Features Of Motility Research Articles

CellPLATO - an unsupervised method for identifying cell behaviour in heterogeneous cell trajectory data.

Advances in imaging, segmentation and tracking have led to the routine generation of large and complex microscopy datasets. New tools are required to process this 'phenomics' type data. Here, we present 'Cell PLasticity Analysis Tool' (cellPLATO), a Python-based analysis software designed for measurement and classification of cell behaviours based on clustering features of cell morphology and motility. Used after segmentation and tracking, the tool extracts features from each cell per timepoint, using them to segregate cells into dimensionally reduced behavioural subtypes. Resultant cell tracks describe a 'behavioural ID' at each timepoint, and similarity analysis allows the grouping of behavioural sequences into discrete trajectories with assigned IDs. Here, we use cellPLATO to investigate the role of IL-15 in modulating human natural killer (NK) cell migration on ICAM-1 or VCAM-1. We find eight behavioural subsets of NK cells based on their shape and migration dynamics between single timepoints, and four trajectories based on sequences of these behaviours over time. Therefore, by using cellPLATO, we show that IL-15 increases plasticity between cell migration behaviours and that different integrin ligands induce different forms of NK cell migration.

A Mathematical Modelling Study of Chemotactic Dynamics in Cell Cultures: The Impact of Spatio-temporal Heterogeneity

As motivated by studies of cellular motility driven by spatiotemporal chemotactic gradients in microdevices, we develop a framework for constructing approximate analytical solutions for the location, speed and cellular densities for cell chemotaxis waves in heterogeneous fields of chemoattractant from the underlying partial differential equation models. In particular, such chemotactic waves are not in general translationally invariant travelling waves, but possess a spatial variation that evolves in time, and may even oscillate back and forth in time, according to the details of the chemotactic gradients. The analytical framework exploits the observation that unbiased cellular diffusive flux is typically small compared to chemotactic fluxes and is first developed and validated for a range of exemplar scenarios. The framework is subsequently applied to more complex models considering the chemoattractant dynamics under more general settings, potentially including those of relevance for representing pathophysiology scenarios in microdevice studies. In particular, even though solutions cannot be constructed in all cases, a wide variety of scenarios can be considered analytically, firstly providing global insight into the important mechanisms and features of cell motility in complex spatiotemporal fields of chemoattractant. Such analytical solutions also provide a means of rapid evaluation of model predictions, with the prospect of application in computationally demanding investigations relating theoretical models and experimental observation, such as Bayesian parameter estimation.

Probing spiroplasma's cytoskeletal motility mechanism through hydrodynamic modelling and experiment.

Nearly all swimming bacteria have evolved to utilize external, helical, rotating appendages called flagella to achieve motility. These flagella are anchored into a cell wall which provides a structural rigidity during the swimming process. Contrary to this, a unique helical bacterium called spiroplasma has neither a cell wall nor flagella, yet still swims in water. Instead, this bacterium utilizes a set of actively deformable cytoskeletal filaments, internal to the cell, which allow for swimming motility. These filaments force the cell's bilayer membrane to deform, however, the interaction between the membrane and these filaments is unclear. Using this information, we have created an algorithm to handle this motility using the regularized stokeslet method which accurately describes spiroplasma's motion and used microscopy at varying viscosities to prove this description. We describe how our simulations found unique features of spiroplasma's motility and what this means for the interaction between spiroplasma's cytoskeleton and membrane.

Mind bomb 2 promotes cell migration and epithelial structure by regulating adhesion complexes and the actin cytoskeleton

Cell migration is essential in animal development and co-opted during metastasis and inflammatory diseases. Some cells migrate collectively, which requires them to balance epithelial characteristics such as stable cell-cell adhesions with features of motility like rapid turnover of adhesions and dynamic cytoskeletal structures. How this is regulated is not entirely clear but important to understand. While investigating Drosophila oogenesis, we found that the putative E3 ubiquitin ligase, Mind bomb 2 (Mib2), is required to promote epithelial stability and the collective cell migration of border cells. Through biochemical analysis, we identified components of Mib2 complexes, which include E-cadherin and α- and β-catenins, as well as actin regulators. We also found that three Mib2 interacting proteins, RhoGAP19D, Supervillin, and Myosin heavy chain-like, affect border cell migration. mib2 mutant main body follicle cells have drastically reduced E-cadherin-based adhesion complexes and diminished actin filaments. We conclude that Mib2 acts to stabilize E-cadherin-based adhesion complexes and promote a robust actin cytoskeletal network, which is important for maintenance of epithelial integrity. The interaction with cadherin adhesion complexes and other cytoskeletal regulators contribute to its role in collective cell migration. Since Mib2 is well conserved, it may have similar functional significance in other organisms.

