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Ymittos Athens, Greece

Nikitaki Z.,National Technical University of Athens | Michalopoulos I.,Academy of Athens BRFAA | Georgakilas A.G.,National Technical University of Athens
Future Medicinal Chemistry | Year: 2015

DNA repair (DR) inhibitors are small molecules that interact with DR proteins in order to disrupt their function and induce a 'strike' to the high fidelity of the mammalian DNA repair systems. Many anticancer therapies aim to harm the DNA of the usually highly proliferative cancer cell, causing it to undergo apoptosis. In response to this, cancer cells attempt to fix the induced lesion and reconstitute its genomic integrity, in turn reducing the efficacy of treatment. To overcome this, DR inhibitors suppress DNA repair proteins' function, increasing the potency and tumor killing effect of chemotherapy or radiotherapy. In this review, we discuss clinically applied novel inhibitors under translational investigation and we apply bioinformatic tools in order to identify repair proteins implicated in more than two phenomenically distinct DNA repair pathways (e.g., base excision repair and nonhomologous end joining), that is, the concept of 'synthetic lethality'. Our study can aid towards the optimization of this therapeutic strategy and, therefore, maximizing treatment effectiveness like in the case of radiation therapy. © 2015 Future Science Ltd. Source

Maneas E.,National and Kapodistrian University of Athens | Maneas E.,Academy of Athens BRFAA | Tzoumas S.,Helmholtz Center Munich | Ntziachristos V.,Helmholtz Center Munich | Spyrou G.,Academy of Athens BRFAA
13th IEEE International Conference on BioInformatics and BioEngineering, IEEE BIBE 2013 | Year: 2013

The aim of this study was the development of a simulator for Multispectral Optoacoustic Tomography (MSOT). The modelling pathway of the simulator was separated into the optical, the acoustic and the reconstruction part in generating finally a photoacoustic image. In this paper, the presented simulation geometry was based on a recently developed MSOT imaging system, but it can be easily modified to other imaging geometries. Through comparison between experimental and simulated data, a validation of the model as well as its limitations, perspectives and modifications are presented. © 2013 IEEE. Source

Paronis E.,Surgery Academy | Samara A.,Academy of Athens BRFAA | Samara A.,University of Oslo | Polyzos A.,Academy of Athens BRFAA | And 2 more authors.
Laboratory Animals | Year: 2015

One of the commonly used animal models in fertility, developmental and neurobiological studies is the laboratory rat. The early recognition of rat pregnancy and confirmation of the exact embryonic day are vital. The aim of this study was to investigate the correlation of maternal weight at the time of conception to its increase throughout gestation, aiming to develop a mathematical model, which can be used for the determination of the exact day of pregnancy, set the threshold, and monitor pregnancy from the onset. We studied a total of 173 Wistar rats with a mean body weight of 238.22±34.9 g. After 72 h at the male’s cages, we considered as Day 0 (D0) the day in which a copulatory plug or sperm was found during the vaginal smear examination. After that period the female animals were transferred into their cages, and weight monitoring started 14 days (D14) after D0, until parturition. Based on the statistical analysis, there is a correlation between maternal body weight at D0 and maternal body weight from D14 to D19. Moreover, the average weight gain from D14 to D19 is positively correlated to initial female body weight, while there is no correlation between each pregnant animal’s weight from D14 to D19 and litter size. A mathematical model was developed as a tool for the verification of the day of pregnancy. In conclusion, continuous monitoring of maternal weight after D14 can be a reliable method for the recognition of pregnancy and determination of the exact gestational day. © The Author(s) 2014. Source

Simone C.,University of Milan | Ramirez A.,University of Milan | Bucchia M.,University of Milan | Rinchetti P.,University of Milan | And 4 more authors.
Cellular and Molecular Life Sciences | Year: 2016

Spinal muscular atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the survival motor neuron 1 gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. Even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It has been demonstrated that non-motor neuronal cells are also involved in disease pathogenesis and could have important therapeutic implications. For these reasons it will be crucial to take this evidence into account for the clinical translation of the novel therapeutic approaches. © 2015 Springer International Publishing. Source

Zervas C.G.,Academy of Athens BRFAA | Psarra E.,Academy of Athens BRFAA | Williams V.,University of Cambridge | Solomon E.,University of Cambridge | And 2 more authors.
Journal of Cell Science | Year: 2011

Integrin-linked kinase (ILK) is an essential component of a multiprotein complex that links actin to the plasma membrane. Here, we have used a genetic approach to examine the molecular interactions that are essential for the assembly of this ILK-containing complex at Drosophila muscle attachment sites (MASs). We show that, downstream of integrins, talin plays a decisive role in the recruitment of three proteins: ILK, PINCH and paxillin. The accumulation of ILK at MASs appears to follow an amplification mechanism, suggesting that numerous binding sites are generated by minimal levels of the upstream integrin and talin effectors. This property suggests that ILK functions as an essential hub in the assembly of its partner proteins at sites of integrin adhesion. We found that PINCH stability, and its subcellular localization at MASs, depends upon ILK function, but that ILK stability and localization is not dependent upon PINCH. An in vivo structure-function analysis of ILK demonstrated that each ILK domain has sufficient information for its independent recruitment at embryonic MASs, whereas at later developmental stages only the kinase domain was effectively recruited. Our data strengthen the view that the ILK complex is assembled sequentially at sites of integrin adhesion by employing multiple molecular interactions, which collectively stabilize the integrin-actin link. © 2011. Published by The Company of Biologists Ltd. Source

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