Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication

The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity to cancer. PcGs silence the expression of the tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53 functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG inhibition has been proposed as a strategy for cancer treatment. However, the recurrent inactivation of pRb/p53 responses in human cancers raises a question regarding the ability of PcG proteins to affect cellular proliferation independently from this checkpoint. Here we demonstrate that PRCs regulate cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53 pathway. We provide evidence that PRCs localize at replication forks, and that loss of their function directly affects the progression and symmetry of DNA replication forks. Thus, we have identified a novel activity by which PcGs can regulate cell proliferation independently of major cell cycle restriction checkpoints. \ua92014 Macmillan Publishers Limited. All rights reserved

Environmental assessment model for pharmaceutical products - Environmental risks related to Active Pharmaceutical Ingredients (API) and carbon footprint in a life cycle perspective

To be able to assess the environmental consequences of pharmaceutical products, reliable, comparable and relevant information is needed about the environmental impacts along the life cycle of the product. This project has developed and proposed a model for environmental assessment of pharmaceutical products, in regard to environmental risks related to emissions of Active Pharmaceutical Ingredient (API) from production processes and product carbon footprint in a life cycle perspective. The two parts is intended to supplement and expand the current environmental classification at Fass.se, which covers environmental risks from release of API from patient excretion in Swedish water recipients. The model is aimed to facilitate comparability of performed assessments of products with the same API and allow for third party review and validation, to ensure credibility and quality of reported results. The environmental risk part of the proposed model includes production stages where API can be/is released to the environment and builds on the current environmental classification at Fass.se. The carbon footprint part of the model covers greenhouse gas emissions in a life cycle perspective. We propose to use the framework described in ISO 14025 for environmental product declarations and initiate the development of Product Category Rules (PCR) for pharmaceutical products. Different potential options for such development are outlined in the report. The proposed model is aimed to deliver product specific environmental assessment results that may be used in a wide variety of different applications to control, manage and reduce impacts along the pharmaceutical value chain and drive improvements in different parts of the chain. The report includes an overview of potential use of the information, such as pharmaceutical benefits subsidy systems, procurement, process and product improvement, guidance in product choice as well as assessments in conjunction with product approval. The actual intended application of results, however, needs to be better understood in order to prioritise and guide further development and implementation of the model.This report proposes a model for environmental assessment of pharmaceutical products, in regard to environmental risks related to emissions of Active Pharmaceutical Ingredient (API) from production processes and product carbon footprint in a life cycle perspective. The proposed model is aimed to deliver results that may be used in different applications. The project has been performed in cooperation with The Research-Based Pharmaceutical Industry (LIF)