Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although development of first-generation thrombopoietic growth factors (recombinant human thrombopoietin [TPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) was stopped due to development of antibodies to PEG-rHuMGDF, nonimmunogenic second-generation thrombopoietic growth factors with unique pharmacologic properties have been developed. TPO peptide mimetics contain TPO receptor-activating peptides inserted into complementarity-determining regions of Fab (Fab 59), attached to the IgG Fc region (AMG 531), or pegylated (Peg-TPOmp). Orally available, TPO nonpeptide mimetics (eltrombopag, AKR-501) bind and activate the TPO receptor by a mechanism different from TPO and may have an additive effect to TPO. TPO agonist antibodies are monoclonal antibodies activating the TPO receptor but modified in size [TPO minibodies; ie, VB22B sc(Fv)(2)] or immunoglobuln type (domain subclass-converted TPO agonist antibodies; ie, MA01G4G344). All second-generation thrombopoietic growth factors stimulate growth of TPO-dependent cell lines via JAK2/STAT signaling pathways and increase platelet counts in animals. When tested in healthy humans, TPO peptide and nonpeptide mimetics produced a dose-dependent rise in platelet count. AMG 531 and eltrombopag markedly increase platelet counts in patients with immune thrombocytopenic purpura, without significant adverse effects. One or more second-generation thrombopoietic growth factors should soon be clinically available for treating thrombocytopenic disorders.
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PMID:New thrombopoietic growth factors. 1728 15

Today several monoclonal antibodies, including the anti-CD20 antibody (rituximab), the anti-CD52 antibody (alemtuzumab) and the anti-CD33 antibody (gemtuzumab ozogamacin) are all integrated in the therapeutic armamentarium of patients with malignant lymphoma, chronic lymphocytic leukaemia and acute myelogenous leukaemia, respectively. Rituximab has also been shown to be highly effective in the treatment of refractory autoimmune haemolytic anemias, idiopathic thrombocytopenia, and relapsing thrombotic thrombocytopenic purpura. New signal transduction inhibitors, dasatinib and nilotinib, are being used in patients with chronic myelogeneous leukaemia who develop resistance to imatinib. Thalidomide, lenalidomide and bortezomib have all been shown to be highly effective in multiple myeloma, and JAK2-inhibitors have entered phase II studies of patients with JAK2-positive primary myelofibrosis and related diseases.
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PMID:[Novel medical treatment modalities in hematology]. 1856 91

Pegylated interferon alfa-2a (pegIFNa) is being increasingly used for treatment of myeloproliferative neoplasms; however, its side effects, including autoimmune complications, are not unusual. We report on a 47-year-old woman with polycythemia vera (PV) treated with pegIFNa and in complete hematologic remission who developed thrombotic thrombocytopenic purpura (TTP). To our knowledge, thrombotic microangiopathy has been reported as a side effect of interferon (IFN) use in patients with hepatitis and chronic myeloid leukemia, but not in those with PV. Our patient had a low ADAMTS13 level due to an inhibitor, which normalized after withholding pegIFNa and initiating treatment for TTP with therapeutic plasma exchange and corticosteroids. She experienced refractory TTP, necessitating treatment with rituximab and splenectomy. Postsplenectomy, she developed a high platelet count, warranting the need to restart treatment for PV. However, JAK2V617F allelic burden by real-time PCR was 0.7%, indicating that the increased platelet count was likely secondary to splenectomy. Therefore, we elected to monitor her counts and JAK2V617F allelic burden closely. With this case report, we hope to alert treating physicians that TTP should be considered as a complication of pegIFNa therapy in PV and that prompt discontinuation of the drug with necessary treatment should be instituted to prevent fatal complications.
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PMID:Thrombotic Thrombocytopenic Purpura Associated With Pegylated Interferon Alfa-2a Use in a Patient With Polycythemia Vera. 2859 55

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after initiating antiretroviral therapy usually involves worsening manifestations of overt infectious disease. Here, we describe a sporadic case of a late-diagnosed HIV-positive man who developed Graves' disease as the first noninfectious IRIS followed by immune thrombocytopenic purpura as the second noninfectious IRIS.
Int J STD AIDS 2018 07
PMID:Sequential occurrence of Graves' disease and immune thrombocytopenic purpura as manifestations of immune reconstitution inflammatory syndrome in an HIV-infected patient. 2936 86