Open journal of hematology最新文献

{"title":"AGEM400(HES), a Novel Erythropoietin Mimetic Peptide Conjugated to Hydroxyethyl Starch with Excellent In Vitro Efficacy","authors":"A. Greindl, C. Kessler, B. Breuer, Udo Haber, A. Rybka, M. Emgenbroich, A. Pötgens, H. Frank","doi":"10.2174/1874276901004010001","DOIUrl":"https://doi.org/10.2174/1874276901004010001","url":null,"abstract":"We developed and tested a compound called AGEM400(HES) that consists of a novel erythropoietin mimetic peptide (EMP) which is produced as a continuous N- to C-linked dimer and is conjugated to biodegradable hydroxyethyl starch (HES). In various in vitro assays, AGEM400(HES) demonstrated excellent efficacy, better than the peptide alone, and comparable to the efficacy of erythropoietin (EPO) and Aranesp (Darbepoietin alpha). The assays included survival assays on EPO-responsive cell lines (EC50 below 1 ng/ml peptide) and clonogenic assays on human bone marrow cells (EC50 1 to 10 ng/ml). AGEM400(HES) caused phosphorylation of STAT5 and ERK signalling proteins in UT7/EPO cells in a similar fashion as EPO. AGEM400(HES) replaced EPO from its receptor and the in vitro activity of AGEM400 (HES) was inhibited by soluble EPO receptor. Antibodies generated in mice and rabbits against EPO did not recognize AGEM400(HES) peptide, and vice versa. A sensitive ELISA was able to detect AGEM400(HES) at low nanogram per ml concentrations which allows for bioanalytics of AGEM400(HES) serum levels in future in vivo studies. As a result, AGEM400(HES) is a promising drug candidate for anemias related to renal insufficiency and/or in oncological settings.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"15 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76244216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel agents in Waldenstrom Macroglobulinemia.","authors":"Antonio Sacco, Xavier Leleu, Giuseppe Rossi, Irene M Ghobrial, Aldo M Roccaro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Waldenström's Macroglobulinemia (WM) is a B-cell disorder characterized by the infiltration of the bone marrow (BM) with lymphoplasmacytic cells, as well as detection of an IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall median survival of only 5-6 years. The success of targeted therapy in multiple myeloma (MM) has led to the development and investigation of more than 30 new compounds in this disease and in other plasma cell dyscrasias WM, both in the preclinical settings and as part of clinical trials. Among therapeutical options, first-line therapies have been based on single-agent or combination regimens with alkylator agents, nucleoside analogues, and the monoclonal antibody anti-CD20. Based on the understanding of the complex interaction between tumor cells and bone marrow microenvironment and the signaling pathways that are deregulated in WM pathogenesis, a number of novel therapeutic agents are now available; and demonstrated significant efficacy in WM. The range of the ORR to these novel agents is between 25-80%. Ongoing and planned future clinical trials include those using PKC inhibitors such as enzastaurin, new proteasome inhibitors such as carfilzomib, histone deacetylase inhibitors such as LBH589, humanized CD20 antibodies such as Ofatumumab, and additional alkylating agents such as bendamustine. These agents, when compared to traditional chemotherapeutic agents, may lead in the future to higher responses, longer remissions and better quality of life for patients with WM. This review will mainly focus on those novel agent that entered clinical trial for the treatment of WM.</p>","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405358/pdf/nihms304917.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30798107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Monoclonal and Polyclonal Antibodies to Hb Bart’s for the Detection of α Thalassemias","authors":"L. Makonkawkeyoon, Somphon Pharephan, W. Tuntiwechapikul, S. Makonkawkeyoon","doi":"10.2174/1874276900903010011","DOIUrl":"https://doi.org/10.2174/1874276900903010011","url":null,"abstract":"Using a mouse monoclonal antibody (mAb) (“2D4”) with high specific reactivity to Hb Bart’s and a rabbit polyclonal antibody (“RPB”) with high reactivity to Hb Bart’s but low reactivity to HbF, an ELISA assay was developed for the quantification of