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Although many SCD patients show increased ferritin levels with repeated RBC transfusions and some patients with RBCEx because of iron in RBC units and constant hemolysis, some patients on maintenance RBCEx therapy have low ferritin levels. Among them, 24 patients received maintenance RBCEx, and 7 patients (13.2% of a total number of patients, 29.2% of patients on maintenance RBCEx) had experienced low ferritin levels at least one point during their maintenance RBCEx treatment courses. THE FIRST REPORT OF THE AMERICAN SOCIETY FOR APHERESIS THROMBOTIC THROMBOCYTOPENIC PURPURA MU... Jay S Raval, MD, 1 Yara Park, MD, 3 Erin Garrett, MD, 3 Tina S Ipe, MD, 4 Poyyapakkam R Sriva... 1 Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 2 Medic... B Purpose: b Treatment of immune thrombotic thrombocytopenic purpura (TTP) is heterogeneous. Little is known about the characteristics and outcomes of patients undergoing ECP treatment with MF or SS, as not all MF patients have blood involvement whereas all SS patients, by definition, have blood involvement and a poorer prognosis. We sought to characterize tandem procedures including: patients demographics, primary diagnosis, ASFA category indications, blood product utilization, adverse events during the procedures and patient outcomes at 24 hours and 30 days after completion of tandem procedures. [Extracted from the article]

Background The efficacy and tolerability of paclitaxel is limited by its low solubility, high systemic exposure, and a lack of selective tumor uptake. Paclitaxel poliglumex (PPX; XYOTAX™) is a macromolecular drug conjugate that was developed to overcome these limitations; the 2′ hydroxyl group of paclitaxel is linked to a biodegradable polymer, poly- l-glutamic acid, to form an inactive polymeric conjugate. PPX was previously shown to accumulate in tumor tissue, presumably by taking advantage of the hyperpermeable tumor vasculature and suppressed lymphatic clearance in tumor tissue. Methods Because anti-tumor activity requires the release of paclitaxel from the polymer-drug conjugate, the current report characterizes PPX biodegradation and release of paclitaxel as determined by quantitative HPLC/mass spectral analysis. Results The identification of monoglutamyl-paclitaxel metabolites in tumor tissue confirmed the in vivo metabolism of PPX in a panel of mouse tumor models. In vitro characterization of the metabolic pathway suggests that PPX can enter tumor cells, and is metabolized to form both mono- and diglutamyl-paclitaxel cleavage products. The intracellular formation of these intermediate metabolites is at least partially dependent on the proteolytic activity of the lysosomal enzyme cathepsin B; PPX metabolism is inhibited by a highly selective inhibitor of cathepsin B, CA-074. Reduced metabolism of PPX in livers and spleens from cathepsin B deficient mice confirms that cathepsin B is an important mediator of PPX metabolism in vivo; however, other proteolytic enzymes may contribute as well. Conclusions The cathepsin B-mediated release of paclitaxel may have therapeutic implications as cathepsin B is upregulated in malignant cells, particularly during tumor progression. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid acyltransferase beta (LPAAT-ß) is an enzyme involved in lipid biosynthesis whose role in tumour progression has been of emerging interest in the last few years. We investigated the expression of LPAAT-ßby reverse transcriptase-polymerase chain reaction and immunohistochemistry in 10 ovarian cell lines as well as in a cohort of 106 ovarian tumours and normal ovaries. Lysophosphatidic acid acyltransferase beta mRNA was found in all cell lines and ovarian tumours examined. Expression of LPAAT-ßprotein was significantly increased in ovarian carcinomas compared to benign ovarian tissue (?2 test P-value=0.001, Kruskal-Wallis test P-value<0.0001). Furthermore, LPAAT-ßexpression was positively associated with higher tumour grade (P=0.044), higher mitotic index (P<0.0001) and tumour stage (P=0.032). Expression of LPAAT-ßwas significantly linked to reduced overall survival time (P=0.024) as well as to shorter progression-free survival time (P=0.012) in patients younger than 60 years. Our study shows that LPAAT-ßis upregulated in ovarian cancer and is more prevalent in poorly differentiated tumours. In addition, LPAAT-ßexpression is a predictor of a worse prognosis in patients younger than 60 years. Further studies are needed to investigate if LPAAT-ßmay serve as a therapeutic target for certain subgroups of patients.British Journal of Cancer (2005) 92, 1729-1736. doi:10.1038/sj.bjc.6602528 www.bjcancer.com Published online 19 April 2005 [ABSTRACT FROM AUTHOR]

The article presents abstracts related to sciences which include carbon emission, cell-autonomous circadian oscillator, and pathogens.