Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile

[EN]Circulating myeloma tumor cells (CTCs) as defined by the presence of peripheral blood (PB) clonal plasma cells (PCs) are a powerful prognostic marker in multiple myeloma (MM). However, the biological features of CTCs and their pathophysiological role in MM remains unexplored. Here, we investigate the phenotypic, cytogenetic, and functional characteristics as well as the circadian distribution of CTCs vs paired bone marrow (BM) clonal PCs from MM patients. Our results show that CTCs typically represent a unique subpopulation of all BM clonal PCs, characterized by downregulation (P < .05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). Fluorescence in situ hybridization analysis of fluorescence-activated cell sorter-sorted CTCs also unraveled different cytogenetic profiles vs paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when cocultured with BM stromal cells. Most interestingly, CTCs showed a circadian distribution which fluctuates in a similar pattern to that of CD34(+) cells, and opposite to stromal cell-derived factor 1 plasma levels and corresponding surface expression of CXC chemokine receptor 4 on clonal PCs, suggesting that in MM, CTCs may egress to PB to colonize/metastasize other sites in the BM during the patients' resting period

Bis(thiosemicarbazones) as bifunctional chelators for the room temperature 64-copper labeling of peptides.

A range of new carboxylate functionalised bis(thiosemicarbazone) ligands and their Cu(II) complexes have been prepared, fully characterised and radiolabeled in high yield with both (64)Cu and (99m)Tc. Conjugation to a bombesin derivative was achieved using standard solid phase synthetic methodologies and the (64)Cu-labeled conjugate was shown to have good tumour uptake in mice with xenografted PC-3 tumours

Using Style to Understand Descriptions of Software Architecture

The software architecture of most systems is described informally and diagrammatically. In order for these descriptions to be meaningful at all, figures are understood by interpreting the boxes and lines in specific, conventionalized ways [5]. The imprecision of these interpretations has a number of limitations. In this paper we consider these conventionalized interpretations as architectural styles and provide a formal framework for their uniform definition. In addition to providing a template for precisely defining new architectural styles, this framework allows for the proof that the notational constraints on a style are sufficient to guarantee the meanings of all described systems and provides a unified semantic base through which different stylistic interpretations can be compared

Copy number abnormalities analysis of CD138⁺⁺ and CD138^low cells.

<p>Log ratio plot of all chromosomes corresponding to CD138⁺⁺ RPMI-8266 cells (n = 3; left panel) and CD138^low RPMI-8266 cells (n = 3; right panel) on the basis of Cytoscan HD array generated with Nexus.</p