Isolation and characterisation of putative colorectal cancer stem cells

The isolation and characterisation of cancer stem cells (CSCs) remain a major challenge. The ‘traditional’ (or ‘stochastic’) model of cancer suggests that cancer cells progress through clonal evolution and therefore, all cancer cells must be destroyed. The alternative model, the ‘hierarchical’ (or CSC) model proposes that a subpopulation of cancer cells, referred to as CSCs, initiates and sustains the continuous expansion of cancer growth. Studies have shown that CSCs are similar to normal stem cells as they are able to self-renew and to differentiate into a non-CSC progeny. However, their proliferation pathways are deregulated, they can form metastasis, trigger recurrences after chemotherapy and are tumourigenic. In the CSC model, the CSCs essentially need to be targeted and eradicated. Although it is recognised that CSCs do exist, there is still a large gap in defining their molecular and functional characteristics. In this study, we have explored different approaches to isolate colorectal CSCs. In the first approach, CSCs were isolated using a putative CSC marker, CD133. Cancer cell suspensions were obtained from patient tumour specimens. Several conditions were used to isolate CD133+ cells by immunoaffinity. Technical difficulties were encountered throughout the procedure that prevented the isolation of CSCs using the CD133 antibody. In the second approach, we determined whether CSCs could be isolated using chemotherapeutic drugs since it has been shown that CSCs are resistant to such treatments. Cancer cells resistant to a short-term exposure with the chemotherapy drug oxaliplatin were isolated from two colorectal cancer cell lines. Data from in vivo tumourigenicity, expression of putative CSC markers and quiescence indicated that the intrinsically resistant cells did not exhibit CSC properties when compared with the untreated population. In the third approach, CSCs were isolated based on the aldehyde dehydrogenase 1 (ALDH1) activity. A high ALDH1 activity has been shown to be a marker of stem cells/CSCs. Immunohistochemistry revealed that ALDH1hi cells expressed more putative CSC markers CD44, CD166, ABCG2 and Lgr-5 than ALDH1lo cells. However, both populations were similarly clonogenic in vitro, they were equally invasive, as resistant to chemotherapeutic regimens and their cell cycle status was similar. In conclusion, the approaches taken to isolate CSCs from cancer tissue samples or cell lines generated limited success. The data suggest that more refined techniques are required to isolate CSCs. On the other hand, they highlight the techniques that should be avoided in future studies. The results also question several concepts of the CSC theory, such as the intrinsic resistance of CSCs, and therefore emphasize on the need of gathering more evidence to validate the CSC model

Combining Static and Dynamic Analysis for Vulnerability Detection

In this paper, we present a hybrid approach for buffer overflow detection in C code. The approach makes use of static and dynamic analysis of the application under investigation. The static part consists in calculating taint dependency sequences (TDS) between user controlled inputs and vulnerable statements. This process is akin to program slice of interest to calculate tainted data- and control-flow path which exhibits the dependence between tainted program inputs and vulnerable statements in the code. The dynamic part consists of executing the program along TDSs to trigger the vulnerability by generating suitable inputs. We use genetic algorithm to generate inputs. We propose a fitness function that approximates the program behavior (control flow) based on the frequencies of the statements along TDSs. This runtime aspect makes the approach faster and accurate. We provide experimental results on the Verisec benchmark to validate our approach.Comment: There are 15 pages with 1 figur

Formal Analysis of Security Properties on the OPC-UA SCADA Protocol

International audienceIndustrial systems are publicly the target of cyberattacks since Stuxnet [1]. Nowadays they are increasingly communicating over insecure media such as Internet. Due to their interaction with the real world, it is crucial to prove the security of their protocols. In this paper, we formally study the security of one of the most used industrial protocols: OPC-UA. Using ProVerif, a well known cryptographic protocol verification tool, we are able to check secrecy and authentication properties. We find several attacks on the protocols and provide countermeasures

Filtrage et vérification de flux métiers dans les systèmes industriels

National audienceDe plus en plus d'attaques informatiques contre les systèmes indus-triels sont présentées par les médias. Ces systèmes tendent à devenir géo-graphiquement distribués et à communiquer via des réseaux vulnérables tels qu'Internet. Régissant de nos jours des domaines tels que la production et la distribution d'énergie, l'assainissement des eaux ou le nucléaire, la sécurité des systèmes industriels devient une priorité pour les gouver-nements. L'une des difficultés de la sécurisation des infrastructures in-dustrielles est la conciliation des propriétés de sécurité avec les attendus métiers en terme de flux. Pour ce faire, nous regardons comment filtrer les messages en tenant compte des aspects métiers. Ensuite, nous nous intéressons à la vérification formelle des propriétés des protocoles de communication industriels. Enfin nous proposons une approche Model-Based Testing permettant de générer des attaques informatiques contre des sys-tèmes industriels

Génération systématique de scénarios d'attaques contre des systèmes industriels

National audienceLes systèmes industriels (SCADA) sont la cible d'attaques informatiques depuis Stuxnet [4] en 2010. De part leur interaction avec le mode physique, leur protection est devenue une priorité pour les agences gouvernementales. Dans cet article, nous proposons une approche de modélisation d'attaquants dans un système industriel incluant la production automatique de scénarios d'attaques. Cette approche se focalise sur les capacités de l'attaquant et ses objectifs en fonc-tion des protocoles de communication auxquels il fait face. La description de l'approche est illustrée à l'aide d'un exemple

Filtrage et vérification de flux métiers dans les systèmes industriels

National audienceDe plus en plus d'attaques informatiques contre les systèmes indus-triels sont présentées par les médias. Ces systèmes tendent à devenir géo-graphiquement distribués et à communiquer via des réseaux vulnérables tels qu'Internet. Régissant de nos jours des domaines tels que la production et la distribution d'énergie, l'assainissement des eaux ou le nucléaire, la sécurité des systèmes industriels devient une priorité pour les gouver-nements. L'une des difficultés de la sécurisation des infrastructures in-dustrielles est la conciliation des propriétés de sécurité avec les attendus métiers en terme de flux. Pour ce faire, nous regardons comment filtrer les messages en tenant compte des aspects métiers. Ensuite, nous nous intéressons à la vérification formelle des propriétés des protocoles de communication industriels. Enfin nous proposons une approche Model-Based Testing permettant de générer des attaques informatiques contre des sys-tèmes industriels

The composition of Event-B models

The transition from classical B [2] to the Event-B language and method [3] has seen the removal of some forms of model structuring and composition, with the intention of reinventing them in future. This work contributes to thatreinvention. Inspired by a proposed method for state-based decomposition and refinement [5] of an Event-B model, we propose a familiar parallel event composition (over disjoint state variable lists), and the less familiar event fusion (over intersecting state variable lists). A brief motivation is provided for these and other forms of composition of models, in terms of feature-based modelling. We show that model consistency is preserved under such compositions. More significantly we show that model composition preserves refinement