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Articles 1 - 28 of 28
Full-Text Articles in Cancer Biology
Human Milk: From Covid-19 Immunity To Breast Cancer Risk Assessment, Vignesh Narayanaswamy
Human Milk: From Covid-19 Immunity To Breast Cancer Risk Assessment, Vignesh Narayanaswamy
Doctoral Dissertations
Breastmilk is a complex biological fluid containing macromolecules including lipids, oligosaccharides, proteins as well as several types of cells. Several studies have reported in detail of these components. My focus is studying the protein component of breastmilk, specifically antibodies, cytokines, and other secreted factors in the setting of different pathogenicity in women. Studies have demonstrated that the levels of numerous cytokines as well as the levels of pathogen-specific antibodies are altered in milk upon either maternal or infant infections. Additionally, there are reports that the levels of certain inflammatory markers are altered in milk among women with breast cancer or …
Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin
Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin
Doctoral Dissertations
The vast majority of breast cancers, ~70%, are not directly related to an inherited genetic mutation. Environmental factors play a dominant role in the etiology of most breast cancers. There is a subset of chemicals that are able to affect the homeostasis of hormones called endocrine disrupting chemicals (EDCs). Many of these chemicals are pervasive and persistent making the chances for lifetime exposure more prevalent. While many of these chemicals have been deemed safe, a subset of them have come under review to reassess their safety. As estrogen is critical for breast development and can act as a mitogen in …
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 …
Extracellular Matrix Stiffness As A Cue To Shape Phenotypic Evolution Of Triple Negative Breast Cancer, Ning-Hsuan Tseng
Extracellular Matrix Stiffness As A Cue To Shape Phenotypic Evolution Of Triple Negative Breast Cancer, Ning-Hsuan Tseng
Doctoral Dissertations
Accumulation of epigenetic and genetic changes results in oncogenic transformation of epithelial cells. During breast cancer metastasis, while the extracellular matrix (ECM) becomes stiffer, breast cancer cells transmit mechanical forces into intracellular tension and activate signaling pathways influencing growth, migration, and metastasis. Once cancer cells detach from the primary tumor, they intravasate into the vasculature, survive in the circulation, extravasate and adapt to a new microenvironment of a secondary site. Throughout the process, only a very small population of cancer cells survive, and they are likely to reside at the metastatic sites for several years. The most frequent metastatic sites …
Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don
Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don
Doctoral Dissertations
Circadian rhythms are 24–hour activity cycles that exist for all organisms, from yeast and bacteria to mammals. Epidemiological data has shown that disruptions to circadian rhythms are associated with various diseases, including cancers. Circadian rhythms are regulated at the cellular level by a "molecular clock,” whose oscillations in protein transcription and translation control a range of downstream pathways. However, the connections between altered rhythms and diseases at the molecular level is unclear. Therefore, in this project, I tracked circadian rhythms in a high-resolution manner and thoroughly analyzed them to more completely reflect circadian behaviors and clock functioning at the molecular …
Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng
Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng
Doctoral Dissertations
Cell surface harbors rich information regarding the status of cell health. Being able to monitor and detect its changes in response to stimuli will provide crucial information in drug discovery, disease diagnosis, and human health. Despite the efforts and breakthroughs made possible through the specific sensing approach, there are significant challenges in extracting the information on the cell surface in a quantitative and reliable way. To address this challenge, I took the approach of array-based, hypothesis-free sensing in which the engineered sensors selectively interact with target analytes, producing a distinct pattern of response that enables analyte identification. This signature-based pattern …
Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter
Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter
Doctoral Dissertations
Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of …
Inter-Individual Variation In Response To Estrogen And Implications For Breast Cancer Risk, Amye L. Black
Inter-Individual Variation In Response To Estrogen And Implications For Breast Cancer Risk, Amye L. Black
Doctoral Dissertations
Breast cancer is the second leading cause of cancer related death among women and the most prevalent cancer type in women worldwide. Many risk factors for breast cancer are related to estrogen exposure and all involve prolonged or high levels of estrogen exposure. However, estrogen exposure during early pregnancy reduces breast cancer risk by up to 50%. Estrogen’s paradoxical role in both contributing to and reducing breast cancer risk is still not understood. We hypothesized that a subset of women may be more sensitive to estrogen exposure, and the following experiments were designed to test this hypothesis and determine if …
Environmental Risk Factors For Inflammatory Bowel Disease: Triclosan And Other Consumer Antimicrobials, Katherine Z. Sanidad
Environmental Risk Factors For Inflammatory Bowel Disease: Triclosan And Other Consumer Antimicrobials, Katherine Z. Sanidad
Doctoral Dissertations
Inflammatory bowel disease (IBD) has become a serious health problem since the incidence and prevalence of IBD has dramatically increased throughout the world. There is evidence that environmental factors are primarily responsible for the increase of IBD, therefore, it is important to identify novel environmental risk factors to reduce the risk of IBD and its associated diseases. Antimicrobials used in consumer products might serve as environmental risk factors for IBD and its associated diseases. Triclosan (TCS), triclocarban (TCC), benzalkonium chloride (BAC), benzethonium chloride (BET), and chloroxylenol (PCMX) are widely used antimicrobial ingredients in consumer products and are ubiquitous contaminants in …
