British Journal of Pharmacology - Volume 169 Issue 8 (August 2013)

Showing 1 to 15 of 16 results

1. Issue Information

Date: Jul 26, 2013, Pages: i-ii

2. Emerging therapeutic aspects in oncology

Date: Jul 26, 2013, Pages: 1647-1651

Cancer remains a peculiarly stubborn disease to treat. Some forms of cancer have seen tremendous advances in the effectiveness of their treatments, whereas other forms have remained resistant to pharmacological control. This lack of hope for success is in part due to the types of drugs that are used in the clinic, and the targeted biological system being based purely on cellular growth rates. However, recent drugs...

3. To breathe or not to breathe: the haematopoietic stem/progenitor cells dilemma

Date: Jul 26, 2013, Pages: 1652-1671

Adult haematopoietic stem/progenitor cells (HSPCs) constitute the lifespan reserve for the generation of all the cellular lineages in the blood. Although massive progress in identifying the cluster of master genes controlling self‐renewal and multipotency has been achieved in the past decade, some aspects of the physiology of HSPCs still need to be clarified. In particular, there is growing interest in the metabolic...

4. Curcumin: an orally bioavailable blocker of TNF and other pro‐inflammatory biomarkers

Date: Jul 26, 2013, Pages: 1672-1692

TNFs are major mediators of inflammation and inflammation‐related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF‐α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF‐α antibody (Humira) and soluble TNF receptor‐II (Enbrel) and...

5. Targeting survival pathways in chronic myeloid leukaemia stem cells

Date: Jul 26, 2013, Pages: 1693-1707

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder characterized by the presence of a fusion oncogene BCR‐ABL, which encodes a protein with constitutive TK activity. The implementation of tyrosine kinase inhibitors (TKIs) marked a major advance in CML therapy; however, there are problems with current treatment. For example, relapse occurs when these drugs are discontinued in the majority of...

6. That which does not kill me makes me stronger; combining ERK 1/2 pathway inhibitors and BH 3 mimetics to kill tumour cells and prevent acquired resistance

Date: Jul 26, 2013, Pages: 1708-1722

Oncogenic mutations in RAS or BRAF can drive the inappropriate activation of the ERK1/2. In many cases, tumour cells adapt to become addicted to this deregulated ERK1/2 signalling for their proliferation, providing a therapeutic window for tumour‐selective growth inhibition. As a result, inhibition of ERK1/2 signalling by BRAF or MEK1/2 inhibitors is an attractive therapeutic strategy. Indeed, the first BRAF ...

7. Death receptors as targets in cancer

Date: Jul 26, 2013, Pages: 1723-1744

Anti‐tumour therapies based on the use pro‐apoptotic receptor agonists, including TNF‐related apoptosis‐inducing ligand (TRAIL) or monoclonal antibodies targeting TRAIL‐R1 or TRAIL‐R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti‐cancer therapies. This brief...

8. Inhibiting the DNA damage response as a therapeutic manoeuvre in cancer

Date: Jul 26, 2013, Pages: 1745-1765

The DNA damage response (DDR), consisting of an orchestrated network of proteins effecting repair and signalling to cell cycle arrest, to allow time to repair, is essential for cell viability and to prevent DNA damage being passed on to daughter cells. The DDR is dysregulated in cancer with some pathways up‐regulated and others down‐regulated or lost. Up‐regulated pathways can confer resistance to anti‐cancer DNA...

9. YL529 , a novel, orally available multikinase inhibitor, potently inhibits angiogenesis and tumour growth in preclinical models

Date: Jul 26, 2013, Pages: 1766-1780

Background and Purpose Targeted chemotherapy using small‐molecule inhibitors of angiogenesis and proliferation is a promising strategy for cancer therapy. Experimental Approach YL529 was developed via computer‐aided drug design, de novo synthesis and high‐throughput screening. The biochemical, pharmacodynamic and toxicological profiles of YL529 were investigated ...

10. Functional and morphological characterization of glutamate transporters in the rat locus coeruleus

Date: Jul 26, 2013, Pages: 1781-1794

Background and Purpose Excitatory amino acid transporters (EAATs) in the CNS contribute to the clearance of glutamate released during neurotransmission. The aim of this study was to explore the role of EAATs in the regulation of locus coeruleus (LC) neurons by glutamate. Experimental Approach We measured the effect of different EAAT subtype inhibitors/enhancers on...

11. The hydrogen sulfide donor, GYY 4137, exhibits anti‐atherosclerotic activity in high fat fed apolipoprotein E −/− mice

Date: Jul 26, 2013, Pages: 1795-1809

Background and Purpose Atherosclerosis is associated with reduced vascular hydrogen sulfide (H2S) biosynthesis. GYY4137 is a novel slow‐releasing H2S compound that may effectively mimic the time course of H2S release in vivo. However, it is not known whether GYY4137 affects atherosclerosis. Experimental Approach RAW 264.7 cells and human blood monocyte‐derived macrophages were...

12. Inosine induces presynaptic inhibition of acetylcholine release by activation of A3 adenosine receptors at the mouse neuromuscular junction

Date: Jul 26, 2013, Pages: 1810-1823

Background and Purpose The role of inosine at the mammalian neuromuscular junction (NMJ) has not been clearly defined. Moreover, inosine was classically considered to be the inactive metabolite of adenosine. Hence, we investigated the effect of inosine on spontaneous and evoked ACh release, the mechanism underlying its modulatory action and the receptor type and signal transduction pathway involved. ...

13. The antipsychotic‐like effects of positive allosteric modulators of metabotropic glutamate m G lu 4 receptors in rodents

Date: Jul 26, 2013, Pages: 1824-1839

Background and Purpose Because agonists at metabotropic glutamate receptors exert beneficial effects in schizophrenia, we have assessed the actions of Lu AF21934 and Lu AF32615, two chemically distinct, selective and brain‐penetrant positive allosteric modulators (PAMs) of the mGlu4 receptor, in several tests reflecting positive, negative and cognitive symptoms of schizophrenia in rodents. ...

14. Feasibility of targeting ischaemia‐related ventricular arrhythmias by mimicry of endogenous protection by endocannabinoids

Date: Jul 26, 2013, Pages: 1840-1848

Background and Purpose The hypothesis that endocannabinoids protect hearts against ventricular fibrillation (VF) induced by myocardial ischaemia and reperfusion was examined, and the concept that cannabinoids may represent a new class of anti‐VF drug was tested. Experimental Approach In rat isolated hearts (Langendorff perfusion), VF evoked by reperfusion after 60 min...

15. Istaroxime stimulates SERCA2a and accelerates calcium cycling in heart failure by relieving phospholamban inhibition

Date: Jul 26, 2013, Pages: 1849-1861

Background and Purpose Calcium handling is known to be deranged in heart failure. Interventions aimed at improving cell Ca2+ cycling may represent a promising approach to heart failure therapy. Istaroxime is a new luso‐inotropic compound that stimulates cardiac contractility and relaxation in healthy and failing animal models and in patients with acute heart failure (AHF) syndrome. Istaroxime is a Na‐K ATPase inhibitor...

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