bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A41: Biomechanics: A new therapeutic innovation deposit – From the proof of concept to the proof of efficacy
Authors: Brossel Remy 
Published: March 2017

Abstract
Malignant tissue can be normalized in vitro using mechanical signals. A biomechanical treatment has been applied to a tumor of human origin grafted subcutaneously in mice and demonstrated the normalizing effect of stress on tumor growth in vivo. Following this Proof of Concept, a feasibility study has been performed to build a prototype for a Proof of Efficacy: Application of a Constraint Field on human pancreatic cancer grafted in the pancreas of mice. Two devices are combined to generate the local constraint: First a generator of Gradient of Magnetic Field (GMF), second magnetizable iron nanoparticles located in the neovessels surrounding the tumor itself. Nanoparticles act as bioactuators transforming magnetic energy in mechanical energy. This feasibility study was performed on the GMF generator with two opposite permanent magnets. The pressure (Pa) created on the neovessels is: P = Fv.L.Ms,v.dB/dx
L is the stroma thickness (m);
Fv is the nanoparticle volume proportion of stroma;
Ms,v is the magnetization of nanoparticles (A/m);
dB/dx is the magnetic induction gradient in stroma thickness direction (T/m).
Iron-core coils are the best means to obtain our goal: A magnetic pressure of about 100 to 500 Pa on the tumor surface. The tumor is a one-centimeter-diameter sphere located at the center of our measured zone, a tube with 3 cm square section.
Three dimensional magnetic simulations with a finite element method show that a magnetic induction gradient of 50 T/m is achievable. This gradient can be maintained permanently, can vary with time, and can have a variable direction in the field of study.
The other variables that increase pressure are: The proportion of iron particles (greater than 100 mg/ml), the thickness of stroma, and the magnetization of particles.
The experimental laboratory environment in which the anesthetized rodents are studied must permit heat dissipation to obtain reproducible results with no influence of temperature. The power losses do not exceed 600 watts, so the use of air-cooling is adequate.
The magnetic induction gradients are strong, but obtainable at the tumor-stroma interface. The progression to a whole human prototype will necessarily require supra-conductor coils.
We will present the data on changes in in vivo human tumor size and configuration with the application of external quantifiable constraint field in the experimental mouse.
Citation Format: Remy Brossel. Biomechanics: A new therapeutic innovation deposit – From the proof of concept to the proof of efficacy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A41.
Abstract A49: Tumor-associated interstitial flow promotes macrophage migration and pro-metastatic M2 phenotype in 3D ECM
Authors: Li Ran , Xing Hao , Lee Tara A. , Azizgolshani Hesham , Kamm Roger D. 
Published: March 2017

Abstract
The growth of solid tumor is often accompanied by an increase in the flow of interstitial fluid (interstitial flow) from the center of the tumor to the surrounding stroma. Recent studies have shown that elevated interstitial flow can influence the migration of cancer cells and fibroblasts. Despite these findings, the effects of interstitial flow on macrophages, one of the key metastasis-promoting tumor-associated stromal cell types, have not been explored. We used microfluidic and transwell flow assays to investigate how high level of interstitial flow (~3 μm/s) often observed in tumor affect macrophage migration and protein expression. We found that interstitial flow not only enhanced macrophage migration speed, but also directed macrophages to migrate against the flow in 3D extracellular matrix. Moreover, we discovered that interstitial flow activated Akt and FAK, two kinases that are crucial for cell migration. Interestingly, interstitial flow also up-regulated macrophage expression of M2 markers Arg I and TGFβ through the activation of JAK1-STAT3/6 pathway. Finally, macrophages treated with interstitial flow were shown to have enhanced abilities to promote cancer cell migration and protrusion formation. Taken together, these results suggest that interstitial flow can promote metastasis through its effects on macrophages. Specifically, since macrophages migrate against the flow, interstitial flow, which emanates from the tumor, can act as a mechanical stimulus to recruit macrophages into tumor tissues. Moreover, interstitial flow can activate macrophages and polarize them toward pro-metastatic M2 phenotype to further promote tumor metastasis and immunosuppression.
Citation Format: Ran Li, Hao Xing, Tara A. Lee, Hesham Azizgolshani, Roger D. Kamm. Tumor-associated interstitial flow promotes macrophage migration and pro-metastatic M2 phenotype in 3D ECM. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A49.
Abstract A63: Collective and individual migration after the epithelial-mesenchymal transition in engineered microenvironments
Authors: Wong Ian Y. 
Published: March 2017

