Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIα subunit of protein kinase A after oral administration

Overexpression of the RIα subunit of cAMP-dependent protein kinase (PKA) has been demonstrated in various human cancers. PKA has been suggested as a potential target for cancer therapy. The goal of the present study was to evaluate an anti-PKA antisense oligonucleotide (mixed-backbone oligonucleotide) as a therapeutic approach to human cancer treatment. The identified oligonucleotide inhibited the growth of cell lines of human colon cancer (LS174T, DLD-1), leukemia (HL-60), breast cancer (MCF-7, MDA-MB-468), and lung cancer (A549) in a time-, concentration-, and sequence-dependent manner. In a dose-dependent manner, the oligonucleotide displayed in vivo antitumor activity in severe combined immunodeficient and nude mice bearing xenografts of human cancers of the colon (LS174T), breast (MDA-MB-468), and lung (A549). The routes of drug administration were intraperitoneal and oral. Synergistic effects were found when the antisense oligonucleotide was used in combination with the cancer chemotherapeutic agent cisplatin. The pharmacokinetics of the oligonucleotide after oral administration of 35S-labeled oligonucleotide into tumor-bearing mice indicated an accumulation and retention of the oligonucleotide in tumor tissue. This study further provides a basis for clinical studies of the antisense oligonucleotide targeted to the RIα subunit of PKA (GEM 231) as a cancer therapeutic agent used alone or in combination with conventional chemotherapy.

Observations on the courts of law in Nova Scotia, Canada, 1775

Contains a discussion of the organization of the courts in Nova Scotia and recommends changes to allow for greater efficiency and logical administration of cases through the system of justice.

Translations of the Ottoman constitutional laws: the Wilayet Administrative Law, the Municipal Law and various other laws

Ottoman constitutional law of the 7th Dhil Hujjah, 1293 AH [December 24, 1876 AD] as amended. -- Regulations of the Chamber of deputies. -- Regulations of the Senate. -- Provisional law of administration of wilayets of the 13th March, 1329 AH [March 26, 1913 AD] as amended. -- Municipal law of the 27th Ramadhan, 1294 AH [October 5, 1877 AD] as amended. -- Law regulating chambers of commerce and industry, dated the 31st May, 1326 AH [June 13, 1910 AD]. -- Provisional law of expropriation on behalf of municipalities dated the 21st Kanun Thani, 1329 AH [February 3, 1914 AD]. -- Regulations of expropriation for public purposes, dated the 24th Tashrin Thani, 1295 AH [December 6, 1879 AD] as amended. -- The Press law of the 16th Tamuz, 1325 AH [July 29, 1910 AD] as amended.

The European Court of Justice and process-oriented review. Research Paper in Law, 01/2012

Structuralism is a theory of U.S. constitutional adjudication according to which courts should seek to improve the decision-making process of the political branches of government so as to render it more democratic.1 In words of John Hart Ely, courts should exercise their judicial-review powers as a ‘representation-reinforcing’ mechanism.2 Structuralism advocates that courts must eliminate the elements of the political decision-making process that are at odds with the structure set out by the authors of the U.S. Constitution. The advantage of this approach, U.S. scholars posit, lies in the fact that it does not require courts to second-guess the policy decisions adopted by the political branches of government. Instead, they limit themselves to enforcing the constitutional structure within which those decisions must be adopted. Of course, this theory of constitutional adjudication, like all theories, has its shortcomings. For example, detractors of structuralism argue that it is difficult, if not impossible, to draw the dividing line between ‘substantive’ and ‘structural’ matters.3 In particular, they claim that, when identifying the ‘structure’ set out by the authors of the U.S. Constitution, courts necessarily base their determinations not on purely structural principles, but on a set of substantive values, evaluating concepts such as democracy, liberty and equality. 4 Without claiming that structuralism should be embraced by the ECJ as the leading theory of judicial review, the purpose of my contribution is to explore how recent case-law reveals that the ECJ has also striven to develop guiding principles which aim to improve the way in which the political institutions of the EU adopt their decisions. In those cases, the ECJ decided not to second-guess the appropriateness of the policy choices made by the EU legislator. Instead, it preferred to examine whether, in reaching an outcome, the EU political institutions had followed the procedural steps mandated by the authors of the Treaties. Stated simply, I argue that judicial deference in relation to ‘substantive outcomes’ has been counterbalanced by a strict ‘process review’. To that effect, I would like to discuss three recent rulings of the ECJ, delivered after the entry into force of the Treaty of Lisbon, where an EU policy measure was challenged indirectly, i.e. via the preliminary reference procedure, namely Vodafone, Volker und Markus Schecke and Test-Achats.5 Whilst in the former case the ECJ ruled that the questions raised by the referring court disclosed no factor of such a kind as to affect the validity of the challenged act, in the latter cases the challenged provisions of an EU act were declared invalid.

