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 36 for “"RTKs"”.
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Multivariate studies of receptor tyrosine kinase function in cancer
Receptor tyrosine kinases (RTKs) are critical regulators of cellular homeostasis in multicellular organisms. They influence cell proliferation, migration, differentiation, and transcriptional activation, among other processes, and are therefore also relevant to cancer biology. Upon interaction with …
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Receptor Tyrosine Kinases-Mediated Acquired Parp Inhibitor Resistance In Breast Cancer
… hyper-activated receptor tyrosine kinases (RTKs), are involved in enhancing DNA damage repair and decreasing affinity of PARP-is to PARP1. Among the candidate RTKs, MET has more small molecules inhibitors that can target it, and thus, my colleagues and I made it a priority in investigating …
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Nuclear Translocation of Met Via Internet Mechanism
<p>MET is one of the receptor tyrosine kinases (RTKs) that are overexpressed in malignant cancer types, including breast cancer. While RTKs are traditionally known for their roles in signaling transduction from the cell surface, recent studies have provided evidence demonstrating that most of RTKs …
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Design and Synthesis of Pyrimidine Fused Heterocycles as Single Agents with Combination Chemotherapy Potential
… one or more of the receptor tyrosine kinases (RTKs)– vascular endothelial growth factor receptor–2 (VEGFR2), platelet derived growth factor receptor–β (PDGFRβ) and epidermal growth factor receptor (EGFR). The complexity of the angiogenic pathways in tumors implies that disrupting a single …
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Synthesis and Molecular Modeling Studies of Bicyclic Inhibitors of Dihydrofolate Reductase, Receptor Tyrosine Kinases and Tubulin
… synthesized and studied as inhibitors of pjDHFR, RTKs and tubulin: </p><p> 1. 2,4-Diamino-6-(substituted-arylmethyl)pyrido[2,3-d]pyrimidines</p><p> 2. 4-((3-Bromophenyl)linked)-6-(substituted-benzyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amines</p><p> 3. …
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Using Xenopus laevis to study the mechanisms governing the early germline development and the formation of vertebrate body plan
… the body plan. Ligand-independent activation of RTKs allows dissecting the receptor-specific signaling outcomes from the pleiotropic effects of the ligands. In this regard, RTK intracellular domains (ICDs) are of interest due to their ability to recapitulate signaling activity in a …
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Predicting angiogenic receptor trafficking and signaling via computational systems biology
… cell responses for receptor tyrosine kinases (RTKs). However, how endocytosis fundamentally mediates signaling for any RTK remains poorly defined. Understanding how endocytosis fundamentally directs intracellular receptor signaling requires receptor-specific endocytosis mechanisms to be …
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An Optogenetic Toolbox for the Interrogation of Dynamic Events During Angiogenesis
… We demonstrated that LightR regulation of RTKs provides spatiotemporal control over VEGFR2 signaling. Furthermore, we demonstrated that previous VVD modifications conserved their effect in RTK regulation. Despite these successes, LightR-VEGFR2 regulation was perturbed in endothelial cells. …
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Modulation of Pi3K-Akt Pathway In Colorectal Cancer
… Expression of several receptor tyrosine kinases (RTKs) increased after AKT inhibition; insulin like growth factor 1 receptor (IGF1R) was significantly upregulated in patients, PDX and cell lines (P</p> <p>The PI3K pathway also modulates tumor immune microenvironment and may influence response to …
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Systems modeling of quantitative kinetic data identifies receptor tyrosine kinase-specific resistance mechanisms to MAPK pathway inhibition in cancer
… of targeted or bypass receptor tyrosine kinases (RTKs). While the latter is often attributed to gene amplification, genetic characterization of tumor biopsies has failed to explain substantial proportions of resistance. We hypothesize that post-synthesis mechanisms governing RTK levels may …
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Design and synthesis of pyrimido[4,5-b]indoles and furo[2,3-d]pyrimidines as single agents with combination chemotherapy potential or as inhibitors of tubulin or thymidylate synthase
… and is mediated by receptor tyrosine kinases (RTKs). Combination chemotherapies of RTK inhibitors with cytotoxic agents that target either TS or tubulin have shown significant promise and several preclinical and clinical studies with such combinations are in progress. Multitargeted single …
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Target Based Design And Synthesis of Heterocycles in the Potential Treatment of Cancer and Opportunistic Infection
… effect is mediated by receptor tyrosine kinases (RTKs) and therefore, RTK inhibitors are used widely in the treatment of various types of cancers. To overcome the limitations of current cancer chemotherapy namely, dose limiting toxicity and multidrug resistance, quinazolines were designed and …
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Discovery of Pyrimidine-based Heterocycles as Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment of Cancer
… of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor (EGFR) in single entities. Single agents with both antiangiogenic activities as well as …
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EXPLORING THE CROSSTALK BETWEEN POLO-LIKE KINASE 1 AND Eph-FAMILY OF RECEPTORS IN CELL DIVISION IN PANCREATIC CANCER MODEL
… a mitotic kinase and Receptor tyrosine kinases (RTKs) which promotes metastatic behaviour. Of the majority of Eph receptors EphA2 is overexpressed in many cancers and in PDAC as well. A wealth of literature has reported an increased expression of PLK1 but therapeutic targeting has not been …
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The Role of p66Shc in Stem Cells: Signalling, Identity and Apoptosis
… the Shc family link receptor tyrosine kinases (RTKs) to downstream signalling, thereby shaping cell fate decisions. While the canonical isoforms p52Shc and p46Shc act as Ras–MAPK transducers, the longer p66Shc isoform harbours an additional CH2 domain that confers distinct regulatory properties. …
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The Interplay of Signal Transduction and Membrane Traffic of the Macrophage Colony Stimulating Factor Receptor (MCSFR) Controls Macrophage Growth
… as well as myelogenous leukemias. Clearance of RTKs from the plasma membrane is an important mechanism for regulating the signal amplitude, however, the exact mechanisms remain elusive. To better define these mechanisms, we characterized MCSFR internalization, endocytic trafficking, and …
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Heparan Sulfate Proteoglycans in Pancreatic Ductal Adenocarcinoma (PDAC)
… enhance the activation of multiple RTKs, thereby promoting resistance to KRAS*-targeted therapy. Overall, our study has provided the rationale for therapeutic targeting of the YAP-SDC1 axis to overcome resistance to KRAS* inhibition and improving the clinical outcome of patients with …
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Understanding Membrane Curvature Sensing
… loop 3 and receptor tyrosine kinase (RTKs) via adaptor proteins. However, a specific recognition motif has not been identified yet. Here, using a combination of biophysical approaches and NMR spectroscopy, I characterised the Endophilin binding motif of ALIX (ALG-2-interacting protein …
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A mechanism of activation of c-MET receptor tyrosine kinase
… recent body of evidence suggesting that certain RTKs are kinase active on cell surface in absence of ligand-induced oligomerization, we hypothesized that oligomerization could be important for other aspects of RTK activation. Using c-MET as our model system, we investigated the role of …
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Dissecting mechanisms and consequences of oncogenic RTK fusion signaling
… thereby resensitizes RTK signaling. Resensitized RTKs promote rapid and pulsatile ERK reactivation originating from paracrine ligands shed by dying cells. Reactivated ERK signaling promotes cell survival, which can be counteracted by combination therapies that block paracrine signaling. EML4-ALK …
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