Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 21 for “"intratumoral heterogeneity"”.
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Rational drug combinations design against intratumoral heterogeneity and clonal evolution
… This results in complex clonal architecture and intratumoral heterogeneity in each patient. This also presents challenges for effective therapeutic intervention - with constant selective pressure to induce or select pre-existing resistant subclones toward drug resistance. …
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The Development of a Printable Device with Gravity-Driven Flow for Live Imaging Glioma Stem Cell Motility
… 13 months with current standard of care. Intratumoral heterogeneity is a common characteristic that hinders GBM treatment in the form of therapy resistant cell subsets and influence on cellular phenotypes. One cell subset in particular, glioma stem cells (GSCs), is frequently left behind …
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Clonal Phenotype Mapping Reveals Genomic Alterations Underlying Tumor Immunosuppression during Immunotherapy
… treatment option, we investigated the role of intratumoral heterogeneity in influencing immune interactions. Using orthotopic clonal replica tumors, we tracked clonal dynamics in response to anti-PD1 therapy and found that while treatment had limited impact on overall tumor volume, it induced …
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NON-GENETIC MECHANISMS OF CHEMORESISTANCE IN ACUTE MYELOID LEUKEMIA
… in leukemic cells has been associated with intratumoral heterogeneity, among which quiescence, specifically, is considered a key factor for cell survival. Experimental evidence collected both from patients and model systems suggests that relapse is due to rare persistent AML cells which …
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A Pan-Cancer Single-Cell Analysis of Intratumoral Copy Number Diversity and Evolution
… studies have revealed extensive inter-patient heterogeneity (IPH) in copy number profiles. However, the extent of intratumoral heterogeneity (ITH) and its evolutionary dynamics remain poorly understood.</p> <p>To address these gaps, we developed Acoustic Cell Tagmentation (ACT), an advanced …
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Investigating The Rare Aneuploid Cells in Normal Breast and Therapeutic Resistance in Triple Negative Breast Cancer Using Single Cell Genomics
… next investigated the tumor evolution and tumor heterogeneity in triple-negative breast cancer (TNBC) under the chemo-resistance context. TNBC is an aggressive subtype that is frequently treated with chemotherapy, but only half of the patients have a complete response. Here, we performed single …
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Computational Approaches to Delineate Transcriptional and Functional Heterogeneity In Pancreatic Cancer
… comprehensively characterize the transcriptional heterogeneity of PDAC. Specifically, focusing on a large PDAC PDX cohort, we focused on a) establishing a PDAC co-expression network to serve as a foundation for quantifying disease diversity within the cohort, while in parallel b) optimizing an …
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Developing a biomaterial model of the glioblastoma perivascular niche to investigate the effects of angiocrine signals on disease progression
… The challenge in treating GBM is a product of intratumoral heterogeneity and a pro-tumorigenic microenvironment. Specifically, the perivascular niche (PVN) of GBM has been shown to facilitate tumor cell invasion and harbor a subpopulation of cancer stem cells, which are implicated in …
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Investigation of anticancer activity and mechanisms of Meso- 2,3-dimercaptosuccinic acid (DMSA) in glioblastoma cell lines
… It is characterized by high intertumoral and intratumoral heterogeneity and a low survival rate. Since 2005, the current gold standard of care for treating newly diagnosed GBM has remained the same: maximal safe resection, concomitant chemoradiation (CRT) with temozolomide (TMZ), and adjuvant …
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Development of a High-Throughput 3D Tumor Model for Bone Sarcomas
… of shear stress present within ES tumors due to intratumoral heterogeneity. In the final part of this thesis we investigated how the simultaneous presence of mesenchymal stem cells (MSCs) and flow perfusion affected drug sensitivity and phenotype of ES cells. We showed that the presence of MSCs …
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Identifying Epigenetic Regulators Of Tumor Dormancy And Recurrence
… the time course, as well as an increase in intratumoral heterogeneity. Based on these results, we developed a novel pair-wise comparison analytical method that performed comparably to the-state-of-the-art method, MAGeCK. Additionally, we developed novel scoring methods for enrichment-based …
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Multiplexed angiogenic biomarker quantification on single cells
… concentrations as well as the cell-by-cell heterogeneity. I establish protocols to measure cell membrane VEGFR, NRP1, Tie2, and PDGFR concentration on several cell and tissue models including human dermal fibroblasts (HDFs) in vitro, a 2D endothelial/fibroblast co-culture model in vitro, and …
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Investigating the expression of plasma membrane calcium ATPase (PMCA) in patient-derived glioblastoma cultures
… tumour in adults, characterised by extensive heterogeneity, rapid progression, and resistance to conventional therapies such as surgery, radiotherapy, and chemotherapy. Despite decades of research, the median survival for glioblastoma patients remains approximately 15 months, and recurrence is …
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Crosstalk between natural killer cells and cancer associated fibroblasts in the tumour microenvironment
… CAF has proven challenging due to their complex intratumoral heterogeneity and plasticity. However, the potential exploitation of NK cell cytotoxicity remains attractive in the field of cancer immunotherapy. This work aimed to investigate the crosstalk between CAF and NK cells and to identify …
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The Impact of Radiation on Glioblastoma Evolution
… implications by examining the influence of intratumoral heterogeneity (ITH) on intrinsic radiosensitivity, by determining the effects of radiation on glioma stem-like cell (GSC) initiated orthotopic xenografts, and by assessing radioresistance with a reirradiation protocol. To determine the …
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DEVELOPMENT OF A BIOINFORMATICS FRAMEWORK TO IDENTIFY CELL SUBPOPULATIONS FROM BULK TRANSCRIPTIONAL DATA
… biological samples are affected by the intrinsic heterogeneity of cells and tissue composition. Nevertheless, in bulk transcriptional profiling, each sample is evaluated without considering the presence of multiple subpopulations. This limitation might be extremely critical when analyzing bulk …
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Detecting and molecular profiling cancer cells in patients
… and diagnoses. Also, a surprising degree of heterogeneity in protein expression both across different patient samples and even within the same tumor was observed, which has important implications for molecular diagnostics and therapeutic drug targeting. In the second section we molecularly …
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IDENTIFICATION OF NCAM1 AS A NOVEL PROGNOSTIC PROSTATE CANCER STEM CELL BIOMARKER
… are mandatory for understanding the intricate intratumoral heterogeneity (spatial and molecular) of PCa and for developing relevant clinical tools to effectively manage patients and tailor therapy. Here, we proposed the surface glycoprotein neural cell adhesion molecule (NCAM1/CD56), a known …
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Potential of metabolic MRI to address unmet clinical needs in localised renal cancer.
… MRI (HP <sup>13</sup>C-MRI) to probe metabolic intratumoral heterogeneity in renal cancer. I discovered that within a single tumour, regions of varying degrees of perfusion and Warburg effect are present, which differ in aggressiveness. Chapter 2 presents my findings in two clinical scenarios: …
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Microenvironmental and metabolic influences in tumor cell redox homeostasis
… environmental selective pressures, and intratumoral heterogeneity. To further advance efficacious and selective anticancer strategies, increased understanding of microenvironmental and metabolic influences in tumor cells redox homeostasis is needed. Poorly arranged and malfunctioning …
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