DIDACTIC FUNDAMENTALS OF MUSICAL TRAINING OF FUTURE CHOREOGRAPHY SPECIALISTS IN DOMESTIC HIGHER EDUCATION INSTITUTIONS

The article considers the didactic conditions of musical training of choreographers in higher education institutions of our state. In this work the structural didactic features of musical competence of choreographers are defined, such as: feature of professional activity planning; ways and methods of performing professional activities; communication techniques; organizational skills of choreographers; features of dance and motor motility. The article also states that the author considers an individual approach to take into account the ways of adapting the properties of studentsʼ nervous system to the requirements of professional activity as an effective method of musical training of choreographers in domestic higher education institutions. The article also deals with an individual approach, which takes into account the individual differences of students, the development of techniques, tools and methods of forming professional and musical skills of choreographers, due to the typological properties of the nervous system. At the heart of the individual approach considered in the study there is the idea of understanding a developing student as a person with a unique set of individual qualities. This involves the recognition of different, but equivalent in effectiveness methods of educational and creative activities that meet the objective requirements of the professional activity of the teacher and the individual characteristics of the future specialist.Also, in this paper, it is noted that in pedagogical science didactics is connected with the methods of teaching courses. The method of teaching folk dance is somewhat different from other choreographic disciplines due to the specifics of national dance. All textbooks, programs and methodical materials on folk choreography are authorʼs versions and naturally cannot be accepted by all experts identically.
 Keywords: musical training, music theory, choreographer, professional training, didactics, didactic bases of training, professional skill, systematic approach to musical training.

Varied presentations of congenital ocular synkinesis: do they all fit congenital cranial dysinnervation disorder spectrum?

Synkinesis results from nerve miswirings and causes aberrant movements of the affected muscles. We present a series of cases of rare congenital ocular synkinesis involving the extraocular muscles and the levator palpebrae superioris and speculate the possibility of classifying these entities in the spectrum of congenital cranial dysinnervation disorder. Records of patients with the diagnosis of congenital ocular synkinesis were analyzed retrospectively. We analyzed the sex, laterality, and complete features of the ocular motility of each patient. Nine patients with congenital ocular synkinesis were included. A slight predominance of women was noted. In terms of laterality, four patients had only the right eye involved, four had only the left eye, and one had both eyes involved. Notably, 55.5% were orthotropic in the primary position. The third, fourth, and sixth cranial nerves were involved in the miswiring in 100%, 44.4%, and 11.1% of the cases, respectively. Congenital synkinesis might present in a very eclectic and uncommon fashion. The aberrant innervation in these cases classifies them into the group of congenital cranial dysinnervation disorders.

Clinical Features of Ocular Motility in Idiopathic Orbital Myositis.

Objective: To elucidate the clinical features of ocular motility and the risk factors for recurrence in idiopathic orbital myositis. Methods: The medical records of 31 patients diagnosed with idiopathic orbital inflammation between 2003 and 2019 were retrospectively reviewed. All patients were initially treated with corticosteroids. Treatment outcome and ocular motility were noted. Results: Twenty-six patients (84%) had unilateral involvement and five patients (16%) were bilateral. Of the 31 patients, 22 patients (71%) showed ocular motility limitation. The mean grading scale of extraocular muscle (EOM) limitation was −1.65 ± 1.80. EOM limitation was found in the same direction of the most affected muscle in 14 patients (64%), while 8 patients (36%) showed duction limitation in the opposite direction. Nine patients (35%) suffered from recurrence. Recurrence was more likely to occur in patients with multiple muscle involvement (p < 0.001). The interval to relapse of symptoms after discontinuation of steroids was significantly shorter in patients with multiple recurrences compared to those with a single recurrence (1.8 ± 0.8 weeks versus 6.0 ± 1.4 weeks, p = 0.020). Conclusions: Idiopathic orbital myositis showed variable degrees of ocular motility limitation, and limitation in the same direction of the action of the affected muscle was more frequent. Recurrent myositis was more likely to have multiple muscle involvement. Rapid relapse of symptoms after discontinuation of steroids was a significant indicator of multiple recurrences.

