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Articles 1 - 12 of 12
Full-Text Articles in Life Sciences
Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney
Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney
Doctoral Dissertations
To metastasize, a cell must travel through circulation to a secondary tissue, and this process causes 90% of all cancer deaths. Although inefficient, metastasis is not random, and only capable seeds in hospitable soils are capable of outgrowing into detectable metastases. The overall hypothesis in this work is that the secondary tissue microenvironment, particularly the extracellular matrix (ECM), mediates metastasis. We posit that the ability of metastatic cells to survive dormancy, exit quiescence, and colonize a tissue depends upon the ability of the soil to sustain survival, and subsequently trigger outgrowth. We created a simple biomaterial platform with systematic control …
The Cellular Context Of Estradiol Regulation In The Zebra Finch Auditory Forebrain, Maaya Ikeda
The Cellular Context Of Estradiol Regulation In The Zebra Finch Auditory Forebrain, Maaya Ikeda
Doctoral Dissertations
Estradiol, traditionally known as a hormone that communicates with distant cells in the body, is also synthesized locally in the brain to act as a neuromodulator. Neuromodulators differ from neurotransmitters in that they simultaneously affect a population of neurons and their actions are not limited to the synapse. One of the many effects of estradiol signaling is rapid modulation of auditory processing in response to external stimuli. The enzyme required for estradiol synthesis, aromatase, is highly expressed in the regions that are involved in higher-order processing of sounds in humans and songbirds. Since zebra finches, a type of songbird, are …
Inhibition Of Dna Methylation In Acquired Tamoxifen-Resistant Breast Cancer: Cell Line Model And Clinical Implications, Stephanie Zimmers
Inhibition Of Dna Methylation In Acquired Tamoxifen-Resistant Breast Cancer: Cell Line Model And Clinical Implications, Stephanie Zimmers
Doctoral Dissertations
One out of every eight American women will develop invasive breast cancer throughout their lifetime. Approximately 70% of breast cancers are estrogen receptor alpha (ER)-positive and can therefore be treated with an anti-estrogen such as tamoxifen. Although tamoxifen treatment has been successful at reducing breast cancer death rates, nearly one-third of women treated with tamoxifen for 5 years will have disease recurrence. Therefore, it is imperative that researchers investigate the mechanisms involved in developing acquired tamoxifen resistance and identify biomarkers that are predictive of acquired resistance. DNA methylation is known to play a role in the development of breast cancer …
Alternative Methods For The Treatment Of Chemo-Resistant Cancers, Kaitlyn Wong
Alternative Methods For The Treatment Of Chemo-Resistant Cancers, Kaitlyn Wong
Doctoral Dissertations
Great strides have been made in cancer therapy in the past century, yet it remains one of the leading causes of death in the United States today. This work aimed to shed light on novel methods to treat a variety of aggressive and often chemo-resistant cancers both in vitro and in vivo. The first aim of this work was to evaluate the therapeutic efficacy of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) prodrugs compared to standard chemotherapeutic agents. Conjugation of polyMPC to drugs such as doxorubicin (Dox) can result in its improved solubility, prolonged half-life and therapeutic efficacy. PolyMPC and polyMPC-Dox (at a …
The Role Of The Formin Protein Family In Membrane Dynamics, Petrus Adrianus Cornelis Van Gisbergen
The Role Of The Formin Protein Family In Membrane Dynamics, Petrus Adrianus Cornelis Van Gisbergen
Doctoral Dissertations
Using molecular genetics, and high end imaging techniques, I assessed the function of the formin protein family in the moss Physcomitrella patens. Formins are proteins that can nucleate and elongate actin filaments. P. patens has 9 formins, divided over three classes. I found that a class II formin (For2A) is essential for polarized growth and specifically binds to the phosphoinositide PI(3,5)P2. Additionally, I show that this formin polymerizes actin filaments in vivo. I demonstrated that binding PI(3,5)P2 is essential for formin function. My work also shows that one of the class I formins (For1F) is involved …
Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen
Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen
Doctoral Dissertations
The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …
Dna-Based Epigenetic Changes In Recurrent And Tamoxifen-Resistant Breast Cancer, Kristin E. Williams
Dna-Based Epigenetic Changes In Recurrent And Tamoxifen-Resistant Breast Cancer, Kristin E. Williams
Doctoral Dissertations