Abstract
Scattering and local dissemination of individual cells from a collective invasion front has been associated with the epithelial-mesenchymal transition (EMT). This phenotypic heterogeneity and plasticity has been challenging to reconstruct using classical assays which only measure population averages at endpoints. Here, we comprehensively track single cell invasion dynamics within engineered microenvironments such as microfabricated pillar arrays as well as 3D biomaterial scaffolds. After EMT induction through the master regulator Snail in mammary epithelial cells, we find distinct phenotypic subpopulations that display collective or individual migration behaviors. We show that these complex behaviors can be physically understood in terms of a phase transition during the solidification of binary alloys. Biologically, this conceptual framework addresses two essential mechanisms—phenotypic cell sorting and interconversion. We present new results to corroborate this model by systematically varying the composition of mosaic populations with both epithelial and EMT phenotypes. We also perturb these behaviors using migration-inhibiting compounds, revealing that different invasion phenotypes are correlated with differences in drug sensitivity. Altogether, this integration of engineered microenvironments with single cell resolution may permit new quantitative insights into the interplay of invasion, drug resistance and heterogeneity.
Citation Format: Ian Y. Wong. Collective and individual migration after the epithelial-mesenchymal transition in engineered microenvironments. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A63.
Abstract B04: From modeling to in vivo tracking: a new platform for the design of delivery vectors that exploit tumor microfluidics
Authors: Nizzero Sara , Litvinov Sergey , Alexeev Dmitry , Economides Athena , Rosa Enrica De , Wolfram Joy , Koumoutsakos Petros , Ferrari Mauro 
Published: March 2017

Abstract
Within the field of oncology, a new perspective has recently emerged, where cancer treatment is viewed as a transport problem that can be addressed with nanomedicine. In fact, because of the unique local conditions of transport and microfluidics in the tumor environment, microparticles and nanoparticles that exhibit specific geometries have proven advantageous to enhance preferential delivery of drugs to tumor tissue. However, the theoretical and modeling backbone required to describe, understand, and manipulate such flow-specific design advantages is currently limited to semi-analytical methods. These methods have proven successful in explaining the power and efficacy of geometrical targeting. Nevertheless, since such approaches have limited predictive power, they are not ideal tools for the systematic development of a new class of efficient and customizable delivery vectors.
In this work, we propose an innovative and rational approach for understanding the delivery of micro- and nanotherapeutics to cancer tissue by modeling transport in tumor microvessels. Specifically, we focus on the differences between healthy and tumor vasculature that affect fluid mechanics.
We tackle this problem with a combined experimental and modeling approach. Our model is based on a Navier-Stokes solver for complex fluids based on dissipative particle dynamics (DPD) simulations, where blood constituents (i.e. red blood cells, neutrophils, platelets) and microparticles/nanoparticles interact through forces or collisions of different nature. The model is calibrated and validated with real-time flow chamber experiments. With this modeling approach, complex geometrical structures and interactions can be implemented with high computational efficiency. We use our innovative platform to analyze the differences in margination of micro- and nanostructures in tumor versus healthy microvasculature. We address the fundamental structural differences between tumor vessels and healthy vessels by systematically reconstructing the characteristic patterns of endothelial fenestrations, radius variability, and blood flow. Our parametric analysis is then compared with in vivo tracking studies in animal models.
Our approach and results open the way to the understanding and rational design of a new class of nanoparticle and microparticle-based delivery strategies that exploit tumor-specific microfluidics.
Citation Format: Sara Nizzero, Sergey Litvinov, Dmitry Alexeev, Athena Economides, Enrica De Rosa, Joy Wolfram, Petros Koumoutsakos, Mauro Ferrari. From modeling to in vivo tracking: a new platform for the design of delivery vectors that exploit tumor microfluidics. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B04.
Abstract B15: Computed tomography for quantitative imaging of live cancer cells with isotropic 3D spatial resolution
Authors: Kelbauskas Laimonas , Shetty Rishabh M. , Cao Bin , Wang Kuo-Chen , Smith Dean , Wang Hong , Chao Shih-Hui , Ashcroft Brian , Kritzer Margaret , Glenn Honor , Niemela Erik , Johnson Roger H. , Eriksson John , Meldrum Deirdre R. 
Published: March 2017