Nanosecond pulsed current under plasma-producing conditions induces morphological alterations and stress fiber formation in human fibrosarcoma HT-1080 cells

Cold atmospheric plasma (CAP) is a promising means for various biomedical applications, including cancer therapy. Although the biological action of CAP is considered to be brought about by synergistic effects of reactive species and electrical factors of CAP, limited information is currently available on the contribution of electrical factors to CAP-induced cell responses. We have previously demonstrated that nanosecond pulsed current (nsPC) under CAP-producing conditions significantly promoted the motility of human HT-1080 cells. In this study, we explored the effects of nsPC on cell morphology associated with cell motility. We observed that nsPC stimulation caused extended cell shape, membrane protrusion formation, and increased cell surface area, but not cell death induction. nsPC stimulation also caused elevated intracellular ROS and Ca2+. HT-1080 cells can undergo two modes of cell motility, namely mesenchymal and ameboid motility, and we found that morphological features of mesenchymal motility was partly shared with nsPC-stimulated cells. Furthermore, nsPC-stimulated cells had extended stress fibers composed of filamentous actin. Taken together, this study provides a novel insight into the electrical aspect of CAP action, and we speculate that nsPC activates a certain mechanism involving intracellular signaling for stress fiber formation, leading to altered cell morphology and increased cell motility.

Modeling random crawling, membrane deformation and intracellular polarity of motile amoeboid cells.

Amoeboid movement is one of the most widespread forms of cell motility that plays a key role in numerous biological contexts. While many aspects of this process are well investigated, the large cell-to-cell variability in the motile characteristics of an otherwise uniform population remains an open question that was largely ignored by previous models. In this article, we present a mathematical model of amoeboid motility that combines noisy bistable kinetics with a dynamic phase field for the cell shape. To capture cell-to-cell variability, we introduce a single parameter for tuning the balance between polarity formation and intracellular noise. We compare numerical simulations of our model to experiments with the social amoeba Dictyostelium discoideum. Despite the simple structure of our model, we found close agreement with the experimental results for the center-of-mass motion as well as for the evolution of the cell shape and the overall intracellular patterns. We thus conjecture that the building blocks of our model capture essential features of amoeboid motility and may serve as a starting point for more detailed descriptions of cell motion in chemical gradients and confined environments.

The relevance of motility in language shift research

Abstract Motility (sometimes referred to as ‘mobility capital’ or ‘mobility potential’) is a still understudied and underutilised concept in both migration and sociolinguistic literature. Perhaps even more than actual mobility, it can shed an important light on the possible connection between language and migration. In this theoretical article, it will be argued that motility can both be a potential catalyst for language shift, but can in other instances also contribute to language maintenance. Inspired by Fishman’s Graded Intergenerational Disruption Scale (GIDS) and Simon and Lewis’ Expanded Graded Intergenerational Scale (EGIDS), it is assumed that the most important factor in processes of language shift is the attitude of parents, in particular their willingness to transmit their heritage language to their children. This willingness is connected with the perception of the value of the heritage language, which might be, in addition to other factors, influenced by the mobility capital the heritage language might give future generations. The interplay between migrant networks in different countries and the country of origin is key in understanding the parents’ decision-making process. Furthermore, the three main features of motility (access, competence and appropriation) fit quite logically in the already existing EGIDS scale. This article thus argues that motility is a valuable and necessary concept for sociolinguistic research and migration scholars alike.