Talking with the “pouvoir constituant” in times of constitutional reform: The European Court of Justice on Private Applicants’ Access to Justice. Research Paper in Law 3/2003

[From the Introduction]. European lawyers, at least those dealing predominantly with institutional matters, are living particularly interesting times since the setting-up of the “European Convention on the Future of Europe” in December 2001.1 As the Convention’s mandate, spelled out in rather broad terms in the European Council’s declaration of Laeken,2 is potentially unlimited, and as the future constitution of the European Union (EU) will be ultimately adopted by the subsequent Intergovernmental Conference (IGC), there appears to be a great possibility to clarify, to simplify and also to reform many of the more controversial elements in the European legal construction. The present debate on the future of the European constitution also highlights the relationship between the pouvoir constituant3 and the European Courts, the Court of Justice (ECJ) and its Court of First Instance (CFI), who have to interpret the basic rules and principles of the EU.4 In that light, the present article will focus on a classic theme of the Court’s case law: the relationship between judges and pouvoir constituant. In the EU, this relationship has traditionally been marked by the ECJ’s role as driving force in the “constitutionalisation” of the EC Treaties – which has, to a large extent, been accepted and even codified by the Member States in subsequent treaty revisions. However, since 1994, the ECJ appears to be more reluctant to act as a “law-maker.”5 The recent judgment in Unión de Pequeños Agricultores (UPA)6 – an important decision by which the ECJ refused to liberalize individuals’ access to the Community Courts – is also interesting in this context. UPA may be seen as another proof of judicial restraint - or even as indicator of the beginning of a new phase in the “constitutional dialogue” between the ECJ and the “Masters of the Treaties.”

The European Court of Justice and the Draft Constitution: A Supreme Court for the Union? Research Paper in Law 8/2003

[Introduction]. The purpose of this paper is twofold. First, it examines selectively the provisions of the draft Constitution pertaining to the Court of Justice and assesses the ways in which the draft Constitution is likely to affect the jurisdiction and the function of the Court. Secondly, it discusses the challenges faced by the Court in relation to the protection of human rights by reference to the recent judgment in Schmidberger.1 Both aspects of the discussion serve to underlie that the Court is assuming the function of the Supreme Court of the Union whose jurisdiction is fundamentally constitutional in character. It has a central role to play not only in relation to matters of economic integration but also in deciding issues of political governance, defining democracy at European and national level, and contributing through the process of judicial harmonisation to the emergence of a European demos. This constitutional jurisdiction of the ECJ is not new but has acquired more importance in recent years and is set to be enhanced under the provisions of the new Constitution. The paper is divided as follows: The first section provides an overview of the way the new Constitution affects the ECJ. The subsequent sections examine respectively Article 28(1) of the draft Constitution, the appointment and tenure of the judiciary, locus standi for private individuals, sanctions against Member States, jurisdiction under the CFSP and the Chapter on freedom, security and justice, preliminary references, other provisions o f the Constitution pertaining to the Court, the principle of subsidiarity, and the judgment in Schmidberger. The final section contains some concluding remarks.

Casual but Smart: The Court’s new clothes in the Area of Freedom Security and Justice (AFSJ) after the Lisbon Treaty. Research Papers in Law, 2/2008

Introduction. Unintended as it was, the European Court of Justice (ECJ, the Court, the Court of the EU) has played an extremely important role in the construction of the Area of Freedom Security and Justice (AFSJ). The AFSJ was set up by the Treaty of Amsterdam in 1997 and only entered into force in May 1999. The fact that this is a new field of EU competence, poses afresh all the fundamental questions – both political and legal – triggered by European integration, namely in terms of: a) distribution of powers between the Union and its Member States, b) attribution of competences between the various EU Institutions, c) direct effect and supremacy of EU rules, d) scope of competence of the ECJ, and e) extent of the protection given to fundamental rights. The above questions have prompted judicial solutions which take into account both the extremely sensible fields of law upon which the AFSJ is anchored, and the EU’s highly inconvenient three-pillar institutional framework.1 The ECJ is the body whose institutional role is to benefit most from this upcoming ‘depilarisation’, possibly more than that of the European Parliament. This structure is on the verge of being abandoned, provided the Treaty of Lisbon enters into force.2 However spectacular this formal boost of the Court’s competence, the changes in real terms are not going to be that dramatic. This apparent contradiction is explained, to a large extent, by the fact that the Court has in many ways ‘provoked’, or even ‘anticipated’, the depilarisation of its own jurisdictional role, already under the existing three-pillar structure. Simply put, under the new – post Treaty of Lisbon – regime, the Court will have full jurisdiction over all AFSJ matters, as those are going to be fully integrated in what is now the first pillar. Some limitations will continue to apply, however, while a special AFSJ procedure will be institutionalised. Indeed, if we look into the new Treaty we may identify general modifications to the Court’s structure and jurisdiction affecting the AFSJ (section 2), modifications in the field of the AFSJ stemming from the abolition of the pillar structure (section 3) and, finally, some rules specifically applicable to the AFSJ (section 4).

