Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma.

The liver tumor immune microenvironment has been thought to possess a critical role in the development and progression of hepatocellular carcinoma (HCC). Despite the approval of immune checkpoint inhibitors (ICIs), such as programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, for several types of cancers, including HCC, liver metastases have shown evidence of resistance or poor response to immunotherapies. Radiation therapy (RT) has displayed evidence of immunosuppressive effects through the upregulation of immune checkpoint molecules post-treatment. However, it was revealed that the limitations of ICIs can be overcome through the use of RT, as it can reshape the liver immune microenvironment. Moreover, ICIs are able to overcome the RT-induced inhibitory signals, effectively restoring anti-tumor activity. Owing to the synergetic effect believed to arise from the combination of ICIs with RT, several clinical trials are currently ongoing to assess the efficacy and safety of this treatment for patients with HCC.

Assessing the resilience of urban areas to traffic-related air pollution: Application in Greater Paris.

Recent studies report that outdoor air pollution will become the main environmental cause of premature death over the next few decades (OECD, 2012; WHO, 2014; World Bank, 2016). Cities are considered hot spots and urban populations are particularly exposed. There is therefore an urgent need to adapt urban systems and urban design to tackle this issue. While most European cities have introduced measures to reduce emissions, action is still required to reduce concentrations and exposure, and a holistic approach to urban design is badly needed. The concept of urban resilience, defined by Holling (1987) as the ability of a city to absorb a disturbance while maintaining its functions and structures, may offer a new paradigm for tackling urban air pollution. We propose to adapt the concept of urban resilience to outdoor air pollution. A method has been developed to assess the resilience of an urban area to outdoor air pollution. Three "resilience capacities" have been identified: the capacity of an urban area to decrease air pollution emissions, the capacity to decrease concentrations and the capacity to decrease exposure. The calculation is based on the analysis of urban design, defined as the pattern of buildings as well as the structural elements that define an urban area (urban morphology; transport network, services and land use). For each resilience capacity, indicators are calculated using a Geographic Information System (GIS) and a grid-based approach. This method has been implemented in the Greater Paris area within a 500m grid-cell system. Greater Paris is one of the densest urban areas in Europe and experiences high air pollution levels. The proposed "quick scan" method helps to localize areas where specific action is needed.

Hemisynthesis, Antitumoral Effect, and Molecular Docking Studies of Ferutinin and Its Analogues.

The natural product ferutinin was shown to act as an agonist to estrogen receptor ERα and agonist/antagonist to ERß featuring a weak antiproliferative activity toward breast cancer cells. To enhance this activity, ferutinin analogues were synthesized by esterification of jaeschkenadiol with different acids. These compounds were assayed for their in vitro antiproliferative activity against estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cell lines. Among the compounds, 3c' exhibited a potent inhibitory selective activity against MCF-7 with IC50 value of 1 µM. Docking simulation of 3c' in the ligand binding domain of the ERs indicated a potential antagonism interaction with both ER subtypes. Functional assay showed that 3c' binds as an antagonist to ERα protein while ferutinin acts as an agonist.