Differential roles of the Drosophila EMT-inducing transcription factors Snail and Serpent in driving primary tumour growth.

Several transcription factors have been identified that activate an epithelial-to-mesenchymal transition (EMT), which endows cells with the capacity to break through basement membranes and migrate away from their site of origin. A key program in development, in recent years it has been shown to be a crucial driver of tumour invasion and metastasis. However, several of these EMT-inducing transcription factors are often expressed long before the initiation of the invasion-metastasis cascade as well as in non-invasive tumours. Increasing evidence suggests that they may promote primary tumour growth, but their precise role in this process remains to be elucidated. To investigate this issue we have focused our studies on two Drosophila transcription factors, the classic EMT inducer Snail and the Drosophila orthologue of hGATAs4/6, Serpent, which drives an alternative mechanism of EMT; both Snail and GATA are specifically expressed in a number of human cancers, particularly at the invasive front and in metastasis. Thus, we recreated conditions of Snail and of Serpent high expression in the fly imaginal wing disc and analysed their effect. While either Snail or Serpent induced a profound loss of epithelial polarity and tissue organisation, Serpent but not Snail also induced an increase in the size of wing discs. Furthermore, the Serpent-induced tumour-like tissues were able to grow extensively when transplanted into the abdomen of adult hosts. We found the differences between Snail and Serpent to correlate with the genetic program they elicit; while activation of either results in an increase in the expression of Yorki target genes, Serpent additionally activates the Ras signalling pathway. These results provide insight into how transcription factors that induce EMT can also promote primary tumour growth, and how in some cases such as GATA factors a ‘multi hit’ effect may be achieved through the aberrant activation of just a single gene

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Prise en charge du cancer du canal anal en 2018

Section : Mise au point / UpdateNational audienceAnal canal cancer is a rare disease accounting for 3% of digestive tract tumours. However, its annual incidence has increased during the two last decades reaching 0.5/100,000 in men and 1.3/100,000 in women in 2012. Squamous carcinoma is the most common histological type, and accounts for more than 80% of anal canal malignancy. The main risk factor is human papillomavirus (HPV), in particular 16 and 18 subtypes. This virus is associated with 50% to 100% of anal canal cancers through the action of E6 and E7 oncoproteins. The decrease of natural clearance of HPV due to the multiplicity of sexual partners and human immunodeficiency virus (HIV) epidemic could partly explain the observed increase of anal cancer incidence. Since eighties and Nigro’s trials management has significantly changed: a multidisciplinary strategy combining radiotherapy and concurrent chemotherapy had replaced the radical surgery. Chemoradiation offered better results considering local control and also allowed a better functional prognosis by sphincter-preservation. Overall 5-year survival varies from 70 to 80% but recurrences, which are mainly loco-regional, benefit from salvage surgery in only 30% of cases. Thus, a close clinical surveillance is justified to diagnose early recurrence. The two newest and most promising therapies are anti-EGFR and anti-PD1. Yet, more randomized trials are required to confirm their efficiency, especially in metastatic disease which is still associated with poor prognosis.Le cancer du canal anal est une tumeur rare représentant 3 % des cancers digestifs dont l’incidence a néanmoins doublé ces 20 dernières années pour atteindre 0,5/100 000 chez l’homme et 1,3/100 000 chez la femme en 2012. Les carcinomes épidermoïdes sont le type histologique le plus fréquent, soit plus de 80 % des cancers du canal anal. Le principal facteur de risque est l’infection à human papillomavirus (HPV), notamment les HPV 16 et 18 dits « à haut risque ». Par l’action des oncoprotéines E6 et E7, ce virus est responsable de 50 à 100 % des cancers du canal anal. La diminution de la clairance naturelle de HPV, en lien avec la multiplicité des partenaires sexuels et l’épidémie de virus de l’immunodéficience humaine, pourra expliquer en grande partie l’augmentation d’incidence du cancer du canal anal. La prise en charge, initialement chirurgicale, a été remplacée par une stratégie multidisciplinaire associant la radiothérapie à une chimiothérapie concomitante à base de mitomycine C et de 5-fluoro-uracile depuis les essais de Nigro et al. dans les années 1980. La radiochimiothérapie (RCT) a non seulement permis un meilleur contrôle locorégional, mais également un meilleur pronostic fonctionnel grâce à la préservation sphinctérienne. La chirurgie garde toutefois des indications en cas de réponse incomplète ou de récidive après RCT. La survie globale est de 70 à 80%à cinq ans. Les récidives, en majorité locales, ne bénéficient d’une chirurgie de sauvetage que dans 30 % des cas, ce qui justifie une surveillance clinique étroite afin de dépister précocement les rechutes. De nouvelles thérapies montrent des résultats intéressants. Parmi celles-ci, les anti-EGFR et les anti-PD1 sont les plus prometteuses et nécessitent des essais cliniques pour confirmer leur efficacité, notamment dans les formes métastatiques au pronostic encore très sombre

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit