The PI3K/AKT/mTOR axis promotes survival and is a frequently mutated pathway in cancer. Yet, inhibitors targeting this pathway are insufficient to induce cancer cell death as single agents in some contexts, including diffuse large B cell lymphoma (DLBCL). In these situations, combinations with inhibitors targeting BCL-2 survival proteins (ABT-199 and ABT-263) may hold potential. Indeed, studies...

The PI3K/AKT/mTOR axis promotes survival and is a frequently mutated pathway in cancer. Yet, inhibitors targeting this pathway are insufficient to induce cancer cell death as single agents in some contexts, including diffuse large B cell lymphoma (DLBCL). In these situations, combinations with inhibitors targeting BCL2 survival proteins (ABT-199 and ABT-263) may hold potential. Indeed, studies ...

Depression is a major psychiatric disorder. It affects millions of people worldwide and inflicts tremendous economic burden on societies. The advent of selective serotonin re-uptake inhibitors as antidepressants has been a revolutionary advance in the treatment of depression and related disorders. However, selective serotonin re-uptake inhibitors are also associated with several undesirable pro...

Alzheimer's disease (AD) was first described by Alois Alzheimer in 1907. AD is the most prevalent dementia- related disease, affecting over 20 million individuals worldwide. Currently, however, only a handful of drugs are available and they are at best only able to offer some relief of symptoms. Acetylcholinesterase (AChE) inhibitors, antioxidants, metal chelators, monoamine oxidase inhibitors,...

The effects of 9 calcium antagonists on ABCG2/BCRP-mediated resistance and transport were examined in HeLa and SN-38-resistant HeLa (HeLa/SN100) cells, overexpressing ABCG2/BCRP. Sensitivity to mitoxantrone, an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly reversed by the coexistence of the calcium antagonists, except for diltiazem a...

Mukadam et al. (2008) report cholinesterase inhibitors to be effective in treating delirium. This suggests that cholinesterase inhibitors have a broader spectrum of effect than the treatment of dementia alone. Acetylcholine itself interacts with various other neurotransmitters. Cancelli et al. (2004) report that a fall in acetylcholine levels, as occurs in dementia, could increase sensitivity t...

Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as tr...

Hypertension is the leading cause of death in developed countries; its management is the subject of guidelines that are regularly reviewed and updated. However, the guidelines from France, the UK, Europe and the USA differ. Some recommendations are graded, whereas others are not. All recommendations emphasize the role of alternative methods for clinical measurement of blood pressure, such as am...

Mukadam et al. (2008) report cholinesterase inhibitors to be effective in treating delirium. This suggests that cholinesterase inhibitors have a broader spectrum of effect than the treatment of dementia alone. Acetylcholine itself interacts with various other neurotransmitters. Cancelli et al. (2004) report that a fall in acetylcholine levels, as occurs in dementia, could increase sensitivity t...