Hb Bart’s in hemolysates of peripheral blood. In the preliminary study, hemoglobin solutions containing 4,000 μg/mL of hemoglobin were analyzed for the concentration of Hb Bart’s in samples collected from the following children and adult subjects of HbH families: 12 children with deletional HbH disease (--/3.7 ) or nondeletional HbH disease (HbH disease with HbCS) (--/ cs ), 12 adults with 0 thalassemia (--/ ), 12 adults with deletional or nondeletional + thalassemia (3.7 / or / cs ) and 12 normal adult subjects ( / ). The mean ± S.D. of Hb Bart’s concentration in those with deletional HbH disease or HbH disease with HbCS, 0 thalassemia, deletional or nondeletional + thalassemia, and normal subjects were 1,374±210 (range 1,164-1,584), 1,118±357 (range 761-1,475), 451 ± 230 (range 221-681), and 0 ng/mL, respectively. When the developed ELISA was further evaluated with additional samples of various types of thalassemia, including: 18 with deletional HbH disease (--/3.7 ); 21 of nondeletional HbH disease (HbH disease with HbCS) (--/ cs ); 33 with 0 thalassemia (--/ ); 19 with nondeletional + thalassemia ( / cs ); 11 with deletional + thalassemia (3.7 / ) and 58 normal subjects ( / ). It was found that the levels of Hb Bart’s in deletional + thalassemia was significantly lower than in 0 thalassemia (p<0.001). The levels of Hb Bart’s in 0 thalassemia was also significantly lower than in nondeletional and deletional HbH diseases (p=0.023 and p<0.001, respectively). When all types of thalassemia were compared with normal subjects, the Hb Bart’s levels in all types of thalassemia were significantly higher (p<0.0001). All of our results indicated that the developed ELISA was highly sensitive and specific for quantitative determination of Hb Bart’s in hemolysates. The ELISA assay might be used as a rapid screening test for the detection of thalassemias in general population.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"51 1","pages":"11-17"},"PeriodicalIF":0.0,"publicationDate":"2009-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88355901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tubular Erythropoietin Receptor Expression Mediates Erythropoietin-Induced Renoprotection","authors":"Annelies De Beuf, A. Verhulst, M. Helbert, G. Spaepen, M. Broe, D. Ysebaert, P. D'Haese","doi":"10.2174/1874276900903010001","DOIUrl":"https://doi.org/10.2174/1874276900903010001","url":null,"abstract":"Erythropoietin (EPO) has been shown to have tissue protective properties by binding to its receptor (EPOR) which is also expressed on non-haematopoietic cells. The mechanisms underlying this protection have not yet been eluci- dated and the renal cell types mediating these effects remain ill-defined. This study aimed to identify the EPOR expression in human tubular epithelial cells (hTECs) and in rat kidney and to investigate the role of EPOR in EPO-mediated renopro- tection. Male Wistar rats were treated with saline or EPO (3000 U/kg, i.p.) 24h prior to sham-operation or 30 min bilateral renal ischemia. Renal morphology and function, tubular regeneration, apoptosis and expression of EPOR, heme- oxygenase-1 (HO-1) and hepatocyte growth factor (HGF) were analyzed. Primary cultures of human proximal (PTC) and distal/collecting duct (DTC) tubular cells were incubated with EPO (5-50-500 ng/mL) either or not in the presence of so- luble EPOR. Total RNA was extracted and mRNA expression of HO-1 was investigated by quantitative RT-PCR. EPOR mRNA could be demonstrated in hTECs and in cortical tubules of the rat kidney. Furthermore, EPOR protein was expressed at the membrane and as intracellular vesicles in hTECs. In vivo, EPO treatment attenuated histological and func- tional renal damage, decreased both cell necrosis and apoptotic cell death, enhanced tubular regeneration and resulted in an upregulation of HO-1 and HGF mRNA. In vitro, EPO administration resulted in an early upregulation of HO-1 mRNA which was restricted to PTC and inhibited by simultaneous addition of supra-equivalent amounts of soluble EPOR. These data strongly suggest that the EPO-mediated renoprotection results from direct interaction of EPO with EPOR on tubular cells.