Showing papers by "Bethan Psaila published in 2010"

Stability of measurement of the immature platelet fraction.

Abstract: Immune Thrombocytopenia (ITP) is a heterogeneous clinical entity for which no simple diagnostic test exists. The Immature Platelet Fraction (IPF), a marker of Reticulated Platelets (RP), is a good indicator of thrombopoiesis and can identify accelerated destruction of platelets by demonstrating compensatory increased platelet production. Measuring IPF is not routinely available in clinical practice; it has proven useful in studies of thrombocytopenia and the novel thrombopoietic agents. A multicenter clinical trial would be needed to explore IPF in management of patients with ITP; such a trial would require central testing. Therefore, we sought to assess the reliability of measured platelet counts and IPF in whole-blood filled EDTA tubes when the same tube is run freshly and again 24 hr after venipuncture. Based on analysis of our 103 samples, it is clear that EDTA tubes are stable at room temperature for 24 hr. Therefore, the results can be used to estimate thrombopoiesis when measured within 24 hr after phlebotomy.

Role of Bone Microenvironment/Metastatic Niche in Cancer Progression

Abstract: Much progress has been made in the detection and treatment of primary malignant tumors in recent years. However, the stages of advanced malignancy are less understood and fewer therapies have been developed specifically to target metastatic spread. Cancer metastasis remains the single most important cause of cancer-related deaths [83]. Tumor progression involves a cascade of distinct events, from local invasion, migration, dissemination in the circulatory system, and eventual establishment at organ-specific sites distant from the primary tumor. Much work has focused on the genetic mutations that confer a cell-intrinsic invasive and migratory phenotype, enabling dissemination and survival of tumor cells in the circulatory system. More recently, the importance of pre-conditioning of the external microenvironment of metastasizing cells by tumor-secreted systemic factors has been highlighted. Paget’s theory first recognized the importance of a “congenial soil” in providing a receptive microenvironment for the disseminating cancer “seed” [61]. Over 100 years later, we have begun to identify the biological elements that contribute to the formation of a supportive site for the metastatic process. The blood–bone marrow axis is emerging as a key mediator in the transformation from a primary tumor to widespread metastatic disease. Tumor-secreted cytokines, chemokines, and disseminated tumor cells themselves home to the bone marrow, effecting changes in the bone marrow stroma and stem cell niches. Conversely, bone marrow-derived factors and cells of the hematopoietic system migrate to the periphery to prime distant sites for the arrival of tumor cells and to establish a favorable microenvironment for tumor progression, the metastatic niche. This chapter focuses on recent advances in the understanding of the role that bone marrow-derived cells and bone marrow stroma play in cancer progression and metastasis. Parallels will be drawn between stem cell niche dynamics within bone marrow and pathological niches for benign and malignant cells at metastatic sites. Potential pharmacological and therapeutic targets in this setting also will be discussed.