ОЭСР и деофшоризация карликовых государств Европы

The article is devoted to studying the issue of the formation of the international legal regulation of the activities of so-called offshore zones – special jurisdictions that specialize in providing financial services to non-residents in conditions of low or zero taxation, stability and confidentiality. Since the late 1990s, the most successful anti-offshore policy has been conducted (in close cooperation with the G20 states) by the Organization for Economic Cooperation and Development (OECD), which has begun to actively use both organizational and international legal methods in its activities. The most successful examples include the OECD adopting the International Standards for the Exchange of Tax Information (Tax Information Exchange Agreements) in 2009, the Base Erosion and Profit Shifting Program in 2013 (which has become its most significant and successful initiative), the Multilateral Competent Authority Agreement in 2014, as well as the Multilateral Convention to Implement Tax Treaty Related Measures to Prevent Base Erosion and Profit Shifting in 2016, and others.However, in Europe the OECD was forced to face a situation where not only member states or specific territories that are in one form or another directly dependent on said states served as offshore zones, but also small (micro) sovereign states that were not its members. The microstates of Europe ended up resisting the OECD's anti-offshore activities for quite a while, since the high profitability of the offshore business made these states accustomed to getting “easy” money, and their population – to the high standard of living, which was largely provided for by these funds. The conducted research allowed the author to draw the conclusion that multiple stages can be singled out in this confrontation, during which the microstates of Europe, somewhat successful at first, were eventually forced to cooperate with the OECD and officially accept the rules the latter, as well as the mechanisms of interstate tax control it introduced. To a large extent, this stemmed from the fact that the microstates feared the G20 countries would levy sanctions against them, as well as because some of the microstates of Europe, in light of the instability of the world financial and economic system, were looking for ways to access the European market by obtaining the status of associated EU members. Nonetheless, while formally adhering to the OECD requirements, the microstates of Europe are still attempting to provide offshore services to nonresidents by transforming and significantly complicating the financial schemes used for such purposes. General scientific methods, the technic method, the concrete-historical and the historicalgenetic methods, as well as the formal-dogmatic and the systemic approaches were used within the framework of the study.Offshores and the settlement of cross-border tax relations is one of the most vital economic problems of our time, yet no fundamental scientific research on the international relations of the OECD and the microstates of Europe has yet been carried out.Выявляются причины, побудившие карликовые государства Европы, не являющиеся членами Организации экономического сотрудничества и развития (ОЭСР), к активному взаимодействию с ней в вопросах ликвидации фактически существовавших на их территориях офшорных зон. Устанавливаются места и роли европейских карликовых государств в качестве налоговых убежищ в международных экономических отношениях, выявляются механизмы, задействованные на международной арене для борьбы с уклонением от уплаты налогов. В задачи исследования входило рассмотрение динамики (становление, изменение и развитие) отношений между ОЭСР и указанными государствами, а также определение условий, влиявших и влияющих на стратегию поведения этой международной экономической организации и карликовых государств Европы в отношении друг друга. Как в отечественной, так и зарубежной доктрине имеется достаточно большой массив научных исследований, посвященных борьбе с офшорами и деятельности ОЭСР в этом направлении, однако научных работ по противостоянию в вопросе ухода от уплаты налогов между этой организацией и не просто офшорными зонами, а пусть и карликовыми, но суверенными европейскими государствами, причем не являющимися членами Европейского Союза и самой ОЭСР, крайне мало, что и предопределило востребованность и актуальность настоящей статьи. В результате проведенного исследования делается вывод о том, что в рамках отношений карликовых государств Европы и ОЭСР в вопросах международной борьбы с уклонением от уплаты налогов можно выделить три этапа, и если в начале этой борьбы рассматриваемые государства имели некоторый успех, в итоге под воздействием ряда факторов (мировой финансово-экономический кризис 2008–2009 гг., наличие у этих государств «особых отношений» с их соседями, учреждение Глобального форума по транспарентности и обмену информацией для целей налогообложения, принятие международных актов, направленных на борьбу с офшорами, и др.) они были вынуждены пойти на сотрудничество с ОЭСР и принять предписанные ею правила, а также установленные ею механизмы межгосударственного контроля в налоговой сфере

Metformin Represses Self-Renewal of the Human Breast Carcinoma Stem Cells via Inhibition of Estrogen Receptor-Mediated OCT4 Expression

Metformin, a Type II diabetic treatment drug, which inhibits transcription of gluconeogenesis genes, has recently been shown to lower the risk of some diabetes-related tumors, including breast cancer. Recently, “cancer stem cells” have been demonstrated to sustain the growth of tumors and are resistant to therapy. To test the hypothesis that metformin might be reducing the risk to breast cancers, the human breast carcinoma cell line, MCF-7, grown in 3-dimensional mammospheres which represent human breast cancer stem cell population, were treated with various known and suspected breast cancer chemicals with and without non-cytotoxic concentrations of metformin. Using OCT4 expression as a marker for the cancer stem cells, the number and size were measured in these cells. Results demonstrated that TCDD (100 nM) and bisphenol A (10 µM) increased the number and size of the mammospheres, as did estrogen (10 nM E2). By monitoring a cancer stem cell marker, OCT4, the stimulation by these chemicals was correlated with the increased expression of OCT4. On the other hand, metformin at 1 and 10 mM concentration dramatically reduced the size and number of mammospheres. Results also demonstrated the metformin reduced the expression of OCT4 in E2 & TCDD mammospheres but not in the bisphenol A mammospheres, suggesting different mechanisms of action of the bisphenol A on human breast carcinoma cells. In addition, these results support the use of 3-dimensional human breast cancer stem cells as a means to screen for potential human breast tumor promoters and breast chemopreventive and chemotherapeutic agents

Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, and significantly enhanced the radiation-induced growth delay of FSaII tumors (s.c.) in the legs of C3H mice. Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. Conclusion: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR

Understanding the benefit of metformin use in cancer treatment

Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a potential anticancer agent. Epidemiological, preclinical and clinical evidence supports the use of metformin as a cancer therapeutic. The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. The evidence supporting a role for metformin in cancer therapy and its potential molecular mechanisms of action are discussed

Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use

Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug–drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress