The analysis of the relationship between multiple myeloma cells and their microenvironment

The bone marrow microenvironment plays a key role in the stimulation of growth and survival of multiple myeloma (MM) cells. We investigated whether membrane microfragments (MFBs) exert a stimulatory effect on mesenchymal stem cell (MSC) gene expression or differentiation. MSCs from patients with multiple myeloma (MMBM-MSCs) proliferated at a slower rate than MSCs from healthy volunteers (BM-MSCs), and fewer MMBM-MSCs adhered to the substrate as compared to BM-MSCs. Phenotypic analysis revealed that MMBM-MSCs and BM-MSCs differed significantly in terms of their CD166 and CXCR4 expressions. In conclusion, our comparative analysis of mesenchymal cells from MM patients and healthy volunteers revealed differences in the genetic and phenotypic profiles of these two populations, their potential for osteodifferentiation, and expression of surface antigens. Moreover, we showed that membrane MFBs may alter the genetic profile of MSCs, leading to disorders of their osteodifferentiation, and interact with the WNT pathway via presentation of the DKK-1 protein

Geldanamycin and its derivatives inhibit the growth of myeloma cells and reduce the expression of the MET receptor

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2014.01.31; Accepted: 2014.03.19; Published: 2014.05.31 Introduction. Geldanamycin (GA) is an ansamycin antibiotic that exhibits potent anti-neoplastic properties. The aim of this study was to assess the impact of GA and its derivatives on the growth and invasiveness of myeloma cell lines and CD138+ cells derived from the bone marrow of patients with multiple myeloma. Materials and methods. We evaluated cell proliferation, survival, apoptosis, cell cycle of my

Effect of heme oxygenase-1 on melanoma development in mice : role of tumor-infiltrating immune cells

Objective: Heme oxygenase-1 (HO-1) is a cytoprotective, proangiogenic and anti-inflammatory enzyme that is often upregulated in tumors. Overexpression of HO-1 in melanoma cells leads to enhanced tumor growth, augmented angiogenesis and resistance to anticancer treatment. The effect of HO-1 in host cells on tumor development is, however, hardly known. Methods and results: To clarify the effect of HO-1 expression in host cells on melanoma progression, C57BL/6xFvB mice of different HO-1 genotypes, HO-1+/+, HO-1+/−, and HO-1−/−, were injected with the syngeneic wild-type murine melanoma B16(F10) cell line. Lack of HO-1 in host cells did not significantly influence the host survival. Nevertheless, in comparison to the wild-type counterparts, the HO-1+/− and HO-1−/− males formed bigger tumors, and more numerous lung nodules; in addition, more of them had liver and spleen micrometastases. Females of all genotypes developed at least 10 times smaller tumors than males. Of importance, the growth of primary and secondary tumors was completely blocked in HO-1+/+ females. This was related to the increased infiltration of leukocytes (mainly lymphocytes T) in primary tumors. Conclusions: Although HO-1 overexpression in melanoma cells can enhance tumor progression in mice, its presence in host cells, including immune cells, can reduce growth and metastasis of melanoma

Case reportVisualisation of early engraftment of transcoronary applied CD34+ cells in the infarct border zone

Successful delivery of progenitor cells to the injury zone is a prerequisite for any effect of myocardial regeneration therapy. This key issue, however, has received far less attention than, for instance, a potential need for cell type selection or ex-vivo expansion, the optimal timing of cell application or multimodal functional evaluation after cellular transplantation. By combining myocardial perfusion scintigraphy, magnetic resonance imaging and 99Tc-HMPAO-labelled autologous bone marrow-derived CD34+ cells visualisation, we show in a 63-year-old man with a large anterior myocardial infarction that transcoronary applied cells (via the central lumen of an inflated over-the-wire balloon positioned in the stent implanted in primary PCI) graft preferentially to the infarct border zone. This is consistent with the idea that the area of myocardial ‘irreversible’ injury (i.e. the no-perfusion zone on perfusion scintigraphy or late enhancement zone on magnetic resonance) remains largely inaccessible to transcoronary-applied cells; thus other techniques need to be considered if the cell delivery is aimed at the zone of irreversible injury. The potency of such combined high-resolution visualisation provides grounds for comparing the efficacy of different methods of cell delivery after a recent myocardial infarction in man

Visualisation of early engraftment of transcoronary applied CD34^{+} cells in the infarct border zone

Successful delivery of progenitor cells to the injury zone is a prerequisite for any effect of myocardial regeneration therapy. This key issue, however, has received far less attention than, for instance, a potential need for cell type selection or ex-vivo expansion, the optimal timing of cell application or multimodal functional evaluation after cellular transplantation. By combining myocardial perfusion scintigraphy, magnetic resonance imaging and 99Tc-HMPAO-labelled autologous bone marrow-derived CD34+ cells visualisation, we show in a 63-year-old man with a large anterior myocardial infarction that transcoronary applied cells (via the central lumen of an inflated over-the-wire balloon positioned in the stent implanted in primary PCI) graft preferentially to the infarct border zone. This is consistent with the idea that the area of myocardial ‘irreversible’ injury (i.e. the no-perfusion zone on perfusion scintigraphy or late enhancement zone on magnetic resonance) remains largely inaccessible to transcoronary-applied cells; thus other techniques need to be considered if the cell delivery is aimed at the zone of irreversible injury. The potency of such combined high-resolution visualisation provides grounds for comparing the efficacy of different methods of cell delivery after a recent myocardial infarction in man