Review for "The potential diagnostic power of CD138+ Microparticles from the plasma analysis for multiple myeloma clinical monitoring"

Background:The analysis of angiogenesis factors in the blood of tumor patients has given diverse results on their prognostic or predictive value. Since mediators of angiogenesis are stored in platelets, their measurement in plasma is sensitive to inadvertent platelet activation during blood processing.Methods:Variants of blood withdrawal and plasma preparation were evaluated by ELISA for the detection of TSP-1, PF-4, VEGF and PD-ECGF. A total of 22 pancreatic cancer patients and 29 healthy volunteers were evaluated.Results:Plasma preparation with the anticoagulant mix of citrate, theophylline, adenosine, dipyridamole (CTAD) and immediate blood processing at 4°C was required for reproducible measurements of TSP-1, PF-4 and VEGF. Blood collection by venflon or inadvertent hemolysis during blood withdrawal caused significantly elevated TSP-1 and PF4 values. When optimized plasma preparation was applied, a significant increase of TSP-1 and VEGF in cancer patients was detected (P = 0.006; P < 0.001).Conclusion:The reliable plasma analysis of circulating platelet-stored angiogenesis factors requires preparation with CTAD at 4°C and blood collection by butterfly needle. Suboptimal procedures of plasma preparation are commonly applied in clinical monitoring of angiogenesis parameters which may account for the differences in reported plasma values and may have masked their predictive or prognostic marker potential.

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Proteasome inhibitors as therapeutics

Essays in Biochemistry ◽

10.1042/bse0410205 ◽

2005 ◽

Vol 41 ◽

pp. 205-218

Author(s):

Constantine S. Mitsiades ◽

Nicholas Mitsiades ◽

Teru Hideshima ◽

Paul G. Richardson ◽

Kenneth C. Anderson

Keyword(s):

Multiple Myeloma ◽

Drug Class ◽

Proteasome Inhibitors ◽

Cell Cycle Regulators ◽

Current State ◽

Intracellular Mechanism ◽

Ubiquitin Proteasome ◽

Proteasome Pathway ◽

Hodgkin's Lymphomas ◽

Clinical Research Data

The ubiquitin–proteasome pathway is a principle intracellular mechanism for controlled protein degradation and has recently emerged as an attractive target for anticancer therapies, because of the pleiotropic cell-cycle regulators and modulators of apoptosis that are controlled by proteasome function. In this chapter, we review the current state of the field of proteasome inhibitors and their prototypic member, bortezomib, which was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma. Particular emphasis is placed on the pre-clinical research data that became the basis for eventual clinical applications of proteasome inhibitors, an overview of the clinical development of this exciting drug class in multiple myeloma, and a appraisal of possible uses in other haematological malignancies, such non-Hodgkin's lymphomas.

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