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Full-Text Articles in Life Sciences
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess
Open Access Theses & Dissertations
Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …
Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario
Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario
Doctoral Dissertations
Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …
Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham
Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham
Legacy Theses & Dissertations (2009 - 2024)
The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …
The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown
The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown
Dartmouth College Ph.D Dissertations
The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model …
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams
Electronic Thesis and Dissertation Repository
B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …
Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna
Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna
Graduate Theses and Dissertations
The Ras superfamily of small G proteins are involved in cell-signaling processes that, if not regulated, may lead to cell multiplication, apoptosis inhibition, and tumorigenesis. They function as molecular switches, which through GTP/GDP exchange cycle, switch on or off cellular activities. Overexpression and/or hyperactivity of these proteins have been linked to many diseases including various cancers. CDC42, a member of the Rho subfamily of the Ras superfamily of small G proteins, participates in the regulation of many cellular processes including cell adhesion, mitosis, and cytoskeletal rearrangements. CDC42 binds to and activates many effector proteins including CDC42-activated kinase (ACK). Abnormal activities …
Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier
Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier
Biomedical Engineering Undergraduate Honors Theses
Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …
Developing Novel Water-Soluble Porphyrins For Potential Use As Photosensitizers In Photodynamic Therapy, Kayla R. Whittington
Developing Novel Water-Soluble Porphyrins For Potential Use As Photosensitizers In Photodynamic Therapy, Kayla R. Whittington
Honors Theses
Photodynamic therapy (PDT) is a treatment modality for various illnesses, including some types of cancer. Lung cancer is the leading cause of cancer death in the United States. The prevalence of lung cancer in certain gender, racial, ethnic, and socioeconomic groups add to existing health disparities in the United States. For this reason, it is necessary to address the social determinants underlying lung cancer disparities, as well as improve treatment options. These treatment options should be cost effective, convenient, and increase survival rates. This research focused on synthesizing novel water-soluble porphyrin compounds for use as photosensitive agents in PDT for …
Analysis Of Invasion Proteins Mmp2, Mmp9, Adam12, And Adam17 In Glioblastoma U87mg Cells Treated With Anti-Cancer Compound 3,4-Dimethoxybenzaldehyde, Andras Muranyi
Honors Theses
This research tested the effectiveness of novel compound 3,4-dimethoxybenzaldehyde, demonstrated to have anti-cancer properties. U87MG Glioblastoma cells were exposed to the compound at its LC50 concentration, then processed to collect proteins from the cells. Proteins were analyzed via Western blotting for specific protein levels of matrix metalloproteinase 2 and 9 (MMP) and disintegrin and metalloprotease 12 and 17 (ADAM). Previous research indicates these proteins are involved in the invasive properties of glioblastoma cells. Westerns were quantified with ImageJ and compared using a one-way ANOVA. Results indicate the compound has minimal effect upon the expression of MMP2, MMP9, ADAM12, ADAM17 proteins.
Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph
Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph
Electronic Theses and Dissertations
The aberrant fibrous, extracellular, and intracellular proteinaceous deposits in cells, organs and tissues are referred to as amyloids. These deposits are dominated by β-sheet structures that have been implicated in several neurodegenerative diseases and cancer. In this work, the types of amyloidosis studied include Parkinson’s disease (PD) using UA196 and NL5901 strains of Caenorhabditis elegans (C. elegans), Alzheimer’s disease (AD) using GMC101 strain of C. elegans, and cancer-associated mutant p53 aggregation in MIA PaCa-2 mutant cells. Several molecules including SK-129, NS132, NS163, bexarotene, a polyphenol (-)-epi-gallocatechine gallate (EGCG), ADH40, RD148, and RD242 were screened in vitro and in …
The Relationship Between Inflammatory Diet Score And Cancer Outcomes: Systematic Review And Meta-Analysis, Eric Han
Honors Undergraduate Theses
Cancer remains one of the most prevalent diseases in the United States and a leading cause of death. Large prospective studies have found significant correlations between dietary intake and cancer. Chronic inflammation promotes pro-cancer inflammatory environments promoting the formation and growth of tumors while preventing effective anti-tumor responses. Nutrition can impact inflammation, with the intake of certain food items increasing biomarkers for systemic inflammation thus, the objective of this research was to explore the relationship between inflammatory diet score measured by the Dietary Inflammatory index and all-cause mortality, cancer-specific mortality, and cancer recurrence among cancer survivors. Web of Science, Medline, …
Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells, Min Zhang
MSU Graduate Theses
The study of the interaction of engineered nanoparticles, including quantum dots (QDs), with cellular constituents and the kinetics of their localization and transport, has provided new insights into their biological consequences in cancers and for the development of effective cancer therapies. The present study aims to elucidate the toxicity and intracellular transport kinetics of CdSe/ZnS and InP/ZnS QDs in late-stage ML-1 thyroid cancer using well-tested HeLa cells as a control. The XTT viability assay showed that ML-1 cells, and non-cancerous mouse fibroblast cells, exhibit no viability defect in response to these QDs, whereas HeLa cell viability decreases. These results suggest …