the protein kinase c agonist pep005 (ingenol 3-angelate) in the treatment of human cancer a balance between efficacy and toxicity蛋白激酶c受体激动剂pep005(ingenol 3-angelate)在人类癌症的治疗疗效和毒性之间的平衡.pdfVIP

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the protein kinase c agonist pep005 (ingenol 3-angelate) in the treatment of human cancer a balance between efficacy and toxicity蛋白激酶c受体激动剂pep005(ingenol 3-angelate)在人类癌症的治疗疗效和毒性之间的平衡.pdf

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the protein kinase c agonist pep005 (ingenol 3-angelate) in the treatment of human cancer a balance between efficacy and toxicity蛋白激酶c受体激动剂pep005(ingenol 3-angelate)在人类癌症的治疗疗效和毒性之间的平衡

Toxins 2010, 2, 174-194; doi:10.3390/toxins2010174 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review The Protein Kinase C Agonist PEP005 (Ingenol 3-Angelate) in the Treatment of Human Cancer: A Balance between Efficacy and Toxicity Elisabeth Ersvaer 1, Astrid Olsnes Kittang 1,2, Peter Hampson 3, Kristoffer Sand 1, Bjørn Tore Gjertsen 1,2, Janet M. Lord 3 and Øystein Bruserud 1,2,* 1 Section for Hematology, The University of Bergen, Bergen, Norway; E-Mails: elisabeth.ersvar@med.uib.no (E.E.); astrid.Olsnes@med.uib.no (A.O.K.); kesand@ (K.S.); bjorn.gjertsen@med.uib.no (B.T.G.) 2 Division of Hematology, Department of Medicine, Haukeland University Hospital, Norway 3 School of Immunity and Infection, Birmingham University Medical School, Birmingham, UK; E-Mails: pxh048@bham.ac.uk (P.H.); J.M.Lord@bham.ac.uk (J.M.L.) * Author to whom correspondence should be addressed; E-Mail: oystein.bruserud@helse-bergen.no; Tel.: +47-559-72-997; Fax: +47-559-75-890. Received: 30 November 2009; in revised form: 7 January 2010 / Accepted: 18 January 2010 / Published: 22 January 2010 Abstract: The diterpene ester ingenol-3-angelate (referred to as PEP005) is derived from the plant Euphorbia peplus . Crude euphorbia extract causes local toxicity and transient inflammation when applied topically and has been used in the treatment of warts, skin keratoses and skin cancer. PEP005 is a broad range activator of the classical (α, β, γ) and novel (δ, ε, η, θ) protein kinase C isoenzymes. Direc