Registered report: tumour vascularization via endothelial differentiation of glioblastoma stem-like cells.

The Nature in 2010 (Ricci-Vitiani et al., 2010). The experiments that will be replicated are those reported in Figure 4B and Supplementary Figure 10B (Ricci-Vitiani et al., 2010), which demonstrate that glioblastoma stem-like cells can derive into endothelial cells, and can be selectively ablated to reduce tumor progression in vivo, and Supplementary Figures S10C and S10D (Ricci-Vitiani et al., 2010), which demonstrate that fully differentiated glioblastoma cells cannot form functionally relevant endothelium. The Reproducibility Project: Cancer Biology is a collaboration between the eLife.

Registered report: the CD47-signal regulated protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.

The Willingham et al., 2012, published in PNAS in 2012. The key experiments being replicated are those reported in Figure 6A-C and Table S4. In these experiments, Willingham et al., 2012 test the safety and efficacy of anti-CD47 antibody treatment in immune competent mice utilizing a syngeneic model of mammary tumor growth in FVB mice. The Reproducibility Project: Cancer Biology is a collaboration between the eLife.

Registered report: Melanoma genome sequencing reveals frequent PREX2 mutations.

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from "Melanoma genome sequencing reveals frequent PREX2 mutations" by Berger and colleagues, published in Nature in 2012 (Berger et al., 2012). The key experiments that will be replicated are those reported in Figure 3B and Supplementary Figure S6. In these experiments, Berger and colleagues show that somatic PREX2 mutations identified through whole-genome sequencing of human melanoma can contribute to enhanced lethality of tumor xenografts in nude mice (Figure 3B, S6B, and S6C; Berger et al., 2012). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.

CNTO 530 increases expression of HbA and HbF in murine models of ß-thalassemia and sickle cell anemia.

CNTO 530 is an erythropoietin receptor agonist MIMETIBODYTM construct. CNTO 530 has been shown to be active in a number of rodent models of acquired anemia (e.g. renal insufficiency and chemotherapy induced anemia). We investigated the efficacy of CNTO 530 in murine models of ß-thalassemia and sickle cell anemia (Berkeley mice). ß- thalassemic mice are deficient in expression of α-globin chain and heterozygous mice are characterized by a clinical syndrome similar to the human ß-thalassemia intermedia. Berkeley mice are knocked out for murine alpha and beta globin and are transgenic for human alpha, beta (sickle) and gamma globin genes. Berkeley mice thus express human sickle hemoglobin A (HbS) and can also express human fetal hemoglobin. These mice express a severe compensated hypochromic microcytic anemia and display the sickle cell phenotype. To test the effectiveness of CNTO 530, mice from both genotypes received a single subcutaneous (s.c.) dose of CNTO 530 or darbepoetin-α (as a comparator) at 10,000 U/kg, a dose shown to cause a similar increase in reticulocytes and hemoglobin in normal mice. Hematologic parameters were evaluated over time. CNTO 530, but not darbepoetin-α, increased reticulocytes, red blood cells and total hemoglobin in ß- thalassemic mice. In Berkeley mice CNTO 530 showed an increase in reticulocytes, red blood cells, F-cells, total hemoglobin and fetal hemoglobin. In conclusion, CNTO 530 is effective in murine models of ß-thalassemia and sickle cell anemia. These data suggest that CNTO 530 may have beneficial effects in patients with genetically mediated hemoglobinopathies.