Transport of the alpha subunit of the voltage gated L‐type calcium channel through the sarcoplasmic reticulum occurs prior to localization to triads and requires the beta subunit but not Stac3 in skeletal muscles

Contraction of skeletal muscle is initiated by excitation-contraction (EC) coupling during which membrane voltage is transduced to intracellular Ca2+ release. EC coupling requires L-type voltage gated Ca2+ channels (the dihydropyridine receptor or DHPR) located at triads, which are junctions between the transverse (T) tubule and sarcoplasmic reticulum (SR) membranes, that sense membrane depolarization in the T tubule membrane. Reduced EC coupling is associated with ageing, and disruptions of EC coupling result in congenital myopathies for which there are few therapies. The precise localization of DHPRs to triads is critical for EC coupling, yet trafficking of the DHPR to triads is not well understood. Using dynamic imaging of zebrafish muscle fibers, we find that DHPR is transported along the longitudinal SR in a microtubule-independent mechanism. Furthermore, transport of DHPR in the SR membrane is differentially affected in null mutants of Stac3 or DHPRβ, two essential components of EC coupling. These findings reveal previously unappreciated features of DHPR motility within the SR prior to assembly at triads.

A mathematical model coupling polarity signaling to cell adhesion explains diverse cell migration patterns.

Protrusion and retraction of lamellipodia are common features of eukaryotic cell motility. As a cell migrates through its extracellular matrix (ECM), lamellipod growth increases cell-ECM contact area and enhances engagement of integrin receptors, locally amplifying ECM input to internal signaling cascades. In contrast, contraction of lamellipodia results in reduced integrin engagement that dampens the level of ECM-induced signaling. These changes in cell shape are both influenced by, and feed back onto ECM signaling. Motivated by experimental observations on melanoma cells lines (1205Lu and SBcl2) migrating on fibronectin (FN) coated topographic substrates (anisotropic post-density arrays), we probe this interplay between intracellular and ECM signaling. Experimentally, cells exhibited one of three lamellipodial dynamics: persistently polarized, random, or oscillatory, with competing lamellipodia oscillating out of phase (Park et al., 2017). Pharmacological treatments, changes in FN density, and substrate topography all affected the fraction of cells exhibiting these behaviours. We use these observations as constraints to test a sequence of hypotheses for how intracellular (GTPase) and ECM signaling jointly regulate lamellipodial dynamics. The models encoding these hypotheses are predicated on mutually antagonistic Rac-Rho signaling, Rac-mediated protrusion (via activation of Arp2/3 actin nucleation) and Rho-mediated contraction (via ROCK phosphorylation of myosin light chain), which are coupled to ECM signaling that is modulated by protrusion/contraction. By testing each model against experimental observations, we identify how the signaling layers interact to generate the diverse range of cell behaviors, and how various molecular perturbations and changes in ECM signaling modulate the fraction of cells exhibiting each. We identify several factors that play distinct but critical roles in generating the observed dynamic: (1) competition between lamellipodia for shared pools of Rac and Rho, (2) activation of RhoA by ECM signaling, and (3) feedback from lamellipodial growth or contraction to cell-ECM contact area and therefore to the ECM signaling level.

Features of Sperm Motility and Circadian Rhythm in Japanese Anchovy (Engraulis japonicus)

Japanese anchovy (Engraulis japonicus) is a commercially and ecologically important fish that exhibits group synchronous and multiple spawning. However, the reproductive characteristics of the male in this species, especially sperm features and activation, are still largely unknown. In this study, we confirmed that features of the sperm and characteristics of the activations, regarding sperm motility and moving velocity. The average size of the sperm was 51 ± 1.3 I¼m in total length and possessed a normal structure with clockwise, anticlockwise, and linear motion. The initial motility at one minute after activation in seawater was 75 ± 12% during spawning time in this species (21:00– 22:00), and the initial moving velocity (196 ± 26 I¼m/sec) remained constant for fifteen minutes post activation. While, comparatively low motility (30 ± 10%) was found until 17:00, and the sperm was almost immotile in the morning (08:00–09:00). Swimming ability was also confirmed with sperm that swam for more than one hour in seawater without an exogenous energy supply derived from the ovary in females, suggesting the trigger for sperm activation in multiple spawning fish is possibly species dependent. This report is the first to demonstrate time specific activation, that is, circadian rhythm, in teleost males.

Age features of uterine motility in infertile women with adenomyosis, uterine fibroids, and their combination

Age features of uterine motility in infertile women with adenomyosis, uterine fibroids, and their combination

Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis: Options and Challenges for Novel Bedside Technologies.

