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  • American Society of Clinical Oncology (ASCO)  (2)
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  • American Society of Clinical Oncology (ASCO)  (2)
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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 517-517
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 517-517
    Abstract: 517 Background: The cause of chemotherapy-induced oral mucositis (COM) is thought to be direct injury and indirect stomatotoxic effects that result from the release of inflammatory mediators, loss of protective salivary constituents, and therapy-induced neutropenia. We previously found that gargling with hangeshashinto (HST), a traditional Japanese medicine, was effective for treatment of COM. Focusing on the pain and inflammation of COM, we reported at ASCO-GI 2013 and DDW 2013 that HST exhibited ameliorating effects in a hamster model of COM and multi-targeted effects on prostaglandin E2 (PGE2) production, followed by identification of active ingredients by PGE2 culture systems and LC-MS/MS. Our aim in this study was to address whether HST affects protective oral constituents. Methods: Human oral keratinocytes (HOK) and human salivary gland (HSG) cells were used for cell culture assays. Expression levels of mRNAs for antimicrobial peptides, extracellular matrixes, keratinocyte growth factor, amylase, COX-1/COX-2, and cNOS/iNOS in cells with or without HST (10–300 μg/mL) treatment were measured by RT-PCR. Results: HST increased gene expressions of some antimicrobial peptides (defensin β1, adrenomedullin, cathelicidin antimicrobial peptide), and amylase 1A in HSG cells. Further, HST dramatically inhibited COX-2 and iNOS mRNAs in IL-1β treated HOK cells, while it exerted no or little effect on expressions of any protective oral constituents in non-treated HOK cells. A random test to identify the ingredients that increase defensin β1 revealed that isoquinoline alkaloids like berberine were active. Conclusions: HST is expected to maintain oral homeostasis through two paths: increased production of antimicrobial peptides and decreased oral damage induced by excessive prostanoids and nitric oxide. HST thus functions as a multitarget agent, indicating that it may be beneficial in COM treatment.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 3_suppl ( 2015-01-20), p. 576-576
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 576-576
    Abstract: 576 Background: Oxaliplatin-induced peripheral neuropathy (OPN) is often observed and is the most frequent dose-limiting toxicity. However, there is no effective therapeutic option for preventing OPN. Goshajinkigan (GJG), a traditional Japanese herbal medicine, has widely been used for disease-assessed neuropathy in Japan. Recently, the preventive effect of GJG against OPN in a placebo-controlled double-blind randomized phase II study was reported (Kono T et al., Cancer Chemother Pharmacol. 2013, 72,1283-90). However, the precise mechanisms underlying preventive effect of GJG are unknown. Methods: To be established the OPN rat model, oxaliplatin (4 mg/kg) was injected intraperitoneally twice weekly for 8 weeks in rats. Animals were treated with oral administration of GJG (0.3, 1.0 g/kg) five times a week for 8 weeks. We performed behavioral tests (acetone test and hot plate test) and pathological examination of neuronal tissue using the OPN rat model. We carried out pharmacokinetic study of GJG and searched for active ingredients in GJG in order to explore the mechanism of GJG. Results: The rats injected with oxaliplatin for a long-term showed both cold hypersensitivity and heat hyposensitivity. Co-administration of GJG ameliorated OPN in the rat. In light and electron microscopic study, scattered axonal damages in sciatic nerve of oxaliplatin groups were observed, which were substantially suppressed by GJG. Pharmacokinetic study revealed that considerable neuroprotective and analgesic ingredients were detected after oral administration of GJG in rat plasma. Some ingredients in GJG significantly suppressed oxidative stress caused by oxaliplatin in the experiment using neuronal cells. Conclusions: Oxaliplatin-induced chronic neuropathy symptoms are similar to human symptoms caused by long-term oxaliplatin administration. Oral administration of GJG in rat substantially diminished OPN, and promises to provide an effective and convenient treatment at risk of developing peripheral neuropathy in oxaliplatin-treated patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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