Efficient Elimination of Cancer Cells by Deoxyglucose-ABT-263/737 Combination Therapy

As single agents, ABT-263 and ABT-737 (ABT), molecular antagonists of the Bcl-2 family, bind tightly to Bcl-2, Bcl-xL and Bcl-w, but not to Mcl-1, and induce apoptosis only in limited cell types. The compound 2-deoxyglucose (2DG), in contrast, partially blocks glycolysis, slowing cell growth but rarely causing cell death. Injected into an animal, 2DG accumulates predominantly in tumors but does not harm other tissues. However, when cells that were highly resistant to ABT were pre-treated with 2DG for 3 hours, ABT became a potent inducer of apoptosis, rapidly releasing cytochrome c from the mitochondria and activating caspases at submicromolar concentrations in a Bak/Bax-dependent manner. Bak is normally sequestered in complexes with Mcl-1 and Bcl-xL. 2DG primes cells by interfering with Bak-Mcl-1 association, making it easier for ABT to dissociate Bak from Bcl-xL, freeing Bak to induce apoptosis. A highly active glucose transporter and Bid, as an agent of the mitochondrial apoptotic signal amplification loop, are necessary for efficient apoptosis induction in this system. This combination treatment of cancer-bearing mice was very effective against tumor xenograft from hormone-independent highly metastasized chemo-resistant human prostate cancer cells, suggesting that the combination treatment may provide a safe and effective alternative to genotoxin-based cancer therapies

Henri IV, the Appellants and the Jesuits

The beginning of serious French interest in the affairs of English Catholicism falls in the first years of the seventeenth century. Since the Reformation, French kings and their ministers had usually felt that Catholicism in England was, on political grounds, to be discouraged rather than advanced; from a more recent date, they had ceased to have a foreign policy at all. Interest in English Catholicism had been left to the Spaniards, who had coped with it as best they could. Two explanations can be offered why things began to take a different turn during the reign of Henri IV. The first is that the reconstruction of what Sully described as “la faction fran9oise dans la Chrestiente” carried with it almost automatically a revival of the anti-English posture traditionally associated with it; the combination is a familiar one.</jats:p

Catholicity and nationality in the northern European counter-reformation

Why choose this subject? First, because I think there is a general historiographical problem about nationality in early-modern Europe, which has been rather abandoned and is perhaps worth another look. Second because, on the Catholic side of the subject, there is a problem of actuality concerning Ireland and a rather different one concerning Holland. Third, because there is a specific and limited issue in the history of English Catholicism. I shall really be concerned with a simple problem raised by Arnold Oskar Meyer in his England and the Catholic Church under Queen Elizabeth: how far the internal conflicts among English Catholics, generally known as the Archpriest controversy, are to be explained as an outbreak or resurgence of ‘nationalism’, a conflict of ‘national’ and ‘Catholic’ tendencies. There have been good reasons for objecting to Meyer’s view that this was the case: his conceptions of national character, of ’puritanism’, were by present standards shaky, and he weakened his personal position by becoming more closely involved with the Third Reich than he perhaps need have been. The recent historiography of the subject has been largely a history of attempts to find an alternative: in the international competition of France and Spain; in the constitutional hostility of gentry and clergy; in the geographical determinism of Braudelian routes; in the ecclesiastical choice between a traditional and a missionary church. Many of them have been made by myself; most recently Christopher Haigh has added another, connected with the continuity or discontinuity of Elizabethan Catholicism with its pre-Reformation predecessor.</jats:p

Blood and baptism: kinship, community and christianity in western Europe from the fourteenth to the seventeenth centuries

Historians of west-European Christianity in its late medieval and early modern phases have recently been much concerned with the relations of the church and the devil. Our subject here, the church and the world, may seem by comparison, and notably for the period immediately preceding the reformation, a well-worn topic; inspired by the achievements of historical demography, we may be tempted to abandon it for more promising researches into the relations of the church and the flesh. This is indeed what I shall be doing here, at least to the degree that ‘flesh and blood’ can be considered as falling under the last heading. Yet, since it may be argued that ‘flesh and blood’ formed, for the average western Christian of this time, a major constituent of his ‘world’ or social environment, I do not feel that I am stretching a point in offering, within the present context, some comments on the subject indicated in my title. I am concerned with the connections of the Church and the ‘world’, meaning by that the complex of human relations it lives in. I am particularly concerned with the structure of one such society, that of western Europe in the immediately pre- and post-reformation age. And I am finally interested in pursuing or criticising some socio-historical arguments about what happened to European Christianity in and after the sixteenth century.</jats:p

Peace in the Post-Reformation

Christians are supposed to love their neighbours, including their enemies. This is never easy. When feud and honour are common realities, it is even harder than usual. This book sketches the history of peace-making between people (not countries) as an activity of churches or of Christianity between the Reformation and the eighteenth century. The story is recounted in four countries (Italy, France, Germany, and England) and in several religious settings (including Roman Catholic, Lutheran, Church of England, and Calvinist). Each version is a variation upon a theme: what the author calls a 'moral tradition' which contrasts, as a continuing imperative, with the novelties of theory and practice introduced by the sixteenth-century reformers. In general the topic has much to say about the destinies of Christianity in each country, and more widely, and strikes a chord which will resonate in both the social and the religious history of the West.</jats:p

Leagues and Associations in Sixteenth-Century French Catholicism

My motives in choosing this subject are: to respond to the invitation of our chairman; to expound the conviction that the persistence of French Catholicism through the crises of the Reformation was largely the result of the voluntary association of French Catholics; and to try to discover whether there was anything in Catholic theological or pastoral teaching of the period which might have given these associations a theoretical perspective, or grounded them in some kind of associative conception of the Church. I add that, despite the very considerable importance of the subject, one might even claim its decisive importance for the outcome of the wars of religion in Europe as a whole, it has (with some shining exceptions) not received very much attention from historians, and that in England essential texts and studies are hard to come by.</jats:p

A Propos of Henry Constable

Nobody will pretend that Henry Constable was more than a minor poet and an indifferent theologian; he is nonetheless a crucial figure in the history of English Catholicism, and it is most important that we should have a clear idea of his motives and opinions. Dr. Rogers has done us a great service by sorting out the bibliographical history of hisExamen pacifique de la Doctrine des Huguenots,and dispelling a number of confusions which had accumulated around it. I propose to supplement his article by producing evidence which, except on a few points, will support and amplify his conclusions and suggest a more concrete biographical background to them.</jats:p