Abstract
Quantitative 3D imaging of live single tumor cells enables direct insights into the intricacies of cellular machinery while offering new ways of assessing intercellular variability. Since its invention, X-ray computed tomography has been indispensable in the clinic for cancer diagnostic and prognostic purposes due to its quantitative manner of imaging owing to the isotropic 3D spatial resolution. Although its principles have recently begun to be implemented in the optical spectral range for single cell imaging, the applications have mainly been directed towards imaging fixed cells in absorption mode for studying an important hallmark of cancer - nuclear architecture. We present an approach that utilizes the concept of computed tomography for quantitative functional 3D imaging of live single cells. The method offers truly isotropic 3D spatial resolution and enables imaging of natural suspension cells, such as non-solid tumor or immune system cells, as opposed to cells attached to substrates, as is common to the majority of other imaging approaches. We report on technical characteristics of the method as well as experimental findings of a nuclear and mitochondrial dynamics study in human myelogenous leukemia and mouse macrophage cells as a validation. The absolute quantification capability of the method makes it a powerful tool in the field of oncology by enabling direct studies of cellular and nuclear architecture dynamics in the context of tumorigenesis and progression.
Citation Format: Laimonas Kelbauskas, Rishabh M. Shetty, Bin Cao, Kuo-Chen Wang, Dean Smith, Hong Wang, Shih-Hui Chao, Brian Ashcroft, Margaret Kritzer, Honor Glenn, Erik Niemela, Roger H. Johnson, John Eriksson, Deirdre R. Meldrum. Computed tomography for quantitative imaging of live cancer cells with isotropic 3D spatial resolution. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B15.
Abstract B52: 2-in-1 “sniper” nanomedicines rescue dendritic cells by two pronged inhibition of JAK2/STAT-3 and p38 MAPK pathways
Authors: Natarajan Siva Kumar , Chandhrasekar Vineethkrishna , Ismail Noha , Swaminathan Sharada , Sengupta Shiladitya , Kulkarni Ashish 
Published: March 2017

Abstract
Immunotherapy has stolen the spotlight as one of the most promising therapeutic strategies for many late stage cancers. Despite exhibiting immense potential, dendritic cell (DC) based immunotherapy has shown limited clinical benefits owing to the antagonistic effects of regulatory T cells. While regulatory T-cells dampen the immune response elicited by T effector cells through known control mechanisms, they also constitute an immune suppressive milieu with several other tumor-derived factors that impair the development and maturation of dendritic cells. This serves as a mechanism for the tumor cells to escape immune surveillance and control. It is well known that inhibition of the JAK2/STAT-3 and p38 MAPK pathways in DCs negates the tumor-induced suppression of their maturation. But it has been shown that inhibition of the STAT-3 pathway alone could counteract the suppressive effects of Interleukin-6 only and inhibition of the p38 MAPK pathway in cancer cells can be counterproductive as it is important for apoptosis. Thus it becomes essential that, to achieve a superior therapeutic response it is imperative to couple the inhibition of STAT-3 along with p38 MAPK pathway and to also ensure that it is targeted towards dendritic cells of the tumor microenvironment. We have catered to these necessities in this study by proposing a novel, supramolecular 2-in-1 nanomedicine designed by the self-assembly of patient compatible lipids that houses a STAT-3 inhibitor and a p38-α inhibitor , thus ensuring the deterministic delivery of both the drugs in a spatially constrained manner. We have shown that the 2-in-1 nanomedicine achieves superior efficacy by releasing both the drugs in a sustained manner during the differentiation of DCs and hence upregulates dendritic cell maturation markers like CD80, CD86 and MHC II. More importantly we aim to program the drug-loaded nanoparticles for selective uptake by dendritic cells of the tumor milieu. In a separate experiment we have shown that dendritic cells favor the uptake of nanoparticles with specific surface charges both in vitro and in vivo in B16F10 mouse melanoma model. Thus we conclude that the proposed 2-in-1 “sniper” nanoparticle can contribute immensely towards a targeted immunotherapy approach for rescuing dendritic cells from immune suppression in aggressive cancers like melanoma.
Note: This abstract was not presented at the conference.
Citation Format: Siva Kumar Natarajan, Vineethkrishna Chandhrasekar, Noha Ismail, Sharada Swaminathan, Shiladitya Sengupta, Ashish Kulkarni. 2-in-1 “sniper” nanomedicines rescue dendritic cells by two pronged inhibition of JAK2/STAT-3 and p38 MAPK pathways. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B52.
Abstract B59: Mathematical Model of Oxygen Transport in Tuberculosis Granulomas
Authors: Datta Meenal , Via Laura , Chen Wei , Baish James , Xu Lei , Barry Clfton , Jain Rakesh 
Published: March 2017