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"93 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2009-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83466220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLE Thrombocytopenia: From Peripheral Platelet Destruction to Central Hemopoietic Defect","authors":"P. Ziakas","doi":"10.2174/1874276900802010111","DOIUrl":"https://doi.org/10.2174/1874276900802010111","url":null,"abstract":"Thrombocytopenia in Systemic Lupus Erythematosus is a common clinical manifestation affecting up to one third of patients in published cohorts. Antiplatelet antibodies, antithrombopoietin antibodies and faulty hemopoiesis have been implicated among other immunologic and non-immunologic causes. This mini review is an uptodate summary of these immunologic phenomena.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"1 1","pages":"111-118"},"PeriodicalIF":0.0,"publicationDate":"2008-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85188537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Eph Receptor Tyrosine Kinases and Ephrin Ligands in Hematopoietic Cell Development and Function","authors":"Michael J. Ting, A. Boyd","doi":"10.2174/1874276900802010103","DOIUrl":"https://doi.org/10.2174/1874276900802010103","url":null,"abstract":"The Eph receptor tyrosine kinases form the largest sub-family of the Receptor tyrosine kinases. Eph receptors interact with membrane bound ligands, termed ephrins. Eph-ephrin interactions have significant roles during mammalian development where they mediate such processes as cell adhesion and migration. Although Eph/ephrin expression is low in adult tissues evidence is accumulating which indicates that Eph and ephrins continue to play significant roles in postembryonic tissues. In this review we describe the current understanding of the function of Eph-ephrin signaling in human and mouse hematopoiesis. Ephs and ephrins have been shown to regulate the differentiation of hematopoietic cells, to direct lymphoid development as well as immune function. Whilst much still remains to be learned about the role of Ephephrin signaling in hematopoieis it is already clear that this system exerts important regulatory effects on differentiation, cell migration and effector function. The possibility that these molecules may be therapeutic targets is also discussed.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"8 1","pages":"103-110"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72702602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects Of Benzene on Human Hematopoiesis","authors":"J. Kirkeleit, T. Riise, B. Gjertsen, B. Moen, M. Bråtveit, Ø. Bruserud","doi":"10.2174/1874276900802010087","DOIUrl":"https://doi.org/10.2174/1874276900802010087","url":null,"abstract":"Benzene, an aromatic hydrocarbon that is a natural component of crude oil and natural gas, is toxic to the blood and blood-forming organs. Epidemiological studies have established an association between benzene exposure and acute myeloid leukemia, and increasing evidence also indicates a possible association between benzene and multiple myeloma. A specific benzene-associated myelodysplastic syndrome has also been suggested. Chronic hematotoxic effects of ben- zene exposure, including reduced lymphocyte, neutrophil and platelet counts in peripheral blood, have been detected at occupational exposure below a level that had previously been considered not to cause any health effects. Whether these abnormalities represent bone marrow damage and/or initial events in the development of a true neoplastic disease is not known. Together with a reported nonlinear relationship between benzene exposure and the level of various metabolites, favoring production of biologically reactive quinones at exposure below 1 part per million, these observations suggest that benzene even at low exposure levels may contribute to the risk of acute myeloid leukemia or myelodysplastic syndrome, especially among genetically susceptible individuals.