Alterations in neutrophil morphology (size, shape, and composition), mechanics (deformability), and motility (chemotaxis and migration) have been observed during sepsis. We combine summarizing features of neutrophil morphology, mechanics, and motility that change during sepsis with an investigation into their clinical utility as markers for sepsis through measurement with novel technologies. We performed an initial literature search in MEDLINE using search terms "neutrophil," "morphology," "mechanics," "dynamics," "motility," "mobility," "spreading," "polarization," "migration," and "chemotaxis." We then combined the results with "sepsis" and "septic shock." We scanned bibliographies of included articles to identify additional articles. Final selection was done after the authors reviewed recovered articles. We included articles based on their relevance for our review topic. When compared with resting conditions, sepsis causes an increase in circulating numbers of larger, more rigid neutrophils that show diminished granularity, migration, and chemotaxis. Combined measurement of these variables could provide a more complete view on neutrophil phenotype manifestation. For that purpose, sophisticated automated hematology analyzers, microscopy, and bedside microfluidic devices provide clinically feasible, high-throughput, and cost-limiting means. We propose that integration of features of neutrophil morphology, mechanics, and motility with these new analytical methods can be useful as markers for diagnosis, prognosis, and monitoring of sepsis and may even contribute to basic understanding of its pathophysiology.

Network Plasticity as Bayesian Inference.

General results from statistical learning theory suggest to understand not only brain computations, but also brain plasticity as probabilistic inference. But a model for that has been missing. We propose that inherently stochastic features of synaptic plasticity and spine motility enable cortical networks of neurons to carry out probabilistic inference by sampling from a posterior distribution of network configurations. This model provides a viable alternative to existing models that propose convergence of parameters to maximum likelihood values. It explains how priors on weight distributions and connection probabilities can be merged optimally with learned experience, how cortical networks can generalize learned information so well to novel experiences, and how they can compensate continuously for unforeseen disturbances of the network. The resulting new theory of network plasticity explains from a functional perspective a number of experimental data on stochastic aspects of synaptic plasticity that previously appeared to be quite puzzling.

Quantification of IFT-Dynein Dynamics in C.elegans

Cytoplasmic dyneins are the main drivers of microtubule-based retrograde transport in eukaryotic cells. Cytoplasmic dynein 1 plays a role in retrograde intracellular transport and cell division, whereas cytoplasmic dynein 2, also known as IFT-dynein, co-operates with kinesin motors to assemble and maintain cilia in a process called intraflagellar transport (IFT). While cytoplasmic dynein 1 has been the subject of many recent studies, relatively little is known about IFT-dynein. Here, we focus on the mechanism and dynamics of IFT-dynein: how does it behave in vivo at the ensemble and single-molecule level?To this end, we use fluorescence microscopy to visualize labeled IFT-dynein motors in the chemosensory cilia of living C. elegans. Transgene worms were generated using the Mos1-mediated single copy insertion (MosSCI) method to ensure endogenous motor expression levels. Time-lapse fluorescence movies showed that IFT-dynein moves in trains consisting of tens of motor proteins. The movies were processed to kymographs, from which location-dependent velocities and motor numbers were obtained using in-house developed kymograph-analysis software. This analysis revealed that IFT-dynein train velocities and motor numbers are dynamic, changing along the cilium. Double-labeled constructs allowed us to look more closely into motor co-operation, determining the dynein:kinesin ratio at different positions in the cilium.To obtain insight into the behavior of individual motors, we employed photoactivation of PA-GFP-labeled IFT-dynein, which allowed, for the first time, the tracking of individual IFT-dynein motors in vivo. Single-motor trajectories revealed distinct features of IFT-dynein motility: diffusive behavior at the ciliary base, pauses, turns, directed motion and switches between these behaviors. This combined ensemble and single-molecule approach has provided novel quantitative insight into IFT-dynein dynamics in living organisms, shedding light on the complex functioning of dynein motors in general.

Tumors of the neural crest: Common themes in development and cancer.

The neural crest (NC) is a remarkable transient structure in the vertebrate embryo that gives rise to a highly versatile population of pluripotent cells that contribute to the formation of multiple tissues and organs throughout the body. In order to achieve their task, NC-derived cells have developed specialized mechanisms to promote (1) their transition from an epithelial to a mesenchymal phenotype, (2) their capacity for extensive migration and cell proliferation, and (3) their ability to produce diverse cell types largely depending on the microenvironment encountered during and after their migratory path. Following embryogenesis, these same features of cellular motility, invasion, and proliferation can become a liability by contributing to tumorigenesis and metastasis. Ample evidence has shown that cancer cells have cleverly co-opted many of the genetic and molecular features used by developing NC cells. This review focuses on tumors that arise from NC-derived tissues and examines mechanistic themes shared during their oncogenic and metastatic development with embryonic NC cell ontogeny.

