release. Our findings suggest that a decrease in cPKC activity and membrane localization are responsible for the reduction in stimulated peptide release following chronic treatment with paclitaxel in sensory neurons.
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    The Experience of Peripheral Neuropathy Symptoms in Breast Cancer Survivors With Diabetes
    (Wolters Kluwer, 2024-07) Storey, Susan; Draucker, Claire; Haunert, Laura; Von Ah, Diane; School of Nursing
    Background Diabetes (type 2) is a risk factor for developing peripheral neuropathy (PN) symptoms in breast cancer survivors (BCS). Because PN symptoms are associated with deficits in physical functioning and quality of life, more information is needed about the effects of PN symptoms on the lives of BCS with diabetes. Objective The aim of this study was to describe the experiences of PN among BCS with diabetes from their own perspectives. Interventions/Methods This substudy is part of a larger investigation examining factors associated with cancer-related cognitive impairment in cancer survivors. Female early-stage (stage I–III) BCS with diabetes and PN symptoms were eligible to participate. A qualitative descriptive approach using purposive sampling and semistructured interviews was used. Participant narratives were summarized using standard content analytic techniques. Results Eleven BCS with diabetes and PN symptoms were interviewed. Participants described PN symptoms that were varied, were often persistent, and had troublesome effects on their physical functioning and quality of life. Participants used a variety of self-management strategies and prescription and over-the-counter medications to manage their PN symptoms. Some said that having both cancer and diabetes exacerbated the PN symptoms and complicated symptom management. Conclusion Peripheral neuropathy symptoms can have a profound effect on the lives of BCS with diabetes and should be addressed by healthcare providers.