Role of the microbiota in hematologic malignancies.

Human beings are inhabited by innumerable microorganisms that interrelate with the host in a reciprocal way, establishing a combined and efficient ecosystem - the microbiota - that can affect healthiness as well as disease. There is evidence that the conformation of the microbiota may influence, and is controlled by, the human immune system. Microbes existing in human tissues offer a multiplicity of advantages that participate in functional actions in the host through the adjustment of essential processes such as immunity, signal transduction, and metabolism. The imbalance of this microbial structure has been connected with the pathogenesis and progression of cancer. We reviewed the present knowledge of the diverse microbial ecosystems and we investigated their potential link to carcinogenesis, and the possibility of using advantageous microbes in controlling and preventing hematologic malignancies.

A novel 2,3-benzodiazepine-4-one derivative AMPA antagonist inhibits G2/M transition and induces apoptosis in human leukemia Jurkat T cell line.

It has been shown that the antagonism of glutamate receptors activity was able inhibit proliferation and induce apoptosis in several neuronal and non-neuronal cancer cell lines. In addition, it has been shown that glutamate might facilitate the spread and growth of leukemia T cells through interactions with AMPA receptors. The aim of the present study was to investigate the modulation of cell cycle elicited by a novel 2,3-benzodiazepine-4-one non-competitive AMPA antagonist derivative in the human leukemia Jurkat T cells. Our results indicated that the 1-(4-amino-3,5-dimethylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4h-2,3-benzodiazepin-4-one, named 1g, exerted a significant growth inhibition of leukemia Jurkat T cells in a time and dose dependent manner, arresting the transition of G2/M phase through activation of Myt-1. The molecule also induced apoptosis through the enhanced expression of the pro-apoptotic p53, and the inhibition of Bcl-2, and Bcl-xl, followed by the activation of caspase-3. The results suggested that compound 1g might act mostly as a cytostatic rather than cytotoxic compound. Although further studies are necessary, in order to identify others specific pathways involved in the activity of the present molecule, the presented results identified a novel molecule acting on specific G2/M checkpoint regulation pathway. Finally, our data suggest that compound 1g might be a good molecule for future development in the cancer research.

Glutamate binding-site ligands of NMDA receptors.

Excitatory neurotransmission mediated by NMDA (N-methyl-D-aspartic acid) receptors plays a key role in both healthy and diseased processes in the brain. Therefore, bioactive compounds that can interact selectively with these receptors have been the aim of extensive research in the search of effective therapeutic agents or, at least, useful pharmacological tools. NMDA receptors are heteromeric ion channels that contain different modulatory sites capable to bind subunit-selective ligands. In particular, the activation of NMDA receptors requires two distinct ligands: glutamate (the endogenous agonist) and glycine (the co-agonist). In view of the renewed interest in this research area and the high therapeutic potential of this target, this review presents an updated survey of ligands which interact with the glutamate binding-site of the NMDA receptors, their rational development, and data on the structure-activity relationship which are of utmost importance for the design of novel lead compounds.