Roughly two-thirds of all breast cancers are Estrogen Receptor a (ER)-positive and can be treated with an anti-estrogen such as Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 years. In addition to this acquired antiestrogen resistance, de novo- or intrinsic-resistance occurs primarily in ER-negative tumors but also occasionally in ER-positive tumors. Aberrant DNA promoter methylation, a major epigenetic mechanism by which gene expression is altered in cancer, is thought to play a role in this resistance. To date, few studies have examined promoter methylation and Tamoxifen resistance in breast cancer. Of the …
Nano Clay-Enhanced Calcium Phosphate Cements And Hydrogels For Biomedical Applications, Udayabhanu Jammalamadaka
Nano Clay-Enhanced Calcium Phosphate Cements And Hydrogels For Biomedical Applications, Udayabhanu Jammalamadaka
Doctoral Dissertations
Biomaterials are used as templates for drug delivery, scaffolds in tissue engineering, grafts in surgeries, and support for tissue regeneration. Novel biomaterial composites are needed to meet multifaceted requirements of compatibility, ease of fabrication and controlled drug delivery. Currently used biomaterials in orthopedics surgeries suffer limitations in toxicity and preventing infections. Polymethyl methacrylate (PMMA) used as bone cement suffers from limitations of thermal necrosis and monomer toxicity calls for development of better cementing biomaterials. A biodegradable/bioresorbable cement with good mechanical properties is needed to address this short coming. Metal implants used in fixing fractures or total joint replacement needs improvements …
Biophysical Studies Of Cell Division Protein Localization Mechanisms In Escherichia Coli, Matthew Wayne Bailey
Biophysical Studies Of Cell Division Protein Localization Mechanisms In Escherichia Coli, Matthew Wayne Bailey
Doctoral Dissertations
How nanometer-scale proteins position accurately within micron-scale bacteria has intrigued both biologists and physicists alike. A critical process requiring precise protein localization is cell division. In most bacteria, cell division starts with the self-assembly of the FtsZ proteins into filaments that form a ring-like structure encircling the cell at its middle, the Z-ring. The Z-ring is a scaffold for additional proteins that synthesize the lateral cell wall which separates the two daughter cells. If division planes are misplaced relative to bacterial chromosomes, also called nucleoids, daughter cells with incomplete genetic material can be produced. In Escherichia coli, research carried out …
Studies Of Kinetochore Mechanobiology In Drosophila, Stuart Cane
Studies Of Kinetochore Mechanobiology In Drosophila, Stuart Cane
Doctoral Dissertations
Kinetochores are large multiprotein structures through which chromosomes engage with the microtubules of the mitotic spindle. All kinetochore pairs must ultimately adopt a bioriented configuration, with their associated sister chromatids linked to opposite spindle poles and poised to segregate equally between two daughter cells. Erroneous, non-bioriented attachments that are left uncorrected lead to chromosome mis-segregation, producing aneuploid daughter cells with unequal numbers of chromosomes. Before anaphase onset, bioriented attachments are selectively stabilized whereas non-bioriented attachments remain unstable and are eliminated. This error correction process relies heavily on the extent of outer kinetochore phosphorylation by an Aurora B kinase activity centered …
Mammalian Egg Activation: The Roles Of Trpv3 Channels And Plcz1, Hoi Chang Lee
Mammalian Egg Activation: The Roles Of Trpv3 Channels And Plcz1, Hoi Chang Lee
Doctoral Dissertations
Calcium channels at the plasma membrane have been suggested to mediate Ca2+ influx during egg activation. The transient receptor potential (TRP) Ca2+ channel, TRPV3, is differentially expressed in oocytes during maturation, being fully active at MII stage. Specific stimulation of TRPV3 channels in mouse eggs promotes Ca2+ influx sufficient to induce egg activation and parthenogenesis. In chapter 2, we explore the function and distribution dynamics of the TRPV3 channel protein during oocyte maturation. Using dsRNA, TrpV3 overexpression, and inhibitors of protein synthesis, we modified the native expression of the channel and showed that the TRPV3 protein is …
Evolvability Of The Skull: A Study Of Genetic Basis And Integration In The Teleost Craniofacial Skeleton, Yinan Hu
Doctoral Dissertations
As the field of evolutionary biology pivots away from a gene-centric view of how adaptive evolution proceeds, renewed emphasis is placed on the origin of phenotypic variation. Understanding the developmental processes that underlie the production of novel traits, and how they might influence evolvability, is considered a primary goal in the on-going “extended evolutionary synthesis”. The following dissertation explores these questions in the context of adaptive radiations in fish, with a focus on morphological variation in the craniofacial skeleton. Specifically, the first chapter investigates the genetic and developmental basis of shape (co-)variation in the feeding apparatus of African cichlid fishes, …