CXCR4 Promotes Neuroblastoma Growth and Therapeutic Resistance through miR-15a/16-1-Mediated ERK and BCL2/Cyclin D1 Pathways.

CXCR4 expression in neuroblastoma tumors correlates with disease severity. In this study, we describe mechanisms by which CXCR4 signaling controls neuroblastoma tumor growth and response to therapy. We found that overexpression of CXCR4 or stimulation with CXCL12 supports neuroblastoma tumorigenesis.

Single Dose of the CXCR4 Antagonist BL-8040 Induces Rapid Mobilization for the Collection of Human CD34 Cells in Healthy Volunteers.

The potential of the high-affinity CXCR4 antagonist BL-8040 as a monotherapy-mobilizing agent and its derived graft composition and quality were evaluated in a phase I clinical study in healthy volunteers (NCT02073019). The first part of the study was a randomized, double-blind, placebo-controlled dose escalation phase. The second part of the study was an open-label phase, in which 8 subjects received a single injection of BL-8040 (1 mg/kg) and approximately 4 hours later underwent a standard leukapheresis procedure.

Irreversible Electroporation versus Radiofrequency Ablation: A Comparison of Local and Systemic Effects in a Small-Animal Model.

Purpose To compare both periablational and systemic effects of two mechanistically different types of ablation: thermal radiofrequency (RF) ablation and electroporative ablation with irreversible electroporation (IRE) in appropriately selected animal models. Materials and Methods Animal experiments were performed according to a protocol approved by the Animal Care Committee of Hebrew University. Female C57BL/6 mice (n = 165) were randomized to undergo either RF or IRE ablation of noncancerous normal liver.

The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells.

The function of imprinted H19 long non-coding RNA is still controversial. It is highly expressed in early embryogenesis and decreases after birth and re-expressed in cancer. To study the role of H19 in oncogenesis and pluripotency, we down-regulated H19 expression in vitro and in vivo in pluripotent human embryonic carcinoma (hEC) and embryonic stem (hES) cells.

Oncogenesis: An "Off-Target" Effect of Radiofrequency Ablation.

Purpose: To compare hepatocellular carcinoma (HCC) development after radiofrequency (RF) ablation, partial surgical hepatectomy, and a sham operation and to inhibit HCC recurrence after RF ablation in a mouse model of spontaneously forming HCC in the setting of chronic inflammation (ie, the MDR2 knockout model).

Materials And Methods: Animal experiments were performed according to an approved animal care committee protocol. The authors compared the survival of MDR2 knockout mice (an inflammation-induced HCC model) that underwent RF ablation, 35% partial hepatectomy (ie, left lobectomy), or a sham operation (controls) by using Kaplan-Meier survival curve analysis.

Radiofrequency Ablation: Inflammatory Changes in the Periablative Zone Can Induce Global Organ Effects, including Liver Regeneration.

Purpose: To determine the kinetics of innate immune and hepatic response to the coagulation necrosis area that remains in situ after radiofrequency (RF) ablation, the cytokine profile of this response, and its local and global effect on the whole organ in a small-animal model.

Materials And Methods: A standardized RF ablation dose (70°C for 5 minutes) was used to ablate more than 7% of the liver in 91 C57BL6 mice (wild type) according to a protocol approved by the animal care committee. The dynamic cellular response in the border zone surrounding ablation-induced coagulation and in the ablated lobe and an untreated lobe were characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (the time points at which cells migrate to necrotic tissues).

The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning.

Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation.

Cardiac protection by preconditioning is generated via an iron-signal created by proteasomal degradation of iron proteins.

Ischemia associated injury of the myocardium is caused by oxidative damage during reperfusion. Myocardial protection by ischemic preconditioning (IPC) was shown to be mediated by a transient 'iron-signal' that leads to the accumulation of apoferritin and sequestration of reactive iron released during the ischemia. Here we identified the source of this 'iron signal' and evaluated its role in the mechanisms of cardiac protection by hypoxic preconditioning.

Zinc-desferrioxamine attenuates retinal degeneration in the rd10 mouse model of retinitis pigmentosa.

Iron-associated oxidative injury plays a role in retinal degeneration such as age-related macular degeneration and retinitis pigmentosa. The metallo-complex zinc-desferrioxamine (Zn/DFO) may ameliorate such injury by chelation of labile iron in combination with release of zinc. We explored whether Zn/DFO can affect the course of retinal degeneration in the rd10 mouse model of retinitis pigmentosa.

Aging is an organ-specific process: changes in homeostasis of iron and redox proteins in the rat.

Organ-specific changes of iron- and redox-related proteins occur with age in the rat. Ferritin, the major iron storage and detoxifying protein, as well as the proteins of the methionine-centered redox cycle (MCRC) were examined in old and young animals, and showed organ-dependent changes. In spleens and livers of aged rats, ferritin (protein) levels were greater than in young ones, and their iron saturation increased, rendering higher ferritin-bound iron (FtBI).

Iron, ferritin and proteins of the methionine-centered redox cycle in young and old rat hearts.

Progressive oxidation of cellular components constitutes a major mechanism of the aging process. An emerging paradigm of redox signaling suggests that low level oxidants activate protective pathways resulting in prolonged cell survival. This report centers on the study of cardiac muscle in young and old rats, including (i) the expression of ferritin (Ft) the major iron storage protein, and (ii) the expression of the major proteins of the methionine-centered redox cycle (MCRC), which controls the cellular methionine redox status.

Heart protection by ischemic preconditioning: a novel pathway initiated by iron and mediated by ferritin.

Ischemic preconditioning is a well-known procedure transiently protecting the heart against injury associated with prolonged ischemia, through mechanism/s only partly understood. The aim of this study was to test whether preconditioning-induced protection of the heart involves an iron-based mechanism, including the generation of an iron signal followed by accumulation of ferritin. In isolated rat hearts perfused in the Langendorff configuration, we measured heart contractility, ferritin levels, ferritin-iron content, and mRNA levels of ferritin subunits.