Cannabinoid receptor ligands as potential anticancer agents--high hopes for new therapies?

OBJECTIVES: The endocannabinoid system is an endogenous lipid signalling network comprising arachidonic-acid-derived ligands, cannabinoid (CB) receptors, transporters and endocannabinoid degrading enzymes. The CB(1) receptor is predominantly expressed in neurons but is also co-expressed with the CB(2) receptor in peripheral tissues. In recent years, CB receptor ligands, including Delta(9)-tetrahydrocannabinol, have been proposed as potential anticancer agents. KEY FINDINGS: This review critically discusses the pharmacology of CB receptor activation as a novel therapeutic anticancer strategy in terms of ligand selectivity, tissue specificity and potency. Intriguingly, antitumour effects mediated by cannabinoids are not confined to inhibition of cancer cell proliferation; cannabinoids also reduce angiogenesis, cell migration and metastasis, inhibit carcinogenesis and attenuate inflammatory processes. In the last decade several new selective CB(1) and CB(2) receptor agents have been described, but most studies in the area of cancer research have used non-selective CB ligands. Moreover, many of these ligands exert prominent CB receptor-independent pharmacological effects, such as activation of the G-protein-coupled receptor GPR55, peroxisome proliferator-activated receptor gamma and the transient receptor potential vanilloid channels. SUMMARY: The role of the endocannabinoid system in tumourigenesis is still poorly understood and the molecular mechanisms of cannabinoid anticancer action need to be elucidated. The development of CB(2)-selective anticancer agents could be advantageous in light of the unwanted central effects exerted by CB(1) receptor ligands. Probably the most interesting question is whether cannabinoids could be useful in chemoprevention or in combination with established chemotherapeutic agents.

Great Britain, Palestine, Russia, and the Jews

Canon Edward Hoare

Great Britain and the Jews

by Albert M. Hyamson

Ireland and Northern Ireland, 1705 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A mapp of the kingdom of Ireland : newly corrected & improv'd by actual observations : divided into its provinces, counties, & baronies, and supply'd with many market towns & other places of note omitted in former mapps ... : together with plans of the citys and fortified towns, as allso a short description of the kingdom by Henry Pratt ; to this map is added a large index of the measur'd distances of ev'ry town from Dublin, of the burroughs, barracks, and post towns with many other improuements and emendations ; I. Harris, sculp. It was published by H. Pratt in 1708. Scale [ca. 1:385,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Irish Grid (Transverse Mercator 1965 (TM-65)) coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, major roads, territorial and administrative boundaries, shoreline features, and more. Relief shown pictorially. Includes also text, index, 16 ancillary town maps, and inset: The sea coasts of Great Britain and Ireland.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Information Guide: United Kingdom. November 2016

A guide to information sources on the United Kingdom of Great Britain and Northern Ireland, with hyperlinks to information within European Sources Online and on external websites (For other language versions of this record click on the original url)

The North Sea autumn spawning Herring (Clupea harengus L.) Spawning Component Abundance Index (SCAI)

The North Sea autumn-spawning herring (Clupea harengus) stock consists of a set of different spawning components. The dynamics of the entire stock have been well characterized, but although time-series of larval abundance indices are available for the individual components, study of the dynamics at the component level has historically been hampered by missing observations and high sampling noise. A simple state-space statistical model is developed that is robust to these problems, gives a good fit to the data, and proves capable of both handling and predicting missing observations well. Furthermore, the sum of the fitted abundance indices across all components proves an excellent proxy for the biomass of the total stock, even though the model utilizes information at the individual-component level. The Orkney-Shetland component appears to have recovered faster from historic depletion events than the other components, whereas the Downs component has been the slowest. These differences give rise to changes in stock composition, which are shown to vary widely within a relatively short time. The modelling framework provides a valuable tool for studying and monitoring the dynamics of the individual components of the North Sea herring stock.

High Albania and its customs in 1908 /

Reprinted from the Journal of the Royal Anthropological Institute, vol XL.

Wireless world.

Mode of access: Internet.

Victoria, Queen and Empress : a jubilee memoir /

Mode of access: Internet.

Les aventures de Kamrup,

Mode of access: Internet.

Queen Anne,

Politics I.--Politics II.--Literature.--Society and manners.

Scotland for the motorist,

Mode of access: Internet.

Journal.

Mode of access: Internet.