However, about 40% of patients relapse and the current classification system does not fully reflect this clinical Dibutyryl-cAMP heterogeneity. Previously, gene expression profiling (GEP) revealed two distinct CBF leukemia subgroups displaying significant outcome
differences and identified apoptotic signaling, MAPKinase signaling and chemotherapy-resistance mechanisms among the most significant differentially regulated pathways. We now tested different inhibitors of the respective pathways in a cell line model (six cell lines reflecting the CBF subgroup-specific gene expression alterations), and found apoptotic signaling to be differentiating between the CBF subgroup models. In accordance, primary samples from newly diagnosed CBF AML patients (n = 23) also showed differential sensitivity to in vitro treatment with a Smac mimetic such as BV6, an antagonist of inhibitor of apoptosis (IAP) proteins, and ABT-737, a BCL2 inhibitor. Furthermore, GEP revealed the BV6-resistant cases to resemble the previously identified unfavorable CBF subgroup. Thus, our current findings show deregulated IAP expression and apoptotic signaling to differentiate clinically relevant CBF subgroups, which were independent of known molecular markers, thereby providing a starting point for novel therapeutic approaches. Leukemia (2011) 25,
1728-1738; doi:10.1038/leu.2011.154; published online 21 June 2011″
“Asthma is a chronic disease of the airways, most commonly driven by immuno-inflammatory responses to ubiquitous airborne antigens. Epidemiological studies have shown that disease is initiated Tideglusib early in life when the immune and respiratory SP600125 in vitro systems are functionally immature and less able to maintain homeostasis in the face of continuous antigen challenge. Here, we examine the cellular and molecular mechanisms that underlie initial
aeroallergen sensitization and the ensuing regulation of secondary responses to inhaled allergens in the airway mucosa. In particular, we focus on how T-regulatory (Treg) cells influence early asthma initiation and the potential of Treg cells as therapeutic targets for drug development in asthma.”
“Background: Clinicians managing thyrotoxic patients with acute abdomen face challenging diagnostic and risky therapeutic dilemmas.
Aim: To analyse the frequency of medical vs. surgical acute abdomen, and to characterize the poorly understood thyrotoxic medical acute abdomen phenomenon.
Design: Retrospective review of case notes.
Methods: All case files with a simultaneous diagnosis of thyrotoxicosis and acute abdomen admitted between 1994 and 2004 were traced and audited.
Results: Thirteen had a history of thyrotoxicosis while 12 were newly diagnosed. The commonest cause was Graves disease. Twenty-three (92) cases were thyrotoxic, of whom six (24) had thyroid crisis, while two (8) had subclinical thyrotoxicosis.