Dynamic gadobutrol-enhanced MRI predicts early response to antivascular but not to antiproliferation therapy in a mouse xenograft model.

Purpose: Dynamic contrast-enhanced magnetic resonance imaging has been described as a method to assess tumor vascularity and, therefore, is discussed as a noninvasive biomarker for drug response prediction in tumor therapies. Because antiangiogenic and antiproliferative drugs are frequently combined for therapy, the aim was to investigate (1) the early response predictability and (2) the extent to which these therapy types influence dynamic contrast-enhanced magnetic resonance imaging with gadobutrol soon after therapy initiation.

Methods: Mice bearing a KPL-4 tumor were treated with either bevacizumab as an antiangiogenic drug or trastuzumab as a cytotoxic anti-tumor drug.

Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles.

Purpose: Magnetic resonance imaging (MRI), one of the most powerful imaging techniques available, usually requires the use of an on-demand designed contrast agent to fully exploit its potential. The blood kinetics of the contrast agent represent an important factor that needs to be considered depending on the objective of the medical examination. For particulate contrast agents, such as superparamagnetic iron oxide nanoparticles (SPIOs), the key parameters are particle size and characteristics of the coating material.

Current limitations of molecular magnetic resonance imaging for tumors as evaluated with high-relaxivity CD105-specific iron oxide nanoparticles.

Objective: Tumor imaging via molecular magnetic resonance imaging (MRI) that uses specific superparamagnetic iron oxide particles (SPIOs) has been addressed in the literature several times in the last 20 years. To our knowledge, none of the reported approaches is currently used for routine clinical diagnostic evaluation, nor are any in clinical development. This raises questions as to whether SPIO-enhanced molecular MRI is sensitive and specific enough for use in clinical practice.

Substantial changes of cellular iron homeostasis during megakaryocytic differentiation of K562 cells.

We investigated the remodeling of iron metabolism during megakaryocytic development of K562 cells. Differentiation was successfully verified by increase of the megakaryocytic marker CD61 and concomitant decrease of the erythroid marker γ-globin. The reduction of erythroid properties was accompanied by changes in the cellular iron content and in the expression of proteins regulating cellular iron homeostasis.

Chimeric toxins inhibit growth of primary oral squamous cell carcinoma cells.

Treatment of oral squamous cell carcinoma (OSCC) is currently based on surgery and radiotherapy. Prolongation of the survival time of patients with progressing tumors is infrequently achieved. To improve the therapeutic options, targeted therapies are a favorable alternative.

Release of the soluble transferrin receptor is directly regulated by binding of its ligand ferritransferrin.

The human transferrin receptor (TfR) is shed by an integral metalloprotease releasing a soluble form (sTfR) into serum. The sTfR reflects the iron demand of the body and is postulated as a regulator of iron homeostasis via binding to the hereditary hemochromatosis protein HFE. To study the role of transferrin in this process, we investigated TfR shedding in HL60 cells and TfR-deficient Chinese hamster ovary cells transfected with human TfR.

Mutational suppression of transferrin receptor shedding can be compensated by distinct metalloproteases acting on alternative sites.

The human transferrin receptor (TfR) is proteolytically cleaved at R100 within the juxtamembrane stalk and to a lesser extent at an alternative site. We examined the effect of stalk mutations on human TfR shedding in transfected CHO cells. Point mutations at R100 led to an increase in alternative shedding while the R100 cleavage product was undetectable.

Processing of the human transferrin receptor at distinct positions within the stalk region by neutrophil elastase and cathepsin G.

The ectodomain of the human transferrin receptor (TfR) is released as soluble TfR into the blood by cleavage within a stalk. The major cleavage site is located C-terminally of Arg-100; alternative cleavage sites are also present. Since the cleavage process is still unclear, we looked for proteases involved in TfR ectodomain release.

Shedding of the transferrin receptor is mediated constitutively by an integral membrane metalloprotease sensitive to tumor necrosis factor alpha protease inhibitor-2.

The transferrin receptor (TfR) is a transmembrane protein that mediates cellular uptake of iron. Although the serum concentration of the soluble TfR (sTfR) is altered in several diseases and used for diagnostic purposes, the identity and regulation of the shedding protease is unknown. In this study we quantified sTfR release from microsomal membranes and leukocytic cell lines in the presence of numerous protease inhibitors and cell activating compounds.