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"1 1","pages":"87-102"},"PeriodicalIF":0.0,"publicationDate":"2008-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82406121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New-Generation Method for Quick and Owren PT","authors":"J. Horsti, H. Uppa, J. Vilpo","doi":"10.2174/1874276900802010081","DOIUrl":"https://doi.org/10.2174/1874276900802010081","url":null,"abstract":"Oral anticoagulant therapy (OAT) calls for continuous control by prothrombin time (PT) test, as the therapeutic range in INR units is very narrow. Warfarin (or coumarin) inhibits coagulation factor synthesis in the liver, but at the same time inactive coagulation factors are formed. The aim here was to measure \"active coagulation factors\" and inhibition in calibrator kits and patient plasmas by a new method for Quick and Owren PT. Four calibration kits and 200 plasma samples obtained from OAT patients were assessed using Quick and Owren PT for INRTot (active coagulation factors + inhibition) and INRAcf (only active coagulation factors). Conspicuous variation in in- hibition was noted between the four calibration kits. The new- generation PT method develops anticoagulation therapy based on active coagulation factors in vivo and improves INR result harmonization for Quick and Owren PT reagents. This new approach improves Quick PT reliability.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"40 1","pages":"81-85"},"PeriodicalIF":0.0,"publicationDate":"2008-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75861934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of Telomerase in CoCl2-Induced Apoptosis of Myeloid Leukemic Cells","authors":"Ya-Bei Xu, Jing Zhang, E. S. Bendirdjian, Yingli Wu, Guoqiang Chen","doi":"10.2174/1874276900802010074","DOIUrl":"https://doi.org/10.2174/1874276900802010074","url":null,"abstract":"Many reports showed that hypoxia-inducible factor-1 (HIF-1 ), the main factor activated by hypoxia, plays a role in the transcriptional regulation of the human telomerase reverse transcriptase (hTERT), one of the critical elements of the oncogenic process. As a hypoxia-mimetic agent, cobalt chloride (CoCl2) can induce the accumulation of HIF-1 . Herein, we demonstrated that hTERT expression was greatly decreased during CoCl2-induced apoptosis in leukemic cell lines while overexpression of hTERT inhibited CoCl2-induced apoptosis. Knockdown of HIF-1 by shRNA in U937 cells did not abrogate CoCl2-induced hTERT downregulation nor CoCl2-induced apoptosis while inducible expression of HIF- 1 decreased the expression of hTERT. Furthermore, CoCl2 could decrease the c-myc protein in all the cells tested, no matter the HIF-1 was silenced or not. Taken together, we demonstrated that downregulation of hTERT contributes to CoCl2-induced apoptosis in leukemic cell lines and HIF-1 is not indispensable for CoCl2 induced downregulation of hTERT.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"5 1","pages":"74-80"},"PeriodicalIF":0.0,"publicationDate":"2008-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81536594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient and Spontaneous Idiopathic Factor V Inhibitor","authors":"D. Laber, L. Bhupalam, G. Kloecker","doi":"10.2174/1874276900802010086","DOIUrl":"https://doi.org/10.2174/1874276900802010086","url":null,"abstract":"We present the case of a 70-year-old woman found to have a prothrombin time (PT) of 26.8 seconds (s) and an activated partial thromboplastin time (PTT) of 71 s prior to an elective endoscopic retrograde cholangiopancreatography for symptomatic choledocholithiasis. She had no personal or family history of bleeding, thrombosis, autoimmune diseases, miscarriages, recent surgery or antibiotic use, and was not anticoagulated. Laboratory studies revealed a hemoglobin of 11 g/dl, and normal leucocyte count, platelet count, serum protein immunoelectrophoresis, D-dimer, fibrinogen, lupus anticoagulants and anticardiolipin antibodies. PT and PTT mixing studies revealed an inhibitor of a coagulation factor in the common pathway. Factor assays II, VIII and IX, were normal. Factor VII and X, both more than 50%, were difficult to quantify secondary to an inhibitor effect in the system, with increasing activity after dilution. Factor V had 5% activity. Factor V inhibitor was 1.6 Bethesda Units. Prednisone 60 mg was started and the ERCP successfully performed with no bleeding complication. Within 6 months the PT, PTT and factor V activity normalized and prednisone was tapered off.","PeriodicalId":89702,"journal":{"name":"Open journal of hematology","volume":"1 1","pages":"86-86"},"PeriodicalIF":0.0,"publicationDate":"2008-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89060156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}