Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

<p>Abstract</p> <p>Background</p> <p>Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting.</p> <p>Objective</p> <p>To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method.</p> <p>Methods</p> <p>We cultured myeloma-positive CD34⁺PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34⁺cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR). We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture.</p> <p>Results</p> <p>Overall recovery of CD34⁺cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34⁺cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34⁺cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34⁺cell selection, and up to 2.3 logs after culture and ΔNGFR selection.</p> <p>Conclusion</p> <p>We conclude that <it>ex-vivo </it>culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.</p

Diabetes, periodontitis, and the subgingival microbiota

Both type 1 and type 2 diabetes have been associated with increased severity of periodontal disease for many years. More recently, the impact of periodontal disease on glycaemic control has been investigated. The role of the oral microbiota in this two-way relationship is at this stage unknown. Further studies, of a longitudinal nature and investigating a wider array of bacterial species, are required in order to conclusively determine if there is a difference in the oral microbiota of diabetics and non-diabetics and whether this difference accounts, on the one hand, for the increased severity of periodontal disease and on the other for the poorer glycaemic control seen in diabetics

ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity

Italian Association for Cancer Research (AIRC—IG 15438) to R.B. and in part by a grant from the Italian Ministry of Health (GR-2010-2307975) to F.F. and by a grant HEALTH-F4-2011-281608 (TIMER) to A.M.. L.C. is recipient of a fellowship from Fondazione Nicola del Roscio

Differences in the subgingival microbial population of chronic periodontitis in subjects with and without type 2 diabetes mellitus-a systematic review

The work was supported by the Department of Periodontology, UCL Eastman Dental Institute, London, U