Combination Regimens Using Dietary Components For The Chemoprevention Of Colorectal Cancer And Inflammation, Christina Dimarco-Crook
Combination Regimens Using Dietary Components For The Chemoprevention Of Colorectal Cancer And Inflammation, Christina Dimarco-Crook
Doctoral Dissertations
ABSTRACT COMBINATION REGIMENS USING DIETARY COMPONENTS FOR THE CHEMOPREVENTION OF COLORECTAL CANCER AND INFLAMMATION September 2018 CHRISTINA DIMARCO-CROOK, B.S., IMMACULATA UNIVERSITY M.S., DREXEL UNIVERSITY Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Hang Xiao Dietary components have been found to effectively modulate multiple deregulated signaling pathways associated with the initiation and progression of carcinogenesis and inflammation in cellular and animal models. However, clinical studies have shown mixed results when examining the efficacy of individual dietary components, perhaps suggestive of the synergism that exists between multiple components within a particular food and the diet as a whole. Additional research is needed …
Influences Of Antroquinonol And 4-Acetylantroquinonol B On Inflammatory Tumorigenesis In The Mcf-7 Breast Cancer Cell Line With Or Without Tnf-Α Stimulation, Ting-Chun Lin
Masters Theses
Breast cancer (BC) is one of the most common cancers among women worldwide that ~25% of new cancer cases diagnosed every year would be BC; moreover, ~15% of cancer deaths per year caused by BC makes it the leading cause of cancer death among women worldwide. To date, though the cause of a large proportion of BC are still unclear, recent studies have revealed that a supportive breast tissue microenvironment is critical for the development and progression of BC, especially the communication with immune cells within breast tissue. Therefore, breast inflammatory microenvironment is currently received a substantial attention in the …
Microenvironment Regulates Fusion Of Breast Cancer Cells, Peiran Zhu
Microenvironment Regulates Fusion Of Breast Cancer Cells, Peiran Zhu
Masters Theses
Fusion of cancer cells has been observed in tumors for more than a century and is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have developed a patterned gel system that can isolate cell fusion events and we demonstrate that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive …
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 …
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 …
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 …
The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu
The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu
Doctoral Dissertations
Among all the cancers, the death rate of colorectal cancer is one of the highest. Evidence from both murine xenograft model and human trials have shown cancer stem cells (CSCs) are responsible for the initiation, metastasis and recurrence of multiple cancers therefore targeting colorectal CSCs would be a promising chemo-preventive/ therapeutic strategy. Polymethoxyflavones including nobiletin (NBT) and 5-demethylatednobiletin (5DN) are exclusively found in citrus peels and have been shown to have anti-cancer effects. Our previous studies in the biotransformation and tissue distribution of NBT and 5DN have shown that in order to fuller evaluate the biological impact of those two …
The Investigation Of Rhodiola Crenulata Root Extract Effects On Obesity Associated Inflammation And The Antineoplastic Mechanism In Breast Cancer Cells, Lotfi M. Bassa
Doctoral Dissertations
Obesity and breast cancer are two disease models that directly affect the United States population, as more than 35% of the adult population is obese [8], and more than 200,000 new cases of breast cancer are diagnosed in the United States per year [34]. Several diseases are associated with obesity including, cardiovascular disease, insulin resistance, increased inflammation and increased cancer risk [9,10]. Therefore it essential to understand the risks associated with obesity as well as to investigate possible preventive and/or therapeutic treatment strategies. Rhodiola crenulata is a Tibetan plant that has been used in Eastern traditional medicine to relieve depression, …
Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli
Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli
Doctoral Dissertations
Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due …
Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick
Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick
Doctoral Dissertations
The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …
Stiffness And Modulus And Independent Controllers Of Breast Cancer Metastasis, Dannielle Ryman
Stiffness And Modulus And Independent Controllers Of Breast Cancer Metastasis, Dannielle Ryman
Masters Theses 1911 - February 2014
One out of eight women in the United States will develop breast cancer during their lifetime. Ninety percent of cancer related deaths are due to metastasis. Metastasis is the biological process where individual or aggregate cancerous cells break away from the primary tumor site and colonize distant, non-adjacent locations throughout the body. It is my objectives to study how mechanical, topographical and biochemical cues affect metastatic breast cancer metastasis at an early developmental stage. ECM components have previously been shown to affect cell motility via ligand-receptor interactions, and physical cues, such as matrix stiffness and protein density. The primary tumor …
Modeling Colorectal Cancer As A 3-Dimensional Disease In A Dish: The Case For Drug Screening Using Organoids, Zebrafish, And Fruit Flies, Michele Markstein
Modeling Colorectal Cancer As A 3-Dimensional Disease In A Dish: The Case For Drug Screening Using Organoids, Zebrafish, And Fruit Flies, Michele Markstein
Michele Markstein
This review discusses recent shifts in the understanding of colorectal cancer as a stem cell based disease, based on findings that tie patient prognosis to the presence of cancer stem cells in colorectal tumors. Currently no drugs specifically target CSCs in colorectal tumors. However, recent advances in the culturing of colorectal stem cells using mammalian organoids, zebrafish, and Drosophila offer promising avenues for anti-CSC drug discovery.
