Person: Wang, Zhihui
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Wang
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Zhihui
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Wang, Zhihui
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Publication A New Concept for Cancer Therapy: Out-Competing the Aggressor(BioMed Central, 2008) Deisboeck, Thomas; Wang, ZhihuiCancer expansion depends on host organ conditions that permit growth. Since such microenvironmental nourishment is limited we argue here that an autologous, therapeutically engineered and faster metabolizing cell strain could potentially out-compete native cancer cell populations for available resources which in turn should contain further cancer growth. This hypothesis aims on turning cancer progression, and its microenvironmental dependency, into a therapeutic opportunity. To illustrate our concept, we developed a three-dimensional computational model that allowed us to investigate the growth dynamics of native tumor cells mixed with genetically engineered cells that exhibit a higher proliferation rate. The simulation results confirm in silico efficacy of such therapeutic cells to combating cancer cells on site in that they can indeed control tumor growth once their proliferation rate exceeds a certain level. While intriguing from a theoretical perspective, this bold, innovative ecology-driven concept bears some significant challenges that warrant critical discussion in the community for further refinement.Publication Life Sciences and the web: a new era for collaboration(Nature Publishing Group, 2008) Sagotsky, Jonathan A; Zhang, Le; Wang, Zhihui; Martin, Sean; Deisboeck, ThomasThe World Wide Web has revolutionized how researchers from various disciplines collaborate over long distances. This is nowhere more important than in the Life Sciences, where interdisciplinary approaches are becoming increasingly powerful as a driver of both integration and discovery. Data access, data quality, identity, and provenance are all critical ingredients to facilitate and accelerate these collaborative enterprises and it is here where Semantic Web technologies promise to have a profound impact. This paper reviews the need for, and explores advantages of as well as challenges with these novel Internet information tools as illustrated with examples from the biomedical community.Publication Simulating Non-small Cell Lung Cancer with a Multiscale Agent-based Model(BioMed Central, 2007) Wang, Zhihui; Zhang, Le; Sagotsky, Jonathan; Deisboeck, ThomasBackground: The epidermal growth factor receptor (EGFR) is frequently overexpressed in many cancers, including non-small cell lung cancer (NSCLC). In silico modeling is considered to be an increasingly promising tool to add useful insights into the dynamics of the EGFR signal transduction pathway. However, most of the previous modeling work focused on the molecular or the cellular level only, neglecting the crucial feedback between these scales as well as the interaction with the heterogeneous biochemical microenvironment. Results: We developed a multiscale model for investigating expansion dynamics of NSCLC within a two-dimensional in silico microenvironment. At the molecular level, a specific EGFR-ERK intracellular signal transduction pathway was implemented. Dynamical alterations of these molecules were used to trigger phenotypic changes at the cellular level. Examining the relationship between extrinsic ligand concentrations, intrinsic molecular profiles and microscopic patterns, the results confirmed that increasing the amount of available growth factor leads to a spatially more aggressive cancer system. Moreover, for the cell closest to nutrient abundance, a phase-transition emerges where a minimal increase in extrinsic ligand abolishes the proliferative phenotype altogether. Conclusion: Our in silico results indicate that in NSCLC, in the presence of a strong extrinsic chemotactic stimulus (and depending on the cell's location) downstream EGFR-ERK signaling may be processed more efficiently, thereby yielding a migration-dominant cell phenotype and overall, an accelerated spatio-temporal expansion rate.Publication Using Magnetic Resonance Microscopy to Study the Growth Dynamics of a Glioma Spheroid in Collagen I: A Case Study(BioMed Central, 2008) Huang, Shuning; Vader, David; Wang, Zhihui; Stemmer-Rachamimov, Anat; Weitz, David; Dai, Guangping; Rosen, Bruce; Deisboeck, ThomasBackground: Highly malignant gliomas are characterized by rapid growth, extensive local tissue infiltration and the resulting overall dismal clinical outcome. Gaining any additional insights into the complex interaction between this aggressive brain tumor and its microenvironment is therefore critical. Currently, the standard imaging modalities to investigate the crucial interface between tumor growth and invasion in vitro are light and confocal laser scanning microscopy. While immensely useful in cell culture, integrating these modalities with this cancer's clinical imaging method of choice, i.e. MRI, is a non-trivial endeavour. However, this integration is necessary, should advanced computational modeling be able to utilize these in vitro data to eventually predict growth behaviour in vivo. We therefore argue that employing the same imaging modality for both the experimental setting and the clinical situation it represents should have significant value from a data integration perspective. In this case study, we have investigated the feasibility of using a specific form of MRI, i.e. magnetic resonance microscopy or MRM, to study the expansion dynamics of a multicellular tumor spheroid in a collagen type I gel. Methods: An U87mEGFR human giloblastoma multicellular spheroid (MTS) containing approximately 4·103 cells was generated and pipetted into a collagen I gel. The sample was then imaged using a T2-weighted 3D spoiled gradient echo pulse sequence on a 14T MRI scanner over a period of 12 hours with a temporal resolution of 3 hours at room temperature. Standard histopathology was performed on the MRM sample, as well as on control samples. Results: We were able to acquire three-dimensional MR images with a spatial resolution of 24 × 24 × 24 μm3. Our MRM data successfully documented the volumetric growth dynamics of an MTS in a collagen I gel over the 12-hour period. The histopathology results confirmed cell viability in the MRM sample, yet displayed distinct patterns of cell proliferation and invasion as compared to control. Conclusion: In this study, we demonstrate that a specific form of MRI, i.e. magnetic resonance microscopy or MRM, can be used to study the dynamic growth of a multicellular tumor spheroid (MTS) with a single cell scale spatial resolution that approaches the level of light microscopy. We argue that MRM can be employed as a complementary non-invasive tool to characterize microscopic MTS expansion, and thus, together with integrative computational modeling, may allow bridging of the experimental and clinical scales more readily.