IL-23R Is Epigenetically Regulated and Modulated by Chemotherapy in Non-Small Cell Lung Cancer.

IL-23R is Epigenetically Regulated and Modulated by Chemotherapy in Non-Small Cell Lung Cancer.

Front Oncol. 2013; 3: 162
Baird AM, Dockry E, Daly A, Stack E, Doherty DG, O’Byrne KJ, Gray SG

The Interleukin-23 (IL-23)/IL-23R signaling axis is an important inflammatory pathway, involved in the stimulation and regulation of the T helper (Th) 17 lymphocytes, resulting in the production of IL-17. Aside from auto-immunity, this cytokine has also been linked to carcinogenesis and polymorphisms in the IL-23R gene are associated with an increased risk for the development of a number of different cancers. Activation of the IL-23 pathway results in the up-regulation of STAT3 and it is thought that the pathological consequences associated with this are in part due to the production of IL-17. We have previously identified IL-23A as pro-proliferative and epigenetically regulated in non-small cell lung cancer (NSCLC). The current study aims to evaluate IL-23R in greater detail in NSCLC. We demonstrate that IL-23R is expressed and epigenetically regulated in NSCLC through histone post-translation modifications and CpG island methylation. In addition, Gemcitabine treatment, a chemotherapy drug used in the treatment of NSCLC, resulted in the up-regulation of the IL-23R. Furthermore, Apilimod (STA 5326), a small molecule which blocks the expression of IL-23 and IL-12, reduced the proliferative capacity of NSCLC cells, particularly in the adenocarcinoma (A549) sub-type. Apilimod is currently undergoing investigation in a number of clinical trials for the treatment of auto-immune conditions such as Crohn’s disease and Rheumatoid Arthritis. Our results may have implications for treating NSCLC patients with Gemcitabine or epigenetic targeted therapies. However, Apilimod may possibly provide a new treatment avenue for NSCLC patients. Work is currently ongoing to further delineate the IL-23/IL-23R axis in this disease. HubMed – drug


Atrial fibrillation in obstructive sleep apnea.

World J Cardiol. 2013 Jun 26; 5(6): 157-63
Goyal SK, Sharma A

Atrial fibrillation (AF) is a common arrhythmia with rising incidence. Obstructive sleep apnea (OSA) is prevalent among patients with AF. This observation has prompted significant research in understanding the relationship between OSA and AF. Multiple studies support a role of OSA in the initiation and progression of AF. This association has been independent of obesity, body mass index and hypertension. Instability of autonomic tone and wide swings in intrathoracic pressure are seen in OSA. These have been mechanistically linked to initiation of AF in OSA patients by lowering atrial effective refractory period, promoting pulmonary vein discharges and atrial dilation. OSA not only promotes initiation of AF but also makes management of AF difficult. Drug therapy and electrical cardioversion for AF are less successful in presence of OSA. There has been higher rate of early and overall recurrence after catheter ablation of AF in patients with OSA. Treatment of OSA with continuous positive airway pressure has been shown to improve control of AF. However, additional studies are needed to establish a stronger relationship between OSA treatment and success of AF therapies. There should be heightened suspicion of OSA in patients with AF. There is a need for guidelines to screen for OSA as a part of AF management. HubMed – drug


Dim scotopic illumination accelerates the reentrainment following simulated jetlags in a diurnal experimental model, Drosophila.

Commun Integr Biol. 2013 Jan 1; 6(1): e22279
Sinam B, Sharma S, Thakurdas P, Kasture M, Shivagaje A, Joshi D

Jetlag results from the misalignment between the endogenous circadian timing and the civil timing after a transmeridian flight. Efficacy of the dim nocturnal illumination (0.03 lx) in accelerating the reentrainment following simulated jetlags in Drosophila biarmipes was examined by subjecting the flies to 24 h light-dark cycles in which the 12 h photophase was at 300 lx for all flies but the scotophase was at 0 and 0.03 lx for the control and experimental flies, respectively. Reentrainment was always faster in the experimental flies than the control ones. Moreover, unlike melatonin, the dimly lit nights accelerated the reentrainment following both, the phase advance and delay of the light-dark cycles. This study might have potential application as a non-drug jetlag treatment. HubMed – drug


Ca(2+) signaling in T-cell subsets with a focus on the role of cav1 channels: possible implications in therapeutics.

Front Immunol. 2013; 4: 150
Pelletier L, Savignac M

HubMed – drug