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.

Decentralisation and Social Services in England

Although Great Britain is not normally credited with the achievement of having been the first nation state to implement measures characteristic of a welfare state (this honour goes to Germany and Bismarck's strategy of promoting social insurance in the 1880s) it nevertheless pioneered many models of welfare services in view of the early onset of industrialisation in that country and the subsequent social problems it created. Organisations like the Mutual Insurance and Friendly Societies, the Charity Organisation Society or the Settlement Movement characterised an early approach to welfare that is based on initiatives at the civil society level and express a sense of self-help or of self-organisation in such a way that it did not involve the state directly. The state, traditionally, dealt with matters of discipline and public order, and for this reason institutions like prisons and workhouses represented the other end of the scale of 'welfare' provisions.

Marginalized Youth. An Introduction.

The life conduct of marginalized groups has become subject to increasing levels of risk in advanced capitalist societies. In particular, children and young people are confronted with the harsh consequences of a “new poverty” in the contemporary era. The demographic complexion of today’s poverty is youthful, as a number of government reports have once again documented in recent years in Australia, Germany, France, Great Britain, the US or Scandinavian countries. Key youth studies have shown a growing fear of the future among young people – especially with regard to the threat of unemployment and poverty. However, these results have not yet produced any fundamental critical political reaction.

The gap between recognition and the 'compensation business' : the claim against Britain for compensation by Kenya's former Mau Mau fighters

During the first Kibaki administration (2002-2007), a movement by the former Mau Mau fighters demanded recognition for the role that they had played in the achievement of independence. They began to demand, also, monetary compensation for past injustices. Why had it taken over 40 years (from independence in 1963) for the former Mau Mau fighters to initiate this movement? What can be observed as the outcome of their movement? To answer these questions, three different historical currents need to be taken into account. These were, respectively, changing trends in the government of Kenya, progress in historical research into the actual circumstances of colonial control, and a realization, based on mounting experience, that launching a legal action against Britain could turn out to be a lucrative initiative. This paper concludes that, regardless of the actual purpose of the legal case, neither of their objectives was certain to be achieved. Two inescapable realities remain: the doubts cast on the reputation of the government by its decision to lift the Mau Mau‟s outlaw status – a decision that was widely seen as a latter-day example of the „Kikuyu favouritism‟ policy followed by the first Kibaki administration – and the popular interpretation of the involvement of Leigh Day, well known in Kenya ever since the unexploded bombs case for its success in obtaining substantial compensation payments, as a vehicle for squeezing large amounts of money from the British government for the benefit of the Kikuyu people.

The British fern gazette.

v.1 (1909-1912)

The British fern gazette.

v.2 (1912-1915)

A catalogue of books [donated by Jasper Mauduit] in the library of Harvard College [at]: Cambridge in New England, 1765

This leatherbound volume lists books donated to the Harvard College Library by Jasper Mauduit, who served as an agent in London on behalf of the Province of the Massachusetts Bay. Entries are arranged alphabetically and by format; i.e. the first page lists all folios whose author, title, or keyword begin with "A," the next page lists all quartos beginning with "A," and the following page lists all "octavo &ca" volumes beginning with "A." The volume continues in a similar manner for each letter of the alphabet. Following a devastating fire in 1764 which destroyed most of the books in the Harvard College Library, Mauduit donated books, as well as money for the purchase of books, to the College. He also acted as an agent of the Society for Propagating the Gospel in New England and Parts Adjacent, using the £300 they donated for the rebuilding of the College library to select and purchase a large number of books. It is not known if the books listed in this catalog are those donated by Mauduit himself, or if they are the donations he purchased on behalf of the Society. The creator of this volume is unknown; although all entries are made in the same hand, the identity of the writer has not been determined. The label attached to the front cover, which refers to the Lime Street address of Mauduit's business in London, suggests that the list might have been prepared by Mauduit himself.

Letter book : manuscript, 1764-1771

Tryon's official letter book containing copies of letters and documents relating to his work as colonial governor of North Carolina; with references concerning drawing a boundary between North Carolina and South Carolina; talks with the Cherokee Indians; the establishment of a postal service; working with the Propagation of the Gospels in Foreign Parts; establishing the Church of England in North Carolina; strengthening the defenses of the colony; maintaining better communication with Great Britain; and other events.

Syria

by W. Hughes.

North Africa or Barbary

I. Marocco (Scale [ca. 1:2,800,000]) -- II. Algier (Scale [ca. 1:2,000,000]) -- III. Tunis and part of Tripoli (Scale [ca. 1:2,000,000]) -- IV. Tripoli (Scale [ca. 1:2,000,000]) -- V. Parts of Tripoli and Egypt (Scale [ca. 1:2,000,000]).

True to trust ; and Croaking Kate & Chirping Jane /

Disbound Original Held in Oak Street Library Facility.

Confucianism and Taouism.

Mode of access: Internet.

The mirage of the streets /

Disbound Original Held in Oak Street Library Facility.