Immunobiology of Heparin-Induced Thrombocytopenia

Sandset, Per Morten

doi:10.1007/82_2010_17

Cited by 4 publications

(1 citation statement)

References 42 publications

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“…Antileukemic immune reactivity is important for the reduced relapse risk after allogeneic stem cell transplantation, and increased T cell reactivity may then strengthen this antileukemic effect [ 90 , 93 , 95 ]. Whether modulation of the chemokine system will alter humoral immune reactivity is not known [ 90 , 96 ]. Finally, the possible leukemia-enhancing effect by increased CXCL12/CXCR4 expression may be counteracted by specific inhibitors [ 97 ], and this may become true also for other chemokines/chemokine receptors.…”

Section: Concluding Remarks: Efficiency Versus mentioning

confidence: 99%

The Protein Kinase C Agonist PEP005 (Ingenol 3-Angelate) in the Treatment of Human Cancer: A Balance between Efficacy and Toxicity

Ersvær

Kittang

Hampson

et al. 2010

Toxins

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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. Direct pro-apoptotic effects of this drug have been demonstrated in several malignant cells, including melanoma cell lines and primary human acute myelogenous leukemia cells. At micromolar concentrations required to kill melanoma cells this agent causes PKC-independent secondary necrosis. In contrast, the killing of leukemic cells occurs in the nanomolar range, requires activation of protein kinase C δ (PKCδ) and is specifically associated with translocation of PKCδ from the cytoplasm to the nuclear membrane. However, in addition to this pro-apoptotic effect the agent seems to have immunostimulatory effects, including: (i) increased chemokine release by malignant cells; (ii) a general increase in proliferation and cytokine release by activated T cells, including T cells derived from patients with chemotherapy-induced lymphopenia; (iii) local infiltration of neutrophils after topical application with increased antibody-dependent cytotoxicity; and (iv) development of specific anti-cancer immune responses by CD8+ T cells in animal models. Published studies mainly describe effects from in vitro investigations or after topical application of the agent, and careful evaluation of the toxicity after systemic administration is required before the possible use of this agent in the treatment of malignancies other than skin cancers.

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Section: Concluding Remarks: Efficiency Versus mentioning

confidence: 99%

The Protein Kinase C Agonist PEP005 (Ingenol 3-Angelate) in the Treatment of Human Cancer: A Balance between Efficacy and Toxicity

Ersvær

Kittang

Hampson

et al. 2010

Toxins

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The Chemokine System in Experimental and Clinical Hematology

Bruserud

Kittang

2010

The Chemokine System in Experimental and Clinical Hematology

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The chemokine family consists of approximately 50 small (8-14 kDa), basic proteins that are expressed and released by a wide range of normal and malignant cells. Based on their molecular structure, these cytokines are divided into the two major subgroups CCL and CXCL chemokines that bind to CCR or CXCR receptors, respectively. These mediators are important for regulation of cell viability, proliferation, differentiation, and migration. Chemokines are important for cell migration during embryogenesis; they are involved in the regulation of complex processes like local recruitment of inflammatory cells, angiogenesis, and regulation of normal as well as leukemic hematopoiesis. Chemokines can be constitutively released by malignant hematopoietic cells as well as by bone marrow stromal cells. This bidirectional crosstalk between malignant hematopoietic cells and neighboring stromal cells may therefore be important for the development and clinical presentation of malignant diseases, and the chemokines or their receptors may also represent a target for specific anticancer therapy at the molecular level.

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Drugs that affect blood coagulation, fibrinolysis, and hemostasis

McRae¹

2012

A Worldwide Yearly Survey of New Data in Adverse Drug Reactions and Interactions

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Immunobiology of Heparin-Induced Thrombocytopenia

Cited by 4 publications

References 42 publications

The Protein Kinase C Agonist PEP005 (Ingenol 3-Angelate) in the Treatment of Human Cancer: A Balance between Efficacy and Toxicity

The Protein Kinase C Agonist PEP005 (Ingenol 3-Angelate) in the Treatment of Human Cancer: A Balance between Efficacy and Toxicity

The Chemokine System in Experimental and Clinical Hematology

Drugs that affect blood coagulation, fibrinolysis, and hemostasis

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