Interactions between MUC1 and p120 Catenin Regulate Dynamic Features of Cell Adhesion, Motility, and Metastasis

The mechanisms by which MUC1 and p120 catenin contribute to progression of cancers from early transformation to metastasis are poorly understood. Here we show that p120 catenin ARM domains 1, 3-5, and 8 mediate interactions between p120 catenin and MUC1, and that these interactions modulate dynamic properties of cell adhesion, motility, and metastasis of pancreatic cancer cells. We also show that different isoforms of p120 catenin, when coexpressed with MUC1, create cells that exhibit distinct patterns of motility in culture (motility independent of cell adhesion, motility within a monolayer while exchanging contacts with other cells, and unified motility while maintaining static epithelial contacts) and patterns of metastasis. The results provide new insight into the dynamic interplay between cell adhesion and motility and the relationship of these to the metastatic process.

Abstract B51: ApoStream™ isolated circulating tumor cells from primary breast cancer patients reveals heterogeneous phenotypes related to epithelial-mesenchymal transition and stem cell markers.

Abstract Background: Detection of circulating tumor cells (CTCs) is an indicator of poor prognosis in patients with metastatic breast cancer and not in primary breast cancer (PBC). The classical phenotypic definition of a CTC is a nucleated cell that is cytokeratin (CK) positive but CD45 negative. Several reports have shown that EpCAM based capture methods detect only a fraction of CTCs and not the heterogeneous subpopulations of CTCs. Moreover, subsets of CTCs may acquire a more aggressive phenotype with features of invasiveness and motility by undergoing an epithelial to mesenchymal transition (EMT) and down regulate the epithelial cell adhesion molecule, EpCAM. EMT is a hallmark of cellular invasion and metastasis and CTCs undergoing EMT may express the putative cancer stem cell like phenotype, CD24lowCD44+. CTCs undergoing EMT (CTC-EMT) are not readily detected by current CTC detection technologies. Thus, it is desirable to isolate CTCs using capture methods independent of EpCAM to recover a heterogeneous CTC population for more extensive characterization. Here we use ApoStream™, a novel antibody-free CTC isolation device that does not rely on EpCAM to capture circulating rare cells, to evaluate the molecular heterogeneity of CTCs. Methods: Baseline blood samples from 14 newly diagnosed PBC patients were collected and processed using ApoStream™. Isolated cells were stained with anti-CK and anti-CD45, and DAPI. In addition, a multiplexed immunofluorescence assay and laser scanning cytometry analysis were applied to identify multiple combinations of CK+CD45− cells for the expression and distribution of EpCAM, vimentin, CD44, CD24, β-catenin and E-cadherin. Results: ApoStream™ recovered both EpCAM+ and EpCAM− cells. CK+CD45− cells were detected in 9 out of 14 PBC patients. The expression of EpCAM− vimentin+ in the CK+CD45− population was heterogeneous across the patient population. E-cadherin and β-catenin were detected in 0-94% (Mean 52 %) and 0-37% (Mean 8 %), respectively of the CK+CD45− population. All patients with CK+CD45− cells had a subset of cells with the putative phenotype of CD44+CD24low cells. Conclusions: Heterogeneous CTC phenotypes with CD44+CD24lowin both EpCAM+ and EpCAM− cells were observed in patients with PBC. Our aim is to correlate ApoStream™ EMT-CTC counts in patients with PBC with the pathological clinical response (pCR). This study will continue to enroll PBC patients and test the hypothesis that low EMT-CTC count patients have higher pCR rates compared to high EMT-CTC count patients. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B51. Citation Format: Kenna L. Anderes, Insiya Jafferji, Vladislava O. Melnikova, Jackson A. Summer, Darren W. Davis, James M. Reuben, Naoto T. Ueno. ApoStream™ isolated circulating tumor cells from primary breast cancer patients reveals heterogeneous phenotypes related to epithelial-mesenchymal transition and stem cell markers. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B51.