Erythropoietin or Darbepoetin for patients with cancer - meta-analysis based on individual patient data

Bohlius, Julia; Trelle, Sven; Weingart, Olaf; Schwarzer, Guido; Brillant, Corinne; Clarke, Mike; Djulbegoviĉ, Benjamin; Piper, Margret; Rades, Dirk; Seidenfeld, Jerome; Somerfield, Mark R.; Steensma, David P.; Schumacher, Martin; Engert, Andreas; Egger, Matthias

doi:10.1002/14651858.cd007303

Cited by 42 publications

(63 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Tissue protective effects of full-length EPO in preclinical studies have been widely reported for a variety of CNS pathologies in recent years [1, 2, 6, 8-10, 27, 28], but a major obstacle to using whole EPO as a long-term therapeutic is the induction of potentially hazardous increases in red cell mass and overall mortality [15,27]. To address this problem, we successfully designed truncated small linear or cyclic EPO-derived peptides from various domains of the full-length molecule and selected the best one for animal models of EAE.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were then pretreated with JM-4, scrambled JM-4, EPO, or 1 of 6 peptide segments derived from EPO (labeled EP-P#1-EP-P#6 with each segment spanning 25 amino acids of the primary structure of EPO beginning at the N terminus, except for EP-P#6, which spans amino acids D136-166R) at a concentration of 1 μg/ml 2 h prior to adding Aβ 25-35 peptide at 40 μM. Twenty-four hours after addition of Aβ [25][26][27][28][29][30][31][32][33][34][35] peptide, cells were harvested and analyzed by fluorescenceactivated cell sorting using allophycocyanin conjugated -Annexin V binding and 7-amino-actinomycin D (7-AAD) staining.…”

Section: Aβ Exposure and Pc12 Apoptosis Assay Analyzing Cytoprotectiomentioning

confidence: 99%

“…Rat neuroendocrine cell line PC12 was differentiated with nerve growth factor and then pretreated with either JM-4 or a scrambled inactive version of JM-4. The cells were exposed to neurotoxic Aβ [25][26][27][28][29][30][31][32][33][34][35] peptide for 24 h and subsequently harvested and analyzed for cell death following staining with 7-AAD or annexin V for apoptosis [26]. Flow cytometry indicated that toxic Aβ exposure induced a massive increase in apoptotic neural crest-derived cells that was fully blocked by pretreatment with JM-4, whereas scrambled JM-4 failed to protect cells from apoptosis (Fig.…”

Section: Jm-4 Provides Neuroprotection Against Cytotoxic Insultmentioning

confidence: 99%

“…Cultured rat PC12 cells were differentiated and then pretreated with JM-4, scrambled JM-4, EPO, or 1 of 6 peptide segments derived from EPO (labeled EP-P#1-EP-P#6; see BMaterials and Methods^for details) at a concentration of 1 μg/ml 2 h prior to adding Aβ [25][26][27][28][29][30][31][32][33][34][35] peptide. Twenty-four hours after the addition of Aβ [25][26][27][28][29][30][31][32][33][34][35] peptide, cells were analyzed by fluorescence-activated cell sorting. Control cells grown in media without toxic exposure exhibited baseline rates of apoptosis below 5-10% (data not shown).…”

Section: Neuroprotection Against Cell Death Is Limited To An Early Sementioning

confidence: 99%

See 3 more Smart Citations

A Distinct Region in Erythropoietin that Induces Immuno/Inflammatory Modulation and Tissue Protection

et al. 2015

View full text Add to dashboard Cite

Beneficial effects of short-term whole-molecule erythropoietin (EPO) therapy have been demonstrated on several animal models of diverse central nervous system pathology. However, the increased hematocrit induced by EPOdriven marrow stimulation greatly limits its potential for side effect-free therapy. We created a library of EPO-derived fragments based on the hypothesis that 2 distinct functions, erythropoiesis and tissue protection, reside in different regions of the molecule. Several small EPO-derived peptides within the Aβ loop of whole EPO molecule were screened for tissue protection in EAE mice. The 19-mer JM-4 peptide that contains 2 cysteine molecules consistently demonstrated the most potent clinical beneficial effects without producing hematocrit alterations in animal models of EAE. The JM-4-induced tissue protection was associated with modulation of the immunoregulatory process that drives inflammation and provokes subsequent autoimmune damage. Like the whole EPO molecule, JM-4 effectively modulated immune/inflammatory reaction within both the peripheral lymphatic tissue and central nervous system. The major effects induced by JM-4 include blocked expansion of monocyte/dendritic antigen presenting cell and T helper 17 cell populations, decreased proinflammatory cytokine production, and sharply enhanced expansion of the regulatory T-cell population. JM-4 shows promise for treatment of a broad spectrum of neural and non-neural conditions associated with inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Aβ Exposure and Pc12 Apoptosis Assay Analyzing Cytoprotectiomentioning

confidence: 99%

Section: Jm-4 Provides Neuroprotection Against Cytotoxic Insultmentioning

confidence: 99%

Section: Neuroprotection Against Cell Death Is Limited To An Early Sementioning

confidence: 99%

See 2 more Smart Citations

A Distinct Region in Erythropoietin that Induces Immuno/Inflammatory Modulation and Tissue Protection

et al. 2015

View full text Add to dashboard Cite

show abstract

“…If more than one reference for an RCT was reported by the systematic reviewers (for example, both a journal article and a conference abstract), we will retrieve all references reported. This will enable investigation of potential selective inclusion resulting from differences in results reported across different sources [31-33]. …”

Section: Methodsmentioning

confidence: 99%

An empirical investigation of the potential impact of selective inclusion of results in systematic reviews of interventions: study protocol

et al. 2013

View full text Add to dashboard Cite

BackgroundSystematic reviewers may encounter a multiplicity of outcome data in the reports of randomised controlled trials included in the review (for example, multiple measurement instruments measuring the same outcome, multiple time points, and final and change from baseline values). The primary objectives of this study are to investigate in a cohort of systematic reviews of randomised controlled trials of interventions for rheumatoid arthritis, osteoarthritis, depressive disorders and anxiety disorders: (i) how often there is multiplicity of outcome data in trial reports; (ii) the association between selection of trial outcome data included in a meta-analysis and the magnitude and statistical significance of the trial result, and; (iii) the impact of the selection of outcome data on meta-analytic results.Methods/DesignForty systematic reviews (20 Cochrane, 20 non-Cochrane) of RCTs published from January 2010 to January 2012 and indexed in the Cochrane Database of Systematic Reviews (CDSR) or PubMed will be randomly sampled. The first meta-analysis of a continuous outcome within each review will be included. From each review protocol (where available) and published review we will extract information regarding which types of outcome data were eligible for inclusion in the meta-analysis (for example, measurement instruments, time points, analyses). From the trial reports we will extract all outcome data that are compatible with the meta-analysis outcome as it is defined in the review and with the outcome data eligibility criteria and hierarchies in the review protocol. The association between selection of trial outcome data included in a meta-analysis and the magnitude and statistical significance of the trial result will be investigated. We will also investigate the impact of the selected trial result on the magnitude of the resulting meta-analytic effect estimates.DiscussionThe strengths of this empirical study are that our objectives and methods are pre-specified and transparent. The results may inform methods guidance for systematic review conduct and reporting, particularly for dealing with multiplicity of randomised controlled trial outcome data.

show abstract