Complementary Genomic Screens Identify Serca As A Therapeutic Target In Notch1 Mutated Cancer, G. Roti, A. Carlton, Kn. Ross, Michele Markstein, K. Pajcini, A. H. Su, N. Perrimon, W. S. Pear, A. L. Kung, S. C. Blacklow, J. C. Aster, K. Stegmaier
Complementary Genomic Screens Identify Serca As A Therapeutic Target In Notch1 Mutated Cancer, G. Roti, A. Carlton, Kn. Ross, Michele Markstein, K. Pajcini, A. H. Su, N. Perrimon, W. S. Pear, A. L. Kung, S. C. Blacklow, J. C. Aster, K. Stegmaier
Michele Markstein
Notch1 is a rational therapeutic target in several human cancers, but as a transcriptional regulator, it poses a drug discovery challenge. To identify Notch1 modulators, we performed two cell-based, high-throughput screens for small-molecule inhibitors and cDNA enhancers of a NOTCH1 allele bearing a leukemia-associated mutation. Sarco/endoplasmic reticulum calcium ATPase (SERCA) channels emerged at the intersection of these complementary screens. SERCA inhibition preferentially impairs the maturation and activity of mutated Notch1 receptors and induces a G0/G1 arrest in NOTCH1-mutated human leukemia cells. A small-molecule SERCA inhibitor has on-target activity in two mouse models of human leukemia and interferes with Notch signaling …
Investigating The Mechanism Of Nur77-Induced Apoptosis In T Cells, Heather E. Fogarty
Investigating The Mechanism Of Nur77-Induced Apoptosis In T Cells, Heather E. Fogarty
Masters Theses 1911 - February 2014
Nur77 is a member of the orphan nuclear receptor family, where it is known to play an important role in apoptosis in both negative selection in T cells and in cancer cell lines. In the development of T cells, it is critical for the immune system to discriminate self from non-self by eliminating auto-reactive cells. It was originally thought that Nur77 initiated apoptosis by activating downstream gene targets. However, it is now clear that Nur77 has its own distinct role outside of the nucleus and the precise mechanisms by which Nur77 induces apoptosis in T cells still needs to be …
Notch Regulation Of Adam12 Expression In Glioblastoma Multiforme, Ala'a S. Alsyaideh
Notch Regulation Of Adam12 Expression In Glioblastoma Multiforme, Ala'a S. Alsyaideh
Masters Theses 1911 - February 2014
Glioblastoma is the most common malignant brain tumor, accounting for 17% of all primary brain tumors in the United States. Despite the available surgical, radiation, and chemical therapeutic options, the invasive and infiltrative nature of the tumor render current treatment options minimally effective. Recent reports have identified multiple regulators of glioblastoma progression and invasiveness. It has been demonstrated that ADAM12, A Disintegrin And Metalloproteinase encoded by ADAM12 gene, is over-expressed in glioblastoma and directly correlated with tumor proliferation. Additionally, dysregulation of the Notch signaling pathway has been implicated in the pathogenesis of many gliomas. Lastly, an evolving role of microRNAs, …
In Vivo Investigations Of Polymer Conjugates As Therapeutics, Elizabeth M. Henchey
In Vivo Investigations Of Polymer Conjugates As Therapeutics, Elizabeth M. Henchey
Masters Theses 1911 - February 2014
Polymer conjugates offer a way to introduce materials into the body that would normally be rejected or cause toxicity. Two polymers are investigated in vivo for uses in chemotherapeutic delivery, protein therapeutics, and DNA transfection. A novel polymer, polyMPC, has the ability to increase doxorubicin loading and its solubility, and is conjugated in a way to release its payload in a low pH environment. Through its conjugation, blood clearance time of doxorubicin is increased, and thus tumor exposure to the drug is increased with a single administration. It can be administered at ten times the concentration of free doxorubicin, and …
Regulation Of Crbp1 In Mammary Epithelial Cells, Stacy L. Pease
Regulation Of Crbp1 In Mammary Epithelial Cells, Stacy L. Pease
Masters Theses 1911 - February 2014
Breast cancer is the second leading cause of death of women in the United States, warranting further investigation into preventative therapies. It has been well documented that early pregnancy results in a lifetime decreased risk of breast cancer in humans and mounting evidence suggests that the retinoic acid pathway may play an important role in this protective effect. Cellular retinol binding protein-1 (CRBP1) is an essential component of the retinoic acid pathway and we propose that it plays an important role in pregnancy-induced protection against breast cancer. In order to investigate the role of CRBP1 in parity-induced protection against breast …