Gender Equality in the Case Law of the European Court of Justice. IES WORKING PAPER 2/2009

The principle of gender equality forms a part of the EU’s social policy and serves equally men and women. So far, fourteen directives concerning gender equality have been adopted in the EU, with the New Equal Treatment Directive as the latest one. The EU has developed different models to promote gender equality: equal treatment, positive action and most recently gender mainstreaming. The equal treatment model is primarily concerned with formal equality and it unfortunately prevails in the ECJ’s rulings. Indeed, this paper argues that so far, the ECJ has not managed to develop a firm and consistent case law on gender equality, nor to stretch it coherently to positive action and gender mainstreaming. It seems that in spite of some progress in promoting the position of women, the ECJ’s case law has recently taken a step backwards with its conservative judgments in e.g. the Cadman case. Overall, this paper aims at summing up and evaluating the most important cases of the ECJ on gender equality.

An Exercise in Legal Honesty: Re-writing the Court of Justice and the Bundesverfassungsgericht. IHS Political Science Series No. 136, February 2014

At a time of crisis – a true state of emergency – both the Court of Justice of the European Union and the German Federal Constitutional Court have failed the rule of law in Europe. Worse still, in their evaluation of the ersatz crisis law, which has been developed in response to financial and sovereign debt crises, both courts have undermined constitutionality throughout Europe. Each jurisdiction has been implicated within the techocratisation of democratic process. Each Court has contributed to an incremental process of the undermining of the political subjectivity of European Citizens. The results are depressing for lawyers who are still attached to notions of constitutionality. Yet, we must also ask whether the Courts could have acted otherwise. Given the original flaws in the construction of Economic and Monetary Union, as well as the politically pre-emptive constraints imposed by global financial markets, each Court might thus be argued to have been forced to suspend immediate legality in a longer term effort to secure the character of the legal jurisdiction as a whole. Crisis can and does defeat the law. Nevertheless, what continues to disturb is the failure of law in Europe to open up any perspective for a return to normal constitutionality post crisis, as well as its apparent inability to give proper and honest consideration to the hardship now being experienced by millions of Europeans within crisis. This contribution accordingly seeks to reimagine each Judgment in a language of legal honesty. Above all, this contribution seeks to suggest a new form of post-national constitutional language; a language which takes as its primary function, proper protection of democratic process against the ever encroaching powers of a post-national executive power. This contribution forms a part of an on-going effort to identify a new basis for the legitimacy of European Law, conducted jointly and severally with Christian Joerges, University of Bremen and Hertie School of Government, Berlin. Differences do remain in our theoretical positions; hence this individual essay. Nevertheless, the congruence between pluralist and conflict of law approaches to the topic are also readily apparent. See, for example, Everson & Joerges (2013).

The Court of Justice of the European Union. College of Europe Research Paper in Law 02/2014

The Court of Justice of the European Union is one of the institutions of the Union. Praised by some as the relentless and steady motor of European integration and attacked by others as an example of a clearly biased institution, more ink has perhaps been spilled over the years on discussing the (de)merits of the Court of Justice than any other Union institution. In face of such considerable literature coming from legal, political science, sociological, and more recently also historical quarters, this chapter cannot but scratch the surface of the vast topic by providing a concise introduction into selected institutional themes in a legal1 and, where possible, diachronic perspective: the structure of the Union courts located in Luxembourg; basic information about the type of judicial business the Court of Justice carries out; the composition of the Court of Justice, including the recent changes made to the way in which judges and advocates-general are selected; the often discussed style and structure of the judgments; and, finally, the even more frequently discussed and recurring question of the legitimacy of the Court of Justice.

Information Guide: Court of Justice of the European Union

A guide to information sources on the Court of Justice of the European Union (CJEU), with hyperlinks to further sources of information within European Sources Online and on external websites.

Plenary papers of the 1999 Conference on Criminal Justice Research and Evaluation--enhancing policy and practice through research.

"Sept. 2000" (v. 3).

Preventing school violence : plenary papers of the 1999 Conference on Criminal Justice Research and Evaluation /

"May 2000."