Dataset Information

A phase II study of up-front red blood cell transfusion before chemotherapy followed by maintenance Erythropoetin-alpha subcutaneous support during chemotherapy of anaemic breast-, colorectal- and ovarian cancer patients

ABSTRACT: Study hypothesis: An upfront Red Blood Cell Transfusion (RBCT) aiming at low-normal Haemoglobin (Hb) levels will ameliorate anemia-caused tumour hypoxia-related resistance to chemotherapy before the start of chemotherapy and may decrease secondary anemia-induced endogenous release of cytokines like Vascular Endothelial Growth Factor (VEGF), osteopontin. The maintenance of optimal Hb levels at this lower-normal range during chemotherapy by weekly maintenance administration of Erythropoetin-alpha (Epo-alpha) subcutaneous (s.c.) at doses with proven safety and efficacy creates optimal conditions for tumour oxygenation, without the presumably high-Hb level associated adverse effects. Primary outcome(s): 1. Hb levels before the start of and during chemotherapy 2. Safety of the pCATS anaemia treatment regimen

DISEASE(S): Ovarian Cancer,Colorectal Cancer,Breast Cancer,Solid Tumors

PROVIDER: 2424172 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Similar Datasets

Project description:The role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-alpha). To gain insight into the common and specific effects of TNF-alpha and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-alpha (10ng/ml) or to hemozoin (12.5microgram/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-alpha were not affected by hemozoin. The genes modulated by TNF-alpha were significantly enriched for those encoding proteins involved in the control of type 1 interferon signalling and the immune response to viral infection. In contrast, genes induced by hemozoin were significantly enriched for functional roles in regulation of transcription and apoptosis. Further analyses by rtPCR revealed that hemozoin increases expression of transcription factors that form part of the integrated stress response which is accompanied by reduced expression of genes involved in DNA repair. This study confirms that hemozoin induces cellular stress on erythroblasts that is additional to and distinct from responses to inflammatory cytokines and identifies new genes that may be involved in the pathogenesis of severe malarial anemia. More generally the respective transcription profiles highlight the varied mechanisms through which erythropoiesis may be disrupted during infectious disease. Erythroblasts derived from PBMCs were enriched to 97% purity for proerythroblast and intermediate/normoblast phases of differentiation using magnetic bead isolation. There were three treatment groups: media, P.falciparum hemozoin (12.5 microgram /ml hematin units) and tumour necrosis factor alpha(10ng/ml). Total RNA using 7.5 x105 cells per treatment from one donor was extracted using Trizol. Highly significant gene ontological findings (where p> x10^-17 but < x10^-7) were confirmed by quantitative PCR.

Dataset Information

A phase II study of up-front red blood cell transfusion before chemotherapy followed by maintenance Erythropoetin-alpha subcutaneous support during chemotherapy of anaemic breast-, colorectal- and ovarian cancer patients

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets