Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy Neurobiology

In this study, using a combination of drug pharmacodynamic analysis in human study participants, disease modeling in rodents, and cell-based assays, we examined whether S1P signaling may represent a potential target in the treatment of chemotherapy-induced neuropathy. To this end, we first investigated the effects of platinum-based drugs on plasma S1P levels in human cancer patients. Our analysis revealed that oxaliplatin treatment specifically increases one S1P species, d16:1 S1P, in these patients. Although d16:1 S1P is an S1P2 agonist, it has lower potency than the most abundant S1P species (d18:1 S1P). Therefore, as d16:1 S1P concentration increases, it is likely to disproportionately activate proinflammatory S1P1 signaling, shifting the balance away from S1P2. We further show that a selective S1P2 agonist, CYM-5478, reduces allodynia in a rat model of cisplatin-induced neuropathy and attenuates the associated inflammatory processes in the dorsal root ganglia, likely by activating stress-response proteins, including ATF3 and HO-1. Cumulatively, the findings of our study suggest that the development of a specific S1P2 agonist may represent a promising therapeutic approach for the management of chemotherapy-induced neuropathy.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Editors ' Picks Source Type: research

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ConclusionThis is an initial report demonstrating the potential of rTMS for the treatment of CIPN. We suggest rTMS could be potentially beneficial and effective as a treatment for pain and dysesthesia in patients with CIPN.
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect deriving from neurotoxic chemotherapeutic agents. The underlying nerve injury can affect proprioception causing impaired postural control, gait difficulties and a higher...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Ergonomics, Human Factors, Anthropometrics, Physiology Source Type: news
AbstractPurpose of ReviewChemotherapy-induced peripheral neuropathy (CIPN) is a common complication of cancer treatment, with conventional treatment limited in its ability for prevention or treatment of symptoms. This review addresses the research assessing the effectiveness and safety of complementary and integrative medicine (CIM) in preventing and treating CIPN-related symptoms.Recent FindingsThe CIM modalities acupuncture, classical massage, omega-3 fatty acids, and the Japanese Kampo medicine Goshanjishen may be of benefit in preventing or treating CIPN. Vitamin E (alpha-tocopherol), glutamine/glutamate, alpha-lipoic ...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
Abstract New therapeutic strategies are needed for pediatric acute myeloid leukemia to reduce disease recurrence and treatment-related morbidity. The Children's Oncology Group Phase III AAML1031 trial tested whether the addition of bortezomib to standard chemotherapy improves survival in pediatric patients with newly diagnosed acute myeloid leukemia. AAML1031 randomized patients younger than 30 years of age with de novo acute myeloid leukemia to standard treatment with or without bortezomib. All patients received the identical chemotherapy backbone with either four intensive chemotherapy courses or three courses f...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
This study compared emotional distress and QOL during FOLFOX in CRC patients with and without CIPN symptoms. This cross-sectional, descriptive, and comparative study recruited 68 CRC patients receiving FOLFOX at a local teaching hospital and at a medical center in southern Taiwan. Self-reported structured questionnaires (oxaliplatin-associated neuropathy questionnaire, profile of mood states short form, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30, version 3.0) were used for 1-time data collection. The Chi-square test, Fisher exact test, and Mann–Whitney U...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
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Source: Supportive Care in Cancer - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 January 2020Source: Chemico-Biological InteractionsAuthor(s): Brian C. Geohagen, Daniel A. Weiser, David M. Loeb, Lars U. Nordstroem, Richard M. LoPachinAbstractCisplatin (CisPt) and other platinum (Pt)-based antineoplastic drugs (e.g., carboplatin, oxaliplatin) are highly effective and widely used in the treatment of solid tumors in both pediatric and adult patients. Although considered to be life-saving as a cancer treatment, Pt-based drugs frequently result in dose-limiting toxicities such as chemotherapy-induced peripheral neuropathies (CIPN). Specifically, irreversible damage to o...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
Abstract FLOT-4 study recently reports that in patients with gastric cancer, perioperative chemotherapy with 5-fluorouracile, leucovorin, oxaliplatin and docetaxel (FLOT regimen) increases survival over standard ECF/ECX regimen (epirubicine, cisplatine and 5-fluorouracile [or capecitabine]). Does this study, make FLOT a new standard of perioperative chemotherapy for localized gastric cancer? Seven hundred and sixteen patients were included into that randomized study. Thirty seven per cent and 46% of the patients received the full planned treatment in the ECF/ECX group and in the FLOT group, respectively. The prima...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Abstract Cisplatin (CisPt) and other platinum (Pt)-based antineoplastic drugs (e.g., carboplatin, oxaliplatin) are highly effective and widely used in the treatment of solid tumors in both pediatric and adult patients. Although considered to be life-saving as a cancer treatment, Pt-based drugs frequently result in dose-limiting toxicities such as chemotherapy-induced peripheral neuropathies (CIPN). Specifically, irreversible damage to outer hair cells and injury of sensory neurons are linked to profound sensorineural hearing loss (ototoxicity), which complicates tumor management and can lead to a poor clinical pro...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
Publication date: Available online 17 January 2020Source: Neuroscience LettersAuthor(s): Lauren M. Styczynski, Katie A. Schappacher, Mark L. BacceiAbstractEarly life administration of vincristine (VNC), commonly used to treat pediatric leukemia, evokes peripheral neuropathy and mechanical pain hypersensitivity in rats that lasts into adolescence. However, the degree to which VNC-evoked neuropathic pain persists throughout adulthood has yet to be examined. It also remains unclear if pediatric VNC exposure can ‘prime’ developing nociceptive pathways and thereby exacerbate chronic pain following subsequent trauma ...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
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