Правила проведения исследований биоаналоговых лекарственных средств (биоаналогов)

В настоящих Правилах изложены основные принципы нормативного регулирования доклинического и клинического изучения биоаналоговых лекарственных средств (далее — биоаналогов), в отношении которых заявлено, что они аналогичны инновационным биологическим лекарственным препаратам

Palaeozoic evolution of the North Tianshan based on palaeomagnetic data – transition from Gondwana towards Pangaea

© 2017 Informa UK Limited, trading as Taylor & Francis GroupWe present new palaeomagnetic data for Cambrian and Ordovician volcanic and sedimentary rocks from the Kyrgyz North Tianshan (NTS) and review available data from the southwestern Central Asian Orogenic Belt (CAOB) to elucidate the tectonic history and evolution of this region during the early Palaeozoic. We observed a coherent evolution of the NTS and the Kazakhstan continent (or Kazakhstania) with a constant northwards movement between the Cambrian and Devonian at ~5 cm/a. After the northwards movement ceased in the Devonian, the accreted terrane assemblage of Kazakhstania occupied a stable latitudinal position at ~30°N until the final amalgamation of Eurasia occurred in the late Carboniferous to early Permian. Amalgamation of the Tarim and Turan blocks caused a counterclockwise bending within the southwestern segment of the CAOB, which occurred in an inconsistent way by a brittle-like response of the upper crust with a large variety of rotational movement. We suggest an evolution of the Kyrgyz CAOB terranes by steady migration away from Gondwana and subsequent capture in a zone of global downwelling at ~30°N, where accretion and subsequent amalgamation of Eurasia occurred with the CAOB terranes in its centre

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

The statin family of drugs target HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, and have been used successfully in the treatment of hypercholesterolemia for the past 15 years. Experimental evidence suggests this key biochemical pathway holds an important role in the carcinogenic process. Moreover, statin administration in vivo can provide an oncoprotective effect. Indeed, in vitro studies have shown the statins can trigger cells of certain tumor types, such as acute myelogenous leukemia, to undergo apoptosis in a sensitive and specific manner. Mechanistic studies show bcl-2 expression is down-regulated in transformed cells undergoing apoptosis in response to statin exposure. In addition, the apoptotic response is in part due to the depletion of the downstream product geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate or other products of the mevalonate pathway including cholesterol. Clinically, preliminary phase I clinical trials have shown the achievable plasma concentration corresponds to the dose range that can trigger apoptosis of tumor types in vitro. Moreover, little toxicity was evident in vivo even at high concentrations. Clearly, additional clinical trials are warranted to further assess the safety and efficacy of statins as novel and immediately available anti-cancer agents. In this article, the experimental evidence supporting a role for the statin family of drugs to this new application will be reviewed