Case Rep Oncol

The pretreatment detection of an activating mutation of EGFR is now routinely performed in metastatic nonsquamous non-small cell lung cancer (NSCLC). The therapeutic impact of such a detection is major, as patients with advanced NSCLC exhibiting a mutation of exon 19 or 21 will benefit from EGFR-tyrosine kinase inhibitors (TKI). The presence of an EGFR resistance mutation, such as T790M in EGFR-TKI-naïve patients, is seldom looked for and is related either to a germinal mutation or to somatically mutated subclones. It has a negative predictive impact. We present the case of a patient with a lung papillary adenocarcinoma and miliary intrapulmonary metastases whose tumor displays a somatic complex heterozygous EGFR mutation, combining L858R (exon 21) and a primary resistance mutation T790M (exon 20), both detected by direct sequencing

Connexin and pannexin (hemi) channels in the liver

The liver was among the first organs in which connexin proteins have been identified. Hepatocytes harbor connexin32 and connexin26, while non-parenchymal liver cells typically express connexin43. Connexins give rise to hemichannels, which dock with counterparts on adjacent cells to form gap junctions. Both hemichannels and gap junctions provide pathways for communication, via paracrine signaling or direct intercellular coupling, respectively. Over the years, hepatocellular gap junctions have been shown to regulate a number of liver-specific functions and to drive liver cell growth. In the last few years, it has become clear that connexin hemichannels are involved in liver cell death, particularly in hepatocyte apoptosis. This also holds true for hemichannels composed of pannexin1, a connexin-like protein recently identified in the liver. Moreover, pannexin1 hemichannels are key players in the regulation of hepatic inflammatory processes. The current paper provides a concise overview of the features of connexins, pannexins and their channels in the liver.This work was financially supported by the grants of the Agency for Innovation by Science and Technology in Flanders (IWT), the University Hospital of the Vrije Universiteit Brussel-Belgium (Willy Gepts Fonds UZ-VUB), the Fund for Scientific Research - Flanders (FWO grants G009514N and G010214N), the European Research Council (ERC Starting Grant 335476), the University of Sao Paulo-Brazil (USP) and the Foundation for Research Support of the State of Sao Paulo (FAPESP SPEC grant 2013/50420-6)

E-cadherin in canine mast cell tumors: Decreased expression and altered subcellular localization in Grade 3 tumors

Mast cell tumors (MCTs) are the most frequent round cell tumors in dogs and comprise approximately 21% of all canine cutaneous tumors. MCTs are highly invasive and metastatic corresponding to the histological grade. E-cadherin is an adhesion molecule expressed in epithelial cells and although it is an epithelial cellular marker, studies have shown expression of E-cadherin in canine round cell tumors. To better characterize the expression pattern of E-cadherin in several different histological grades of MCTs in dogs, the expression and localization of the adhesion molecule was investigated using immunohistochemistry. For this purpose, 18 cutaneous MCTs were classified into three histological grades, 1, 2 or 3. Clinical history and follow-up data were available for all of the dogs. Cytoplasmic and nuclear expressions of E-cadherin in all three types of tumors were verified by immunostaining using two different antibodies. There was decreased E-cadherin expression in the more aggressive MCTs (Grade 3), suggesting an association between E-cadherin and tumor aggressiveness. Additionally, the loss of E-cadherin expression in either the cytoplasm or nucleus in more aggressive and undifferentiated tumor types confirmed the importance of cellular adhesion in tumor behavior. (C) 2012 Published by Elsevier Ltd.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2009/12827-1]; [2010/08523-4

Disability Policies in France: Changes and Tensions between the Category-based, Universalist and Personalized Approaches

In this article, the authors show that the current French disability policy is traversed by conflicts between three different approaches to disability which came about at different periods in history. They begin by looking at the origins of disability policy in France. This policy was developed during the 20th century, from notions of repair, indemnification and compensation through rehabilitation. It became institutionalized in 1975, when two laws were passed, giving it the form of a category-based policy. Between 1970 and 2000, affected by the international situation, this policy came into conflict with a universalist policy. More recently there has been a desire to develop a personalized approach. Finally, the authors use two examples (taken from recent debates on the implementation in France of the new law of 11 February 2005) to show the tensions that have led to the coexistence of these three approaches within current disability policy

Inhibiteurs du check-point immunitaire en néo-adjuvant dans les cancers bronchiques non à petites cellules localisés : Essai clinique de phase II IFCT-1601 IoNESCO

International audienceBackgroundProgrammed cell death-ligand 1 (PD-L1) is a checkpoint receptor that facilitates immune evasion by tumor cells, through interaction with programmed cell death-1 (PD-1), a receptor expressed by T-cells. Durvalumab is an anti-PD-L1 monoclonal antibody that blocks PD-L1 interaction with PD-1 on T-cells, countering the tumor's immune-evading tactics. Phase I/II studies demonstrated durable responses and manageable tolerability in heavily pre-treated patients with non-small cell lung cancer (NSCLC).MethodsThis phase II study is designed to administrate three durvalumab IV infusions (10 mg/kg at day 1, 15, 29) before surgery, to patients with pathologically confirmed NSCLC, clinical stage IB (> 4 cm) or stage II, ≥ 18 years of age, WHO performans status 0–1, without selection on PD-L1 expression. Preoperative chemotherapy and radiation therapy are not permitted. The primary objective is feasibility of complete surgical resection. Major pathological response on surgical tissue, defined as 10% or less remaining tumor cells, will be a secondary objective. Additional secondary objectives include tolerance, adverse effects, delay between start of treatment and surgery, response rate (RECIST 1.1), metabolic response rate, postoperative adverse events, disease-free survival and overall survival. A rate of complete resection 4 cm) ou II. La chimiothérapie et la radiothérapie préopératoire ne sont pas permises. L’objectif principal est la faisabilité d’une résection chirurgicale complète. Un taux de résection complète < 85 % (P0) est considéré comme inacceptable. Avec une hypothèse P1 de 95 %, une puissance de 90 % et un risque alpha de 5 %, 81 patients sont nécessaires. La réponse histologique majeure (≤ 10 % de cellules tumorales résiduelles sur la pièce opératoire) est un objectif secondaire. Les autres objectifs sont le délai entre traitement et chirurgie, les taux de réponse radiologique et métabolique, les évènements indésirables, la survie sans récidive et globale.Résultats attendusL’immunothérapie néo-adjuvante est faisable et pourrait améliorer la survie des CBNPC de stade précoce