Abstract
Pulmonary granulomas—the hallmark of Mycobacterium tuberculosis (MTB) infection—are dense cellular lesions that, like solid tumors, often feature regions of hypoxia and necrosis partially due to limited transport of oxygen. Low oxygen in granulomas can impair the host immune response, while MTB are able to adapt and persist in hypoxic environments. Here, we used a physiologically based mathematical model of oxygen diffusion and consumption, based on models originally derived for avascular tumors, to calculate oxygen profiles within the granuloma, assuming Michaelis-Menten kinetics. An approximate analytical solution—using a priori and newly estimated parameters from experimental data in a rabbit model of tuberculosis—was able to predict the size of hypoxic and necrotic regions in agreement with experimental results from the animal model. Such quantitative understanding of transport limitations can inform future tuberculosis therapeutic strategies that may include adjunct host-directed therapies that facilitate oxygen and drug delivery for more effective treatment.
Citation Format: Meenal Datta, Laura Via, Wei Chen, James Baish, Lei Xu, Clfton Barry, Rakesh Jain. Mathematical Model of Oxygen Transport in Tuberculosis Granulomas. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B59.
Abstract IA07: Single cell functional proteomics and metabolomics: A conduit to physicochemical models of tumor biology
Authors: Heath James R. 
Published: March 2017

Abstract
Advances in single cell methods have opened up fundamentally new ways to think about biology. One new concept involves specific experiments that provide a direct and quantitative bridge between complex biological phenomena and the physico-chemical laws. To this end, we have developed microchip-based methods for measuring large panels of functional proteins and metabolites from statistical numbers of single cells. Functional proteins include secreted signaling proteins that provide measures of immune cell behaviors, and phosphorylated (activated) enzymes that reflect intracellular signaling flux and are often hyperactivated (and thus constitute drug targets) in cancers. For metabolites, we have focused on those associated with cellular energy flux. Importantly, cells sense and respond to their environments by adjusting the levels of such analytes. The following observations are the basis for connecting such measurements to the physico-chemical laws:
1. Cells are finite systems in a thermodynamic sense. This means that otherwise identical cells will have different numbers of the measured analytes.
2. A histogram of levels of the analytes versus frequency of observation across many single cells represents the fluctuations of those cells. In the maximum entropy formulation of thermodynamics, fluctuations can be used to identify the stable steady state of the cells (the state of minimum free energy), as well as constraints that prevent (constrain) the cells from reaching that steady state.
3. When many analytes are measured from the same cells, analyte-analyte correlations are extracted. If the measurements are quantitative (as are ours), then relationships between the chemical potential of a given analyte and its copy numbers is established. These to values represent cognate intensive and extensive parameters, and can allow for precise predictions for how cells respond to a weak perturbation through the Principle of Le Chatelier. They also provide an approach for distinguishing between weak and strong perturbations, since strong perturbations cause a cell-state change, while weak perturbations do not.
In this talk, I will discuss provide detail on the above described experimental platforms, and describe how analyses based on these concepts can yield insight into clinically meaningful problems associated with therapy resistance in glioblastoma and melanoma.
Citation Format: James R. Heath. Single cell functional proteomics and metabolomics: A conduit to physicochemical models of tumor biology. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA07.
Abstract IA20: Material-based therapeutic cancer vaccines
Authors: Mooney David J. 
Published: March 2017

Abstract
The recent successes of checkpoint blockade therapy demonstrate the power of immunotherapy. The correlation between patient response to these therapies and the extent of T cell infiltration into tumors suggest that vaccines capable of generating robust T cell responses to cancer antigens may lead to a greater fraction of patients responding to checkpoint blockade. Therapeutic cancer vaccines often depend on extensive manipulation of antigen presenting cells in the laboratory, but subsequent cell infusion typically leads to large-scale cell death and limited efficacy. We are instead developing biomaterials that provide controlled delivery of immunomodulatory factors, in certain ways mimicking aspects of microbial infection, to resident dendritic cells in order to bypass the need to manipulate cells in the laboratory. These material strategies allow control over immune cell trafficking and activation, cause tumor regression in preclinical models, and are currently in a Phase I clinical trial. Recent preclinical studies demonstrate synergy between these material-based vaccines and anti-PD1/CTLA4.
Citation Format: David J. Mooney. Material-based therapeutic cancer vaccines. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA20.