Tumor microenvironment-induced tumor cell plasticity: relationship with hypoxic stress and impact on tumor resistance.

The role of tumor interaction with stromal components during carcinogenesis is crucial for the design of efficient cancer treatment approaches. It is widely admitted that tumor hypoxic stress is associated with tumor aggressiveness and thus impacts susceptibility and resistance to different types of treatments. Notable biological processes that hypoxia functions in include its regulation of tumor heterogeneity and plasticity. While hypoxia has been reported as a major player in tumor survival and dissemination regulation, the significance of hypoxia inducible factors in cancer stem cell development remains poorly understood. Several reports indicate that the emergence of cancer stem cells in addition to their phenotype and function within a hypoxic tumor microenvironment impacts cancer progression. In this respect, evidence showed that cancer stem cells are key elements of intratumoral heterogeneity and more importantly are responsible for tumor relapse and escape to treatments. This paper briefly reviews our current knowledge of the interaction between tumor hypoxic stress and its role in stemness acquisition and maintenance. Our review extensively covers the influence of hypoxia on the formation and maintenance of cancer stem cells and discusses the potential of targeting hypoxia-induced alterations in the expression and function of the so far known stem cell markers in cancer therapy approaches. We believe that a better and integrated understanding of the effect of hypoxia on stemness during carcinogenesis might lead to new strategies for exploiting hypoxia-associated pathways and their targeting in the clinical setting in order to overcome resistance mechanisms. More importantly, at the present time, efforts are oriented towards the design of innovative therapeutical approaches that specifically target cancer stem cells.

[Analysis of the quality of data issued from Beirut's hospitals in order to measure short-term health effects of air pollution]. / Analyse de la qualité des données issues des hôpitaux de Beyrouth Municipe pour mesurer les effets à court terme de la pollution atmosphérique.

BACKGROUND: The effects of air pollution on human health have been the subject of much public health research. Several techniques and methods of analysis have been developed. Thus, Beirut Air Pollution and Health Effects (BAPHE) was designed to develop a methodology adapted to the context of the city of Beirut in order to quantify the short-term health effects of air pollution. METHODS: The quality of data collected from emergency units was analyzed in order to properly estimate hospitalizations via these units. This study examined the process of selecting and validating health and pollution indicators. RESULTS: The different sources of data from emergency units were not correlated. BAPHE was therefore reoriented towards collecting health data from the emergency registry of each hospital. A pilot study determined the appropriate health indicators for BAPHE and created a classification methodology for data collection. CONCLUSION: In Lebanon, several studies have attempted to indirectly assess the impact of air pollution on health. They had limitations and weaknesses and offered no recommendations regarding the sources and quality of data. The present analysis will be useful for BAPHE and for planning further studies.

Regulation of Golgi structure through heterotrimeric G proteins.

We have previously shown that ilimaquinone (IQ), a marine sponge metabolite, causes complete vesiculation of the Golgi stacks. By reconstituting the IQ-mediated vesiculation of the Golgi apparatus in permeabilized cells, we now demonstrate that this process does not require ARF and coatomers, which are necessary for the formation of Golgi-derived COPI vesicles. We find that IQ-mediated Golgi vesiculation is inhibited by G alpha(s)-GDP and G alpha(i3)-GDP. Interestingly, adding betagamma subunits in the absence of IQ is sufficient to vesiculate Golgi stacks. Our findings reveal that IQ-mediated Golgi vesiculation occurs through activation of heterotrimeric G proteins and that it is the free betagamma, and not the activated alpha subunit, that triggers Golgi vesiculation.